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In‐Hospital Stroke Alerts

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Code stroke: Multicenter experience with in‐hospital stroke alerts

Acute change in neurologic status in a hospitalized patient is an emergency requiring timely coordinated evaluation. To address this need, many hospitals have created a mechanism for in‐hospital stroke alerts utilizing generalized rapid response teams or specialized stroke teams.[1, 2, 3] The common purpose is to quickly diagnose new ischemic stroke within the time window for thrombolytic therapy.

Even when acute change in neurologic status is not due to brain ischemia, it may represent a new metabolic disturbance or reflect developing serious systemic illness. Sepsis, hypoglycemia, cardiac arrhythmia, respiratory failure, severe electrolyte disturbances, seizures, or delirium may first manifest as a change in neurologic status.

Prior research on stroke alerts has largely focused on patients who present from the community to the emergency department (ED).[4, 5, 6, 7, 8] Patients who develop acute neurologic symptoms during hospitalization have different risk factors and exposures compared to patients in the community.[9] This study represents the experience of a multistate quality improvement initiative for in‐hospital stroke. We characterize etiologies for symptoms triggering in‐hospital stroke alerts and thrombolytic treatment for in‐hospital strokes.

PATIENTS AND METHODS

The National Stroke Association's (NSA) initiative, Improving In‐Hospital Stroke Response: A Team‐based Quality Improvement Program, included data collection for all in‐hospital stroke alerts over a 12‐month period.[10] Six Joint Commission certified primary stroke centers from Michigan, South Carolina, Pennsylvania, Colorado, Washington, and North Carolina completed the 1‐year quality improvement initiative. One additional site withdrew from the program after the first quarter and was not included in this analysis. Sites prospectively reported deidentified patient‐level data on all adult in‐hospital stroke alerts from July 2010 to June 2011 to the NSA. At all sites, any provider could activate the in‐hospital stroke response system. Stroke alerts were evaluated by a rapid response team with stroke training. The providers on the stroke rapid response team varied between sites. A nurse with stroke training was 1 of the first responders on the stroke response team at all sites.

The NSA in‐hospital stroke‐alert criteria included the following symptoms occurring in the last 24‐hours, even if they resolved: (1) sudden numbness or weakness of the face, arm or leg, especially on 1 side of the body; (2) sudden confusion, trouble speaking or understanding; (3) sudden trouble seeing in 1 or both eyes; (4) sudden trouble walking, dizziness, loss of balance or coordination; and (5) sudden, severe headache with no known cause. Hospitals reported location, service, age, sex, race, symptoms triggering the stroke alert, free text entry of final clinical diagnosis following the completion of stroke alert evaluation, treatment with intravenous or intra‐arterial/mechanical thrombolysis, and any contraindications to intravenous thrombolysis. We categorized stroke mimics using the responses in the final diagnosis field after the data collection period was complete. Strokes were categorized as ischemic stroke, transient ischemic attack (TIA), or intracranial hemorrhage (intraparenchymal, intraventricular, epidural, subdural, or subarachnoid). Stroke mimics were subdivided according to the categories in Table 1. Lack of certainty in the final diagnosis was handled by creating a category of possible TIA, which includes alternative diagnosis versus TIA or the qualifier possible before TIA. Patients with final diagnoses unable to be determined were classified as stroke mimics. Institutional review board exemption was obtained for the deidentified prospective data registry of this quality‐improvement program.

Final Diagnosis Following In‐Hospital Stroke Alert
Diagnosis No. (N=393) %
  • NOTE: Abbreviations: NOS, not otherwise specified; TIA, transient ischemic attack.

Ischemic stroke 167 42.5%
TIA (definite, probable, or likely) 27 6.9%
TIA (possible or versus a mimic) 7 1.8%
Syncope, hypotension, presyncope, bradycardia 23 5.9%
Seizure 23 5.9%
Delirium/encephalopathy/acute confusional state/dementia 23 5.9%
Stroke mimic NOS 21 5.3%
Other (examples include Parkinson's crisis, musculoskeletal, primary ophthalmologic diagnosis, or cardiovascular ischemia) 17 4.3%
Final diagnosis uncertain 16 4.1%
Medication effect (sedation due to narcotics, limb weakness due to epidural anesthetic, pupil dilation from ipratropium) 15 3.8%
Metabolic (hypoglycemia, electrolyte abnormality, hypercarbia, acid/base disorders, respiratory failure) 12 3.1%
Intracranial hemorrhage (intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma) 11 2.8%
Conversion disorder/psychiatric/functional/medically unexplained symptoms 7 1.8%
Old deficit due to remote stroke 6 1.5%
Peripheral neuropathy (Bell's palsy, cranial nerve palsy, compression neuropathy) 6 1.5%
Sepsis/emnfection 5 1.3%
Migraine 4 1.0%
Peripheral vestibular dysfunction 3 0.8%

RESULTS

During the 12‐month data collection period, 393 in‐hospital stroke alerts were reported to the NSA. Hospitals reported an average of 65.5 in‐hospital stroke alerts (range, 27156; standard deviation 46.8) (Table 2). Median age was 70 years (range, 18 to >89 years, interquartile range [IQR], 6280 years). Of the stoke alert patients, 52.8% were female, 81.7% were white, 12.7% were black, 2.9% were Hispanic, and 2.7% were other or were unable to be determined. The most common primary services were medicine/hospitalist (36.4%), cardiology (19.5%), cardiothoracic/vascular surgery (13%), and orthopedic surgery (8.6%).

Participating Site Characteristics
All Six Sites Site A Site B Site C Site D Site E Site F
  • NOTE: Abbreviations: IQR, interquartile range. *Lower limit of confidence range represents estimate if all possible transient ischemic attack and final diagnosis unknown represented true ischemic strokes. Upper limit of confidence range represents estimate if all possible transient ischemic attack and final diagnosis uncertain represented stroke mimics.

No. of stroke alerts 393 156 72 50 49 39 27
Median age, y, (IQR 25th to 75th percentile), no. with data for this demographic 70.0 (6280) 376 71.0 (63.081.0) 156 68.0 (58.879.3) 72 76.5 (65.585.0) 50 71.0 (63.078.5) 48 75.0 (58.584.5) 23 77.0 (66.084.5) 27
Sex, % female, no. with data for this demographic 52.8%, 377 48.7%, 156 63.9%, 72 52%, 50 49.0%, 49 52.2%, 23 55.6%, 27
Race, no. (%)
White 308 (81.7%) 146 (93.6%) 40 (55.6%) 47 (94%) 39 (80.0%) 15 (65.2%) 21 (77.8%)
Black or African American 48 (12.7%) 3 (1.9%) 32 (44.4%) 1 (2%) 6 (12.2%) 0 (0%) 6 (22.2%)
Hispanic 11 (2.9%) 3 (1.9%) 0 (0%) 1 (2%) 1 (2.0%) 6 (26.1%) 0 (0%)
Other or unable to determine 10 (2.7%) 4 (2.6%) 0 (0%) 1 (2%) 3 (6.1%) 2 (8.7%) 0 (0%)
No. with data for this demographic 377 156 72 50 49 23 27
Service caring for patient, no. (%)
General medicine 123 (36.4%) 44 (32.1%) 29 (40.3%) 21 (46.7%) 11 (22.9%) 7 (77.7%) 11 (40.7%)
Cardiology 66 (19.5%) 36 (26.3%) 11 (15.3%) 10 (22.2%) 9 (18.8%) 0 (0%) 0 (0%)
Cardiothoracic/vascular surgery 44 (13.0%) 21 (15.3%) 8 (11.1%) 3 (6.7%) 11 (22.9%) 0 (0%) 1 (3.7%)
Orthopedic surgery 29 (8.6%) 17 (12.4%) 4 (5.6%) 3 (6.7%) 2 (4.2%) 0 (0%) 3 (11.1%)
Family practice 13 (3.8%) 2 (1.5%) 1 (1.4%) 1 (2.2%) 0 (0%) 0 (0%) 9 (33.3%)
Pulmonology/critical care 11 (3.3%) 4 (2.9%) 4 (5.6%) 2 (4.4%) 1 (2.1%) 0 (0%) 0 (0%)
General surgery 11 (3.3%) 4 (2.9%) 1 (1.4%) 3 (6.7%) 2 (4.2%) 0 (0%) 1 (3.7%)
Other 41 (12.1%) 9 (6.6%) 14 (19.4%) 2 (4.4%) 12 (25.0%) 2 (22.2) 2 (7.4%)
No. with data for this demographic 338 137 72 45 48 9 27
In‐hospital stroke alert mimic rate
Percent stroke mimics(confidence range)* 46.1% (42.0%47.8%) 48.7% (42.9%51.3%) 50.0% (50.0%50.0%) 28.0% (28.0%30.0%) 42.9% (36.7%46.9%) 66.7% (56.4%66.7%) 29.6% (29.6%29.6%)

Of the stroke alert patients, 167 (42.5%) were found to have ischemic stroke, 27 (6.9%) TIA, 11 (2.8%) intracranial hemorrhage, and 7 (1.8%) had TIA possible or considered along with a stroke mimic in the final diagnosis. The stroke mimic rate was 46.1%, with a confidence range of 42.0% to 47.8% depending on the true pathologic cause of the alerts in the categories possible TIA and final diagnosis uncertain. Participating hospitals had an alarm rate for stroke mimics ranging from 28.0% to 66.7% (median, 45.8%; IQR, 32.9%49.7%) (Table 2). The most common stroke mimics were seizure, hypotension, and delirium (Table 1). Data were available on symptoms that triggered the alert in 373 (94.9%) of cases. Eighteen alerts (4.8%) were for symptoms clearly not included in the NSA stroke alert criteria. The final diagnosis was acute ischemic stroke/TIA or intracranial hemorrhage in 4 of these 18 (22.2%) nonconforming alerts. If alerts called for a decrease in consciousness were also considered nonconforming, then 67 alerts (18.0%) could be categorized as nonconforming. However, 24 of these 67 alerts (35.8%) had a final diagnosis of acute ischemic stroke/TIA or intracranial hemorrhage.

For 194 patients with a final diagnosis of ischemic stroke or TIA, intravenous thrombolysis alone was used for 16 in‐hospital stroke patients (8.2%), 20 received intra‐arterial/mechanical thrombolysis alone (10.3%), and 2 patients received both (1%) (Table 3). No patient with a stroke mimic received thrombolysis.

In‐Hospital Stroke Thrombolysis Rates and Contraindications
  • NOTE: Abbreviations: IA, intra‐arterial; IV, intravenous; TIA, transient ischemic attack; tPA, tissue plasminogen activator. *Definitions for IV exclusions. Multiple: any time more than 1 valid contraindication to IV tPA was listed. Examples would include: recent myocardial infarction on anticoagulation, out of time window and recent myocardial infarction, recent stroke, and advanced age with high National Institute of Health Stroke Scale, no clear onset time, and history of hemorrhagic stroke. Time based: if the sole listed contraindication related to time from onset of brain ischemia. Examples include outside of treatment window, time delay, subacute strokes on imaging, or unknown time last known normal. Medical contraindications: examples include arterial‐venous malformation noted on computed tomography scan, history of recent stroke, history of recent myocardial infarction, gastrointestinal bleeding, or hematuria. Surgical/procedural: recent surgery such as femoral bypass, coronary artery bypass, orthopedic surgery, bowel resection, or invasive procedure such as thoracentesis, arterial puncture at noncompressable site, or cardiac catheterization. Contraindication not otherwise specified: contraindication to IV thrombolysis present but no specific contraindication listed. Minor or improving symptoms: examples include low scores on the National Institute of Health Stroke Scale or rapid improvement in symptoms. Anticoagulation: IV thrombolysis contraindicated due to use of anticoagulation product. Examples include use of warfarin with elevated international normalized ratio or treatment with therapeutic heparin or low‐molecular‐weight heparin. Other: if contraindication was listed but did not meet approved list of contraindications or if no contraindication to IV thrombolysis was listed but the patient was treated only with intra‐arterial or mechanical thrombolysis. Examples include epistaxis or diabetic retinopathy or basilar artery thrombosis treated with IA thrombolysis. Goals of care: patient preferences or goals represent the reason for not considering thrombolysis or if patient/family declined thrombolysis. Examples include comfort measures only status or family declined. Missing: field for contraindication left blank or notated as unable to determine. Seizure at onset of symptoms: for patients with final diagnosis of stroke this would represent onset seizures rather than seizure mimicking stroke, but at the time of the initial stroke alert the seizure was felt to be a contraindication to thrombolysis.

Treatment of stroke alerts with final diagnosis of ischemic stroke or TIA, no. (%), n=194
Treated with IV thrombolysis alone 16 (8.2%)
Treated with IA or mechanical thrombolysis alone 20 (10.3%)
Treated with both IV and IA/mechanical thrombolysis 2 (1.0%)
Contraindication to IV thrombolysis for patients not treated with IV thrombolysis, no. (%), n=176*
Multiple 42 (23.9%)
Time based 27 (15.3%)
Medical 25 (14.2%)
Contraindication not otherwise specified 24 (13.6%)
Surgical/procedural 20 (11.4%)
Minor or rapidly improving symptoms 19 (10.8%)
Anticoagulation 7 (4.0%)
Other 4 (2.3%)
Goals of care 3 (1.7%)
Data unavailable 3 (1.7%)
Seizure at onset of symptoms 2 (1.1%)

DISCUSSION

Given the protean manifestations of brain ischemia, and significant symptom overlap with many mimics, stroke alert criteria casts a wide net in order not to miss or delay evaluation and treatment of true brain ischemia. Time is critical given the association of improved outcomes with more rapid delivery of treatment.[11] The inevitable consequence of the combination of time pressure and clinical uncertainty based solely on physical exam will be alerts due to stroke mimics. Our analysis reveals many of these alternative diagnoses also require urgent evaluation and treatment.

Prior research has found a large proportion of in‐hospital stroke alerts are not for cerebrovascular events.[1, 4, 12] We observed an average of 46.1% of in‐hospital stroke alerts were due to mimics. This rate is substantially higher than described in studies of stroke mimics in the ED.[7, 13, 14] The largest analysis over a 10‐year period from 2 hospitals in Washington found a 30% stroke mimic rate and concluded that in‐hospital location for symptom onset was a statistically significant predictor of being a mimic rather than a cerebrovascular event.[4] One single‐center trial in North Carolina found markedly higher mimic rates for in‐hospital stroke alerts (73%) versus ED stroke alerts (49%).[12] Assessment of neurologic symptoms is challenging in patients already hospitalized for acute medical conditions. The interaction of systemic illness, medications, and surgery seen in the hospital setting may make it more difficult to distinguish between cerebrovascular events and their many mimics.

Interpretation of NSA criteria for calling a stroke code likely varied within and between sites, and inter‐rater reliability of physical signs was not assessed, which is a limitation of the data. Observed rates of stroke for alerts that did not conform to the NSA criteria suggest that clinical judgment remains valuable. Final diagnoses were assigned by the stroke programs, and reliability of this assessment was not evaluated. Sites were not asked to use a specific categorization scheme to group final diagnoses. This analysis was limited to stroke centers with existing infrastructure to respond to stroke alerts and participated in an explicit quality‐improvement initiative on in‐hospital stroke response. Mimic and thrombolysis treatment rates may be different for hospitals without this stroke expertise.

Clinical uncertainty as to final diagnosis was addressed with the inclusion of confidence intervals accounting for potential misdiagnosis of the events in the categories of possible TIA or in the cases where the final diagnosis was unknown. Other studies have categorized TIA versus an alternative diagnosis as stroke mimic, and so our methodology is expected to yield a conservative estimate of the stroke mimic rate. Delirium is often a multifactorial phenomenon, so there may be an element of overlap between this category and other more specific mimic etiologies such as infection, hypotension, metabolic, or medication effect.

This initiative did not have the ability to assess the false negative rate of stroke team activation (failure to identify stroke symptoms in time for acute evaluation). It is not possible to calculate the sensitivity of stroke alerts in each center or conclude the optimal rate of false alarms. The finding of inter‐institutional variability in stroke alerts due to true brain ischemia could be explained by differences in staff education, systematic differences in the patient populations cared for among hospitals, or variation in institutional acceptance of having activated the stroke response team for cases with lower pretest probability of stroke. Sensitivity of alert criteria is more important than specificity, given the consequences of missing a potentially treatable emergent condition.

In conclusion, in this multi‐institution analysis of in‐hospital stroke alerts, a substantial proportion of in‐hospital strokes received thrombolytic therapy. Almost half of stroke alerts will not be for stroke or TIA. For many patients in our study, a change in neurologic status represented a harbinger of a change in general medical condition (hemorrhage, hypotension, hypoglycemia, or respiratory failure). Rapid response systems used for stroke in the hospital need to be trained and prepared to respond to a variety of acute medical conditions that extend beyond ischemic stroke.

Acknowledgements

This work was possible through the National Stroke Association's (NSA) In‐hospital Stroke Quality Improvement Initiative and NSA staff members including Jane Staller, MEd, Miranda N. Bretz, MS, and Amy K. Jensen.

Disclosures: This quality improvement project was funded by an educational grant to the National Stroke Association from Genentech, Inc. and Penumbra, Inc. The funding organizations had no role in the design, content, or preparation of this manuscript. The authors report no conflicts of interest.

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References
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  2. Nolan S, Naylor G, Burns M. Code gray—an organized approach to inpatient stroke. Crit Care Nurs Q. 2003;26:296302.
  3. Daly M, Orto V, Wood C. ID, Stat: rapid response to in‐hospital stroke patients. Nurs Manage. 2009;40:3438.
  4. Merino JG, Luby M, Benson RT, et al. Predictors of acute stroke mimics in 8187 patients referred to a stroke service. J Stroke Cerebrovasc Dis. 2013;22:e397e403.
  5. Forster A, Griebe M, Wolf ME, Szabo K, Hennerici MG, Kern R. How to identify stroke mimics in patients eligible for intravenous thrombolysis? J Neurol. 2012;259:13471353.
  6. Hand PJ, Kwan J, Lindley RI, Dennis MS, Wardlaw JM. Distinguishing between stroke and mimic at the bedside: The Brain Attack Study. Stroke. 2006;37:769775.
  7. Hemmen TM, Meyer BC, McClean TL, Lyden PD. Identification of nonischemic stroke mimics among 411 code strokes at the University of California, San Diego, Stroke Center. J Stroke Cerebrovasc Dis. 2008;17:2325.
  8. Tobin WO, Hentz JG, Bobrow BJ, Demaerschalk BM. Identification of stroke mimics in the emergency department setting. J Brain Dis. 2009;1:1922.
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Acute change in neurologic status in a hospitalized patient is an emergency requiring timely coordinated evaluation. To address this need, many hospitals have created a mechanism for in‐hospital stroke alerts utilizing generalized rapid response teams or specialized stroke teams.[1, 2, 3] The common purpose is to quickly diagnose new ischemic stroke within the time window for thrombolytic therapy.

Even when acute change in neurologic status is not due to brain ischemia, it may represent a new metabolic disturbance or reflect developing serious systemic illness. Sepsis, hypoglycemia, cardiac arrhythmia, respiratory failure, severe electrolyte disturbances, seizures, or delirium may first manifest as a change in neurologic status.

Prior research on stroke alerts has largely focused on patients who present from the community to the emergency department (ED).[4, 5, 6, 7, 8] Patients who develop acute neurologic symptoms during hospitalization have different risk factors and exposures compared to patients in the community.[9] This study represents the experience of a multistate quality improvement initiative for in‐hospital stroke. We characterize etiologies for symptoms triggering in‐hospital stroke alerts and thrombolytic treatment for in‐hospital strokes.

PATIENTS AND METHODS

The National Stroke Association's (NSA) initiative, Improving In‐Hospital Stroke Response: A Team‐based Quality Improvement Program, included data collection for all in‐hospital stroke alerts over a 12‐month period.[10] Six Joint Commission certified primary stroke centers from Michigan, South Carolina, Pennsylvania, Colorado, Washington, and North Carolina completed the 1‐year quality improvement initiative. One additional site withdrew from the program after the first quarter and was not included in this analysis. Sites prospectively reported deidentified patient‐level data on all adult in‐hospital stroke alerts from July 2010 to June 2011 to the NSA. At all sites, any provider could activate the in‐hospital stroke response system. Stroke alerts were evaluated by a rapid response team with stroke training. The providers on the stroke rapid response team varied between sites. A nurse with stroke training was 1 of the first responders on the stroke response team at all sites.

The NSA in‐hospital stroke‐alert criteria included the following symptoms occurring in the last 24‐hours, even if they resolved: (1) sudden numbness or weakness of the face, arm or leg, especially on 1 side of the body; (2) sudden confusion, trouble speaking or understanding; (3) sudden trouble seeing in 1 or both eyes; (4) sudden trouble walking, dizziness, loss of balance or coordination; and (5) sudden, severe headache with no known cause. Hospitals reported location, service, age, sex, race, symptoms triggering the stroke alert, free text entry of final clinical diagnosis following the completion of stroke alert evaluation, treatment with intravenous or intra‐arterial/mechanical thrombolysis, and any contraindications to intravenous thrombolysis. We categorized stroke mimics using the responses in the final diagnosis field after the data collection period was complete. Strokes were categorized as ischemic stroke, transient ischemic attack (TIA), or intracranial hemorrhage (intraparenchymal, intraventricular, epidural, subdural, or subarachnoid). Stroke mimics were subdivided according to the categories in Table 1. Lack of certainty in the final diagnosis was handled by creating a category of possible TIA, which includes alternative diagnosis versus TIA or the qualifier possible before TIA. Patients with final diagnoses unable to be determined were classified as stroke mimics. Institutional review board exemption was obtained for the deidentified prospective data registry of this quality‐improvement program.

Final Diagnosis Following In‐Hospital Stroke Alert
Diagnosis No. (N=393) %
  • NOTE: Abbreviations: NOS, not otherwise specified; TIA, transient ischemic attack.

Ischemic stroke 167 42.5%
TIA (definite, probable, or likely) 27 6.9%
TIA (possible or versus a mimic) 7 1.8%
Syncope, hypotension, presyncope, bradycardia 23 5.9%
Seizure 23 5.9%
Delirium/encephalopathy/acute confusional state/dementia 23 5.9%
Stroke mimic NOS 21 5.3%
Other (examples include Parkinson's crisis, musculoskeletal, primary ophthalmologic diagnosis, or cardiovascular ischemia) 17 4.3%
Final diagnosis uncertain 16 4.1%
Medication effect (sedation due to narcotics, limb weakness due to epidural anesthetic, pupil dilation from ipratropium) 15 3.8%
Metabolic (hypoglycemia, electrolyte abnormality, hypercarbia, acid/base disorders, respiratory failure) 12 3.1%
Intracranial hemorrhage (intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma) 11 2.8%
Conversion disorder/psychiatric/functional/medically unexplained symptoms 7 1.8%
Old deficit due to remote stroke 6 1.5%
Peripheral neuropathy (Bell's palsy, cranial nerve palsy, compression neuropathy) 6 1.5%
Sepsis/emnfection 5 1.3%
Migraine 4 1.0%
Peripheral vestibular dysfunction 3 0.8%

RESULTS

During the 12‐month data collection period, 393 in‐hospital stroke alerts were reported to the NSA. Hospitals reported an average of 65.5 in‐hospital stroke alerts (range, 27156; standard deviation 46.8) (Table 2). Median age was 70 years (range, 18 to >89 years, interquartile range [IQR], 6280 years). Of the stoke alert patients, 52.8% were female, 81.7% were white, 12.7% were black, 2.9% were Hispanic, and 2.7% were other or were unable to be determined. The most common primary services were medicine/hospitalist (36.4%), cardiology (19.5%), cardiothoracic/vascular surgery (13%), and orthopedic surgery (8.6%).

Participating Site Characteristics
All Six Sites Site A Site B Site C Site D Site E Site F
  • NOTE: Abbreviations: IQR, interquartile range. *Lower limit of confidence range represents estimate if all possible transient ischemic attack and final diagnosis unknown represented true ischemic strokes. Upper limit of confidence range represents estimate if all possible transient ischemic attack and final diagnosis uncertain represented stroke mimics.

No. of stroke alerts 393 156 72 50 49 39 27
Median age, y, (IQR 25th to 75th percentile), no. with data for this demographic 70.0 (6280) 376 71.0 (63.081.0) 156 68.0 (58.879.3) 72 76.5 (65.585.0) 50 71.0 (63.078.5) 48 75.0 (58.584.5) 23 77.0 (66.084.5) 27
Sex, % female, no. with data for this demographic 52.8%, 377 48.7%, 156 63.9%, 72 52%, 50 49.0%, 49 52.2%, 23 55.6%, 27
Race, no. (%)
White 308 (81.7%) 146 (93.6%) 40 (55.6%) 47 (94%) 39 (80.0%) 15 (65.2%) 21 (77.8%)
Black or African American 48 (12.7%) 3 (1.9%) 32 (44.4%) 1 (2%) 6 (12.2%) 0 (0%) 6 (22.2%)
Hispanic 11 (2.9%) 3 (1.9%) 0 (0%) 1 (2%) 1 (2.0%) 6 (26.1%) 0 (0%)
Other or unable to determine 10 (2.7%) 4 (2.6%) 0 (0%) 1 (2%) 3 (6.1%) 2 (8.7%) 0 (0%)
No. with data for this demographic 377 156 72 50 49 23 27
Service caring for patient, no. (%)
General medicine 123 (36.4%) 44 (32.1%) 29 (40.3%) 21 (46.7%) 11 (22.9%) 7 (77.7%) 11 (40.7%)
Cardiology 66 (19.5%) 36 (26.3%) 11 (15.3%) 10 (22.2%) 9 (18.8%) 0 (0%) 0 (0%)
Cardiothoracic/vascular surgery 44 (13.0%) 21 (15.3%) 8 (11.1%) 3 (6.7%) 11 (22.9%) 0 (0%) 1 (3.7%)
Orthopedic surgery 29 (8.6%) 17 (12.4%) 4 (5.6%) 3 (6.7%) 2 (4.2%) 0 (0%) 3 (11.1%)
Family practice 13 (3.8%) 2 (1.5%) 1 (1.4%) 1 (2.2%) 0 (0%) 0 (0%) 9 (33.3%)
Pulmonology/critical care 11 (3.3%) 4 (2.9%) 4 (5.6%) 2 (4.4%) 1 (2.1%) 0 (0%) 0 (0%)
General surgery 11 (3.3%) 4 (2.9%) 1 (1.4%) 3 (6.7%) 2 (4.2%) 0 (0%) 1 (3.7%)
Other 41 (12.1%) 9 (6.6%) 14 (19.4%) 2 (4.4%) 12 (25.0%) 2 (22.2) 2 (7.4%)
No. with data for this demographic 338 137 72 45 48 9 27
In‐hospital stroke alert mimic rate
Percent stroke mimics(confidence range)* 46.1% (42.0%47.8%) 48.7% (42.9%51.3%) 50.0% (50.0%50.0%) 28.0% (28.0%30.0%) 42.9% (36.7%46.9%) 66.7% (56.4%66.7%) 29.6% (29.6%29.6%)

Of the stroke alert patients, 167 (42.5%) were found to have ischemic stroke, 27 (6.9%) TIA, 11 (2.8%) intracranial hemorrhage, and 7 (1.8%) had TIA possible or considered along with a stroke mimic in the final diagnosis. The stroke mimic rate was 46.1%, with a confidence range of 42.0% to 47.8% depending on the true pathologic cause of the alerts in the categories possible TIA and final diagnosis uncertain. Participating hospitals had an alarm rate for stroke mimics ranging from 28.0% to 66.7% (median, 45.8%; IQR, 32.9%49.7%) (Table 2). The most common stroke mimics were seizure, hypotension, and delirium (Table 1). Data were available on symptoms that triggered the alert in 373 (94.9%) of cases. Eighteen alerts (4.8%) were for symptoms clearly not included in the NSA stroke alert criteria. The final diagnosis was acute ischemic stroke/TIA or intracranial hemorrhage in 4 of these 18 (22.2%) nonconforming alerts. If alerts called for a decrease in consciousness were also considered nonconforming, then 67 alerts (18.0%) could be categorized as nonconforming. However, 24 of these 67 alerts (35.8%) had a final diagnosis of acute ischemic stroke/TIA or intracranial hemorrhage.

For 194 patients with a final diagnosis of ischemic stroke or TIA, intravenous thrombolysis alone was used for 16 in‐hospital stroke patients (8.2%), 20 received intra‐arterial/mechanical thrombolysis alone (10.3%), and 2 patients received both (1%) (Table 3). No patient with a stroke mimic received thrombolysis.

In‐Hospital Stroke Thrombolysis Rates and Contraindications
  • NOTE: Abbreviations: IA, intra‐arterial; IV, intravenous; TIA, transient ischemic attack; tPA, tissue plasminogen activator. *Definitions for IV exclusions. Multiple: any time more than 1 valid contraindication to IV tPA was listed. Examples would include: recent myocardial infarction on anticoagulation, out of time window and recent myocardial infarction, recent stroke, and advanced age with high National Institute of Health Stroke Scale, no clear onset time, and history of hemorrhagic stroke. Time based: if the sole listed contraindication related to time from onset of brain ischemia. Examples include outside of treatment window, time delay, subacute strokes on imaging, or unknown time last known normal. Medical contraindications: examples include arterial‐venous malformation noted on computed tomography scan, history of recent stroke, history of recent myocardial infarction, gastrointestinal bleeding, or hematuria. Surgical/procedural: recent surgery such as femoral bypass, coronary artery bypass, orthopedic surgery, bowel resection, or invasive procedure such as thoracentesis, arterial puncture at noncompressable site, or cardiac catheterization. Contraindication not otherwise specified: contraindication to IV thrombolysis present but no specific contraindication listed. Minor or improving symptoms: examples include low scores on the National Institute of Health Stroke Scale or rapid improvement in symptoms. Anticoagulation: IV thrombolysis contraindicated due to use of anticoagulation product. Examples include use of warfarin with elevated international normalized ratio or treatment with therapeutic heparin or low‐molecular‐weight heparin. Other: if contraindication was listed but did not meet approved list of contraindications or if no contraindication to IV thrombolysis was listed but the patient was treated only with intra‐arterial or mechanical thrombolysis. Examples include epistaxis or diabetic retinopathy or basilar artery thrombosis treated with IA thrombolysis. Goals of care: patient preferences or goals represent the reason for not considering thrombolysis or if patient/family declined thrombolysis. Examples include comfort measures only status or family declined. Missing: field for contraindication left blank or notated as unable to determine. Seizure at onset of symptoms: for patients with final diagnosis of stroke this would represent onset seizures rather than seizure mimicking stroke, but at the time of the initial stroke alert the seizure was felt to be a contraindication to thrombolysis.

Treatment of stroke alerts with final diagnosis of ischemic stroke or TIA, no. (%), n=194
Treated with IV thrombolysis alone 16 (8.2%)
Treated with IA or mechanical thrombolysis alone 20 (10.3%)
Treated with both IV and IA/mechanical thrombolysis 2 (1.0%)
Contraindication to IV thrombolysis for patients not treated with IV thrombolysis, no. (%), n=176*
Multiple 42 (23.9%)
Time based 27 (15.3%)
Medical 25 (14.2%)
Contraindication not otherwise specified 24 (13.6%)
Surgical/procedural 20 (11.4%)
Minor or rapidly improving symptoms 19 (10.8%)
Anticoagulation 7 (4.0%)
Other 4 (2.3%)
Goals of care 3 (1.7%)
Data unavailable 3 (1.7%)
Seizure at onset of symptoms 2 (1.1%)

DISCUSSION

Given the protean manifestations of brain ischemia, and significant symptom overlap with many mimics, stroke alert criteria casts a wide net in order not to miss or delay evaluation and treatment of true brain ischemia. Time is critical given the association of improved outcomes with more rapid delivery of treatment.[11] The inevitable consequence of the combination of time pressure and clinical uncertainty based solely on physical exam will be alerts due to stroke mimics. Our analysis reveals many of these alternative diagnoses also require urgent evaluation and treatment.

Prior research has found a large proportion of in‐hospital stroke alerts are not for cerebrovascular events.[1, 4, 12] We observed an average of 46.1% of in‐hospital stroke alerts were due to mimics. This rate is substantially higher than described in studies of stroke mimics in the ED.[7, 13, 14] The largest analysis over a 10‐year period from 2 hospitals in Washington found a 30% stroke mimic rate and concluded that in‐hospital location for symptom onset was a statistically significant predictor of being a mimic rather than a cerebrovascular event.[4] One single‐center trial in North Carolina found markedly higher mimic rates for in‐hospital stroke alerts (73%) versus ED stroke alerts (49%).[12] Assessment of neurologic symptoms is challenging in patients already hospitalized for acute medical conditions. The interaction of systemic illness, medications, and surgery seen in the hospital setting may make it more difficult to distinguish between cerebrovascular events and their many mimics.

Interpretation of NSA criteria for calling a stroke code likely varied within and between sites, and inter‐rater reliability of physical signs was not assessed, which is a limitation of the data. Observed rates of stroke for alerts that did not conform to the NSA criteria suggest that clinical judgment remains valuable. Final diagnoses were assigned by the stroke programs, and reliability of this assessment was not evaluated. Sites were not asked to use a specific categorization scheme to group final diagnoses. This analysis was limited to stroke centers with existing infrastructure to respond to stroke alerts and participated in an explicit quality‐improvement initiative on in‐hospital stroke response. Mimic and thrombolysis treatment rates may be different for hospitals without this stroke expertise.

Clinical uncertainty as to final diagnosis was addressed with the inclusion of confidence intervals accounting for potential misdiagnosis of the events in the categories of possible TIA or in the cases where the final diagnosis was unknown. Other studies have categorized TIA versus an alternative diagnosis as stroke mimic, and so our methodology is expected to yield a conservative estimate of the stroke mimic rate. Delirium is often a multifactorial phenomenon, so there may be an element of overlap between this category and other more specific mimic etiologies such as infection, hypotension, metabolic, or medication effect.

This initiative did not have the ability to assess the false negative rate of stroke team activation (failure to identify stroke symptoms in time for acute evaluation). It is not possible to calculate the sensitivity of stroke alerts in each center or conclude the optimal rate of false alarms. The finding of inter‐institutional variability in stroke alerts due to true brain ischemia could be explained by differences in staff education, systematic differences in the patient populations cared for among hospitals, or variation in institutional acceptance of having activated the stroke response team for cases with lower pretest probability of stroke. Sensitivity of alert criteria is more important than specificity, given the consequences of missing a potentially treatable emergent condition.

In conclusion, in this multi‐institution analysis of in‐hospital stroke alerts, a substantial proportion of in‐hospital strokes received thrombolytic therapy. Almost half of stroke alerts will not be for stroke or TIA. For many patients in our study, a change in neurologic status represented a harbinger of a change in general medical condition (hemorrhage, hypotension, hypoglycemia, or respiratory failure). Rapid response systems used for stroke in the hospital need to be trained and prepared to respond to a variety of acute medical conditions that extend beyond ischemic stroke.

Acknowledgements

This work was possible through the National Stroke Association's (NSA) In‐hospital Stroke Quality Improvement Initiative and NSA staff members including Jane Staller, MEd, Miranda N. Bretz, MS, and Amy K. Jensen.

Disclosures: This quality improvement project was funded by an educational grant to the National Stroke Association from Genentech, Inc. and Penumbra, Inc. The funding organizations had no role in the design, content, or preparation of this manuscript. The authors report no conflicts of interest.

Acute change in neurologic status in a hospitalized patient is an emergency requiring timely coordinated evaluation. To address this need, many hospitals have created a mechanism for in‐hospital stroke alerts utilizing generalized rapid response teams or specialized stroke teams.[1, 2, 3] The common purpose is to quickly diagnose new ischemic stroke within the time window for thrombolytic therapy.

Even when acute change in neurologic status is not due to brain ischemia, it may represent a new metabolic disturbance or reflect developing serious systemic illness. Sepsis, hypoglycemia, cardiac arrhythmia, respiratory failure, severe electrolyte disturbances, seizures, or delirium may first manifest as a change in neurologic status.

Prior research on stroke alerts has largely focused on patients who present from the community to the emergency department (ED).[4, 5, 6, 7, 8] Patients who develop acute neurologic symptoms during hospitalization have different risk factors and exposures compared to patients in the community.[9] This study represents the experience of a multistate quality improvement initiative for in‐hospital stroke. We characterize etiologies for symptoms triggering in‐hospital stroke alerts and thrombolytic treatment for in‐hospital strokes.

PATIENTS AND METHODS

The National Stroke Association's (NSA) initiative, Improving In‐Hospital Stroke Response: A Team‐based Quality Improvement Program, included data collection for all in‐hospital stroke alerts over a 12‐month period.[10] Six Joint Commission certified primary stroke centers from Michigan, South Carolina, Pennsylvania, Colorado, Washington, and North Carolina completed the 1‐year quality improvement initiative. One additional site withdrew from the program after the first quarter and was not included in this analysis. Sites prospectively reported deidentified patient‐level data on all adult in‐hospital stroke alerts from July 2010 to June 2011 to the NSA. At all sites, any provider could activate the in‐hospital stroke response system. Stroke alerts were evaluated by a rapid response team with stroke training. The providers on the stroke rapid response team varied between sites. A nurse with stroke training was 1 of the first responders on the stroke response team at all sites.

The NSA in‐hospital stroke‐alert criteria included the following symptoms occurring in the last 24‐hours, even if they resolved: (1) sudden numbness or weakness of the face, arm or leg, especially on 1 side of the body; (2) sudden confusion, trouble speaking or understanding; (3) sudden trouble seeing in 1 or both eyes; (4) sudden trouble walking, dizziness, loss of balance or coordination; and (5) sudden, severe headache with no known cause. Hospitals reported location, service, age, sex, race, symptoms triggering the stroke alert, free text entry of final clinical diagnosis following the completion of stroke alert evaluation, treatment with intravenous or intra‐arterial/mechanical thrombolysis, and any contraindications to intravenous thrombolysis. We categorized stroke mimics using the responses in the final diagnosis field after the data collection period was complete. Strokes were categorized as ischemic stroke, transient ischemic attack (TIA), or intracranial hemorrhage (intraparenchymal, intraventricular, epidural, subdural, or subarachnoid). Stroke mimics were subdivided according to the categories in Table 1. Lack of certainty in the final diagnosis was handled by creating a category of possible TIA, which includes alternative diagnosis versus TIA or the qualifier possible before TIA. Patients with final diagnoses unable to be determined were classified as stroke mimics. Institutional review board exemption was obtained for the deidentified prospective data registry of this quality‐improvement program.

Final Diagnosis Following In‐Hospital Stroke Alert
Diagnosis No. (N=393) %
  • NOTE: Abbreviations: NOS, not otherwise specified; TIA, transient ischemic attack.

Ischemic stroke 167 42.5%
TIA (definite, probable, or likely) 27 6.9%
TIA (possible or versus a mimic) 7 1.8%
Syncope, hypotension, presyncope, bradycardia 23 5.9%
Seizure 23 5.9%
Delirium/encephalopathy/acute confusional state/dementia 23 5.9%
Stroke mimic NOS 21 5.3%
Other (examples include Parkinson's crisis, musculoskeletal, primary ophthalmologic diagnosis, or cardiovascular ischemia) 17 4.3%
Final diagnosis uncertain 16 4.1%
Medication effect (sedation due to narcotics, limb weakness due to epidural anesthetic, pupil dilation from ipratropium) 15 3.8%
Metabolic (hypoglycemia, electrolyte abnormality, hypercarbia, acid/base disorders, respiratory failure) 12 3.1%
Intracranial hemorrhage (intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma) 11 2.8%
Conversion disorder/psychiatric/functional/medically unexplained symptoms 7 1.8%
Old deficit due to remote stroke 6 1.5%
Peripheral neuropathy (Bell's palsy, cranial nerve palsy, compression neuropathy) 6 1.5%
Sepsis/emnfection 5 1.3%
Migraine 4 1.0%
Peripheral vestibular dysfunction 3 0.8%

RESULTS

During the 12‐month data collection period, 393 in‐hospital stroke alerts were reported to the NSA. Hospitals reported an average of 65.5 in‐hospital stroke alerts (range, 27156; standard deviation 46.8) (Table 2). Median age was 70 years (range, 18 to >89 years, interquartile range [IQR], 6280 years). Of the stoke alert patients, 52.8% were female, 81.7% were white, 12.7% were black, 2.9% were Hispanic, and 2.7% were other or were unable to be determined. The most common primary services were medicine/hospitalist (36.4%), cardiology (19.5%), cardiothoracic/vascular surgery (13%), and orthopedic surgery (8.6%).

Participating Site Characteristics
All Six Sites Site A Site B Site C Site D Site E Site F
  • NOTE: Abbreviations: IQR, interquartile range. *Lower limit of confidence range represents estimate if all possible transient ischemic attack and final diagnosis unknown represented true ischemic strokes. Upper limit of confidence range represents estimate if all possible transient ischemic attack and final diagnosis uncertain represented stroke mimics.

No. of stroke alerts 393 156 72 50 49 39 27
Median age, y, (IQR 25th to 75th percentile), no. with data for this demographic 70.0 (6280) 376 71.0 (63.081.0) 156 68.0 (58.879.3) 72 76.5 (65.585.0) 50 71.0 (63.078.5) 48 75.0 (58.584.5) 23 77.0 (66.084.5) 27
Sex, % female, no. with data for this demographic 52.8%, 377 48.7%, 156 63.9%, 72 52%, 50 49.0%, 49 52.2%, 23 55.6%, 27
Race, no. (%)
White 308 (81.7%) 146 (93.6%) 40 (55.6%) 47 (94%) 39 (80.0%) 15 (65.2%) 21 (77.8%)
Black or African American 48 (12.7%) 3 (1.9%) 32 (44.4%) 1 (2%) 6 (12.2%) 0 (0%) 6 (22.2%)
Hispanic 11 (2.9%) 3 (1.9%) 0 (0%) 1 (2%) 1 (2.0%) 6 (26.1%) 0 (0%)
Other or unable to determine 10 (2.7%) 4 (2.6%) 0 (0%) 1 (2%) 3 (6.1%) 2 (8.7%) 0 (0%)
No. with data for this demographic 377 156 72 50 49 23 27
Service caring for patient, no. (%)
General medicine 123 (36.4%) 44 (32.1%) 29 (40.3%) 21 (46.7%) 11 (22.9%) 7 (77.7%) 11 (40.7%)
Cardiology 66 (19.5%) 36 (26.3%) 11 (15.3%) 10 (22.2%) 9 (18.8%) 0 (0%) 0 (0%)
Cardiothoracic/vascular surgery 44 (13.0%) 21 (15.3%) 8 (11.1%) 3 (6.7%) 11 (22.9%) 0 (0%) 1 (3.7%)
Orthopedic surgery 29 (8.6%) 17 (12.4%) 4 (5.6%) 3 (6.7%) 2 (4.2%) 0 (0%) 3 (11.1%)
Family practice 13 (3.8%) 2 (1.5%) 1 (1.4%) 1 (2.2%) 0 (0%) 0 (0%) 9 (33.3%)
Pulmonology/critical care 11 (3.3%) 4 (2.9%) 4 (5.6%) 2 (4.4%) 1 (2.1%) 0 (0%) 0 (0%)
General surgery 11 (3.3%) 4 (2.9%) 1 (1.4%) 3 (6.7%) 2 (4.2%) 0 (0%) 1 (3.7%)
Other 41 (12.1%) 9 (6.6%) 14 (19.4%) 2 (4.4%) 12 (25.0%) 2 (22.2) 2 (7.4%)
No. with data for this demographic 338 137 72 45 48 9 27
In‐hospital stroke alert mimic rate
Percent stroke mimics(confidence range)* 46.1% (42.0%47.8%) 48.7% (42.9%51.3%) 50.0% (50.0%50.0%) 28.0% (28.0%30.0%) 42.9% (36.7%46.9%) 66.7% (56.4%66.7%) 29.6% (29.6%29.6%)

Of the stroke alert patients, 167 (42.5%) were found to have ischemic stroke, 27 (6.9%) TIA, 11 (2.8%) intracranial hemorrhage, and 7 (1.8%) had TIA possible or considered along with a stroke mimic in the final diagnosis. The stroke mimic rate was 46.1%, with a confidence range of 42.0% to 47.8% depending on the true pathologic cause of the alerts in the categories possible TIA and final diagnosis uncertain. Participating hospitals had an alarm rate for stroke mimics ranging from 28.0% to 66.7% (median, 45.8%; IQR, 32.9%49.7%) (Table 2). The most common stroke mimics were seizure, hypotension, and delirium (Table 1). Data were available on symptoms that triggered the alert in 373 (94.9%) of cases. Eighteen alerts (4.8%) were for symptoms clearly not included in the NSA stroke alert criteria. The final diagnosis was acute ischemic stroke/TIA or intracranial hemorrhage in 4 of these 18 (22.2%) nonconforming alerts. If alerts called for a decrease in consciousness were also considered nonconforming, then 67 alerts (18.0%) could be categorized as nonconforming. However, 24 of these 67 alerts (35.8%) had a final diagnosis of acute ischemic stroke/TIA or intracranial hemorrhage.

For 194 patients with a final diagnosis of ischemic stroke or TIA, intravenous thrombolysis alone was used for 16 in‐hospital stroke patients (8.2%), 20 received intra‐arterial/mechanical thrombolysis alone (10.3%), and 2 patients received both (1%) (Table 3). No patient with a stroke mimic received thrombolysis.

In‐Hospital Stroke Thrombolysis Rates and Contraindications
  • NOTE: Abbreviations: IA, intra‐arterial; IV, intravenous; TIA, transient ischemic attack; tPA, tissue plasminogen activator. *Definitions for IV exclusions. Multiple: any time more than 1 valid contraindication to IV tPA was listed. Examples would include: recent myocardial infarction on anticoagulation, out of time window and recent myocardial infarction, recent stroke, and advanced age with high National Institute of Health Stroke Scale, no clear onset time, and history of hemorrhagic stroke. Time based: if the sole listed contraindication related to time from onset of brain ischemia. Examples include outside of treatment window, time delay, subacute strokes on imaging, or unknown time last known normal. Medical contraindications: examples include arterial‐venous malformation noted on computed tomography scan, history of recent stroke, history of recent myocardial infarction, gastrointestinal bleeding, or hematuria. Surgical/procedural: recent surgery such as femoral bypass, coronary artery bypass, orthopedic surgery, bowel resection, or invasive procedure such as thoracentesis, arterial puncture at noncompressable site, or cardiac catheterization. Contraindication not otherwise specified: contraindication to IV thrombolysis present but no specific contraindication listed. Minor or improving symptoms: examples include low scores on the National Institute of Health Stroke Scale or rapid improvement in symptoms. Anticoagulation: IV thrombolysis contraindicated due to use of anticoagulation product. Examples include use of warfarin with elevated international normalized ratio or treatment with therapeutic heparin or low‐molecular‐weight heparin. Other: if contraindication was listed but did not meet approved list of contraindications or if no contraindication to IV thrombolysis was listed but the patient was treated only with intra‐arterial or mechanical thrombolysis. Examples include epistaxis or diabetic retinopathy or basilar artery thrombosis treated with IA thrombolysis. Goals of care: patient preferences or goals represent the reason for not considering thrombolysis or if patient/family declined thrombolysis. Examples include comfort measures only status or family declined. Missing: field for contraindication left blank or notated as unable to determine. Seizure at onset of symptoms: for patients with final diagnosis of stroke this would represent onset seizures rather than seizure mimicking stroke, but at the time of the initial stroke alert the seizure was felt to be a contraindication to thrombolysis.

Treatment of stroke alerts with final diagnosis of ischemic stroke or TIA, no. (%), n=194
Treated with IV thrombolysis alone 16 (8.2%)
Treated with IA or mechanical thrombolysis alone 20 (10.3%)
Treated with both IV and IA/mechanical thrombolysis 2 (1.0%)
Contraindication to IV thrombolysis for patients not treated with IV thrombolysis, no. (%), n=176*
Multiple 42 (23.9%)
Time based 27 (15.3%)
Medical 25 (14.2%)
Contraindication not otherwise specified 24 (13.6%)
Surgical/procedural 20 (11.4%)
Minor or rapidly improving symptoms 19 (10.8%)
Anticoagulation 7 (4.0%)
Other 4 (2.3%)
Goals of care 3 (1.7%)
Data unavailable 3 (1.7%)
Seizure at onset of symptoms 2 (1.1%)

DISCUSSION

Given the protean manifestations of brain ischemia, and significant symptom overlap with many mimics, stroke alert criteria casts a wide net in order not to miss or delay evaluation and treatment of true brain ischemia. Time is critical given the association of improved outcomes with more rapid delivery of treatment.[11] The inevitable consequence of the combination of time pressure and clinical uncertainty based solely on physical exam will be alerts due to stroke mimics. Our analysis reveals many of these alternative diagnoses also require urgent evaluation and treatment.

Prior research has found a large proportion of in‐hospital stroke alerts are not for cerebrovascular events.[1, 4, 12] We observed an average of 46.1% of in‐hospital stroke alerts were due to mimics. This rate is substantially higher than described in studies of stroke mimics in the ED.[7, 13, 14] The largest analysis over a 10‐year period from 2 hospitals in Washington found a 30% stroke mimic rate and concluded that in‐hospital location for symptom onset was a statistically significant predictor of being a mimic rather than a cerebrovascular event.[4] One single‐center trial in North Carolina found markedly higher mimic rates for in‐hospital stroke alerts (73%) versus ED stroke alerts (49%).[12] Assessment of neurologic symptoms is challenging in patients already hospitalized for acute medical conditions. The interaction of systemic illness, medications, and surgery seen in the hospital setting may make it more difficult to distinguish between cerebrovascular events and their many mimics.

Interpretation of NSA criteria for calling a stroke code likely varied within and between sites, and inter‐rater reliability of physical signs was not assessed, which is a limitation of the data. Observed rates of stroke for alerts that did not conform to the NSA criteria suggest that clinical judgment remains valuable. Final diagnoses were assigned by the stroke programs, and reliability of this assessment was not evaluated. Sites were not asked to use a specific categorization scheme to group final diagnoses. This analysis was limited to stroke centers with existing infrastructure to respond to stroke alerts and participated in an explicit quality‐improvement initiative on in‐hospital stroke response. Mimic and thrombolysis treatment rates may be different for hospitals without this stroke expertise.

Clinical uncertainty as to final diagnosis was addressed with the inclusion of confidence intervals accounting for potential misdiagnosis of the events in the categories of possible TIA or in the cases where the final diagnosis was unknown. Other studies have categorized TIA versus an alternative diagnosis as stroke mimic, and so our methodology is expected to yield a conservative estimate of the stroke mimic rate. Delirium is often a multifactorial phenomenon, so there may be an element of overlap between this category and other more specific mimic etiologies such as infection, hypotension, metabolic, or medication effect.

This initiative did not have the ability to assess the false negative rate of stroke team activation (failure to identify stroke symptoms in time for acute evaluation). It is not possible to calculate the sensitivity of stroke alerts in each center or conclude the optimal rate of false alarms. The finding of inter‐institutional variability in stroke alerts due to true brain ischemia could be explained by differences in staff education, systematic differences in the patient populations cared for among hospitals, or variation in institutional acceptance of having activated the stroke response team for cases with lower pretest probability of stroke. Sensitivity of alert criteria is more important than specificity, given the consequences of missing a potentially treatable emergent condition.

In conclusion, in this multi‐institution analysis of in‐hospital stroke alerts, a substantial proportion of in‐hospital strokes received thrombolytic therapy. Almost half of stroke alerts will not be for stroke or TIA. For many patients in our study, a change in neurologic status represented a harbinger of a change in general medical condition (hemorrhage, hypotension, hypoglycemia, or respiratory failure). Rapid response systems used for stroke in the hospital need to be trained and prepared to respond to a variety of acute medical conditions that extend beyond ischemic stroke.

Acknowledgements

This work was possible through the National Stroke Association's (NSA) In‐hospital Stroke Quality Improvement Initiative and NSA staff members including Jane Staller, MEd, Miranda N. Bretz, MS, and Amy K. Jensen.

Disclosures: This quality improvement project was funded by an educational grant to the National Stroke Association from Genentech, Inc. and Penumbra, Inc. The funding organizations had no role in the design, content, or preparation of this manuscript. The authors report no conflicts of interest.

References
  1. Cumbler E, Anderson T, Neumann R, Jones W, Brega K. Stroke alert program improves recognition and evaluation time of in‐hospital ischemic stroke. J Stroke Cerebrovasc Dis. 2010;19:494496.
  2. Nolan S, Naylor G, Burns M. Code gray—an organized approach to inpatient stroke. Crit Care Nurs Q. 2003;26:296302.
  3. Daly M, Orto V, Wood C. ID, Stat: rapid response to in‐hospital stroke patients. Nurs Manage. 2009;40:3438.
  4. Merino JG, Luby M, Benson RT, et al. Predictors of acute stroke mimics in 8187 patients referred to a stroke service. J Stroke Cerebrovasc Dis. 2013;22:e397e403.
  5. Forster A, Griebe M, Wolf ME, Szabo K, Hennerici MG, Kern R. How to identify stroke mimics in patients eligible for intravenous thrombolysis? J Neurol. 2012;259:13471353.
  6. Hand PJ, Kwan J, Lindley RI, Dennis MS, Wardlaw JM. Distinguishing between stroke and mimic at the bedside: The Brain Attack Study. Stroke. 2006;37:769775.
  7. Hemmen TM, Meyer BC, McClean TL, Lyden PD. Identification of nonischemic stroke mimics among 411 code strokes at the University of California, San Diego, Stroke Center. J Stroke Cerebrovasc Dis. 2008;17:2325.
  8. Tobin WO, Hentz JG, Bobrow BJ, Demaerschalk BM. Identification of stroke mimics in the emergency department setting. J Brain Dis. 2009;1:1922.
  9. Park JH, Cho HJ, Kim DW, et al. Comparison of the characteristics for in‐hospital and out‐of‐hospital ischaemic strokes. Eur J Neur. 2009;16:582588.
  10. National Stroke Association. Improving in‐hospital stroke through quality improvement interventions webinar. Available at: http://www.stroke.org/we‐can‐help/healthcare‐professionals/improve‐your‐skills/pre‐hospital‐acute‐stroke‐programs‐4. Accessed December 18, 2014.
  11. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309:24802488.
  12. Husseini NE, Goldstein LB. “Code Stroke”: hospitalized versus emergency department patients. J Stroke Cerebrovasc Dis. 2013;22:345348.
  13. Harbison J, Hossain O, Jenkinson D, et al. Diagnostic accuracy of stroke referrals from primary care, emergency room physicians, and ambulance staff using the face arm speech test. Stroke. 2003;34:7176.
  14. Heckmann JG, Stadter M, Dütsch M, Handschu R, Rauch C, Neundörfer B. Hospitalization of non‐stroke patients in a stroke unit [in German]. Dtsch Med Wochenschr. 2004;129:731735.
References
  1. Cumbler E, Anderson T, Neumann R, Jones W, Brega K. Stroke alert program improves recognition and evaluation time of in‐hospital ischemic stroke. J Stroke Cerebrovasc Dis. 2010;19:494496.
  2. Nolan S, Naylor G, Burns M. Code gray—an organized approach to inpatient stroke. Crit Care Nurs Q. 2003;26:296302.
  3. Daly M, Orto V, Wood C. ID, Stat: rapid response to in‐hospital stroke patients. Nurs Manage. 2009;40:3438.
  4. Merino JG, Luby M, Benson RT, et al. Predictors of acute stroke mimics in 8187 patients referred to a stroke service. J Stroke Cerebrovasc Dis. 2013;22:e397e403.
  5. Forster A, Griebe M, Wolf ME, Szabo K, Hennerici MG, Kern R. How to identify stroke mimics in patients eligible for intravenous thrombolysis? J Neurol. 2012;259:13471353.
  6. Hand PJ, Kwan J, Lindley RI, Dennis MS, Wardlaw JM. Distinguishing between stroke and mimic at the bedside: The Brain Attack Study. Stroke. 2006;37:769775.
  7. Hemmen TM, Meyer BC, McClean TL, Lyden PD. Identification of nonischemic stroke mimics among 411 code strokes at the University of California, San Diego, Stroke Center. J Stroke Cerebrovasc Dis. 2008;17:2325.
  8. Tobin WO, Hentz JG, Bobrow BJ, Demaerschalk BM. Identification of stroke mimics in the emergency department setting. J Brain Dis. 2009;1:1922.
  9. Park JH, Cho HJ, Kim DW, et al. Comparison of the characteristics for in‐hospital and out‐of‐hospital ischaemic strokes. Eur J Neur. 2009;16:582588.
  10. National Stroke Association. Improving in‐hospital stroke through quality improvement interventions webinar. Available at: http://www.stroke.org/we‐can‐help/healthcare‐professionals/improve‐your‐skills/pre‐hospital‐acute‐stroke‐programs‐4. Accessed December 18, 2014.
  11. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309:24802488.
  12. Husseini NE, Goldstein LB. “Code Stroke”: hospitalized versus emergency department patients. J Stroke Cerebrovasc Dis. 2013;22:345348.
  13. Harbison J, Hossain O, Jenkinson D, et al. Diagnostic accuracy of stroke referrals from primary care, emergency room physicians, and ambulance staff using the face arm speech test. Stroke. 2003;34:7176.
  14. Heckmann JG, Stadter M, Dütsch M, Handschu R, Rauch C, Neundörfer B. Hospitalization of non‐stroke patients in a stroke unit [in German]. Dtsch Med Wochenschr. 2004;129:731735.
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Address for correspondence and reprint requests: Ethan Cumbler, MD, Associate Professor, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, 12401 E. 17th Ave., Mail Stop F782, Aurora, CO 80045; Telephone: 702‐848‐4289; Fax: 720‐848‐4293; E‐mail: [email protected]
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Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

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Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56–1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: Comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Visit our website for more information on the use of proton pump inhibitors.


 

 

 

 

 

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Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56–1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: Comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Visit our website for more information on the use of proton pump inhibitors.


 

 

 

 

 

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56–1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: Comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Visit our website for more information on the use of proton pump inhibitors.


 

 

 

 

 

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Intravenous Haloperidol Does Not Prevent ICU Delirium

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Intravenous Haloperidol Does Not Prevent ICU Delirium

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Visit our website for more information on treating delirium in hospitalized patients.

 

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Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Visit our website for more information on treating delirium in hospitalized patients.

 

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Visit our website for more information on treating delirium in hospitalized patients.

 

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Reviews of Research on Haloperidol and ICU Delirium, Proton Pump Inhibitors, Thrombolytics and Stroke

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Reviews of Research on Haloperidol and ICU Delirium, Proton Pump Inhibitors, Thrombolytics and Stroke

 

In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Intravenous haloperidol does not prevent ICU delirium
  2. Predicting delirium risk in hospitalized adults
  3. Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
  4. Probiotic benefit questioned in the elderly
  5. Colchicine and NSAID better than NSAID alone for acute pericarditis
  6. Improvement needed in patient understanding at hospital discharge
  7. Effectiveness of a multihospital effort to reduce rehospitalization
  8. Hospitals profit from preventing surgical site infections
  9. Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
  10. Hospital-acquired anemia associated with higher mortality, increased LOS
  11. Thrombolytics and stroke: the faster the better

Intravenous Haloperidol Does Not Prevent ICU Delirium

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Predicting Delirium Risk in Hospitalized Adults

Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?

Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.

Study design: Prospective cohort study, with separate derivation and validation cohorts.

Setting: Two academic hospitals and a VA hospital in San Francisco.

Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).

These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.

 

 

Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.

Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.

Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Probiotic Benefit Questioned in the Elderly

Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?

Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.

Study Design: Randomized, double-blind, placebo-controlled trial.

Setting: Multicenter trial in the United Kingdom.

Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).

Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.

Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.

Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.

 

 

Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis

Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?

Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.

Study design: Double-blinded, randomized, controlled trial.

Setting: Multicenter in Northern Italy.

Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.

It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.

Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.

Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

Improvement Needed in Patient Understanding at Hospital Discharge

Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?

Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.

Study Design: Prospective, observational cohort study.

Setting: An urban, academic medical center.

Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.

Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.

Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.

Effectiveness of a Multihospital Effort to Reduce Rehospitalization

Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?

 

 

Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.

Study design: Semi-controlled, pre-post study.

Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.

Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.

Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).

Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.

Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.

Hospitals Profit from Preventing Surgical Site Infections

Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?

Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.

Study design: Retrospective study.

Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.

Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.

Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.

Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.

Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR

Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?

 

 

Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.

Study design: Retrospective cohort study.

Setting: Two tertiary care EDs in Canada.

Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.

Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.

Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.

Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.

Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS

Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?

Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.

Study design: Retrospective cohort study.

Setting: Large academic health system in Ohio.

Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.

Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.

Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.

Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.

Thrombolytics and Stroke: The Faster the Better

Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?

Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.

Study design: Observational study.

 

 

Setting: Patient information from 1998 to 2012 from 10 European stroke centers.

Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.

Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.

Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.

Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.

Clinical Shorts

FLUOROQUINOLONES CAN CAUSE BOTH HYPOGLYCEMIA AND HYPERGLYCEMIA IN DIABETIC PATIENTS

A large cohort study showed an increased rate of both hypo- and hyperglycemia in diabetic patients treated with fluoroquinolones vs. macrolides; of the fluoroquinolones used, moxifloxacin was the worst offender.

Citation: Chou HW, Wang JL, Chang CH, Lee JJ, Shau WY, Lai MS. Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan. Clin Infect Dis. 2013;57(7):971–980.

INTRAVENOUS IRON: BENEFITS AND HARMS

Meta-analysis shows IV iron increases hemoglobin levels and reduces the need for red blood cell transfusion in patients with iron deficiency anemia. However, IV iron also increased risk of infection.

Citation: Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomized clinical trials. BMJ. 2013;347:f4822.

PATIENTS THINK PLACEBOS ARE APPROPRIATE IN SOME SITUATIONS

In patient surveys, placebos could be appropriate if no harm occurred and if the physicians gave honest opinions about placebos. Two thirds of patients would consider a placebo in some instances.

Citation: Hull SC, Colloca L, Avins A, et al. Patients’ attitudes about the use of placebo treatments: telephone survey. BMJ. 2013;347:f3757.

NEW ORAL ANTICOAGULANTS EFFECTIVE FOR THROMBOPROPHYLAXIS AFTER TOTAL HIP AND TOTAL KNEE REPLACEMENT

A metasynthesis of six reviews concludes that oral factor Xa inhibitors and direct thrombin inhibitors are effective after TKA-THA; compared to LMWH, the factor Xa inhibitors’ marginal clinical benefits are offset by their increased risk for bleeding.

Citation: Adam SS, McDuffie JR, Lachiewicz PF, Ortel TL, Williams JW. Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review. Ann Intern Med. 2013;159(4):275-284.

Issue
The Hospitalist - 2013(12)
Publications
Topics
Sections

 

In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Intravenous haloperidol does not prevent ICU delirium
  2. Predicting delirium risk in hospitalized adults
  3. Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
  4. Probiotic benefit questioned in the elderly
  5. Colchicine and NSAID better than NSAID alone for acute pericarditis
  6. Improvement needed in patient understanding at hospital discharge
  7. Effectiveness of a multihospital effort to reduce rehospitalization
  8. Hospitals profit from preventing surgical site infections
  9. Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
  10. Hospital-acquired anemia associated with higher mortality, increased LOS
  11. Thrombolytics and stroke: the faster the better

Intravenous Haloperidol Does Not Prevent ICU Delirium

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Predicting Delirium Risk in Hospitalized Adults

Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?

Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.

Study design: Prospective cohort study, with separate derivation and validation cohorts.

Setting: Two academic hospitals and a VA hospital in San Francisco.

Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).

These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.

 

 

Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.

Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.

Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Probiotic Benefit Questioned in the Elderly

Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?

Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.

Study Design: Randomized, double-blind, placebo-controlled trial.

Setting: Multicenter trial in the United Kingdom.

Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).

Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.

Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.

Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.

 

 

Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis

Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?

Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.

Study design: Double-blinded, randomized, controlled trial.

Setting: Multicenter in Northern Italy.

Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.

It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.

Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.

Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

Improvement Needed in Patient Understanding at Hospital Discharge

Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?

Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.

Study Design: Prospective, observational cohort study.

Setting: An urban, academic medical center.

Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.

Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.

Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.

Effectiveness of a Multihospital Effort to Reduce Rehospitalization

Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?

 

 

Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.

Study design: Semi-controlled, pre-post study.

Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.

Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.

Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).

Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.

Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.

Hospitals Profit from Preventing Surgical Site Infections

Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?

Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.

Study design: Retrospective study.

Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.

Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.

Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.

Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.

Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR

Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?

 

 

Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.

Study design: Retrospective cohort study.

Setting: Two tertiary care EDs in Canada.

Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.

Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.

Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.

Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.

Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS

Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?

Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.

Study design: Retrospective cohort study.

Setting: Large academic health system in Ohio.

Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.

Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.

Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.

Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.

Thrombolytics and Stroke: The Faster the Better

Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?

Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.

Study design: Observational study.

 

 

Setting: Patient information from 1998 to 2012 from 10 European stroke centers.

Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.

Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.

Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.

Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.

Clinical Shorts

FLUOROQUINOLONES CAN CAUSE BOTH HYPOGLYCEMIA AND HYPERGLYCEMIA IN DIABETIC PATIENTS

A large cohort study showed an increased rate of both hypo- and hyperglycemia in diabetic patients treated with fluoroquinolones vs. macrolides; of the fluoroquinolones used, moxifloxacin was the worst offender.

Citation: Chou HW, Wang JL, Chang CH, Lee JJ, Shau WY, Lai MS. Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan. Clin Infect Dis. 2013;57(7):971–980.

INTRAVENOUS IRON: BENEFITS AND HARMS

Meta-analysis shows IV iron increases hemoglobin levels and reduces the need for red blood cell transfusion in patients with iron deficiency anemia. However, IV iron also increased risk of infection.

Citation: Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomized clinical trials. BMJ. 2013;347:f4822.

PATIENTS THINK PLACEBOS ARE APPROPRIATE IN SOME SITUATIONS

In patient surveys, placebos could be appropriate if no harm occurred and if the physicians gave honest opinions about placebos. Two thirds of patients would consider a placebo in some instances.

Citation: Hull SC, Colloca L, Avins A, et al. Patients’ attitudes about the use of placebo treatments: telephone survey. BMJ. 2013;347:f3757.

NEW ORAL ANTICOAGULANTS EFFECTIVE FOR THROMBOPROPHYLAXIS AFTER TOTAL HIP AND TOTAL KNEE REPLACEMENT

A metasynthesis of six reviews concludes that oral factor Xa inhibitors and direct thrombin inhibitors are effective after TKA-THA; compared to LMWH, the factor Xa inhibitors’ marginal clinical benefits are offset by their increased risk for bleeding.

Citation: Adam SS, McDuffie JR, Lachiewicz PF, Ortel TL, Williams JW. Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review. Ann Intern Med. 2013;159(4):275-284.

 

In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Intravenous haloperidol does not prevent ICU delirium
  2. Predicting delirium risk in hospitalized adults
  3. Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
  4. Probiotic benefit questioned in the elderly
  5. Colchicine and NSAID better than NSAID alone for acute pericarditis
  6. Improvement needed in patient understanding at hospital discharge
  7. Effectiveness of a multihospital effort to reduce rehospitalization
  8. Hospitals profit from preventing surgical site infections
  9. Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
  10. Hospital-acquired anemia associated with higher mortality, increased LOS
  11. Thrombolytics and stroke: the faster the better

Intravenous Haloperidol Does Not Prevent ICU Delirium

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Predicting Delirium Risk in Hospitalized Adults

Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?

Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.

Study design: Prospective cohort study, with separate derivation and validation cohorts.

Setting: Two academic hospitals and a VA hospital in San Francisco.

Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).

These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.

 

 

Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.

Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.

Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Probiotic Benefit Questioned in the Elderly

Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?

Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.

Study Design: Randomized, double-blind, placebo-controlled trial.

Setting: Multicenter trial in the United Kingdom.

Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).

Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.

Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.

Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.

 

 

Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis

Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?

Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.

Study design: Double-blinded, randomized, controlled trial.

Setting: Multicenter in Northern Italy.

Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.

It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.

Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.

Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

Improvement Needed in Patient Understanding at Hospital Discharge

Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?

Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.

Study Design: Prospective, observational cohort study.

Setting: An urban, academic medical center.

Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.

Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.

Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.

Effectiveness of a Multihospital Effort to Reduce Rehospitalization

Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?

 

 

Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.

Study design: Semi-controlled, pre-post study.

Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.

Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.

Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).

Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.

Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.

Hospitals Profit from Preventing Surgical Site Infections

Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?

Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.

Study design: Retrospective study.

Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.

Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.

Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.

Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.

Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR

Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?

 

 

Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.

Study design: Retrospective cohort study.

Setting: Two tertiary care EDs in Canada.

Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.

Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.

Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.

Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.

Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS

Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?

Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.

Study design: Retrospective cohort study.

Setting: Large academic health system in Ohio.

Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.

Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.

Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.

Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.

Thrombolytics and Stroke: The Faster the Better

Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?

Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.

Study design: Observational study.

 

 

Setting: Patient information from 1998 to 2012 from 10 European stroke centers.

Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.

Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.

Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.

Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.

Clinical Shorts

FLUOROQUINOLONES CAN CAUSE BOTH HYPOGLYCEMIA AND HYPERGLYCEMIA IN DIABETIC PATIENTS

A large cohort study showed an increased rate of both hypo- and hyperglycemia in diabetic patients treated with fluoroquinolones vs. macrolides; of the fluoroquinolones used, moxifloxacin was the worst offender.

Citation: Chou HW, Wang JL, Chang CH, Lee JJ, Shau WY, Lai MS. Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan. Clin Infect Dis. 2013;57(7):971–980.

INTRAVENOUS IRON: BENEFITS AND HARMS

Meta-analysis shows IV iron increases hemoglobin levels and reduces the need for red blood cell transfusion in patients with iron deficiency anemia. However, IV iron also increased risk of infection.

Citation: Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomized clinical trials. BMJ. 2013;347:f4822.

PATIENTS THINK PLACEBOS ARE APPROPRIATE IN SOME SITUATIONS

In patient surveys, placebos could be appropriate if no harm occurred and if the physicians gave honest opinions about placebos. Two thirds of patients would consider a placebo in some instances.

Citation: Hull SC, Colloca L, Avins A, et al. Patients’ attitudes about the use of placebo treatments: telephone survey. BMJ. 2013;347:f3757.

NEW ORAL ANTICOAGULANTS EFFECTIVE FOR THROMBOPROPHYLAXIS AFTER TOTAL HIP AND TOTAL KNEE REPLACEMENT

A metasynthesis of six reviews concludes that oral factor Xa inhibitors and direct thrombin inhibitors are effective after TKA-THA; compared to LMWH, the factor Xa inhibitors’ marginal clinical benefits are offset by their increased risk for bleeding.

Citation: Adam SS, McDuffie JR, Lachiewicz PF, Ortel TL, Williams JW. Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review. Ann Intern Med. 2013;159(4):275-284.

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Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.

 

For more physician reviews of recent HM-relevant literature, visit our website.

 



 

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Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.

 

For more physician reviews of recent HM-relevant literature, visit our website.

 



 

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.

 

For more physician reviews of recent HM-relevant literature, visit our website.

 



 

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In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
  2. Radiation exposure in integrated healthcare systems, 1996-2010
  3. Postoperative troponin predicts 30-day mortality
  4. Clinical prediction model of mortality in acute heart failure
  5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
  6. Early surgery for high-risk, native-valve endocarditis patients
  7. Risk factors after ED visit for syncope
  8. Acute hyperglycemia in CAP patients
  9. Hospital delirium associated with cognitive decline, institutionalization, and death
  10. Seven-day ciprofloxacin effective against acute pyelonephritis
  11. Advance directives in community patients with heart failure
  12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
  13. Simulation training improves lumbar puncture skills
  14. PCP referrals to hospitals and publicly reported data
  15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

 

 

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

 

 

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

 

 

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

 

 

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

 

 

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

 

 

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

 

 

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Issue
The Hospitalist - 2012(10)
Publications
Sections

In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
  2. Radiation exposure in integrated healthcare systems, 1996-2010
  3. Postoperative troponin predicts 30-day mortality
  4. Clinical prediction model of mortality in acute heart failure
  5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
  6. Early surgery for high-risk, native-valve endocarditis patients
  7. Risk factors after ED visit for syncope
  8. Acute hyperglycemia in CAP patients
  9. Hospital delirium associated with cognitive decline, institutionalization, and death
  10. Seven-day ciprofloxacin effective against acute pyelonephritis
  11. Advance directives in community patients with heart failure
  12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
  13. Simulation training improves lumbar puncture skills
  14. PCP referrals to hospitals and publicly reported data
  15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

 

 

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

 

 

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

 

 

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

 

 

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

 

 

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

 

 

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

 

 

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
  2. Radiation exposure in integrated healthcare systems, 1996-2010
  3. Postoperative troponin predicts 30-day mortality
  4. Clinical prediction model of mortality in acute heart failure
  5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
  6. Early surgery for high-risk, native-valve endocarditis patients
  7. Risk factors after ED visit for syncope
  8. Acute hyperglycemia in CAP patients
  9. Hospital delirium associated with cognitive decline, institutionalization, and death
  10. Seven-day ciprofloxacin effective against acute pyelonephritis
  11. Advance directives in community patients with heart failure
  12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
  13. Simulation training improves lumbar puncture skills
  14. PCP referrals to hospitals and publicly reported data
  15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

 

 

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

 

 

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

 

 

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

 

 

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

 

 

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

 

 

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

 

 

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

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Clinical question: Which clinical decision rule—Wells rule, simplified Wells rule, revised Geneva score, or simplified revised Geneva score—is the best for evaluating a patient with a possible acute pulmonary embolism?

Background: The use of standardized clinical decision rules to determine the probability of an acute pulmonary embolism (PE) has significantly improved the diagnostic evaluation of patients with suspected PE. Several clinical decision rules are available and widely used, but they have not been previously directly compared.

Study design: Prospective cohort.

Setting: Seven hospitals in the Netherlands.

Synopsis: A total of 807 patients with suspected first episode of acute PE had a sequential workup with clinical probability assessment and D-dimer testing. When PE was considered unlikely according to all four clinical decision rules and a normal D-dimer result, PE was excluded. In the remaining patients, a CT scan was used to confirm or exclude the diagnosis.

The prevalence of PE was 23%. Combined with a normal D-dimer, the decision rules excluded PE in 22% to 24% of patients. Thirty percent of patients had discordant decision rule outcomes, but PE was not detected by CT in any of these patients when combined with a normal D-dimer.

This study has practical limitations because management was based on a combination of four decision rules and D-dimer testing rather than only one rule and D-dimer testing, which is the more realistic clinical approach.

Bottom line: When used correctly and in conjunction with a D-dimer result, the Wells rule, simplified Wells rule, revised Geneva score, and simplified revised Geneva score all perform similarly in the exclusion of acute PE.

Citation: Douma RA, Mos IC, Erkens PM, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med. 2011;154:709-718.

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Clinical question: Which clinical decision rule—Wells rule, simplified Wells rule, revised Geneva score, or simplified revised Geneva score—is the best for evaluating a patient with a possible acute pulmonary embolism?

Background: The use of standardized clinical decision rules to determine the probability of an acute pulmonary embolism (PE) has significantly improved the diagnostic evaluation of patients with suspected PE. Several clinical decision rules are available and widely used, but they have not been previously directly compared.

Study design: Prospective cohort.

Setting: Seven hospitals in the Netherlands.

Synopsis: A total of 807 patients with suspected first episode of acute PE had a sequential workup with clinical probability assessment and D-dimer testing. When PE was considered unlikely according to all four clinical decision rules and a normal D-dimer result, PE was excluded. In the remaining patients, a CT scan was used to confirm or exclude the diagnosis.

The prevalence of PE was 23%. Combined with a normal D-dimer, the decision rules excluded PE in 22% to 24% of patients. Thirty percent of patients had discordant decision rule outcomes, but PE was not detected by CT in any of these patients when combined with a normal D-dimer.

This study has practical limitations because management was based on a combination of four decision rules and D-dimer testing rather than only one rule and D-dimer testing, which is the more realistic clinical approach.

Bottom line: When used correctly and in conjunction with a D-dimer result, the Wells rule, simplified Wells rule, revised Geneva score, and simplified revised Geneva score all perform similarly in the exclusion of acute PE.

Citation: Douma RA, Mos IC, Erkens PM, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med. 2011;154:709-718.

For more of physician reviews of HM-related literature, check out this month's"In the Literature".

Clinical question: Which clinical decision rule—Wells rule, simplified Wells rule, revised Geneva score, or simplified revised Geneva score—is the best for evaluating a patient with a possible acute pulmonary embolism?

Background: The use of standardized clinical decision rules to determine the probability of an acute pulmonary embolism (PE) has significantly improved the diagnostic evaluation of patients with suspected PE. Several clinical decision rules are available and widely used, but they have not been previously directly compared.

Study design: Prospective cohort.

Setting: Seven hospitals in the Netherlands.

Synopsis: A total of 807 patients with suspected first episode of acute PE had a sequential workup with clinical probability assessment and D-dimer testing. When PE was considered unlikely according to all four clinical decision rules and a normal D-dimer result, PE was excluded. In the remaining patients, a CT scan was used to confirm or exclude the diagnosis.

The prevalence of PE was 23%. Combined with a normal D-dimer, the decision rules excluded PE in 22% to 24% of patients. Thirty percent of patients had discordant decision rule outcomes, but PE was not detected by CT in any of these patients when combined with a normal D-dimer.

This study has practical limitations because management was based on a combination of four decision rules and D-dimer testing rather than only one rule and D-dimer testing, which is the more realistic clinical approach.

Bottom line: When used correctly and in conjunction with a D-dimer result, the Wells rule, simplified Wells rule, revised Geneva score, and simplified revised Geneva score all perform similarly in the exclusion of acute PE.

Citation: Douma RA, Mos IC, Erkens PM, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med. 2011;154:709-718.

For more of physician reviews of HM-related literature, check out this month's"In the Literature".

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Clinical question: When do venous thromboembolism (VTE) events occur after cancer surgery?

Background: Cancer is a known risk factor for VTE. Prophylaxis for VTE after cancer surgery is commonly stopped at the time of hospital discharge despite evidence for extended-duration treatment.

Study design: Retrospective cohort.

Setting: Patients reported to the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

Synopsis: The authors examined the records of 46,656 patients who underwent surgery for one of nine specified cancers. Overall VTE rate was 1.6% (1.0% deep venous thrombosis and 0.6% pulmonary embolism), with 33.4% of VTE events occurring after hospital discharge. VTE risk was highest after esophagogastric and hepatopancreaticobiliary surgery, followed by lung, rectum, ovary/uterus, colon, and prostate. Breast and thyroid/parathyroid surgeries had the lowest incidence of VTE. VTE was associated with increased 30-day mortality. Use of VTE prophylaxis during or after hospitalization was not recorded.

Bottom line: Elevated VTE risk persists following hospital discharge after cancer surgery and consideration should be given to extended-duration thromboprophylaxis. Optimal duration of prophylaxis and its risks and benefits remain poorly defined.

Citation: Merkow RP, Bilimoria KY, McCarter MD, et al. Post-discharge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis. Ann Surg. 2011;254:131-137.

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Clinical question: When do venous thromboembolism (VTE) events occur after cancer surgery?

Background: Cancer is a known risk factor for VTE. Prophylaxis for VTE after cancer surgery is commonly stopped at the time of hospital discharge despite evidence for extended-duration treatment.

Study design: Retrospective cohort.

Setting: Patients reported to the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

Synopsis: The authors examined the records of 46,656 patients who underwent surgery for one of nine specified cancers. Overall VTE rate was 1.6% (1.0% deep venous thrombosis and 0.6% pulmonary embolism), with 33.4% of VTE events occurring after hospital discharge. VTE risk was highest after esophagogastric and hepatopancreaticobiliary surgery, followed by lung, rectum, ovary/uterus, colon, and prostate. Breast and thyroid/parathyroid surgeries had the lowest incidence of VTE. VTE was associated with increased 30-day mortality. Use of VTE prophylaxis during or after hospitalization was not recorded.

Bottom line: Elevated VTE risk persists following hospital discharge after cancer surgery and consideration should be given to extended-duration thromboprophylaxis. Optimal duration of prophylaxis and its risks and benefits remain poorly defined.

Citation: Merkow RP, Bilimoria KY, McCarter MD, et al. Post-discharge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis. Ann Surg. 2011;254:131-137.

For more physician reviews of HM-related literature, visit our website.

Clinical question: When do venous thromboembolism (VTE) events occur after cancer surgery?

Background: Cancer is a known risk factor for VTE. Prophylaxis for VTE after cancer surgery is commonly stopped at the time of hospital discharge despite evidence for extended-duration treatment.

Study design: Retrospective cohort.

Setting: Patients reported to the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

Synopsis: The authors examined the records of 46,656 patients who underwent surgery for one of nine specified cancers. Overall VTE rate was 1.6% (1.0% deep venous thrombosis and 0.6% pulmonary embolism), with 33.4% of VTE events occurring after hospital discharge. VTE risk was highest after esophagogastric and hepatopancreaticobiliary surgery, followed by lung, rectum, ovary/uterus, colon, and prostate. Breast and thyroid/parathyroid surgeries had the lowest incidence of VTE. VTE was associated with increased 30-day mortality. Use of VTE prophylaxis during or after hospitalization was not recorded.

Bottom line: Elevated VTE risk persists following hospital discharge after cancer surgery and consideration should be given to extended-duration thromboprophylaxis. Optimal duration of prophylaxis and its risks and benefits remain poorly defined.

Citation: Merkow RP, Bilimoria KY, McCarter MD, et al. Post-discharge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis. Ann Surg. 2011;254:131-137.

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In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Use of a Care-Transitions Intervention Reduces 30-Day Hospital Readmissions
  2. Routine Chest Radiographs after Pneumonia to Rule Out Lung Cancer Have Low Diagnostic Yield
  3. Hospitalist Care Shifts Costs to the Outpatient Environment
  4. Stopping Smoking at Any Time before Surgery Is Safe
  5. Hospitalization for Infection Increases Risk of Stroke
  6. Longer Duration of Perioperative Antibiotics May Be Beneficial after Cardiac Surgery
  7. Stroke Unit Care Combined with Early Supported Discharge Improves Outcomes
  8. Criteria May Help Identify Patients at Risk for Infective Endocarditis

Use of a Care-Transitions Intervention Reduces 30-Day Hospital Readmissions

Clinical question: Does use of a specific care-transitions intervention (CTI) reduce 30-day hospital readmissions in a nonintegrated healthcare system?

Background: Previous interventions addressing improved communication between members of the healthcare team, patients, and families at time of discharge show promise for reducing hospital readmissions. Although these interventions revealed positive results, no research has been completed within a system where healthcare is integrated across settings.

Study design: Quasi-experimental prospective cohort study.

Setting: Six Rhode Island acute-care hospitals, including two community hospitals, three teaching hospitals, and a tertiary-care center and teaching hospital. Facilities ranged from 129 beds to 719 beds.

Synopsis: The CTI is a patient-centered intervention occurring across 30 days. The intervention includes a home visit by a coach within three days of hospital discharge, a telephone call within seven to 10 days of discharge, and a final telephone call no later than 30 days after admission. During these contacts, coaches encourage patient and family participation in care, and active communication with their primary-care provider regarding their disease state. A convenience sample of fee-for-service Medicare beneficiaries was identified by admission diagnoses of acute myocardial infarction, congestive heart failure, or specific pulmonary conditions. Overall, 74% participants completed the entire intervention. The odds of a hospital readmission were significantly lower in the intervention population compared with those who did not receive the intervention (OR 0.61; 95% CI, 0.42-0.88).

Study design: Study design was limited by ability to provide coaching (only 8% of total population was approached), and therefore may not be representative of a typical integrated healthcare setting. In addition, the sample consisted of a convenience sample, which may limit generalizability.

Bottom line: The CTI appears to decrease the rate of 30-day hospital readmissions in Medicare patients with certain cardiac and pulmonary diagnoses.

Citation: Voss R, Gardner R, Baier R, Butterfield K, Lehrman S, Gravenstein S. The care transitions intervention: translating from efficacy to effectiveness. Arch Intern Med. 2011;171:1232-1237.

Routine Chest Radiographs after Pneumonia to Rule Out Lung Cancer Have Low Diagnostic Yield

Clinical question: What is the incidence of new lung cancer detected on routine post-pneumonia chest radiographs?

Background: Routine chest radiographs have been recommended four to eight weeks after resolution of pneumonia to exclude underlying lung cancer. The diagnostic yield of this practice is uncertain.

Study design: Population-based cohort.

Setting: Seven emergency departments and six hospitals in Edmonton, Alberta, Canada.

Synopsis: Authors enrolled 3,398 patients with clinical and radiographic evidence of pneumonia. Of these, 59% were aged 50 and older, 52% were male, 17% were current smokers, 18% had COPD, and 49% were treated as inpatients. At 90-day follow-up, 1.1% of patients received a new diagnosis of lung cancer, with incidence steadily increasing to 2.2% at three-year follow-up. In multivariate analysis, age 50 and older, male sex, and current smoking were independent predictors of post-pneumonia new lung cancer diagnosis. Limiting follow-up chest radiographs to patients aged 50 and older would have detected 98% of new lung cancers and improved diagnostic yield to 2.8%.

 

 

Bottom line: Routine post-pneumonia chest radiographs for lung cancer screening have low diagnostic yield that is only marginally improved by selecting high-risk populations.

Citation: Tang KL, Eurich DT, Minhas-Sandhu JK, Marrie TJ, Majumdar SR. Incidence, correlates, and chest radiographic yield of new lung cancer diagnosis in 3398 patients with pneumonia. Arch Intern Med. 2011;171:1193-1198.

Hospitalist Care Shifts Costs to the Outpatient Environment

Clinical question: How does hospitalist care affect medical utilization costs after hospital discharge?

Background: The number of patients cared for by hospitalists is growing rapidly. Some studies have shown hospitalists to decrease length of stay and inpatient costs. The impact of shorter hospitalization on outpatient medical utilization and costs is not known.

Study design: Population-based national cohort.

Setting: Hospitalized Medicare patients.

Synopsis: In this study of 58,125 Medicare admissions at 454 hospitals, hospitalist care was associated with a 0.64-day shorter adjusted length of stay and $282 lower hospital charges compared with patients cared for by their primary-care physicians (PCPs). This was offset by $332 higher Medicare spending in the 30 days following hospitalization. Patients cared for by hospitalists were less likely to be discharged home (OR 0.82, 95% CI, 0.78-0.86), and were more likely to require emergency department visits (OR 1.18, 95% CI, 1.12-1.24) and readmissions (OR 1.08, 95% CI, 1.02-1.14). The authors postulate that shorter length of stay associated with hospitalist care is achieved at the expense of shifting costs to the outpatient environment. The discharged patients are sicker and, as a result, require more skilled care and repeat hospital visits.

Bottom line: Hospitalist care may be associated with higher overall costs and more medical utilization.

Citation: Kuo YF, Goodwin JS. Association of hospitalist care with medical utilization after discharge: evidence of cost shift from a cohort study. Ann Intern Med. 2011;155:152-159.

Stopping Smoking at Any Time before Surgery Is Safe

Clinical question: Is smoking cessation within eight weeks of surgery safe?

Background: Smoking cessation before surgery can decrease the risk of surgical complications. However, several studies found increased risk for perioperative complications when smoking was stopped within eight weeks of surgery. These findings created uncertainty about general safety of tobacco cessation counseling before surgery.

Study design: Systematic review and meta-analysis.

Setting: Smokers undergoing any type of surgery.

Synopsis: The authors identified nine studies involving 889 patients that compared smokers who quit within eight weeks of surgery with those who continued to smoke. There was considerable heterogeneity in the studies but no overall difference in perioperative complications between those who quit smoking and those who continued to smoke (OR 0.78, 95% CI, 0.57-1.07). The subset of studies examining pulmonary complications also found no difference (OR 1.18, 95% CI, 0.95-1.46).

Bottom line: Smoking cessation at any time before surgery appears to be safe.

Citation: Myers K, Hajek P, Hinds C, McRobbie H. Stopping smoking shortly before surgery and postoperative complications: a systematic review and meta-analysis. Arch Intern Med. 2011;171:983-989.

Hospitalization for Infection Increases Risk of Stroke

Clinical question: Can infection act as a precipitant for acute ischemic stroke?

Background: Little is known about precipitants of acute ischemic stroke. Severe infections have been shown to promote hypercoagulability and platelet activation, and to induce endothelial dysfunction. Authors postulated that infections severe enough to warrant hospitalization might transiently increase the risk for stroke.

Study design: Case-crossover analysis of data from a multicenter prospective cohort (Cardiovascular Health Study).

 

 

Setting: Medicare patients in four communities.

Synopsis: During a median follow-up of 12.2 years, 669 strokes occurred in 5,639 study participants. Hospitalization for infection within 14 days was associated with increased risk of stroke (OR 8.0, 95% CI, 1.6-77.3), and the risk remained elevated for hospitalizations within 90 days (OR 3.4, 95% CI, 1.8-6.5). The findings remained significant after adjusting for comorbidities, including age, sex, race, smoking, and diabetes. The number of patients hospitalized for infection before stroke was small—eight within 14 days, and 29 within 90 days.

Bottom line: Infection severe enough to require hospitalization may act as a trigger for acute ischemic stroke.

Citation: Elkind MS, Carty CL, O’Meara ES, et al. Hospitalization for infection and risk of acute ischemic stroke: the Cardiovascular Health Study. Stroke. 2011;42:1851-1856.

Longer Duration of Perioperative Antibiotics May Be Beneficial after Cardiac Surgery

Clinical question: Is antibiotic prophylaxis for 24 or more hours better than shorter duration of treatment after cardiac surgery?

Background: Sternal surgical site infections are a serious complication of cardiac surgery. The optimal duration of perioperative antibiotic prophylaxis is not known, with recommendations ranging from a single dose to 72 hours. The Society of Thoracic Surgeons’ recommendation for 24 to 72 hours of prophylaxis is not based on a systematic review and meta-analysis.

Study design: Systematic review and meta-analysis.

Setting: Adult patients undergoing open-heart surgery who received perioperative antibiotic prophylaxis.

Synopsis: Authors identified 12 trials encompassing 7,893 patients. Compared with prophylaxis of ≥24 hours, prophylaxis of <24 hours was associated with a higher risk of sternal surgical site infections (RR 1.38, 95% CI, 1.13-1.69) and deep infections (RR 1.68, 95% CI, 1.12-2.53). There was no difference in mortality, other infections, or adverse events. Most studies had methodological limitations with a high risk for bias.

Bottom line: Perioperative antibiotic prophylaxis of ≥24 hours reduces sternal surgical infections.

Citation: Mertz D, Johnstone J, Loeb M. Does duration of perioperative antibiotic prophylaxis matter in cardiac surgery? A systematic review and meta-analysis. Ann Surg. 2011;254:48-54.

Stroke Unit Care Combined with Early Supported Discharge Improves Outcomes

Clinical question: Does early supported discharge (ESD) improve outcomes more than conventional follow-up in stroke patients?

Background: ESD is a mobile team that coordinates follow-up and rehabilitation. Previous studies have shown it to be beneficial in patients with mild to moderate disability at one year, but long-term effects of ESD are not known.

Study design: Randomized controlled trial.

Setting: Single center in Norway.

Synopsis: Stroke-unit patients were recruited and received standard care or ESD after discharge. All 320 patients received standard acute care. The proportion of patients with modified Rankin Score (mRS) of ≤2 was not significantly different in the two groups but identified a trend toward improvement in the intervention group (38% vs. 30%, P=0.106). More patients receiving conventional follow-up died or were institutionalized (P=0.032) but mortality rates at five years were similar (ESD 46% vs. 51%). Secondary outcomes (Scandinavian Stroke Scale, Barthel Index, Frenchay Activity Index, and Mini Mental Status Examination) were not statistically different. Predictors of good outcome in the ESD group included young age, low mRS, and living with others.

This study recruited patients from 1995 to 1997 and followed the patients for five years. Limitations to the applicability include advances in stroke rehabilitation in the last 10 years. The cost of a mobile multidisciplinary team consisting of a physiotherapist, occupational therapist, nurse, and part-time physician was not discussed and may limit the availability to many patients.

 

 

Bottom line: Early supported discharge may increase the proportion of patients living at home five years after stroke.

Citation: Fjaertoft H, Rohweder G, Indredavik B. Stroke unit care combined with early supported discharge improves 5-year outcome: a randomized controlled trial. Stroke. 2011;42:1707-1711.

Criteria May Help Identify Patients at Risk for Infective Endocarditis

Clinical question: Which patients with Staphylococcus aureus bacteremia benefit the most from transesophageal echocardiography?

Background: Infective endocarditis is a serious complication of S. aureus bacteremia (SAB), occurring in 5% to 17% of patients with documented SAB. It has been recommended to perform transesophageal echocardiography (TEE) in all patients with SAB. Large variation exists in rates of TEE, and identifying patients at low risk for endocarditis may help with more appropriate utilization of this test.

Study design: Retrospective cohort analysis.

Setting: Two university-based German tertiary hospitals (INSTINCT cohort) and one North American university-based hospital from October 1994 to December 2009 (SABG cohort).

Synopsis: A total of 736 cases of nosocomial SAB were analyzed. Age, source of infection, and 30-day and 90-day case fatality rates were similar between the two cohorts. Patients were followed during the index hospitalization and for three months after discharge.

Patients with infective endocarditis were more likely to have prolonged bacteremia; a permanent intracardiac device, such as a pacemaker or a heart valve; be recipients of hemodialysis; and have osteomyelitis. Of the 83 patients who did not fulfill any of the prediction criteria, no cases of infective endocarditis were found.

Bottom line: A set of simple criteria may help identify patients with nosocomial SAB who are at risk for infective endocarditis. The subset of patients who do not meet any of these criteria may not need diagnostic evaluation with TEE.

Citation: Kaasch, AJ, Fowler VG Jr., Rieg S, et al. Use of a simple criteria set for guiding echocardiography in nosocomial Staphylococcus aureus bacteremia. Clin Infect Dis. 2011;53:1-9.

CLINICAL SHORTS

PULMONARY NODULE NEEDLE BIOPSIES FREQUENTLY RESULT IN SERIOUS COMPLICATIONS

In a discharge database analysis, pneumothorax complicated 15% of all biopsies, with 44% requiring chest tube placement. Pulmonary hemorrhage occurred 1% of the time with 18% needing blood transfusions.

Citation: Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155:137-144.

CUMULATIVE ANTIBIOTIC EXPOSURES ASSOCIATED WITH RISK OF CLOSTRIDIUM DIFFICILE INFECTION

Retrospective cohort study of 7,792 patients during 10,154 hospitalizations found that cumulative dose, number, and duration of antibiotics were independently associated with the development of Clostridium difficile infection.

Citation: Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53:42-48.

NESIRITIDE IN ACUTE HEART FAILURE HAS NO SIGNIFICANT EFFECT ON DYSPNEA, MORTALITY, OR RENAL FAILURE

A trial of 714 patients with acute heart failure randomized to receive nesiritide or placebo found no difference in death, rehospitalization, renal failure, or dyspnea. The nesiritide group experienced significantly more hypotension.

Citation: O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Eng J Med. 2011;365:32-43.

PROTON PUMP INHIBITOR THERAPY IS MODESTLY ASSOCIATED WITH INCREASED RISK OF HIP AND VERTEBRAL FRACTURES

A meta-analysis of 10 controlled observational studies found that use of proton pump inhibitors is associated with a modest increase in the risk of hip (OR 1.25; 95% CI, 1.14-1.37) and vertebral fractures (OR 1.50; 95% CI, 1.32-1.72). These results should be interpreted with caution as it is unclear if this represents causation or unmeasured confounding.

Citation: Ngamruengphong S, Leontiadis GI, Radhi S, Dentino A, Nugent K. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2011;106:1209-1218.

STROKE PATIENTS HAVE HIGHER RATES OF REHOSPITALIZATION

One- and five-year mortality in Medicare stroke patients is six times and two times higher, respectively, than in non-stroke patients. Readmission rates for stroke patients are 2.5 and 1.3 times higher, respectively.

Citation: Lakashminarayan K, Schissel C, Anderson DC, et al. Five-year rehospitalization outcomes in a cohort of patients with acute ischemic stroke: Medicare linkage study. Stroke. 2011;42:1556-1562.

PROTON PUMP INHIBITORS REDUCE THE RISK OF GASTROINTESTINAL BLEEDING IN THE GENERAL POPULATION AND IN PATIENTS ON ANTITHROMBOTIC OR ANTI-INFLAMMATORY THERAPY

A population-based, nested case-control study found that proton pump inhibitor use is associated with a 20% lower risk of upper gastrointestinal bleeding in the general population. The risk reduction increases to 50% to 80% in users of gastrotoxic agents.

Citation: Lin KJ, Hernandez-Diaz S, Garcia Rodriguez LA. Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology. 2011;141:71-79

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In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Use of a Care-Transitions Intervention Reduces 30-Day Hospital Readmissions
  2. Routine Chest Radiographs after Pneumonia to Rule Out Lung Cancer Have Low Diagnostic Yield
  3. Hospitalist Care Shifts Costs to the Outpatient Environment
  4. Stopping Smoking at Any Time before Surgery Is Safe
  5. Hospitalization for Infection Increases Risk of Stroke
  6. Longer Duration of Perioperative Antibiotics May Be Beneficial after Cardiac Surgery
  7. Stroke Unit Care Combined with Early Supported Discharge Improves Outcomes
  8. Criteria May Help Identify Patients at Risk for Infective Endocarditis

Use of a Care-Transitions Intervention Reduces 30-Day Hospital Readmissions

Clinical question: Does use of a specific care-transitions intervention (CTI) reduce 30-day hospital readmissions in a nonintegrated healthcare system?

Background: Previous interventions addressing improved communication between members of the healthcare team, patients, and families at time of discharge show promise for reducing hospital readmissions. Although these interventions revealed positive results, no research has been completed within a system where healthcare is integrated across settings.

Study design: Quasi-experimental prospective cohort study.

Setting: Six Rhode Island acute-care hospitals, including two community hospitals, three teaching hospitals, and a tertiary-care center and teaching hospital. Facilities ranged from 129 beds to 719 beds.

Synopsis: The CTI is a patient-centered intervention occurring across 30 days. The intervention includes a home visit by a coach within three days of hospital discharge, a telephone call within seven to 10 days of discharge, and a final telephone call no later than 30 days after admission. During these contacts, coaches encourage patient and family participation in care, and active communication with their primary-care provider regarding their disease state. A convenience sample of fee-for-service Medicare beneficiaries was identified by admission diagnoses of acute myocardial infarction, congestive heart failure, or specific pulmonary conditions. Overall, 74% participants completed the entire intervention. The odds of a hospital readmission were significantly lower in the intervention population compared with those who did not receive the intervention (OR 0.61; 95% CI, 0.42-0.88).

Study design: Study design was limited by ability to provide coaching (only 8% of total population was approached), and therefore may not be representative of a typical integrated healthcare setting. In addition, the sample consisted of a convenience sample, which may limit generalizability.

Bottom line: The CTI appears to decrease the rate of 30-day hospital readmissions in Medicare patients with certain cardiac and pulmonary diagnoses.

Citation: Voss R, Gardner R, Baier R, Butterfield K, Lehrman S, Gravenstein S. The care transitions intervention: translating from efficacy to effectiveness. Arch Intern Med. 2011;171:1232-1237.

Routine Chest Radiographs after Pneumonia to Rule Out Lung Cancer Have Low Diagnostic Yield

Clinical question: What is the incidence of new lung cancer detected on routine post-pneumonia chest radiographs?

Background: Routine chest radiographs have been recommended four to eight weeks after resolution of pneumonia to exclude underlying lung cancer. The diagnostic yield of this practice is uncertain.

Study design: Population-based cohort.

Setting: Seven emergency departments and six hospitals in Edmonton, Alberta, Canada.

Synopsis: Authors enrolled 3,398 patients with clinical and radiographic evidence of pneumonia. Of these, 59% were aged 50 and older, 52% were male, 17% were current smokers, 18% had COPD, and 49% were treated as inpatients. At 90-day follow-up, 1.1% of patients received a new diagnosis of lung cancer, with incidence steadily increasing to 2.2% at three-year follow-up. In multivariate analysis, age 50 and older, male sex, and current smoking were independent predictors of post-pneumonia new lung cancer diagnosis. Limiting follow-up chest radiographs to patients aged 50 and older would have detected 98% of new lung cancers and improved diagnostic yield to 2.8%.

 

 

Bottom line: Routine post-pneumonia chest radiographs for lung cancer screening have low diagnostic yield that is only marginally improved by selecting high-risk populations.

Citation: Tang KL, Eurich DT, Minhas-Sandhu JK, Marrie TJ, Majumdar SR. Incidence, correlates, and chest radiographic yield of new lung cancer diagnosis in 3398 patients with pneumonia. Arch Intern Med. 2011;171:1193-1198.

Hospitalist Care Shifts Costs to the Outpatient Environment

Clinical question: How does hospitalist care affect medical utilization costs after hospital discharge?

Background: The number of patients cared for by hospitalists is growing rapidly. Some studies have shown hospitalists to decrease length of stay and inpatient costs. The impact of shorter hospitalization on outpatient medical utilization and costs is not known.

Study design: Population-based national cohort.

Setting: Hospitalized Medicare patients.

Synopsis: In this study of 58,125 Medicare admissions at 454 hospitals, hospitalist care was associated with a 0.64-day shorter adjusted length of stay and $282 lower hospital charges compared with patients cared for by their primary-care physicians (PCPs). This was offset by $332 higher Medicare spending in the 30 days following hospitalization. Patients cared for by hospitalists were less likely to be discharged home (OR 0.82, 95% CI, 0.78-0.86), and were more likely to require emergency department visits (OR 1.18, 95% CI, 1.12-1.24) and readmissions (OR 1.08, 95% CI, 1.02-1.14). The authors postulate that shorter length of stay associated with hospitalist care is achieved at the expense of shifting costs to the outpatient environment. The discharged patients are sicker and, as a result, require more skilled care and repeat hospital visits.

Bottom line: Hospitalist care may be associated with higher overall costs and more medical utilization.

Citation: Kuo YF, Goodwin JS. Association of hospitalist care with medical utilization after discharge: evidence of cost shift from a cohort study. Ann Intern Med. 2011;155:152-159.

Stopping Smoking at Any Time before Surgery Is Safe

Clinical question: Is smoking cessation within eight weeks of surgery safe?

Background: Smoking cessation before surgery can decrease the risk of surgical complications. However, several studies found increased risk for perioperative complications when smoking was stopped within eight weeks of surgery. These findings created uncertainty about general safety of tobacco cessation counseling before surgery.

Study design: Systematic review and meta-analysis.

Setting: Smokers undergoing any type of surgery.

Synopsis: The authors identified nine studies involving 889 patients that compared smokers who quit within eight weeks of surgery with those who continued to smoke. There was considerable heterogeneity in the studies but no overall difference in perioperative complications between those who quit smoking and those who continued to smoke (OR 0.78, 95% CI, 0.57-1.07). The subset of studies examining pulmonary complications also found no difference (OR 1.18, 95% CI, 0.95-1.46).

Bottom line: Smoking cessation at any time before surgery appears to be safe.

Citation: Myers K, Hajek P, Hinds C, McRobbie H. Stopping smoking shortly before surgery and postoperative complications: a systematic review and meta-analysis. Arch Intern Med. 2011;171:983-989.

Hospitalization for Infection Increases Risk of Stroke

Clinical question: Can infection act as a precipitant for acute ischemic stroke?

Background: Little is known about precipitants of acute ischemic stroke. Severe infections have been shown to promote hypercoagulability and platelet activation, and to induce endothelial dysfunction. Authors postulated that infections severe enough to warrant hospitalization might transiently increase the risk for stroke.

Study design: Case-crossover analysis of data from a multicenter prospective cohort (Cardiovascular Health Study).

 

 

Setting: Medicare patients in four communities.

Synopsis: During a median follow-up of 12.2 years, 669 strokes occurred in 5,639 study participants. Hospitalization for infection within 14 days was associated with increased risk of stroke (OR 8.0, 95% CI, 1.6-77.3), and the risk remained elevated for hospitalizations within 90 days (OR 3.4, 95% CI, 1.8-6.5). The findings remained significant after adjusting for comorbidities, including age, sex, race, smoking, and diabetes. The number of patients hospitalized for infection before stroke was small—eight within 14 days, and 29 within 90 days.

Bottom line: Infection severe enough to require hospitalization may act as a trigger for acute ischemic stroke.

Citation: Elkind MS, Carty CL, O’Meara ES, et al. Hospitalization for infection and risk of acute ischemic stroke: the Cardiovascular Health Study. Stroke. 2011;42:1851-1856.

Longer Duration of Perioperative Antibiotics May Be Beneficial after Cardiac Surgery

Clinical question: Is antibiotic prophylaxis for 24 or more hours better than shorter duration of treatment after cardiac surgery?

Background: Sternal surgical site infections are a serious complication of cardiac surgery. The optimal duration of perioperative antibiotic prophylaxis is not known, with recommendations ranging from a single dose to 72 hours. The Society of Thoracic Surgeons’ recommendation for 24 to 72 hours of prophylaxis is not based on a systematic review and meta-analysis.

Study design: Systematic review and meta-analysis.

Setting: Adult patients undergoing open-heart surgery who received perioperative antibiotic prophylaxis.

Synopsis: Authors identified 12 trials encompassing 7,893 patients. Compared with prophylaxis of ≥24 hours, prophylaxis of <24 hours was associated with a higher risk of sternal surgical site infections (RR 1.38, 95% CI, 1.13-1.69) and deep infections (RR 1.68, 95% CI, 1.12-2.53). There was no difference in mortality, other infections, or adverse events. Most studies had methodological limitations with a high risk for bias.

Bottom line: Perioperative antibiotic prophylaxis of ≥24 hours reduces sternal surgical infections.

Citation: Mertz D, Johnstone J, Loeb M. Does duration of perioperative antibiotic prophylaxis matter in cardiac surgery? A systematic review and meta-analysis. Ann Surg. 2011;254:48-54.

Stroke Unit Care Combined with Early Supported Discharge Improves Outcomes

Clinical question: Does early supported discharge (ESD) improve outcomes more than conventional follow-up in stroke patients?

Background: ESD is a mobile team that coordinates follow-up and rehabilitation. Previous studies have shown it to be beneficial in patients with mild to moderate disability at one year, but long-term effects of ESD are not known.

Study design: Randomized controlled trial.

Setting: Single center in Norway.

Synopsis: Stroke-unit patients were recruited and received standard care or ESD after discharge. All 320 patients received standard acute care. The proportion of patients with modified Rankin Score (mRS) of ≤2 was not significantly different in the two groups but identified a trend toward improvement in the intervention group (38% vs. 30%, P=0.106). More patients receiving conventional follow-up died or were institutionalized (P=0.032) but mortality rates at five years were similar (ESD 46% vs. 51%). Secondary outcomes (Scandinavian Stroke Scale, Barthel Index, Frenchay Activity Index, and Mini Mental Status Examination) were not statistically different. Predictors of good outcome in the ESD group included young age, low mRS, and living with others.

This study recruited patients from 1995 to 1997 and followed the patients for five years. Limitations to the applicability include advances in stroke rehabilitation in the last 10 years. The cost of a mobile multidisciplinary team consisting of a physiotherapist, occupational therapist, nurse, and part-time physician was not discussed and may limit the availability to many patients.

 

 

Bottom line: Early supported discharge may increase the proportion of patients living at home five years after stroke.

Citation: Fjaertoft H, Rohweder G, Indredavik B. Stroke unit care combined with early supported discharge improves 5-year outcome: a randomized controlled trial. Stroke. 2011;42:1707-1711.

Criteria May Help Identify Patients at Risk for Infective Endocarditis

Clinical question: Which patients with Staphylococcus aureus bacteremia benefit the most from transesophageal echocardiography?

Background: Infective endocarditis is a serious complication of S. aureus bacteremia (SAB), occurring in 5% to 17% of patients with documented SAB. It has been recommended to perform transesophageal echocardiography (TEE) in all patients with SAB. Large variation exists in rates of TEE, and identifying patients at low risk for endocarditis may help with more appropriate utilization of this test.

Study design: Retrospective cohort analysis.

Setting: Two university-based German tertiary hospitals (INSTINCT cohort) and one North American university-based hospital from October 1994 to December 2009 (SABG cohort).

Synopsis: A total of 736 cases of nosocomial SAB were analyzed. Age, source of infection, and 30-day and 90-day case fatality rates were similar between the two cohorts. Patients were followed during the index hospitalization and for three months after discharge.

Patients with infective endocarditis were more likely to have prolonged bacteremia; a permanent intracardiac device, such as a pacemaker or a heart valve; be recipients of hemodialysis; and have osteomyelitis. Of the 83 patients who did not fulfill any of the prediction criteria, no cases of infective endocarditis were found.

Bottom line: A set of simple criteria may help identify patients with nosocomial SAB who are at risk for infective endocarditis. The subset of patients who do not meet any of these criteria may not need diagnostic evaluation with TEE.

Citation: Kaasch, AJ, Fowler VG Jr., Rieg S, et al. Use of a simple criteria set for guiding echocardiography in nosocomial Staphylococcus aureus bacteremia. Clin Infect Dis. 2011;53:1-9.

CLINICAL SHORTS

PULMONARY NODULE NEEDLE BIOPSIES FREQUENTLY RESULT IN SERIOUS COMPLICATIONS

In a discharge database analysis, pneumothorax complicated 15% of all biopsies, with 44% requiring chest tube placement. Pulmonary hemorrhage occurred 1% of the time with 18% needing blood transfusions.

Citation: Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155:137-144.

CUMULATIVE ANTIBIOTIC EXPOSURES ASSOCIATED WITH RISK OF CLOSTRIDIUM DIFFICILE INFECTION

Retrospective cohort study of 7,792 patients during 10,154 hospitalizations found that cumulative dose, number, and duration of antibiotics were independently associated with the development of Clostridium difficile infection.

Citation: Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53:42-48.

NESIRITIDE IN ACUTE HEART FAILURE HAS NO SIGNIFICANT EFFECT ON DYSPNEA, MORTALITY, OR RENAL FAILURE

A trial of 714 patients with acute heart failure randomized to receive nesiritide or placebo found no difference in death, rehospitalization, renal failure, or dyspnea. The nesiritide group experienced significantly more hypotension.

Citation: O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Eng J Med. 2011;365:32-43.

PROTON PUMP INHIBITOR THERAPY IS MODESTLY ASSOCIATED WITH INCREASED RISK OF HIP AND VERTEBRAL FRACTURES

A meta-analysis of 10 controlled observational studies found that use of proton pump inhibitors is associated with a modest increase in the risk of hip (OR 1.25; 95% CI, 1.14-1.37) and vertebral fractures (OR 1.50; 95% CI, 1.32-1.72). These results should be interpreted with caution as it is unclear if this represents causation or unmeasured confounding.

Citation: Ngamruengphong S, Leontiadis GI, Radhi S, Dentino A, Nugent K. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2011;106:1209-1218.

STROKE PATIENTS HAVE HIGHER RATES OF REHOSPITALIZATION

One- and five-year mortality in Medicare stroke patients is six times and two times higher, respectively, than in non-stroke patients. Readmission rates for stroke patients are 2.5 and 1.3 times higher, respectively.

Citation: Lakashminarayan K, Schissel C, Anderson DC, et al. Five-year rehospitalization outcomes in a cohort of patients with acute ischemic stroke: Medicare linkage study. Stroke. 2011;42:1556-1562.

PROTON PUMP INHIBITORS REDUCE THE RISK OF GASTROINTESTINAL BLEEDING IN THE GENERAL POPULATION AND IN PATIENTS ON ANTITHROMBOTIC OR ANTI-INFLAMMATORY THERAPY

A population-based, nested case-control study found that proton pump inhibitor use is associated with a 20% lower risk of upper gastrointestinal bleeding in the general population. The risk reduction increases to 50% to 80% in users of gastrotoxic agents.

Citation: Lin KJ, Hernandez-Diaz S, Garcia Rodriguez LA. Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology. 2011;141:71-79

In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Use of a Care-Transitions Intervention Reduces 30-Day Hospital Readmissions
  2. Routine Chest Radiographs after Pneumonia to Rule Out Lung Cancer Have Low Diagnostic Yield
  3. Hospitalist Care Shifts Costs to the Outpatient Environment
  4. Stopping Smoking at Any Time before Surgery Is Safe
  5. Hospitalization for Infection Increases Risk of Stroke
  6. Longer Duration of Perioperative Antibiotics May Be Beneficial after Cardiac Surgery
  7. Stroke Unit Care Combined with Early Supported Discharge Improves Outcomes
  8. Criteria May Help Identify Patients at Risk for Infective Endocarditis

Use of a Care-Transitions Intervention Reduces 30-Day Hospital Readmissions

Clinical question: Does use of a specific care-transitions intervention (CTI) reduce 30-day hospital readmissions in a nonintegrated healthcare system?

Background: Previous interventions addressing improved communication between members of the healthcare team, patients, and families at time of discharge show promise for reducing hospital readmissions. Although these interventions revealed positive results, no research has been completed within a system where healthcare is integrated across settings.

Study design: Quasi-experimental prospective cohort study.

Setting: Six Rhode Island acute-care hospitals, including two community hospitals, three teaching hospitals, and a tertiary-care center and teaching hospital. Facilities ranged from 129 beds to 719 beds.

Synopsis: The CTI is a patient-centered intervention occurring across 30 days. The intervention includes a home visit by a coach within three days of hospital discharge, a telephone call within seven to 10 days of discharge, and a final telephone call no later than 30 days after admission. During these contacts, coaches encourage patient and family participation in care, and active communication with their primary-care provider regarding their disease state. A convenience sample of fee-for-service Medicare beneficiaries was identified by admission diagnoses of acute myocardial infarction, congestive heart failure, or specific pulmonary conditions. Overall, 74% participants completed the entire intervention. The odds of a hospital readmission were significantly lower in the intervention population compared with those who did not receive the intervention (OR 0.61; 95% CI, 0.42-0.88).

Study design: Study design was limited by ability to provide coaching (only 8% of total population was approached), and therefore may not be representative of a typical integrated healthcare setting. In addition, the sample consisted of a convenience sample, which may limit generalizability.

Bottom line: The CTI appears to decrease the rate of 30-day hospital readmissions in Medicare patients with certain cardiac and pulmonary diagnoses.

Citation: Voss R, Gardner R, Baier R, Butterfield K, Lehrman S, Gravenstein S. The care transitions intervention: translating from efficacy to effectiveness. Arch Intern Med. 2011;171:1232-1237.

Routine Chest Radiographs after Pneumonia to Rule Out Lung Cancer Have Low Diagnostic Yield

Clinical question: What is the incidence of new lung cancer detected on routine post-pneumonia chest radiographs?

Background: Routine chest radiographs have been recommended four to eight weeks after resolution of pneumonia to exclude underlying lung cancer. The diagnostic yield of this practice is uncertain.

Study design: Population-based cohort.

Setting: Seven emergency departments and six hospitals in Edmonton, Alberta, Canada.

Synopsis: Authors enrolled 3,398 patients with clinical and radiographic evidence of pneumonia. Of these, 59% were aged 50 and older, 52% were male, 17% were current smokers, 18% had COPD, and 49% were treated as inpatients. At 90-day follow-up, 1.1% of patients received a new diagnosis of lung cancer, with incidence steadily increasing to 2.2% at three-year follow-up. In multivariate analysis, age 50 and older, male sex, and current smoking were independent predictors of post-pneumonia new lung cancer diagnosis. Limiting follow-up chest radiographs to patients aged 50 and older would have detected 98% of new lung cancers and improved diagnostic yield to 2.8%.

 

 

Bottom line: Routine post-pneumonia chest radiographs for lung cancer screening have low diagnostic yield that is only marginally improved by selecting high-risk populations.

Citation: Tang KL, Eurich DT, Minhas-Sandhu JK, Marrie TJ, Majumdar SR. Incidence, correlates, and chest radiographic yield of new lung cancer diagnosis in 3398 patients with pneumonia. Arch Intern Med. 2011;171:1193-1198.

Hospitalist Care Shifts Costs to the Outpatient Environment

Clinical question: How does hospitalist care affect medical utilization costs after hospital discharge?

Background: The number of patients cared for by hospitalists is growing rapidly. Some studies have shown hospitalists to decrease length of stay and inpatient costs. The impact of shorter hospitalization on outpatient medical utilization and costs is not known.

Study design: Population-based national cohort.

Setting: Hospitalized Medicare patients.

Synopsis: In this study of 58,125 Medicare admissions at 454 hospitals, hospitalist care was associated with a 0.64-day shorter adjusted length of stay and $282 lower hospital charges compared with patients cared for by their primary-care physicians (PCPs). This was offset by $332 higher Medicare spending in the 30 days following hospitalization. Patients cared for by hospitalists were less likely to be discharged home (OR 0.82, 95% CI, 0.78-0.86), and were more likely to require emergency department visits (OR 1.18, 95% CI, 1.12-1.24) and readmissions (OR 1.08, 95% CI, 1.02-1.14). The authors postulate that shorter length of stay associated with hospitalist care is achieved at the expense of shifting costs to the outpatient environment. The discharged patients are sicker and, as a result, require more skilled care and repeat hospital visits.

Bottom line: Hospitalist care may be associated with higher overall costs and more medical utilization.

Citation: Kuo YF, Goodwin JS. Association of hospitalist care with medical utilization after discharge: evidence of cost shift from a cohort study. Ann Intern Med. 2011;155:152-159.

Stopping Smoking at Any Time before Surgery Is Safe

Clinical question: Is smoking cessation within eight weeks of surgery safe?

Background: Smoking cessation before surgery can decrease the risk of surgical complications. However, several studies found increased risk for perioperative complications when smoking was stopped within eight weeks of surgery. These findings created uncertainty about general safety of tobacco cessation counseling before surgery.

Study design: Systematic review and meta-analysis.

Setting: Smokers undergoing any type of surgery.

Synopsis: The authors identified nine studies involving 889 patients that compared smokers who quit within eight weeks of surgery with those who continued to smoke. There was considerable heterogeneity in the studies but no overall difference in perioperative complications between those who quit smoking and those who continued to smoke (OR 0.78, 95% CI, 0.57-1.07). The subset of studies examining pulmonary complications also found no difference (OR 1.18, 95% CI, 0.95-1.46).

Bottom line: Smoking cessation at any time before surgery appears to be safe.

Citation: Myers K, Hajek P, Hinds C, McRobbie H. Stopping smoking shortly before surgery and postoperative complications: a systematic review and meta-analysis. Arch Intern Med. 2011;171:983-989.

Hospitalization for Infection Increases Risk of Stroke

Clinical question: Can infection act as a precipitant for acute ischemic stroke?

Background: Little is known about precipitants of acute ischemic stroke. Severe infections have been shown to promote hypercoagulability and platelet activation, and to induce endothelial dysfunction. Authors postulated that infections severe enough to warrant hospitalization might transiently increase the risk for stroke.

Study design: Case-crossover analysis of data from a multicenter prospective cohort (Cardiovascular Health Study).

 

 

Setting: Medicare patients in four communities.

Synopsis: During a median follow-up of 12.2 years, 669 strokes occurred in 5,639 study participants. Hospitalization for infection within 14 days was associated with increased risk of stroke (OR 8.0, 95% CI, 1.6-77.3), and the risk remained elevated for hospitalizations within 90 days (OR 3.4, 95% CI, 1.8-6.5). The findings remained significant after adjusting for comorbidities, including age, sex, race, smoking, and diabetes. The number of patients hospitalized for infection before stroke was small—eight within 14 days, and 29 within 90 days.

Bottom line: Infection severe enough to require hospitalization may act as a trigger for acute ischemic stroke.

Citation: Elkind MS, Carty CL, O’Meara ES, et al. Hospitalization for infection and risk of acute ischemic stroke: the Cardiovascular Health Study. Stroke. 2011;42:1851-1856.

Longer Duration of Perioperative Antibiotics May Be Beneficial after Cardiac Surgery

Clinical question: Is antibiotic prophylaxis for 24 or more hours better than shorter duration of treatment after cardiac surgery?

Background: Sternal surgical site infections are a serious complication of cardiac surgery. The optimal duration of perioperative antibiotic prophylaxis is not known, with recommendations ranging from a single dose to 72 hours. The Society of Thoracic Surgeons’ recommendation for 24 to 72 hours of prophylaxis is not based on a systematic review and meta-analysis.

Study design: Systematic review and meta-analysis.

Setting: Adult patients undergoing open-heart surgery who received perioperative antibiotic prophylaxis.

Synopsis: Authors identified 12 trials encompassing 7,893 patients. Compared with prophylaxis of ≥24 hours, prophylaxis of <24 hours was associated with a higher risk of sternal surgical site infections (RR 1.38, 95% CI, 1.13-1.69) and deep infections (RR 1.68, 95% CI, 1.12-2.53). There was no difference in mortality, other infections, or adverse events. Most studies had methodological limitations with a high risk for bias.

Bottom line: Perioperative antibiotic prophylaxis of ≥24 hours reduces sternal surgical infections.

Citation: Mertz D, Johnstone J, Loeb M. Does duration of perioperative antibiotic prophylaxis matter in cardiac surgery? A systematic review and meta-analysis. Ann Surg. 2011;254:48-54.

Stroke Unit Care Combined with Early Supported Discharge Improves Outcomes

Clinical question: Does early supported discharge (ESD) improve outcomes more than conventional follow-up in stroke patients?

Background: ESD is a mobile team that coordinates follow-up and rehabilitation. Previous studies have shown it to be beneficial in patients with mild to moderate disability at one year, but long-term effects of ESD are not known.

Study design: Randomized controlled trial.

Setting: Single center in Norway.

Synopsis: Stroke-unit patients were recruited and received standard care or ESD after discharge. All 320 patients received standard acute care. The proportion of patients with modified Rankin Score (mRS) of ≤2 was not significantly different in the two groups but identified a trend toward improvement in the intervention group (38% vs. 30%, P=0.106). More patients receiving conventional follow-up died or were institutionalized (P=0.032) but mortality rates at five years were similar (ESD 46% vs. 51%). Secondary outcomes (Scandinavian Stroke Scale, Barthel Index, Frenchay Activity Index, and Mini Mental Status Examination) were not statistically different. Predictors of good outcome in the ESD group included young age, low mRS, and living with others.

This study recruited patients from 1995 to 1997 and followed the patients for five years. Limitations to the applicability include advances in stroke rehabilitation in the last 10 years. The cost of a mobile multidisciplinary team consisting of a physiotherapist, occupational therapist, nurse, and part-time physician was not discussed and may limit the availability to many patients.

 

 

Bottom line: Early supported discharge may increase the proportion of patients living at home five years after stroke.

Citation: Fjaertoft H, Rohweder G, Indredavik B. Stroke unit care combined with early supported discharge improves 5-year outcome: a randomized controlled trial. Stroke. 2011;42:1707-1711.

Criteria May Help Identify Patients at Risk for Infective Endocarditis

Clinical question: Which patients with Staphylococcus aureus bacteremia benefit the most from transesophageal echocardiography?

Background: Infective endocarditis is a serious complication of S. aureus bacteremia (SAB), occurring in 5% to 17% of patients with documented SAB. It has been recommended to perform transesophageal echocardiography (TEE) in all patients with SAB. Large variation exists in rates of TEE, and identifying patients at low risk for endocarditis may help with more appropriate utilization of this test.

Study design: Retrospective cohort analysis.

Setting: Two university-based German tertiary hospitals (INSTINCT cohort) and one North American university-based hospital from October 1994 to December 2009 (SABG cohort).

Synopsis: A total of 736 cases of nosocomial SAB were analyzed. Age, source of infection, and 30-day and 90-day case fatality rates were similar between the two cohorts. Patients were followed during the index hospitalization and for three months after discharge.

Patients with infective endocarditis were more likely to have prolonged bacteremia; a permanent intracardiac device, such as a pacemaker or a heart valve; be recipients of hemodialysis; and have osteomyelitis. Of the 83 patients who did not fulfill any of the prediction criteria, no cases of infective endocarditis were found.

Bottom line: A set of simple criteria may help identify patients with nosocomial SAB who are at risk for infective endocarditis. The subset of patients who do not meet any of these criteria may not need diagnostic evaluation with TEE.

Citation: Kaasch, AJ, Fowler VG Jr., Rieg S, et al. Use of a simple criteria set for guiding echocardiography in nosocomial Staphylococcus aureus bacteremia. Clin Infect Dis. 2011;53:1-9.

CLINICAL SHORTS

PULMONARY NODULE NEEDLE BIOPSIES FREQUENTLY RESULT IN SERIOUS COMPLICATIONS

In a discharge database analysis, pneumothorax complicated 15% of all biopsies, with 44% requiring chest tube placement. Pulmonary hemorrhage occurred 1% of the time with 18% needing blood transfusions.

Citation: Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155:137-144.

CUMULATIVE ANTIBIOTIC EXPOSURES ASSOCIATED WITH RISK OF CLOSTRIDIUM DIFFICILE INFECTION

Retrospective cohort study of 7,792 patients during 10,154 hospitalizations found that cumulative dose, number, and duration of antibiotics were independently associated with the development of Clostridium difficile infection.

Citation: Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53:42-48.

NESIRITIDE IN ACUTE HEART FAILURE HAS NO SIGNIFICANT EFFECT ON DYSPNEA, MORTALITY, OR RENAL FAILURE

A trial of 714 patients with acute heart failure randomized to receive nesiritide or placebo found no difference in death, rehospitalization, renal failure, or dyspnea. The nesiritide group experienced significantly more hypotension.

Citation: O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Eng J Med. 2011;365:32-43.

PROTON PUMP INHIBITOR THERAPY IS MODESTLY ASSOCIATED WITH INCREASED RISK OF HIP AND VERTEBRAL FRACTURES

A meta-analysis of 10 controlled observational studies found that use of proton pump inhibitors is associated with a modest increase in the risk of hip (OR 1.25; 95% CI, 1.14-1.37) and vertebral fractures (OR 1.50; 95% CI, 1.32-1.72). These results should be interpreted with caution as it is unclear if this represents causation or unmeasured confounding.

Citation: Ngamruengphong S, Leontiadis GI, Radhi S, Dentino A, Nugent K. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2011;106:1209-1218.

STROKE PATIENTS HAVE HIGHER RATES OF REHOSPITALIZATION

One- and five-year mortality in Medicare stroke patients is six times and two times higher, respectively, than in non-stroke patients. Readmission rates for stroke patients are 2.5 and 1.3 times higher, respectively.

Citation: Lakashminarayan K, Schissel C, Anderson DC, et al. Five-year rehospitalization outcomes in a cohort of patients with acute ischemic stroke: Medicare linkage study. Stroke. 2011;42:1556-1562.

PROTON PUMP INHIBITORS REDUCE THE RISK OF GASTROINTESTINAL BLEEDING IN THE GENERAL POPULATION AND IN PATIENTS ON ANTITHROMBOTIC OR ANTI-INFLAMMATORY THERAPY

A population-based, nested case-control study found that proton pump inhibitor use is associated with a 20% lower risk of upper gastrointestinal bleeding in the general population. The risk reduction increases to 50% to 80% in users of gastrotoxic agents.

Citation: Lin KJ, Hernandez-Diaz S, Garcia Rodriguez LA. Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology. 2011;141:71-79

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