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Record Attendance, Key Issues Highlight Pediatric Hospital Medicine's 10th Anniversary
With a record number of attendees, Pediatric Hospital Medicine 2013 (PHM) swept into New Orleans last month, carrying with it unbridled enthusiasm about the past, present, and future.
Virginia Moyer, MD, MPH, vice president for maintenance of certification and quality for the American Board of Pediatrics (ABP) and professor of pediatrics and chief of academic general pediatrics at Texas Children’s Hospital, delivered a keynote address to 700 attendees that focused on the challenges and opportunities of providing evidence-based, high-quality care in the hospital, as well as ABP’s role in meeting these challenges.
“If evidence-based medicine is an individual sport,” Dr. Moyer said, “then quality improvement is a team sport.”
Barriers to quality improvement (QI)— such as lack of will, lack of data, and lack of training—can be surmounted in a team environment, she said. ABP is continuing in its efforts to support QI education through its Maintenance of Certification (MOC) Part 4 modules, as well as other educational activities.
Other highlights of the 10th annual Pediatric Hospital Medicine meeting:
- The addition of a new “Community Hospitalists” track was given high marks by those in attendance. It covered such topics as perioperative management of medically complex pediatric patients, community-acquired pneumonia, and osteomyelitis.
- A 10-year retrospective of pediatric hospital medicine was given by a panel of notable pediatric hospitalists, including Erin Stucky Fisher, MD, FAAP, MHM, chief of hospital medicine at Rady Children’s Hospital in San Diego; Mary Ottolini, MD, MPH, chief of hospital medicine at Children’s National Medical Center in Washington; Jack Percelay, MD, MPH, FAAP, associate clinical professor at Pace University; and Daniel Rauch, MD, FAAP, pediatric hospitalist program director at the NYU School of Medicine in New York City. A host of new programs has been established by the PHM community, including the Quality Improvement Innovation Networks (QuIIN); the Value in Pediatrics (VIP) network; the International Network for Simulation-Based Pediatric Innovation, Research, and Education (INSPIRE); patient- and family-centered rounds; and the I-PASS Handoff Program. The panel also discussed future challenges, including reduction of unnecessary treatments, interfacing, and perhaps incorporating “hyphen hospitalists,” and learning from advances made by the adult HM community.
- The ever-popular “Top Articles in Pediatric Hospital Medicine” session was presented by H. Barrett Fromme, MD, associate professor of pediatrics at the University of Chicago, and Ben Bauer, MD, director of pediatric hospital medicine at Riley Hospital for Children at Indiana University Health in Indianapolis, which was met with raucous approval by the audience. The presentation not only educated those in attendance about the most cutting-edge pediatric literature, but it also included dance moves most likely to attract the opposite sex and clothing appropriate for the Australian pediatric hospitalist.
- The three presidents of the sponsoring societies—Thomas McInerney, MD, FAAP, of the American Academy of Pediatrics, David Keller, MD, of the Academic Pediatric Association, and Eric Howell, MD, SFHM, of SHM—presented each society’s contributions to the growth of PHM, as well as future areas for cooperative sponsorship. These include the development of the AAP Section of Hospital Medicine Library website, the APA Quality Scholars program, and SHM’s efforts to increase interest in hospital medicine in medical students and trainees. “Ask not what hospital medicine can do for you,” Dr. Howell implored, “ask what you can do for hospital medicine!”
- Members of the Joint Council of Pediatric Hospital Medicine (JCPHM) presented the recent recommendations of the council arising from an April 2013 meeting with the ABP in Chapel Hill, N.C. Despite acknowledgements that no decision will be met with uniform satisfaction by all the stakeholders, the JCPHM concluded that the path that would best advance the field of PHM, provide for high-quality care of hospitalized children, and ensure the public trust would be a two-year fellowship sponsored by ABP. This would ultimately lead to approved certification eligibility for fellowship graduates by the American Board of Medical Specialties (ABMS); it would also make provisions for “grandfathering” in current pediatric hospitalists. Concerns from med-peds, community hospitalists, and recent residency graduate communities were addressed by the panel.
- A recurrent theme of reducing unnecessary treatments, interventions, and, perhaps, hospitalizations was summarized eloquently by Alan Schroeder, MD, director of the pediatric ICU and chief of pediatric inpatient care at Santa Clara (Calif.) Valley Health. Barriers to reducing unnecessary care can be substantial, including pressure from families, pressure from colleagues, profit motive, and the “n’s of 1,” according to Dr. Schroeder. Ultimately, however, avoiding testing and treatments that have no benefit to children will improve care. “Ask, ‘How will this test benefit my patient?’ not ‘How will this test change management?’” Dr. Schroeder advised. TH
10: years in existence
720: attendees
220: scientific abstracts
9: tracks
Dr. Chang is The Hospitalist’s pediatric editor and a med-peds-trained hospitalist working at the University of California San Diego and Rady Children’s Hospital.
With a record number of attendees, Pediatric Hospital Medicine 2013 (PHM) swept into New Orleans last month, carrying with it unbridled enthusiasm about the past, present, and future.
Virginia Moyer, MD, MPH, vice president for maintenance of certification and quality for the American Board of Pediatrics (ABP) and professor of pediatrics and chief of academic general pediatrics at Texas Children’s Hospital, delivered a keynote address to 700 attendees that focused on the challenges and opportunities of providing evidence-based, high-quality care in the hospital, as well as ABP’s role in meeting these challenges.
“If evidence-based medicine is an individual sport,” Dr. Moyer said, “then quality improvement is a team sport.”
Barriers to quality improvement (QI)— such as lack of will, lack of data, and lack of training—can be surmounted in a team environment, she said. ABP is continuing in its efforts to support QI education through its Maintenance of Certification (MOC) Part 4 modules, as well as other educational activities.
Other highlights of the 10th annual Pediatric Hospital Medicine meeting:
- The addition of a new “Community Hospitalists” track was given high marks by those in attendance. It covered such topics as perioperative management of medically complex pediatric patients, community-acquired pneumonia, and osteomyelitis.
- A 10-year retrospective of pediatric hospital medicine was given by a panel of notable pediatric hospitalists, including Erin Stucky Fisher, MD, FAAP, MHM, chief of hospital medicine at Rady Children’s Hospital in San Diego; Mary Ottolini, MD, MPH, chief of hospital medicine at Children’s National Medical Center in Washington; Jack Percelay, MD, MPH, FAAP, associate clinical professor at Pace University; and Daniel Rauch, MD, FAAP, pediatric hospitalist program director at the NYU School of Medicine in New York City. A host of new programs has been established by the PHM community, including the Quality Improvement Innovation Networks (QuIIN); the Value in Pediatrics (VIP) network; the International Network for Simulation-Based Pediatric Innovation, Research, and Education (INSPIRE); patient- and family-centered rounds; and the I-PASS Handoff Program. The panel also discussed future challenges, including reduction of unnecessary treatments, interfacing, and perhaps incorporating “hyphen hospitalists,” and learning from advances made by the adult HM community.
- The ever-popular “Top Articles in Pediatric Hospital Medicine” session was presented by H. Barrett Fromme, MD, associate professor of pediatrics at the University of Chicago, and Ben Bauer, MD, director of pediatric hospital medicine at Riley Hospital for Children at Indiana University Health in Indianapolis, which was met with raucous approval by the audience. The presentation not only educated those in attendance about the most cutting-edge pediatric literature, but it also included dance moves most likely to attract the opposite sex and clothing appropriate for the Australian pediatric hospitalist.
- The three presidents of the sponsoring societies—Thomas McInerney, MD, FAAP, of the American Academy of Pediatrics, David Keller, MD, of the Academic Pediatric Association, and Eric Howell, MD, SFHM, of SHM—presented each society’s contributions to the growth of PHM, as well as future areas for cooperative sponsorship. These include the development of the AAP Section of Hospital Medicine Library website, the APA Quality Scholars program, and SHM’s efforts to increase interest in hospital medicine in medical students and trainees. “Ask not what hospital medicine can do for you,” Dr. Howell implored, “ask what you can do for hospital medicine!”
- Members of the Joint Council of Pediatric Hospital Medicine (JCPHM) presented the recent recommendations of the council arising from an April 2013 meeting with the ABP in Chapel Hill, N.C. Despite acknowledgements that no decision will be met with uniform satisfaction by all the stakeholders, the JCPHM concluded that the path that would best advance the field of PHM, provide for high-quality care of hospitalized children, and ensure the public trust would be a two-year fellowship sponsored by ABP. This would ultimately lead to approved certification eligibility for fellowship graduates by the American Board of Medical Specialties (ABMS); it would also make provisions for “grandfathering” in current pediatric hospitalists. Concerns from med-peds, community hospitalists, and recent residency graduate communities were addressed by the panel.
- A recurrent theme of reducing unnecessary treatments, interventions, and, perhaps, hospitalizations was summarized eloquently by Alan Schroeder, MD, director of the pediatric ICU and chief of pediatric inpatient care at Santa Clara (Calif.) Valley Health. Barriers to reducing unnecessary care can be substantial, including pressure from families, pressure from colleagues, profit motive, and the “n’s of 1,” according to Dr. Schroeder. Ultimately, however, avoiding testing and treatments that have no benefit to children will improve care. “Ask, ‘How will this test benefit my patient?’ not ‘How will this test change management?’” Dr. Schroeder advised. TH
10: years in existence
720: attendees
220: scientific abstracts
9: tracks
Dr. Chang is The Hospitalist’s pediatric editor and a med-peds-trained hospitalist working at the University of California San Diego and Rady Children’s Hospital.
With a record number of attendees, Pediatric Hospital Medicine 2013 (PHM) swept into New Orleans last month, carrying with it unbridled enthusiasm about the past, present, and future.
Virginia Moyer, MD, MPH, vice president for maintenance of certification and quality for the American Board of Pediatrics (ABP) and professor of pediatrics and chief of academic general pediatrics at Texas Children’s Hospital, delivered a keynote address to 700 attendees that focused on the challenges and opportunities of providing evidence-based, high-quality care in the hospital, as well as ABP’s role in meeting these challenges.
“If evidence-based medicine is an individual sport,” Dr. Moyer said, “then quality improvement is a team sport.”
Barriers to quality improvement (QI)— such as lack of will, lack of data, and lack of training—can be surmounted in a team environment, she said. ABP is continuing in its efforts to support QI education through its Maintenance of Certification (MOC) Part 4 modules, as well as other educational activities.
Other highlights of the 10th annual Pediatric Hospital Medicine meeting:
- The addition of a new “Community Hospitalists” track was given high marks by those in attendance. It covered such topics as perioperative management of medically complex pediatric patients, community-acquired pneumonia, and osteomyelitis.
- A 10-year retrospective of pediatric hospital medicine was given by a panel of notable pediatric hospitalists, including Erin Stucky Fisher, MD, FAAP, MHM, chief of hospital medicine at Rady Children’s Hospital in San Diego; Mary Ottolini, MD, MPH, chief of hospital medicine at Children’s National Medical Center in Washington; Jack Percelay, MD, MPH, FAAP, associate clinical professor at Pace University; and Daniel Rauch, MD, FAAP, pediatric hospitalist program director at the NYU School of Medicine in New York City. A host of new programs has been established by the PHM community, including the Quality Improvement Innovation Networks (QuIIN); the Value in Pediatrics (VIP) network; the International Network for Simulation-Based Pediatric Innovation, Research, and Education (INSPIRE); patient- and family-centered rounds; and the I-PASS Handoff Program. The panel also discussed future challenges, including reduction of unnecessary treatments, interfacing, and perhaps incorporating “hyphen hospitalists,” and learning from advances made by the adult HM community.
- The ever-popular “Top Articles in Pediatric Hospital Medicine” session was presented by H. Barrett Fromme, MD, associate professor of pediatrics at the University of Chicago, and Ben Bauer, MD, director of pediatric hospital medicine at Riley Hospital for Children at Indiana University Health in Indianapolis, which was met with raucous approval by the audience. The presentation not only educated those in attendance about the most cutting-edge pediatric literature, but it also included dance moves most likely to attract the opposite sex and clothing appropriate for the Australian pediatric hospitalist.
- The three presidents of the sponsoring societies—Thomas McInerney, MD, FAAP, of the American Academy of Pediatrics, David Keller, MD, of the Academic Pediatric Association, and Eric Howell, MD, SFHM, of SHM—presented each society’s contributions to the growth of PHM, as well as future areas for cooperative sponsorship. These include the development of the AAP Section of Hospital Medicine Library website, the APA Quality Scholars program, and SHM’s efforts to increase interest in hospital medicine in medical students and trainees. “Ask not what hospital medicine can do for you,” Dr. Howell implored, “ask what you can do for hospital medicine!”
- Members of the Joint Council of Pediatric Hospital Medicine (JCPHM) presented the recent recommendations of the council arising from an April 2013 meeting with the ABP in Chapel Hill, N.C. Despite acknowledgements that no decision will be met with uniform satisfaction by all the stakeholders, the JCPHM concluded that the path that would best advance the field of PHM, provide for high-quality care of hospitalized children, and ensure the public trust would be a two-year fellowship sponsored by ABP. This would ultimately lead to approved certification eligibility for fellowship graduates by the American Board of Medical Specialties (ABMS); it would also make provisions for “grandfathering” in current pediatric hospitalists. Concerns from med-peds, community hospitalists, and recent residency graduate communities were addressed by the panel.
- A recurrent theme of reducing unnecessary treatments, interventions, and, perhaps, hospitalizations was summarized eloquently by Alan Schroeder, MD, director of the pediatric ICU and chief of pediatric inpatient care at Santa Clara (Calif.) Valley Health. Barriers to reducing unnecessary care can be substantial, including pressure from families, pressure from colleagues, profit motive, and the “n’s of 1,” according to Dr. Schroeder. Ultimately, however, avoiding testing and treatments that have no benefit to children will improve care. “Ask, ‘How will this test benefit my patient?’ not ‘How will this test change management?’” Dr. Schroeder advised. TH
10: years in existence
720: attendees
220: scientific abstracts
9: tracks
Dr. Chang is The Hospitalist’s pediatric editor and a med-peds-trained hospitalist working at the University of California San Diego and Rady Children’s Hospital.
Delirium Superimposed on Dementia
Much attention has been given recently to hospitalized older adults, the critical 30‐day period, and posthospital syndrome.[1] What is missing from this dialogue is the contribution and significance of underlying cognitive impairment. By 2050, 14 million older persons in the United States are expected to have dementia.[2] Increasing numbers of older adults diagnosed with dementia are hospitalized and are at increased risk of developing delirium; in fact, delirium occurs in over half of hospitalized persons with dementia.[3] Further, current evidence suggests that delirium may accelerate the clinical course and trajectory of cognitive decline, and may be associated with considerably worse long‐term outcomes, including prolonged hospitalization, rehospitalization within 30 days, nursing home placement, and death.[3, 4, 5, 6] However, the problem of delirium superimposed on dementia (DSD) remains a neglected area of investigation in hospitalized patients. Delirium is superimposed on dementia when an acute change in mental status (characterized by a fluctuating course, inattention, and either disorganized thinking or altered level of consciousness) is layered on top of preexisting dementia.[4]
Despite the poor outcomes and high prevalence of DSD, little is known about the natural history in hospitalized older adults with dementia. Delirium studies often exclude persons with dementia, even though the prevalence of DSD is extremely high in both community (13%19%) and hospital (40%89%) populations and associated with higher costs and utilization compared to dementia and delirium alone.[4, 5, 7] In 1 study, annual costs for DSD were $9566 compared to $7557 for dementia alone.[7] The few risk‐factor studies of DSD were conducted in intensive care unit (ICU) or long‐term care settings.[8, 9]
The purpose of this study was to describe the incidence, risk factors, and outcomes associated with incident delirium in a prospective cohort of hospitalized older adults with dementia. The study aims were to: (1) estimate the incidence of new delirium in hospitalized persons with dementia, (2) identify the risk factors associated with incident delirium superimposed on dementia in this sample, (3) describe the outcomes associated with development of delirium, and (4) evaluate the contributions of delirium severity and duration to outcomes.
METHODS
This 24‐month prospective cohort study recruited and enrolled consecutive hospital admissions with dementia in a 300‐bed community hospital in central Pennsylvania from July 2006 through November 2008. Data were collected daily from patients during hospitalization, followed by a 1‐month posthospitalization interview with patients and their caregivers in the community setting. Patients were included if they spoke English, had been hospitalized fewer than 24 hours, and met the screening criteria for dementia. Patients were excluded if they had any significant neurological condition associated with cognitive impairment other than dementia (eg, brain tumor), a major acute psychiatric disorder, were unable to communicate, or had no caregiver to interview. The interviewers included experienced research assistants (RAs) who were either registered nurses or trained in a health‐related field. All staff training of instruments were done with scripted training manuals and video training using manuals for the Confusion Assessment Method (CAM). After training was completed, final inter‐rater reliability assessments were conducted until staff reached 100% agreement. The RAs were blinded to the aims and completed over 10 hours of training. Inter‐rater reliability checks were conducted on 10% of the sample in the field with >90% agreement attained on all instruments. This study was reviewed by and approved by The Pennsylvania State University institutional review board, and consent was received from all subjects.
Study Measures
Dementia was defined by meeting all 3 criteria of a Modified Blessed Dementia Rating Score of >3, an Informant Questionnaire on Cognitive Decline in the Elderly of 3.3, and documented dementia symptoms of at least 6 months' duration prior to current illness.[10, 11, 12] The Mini‐Mental State Examination (MMSE), purchased from Psychological Assessment Resources, Inc. (Lutz, FL), was used to measure change from day to day and aid in the measurement of delirium, but was not used to establish the diagnosis of dementia. Both the Clinical Dementia Rating Scale[13] and the Global Deterioration Scale (GDS)[14] were used to measure dementia stage and severity.
Delirium and delirium severity were defined according to the validated CAM algorithm;[15] the Delirium Rating Scale‐Revised‐98 was used for delirium severity.[16] In a recent review, the CAM showed an overall sensitivity of 94% and specificity of 89%.[17] In the present study, delirium was measured in a comprehensive and structured interview that involved the MMSE and CAM criteria, and was based on a 24‐hour period of observations, interviews with nurses and family members, and chart review. The CAM was completed daily during patient hospitalization and the follow‐up interviews. The CAM assesses 4 criteria including acute and fluctuating nature, inattention, disorganized thought, and altered level of consciousness. Delirium was recorded by the research staff as present or absent each day based on full CAM criteria. Because the goal of the present study focused on full CAM delirium, subsyndromal delirium was not presented in this article.
Delirium duration was defined as the number of days with a positive rating. Data were collected daily from patients during hospitalization, followed by a single interview at 1‐month posthospitalization with patients and their caregivers. Most interviews were in person.
Delirium Risk Factors
Central nervous system‐active drug use was defined by 2005 American Hospital Formulary Services classification.[18] The Beers criteria were used to define potentially inappropriate medication use.[19] The Cornell scale for depression in persons with dementia was used, with a cut point of 12 indicating depression.[20] Functional status change was measured via the Katz Index of Activities of Daily Living (ADLs) and Lawton Instrumental Activities Of Daily Living (IADLs) change scores.[21] Comorbid conditions were classified with a weighted index that took into account both the number and seriousness of different comorbid diseases.[22] Pain was measured using the Pain Assessment in Advanced Dementia (PAINAD) scale.[23] Dehydration was defined using the blood urea nitrogen (BUN)/creatinine ratio and/or any chart diagnosis of dehydration. Admission lab values (BUN/creatinine) were abstracted from the medical records.
Primary Outcomes
The primary outcomes measured were full CAM delirium, index hospitalization length of stay, cognitive decline (change in MMSE and GDS scores), death, and functional status change (change from baseline to discharge score). One‐month mortality was measured by chart review and follow‐up family interviews performed at 1 month via telephone or in‐person interviews. Mortality was not verified by additional methods.
Statistical Analysis
All statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, NC), and statistical significance was assessed using an level of 0.05 unless otherwise noted. Descriptive statistics were calculated on all characteristics by incident delirium status.
Potential risk factors for incident delirium were examined using [2] and t tests, where appropriate. Simple proportional hazards models were used to estimate the relative risk (RR) and 95% confidence interval (CI) for incident delirium. A stepwise model‐building procedure under a proportional hazards model was used to build a final model for incident delirium that contained all variables that were statistically significant at the 0.05 level or that had an RR of 1.5 or greater. Adjusted RR and corresponding 95% CI were determined. The outcome in each model was the number of days from admission to an incident delirium diagnosis. Subjects without incident delirium were censored using their length of stay as the total number of days they were at risk for developing delirium.
Finally, to examine the relationships between incident delirium, maximum incident delirium severity and the number of inpatient days positive for delirium with the outcomes of death, impaired in 2 or more IADLs at follow‐up, impaired in 2 or more ADLs at follow‐up, length of stay, change in IADLs from admission to follow‐up, and change in ADLs from admission to follow‐up, logistic regression (for the dichotomous outcome of mortality), analysis of covariance or linear regression (depending on the whether the independent variable was categorical or continuous) was performed controlling for age, gender, and GDS score.
RESULTS
Of 256 eligible patients, dual consent was obtained from 154 patient and 154 family research subjects (308 consents). The refusal rate was 39% (n=102). Fourteen subjects were consented and enrolled but later dropped out due to family/proxy concerns regarding the patient's ability to participate in interviews. Thus, the final sample included 139 patients.
Descriptive statistics for baseline measures are given in Table 1. Briefly, the average age of subjects was 83 years (standard deviation [SD]=7); 41% were male; 57% were single, divorced, or widowed; and the average number of years of education was 12 years (SD=3). Thirty‐three percent were dehydrated on admission, and 33% had fallen within 2 weeks prior to admission. Thirty‐four percent had an infection at baseline, and 36% had some sensory impairment.
Factor | Delirium, N=44, 31.7% | No Delirium, N=95, 68.3% | Relative Risk | 95% CI | P Value |
---|---|---|---|---|---|
| |||||
Demographic covariates | |||||
Age, y, mean (SD) | 85.9 (5.9) | 82.4 (7.0) | 1.07 | 1.021.12 | 0.0051 |
Male gender, n (%) | 23 (52.3) | 33 (34.7) | 1.83 | 1.013.31 | 0.0456 |
Single/divorced/widowed, n (%) | 23 (52.3) | 56 (60.2) | 0.81 | 0.451.47 | 0.4882 |
Education, y, mean (SD) | 12.6 (3.2) | 12.1 (3.0) | 1.06 | 0.951.17 | 0.3146 |
Clinical covariates | |||||
Dehydration, n (%) | 12 (30.8) | 30 (33.7) | 0.88 | 0.451.74 | 0.7152 |
Fall in last 2 weeks, n (%) | 14 (41.2) | 21 (29.6) | 1.73* | 0.873.43 | 0.1186 |
Infection, n (%) | 13 (40.6) | 21 (30.9) | 1.42 | 0.702.88 | 0.3328 |
Sensory impairment, n (%) | 16 (36.4) | 33 (34.7) | 1.04 | 0.561.91 | 0.9132 |
Lawton score, mean (SD) | 1.6 (1.3) | 2.3 (2.0) | 0.84 | 0.701.01 | 0.0592 |
Katz impaired score, mean (SD) | 2.3 (2.0) | 3.4 (2.1) | 0.82 | 0.710.95 | 0.0072 |
Charlson score, mean (SD) | 2.5 (1.8) | 2.3 (1.4) | 1.06 | 0.861.30 | 0.6013 |
BUN, mean (SD) | 28.2 (17.6) | 25.6 (15.3) | 1.01 | 0.991.03 | 0.4175 |
Creatinine, mean (SD) | 1.6 (1.3) | 2.4 (6.8) | 0.99 | 0.901.08 | 0.7356 |
Cornell Depression score, mean (SD) | 1.6 (0.8) | 1.2 (0.9) | 1.35 | 0.991.83 | 0.0553 |
Global Deterioration score, mean (SD) | 4.7 (1.2) | 3.9 (1.3) | 1.45* | 1.141.86 | 0.0027 |
PAINAD score, mean (SD) | 2.1 (3.0) | 2.0 (2.9) | 1.01 | 0.911.12 | 0.8540 |
Total number of regular medications, mean (SD) | 11.5 (4.6) | 11.0 (5.0) | 1.00 | 0.941.67 | 0.9771 |
Total number of Beers medications, mean (SD) | 0.3 (0.7) | 0.4 (0.7) | 0.76 | 0.461.27 | 0.2933 |
Cognitive impairment covariates | |||||
MMSE score, mean (SD) | 12.7 (6.8) | 17.1 (6.6) | 0.94 | 0.900.98 | 0.0019 |
Blessed score, mean (SD) | 9.5 (3.5) | 7.7 (2.9) | 1.14 | 1.041.24 | 0.0038 |
Measures of deliriumcovariates for follow‐up outcomes | |||||
Maximum incident delirium severity, mean (SD) | 15.4 (5.6) | 8.7 (6.1) | <0.0001 | ||
Inpatient days with positive CAM, mean (SD) | 2.0 (1.1) | 0.2 (1.4) | <0.0001 | ||
Follow‐up outcomes | |||||
Mortality, n (%) | 11 (25.0) | 9 (9.5) | 0.0153 | ||
Length of stay, mean (SD) | 9.1 (4.4) | 5.7 (4.1) | <0.0001 | ||
Change in Lawton IADLs from admission to follow‐up, mean (SD) | 0.4 (1.5) | 0.2 (1.8) | 0.5094 | ||
Change in Katz impaired ADLs from admission to follow‐up, mean (SD) | 0.3 (1.7) | 0.4 (1.6) | 0.6919 |
The overall incidence of delirium was 32% (44/139) and the range of days to incident delirium was 1 to 8 days. During the baseline period (Table 1), subjects with delirium were older, more likely to be male, had lower Katz impairment scores, higher GDS score, lower MMSE scores on admission, and higher Blessed scores than subjects without delirium. Slightly more persons with delirium had a prior fall, although the RR was not statistically significant. Length of stay measured at discharge was significantly higher for those with delirium (mean=9.1) than those without delirium (mean=5.7) (P<0.0001). Subjects with delirium were more likely to have died at 1 month than those without delirium (P=0.0153).
In addition, we analyzed the adjusted relative risk estimates for the final model of incident delirium. Significant risk factors or risk factors with RR estimates at least 1.5 (or <0.66 if protective [Table 1]) that were examined in a more comprehensive multiple proportional hazards model included age, gender, having had a fall in the last 2 weeks, number of impaired ADLs (based on Katz), GDS scores, MMSE scores at baseline, and Blessed scores at baseline. The final proportional hazards included gender and GDS score. Males were nearly 1.8 times as likely to develop delirium than females, and for every 1 unit increase in the GDS, subjects were 1.5 times more likely to develop delirium.
Finally, Table 2 gives the results of examining outcomes related to incident delirium measures. For mortality, there were no statistically significant predictors of death after controlling for age, gender, or GDS. For length of stay, subjects with incident delirium had significantly longer lengths of stay, as incident delirium severity increased by 1 unit the length of stay increased by 0.4 days, and as the number of inpatient days with delirium increased by 1 day the length of stay increased by 1.8 days. For change in the impaired Katz ADLs from admission to follow‐up, as incident delirium severity increased by 1 unit the change in impaired Katz ADLs increased by 0.05 units.
Variable | |||
---|---|---|---|
Outcome mortality | Level | Adjusted Estimate of Associationa | P Value |
| |||
Incident delirium, OR (95% CI)b | Yes | 2.33 (0.82‐6.61) | 0.1130 |
No | 1.00 | ||
Maximum incident delirium severity, OR (95% CI)b | 1.05 (0.961.14) | 0.2719 | |
Number of inpatient days with positive delirium, OR (95% CI)b | 1.15 (0.891.49) | 0.2871 | |
Outcome LOS | |||
Incident delirium, mean (SE)c | Yes | 9.2 (0.7) | <0.0001 |
No | 5.6 (0.5) | ||
Maximum incident delirium severity, slope (SE)d | 0.43 (0.06) | <0.0001 | |
Number of inpatient days with positive delirium, slope (SE)d | 1.80 (0.21) | <0.0001 | |
Outcomechange in Lawton IADLs from admission to follow‐up | |||
Incident delirium, mean (SE)c | Yes | 0.51 (0.33) | 0.3787 |
No | 0.15 (0.20) | ||
Maximum incident delirium severity, slope (SE)d | 0.003 (0.03) | 0.9260 | |
Number of inpatient days with positive delirium, slope (SE)d | 0.16 (0.11) | 0.1497 | |
Outcomechange in Katz impaired ADLs from admission to follow‐up | |||
Incident delirium, mean (SE)c | Yes | 0.19 (0.26) | 0.5086 |
No | 0.40 (0.17) | ||
Maximum incident delirium severity, slope (SE)d | 0.05 (0.03) | 0.0437 | |
Number of inpatient days with positive delirium, slope (SE)d | 0.13 (0.09) | 0.1717 |
DISCUSSION
The most compelling finding from this study is the high incidence of delirium in hospitalized older adults with dementia and the association with poor clinical outcomes in those who develop delirium superimposed on dementia. DSD is difficult to detect and prevent; persons with DSD are at risk for poor quality of life. Those with delirium had a 25% short‐term mortality rate (P=0.0153), substantially increased length of stay (9.1 vs 5.1 days with an odds ratio of 1.8) and poorer physical function at discharge and follow‐up. At 1 month follow‐up, subjects with delirium had greater functional decline and lower GDS scores than those without delirium.
The incidence of delirium in this study was high (32%). Being delirious any time was associated with death and poor function. Delirium was also associated with the stage of the persons' baseline dementia, advanced age, lower MMSE scores, and falling before admission.
Previous studies have found delirium associated with increased mortality. Three studies found that within 1 year of a delirium episode, a significant number of persons died or were institutionalized.[24, 25, 26] Other research has reported death within 1 year of documented delirium episodes, and a 3‐fold increased rate of death in the ICU.[24, 27, 28, 29, 30, 31, 32] This study is 1 of only a few to focus on increased mortality with DSD and to focus uniquely on hospitalized patients with delirium and dementia.
The main risk factors for delirium in this study were male sex and severity of dementia. Our results, combined with those from other recent studies by Voyer and colleagues,[8, 33, 34] point to the critical importance of screening for dementia in hospitalized older adults as dementia severity is a significant indicator of delirium severity. For instance, Voyer and colleagues[34] reported that persons with mild dementia were likely to experience a mild delirium, whereas those with a more severe level of dementia were more likely to experience moderate to severe delirium. Our findings show that those who experienced episodes of delirium represented a highly vulnerable population with advanced dementia, sensory impairment, more falls and dehydration at admission, and higher Blessed scores. A recent study by Saczynski and colleagues[35] found 40% of patients who had experienced postoperative delirium did not return to their baseline at 6 months. Clearly, preventing delirium should be a critical priority to prevent such deterioration in the highly vulnerable population of hospitalized patients with dementia.
Patients in this study were on a mean of over 11 medications. One‐third of dementia patients in our study had also experienced a fall and dehydration at baseline. Other studies have found a relationship between cognitive decline, falling, and medications.[36] Many of these patients came into the hospital with potentially modifiable and preventable community or ambulatory care conditions of polypharmacy, falling, sensory impairment, and dehydration.
Importantly, in our study, length of stay was significantly higher (9.1 vs 5.7) for those with delirium compared to those without delirium. This finding is alarming when examining the economic impact of preventing delirium. Previous studies have found the cost of delirious episodes rivals those for diabetes and heart disease, and that decreasing length of stay by just 1 day would save over $20 million dollars per year.[4, 37]
In summary, this study is 1 of the first to report a high incidence of DSD and poorer outcomes for persons who experience delirium compared to those with dementia alone. This is 1 of only a few studies examining unique risk factors and delirium severity for DSD in the acute care setting. Findings from the current study report potential risk factors for development of incident delirium and highlight the challenge of preventing DSD before and during hospitalization. The generalizability of this study may be limited by the use of a nondiverse study population drawn from a single hospital in the northeast United States, though the use of a community hospital increases the relevance to real‐world practice settings. Determination of baseline cognitive status and the differentiation of delirium and dementia are difficult, but validated, state‐of‐the‐art methods were used that have been applied in previous studies.
This study provides fundamental methodological improvements over previous work, and advances the science by providing valuable data on the natural history, correlates, and outcomes of DSD. The strengths of this study include the prospective cohort design, the daily assessment for delirium based on a 24‐hour period, methods for determining cognitive status at baseline in this difficult population, and utilizing strict blinding of the well‐trained outcome assessors.
This study lays the groundwork for future studies to improve care for persons with dementia who present to acute care and to plan prevention programs for delirium before they are admitted to the hospital. We must be able to translate best practice for DSD into the acute care and community settings to prevent or minimize effects of delirium in persons with dementia. Interventions to increase early detection of delirium by hospital staff have the potential to decrease the severity and duration of delirium and prevent unnecessary suffering and costs from the complications of delirium and preventable readmissions to the hospital.
Thus, this study holds substantial clinical and economic implications for this population in the acute care setting, and will direct future studies leading to changes in real‐world practice settings for persons with dementia.
Disclosures
Drs. Fick, Inouye, and Steis acknowledge support for this project described by grants number R03 AG023216 (DMF) and number P01AG031720 (SKI) from the National Institute of Aging (NIA). This study and its contents are solely the responsibilities of the authors and do not necessarily represent the official views of the National Institutes of Health/NIA. The principal investigator, Dr. Fick, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no conflicts of interest.
funding section: Dr. Inouye holds the Milton and Shirley F. Levy Family Chair.
- Post‐hospital syndrome—an acquired, transient condition of generalized risk. N Engl J Med. 2013;368(2):100–102. .
- Alzheimer's Association. Alzheimer's disease facts and figures. Alzheimers Dement. 2012;8(2):131–168.
- Delirium superimposed on dementia: accuracy of nurse documentation. J Gerontol Nurs. 2012;38(1):32–42. , .
- Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2002;50(10):1723–1732. , , .
- Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009;72(18):1570–1575. , , , et al.
- Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Intern Med. 2012;156(12):848–856, W296. , , , et al.
- Delirium superimposed on dementia in a community‐dwelling managed care population: a 3‐year retrospective study of occurrence, costs, and utilization. J Gerontol. 2005;60A(6):748–753. , , , .
- Factors associated with delirium severity among older persons with dementia. J Neurosci Nurs. 2011;43(2):62–69. , , , .
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- Validation of the Delirium Rating Scale‐Revised‐98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001;13(2):229–242. , , , , , .
- The confusion assessment method: a systematic review of current usage. J Am Geriatr Soc. 2008;56(5):823–830. , , , .
- American Society of Health‐System Pharmacists. AHFS Drug Information. Bethesda, MD: American Society of Health‐System Pharmacists; 2005.
- Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts [published correction appears in Arch Intern Med. 2004;164:298]. Arch Intern Med 2003;163(22):2716–2724. , , , , , .
- Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988;23(3):271–284. , , , .
- Assessing self‐maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc. 1983;31(12):721–726. .
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. , , , .
- Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J Am Med Dir Assoc. 2003;4(1):9–15. , , .
- Prevalence and outcomes of delirium in community and non‐acute care settings in people without dementia: a report from the Canadian Study of Health and Aging. BMC Med. 2006;4:15. , , .
- Prognostic significance of delirium in frail older people. Dementia. 2005;19(2‐3):158–163. , , , .
- Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta‐analysis. JAMA. 2010;304(4):443–451. , , , , , .
- Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753–1762. , , , et al.
- Delirium subtypes and 1‐year mortality among elderly patients discharged from a post‐acute rehabilitation facility. J Gerontol. 2007;62A(10):1182–1183. , , , .
- Delirium in older patients admitted to general internal medicine. J Geriatr Psychiatry Neurol. 2006;19(2):83–90. , , , , , .
- Association between psychomotor activity delirium subtypes and mortality among newly admitted postacute facility patients. J Gerontol. 2007;62A(2):174–179. , , , .
- Premature death associated with delirium at 1‐year follow‐up. Arch Intern Med. 2005;165:1657–1662. , , , , , .
- Older adults discharged from the hospital with delirium: 1‐year outcomes. J Am Geriatr Soc. 2006;54(8):1245–1250. , , , et al.
- Influence of prior cognitive impairment on the severity of delirium symptoms among older patients. J Neurosci Nurs. 2006;38(2):90–101. , , , .
- Factors associated with delirium severity among older patients. J Clin Nurs. 2007;16:819–831. , , , , .
- Cognitive trajectories after postoperative delirium. N Engl J Med. 2012;367(1):30–39. , , , et al.
- Effect of central nervous system medication use on decline in cognition in community‐dwelling older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2009;57(2):243–250. , , , et al.
- One‐year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168(1):27. , , , , .
Much attention has been given recently to hospitalized older adults, the critical 30‐day period, and posthospital syndrome.[1] What is missing from this dialogue is the contribution and significance of underlying cognitive impairment. By 2050, 14 million older persons in the United States are expected to have dementia.[2] Increasing numbers of older adults diagnosed with dementia are hospitalized and are at increased risk of developing delirium; in fact, delirium occurs in over half of hospitalized persons with dementia.[3] Further, current evidence suggests that delirium may accelerate the clinical course and trajectory of cognitive decline, and may be associated with considerably worse long‐term outcomes, including prolonged hospitalization, rehospitalization within 30 days, nursing home placement, and death.[3, 4, 5, 6] However, the problem of delirium superimposed on dementia (DSD) remains a neglected area of investigation in hospitalized patients. Delirium is superimposed on dementia when an acute change in mental status (characterized by a fluctuating course, inattention, and either disorganized thinking or altered level of consciousness) is layered on top of preexisting dementia.[4]
Despite the poor outcomes and high prevalence of DSD, little is known about the natural history in hospitalized older adults with dementia. Delirium studies often exclude persons with dementia, even though the prevalence of DSD is extremely high in both community (13%19%) and hospital (40%89%) populations and associated with higher costs and utilization compared to dementia and delirium alone.[4, 5, 7] In 1 study, annual costs for DSD were $9566 compared to $7557 for dementia alone.[7] The few risk‐factor studies of DSD were conducted in intensive care unit (ICU) or long‐term care settings.[8, 9]
The purpose of this study was to describe the incidence, risk factors, and outcomes associated with incident delirium in a prospective cohort of hospitalized older adults with dementia. The study aims were to: (1) estimate the incidence of new delirium in hospitalized persons with dementia, (2) identify the risk factors associated with incident delirium superimposed on dementia in this sample, (3) describe the outcomes associated with development of delirium, and (4) evaluate the contributions of delirium severity and duration to outcomes.
METHODS
This 24‐month prospective cohort study recruited and enrolled consecutive hospital admissions with dementia in a 300‐bed community hospital in central Pennsylvania from July 2006 through November 2008. Data were collected daily from patients during hospitalization, followed by a 1‐month posthospitalization interview with patients and their caregivers in the community setting. Patients were included if they spoke English, had been hospitalized fewer than 24 hours, and met the screening criteria for dementia. Patients were excluded if they had any significant neurological condition associated with cognitive impairment other than dementia (eg, brain tumor), a major acute psychiatric disorder, were unable to communicate, or had no caregiver to interview. The interviewers included experienced research assistants (RAs) who were either registered nurses or trained in a health‐related field. All staff training of instruments were done with scripted training manuals and video training using manuals for the Confusion Assessment Method (CAM). After training was completed, final inter‐rater reliability assessments were conducted until staff reached 100% agreement. The RAs were blinded to the aims and completed over 10 hours of training. Inter‐rater reliability checks were conducted on 10% of the sample in the field with >90% agreement attained on all instruments. This study was reviewed by and approved by The Pennsylvania State University institutional review board, and consent was received from all subjects.
Study Measures
Dementia was defined by meeting all 3 criteria of a Modified Blessed Dementia Rating Score of >3, an Informant Questionnaire on Cognitive Decline in the Elderly of 3.3, and documented dementia symptoms of at least 6 months' duration prior to current illness.[10, 11, 12] The Mini‐Mental State Examination (MMSE), purchased from Psychological Assessment Resources, Inc. (Lutz, FL), was used to measure change from day to day and aid in the measurement of delirium, but was not used to establish the diagnosis of dementia. Both the Clinical Dementia Rating Scale[13] and the Global Deterioration Scale (GDS)[14] were used to measure dementia stage and severity.
Delirium and delirium severity were defined according to the validated CAM algorithm;[15] the Delirium Rating Scale‐Revised‐98 was used for delirium severity.[16] In a recent review, the CAM showed an overall sensitivity of 94% and specificity of 89%.[17] In the present study, delirium was measured in a comprehensive and structured interview that involved the MMSE and CAM criteria, and was based on a 24‐hour period of observations, interviews with nurses and family members, and chart review. The CAM was completed daily during patient hospitalization and the follow‐up interviews. The CAM assesses 4 criteria including acute and fluctuating nature, inattention, disorganized thought, and altered level of consciousness. Delirium was recorded by the research staff as present or absent each day based on full CAM criteria. Because the goal of the present study focused on full CAM delirium, subsyndromal delirium was not presented in this article.
Delirium duration was defined as the number of days with a positive rating. Data were collected daily from patients during hospitalization, followed by a single interview at 1‐month posthospitalization with patients and their caregivers. Most interviews were in person.
Delirium Risk Factors
Central nervous system‐active drug use was defined by 2005 American Hospital Formulary Services classification.[18] The Beers criteria were used to define potentially inappropriate medication use.[19] The Cornell scale for depression in persons with dementia was used, with a cut point of 12 indicating depression.[20] Functional status change was measured via the Katz Index of Activities of Daily Living (ADLs) and Lawton Instrumental Activities Of Daily Living (IADLs) change scores.[21] Comorbid conditions were classified with a weighted index that took into account both the number and seriousness of different comorbid diseases.[22] Pain was measured using the Pain Assessment in Advanced Dementia (PAINAD) scale.[23] Dehydration was defined using the blood urea nitrogen (BUN)/creatinine ratio and/or any chart diagnosis of dehydration. Admission lab values (BUN/creatinine) were abstracted from the medical records.
Primary Outcomes
The primary outcomes measured were full CAM delirium, index hospitalization length of stay, cognitive decline (change in MMSE and GDS scores), death, and functional status change (change from baseline to discharge score). One‐month mortality was measured by chart review and follow‐up family interviews performed at 1 month via telephone or in‐person interviews. Mortality was not verified by additional methods.
Statistical Analysis
All statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, NC), and statistical significance was assessed using an level of 0.05 unless otherwise noted. Descriptive statistics were calculated on all characteristics by incident delirium status.
Potential risk factors for incident delirium were examined using [2] and t tests, where appropriate. Simple proportional hazards models were used to estimate the relative risk (RR) and 95% confidence interval (CI) for incident delirium. A stepwise model‐building procedure under a proportional hazards model was used to build a final model for incident delirium that contained all variables that were statistically significant at the 0.05 level or that had an RR of 1.5 or greater. Adjusted RR and corresponding 95% CI were determined. The outcome in each model was the number of days from admission to an incident delirium diagnosis. Subjects without incident delirium were censored using their length of stay as the total number of days they were at risk for developing delirium.
Finally, to examine the relationships between incident delirium, maximum incident delirium severity and the number of inpatient days positive for delirium with the outcomes of death, impaired in 2 or more IADLs at follow‐up, impaired in 2 or more ADLs at follow‐up, length of stay, change in IADLs from admission to follow‐up, and change in ADLs from admission to follow‐up, logistic regression (for the dichotomous outcome of mortality), analysis of covariance or linear regression (depending on the whether the independent variable was categorical or continuous) was performed controlling for age, gender, and GDS score.
RESULTS
Of 256 eligible patients, dual consent was obtained from 154 patient and 154 family research subjects (308 consents). The refusal rate was 39% (n=102). Fourteen subjects were consented and enrolled but later dropped out due to family/proxy concerns regarding the patient's ability to participate in interviews. Thus, the final sample included 139 patients.
Descriptive statistics for baseline measures are given in Table 1. Briefly, the average age of subjects was 83 years (standard deviation [SD]=7); 41% were male; 57% were single, divorced, or widowed; and the average number of years of education was 12 years (SD=3). Thirty‐three percent were dehydrated on admission, and 33% had fallen within 2 weeks prior to admission. Thirty‐four percent had an infection at baseline, and 36% had some sensory impairment.
Factor | Delirium, N=44, 31.7% | No Delirium, N=95, 68.3% | Relative Risk | 95% CI | P Value |
---|---|---|---|---|---|
| |||||
Demographic covariates | |||||
Age, y, mean (SD) | 85.9 (5.9) | 82.4 (7.0) | 1.07 | 1.021.12 | 0.0051 |
Male gender, n (%) | 23 (52.3) | 33 (34.7) | 1.83 | 1.013.31 | 0.0456 |
Single/divorced/widowed, n (%) | 23 (52.3) | 56 (60.2) | 0.81 | 0.451.47 | 0.4882 |
Education, y, mean (SD) | 12.6 (3.2) | 12.1 (3.0) | 1.06 | 0.951.17 | 0.3146 |
Clinical covariates | |||||
Dehydration, n (%) | 12 (30.8) | 30 (33.7) | 0.88 | 0.451.74 | 0.7152 |
Fall in last 2 weeks, n (%) | 14 (41.2) | 21 (29.6) | 1.73* | 0.873.43 | 0.1186 |
Infection, n (%) | 13 (40.6) | 21 (30.9) | 1.42 | 0.702.88 | 0.3328 |
Sensory impairment, n (%) | 16 (36.4) | 33 (34.7) | 1.04 | 0.561.91 | 0.9132 |
Lawton score, mean (SD) | 1.6 (1.3) | 2.3 (2.0) | 0.84 | 0.701.01 | 0.0592 |
Katz impaired score, mean (SD) | 2.3 (2.0) | 3.4 (2.1) | 0.82 | 0.710.95 | 0.0072 |
Charlson score, mean (SD) | 2.5 (1.8) | 2.3 (1.4) | 1.06 | 0.861.30 | 0.6013 |
BUN, mean (SD) | 28.2 (17.6) | 25.6 (15.3) | 1.01 | 0.991.03 | 0.4175 |
Creatinine, mean (SD) | 1.6 (1.3) | 2.4 (6.8) | 0.99 | 0.901.08 | 0.7356 |
Cornell Depression score, mean (SD) | 1.6 (0.8) | 1.2 (0.9) | 1.35 | 0.991.83 | 0.0553 |
Global Deterioration score, mean (SD) | 4.7 (1.2) | 3.9 (1.3) | 1.45* | 1.141.86 | 0.0027 |
PAINAD score, mean (SD) | 2.1 (3.0) | 2.0 (2.9) | 1.01 | 0.911.12 | 0.8540 |
Total number of regular medications, mean (SD) | 11.5 (4.6) | 11.0 (5.0) | 1.00 | 0.941.67 | 0.9771 |
Total number of Beers medications, mean (SD) | 0.3 (0.7) | 0.4 (0.7) | 0.76 | 0.461.27 | 0.2933 |
Cognitive impairment covariates | |||||
MMSE score, mean (SD) | 12.7 (6.8) | 17.1 (6.6) | 0.94 | 0.900.98 | 0.0019 |
Blessed score, mean (SD) | 9.5 (3.5) | 7.7 (2.9) | 1.14 | 1.041.24 | 0.0038 |
Measures of deliriumcovariates for follow‐up outcomes | |||||
Maximum incident delirium severity, mean (SD) | 15.4 (5.6) | 8.7 (6.1) | <0.0001 | ||
Inpatient days with positive CAM, mean (SD) | 2.0 (1.1) | 0.2 (1.4) | <0.0001 | ||
Follow‐up outcomes | |||||
Mortality, n (%) | 11 (25.0) | 9 (9.5) | 0.0153 | ||
Length of stay, mean (SD) | 9.1 (4.4) | 5.7 (4.1) | <0.0001 | ||
Change in Lawton IADLs from admission to follow‐up, mean (SD) | 0.4 (1.5) | 0.2 (1.8) | 0.5094 | ||
Change in Katz impaired ADLs from admission to follow‐up, mean (SD) | 0.3 (1.7) | 0.4 (1.6) | 0.6919 |
The overall incidence of delirium was 32% (44/139) and the range of days to incident delirium was 1 to 8 days. During the baseline period (Table 1), subjects with delirium were older, more likely to be male, had lower Katz impairment scores, higher GDS score, lower MMSE scores on admission, and higher Blessed scores than subjects without delirium. Slightly more persons with delirium had a prior fall, although the RR was not statistically significant. Length of stay measured at discharge was significantly higher for those with delirium (mean=9.1) than those without delirium (mean=5.7) (P<0.0001). Subjects with delirium were more likely to have died at 1 month than those without delirium (P=0.0153).
In addition, we analyzed the adjusted relative risk estimates for the final model of incident delirium. Significant risk factors or risk factors with RR estimates at least 1.5 (or <0.66 if protective [Table 1]) that were examined in a more comprehensive multiple proportional hazards model included age, gender, having had a fall in the last 2 weeks, number of impaired ADLs (based on Katz), GDS scores, MMSE scores at baseline, and Blessed scores at baseline. The final proportional hazards included gender and GDS score. Males were nearly 1.8 times as likely to develop delirium than females, and for every 1 unit increase in the GDS, subjects were 1.5 times more likely to develop delirium.
Finally, Table 2 gives the results of examining outcomes related to incident delirium measures. For mortality, there were no statistically significant predictors of death after controlling for age, gender, or GDS. For length of stay, subjects with incident delirium had significantly longer lengths of stay, as incident delirium severity increased by 1 unit the length of stay increased by 0.4 days, and as the number of inpatient days with delirium increased by 1 day the length of stay increased by 1.8 days. For change in the impaired Katz ADLs from admission to follow‐up, as incident delirium severity increased by 1 unit the change in impaired Katz ADLs increased by 0.05 units.
Variable | |||
---|---|---|---|
Outcome mortality | Level | Adjusted Estimate of Associationa | P Value |
| |||
Incident delirium, OR (95% CI)b | Yes | 2.33 (0.82‐6.61) | 0.1130 |
No | 1.00 | ||
Maximum incident delirium severity, OR (95% CI)b | 1.05 (0.961.14) | 0.2719 | |
Number of inpatient days with positive delirium, OR (95% CI)b | 1.15 (0.891.49) | 0.2871 | |
Outcome LOS | |||
Incident delirium, mean (SE)c | Yes | 9.2 (0.7) | <0.0001 |
No | 5.6 (0.5) | ||
Maximum incident delirium severity, slope (SE)d | 0.43 (0.06) | <0.0001 | |
Number of inpatient days with positive delirium, slope (SE)d | 1.80 (0.21) | <0.0001 | |
Outcomechange in Lawton IADLs from admission to follow‐up | |||
Incident delirium, mean (SE)c | Yes | 0.51 (0.33) | 0.3787 |
No | 0.15 (0.20) | ||
Maximum incident delirium severity, slope (SE)d | 0.003 (0.03) | 0.9260 | |
Number of inpatient days with positive delirium, slope (SE)d | 0.16 (0.11) | 0.1497 | |
Outcomechange in Katz impaired ADLs from admission to follow‐up | |||
Incident delirium, mean (SE)c | Yes | 0.19 (0.26) | 0.5086 |
No | 0.40 (0.17) | ||
Maximum incident delirium severity, slope (SE)d | 0.05 (0.03) | 0.0437 | |
Number of inpatient days with positive delirium, slope (SE)d | 0.13 (0.09) | 0.1717 |
DISCUSSION
The most compelling finding from this study is the high incidence of delirium in hospitalized older adults with dementia and the association with poor clinical outcomes in those who develop delirium superimposed on dementia. DSD is difficult to detect and prevent; persons with DSD are at risk for poor quality of life. Those with delirium had a 25% short‐term mortality rate (P=0.0153), substantially increased length of stay (9.1 vs 5.1 days with an odds ratio of 1.8) and poorer physical function at discharge and follow‐up. At 1 month follow‐up, subjects with delirium had greater functional decline and lower GDS scores than those without delirium.
The incidence of delirium in this study was high (32%). Being delirious any time was associated with death and poor function. Delirium was also associated with the stage of the persons' baseline dementia, advanced age, lower MMSE scores, and falling before admission.
Previous studies have found delirium associated with increased mortality. Three studies found that within 1 year of a delirium episode, a significant number of persons died or were institutionalized.[24, 25, 26] Other research has reported death within 1 year of documented delirium episodes, and a 3‐fold increased rate of death in the ICU.[24, 27, 28, 29, 30, 31, 32] This study is 1 of only a few to focus on increased mortality with DSD and to focus uniquely on hospitalized patients with delirium and dementia.
The main risk factors for delirium in this study were male sex and severity of dementia. Our results, combined with those from other recent studies by Voyer and colleagues,[8, 33, 34] point to the critical importance of screening for dementia in hospitalized older adults as dementia severity is a significant indicator of delirium severity. For instance, Voyer and colleagues[34] reported that persons with mild dementia were likely to experience a mild delirium, whereas those with a more severe level of dementia were more likely to experience moderate to severe delirium. Our findings show that those who experienced episodes of delirium represented a highly vulnerable population with advanced dementia, sensory impairment, more falls and dehydration at admission, and higher Blessed scores. A recent study by Saczynski and colleagues[35] found 40% of patients who had experienced postoperative delirium did not return to their baseline at 6 months. Clearly, preventing delirium should be a critical priority to prevent such deterioration in the highly vulnerable population of hospitalized patients with dementia.
Patients in this study were on a mean of over 11 medications. One‐third of dementia patients in our study had also experienced a fall and dehydration at baseline. Other studies have found a relationship between cognitive decline, falling, and medications.[36] Many of these patients came into the hospital with potentially modifiable and preventable community or ambulatory care conditions of polypharmacy, falling, sensory impairment, and dehydration.
Importantly, in our study, length of stay was significantly higher (9.1 vs 5.7) for those with delirium compared to those without delirium. This finding is alarming when examining the economic impact of preventing delirium. Previous studies have found the cost of delirious episodes rivals those for diabetes and heart disease, and that decreasing length of stay by just 1 day would save over $20 million dollars per year.[4, 37]
In summary, this study is 1 of the first to report a high incidence of DSD and poorer outcomes for persons who experience delirium compared to those with dementia alone. This is 1 of only a few studies examining unique risk factors and delirium severity for DSD in the acute care setting. Findings from the current study report potential risk factors for development of incident delirium and highlight the challenge of preventing DSD before and during hospitalization. The generalizability of this study may be limited by the use of a nondiverse study population drawn from a single hospital in the northeast United States, though the use of a community hospital increases the relevance to real‐world practice settings. Determination of baseline cognitive status and the differentiation of delirium and dementia are difficult, but validated, state‐of‐the‐art methods were used that have been applied in previous studies.
This study provides fundamental methodological improvements over previous work, and advances the science by providing valuable data on the natural history, correlates, and outcomes of DSD. The strengths of this study include the prospective cohort design, the daily assessment for delirium based on a 24‐hour period, methods for determining cognitive status at baseline in this difficult population, and utilizing strict blinding of the well‐trained outcome assessors.
This study lays the groundwork for future studies to improve care for persons with dementia who present to acute care and to plan prevention programs for delirium before they are admitted to the hospital. We must be able to translate best practice for DSD into the acute care and community settings to prevent or minimize effects of delirium in persons with dementia. Interventions to increase early detection of delirium by hospital staff have the potential to decrease the severity and duration of delirium and prevent unnecessary suffering and costs from the complications of delirium and preventable readmissions to the hospital.
Thus, this study holds substantial clinical and economic implications for this population in the acute care setting, and will direct future studies leading to changes in real‐world practice settings for persons with dementia.
Disclosures
Drs. Fick, Inouye, and Steis acknowledge support for this project described by grants number R03 AG023216 (DMF) and number P01AG031720 (SKI) from the National Institute of Aging (NIA). This study and its contents are solely the responsibilities of the authors and do not necessarily represent the official views of the National Institutes of Health/NIA. The principal investigator, Dr. Fick, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no conflicts of interest.
funding section: Dr. Inouye holds the Milton and Shirley F. Levy Family Chair.
Much attention has been given recently to hospitalized older adults, the critical 30‐day period, and posthospital syndrome.[1] What is missing from this dialogue is the contribution and significance of underlying cognitive impairment. By 2050, 14 million older persons in the United States are expected to have dementia.[2] Increasing numbers of older adults diagnosed with dementia are hospitalized and are at increased risk of developing delirium; in fact, delirium occurs in over half of hospitalized persons with dementia.[3] Further, current evidence suggests that delirium may accelerate the clinical course and trajectory of cognitive decline, and may be associated with considerably worse long‐term outcomes, including prolonged hospitalization, rehospitalization within 30 days, nursing home placement, and death.[3, 4, 5, 6] However, the problem of delirium superimposed on dementia (DSD) remains a neglected area of investigation in hospitalized patients. Delirium is superimposed on dementia when an acute change in mental status (characterized by a fluctuating course, inattention, and either disorganized thinking or altered level of consciousness) is layered on top of preexisting dementia.[4]
Despite the poor outcomes and high prevalence of DSD, little is known about the natural history in hospitalized older adults with dementia. Delirium studies often exclude persons with dementia, even though the prevalence of DSD is extremely high in both community (13%19%) and hospital (40%89%) populations and associated with higher costs and utilization compared to dementia and delirium alone.[4, 5, 7] In 1 study, annual costs for DSD were $9566 compared to $7557 for dementia alone.[7] The few risk‐factor studies of DSD were conducted in intensive care unit (ICU) or long‐term care settings.[8, 9]
The purpose of this study was to describe the incidence, risk factors, and outcomes associated with incident delirium in a prospective cohort of hospitalized older adults with dementia. The study aims were to: (1) estimate the incidence of new delirium in hospitalized persons with dementia, (2) identify the risk factors associated with incident delirium superimposed on dementia in this sample, (3) describe the outcomes associated with development of delirium, and (4) evaluate the contributions of delirium severity and duration to outcomes.
METHODS
This 24‐month prospective cohort study recruited and enrolled consecutive hospital admissions with dementia in a 300‐bed community hospital in central Pennsylvania from July 2006 through November 2008. Data were collected daily from patients during hospitalization, followed by a 1‐month posthospitalization interview with patients and their caregivers in the community setting. Patients were included if they spoke English, had been hospitalized fewer than 24 hours, and met the screening criteria for dementia. Patients were excluded if they had any significant neurological condition associated with cognitive impairment other than dementia (eg, brain tumor), a major acute psychiatric disorder, were unable to communicate, or had no caregiver to interview. The interviewers included experienced research assistants (RAs) who were either registered nurses or trained in a health‐related field. All staff training of instruments were done with scripted training manuals and video training using manuals for the Confusion Assessment Method (CAM). After training was completed, final inter‐rater reliability assessments were conducted until staff reached 100% agreement. The RAs were blinded to the aims and completed over 10 hours of training. Inter‐rater reliability checks were conducted on 10% of the sample in the field with >90% agreement attained on all instruments. This study was reviewed by and approved by The Pennsylvania State University institutional review board, and consent was received from all subjects.
Study Measures
Dementia was defined by meeting all 3 criteria of a Modified Blessed Dementia Rating Score of >3, an Informant Questionnaire on Cognitive Decline in the Elderly of 3.3, and documented dementia symptoms of at least 6 months' duration prior to current illness.[10, 11, 12] The Mini‐Mental State Examination (MMSE), purchased from Psychological Assessment Resources, Inc. (Lutz, FL), was used to measure change from day to day and aid in the measurement of delirium, but was not used to establish the diagnosis of dementia. Both the Clinical Dementia Rating Scale[13] and the Global Deterioration Scale (GDS)[14] were used to measure dementia stage and severity.
Delirium and delirium severity were defined according to the validated CAM algorithm;[15] the Delirium Rating Scale‐Revised‐98 was used for delirium severity.[16] In a recent review, the CAM showed an overall sensitivity of 94% and specificity of 89%.[17] In the present study, delirium was measured in a comprehensive and structured interview that involved the MMSE and CAM criteria, and was based on a 24‐hour period of observations, interviews with nurses and family members, and chart review. The CAM was completed daily during patient hospitalization and the follow‐up interviews. The CAM assesses 4 criteria including acute and fluctuating nature, inattention, disorganized thought, and altered level of consciousness. Delirium was recorded by the research staff as present or absent each day based on full CAM criteria. Because the goal of the present study focused on full CAM delirium, subsyndromal delirium was not presented in this article.
Delirium duration was defined as the number of days with a positive rating. Data were collected daily from patients during hospitalization, followed by a single interview at 1‐month posthospitalization with patients and their caregivers. Most interviews were in person.
Delirium Risk Factors
Central nervous system‐active drug use was defined by 2005 American Hospital Formulary Services classification.[18] The Beers criteria were used to define potentially inappropriate medication use.[19] The Cornell scale for depression in persons with dementia was used, with a cut point of 12 indicating depression.[20] Functional status change was measured via the Katz Index of Activities of Daily Living (ADLs) and Lawton Instrumental Activities Of Daily Living (IADLs) change scores.[21] Comorbid conditions were classified with a weighted index that took into account both the number and seriousness of different comorbid diseases.[22] Pain was measured using the Pain Assessment in Advanced Dementia (PAINAD) scale.[23] Dehydration was defined using the blood urea nitrogen (BUN)/creatinine ratio and/or any chart diagnosis of dehydration. Admission lab values (BUN/creatinine) were abstracted from the medical records.
Primary Outcomes
The primary outcomes measured were full CAM delirium, index hospitalization length of stay, cognitive decline (change in MMSE and GDS scores), death, and functional status change (change from baseline to discharge score). One‐month mortality was measured by chart review and follow‐up family interviews performed at 1 month via telephone or in‐person interviews. Mortality was not verified by additional methods.
Statistical Analysis
All statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, NC), and statistical significance was assessed using an level of 0.05 unless otherwise noted. Descriptive statistics were calculated on all characteristics by incident delirium status.
Potential risk factors for incident delirium were examined using [2] and t tests, where appropriate. Simple proportional hazards models were used to estimate the relative risk (RR) and 95% confidence interval (CI) for incident delirium. A stepwise model‐building procedure under a proportional hazards model was used to build a final model for incident delirium that contained all variables that were statistically significant at the 0.05 level or that had an RR of 1.5 or greater. Adjusted RR and corresponding 95% CI were determined. The outcome in each model was the number of days from admission to an incident delirium diagnosis. Subjects without incident delirium were censored using their length of stay as the total number of days they were at risk for developing delirium.
Finally, to examine the relationships between incident delirium, maximum incident delirium severity and the number of inpatient days positive for delirium with the outcomes of death, impaired in 2 or more IADLs at follow‐up, impaired in 2 or more ADLs at follow‐up, length of stay, change in IADLs from admission to follow‐up, and change in ADLs from admission to follow‐up, logistic regression (for the dichotomous outcome of mortality), analysis of covariance or linear regression (depending on the whether the independent variable was categorical or continuous) was performed controlling for age, gender, and GDS score.
RESULTS
Of 256 eligible patients, dual consent was obtained from 154 patient and 154 family research subjects (308 consents). The refusal rate was 39% (n=102). Fourteen subjects were consented and enrolled but later dropped out due to family/proxy concerns regarding the patient's ability to participate in interviews. Thus, the final sample included 139 patients.
Descriptive statistics for baseline measures are given in Table 1. Briefly, the average age of subjects was 83 years (standard deviation [SD]=7); 41% were male; 57% were single, divorced, or widowed; and the average number of years of education was 12 years (SD=3). Thirty‐three percent were dehydrated on admission, and 33% had fallen within 2 weeks prior to admission. Thirty‐four percent had an infection at baseline, and 36% had some sensory impairment.
Factor | Delirium, N=44, 31.7% | No Delirium, N=95, 68.3% | Relative Risk | 95% CI | P Value |
---|---|---|---|---|---|
| |||||
Demographic covariates | |||||
Age, y, mean (SD) | 85.9 (5.9) | 82.4 (7.0) | 1.07 | 1.021.12 | 0.0051 |
Male gender, n (%) | 23 (52.3) | 33 (34.7) | 1.83 | 1.013.31 | 0.0456 |
Single/divorced/widowed, n (%) | 23 (52.3) | 56 (60.2) | 0.81 | 0.451.47 | 0.4882 |
Education, y, mean (SD) | 12.6 (3.2) | 12.1 (3.0) | 1.06 | 0.951.17 | 0.3146 |
Clinical covariates | |||||
Dehydration, n (%) | 12 (30.8) | 30 (33.7) | 0.88 | 0.451.74 | 0.7152 |
Fall in last 2 weeks, n (%) | 14 (41.2) | 21 (29.6) | 1.73* | 0.873.43 | 0.1186 |
Infection, n (%) | 13 (40.6) | 21 (30.9) | 1.42 | 0.702.88 | 0.3328 |
Sensory impairment, n (%) | 16 (36.4) | 33 (34.7) | 1.04 | 0.561.91 | 0.9132 |
Lawton score, mean (SD) | 1.6 (1.3) | 2.3 (2.0) | 0.84 | 0.701.01 | 0.0592 |
Katz impaired score, mean (SD) | 2.3 (2.0) | 3.4 (2.1) | 0.82 | 0.710.95 | 0.0072 |
Charlson score, mean (SD) | 2.5 (1.8) | 2.3 (1.4) | 1.06 | 0.861.30 | 0.6013 |
BUN, mean (SD) | 28.2 (17.6) | 25.6 (15.3) | 1.01 | 0.991.03 | 0.4175 |
Creatinine, mean (SD) | 1.6 (1.3) | 2.4 (6.8) | 0.99 | 0.901.08 | 0.7356 |
Cornell Depression score, mean (SD) | 1.6 (0.8) | 1.2 (0.9) | 1.35 | 0.991.83 | 0.0553 |
Global Deterioration score, mean (SD) | 4.7 (1.2) | 3.9 (1.3) | 1.45* | 1.141.86 | 0.0027 |
PAINAD score, mean (SD) | 2.1 (3.0) | 2.0 (2.9) | 1.01 | 0.911.12 | 0.8540 |
Total number of regular medications, mean (SD) | 11.5 (4.6) | 11.0 (5.0) | 1.00 | 0.941.67 | 0.9771 |
Total number of Beers medications, mean (SD) | 0.3 (0.7) | 0.4 (0.7) | 0.76 | 0.461.27 | 0.2933 |
Cognitive impairment covariates | |||||
MMSE score, mean (SD) | 12.7 (6.8) | 17.1 (6.6) | 0.94 | 0.900.98 | 0.0019 |
Blessed score, mean (SD) | 9.5 (3.5) | 7.7 (2.9) | 1.14 | 1.041.24 | 0.0038 |
Measures of deliriumcovariates for follow‐up outcomes | |||||
Maximum incident delirium severity, mean (SD) | 15.4 (5.6) | 8.7 (6.1) | <0.0001 | ||
Inpatient days with positive CAM, mean (SD) | 2.0 (1.1) | 0.2 (1.4) | <0.0001 | ||
Follow‐up outcomes | |||||
Mortality, n (%) | 11 (25.0) | 9 (9.5) | 0.0153 | ||
Length of stay, mean (SD) | 9.1 (4.4) | 5.7 (4.1) | <0.0001 | ||
Change in Lawton IADLs from admission to follow‐up, mean (SD) | 0.4 (1.5) | 0.2 (1.8) | 0.5094 | ||
Change in Katz impaired ADLs from admission to follow‐up, mean (SD) | 0.3 (1.7) | 0.4 (1.6) | 0.6919 |
The overall incidence of delirium was 32% (44/139) and the range of days to incident delirium was 1 to 8 days. During the baseline period (Table 1), subjects with delirium were older, more likely to be male, had lower Katz impairment scores, higher GDS score, lower MMSE scores on admission, and higher Blessed scores than subjects without delirium. Slightly more persons with delirium had a prior fall, although the RR was not statistically significant. Length of stay measured at discharge was significantly higher for those with delirium (mean=9.1) than those without delirium (mean=5.7) (P<0.0001). Subjects with delirium were more likely to have died at 1 month than those without delirium (P=0.0153).
In addition, we analyzed the adjusted relative risk estimates for the final model of incident delirium. Significant risk factors or risk factors with RR estimates at least 1.5 (or <0.66 if protective [Table 1]) that were examined in a more comprehensive multiple proportional hazards model included age, gender, having had a fall in the last 2 weeks, number of impaired ADLs (based on Katz), GDS scores, MMSE scores at baseline, and Blessed scores at baseline. The final proportional hazards included gender and GDS score. Males were nearly 1.8 times as likely to develop delirium than females, and for every 1 unit increase in the GDS, subjects were 1.5 times more likely to develop delirium.
Finally, Table 2 gives the results of examining outcomes related to incident delirium measures. For mortality, there were no statistically significant predictors of death after controlling for age, gender, or GDS. For length of stay, subjects with incident delirium had significantly longer lengths of stay, as incident delirium severity increased by 1 unit the length of stay increased by 0.4 days, and as the number of inpatient days with delirium increased by 1 day the length of stay increased by 1.8 days. For change in the impaired Katz ADLs from admission to follow‐up, as incident delirium severity increased by 1 unit the change in impaired Katz ADLs increased by 0.05 units.
Variable | |||
---|---|---|---|
Outcome mortality | Level | Adjusted Estimate of Associationa | P Value |
| |||
Incident delirium, OR (95% CI)b | Yes | 2.33 (0.82‐6.61) | 0.1130 |
No | 1.00 | ||
Maximum incident delirium severity, OR (95% CI)b | 1.05 (0.961.14) | 0.2719 | |
Number of inpatient days with positive delirium, OR (95% CI)b | 1.15 (0.891.49) | 0.2871 | |
Outcome LOS | |||
Incident delirium, mean (SE)c | Yes | 9.2 (0.7) | <0.0001 |
No | 5.6 (0.5) | ||
Maximum incident delirium severity, slope (SE)d | 0.43 (0.06) | <0.0001 | |
Number of inpatient days with positive delirium, slope (SE)d | 1.80 (0.21) | <0.0001 | |
Outcomechange in Lawton IADLs from admission to follow‐up | |||
Incident delirium, mean (SE)c | Yes | 0.51 (0.33) | 0.3787 |
No | 0.15 (0.20) | ||
Maximum incident delirium severity, slope (SE)d | 0.003 (0.03) | 0.9260 | |
Number of inpatient days with positive delirium, slope (SE)d | 0.16 (0.11) | 0.1497 | |
Outcomechange in Katz impaired ADLs from admission to follow‐up | |||
Incident delirium, mean (SE)c | Yes | 0.19 (0.26) | 0.5086 |
No | 0.40 (0.17) | ||
Maximum incident delirium severity, slope (SE)d | 0.05 (0.03) | 0.0437 | |
Number of inpatient days with positive delirium, slope (SE)d | 0.13 (0.09) | 0.1717 |
DISCUSSION
The most compelling finding from this study is the high incidence of delirium in hospitalized older adults with dementia and the association with poor clinical outcomes in those who develop delirium superimposed on dementia. DSD is difficult to detect and prevent; persons with DSD are at risk for poor quality of life. Those with delirium had a 25% short‐term mortality rate (P=0.0153), substantially increased length of stay (9.1 vs 5.1 days with an odds ratio of 1.8) and poorer physical function at discharge and follow‐up. At 1 month follow‐up, subjects with delirium had greater functional decline and lower GDS scores than those without delirium.
The incidence of delirium in this study was high (32%). Being delirious any time was associated with death and poor function. Delirium was also associated with the stage of the persons' baseline dementia, advanced age, lower MMSE scores, and falling before admission.
Previous studies have found delirium associated with increased mortality. Three studies found that within 1 year of a delirium episode, a significant number of persons died or were institutionalized.[24, 25, 26] Other research has reported death within 1 year of documented delirium episodes, and a 3‐fold increased rate of death in the ICU.[24, 27, 28, 29, 30, 31, 32] This study is 1 of only a few to focus on increased mortality with DSD and to focus uniquely on hospitalized patients with delirium and dementia.
The main risk factors for delirium in this study were male sex and severity of dementia. Our results, combined with those from other recent studies by Voyer and colleagues,[8, 33, 34] point to the critical importance of screening for dementia in hospitalized older adults as dementia severity is a significant indicator of delirium severity. For instance, Voyer and colleagues[34] reported that persons with mild dementia were likely to experience a mild delirium, whereas those with a more severe level of dementia were more likely to experience moderate to severe delirium. Our findings show that those who experienced episodes of delirium represented a highly vulnerable population with advanced dementia, sensory impairment, more falls and dehydration at admission, and higher Blessed scores. A recent study by Saczynski and colleagues[35] found 40% of patients who had experienced postoperative delirium did not return to their baseline at 6 months. Clearly, preventing delirium should be a critical priority to prevent such deterioration in the highly vulnerable population of hospitalized patients with dementia.
Patients in this study were on a mean of over 11 medications. One‐third of dementia patients in our study had also experienced a fall and dehydration at baseline. Other studies have found a relationship between cognitive decline, falling, and medications.[36] Many of these patients came into the hospital with potentially modifiable and preventable community or ambulatory care conditions of polypharmacy, falling, sensory impairment, and dehydration.
Importantly, in our study, length of stay was significantly higher (9.1 vs 5.7) for those with delirium compared to those without delirium. This finding is alarming when examining the economic impact of preventing delirium. Previous studies have found the cost of delirious episodes rivals those for diabetes and heart disease, and that decreasing length of stay by just 1 day would save over $20 million dollars per year.[4, 37]
In summary, this study is 1 of the first to report a high incidence of DSD and poorer outcomes for persons who experience delirium compared to those with dementia alone. This is 1 of only a few studies examining unique risk factors and delirium severity for DSD in the acute care setting. Findings from the current study report potential risk factors for development of incident delirium and highlight the challenge of preventing DSD before and during hospitalization. The generalizability of this study may be limited by the use of a nondiverse study population drawn from a single hospital in the northeast United States, though the use of a community hospital increases the relevance to real‐world practice settings. Determination of baseline cognitive status and the differentiation of delirium and dementia are difficult, but validated, state‐of‐the‐art methods were used that have been applied in previous studies.
This study provides fundamental methodological improvements over previous work, and advances the science by providing valuable data on the natural history, correlates, and outcomes of DSD. The strengths of this study include the prospective cohort design, the daily assessment for delirium based on a 24‐hour period, methods for determining cognitive status at baseline in this difficult population, and utilizing strict blinding of the well‐trained outcome assessors.
This study lays the groundwork for future studies to improve care for persons with dementia who present to acute care and to plan prevention programs for delirium before they are admitted to the hospital. We must be able to translate best practice for DSD into the acute care and community settings to prevent or minimize effects of delirium in persons with dementia. Interventions to increase early detection of delirium by hospital staff have the potential to decrease the severity and duration of delirium and prevent unnecessary suffering and costs from the complications of delirium and preventable readmissions to the hospital.
Thus, this study holds substantial clinical and economic implications for this population in the acute care setting, and will direct future studies leading to changes in real‐world practice settings for persons with dementia.
Disclosures
Drs. Fick, Inouye, and Steis acknowledge support for this project described by grants number R03 AG023216 (DMF) and number P01AG031720 (SKI) from the National Institute of Aging (NIA). This study and its contents are solely the responsibilities of the authors and do not necessarily represent the official views of the National Institutes of Health/NIA. The principal investigator, Dr. Fick, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no conflicts of interest.
funding section: Dr. Inouye holds the Milton and Shirley F. Levy Family Chair.
- Post‐hospital syndrome—an acquired, transient condition of generalized risk. N Engl J Med. 2013;368(2):100–102. .
- Alzheimer's Association. Alzheimer's disease facts and figures. Alzheimers Dement. 2012;8(2):131–168.
- Delirium superimposed on dementia: accuracy of nurse documentation. J Gerontol Nurs. 2012;38(1):32–42. , .
- Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2002;50(10):1723–1732. , , .
- Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009;72(18):1570–1575. , , , et al.
- Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Intern Med. 2012;156(12):848–856, W296. , , , et al.
- Delirium superimposed on dementia in a community‐dwelling managed care population: a 3‐year retrospective study of occurrence, costs, and utilization. J Gerontol. 2005;60A(6):748–753. , , , .
- Factors associated with delirium severity among older persons with dementia. J Neurosci Nurs. 2011;43(2):62–69. , , , .
- Delirium in the intensive care unit. Crit Care 2008;12(suppl 3):S3. , , .
- Correlations of Mini‐Mental State and Modified Rating Scale to measures of transitional health status in dementia. J Gerontol. 1987;42(1):33–36. , , .
- Population‐based norms for the Mini‐Mental State Examination by age and educational level. JAMA. 1993;269(18):2386–2391. , , , .
- The mini‐mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40(9):922–935. , .
- A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140:566–572. , , , , .
- The GDS/FAST staging system. Int Psychogeriatr. 1997;9(suppl 1):167–171. , .
- Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113(12):941–948. , , , , , .
- Validation of the Delirium Rating Scale‐Revised‐98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001;13(2):229–242. , , , , , .
- The confusion assessment method: a systematic review of current usage. J Am Geriatr Soc. 2008;56(5):823–830. , , , .
- American Society of Health‐System Pharmacists. AHFS Drug Information. Bethesda, MD: American Society of Health‐System Pharmacists; 2005.
- Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts [published correction appears in Arch Intern Med. 2004;164:298]. Arch Intern Med 2003;163(22):2716–2724. , , , , , .
- Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988;23(3):271–284. , , , .
- Assessing self‐maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc. 1983;31(12):721–726. .
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. , , , .
- Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J Am Med Dir Assoc. 2003;4(1):9–15. , , .
- Prevalence and outcomes of delirium in community and non‐acute care settings in people without dementia: a report from the Canadian Study of Health and Aging. BMC Med. 2006;4:15. , , .
- Prognostic significance of delirium in frail older people. Dementia. 2005;19(2‐3):158–163. , , , .
- Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta‐analysis. JAMA. 2010;304(4):443–451. , , , , , .
- Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753–1762. , , , et al.
- Delirium subtypes and 1‐year mortality among elderly patients discharged from a post‐acute rehabilitation facility. J Gerontol. 2007;62A(10):1182–1183. , , , .
- Delirium in older patients admitted to general internal medicine. J Geriatr Psychiatry Neurol. 2006;19(2):83–90. , , , , , .
- Association between psychomotor activity delirium subtypes and mortality among newly admitted postacute facility patients. J Gerontol. 2007;62A(2):174–179. , , , .
- Premature death associated with delirium at 1‐year follow‐up. Arch Intern Med. 2005;165:1657–1662. , , , , , .
- Older adults discharged from the hospital with delirium: 1‐year outcomes. J Am Geriatr Soc. 2006;54(8):1245–1250. , , , et al.
- Influence of prior cognitive impairment on the severity of delirium symptoms among older patients. J Neurosci Nurs. 2006;38(2):90–101. , , , .
- Factors associated with delirium severity among older patients. J Clin Nurs. 2007;16:819–831. , , , , .
- Cognitive trajectories after postoperative delirium. N Engl J Med. 2012;367(1):30–39. , , , et al.
- Effect of central nervous system medication use on decline in cognition in community‐dwelling older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2009;57(2):243–250. , , , et al.
- One‐year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168(1):27. , , , , .
- Post‐hospital syndrome—an acquired, transient condition of generalized risk. N Engl J Med. 2013;368(2):100–102. .
- Alzheimer's Association. Alzheimer's disease facts and figures. Alzheimers Dement. 2012;8(2):131–168.
- Delirium superimposed on dementia: accuracy of nurse documentation. J Gerontol Nurs. 2012;38(1):32–42. , .
- Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2002;50(10):1723–1732. , , .
- Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009;72(18):1570–1575. , , , et al.
- Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Intern Med. 2012;156(12):848–856, W296. , , , et al.
- Delirium superimposed on dementia in a community‐dwelling managed care population: a 3‐year retrospective study of occurrence, costs, and utilization. J Gerontol. 2005;60A(6):748–753. , , , .
- Factors associated with delirium severity among older persons with dementia. J Neurosci Nurs. 2011;43(2):62–69. , , , .
- Delirium in the intensive care unit. Crit Care 2008;12(suppl 3):S3. , , .
- Correlations of Mini‐Mental State and Modified Rating Scale to measures of transitional health status in dementia. J Gerontol. 1987;42(1):33–36. , , .
- Population‐based norms for the Mini‐Mental State Examination by age and educational level. JAMA. 1993;269(18):2386–2391. , , , .
- The mini‐mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40(9):922–935. , .
- A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140:566–572. , , , , .
- The GDS/FAST staging system. Int Psychogeriatr. 1997;9(suppl 1):167–171. , .
- Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113(12):941–948. , , , , , .
- Validation of the Delirium Rating Scale‐Revised‐98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001;13(2):229–242. , , , , , .
- The confusion assessment method: a systematic review of current usage. J Am Geriatr Soc. 2008;56(5):823–830. , , , .
- American Society of Health‐System Pharmacists. AHFS Drug Information. Bethesda, MD: American Society of Health‐System Pharmacists; 2005.
- Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts [published correction appears in Arch Intern Med. 2004;164:298]. Arch Intern Med 2003;163(22):2716–2724. , , , , , .
- Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988;23(3):271–284. , , , .
- Assessing self‐maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc. 1983;31(12):721–726. .
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. , , , .
- Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J Am Med Dir Assoc. 2003;4(1):9–15. , , .
- Prevalence and outcomes of delirium in community and non‐acute care settings in people without dementia: a report from the Canadian Study of Health and Aging. BMC Med. 2006;4:15. , , .
- Prognostic significance of delirium in frail older people. Dementia. 2005;19(2‐3):158–163. , , , .
- Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta‐analysis. JAMA. 2010;304(4):443–451. , , , , , .
- Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753–1762. , , , et al.
- Delirium subtypes and 1‐year mortality among elderly patients discharged from a post‐acute rehabilitation facility. J Gerontol. 2007;62A(10):1182–1183. , , , .
- Delirium in older patients admitted to general internal medicine. J Geriatr Psychiatry Neurol. 2006;19(2):83–90. , , , , , .
- Association between psychomotor activity delirium subtypes and mortality among newly admitted postacute facility patients. J Gerontol. 2007;62A(2):174–179. , , , .
- Premature death associated with delirium at 1‐year follow‐up. Arch Intern Med. 2005;165:1657–1662. , , , , , .
- Older adults discharged from the hospital with delirium: 1‐year outcomes. J Am Geriatr Soc. 2006;54(8):1245–1250. , , , et al.
- Influence of prior cognitive impairment on the severity of delirium symptoms among older patients. J Neurosci Nurs. 2006;38(2):90–101. , , , .
- Factors associated with delirium severity among older patients. J Clin Nurs. 2007;16:819–831. , , , , .
- Cognitive trajectories after postoperative delirium. N Engl J Med. 2012;367(1):30–39. , , , et al.
- Effect of central nervous system medication use on decline in cognition in community‐dwelling older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2009;57(2):243–250. , , , et al.
- One‐year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168(1):27. , , , , .
Copyright © 2013 Society of Hospital Medicine
Choosing Wisely in Pediatric Medicine
Overuse in medicine is a significant and under‐recognized problem. Don Berwick estimated that waste accounts for at least 20% of healthcare expenditures in the United States, with overtreatment as one of the largest categories.[1] A commentary by Schroeder et al. challenged pediatricians to incorporate this knowledge into our own patient safety and quality movement.[2] Recently published data suggest that we are far from achieving the patient safety goals set forth in the Institute of Medicine's landmark To Err is Human[3] report, despite more than a decade of national, local, and regional efforts.[4] One way to reduce waste and improve patient safety is to eliminate practices of unproven benefit. Therapies or tests that may initially seem promising are often proven to be not only unhelpful but actually harmful. The recommendation of the US Preventive Services Task Force against routine screening for prostate specific antigen is an example of how a common test initially thought of as lifesaving actually increases harm.[5]
The American Board of Internal Medicine Foundation (ABIM‐F) recently announced the Choosing Wisely campaign. Through this campaign the Foundation encourages physicians, patients and other healthcare stakeholders to think and talk about medical tests and procedures that may be unnecessary.[6] The primary output of this challenge is the development of a list of 5 tests and or therapies that physicians and patients should question. The ABIM‐F approached different medical societies to develop these lists within their own specialties. The Society of Hospital Medicine (SHM) joined the Choosing Wisely campaign in April 2012, and agreed to develop a list of 5 therapies and tests for adult hospital medicine and pediatric hospital medicine. Here we present the contribution of the pediatric workgroup detailing the methodology and process for developing the list, as well as summarizing the evidence supporting each recommendation.
METHODS
In the spring of 2012, the pediatric committee of the SHM convened a workgroup of pediatric hospitalists to develop a top 5 list for the field. This workgroup was composed of experienced pediatric hospitalists representing diverse geographic locations of the United States and a mix of academic and nonacademic practice settings. The group, consisting of 4 women and 9 men, began by proposing candidate recommendations after discussion with colleagues at their different practice sites. The group was charged to maintain a focus on overuse practices that had a strong basis in evidence, were frequently encountered at their practice sites, and achieved significant consensus among their colleagues. Figure 1 shows the process map describing the method for the development of the pediatric recommendations. All workgroup participants were queried as to conflict of interest relevant to this work and none were identified.

Literature Review
After the generation of the initial top 20 list, 2 reviewers conducted independent literature searches in PubMed, MEDLINE, and the Cochrane Library on the proposed topics. The reviewers also conducted generic Internet searches. Key search terms included pediatric asthma, bronchiolitis, chest radiograph, systemic corticosteroids, gastroesophageal reflux disease (GERD), infant, child, acid suppression therapy, continuous pulse oximetry, pneumonia, gastroenteritis, viral testing, blood culture, and soft tissue infections. To ensure that the reviewers included all studies relevant to the searches, they utilized broad terms. The search included all literature published through 2012, and nonEnglish language publications were included in the search. Studies selected and included in the review were based upon common criteria including whether the article discussed an evaluation of efficacy and/or utility of treatment, included a pediatric population in the guidelines or study, reviewed the harm associated with the administration of a particular test or treatment, and explored the cost associated with the test or treatment.
The Delphi Panel
Members of the workgroup formed a Delphi panel except for 1 member (R.Q.) who served as the nonvoting moderator. The members of the Delphi panel considered the results of the literature search for each recommendation along with the collated feedback from hospitalist listserves as described in Figure 1. Each panel member received a voting instrument with the candidate tests and treatments for the first round of Delphi voting. The panel utilized a modified Delphi method or the RAND Corporation (RAND)/University of California at Los Angeles (UCLA) appropriateness method as described in previous publications of quality indicator development in pediatrics.[7] Each panelist scored the candidate tests and treatments and forwarded the scores to the moderator. Subsequently, all the members of the Delphi panel met through a conference call to carry out the second round of voting. The deidentified collated results of the first round of Delphi voting were made available and discussed during the call. The moderator collated the final results, and the final 5 recommendations were those that had the highest score after the second round of Delphi voting.
Volume and Costs
During deliberations, the committee took into account the prevalence and cost rankings of our most common pediatric inpatient diagnoses. This was done using the Agency for Healthcare Research and Quality's (AHRQ) Healthcare Utilization Project (HCUP), specifically, the Kids' Inpatient Database (KID). HCUP includes the largest collection of longitudinal hospital care data in the United States, encompassing all‐payer discharge‐level information. We excluded normal newborn hospitalizations, and looked at the top 10 acute inpatient diagnoses in terms of both volume and aggregate costs.
RESULTS
The initial list of 20 candidate tests and treatments as well as the refined list of 11 recommendations can be found as electronic supplements to this publication (see Supporting Table 1 and Supporting Table 2 in the online version of this article). The format and language of the list of 11 recommendations were chosen to mesh with that typically used in the ABIM‐F Choosing Wisely campaign. During the Delphi panel, there was strong group consensus about combining items 1 and 2 (chest radiographs in asthma and bronchiolitis) into a single recommendation.
Do not order chest radiographs in children with asthma or bronchiolitis. |
Do not use bronchodilators in children with bronchiolitis. |
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection. |
Do not treat gastroesophageal reflux in infants routinely with acid suppression therapy. |
Do not use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. |
The top 5 recommendations based on the result of the second round of Delphi scoring are shown in Table 1 and described below along with a detailed evidence summary.
Do not order chest radiographs in children with asthma or bronchiolitis.
The National Heart and Lung Institute's guidelines for the management of asthma, published in 1987, recommend against routinely obtaining chest radiographs in patients with asthma or asthma exacerbations.[8] Supporting this recommendation are several studies that show a low overall yield when obtaining chest radiographs for wheezing patients.[9, 10, 11] Most relevant, studies that evaluated the clinical utility of radiographs in patients with asthma have demonstrated that they influence clinical management in less than 2% of cases.[12] A quality improvement project aimed at decreasing the rate of chest radiographs obtained in patients with asthma demonstrated that close to 60% of patients admitted to the hospital had chest radiographs performed, and that significant overall reductions can be achieved (45.3%28.9%, P=0.0005) without impacting clinical outcomes negatively.[13]
Similarly, the Subcommittee on Diagnosis and Management of Bronchiolitis of the American Academy of Pediatrics recommends against routinely obtaining radiographs during the evaluation for bronchiolitis.[14] Studies assessing the utility of chest x‐rays in these children demonstrate an even lower incidence of abnormalities (0.75%) and indicate that, despite this low incidence, physicians are more likely to treat with antibiotics when radiographs are obtained.[15] There is also evidence that chest radiographs in patients with bronchiolitis are not useful in predicting severity of illness.[16] Furthermore, cost‐effective analyses have demonstrated that omitting chest radiographs in bronchiolitis is actually cost‐effective, without compromising diagnostic accuracy.[17] In a recently published national benchmarking inpatient collaborative, Ralston et al. demonstrated that the majority of patients admitted to the hospital with bronchiolitis have chest radiographs performed at a rate of 64% (interquartile range [IQR], 54%81%).[18]
In both bronchiolitis and asthma, the elimination of unnecessary radiographs has the potential to decrease costs, reduce radiation exposure, and minimize the overuse of antibiotics that often occurs secondary to false positive results.
Do not use bronchodilators in children with bronchiolitis.
Ralston showed that 70% (IQR, 59%83%) of admitted bronchiolitis patients received bronchodilators with an average of 7.9 doses per patient (IQR, 4.69.8). National guidelines for bronchiolitis suggest a very limited role of bronchodilators in patients with bronchiolitis.[14] The first meta‐analyses of studies related to the question of ‐agonist efficacy in bronchiolitis were published in the late 1990s, revealing minimal or no treatment effects.[19, 20] Since then, further research has solidified these findings, and fairly definitive statements can be made based on a recent comprehensive meta‐analysis.[21] The pooled data do not show any effect on hospitalization rates, hospital length of stay, or other inpatient outcomes in bronchiolitis. They do show a small change in clinical scores documented in the outpatient setting, though these scores have not correlated with any detectable difference in outcomes. Routine use of ‐agonists in the inpatient setting has no proven benefit, and given the large amount of consistent data, there is no compelling reason for further study of this therapy in the inpatient setting.
Epinephrine, a combined ‐ and ‐agonist, has been extensively evaluated in bronchiolitis as well. Like albuterol, epinephrine has been reported to have no effect on hospital length of stay in bronchiolitis.[22] The issue of admission rates after epinephrine is complicated by 1 very large study that combined epinephrine with dexamethasone and reported a decreased admission rate, though only at 7 days after therapy; however, this effect was nullified after adjustment for multiple comparisons.[23] When the end point is improvement of respiratory scores, epinephrine may perform better than albuterol in studies where they are directly compared; however, there is no evidence that repeated usage of epinephrine has any impact on any clinical outcome for inpatients.[24, 25]
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection
In their summary of evidence, the Subcommittee on Diagnosis and Management of Bronchiolitis of the American Academy of Pediatrics recommends against routinely using systemic corticosteroids for infants with bronchiolitis.[14] The previously reference bronchiolitis benchmarking study demonstrated that admitted patients received steroids at a rate of 21% (IQR, 14%26%). The poor efficacy of corticosteroids in children with bronchiolitis under 2 years of age is well demonstrated in the literature. A large, blinded, randomized, controlled study compared systemic oral corticosteroids to placebo in hospitalized children 10 months to 6 years of age with viral wheezing.[26] This study showed no benefit of corticosteroids over placebo in length of stay or parental report of symptoms 1 week later. In the study, a subanalysis of children with eczema and family history of asthma also demonstrated no benefit of systemic corticosteroids. Large systematic reviews further argue that there is no effect of corticosteroids on the likelihood of admission or length of stay in infants with bronchiolitis.[27, 28] One 4‐armed prospective study of children 6 weeks to 12 months of age found no efficacy of dexamethasone over placebo.[23] There was modest benefit of dexamethasone in conjunction with racemic epinephrine; however, this benefit disappeared after adjustment for multiple comparisons. Three smaller studies showing benefit of systemic corticosteroids, however, were highly problematic. They have included older children, were retrospective, or demonstrated inconsistent results.[29, 30] A smaller study showed benefit for children over 2 years of age, but none for children under 2 years of age.[31] Premature infants are at increased risk of asthma, which typically responds well to corticosteroids as these children get older. However, a retrospective study of premature infants under 2 years of age with bronchiolitis demonstrated no association between corticosteroid use and length of stay, even in the subset of premature infants responding to albuterol.[32]
Systemic corticosteroid use in children is not harmless. Children under 2 years of age are especially vulnerable to the decreased growth velocity seen as a side effect of systemic corticosteroids.[33] Corticosteroids may also negatively impact the course of infectious illness. For instance, in children hospitalized with pneumonia but not receiving ‐agonists (ie, patients who are unlikely to have asthma), length of stay is prolonged and readmission is higher in those who receive corticosteroids.[34]
Do not treat gastroesophageal reflux in infants routinely with acid suppression therapy.
From 2000 to 2005, the incidence of infants diagnosed with gastroeshopaheal reflux (GER) tripled (3.4%12.3%), and the use of proton pump inhibitors (PPIs) doubled (31.5%62.6%).[35] Patients diagnosed with GER and treated with antireflux medication incurred 1.8 times higher healthcare costs in 1 study compared to healthy controls.[36] Though common, the use of acid suppressive medications in infants lacks evidence for efficacy in the majority of the clinical scenarios in which they are prescribed.[37, 38] PPIs have failed to outperform placebo for typical infant reflux, which is generally developmental and not pathologic.[39, 40] Furthermore, prompted by findings in adults, multiple pediatric investigators have now catalogued the potential risks associated with acid blockade in children in multiple clinical settings. Specifically, increased risk of pneumonia has been documented in inpatients and outpatients, and increased risk of necrotizing enterocolitis and other serious infections have been documented in intensive care unit settings.[41] In the absence of data supporting efficacy and given the emerging data on risk, empiric acid suppression in infants with reflux is wasteful and potentially harmful.
Do not use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen.
Pulse oximetry use has become widespread in the management of infants with bronchiolitis and likely accounts for the dramatic increase in bronchiolitis hospitalization rates in recent years.[14, 42, 43, 44, 45, 46, 47] Despite this increase in hospitalization rate, there was no change in mortality from bronchiolitis between 1979 and 1997.[48] The continuous monitoring of oxygen saturations in hospitalized infants with bronchiolitis may lead to overdiagnosis of hypoxemia and subsequent oxygen use that is of no apparent benefit to the child. Schroeder et al. demonstrated that 26% of a sample of infants hospitalized with bronchiolitis had a prolonged length of stay because of a perceived need for oxygen based on pulse oximetry readings.[43] Unger and Cunningham showed that the need for oxygen was the final determinant of length of stay in 58% of cases, and Cunningham and Murray suggested that using an oxygen saturation cutoff of 94% instead of 90% might increase the length of stay by 22 hours.[44, 49]
It has been previously shown that hypoxia is normative in infants. Healthy infants experience multiple episodes of SpO2 90% while sleeping.[50] This finding strengthens the notion that detection of low saturations in infants convalescing from bronchiolitis may simply reflect overdiagnosis. Among children with chronic severe asthma, who presumably have experienced episodes of hypoxia throughout childhood, there is no difference in school performance compared to healthy controls.[51]
The practice parameter on bronchiolitis from the American Academy of Pediatrics states: as the child's clinical course improves, continuous measurement of SpO2 is not routinely needed, which is a recommendation based on expert consensus.[14] There is at least one ongoing randomized trial comparing the use of continuous versus intermittent pulse oximetry in hospitalized infants with bronchiolitis who are weaned off oxygen (
DISCUSSION
Berwick and Hackbarth define overtreatment as: waste that comes from subjecting patients to care that, according to sound science and the patients' own preferences, cannot possibly help themcare rooted in outmoded habits, supply‐driven behaviors, and ignoring science.[1] With this project, we tried to capture common clinical sources of waste in the inpatient pediatric setting. This is an inherently difficult project because of the absence of solid evidence to inform every decision point in medicine. Although there is always room for improvement in our evidence base, our group intentionally gravitated to areas where the evidence was robust.
The primary strength of this work is the use of the RAND/UCLA appropriateness method or modified Delphi method. Several publications have validated this methodology as a sound strategy to assess quality indicators and issues related to overuse.[7, 53] To our knowledge, we are the first group to report the use of this methodology to develop a list such as the list reported here.
There were some challenges inherent to this project that can be considered limitations of the work. One perceived limitation of our list is the heavy concentration on respiratory diagnoses, especially bronchiolitis and asthma. We do not feel this is a genuine limitation, as the recommendations were partly driven by volume and costs as assessed by the KID database. Among the top 10 acute inpatient diagnoses in pediatrics, respiratory diagnoses are the most common, including bronchiolitis, pneumonia, and asthma. Pneumonia or bronchiolitis has been the most common medical diagnosis in inpatient pediatrics for the past decade, and both are always in the top 10 for costs as well.[54] Thus, the impact of decreasing overuse for these conditions will be highly significant from a simple volume standpoint.
The primary limitation of this work is the lack of implementation strategies. Although the Choosing Wisely campaign has plans for dissemination of the lists, compliance with the recommendations may be suboptimal. Although the development process followed an accepted methodology, shortcomings include the lack of wide, local, multidisciplinary (including parents or caretakers) consultation. Other barriers to compliance with these recommendations exist. Despite evidence that bronchiolitis is a benign self‐limited disease that does not respond to bronchodilators and steroids, the drive to identify and correct all abnormalities, such as wheezing or low oxygen saturation in a nontoxic infant with bronchiolitis, seems to trump the obligation to do no harm in daily practice.[55] This behavior may result from pressure by patients, families, nurses, or peers and is deeply embedded in our medical culture, where action is preferred to inaction without full knowledge or consideration of risks. Doctors and nurses have become attached to the pulse oximeter, believing somehow that the number displayed is less subjective and holds more predictive value than careful evaluation of the patient's respiratory status. Other pressures, such as direct to consumer marketing have made acid reflux a household term that is easily treated with over‐the‐counter medications. Considerations of the care continuum will also serve as barriers. Chest x‐rays, for example, are frequently obtained prior to admission to the hospital before the hospitalist is involved.
To overcome these limitations, the study of individual and organizational adoption of innovation might be relevant. Though it is complex and often more descriptive than proscriptive, a few salient features have emerged. Champions and opinion leaders make a difference, local culture is dominant, social networking is important, simple innovations that can be trialed on a small scale are adaptable by the user and have observable benefits, are more likely to be adopted.[56] Fortunately, the top 5 list meets many of these criteria, but also faces the daunting challenges of inertia, lack of financial incentive, inability to break with old habits, and fear of lawsuits and perceived patient/parent dissatisfaction. Ongoing evaluation, feedback, and audit will be necessary to detect and sustain change.
CONCLUSION
We have identified 5 tests or therapies overused in inpatient general pediatrics. One goal of the Choosing Wisely campaign is to begin to change social norms related to physician behavior. We hope by asking clinicians to consider doing less for common conditions in inpatient pediatrics, that they will increasingly consider the known and unanticipated risks of any medical interventions they choose to use. Finally, we would like to encourage all pediatricians to embrace the idea of good stewardship and join us in prioritizing and addressing waste and overuse as important patient safety issues as well as threats to the sustainability of our healthcare system.
Acknowledgments
The authors thank Drs. Doug Carlson, James O'Callaghan, and Karen Smith from the Society of Hospital Medicine's Pediatric and Quality and Safety Committees for their support of this effort.
Disclosure: Nothing to report.
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- Safely doing less: a missing component of the patient safety dialogue. Pediatrics. 2011;128:e1596–e1597. , , .
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- Temporal trends in rates of patient harm resulting from medical care. N Engl J Med. 2010;363:2124–2134. , , , , , .
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- The quality of ambulatory care delivered to children in the United States. N Engl J Med. 2007;357:1515–1523. , , , et al.
- National Asthma Education and Prevention Program. Expert panel report 3 (EPR‐3): guidelines for the diagnosis and management of asthma—summary report 2007. J Allergy Clin Immunol. 2007;120:S94–S138.
- The chest x‐ray and childhood acute asthma. Aust Clin Rev. 1993;13:153–156. , .
- Clinical factors associated with focal infiltrates in wheezing infants and toddlers. Clin Pediatr (Phila). 2000;39:387–393. , , , .
- Chest radiographs in the pediatric emergency department for children < or = 18 months of age with wheezing. Clin Pediatr (Phila). 1999;38:395–399. , , , .
- Clinical predictors of pneumonia among children with wheezing. Pediatrics. 2009;124:e29–e36. , , , , , .
- Reduce the rads: a quality assurance project on reducing unnecessary chest X‐rays in children with asthma. J Paediatr Child Health. 2005;41:107–111. , .
- American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774–1793.
- Evaluation of the utility of radiography in acute bronchiolitis. J Pediatr. 2007;150:429–433. , , , et al.
- Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis. Acta Paediatr. 2011;100:e17–e23. , , , et al.
- A cost effectiveness analysis of omitting radiography in diagnosis of acute bronchiolitis. Pediatr Pulmonol. 2009;44:122–127. , , , et al.
- Decreasing unnecessary utilization in acute bronchiolitis care: results from the value in inpatient pediatrics network. J Hosp Med. 2013;8:25–30. , , , et al.
- Efficacy of bronchodilator therapy in bronchiolitis. A meta‐analysis. Arch Pediatr Adolesc Med. 1996;150:1166–1172. , , , .
- Efficacy of beta2‐agonists in bronchiolitis: a reappraisal and meta‐analysis. Pediatrics. 1997;100:233–239. , .
- Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2010;(12):CD001266. , .
- Epinephrine for bronchiolitis. Cochrane Database Syst Rev. 2011;(6):CD003123. , , , et al.
- Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360:2079–2089. , , , et al.
- A multicenter, randomized, double‐blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med. 2003;349:27–35. , , , et al.
- A randomized, controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis. J Pediatr. 2002;141:818–824. , , , .
- Oral prednisolone for preschool children with acute virus‐induced wheezing. N Engl J Med. 2009;360:329–338. , , , et al.
- Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2010;(10):CD004878. , , , et al.
- Systemic corticosteroids in infant bronchiolitis: a meta‐analysis. Pediatrics. 2000;105:E44. , , , , .
- Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics. 1993;92:513–518. , , , .
- Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial. Pediatrics. 1990;86:350–356. , , .
- Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet. 1987;1:879–882. , , , , .
- The clinical management of preterm infants with bronchiolitis. Hosp Pediatr. 2013;3:244–250. , , , , .
- Glucocorticoids and growth in asthmatic children. Pediatr Allergy Immunol. 1995;6:145–154. , .
- Adjunct corticosteroids in children hospitalized with community‐acquired pneumonia. Pediatrics. 2011;127:e255–e263. , , , , , .
- Pediatric gastroesophageal reflux disease and acid‐related conditions: trends in incidence of diagnosis and acid suppression therapy. J Med Econ. 2009;12:348–355. , , , , , .
- Healthcare costs of GERD and acid‐related conditions in pediatric patients, with comparison between histamine‐2 receptor antagonists and proton pump inhibitors. Curr Med Res Opin. 2009;25:2703–2709. , , , , , .
- Are we overprescribing antireflux medications for infants with regurgitation? Pediatrics. 2007;120:946–949. , , , .
- Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr. 2007;45:421–427. , , , , .
- Efficacy of proton‐pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925–935. , , , , , .
- Effectiveness and safety of proton pump inhibitors in infantile gastroesophageal reflux disease. Ann Pharmacother. 2010;44:572–576. .
- Are there risks associated with empric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease? Hosp Pediatr. 2013;3:16–23. .
- Bronchiolitis management preferences and the influence of pulse oximetry and respiratory rate on the decision to admit. Pediatrics. 2003;111:e45–e51. , , , .
- Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations. Arch Pediatr Adolesc Med. 2004;158:527–530. , , , .
- Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis. Pediatrics. 2008;121:470–475. , .
- Oxygen therapy for bronchiolitis. Pediatrics. 2007;120:686–687; author reply 687–688. .
- Bronchiolitis‐associated hospitalizations among US children, 1980–1996. JAMA. 1999;282:1440–1446. , , , , , .
- Bronchiolitis: recent evidence on diagnosis and management. Pediatrics. 2010;125:342–349. , .
- Bronchiolitis‐associated mortality and estimates of respiratory syncytial virus‐associated deaths among US children, 1979–1997. J Infect Dis. 2001;183:16–22. , , , , .
- Observational study of two oxygen saturation targets for discharge in bronchiolitis. Arch Dis Child. 2012;97:361–363. , .
- Longitudinal assessment of hemoglobin oxygen saturation in preterm and term infants in the first six months of life. J Pediatr. 2011;159:377–383.e1. , , , et al.
- The impact of severe asthma on schoolchildren. J Asthma. 1999;36:409–417. , .
- Multi‐center, randomized trial of pulse oximetry monitoring strategies for children hospitalized for bronchiolitis. Abstract presented at: ID Week 2012; October 2012; San Diego, CA. , .
- The appropriateness method has acceptable reliability and validity for assessing overuse and underuse of surgical procedures. J Clin Epidemiol. 2012;65:1133–1143. , , , .
- Agency for Healthcare Research and Quality. HCUPnet. Kids inpatient database 2009. Available at: http://hcupnet.ahrq.gov. Accessed November 6, 2012.
- Too little? Too much? Primary care physicians' views on US health care: a brief report. Arch Intern Med. 2011;171:1582–1585. , , .
- How to implement change in clinical practice. Paediatr Respir Rev. 2003;4:340–346. .
Overuse in medicine is a significant and under‐recognized problem. Don Berwick estimated that waste accounts for at least 20% of healthcare expenditures in the United States, with overtreatment as one of the largest categories.[1] A commentary by Schroeder et al. challenged pediatricians to incorporate this knowledge into our own patient safety and quality movement.[2] Recently published data suggest that we are far from achieving the patient safety goals set forth in the Institute of Medicine's landmark To Err is Human[3] report, despite more than a decade of national, local, and regional efforts.[4] One way to reduce waste and improve patient safety is to eliminate practices of unproven benefit. Therapies or tests that may initially seem promising are often proven to be not only unhelpful but actually harmful. The recommendation of the US Preventive Services Task Force against routine screening for prostate specific antigen is an example of how a common test initially thought of as lifesaving actually increases harm.[5]
The American Board of Internal Medicine Foundation (ABIM‐F) recently announced the Choosing Wisely campaign. Through this campaign the Foundation encourages physicians, patients and other healthcare stakeholders to think and talk about medical tests and procedures that may be unnecessary.[6] The primary output of this challenge is the development of a list of 5 tests and or therapies that physicians and patients should question. The ABIM‐F approached different medical societies to develop these lists within their own specialties. The Society of Hospital Medicine (SHM) joined the Choosing Wisely campaign in April 2012, and agreed to develop a list of 5 therapies and tests for adult hospital medicine and pediatric hospital medicine. Here we present the contribution of the pediatric workgroup detailing the methodology and process for developing the list, as well as summarizing the evidence supporting each recommendation.
METHODS
In the spring of 2012, the pediatric committee of the SHM convened a workgroup of pediatric hospitalists to develop a top 5 list for the field. This workgroup was composed of experienced pediatric hospitalists representing diverse geographic locations of the United States and a mix of academic and nonacademic practice settings. The group, consisting of 4 women and 9 men, began by proposing candidate recommendations after discussion with colleagues at their different practice sites. The group was charged to maintain a focus on overuse practices that had a strong basis in evidence, were frequently encountered at their practice sites, and achieved significant consensus among their colleagues. Figure 1 shows the process map describing the method for the development of the pediatric recommendations. All workgroup participants were queried as to conflict of interest relevant to this work and none were identified.

Literature Review
After the generation of the initial top 20 list, 2 reviewers conducted independent literature searches in PubMed, MEDLINE, and the Cochrane Library on the proposed topics. The reviewers also conducted generic Internet searches. Key search terms included pediatric asthma, bronchiolitis, chest radiograph, systemic corticosteroids, gastroesophageal reflux disease (GERD), infant, child, acid suppression therapy, continuous pulse oximetry, pneumonia, gastroenteritis, viral testing, blood culture, and soft tissue infections. To ensure that the reviewers included all studies relevant to the searches, they utilized broad terms. The search included all literature published through 2012, and nonEnglish language publications were included in the search. Studies selected and included in the review were based upon common criteria including whether the article discussed an evaluation of efficacy and/or utility of treatment, included a pediatric population in the guidelines or study, reviewed the harm associated with the administration of a particular test or treatment, and explored the cost associated with the test or treatment.
The Delphi Panel
Members of the workgroup formed a Delphi panel except for 1 member (R.Q.) who served as the nonvoting moderator. The members of the Delphi panel considered the results of the literature search for each recommendation along with the collated feedback from hospitalist listserves as described in Figure 1. Each panel member received a voting instrument with the candidate tests and treatments for the first round of Delphi voting. The panel utilized a modified Delphi method or the RAND Corporation (RAND)/University of California at Los Angeles (UCLA) appropriateness method as described in previous publications of quality indicator development in pediatrics.[7] Each panelist scored the candidate tests and treatments and forwarded the scores to the moderator. Subsequently, all the members of the Delphi panel met through a conference call to carry out the second round of voting. The deidentified collated results of the first round of Delphi voting were made available and discussed during the call. The moderator collated the final results, and the final 5 recommendations were those that had the highest score after the second round of Delphi voting.
Volume and Costs
During deliberations, the committee took into account the prevalence and cost rankings of our most common pediatric inpatient diagnoses. This was done using the Agency for Healthcare Research and Quality's (AHRQ) Healthcare Utilization Project (HCUP), specifically, the Kids' Inpatient Database (KID). HCUP includes the largest collection of longitudinal hospital care data in the United States, encompassing all‐payer discharge‐level information. We excluded normal newborn hospitalizations, and looked at the top 10 acute inpatient diagnoses in terms of both volume and aggregate costs.
RESULTS
The initial list of 20 candidate tests and treatments as well as the refined list of 11 recommendations can be found as electronic supplements to this publication (see Supporting Table 1 and Supporting Table 2 in the online version of this article). The format and language of the list of 11 recommendations were chosen to mesh with that typically used in the ABIM‐F Choosing Wisely campaign. During the Delphi panel, there was strong group consensus about combining items 1 and 2 (chest radiographs in asthma and bronchiolitis) into a single recommendation.
Do not order chest radiographs in children with asthma or bronchiolitis. |
Do not use bronchodilators in children with bronchiolitis. |
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection. |
Do not treat gastroesophageal reflux in infants routinely with acid suppression therapy. |
Do not use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. |
The top 5 recommendations based on the result of the second round of Delphi scoring are shown in Table 1 and described below along with a detailed evidence summary.
Do not order chest radiographs in children with asthma or bronchiolitis.
The National Heart and Lung Institute's guidelines for the management of asthma, published in 1987, recommend against routinely obtaining chest radiographs in patients with asthma or asthma exacerbations.[8] Supporting this recommendation are several studies that show a low overall yield when obtaining chest radiographs for wheezing patients.[9, 10, 11] Most relevant, studies that evaluated the clinical utility of radiographs in patients with asthma have demonstrated that they influence clinical management in less than 2% of cases.[12] A quality improvement project aimed at decreasing the rate of chest radiographs obtained in patients with asthma demonstrated that close to 60% of patients admitted to the hospital had chest radiographs performed, and that significant overall reductions can be achieved (45.3%28.9%, P=0.0005) without impacting clinical outcomes negatively.[13]
Similarly, the Subcommittee on Diagnosis and Management of Bronchiolitis of the American Academy of Pediatrics recommends against routinely obtaining radiographs during the evaluation for bronchiolitis.[14] Studies assessing the utility of chest x‐rays in these children demonstrate an even lower incidence of abnormalities (0.75%) and indicate that, despite this low incidence, physicians are more likely to treat with antibiotics when radiographs are obtained.[15] There is also evidence that chest radiographs in patients with bronchiolitis are not useful in predicting severity of illness.[16] Furthermore, cost‐effective analyses have demonstrated that omitting chest radiographs in bronchiolitis is actually cost‐effective, without compromising diagnostic accuracy.[17] In a recently published national benchmarking inpatient collaborative, Ralston et al. demonstrated that the majority of patients admitted to the hospital with bronchiolitis have chest radiographs performed at a rate of 64% (interquartile range [IQR], 54%81%).[18]
In both bronchiolitis and asthma, the elimination of unnecessary radiographs has the potential to decrease costs, reduce radiation exposure, and minimize the overuse of antibiotics that often occurs secondary to false positive results.
Do not use bronchodilators in children with bronchiolitis.
Ralston showed that 70% (IQR, 59%83%) of admitted bronchiolitis patients received bronchodilators with an average of 7.9 doses per patient (IQR, 4.69.8). National guidelines for bronchiolitis suggest a very limited role of bronchodilators in patients with bronchiolitis.[14] The first meta‐analyses of studies related to the question of ‐agonist efficacy in bronchiolitis were published in the late 1990s, revealing minimal or no treatment effects.[19, 20] Since then, further research has solidified these findings, and fairly definitive statements can be made based on a recent comprehensive meta‐analysis.[21] The pooled data do not show any effect on hospitalization rates, hospital length of stay, or other inpatient outcomes in bronchiolitis. They do show a small change in clinical scores documented in the outpatient setting, though these scores have not correlated with any detectable difference in outcomes. Routine use of ‐agonists in the inpatient setting has no proven benefit, and given the large amount of consistent data, there is no compelling reason for further study of this therapy in the inpatient setting.
Epinephrine, a combined ‐ and ‐agonist, has been extensively evaluated in bronchiolitis as well. Like albuterol, epinephrine has been reported to have no effect on hospital length of stay in bronchiolitis.[22] The issue of admission rates after epinephrine is complicated by 1 very large study that combined epinephrine with dexamethasone and reported a decreased admission rate, though only at 7 days after therapy; however, this effect was nullified after adjustment for multiple comparisons.[23] When the end point is improvement of respiratory scores, epinephrine may perform better than albuterol in studies where they are directly compared; however, there is no evidence that repeated usage of epinephrine has any impact on any clinical outcome for inpatients.[24, 25]
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection
In their summary of evidence, the Subcommittee on Diagnosis and Management of Bronchiolitis of the American Academy of Pediatrics recommends against routinely using systemic corticosteroids for infants with bronchiolitis.[14] The previously reference bronchiolitis benchmarking study demonstrated that admitted patients received steroids at a rate of 21% (IQR, 14%26%). The poor efficacy of corticosteroids in children with bronchiolitis under 2 years of age is well demonstrated in the literature. A large, blinded, randomized, controlled study compared systemic oral corticosteroids to placebo in hospitalized children 10 months to 6 years of age with viral wheezing.[26] This study showed no benefit of corticosteroids over placebo in length of stay or parental report of symptoms 1 week later. In the study, a subanalysis of children with eczema and family history of asthma also demonstrated no benefit of systemic corticosteroids. Large systematic reviews further argue that there is no effect of corticosteroids on the likelihood of admission or length of stay in infants with bronchiolitis.[27, 28] One 4‐armed prospective study of children 6 weeks to 12 months of age found no efficacy of dexamethasone over placebo.[23] There was modest benefit of dexamethasone in conjunction with racemic epinephrine; however, this benefit disappeared after adjustment for multiple comparisons. Three smaller studies showing benefit of systemic corticosteroids, however, were highly problematic. They have included older children, were retrospective, or demonstrated inconsistent results.[29, 30] A smaller study showed benefit for children over 2 years of age, but none for children under 2 years of age.[31] Premature infants are at increased risk of asthma, which typically responds well to corticosteroids as these children get older. However, a retrospective study of premature infants under 2 years of age with bronchiolitis demonstrated no association between corticosteroid use and length of stay, even in the subset of premature infants responding to albuterol.[32]
Systemic corticosteroid use in children is not harmless. Children under 2 years of age are especially vulnerable to the decreased growth velocity seen as a side effect of systemic corticosteroids.[33] Corticosteroids may also negatively impact the course of infectious illness. For instance, in children hospitalized with pneumonia but not receiving ‐agonists (ie, patients who are unlikely to have asthma), length of stay is prolonged and readmission is higher in those who receive corticosteroids.[34]
Do not treat gastroesophageal reflux in infants routinely with acid suppression therapy.
From 2000 to 2005, the incidence of infants diagnosed with gastroeshopaheal reflux (GER) tripled (3.4%12.3%), and the use of proton pump inhibitors (PPIs) doubled (31.5%62.6%).[35] Patients diagnosed with GER and treated with antireflux medication incurred 1.8 times higher healthcare costs in 1 study compared to healthy controls.[36] Though common, the use of acid suppressive medications in infants lacks evidence for efficacy in the majority of the clinical scenarios in which they are prescribed.[37, 38] PPIs have failed to outperform placebo for typical infant reflux, which is generally developmental and not pathologic.[39, 40] Furthermore, prompted by findings in adults, multiple pediatric investigators have now catalogued the potential risks associated with acid blockade in children in multiple clinical settings. Specifically, increased risk of pneumonia has been documented in inpatients and outpatients, and increased risk of necrotizing enterocolitis and other serious infections have been documented in intensive care unit settings.[41] In the absence of data supporting efficacy and given the emerging data on risk, empiric acid suppression in infants with reflux is wasteful and potentially harmful.
Do not use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen.
Pulse oximetry use has become widespread in the management of infants with bronchiolitis and likely accounts for the dramatic increase in bronchiolitis hospitalization rates in recent years.[14, 42, 43, 44, 45, 46, 47] Despite this increase in hospitalization rate, there was no change in mortality from bronchiolitis between 1979 and 1997.[48] The continuous monitoring of oxygen saturations in hospitalized infants with bronchiolitis may lead to overdiagnosis of hypoxemia and subsequent oxygen use that is of no apparent benefit to the child. Schroeder et al. demonstrated that 26% of a sample of infants hospitalized with bronchiolitis had a prolonged length of stay because of a perceived need for oxygen based on pulse oximetry readings.[43] Unger and Cunningham showed that the need for oxygen was the final determinant of length of stay in 58% of cases, and Cunningham and Murray suggested that using an oxygen saturation cutoff of 94% instead of 90% might increase the length of stay by 22 hours.[44, 49]
It has been previously shown that hypoxia is normative in infants. Healthy infants experience multiple episodes of SpO2 90% while sleeping.[50] This finding strengthens the notion that detection of low saturations in infants convalescing from bronchiolitis may simply reflect overdiagnosis. Among children with chronic severe asthma, who presumably have experienced episodes of hypoxia throughout childhood, there is no difference in school performance compared to healthy controls.[51]
The practice parameter on bronchiolitis from the American Academy of Pediatrics states: as the child's clinical course improves, continuous measurement of SpO2 is not routinely needed, which is a recommendation based on expert consensus.[14] There is at least one ongoing randomized trial comparing the use of continuous versus intermittent pulse oximetry in hospitalized infants with bronchiolitis who are weaned off oxygen (
DISCUSSION
Berwick and Hackbarth define overtreatment as: waste that comes from subjecting patients to care that, according to sound science and the patients' own preferences, cannot possibly help themcare rooted in outmoded habits, supply‐driven behaviors, and ignoring science.[1] With this project, we tried to capture common clinical sources of waste in the inpatient pediatric setting. This is an inherently difficult project because of the absence of solid evidence to inform every decision point in medicine. Although there is always room for improvement in our evidence base, our group intentionally gravitated to areas where the evidence was robust.
The primary strength of this work is the use of the RAND/UCLA appropriateness method or modified Delphi method. Several publications have validated this methodology as a sound strategy to assess quality indicators and issues related to overuse.[7, 53] To our knowledge, we are the first group to report the use of this methodology to develop a list such as the list reported here.
There were some challenges inherent to this project that can be considered limitations of the work. One perceived limitation of our list is the heavy concentration on respiratory diagnoses, especially bronchiolitis and asthma. We do not feel this is a genuine limitation, as the recommendations were partly driven by volume and costs as assessed by the KID database. Among the top 10 acute inpatient diagnoses in pediatrics, respiratory diagnoses are the most common, including bronchiolitis, pneumonia, and asthma. Pneumonia or bronchiolitis has been the most common medical diagnosis in inpatient pediatrics for the past decade, and both are always in the top 10 for costs as well.[54] Thus, the impact of decreasing overuse for these conditions will be highly significant from a simple volume standpoint.
The primary limitation of this work is the lack of implementation strategies. Although the Choosing Wisely campaign has plans for dissemination of the lists, compliance with the recommendations may be suboptimal. Although the development process followed an accepted methodology, shortcomings include the lack of wide, local, multidisciplinary (including parents or caretakers) consultation. Other barriers to compliance with these recommendations exist. Despite evidence that bronchiolitis is a benign self‐limited disease that does not respond to bronchodilators and steroids, the drive to identify and correct all abnormalities, such as wheezing or low oxygen saturation in a nontoxic infant with bronchiolitis, seems to trump the obligation to do no harm in daily practice.[55] This behavior may result from pressure by patients, families, nurses, or peers and is deeply embedded in our medical culture, where action is preferred to inaction without full knowledge or consideration of risks. Doctors and nurses have become attached to the pulse oximeter, believing somehow that the number displayed is less subjective and holds more predictive value than careful evaluation of the patient's respiratory status. Other pressures, such as direct to consumer marketing have made acid reflux a household term that is easily treated with over‐the‐counter medications. Considerations of the care continuum will also serve as barriers. Chest x‐rays, for example, are frequently obtained prior to admission to the hospital before the hospitalist is involved.
To overcome these limitations, the study of individual and organizational adoption of innovation might be relevant. Though it is complex and often more descriptive than proscriptive, a few salient features have emerged. Champions and opinion leaders make a difference, local culture is dominant, social networking is important, simple innovations that can be trialed on a small scale are adaptable by the user and have observable benefits, are more likely to be adopted.[56] Fortunately, the top 5 list meets many of these criteria, but also faces the daunting challenges of inertia, lack of financial incentive, inability to break with old habits, and fear of lawsuits and perceived patient/parent dissatisfaction. Ongoing evaluation, feedback, and audit will be necessary to detect and sustain change.
CONCLUSION
We have identified 5 tests or therapies overused in inpatient general pediatrics. One goal of the Choosing Wisely campaign is to begin to change social norms related to physician behavior. We hope by asking clinicians to consider doing less for common conditions in inpatient pediatrics, that they will increasingly consider the known and unanticipated risks of any medical interventions they choose to use. Finally, we would like to encourage all pediatricians to embrace the idea of good stewardship and join us in prioritizing and addressing waste and overuse as important patient safety issues as well as threats to the sustainability of our healthcare system.
Acknowledgments
The authors thank Drs. Doug Carlson, James O'Callaghan, and Karen Smith from the Society of Hospital Medicine's Pediatric and Quality and Safety Committees for their support of this effort.
Disclosure: Nothing to report.
Overuse in medicine is a significant and under‐recognized problem. Don Berwick estimated that waste accounts for at least 20% of healthcare expenditures in the United States, with overtreatment as one of the largest categories.[1] A commentary by Schroeder et al. challenged pediatricians to incorporate this knowledge into our own patient safety and quality movement.[2] Recently published data suggest that we are far from achieving the patient safety goals set forth in the Institute of Medicine's landmark To Err is Human[3] report, despite more than a decade of national, local, and regional efforts.[4] One way to reduce waste and improve patient safety is to eliminate practices of unproven benefit. Therapies or tests that may initially seem promising are often proven to be not only unhelpful but actually harmful. The recommendation of the US Preventive Services Task Force against routine screening for prostate specific antigen is an example of how a common test initially thought of as lifesaving actually increases harm.[5]
The American Board of Internal Medicine Foundation (ABIM‐F) recently announced the Choosing Wisely campaign. Through this campaign the Foundation encourages physicians, patients and other healthcare stakeholders to think and talk about medical tests and procedures that may be unnecessary.[6] The primary output of this challenge is the development of a list of 5 tests and or therapies that physicians and patients should question. The ABIM‐F approached different medical societies to develop these lists within their own specialties. The Society of Hospital Medicine (SHM) joined the Choosing Wisely campaign in April 2012, and agreed to develop a list of 5 therapies and tests for adult hospital medicine and pediatric hospital medicine. Here we present the contribution of the pediatric workgroup detailing the methodology and process for developing the list, as well as summarizing the evidence supporting each recommendation.
METHODS
In the spring of 2012, the pediatric committee of the SHM convened a workgroup of pediatric hospitalists to develop a top 5 list for the field. This workgroup was composed of experienced pediatric hospitalists representing diverse geographic locations of the United States and a mix of academic and nonacademic practice settings. The group, consisting of 4 women and 9 men, began by proposing candidate recommendations after discussion with colleagues at their different practice sites. The group was charged to maintain a focus on overuse practices that had a strong basis in evidence, were frequently encountered at their practice sites, and achieved significant consensus among their colleagues. Figure 1 shows the process map describing the method for the development of the pediatric recommendations. All workgroup participants were queried as to conflict of interest relevant to this work and none were identified.

Literature Review
After the generation of the initial top 20 list, 2 reviewers conducted independent literature searches in PubMed, MEDLINE, and the Cochrane Library on the proposed topics. The reviewers also conducted generic Internet searches. Key search terms included pediatric asthma, bronchiolitis, chest radiograph, systemic corticosteroids, gastroesophageal reflux disease (GERD), infant, child, acid suppression therapy, continuous pulse oximetry, pneumonia, gastroenteritis, viral testing, blood culture, and soft tissue infections. To ensure that the reviewers included all studies relevant to the searches, they utilized broad terms. The search included all literature published through 2012, and nonEnglish language publications were included in the search. Studies selected and included in the review were based upon common criteria including whether the article discussed an evaluation of efficacy and/or utility of treatment, included a pediatric population in the guidelines or study, reviewed the harm associated with the administration of a particular test or treatment, and explored the cost associated with the test or treatment.
The Delphi Panel
Members of the workgroup formed a Delphi panel except for 1 member (R.Q.) who served as the nonvoting moderator. The members of the Delphi panel considered the results of the literature search for each recommendation along with the collated feedback from hospitalist listserves as described in Figure 1. Each panel member received a voting instrument with the candidate tests and treatments for the first round of Delphi voting. The panel utilized a modified Delphi method or the RAND Corporation (RAND)/University of California at Los Angeles (UCLA) appropriateness method as described in previous publications of quality indicator development in pediatrics.[7] Each panelist scored the candidate tests and treatments and forwarded the scores to the moderator. Subsequently, all the members of the Delphi panel met through a conference call to carry out the second round of voting. The deidentified collated results of the first round of Delphi voting were made available and discussed during the call. The moderator collated the final results, and the final 5 recommendations were those that had the highest score after the second round of Delphi voting.
Volume and Costs
During deliberations, the committee took into account the prevalence and cost rankings of our most common pediatric inpatient diagnoses. This was done using the Agency for Healthcare Research and Quality's (AHRQ) Healthcare Utilization Project (HCUP), specifically, the Kids' Inpatient Database (KID). HCUP includes the largest collection of longitudinal hospital care data in the United States, encompassing all‐payer discharge‐level information. We excluded normal newborn hospitalizations, and looked at the top 10 acute inpatient diagnoses in terms of both volume and aggregate costs.
RESULTS
The initial list of 20 candidate tests and treatments as well as the refined list of 11 recommendations can be found as electronic supplements to this publication (see Supporting Table 1 and Supporting Table 2 in the online version of this article). The format and language of the list of 11 recommendations were chosen to mesh with that typically used in the ABIM‐F Choosing Wisely campaign. During the Delphi panel, there was strong group consensus about combining items 1 and 2 (chest radiographs in asthma and bronchiolitis) into a single recommendation.
Do not order chest radiographs in children with asthma or bronchiolitis. |
Do not use bronchodilators in children with bronchiolitis. |
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection. |
Do not treat gastroesophageal reflux in infants routinely with acid suppression therapy. |
Do not use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. |
The top 5 recommendations based on the result of the second round of Delphi scoring are shown in Table 1 and described below along with a detailed evidence summary.
Do not order chest radiographs in children with asthma or bronchiolitis.
The National Heart and Lung Institute's guidelines for the management of asthma, published in 1987, recommend against routinely obtaining chest radiographs in patients with asthma or asthma exacerbations.[8] Supporting this recommendation are several studies that show a low overall yield when obtaining chest radiographs for wheezing patients.[9, 10, 11] Most relevant, studies that evaluated the clinical utility of radiographs in patients with asthma have demonstrated that they influence clinical management in less than 2% of cases.[12] A quality improvement project aimed at decreasing the rate of chest radiographs obtained in patients with asthma demonstrated that close to 60% of patients admitted to the hospital had chest radiographs performed, and that significant overall reductions can be achieved (45.3%28.9%, P=0.0005) without impacting clinical outcomes negatively.[13]
Similarly, the Subcommittee on Diagnosis and Management of Bronchiolitis of the American Academy of Pediatrics recommends against routinely obtaining radiographs during the evaluation for bronchiolitis.[14] Studies assessing the utility of chest x‐rays in these children demonstrate an even lower incidence of abnormalities (0.75%) and indicate that, despite this low incidence, physicians are more likely to treat with antibiotics when radiographs are obtained.[15] There is also evidence that chest radiographs in patients with bronchiolitis are not useful in predicting severity of illness.[16] Furthermore, cost‐effective analyses have demonstrated that omitting chest radiographs in bronchiolitis is actually cost‐effective, without compromising diagnostic accuracy.[17] In a recently published national benchmarking inpatient collaborative, Ralston et al. demonstrated that the majority of patients admitted to the hospital with bronchiolitis have chest radiographs performed at a rate of 64% (interquartile range [IQR], 54%81%).[18]
In both bronchiolitis and asthma, the elimination of unnecessary radiographs has the potential to decrease costs, reduce radiation exposure, and minimize the overuse of antibiotics that often occurs secondary to false positive results.
Do not use bronchodilators in children with bronchiolitis.
Ralston showed that 70% (IQR, 59%83%) of admitted bronchiolitis patients received bronchodilators with an average of 7.9 doses per patient (IQR, 4.69.8). National guidelines for bronchiolitis suggest a very limited role of bronchodilators in patients with bronchiolitis.[14] The first meta‐analyses of studies related to the question of ‐agonist efficacy in bronchiolitis were published in the late 1990s, revealing minimal or no treatment effects.[19, 20] Since then, further research has solidified these findings, and fairly definitive statements can be made based on a recent comprehensive meta‐analysis.[21] The pooled data do not show any effect on hospitalization rates, hospital length of stay, or other inpatient outcomes in bronchiolitis. They do show a small change in clinical scores documented in the outpatient setting, though these scores have not correlated with any detectable difference in outcomes. Routine use of ‐agonists in the inpatient setting has no proven benefit, and given the large amount of consistent data, there is no compelling reason for further study of this therapy in the inpatient setting.
Epinephrine, a combined ‐ and ‐agonist, has been extensively evaluated in bronchiolitis as well. Like albuterol, epinephrine has been reported to have no effect on hospital length of stay in bronchiolitis.[22] The issue of admission rates after epinephrine is complicated by 1 very large study that combined epinephrine with dexamethasone and reported a decreased admission rate, though only at 7 days after therapy; however, this effect was nullified after adjustment for multiple comparisons.[23] When the end point is improvement of respiratory scores, epinephrine may perform better than albuterol in studies where they are directly compared; however, there is no evidence that repeated usage of epinephrine has any impact on any clinical outcome for inpatients.[24, 25]
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection
In their summary of evidence, the Subcommittee on Diagnosis and Management of Bronchiolitis of the American Academy of Pediatrics recommends against routinely using systemic corticosteroids for infants with bronchiolitis.[14] The previously reference bronchiolitis benchmarking study demonstrated that admitted patients received steroids at a rate of 21% (IQR, 14%26%). The poor efficacy of corticosteroids in children with bronchiolitis under 2 years of age is well demonstrated in the literature. A large, blinded, randomized, controlled study compared systemic oral corticosteroids to placebo in hospitalized children 10 months to 6 years of age with viral wheezing.[26] This study showed no benefit of corticosteroids over placebo in length of stay or parental report of symptoms 1 week later. In the study, a subanalysis of children with eczema and family history of asthma also demonstrated no benefit of systemic corticosteroids. Large systematic reviews further argue that there is no effect of corticosteroids on the likelihood of admission or length of stay in infants with bronchiolitis.[27, 28] One 4‐armed prospective study of children 6 weeks to 12 months of age found no efficacy of dexamethasone over placebo.[23] There was modest benefit of dexamethasone in conjunction with racemic epinephrine; however, this benefit disappeared after adjustment for multiple comparisons. Three smaller studies showing benefit of systemic corticosteroids, however, were highly problematic. They have included older children, were retrospective, or demonstrated inconsistent results.[29, 30] A smaller study showed benefit for children over 2 years of age, but none for children under 2 years of age.[31] Premature infants are at increased risk of asthma, which typically responds well to corticosteroids as these children get older. However, a retrospective study of premature infants under 2 years of age with bronchiolitis demonstrated no association between corticosteroid use and length of stay, even in the subset of premature infants responding to albuterol.[32]
Systemic corticosteroid use in children is not harmless. Children under 2 years of age are especially vulnerable to the decreased growth velocity seen as a side effect of systemic corticosteroids.[33] Corticosteroids may also negatively impact the course of infectious illness. For instance, in children hospitalized with pneumonia but not receiving ‐agonists (ie, patients who are unlikely to have asthma), length of stay is prolonged and readmission is higher in those who receive corticosteroids.[34]
Do not treat gastroesophageal reflux in infants routinely with acid suppression therapy.
From 2000 to 2005, the incidence of infants diagnosed with gastroeshopaheal reflux (GER) tripled (3.4%12.3%), and the use of proton pump inhibitors (PPIs) doubled (31.5%62.6%).[35] Patients diagnosed with GER and treated with antireflux medication incurred 1.8 times higher healthcare costs in 1 study compared to healthy controls.[36] Though common, the use of acid suppressive medications in infants lacks evidence for efficacy in the majority of the clinical scenarios in which they are prescribed.[37, 38] PPIs have failed to outperform placebo for typical infant reflux, which is generally developmental and not pathologic.[39, 40] Furthermore, prompted by findings in adults, multiple pediatric investigators have now catalogued the potential risks associated with acid blockade in children in multiple clinical settings. Specifically, increased risk of pneumonia has been documented in inpatients and outpatients, and increased risk of necrotizing enterocolitis and other serious infections have been documented in intensive care unit settings.[41] In the absence of data supporting efficacy and given the emerging data on risk, empiric acid suppression in infants with reflux is wasteful and potentially harmful.
Do not use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen.
Pulse oximetry use has become widespread in the management of infants with bronchiolitis and likely accounts for the dramatic increase in bronchiolitis hospitalization rates in recent years.[14, 42, 43, 44, 45, 46, 47] Despite this increase in hospitalization rate, there was no change in mortality from bronchiolitis between 1979 and 1997.[48] The continuous monitoring of oxygen saturations in hospitalized infants with bronchiolitis may lead to overdiagnosis of hypoxemia and subsequent oxygen use that is of no apparent benefit to the child. Schroeder et al. demonstrated that 26% of a sample of infants hospitalized with bronchiolitis had a prolonged length of stay because of a perceived need for oxygen based on pulse oximetry readings.[43] Unger and Cunningham showed that the need for oxygen was the final determinant of length of stay in 58% of cases, and Cunningham and Murray suggested that using an oxygen saturation cutoff of 94% instead of 90% might increase the length of stay by 22 hours.[44, 49]
It has been previously shown that hypoxia is normative in infants. Healthy infants experience multiple episodes of SpO2 90% while sleeping.[50] This finding strengthens the notion that detection of low saturations in infants convalescing from bronchiolitis may simply reflect overdiagnosis. Among children with chronic severe asthma, who presumably have experienced episodes of hypoxia throughout childhood, there is no difference in school performance compared to healthy controls.[51]
The practice parameter on bronchiolitis from the American Academy of Pediatrics states: as the child's clinical course improves, continuous measurement of SpO2 is not routinely needed, which is a recommendation based on expert consensus.[14] There is at least one ongoing randomized trial comparing the use of continuous versus intermittent pulse oximetry in hospitalized infants with bronchiolitis who are weaned off oxygen (
DISCUSSION
Berwick and Hackbarth define overtreatment as: waste that comes from subjecting patients to care that, according to sound science and the patients' own preferences, cannot possibly help themcare rooted in outmoded habits, supply‐driven behaviors, and ignoring science.[1] With this project, we tried to capture common clinical sources of waste in the inpatient pediatric setting. This is an inherently difficult project because of the absence of solid evidence to inform every decision point in medicine. Although there is always room for improvement in our evidence base, our group intentionally gravitated to areas where the evidence was robust.
The primary strength of this work is the use of the RAND/UCLA appropriateness method or modified Delphi method. Several publications have validated this methodology as a sound strategy to assess quality indicators and issues related to overuse.[7, 53] To our knowledge, we are the first group to report the use of this methodology to develop a list such as the list reported here.
There were some challenges inherent to this project that can be considered limitations of the work. One perceived limitation of our list is the heavy concentration on respiratory diagnoses, especially bronchiolitis and asthma. We do not feel this is a genuine limitation, as the recommendations were partly driven by volume and costs as assessed by the KID database. Among the top 10 acute inpatient diagnoses in pediatrics, respiratory diagnoses are the most common, including bronchiolitis, pneumonia, and asthma. Pneumonia or bronchiolitis has been the most common medical diagnosis in inpatient pediatrics for the past decade, and both are always in the top 10 for costs as well.[54] Thus, the impact of decreasing overuse for these conditions will be highly significant from a simple volume standpoint.
The primary limitation of this work is the lack of implementation strategies. Although the Choosing Wisely campaign has plans for dissemination of the lists, compliance with the recommendations may be suboptimal. Although the development process followed an accepted methodology, shortcomings include the lack of wide, local, multidisciplinary (including parents or caretakers) consultation. Other barriers to compliance with these recommendations exist. Despite evidence that bronchiolitis is a benign self‐limited disease that does not respond to bronchodilators and steroids, the drive to identify and correct all abnormalities, such as wheezing or low oxygen saturation in a nontoxic infant with bronchiolitis, seems to trump the obligation to do no harm in daily practice.[55] This behavior may result from pressure by patients, families, nurses, or peers and is deeply embedded in our medical culture, where action is preferred to inaction without full knowledge or consideration of risks. Doctors and nurses have become attached to the pulse oximeter, believing somehow that the number displayed is less subjective and holds more predictive value than careful evaluation of the patient's respiratory status. Other pressures, such as direct to consumer marketing have made acid reflux a household term that is easily treated with over‐the‐counter medications. Considerations of the care continuum will also serve as barriers. Chest x‐rays, for example, are frequently obtained prior to admission to the hospital before the hospitalist is involved.
To overcome these limitations, the study of individual and organizational adoption of innovation might be relevant. Though it is complex and often more descriptive than proscriptive, a few salient features have emerged. Champions and opinion leaders make a difference, local culture is dominant, social networking is important, simple innovations that can be trialed on a small scale are adaptable by the user and have observable benefits, are more likely to be adopted.[56] Fortunately, the top 5 list meets many of these criteria, but also faces the daunting challenges of inertia, lack of financial incentive, inability to break with old habits, and fear of lawsuits and perceived patient/parent dissatisfaction. Ongoing evaluation, feedback, and audit will be necessary to detect and sustain change.
CONCLUSION
We have identified 5 tests or therapies overused in inpatient general pediatrics. One goal of the Choosing Wisely campaign is to begin to change social norms related to physician behavior. We hope by asking clinicians to consider doing less for common conditions in inpatient pediatrics, that they will increasingly consider the known and unanticipated risks of any medical interventions they choose to use. Finally, we would like to encourage all pediatricians to embrace the idea of good stewardship and join us in prioritizing and addressing waste and overuse as important patient safety issues as well as threats to the sustainability of our healthcare system.
Acknowledgments
The authors thank Drs. Doug Carlson, James O'Callaghan, and Karen Smith from the Society of Hospital Medicine's Pediatric and Quality and Safety Committees for their support of this effort.
Disclosure: Nothing to report.
- Eliminating waste in US health care. JAMA. 2012;307:1513–1516. , .
- Safely doing less: a missing component of the patient safety dialogue. Pediatrics. 2011;128:e1596–e1597. , , .
- To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press; 2000. , , .
- Temporal trends in rates of patient harm resulting from medical care. N Engl J Med. 2010;363:2124–2134. , , , , , .
- Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120–134. .
- Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–1802. , .
- The quality of ambulatory care delivered to children in the United States. N Engl J Med. 2007;357:1515–1523. , , , et al.
- National Asthma Education and Prevention Program. Expert panel report 3 (EPR‐3): guidelines for the diagnosis and management of asthma—summary report 2007. J Allergy Clin Immunol. 2007;120:S94–S138.
- The chest x‐ray and childhood acute asthma. Aust Clin Rev. 1993;13:153–156. , .
- Clinical factors associated with focal infiltrates in wheezing infants and toddlers. Clin Pediatr (Phila). 2000;39:387–393. , , , .
- Chest radiographs in the pediatric emergency department for children < or = 18 months of age with wheezing. Clin Pediatr (Phila). 1999;38:395–399. , , , .
- Clinical predictors of pneumonia among children with wheezing. Pediatrics. 2009;124:e29–e36. , , , , , .
- Reduce the rads: a quality assurance project on reducing unnecessary chest X‐rays in children with asthma. J Paediatr Child Health. 2005;41:107–111. , .
- American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774–1793.
- Evaluation of the utility of radiography in acute bronchiolitis. J Pediatr. 2007;150:429–433. , , , et al.
- Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis. Acta Paediatr. 2011;100:e17–e23. , , , et al.
- A cost effectiveness analysis of omitting radiography in diagnosis of acute bronchiolitis. Pediatr Pulmonol. 2009;44:122–127. , , , et al.
- Decreasing unnecessary utilization in acute bronchiolitis care: results from the value in inpatient pediatrics network. J Hosp Med. 2013;8:25–30. , , , et al.
- Efficacy of bronchodilator therapy in bronchiolitis. A meta‐analysis. Arch Pediatr Adolesc Med. 1996;150:1166–1172. , , , .
- Efficacy of beta2‐agonists in bronchiolitis: a reappraisal and meta‐analysis. Pediatrics. 1997;100:233–239. , .
- Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2010;(12):CD001266. , .
- Epinephrine for bronchiolitis. Cochrane Database Syst Rev. 2011;(6):CD003123. , , , et al.
- Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360:2079–2089. , , , et al.
- A multicenter, randomized, double‐blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med. 2003;349:27–35. , , , et al.
- A randomized, controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis. J Pediatr. 2002;141:818–824. , , , .
- Oral prednisolone for preschool children with acute virus‐induced wheezing. N Engl J Med. 2009;360:329–338. , , , et al.
- Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2010;(10):CD004878. , , , et al.
- Systemic corticosteroids in infant bronchiolitis: a meta‐analysis. Pediatrics. 2000;105:E44. , , , , .
- Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics. 1993;92:513–518. , , , .
- Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial. Pediatrics. 1990;86:350–356. , , .
- Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet. 1987;1:879–882. , , , , .
- The clinical management of preterm infants with bronchiolitis. Hosp Pediatr. 2013;3:244–250. , , , , .
- Glucocorticoids and growth in asthmatic children. Pediatr Allergy Immunol. 1995;6:145–154. , .
- Adjunct corticosteroids in children hospitalized with community‐acquired pneumonia. Pediatrics. 2011;127:e255–e263. , , , , , .
- Pediatric gastroesophageal reflux disease and acid‐related conditions: trends in incidence of diagnosis and acid suppression therapy. J Med Econ. 2009;12:348–355. , , , , , .
- Healthcare costs of GERD and acid‐related conditions in pediatric patients, with comparison between histamine‐2 receptor antagonists and proton pump inhibitors. Curr Med Res Opin. 2009;25:2703–2709. , , , , , .
- Are we overprescribing antireflux medications for infants with regurgitation? Pediatrics. 2007;120:946–949. , , , .
- Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr. 2007;45:421–427. , , , , .
- Efficacy of proton‐pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925–935. , , , , , .
- Effectiveness and safety of proton pump inhibitors in infantile gastroesophageal reflux disease. Ann Pharmacother. 2010;44:572–576. .
- Are there risks associated with empric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease? Hosp Pediatr. 2013;3:16–23. .
- Bronchiolitis management preferences and the influence of pulse oximetry and respiratory rate on the decision to admit. Pediatrics. 2003;111:e45–e51. , , , .
- Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations. Arch Pediatr Adolesc Med. 2004;158:527–530. , , , .
- Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis. Pediatrics. 2008;121:470–475. , .
- Oxygen therapy for bronchiolitis. Pediatrics. 2007;120:686–687; author reply 687–688. .
- Bronchiolitis‐associated hospitalizations among US children, 1980–1996. JAMA. 1999;282:1440–1446. , , , , , .
- Bronchiolitis: recent evidence on diagnosis and management. Pediatrics. 2010;125:342–349. , .
- Bronchiolitis‐associated mortality and estimates of respiratory syncytial virus‐associated deaths among US children, 1979–1997. J Infect Dis. 2001;183:16–22. , , , , .
- Observational study of two oxygen saturation targets for discharge in bronchiolitis. Arch Dis Child. 2012;97:361–363. , .
- Longitudinal assessment of hemoglobin oxygen saturation in preterm and term infants in the first six months of life. J Pediatr. 2011;159:377–383.e1. , , , et al.
- The impact of severe asthma on schoolchildren. J Asthma. 1999;36:409–417. , .
- Multi‐center, randomized trial of pulse oximetry monitoring strategies for children hospitalized for bronchiolitis. Abstract presented at: ID Week 2012; October 2012; San Diego, CA. , .
- The appropriateness method has acceptable reliability and validity for assessing overuse and underuse of surgical procedures. J Clin Epidemiol. 2012;65:1133–1143. , , , .
- Agency for Healthcare Research and Quality. HCUPnet. Kids inpatient database 2009. Available at: http://hcupnet.ahrq.gov. Accessed November 6, 2012.
- Too little? Too much? Primary care physicians' views on US health care: a brief report. Arch Intern Med. 2011;171:1582–1585. , , .
- How to implement change in clinical practice. Paediatr Respir Rev. 2003;4:340–346. .
- Eliminating waste in US health care. JAMA. 2012;307:1513–1516. , .
- Safely doing less: a missing component of the patient safety dialogue. Pediatrics. 2011;128:e1596–e1597. , , .
- To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press; 2000. , , .
- Temporal trends in rates of patient harm resulting from medical care. N Engl J Med. 2010;363:2124–2134. , , , , , .
- Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120–134. .
- Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–1802. , .
- The quality of ambulatory care delivered to children in the United States. N Engl J Med. 2007;357:1515–1523. , , , et al.
- National Asthma Education and Prevention Program. Expert panel report 3 (EPR‐3): guidelines for the diagnosis and management of asthma—summary report 2007. J Allergy Clin Immunol. 2007;120:S94–S138.
- The chest x‐ray and childhood acute asthma. Aust Clin Rev. 1993;13:153–156. , .
- Clinical factors associated with focal infiltrates in wheezing infants and toddlers. Clin Pediatr (Phila). 2000;39:387–393. , , , .
- Chest radiographs in the pediatric emergency department for children < or = 18 months of age with wheezing. Clin Pediatr (Phila). 1999;38:395–399. , , , .
- Clinical predictors of pneumonia among children with wheezing. Pediatrics. 2009;124:e29–e36. , , , , , .
- Reduce the rads: a quality assurance project on reducing unnecessary chest X‐rays in children with asthma. J Paediatr Child Health. 2005;41:107–111. , .
- American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774–1793.
- Evaluation of the utility of radiography in acute bronchiolitis. J Pediatr. 2007;150:429–433. , , , et al.
- Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis. Acta Paediatr. 2011;100:e17–e23. , , , et al.
- A cost effectiveness analysis of omitting radiography in diagnosis of acute bronchiolitis. Pediatr Pulmonol. 2009;44:122–127. , , , et al.
- Decreasing unnecessary utilization in acute bronchiolitis care: results from the value in inpatient pediatrics network. J Hosp Med. 2013;8:25–30. , , , et al.
- Efficacy of bronchodilator therapy in bronchiolitis. A meta‐analysis. Arch Pediatr Adolesc Med. 1996;150:1166–1172. , , , .
- Efficacy of beta2‐agonists in bronchiolitis: a reappraisal and meta‐analysis. Pediatrics. 1997;100:233–239. , .
- Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2010;(12):CD001266. , .
- Epinephrine for bronchiolitis. Cochrane Database Syst Rev. 2011;(6):CD003123. , , , et al.
- Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360:2079–2089. , , , et al.
- A multicenter, randomized, double‐blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med. 2003;349:27–35. , , , et al.
- A randomized, controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis. J Pediatr. 2002;141:818–824. , , , .
- Oral prednisolone for preschool children with acute virus‐induced wheezing. N Engl J Med. 2009;360:329–338. , , , et al.
- Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2010;(10):CD004878. , , , et al.
- Systemic corticosteroids in infant bronchiolitis: a meta‐analysis. Pediatrics. 2000;105:E44. , , , , .
- Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics. 1993;92:513–518. , , , .
- Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial. Pediatrics. 1990;86:350–356. , , .
- Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet. 1987;1:879–882. , , , , .
- The clinical management of preterm infants with bronchiolitis. Hosp Pediatr. 2013;3:244–250. , , , , .
- Glucocorticoids and growth in asthmatic children. Pediatr Allergy Immunol. 1995;6:145–154. , .
- Adjunct corticosteroids in children hospitalized with community‐acquired pneumonia. Pediatrics. 2011;127:e255–e263. , , , , , .
- Pediatric gastroesophageal reflux disease and acid‐related conditions: trends in incidence of diagnosis and acid suppression therapy. J Med Econ. 2009;12:348–355. , , , , , .
- Healthcare costs of GERD and acid‐related conditions in pediatric patients, with comparison between histamine‐2 receptor antagonists and proton pump inhibitors. Curr Med Res Opin. 2009;25:2703–2709. , , , , , .
- Are we overprescribing antireflux medications for infants with regurgitation? Pediatrics. 2007;120:946–949. , , , .
- Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr. 2007;45:421–427. , , , , .
- Efficacy of proton‐pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925–935. , , , , , .
- Effectiveness and safety of proton pump inhibitors in infantile gastroesophageal reflux disease. Ann Pharmacother. 2010;44:572–576. .
- Are there risks associated with empric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease? Hosp Pediatr. 2013;3:16–23. .
- Bronchiolitis management preferences and the influence of pulse oximetry and respiratory rate on the decision to admit. Pediatrics. 2003;111:e45–e51. , , , .
- Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations. Arch Pediatr Adolesc Med. 2004;158:527–530. , , , .
- Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis. Pediatrics. 2008;121:470–475. , .
- Oxygen therapy for bronchiolitis. Pediatrics. 2007;120:686–687; author reply 687–688. .
- Bronchiolitis‐associated hospitalizations among US children, 1980–1996. JAMA. 1999;282:1440–1446. , , , , , .
- Bronchiolitis: recent evidence on diagnosis and management. Pediatrics. 2010;125:342–349. , .
- Bronchiolitis‐associated mortality and estimates of respiratory syncytial virus‐associated deaths among US children, 1979–1997. J Infect Dis. 2001;183:16–22. , , , , .
- Observational study of two oxygen saturation targets for discharge in bronchiolitis. Arch Dis Child. 2012;97:361–363. , .
- Longitudinal assessment of hemoglobin oxygen saturation in preterm and term infants in the first six months of life. J Pediatr. 2011;159:377–383.e1. , , , et al.
- The impact of severe asthma on schoolchildren. J Asthma. 1999;36:409–417. , .
- Multi‐center, randomized trial of pulse oximetry monitoring strategies for children hospitalized for bronchiolitis. Abstract presented at: ID Week 2012; October 2012; San Diego, CA. , .
- The appropriateness method has acceptable reliability and validity for assessing overuse and underuse of surgical procedures. J Clin Epidemiol. 2012;65:1133–1143. , , , .
- Agency for Healthcare Research and Quality. HCUPnet. Kids inpatient database 2009. Available at: http://hcupnet.ahrq.gov. Accessed November 6, 2012.
- Too little? Too much? Primary care physicians' views on US health care: a brief report. Arch Intern Med. 2011;171:1582–1585. , , .
- How to implement change in clinical practice. Paediatr Respir Rev. 2003;4:340–346. .
Copyright © 2013 Society of Hospital Medicine
Choosing Wisely in Hospital Medicine
The overuse of medical tests and treatments is a growing concern. A recent survey revealed that 2 in 5 primary care physicians perceive that patients in their own practice are receiving too much care.[1] Twenty‐eight percent of the physicians indicated they provide more care than they should. When queried about reasons for the aggressiveness of care, responses included fear of malpractice litigation, adherence to clinical performance measures that require following protocols, and inadequacy of time spent with patients. Overutilization of healthcare resources is a complex issue promulgated not only by the factors cited by the physicians but also a culture in the United States habituated to believe more care is better care.[2, 3, 4] In 2010, $2.6 trillion was spent on healthcare, an increase of $1.3 trillion between 2000 and 2010.5 As much as 30% of healthcare spending may be wasted.[6] Because physicians influence approximately 80% of healthcare expenditures, including ordering tests and treatments, it is imperative that physicians take a leadership role in reversing this trend.[7]
In response to this need, several physician‐led projects have emerged.[8, 9, 10] One such initiative is the American Board of Internal Medicine Foundation's (ABIM‐F's) Choosing Wisely campaign.[11] The ABIM‐F contacted a variety of specialty societies and asked each to identify the 5 top tests or treatments relevant to their specialty that may frequently be overused. Phase 1 of the Choosing Wisely campaign was launched in April 2012 with 9 specialty societies participating. The second phase was unveiled in February 2013 and comprised of 16 additional groups including the Society of Hospital Medicine (SHM). The SHM represents 35,000 hospitalists in the United States whose primary focus is the general medical care of hospitalized patients. This is especially important because almost one‐third of total US healthcare expenditures are on hospital care,[12] and hospitalists care for an increasing number of hospitalized patients.[13] In this article, we describe the used to derive the adult hospital medicine Choosing processes Wisely list, review the tests and treatments that the SHM's Choosing Wisely Subcommittee chose, and discuss potential next steps in implementation of the adult hospital medicine recommendations.
METHODOLOGY
Upon invitation to participate in the Choosing Wisely campaign, SHM's Hospital Quality and Patient Safety (HQPS) Committee formally convened the Choosing Wisely Subcommittee. The subcommittee identified and executed a methodology (see Supporting Figure 1 and Supporting Table 1 in the online version of this article) to create the list of 5 tests and treatments that the SHM submitted to the ABIM‐F. All subcommittee members participated fully in the voting and refinement process. The Choosing Wisely Subcommittee worked closely with the SHM's Pediatrics Choosing Wisely Subcommittee to develop both adult and pediatric lists.
Convening the Choosing Wisely Subcommittee
The HQPS Committee convened a subcommittee consisting of 9 members. The subcommittee represented a diverse group of hospitalists reflecting different institution types, geographic regions, and experience. All Choosing Wisely Subcommittee members signed conflict of interest statements and reported no conflict related to the conclusions, implications, or opinions stated. The subcommittee did not consult other external stakeholders in the development of recommendations.
Identification and Refinement of Potential Wasteful Practices
To generate an initial list of potential recommendations, members of all of the SHM committees were surveyed and asked to submit 5 tests and treatments that are inappropriately used or overused. SHM staff removed duplicates and categorized submissions by topic, highlighting overlapping recommendations. Tests and treatments that are used infrequently and items included in phase 1 society lists were also excluded. Subcommittee members then ranked the resultant list using a 5‐point Likert scale. All SHM members were then given the opportunity to rank their agreement with the tests and treatments on the list, as refined at the time based upon their own experience and consideration of the following criteria: tests and procedures within the control and purview of hospital medicine, the frequency with which the tests or procedures occur, and the significance of associated costs. This was accomplished via electronic survey.
Establishing an Evidence Base
SHM staff conducted a literature review of the list of tests and treatments that was further refined by the SHM membership's ranking using a standard template. Two reviewers (W.N. and J.G.) conducted an independent literature review of the remaining tests and treatments using PubMed, MEDLINE, and Cochrane Library. The reviewers also conducted generic Internet searches. The literature review included all literature published through 2012 as well as nonEnglish language publications. The reviewers included clinical research guidelines and primary and secondary research studies. Studies included in the review were based upon common criteria including whether the article discussed an evaluation of efficacy and/or utility of treatment, reviewed the harm associated with the administration of a test or treatment, and explored the cost associated with the test or treatment as well as the overall strength of evidence. Additionally, the reference lists included in articles were reviewed to identify supplementary literature sources. The reviewers read and analyzed the articles identified in the initial search for relevant subject matter and summarized the findings in a table.
Delphi Panels
A Delphi scoring process was utilized to complete list refinement.[14] Subcommittee members anonymously voted via email for the strength of the test and treatment recommendation based upon specific criteria. To assist with this process, they received a copy of the completed literature review and an evidence summary of the literature. The following categories were used to guide the scoring: validity/evidence base to support, feasibility of implementation, frequency of occurrence, cost of occurrence, yield/emmpact, harm, and potential to improve. Results were aggregated and shared with the Choosing Wisely Subcommittee. The subcommittee conferred a final time, editing the recommendations for clarification and improved wording. A second anonymous vote was then conducted for the remaining tests and treatments through a revised scoring spreadsheet. The penultimate list was presented to the SHM's Board. Upon the Board's approval, the final list was submitted to the ABIM‐F.
RESULTS
The results of each stage of the list development process are shown in the online supporting information (see Supporting Figure 1 and Supporting Table 1 in the online version of this article). The initial survey of SHM committee members garnered in excess of 150 tests and treatments from approximately 40 SHM committee members. The subsequent list refinement by SHM staff narrowed this list to 65 items, which were then further reduced to 15 items after ranking by members of the subcommittee (see Supporting Figure 1 and Supporting Table 1 in the online version of this article). Voting by members of the general SHM membership further reduced the list to 11 tests and treatments.
The final list of 5 tests and treatments submitted to the ABIM‐F were:
- Do not place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days for urologic procedures; use weights instead to monitor diuresis).
- Do not prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for gastrointestinal (GI) complications.
- Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms or active coronary disease, heart failure, or stroke.
- Do not order continuous telemetry monitoring outside of the intensive care unit (ICU) without using a protocol that governs continuation.
- Do not perform repetitive complete blood count (CBC) and chemistry testing in the face of clinical and lab stability (Table 1).
|
Test/Treatment Recommendations |
Do not place, or leave in place, urinary catheters for incontinence or convenience, or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days or urologic procedures; use weights instead to monitor diuresis).[21, 50] |
Do not prescribe GI prophylaxis to medical inpatients without clear‐cut indication or high risk for GI complication.[24] |
Avoid transfusing red blood cells just because hemoglobin levels are below arbitrary thresholds such as 10, 9, or even 8 mg/dL in the absence of symptoms.[29, 51] |
Avoid overuse/unnecessary use of telemetry monitoring in the hospital, particularly for patients at low risk for adverse cardiac outcomes.[35, 43, 52, 53] |
Do not perform repetitive CBC and chemistry testing in the face of clinical and lab stability.[44, 54, 55] |
RECOMMENDATIONS
Do not place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days for urologic procedures; use weights instead to monitor diuresis).
Despite guidelines identifying appropriate indications for the placement of urinary catheters, urinary tract infections due to catheter use remain the most frequent type of infection in acute care settings. Nearly 1 in every 5 patients in the hospital receives an indwelling catheter, and up to half are placed inappropriately.[15] Twenty‐six percent of patients who have indwelling catheters for 2 to 10 days will develop bacteriuria; subsequently, 24% of those patients will develop a catheter‐associated urinary tract infection (CAUTI).[15] More than 13,000 deaths due to CAUTI occur annually.[16] In addition to urinary tract infections and their complications, additional adverse outcomes related to indwelling catheters include formation of encrustations and restrictions to flow, prolonged hospital stay, and exposure to multidrug resistant organisms due to increased use of antibiotics. Evidence suggests that infections due to catheters are frequently preventable.[17, 18]
The economic burden associated with indwelling catheter complications is also substantial. Each episode of symptomatic urinary tract infection adds $676 in incremental costs, and catheter‐related bacteremia costs at least $2836.15 According to Scott, nearly 450,000 CAUTIs were estimated to have occurred in 2007, resulting in direct medical costs of between $340 to $370 million.[19]
Several organizations simultaneously released guidelines to provide a roadmap for appropriate catheter use and prevention of CAUTIs.[20, 21] Despite explicit guidelines, the Centers for Disease Control and Prevention recently reported that there was no improvement in CAUTIs between 2010 and 2011.[22] Implementing these strategies for CAUTI reduction include establishing a multidisciplinary team that applies a clear protocol, with daily reminders about catheters and stop orders for catheter discontinuation.
Do not prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for GI complications.
Stress ulcer prophylaxis in the hospital with proton pump inhibitors (PPIs) or histamine‐2 antagonists are common. As many as 71% of patients admitted to the hospital receive some form of prophylaxis without appropriate indication.[23] Guidelines exist for appropriate use; however, therapy is commonly used in the inpatient setting for indications not investigated or supported by the literature.[24]
Inappropriate prescribing practices have been associated with multiple adverse events, including drug interactions, hospital‐acquired infections, and increased costs of care. Although consensus among physicians regarding whether GI prophylaxis causes harm is lacking, studies demonstrate a strong correlation between use of PPIs and common adverse events such as pneumonia and Clostridium difficile infection.[25, 26] For instance, inpatients receiving PPIs were 3.6 times more likely to develop C. difficile‐associated diarrhea than inpatients not exposed to PPIs.[27]
The American Society of Health‐System Pharmacists Therapeutic Guidelines on Stress Ulcer Prophylaxis provide guidance regarding the optimal indication for administration of acid‐suppression medication for patients in the hospital setting. The clinical guidelines specify that stress ulcer prophylaxis is not recommended for adult patients in non‐ICU settings. The recommendations are applicable to general medical and surgical patients with fewer than 2 risk factors for clinically important bleeding. Indications for use of stress ulcer prophylaxis in the ICU include coagulopathy and mechanical ventilation.[24]
Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms or active coronary disease, heart failure, or stroke.
Anemia is a frequent comorbid condition in hospitalized patients. Correcting anemia by means of allogeneic blood transfusions with the goal of maximizing oxygen delivery is common practice in many hospitals. Varied threshold levels of hemoglobin and hematocrit are used, which is unsupported by evidence.[28, 29]
Acute anemia with normovolemic hemodilution has been proven safe in patients with coronary artery disease, heart valve disease, and the elderly. A restrictive transfusion approach with hemoglobin cutoff of 7 g/dL, as opposed to higher thresholds, has shown improved outcomes (lower mortality and lower rate of rebleeding) in adult and pediatric critical care as well as surgical patients.[30] Large studies in patients with acute myocardial infarction demonstrated that restrictive transfusional strategies are associated with decreased in‐hospital mortality, rate of reinfarction, and worsening heart failure, as well as 30‐day mortality.[31] A randomized trial in patients with active GI bleeding showed that a restrictive strategy of hemoglobin threshold of 7 g/dL was associated with improved outcomes (less mortality, less rate of rebleeding), compared with a strategy to transfuse patients with hemoglobin less than 9 g/dL.[32] In addition, increased awareness of the high cost of blood ($700$900 per unit) associated with the blood banking process as well as risk of potential infectious and noninfectious adverse reactions (eg, human immunodeficiency virus, hepatitis C virus, transfusion‐related lung injury, transfusion‐related circulatory overload) must be considered in the risk/benefit equation.[28]
Based on current available evidence, the American Association of Blood Banks recommends adhering to a restrictive transfusion strategy (7 g/dL) in hospitalized stable patients, and this threshold is raised to 8 g/dL in patients with preexisting cardiovascular disease or with active symptoms.[28] This should be combined with techniques such as preoperative anemia optimization by hematinics replacement (eg, iron, vitamin B12, folate, erythropoietin), intraoperative strategies (eg, antifibrinolytics, hypotension, normovolemic hemodilution, etc.), and postoperative strategies (eg, intraoperative cell salvage). These strategies have been shown to result in parsimonious red blood cell utilization as well as in substantial healthcare cost savings.[33]
Do not order continuous telemetry monitoring outside of the ICU without using a protocol that governs continuation.
Telemetry use in the hospital is common and clearly has a role for patients with certain cardiac conditions and those at risk for cardiac events. Telemetry is resource intensive, requiring dedicated multidisciplinary staff with specialized training. Many hospitals lack the ability to maintain and staff telemetry beds.[34] Physicians may overestimate the role of telemetry in guiding patient management.[35] One study concluded that only 12.6% of patients on a non‐ICU cardiac telemetry unit required telemetric monitoring, and only 7% received modified management as a result of telemetry findings.[36]
Inappropriate utilization of telemetry can be linked to increased length of stay or boarding in the emergency department, reduced hospital throughput, increased ambulance diversion, and increased operational costs.[37] In addition, the use of telemetry can lead to a false sense of security and alarm fatigue.[38] Telemetry artifacts may result in unnecessary testing and procedures for patients.[39] Furthermore, to accommodate the need for telemetry, frequent room changes may occur that may lead to decreased patient satisfaction. Low‐risk chest pain patients (hemodynamically stable with negative biomarkers, no electrocardiogram changes, and no indication for invasive procedure) do not require telemetry monitoring, because it rarely affects direct care of these patients.[36, 40] A 2009 study concluded that telemetry monitoring does not affect the care or the outcome of low‐risk patients.[41] Patients with other diagnoses, such as chronic obstructive pulmonary disease exacerbation or hemodynamically stable pulmonary embolism, and those requiring blood transfusions, are often placed in monitored beds without evidence that this will impact their care.[37]
The American Heart Association has published guidelines on the use of cardiac telemetry.[35] Patients are risk stratified into 3 categories, with class III patients being those who are low risk and do not require telemetry. Seventy percent of patients with the top 10 diagnoses that were admitted from the emergency department may clinically warrant telemetry.[37] Implementing a systematic evidence‐based approach to telemetry use can decrease unnecessary telemetry days,[42] reduce costs, and avoid unnecessary testing for rhythm artifacts.[39, 43]
Do not perform repetitive complete blood count (CBC) and chemistry testing in the face of clinical and lab stability.
Although unnecessary laboratory testing is widely perceived as ineffective and wasteful, no national guideline or consensus statement exists regarding the utility or timing of repetitive laboratory testing. Multiple studies showed no difference in readmission rates, transfers to ICUs, lengths of stay, rates of adverse events, or mortality when the frequency of laboratory testing was reduced. Charges for daily laboratory testing were estimated to be $150/patient/day.[44] In a study at a university‐associated teaching hospital, an intervention to reduce the frequency of laboratory testing was associated with a total decrease of nearly 98,000 tests over a 3‐year period.[45] The cost savings in this study was estimated to be almost $2 million over the same time period. A second study at a teaching hospital, involving a computerized physician order entry (CPOE)‐based intervention, showed a reduction of almost 72,000 tests over a 1‐year period, which reduced the total number of inpatient phlebotomies by approximately 21%.[46]
The cost of routine, daily laboratory testing for a given patient or health system is not insignificant. When healthcare providers are made aware of the cost of daily laboratory testing, this might reduce the number of laboratory tests ordered and result in significant savings for a health system, as well as improve the patient experience.[44]
Developing guidelines or strategies to reduce repetitive laboratory testing in the face of clinical or laboratory stability would likely produce significant cost savings for both the individual patient as well as the health system, and could possibly would likely improve the hospital experience for many patients. Widespread adoption of CPOE by the US healthcare system has the potential to facilitate decision support that can change laboratory ordering practices.
DISCUSSION
Eliminating waste in healthcare is a priority for physicians,[6, 7, 8, 9, 10] and the ABIM‐F's Choosing Wisely campaign is a key component of this effort.[11] The SHM chose 5 tests and treatments relevant to the specialty of hospital medicine that occur at a high frequency, have significant cost and affect to patients, and that can feasibly be impacted. Given that a high percentage of healthcare costs occur in the hospital[5] and hospitalists care for an increasing number of these patients,[13] successful implementation of the SHM's adult hospital medicine Choosing Wisely list has great potential to decrease waste in the hospital, reduce harm, and improve patient outcomes.
The methodology chosen to develop the adult Choosing Wisely recommendations was intended to be both pragmatic and evidence based. A broad range of opinions was solicited, including from the SHM's general membership. The final refinement included a literature review and a Delphi process.
Review of cost and utilization data to determine the scope of the problem was used for decision‐making by subcommittee members to formulate the SHM's recommendations. For some recommendations, there were significant data, whereas for others, this information was sparse. As has been noted, we were unable to identify the total number of patients in the United States who receive telemetry on an annual basis, and thus were unable to make an estimate about the total population that would be impacted by improved utilization. However, several studies do indicate inappropriate use in significant patient populations and widespread use of the resource. Similarly, we were able to identify the costs associated with a CBC, but were unable to calculate the total number of CBCs administered annually. In the absence of these data, subcommittee members utilized other criteria, including frequency of test or treatment, patient harm or benefit, and utility for making treatment/management decisions.
In general, the tests and treatments contained in the adult hospital medicine Choosing Wisely list are not requested by patients. As such, physicians' choices play a greater role, potentially magnifying the impact hospitalists could make. Overuse of medical tests is multifactorial, and culture plays a significant role in the United States.[2, 3, 4] Although each of the tests and treatments identified by the SHM is within the purview of hospitalists, ensuring that guidelines are reliably followed will require interdisciplinary process changes. Ample opportunity exists to partner with nurses (urinary catheters and telemetry), pharmacists (stress ulcer prophylaxis), blood banks, and laboratories (transfusions and lab testing), as well as other healthcare providers and physicians in multiple specialties.
Successful implementation of each guideline will require improvement of systems within hospitals to drive reliability.[47] Provider education, training programs, protocols and reminders may prove to be significant catalysts in overcoming misinformation or no information about specific guidelines. More importantly, interdisciplinary teams will need to assess the current practice patterns within their hospitals prior to implementing solutions that standardize and automate the ordering processes for these tests and treatments.[48] Additionally, the culture within individual patient care units will need to be modified.[49] The challenge of changing the behavior of multiple stakeholders and hardwiring systems changes represent significant potential barriers to success.
There are several potential concerns with the recommendations. Concepts such as high risk and clinical stability exist in several of the recommendations. In most cases, specific guidelines exist that explicitly define the appropriate use of the test or treatment. Where they do not, implementers will need to define the operational definitions, such as the number of normal CBCs that define stability. Although the recommendations are based on the best evidence available, consensus still plays a role. As has been noted, the risk of malpractice litigation influences physicians' decisions.[1] Although evidence‐based recommendations such as these help shape the standard of care and mitigate risk, they may not completely eliminate this concern. Providers should always weigh the risks and benefits of any test or treatment. Finally, the approach taken to establish the list was both pragmatic and evidence based. Published evidence was not reviewed until the list was honed to 11. When the evidence was reviewed, the strength of the evidence was judged in a subjective manner by members of the committee as part of the Delphi panel voting.
CONCLUSION
As healthcare providers enter an era of more cost conscious decision‐making about provision of care based upon necessity, hospitalists have an excellent opportunity to impact overutilization. The 5 recommendations comprising the adult hospital medicine Choosing Wisely list offer an explicit starting point. The SHM hopes to lead this process during the coming months and years and to offer additional recommendations, providing a foundation for hospitalists to decrease unnecessary tests and treatments and improve healthcare value.
Acknowledgments
The authors thank the additional members of the Choosing Wisely subcommittee of the SHM's Healthcare Quality and Patient Safety Committee: Krishna Das, MD; Shelley Taylor, MD; Kevin O'Leary, MD; and Nasim Afsarmanesh, MD. The authors also thank SHM staff who were involved in all facets of the recommendation development process, particularly Brendon Shank, who provided significant input into the survey and dissemination process.
Disclosure
Nothing to report.
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- Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm. 2007;64:1396–1400. , .
- ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;56:347–379. .
- Risk of community‐acquired pneumonia and use of gastric acid‐suppressive drugs. JAMA. 2004;292:1955–1960. , , , , , .
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- Gastric acid suppression by proton pump inhibitors as a risk factor for clostridium difficile‐associated diarrhea in hospitalized patients. Am J Gastroenterol. 2008;103:2308–2313. , , , .
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- Catheter‐associated urinary tract infection and the Medicare rule changes. Ann Intern Med. 2009;150:877–884. , , , , .
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The overuse of medical tests and treatments is a growing concern. A recent survey revealed that 2 in 5 primary care physicians perceive that patients in their own practice are receiving too much care.[1] Twenty‐eight percent of the physicians indicated they provide more care than they should. When queried about reasons for the aggressiveness of care, responses included fear of malpractice litigation, adherence to clinical performance measures that require following protocols, and inadequacy of time spent with patients. Overutilization of healthcare resources is a complex issue promulgated not only by the factors cited by the physicians but also a culture in the United States habituated to believe more care is better care.[2, 3, 4] In 2010, $2.6 trillion was spent on healthcare, an increase of $1.3 trillion between 2000 and 2010.5 As much as 30% of healthcare spending may be wasted.[6] Because physicians influence approximately 80% of healthcare expenditures, including ordering tests and treatments, it is imperative that physicians take a leadership role in reversing this trend.[7]
In response to this need, several physician‐led projects have emerged.[8, 9, 10] One such initiative is the American Board of Internal Medicine Foundation's (ABIM‐F's) Choosing Wisely campaign.[11] The ABIM‐F contacted a variety of specialty societies and asked each to identify the 5 top tests or treatments relevant to their specialty that may frequently be overused. Phase 1 of the Choosing Wisely campaign was launched in April 2012 with 9 specialty societies participating. The second phase was unveiled in February 2013 and comprised of 16 additional groups including the Society of Hospital Medicine (SHM). The SHM represents 35,000 hospitalists in the United States whose primary focus is the general medical care of hospitalized patients. This is especially important because almost one‐third of total US healthcare expenditures are on hospital care,[12] and hospitalists care for an increasing number of hospitalized patients.[13] In this article, we describe the used to derive the adult hospital medicine Choosing processes Wisely list, review the tests and treatments that the SHM's Choosing Wisely Subcommittee chose, and discuss potential next steps in implementation of the adult hospital medicine recommendations.
METHODOLOGY
Upon invitation to participate in the Choosing Wisely campaign, SHM's Hospital Quality and Patient Safety (HQPS) Committee formally convened the Choosing Wisely Subcommittee. The subcommittee identified and executed a methodology (see Supporting Figure 1 and Supporting Table 1 in the online version of this article) to create the list of 5 tests and treatments that the SHM submitted to the ABIM‐F. All subcommittee members participated fully in the voting and refinement process. The Choosing Wisely Subcommittee worked closely with the SHM's Pediatrics Choosing Wisely Subcommittee to develop both adult and pediatric lists.
Convening the Choosing Wisely Subcommittee
The HQPS Committee convened a subcommittee consisting of 9 members. The subcommittee represented a diverse group of hospitalists reflecting different institution types, geographic regions, and experience. All Choosing Wisely Subcommittee members signed conflict of interest statements and reported no conflict related to the conclusions, implications, or opinions stated. The subcommittee did not consult other external stakeholders in the development of recommendations.
Identification and Refinement of Potential Wasteful Practices
To generate an initial list of potential recommendations, members of all of the SHM committees were surveyed and asked to submit 5 tests and treatments that are inappropriately used or overused. SHM staff removed duplicates and categorized submissions by topic, highlighting overlapping recommendations. Tests and treatments that are used infrequently and items included in phase 1 society lists were also excluded. Subcommittee members then ranked the resultant list using a 5‐point Likert scale. All SHM members were then given the opportunity to rank their agreement with the tests and treatments on the list, as refined at the time based upon their own experience and consideration of the following criteria: tests and procedures within the control and purview of hospital medicine, the frequency with which the tests or procedures occur, and the significance of associated costs. This was accomplished via electronic survey.
Establishing an Evidence Base
SHM staff conducted a literature review of the list of tests and treatments that was further refined by the SHM membership's ranking using a standard template. Two reviewers (W.N. and J.G.) conducted an independent literature review of the remaining tests and treatments using PubMed, MEDLINE, and Cochrane Library. The reviewers also conducted generic Internet searches. The literature review included all literature published through 2012 as well as nonEnglish language publications. The reviewers included clinical research guidelines and primary and secondary research studies. Studies included in the review were based upon common criteria including whether the article discussed an evaluation of efficacy and/or utility of treatment, reviewed the harm associated with the administration of a test or treatment, and explored the cost associated with the test or treatment as well as the overall strength of evidence. Additionally, the reference lists included in articles were reviewed to identify supplementary literature sources. The reviewers read and analyzed the articles identified in the initial search for relevant subject matter and summarized the findings in a table.
Delphi Panels
A Delphi scoring process was utilized to complete list refinement.[14] Subcommittee members anonymously voted via email for the strength of the test and treatment recommendation based upon specific criteria. To assist with this process, they received a copy of the completed literature review and an evidence summary of the literature. The following categories were used to guide the scoring: validity/evidence base to support, feasibility of implementation, frequency of occurrence, cost of occurrence, yield/emmpact, harm, and potential to improve. Results were aggregated and shared with the Choosing Wisely Subcommittee. The subcommittee conferred a final time, editing the recommendations for clarification and improved wording. A second anonymous vote was then conducted for the remaining tests and treatments through a revised scoring spreadsheet. The penultimate list was presented to the SHM's Board. Upon the Board's approval, the final list was submitted to the ABIM‐F.
RESULTS
The results of each stage of the list development process are shown in the online supporting information (see Supporting Figure 1 and Supporting Table 1 in the online version of this article). The initial survey of SHM committee members garnered in excess of 150 tests and treatments from approximately 40 SHM committee members. The subsequent list refinement by SHM staff narrowed this list to 65 items, which were then further reduced to 15 items after ranking by members of the subcommittee (see Supporting Figure 1 and Supporting Table 1 in the online version of this article). Voting by members of the general SHM membership further reduced the list to 11 tests and treatments.
The final list of 5 tests and treatments submitted to the ABIM‐F were:
- Do not place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days for urologic procedures; use weights instead to monitor diuresis).
- Do not prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for gastrointestinal (GI) complications.
- Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms or active coronary disease, heart failure, or stroke.
- Do not order continuous telemetry monitoring outside of the intensive care unit (ICU) without using a protocol that governs continuation.
- Do not perform repetitive complete blood count (CBC) and chemistry testing in the face of clinical and lab stability (Table 1).
|
Test/Treatment Recommendations |
Do not place, or leave in place, urinary catheters for incontinence or convenience, or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days or urologic procedures; use weights instead to monitor diuresis).[21, 50] |
Do not prescribe GI prophylaxis to medical inpatients without clear‐cut indication or high risk for GI complication.[24] |
Avoid transfusing red blood cells just because hemoglobin levels are below arbitrary thresholds such as 10, 9, or even 8 mg/dL in the absence of symptoms.[29, 51] |
Avoid overuse/unnecessary use of telemetry monitoring in the hospital, particularly for patients at low risk for adverse cardiac outcomes.[35, 43, 52, 53] |
Do not perform repetitive CBC and chemistry testing in the face of clinical and lab stability.[44, 54, 55] |
RECOMMENDATIONS
Do not place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days for urologic procedures; use weights instead to monitor diuresis).
Despite guidelines identifying appropriate indications for the placement of urinary catheters, urinary tract infections due to catheter use remain the most frequent type of infection in acute care settings. Nearly 1 in every 5 patients in the hospital receives an indwelling catheter, and up to half are placed inappropriately.[15] Twenty‐six percent of patients who have indwelling catheters for 2 to 10 days will develop bacteriuria; subsequently, 24% of those patients will develop a catheter‐associated urinary tract infection (CAUTI).[15] More than 13,000 deaths due to CAUTI occur annually.[16] In addition to urinary tract infections and their complications, additional adverse outcomes related to indwelling catheters include formation of encrustations and restrictions to flow, prolonged hospital stay, and exposure to multidrug resistant organisms due to increased use of antibiotics. Evidence suggests that infections due to catheters are frequently preventable.[17, 18]
The economic burden associated with indwelling catheter complications is also substantial. Each episode of symptomatic urinary tract infection adds $676 in incremental costs, and catheter‐related bacteremia costs at least $2836.15 According to Scott, nearly 450,000 CAUTIs were estimated to have occurred in 2007, resulting in direct medical costs of between $340 to $370 million.[19]
Several organizations simultaneously released guidelines to provide a roadmap for appropriate catheter use and prevention of CAUTIs.[20, 21] Despite explicit guidelines, the Centers for Disease Control and Prevention recently reported that there was no improvement in CAUTIs between 2010 and 2011.[22] Implementing these strategies for CAUTI reduction include establishing a multidisciplinary team that applies a clear protocol, with daily reminders about catheters and stop orders for catheter discontinuation.
Do not prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for GI complications.
Stress ulcer prophylaxis in the hospital with proton pump inhibitors (PPIs) or histamine‐2 antagonists are common. As many as 71% of patients admitted to the hospital receive some form of prophylaxis without appropriate indication.[23] Guidelines exist for appropriate use; however, therapy is commonly used in the inpatient setting for indications not investigated or supported by the literature.[24]
Inappropriate prescribing practices have been associated with multiple adverse events, including drug interactions, hospital‐acquired infections, and increased costs of care. Although consensus among physicians regarding whether GI prophylaxis causes harm is lacking, studies demonstrate a strong correlation between use of PPIs and common adverse events such as pneumonia and Clostridium difficile infection.[25, 26] For instance, inpatients receiving PPIs were 3.6 times more likely to develop C. difficile‐associated diarrhea than inpatients not exposed to PPIs.[27]
The American Society of Health‐System Pharmacists Therapeutic Guidelines on Stress Ulcer Prophylaxis provide guidance regarding the optimal indication for administration of acid‐suppression medication for patients in the hospital setting. The clinical guidelines specify that stress ulcer prophylaxis is not recommended for adult patients in non‐ICU settings. The recommendations are applicable to general medical and surgical patients with fewer than 2 risk factors for clinically important bleeding. Indications for use of stress ulcer prophylaxis in the ICU include coagulopathy and mechanical ventilation.[24]
Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms or active coronary disease, heart failure, or stroke.
Anemia is a frequent comorbid condition in hospitalized patients. Correcting anemia by means of allogeneic blood transfusions with the goal of maximizing oxygen delivery is common practice in many hospitals. Varied threshold levels of hemoglobin and hematocrit are used, which is unsupported by evidence.[28, 29]
Acute anemia with normovolemic hemodilution has been proven safe in patients with coronary artery disease, heart valve disease, and the elderly. A restrictive transfusion approach with hemoglobin cutoff of 7 g/dL, as opposed to higher thresholds, has shown improved outcomes (lower mortality and lower rate of rebleeding) in adult and pediatric critical care as well as surgical patients.[30] Large studies in patients with acute myocardial infarction demonstrated that restrictive transfusional strategies are associated with decreased in‐hospital mortality, rate of reinfarction, and worsening heart failure, as well as 30‐day mortality.[31] A randomized trial in patients with active GI bleeding showed that a restrictive strategy of hemoglobin threshold of 7 g/dL was associated with improved outcomes (less mortality, less rate of rebleeding), compared with a strategy to transfuse patients with hemoglobin less than 9 g/dL.[32] In addition, increased awareness of the high cost of blood ($700$900 per unit) associated with the blood banking process as well as risk of potential infectious and noninfectious adverse reactions (eg, human immunodeficiency virus, hepatitis C virus, transfusion‐related lung injury, transfusion‐related circulatory overload) must be considered in the risk/benefit equation.[28]
Based on current available evidence, the American Association of Blood Banks recommends adhering to a restrictive transfusion strategy (7 g/dL) in hospitalized stable patients, and this threshold is raised to 8 g/dL in patients with preexisting cardiovascular disease or with active symptoms.[28] This should be combined with techniques such as preoperative anemia optimization by hematinics replacement (eg, iron, vitamin B12, folate, erythropoietin), intraoperative strategies (eg, antifibrinolytics, hypotension, normovolemic hemodilution, etc.), and postoperative strategies (eg, intraoperative cell salvage). These strategies have been shown to result in parsimonious red blood cell utilization as well as in substantial healthcare cost savings.[33]
Do not order continuous telemetry monitoring outside of the ICU without using a protocol that governs continuation.
Telemetry use in the hospital is common and clearly has a role for patients with certain cardiac conditions and those at risk for cardiac events. Telemetry is resource intensive, requiring dedicated multidisciplinary staff with specialized training. Many hospitals lack the ability to maintain and staff telemetry beds.[34] Physicians may overestimate the role of telemetry in guiding patient management.[35] One study concluded that only 12.6% of patients on a non‐ICU cardiac telemetry unit required telemetric monitoring, and only 7% received modified management as a result of telemetry findings.[36]
Inappropriate utilization of telemetry can be linked to increased length of stay or boarding in the emergency department, reduced hospital throughput, increased ambulance diversion, and increased operational costs.[37] In addition, the use of telemetry can lead to a false sense of security and alarm fatigue.[38] Telemetry artifacts may result in unnecessary testing and procedures for patients.[39] Furthermore, to accommodate the need for telemetry, frequent room changes may occur that may lead to decreased patient satisfaction. Low‐risk chest pain patients (hemodynamically stable with negative biomarkers, no electrocardiogram changes, and no indication for invasive procedure) do not require telemetry monitoring, because it rarely affects direct care of these patients.[36, 40] A 2009 study concluded that telemetry monitoring does not affect the care or the outcome of low‐risk patients.[41] Patients with other diagnoses, such as chronic obstructive pulmonary disease exacerbation or hemodynamically stable pulmonary embolism, and those requiring blood transfusions, are often placed in monitored beds without evidence that this will impact their care.[37]
The American Heart Association has published guidelines on the use of cardiac telemetry.[35] Patients are risk stratified into 3 categories, with class III patients being those who are low risk and do not require telemetry. Seventy percent of patients with the top 10 diagnoses that were admitted from the emergency department may clinically warrant telemetry.[37] Implementing a systematic evidence‐based approach to telemetry use can decrease unnecessary telemetry days,[42] reduce costs, and avoid unnecessary testing for rhythm artifacts.[39, 43]
Do not perform repetitive complete blood count (CBC) and chemistry testing in the face of clinical and lab stability.
Although unnecessary laboratory testing is widely perceived as ineffective and wasteful, no national guideline or consensus statement exists regarding the utility or timing of repetitive laboratory testing. Multiple studies showed no difference in readmission rates, transfers to ICUs, lengths of stay, rates of adverse events, or mortality when the frequency of laboratory testing was reduced. Charges for daily laboratory testing were estimated to be $150/patient/day.[44] In a study at a university‐associated teaching hospital, an intervention to reduce the frequency of laboratory testing was associated with a total decrease of nearly 98,000 tests over a 3‐year period.[45] The cost savings in this study was estimated to be almost $2 million over the same time period. A second study at a teaching hospital, involving a computerized physician order entry (CPOE)‐based intervention, showed a reduction of almost 72,000 tests over a 1‐year period, which reduced the total number of inpatient phlebotomies by approximately 21%.[46]
The cost of routine, daily laboratory testing for a given patient or health system is not insignificant. When healthcare providers are made aware of the cost of daily laboratory testing, this might reduce the number of laboratory tests ordered and result in significant savings for a health system, as well as improve the patient experience.[44]
Developing guidelines or strategies to reduce repetitive laboratory testing in the face of clinical or laboratory stability would likely produce significant cost savings for both the individual patient as well as the health system, and could possibly would likely improve the hospital experience for many patients. Widespread adoption of CPOE by the US healthcare system has the potential to facilitate decision support that can change laboratory ordering practices.
DISCUSSION
Eliminating waste in healthcare is a priority for physicians,[6, 7, 8, 9, 10] and the ABIM‐F's Choosing Wisely campaign is a key component of this effort.[11] The SHM chose 5 tests and treatments relevant to the specialty of hospital medicine that occur at a high frequency, have significant cost and affect to patients, and that can feasibly be impacted. Given that a high percentage of healthcare costs occur in the hospital[5] and hospitalists care for an increasing number of these patients,[13] successful implementation of the SHM's adult hospital medicine Choosing Wisely list has great potential to decrease waste in the hospital, reduce harm, and improve patient outcomes.
The methodology chosen to develop the adult Choosing Wisely recommendations was intended to be both pragmatic and evidence based. A broad range of opinions was solicited, including from the SHM's general membership. The final refinement included a literature review and a Delphi process.
Review of cost and utilization data to determine the scope of the problem was used for decision‐making by subcommittee members to formulate the SHM's recommendations. For some recommendations, there were significant data, whereas for others, this information was sparse. As has been noted, we were unable to identify the total number of patients in the United States who receive telemetry on an annual basis, and thus were unable to make an estimate about the total population that would be impacted by improved utilization. However, several studies do indicate inappropriate use in significant patient populations and widespread use of the resource. Similarly, we were able to identify the costs associated with a CBC, but were unable to calculate the total number of CBCs administered annually. In the absence of these data, subcommittee members utilized other criteria, including frequency of test or treatment, patient harm or benefit, and utility for making treatment/management decisions.
In general, the tests and treatments contained in the adult hospital medicine Choosing Wisely list are not requested by patients. As such, physicians' choices play a greater role, potentially magnifying the impact hospitalists could make. Overuse of medical tests is multifactorial, and culture plays a significant role in the United States.[2, 3, 4] Although each of the tests and treatments identified by the SHM is within the purview of hospitalists, ensuring that guidelines are reliably followed will require interdisciplinary process changes. Ample opportunity exists to partner with nurses (urinary catheters and telemetry), pharmacists (stress ulcer prophylaxis), blood banks, and laboratories (transfusions and lab testing), as well as other healthcare providers and physicians in multiple specialties.
Successful implementation of each guideline will require improvement of systems within hospitals to drive reliability.[47] Provider education, training programs, protocols and reminders may prove to be significant catalysts in overcoming misinformation or no information about specific guidelines. More importantly, interdisciplinary teams will need to assess the current practice patterns within their hospitals prior to implementing solutions that standardize and automate the ordering processes for these tests and treatments.[48] Additionally, the culture within individual patient care units will need to be modified.[49] The challenge of changing the behavior of multiple stakeholders and hardwiring systems changes represent significant potential barriers to success.
There are several potential concerns with the recommendations. Concepts such as high risk and clinical stability exist in several of the recommendations. In most cases, specific guidelines exist that explicitly define the appropriate use of the test or treatment. Where they do not, implementers will need to define the operational definitions, such as the number of normal CBCs that define stability. Although the recommendations are based on the best evidence available, consensus still plays a role. As has been noted, the risk of malpractice litigation influences physicians' decisions.[1] Although evidence‐based recommendations such as these help shape the standard of care and mitigate risk, they may not completely eliminate this concern. Providers should always weigh the risks and benefits of any test or treatment. Finally, the approach taken to establish the list was both pragmatic and evidence based. Published evidence was not reviewed until the list was honed to 11. When the evidence was reviewed, the strength of the evidence was judged in a subjective manner by members of the committee as part of the Delphi panel voting.
CONCLUSION
As healthcare providers enter an era of more cost conscious decision‐making about provision of care based upon necessity, hospitalists have an excellent opportunity to impact overutilization. The 5 recommendations comprising the adult hospital medicine Choosing Wisely list offer an explicit starting point. The SHM hopes to lead this process during the coming months and years and to offer additional recommendations, providing a foundation for hospitalists to decrease unnecessary tests and treatments and improve healthcare value.
Acknowledgments
The authors thank the additional members of the Choosing Wisely subcommittee of the SHM's Healthcare Quality and Patient Safety Committee: Krishna Das, MD; Shelley Taylor, MD; Kevin O'Leary, MD; and Nasim Afsarmanesh, MD. The authors also thank SHM staff who were involved in all facets of the recommendation development process, particularly Brendon Shank, who provided significant input into the survey and dissemination process.
Disclosure
Nothing to report.
The overuse of medical tests and treatments is a growing concern. A recent survey revealed that 2 in 5 primary care physicians perceive that patients in their own practice are receiving too much care.[1] Twenty‐eight percent of the physicians indicated they provide more care than they should. When queried about reasons for the aggressiveness of care, responses included fear of malpractice litigation, adherence to clinical performance measures that require following protocols, and inadequacy of time spent with patients. Overutilization of healthcare resources is a complex issue promulgated not only by the factors cited by the physicians but also a culture in the United States habituated to believe more care is better care.[2, 3, 4] In 2010, $2.6 trillion was spent on healthcare, an increase of $1.3 trillion between 2000 and 2010.5 As much as 30% of healthcare spending may be wasted.[6] Because physicians influence approximately 80% of healthcare expenditures, including ordering tests and treatments, it is imperative that physicians take a leadership role in reversing this trend.[7]
In response to this need, several physician‐led projects have emerged.[8, 9, 10] One such initiative is the American Board of Internal Medicine Foundation's (ABIM‐F's) Choosing Wisely campaign.[11] The ABIM‐F contacted a variety of specialty societies and asked each to identify the 5 top tests or treatments relevant to their specialty that may frequently be overused. Phase 1 of the Choosing Wisely campaign was launched in April 2012 with 9 specialty societies participating. The second phase was unveiled in February 2013 and comprised of 16 additional groups including the Society of Hospital Medicine (SHM). The SHM represents 35,000 hospitalists in the United States whose primary focus is the general medical care of hospitalized patients. This is especially important because almost one‐third of total US healthcare expenditures are on hospital care,[12] and hospitalists care for an increasing number of hospitalized patients.[13] In this article, we describe the used to derive the adult hospital medicine Choosing processes Wisely list, review the tests and treatments that the SHM's Choosing Wisely Subcommittee chose, and discuss potential next steps in implementation of the adult hospital medicine recommendations.
METHODOLOGY
Upon invitation to participate in the Choosing Wisely campaign, SHM's Hospital Quality and Patient Safety (HQPS) Committee formally convened the Choosing Wisely Subcommittee. The subcommittee identified and executed a methodology (see Supporting Figure 1 and Supporting Table 1 in the online version of this article) to create the list of 5 tests and treatments that the SHM submitted to the ABIM‐F. All subcommittee members participated fully in the voting and refinement process. The Choosing Wisely Subcommittee worked closely with the SHM's Pediatrics Choosing Wisely Subcommittee to develop both adult and pediatric lists.
Convening the Choosing Wisely Subcommittee
The HQPS Committee convened a subcommittee consisting of 9 members. The subcommittee represented a diverse group of hospitalists reflecting different institution types, geographic regions, and experience. All Choosing Wisely Subcommittee members signed conflict of interest statements and reported no conflict related to the conclusions, implications, or opinions stated. The subcommittee did not consult other external stakeholders in the development of recommendations.
Identification and Refinement of Potential Wasteful Practices
To generate an initial list of potential recommendations, members of all of the SHM committees were surveyed and asked to submit 5 tests and treatments that are inappropriately used or overused. SHM staff removed duplicates and categorized submissions by topic, highlighting overlapping recommendations. Tests and treatments that are used infrequently and items included in phase 1 society lists were also excluded. Subcommittee members then ranked the resultant list using a 5‐point Likert scale. All SHM members were then given the opportunity to rank their agreement with the tests and treatments on the list, as refined at the time based upon their own experience and consideration of the following criteria: tests and procedures within the control and purview of hospital medicine, the frequency with which the tests or procedures occur, and the significance of associated costs. This was accomplished via electronic survey.
Establishing an Evidence Base
SHM staff conducted a literature review of the list of tests and treatments that was further refined by the SHM membership's ranking using a standard template. Two reviewers (W.N. and J.G.) conducted an independent literature review of the remaining tests and treatments using PubMed, MEDLINE, and Cochrane Library. The reviewers also conducted generic Internet searches. The literature review included all literature published through 2012 as well as nonEnglish language publications. The reviewers included clinical research guidelines and primary and secondary research studies. Studies included in the review were based upon common criteria including whether the article discussed an evaluation of efficacy and/or utility of treatment, reviewed the harm associated with the administration of a test or treatment, and explored the cost associated with the test or treatment as well as the overall strength of evidence. Additionally, the reference lists included in articles were reviewed to identify supplementary literature sources. The reviewers read and analyzed the articles identified in the initial search for relevant subject matter and summarized the findings in a table.
Delphi Panels
A Delphi scoring process was utilized to complete list refinement.[14] Subcommittee members anonymously voted via email for the strength of the test and treatment recommendation based upon specific criteria. To assist with this process, they received a copy of the completed literature review and an evidence summary of the literature. The following categories were used to guide the scoring: validity/evidence base to support, feasibility of implementation, frequency of occurrence, cost of occurrence, yield/emmpact, harm, and potential to improve. Results were aggregated and shared with the Choosing Wisely Subcommittee. The subcommittee conferred a final time, editing the recommendations for clarification and improved wording. A second anonymous vote was then conducted for the remaining tests and treatments through a revised scoring spreadsheet. The penultimate list was presented to the SHM's Board. Upon the Board's approval, the final list was submitted to the ABIM‐F.
RESULTS
The results of each stage of the list development process are shown in the online supporting information (see Supporting Figure 1 and Supporting Table 1 in the online version of this article). The initial survey of SHM committee members garnered in excess of 150 tests and treatments from approximately 40 SHM committee members. The subsequent list refinement by SHM staff narrowed this list to 65 items, which were then further reduced to 15 items after ranking by members of the subcommittee (see Supporting Figure 1 and Supporting Table 1 in the online version of this article). Voting by members of the general SHM membership further reduced the list to 11 tests and treatments.
The final list of 5 tests and treatments submitted to the ABIM‐F were:
- Do not place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days for urologic procedures; use weights instead to monitor diuresis).
- Do not prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for gastrointestinal (GI) complications.
- Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms or active coronary disease, heart failure, or stroke.
- Do not order continuous telemetry monitoring outside of the intensive care unit (ICU) without using a protocol that governs continuation.
- Do not perform repetitive complete blood count (CBC) and chemistry testing in the face of clinical and lab stability (Table 1).
|
Test/Treatment Recommendations |
Do not place, or leave in place, urinary catheters for incontinence or convenience, or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days or urologic procedures; use weights instead to monitor diuresis).[21, 50] |
Do not prescribe GI prophylaxis to medical inpatients without clear‐cut indication or high risk for GI complication.[24] |
Avoid transfusing red blood cells just because hemoglobin levels are below arbitrary thresholds such as 10, 9, or even 8 mg/dL in the absence of symptoms.[29, 51] |
Avoid overuse/unnecessary use of telemetry monitoring in the hospital, particularly for patients at low risk for adverse cardiac outcomes.[35, 43, 52, 53] |
Do not perform repetitive CBC and chemistry testing in the face of clinical and lab stability.[44, 54, 55] |
RECOMMENDATIONS
Do not place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for noncritically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days for urologic procedures; use weights instead to monitor diuresis).
Despite guidelines identifying appropriate indications for the placement of urinary catheters, urinary tract infections due to catheter use remain the most frequent type of infection in acute care settings. Nearly 1 in every 5 patients in the hospital receives an indwelling catheter, and up to half are placed inappropriately.[15] Twenty‐six percent of patients who have indwelling catheters for 2 to 10 days will develop bacteriuria; subsequently, 24% of those patients will develop a catheter‐associated urinary tract infection (CAUTI).[15] More than 13,000 deaths due to CAUTI occur annually.[16] In addition to urinary tract infections and their complications, additional adverse outcomes related to indwelling catheters include formation of encrustations and restrictions to flow, prolonged hospital stay, and exposure to multidrug resistant organisms due to increased use of antibiotics. Evidence suggests that infections due to catheters are frequently preventable.[17, 18]
The economic burden associated with indwelling catheter complications is also substantial. Each episode of symptomatic urinary tract infection adds $676 in incremental costs, and catheter‐related bacteremia costs at least $2836.15 According to Scott, nearly 450,000 CAUTIs were estimated to have occurred in 2007, resulting in direct medical costs of between $340 to $370 million.[19]
Several organizations simultaneously released guidelines to provide a roadmap for appropriate catheter use and prevention of CAUTIs.[20, 21] Despite explicit guidelines, the Centers for Disease Control and Prevention recently reported that there was no improvement in CAUTIs between 2010 and 2011.[22] Implementing these strategies for CAUTI reduction include establishing a multidisciplinary team that applies a clear protocol, with daily reminders about catheters and stop orders for catheter discontinuation.
Do not prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for GI complications.
Stress ulcer prophylaxis in the hospital with proton pump inhibitors (PPIs) or histamine‐2 antagonists are common. As many as 71% of patients admitted to the hospital receive some form of prophylaxis without appropriate indication.[23] Guidelines exist for appropriate use; however, therapy is commonly used in the inpatient setting for indications not investigated or supported by the literature.[24]
Inappropriate prescribing practices have been associated with multiple adverse events, including drug interactions, hospital‐acquired infections, and increased costs of care. Although consensus among physicians regarding whether GI prophylaxis causes harm is lacking, studies demonstrate a strong correlation between use of PPIs and common adverse events such as pneumonia and Clostridium difficile infection.[25, 26] For instance, inpatients receiving PPIs were 3.6 times more likely to develop C. difficile‐associated diarrhea than inpatients not exposed to PPIs.[27]
The American Society of Health‐System Pharmacists Therapeutic Guidelines on Stress Ulcer Prophylaxis provide guidance regarding the optimal indication for administration of acid‐suppression medication for patients in the hospital setting. The clinical guidelines specify that stress ulcer prophylaxis is not recommended for adult patients in non‐ICU settings. The recommendations are applicable to general medical and surgical patients with fewer than 2 risk factors for clinically important bleeding. Indications for use of stress ulcer prophylaxis in the ICU include coagulopathy and mechanical ventilation.[24]
Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms or active coronary disease, heart failure, or stroke.
Anemia is a frequent comorbid condition in hospitalized patients. Correcting anemia by means of allogeneic blood transfusions with the goal of maximizing oxygen delivery is common practice in many hospitals. Varied threshold levels of hemoglobin and hematocrit are used, which is unsupported by evidence.[28, 29]
Acute anemia with normovolemic hemodilution has been proven safe in patients with coronary artery disease, heart valve disease, and the elderly. A restrictive transfusion approach with hemoglobin cutoff of 7 g/dL, as opposed to higher thresholds, has shown improved outcomes (lower mortality and lower rate of rebleeding) in adult and pediatric critical care as well as surgical patients.[30] Large studies in patients with acute myocardial infarction demonstrated that restrictive transfusional strategies are associated with decreased in‐hospital mortality, rate of reinfarction, and worsening heart failure, as well as 30‐day mortality.[31] A randomized trial in patients with active GI bleeding showed that a restrictive strategy of hemoglobin threshold of 7 g/dL was associated with improved outcomes (less mortality, less rate of rebleeding), compared with a strategy to transfuse patients with hemoglobin less than 9 g/dL.[32] In addition, increased awareness of the high cost of blood ($700$900 per unit) associated with the blood banking process as well as risk of potential infectious and noninfectious adverse reactions (eg, human immunodeficiency virus, hepatitis C virus, transfusion‐related lung injury, transfusion‐related circulatory overload) must be considered in the risk/benefit equation.[28]
Based on current available evidence, the American Association of Blood Banks recommends adhering to a restrictive transfusion strategy (7 g/dL) in hospitalized stable patients, and this threshold is raised to 8 g/dL in patients with preexisting cardiovascular disease or with active symptoms.[28] This should be combined with techniques such as preoperative anemia optimization by hematinics replacement (eg, iron, vitamin B12, folate, erythropoietin), intraoperative strategies (eg, antifibrinolytics, hypotension, normovolemic hemodilution, etc.), and postoperative strategies (eg, intraoperative cell salvage). These strategies have been shown to result in parsimonious red blood cell utilization as well as in substantial healthcare cost savings.[33]
Do not order continuous telemetry monitoring outside of the ICU without using a protocol that governs continuation.
Telemetry use in the hospital is common and clearly has a role for patients with certain cardiac conditions and those at risk for cardiac events. Telemetry is resource intensive, requiring dedicated multidisciplinary staff with specialized training. Many hospitals lack the ability to maintain and staff telemetry beds.[34] Physicians may overestimate the role of telemetry in guiding patient management.[35] One study concluded that only 12.6% of patients on a non‐ICU cardiac telemetry unit required telemetric monitoring, and only 7% received modified management as a result of telemetry findings.[36]
Inappropriate utilization of telemetry can be linked to increased length of stay or boarding in the emergency department, reduced hospital throughput, increased ambulance diversion, and increased operational costs.[37] In addition, the use of telemetry can lead to a false sense of security and alarm fatigue.[38] Telemetry artifacts may result in unnecessary testing and procedures for patients.[39] Furthermore, to accommodate the need for telemetry, frequent room changes may occur that may lead to decreased patient satisfaction. Low‐risk chest pain patients (hemodynamically stable with negative biomarkers, no electrocardiogram changes, and no indication for invasive procedure) do not require telemetry monitoring, because it rarely affects direct care of these patients.[36, 40] A 2009 study concluded that telemetry monitoring does not affect the care or the outcome of low‐risk patients.[41] Patients with other diagnoses, such as chronic obstructive pulmonary disease exacerbation or hemodynamically stable pulmonary embolism, and those requiring blood transfusions, are often placed in monitored beds without evidence that this will impact their care.[37]
The American Heart Association has published guidelines on the use of cardiac telemetry.[35] Patients are risk stratified into 3 categories, with class III patients being those who are low risk and do not require telemetry. Seventy percent of patients with the top 10 diagnoses that were admitted from the emergency department may clinically warrant telemetry.[37] Implementing a systematic evidence‐based approach to telemetry use can decrease unnecessary telemetry days,[42] reduce costs, and avoid unnecessary testing for rhythm artifacts.[39, 43]
Do not perform repetitive complete blood count (CBC) and chemistry testing in the face of clinical and lab stability.
Although unnecessary laboratory testing is widely perceived as ineffective and wasteful, no national guideline or consensus statement exists regarding the utility or timing of repetitive laboratory testing. Multiple studies showed no difference in readmission rates, transfers to ICUs, lengths of stay, rates of adverse events, or mortality when the frequency of laboratory testing was reduced. Charges for daily laboratory testing were estimated to be $150/patient/day.[44] In a study at a university‐associated teaching hospital, an intervention to reduce the frequency of laboratory testing was associated with a total decrease of nearly 98,000 tests over a 3‐year period.[45] The cost savings in this study was estimated to be almost $2 million over the same time period. A second study at a teaching hospital, involving a computerized physician order entry (CPOE)‐based intervention, showed a reduction of almost 72,000 tests over a 1‐year period, which reduced the total number of inpatient phlebotomies by approximately 21%.[46]
The cost of routine, daily laboratory testing for a given patient or health system is not insignificant. When healthcare providers are made aware of the cost of daily laboratory testing, this might reduce the number of laboratory tests ordered and result in significant savings for a health system, as well as improve the patient experience.[44]
Developing guidelines or strategies to reduce repetitive laboratory testing in the face of clinical or laboratory stability would likely produce significant cost savings for both the individual patient as well as the health system, and could possibly would likely improve the hospital experience for many patients. Widespread adoption of CPOE by the US healthcare system has the potential to facilitate decision support that can change laboratory ordering practices.
DISCUSSION
Eliminating waste in healthcare is a priority for physicians,[6, 7, 8, 9, 10] and the ABIM‐F's Choosing Wisely campaign is a key component of this effort.[11] The SHM chose 5 tests and treatments relevant to the specialty of hospital medicine that occur at a high frequency, have significant cost and affect to patients, and that can feasibly be impacted. Given that a high percentage of healthcare costs occur in the hospital[5] and hospitalists care for an increasing number of these patients,[13] successful implementation of the SHM's adult hospital medicine Choosing Wisely list has great potential to decrease waste in the hospital, reduce harm, and improve patient outcomes.
The methodology chosen to develop the adult Choosing Wisely recommendations was intended to be both pragmatic and evidence based. A broad range of opinions was solicited, including from the SHM's general membership. The final refinement included a literature review and a Delphi process.
Review of cost and utilization data to determine the scope of the problem was used for decision‐making by subcommittee members to formulate the SHM's recommendations. For some recommendations, there were significant data, whereas for others, this information was sparse. As has been noted, we were unable to identify the total number of patients in the United States who receive telemetry on an annual basis, and thus were unable to make an estimate about the total population that would be impacted by improved utilization. However, several studies do indicate inappropriate use in significant patient populations and widespread use of the resource. Similarly, we were able to identify the costs associated with a CBC, but were unable to calculate the total number of CBCs administered annually. In the absence of these data, subcommittee members utilized other criteria, including frequency of test or treatment, patient harm or benefit, and utility for making treatment/management decisions.
In general, the tests and treatments contained in the adult hospital medicine Choosing Wisely list are not requested by patients. As such, physicians' choices play a greater role, potentially magnifying the impact hospitalists could make. Overuse of medical tests is multifactorial, and culture plays a significant role in the United States.[2, 3, 4] Although each of the tests and treatments identified by the SHM is within the purview of hospitalists, ensuring that guidelines are reliably followed will require interdisciplinary process changes. Ample opportunity exists to partner with nurses (urinary catheters and telemetry), pharmacists (stress ulcer prophylaxis), blood banks, and laboratories (transfusions and lab testing), as well as other healthcare providers and physicians in multiple specialties.
Successful implementation of each guideline will require improvement of systems within hospitals to drive reliability.[47] Provider education, training programs, protocols and reminders may prove to be significant catalysts in overcoming misinformation or no information about specific guidelines. More importantly, interdisciplinary teams will need to assess the current practice patterns within their hospitals prior to implementing solutions that standardize and automate the ordering processes for these tests and treatments.[48] Additionally, the culture within individual patient care units will need to be modified.[49] The challenge of changing the behavior of multiple stakeholders and hardwiring systems changes represent significant potential barriers to success.
There are several potential concerns with the recommendations. Concepts such as high risk and clinical stability exist in several of the recommendations. In most cases, specific guidelines exist that explicitly define the appropriate use of the test or treatment. Where they do not, implementers will need to define the operational definitions, such as the number of normal CBCs that define stability. Although the recommendations are based on the best evidence available, consensus still plays a role. As has been noted, the risk of malpractice litigation influences physicians' decisions.[1] Although evidence‐based recommendations such as these help shape the standard of care and mitigate risk, they may not completely eliminate this concern. Providers should always weigh the risks and benefits of any test or treatment. Finally, the approach taken to establish the list was both pragmatic and evidence based. Published evidence was not reviewed until the list was honed to 11. When the evidence was reviewed, the strength of the evidence was judged in a subjective manner by members of the committee as part of the Delphi panel voting.
CONCLUSION
As healthcare providers enter an era of more cost conscious decision‐making about provision of care based upon necessity, hospitalists have an excellent opportunity to impact overutilization. The 5 recommendations comprising the adult hospital medicine Choosing Wisely list offer an explicit starting point. The SHM hopes to lead this process during the coming months and years and to offer additional recommendations, providing a foundation for hospitalists to decrease unnecessary tests and treatments and improve healthcare value.
Acknowledgments
The authors thank the additional members of the Choosing Wisely subcommittee of the SHM's Healthcare Quality and Patient Safety Committee: Krishna Das, MD; Shelley Taylor, MD; Kevin O'Leary, MD; and Nasim Afsarmanesh, MD. The authors also thank SHM staff who were involved in all facets of the recommendation development process, particularly Brendon Shank, who provided significant input into the survey and dissemination process.
Disclosure
Nothing to report.
- Too little? Too much? Primary care physicians' views on US health care: a brief report. Arch Intern Med. 2011;171:1582–1585. , , .
- Evidence that consumers are skeptical about evidence‐based health care. Health Aff (Millwood). 2010;29:1400–1406. , , , et al.
- Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–1802. , .
- Too much treatment? Aggressive medical care can lead to more pain, with no gain. Consum Rep. 2008;73:40–44.
- Centers for Medicare and Medicaid Services. Historical national health expenditure data. Available at: http://www.cms.gov/Research‐Statistics‐Data‐and‐Systems/Statistics‐Trends‐and‐Reports/NationalHealthExpendData/NationalHealthAccountsHistorical.html. Accessed February 12, 2013.
- Eliminating waste in US health care. JAMA. 2012;307:1513–1516. , .
- Change the microenvironment: delivery system reform essential to controlling costs. Available at: http://www.commonwealthfund.org/Publications/Commentaries/2009/Apr/Change‐the‐Microenvironment.aspx. Accessed February 12, 2013. .
- Costs of care. Available at: http://www.costsofcare.org. Accessed February 12, 2013.
- Less is more: how less health care can result in better health. Arch Intern Med. 2010;170:749–750. , .
- Clinical Guidelines Committee of the American College of Physicians. High‐value, cost‐conscious health care: concepts for clinicians to evaluate the benefits, harms, and costs of medical interventions. Ann Intern Med. 2011;154:174–180. , , , ;
- ABIM Foundation. U.S. physician groups identify commonly used tests or procedures they say are often not necessary. Available at: http://www.abimfoundation.org/News/ABIM‐Foundation‐News/2012/Choosing‐Wisely.aspx. Accessed February 12, 2013.
- Addressing requests by patients for nonbeneficial interventions. JAMA. 2012;307:149–150. , .
- Growth in the care of older patients by hospitalists in the United States. N Engl J Med. 2009;360:1102–1112. , , , .
- The appropriateness method has acceptable reliability and validity for assessing overuse and underuse of surgical procedures. J Clin Epidemiol. 2012;65:1133–1143. , , , .
- Clinical and economic consequences of nosocomial catheter‐related bacteriuria. Am J Infect Control. 2000;28:68–75. .
- Estimating health care‐associated infections and deaths in U.S. hospitals, 2002. Public Health Rep. 2007;122:160–166. , , , et al.
- A compendium of strategies to prevent healthcare‐associated infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29(suppl 1): S12–S21. , , , et al.
- Strategies to prevent catheter‐associated urinary tract infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29(suppl 1):S41–S50. , , , et al.
- The direct medical costs of healthcare‐associated infections in U.S. hospitals and the benefits of prevention. Available at: http://www.cdc.gov/hai/pdfs/hai/scott_costpaper.pdf. Accessed February 12, 2013. .
- Healthcare Infection Control Practices Advisory Committee, guideline for prevention of catheter‐associated urinary tract infections 2009. Infect Control Hosp Epidemiol. 2010;31:319–326. , , , , .
- Diagnosis, prevention, and treatment of catheter‐associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625–663. , , , et al.
- 2011 National and State Healthcare‐Associated Infection Standardized Infection Ratio Report. Available at: http://www.cdc.gov/hai/pdfs/SIR/SIR‐Report_02_07_2013.pdf. Accessed February 13, 2013. , , , et al.
- Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm. 2007;64:1396–1400. , .
- ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;56:347–379. .
- Risk of community‐acquired pneumonia and use of gastric acid‐suppressive drugs. JAMA. 2004;292:1955–1960. , , , , , .
- Acid‐suppressive medication use and the risk for hospital‐acquired pneumonia. JAMA. 2009;301:2120–2128. , , , .
- Gastric acid suppression by proton pump inhibitors as a risk factor for clostridium difficile‐associated diarrhea in hospitalized patients. Am J Gastroenterol. 2008;103:2308–2313. , , , .
- Red blood cell transfusion: a clinical practice guideline from the AABB*. Ann Intern Med. 2012;157:49–58. , , , et al.
- Guidelines for the clinical use of red cell transfusions. Br J Haematol. 2001;113:24–31. , , , et al.
- Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion. 2002;42:812–818. , , , .
- Association of blood transfusion with increased mortality in myocardial infarction: a meta‐analysis and diversity‐adjusted study sequential analysis. JAMA Intern Med 2013;173:132–139. , , , , .
- Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11–21. , , , et al.
- Economic impact of inappropriate blood transfusions in coronary artery bypass graft surgery. Am J Med. 1993;94:509–514. , , , .
- The use and effectiveness of electrocardiographic telemetry monitoring in a community hospital general care setting. Anesth Analg. 2003;97:1483–1487. , , , , , .
- ACC/AHA guidelines for ambulatory electrocardiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography). Circulation. 1999;100:886–893. , , , et al.
- Role of telemetry monitoring in the non‐intensive care unit. Am J Cardiol. 1995;76:960–965. , , , et al.
- When do patients need admission to a telemetry bed? J Emerg Med. 2007;33:53–60. , .
- Electrocardiographic monitoring in the hospitalized patient: a diagnostic intervention of uncertain clinical impact. Am J Emerg Med. 2008;26:1047–1055. , .
- Clinical consequences of electrocardiographic artifact mimicking ventricular tachycardia. N Engl J Med. 1999;341:1270–1274. , , , , .
- Inpatient telemetry does not need to be used in the management of older patients hospitalized with chest pain at low risk for in‐hospital coronary events and mortality. J Gerontol A Biol Sci Med Sci. 2005;60:605–606. , , , .
- Telemetry monitoring guidelines for efficient and safe delivery of cardiac rhythm monitoring to noncritical hospital inpatients. Crit Pathw Cardiol. 2009;8:125–126. , , , , .
- Agency for Healthcare Research and Quality. Winawer N. Redesign of telemetry unit admission and transfer criteria leads to improved patient flow and reduced emergency department waiting times. Available at: http://www.innovations.ahrq.gov/content.aspx?id=2239. Accessed February 12, 2013.
- Is telemetry monitoring necessary in low‐risk suspected acute chest pain syndromes? Chest. 2002;122:517–523. , , , et al.
- Surgical vampires and rising health care expenditure: reducing the cost of daily phlebotomy. Arch Surg. 2011;146:524–527. , .
- A cost‐effective method for reducing the volume of laboratory tests in a university‐associated teaching hospital. Mt Sinai J Med. 2006;73:787–794. , , , et al.
- Reducing unnecessary inpatient laboratory testing in a teaching hospital. Am J Clin Pathol. 2006;126:200–206. , , , et al.
- Making noncatastrophic health care processes reliable: learning to walk before running in creating high‐reliability organizations. Health Serv Res. 2006;41:1677–1689. .
- What have we learned about interventions to reduce medical errors? Annu Rev Public Health. 2010;31:479–497. , , , et al.
- Safe Patients, Smart Hospitals: How One Doctor's Checklist Can Help Us Change Health Care From The Inside Out. New York, NY: Hudson Street Press; 2010. , .
- Catheter‐associated urinary tract infection and the Medicare rule changes. Ann Intern Med. 2009;150:877–884. , , , , .
- Consensus conference. Perioperative red blood cell transfusion. JAMA. 1988;260:2700–2703.
- Is telemetry overused? Is it as helpful as thought? Cleve Clin J Med. 2009;76:368–372. , , , , , .
- Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38:1655–1711. , , , et al.
- Diagnostic blood loss from phlebotomy and hospital‐acquired anemia during acute myocardial infarction. Arch Intern Med. 2011;171:1646–1653. , , , et al.
- Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels. J Gen Intern Med. 2005;20:520–524. , , , , .
- Too little? Too much? Primary care physicians' views on US health care: a brief report. Arch Intern Med. 2011;171:1582–1585. , , .
- Evidence that consumers are skeptical about evidence‐based health care. Health Aff (Millwood). 2010;29:1400–1406. , , , et al.
- Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–1802. , .
- Too much treatment? Aggressive medical care can lead to more pain, with no gain. Consum Rep. 2008;73:40–44.
- Centers for Medicare and Medicaid Services. Historical national health expenditure data. Available at: http://www.cms.gov/Research‐Statistics‐Data‐and‐Systems/Statistics‐Trends‐and‐Reports/NationalHealthExpendData/NationalHealthAccountsHistorical.html. Accessed February 12, 2013.
- Eliminating waste in US health care. JAMA. 2012;307:1513–1516. , .
- Change the microenvironment: delivery system reform essential to controlling costs. Available at: http://www.commonwealthfund.org/Publications/Commentaries/2009/Apr/Change‐the‐Microenvironment.aspx. Accessed February 12, 2013. .
- Costs of care. Available at: http://www.costsofcare.org. Accessed February 12, 2013.
- Less is more: how less health care can result in better health. Arch Intern Med. 2010;170:749–750. , .
- Clinical Guidelines Committee of the American College of Physicians. High‐value, cost‐conscious health care: concepts for clinicians to evaluate the benefits, harms, and costs of medical interventions. Ann Intern Med. 2011;154:174–180. , , , ;
- ABIM Foundation. U.S. physician groups identify commonly used tests or procedures they say are often not necessary. Available at: http://www.abimfoundation.org/News/ABIM‐Foundation‐News/2012/Choosing‐Wisely.aspx. Accessed February 12, 2013.
- Addressing requests by patients for nonbeneficial interventions. JAMA. 2012;307:149–150. , .
- Growth in the care of older patients by hospitalists in the United States. N Engl J Med. 2009;360:1102–1112. , , , .
- The appropriateness method has acceptable reliability and validity for assessing overuse and underuse of surgical procedures. J Clin Epidemiol. 2012;65:1133–1143. , , , .
- Clinical and economic consequences of nosocomial catheter‐related bacteriuria. Am J Infect Control. 2000;28:68–75. .
- Estimating health care‐associated infections and deaths in U.S. hospitals, 2002. Public Health Rep. 2007;122:160–166. , , , et al.
- A compendium of strategies to prevent healthcare‐associated infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29(suppl 1): S12–S21. , , , et al.
- Strategies to prevent catheter‐associated urinary tract infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29(suppl 1):S41–S50. , , , et al.
- The direct medical costs of healthcare‐associated infections in U.S. hospitals and the benefits of prevention. Available at: http://www.cdc.gov/hai/pdfs/hai/scott_costpaper.pdf. Accessed February 12, 2013. .
- Healthcare Infection Control Practices Advisory Committee, guideline for prevention of catheter‐associated urinary tract infections 2009. Infect Control Hosp Epidemiol. 2010;31:319–326. , , , , .
- Diagnosis, prevention, and treatment of catheter‐associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625–663. , , , et al.
- 2011 National and State Healthcare‐Associated Infection Standardized Infection Ratio Report. Available at: http://www.cdc.gov/hai/pdfs/SIR/SIR‐Report_02_07_2013.pdf. Accessed February 13, 2013. , , , et al.
- Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm. 2007;64:1396–1400. , .
- ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;56:347–379. .
- Risk of community‐acquired pneumonia and use of gastric acid‐suppressive drugs. JAMA. 2004;292:1955–1960. , , , , , .
- Acid‐suppressive medication use and the risk for hospital‐acquired pneumonia. JAMA. 2009;301:2120–2128. , , , .
- Gastric acid suppression by proton pump inhibitors as a risk factor for clostridium difficile‐associated diarrhea in hospitalized patients. Am J Gastroenterol. 2008;103:2308–2313. , , , .
- Red blood cell transfusion: a clinical practice guideline from the AABB*. Ann Intern Med. 2012;157:49–58. , , , et al.
- Guidelines for the clinical use of red cell transfusions. Br J Haematol. 2001;113:24–31. , , , et al.
- Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion. 2002;42:812–818. , , , .
- Association of blood transfusion with increased mortality in myocardial infarction: a meta‐analysis and diversity‐adjusted study sequential analysis. JAMA Intern Med 2013;173:132–139. , , , , .
- Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11–21. , , , et al.
- Economic impact of inappropriate blood transfusions in coronary artery bypass graft surgery. Am J Med. 1993;94:509–514. , , , .
- The use and effectiveness of electrocardiographic telemetry monitoring in a community hospital general care setting. Anesth Analg. 2003;97:1483–1487. , , , , , .
- ACC/AHA guidelines for ambulatory electrocardiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography). Circulation. 1999;100:886–893. , , , et al.
- Role of telemetry monitoring in the non‐intensive care unit. Am J Cardiol. 1995;76:960–965. , , , et al.
- When do patients need admission to a telemetry bed? J Emerg Med. 2007;33:53–60. , .
- Electrocardiographic monitoring in the hospitalized patient: a diagnostic intervention of uncertain clinical impact. Am J Emerg Med. 2008;26:1047–1055. , .
- Clinical consequences of electrocardiographic artifact mimicking ventricular tachycardia. N Engl J Med. 1999;341:1270–1274. , , , , .
- Inpatient telemetry does not need to be used in the management of older patients hospitalized with chest pain at low risk for in‐hospital coronary events and mortality. J Gerontol A Biol Sci Med Sci. 2005;60:605–606. , , , .
- Telemetry monitoring guidelines for efficient and safe delivery of cardiac rhythm monitoring to noncritical hospital inpatients. Crit Pathw Cardiol. 2009;8:125–126. , , , , .
- Agency for Healthcare Research and Quality. Winawer N. Redesign of telemetry unit admission and transfer criteria leads to improved patient flow and reduced emergency department waiting times. Available at: http://www.innovations.ahrq.gov/content.aspx?id=2239. Accessed February 12, 2013.
- Is telemetry monitoring necessary in low‐risk suspected acute chest pain syndromes? Chest. 2002;122:517–523. , , , et al.
- Surgical vampires and rising health care expenditure: reducing the cost of daily phlebotomy. Arch Surg. 2011;146:524–527. , .
- A cost‐effective method for reducing the volume of laboratory tests in a university‐associated teaching hospital. Mt Sinai J Med. 2006;73:787–794. , , , et al.
- Reducing unnecessary inpatient laboratory testing in a teaching hospital. Am J Clin Pathol. 2006;126:200–206. , , , et al.
- Making noncatastrophic health care processes reliable: learning to walk before running in creating high‐reliability organizations. Health Serv Res. 2006;41:1677–1689. .
- What have we learned about interventions to reduce medical errors? Annu Rev Public Health. 2010;31:479–497. , , , et al.
- Safe Patients, Smart Hospitals: How One Doctor's Checklist Can Help Us Change Health Care From The Inside Out. New York, NY: Hudson Street Press; 2010. , .
- Catheter‐associated urinary tract infection and the Medicare rule changes. Ann Intern Med. 2009;150:877–884. , , , , .
- Consensus conference. Perioperative red blood cell transfusion. JAMA. 1988;260:2700–2703.
- Is telemetry overused? Is it as helpful as thought? Cleve Clin J Med. 2009;76:368–372. , , , , , .
- Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38:1655–1711. , , , et al.
- Diagnostic blood loss from phlebotomy and hospital‐acquired anemia during acute myocardial infarction. Arch Intern Med. 2011;171:1646–1653. , , , et al.
- Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels. J Gen Intern Med. 2005;20:520–524. , , , , .
Copyright © 2013 Society of Hospital Medicine
Focusing on Value
Over the last 30 years, rounds of therapeutic treatments with cost consciousness and cost containment have been administered to the healthcare industry, with generally disappointing clinical response. The last treatment cycle came in the 1990s, with the combination therapy of prospective payment and managed care, treatments that produced a transient remission in cost inflation but that left the healthcare system spent and decidedly unenthusiastic about another round of intensive therapy. For the next 15 years or so, the underlying conditions remained untreated, and unsurprisingly, runaway healthcare inflation returned. To continue this metaphor only a bit further, in 2013 the healthcare system is again facing intensive treatments, but in this case the treatments seem more likely to produce a strong and durable clinical response.
Although some argue that current efforts shall also pass, we believe that the present day is clearly different. A major difference is the implementation of the Affordable Care Act, which creates new structures to facilitate and incentives to promote cost reductions. More importantly, there has been a sea change in how the publicnot just payors or employersview healthcare costs. The ideas that care is too expensive and that much of it adds no value to patients have gained wide acceptance across the political spectrum, among patients, and increasingly among physicians.
It was in this context that the American Board of Internal Medicine Foundation (ABIMF) launched its Choosing Wisely campaign in 2011.[1] The stated goal of the campaign was to promote important conversations [between doctors and patients] necessary to ensure the right care is delivered at the right time. Importantly, this careful framing successfully avoided the caricatures of rationing or death panels, reactions that doomed prior efforts to engage all stakeholders in a reasoned national dialogue about costs and value.
The ABIMF chose an approach of having physicians identify tests and procedures that may be unnecessary in certain situations. Working with Consumer Reports, the Foundation asked a wide range of medical specialty societies to develop their own list of tests and procedures that could potentially be avoided with no harm to patients. The vast majority, 25 as of July 2013, chose to participate.
In February 2013, the Society of Hospital Medicine (SHM) joined the initiative when it posted adult and pediatric versions of Five Things Physicians and Patients Should Question.[2] We are pleased to publish summaries of the recommendations and the processes by which the 2 working groups produced their lists in the Journal of Hospital Medicine.[3, 4]
In reading these articles, we are struck by the importance of the SHM's work to reduce costs and improve value. However, it really is a first step: both articles must now catalyze a body of work to create and sustain meaningful change.
Although many of the 10 targets have strong face validity, it is not clear whether they are in fact the most common, costly, or low‐value practices under the purview of hospitalists. Given the fact that the selection process involved both evidence‐based reviews and consensus, it is possible that other, potentially more contentious, practices may provide even more bang for the buck, or in this case, nonbuck.
Nevertheless, these are quibbles. These lists are good starting points, and in fact many hospitalist groups, including our own, are using the SHM practices as a foundation for our waste‐reduction efforts. The next challenge will be translating these recommendations into actionable measures and then clinical practice. For example, 1 of the adult recommendations is to avoid repeat blood counts and chemistries in patients who are clinically stable. Concepts of clinical stability are notoriously difficult to define within specific patient subgroups, much less across the diverse patient populations seen by hospitalists. One approach here would be to narrow the focus (eg, do not order repeated blood counts in patients with gastrointestinal bleeding whose labs have been stable for 48 hours), but this step would limit the cost savings. Other measures, such as those related to urinary catheters, are more clearly defined and seem closer to being widely adoptable.
For all these measures, the ultimate question remains: How much can actually be saved and how do we measure the savings? The marginal cost of a complete blood count is extraordinarily small in comparison to an entire hospital stay, but it is possible that eliminating redundant testing also reduces the costs related to follow‐up of false positive findings. Reducing the use of urinary catheters can cut the costs of urinary tract infections and the complications of treatment, but these costs could be offset by the higher‐level nursing care needed to mobilize patients earlier or assist patients in toileting, squeezing the proverbial balloon. For all these measures, it is unclear whether what might be relatively small variable cost reductions related to specific tests/procedures can lead to subsequent reduction in fixed costs related to facilities and equipment, where more than 70% of healthcare costs lie.[5] In other words, reducing the number of lab technicians and the amount of laboratory equipment needed will lead to far greater cost reductions than reducing individual test utilization.
None of this is to say that the Choosing Wisely campaign is without merit. To the contrary, the campaign and the efforts of the SHM are early and critical steps in changing the behavior of a profession. Since the early days of hospital medicine, hospitalists have embraced cost reduction and value improvement as a central focus. By successfully engaging consumers and the community of medical specialties, Choosing Wisely has created a language and a framework that will allow our field and others to tackle the crucial work of resource stewardship with new purpose, and we hope, unprecedented success.
Disclosures
Dr. Wachter is immediate past‐chair of the American Board of Internal Medicine (ABIM) and serves on the ABIM Foundation's Board of Trustees. Dr. Auerbach receives honoraria from the American Board of Internal Medicine as a contributor to the Maintenance of Certification question pool.
- Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–1802. , .
- Are you choosing wisely? 2013. Available at: http://www.hospitalmedicine.org/AM/Template.cfm?Section=Quality_Improvement8:486–492.
- Choosing Wisely in inpatient pediatrics: 5 opportunities for improved healthcare value. J Hosp Med. 2013;8:479–485. , , , et al.
- Distribution of variable vs fixed costs of hospital care. JAMA. 1999;281:644–649. , , , et al.
Over the last 30 years, rounds of therapeutic treatments with cost consciousness and cost containment have been administered to the healthcare industry, with generally disappointing clinical response. The last treatment cycle came in the 1990s, with the combination therapy of prospective payment and managed care, treatments that produced a transient remission in cost inflation but that left the healthcare system spent and decidedly unenthusiastic about another round of intensive therapy. For the next 15 years or so, the underlying conditions remained untreated, and unsurprisingly, runaway healthcare inflation returned. To continue this metaphor only a bit further, in 2013 the healthcare system is again facing intensive treatments, but in this case the treatments seem more likely to produce a strong and durable clinical response.
Although some argue that current efforts shall also pass, we believe that the present day is clearly different. A major difference is the implementation of the Affordable Care Act, which creates new structures to facilitate and incentives to promote cost reductions. More importantly, there has been a sea change in how the publicnot just payors or employersview healthcare costs. The ideas that care is too expensive and that much of it adds no value to patients have gained wide acceptance across the political spectrum, among patients, and increasingly among physicians.
It was in this context that the American Board of Internal Medicine Foundation (ABIMF) launched its Choosing Wisely campaign in 2011.[1] The stated goal of the campaign was to promote important conversations [between doctors and patients] necessary to ensure the right care is delivered at the right time. Importantly, this careful framing successfully avoided the caricatures of rationing or death panels, reactions that doomed prior efforts to engage all stakeholders in a reasoned national dialogue about costs and value.
The ABIMF chose an approach of having physicians identify tests and procedures that may be unnecessary in certain situations. Working with Consumer Reports, the Foundation asked a wide range of medical specialty societies to develop their own list of tests and procedures that could potentially be avoided with no harm to patients. The vast majority, 25 as of July 2013, chose to participate.
In February 2013, the Society of Hospital Medicine (SHM) joined the initiative when it posted adult and pediatric versions of Five Things Physicians and Patients Should Question.[2] We are pleased to publish summaries of the recommendations and the processes by which the 2 working groups produced their lists in the Journal of Hospital Medicine.[3, 4]
In reading these articles, we are struck by the importance of the SHM's work to reduce costs and improve value. However, it really is a first step: both articles must now catalyze a body of work to create and sustain meaningful change.
Although many of the 10 targets have strong face validity, it is not clear whether they are in fact the most common, costly, or low‐value practices under the purview of hospitalists. Given the fact that the selection process involved both evidence‐based reviews and consensus, it is possible that other, potentially more contentious, practices may provide even more bang for the buck, or in this case, nonbuck.
Nevertheless, these are quibbles. These lists are good starting points, and in fact many hospitalist groups, including our own, are using the SHM practices as a foundation for our waste‐reduction efforts. The next challenge will be translating these recommendations into actionable measures and then clinical practice. For example, 1 of the adult recommendations is to avoid repeat blood counts and chemistries in patients who are clinically stable. Concepts of clinical stability are notoriously difficult to define within specific patient subgroups, much less across the diverse patient populations seen by hospitalists. One approach here would be to narrow the focus (eg, do not order repeated blood counts in patients with gastrointestinal bleeding whose labs have been stable for 48 hours), but this step would limit the cost savings. Other measures, such as those related to urinary catheters, are more clearly defined and seem closer to being widely adoptable.
For all these measures, the ultimate question remains: How much can actually be saved and how do we measure the savings? The marginal cost of a complete blood count is extraordinarily small in comparison to an entire hospital stay, but it is possible that eliminating redundant testing also reduces the costs related to follow‐up of false positive findings. Reducing the use of urinary catheters can cut the costs of urinary tract infections and the complications of treatment, but these costs could be offset by the higher‐level nursing care needed to mobilize patients earlier or assist patients in toileting, squeezing the proverbial balloon. For all these measures, it is unclear whether what might be relatively small variable cost reductions related to specific tests/procedures can lead to subsequent reduction in fixed costs related to facilities and equipment, where more than 70% of healthcare costs lie.[5] In other words, reducing the number of lab technicians and the amount of laboratory equipment needed will lead to far greater cost reductions than reducing individual test utilization.
None of this is to say that the Choosing Wisely campaign is without merit. To the contrary, the campaign and the efforts of the SHM are early and critical steps in changing the behavior of a profession. Since the early days of hospital medicine, hospitalists have embraced cost reduction and value improvement as a central focus. By successfully engaging consumers and the community of medical specialties, Choosing Wisely has created a language and a framework that will allow our field and others to tackle the crucial work of resource stewardship with new purpose, and we hope, unprecedented success.
Disclosures
Dr. Wachter is immediate past‐chair of the American Board of Internal Medicine (ABIM) and serves on the ABIM Foundation's Board of Trustees. Dr. Auerbach receives honoraria from the American Board of Internal Medicine as a contributor to the Maintenance of Certification question pool.
Over the last 30 years, rounds of therapeutic treatments with cost consciousness and cost containment have been administered to the healthcare industry, with generally disappointing clinical response. The last treatment cycle came in the 1990s, with the combination therapy of prospective payment and managed care, treatments that produced a transient remission in cost inflation but that left the healthcare system spent and decidedly unenthusiastic about another round of intensive therapy. For the next 15 years or so, the underlying conditions remained untreated, and unsurprisingly, runaway healthcare inflation returned. To continue this metaphor only a bit further, in 2013 the healthcare system is again facing intensive treatments, but in this case the treatments seem more likely to produce a strong and durable clinical response.
Although some argue that current efforts shall also pass, we believe that the present day is clearly different. A major difference is the implementation of the Affordable Care Act, which creates new structures to facilitate and incentives to promote cost reductions. More importantly, there has been a sea change in how the publicnot just payors or employersview healthcare costs. The ideas that care is too expensive and that much of it adds no value to patients have gained wide acceptance across the political spectrum, among patients, and increasingly among physicians.
It was in this context that the American Board of Internal Medicine Foundation (ABIMF) launched its Choosing Wisely campaign in 2011.[1] The stated goal of the campaign was to promote important conversations [between doctors and patients] necessary to ensure the right care is delivered at the right time. Importantly, this careful framing successfully avoided the caricatures of rationing or death panels, reactions that doomed prior efforts to engage all stakeholders in a reasoned national dialogue about costs and value.
The ABIMF chose an approach of having physicians identify tests and procedures that may be unnecessary in certain situations. Working with Consumer Reports, the Foundation asked a wide range of medical specialty societies to develop their own list of tests and procedures that could potentially be avoided with no harm to patients. The vast majority, 25 as of July 2013, chose to participate.
In February 2013, the Society of Hospital Medicine (SHM) joined the initiative when it posted adult and pediatric versions of Five Things Physicians and Patients Should Question.[2] We are pleased to publish summaries of the recommendations and the processes by which the 2 working groups produced their lists in the Journal of Hospital Medicine.[3, 4]
In reading these articles, we are struck by the importance of the SHM's work to reduce costs and improve value. However, it really is a first step: both articles must now catalyze a body of work to create and sustain meaningful change.
Although many of the 10 targets have strong face validity, it is not clear whether they are in fact the most common, costly, or low‐value practices under the purview of hospitalists. Given the fact that the selection process involved both evidence‐based reviews and consensus, it is possible that other, potentially more contentious, practices may provide even more bang for the buck, or in this case, nonbuck.
Nevertheless, these are quibbles. These lists are good starting points, and in fact many hospitalist groups, including our own, are using the SHM practices as a foundation for our waste‐reduction efforts. The next challenge will be translating these recommendations into actionable measures and then clinical practice. For example, 1 of the adult recommendations is to avoid repeat blood counts and chemistries in patients who are clinically stable. Concepts of clinical stability are notoriously difficult to define within specific patient subgroups, much less across the diverse patient populations seen by hospitalists. One approach here would be to narrow the focus (eg, do not order repeated blood counts in patients with gastrointestinal bleeding whose labs have been stable for 48 hours), but this step would limit the cost savings. Other measures, such as those related to urinary catheters, are more clearly defined and seem closer to being widely adoptable.
For all these measures, the ultimate question remains: How much can actually be saved and how do we measure the savings? The marginal cost of a complete blood count is extraordinarily small in comparison to an entire hospital stay, but it is possible that eliminating redundant testing also reduces the costs related to follow‐up of false positive findings. Reducing the use of urinary catheters can cut the costs of urinary tract infections and the complications of treatment, but these costs could be offset by the higher‐level nursing care needed to mobilize patients earlier or assist patients in toileting, squeezing the proverbial balloon. For all these measures, it is unclear whether what might be relatively small variable cost reductions related to specific tests/procedures can lead to subsequent reduction in fixed costs related to facilities and equipment, where more than 70% of healthcare costs lie.[5] In other words, reducing the number of lab technicians and the amount of laboratory equipment needed will lead to far greater cost reductions than reducing individual test utilization.
None of this is to say that the Choosing Wisely campaign is without merit. To the contrary, the campaign and the efforts of the SHM are early and critical steps in changing the behavior of a profession. Since the early days of hospital medicine, hospitalists have embraced cost reduction and value improvement as a central focus. By successfully engaging consumers and the community of medical specialties, Choosing Wisely has created a language and a framework that will allow our field and others to tackle the crucial work of resource stewardship with new purpose, and we hope, unprecedented success.
Disclosures
Dr. Wachter is immediate past‐chair of the American Board of Internal Medicine (ABIM) and serves on the ABIM Foundation's Board of Trustees. Dr. Auerbach receives honoraria from the American Board of Internal Medicine as a contributor to the Maintenance of Certification question pool.
- Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–1802. , .
- Are you choosing wisely? 2013. Available at: http://www.hospitalmedicine.org/AM/Template.cfm?Section=Quality_Improvement8:486–492.
- Choosing Wisely in inpatient pediatrics: 5 opportunities for improved healthcare value. J Hosp Med. 2013;8:479–485. , , , et al.
- Distribution of variable vs fixed costs of hospital care. JAMA. 1999;281:644–649. , , , et al.
- Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307:1801–1802. , .
- Are you choosing wisely? 2013. Available at: http://www.hospitalmedicine.org/AM/Template.cfm?Section=Quality_Improvement8:486–492.
- Choosing Wisely in inpatient pediatrics: 5 opportunities for improved healthcare value. J Hosp Med. 2013;8:479–485. , , , et al.
- Distribution of variable vs fixed costs of hospital care. JAMA. 1999;281:644–649. , , , et al.
Procalcitonin‐Guided Antibiotic Therapy
Many serum biomarkers have been identified in recent years with a wide range of potential applications, including diagnosis of local and systemic infections, differentiation of bacterial and fungal infections from viral syndromes or noninfectious conditions, prognostic stratification of patients, and enhanced management of antibiotic therapy. Currently, there are at least 178 serum biomarkers that have potential roles to guide antibiotic therapy, and among these, procalcitonin has been the most extensively studied biomarker.[1, 2]
Procalcitonin is the prohormone precursor of calcitonin that is expressed primarily in C cells of the thyroid gland. Conversion of procalcitonin to calcitonin is inhibited by various cytokines and bacterial endotoxins. Procalcitonin's primary diagnostic utility is thought to be in establishing the presence of bacterial infections, because serum procalcitonin levels rise and fall rapidly in bacterial infections.[3, 4, 5] In healthy individuals, procalcitonin levels are very low. In systemic infections, including sepsis, procalcitonin levels are generally greater than 0.5 to 2 ng/mL, but often reach levels 10 ng/mL, which correlates with severity of illness and a poor prognosis. In patients with respiratory tract infections, procalcitonin levels are less elevated, and a cutoff of 0.25 ng/mL seems to be most predictive of a bacterial respiratory tract infection requiring antibiotic therapy.[6, 7, 8] Procalcitonin levels decrease to <0.25 ng/mL as infection resolves, and a decline in procalcitonin level may guide decisions about discontinuation of antibiotic therapy.[5]
The purpose of this systematic review was to synthesize comparative studies examining the use of procalcitonin to guide antibiotic therapy in patients with suspected local or systemic infections in different patient populations. We are aware of 6 previously published systematic reviews evaluating the utility of procalcitonin guidance in the management of infections.[9, 10, 11, 12, 13, 14] Our systematic review included more studies and pooled patients into the most clinically similar groups compared to other systematic reviews.
METHODS
This review is based on a comparative effectiveness review prepared for the Agency for Healthcare Research and Quality's Effective Health Care Program.[15] A standard protocol consistent with the Methods Guide for Effectiveness and Comparative Effectiveness Reviews[16] was followed. A detailed description of the methods is available online (
Study Question
In selected populations of patients with suspected local or systemic infection, what are the effects of using procalcitonin measurement plus clinical criteria for infection to guide initiation, intensification, and/or discontinuation of antibiotic therapy when compared to clinical criteria for infection alone?
Search Strategy
MEDLINE and EMBASE were searched from January 1, 1990 through December 16, 2011, and the Cochrane Controlled Trials register was searched with no date restriction for randomized and nonrandomized comparative studies using the following search terms: procalcitonin AND chronic obstructive pulmonary disease; COPD; critical illness; critically ill; febrile neutropenia; ICU; intensive care; intensive care unit; postoperative complication(s); postoperative infection(s); postsurgical infection(s); sepsis; septic; surgical wound infection; systemic inflammatory response syndrome OR postoperative infection. In addition, a search for systematic reviews was conducted in MEDLINE, the Cochrane Database of Systematic Reviews, and Web sites of the National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme. Gray literature, including databases with regulatory information, clinical trial registries, abstracts and conference papers, grants and federally funded research, and manufacturing information was searched from January 1, 2006 to June 28, 2011.
Study Selection
A single reviewer screened abstracts and selected studies looking at procalcitonin‐guided antibiotic therapy. Second and third reviewers were consulted to screen articles when needed. Studies were included if they fulfilled all of the following criteria: (1) randomized, controlled trial or nonrandomized comparative study; (2) adult and/or pediatric patients with known or suspected local or systemic infection, including critically ill patients with sepsis syndrome or ventilator‐associated pneumonia, adults with respiratory tract infections, neonates with sepsis, children with fever of unknown source, and postoperative patients at risk of infection; (3) interventions included initiation, intensification, and/or discontinuation of antibiotic therapy guided by procalcitonin plus clinical criteria; (4) primary outcomes included antibiotic usage (antibiotic prescription rate, total antibiotic exposure, duration of antibiotic therapy, and days without antibiotic therapy); and (5) secondary outcomes included morbidity (antibiotic adverse events, hospital and/or intensive care unit length of stay), mortality, and quality of life.
Studies with any of the following criteria were excluded: published in non‐English language, not reporting primary data from original research, not a randomized, controlled trial or nonrandomized comparative study, not reporting relevant outcomes.
Data Extraction and Quality Assessment
A single reviewer abstracted data and a second reviewer confirmed accuracy. Disagreements between reviewers were resolved by group discussion among the research team and final quality rating was assigned by consensus adjudication. Data elements were abstracted into the following categories: quality assessment, applicability and clinical diversity assessment, and outcome assessment. Quality of included studies was assessed using the US Preventive Services Task Force framework[17] by at least 2 independent reviewers. Three quality categories were used: good, fair, and poor.
Data Synthesis and Analysis
The decision to incorporate formal data synthesis in this review was made after completing the formal literature search, and the decision to pool studies was based on the specific number of studies with similar questions and outcomes. If a meta‐analysis could be performed, subgroup and sensitivity analyses were based on clinical similarity of available studies and reporting of mean and standard deviation. The pooling method involved inverse variance weighting and a random effects model.
The strength of evidence was graded using the Methods Guide,[16] a system based on the Grading of Recommendations Assessment, Development and Evaluation Working Group.[18] The following domains were addressed: risk of bias, consistency, directness, and precision. The overall strength of evidence was graded as high, moderate, low, or insufficient. The final strength of evidence grading was made by consensus adjudication among the authors.
RESULTS
Of the 2000 studies identified through the literature search, 1986 were excluded and 14 studies[19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32] were included. Search of gray literature yielded 4 published studies.[33, 34, 35, 36] A total of 18 randomized, controlled trials comparing procalcitonin guidance to use of clinical criteria alone to manage antibiotic therapy in patients with infections were included. The PRISMA diagram (Figure 1) depicts the flow of search screening and study selection. We sought, but did not find, nonrandomized comparative studies of populations, comparisons, interventions, and outcomes that were not adequately studied in randomized, controlled trials.

Data were pooled into clinically similar groups that were reviewed separately: (1) adult intensive care unit (ICU) patients, including patients with ventilator‐associated pneumonia; (2) adult patients with respiratory tract infections; (3) neonates with suspected sepsis; (4) children between 1 to 36 months of age with fever of unknown source; and (5) postoperative patients at risk of infection. Tables summarizing study quality and outcome measures with strength of evidence are available online (
Outcome | Author, Year | N | PCT‐Guided Therapya | Controla | Difference PCT‐CTRL (95% CI) | P Value |
---|---|---|---|---|---|---|
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
ABT Duration, d | Hochreiter, 2009[22] | 110 | 5.9 | 7.9 | 2.0 (2.5 to 1.5) | <0.001 |
Nobre, 2008[19] | 79 | 66 | 9.5 (ITT), 10 (PP) | 2.6 (5.5 to 0.3), 3.2 (1.1 to5.4) | 0.15, 0.003 | |
Schroeder, 2009[20] | 27 | 6.6 | 8.3 | 1.7 (2.4 to 1.0) | <0.001 | |
Stolz, 2009[21] | 101 | 10 (616)b | 15 (1023)b | 5 | 0.049 | |
Bouadma, 2010[23] | 621 | 10.3 | 13.3 | 3.0 (4.20 to 1.80) | <0.0001 | |
Days without ABTs, day 28 | Nobre, 2008[19] | 79 | 15.3, 17.4 | 13, 13.6 | 2.3 (5.9 to 1.8), 3.8 (0.1 to 7.5)c | 0.28, 0.04 |
Stolz, 2009[21] | 101 | 13 (221)b | 9.5 (1.517)b | 3.5 | 0.049 | |
Bouadma, 2010[23] | 621 | 14.3 | 11.6 | 2.7 (1.4 to 4.1) | <0.001 | |
Total ABT exposured | Nobre, 2008[19] | 79 | 541 | 644 | 1.1e (0.9 to 1.3), 1.3e (1.1 to 1,5)c | 0.07, 0.0002 |
504 | 655 | |||||
Stolz, 2009[21] | 101 | 1077 | 1341 | |||
Bouadma, 2010[23]d | 621 | 653 | 812 | 159 (185 to 131) | <0.001 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
ABT duration, days | Jensen, 2011[33] | 1200 | 6 (311)b | 4 (310)b | NR | NR |
Days spent in ICU on 3 ABTs | Jensen, 2011[33] | 1200 | 3570/5447 (65.5%) | 2721/4717 (57.7%) | 7.9% (6.0 to 9.7) | 0.002 |
Adult patients with respiratory tract infections | ||||||
ABT duration, da | Schuetz, 2009[2][5] | 1359 | 5.7 | 8.7 | 3.0 | |
Christ‐Crain, 2004[30] | 243 | 10.9 | 12.8 | 1.9 (3.1 to 0.7) | 0.002 | |
Kristoffersen, 2009[26] | 210 | 5.1 | 6.8 | 1.7 | ||
Briel, 2008[27] | 458 | 6.2 | 7.1 | 1.0 (1.7 to 0.4) | <0.05 | |
Long, 20113[5] | 162 | 5 (36)f | 7 (59)f | 2.0 | <0.001 | |
Burkhardt, 2010[34] | 550 | 7.8 | 7.7 | 0.1 (0.7 to 0.9) | 0.8 | |
Christ‐Crain, 2006[29] | 302 | 5.8 | 12.9 | 7.1(8.4 to 5.8) | <0.0001 | |
Antibiotic prescription rate, % | Schuetz, 2009[2][5] | 1359 | 506/671 (75.4%) | 603/688 (87.6%) | 12.2% (16.3 to 8.1) | <0.05 |
Christ‐Crain, 2004[30] | 243 | 55/124 (44.4%) | 99/119 (83.2%) | 38.8% (49.9 to 27.8) | <0.0001 | |
Kristoffersen, 2009[26] | 210 | 88/103 (85.4%) | 85/107 (79.4%) | 6.0% (4.3 to 16.2) | 0.25 | |
Briel, 2008[27] | 458 | 58/232 (25.0%) | 219/226 (96.9%) | 72% (78 to 66) | <0.05 | |
Long, 20113[5] | 162 | NR (84.4%) | NR (97.5%) | 13.1% | 0.004 | |
Stolz, 2007[28] | 208 | 41/102 (40.2%) | 76/106 (71.7%) | 31.5% (44.3 to 18.7) | <0.0001 | |
Christ‐Crain, 2006[29] | 302 | 128/151 (84.8%) | 149/151 (98.79%) | 13.9% (19.9 to 7.9) | <0.0001 | |
Burkhardt, 2010[34] | 550 | 84/275 (30.5%) | 89/275 (32.4%) | 1.8% (9.6 to 5.9) | 0.701 | |
Total ABT exposure | Stolz, 2007[28] | 208 | NR | NR | 31.5% (18.7 to 44.3) | <0.0001 |
Long, 20113[5] | 162 | NR | NR | NR | ||
Christ‐Crain, 2006[29] | 302 | 136g | 323g | |||
Christ‐Crain, 2004[30] | 243 | 332g | 661g | |||
Neonates with sepsis | ||||||
ABTs 72 hours, % | Stocker, 2010[31] | All neonates (N=121) | 33/60 (55%) | 50/61 (82%) | 27.0 (42.8 to 11.1) | 0.002 |
Infection proven/probably (N=21) | 9/9 (100%) | 12/12 (100%) | 0% (0 to 0) | NA | ||
Infection possible (N=40) | 13/21 (61.9%) | 19/19 (100%) | 38.1 (58.9 to 17.3) | 0.003 | ||
Infection unlikely (N=60) | 11/30 (36.7%) | 19/30 (63.3%) | 26.6 (51.1 to 2.3) | 0.038 | ||
ABT duration, h | Stocker, 2010[31] | All neonates (N=121) | 79.1 | 101.5 | 22.4 | 0.012 |
Infection proven/probably (N=21) | 177.8 | 170.8 | 7 | NSS | ||
Infection possible (N=40) | 83.4 | 111.5 | 28.1 | <0.001 | ||
Infection unlikely (N=60) | 46.5 | 67.4 | 20.9 | 0.001 | ||
Children ages 136 months with fever of unknown source | ||||||
Antibiotic prescription rate, % | Manzano, 2010[36] | All children (N=384) | 48/192 (25%) | 54/192 (28.0%) | 3.1 (12.0 to 5.7) | 0.49 |
No SBI or neutropenia (N=312) | 14/158 (9%) | 16/154 (10%) | 1.5 (8.1 to 5.0) | 0.65 | ||
Adult postoperative patients at risk of infection | ||||||
ABT duration, d | Chromik, 2006[32] | All patients (N=20) | 5.5 | 9 | 3.5 | 0.27 |
Outcome | Author, Year | N | PCTa | Controla | Difference, PCT‐CTRL (95% CI) | P Value |
---|---|---|---|---|---|---|
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
ICU LOS, days | Hochreiter, 2009[22] | 110 | 15.5 | 17.7 | 2.2 | 0.046 |
Nobre, 2008[19] | 79 | 4 | 7 | 4.6 (8.2 to 1.0) | 0.02 | |
Schroeder, 2009[20] | 27 | 16.4 | 16.7 | 0.3 (5.6 to 5.0) | NSS | |
Bouadma, 2010[23] | 621 | 15.9 | 14.4 | 1.5 (0.9 to 3.1) | 0.23 | |
Hospital LOS, days | Nobre, 2008[19] | 79 | 17 | 23.5 | 2.5 (6.5 to 1.5) | 0.85 |
Stolz, 2009[21] | 101 | 26 (721)b | 26 (16.822.3)b | 0 | 0.15 | |
Bouadma, 2010[23] | 621 | 26.1 | 26.4 | 0.3 (3.2 to 2.7) | 0.87 | |
ICU‐free days alive, 128 | Stolz, 2009[21] | 101 | 10 (018)b | 8.5 (018)c | 1.5 | 0.53 |
SOFA day 28 | Bouadma, 2010[23] | 621 | 1.5 | 0.9 | 0.6 (0.0, 1.1) | 0.037 |
SOFA score max | Schroeder, 2009[20] | 27 | 7.3 | 8.3 | 8.1 (4.1 to 1.7) | NSS |
SAPS II score | Hochreiter, 2009[22] | 110 | 40.1 | 40.5 | 0.4 (6.4 to 5.6) | >0.05 |
Days without MV | Stolz, 2009[21] | 101 | 21 (224)b | 19 (8.522.5)b | 2.0 | 0.46 |
Bouadma, 2010[23] | 621 | 16.2 | 16.9 | 0.7 (2.4 to 1.1) | 0.47 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
ICU LOS, da | Svoboda, 2007[24] | 72 | 16.1 | 19.4 | 3.3 (7.0 to 0.4) | 0.09 |
Jensen, 2011[33] | 1200 | 6 (312)b | 5 (311)b | 1 | 0.004 | |
SOFA scorea | Svoboda, 2007[24] | 72 | 7.9 | 9.3 | 1.4 (2.8 to 0.0) | 0.06 |
Days on MVa | Svoboda, 2007[24] | 72 | 10.3 | 13.9 | 3.6 (7.6 to 0.4) | 0.08 |
Jensen, 2011[33] | 1200 | 3569 (65.5%) | 2861 (60.7%) | 4.9% (3 to 6.7) | <0.0001 | |
Percent days in ICU with GFR <60 | Jensen, 2011[33] | 1200 | 2796 (51.3%) | 2187 (46.4%) | 5.0 % (3.0 to 6.9) | <0.0001 |
Adult patients with respiratory tract infections | ||||||
Hospital LOS, da | Schuetz, 2009[2][5] | 1359 | 9.4 | 9.2 | 0.2 | |
Christ‐Crain, 2004[30] | 224 | 10.78.9 | 11.210.6 | 0.5 (3.0 to 2.0) | 0.69 | |
Kristoffersen, 2009[26] | 210 | 5.9 | 6.7 | 0.8 | 0.22 | |
Stolz, 2007[28] | 208 | 9 (115)b | 10 (115)b | 1 | 0.96 | |
Christ‐Crain, 2006[29] | 302 | 12.09.1 | 13.09.0 | 1 (3.0 to 1.0) | 0.34 | |
ICU admission, % | Schuetz, 2009[2][5] | 1359 | 43/671 (6.4%) | 60/688 (8.7%) | 2.3% (5.2 to 0.4) | 0.12 |
Christ‐Crain, 2004[30] | 224 | 5/124 (4.0%) | 6/119 (5.0%) | 1.0% (6.2 to 4.2) | 0.71 | |
Kristoffersen, 2009[26] | 210 | 7/103 (6.8%) | 5/107 (4.7%) | 2.1% (4.2 to 8.4) | 0.51 | |
Stolz, 2007[28] | 208 | 8/102 (7.8%) | 11/106 (10.4%) | 2.5% (10.3 to 5.3) | 0.53 | |
Christ‐Crain, 2006[29] | 302 | 20/151 (13.2%) | 21/151 (13.94%) | 0.7% (8.4 to 7.1) | 0.87 | |
Antibiotic adverse events | Schuetz, 2009[2][5]c | 1359 | 133/671 (19.8%) | 193/688 (28.1%) | 8.2% (12.7 to 3.7) | |
Briel, 2008[27]d | 458 | 2.34.6 days | 3.66.1 days | 1.1 days (2.1 to 0.1) | <0.05 | |
Burkhardt, 2010[34]e | 550 | 11 /59 (18.6%) | 16/101 (15.8%) | 2.8% (9.4 to 15.0) | 0.65 | |
Restricted activity, df | Briel, 2008[27] | 458 | 8.73.9 | 8.63.9 | 0.2 (0.4 to 0.9) | >0.05 |
Burkhardt, 2010[34] | 550 | 9.1 | 8.8 | 0.25 (0.52 to 1.03) | >0.05 | |
Neonates with sepsis | ||||||
Recurrence of infection | Stocker, 2010[31] | 121 | 32% | 39% | 7 | 0.45 |
Children ages 136 months with fever of unknown source | ||||||
Hospitalization rate | Manzano, 2010[36] | All children (N=384) | 50/192 (26%) | 48/192 (25%) | 1 (8 to 10) | 0.81 |
No SBI or neutropenia (N=312) | 16/158 (10%) | 11/154 (7%) | 3 (3 to 10) | 0.34 | ||
Adult postoperative patients at risk of infection | ||||||
Hospital LOS, days | Chromik, 2006[32] | 20 | 18 | 30 | 12 | 0.057 |
Local wound infection, % | Chromik, 2006[32] | 20 | 1/10 | 2/10 | 10 (41.0 to 21.0) | 0.53 |
Systemic infection, % | Chromik, 2006[32] | 20 | 3/10 | 7/10 | 40.0 (80.2 to 0.2) | 0.07 |
Sepsis/SIRS, % | Chromik, 2006[32] | 20 | 2/10 | 8/10 | 60.0 (95.1 to 24.9) | 0.007 |
Mortality | Mortality | Difference | ||||
---|---|---|---|---|---|---|
Outcome | Author, Year | N | PCT‐Guided Therapy | Control | PCT‐CTRL (95% CI) | P Value |
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
28‐day mortality | Nobre, 2008[19] | 79 | 8/39 (20.5%) | 8/40 (20.0%) | 0.5 (17.2 to 18.2), | 0.95 |
5/31 (16.1%) | 6/37 (16.2%) | 0.1 (17.7 to 17.5)a | 0.99 | |||
Stolz, 2009[21] | 101 | 8/51 (15.7%) | 12/50 (24.0%) | 8.3 (23.8 to 7.2) | 0.29 | |
Bouadma, 2010[23] | 621 | 65/307 (21.2%) | 64/314 (20.4%) | 0.8 (5.6 to 7.2) | 0.81 | |
60‐day mortality | Bouadma, 2010[23] | 621 | 92/307 (30.0%) | 82/314 (26.1%) | 3.9 (3.2 to 10.9) | 0.29 |
In‐hospital mortality | Nobre, 2008[19] | 79 | 9/39 (23.1%) | 9/40 (22.5%) | 0.6 (17.9 to 19.1) | 0.95 |
6/31 (19.4%) | 7/37 (18.9%) | 0.4+ (18.3 to 19.2) | 0.96 | |||
Stolz, 2009[21] | 101 | 10/51 (19.6%) | 14/50 (28.0%) | 8.4, (24.9 to 8.1) | 0.32 | |
Hochreiter, 2009[22] | 110 | 15/57 (26.3%) | 14/53 (26.4%) | 0.1, (16.6 to 16.4) | 0.99 | |
Schroeder, 2009[20] | 27 | 3/14 (21.4%) | 3/13 (23.1%) | 1.7, (33.1 to 29.8) | 0.92 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
28‐day mortality | Svoboda, 2007[24] | 72 | 10/38 (26.3%) | 13/34 (38.2%) | 11.9 (33.4 to 9.6) | 0.28 |
28‐day mortality | Jensen, 2011[33] | 1200 | 190/604 (31.5%) | 191/596 (32.0%) | 0.6 (4.7 to 5.9) | 0.83 |
Adult patients with respiratory tract infections | ||||||
6‐month mortality | Stolz, 2007[28] | 208 | 5/102 (4.9%) | 9/106 (8.5%) | 3.6% (10.3 to 3.2%) | 0.30 |
6‐week mortality | Christ‐Crain, 2006[29] | 302 | 18/151 (11.9%) | 20/151 (13.2%) | 1.3% (8.8 to 6.2) | 0.73 |
28‐day mortality | Christ‐Crain, 2004[30] | 243 | 4/124(3.2%) | 4/119 (3.4%) | 0.1% (4.6 to 4.4) | 0.95 |
Schuetz, 2009 (30‐day)[25] | 1359 | 34/671(5.1%) | 33/688(4.8%) | 0.3% (2.1 to 2.5) | 0.82 | |
Briel, 2008[27] | 458 | 0/231(0%) | 1/224 (0.4%) | 0.4% (1.3 to 0.4) | 0.31 | |
Burkhardt, 2010[34] | 550 | 0/275(0%) | 0/275 (0%) | 0 | ||
Kristoffersen, 2009[26] | 210 | 2/103(1.9%) | 1/107 (0.9%) | 1.0% (2.2 to 4.2) | 0.54 | |
Long, 20113[5] | 162 | 0/81 (0%) | 0/81 (0%) | 0 | ||
Neonates with sepsis | ||||||
Mortality (in‐hospital) | Stocker, 2010[31] | 121 | 0% | 0% | 0 (0 to 0) | NA |
Children ages 136 months with fever of unknown source | ||||||
Mortality | Manzano, 2010[36] | 384 | All children | 0% | 0% | 0 (0 to 0) |
Adult postoperative patients at risk of infection | ||||||
Mortality | Chromik, 2006[32] | 20 | 1/10 (10%) | 3/10 (30%) | 20 (54.0 to 14.0) | 0.07 |
Adult ICU Patients: Procalcitonin‐Guided Antibiotic Discontinuation
Five studies[19, 20, 21, 22, 23] (N=938) addressed procalcitonin‐guided discontinuation of antibiotic therapy in adult ICU patients. Four studies conducted superiority analyses for mortality with procalcitonin‐guided therapy, whereas 1 study conducted a noninferiority analysis. Absolute procalcitonin values for discontinuation of antibiotics ranged from 0.25 to 1 ng/mL. Physicians in control groups administered antibiotics according to their standard practice.
Antibiotic Usage
The absolute reduction in duration of antibiotic usage with procalcitonin guidance in these studies ranged from 1.7 to 5 days, and the relative reduction ranged from 21% to 38%. Meta‐analysis of antibiotic duration in adult ICU patients was performed (Figure 2A).

Morbidity
Procalcitonin‐guided antibiotic discontinuation did not increase morbidity, including ICU length of stay (LOS). Meta‐analysis of ICU LOS is displayed in Figure 2B. Limited data on adverse antibiotic events were reported (Table 2).
Mortality
There was no increase in mortality as a result of shorter duration of antibiotic therapy. Meta‐analysis of short‐term mortality (28‐day or in‐hospital mortality) showed a mortality difference of 0.43% favoring procalcitonin‐guided therapy, and a 95% confidence interval (CI) of 6% to 5% (Figure 2C).
Adult ICU Patients: Procalcitonin‐Guided Antibiotic Intensification
Two studies[24, 33] (N=1272) addressed procalcitonin‐guided intensification of antibiotic therapy in adult ICU patients. The Jensen et al. study[33] was a large (N=1200), high‐quality study that used a detailed algorithm for broadening antibiotic therapy in patients with elevated procalcitonin. The Jensen et al. study also educated physicians about empiric therapy and intensification of antibiotic therapy. A second study[24] was too small (N=72) and lacked sufficient details to be informative.
Antibiotic Usage
The Jensen et al. study found a 2‐day increase, or 50% relative increase, in the duration of antibiotic therapy and a 7.9% absolute increase (P=0.002) in the number of days on 3 antibiotics with procalcitonin‐guided intensification.
Morbidity
The Jensen et al. study showed a significant 1‐day increase in ICU LOS (P=0.004) and a significant increase in organ dysfunction. Specifically, patients had a highly statistically significant 5% increase in days on mechanical ventilation (P<0.0001) and 5% increase in days with abnormal renal function (P<0.0001).
Mortality
The Jensen et al. study was a superiority trial powered to test a 7.5% decrease in 28‐day mortality, but no significant difference in mortality was observed with procalcitonin‐guided intensification (31.5% vs 32.0, P=0.83).
Adult Patients With Respiratory Tract Infections
Eight studies[25, 26, 27, 28, 29, 30, 34, 35] (N=3492) addressed initiation and/or discontinuation of antibiotics in adult patients with acute upper and lower respiratory tract infections, including community‐acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease, and acute bronchitis. Settings included primary care clinics, emergency departments, and hospital wards. Physicians in control groups administered antibiotics according to their own standard practices and/or evidence‐based guidelines. All studies encouraged initiation of antibiotics with procalcitonin levels >0.25 ng/mL, and 4 studies strongly encouraged antibiotics with procalcitonin levels >0.5 ng/mL.
Antibiotic Usage
Procalcitonin guidance reduced antibiotic duration, antibiotic prescription rate, and total antibiotic exposure. Absolute reduction in antibiotic duration ranged from 1 to 7 days, and relative reductions ranged from 13% to 55%. Four of the 8 studies reported sufficient details to be pooled into a meta‐analysis (Figure 3A) with a statistically significant pooled mean difference of 2.35 days favoring procalcitonin (95% CI: 4.38 to 0.33). Procalcitonin guidance also reduced antibiotic prescription rate with absolute reductions ranging from 2% to 7% and relative reductions ranging from 1.8% to 72%. Meta‐analysis of prescription rates from 8 studies (Figure 3B) yielded a statistically significant pooled risk difference of 22% (95% CI: 41% to 4%). Total antibiotic exposure was consistently reduced in the 4 studies reporting this outcome.

Morbidity
Procalcitonin guidance did not increase hospital LOS or ICU admission rates. Meta‐analysis of ICU admission rates from 5 studies (Figure 3C) produced a risk difference of 1%, with a narrow 95% CI (4% to 1%). There was insufficient evidence to judge the effect on days of restricted activity or antibiotic adverse events.
Mortality
Procalcitonin guidance did not increase mortality, and meta‐analysis of 4 studies (Figure 3D) produced a risk difference of 0.3% with a narrow 95% CI (1% to 2%), with no statistical heterogeneity (I2=0%).
Neonates With Sepsis
One study[31] (N=121) evaluated procalcitonin‐guided antibiotic therapy for suspected neonatal sepsis. Neonatal sepsis was suspected on the basis of risk factors and clinical signs and symptoms. Antibiotic initiation or discontinuation was based on a procalcitonin nomogram. Antibiotic therapy in the control group was based on the physician's assessment. The quality of this study was rated good, and strength of evidence was rated moderate for antibiotic usage and insufficient for morbidity and mortality outcomes.
Antibiotic Usage
Duration of antibiotic therapy was decreased by 22.4 hours (P=0.012), a 24% relative reduction, and the proportion of neonates on antibiotics 72 hours was reduced by 27% (P=0.002). The largest reduction in antibiotic duration was seen in the 80% to 85% of neonates who were categorized as having possible or infection or unlikely to have infection.
Morbidity
A statistically insignificant 7% reduction in rate of recurrence of infection was seen with procalcitonin‐guided antibiotic therapy (P=0.45).
Mortality
No in‐hospital deaths occurred in either the procalcitonin or control group.
Children Ages 1 to 36 Months With Fever of Unknown Source
One study[36] (N=384) evaluated procalcitonin‐guided antibiotic therapy for fever of unknown source in children 1 to 36 months of age, but the overall strength of evidence was judged insufficient to draw conclusions.
Antibiotic Usage
A statistically insignificant reduction of 3.1% in antibiotic prescription rate was seen with procalcitonin‐guided antibiotic therapy (P=0.49).
Morbidity
Rate of hospitalization was relatively low, and no significant difference was seen between procalcitonin and control groups.
Mortality
In‐hospital mortality was reported as 0% in both arms.
Adult Postoperative Patients at Risk of Infection
One study[32] (N =250) monitored procalcitonin in consecutive patients after colorectal surgery to identify patients at risk of infection who might benefit from prophylactic antibiotic therapy. Two hundred thirty patients had normal procalcitonin levels. Twenty patients with elevated procalcitonin levels (>1.5 ng/mL) were randomized to receive prophylactic antibiotic therapy with ceftriaxone or no antibiotics. The strength of evidence was judged insufficient to draw conclusions from this study.
Antibiotic Usage
Duration of antibiotic therapy was reduced by 3.5% but was not statistically insignificant (P=0.27).
Morbidity
Procalcitonin guidance reduced the incidence of sepsis/systemic inflammatory response syndrome by 60% (p=0.007). The incidences of local and systemic infection were reduced with procalcitonin guidance but were not statistically significant (10%, P=0.53; and 40%, P=0.07, respectively).
Mortality
Mortality was 20% higher in the control arm but was not statistically significant (P=0.07).
DISCUSSION
Summary of the Main Findings
Diagnosis of sepsis or other serious infections in critically ill patients is challenging because clinical criteria for diagnosis overlap with noninfectious causes of the systemic inflammatory response syndrome. Initiation of antibiotic therapy for presumed sepsis is necessary while diagnostic evaluation is ongoing, because delaying antibiotic therapy is associated with increased mortality.[37, 38, 39] Our review found that procalcitonin guidance significantly reduced antibiotic usage in adult ICU patients by reducing the duration of antibiotic therapy, rather than decreasing the initiation of antibiotics, without increasing morbidity or mortality.
In contrast, the use of procalcitonin as an indicator of need for intensification of antibiotic therapy in adult ICU patients should be discouraged because this approach was associated with increased morbidity. The large, well‐designed study by Jensen[33] showed that antibiotic intensification in response to elevated procalcitonin measurement was associated with increased morbidity: a longer ICU LOS, an increase in days on mechanical ventilation, and an increase in days with abnormal renal function. The authors concluded that the increased morbidity could only be explained by clinical harms of increased exposure to broad‐spectrum antibiotics.
Clinical and microbiological evaluations are neither sensitive nor specific for differentiating bacterial from viral respiratory tract infections. Procalcitonin can guide initiation of antibiotic therapy in adults with suspected bacterial respiratory tract infection. Our review showed that procalcitonin guidance significantly reduced antibiotic usage with respect to antibiotic prescription rate, duration of antibiotic therapy, and total exposure to antibiotic therapy in adult patients with respiratory tract infections.
The role of procalcitonin‐guided therapy in other populations is less clear. One study in postoperative colorectal surgery patients reported that elevated procalcitonin levels may identify patients at risk for infection who benefit from prophylactic antibiotic therapy.[32] Patients with elevated procalcitonin levels who received prophylactic antibiotic therapy had a significant decrease in the incidence and severity of systemic infections, whereas patients with normal procalcitonin levels did not require any additional surgical or medical therapy. Although these findings are promising, more data in postoperative patients are needed.
The utility of procalcitonin in pediatric settings is a significant gap in the present literature. One study[31] in neonates with suspected sepsis showed a significant decrease in the proportion of neonates started on empiric antibiotic therapy and a decrease in the duration of antibiotic therapy with procalcitonin guidance. However, there was insufficient evidence that procalcitonin guidance does not increase morbidity or mortality.
Comparison to Other Systematic Reviews
Six systematic reviews of procalcitonin guidance in the management of patients with infections were published prior to our review.[9, 10, 11, 12, 13, 14] Our systematic review differs from past reviews in the number of studies included and the pooling of studies according to patient population, type and severity of infection, and different uses of procalcitonin measurements, either for initiation, discontinuation, or intensification of antibiotic therapy. Previous systematic reviews included 7 to 14 studies, whereas ours included 18 randomized, controlled trials. One previous review[13] included and pooled the Jensen et al. study[33] with other studies of adult ICU patients. We evaluated the Jensen et al. study separately because it uniquely looked at procalcitonin‐guided antibiotic intensification in adult ICU patients, in contrast to other studies that looked at procalcitonin‐guided antibiotic discontinuation. We addressed pediatric populations separately from adult patients, and recognizing that there are distinct groups within the pediatric population, we separately grouped neonates and children ages 1 to 36 months. Despite these differences, our review and other systematic reviews, we came to similar conclusions: procalcitonin‐guided antibiotic decision making compared to clinical criteria‐guided antibiotic decision making reduces antibiotic usage without increasing morbidity or mortality.
Limitations
An important limitation of this review was the uncertainty about the noninferiority margin for morbidity and mortality in adult ICU patients. Only the Bouadma et al. study[23] did a power analysis and predefined a margin for noninferiority for 28‐ and 60‐day mortality. Meta‐analysis of all 5 ICU studies showed a pooled point estimate of 0.43% in mortality and a 95% CI of 6% to 5% for difference in mortality between procalcitonin‐guided therapy versus standard care. A 10% noninferiority margin for mortality has been recommended by the Infectious Diseases Society of America and American College of Chest Physicians, but there is concern that a 10% margin for mortality may be too high. Presently, 2 large trials are in progress that may yield more precise estimates of mortality in the future.
Differences in reporting of total antibiotic exposure and morbidity outcomes limited our ability to pool data. Total antibiotic exposure is conventionally reported as mean days per 1000 days of follow‐up, but some studies only reported relative or absolute differences. Likewise, morbidity was reported with different severity of illness scales, including Sepsis‐Related Organ Failure Assessment, Simplified Acute Physiology (SAP) II, SAP III, and Acute Physiology and Chronic Health Evaluation II, which limited comparisons across studies.
Research Gaps
We identified gaps in the available literature and opportunities for future research. First, the safety and efficacy of procalcitonin‐guided antibiotic therapy needs to be studied in patient populations excluded from current randomized controlled studies, such as immunocompromised patients and pregnant women. Patients who are immunocompromised or have chronic conditions, such as cystic fibrosis, account for a significant percentage of community‐acquired respiratory tract infections and are often treated empirically.[29, 30] Second, standardized reporting of antibiotic adverse events and emergence of antibiotic resistance is needed. Strategies to reduce antibiotic usage have been associated with reductions in antibiotic adverse events, such as Clostridium difficile colitis and superinfection with multi‐drug resistant Gram‐negative bacteria.[37, 40, 41] Few studies in our review reported allergic reactions or adverse events of antibiotic therapy, [25, 27, 34] and only 1 reported antibiotic resistance.[19] Third, procalcitonin guidance should be compared to other strategies to reduce antibiotic usage, such as structured implementation of practice guidelines and antibiotic stewardship programs.[42] One single‐arm study describes how procalcitonin can be used in antibiotic stewardship programs to decrease the duration of antibiotic therapy,[43] but additional studies are needed. Finally, generalizing results from those studies that were conducted primarily in Europe would depend on similar use of and adherence to study‐based algorithms. Newer observational studies have demonstrated reduced antibiotic usage with implementation of procalcitonin algorithms in real‐life settings in Europe, but algorithm adherence was significantly less in the United States.[44, 45]
In summary, our systematic review found that procalcitonin‐guided antibiotic therapy can significantly reduce antibiotic usage in adult ICU patients without affecting morbidity or mortality. Procalcitonin should not be used to guide intensification of antibiotic therapy in adult ICU patients because this approach may increase morbidity. In adults with respiratory infections, procalcitonin guidance can significantly reduce antibiotic usage without adversely affecting morbidity or mortality. There is insufficient evidence to recommend procalcitonin‐guided antibiotic therapy in neonates with sepsis, children with fever of unknown source, or postoperative patients at risk for infection.
Acknowledgments
Disclosures: This project was funded under contract HHSA 2902007‐10058 from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services. The authors of this article are responsible for its content, including any clinical treatment recommendations. No statement in this article should be construed as an official position of AHRQ or of the US Department of Health and Human Services. There are no conflicts of interest reported by any of the authors.
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- Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012;(9):CD007498. , , , et al.
- Prepared by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence‐based Practice Center under contract no. 290–2007‐10058‐I. Procalcitonin‐guided antibiotic therapy. Comparative effectiveness review No. 78. AHRQ publication no. 12(13)‐EHC124‐EF. Rockville, MD: Agency for Healthcare Research and Quality. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm. Published Accessed October 2012. , , , , , .
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- Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. 2008;177(5):498–505. , , , , .
- Procalcitonin (PCT)‐guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg. 2009;394(2):221–226. , , , et al.
- Procalcitonin for reduced antibiotic exposure in ventilator‐associated pneumonia: a randomised study. Eur Respir J. 2009;34(6):1364–1375. , , , et al.
- Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care. 2009;13(3):R83. , , , et al.
- Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375(9713):463–474. , , , et al.
- Can procalcitonin help us in timing of re‐intervention in septic patients after multiple trauma or major surgery? Hepatogastroenterology. 2007;54(74):359–363. , , , , .
- Effect of procalcitonin‐based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059–1066. , , , et al.
- Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission—a randomized trial. Clin Microbiol Infect. 2009;15(5):481–487. , , , et al.
- Procalcitonin‐guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008;168(18):2000–2007; discussion 2007–2008. , , , et al.
- Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin‐guidance with standard therapy. Chest. 2007;131(1):9–19. , , , et al.
- Procalcitonin guidance of antibiotic therapy in community‐acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84–93. , , , et al.
- Effect of procalcitonin‐guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster‐randomised, single‐blinded intervention trial. Lancet. 2004;363(9409):600–607. , , , et al.
- Use of procalcitonin‐guided decision‐making to shorten antibiotic therapy in suspected neonatal early‐onset sepsis: prospective randomized intervention trial. Neonatology. 2010;97(2):165–174. , , , , .
- Pre‐emptive antibiotic treatment vs “standard” treatment in patients with elevated serum procalcitonin levels after elective colorectal surgery: a prospective randomised pilot study. Langenbecks Arch Surg. 2006;391(3):187–194. , , , , , .
- Procalcitonin‐guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med. 2011;39(9):2048–2058. , , , et al.
- Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J. 2010;36(3):601–607. , , , et al.
- Procalcitonin guidance for reduction of antibiotic use in low‐risk outpatients with community‐acquired pneumonia. Respirology. 2011;16(5):819–824. , , , , , .
- Impact of procalcitonin on the management of children aged 1 to 36 months presenting with fever without source: a randomized controlled trial. Am J Emerg Med. 2010;28(6):647–653. , , , , , .
- Experience with a clinical guideline for the treatment of ventilator‐associated pneumonia. Crit Care Med. 2001;29(6):1109–1115. , , , , , .
- Diagnostic value of procalcitonin, interleukin‐6, and interleukin‐8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164(3):396–402. , , , et al.
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- Use of procalcitonin (PCT) to guide discontinuation of antibiotic use in an unspecified sepsis is an antimicrobial stewardship program (ASP). Eur J Clin Microbiol Infect Dis. 2011;30(7):853–855. , , , , .
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Many serum biomarkers have been identified in recent years with a wide range of potential applications, including diagnosis of local and systemic infections, differentiation of bacterial and fungal infections from viral syndromes or noninfectious conditions, prognostic stratification of patients, and enhanced management of antibiotic therapy. Currently, there are at least 178 serum biomarkers that have potential roles to guide antibiotic therapy, and among these, procalcitonin has been the most extensively studied biomarker.[1, 2]
Procalcitonin is the prohormone precursor of calcitonin that is expressed primarily in C cells of the thyroid gland. Conversion of procalcitonin to calcitonin is inhibited by various cytokines and bacterial endotoxins. Procalcitonin's primary diagnostic utility is thought to be in establishing the presence of bacterial infections, because serum procalcitonin levels rise and fall rapidly in bacterial infections.[3, 4, 5] In healthy individuals, procalcitonin levels are very low. In systemic infections, including sepsis, procalcitonin levels are generally greater than 0.5 to 2 ng/mL, but often reach levels 10 ng/mL, which correlates with severity of illness and a poor prognosis. In patients with respiratory tract infections, procalcitonin levels are less elevated, and a cutoff of 0.25 ng/mL seems to be most predictive of a bacterial respiratory tract infection requiring antibiotic therapy.[6, 7, 8] Procalcitonin levels decrease to <0.25 ng/mL as infection resolves, and a decline in procalcitonin level may guide decisions about discontinuation of antibiotic therapy.[5]
The purpose of this systematic review was to synthesize comparative studies examining the use of procalcitonin to guide antibiotic therapy in patients with suspected local or systemic infections in different patient populations. We are aware of 6 previously published systematic reviews evaluating the utility of procalcitonin guidance in the management of infections.[9, 10, 11, 12, 13, 14] Our systematic review included more studies and pooled patients into the most clinically similar groups compared to other systematic reviews.
METHODS
This review is based on a comparative effectiveness review prepared for the Agency for Healthcare Research and Quality's Effective Health Care Program.[15] A standard protocol consistent with the Methods Guide for Effectiveness and Comparative Effectiveness Reviews[16] was followed. A detailed description of the methods is available online (
Study Question
In selected populations of patients with suspected local or systemic infection, what are the effects of using procalcitonin measurement plus clinical criteria for infection to guide initiation, intensification, and/or discontinuation of antibiotic therapy when compared to clinical criteria for infection alone?
Search Strategy
MEDLINE and EMBASE were searched from January 1, 1990 through December 16, 2011, and the Cochrane Controlled Trials register was searched with no date restriction for randomized and nonrandomized comparative studies using the following search terms: procalcitonin AND chronic obstructive pulmonary disease; COPD; critical illness; critically ill; febrile neutropenia; ICU; intensive care; intensive care unit; postoperative complication(s); postoperative infection(s); postsurgical infection(s); sepsis; septic; surgical wound infection; systemic inflammatory response syndrome OR postoperative infection. In addition, a search for systematic reviews was conducted in MEDLINE, the Cochrane Database of Systematic Reviews, and Web sites of the National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme. Gray literature, including databases with regulatory information, clinical trial registries, abstracts and conference papers, grants and federally funded research, and manufacturing information was searched from January 1, 2006 to June 28, 2011.
Study Selection
A single reviewer screened abstracts and selected studies looking at procalcitonin‐guided antibiotic therapy. Second and third reviewers were consulted to screen articles when needed. Studies were included if they fulfilled all of the following criteria: (1) randomized, controlled trial or nonrandomized comparative study; (2) adult and/or pediatric patients with known or suspected local or systemic infection, including critically ill patients with sepsis syndrome or ventilator‐associated pneumonia, adults with respiratory tract infections, neonates with sepsis, children with fever of unknown source, and postoperative patients at risk of infection; (3) interventions included initiation, intensification, and/or discontinuation of antibiotic therapy guided by procalcitonin plus clinical criteria; (4) primary outcomes included antibiotic usage (antibiotic prescription rate, total antibiotic exposure, duration of antibiotic therapy, and days without antibiotic therapy); and (5) secondary outcomes included morbidity (antibiotic adverse events, hospital and/or intensive care unit length of stay), mortality, and quality of life.
Studies with any of the following criteria were excluded: published in non‐English language, not reporting primary data from original research, not a randomized, controlled trial or nonrandomized comparative study, not reporting relevant outcomes.
Data Extraction and Quality Assessment
A single reviewer abstracted data and a second reviewer confirmed accuracy. Disagreements between reviewers were resolved by group discussion among the research team and final quality rating was assigned by consensus adjudication. Data elements were abstracted into the following categories: quality assessment, applicability and clinical diversity assessment, and outcome assessment. Quality of included studies was assessed using the US Preventive Services Task Force framework[17] by at least 2 independent reviewers. Three quality categories were used: good, fair, and poor.
Data Synthesis and Analysis
The decision to incorporate formal data synthesis in this review was made after completing the formal literature search, and the decision to pool studies was based on the specific number of studies with similar questions and outcomes. If a meta‐analysis could be performed, subgroup and sensitivity analyses were based on clinical similarity of available studies and reporting of mean and standard deviation. The pooling method involved inverse variance weighting and a random effects model.
The strength of evidence was graded using the Methods Guide,[16] a system based on the Grading of Recommendations Assessment, Development and Evaluation Working Group.[18] The following domains were addressed: risk of bias, consistency, directness, and precision. The overall strength of evidence was graded as high, moderate, low, or insufficient. The final strength of evidence grading was made by consensus adjudication among the authors.
RESULTS
Of the 2000 studies identified through the literature search, 1986 were excluded and 14 studies[19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32] were included. Search of gray literature yielded 4 published studies.[33, 34, 35, 36] A total of 18 randomized, controlled trials comparing procalcitonin guidance to use of clinical criteria alone to manage antibiotic therapy in patients with infections were included. The PRISMA diagram (Figure 1) depicts the flow of search screening and study selection. We sought, but did not find, nonrandomized comparative studies of populations, comparisons, interventions, and outcomes that were not adequately studied in randomized, controlled trials.

Data were pooled into clinically similar groups that were reviewed separately: (1) adult intensive care unit (ICU) patients, including patients with ventilator‐associated pneumonia; (2) adult patients with respiratory tract infections; (3) neonates with suspected sepsis; (4) children between 1 to 36 months of age with fever of unknown source; and (5) postoperative patients at risk of infection. Tables summarizing study quality and outcome measures with strength of evidence are available online (
Outcome | Author, Year | N | PCT‐Guided Therapya | Controla | Difference PCT‐CTRL (95% CI) | P Value |
---|---|---|---|---|---|---|
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
ABT Duration, d | Hochreiter, 2009[22] | 110 | 5.9 | 7.9 | 2.0 (2.5 to 1.5) | <0.001 |
Nobre, 2008[19] | 79 | 66 | 9.5 (ITT), 10 (PP) | 2.6 (5.5 to 0.3), 3.2 (1.1 to5.4) | 0.15, 0.003 | |
Schroeder, 2009[20] | 27 | 6.6 | 8.3 | 1.7 (2.4 to 1.0) | <0.001 | |
Stolz, 2009[21] | 101 | 10 (616)b | 15 (1023)b | 5 | 0.049 | |
Bouadma, 2010[23] | 621 | 10.3 | 13.3 | 3.0 (4.20 to 1.80) | <0.0001 | |
Days without ABTs, day 28 | Nobre, 2008[19] | 79 | 15.3, 17.4 | 13, 13.6 | 2.3 (5.9 to 1.8), 3.8 (0.1 to 7.5)c | 0.28, 0.04 |
Stolz, 2009[21] | 101 | 13 (221)b | 9.5 (1.517)b | 3.5 | 0.049 | |
Bouadma, 2010[23] | 621 | 14.3 | 11.6 | 2.7 (1.4 to 4.1) | <0.001 | |
Total ABT exposured | Nobre, 2008[19] | 79 | 541 | 644 | 1.1e (0.9 to 1.3), 1.3e (1.1 to 1,5)c | 0.07, 0.0002 |
504 | 655 | |||||
Stolz, 2009[21] | 101 | 1077 | 1341 | |||
Bouadma, 2010[23]d | 621 | 653 | 812 | 159 (185 to 131) | <0.001 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
ABT duration, days | Jensen, 2011[33] | 1200 | 6 (311)b | 4 (310)b | NR | NR |
Days spent in ICU on 3 ABTs | Jensen, 2011[33] | 1200 | 3570/5447 (65.5%) | 2721/4717 (57.7%) | 7.9% (6.0 to 9.7) | 0.002 |
Adult patients with respiratory tract infections | ||||||
ABT duration, da | Schuetz, 2009[2][5] | 1359 | 5.7 | 8.7 | 3.0 | |
Christ‐Crain, 2004[30] | 243 | 10.9 | 12.8 | 1.9 (3.1 to 0.7) | 0.002 | |
Kristoffersen, 2009[26] | 210 | 5.1 | 6.8 | 1.7 | ||
Briel, 2008[27] | 458 | 6.2 | 7.1 | 1.0 (1.7 to 0.4) | <0.05 | |
Long, 20113[5] | 162 | 5 (36)f | 7 (59)f | 2.0 | <0.001 | |
Burkhardt, 2010[34] | 550 | 7.8 | 7.7 | 0.1 (0.7 to 0.9) | 0.8 | |
Christ‐Crain, 2006[29] | 302 | 5.8 | 12.9 | 7.1(8.4 to 5.8) | <0.0001 | |
Antibiotic prescription rate, % | Schuetz, 2009[2][5] | 1359 | 506/671 (75.4%) | 603/688 (87.6%) | 12.2% (16.3 to 8.1) | <0.05 |
Christ‐Crain, 2004[30] | 243 | 55/124 (44.4%) | 99/119 (83.2%) | 38.8% (49.9 to 27.8) | <0.0001 | |
Kristoffersen, 2009[26] | 210 | 88/103 (85.4%) | 85/107 (79.4%) | 6.0% (4.3 to 16.2) | 0.25 | |
Briel, 2008[27] | 458 | 58/232 (25.0%) | 219/226 (96.9%) | 72% (78 to 66) | <0.05 | |
Long, 20113[5] | 162 | NR (84.4%) | NR (97.5%) | 13.1% | 0.004 | |
Stolz, 2007[28] | 208 | 41/102 (40.2%) | 76/106 (71.7%) | 31.5% (44.3 to 18.7) | <0.0001 | |
Christ‐Crain, 2006[29] | 302 | 128/151 (84.8%) | 149/151 (98.79%) | 13.9% (19.9 to 7.9) | <0.0001 | |
Burkhardt, 2010[34] | 550 | 84/275 (30.5%) | 89/275 (32.4%) | 1.8% (9.6 to 5.9) | 0.701 | |
Total ABT exposure | Stolz, 2007[28] | 208 | NR | NR | 31.5% (18.7 to 44.3) | <0.0001 |
Long, 20113[5] | 162 | NR | NR | NR | ||
Christ‐Crain, 2006[29] | 302 | 136g | 323g | |||
Christ‐Crain, 2004[30] | 243 | 332g | 661g | |||
Neonates with sepsis | ||||||
ABTs 72 hours, % | Stocker, 2010[31] | All neonates (N=121) | 33/60 (55%) | 50/61 (82%) | 27.0 (42.8 to 11.1) | 0.002 |
Infection proven/probably (N=21) | 9/9 (100%) | 12/12 (100%) | 0% (0 to 0) | NA | ||
Infection possible (N=40) | 13/21 (61.9%) | 19/19 (100%) | 38.1 (58.9 to 17.3) | 0.003 | ||
Infection unlikely (N=60) | 11/30 (36.7%) | 19/30 (63.3%) | 26.6 (51.1 to 2.3) | 0.038 | ||
ABT duration, h | Stocker, 2010[31] | All neonates (N=121) | 79.1 | 101.5 | 22.4 | 0.012 |
Infection proven/probably (N=21) | 177.8 | 170.8 | 7 | NSS | ||
Infection possible (N=40) | 83.4 | 111.5 | 28.1 | <0.001 | ||
Infection unlikely (N=60) | 46.5 | 67.4 | 20.9 | 0.001 | ||
Children ages 136 months with fever of unknown source | ||||||
Antibiotic prescription rate, % | Manzano, 2010[36] | All children (N=384) | 48/192 (25%) | 54/192 (28.0%) | 3.1 (12.0 to 5.7) | 0.49 |
No SBI or neutropenia (N=312) | 14/158 (9%) | 16/154 (10%) | 1.5 (8.1 to 5.0) | 0.65 | ||
Adult postoperative patients at risk of infection | ||||||
ABT duration, d | Chromik, 2006[32] | All patients (N=20) | 5.5 | 9 | 3.5 | 0.27 |
Outcome | Author, Year | N | PCTa | Controla | Difference, PCT‐CTRL (95% CI) | P Value |
---|---|---|---|---|---|---|
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
ICU LOS, days | Hochreiter, 2009[22] | 110 | 15.5 | 17.7 | 2.2 | 0.046 |
Nobre, 2008[19] | 79 | 4 | 7 | 4.6 (8.2 to 1.0) | 0.02 | |
Schroeder, 2009[20] | 27 | 16.4 | 16.7 | 0.3 (5.6 to 5.0) | NSS | |
Bouadma, 2010[23] | 621 | 15.9 | 14.4 | 1.5 (0.9 to 3.1) | 0.23 | |
Hospital LOS, days | Nobre, 2008[19] | 79 | 17 | 23.5 | 2.5 (6.5 to 1.5) | 0.85 |
Stolz, 2009[21] | 101 | 26 (721)b | 26 (16.822.3)b | 0 | 0.15 | |
Bouadma, 2010[23] | 621 | 26.1 | 26.4 | 0.3 (3.2 to 2.7) | 0.87 | |
ICU‐free days alive, 128 | Stolz, 2009[21] | 101 | 10 (018)b | 8.5 (018)c | 1.5 | 0.53 |
SOFA day 28 | Bouadma, 2010[23] | 621 | 1.5 | 0.9 | 0.6 (0.0, 1.1) | 0.037 |
SOFA score max | Schroeder, 2009[20] | 27 | 7.3 | 8.3 | 8.1 (4.1 to 1.7) | NSS |
SAPS II score | Hochreiter, 2009[22] | 110 | 40.1 | 40.5 | 0.4 (6.4 to 5.6) | >0.05 |
Days without MV | Stolz, 2009[21] | 101 | 21 (224)b | 19 (8.522.5)b | 2.0 | 0.46 |
Bouadma, 2010[23] | 621 | 16.2 | 16.9 | 0.7 (2.4 to 1.1) | 0.47 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
ICU LOS, da | Svoboda, 2007[24] | 72 | 16.1 | 19.4 | 3.3 (7.0 to 0.4) | 0.09 |
Jensen, 2011[33] | 1200 | 6 (312)b | 5 (311)b | 1 | 0.004 | |
SOFA scorea | Svoboda, 2007[24] | 72 | 7.9 | 9.3 | 1.4 (2.8 to 0.0) | 0.06 |
Days on MVa | Svoboda, 2007[24] | 72 | 10.3 | 13.9 | 3.6 (7.6 to 0.4) | 0.08 |
Jensen, 2011[33] | 1200 | 3569 (65.5%) | 2861 (60.7%) | 4.9% (3 to 6.7) | <0.0001 | |
Percent days in ICU with GFR <60 | Jensen, 2011[33] | 1200 | 2796 (51.3%) | 2187 (46.4%) | 5.0 % (3.0 to 6.9) | <0.0001 |
Adult patients with respiratory tract infections | ||||||
Hospital LOS, da | Schuetz, 2009[2][5] | 1359 | 9.4 | 9.2 | 0.2 | |
Christ‐Crain, 2004[30] | 224 | 10.78.9 | 11.210.6 | 0.5 (3.0 to 2.0) | 0.69 | |
Kristoffersen, 2009[26] | 210 | 5.9 | 6.7 | 0.8 | 0.22 | |
Stolz, 2007[28] | 208 | 9 (115)b | 10 (115)b | 1 | 0.96 | |
Christ‐Crain, 2006[29] | 302 | 12.09.1 | 13.09.0 | 1 (3.0 to 1.0) | 0.34 | |
ICU admission, % | Schuetz, 2009[2][5] | 1359 | 43/671 (6.4%) | 60/688 (8.7%) | 2.3% (5.2 to 0.4) | 0.12 |
Christ‐Crain, 2004[30] | 224 | 5/124 (4.0%) | 6/119 (5.0%) | 1.0% (6.2 to 4.2) | 0.71 | |
Kristoffersen, 2009[26] | 210 | 7/103 (6.8%) | 5/107 (4.7%) | 2.1% (4.2 to 8.4) | 0.51 | |
Stolz, 2007[28] | 208 | 8/102 (7.8%) | 11/106 (10.4%) | 2.5% (10.3 to 5.3) | 0.53 | |
Christ‐Crain, 2006[29] | 302 | 20/151 (13.2%) | 21/151 (13.94%) | 0.7% (8.4 to 7.1) | 0.87 | |
Antibiotic adverse events | Schuetz, 2009[2][5]c | 1359 | 133/671 (19.8%) | 193/688 (28.1%) | 8.2% (12.7 to 3.7) | |
Briel, 2008[27]d | 458 | 2.34.6 days | 3.66.1 days | 1.1 days (2.1 to 0.1) | <0.05 | |
Burkhardt, 2010[34]e | 550 | 11 /59 (18.6%) | 16/101 (15.8%) | 2.8% (9.4 to 15.0) | 0.65 | |
Restricted activity, df | Briel, 2008[27] | 458 | 8.73.9 | 8.63.9 | 0.2 (0.4 to 0.9) | >0.05 |
Burkhardt, 2010[34] | 550 | 9.1 | 8.8 | 0.25 (0.52 to 1.03) | >0.05 | |
Neonates with sepsis | ||||||
Recurrence of infection | Stocker, 2010[31] | 121 | 32% | 39% | 7 | 0.45 |
Children ages 136 months with fever of unknown source | ||||||
Hospitalization rate | Manzano, 2010[36] | All children (N=384) | 50/192 (26%) | 48/192 (25%) | 1 (8 to 10) | 0.81 |
No SBI or neutropenia (N=312) | 16/158 (10%) | 11/154 (7%) | 3 (3 to 10) | 0.34 | ||
Adult postoperative patients at risk of infection | ||||||
Hospital LOS, days | Chromik, 2006[32] | 20 | 18 | 30 | 12 | 0.057 |
Local wound infection, % | Chromik, 2006[32] | 20 | 1/10 | 2/10 | 10 (41.0 to 21.0) | 0.53 |
Systemic infection, % | Chromik, 2006[32] | 20 | 3/10 | 7/10 | 40.0 (80.2 to 0.2) | 0.07 |
Sepsis/SIRS, % | Chromik, 2006[32] | 20 | 2/10 | 8/10 | 60.0 (95.1 to 24.9) | 0.007 |
Mortality | Mortality | Difference | ||||
---|---|---|---|---|---|---|
Outcome | Author, Year | N | PCT‐Guided Therapy | Control | PCT‐CTRL (95% CI) | P Value |
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
28‐day mortality | Nobre, 2008[19] | 79 | 8/39 (20.5%) | 8/40 (20.0%) | 0.5 (17.2 to 18.2), | 0.95 |
5/31 (16.1%) | 6/37 (16.2%) | 0.1 (17.7 to 17.5)a | 0.99 | |||
Stolz, 2009[21] | 101 | 8/51 (15.7%) | 12/50 (24.0%) | 8.3 (23.8 to 7.2) | 0.29 | |
Bouadma, 2010[23] | 621 | 65/307 (21.2%) | 64/314 (20.4%) | 0.8 (5.6 to 7.2) | 0.81 | |
60‐day mortality | Bouadma, 2010[23] | 621 | 92/307 (30.0%) | 82/314 (26.1%) | 3.9 (3.2 to 10.9) | 0.29 |
In‐hospital mortality | Nobre, 2008[19] | 79 | 9/39 (23.1%) | 9/40 (22.5%) | 0.6 (17.9 to 19.1) | 0.95 |
6/31 (19.4%) | 7/37 (18.9%) | 0.4+ (18.3 to 19.2) | 0.96 | |||
Stolz, 2009[21] | 101 | 10/51 (19.6%) | 14/50 (28.0%) | 8.4, (24.9 to 8.1) | 0.32 | |
Hochreiter, 2009[22] | 110 | 15/57 (26.3%) | 14/53 (26.4%) | 0.1, (16.6 to 16.4) | 0.99 | |
Schroeder, 2009[20] | 27 | 3/14 (21.4%) | 3/13 (23.1%) | 1.7, (33.1 to 29.8) | 0.92 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
28‐day mortality | Svoboda, 2007[24] | 72 | 10/38 (26.3%) | 13/34 (38.2%) | 11.9 (33.4 to 9.6) | 0.28 |
28‐day mortality | Jensen, 2011[33] | 1200 | 190/604 (31.5%) | 191/596 (32.0%) | 0.6 (4.7 to 5.9) | 0.83 |
Adult patients with respiratory tract infections | ||||||
6‐month mortality | Stolz, 2007[28] | 208 | 5/102 (4.9%) | 9/106 (8.5%) | 3.6% (10.3 to 3.2%) | 0.30 |
6‐week mortality | Christ‐Crain, 2006[29] | 302 | 18/151 (11.9%) | 20/151 (13.2%) | 1.3% (8.8 to 6.2) | 0.73 |
28‐day mortality | Christ‐Crain, 2004[30] | 243 | 4/124(3.2%) | 4/119 (3.4%) | 0.1% (4.6 to 4.4) | 0.95 |
Schuetz, 2009 (30‐day)[25] | 1359 | 34/671(5.1%) | 33/688(4.8%) | 0.3% (2.1 to 2.5) | 0.82 | |
Briel, 2008[27] | 458 | 0/231(0%) | 1/224 (0.4%) | 0.4% (1.3 to 0.4) | 0.31 | |
Burkhardt, 2010[34] | 550 | 0/275(0%) | 0/275 (0%) | 0 | ||
Kristoffersen, 2009[26] | 210 | 2/103(1.9%) | 1/107 (0.9%) | 1.0% (2.2 to 4.2) | 0.54 | |
Long, 20113[5] | 162 | 0/81 (0%) | 0/81 (0%) | 0 | ||
Neonates with sepsis | ||||||
Mortality (in‐hospital) | Stocker, 2010[31] | 121 | 0% | 0% | 0 (0 to 0) | NA |
Children ages 136 months with fever of unknown source | ||||||
Mortality | Manzano, 2010[36] | 384 | All children | 0% | 0% | 0 (0 to 0) |
Adult postoperative patients at risk of infection | ||||||
Mortality | Chromik, 2006[32] | 20 | 1/10 (10%) | 3/10 (30%) | 20 (54.0 to 14.0) | 0.07 |
Adult ICU Patients: Procalcitonin‐Guided Antibiotic Discontinuation
Five studies[19, 20, 21, 22, 23] (N=938) addressed procalcitonin‐guided discontinuation of antibiotic therapy in adult ICU patients. Four studies conducted superiority analyses for mortality with procalcitonin‐guided therapy, whereas 1 study conducted a noninferiority analysis. Absolute procalcitonin values for discontinuation of antibiotics ranged from 0.25 to 1 ng/mL. Physicians in control groups administered antibiotics according to their standard practice.
Antibiotic Usage
The absolute reduction in duration of antibiotic usage with procalcitonin guidance in these studies ranged from 1.7 to 5 days, and the relative reduction ranged from 21% to 38%. Meta‐analysis of antibiotic duration in adult ICU patients was performed (Figure 2A).

Morbidity
Procalcitonin‐guided antibiotic discontinuation did not increase morbidity, including ICU length of stay (LOS). Meta‐analysis of ICU LOS is displayed in Figure 2B. Limited data on adverse antibiotic events were reported (Table 2).
Mortality
There was no increase in mortality as a result of shorter duration of antibiotic therapy. Meta‐analysis of short‐term mortality (28‐day or in‐hospital mortality) showed a mortality difference of 0.43% favoring procalcitonin‐guided therapy, and a 95% confidence interval (CI) of 6% to 5% (Figure 2C).
Adult ICU Patients: Procalcitonin‐Guided Antibiotic Intensification
Two studies[24, 33] (N=1272) addressed procalcitonin‐guided intensification of antibiotic therapy in adult ICU patients. The Jensen et al. study[33] was a large (N=1200), high‐quality study that used a detailed algorithm for broadening antibiotic therapy in patients with elevated procalcitonin. The Jensen et al. study also educated physicians about empiric therapy and intensification of antibiotic therapy. A second study[24] was too small (N=72) and lacked sufficient details to be informative.
Antibiotic Usage
The Jensen et al. study found a 2‐day increase, or 50% relative increase, in the duration of antibiotic therapy and a 7.9% absolute increase (P=0.002) in the number of days on 3 antibiotics with procalcitonin‐guided intensification.
Morbidity
The Jensen et al. study showed a significant 1‐day increase in ICU LOS (P=0.004) and a significant increase in organ dysfunction. Specifically, patients had a highly statistically significant 5% increase in days on mechanical ventilation (P<0.0001) and 5% increase in days with abnormal renal function (P<0.0001).
Mortality
The Jensen et al. study was a superiority trial powered to test a 7.5% decrease in 28‐day mortality, but no significant difference in mortality was observed with procalcitonin‐guided intensification (31.5% vs 32.0, P=0.83).
Adult Patients With Respiratory Tract Infections
Eight studies[25, 26, 27, 28, 29, 30, 34, 35] (N=3492) addressed initiation and/or discontinuation of antibiotics in adult patients with acute upper and lower respiratory tract infections, including community‐acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease, and acute bronchitis. Settings included primary care clinics, emergency departments, and hospital wards. Physicians in control groups administered antibiotics according to their own standard practices and/or evidence‐based guidelines. All studies encouraged initiation of antibiotics with procalcitonin levels >0.25 ng/mL, and 4 studies strongly encouraged antibiotics with procalcitonin levels >0.5 ng/mL.
Antibiotic Usage
Procalcitonin guidance reduced antibiotic duration, antibiotic prescription rate, and total antibiotic exposure. Absolute reduction in antibiotic duration ranged from 1 to 7 days, and relative reductions ranged from 13% to 55%. Four of the 8 studies reported sufficient details to be pooled into a meta‐analysis (Figure 3A) with a statistically significant pooled mean difference of 2.35 days favoring procalcitonin (95% CI: 4.38 to 0.33). Procalcitonin guidance also reduced antibiotic prescription rate with absolute reductions ranging from 2% to 7% and relative reductions ranging from 1.8% to 72%. Meta‐analysis of prescription rates from 8 studies (Figure 3B) yielded a statistically significant pooled risk difference of 22% (95% CI: 41% to 4%). Total antibiotic exposure was consistently reduced in the 4 studies reporting this outcome.

Morbidity
Procalcitonin guidance did not increase hospital LOS or ICU admission rates. Meta‐analysis of ICU admission rates from 5 studies (Figure 3C) produced a risk difference of 1%, with a narrow 95% CI (4% to 1%). There was insufficient evidence to judge the effect on days of restricted activity or antibiotic adverse events.
Mortality
Procalcitonin guidance did not increase mortality, and meta‐analysis of 4 studies (Figure 3D) produced a risk difference of 0.3% with a narrow 95% CI (1% to 2%), with no statistical heterogeneity (I2=0%).
Neonates With Sepsis
One study[31] (N=121) evaluated procalcitonin‐guided antibiotic therapy for suspected neonatal sepsis. Neonatal sepsis was suspected on the basis of risk factors and clinical signs and symptoms. Antibiotic initiation or discontinuation was based on a procalcitonin nomogram. Antibiotic therapy in the control group was based on the physician's assessment. The quality of this study was rated good, and strength of evidence was rated moderate for antibiotic usage and insufficient for morbidity and mortality outcomes.
Antibiotic Usage
Duration of antibiotic therapy was decreased by 22.4 hours (P=0.012), a 24% relative reduction, and the proportion of neonates on antibiotics 72 hours was reduced by 27% (P=0.002). The largest reduction in antibiotic duration was seen in the 80% to 85% of neonates who were categorized as having possible or infection or unlikely to have infection.
Morbidity
A statistically insignificant 7% reduction in rate of recurrence of infection was seen with procalcitonin‐guided antibiotic therapy (P=0.45).
Mortality
No in‐hospital deaths occurred in either the procalcitonin or control group.
Children Ages 1 to 36 Months With Fever of Unknown Source
One study[36] (N=384) evaluated procalcitonin‐guided antibiotic therapy for fever of unknown source in children 1 to 36 months of age, but the overall strength of evidence was judged insufficient to draw conclusions.
Antibiotic Usage
A statistically insignificant reduction of 3.1% in antibiotic prescription rate was seen with procalcitonin‐guided antibiotic therapy (P=0.49).
Morbidity
Rate of hospitalization was relatively low, and no significant difference was seen between procalcitonin and control groups.
Mortality
In‐hospital mortality was reported as 0% in both arms.
Adult Postoperative Patients at Risk of Infection
One study[32] (N =250) monitored procalcitonin in consecutive patients after colorectal surgery to identify patients at risk of infection who might benefit from prophylactic antibiotic therapy. Two hundred thirty patients had normal procalcitonin levels. Twenty patients with elevated procalcitonin levels (>1.5 ng/mL) were randomized to receive prophylactic antibiotic therapy with ceftriaxone or no antibiotics. The strength of evidence was judged insufficient to draw conclusions from this study.
Antibiotic Usage
Duration of antibiotic therapy was reduced by 3.5% but was not statistically insignificant (P=0.27).
Morbidity
Procalcitonin guidance reduced the incidence of sepsis/systemic inflammatory response syndrome by 60% (p=0.007). The incidences of local and systemic infection were reduced with procalcitonin guidance but were not statistically significant (10%, P=0.53; and 40%, P=0.07, respectively).
Mortality
Mortality was 20% higher in the control arm but was not statistically significant (P=0.07).
DISCUSSION
Summary of the Main Findings
Diagnosis of sepsis or other serious infections in critically ill patients is challenging because clinical criteria for diagnosis overlap with noninfectious causes of the systemic inflammatory response syndrome. Initiation of antibiotic therapy for presumed sepsis is necessary while diagnostic evaluation is ongoing, because delaying antibiotic therapy is associated with increased mortality.[37, 38, 39] Our review found that procalcitonin guidance significantly reduced antibiotic usage in adult ICU patients by reducing the duration of antibiotic therapy, rather than decreasing the initiation of antibiotics, without increasing morbidity or mortality.
In contrast, the use of procalcitonin as an indicator of need for intensification of antibiotic therapy in adult ICU patients should be discouraged because this approach was associated with increased morbidity. The large, well‐designed study by Jensen[33] showed that antibiotic intensification in response to elevated procalcitonin measurement was associated with increased morbidity: a longer ICU LOS, an increase in days on mechanical ventilation, and an increase in days with abnormal renal function. The authors concluded that the increased morbidity could only be explained by clinical harms of increased exposure to broad‐spectrum antibiotics.
Clinical and microbiological evaluations are neither sensitive nor specific for differentiating bacterial from viral respiratory tract infections. Procalcitonin can guide initiation of antibiotic therapy in adults with suspected bacterial respiratory tract infection. Our review showed that procalcitonin guidance significantly reduced antibiotic usage with respect to antibiotic prescription rate, duration of antibiotic therapy, and total exposure to antibiotic therapy in adult patients with respiratory tract infections.
The role of procalcitonin‐guided therapy in other populations is less clear. One study in postoperative colorectal surgery patients reported that elevated procalcitonin levels may identify patients at risk for infection who benefit from prophylactic antibiotic therapy.[32] Patients with elevated procalcitonin levels who received prophylactic antibiotic therapy had a significant decrease in the incidence and severity of systemic infections, whereas patients with normal procalcitonin levels did not require any additional surgical or medical therapy. Although these findings are promising, more data in postoperative patients are needed.
The utility of procalcitonin in pediatric settings is a significant gap in the present literature. One study[31] in neonates with suspected sepsis showed a significant decrease in the proportion of neonates started on empiric antibiotic therapy and a decrease in the duration of antibiotic therapy with procalcitonin guidance. However, there was insufficient evidence that procalcitonin guidance does not increase morbidity or mortality.
Comparison to Other Systematic Reviews
Six systematic reviews of procalcitonin guidance in the management of patients with infections were published prior to our review.[9, 10, 11, 12, 13, 14] Our systematic review differs from past reviews in the number of studies included and the pooling of studies according to patient population, type and severity of infection, and different uses of procalcitonin measurements, either for initiation, discontinuation, or intensification of antibiotic therapy. Previous systematic reviews included 7 to 14 studies, whereas ours included 18 randomized, controlled trials. One previous review[13] included and pooled the Jensen et al. study[33] with other studies of adult ICU patients. We evaluated the Jensen et al. study separately because it uniquely looked at procalcitonin‐guided antibiotic intensification in adult ICU patients, in contrast to other studies that looked at procalcitonin‐guided antibiotic discontinuation. We addressed pediatric populations separately from adult patients, and recognizing that there are distinct groups within the pediatric population, we separately grouped neonates and children ages 1 to 36 months. Despite these differences, our review and other systematic reviews, we came to similar conclusions: procalcitonin‐guided antibiotic decision making compared to clinical criteria‐guided antibiotic decision making reduces antibiotic usage without increasing morbidity or mortality.
Limitations
An important limitation of this review was the uncertainty about the noninferiority margin for morbidity and mortality in adult ICU patients. Only the Bouadma et al. study[23] did a power analysis and predefined a margin for noninferiority for 28‐ and 60‐day mortality. Meta‐analysis of all 5 ICU studies showed a pooled point estimate of 0.43% in mortality and a 95% CI of 6% to 5% for difference in mortality between procalcitonin‐guided therapy versus standard care. A 10% noninferiority margin for mortality has been recommended by the Infectious Diseases Society of America and American College of Chest Physicians, but there is concern that a 10% margin for mortality may be too high. Presently, 2 large trials are in progress that may yield more precise estimates of mortality in the future.
Differences in reporting of total antibiotic exposure and morbidity outcomes limited our ability to pool data. Total antibiotic exposure is conventionally reported as mean days per 1000 days of follow‐up, but some studies only reported relative or absolute differences. Likewise, morbidity was reported with different severity of illness scales, including Sepsis‐Related Organ Failure Assessment, Simplified Acute Physiology (SAP) II, SAP III, and Acute Physiology and Chronic Health Evaluation II, which limited comparisons across studies.
Research Gaps
We identified gaps in the available literature and opportunities for future research. First, the safety and efficacy of procalcitonin‐guided antibiotic therapy needs to be studied in patient populations excluded from current randomized controlled studies, such as immunocompromised patients and pregnant women. Patients who are immunocompromised or have chronic conditions, such as cystic fibrosis, account for a significant percentage of community‐acquired respiratory tract infections and are often treated empirically.[29, 30] Second, standardized reporting of antibiotic adverse events and emergence of antibiotic resistance is needed. Strategies to reduce antibiotic usage have been associated with reductions in antibiotic adverse events, such as Clostridium difficile colitis and superinfection with multi‐drug resistant Gram‐negative bacteria.[37, 40, 41] Few studies in our review reported allergic reactions or adverse events of antibiotic therapy, [25, 27, 34] and only 1 reported antibiotic resistance.[19] Third, procalcitonin guidance should be compared to other strategies to reduce antibiotic usage, such as structured implementation of practice guidelines and antibiotic stewardship programs.[42] One single‐arm study describes how procalcitonin can be used in antibiotic stewardship programs to decrease the duration of antibiotic therapy,[43] but additional studies are needed. Finally, generalizing results from those studies that were conducted primarily in Europe would depend on similar use of and adherence to study‐based algorithms. Newer observational studies have demonstrated reduced antibiotic usage with implementation of procalcitonin algorithms in real‐life settings in Europe, but algorithm adherence was significantly less in the United States.[44, 45]
In summary, our systematic review found that procalcitonin‐guided antibiotic therapy can significantly reduce antibiotic usage in adult ICU patients without affecting morbidity or mortality. Procalcitonin should not be used to guide intensification of antibiotic therapy in adult ICU patients because this approach may increase morbidity. In adults with respiratory infections, procalcitonin guidance can significantly reduce antibiotic usage without adversely affecting morbidity or mortality. There is insufficient evidence to recommend procalcitonin‐guided antibiotic therapy in neonates with sepsis, children with fever of unknown source, or postoperative patients at risk for infection.
Acknowledgments
Disclosures: This project was funded under contract HHSA 2902007‐10058 from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services. The authors of this article are responsible for its content, including any clinical treatment recommendations. No statement in this article should be construed as an official position of AHRQ or of the US Department of Health and Human Services. There are no conflicts of interest reported by any of the authors.
Many serum biomarkers have been identified in recent years with a wide range of potential applications, including diagnosis of local and systemic infections, differentiation of bacterial and fungal infections from viral syndromes or noninfectious conditions, prognostic stratification of patients, and enhanced management of antibiotic therapy. Currently, there are at least 178 serum biomarkers that have potential roles to guide antibiotic therapy, and among these, procalcitonin has been the most extensively studied biomarker.[1, 2]
Procalcitonin is the prohormone precursor of calcitonin that is expressed primarily in C cells of the thyroid gland. Conversion of procalcitonin to calcitonin is inhibited by various cytokines and bacterial endotoxins. Procalcitonin's primary diagnostic utility is thought to be in establishing the presence of bacterial infections, because serum procalcitonin levels rise and fall rapidly in bacterial infections.[3, 4, 5] In healthy individuals, procalcitonin levels are very low. In systemic infections, including sepsis, procalcitonin levels are generally greater than 0.5 to 2 ng/mL, but often reach levels 10 ng/mL, which correlates with severity of illness and a poor prognosis. In patients with respiratory tract infections, procalcitonin levels are less elevated, and a cutoff of 0.25 ng/mL seems to be most predictive of a bacterial respiratory tract infection requiring antibiotic therapy.[6, 7, 8] Procalcitonin levels decrease to <0.25 ng/mL as infection resolves, and a decline in procalcitonin level may guide decisions about discontinuation of antibiotic therapy.[5]
The purpose of this systematic review was to synthesize comparative studies examining the use of procalcitonin to guide antibiotic therapy in patients with suspected local or systemic infections in different patient populations. We are aware of 6 previously published systematic reviews evaluating the utility of procalcitonin guidance in the management of infections.[9, 10, 11, 12, 13, 14] Our systematic review included more studies and pooled patients into the most clinically similar groups compared to other systematic reviews.
METHODS
This review is based on a comparative effectiveness review prepared for the Agency for Healthcare Research and Quality's Effective Health Care Program.[15] A standard protocol consistent with the Methods Guide for Effectiveness and Comparative Effectiveness Reviews[16] was followed. A detailed description of the methods is available online (
Study Question
In selected populations of patients with suspected local or systemic infection, what are the effects of using procalcitonin measurement plus clinical criteria for infection to guide initiation, intensification, and/or discontinuation of antibiotic therapy when compared to clinical criteria for infection alone?
Search Strategy
MEDLINE and EMBASE were searched from January 1, 1990 through December 16, 2011, and the Cochrane Controlled Trials register was searched with no date restriction for randomized and nonrandomized comparative studies using the following search terms: procalcitonin AND chronic obstructive pulmonary disease; COPD; critical illness; critically ill; febrile neutropenia; ICU; intensive care; intensive care unit; postoperative complication(s); postoperative infection(s); postsurgical infection(s); sepsis; septic; surgical wound infection; systemic inflammatory response syndrome OR postoperative infection. In addition, a search for systematic reviews was conducted in MEDLINE, the Cochrane Database of Systematic Reviews, and Web sites of the National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme. Gray literature, including databases with regulatory information, clinical trial registries, abstracts and conference papers, grants and federally funded research, and manufacturing information was searched from January 1, 2006 to June 28, 2011.
Study Selection
A single reviewer screened abstracts and selected studies looking at procalcitonin‐guided antibiotic therapy. Second and third reviewers were consulted to screen articles when needed. Studies were included if they fulfilled all of the following criteria: (1) randomized, controlled trial or nonrandomized comparative study; (2) adult and/or pediatric patients with known or suspected local or systemic infection, including critically ill patients with sepsis syndrome or ventilator‐associated pneumonia, adults with respiratory tract infections, neonates with sepsis, children with fever of unknown source, and postoperative patients at risk of infection; (3) interventions included initiation, intensification, and/or discontinuation of antibiotic therapy guided by procalcitonin plus clinical criteria; (4) primary outcomes included antibiotic usage (antibiotic prescription rate, total antibiotic exposure, duration of antibiotic therapy, and days without antibiotic therapy); and (5) secondary outcomes included morbidity (antibiotic adverse events, hospital and/or intensive care unit length of stay), mortality, and quality of life.
Studies with any of the following criteria were excluded: published in non‐English language, not reporting primary data from original research, not a randomized, controlled trial or nonrandomized comparative study, not reporting relevant outcomes.
Data Extraction and Quality Assessment
A single reviewer abstracted data and a second reviewer confirmed accuracy. Disagreements between reviewers were resolved by group discussion among the research team and final quality rating was assigned by consensus adjudication. Data elements were abstracted into the following categories: quality assessment, applicability and clinical diversity assessment, and outcome assessment. Quality of included studies was assessed using the US Preventive Services Task Force framework[17] by at least 2 independent reviewers. Three quality categories were used: good, fair, and poor.
Data Synthesis and Analysis
The decision to incorporate formal data synthesis in this review was made after completing the formal literature search, and the decision to pool studies was based on the specific number of studies with similar questions and outcomes. If a meta‐analysis could be performed, subgroup and sensitivity analyses were based on clinical similarity of available studies and reporting of mean and standard deviation. The pooling method involved inverse variance weighting and a random effects model.
The strength of evidence was graded using the Methods Guide,[16] a system based on the Grading of Recommendations Assessment, Development and Evaluation Working Group.[18] The following domains were addressed: risk of bias, consistency, directness, and precision. The overall strength of evidence was graded as high, moderate, low, or insufficient. The final strength of evidence grading was made by consensus adjudication among the authors.
RESULTS
Of the 2000 studies identified through the literature search, 1986 were excluded and 14 studies[19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32] were included. Search of gray literature yielded 4 published studies.[33, 34, 35, 36] A total of 18 randomized, controlled trials comparing procalcitonin guidance to use of clinical criteria alone to manage antibiotic therapy in patients with infections were included. The PRISMA diagram (Figure 1) depicts the flow of search screening and study selection. We sought, but did not find, nonrandomized comparative studies of populations, comparisons, interventions, and outcomes that were not adequately studied in randomized, controlled trials.

Data were pooled into clinically similar groups that were reviewed separately: (1) adult intensive care unit (ICU) patients, including patients with ventilator‐associated pneumonia; (2) adult patients with respiratory tract infections; (3) neonates with suspected sepsis; (4) children between 1 to 36 months of age with fever of unknown source; and (5) postoperative patients at risk of infection. Tables summarizing study quality and outcome measures with strength of evidence are available online (
Outcome | Author, Year | N | PCT‐Guided Therapya | Controla | Difference PCT‐CTRL (95% CI) | P Value |
---|---|---|---|---|---|---|
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
ABT Duration, d | Hochreiter, 2009[22] | 110 | 5.9 | 7.9 | 2.0 (2.5 to 1.5) | <0.001 |
Nobre, 2008[19] | 79 | 66 | 9.5 (ITT), 10 (PP) | 2.6 (5.5 to 0.3), 3.2 (1.1 to5.4) | 0.15, 0.003 | |
Schroeder, 2009[20] | 27 | 6.6 | 8.3 | 1.7 (2.4 to 1.0) | <0.001 | |
Stolz, 2009[21] | 101 | 10 (616)b | 15 (1023)b | 5 | 0.049 | |
Bouadma, 2010[23] | 621 | 10.3 | 13.3 | 3.0 (4.20 to 1.80) | <0.0001 | |
Days without ABTs, day 28 | Nobre, 2008[19] | 79 | 15.3, 17.4 | 13, 13.6 | 2.3 (5.9 to 1.8), 3.8 (0.1 to 7.5)c | 0.28, 0.04 |
Stolz, 2009[21] | 101 | 13 (221)b | 9.5 (1.517)b | 3.5 | 0.049 | |
Bouadma, 2010[23] | 621 | 14.3 | 11.6 | 2.7 (1.4 to 4.1) | <0.001 | |
Total ABT exposured | Nobre, 2008[19] | 79 | 541 | 644 | 1.1e (0.9 to 1.3), 1.3e (1.1 to 1,5)c | 0.07, 0.0002 |
504 | 655 | |||||
Stolz, 2009[21] | 101 | 1077 | 1341 | |||
Bouadma, 2010[23]d | 621 | 653 | 812 | 159 (185 to 131) | <0.001 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
ABT duration, days | Jensen, 2011[33] | 1200 | 6 (311)b | 4 (310)b | NR | NR |
Days spent in ICU on 3 ABTs | Jensen, 2011[33] | 1200 | 3570/5447 (65.5%) | 2721/4717 (57.7%) | 7.9% (6.0 to 9.7) | 0.002 |
Adult patients with respiratory tract infections | ||||||
ABT duration, da | Schuetz, 2009[2][5] | 1359 | 5.7 | 8.7 | 3.0 | |
Christ‐Crain, 2004[30] | 243 | 10.9 | 12.8 | 1.9 (3.1 to 0.7) | 0.002 | |
Kristoffersen, 2009[26] | 210 | 5.1 | 6.8 | 1.7 | ||
Briel, 2008[27] | 458 | 6.2 | 7.1 | 1.0 (1.7 to 0.4) | <0.05 | |
Long, 20113[5] | 162 | 5 (36)f | 7 (59)f | 2.0 | <0.001 | |
Burkhardt, 2010[34] | 550 | 7.8 | 7.7 | 0.1 (0.7 to 0.9) | 0.8 | |
Christ‐Crain, 2006[29] | 302 | 5.8 | 12.9 | 7.1(8.4 to 5.8) | <0.0001 | |
Antibiotic prescription rate, % | Schuetz, 2009[2][5] | 1359 | 506/671 (75.4%) | 603/688 (87.6%) | 12.2% (16.3 to 8.1) | <0.05 |
Christ‐Crain, 2004[30] | 243 | 55/124 (44.4%) | 99/119 (83.2%) | 38.8% (49.9 to 27.8) | <0.0001 | |
Kristoffersen, 2009[26] | 210 | 88/103 (85.4%) | 85/107 (79.4%) | 6.0% (4.3 to 16.2) | 0.25 | |
Briel, 2008[27] | 458 | 58/232 (25.0%) | 219/226 (96.9%) | 72% (78 to 66) | <0.05 | |
Long, 20113[5] | 162 | NR (84.4%) | NR (97.5%) | 13.1% | 0.004 | |
Stolz, 2007[28] | 208 | 41/102 (40.2%) | 76/106 (71.7%) | 31.5% (44.3 to 18.7) | <0.0001 | |
Christ‐Crain, 2006[29] | 302 | 128/151 (84.8%) | 149/151 (98.79%) | 13.9% (19.9 to 7.9) | <0.0001 | |
Burkhardt, 2010[34] | 550 | 84/275 (30.5%) | 89/275 (32.4%) | 1.8% (9.6 to 5.9) | 0.701 | |
Total ABT exposure | Stolz, 2007[28] | 208 | NR | NR | 31.5% (18.7 to 44.3) | <0.0001 |
Long, 20113[5] | 162 | NR | NR | NR | ||
Christ‐Crain, 2006[29] | 302 | 136g | 323g | |||
Christ‐Crain, 2004[30] | 243 | 332g | 661g | |||
Neonates with sepsis | ||||||
ABTs 72 hours, % | Stocker, 2010[31] | All neonates (N=121) | 33/60 (55%) | 50/61 (82%) | 27.0 (42.8 to 11.1) | 0.002 |
Infection proven/probably (N=21) | 9/9 (100%) | 12/12 (100%) | 0% (0 to 0) | NA | ||
Infection possible (N=40) | 13/21 (61.9%) | 19/19 (100%) | 38.1 (58.9 to 17.3) | 0.003 | ||
Infection unlikely (N=60) | 11/30 (36.7%) | 19/30 (63.3%) | 26.6 (51.1 to 2.3) | 0.038 | ||
ABT duration, h | Stocker, 2010[31] | All neonates (N=121) | 79.1 | 101.5 | 22.4 | 0.012 |
Infection proven/probably (N=21) | 177.8 | 170.8 | 7 | NSS | ||
Infection possible (N=40) | 83.4 | 111.5 | 28.1 | <0.001 | ||
Infection unlikely (N=60) | 46.5 | 67.4 | 20.9 | 0.001 | ||
Children ages 136 months with fever of unknown source | ||||||
Antibiotic prescription rate, % | Manzano, 2010[36] | All children (N=384) | 48/192 (25%) | 54/192 (28.0%) | 3.1 (12.0 to 5.7) | 0.49 |
No SBI or neutropenia (N=312) | 14/158 (9%) | 16/154 (10%) | 1.5 (8.1 to 5.0) | 0.65 | ||
Adult postoperative patients at risk of infection | ||||||
ABT duration, d | Chromik, 2006[32] | All patients (N=20) | 5.5 | 9 | 3.5 | 0.27 |
Outcome | Author, Year | N | PCTa | Controla | Difference, PCT‐CTRL (95% CI) | P Value |
---|---|---|---|---|---|---|
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
ICU LOS, days | Hochreiter, 2009[22] | 110 | 15.5 | 17.7 | 2.2 | 0.046 |
Nobre, 2008[19] | 79 | 4 | 7 | 4.6 (8.2 to 1.0) | 0.02 | |
Schroeder, 2009[20] | 27 | 16.4 | 16.7 | 0.3 (5.6 to 5.0) | NSS | |
Bouadma, 2010[23] | 621 | 15.9 | 14.4 | 1.5 (0.9 to 3.1) | 0.23 | |
Hospital LOS, days | Nobre, 2008[19] | 79 | 17 | 23.5 | 2.5 (6.5 to 1.5) | 0.85 |
Stolz, 2009[21] | 101 | 26 (721)b | 26 (16.822.3)b | 0 | 0.15 | |
Bouadma, 2010[23] | 621 | 26.1 | 26.4 | 0.3 (3.2 to 2.7) | 0.87 | |
ICU‐free days alive, 128 | Stolz, 2009[21] | 101 | 10 (018)b | 8.5 (018)c | 1.5 | 0.53 |
SOFA day 28 | Bouadma, 2010[23] | 621 | 1.5 | 0.9 | 0.6 (0.0, 1.1) | 0.037 |
SOFA score max | Schroeder, 2009[20] | 27 | 7.3 | 8.3 | 8.1 (4.1 to 1.7) | NSS |
SAPS II score | Hochreiter, 2009[22] | 110 | 40.1 | 40.5 | 0.4 (6.4 to 5.6) | >0.05 |
Days without MV | Stolz, 2009[21] | 101 | 21 (224)b | 19 (8.522.5)b | 2.0 | 0.46 |
Bouadma, 2010[23] | 621 | 16.2 | 16.9 | 0.7 (2.4 to 1.1) | 0.47 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
ICU LOS, da | Svoboda, 2007[24] | 72 | 16.1 | 19.4 | 3.3 (7.0 to 0.4) | 0.09 |
Jensen, 2011[33] | 1200 | 6 (312)b | 5 (311)b | 1 | 0.004 | |
SOFA scorea | Svoboda, 2007[24] | 72 | 7.9 | 9.3 | 1.4 (2.8 to 0.0) | 0.06 |
Days on MVa | Svoboda, 2007[24] | 72 | 10.3 | 13.9 | 3.6 (7.6 to 0.4) | 0.08 |
Jensen, 2011[33] | 1200 | 3569 (65.5%) | 2861 (60.7%) | 4.9% (3 to 6.7) | <0.0001 | |
Percent days in ICU with GFR <60 | Jensen, 2011[33] | 1200 | 2796 (51.3%) | 2187 (46.4%) | 5.0 % (3.0 to 6.9) | <0.0001 |
Adult patients with respiratory tract infections | ||||||
Hospital LOS, da | Schuetz, 2009[2][5] | 1359 | 9.4 | 9.2 | 0.2 | |
Christ‐Crain, 2004[30] | 224 | 10.78.9 | 11.210.6 | 0.5 (3.0 to 2.0) | 0.69 | |
Kristoffersen, 2009[26] | 210 | 5.9 | 6.7 | 0.8 | 0.22 | |
Stolz, 2007[28] | 208 | 9 (115)b | 10 (115)b | 1 | 0.96 | |
Christ‐Crain, 2006[29] | 302 | 12.09.1 | 13.09.0 | 1 (3.0 to 1.0) | 0.34 | |
ICU admission, % | Schuetz, 2009[2][5] | 1359 | 43/671 (6.4%) | 60/688 (8.7%) | 2.3% (5.2 to 0.4) | 0.12 |
Christ‐Crain, 2004[30] | 224 | 5/124 (4.0%) | 6/119 (5.0%) | 1.0% (6.2 to 4.2) | 0.71 | |
Kristoffersen, 2009[26] | 210 | 7/103 (6.8%) | 5/107 (4.7%) | 2.1% (4.2 to 8.4) | 0.51 | |
Stolz, 2007[28] | 208 | 8/102 (7.8%) | 11/106 (10.4%) | 2.5% (10.3 to 5.3) | 0.53 | |
Christ‐Crain, 2006[29] | 302 | 20/151 (13.2%) | 21/151 (13.94%) | 0.7% (8.4 to 7.1) | 0.87 | |
Antibiotic adverse events | Schuetz, 2009[2][5]c | 1359 | 133/671 (19.8%) | 193/688 (28.1%) | 8.2% (12.7 to 3.7) | |
Briel, 2008[27]d | 458 | 2.34.6 days | 3.66.1 days | 1.1 days (2.1 to 0.1) | <0.05 | |
Burkhardt, 2010[34]e | 550 | 11 /59 (18.6%) | 16/101 (15.8%) | 2.8% (9.4 to 15.0) | 0.65 | |
Restricted activity, df | Briel, 2008[27] | 458 | 8.73.9 | 8.63.9 | 0.2 (0.4 to 0.9) | >0.05 |
Burkhardt, 2010[34] | 550 | 9.1 | 8.8 | 0.25 (0.52 to 1.03) | >0.05 | |
Neonates with sepsis | ||||||
Recurrence of infection | Stocker, 2010[31] | 121 | 32% | 39% | 7 | 0.45 |
Children ages 136 months with fever of unknown source | ||||||
Hospitalization rate | Manzano, 2010[36] | All children (N=384) | 50/192 (26%) | 48/192 (25%) | 1 (8 to 10) | 0.81 |
No SBI or neutropenia (N=312) | 16/158 (10%) | 11/154 (7%) | 3 (3 to 10) | 0.34 | ||
Adult postoperative patients at risk of infection | ||||||
Hospital LOS, days | Chromik, 2006[32] | 20 | 18 | 30 | 12 | 0.057 |
Local wound infection, % | Chromik, 2006[32] | 20 | 1/10 | 2/10 | 10 (41.0 to 21.0) | 0.53 |
Systemic infection, % | Chromik, 2006[32] | 20 | 3/10 | 7/10 | 40.0 (80.2 to 0.2) | 0.07 |
Sepsis/SIRS, % | Chromik, 2006[32] | 20 | 2/10 | 8/10 | 60.0 (95.1 to 24.9) | 0.007 |
Mortality | Mortality | Difference | ||||
---|---|---|---|---|---|---|
Outcome | Author, Year | N | PCT‐Guided Therapy | Control | PCT‐CTRL (95% CI) | P Value |
| ||||||
Critically ill adult patients: procalcitonin‐guided antibiotic discontinuation | ||||||
28‐day mortality | Nobre, 2008[19] | 79 | 8/39 (20.5%) | 8/40 (20.0%) | 0.5 (17.2 to 18.2), | 0.95 |
5/31 (16.1%) | 6/37 (16.2%) | 0.1 (17.7 to 17.5)a | 0.99 | |||
Stolz, 2009[21] | 101 | 8/51 (15.7%) | 12/50 (24.0%) | 8.3 (23.8 to 7.2) | 0.29 | |
Bouadma, 2010[23] | 621 | 65/307 (21.2%) | 64/314 (20.4%) | 0.8 (5.6 to 7.2) | 0.81 | |
60‐day mortality | Bouadma, 2010[23] | 621 | 92/307 (30.0%) | 82/314 (26.1%) | 3.9 (3.2 to 10.9) | 0.29 |
In‐hospital mortality | Nobre, 2008[19] | 79 | 9/39 (23.1%) | 9/40 (22.5%) | 0.6 (17.9 to 19.1) | 0.95 |
6/31 (19.4%) | 7/37 (18.9%) | 0.4+ (18.3 to 19.2) | 0.96 | |||
Stolz, 2009[21] | 101 | 10/51 (19.6%) | 14/50 (28.0%) | 8.4, (24.9 to 8.1) | 0.32 | |
Hochreiter, 2009[22] | 110 | 15/57 (26.3%) | 14/53 (26.4%) | 0.1, (16.6 to 16.4) | 0.99 | |
Schroeder, 2009[20] | 27 | 3/14 (21.4%) | 3/13 (23.1%) | 1.7, (33.1 to 29.8) | 0.92 | |
Critically ill adult patients: procalcitonin‐guided antibiotic intensification | ||||||
28‐day mortality | Svoboda, 2007[24] | 72 | 10/38 (26.3%) | 13/34 (38.2%) | 11.9 (33.4 to 9.6) | 0.28 |
28‐day mortality | Jensen, 2011[33] | 1200 | 190/604 (31.5%) | 191/596 (32.0%) | 0.6 (4.7 to 5.9) | 0.83 |
Adult patients with respiratory tract infections | ||||||
6‐month mortality | Stolz, 2007[28] | 208 | 5/102 (4.9%) | 9/106 (8.5%) | 3.6% (10.3 to 3.2%) | 0.30 |
6‐week mortality | Christ‐Crain, 2006[29] | 302 | 18/151 (11.9%) | 20/151 (13.2%) | 1.3% (8.8 to 6.2) | 0.73 |
28‐day mortality | Christ‐Crain, 2004[30] | 243 | 4/124(3.2%) | 4/119 (3.4%) | 0.1% (4.6 to 4.4) | 0.95 |
Schuetz, 2009 (30‐day)[25] | 1359 | 34/671(5.1%) | 33/688(4.8%) | 0.3% (2.1 to 2.5) | 0.82 | |
Briel, 2008[27] | 458 | 0/231(0%) | 1/224 (0.4%) | 0.4% (1.3 to 0.4) | 0.31 | |
Burkhardt, 2010[34] | 550 | 0/275(0%) | 0/275 (0%) | 0 | ||
Kristoffersen, 2009[26] | 210 | 2/103(1.9%) | 1/107 (0.9%) | 1.0% (2.2 to 4.2) | 0.54 | |
Long, 20113[5] | 162 | 0/81 (0%) | 0/81 (0%) | 0 | ||
Neonates with sepsis | ||||||
Mortality (in‐hospital) | Stocker, 2010[31] | 121 | 0% | 0% | 0 (0 to 0) | NA |
Children ages 136 months with fever of unknown source | ||||||
Mortality | Manzano, 2010[36] | 384 | All children | 0% | 0% | 0 (0 to 0) |
Adult postoperative patients at risk of infection | ||||||
Mortality | Chromik, 2006[32] | 20 | 1/10 (10%) | 3/10 (30%) | 20 (54.0 to 14.0) | 0.07 |
Adult ICU Patients: Procalcitonin‐Guided Antibiotic Discontinuation
Five studies[19, 20, 21, 22, 23] (N=938) addressed procalcitonin‐guided discontinuation of antibiotic therapy in adult ICU patients. Four studies conducted superiority analyses for mortality with procalcitonin‐guided therapy, whereas 1 study conducted a noninferiority analysis. Absolute procalcitonin values for discontinuation of antibiotics ranged from 0.25 to 1 ng/mL. Physicians in control groups administered antibiotics according to their standard practice.
Antibiotic Usage
The absolute reduction in duration of antibiotic usage with procalcitonin guidance in these studies ranged from 1.7 to 5 days, and the relative reduction ranged from 21% to 38%. Meta‐analysis of antibiotic duration in adult ICU patients was performed (Figure 2A).

Morbidity
Procalcitonin‐guided antibiotic discontinuation did not increase morbidity, including ICU length of stay (LOS). Meta‐analysis of ICU LOS is displayed in Figure 2B. Limited data on adverse antibiotic events were reported (Table 2).
Mortality
There was no increase in mortality as a result of shorter duration of antibiotic therapy. Meta‐analysis of short‐term mortality (28‐day or in‐hospital mortality) showed a mortality difference of 0.43% favoring procalcitonin‐guided therapy, and a 95% confidence interval (CI) of 6% to 5% (Figure 2C).
Adult ICU Patients: Procalcitonin‐Guided Antibiotic Intensification
Two studies[24, 33] (N=1272) addressed procalcitonin‐guided intensification of antibiotic therapy in adult ICU patients. The Jensen et al. study[33] was a large (N=1200), high‐quality study that used a detailed algorithm for broadening antibiotic therapy in patients with elevated procalcitonin. The Jensen et al. study also educated physicians about empiric therapy and intensification of antibiotic therapy. A second study[24] was too small (N=72) and lacked sufficient details to be informative.
Antibiotic Usage
The Jensen et al. study found a 2‐day increase, or 50% relative increase, in the duration of antibiotic therapy and a 7.9% absolute increase (P=0.002) in the number of days on 3 antibiotics with procalcitonin‐guided intensification.
Morbidity
The Jensen et al. study showed a significant 1‐day increase in ICU LOS (P=0.004) and a significant increase in organ dysfunction. Specifically, patients had a highly statistically significant 5% increase in days on mechanical ventilation (P<0.0001) and 5% increase in days with abnormal renal function (P<0.0001).
Mortality
The Jensen et al. study was a superiority trial powered to test a 7.5% decrease in 28‐day mortality, but no significant difference in mortality was observed with procalcitonin‐guided intensification (31.5% vs 32.0, P=0.83).
Adult Patients With Respiratory Tract Infections
Eight studies[25, 26, 27, 28, 29, 30, 34, 35] (N=3492) addressed initiation and/or discontinuation of antibiotics in adult patients with acute upper and lower respiratory tract infections, including community‐acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease, and acute bronchitis. Settings included primary care clinics, emergency departments, and hospital wards. Physicians in control groups administered antibiotics according to their own standard practices and/or evidence‐based guidelines. All studies encouraged initiation of antibiotics with procalcitonin levels >0.25 ng/mL, and 4 studies strongly encouraged antibiotics with procalcitonin levels >0.5 ng/mL.
Antibiotic Usage
Procalcitonin guidance reduced antibiotic duration, antibiotic prescription rate, and total antibiotic exposure. Absolute reduction in antibiotic duration ranged from 1 to 7 days, and relative reductions ranged from 13% to 55%. Four of the 8 studies reported sufficient details to be pooled into a meta‐analysis (Figure 3A) with a statistically significant pooled mean difference of 2.35 days favoring procalcitonin (95% CI: 4.38 to 0.33). Procalcitonin guidance also reduced antibiotic prescription rate with absolute reductions ranging from 2% to 7% and relative reductions ranging from 1.8% to 72%. Meta‐analysis of prescription rates from 8 studies (Figure 3B) yielded a statistically significant pooled risk difference of 22% (95% CI: 41% to 4%). Total antibiotic exposure was consistently reduced in the 4 studies reporting this outcome.

Morbidity
Procalcitonin guidance did not increase hospital LOS or ICU admission rates. Meta‐analysis of ICU admission rates from 5 studies (Figure 3C) produced a risk difference of 1%, with a narrow 95% CI (4% to 1%). There was insufficient evidence to judge the effect on days of restricted activity or antibiotic adverse events.
Mortality
Procalcitonin guidance did not increase mortality, and meta‐analysis of 4 studies (Figure 3D) produced a risk difference of 0.3% with a narrow 95% CI (1% to 2%), with no statistical heterogeneity (I2=0%).
Neonates With Sepsis
One study[31] (N=121) evaluated procalcitonin‐guided antibiotic therapy for suspected neonatal sepsis. Neonatal sepsis was suspected on the basis of risk factors and clinical signs and symptoms. Antibiotic initiation or discontinuation was based on a procalcitonin nomogram. Antibiotic therapy in the control group was based on the physician's assessment. The quality of this study was rated good, and strength of evidence was rated moderate for antibiotic usage and insufficient for morbidity and mortality outcomes.
Antibiotic Usage
Duration of antibiotic therapy was decreased by 22.4 hours (P=0.012), a 24% relative reduction, and the proportion of neonates on antibiotics 72 hours was reduced by 27% (P=0.002). The largest reduction in antibiotic duration was seen in the 80% to 85% of neonates who were categorized as having possible or infection or unlikely to have infection.
Morbidity
A statistically insignificant 7% reduction in rate of recurrence of infection was seen with procalcitonin‐guided antibiotic therapy (P=0.45).
Mortality
No in‐hospital deaths occurred in either the procalcitonin or control group.
Children Ages 1 to 36 Months With Fever of Unknown Source
One study[36] (N=384) evaluated procalcitonin‐guided antibiotic therapy for fever of unknown source in children 1 to 36 months of age, but the overall strength of evidence was judged insufficient to draw conclusions.
Antibiotic Usage
A statistically insignificant reduction of 3.1% in antibiotic prescription rate was seen with procalcitonin‐guided antibiotic therapy (P=0.49).
Morbidity
Rate of hospitalization was relatively low, and no significant difference was seen between procalcitonin and control groups.
Mortality
In‐hospital mortality was reported as 0% in both arms.
Adult Postoperative Patients at Risk of Infection
One study[32] (N =250) monitored procalcitonin in consecutive patients after colorectal surgery to identify patients at risk of infection who might benefit from prophylactic antibiotic therapy. Two hundred thirty patients had normal procalcitonin levels. Twenty patients with elevated procalcitonin levels (>1.5 ng/mL) were randomized to receive prophylactic antibiotic therapy with ceftriaxone or no antibiotics. The strength of evidence was judged insufficient to draw conclusions from this study.
Antibiotic Usage
Duration of antibiotic therapy was reduced by 3.5% but was not statistically insignificant (P=0.27).
Morbidity
Procalcitonin guidance reduced the incidence of sepsis/systemic inflammatory response syndrome by 60% (p=0.007). The incidences of local and systemic infection were reduced with procalcitonin guidance but were not statistically significant (10%, P=0.53; and 40%, P=0.07, respectively).
Mortality
Mortality was 20% higher in the control arm but was not statistically significant (P=0.07).
DISCUSSION
Summary of the Main Findings
Diagnosis of sepsis or other serious infections in critically ill patients is challenging because clinical criteria for diagnosis overlap with noninfectious causes of the systemic inflammatory response syndrome. Initiation of antibiotic therapy for presumed sepsis is necessary while diagnostic evaluation is ongoing, because delaying antibiotic therapy is associated with increased mortality.[37, 38, 39] Our review found that procalcitonin guidance significantly reduced antibiotic usage in adult ICU patients by reducing the duration of antibiotic therapy, rather than decreasing the initiation of antibiotics, without increasing morbidity or mortality.
In contrast, the use of procalcitonin as an indicator of need for intensification of antibiotic therapy in adult ICU patients should be discouraged because this approach was associated with increased morbidity. The large, well‐designed study by Jensen[33] showed that antibiotic intensification in response to elevated procalcitonin measurement was associated with increased morbidity: a longer ICU LOS, an increase in days on mechanical ventilation, and an increase in days with abnormal renal function. The authors concluded that the increased morbidity could only be explained by clinical harms of increased exposure to broad‐spectrum antibiotics.
Clinical and microbiological evaluations are neither sensitive nor specific for differentiating bacterial from viral respiratory tract infections. Procalcitonin can guide initiation of antibiotic therapy in adults with suspected bacterial respiratory tract infection. Our review showed that procalcitonin guidance significantly reduced antibiotic usage with respect to antibiotic prescription rate, duration of antibiotic therapy, and total exposure to antibiotic therapy in adult patients with respiratory tract infections.
The role of procalcitonin‐guided therapy in other populations is less clear. One study in postoperative colorectal surgery patients reported that elevated procalcitonin levels may identify patients at risk for infection who benefit from prophylactic antibiotic therapy.[32] Patients with elevated procalcitonin levels who received prophylactic antibiotic therapy had a significant decrease in the incidence and severity of systemic infections, whereas patients with normal procalcitonin levels did not require any additional surgical or medical therapy. Although these findings are promising, more data in postoperative patients are needed.
The utility of procalcitonin in pediatric settings is a significant gap in the present literature. One study[31] in neonates with suspected sepsis showed a significant decrease in the proportion of neonates started on empiric antibiotic therapy and a decrease in the duration of antibiotic therapy with procalcitonin guidance. However, there was insufficient evidence that procalcitonin guidance does not increase morbidity or mortality.
Comparison to Other Systematic Reviews
Six systematic reviews of procalcitonin guidance in the management of patients with infections were published prior to our review.[9, 10, 11, 12, 13, 14] Our systematic review differs from past reviews in the number of studies included and the pooling of studies according to patient population, type and severity of infection, and different uses of procalcitonin measurements, either for initiation, discontinuation, or intensification of antibiotic therapy. Previous systematic reviews included 7 to 14 studies, whereas ours included 18 randomized, controlled trials. One previous review[13] included and pooled the Jensen et al. study[33] with other studies of adult ICU patients. We evaluated the Jensen et al. study separately because it uniquely looked at procalcitonin‐guided antibiotic intensification in adult ICU patients, in contrast to other studies that looked at procalcitonin‐guided antibiotic discontinuation. We addressed pediatric populations separately from adult patients, and recognizing that there are distinct groups within the pediatric population, we separately grouped neonates and children ages 1 to 36 months. Despite these differences, our review and other systematic reviews, we came to similar conclusions: procalcitonin‐guided antibiotic decision making compared to clinical criteria‐guided antibiotic decision making reduces antibiotic usage without increasing morbidity or mortality.
Limitations
An important limitation of this review was the uncertainty about the noninferiority margin for morbidity and mortality in adult ICU patients. Only the Bouadma et al. study[23] did a power analysis and predefined a margin for noninferiority for 28‐ and 60‐day mortality. Meta‐analysis of all 5 ICU studies showed a pooled point estimate of 0.43% in mortality and a 95% CI of 6% to 5% for difference in mortality between procalcitonin‐guided therapy versus standard care. A 10% noninferiority margin for mortality has been recommended by the Infectious Diseases Society of America and American College of Chest Physicians, but there is concern that a 10% margin for mortality may be too high. Presently, 2 large trials are in progress that may yield more precise estimates of mortality in the future.
Differences in reporting of total antibiotic exposure and morbidity outcomes limited our ability to pool data. Total antibiotic exposure is conventionally reported as mean days per 1000 days of follow‐up, but some studies only reported relative or absolute differences. Likewise, morbidity was reported with different severity of illness scales, including Sepsis‐Related Organ Failure Assessment, Simplified Acute Physiology (SAP) II, SAP III, and Acute Physiology and Chronic Health Evaluation II, which limited comparisons across studies.
Research Gaps
We identified gaps in the available literature and opportunities for future research. First, the safety and efficacy of procalcitonin‐guided antibiotic therapy needs to be studied in patient populations excluded from current randomized controlled studies, such as immunocompromised patients and pregnant women. Patients who are immunocompromised or have chronic conditions, such as cystic fibrosis, account for a significant percentage of community‐acquired respiratory tract infections and are often treated empirically.[29, 30] Second, standardized reporting of antibiotic adverse events and emergence of antibiotic resistance is needed. Strategies to reduce antibiotic usage have been associated with reductions in antibiotic adverse events, such as Clostridium difficile colitis and superinfection with multi‐drug resistant Gram‐negative bacteria.[37, 40, 41] Few studies in our review reported allergic reactions or adverse events of antibiotic therapy, [25, 27, 34] and only 1 reported antibiotic resistance.[19] Third, procalcitonin guidance should be compared to other strategies to reduce antibiotic usage, such as structured implementation of practice guidelines and antibiotic stewardship programs.[42] One single‐arm study describes how procalcitonin can be used in antibiotic stewardship programs to decrease the duration of antibiotic therapy,[43] but additional studies are needed. Finally, generalizing results from those studies that were conducted primarily in Europe would depend on similar use of and adherence to study‐based algorithms. Newer observational studies have demonstrated reduced antibiotic usage with implementation of procalcitonin algorithms in real‐life settings in Europe, but algorithm adherence was significantly less in the United States.[44, 45]
In summary, our systematic review found that procalcitonin‐guided antibiotic therapy can significantly reduce antibiotic usage in adult ICU patients without affecting morbidity or mortality. Procalcitonin should not be used to guide intensification of antibiotic therapy in adult ICU patients because this approach may increase morbidity. In adults with respiratory infections, procalcitonin guidance can significantly reduce antibiotic usage without adversely affecting morbidity or mortality. There is insufficient evidence to recommend procalcitonin‐guided antibiotic therapy in neonates with sepsis, children with fever of unknown source, or postoperative patients at risk for infection.
Acknowledgments
Disclosures: This project was funded under contract HHSA 2902007‐10058 from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services. The authors of this article are responsible for its content, including any clinical treatment recommendations. No statement in this article should be construed as an official position of AHRQ or of the US Department of Health and Human Services. There are no conflicts of interest reported by any of the authors.
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- Biomarkers of sepsis. Crit Care Med. 2009;37(7):2290–2298. , .
- Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med. 1998;24(8):888–889. , , .
- Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab. 1994;79(6):1605–1608. , , , et al.
- Procalcitonin kinetics as a prognostic marker of ventilator‐associated pneumonia. Am J Respir Crit Care Med. 2005;171(1):48–53. , , , et al.
- Serum procalcitonin and C‐reactive protein levels as markers of bacterial infection: a systematic review and meta‐analysis. Clin Infect Dis. 2004;39(2):206–217. , , , , .
- Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators. Eur Respir J. 2007;30(3):556–573. , .
- Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis. 1998;26(3):664–672. , , , et al.
- Effect of procalcitonin‐guided treatment in patients with infections: a systematic review and meta‐analysis. Infection. 2009;37(6):497–507. , , , , .
- Procalcitonin to guide duration of antimicrobial therapy in intensive care units: a systematic review. Clin Infect Dis. 2011;53(4):379–387. , .
- Procalcitonin‐guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta‐analysis of randomized controlled trials. Crit Care Med. 2010;38(11):2229–2241. , , , , .
- Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171(15):1322–1331. , , , .
- An ESCIM systematic review and meta‐analysis of procalcitonin‐guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care Med. 2012;38:940–949. , , , , , .
- Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012;(9):CD007498. , , , et al.
- Prepared by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence‐based Practice Center under contract no. 290–2007‐10058‐I. Procalcitonin‐guided antibiotic therapy. Comparative effectiveness review No. 78. AHRQ publication no. 12(13)‐EHC124‐EF. Rockville, MD: Agency for Healthcare Research and Quality. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm. Published Accessed October 2012. , , , , , .
- Methods Guide for Effectiveness and Comparative Effectiveness Reviews. AHRQ publication no. 10(11)‐EHC063‐EF. Rockville, MD: Agency for Healthcare Research and Quality; 2011.
- Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3 suppl):21–35. , , , et al.
- AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—agency for healthcare research and quality and the effective health‐care program. J Clin Epidemiol. 2010;63(5):513–523. , , , et al.
- Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. 2008;177(5):498–505. , , , , .
- Procalcitonin (PCT)‐guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg. 2009;394(2):221–226. , , , et al.
- Procalcitonin for reduced antibiotic exposure in ventilator‐associated pneumonia: a randomised study. Eur Respir J. 2009;34(6):1364–1375. , , , et al.
- Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care. 2009;13(3):R83. , , , et al.
- Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375(9713):463–474. , , , et al.
- Can procalcitonin help us in timing of re‐intervention in septic patients after multiple trauma or major surgery? Hepatogastroenterology. 2007;54(74):359–363. , , , , .
- Effect of procalcitonin‐based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059–1066. , , , et al.
- Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission—a randomized trial. Clin Microbiol Infect. 2009;15(5):481–487. , , , et al.
- Procalcitonin‐guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008;168(18):2000–2007; discussion 2007–2008. , , , et al.
- Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin‐guidance with standard therapy. Chest. 2007;131(1):9–19. , , , et al.
- Procalcitonin guidance of antibiotic therapy in community‐acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84–93. , , , et al.
- Effect of procalcitonin‐guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster‐randomised, single‐blinded intervention trial. Lancet. 2004;363(9409):600–607. , , , et al.
- Use of procalcitonin‐guided decision‐making to shorten antibiotic therapy in suspected neonatal early‐onset sepsis: prospective randomized intervention trial. Neonatology. 2010;97(2):165–174. , , , , .
- Pre‐emptive antibiotic treatment vs “standard” treatment in patients with elevated serum procalcitonin levels after elective colorectal surgery: a prospective randomised pilot study. Langenbecks Arch Surg. 2006;391(3):187–194. , , , , , .
- Procalcitonin‐guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med. 2011;39(9):2048–2058. , , , et al.
- Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J. 2010;36(3):601–607. , , , et al.
- Procalcitonin guidance for reduction of antibiotic use in low‐risk outpatients with community‐acquired pneumonia. Respirology. 2011;16(5):819–824. , , , , , .
- Impact of procalcitonin on the management of children aged 1 to 36 months presenting with fever without source: a randomized controlled trial. Am J Emerg Med. 2010;28(6):647–653. , , , , , .
- Experience with a clinical guideline for the treatment of ventilator‐associated pneumonia. Crit Care Med. 2001;29(6):1109–1115. , , , , , .
- Diagnostic value of procalcitonin, interleukin‐6, and interleukin‐8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164(3):396–402. , , , et al.
- Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115(2):462–474. , , , .
- Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol. 2003;24(9):699–706. , , , , .
- Comparison of 8 vs 15 days of antibiotic therapy for ventilator‐associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588–2598. , , , et al.
- Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159–177. , , , et al.
- Use of procalcitonin (PCT) to guide discontinuation of antibiotic use in an unspecified sepsis is an antimicrobial stewardship program (ASP). Eur J Clin Microbiol Infect Dis. 2011;30(7):853–855. , , , , .
- Effectiveness and safety of procalcitonin‐guided antibiotic therapy in lower respiratory tract infections in “real life.” Arch Intern Med. 2012;172(9):715–722. , , , et al.
- Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post‐study survey. Eur J Clin Microbiol Infect Dis. 2012;29(3):269–277. , , , et al.
Smartphone Policy for Attending Rounds
Despite the many benefits of smartphones for physicians, there are also potential downsides to utilizing these devices in the patient care setting. Prior research at our hospital found that smartphone use during inpatient attending rounds can distract faculty and residents, and nearly 80% of attendings favored the institution of codes of conduct governing appropriate use of smartphones during rounds.[1] Based on these findings, a policy regulating faculty and resident smartphone use was instituted in February 2012 in the Departments of Medicine and Pediatrics at our hospital.[1]
Although our faculty's enthusiasm for the smartphone policy was clear, residents' attitudes toward this new regulation were unknown. Born in the 1980s, today's residents are members of the millennial generation, who seamlessly integrate technology into their lives.[2, 3, 4, 5] Millennials generally do not perceive their multitasking with technology to be rude or distracting.[2] Having grown up with the Internet, they employ digital tools as an inherent sixth sense,[3] and view their use of technology as the defining characteristic of their generation.[5]
Housestaff feedback was instrumental in shaping the specifics of the smartphone policy.[1] However, given the primacy of technology in the life of the millennial, it is plausible that residents would resent restrictions on their smartphone use. Such resentment could limit a policy's effectiveness, as well as negatively impact resident morale. With increasing discussion about the need to manage personal electronic device use in the patient care setting,[2, 6, 7, 8] we sought to assess residents' attitudes toward our hospital's smartphone policy.
METHODS
A brief survey instrument was designed to increase housestaff awareness of and evaluate their attitudes toward the smartphone policy. In November 2012, the anonymous survey was administered via SurveyMonkey (
The survey provided a summary of the policy: The smartphone code of conduct policy was instituted to minimize distraction during attending rounds. The policy applies to all team members, including faculty, and essentially states that at the start of attending rounds, all phones must be silenced or turned off. These devices are to be used during rounds only for patient care or for urgent personal/family concerns. Any use must be made explicit to the person leading rounds. Residents also received a copy of the complete policy as an attachment to the request email. A copy of this policy is available as an appendix to Katz‐Sidlow et al.[1]
The survey requested information regarding departmental affiliation, and asked whether the resident had prior awareness of the smartphone policy. Residents' attitudes were evaluated by asking for their level of agreement with the following statement: It is a good idea to have clear guidelines and expectations about how team members should use smartphones during attending rounds. This statement was graded on a 4‐point frequency scale (strongly disagree, disagree, agree, or strongly agree). Residents' attitudes were further explored in a follow‐up question: Which statement most closely expresses your feelings? Three options were offered: (1) There should be no guidelines as to how team members should use smartphones during inpatient attending rounds. Every person should decide for him/herself how and when to use the phone during rounds. (2) I agree that a smartphone code of conduct for attending rounds is a good idea, but I suggest modifying the current policy (please use the text box below to explain). (3) I agree with the current smartphone code of conduct policy for attending rounds. A text box was provided for comments.
RESULTS
The overall response rate was 65% (93/142), representing 58% (57/98) of all Department of Medicine residents and 82% (36/44) of all Department of Pediatrics residents. Seventy‐one percent of respondents (57% Department of Medicine; 92% Department of Pediatrics) indicated a prior knowledge of the smartphone policy.
Overall, 82% of respondents agreed or strongly agreed with the statement, It is a good idea to have clear guidelines and expectations about how team members should use smartphones during attending rounds (Figure 1). Residents' responses to the follow‐up question revealed that nearly 60% agreed with the stipulations of the current policy; another 18% believed that a policy is needed, but felt that the current code should be modified. Only one resident provided a modification suggestion, which was to expand the policy to include resident work rounds.

Responses to these 2 questions differed slightly for trainees with an awareness of the preexisting policy as compared to those without prior awareness; however, these differences were not statistically significant.
CONCLUSIONS
Despite concerns that residents would resent policies regulating their use of technology, we found that the majority of residents indicated a desire for, and acceptance of, clear guidelines regarding smartphone use during inpatient rounds. Our findings are in line with prior research suggesting that millennials appreciate a structured work environment and explicit guidance regarding workplace expectations.[2, 3, 4] To minimize distraction and support residents' professionalism, we recommend that training programs develop and implement clear expectations regarding smartphone use in the active patient care setting.
- Smartphone use during inpatient attending rounds: prevalence, patterns and potential for distraction. J Hosp Med. 2012;7:595–599. , , , .
- The challenges and opportunities of teaching “generation y.” J Grad Med Educ. 2011;3:458–461. , .
- Millennials and the world of work: an organization and management perspective. J Bus Psychol. 2010;25:211–223. , .
- Is your residency program ready for generation y? J Surg Educ. 2010;67:108–111. , , .
- Pew Research Center. Millennials: a portrait of generation next. Pew Research Center Web site. February 2010. Available at: http://www.pewsocialtrends.org/files/2010/10/millennials‐confident‐connected‐open‐to‐change.pdf. Accessed May 9, 2013.
- Spotlight case. Order interrupted by text: multitasking mishap. Agency for Healthcare Research and Quality Web site. December 2011. Available at: http://webmm.ahrq.gov/case.aspx?caseID=257. Accessed May 9, 2013. .
- Training health care professionals to deal with an explosion of electronic distraction. Neurocrit Care. 2013;18:115–117. .
- ECRI Institute. Top 10 health technology hazards for 2013. ECRI Institute Web site. Available at: https://www.ecri.org/Documents/Secure/Health_Devices_Top_10_Hazards_2013.pdf. Accessed May 9, 2013.
Despite the many benefits of smartphones for physicians, there are also potential downsides to utilizing these devices in the patient care setting. Prior research at our hospital found that smartphone use during inpatient attending rounds can distract faculty and residents, and nearly 80% of attendings favored the institution of codes of conduct governing appropriate use of smartphones during rounds.[1] Based on these findings, a policy regulating faculty and resident smartphone use was instituted in February 2012 in the Departments of Medicine and Pediatrics at our hospital.[1]
Although our faculty's enthusiasm for the smartphone policy was clear, residents' attitudes toward this new regulation were unknown. Born in the 1980s, today's residents are members of the millennial generation, who seamlessly integrate technology into their lives.[2, 3, 4, 5] Millennials generally do not perceive their multitasking with technology to be rude or distracting.[2] Having grown up with the Internet, they employ digital tools as an inherent sixth sense,[3] and view their use of technology as the defining characteristic of their generation.[5]
Housestaff feedback was instrumental in shaping the specifics of the smartphone policy.[1] However, given the primacy of technology in the life of the millennial, it is plausible that residents would resent restrictions on their smartphone use. Such resentment could limit a policy's effectiveness, as well as negatively impact resident morale. With increasing discussion about the need to manage personal electronic device use in the patient care setting,[2, 6, 7, 8] we sought to assess residents' attitudes toward our hospital's smartphone policy.
METHODS
A brief survey instrument was designed to increase housestaff awareness of and evaluate their attitudes toward the smartphone policy. In November 2012, the anonymous survey was administered via SurveyMonkey (
The survey provided a summary of the policy: The smartphone code of conduct policy was instituted to minimize distraction during attending rounds. The policy applies to all team members, including faculty, and essentially states that at the start of attending rounds, all phones must be silenced or turned off. These devices are to be used during rounds only for patient care or for urgent personal/family concerns. Any use must be made explicit to the person leading rounds. Residents also received a copy of the complete policy as an attachment to the request email. A copy of this policy is available as an appendix to Katz‐Sidlow et al.[1]
The survey requested information regarding departmental affiliation, and asked whether the resident had prior awareness of the smartphone policy. Residents' attitudes were evaluated by asking for their level of agreement with the following statement: It is a good idea to have clear guidelines and expectations about how team members should use smartphones during attending rounds. This statement was graded on a 4‐point frequency scale (strongly disagree, disagree, agree, or strongly agree). Residents' attitudes were further explored in a follow‐up question: Which statement most closely expresses your feelings? Three options were offered: (1) There should be no guidelines as to how team members should use smartphones during inpatient attending rounds. Every person should decide for him/herself how and when to use the phone during rounds. (2) I agree that a smartphone code of conduct for attending rounds is a good idea, but I suggest modifying the current policy (please use the text box below to explain). (3) I agree with the current smartphone code of conduct policy for attending rounds. A text box was provided for comments.
RESULTS
The overall response rate was 65% (93/142), representing 58% (57/98) of all Department of Medicine residents and 82% (36/44) of all Department of Pediatrics residents. Seventy‐one percent of respondents (57% Department of Medicine; 92% Department of Pediatrics) indicated a prior knowledge of the smartphone policy.
Overall, 82% of respondents agreed or strongly agreed with the statement, It is a good idea to have clear guidelines and expectations about how team members should use smartphones during attending rounds (Figure 1). Residents' responses to the follow‐up question revealed that nearly 60% agreed with the stipulations of the current policy; another 18% believed that a policy is needed, but felt that the current code should be modified. Only one resident provided a modification suggestion, which was to expand the policy to include resident work rounds.

Responses to these 2 questions differed slightly for trainees with an awareness of the preexisting policy as compared to those without prior awareness; however, these differences were not statistically significant.
CONCLUSIONS
Despite concerns that residents would resent policies regulating their use of technology, we found that the majority of residents indicated a desire for, and acceptance of, clear guidelines regarding smartphone use during inpatient rounds. Our findings are in line with prior research suggesting that millennials appreciate a structured work environment and explicit guidance regarding workplace expectations.[2, 3, 4] To minimize distraction and support residents' professionalism, we recommend that training programs develop and implement clear expectations regarding smartphone use in the active patient care setting.
Despite the many benefits of smartphones for physicians, there are also potential downsides to utilizing these devices in the patient care setting. Prior research at our hospital found that smartphone use during inpatient attending rounds can distract faculty and residents, and nearly 80% of attendings favored the institution of codes of conduct governing appropriate use of smartphones during rounds.[1] Based on these findings, a policy regulating faculty and resident smartphone use was instituted in February 2012 in the Departments of Medicine and Pediatrics at our hospital.[1]
Although our faculty's enthusiasm for the smartphone policy was clear, residents' attitudes toward this new regulation were unknown. Born in the 1980s, today's residents are members of the millennial generation, who seamlessly integrate technology into their lives.[2, 3, 4, 5] Millennials generally do not perceive their multitasking with technology to be rude or distracting.[2] Having grown up with the Internet, they employ digital tools as an inherent sixth sense,[3] and view their use of technology as the defining characteristic of their generation.[5]
Housestaff feedback was instrumental in shaping the specifics of the smartphone policy.[1] However, given the primacy of technology in the life of the millennial, it is plausible that residents would resent restrictions on their smartphone use. Such resentment could limit a policy's effectiveness, as well as negatively impact resident morale. With increasing discussion about the need to manage personal electronic device use in the patient care setting,[2, 6, 7, 8] we sought to assess residents' attitudes toward our hospital's smartphone policy.
METHODS
A brief survey instrument was designed to increase housestaff awareness of and evaluate their attitudes toward the smartphone policy. In November 2012, the anonymous survey was administered via SurveyMonkey (
The survey provided a summary of the policy: The smartphone code of conduct policy was instituted to minimize distraction during attending rounds. The policy applies to all team members, including faculty, and essentially states that at the start of attending rounds, all phones must be silenced or turned off. These devices are to be used during rounds only for patient care or for urgent personal/family concerns. Any use must be made explicit to the person leading rounds. Residents also received a copy of the complete policy as an attachment to the request email. A copy of this policy is available as an appendix to Katz‐Sidlow et al.[1]
The survey requested information regarding departmental affiliation, and asked whether the resident had prior awareness of the smartphone policy. Residents' attitudes were evaluated by asking for their level of agreement with the following statement: It is a good idea to have clear guidelines and expectations about how team members should use smartphones during attending rounds. This statement was graded on a 4‐point frequency scale (strongly disagree, disagree, agree, or strongly agree). Residents' attitudes were further explored in a follow‐up question: Which statement most closely expresses your feelings? Three options were offered: (1) There should be no guidelines as to how team members should use smartphones during inpatient attending rounds. Every person should decide for him/herself how and when to use the phone during rounds. (2) I agree that a smartphone code of conduct for attending rounds is a good idea, but I suggest modifying the current policy (please use the text box below to explain). (3) I agree with the current smartphone code of conduct policy for attending rounds. A text box was provided for comments.
RESULTS
The overall response rate was 65% (93/142), representing 58% (57/98) of all Department of Medicine residents and 82% (36/44) of all Department of Pediatrics residents. Seventy‐one percent of respondents (57% Department of Medicine; 92% Department of Pediatrics) indicated a prior knowledge of the smartphone policy.
Overall, 82% of respondents agreed or strongly agreed with the statement, It is a good idea to have clear guidelines and expectations about how team members should use smartphones during attending rounds (Figure 1). Residents' responses to the follow‐up question revealed that nearly 60% agreed with the stipulations of the current policy; another 18% believed that a policy is needed, but felt that the current code should be modified. Only one resident provided a modification suggestion, which was to expand the policy to include resident work rounds.

Responses to these 2 questions differed slightly for trainees with an awareness of the preexisting policy as compared to those without prior awareness; however, these differences were not statistically significant.
CONCLUSIONS
Despite concerns that residents would resent policies regulating their use of technology, we found that the majority of residents indicated a desire for, and acceptance of, clear guidelines regarding smartphone use during inpatient rounds. Our findings are in line with prior research suggesting that millennials appreciate a structured work environment and explicit guidance regarding workplace expectations.[2, 3, 4] To minimize distraction and support residents' professionalism, we recommend that training programs develop and implement clear expectations regarding smartphone use in the active patient care setting.
- Smartphone use during inpatient attending rounds: prevalence, patterns and potential for distraction. J Hosp Med. 2012;7:595–599. , , , .
- The challenges and opportunities of teaching “generation y.” J Grad Med Educ. 2011;3:458–461. , .
- Millennials and the world of work: an organization and management perspective. J Bus Psychol. 2010;25:211–223. , .
- Is your residency program ready for generation y? J Surg Educ. 2010;67:108–111. , , .
- Pew Research Center. Millennials: a portrait of generation next. Pew Research Center Web site. February 2010. Available at: http://www.pewsocialtrends.org/files/2010/10/millennials‐confident‐connected‐open‐to‐change.pdf. Accessed May 9, 2013.
- Spotlight case. Order interrupted by text: multitasking mishap. Agency for Healthcare Research and Quality Web site. December 2011. Available at: http://webmm.ahrq.gov/case.aspx?caseID=257. Accessed May 9, 2013. .
- Training health care professionals to deal with an explosion of electronic distraction. Neurocrit Care. 2013;18:115–117. .
- ECRI Institute. Top 10 health technology hazards for 2013. ECRI Institute Web site. Available at: https://www.ecri.org/Documents/Secure/Health_Devices_Top_10_Hazards_2013.pdf. Accessed May 9, 2013.
- Smartphone use during inpatient attending rounds: prevalence, patterns and potential for distraction. J Hosp Med. 2012;7:595–599. , , , .
- The challenges and opportunities of teaching “generation y.” J Grad Med Educ. 2011;3:458–461. , .
- Millennials and the world of work: an organization and management perspective. J Bus Psychol. 2010;25:211–223. , .
- Is your residency program ready for generation y? J Surg Educ. 2010;67:108–111. , , .
- Pew Research Center. Millennials: a portrait of generation next. Pew Research Center Web site. February 2010. Available at: http://www.pewsocialtrends.org/files/2010/10/millennials‐confident‐connected‐open‐to‐change.pdf. Accessed May 9, 2013.
- Spotlight case. Order interrupted by text: multitasking mishap. Agency for Healthcare Research and Quality Web site. December 2011. Available at: http://webmm.ahrq.gov/case.aspx?caseID=257. Accessed May 9, 2013. .
- Training health care professionals to deal with an explosion of electronic distraction. Neurocrit Care. 2013;18:115–117. .
- ECRI Institute. Top 10 health technology hazards for 2013. ECRI Institute Web site. Available at: https://www.ecri.org/Documents/Secure/Health_Devices_Top_10_Hazards_2013.pdf. Accessed May 9, 2013.
Apps for your smart phone
The number of health apps continues to grow at a rapid pace, and if you’re in search of more apps to download and experiment with, Dr. Craig Burkhart has a list for you.
To give a sense of how fast health apps are arriving in the market, Dr. Burkhart of the University of North Carolina at Chapel Hill, broke down the number of health applications for Apple devices at the times of American Academy of Dermatology’s meetings: At the 2012 AAD annual meeting, there were 5,000 iOS health apps. That number went up to 13,000 during the 2012 Summer AAD, and 40,000 at the 2013 AAD annual meeting.
He listed some of his favorites during the 2013 AAD summer academy meeting:
1password – to remember passwords
Byword – a simple writing app
Drafts – to automate text actions, also good for transcriptions
Dropbox – to store and share documents, large or small
Epocrates – for drug reference
Evernote – for note-taking
Flipboard – popular news reader
Google Drive – for documents and spreadsheets
Launch Center Pro – to get quick shortcuts for specific features buried in apps
Mind Node – for mind mapping
Omnifocus – for task management, based on GDT system
PDF Pen and Good Reader – PDF readers with annotating capabilities
PubMed Mobile – to search PubMed for journal articles
Read by QXMD – to keep up with medical and scientific research
Scanner Pro – to capture documents and receipts as PDF
Text Expander Touch – for those who write
Tweetbot – if you use twitter for news
What health apps would you recommend to your colleagues? Write to [email protected] and let us know, or post your favorites on the Skin & Allergy News Facebook page.
Dr. Burkhart had no disclosures relevant to mobile apps.
[email protected] On Twitter @NaseemSMiller
The number of health apps continues to grow at a rapid pace, and if you’re in search of more apps to download and experiment with, Dr. Craig Burkhart has a list for you.
To give a sense of how fast health apps are arriving in the market, Dr. Burkhart of the University of North Carolina at Chapel Hill, broke down the number of health applications for Apple devices at the times of American Academy of Dermatology’s meetings: At the 2012 AAD annual meeting, there were 5,000 iOS health apps. That number went up to 13,000 during the 2012 Summer AAD, and 40,000 at the 2013 AAD annual meeting.
He listed some of his favorites during the 2013 AAD summer academy meeting:
1password – to remember passwords
Byword – a simple writing app
Drafts – to automate text actions, also good for transcriptions
Dropbox – to store and share documents, large or small
Epocrates – for drug reference
Evernote – for note-taking
Flipboard – popular news reader
Google Drive – for documents and spreadsheets
Launch Center Pro – to get quick shortcuts for specific features buried in apps
Mind Node – for mind mapping
Omnifocus – for task management, based on GDT system
PDF Pen and Good Reader – PDF readers with annotating capabilities
PubMed Mobile – to search PubMed for journal articles
Read by QXMD – to keep up with medical and scientific research
Scanner Pro – to capture documents and receipts as PDF
Text Expander Touch – for those who write
Tweetbot – if you use twitter for news
What health apps would you recommend to your colleagues? Write to [email protected] and let us know, or post your favorites on the Skin & Allergy News Facebook page.
Dr. Burkhart had no disclosures relevant to mobile apps.
[email protected] On Twitter @NaseemSMiller
The number of health apps continues to grow at a rapid pace, and if you’re in search of more apps to download and experiment with, Dr. Craig Burkhart has a list for you.
To give a sense of how fast health apps are arriving in the market, Dr. Burkhart of the University of North Carolina at Chapel Hill, broke down the number of health applications for Apple devices at the times of American Academy of Dermatology’s meetings: At the 2012 AAD annual meeting, there were 5,000 iOS health apps. That number went up to 13,000 during the 2012 Summer AAD, and 40,000 at the 2013 AAD annual meeting.
He listed some of his favorites during the 2013 AAD summer academy meeting:
1password – to remember passwords
Byword – a simple writing app
Drafts – to automate text actions, also good for transcriptions
Dropbox – to store and share documents, large or small
Epocrates – for drug reference
Evernote – for note-taking
Flipboard – popular news reader
Google Drive – for documents and spreadsheets
Launch Center Pro – to get quick shortcuts for specific features buried in apps
Mind Node – for mind mapping
Omnifocus – for task management, based on GDT system
PDF Pen and Good Reader – PDF readers with annotating capabilities
PubMed Mobile – to search PubMed for journal articles
Read by QXMD – to keep up with medical and scientific research
Scanner Pro – to capture documents and receipts as PDF
Text Expander Touch – for those who write
Tweetbot – if you use twitter for news
What health apps would you recommend to your colleagues? Write to [email protected] and let us know, or post your favorites on the Skin & Allergy News Facebook page.
Dr. Burkhart had no disclosures relevant to mobile apps.
[email protected] On Twitter @NaseemSMiller
Turn up the tunes in the ICU
Clinical question
Can patient-directed music therapy decrease anxiety and reduce sedative use in the intensive care unit?
Bottom line
Patient-directed music therapy in the intensive care unit (ICU) reduces anxiety in awake, ventilated patients while also decreasing the intensity and frequency of sedative use. (LOE = 1b-)
Reference
Study design
Randomized controlled trial (nonblinded);
Allocation
Concealed
Setting
Inpatient (ICU only)
Synopsis
These investigators studied the effects of patient-directed music therapy in reducing anxiety and sedative use in the ICU. Patients using ventilatory support for acute respiratory failure who were alert enough to consent and operate a music player were randomized, using concealed allocation, to 1 of 3 groups: (1) the use of headphones to listen to music (n = 126), (2) the use of noise-cancelling headphones to block out ICU noise (n = 122), and (3) usual care (n = 125). Only 5% of patients who were assessed for eligibility actually underwent randomization, as patients who were unable to consent because of confusion or deep sedation were excluded. A music therapist helped patients in group 1 select their preferred music. These patients were then directed and prompted to listen to music via headphones as often as desired. In group 2, patients were encouraged to wear noise-cancelling headphones whenever they wanted to block out ICU noise. Patients in all 3 groups had similar baseline characteristics, including anxiety scores at study entry and intensity and frequency of sedation 24 hours prior to enrollment. There was a wide range of Acute Physiology, Age and Chronic Health Evaluation III (APACHE III) scores, but the mean fell between 62 and 66 in all 3 groups. A research nurse administered a 100-mm anxiety visual analog scale to patients daily when feasible.
Patients in the music therapy group listened to music for an average of 80 minutes per day; those in the noise-cancelling group wore their headphones for 34 minutes per day. After adjusting for APACHE III scores and sedation frequency and intensity, the use of music therapy lowered anxiety scores by 19 mm compared with usual care (relative decrease of 36%; P = .003). The music group also had decreased sedation intensity (P = .05) and frequency (P = .01) over time when compared with usual care after adjustments were made for imbalances. For example, by day 5, patients in the music group received 3 doses per day of sedative medication, while those in the usual care group received 5 doses. The music therapy group also showed reduction in sedation frequency when compared with the noise-cancelling headphones group, but there were no significant differences detected in anxiety scoring or sedation intensity between these 2 groups. The study did not examine ICU length of stay or other clinical outcomes.
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.
Clinical question
Can patient-directed music therapy decrease anxiety and reduce sedative use in the intensive care unit?
Bottom line
Patient-directed music therapy in the intensive care unit (ICU) reduces anxiety in awake, ventilated patients while also decreasing the intensity and frequency of sedative use. (LOE = 1b-)
Reference
Study design
Randomized controlled trial (nonblinded);
Allocation
Concealed
Setting
Inpatient (ICU only)
Synopsis
These investigators studied the effects of patient-directed music therapy in reducing anxiety and sedative use in the ICU. Patients using ventilatory support for acute respiratory failure who were alert enough to consent and operate a music player were randomized, using concealed allocation, to 1 of 3 groups: (1) the use of headphones to listen to music (n = 126), (2) the use of noise-cancelling headphones to block out ICU noise (n = 122), and (3) usual care (n = 125). Only 5% of patients who were assessed for eligibility actually underwent randomization, as patients who were unable to consent because of confusion or deep sedation were excluded. A music therapist helped patients in group 1 select their preferred music. These patients were then directed and prompted to listen to music via headphones as often as desired. In group 2, patients were encouraged to wear noise-cancelling headphones whenever they wanted to block out ICU noise. Patients in all 3 groups had similar baseline characteristics, including anxiety scores at study entry and intensity and frequency of sedation 24 hours prior to enrollment. There was a wide range of Acute Physiology, Age and Chronic Health Evaluation III (APACHE III) scores, but the mean fell between 62 and 66 in all 3 groups. A research nurse administered a 100-mm anxiety visual analog scale to patients daily when feasible.
Patients in the music therapy group listened to music for an average of 80 minutes per day; those in the noise-cancelling group wore their headphones for 34 minutes per day. After adjusting for APACHE III scores and sedation frequency and intensity, the use of music therapy lowered anxiety scores by 19 mm compared with usual care (relative decrease of 36%; P = .003). The music group also had decreased sedation intensity (P = .05) and frequency (P = .01) over time when compared with usual care after adjustments were made for imbalances. For example, by day 5, patients in the music group received 3 doses per day of sedative medication, while those in the usual care group received 5 doses. The music therapy group also showed reduction in sedation frequency when compared with the noise-cancelling headphones group, but there were no significant differences detected in anxiety scoring or sedation intensity between these 2 groups. The study did not examine ICU length of stay or other clinical outcomes.
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.
Clinical question
Can patient-directed music therapy decrease anxiety and reduce sedative use in the intensive care unit?
Bottom line
Patient-directed music therapy in the intensive care unit (ICU) reduces anxiety in awake, ventilated patients while also decreasing the intensity and frequency of sedative use. (LOE = 1b-)
Reference
Study design
Randomized controlled trial (nonblinded);
Allocation
Concealed
Setting
Inpatient (ICU only)
Synopsis
These investigators studied the effects of patient-directed music therapy in reducing anxiety and sedative use in the ICU. Patients using ventilatory support for acute respiratory failure who were alert enough to consent and operate a music player were randomized, using concealed allocation, to 1 of 3 groups: (1) the use of headphones to listen to music (n = 126), (2) the use of noise-cancelling headphones to block out ICU noise (n = 122), and (3) usual care (n = 125). Only 5% of patients who were assessed for eligibility actually underwent randomization, as patients who were unable to consent because of confusion or deep sedation were excluded. A music therapist helped patients in group 1 select their preferred music. These patients were then directed and prompted to listen to music via headphones as often as desired. In group 2, patients were encouraged to wear noise-cancelling headphones whenever they wanted to block out ICU noise. Patients in all 3 groups had similar baseline characteristics, including anxiety scores at study entry and intensity and frequency of sedation 24 hours prior to enrollment. There was a wide range of Acute Physiology, Age and Chronic Health Evaluation III (APACHE III) scores, but the mean fell between 62 and 66 in all 3 groups. A research nurse administered a 100-mm anxiety visual analog scale to patients daily when feasible.
Patients in the music therapy group listened to music for an average of 80 minutes per day; those in the noise-cancelling group wore their headphones for 34 minutes per day. After adjusting for APACHE III scores and sedation frequency and intensity, the use of music therapy lowered anxiety scores by 19 mm compared with usual care (relative decrease of 36%; P = .003). The music group also had decreased sedation intensity (P = .05) and frequency (P = .01) over time when compared with usual care after adjustments were made for imbalances. For example, by day 5, patients in the music group received 3 doses per day of sedative medication, while those in the usual care group received 5 doses. The music therapy group also showed reduction in sedation frequency when compared with the noise-cancelling headphones group, but there were no significant differences detected in anxiety scoring or sedation intensity between these 2 groups. The study did not examine ICU length of stay or other clinical outcomes.
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.