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Inhibitor strengthens RBCs in PNH
Credit: NHLBI
The apoptosis inhibitor aurin tricarboxylic acid (ATA) is active against paroxysmal nocturnal hemoglobinemia (PNH), according to research published in PLOS ONE.
PNH is a rare condition in which red blood cells (RBCs) become vulnerable to attacks by the complement immune system and subsequently rupture.
This can lead to complications such as anemia, kidney disease, and fatal thromboses.
PNH results from a lack of 2 proteins that protect RBCs from destruction: decay-accelerating factor (CD55), an inhibitor of alternative pathway C3 convertase, and protectin (CD59), an inhibitor of membrane attack complex (MAC) formation.
Because previous studies suggested that ATA selectively blocks complement activation at the C3 convertase stage and MAC formation at the C9 insertion stage, researchers thought ATA might prove effective against PNH.
First, they compared RBCs from 5 patients with PNH (who were on long-term treatment with eculizumab) to RBCs from healthy individuals.
Despite the eculizumab, the PNH patients’ RBCs were twice as vulnerable to complement-induced lysis as the healthy subjects’ RBCs. And western blot revealed both C3 and C5 convertases on the membranes of patients’ RBCs.
However, when the researchers added ATA to patients’ blood samples, the RBCs were protected from complement attack. In fact, the drug restored the RBCs’ resistance to the same level as normal RBCs.
“Our study suggests that ATA could offer more complete protection as an oral treatment for PNH, while eliminating the need for infusions,” said study author Patrick McGeer, MD, PhD, of the University of British Columbia in Vancouver, Canada.
“PNH is a disease that may happen to anyone through a chance mutation, and, if nature were to design a perfect fix for this mutation, it would be ATA.”
Dr McGeer added that many diseases are caused or worsened by an overactive complement immune system. So his group’s findings could have implications for conditions such as Alzheimer’s disease, Parkinson’s disease, macular degeneration, amyotrophic lateral sclerosis, multiple sclerosis, and rheumatoid arthritis.
He and his colleagues are now proceeding with further testing, and Dr McGeer expects ATA could be available in clinics within a year. 
Credit: NHLBI
The apoptosis inhibitor aurin tricarboxylic acid (ATA) is active against paroxysmal nocturnal hemoglobinemia (PNH), according to research published in PLOS ONE.
PNH is a rare condition in which red blood cells (RBCs) become vulnerable to attacks by the complement immune system and subsequently rupture.
This can lead to complications such as anemia, kidney disease, and fatal thromboses.
PNH results from a lack of 2 proteins that protect RBCs from destruction: decay-accelerating factor (CD55), an inhibitor of alternative pathway C3 convertase, and protectin (CD59), an inhibitor of membrane attack complex (MAC) formation.
Because previous studies suggested that ATA selectively blocks complement activation at the C3 convertase stage and MAC formation at the C9 insertion stage, researchers thought ATA might prove effective against PNH.
First, they compared RBCs from 5 patients with PNH (who were on long-term treatment with eculizumab) to RBCs from healthy individuals.
Despite the eculizumab, the PNH patients’ RBCs were twice as vulnerable to complement-induced lysis as the healthy subjects’ RBCs. And western blot revealed both C3 and C5 convertases on the membranes of patients’ RBCs.
However, when the researchers added ATA to patients’ blood samples, the RBCs were protected from complement attack. In fact, the drug restored the RBCs’ resistance to the same level as normal RBCs.
“Our study suggests that ATA could offer more complete protection as an oral treatment for PNH, while eliminating the need for infusions,” said study author Patrick McGeer, MD, PhD, of the University of British Columbia in Vancouver, Canada.
“PNH is a disease that may happen to anyone through a chance mutation, and, if nature were to design a perfect fix for this mutation, it would be ATA.”
Dr McGeer added that many diseases are caused or worsened by an overactive complement immune system. So his group’s findings could have implications for conditions such as Alzheimer’s disease, Parkinson’s disease, macular degeneration, amyotrophic lateral sclerosis, multiple sclerosis, and rheumatoid arthritis.
He and his colleagues are now proceeding with further testing, and Dr McGeer expects ATA could be available in clinics within a year.
Credit: NHLBI
The apoptosis inhibitor aurin tricarboxylic acid (ATA) is active against paroxysmal nocturnal hemoglobinemia (PNH), according to research published in PLOS ONE.
PNH is a rare condition in which red blood cells (RBCs) become vulnerable to attacks by the complement immune system and subsequently rupture.
This can lead to complications such as anemia, kidney disease, and fatal thromboses.
PNH results from a lack of 2 proteins that protect RBCs from destruction: decay-accelerating factor (CD55), an inhibitor of alternative pathway C3 convertase, and protectin (CD59), an inhibitor of membrane attack complex (MAC) formation.
Because previous studies suggested that ATA selectively blocks complement activation at the C3 convertase stage and MAC formation at the C9 insertion stage, researchers thought ATA might prove effective against PNH.
First, they compared RBCs from 5 patients with PNH (who were on long-term treatment with eculizumab) to RBCs from healthy individuals.
Despite the eculizumab, the PNH patients’ RBCs were twice as vulnerable to complement-induced lysis as the healthy subjects’ RBCs. And western blot revealed both C3 and C5 convertases on the membranes of patients’ RBCs.
However, when the researchers added ATA to patients’ blood samples, the RBCs were protected from complement attack. In fact, the drug restored the RBCs’ resistance to the same level as normal RBCs.
“Our study suggests that ATA could offer more complete protection as an oral treatment for PNH, while eliminating the need for infusions,” said study author Patrick McGeer, MD, PhD, of the University of British Columbia in Vancouver, Canada.
“PNH is a disease that may happen to anyone through a chance mutation, and, if nature were to design a perfect fix for this mutation, it would be ATA.”
Dr McGeer added that many diseases are caused or worsened by an overactive complement immune system. So his group’s findings could have implications for conditions such as Alzheimer’s disease, Parkinson’s disease, macular degeneration, amyotrophic lateral sclerosis, multiple sclerosis, and rheumatoid arthritis.
He and his colleagues are now proceeding with further testing, and Dr McGeer expects ATA could be available in clinics within a year.
Measuring Agreement After CICU Handoffs
Increasing attention has been paid to the need for effective handoffs between healthcare providers since the Joint Commission identified standardized handoff protocols as a National Patient Safety Goal in 2006.1 Aside from adverse consequences for patients, poor handoffs produce provider uncertainty about care plans.[2, 3] Agreement on clinical information after a handoff is critical because a significant proportion of data is not documented in the medical record, leaving providers reliant on verbal communication.[4, 5, 6] Providers may enter the handoff with differing opinions; however, to mitigate the potential safety consequences of discontinuity of care,[7] the goal should be to achieve consensus about proposed courses of action.
Given the recent focus on improving handoffs, rigorous, outcome‐driven measures of handoff quality are clearly needed, but measuring shift‐to‐shift handoff quality has proved challenging.[8, 9] Previous studies of physician handoffs surveyed receivers for satisfaction,[10, 11] compared reported omissions to audio recordings,[3] and developed evaluation tools for receivers to rate handoffs.[12, 13, 14, 15] None directly assess the underlying goal of a handoff: the transfer of understanding from sender to receiver, enabling safe transfer of patient care responsibility.[16] We therefore chose to measure agreement on patient condition and treatment plans following handoff as an indicator of the quality of the shared clinical understanding formed. Advantages of piloting this approach in the pediatric cardiac intensive care unit (CICU) include the relatively homogenous patient population and small number of medical providers. If effective, the strategy of tool development and evaluation could be generalized to different clinical environments and provider groups.
Our aim was to develop and validate a tool to measure the level of shared clinical understanding regarding the condition and treatment plan of a CICU patient after handoff. The tool we designed was the pediatric cardiology Patient Knowledge Assessment Tool (PKAT), a brief, multiple‐item questionnaire focused on key data elements for individual CICU patients. Although variation in provider opinion helps detect diagnostic or treatment errors,[8] the PKAT is based on the assumption that achieving consensus on clinical status and the next steps of care is the goal of the handoff.
METHODS
Setting
The CICU is a 24‐bed medical and surgical unit in a 500‐bed free standing children's hospital. CICU attending physicians work 12‐ or 24‐hour shifts and supervise front line clinicians (including subspecialty fellows, nurse practitioners, and hospitalists, referred to as clinicians in this article) who work day or night shifts. Handoffs occur twice daily, with no significant differences in handoff practices between the 2 times. Attending physicians (referred to as attendings in this article) conduct parallel but separate handoffs from clinicians. All providers work exclusively in the CICU with the exception of fellows, who rotate monthly.
This study was approved by the institutional review board at The Children's Hospital of Philadelphia. All provider subjects provided informed consent. Consent for patient subjects was waived.
Development of the PKAT
We developed the PKAT content domains based on findings from previous studies,[2, 3] unpublished survey data about handoff omissions in our CICU, and CICU attending expert opinion. Pilot testing included 39 attendings and clinicians involved in 60 handoffs representing a wide variety of admissions. Participants were encouraged to share opinions on tool content and design with study staff. The PKAT (see Supporting Information, Appendix, in the online version of this article) was refined iteratively based on this feedback.
Video Simulation Testing
We used video simulation to test the PKAT for inter‐rater reliability. Nine patient handoff scenarios were written with varying levels of patient complexity and clarity of dialogue. The scenarios were filmed using the same actors and location to minimize variability aside from content. We recruited 10 experienced provider subjects (attendings and senior fellows) to minimize the effect of knowledge deficits. For each simulated handoff, subjects were encouraged to annotate a mock sign‐out sheet, which mimicked the content and format of the CICU sign‐out sheet. After watching all 9 scenarios, subjects completed a PKAT for each handoff from the perspective of the receiver based on the videotape. These standardized conditions allowed for assessment of inter‐rater reliability.
In Situ Testing
We then tested the PKAT in situ in the CICU to assess construct validity. We chose to study the morning handoff because the timing and location are more consistent. We planned to study 90 patient handoffs because the standard practice for testing a new psychometric instrument is to collect 10 observations per item.[17] On study days, 4 providers completed a PKAT for each selected handoff: the sending attending, receiving attending, sending clinician, and receiving clinician.
Study days were scheduled over 2 months to encompass a range of providers. Given the small number of attendings, we did not exclude those who had participated in video simulation testing. On study days, 6 patients were enrolled using stratified sampling to ensure adequate representation of new admissions (ie, admitted within 24 hours). The sending attending received the PKAT forms prior to the handoff. The receiving attending and clinicians received the PKAT after handoff. This difference in administration was due to logistic concerns: sending attendings requested to receive the PKATs earlier because they had to complete all 6 PKATs, whereas other providers completed 3 or fewer per day. Thus, sending attendings could complete the PKAT before or after the handoff, whereas all other participants completed the instrument after the handoff.
To test for construct validity, we gathered data on participating providers and patients, hypothesizing that PKAT agreement levels would decrease in response to less experienced providers or more complex patients. Provider characteristics included previous handoff education and amount of time worked in our CICU. Attending CICU experience was dichotomized into first year versus second or greater year. Clinician experience was dichotomized into first or second month versus third or greater month of CICU service. Each PKAT asked the handoff receiver whether he or she had recently cared for this patient or gathered information prior to handoff (eg, speaking to bedside nurse).
Recorded patient characteristics included age, length of stay, and admission type including neonatal/preoperative observation, postoperative (first 7 days after operation), prolonged postoperative (>7 days after operation), and medical (all others). In recognition of differences in handoffs during the first 24 hours of admission and the right‐skewed length of stay in the CICU, we analyzed length of stay based on the following categories: new admission (<24 hours), days 2 to 7, days 8 to 14, days 15 to 31, and >31 days. Because the number of active medications has been shown to correlate with treatment regimen complexity[18] and physician ratings of illness severity,[19] we recorded this number as a surrogate measure of patient complexity. For analytic purposes, we categorized the number of active medications into quartiles.
Provider subject characteristics and PKAT responses were collected using paper forms and entered into REDCap (Research Electronic Data Capture; REDCap Consortium,
Statistical Analysis
The primary outcome measure was the PKAT agreement level among providers evaluating the same handoff. For the reliability assessment, we calculated agreement across all providers analyzing the simulation videos, expecting that multiple providers should have high agreement for the same scenarios if the instrument has high inter‐rater reliability. For the validity assessment, we calculated agreement for each individual handoff by item and then calculated average levels of agreement for each item across provider and patient characteristics. We analyzed handoffs between attendings and clinicians separately. For items with mutually exclusive responses, simple yes/no agreement was calculated. For items requiring at least 1 response, agreement was coded when both respondents selected at least 1 response in common. For items that did not require a selection, credit was given if both subjects agreed that none of the conditions were present or if they agreed that at least 1 condition was present. In a secondary analysis, we repeated the analyses with unique sender‐receiver pair as the unit of analysis to account for correlation in the pair interaction.
Summary statistics were used to describe provider and patient characteristics. Mean rates of agreement with 95% confidence intervals were calculated for each item. The Wilcoxon rank sum test was used to compare mean results between groups (eg, attendings vs clinicians). A nonparametric test for trend, which is an extension of the Wilcoxon rank sum test,[21] was used to compare mean results across ordered categories (eg, length of stay). All tests of significance were at P<0.05 level and 2‐tailed. All statistical analysis was done using Stata 12 (StataCorp, College Station, TX).
RESULTS
Provider subject types are represented in Table 1. Handoffs between these 29 individuals resulted in 70 unique sender and receiver combinations with a median of 2 PKATs completed per unique sender‐receiver pair (range, 115). Attendings had lower rates of handoff education than clinicians (11% vs 85% for in situ testing participants, P=0.01). Attendings participating in in situ testing had worked in the CICU for a median of 3 years (range, 116 years). Clinicians participating in in situ testing had a median of 3 months of CICU experience (range, 195 months). Providers were 100% compliant with PKAT completion.
| Simulation Testing, n=10 | In Situ Testing, n=29 | |
|---|---|---|
| ||
| Attending physicians | 40% (4) | 31% (9) |
| Clinicians | 60% (6) | 69% (20) |
| Clinician type | ||
| Cardiology | 67% (4) | 35% (7) |
| Critical care medicine | 33% (2) | 25% (5) |
| CICU nurse practitioner | 25% (5) | |
| Anesthesia | 5% (1) | |
| Neonatology | 5% (1) | |
| Hospitalist | 5% (1) | |
Video Simulation Testing
Inter‐rater agreement is shown in Figure 1. Raters achieved perfect agreement for 8/9 questions on at least 1 scenario, supporting high inter‐rater reliability for these items. Some items had particularly high reliability. For example, on item 3, subjects achieved perfect agreement for 5/9 scenarios, making 1 both the median and maximum value. Because item 7 (barriers to transfer) did not demonstrate high inter‐rater agreement, we excluded it from the in situ analysis.
In Situ Testing
Characteristics of patients whose handoffs were selected for in situ testing are listed in Table 2. Because some patients were selected on multiple study days, these 90 handoffs represented 58 unique patients. These 58 patients are representative of the CICU population (data not shown). The number of handoffs studied per patient ranged from 1 to 7 (median 1). A total of 19 patients were included in the study more than once; 13 were included twice.
| Characteristic | Categories | Percentage |
|---|---|---|
| ||
| Age | <1 month | 30 |
| 112 months | 34 | |
| 112 years | 28 | |
| 1318 years | 6 | |
| >18 years | 2 | |
| Type of admission | Postnatal observation/preoperative | 20 |
| Postoperative | 29 | |
| Prolonged postoperative (>7 days) | 33 | |
| Other admission | 18 | |
| CICU days | 1 | 31 |
| 27 | 22 | |
| 814 | 10 | |
| 1531 | 13 | |
| >31 | 23 | |
| Active medications | <8 | 26 |
| 811 | 26 | |
| 1218 | 26 | |
| >18 | 23 | |
Rates of agreement between handoff pairs, stratified by attending versus clinician, are shown in Table 3. Overall mean levels of agreement ranged from 0.41 to 0.87 (median 0.77). Except for the ratio of pulmonary to systemic blood flow question, there were no significant differences in agreement between attendings as compared to clinicians. When this analysis was repeated with unique sender‐receiver pair as the unit of analysis to account for within‐pair clustering, we obtained qualitatively similar results (data not shown).
| PKAT Item | Agreement Level | ||||
|---|---|---|---|---|---|
| Attending Physician Pair | Clinician Pair | Pa | |||
| Mean | 95% CI | Mean | 95% CI | ||
| |||||
| Clinical condition | 0.71 | 0.620.81 | 0.78 | 0.690.87 | 0.31 |
| Cardiovascular plan | 0.76 | 0.670.85 | 0.68 | 0.580.78 | 0.25 |
| Respiratory plan | 0.67 | 0.580.78 | 0.76 | 0.670.85 | 0.26 |
| Source of pulmonary blood flow | 0.83 | 0.750.91 | 0.87 | 0.800.94 | 0.53 |
| Ratio of pulmonary to systemic flow | 0.67 | 0.570.77 | 0.41 | 0.310.51 | <0.01 |
| Anticoagulation indication | 0.79 | 0.700.87 | 0.77 | 0.680.86 | 0.72 |
| Active cardiovascular issues | 0.87 | 0.800.94 | 0.76 | 0.670.85 | 0.06 |
| Active noncardiovascular issues | 0.80 | 0.720.88 | 0.78 | 0.690.87 | 0.72 |
Both length of stay and increasing number of medications affected agreement levels for PKAT items (Table 4). Increasing length of stay correlated directly with agreement on cardiovascular plan and ratio of pulmonary to systemic flow and inversely with indication for anticoagulation. Increasing number of medications had an inverse correlation with agreement on indication for anticoagulation, active cardiovascular issues, and active noncardiovascular issues.
| Item | CICU LOS | No. of Active Medications | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 Day (n=56) | 27 Days (n=40) | 814 Days (n=18) | 1531 Days (n=24) | >31 Days (n=42) | Pa | 8 (n=46) | 811 (n=46) | 1218 (n=46) | >18 (n=42) | Pa | |
| |||||||||||
| Clinical condition | 0.75 | 0.63 | 0.78 | 0.83 | 0.79 | 0.29 | 0.71 | 0.70 | 0.78 | 0.79 | 0.32 |
| Cardiovascular plan | 0.59 | 0.73 | 0.67 | 0.79 | 0.86 | <0.01 | 0.63 | 0.72 | 0.63 | 0.81 | 0.16 |
| Respiratory plan | 0.68 | 0.78 | 0.61 | 0.83 | 0.69 | 0.79 | 0.67 | 0.72 | 0.78 | 0.69 | 0.68 |
| Source of pulmonary blood flow | 0.93 | 0.75 | 0.72 | 0.96 | 0.83 | 0.63 | 0.72 | 0.91 | 0.98 | 0.79 | 0.22 |
| Ratio of pulmonary to systemic flow | 0.45 | 0.40 | 0.67 | 0.75 | 0.62 | 0.01 | 0.46 | 0.52 | 0.52 | 0.67 | 0.06 |
| Anticoagulation indication | 0.89 | 0.83 | 0.89 | 0.67 | 0.60 | <0.01 | 0.93 | 0.78 | 0.76 | 0.62 | <0.01 |
| Active cardiovascular issues | 0.86 | 0.78 | 0.72 | 0.92 | 0.76 | 0.52 | 0.87 | 0.76 | 0.54 | 0.55 | <0.01 |
| Active noncardiovascular issues | 0.86 | 0.80 | 0.72 | 0.75 | 0.74 | 0.12 | 0.83 | 0.83 | 0.76 | 0.52 | <0.01 |
In contrast, there were no significant differences in item agreement levels based on provider characteristics, including experience, handoff education, prehandoff preparation, or continuity (data not shown).
CONCLUSIONS
Our results provide initial evidence of reliability and validity of scores for a novel tool, the PKAT, designed to assess providers' shared clinical understanding of a pediatric CICU patient's condition and treatment plan. Because this information should be mutually understood following any handoff, we believe this tool or similar agreement assessments could be used to measure handoff quality across a range of clinical settings. Under the standardized conditions of video simulation, experienced CICU providers achieved high levels of agreement on the PKAT, demonstrating inter‐rater reliability. In situ testing results suggest that the PKAT can validly identify differences in understanding between providers for both routine and complex patients.
The achievement of 100% compliance with in situ testing demonstrates that this type of tool can feasibly be used in a real‐time clinical environment. As expected, mean agreement levels in situ were lower than levels achieved in video simulation. By item, mean levels of agreement for attending and clinician pairs were similar.
Our assessment of PKAT validity demonstrated mixed results. On the one hand, PKAT agreement did not vary significantly by any measured provider characteristics. Consistent with the lack of difference between attendings and clinicians, more experienced providers in both groups did not achieve higher levels of agreement. This finding is surprising, and may illustrate that unmeasured provider characteristics, such as content knowledge, obscure the effects of experience or other measured variables on agreement levels. Alternatively, providing the PKAT to the sending attending prior to the handoff, rather than afterward as for the receiving attendings and clinicians, might have artificially lowered attending agreement levels, concealing a difference due to experience.
On the other hand, construct validity of several items was supported by the difference in agreement levels based on patient characteristics. Agreement levels varied on 5/8 questions as patients became more complex, either defined by length of stay or number of medications. These differences show that agreement on PKAT items responds to changes in handoff complexity, a form of construct validity. Furthermore, these findings suggest that handoffs of more chronic or complex patients may require more attention for components prone to disagreement in these settings. Although complexity and longer length of stay are nonmodifiable risk factors, identifying these handoffs as more susceptible to disagreement provides potential targets for intervention.
It is important to move beyond he said/she said evaluations to assess shared understanding after a handoff, because high fidelity transfer of information is necessary for safe transfer of responsibility. The PKAT addresses this key component of handoff quality in a novel fashion. Although high‐fidelity information transfer may correlate with receiving provider satisfaction, this relationship has not yet been explored. Future studies will evaluate the association between receiver evaluations of handoffs and PKAT agreement, as well as the relationship between PKAT performance and subsequent patient outcomes.
Limitations of this approach include the challenges inherent in reducing a complex understanding of a patient to a multiple‐item instrument. Furthermore, PKAT use may influence handoff content due to the Hawthorne effect. Although our analysis rests on the argument that agreement is the goal of a handoff, some differences of opinion within the care team enrich resilience. Regardless, to maintain continuity of care, providers need to reach agreement on the next steps in a patient's care during the handoff. Because we focused only on agreement, this approach does not compare respondents' answers to a verifiable source of truth, if it exists. Therefore, 2 respondents who agree on the wrong answer receive the same score as 2 who agree on the right answer. Other limitations include using the number of medications as a marker of handoff complexity. Finally, conducting this study in a single CICU limits generalizability. However, we believe that all PKAT items are generalizable to other pediatric CICUs, and that several are generalizable to other pediatric intensive care settings. The approach of measuring shared understanding could be generalized more widely with development of items specific to different clinical settings.
Because the PKAT can be completed and scored quickly, it could be used as a real‐time measure of quality improvement interventions such as the introduction of a standardized handoff protocol. Alternatively, provider pairs could use the PKAT as a final handoff safety check to confirm consensus before transfer of responsibility. The concept of measuring shared clinical understanding could be extended to develop similar instruments for different clinical settings.
Acknowledgements
The authors thank the CICU providers for their enthusiasm for and participation in this study. The authors also thank Margaret Wolff, MD, Newton Buchanan, and the Center for Simulation, Advanced Education and Innovation at The Children's Hospital of Philadelphia for assistance in filming the video scenarios.
Disclosures: Dr. Bates was supported in part by NICHD/T32 HD060550 and NHLBI/T32 HL07915 grant funding. Dr. Metlay was supported by a Mid‐Career Investigator Award in Patient Oriented Research (K24‐AI073957). The authors report no conflicts of interest.
- , . The published literature on handoffs in hospitals: deficiencies identified in an extensive review. Quality and Safety in Health Care. 2010;19(6):493–497. doi: 10.1136/qshc.2009.033480.
- . Communication failures in patient sign‐out and suggestions for improvement: a critical incident analysis. Qual Saf Health Care. 2005;14(6):401–407.
- , , , , . Consequences of inadequate sign‐out for patient care. Arch Intern Med. 2008;168(16):1755–1760.
- , , , , , . Nursing handovers: do we really need them? J Nurs Manag. 2004;12(1):37–42.
- , , , et al. Assessing clinical handover between paramedics and the trauma team. Injury. 2010;41(5):460–464.
- , , , , . Answering questions on call: Pediatric resident physicians' use of handoffs and other resources. J Hosp Med. 2013;8(6):328–333.
- , , , , . Managing discontinuity in academic medical centers: strategies for a safe and effective resident sign‐out. J Hosp Med. 2006;1(4):257–266.
- , . Patient handoffs: standardized and reliable measurement tools remain elusive. Jt Comm J Qual Patient Saf. 2010;36(2):52–61.
- , , , , . Improving measurement in clinical handover. Qual Saf Health Care. 2009;18(4):272–276.
- , , , . Adequacy of information transferred at resident sign‐out (inhospital handover of care): a prospective survey. Qual Saf Health Care. 2008;17(1):6–10.
- , , . Standardized Sign‐out reduces intern perception of medical errors on the general internal medicine ward. Teach Learn Med. 2009;21(2):121–126.
- , , , et al. Hand‐off education and evaluation: piloting the observed simulated hand‐off experience (OSHE). J Gen Intern Med. 2009;25(2):129–134.
- , , , , . Assessing the quality of patient handoffs at care transitions. Qual Saf Health Care. 2010;19(6):1–5.
- , , , , . Implementing peer evaluation of handoffs: associations with experience and workload. J Hosp Med. 2013;8(3):132–136.
- , , , et al. Development of a handoff evaluation tool for shift‐to‐shift physician handoffs: the handoff CEX. J Hosp Med. 2013;8(4):191–200.
- , . The effects of patient handoff characteristics on subsequent care: a systematic review and areas for future research. Acad Med. 2012;87(8):1105–1124.
- . Construct validity in organizational behavior. In: Cummings LL, Stawe BM, eds. Research in Organizational Behavior. Vol 2. Greenwich, CT: JAI Press; 1980:3–43.
- , , , , . Development and validation of the medication regimen complexity index. Ann Pharmacother. 2004;38(9):1369–1376.
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- . A Wilcoxon‐type test for trend. Stat Med. 1985;4(1):87–90.
Increasing attention has been paid to the need for effective handoffs between healthcare providers since the Joint Commission identified standardized handoff protocols as a National Patient Safety Goal in 2006.1 Aside from adverse consequences for patients, poor handoffs produce provider uncertainty about care plans.[2, 3] Agreement on clinical information after a handoff is critical because a significant proportion of data is not documented in the medical record, leaving providers reliant on verbal communication.[4, 5, 6] Providers may enter the handoff with differing opinions; however, to mitigate the potential safety consequences of discontinuity of care,[7] the goal should be to achieve consensus about proposed courses of action.
Given the recent focus on improving handoffs, rigorous, outcome‐driven measures of handoff quality are clearly needed, but measuring shift‐to‐shift handoff quality has proved challenging.[8, 9] Previous studies of physician handoffs surveyed receivers for satisfaction,[10, 11] compared reported omissions to audio recordings,[3] and developed evaluation tools for receivers to rate handoffs.[12, 13, 14, 15] None directly assess the underlying goal of a handoff: the transfer of understanding from sender to receiver, enabling safe transfer of patient care responsibility.[16] We therefore chose to measure agreement on patient condition and treatment plans following handoff as an indicator of the quality of the shared clinical understanding formed. Advantages of piloting this approach in the pediatric cardiac intensive care unit (CICU) include the relatively homogenous patient population and small number of medical providers. If effective, the strategy of tool development and evaluation could be generalized to different clinical environments and provider groups.
Our aim was to develop and validate a tool to measure the level of shared clinical understanding regarding the condition and treatment plan of a CICU patient after handoff. The tool we designed was the pediatric cardiology Patient Knowledge Assessment Tool (PKAT), a brief, multiple‐item questionnaire focused on key data elements for individual CICU patients. Although variation in provider opinion helps detect diagnostic or treatment errors,[8] the PKAT is based on the assumption that achieving consensus on clinical status and the next steps of care is the goal of the handoff.
METHODS
Setting
The CICU is a 24‐bed medical and surgical unit in a 500‐bed free standing children's hospital. CICU attending physicians work 12‐ or 24‐hour shifts and supervise front line clinicians (including subspecialty fellows, nurse practitioners, and hospitalists, referred to as clinicians in this article) who work day or night shifts. Handoffs occur twice daily, with no significant differences in handoff practices between the 2 times. Attending physicians (referred to as attendings in this article) conduct parallel but separate handoffs from clinicians. All providers work exclusively in the CICU with the exception of fellows, who rotate monthly.
This study was approved by the institutional review board at The Children's Hospital of Philadelphia. All provider subjects provided informed consent. Consent for patient subjects was waived.
Development of the PKAT
We developed the PKAT content domains based on findings from previous studies,[2, 3] unpublished survey data about handoff omissions in our CICU, and CICU attending expert opinion. Pilot testing included 39 attendings and clinicians involved in 60 handoffs representing a wide variety of admissions. Participants were encouraged to share opinions on tool content and design with study staff. The PKAT (see Supporting Information, Appendix, in the online version of this article) was refined iteratively based on this feedback.
Video Simulation Testing
We used video simulation to test the PKAT for inter‐rater reliability. Nine patient handoff scenarios were written with varying levels of patient complexity and clarity of dialogue. The scenarios were filmed using the same actors and location to minimize variability aside from content. We recruited 10 experienced provider subjects (attendings and senior fellows) to minimize the effect of knowledge deficits. For each simulated handoff, subjects were encouraged to annotate a mock sign‐out sheet, which mimicked the content and format of the CICU sign‐out sheet. After watching all 9 scenarios, subjects completed a PKAT for each handoff from the perspective of the receiver based on the videotape. These standardized conditions allowed for assessment of inter‐rater reliability.
In Situ Testing
We then tested the PKAT in situ in the CICU to assess construct validity. We chose to study the morning handoff because the timing and location are more consistent. We planned to study 90 patient handoffs because the standard practice for testing a new psychometric instrument is to collect 10 observations per item.[17] On study days, 4 providers completed a PKAT for each selected handoff: the sending attending, receiving attending, sending clinician, and receiving clinician.
Study days were scheduled over 2 months to encompass a range of providers. Given the small number of attendings, we did not exclude those who had participated in video simulation testing. On study days, 6 patients were enrolled using stratified sampling to ensure adequate representation of new admissions (ie, admitted within 24 hours). The sending attending received the PKAT forms prior to the handoff. The receiving attending and clinicians received the PKAT after handoff. This difference in administration was due to logistic concerns: sending attendings requested to receive the PKATs earlier because they had to complete all 6 PKATs, whereas other providers completed 3 or fewer per day. Thus, sending attendings could complete the PKAT before or after the handoff, whereas all other participants completed the instrument after the handoff.
To test for construct validity, we gathered data on participating providers and patients, hypothesizing that PKAT agreement levels would decrease in response to less experienced providers or more complex patients. Provider characteristics included previous handoff education and amount of time worked in our CICU. Attending CICU experience was dichotomized into first year versus second or greater year. Clinician experience was dichotomized into first or second month versus third or greater month of CICU service. Each PKAT asked the handoff receiver whether he or she had recently cared for this patient or gathered information prior to handoff (eg, speaking to bedside nurse).
Recorded patient characteristics included age, length of stay, and admission type including neonatal/preoperative observation, postoperative (first 7 days after operation), prolonged postoperative (>7 days after operation), and medical (all others). In recognition of differences in handoffs during the first 24 hours of admission and the right‐skewed length of stay in the CICU, we analyzed length of stay based on the following categories: new admission (<24 hours), days 2 to 7, days 8 to 14, days 15 to 31, and >31 days. Because the number of active medications has been shown to correlate with treatment regimen complexity[18] and physician ratings of illness severity,[19] we recorded this number as a surrogate measure of patient complexity. For analytic purposes, we categorized the number of active medications into quartiles.
Provider subject characteristics and PKAT responses were collected using paper forms and entered into REDCap (Research Electronic Data Capture; REDCap Consortium,
Statistical Analysis
The primary outcome measure was the PKAT agreement level among providers evaluating the same handoff. For the reliability assessment, we calculated agreement across all providers analyzing the simulation videos, expecting that multiple providers should have high agreement for the same scenarios if the instrument has high inter‐rater reliability. For the validity assessment, we calculated agreement for each individual handoff by item and then calculated average levels of agreement for each item across provider and patient characteristics. We analyzed handoffs between attendings and clinicians separately. For items with mutually exclusive responses, simple yes/no agreement was calculated. For items requiring at least 1 response, agreement was coded when both respondents selected at least 1 response in common. For items that did not require a selection, credit was given if both subjects agreed that none of the conditions were present or if they agreed that at least 1 condition was present. In a secondary analysis, we repeated the analyses with unique sender‐receiver pair as the unit of analysis to account for correlation in the pair interaction.
Summary statistics were used to describe provider and patient characteristics. Mean rates of agreement with 95% confidence intervals were calculated for each item. The Wilcoxon rank sum test was used to compare mean results between groups (eg, attendings vs clinicians). A nonparametric test for trend, which is an extension of the Wilcoxon rank sum test,[21] was used to compare mean results across ordered categories (eg, length of stay). All tests of significance were at P<0.05 level and 2‐tailed. All statistical analysis was done using Stata 12 (StataCorp, College Station, TX).
RESULTS
Provider subject types are represented in Table 1. Handoffs between these 29 individuals resulted in 70 unique sender and receiver combinations with a median of 2 PKATs completed per unique sender‐receiver pair (range, 115). Attendings had lower rates of handoff education than clinicians (11% vs 85% for in situ testing participants, P=0.01). Attendings participating in in situ testing had worked in the CICU for a median of 3 years (range, 116 years). Clinicians participating in in situ testing had a median of 3 months of CICU experience (range, 195 months). Providers were 100% compliant with PKAT completion.
| Simulation Testing, n=10 | In Situ Testing, n=29 | |
|---|---|---|
| ||
| Attending physicians | 40% (4) | 31% (9) |
| Clinicians | 60% (6) | 69% (20) |
| Clinician type | ||
| Cardiology | 67% (4) | 35% (7) |
| Critical care medicine | 33% (2) | 25% (5) |
| CICU nurse practitioner | 25% (5) | |
| Anesthesia | 5% (1) | |
| Neonatology | 5% (1) | |
| Hospitalist | 5% (1) | |
Video Simulation Testing
Inter‐rater agreement is shown in Figure 1. Raters achieved perfect agreement for 8/9 questions on at least 1 scenario, supporting high inter‐rater reliability for these items. Some items had particularly high reliability. For example, on item 3, subjects achieved perfect agreement for 5/9 scenarios, making 1 both the median and maximum value. Because item 7 (barriers to transfer) did not demonstrate high inter‐rater agreement, we excluded it from the in situ analysis.
In Situ Testing
Characteristics of patients whose handoffs were selected for in situ testing are listed in Table 2. Because some patients were selected on multiple study days, these 90 handoffs represented 58 unique patients. These 58 patients are representative of the CICU population (data not shown). The number of handoffs studied per patient ranged from 1 to 7 (median 1). A total of 19 patients were included in the study more than once; 13 were included twice.
| Characteristic | Categories | Percentage |
|---|---|---|
| ||
| Age | <1 month | 30 |
| 112 months | 34 | |
| 112 years | 28 | |
| 1318 years | 6 | |
| >18 years | 2 | |
| Type of admission | Postnatal observation/preoperative | 20 |
| Postoperative | 29 | |
| Prolonged postoperative (>7 days) | 33 | |
| Other admission | 18 | |
| CICU days | 1 | 31 |
| 27 | 22 | |
| 814 | 10 | |
| 1531 | 13 | |
| >31 | 23 | |
| Active medications | <8 | 26 |
| 811 | 26 | |
| 1218 | 26 | |
| >18 | 23 | |
Rates of agreement between handoff pairs, stratified by attending versus clinician, are shown in Table 3. Overall mean levels of agreement ranged from 0.41 to 0.87 (median 0.77). Except for the ratio of pulmonary to systemic blood flow question, there were no significant differences in agreement between attendings as compared to clinicians. When this analysis was repeated with unique sender‐receiver pair as the unit of analysis to account for within‐pair clustering, we obtained qualitatively similar results (data not shown).
| PKAT Item | Agreement Level | ||||
|---|---|---|---|---|---|
| Attending Physician Pair | Clinician Pair | Pa | |||
| Mean | 95% CI | Mean | 95% CI | ||
| |||||
| Clinical condition | 0.71 | 0.620.81 | 0.78 | 0.690.87 | 0.31 |
| Cardiovascular plan | 0.76 | 0.670.85 | 0.68 | 0.580.78 | 0.25 |
| Respiratory plan | 0.67 | 0.580.78 | 0.76 | 0.670.85 | 0.26 |
| Source of pulmonary blood flow | 0.83 | 0.750.91 | 0.87 | 0.800.94 | 0.53 |
| Ratio of pulmonary to systemic flow | 0.67 | 0.570.77 | 0.41 | 0.310.51 | <0.01 |
| Anticoagulation indication | 0.79 | 0.700.87 | 0.77 | 0.680.86 | 0.72 |
| Active cardiovascular issues | 0.87 | 0.800.94 | 0.76 | 0.670.85 | 0.06 |
| Active noncardiovascular issues | 0.80 | 0.720.88 | 0.78 | 0.690.87 | 0.72 |
Both length of stay and increasing number of medications affected agreement levels for PKAT items (Table 4). Increasing length of stay correlated directly with agreement on cardiovascular plan and ratio of pulmonary to systemic flow and inversely with indication for anticoagulation. Increasing number of medications had an inverse correlation with agreement on indication for anticoagulation, active cardiovascular issues, and active noncardiovascular issues.
| Item | CICU LOS | No. of Active Medications | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 Day (n=56) | 27 Days (n=40) | 814 Days (n=18) | 1531 Days (n=24) | >31 Days (n=42) | Pa | 8 (n=46) | 811 (n=46) | 1218 (n=46) | >18 (n=42) | Pa | |
| |||||||||||
| Clinical condition | 0.75 | 0.63 | 0.78 | 0.83 | 0.79 | 0.29 | 0.71 | 0.70 | 0.78 | 0.79 | 0.32 |
| Cardiovascular plan | 0.59 | 0.73 | 0.67 | 0.79 | 0.86 | <0.01 | 0.63 | 0.72 | 0.63 | 0.81 | 0.16 |
| Respiratory plan | 0.68 | 0.78 | 0.61 | 0.83 | 0.69 | 0.79 | 0.67 | 0.72 | 0.78 | 0.69 | 0.68 |
| Source of pulmonary blood flow | 0.93 | 0.75 | 0.72 | 0.96 | 0.83 | 0.63 | 0.72 | 0.91 | 0.98 | 0.79 | 0.22 |
| Ratio of pulmonary to systemic flow | 0.45 | 0.40 | 0.67 | 0.75 | 0.62 | 0.01 | 0.46 | 0.52 | 0.52 | 0.67 | 0.06 |
| Anticoagulation indication | 0.89 | 0.83 | 0.89 | 0.67 | 0.60 | <0.01 | 0.93 | 0.78 | 0.76 | 0.62 | <0.01 |
| Active cardiovascular issues | 0.86 | 0.78 | 0.72 | 0.92 | 0.76 | 0.52 | 0.87 | 0.76 | 0.54 | 0.55 | <0.01 |
| Active noncardiovascular issues | 0.86 | 0.80 | 0.72 | 0.75 | 0.74 | 0.12 | 0.83 | 0.83 | 0.76 | 0.52 | <0.01 |
In contrast, there were no significant differences in item agreement levels based on provider characteristics, including experience, handoff education, prehandoff preparation, or continuity (data not shown).
CONCLUSIONS
Our results provide initial evidence of reliability and validity of scores for a novel tool, the PKAT, designed to assess providers' shared clinical understanding of a pediatric CICU patient's condition and treatment plan. Because this information should be mutually understood following any handoff, we believe this tool or similar agreement assessments could be used to measure handoff quality across a range of clinical settings. Under the standardized conditions of video simulation, experienced CICU providers achieved high levels of agreement on the PKAT, demonstrating inter‐rater reliability. In situ testing results suggest that the PKAT can validly identify differences in understanding between providers for both routine and complex patients.
The achievement of 100% compliance with in situ testing demonstrates that this type of tool can feasibly be used in a real‐time clinical environment. As expected, mean agreement levels in situ were lower than levels achieved in video simulation. By item, mean levels of agreement for attending and clinician pairs were similar.
Our assessment of PKAT validity demonstrated mixed results. On the one hand, PKAT agreement did not vary significantly by any measured provider characteristics. Consistent with the lack of difference between attendings and clinicians, more experienced providers in both groups did not achieve higher levels of agreement. This finding is surprising, and may illustrate that unmeasured provider characteristics, such as content knowledge, obscure the effects of experience or other measured variables on agreement levels. Alternatively, providing the PKAT to the sending attending prior to the handoff, rather than afterward as for the receiving attendings and clinicians, might have artificially lowered attending agreement levels, concealing a difference due to experience.
On the other hand, construct validity of several items was supported by the difference in agreement levels based on patient characteristics. Agreement levels varied on 5/8 questions as patients became more complex, either defined by length of stay or number of medications. These differences show that agreement on PKAT items responds to changes in handoff complexity, a form of construct validity. Furthermore, these findings suggest that handoffs of more chronic or complex patients may require more attention for components prone to disagreement in these settings. Although complexity and longer length of stay are nonmodifiable risk factors, identifying these handoffs as more susceptible to disagreement provides potential targets for intervention.
It is important to move beyond he said/she said evaluations to assess shared understanding after a handoff, because high fidelity transfer of information is necessary for safe transfer of responsibility. The PKAT addresses this key component of handoff quality in a novel fashion. Although high‐fidelity information transfer may correlate with receiving provider satisfaction, this relationship has not yet been explored. Future studies will evaluate the association between receiver evaluations of handoffs and PKAT agreement, as well as the relationship between PKAT performance and subsequent patient outcomes.
Limitations of this approach include the challenges inherent in reducing a complex understanding of a patient to a multiple‐item instrument. Furthermore, PKAT use may influence handoff content due to the Hawthorne effect. Although our analysis rests on the argument that agreement is the goal of a handoff, some differences of opinion within the care team enrich resilience. Regardless, to maintain continuity of care, providers need to reach agreement on the next steps in a patient's care during the handoff. Because we focused only on agreement, this approach does not compare respondents' answers to a verifiable source of truth, if it exists. Therefore, 2 respondents who agree on the wrong answer receive the same score as 2 who agree on the right answer. Other limitations include using the number of medications as a marker of handoff complexity. Finally, conducting this study in a single CICU limits generalizability. However, we believe that all PKAT items are generalizable to other pediatric CICUs, and that several are generalizable to other pediatric intensive care settings. The approach of measuring shared understanding could be generalized more widely with development of items specific to different clinical settings.
Because the PKAT can be completed and scored quickly, it could be used as a real‐time measure of quality improvement interventions such as the introduction of a standardized handoff protocol. Alternatively, provider pairs could use the PKAT as a final handoff safety check to confirm consensus before transfer of responsibility. The concept of measuring shared clinical understanding could be extended to develop similar instruments for different clinical settings.
Acknowledgements
The authors thank the CICU providers for their enthusiasm for and participation in this study. The authors also thank Margaret Wolff, MD, Newton Buchanan, and the Center for Simulation, Advanced Education and Innovation at The Children's Hospital of Philadelphia for assistance in filming the video scenarios.
Disclosures: Dr. Bates was supported in part by NICHD/T32 HD060550 and NHLBI/T32 HL07915 grant funding. Dr. Metlay was supported by a Mid‐Career Investigator Award in Patient Oriented Research (K24‐AI073957). The authors report no conflicts of interest.
Increasing attention has been paid to the need for effective handoffs between healthcare providers since the Joint Commission identified standardized handoff protocols as a National Patient Safety Goal in 2006.1 Aside from adverse consequences for patients, poor handoffs produce provider uncertainty about care plans.[2, 3] Agreement on clinical information after a handoff is critical because a significant proportion of data is not documented in the medical record, leaving providers reliant on verbal communication.[4, 5, 6] Providers may enter the handoff with differing opinions; however, to mitigate the potential safety consequences of discontinuity of care,[7] the goal should be to achieve consensus about proposed courses of action.
Given the recent focus on improving handoffs, rigorous, outcome‐driven measures of handoff quality are clearly needed, but measuring shift‐to‐shift handoff quality has proved challenging.[8, 9] Previous studies of physician handoffs surveyed receivers for satisfaction,[10, 11] compared reported omissions to audio recordings,[3] and developed evaluation tools for receivers to rate handoffs.[12, 13, 14, 15] None directly assess the underlying goal of a handoff: the transfer of understanding from sender to receiver, enabling safe transfer of patient care responsibility.[16] We therefore chose to measure agreement on patient condition and treatment plans following handoff as an indicator of the quality of the shared clinical understanding formed. Advantages of piloting this approach in the pediatric cardiac intensive care unit (CICU) include the relatively homogenous patient population and small number of medical providers. If effective, the strategy of tool development and evaluation could be generalized to different clinical environments and provider groups.
Our aim was to develop and validate a tool to measure the level of shared clinical understanding regarding the condition and treatment plan of a CICU patient after handoff. The tool we designed was the pediatric cardiology Patient Knowledge Assessment Tool (PKAT), a brief, multiple‐item questionnaire focused on key data elements for individual CICU patients. Although variation in provider opinion helps detect diagnostic or treatment errors,[8] the PKAT is based on the assumption that achieving consensus on clinical status and the next steps of care is the goal of the handoff.
METHODS
Setting
The CICU is a 24‐bed medical and surgical unit in a 500‐bed free standing children's hospital. CICU attending physicians work 12‐ or 24‐hour shifts and supervise front line clinicians (including subspecialty fellows, nurse practitioners, and hospitalists, referred to as clinicians in this article) who work day or night shifts. Handoffs occur twice daily, with no significant differences in handoff practices between the 2 times. Attending physicians (referred to as attendings in this article) conduct parallel but separate handoffs from clinicians. All providers work exclusively in the CICU with the exception of fellows, who rotate monthly.
This study was approved by the institutional review board at The Children's Hospital of Philadelphia. All provider subjects provided informed consent. Consent for patient subjects was waived.
Development of the PKAT
We developed the PKAT content domains based on findings from previous studies,[2, 3] unpublished survey data about handoff omissions in our CICU, and CICU attending expert opinion. Pilot testing included 39 attendings and clinicians involved in 60 handoffs representing a wide variety of admissions. Participants were encouraged to share opinions on tool content and design with study staff. The PKAT (see Supporting Information, Appendix, in the online version of this article) was refined iteratively based on this feedback.
Video Simulation Testing
We used video simulation to test the PKAT for inter‐rater reliability. Nine patient handoff scenarios were written with varying levels of patient complexity and clarity of dialogue. The scenarios were filmed using the same actors and location to minimize variability aside from content. We recruited 10 experienced provider subjects (attendings and senior fellows) to minimize the effect of knowledge deficits. For each simulated handoff, subjects were encouraged to annotate a mock sign‐out sheet, which mimicked the content and format of the CICU sign‐out sheet. After watching all 9 scenarios, subjects completed a PKAT for each handoff from the perspective of the receiver based on the videotape. These standardized conditions allowed for assessment of inter‐rater reliability.
In Situ Testing
We then tested the PKAT in situ in the CICU to assess construct validity. We chose to study the morning handoff because the timing and location are more consistent. We planned to study 90 patient handoffs because the standard practice for testing a new psychometric instrument is to collect 10 observations per item.[17] On study days, 4 providers completed a PKAT for each selected handoff: the sending attending, receiving attending, sending clinician, and receiving clinician.
Study days were scheduled over 2 months to encompass a range of providers. Given the small number of attendings, we did not exclude those who had participated in video simulation testing. On study days, 6 patients were enrolled using stratified sampling to ensure adequate representation of new admissions (ie, admitted within 24 hours). The sending attending received the PKAT forms prior to the handoff. The receiving attending and clinicians received the PKAT after handoff. This difference in administration was due to logistic concerns: sending attendings requested to receive the PKATs earlier because they had to complete all 6 PKATs, whereas other providers completed 3 or fewer per day. Thus, sending attendings could complete the PKAT before or after the handoff, whereas all other participants completed the instrument after the handoff.
To test for construct validity, we gathered data on participating providers and patients, hypothesizing that PKAT agreement levels would decrease in response to less experienced providers or more complex patients. Provider characteristics included previous handoff education and amount of time worked in our CICU. Attending CICU experience was dichotomized into first year versus second or greater year. Clinician experience was dichotomized into first or second month versus third or greater month of CICU service. Each PKAT asked the handoff receiver whether he or she had recently cared for this patient or gathered information prior to handoff (eg, speaking to bedside nurse).
Recorded patient characteristics included age, length of stay, and admission type including neonatal/preoperative observation, postoperative (first 7 days after operation), prolonged postoperative (>7 days after operation), and medical (all others). In recognition of differences in handoffs during the first 24 hours of admission and the right‐skewed length of stay in the CICU, we analyzed length of stay based on the following categories: new admission (<24 hours), days 2 to 7, days 8 to 14, days 15 to 31, and >31 days. Because the number of active medications has been shown to correlate with treatment regimen complexity[18] and physician ratings of illness severity,[19] we recorded this number as a surrogate measure of patient complexity. For analytic purposes, we categorized the number of active medications into quartiles.
Provider subject characteristics and PKAT responses were collected using paper forms and entered into REDCap (Research Electronic Data Capture; REDCap Consortium,
Statistical Analysis
The primary outcome measure was the PKAT agreement level among providers evaluating the same handoff. For the reliability assessment, we calculated agreement across all providers analyzing the simulation videos, expecting that multiple providers should have high agreement for the same scenarios if the instrument has high inter‐rater reliability. For the validity assessment, we calculated agreement for each individual handoff by item and then calculated average levels of agreement for each item across provider and patient characteristics. We analyzed handoffs between attendings and clinicians separately. For items with mutually exclusive responses, simple yes/no agreement was calculated. For items requiring at least 1 response, agreement was coded when both respondents selected at least 1 response in common. For items that did not require a selection, credit was given if both subjects agreed that none of the conditions were present or if they agreed that at least 1 condition was present. In a secondary analysis, we repeated the analyses with unique sender‐receiver pair as the unit of analysis to account for correlation in the pair interaction.
Summary statistics were used to describe provider and patient characteristics. Mean rates of agreement with 95% confidence intervals were calculated for each item. The Wilcoxon rank sum test was used to compare mean results between groups (eg, attendings vs clinicians). A nonparametric test for trend, which is an extension of the Wilcoxon rank sum test,[21] was used to compare mean results across ordered categories (eg, length of stay). All tests of significance were at P<0.05 level and 2‐tailed. All statistical analysis was done using Stata 12 (StataCorp, College Station, TX).
RESULTS
Provider subject types are represented in Table 1. Handoffs between these 29 individuals resulted in 70 unique sender and receiver combinations with a median of 2 PKATs completed per unique sender‐receiver pair (range, 115). Attendings had lower rates of handoff education than clinicians (11% vs 85% for in situ testing participants, P=0.01). Attendings participating in in situ testing had worked in the CICU for a median of 3 years (range, 116 years). Clinicians participating in in situ testing had a median of 3 months of CICU experience (range, 195 months). Providers were 100% compliant with PKAT completion.
| Simulation Testing, n=10 | In Situ Testing, n=29 | |
|---|---|---|
| ||
| Attending physicians | 40% (4) | 31% (9) |
| Clinicians | 60% (6) | 69% (20) |
| Clinician type | ||
| Cardiology | 67% (4) | 35% (7) |
| Critical care medicine | 33% (2) | 25% (5) |
| CICU nurse practitioner | 25% (5) | |
| Anesthesia | 5% (1) | |
| Neonatology | 5% (1) | |
| Hospitalist | 5% (1) | |
Video Simulation Testing
Inter‐rater agreement is shown in Figure 1. Raters achieved perfect agreement for 8/9 questions on at least 1 scenario, supporting high inter‐rater reliability for these items. Some items had particularly high reliability. For example, on item 3, subjects achieved perfect agreement for 5/9 scenarios, making 1 both the median and maximum value. Because item 7 (barriers to transfer) did not demonstrate high inter‐rater agreement, we excluded it from the in situ analysis.
In Situ Testing
Characteristics of patients whose handoffs were selected for in situ testing are listed in Table 2. Because some patients were selected on multiple study days, these 90 handoffs represented 58 unique patients. These 58 patients are representative of the CICU population (data not shown). The number of handoffs studied per patient ranged from 1 to 7 (median 1). A total of 19 patients were included in the study more than once; 13 were included twice.
| Characteristic | Categories | Percentage |
|---|---|---|
| ||
| Age | <1 month | 30 |
| 112 months | 34 | |
| 112 years | 28 | |
| 1318 years | 6 | |
| >18 years | 2 | |
| Type of admission | Postnatal observation/preoperative | 20 |
| Postoperative | 29 | |
| Prolonged postoperative (>7 days) | 33 | |
| Other admission | 18 | |
| CICU days | 1 | 31 |
| 27 | 22 | |
| 814 | 10 | |
| 1531 | 13 | |
| >31 | 23 | |
| Active medications | <8 | 26 |
| 811 | 26 | |
| 1218 | 26 | |
| >18 | 23 | |
Rates of agreement between handoff pairs, stratified by attending versus clinician, are shown in Table 3. Overall mean levels of agreement ranged from 0.41 to 0.87 (median 0.77). Except for the ratio of pulmonary to systemic blood flow question, there were no significant differences in agreement between attendings as compared to clinicians. When this analysis was repeated with unique sender‐receiver pair as the unit of analysis to account for within‐pair clustering, we obtained qualitatively similar results (data not shown).
| PKAT Item | Agreement Level | ||||
|---|---|---|---|---|---|
| Attending Physician Pair | Clinician Pair | Pa | |||
| Mean | 95% CI | Mean | 95% CI | ||
| |||||
| Clinical condition | 0.71 | 0.620.81 | 0.78 | 0.690.87 | 0.31 |
| Cardiovascular plan | 0.76 | 0.670.85 | 0.68 | 0.580.78 | 0.25 |
| Respiratory plan | 0.67 | 0.580.78 | 0.76 | 0.670.85 | 0.26 |
| Source of pulmonary blood flow | 0.83 | 0.750.91 | 0.87 | 0.800.94 | 0.53 |
| Ratio of pulmonary to systemic flow | 0.67 | 0.570.77 | 0.41 | 0.310.51 | <0.01 |
| Anticoagulation indication | 0.79 | 0.700.87 | 0.77 | 0.680.86 | 0.72 |
| Active cardiovascular issues | 0.87 | 0.800.94 | 0.76 | 0.670.85 | 0.06 |
| Active noncardiovascular issues | 0.80 | 0.720.88 | 0.78 | 0.690.87 | 0.72 |
Both length of stay and increasing number of medications affected agreement levels for PKAT items (Table 4). Increasing length of stay correlated directly with agreement on cardiovascular plan and ratio of pulmonary to systemic flow and inversely with indication for anticoagulation. Increasing number of medications had an inverse correlation with agreement on indication for anticoagulation, active cardiovascular issues, and active noncardiovascular issues.
| Item | CICU LOS | No. of Active Medications | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 Day (n=56) | 27 Days (n=40) | 814 Days (n=18) | 1531 Days (n=24) | >31 Days (n=42) | Pa | 8 (n=46) | 811 (n=46) | 1218 (n=46) | >18 (n=42) | Pa | |
| |||||||||||
| Clinical condition | 0.75 | 0.63 | 0.78 | 0.83 | 0.79 | 0.29 | 0.71 | 0.70 | 0.78 | 0.79 | 0.32 |
| Cardiovascular plan | 0.59 | 0.73 | 0.67 | 0.79 | 0.86 | <0.01 | 0.63 | 0.72 | 0.63 | 0.81 | 0.16 |
| Respiratory plan | 0.68 | 0.78 | 0.61 | 0.83 | 0.69 | 0.79 | 0.67 | 0.72 | 0.78 | 0.69 | 0.68 |
| Source of pulmonary blood flow | 0.93 | 0.75 | 0.72 | 0.96 | 0.83 | 0.63 | 0.72 | 0.91 | 0.98 | 0.79 | 0.22 |
| Ratio of pulmonary to systemic flow | 0.45 | 0.40 | 0.67 | 0.75 | 0.62 | 0.01 | 0.46 | 0.52 | 0.52 | 0.67 | 0.06 |
| Anticoagulation indication | 0.89 | 0.83 | 0.89 | 0.67 | 0.60 | <0.01 | 0.93 | 0.78 | 0.76 | 0.62 | <0.01 |
| Active cardiovascular issues | 0.86 | 0.78 | 0.72 | 0.92 | 0.76 | 0.52 | 0.87 | 0.76 | 0.54 | 0.55 | <0.01 |
| Active noncardiovascular issues | 0.86 | 0.80 | 0.72 | 0.75 | 0.74 | 0.12 | 0.83 | 0.83 | 0.76 | 0.52 | <0.01 |
In contrast, there were no significant differences in item agreement levels based on provider characteristics, including experience, handoff education, prehandoff preparation, or continuity (data not shown).
CONCLUSIONS
Our results provide initial evidence of reliability and validity of scores for a novel tool, the PKAT, designed to assess providers' shared clinical understanding of a pediatric CICU patient's condition and treatment plan. Because this information should be mutually understood following any handoff, we believe this tool or similar agreement assessments could be used to measure handoff quality across a range of clinical settings. Under the standardized conditions of video simulation, experienced CICU providers achieved high levels of agreement on the PKAT, demonstrating inter‐rater reliability. In situ testing results suggest that the PKAT can validly identify differences in understanding between providers for both routine and complex patients.
The achievement of 100% compliance with in situ testing demonstrates that this type of tool can feasibly be used in a real‐time clinical environment. As expected, mean agreement levels in situ were lower than levels achieved in video simulation. By item, mean levels of agreement for attending and clinician pairs were similar.
Our assessment of PKAT validity demonstrated mixed results. On the one hand, PKAT agreement did not vary significantly by any measured provider characteristics. Consistent with the lack of difference between attendings and clinicians, more experienced providers in both groups did not achieve higher levels of agreement. This finding is surprising, and may illustrate that unmeasured provider characteristics, such as content knowledge, obscure the effects of experience or other measured variables on agreement levels. Alternatively, providing the PKAT to the sending attending prior to the handoff, rather than afterward as for the receiving attendings and clinicians, might have artificially lowered attending agreement levels, concealing a difference due to experience.
On the other hand, construct validity of several items was supported by the difference in agreement levels based on patient characteristics. Agreement levels varied on 5/8 questions as patients became more complex, either defined by length of stay or number of medications. These differences show that agreement on PKAT items responds to changes in handoff complexity, a form of construct validity. Furthermore, these findings suggest that handoffs of more chronic or complex patients may require more attention for components prone to disagreement in these settings. Although complexity and longer length of stay are nonmodifiable risk factors, identifying these handoffs as more susceptible to disagreement provides potential targets for intervention.
It is important to move beyond he said/she said evaluations to assess shared understanding after a handoff, because high fidelity transfer of information is necessary for safe transfer of responsibility. The PKAT addresses this key component of handoff quality in a novel fashion. Although high‐fidelity information transfer may correlate with receiving provider satisfaction, this relationship has not yet been explored. Future studies will evaluate the association between receiver evaluations of handoffs and PKAT agreement, as well as the relationship between PKAT performance and subsequent patient outcomes.
Limitations of this approach include the challenges inherent in reducing a complex understanding of a patient to a multiple‐item instrument. Furthermore, PKAT use may influence handoff content due to the Hawthorne effect. Although our analysis rests on the argument that agreement is the goal of a handoff, some differences of opinion within the care team enrich resilience. Regardless, to maintain continuity of care, providers need to reach agreement on the next steps in a patient's care during the handoff. Because we focused only on agreement, this approach does not compare respondents' answers to a verifiable source of truth, if it exists. Therefore, 2 respondents who agree on the wrong answer receive the same score as 2 who agree on the right answer. Other limitations include using the number of medications as a marker of handoff complexity. Finally, conducting this study in a single CICU limits generalizability. However, we believe that all PKAT items are generalizable to other pediatric CICUs, and that several are generalizable to other pediatric intensive care settings. The approach of measuring shared understanding could be generalized more widely with development of items specific to different clinical settings.
Because the PKAT can be completed and scored quickly, it could be used as a real‐time measure of quality improvement interventions such as the introduction of a standardized handoff protocol. Alternatively, provider pairs could use the PKAT as a final handoff safety check to confirm consensus before transfer of responsibility. The concept of measuring shared clinical understanding could be extended to develop similar instruments for different clinical settings.
Acknowledgements
The authors thank the CICU providers for their enthusiasm for and participation in this study. The authors also thank Margaret Wolff, MD, Newton Buchanan, and the Center for Simulation, Advanced Education and Innovation at The Children's Hospital of Philadelphia for assistance in filming the video scenarios.
Disclosures: Dr. Bates was supported in part by NICHD/T32 HD060550 and NHLBI/T32 HL07915 grant funding. Dr. Metlay was supported by a Mid‐Career Investigator Award in Patient Oriented Research (K24‐AI073957). The authors report no conflicts of interest.
- , . The published literature on handoffs in hospitals: deficiencies identified in an extensive review. Quality and Safety in Health Care. 2010;19(6):493–497. doi: 10.1136/qshc.2009.033480.
- . Communication failures in patient sign‐out and suggestions for improvement: a critical incident analysis. Qual Saf Health Care. 2005;14(6):401–407.
- , , , , . Consequences of inadequate sign‐out for patient care. Arch Intern Med. 2008;168(16):1755–1760.
- , , , , , . Nursing handovers: do we really need them? J Nurs Manag. 2004;12(1):37–42.
- , , , et al. Assessing clinical handover between paramedics and the trauma team. Injury. 2010;41(5):460–464.
- , , , , . Answering questions on call: Pediatric resident physicians' use of handoffs and other resources. J Hosp Med. 2013;8(6):328–333.
- , , , , . Managing discontinuity in academic medical centers: strategies for a safe and effective resident sign‐out. J Hosp Med. 2006;1(4):257–266.
- , . Patient handoffs: standardized and reliable measurement tools remain elusive. Jt Comm J Qual Patient Saf. 2010;36(2):52–61.
- , , , , . Improving measurement in clinical handover. Qual Saf Health Care. 2009;18(4):272–276.
- , , , . Adequacy of information transferred at resident sign‐out (inhospital handover of care): a prospective survey. Qual Saf Health Care. 2008;17(1):6–10.
- , , . Standardized Sign‐out reduces intern perception of medical errors on the general internal medicine ward. Teach Learn Med. 2009;21(2):121–126.
- , , , et al. Hand‐off education and evaluation: piloting the observed simulated hand‐off experience (OSHE). J Gen Intern Med. 2009;25(2):129–134.
- , , , , . Assessing the quality of patient handoffs at care transitions. Qual Saf Health Care. 2010;19(6):1–5.
- , , , , . Implementing peer evaluation of handoffs: associations with experience and workload. J Hosp Med. 2013;8(3):132–136.
- , , , et al. Development of a handoff evaluation tool for shift‐to‐shift physician handoffs: the handoff CEX. J Hosp Med. 2013;8(4):191–200.
- , . The effects of patient handoff characteristics on subsequent care: a systematic review and areas for future research. Acad Med. 2012;87(8):1105–1124.
- . Construct validity in organizational behavior. In: Cummings LL, Stawe BM, eds. Research in Organizational Behavior. Vol 2. Greenwich, CT: JAI Press; 1980:3–43.
- , , , , . Development and validation of the medication regimen complexity index. Ann Pharmacother. 2004;38(9):1369–1376.
- , , . A chronic disease score from automated pharmacy data. J Clin Epidemiol. 1992;45(2):197–203.
- , , , , , . Research electronic data capture (REDCap)—a metadata‐driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381.
- . A Wilcoxon‐type test for trend. Stat Med. 1985;4(1):87–90.
- , . The published literature on handoffs in hospitals: deficiencies identified in an extensive review. Quality and Safety in Health Care. 2010;19(6):493–497. doi: 10.1136/qshc.2009.033480.
- . Communication failures in patient sign‐out and suggestions for improvement: a critical incident analysis. Qual Saf Health Care. 2005;14(6):401–407.
- , , , , . Consequences of inadequate sign‐out for patient care. Arch Intern Med. 2008;168(16):1755–1760.
- , , , , , . Nursing handovers: do we really need them? J Nurs Manag. 2004;12(1):37–42.
- , , , et al. Assessing clinical handover between paramedics and the trauma team. Injury. 2010;41(5):460–464.
- , , , , . Answering questions on call: Pediatric resident physicians' use of handoffs and other resources. J Hosp Med. 2013;8(6):328–333.
- , , , , . Managing discontinuity in academic medical centers: strategies for a safe and effective resident sign‐out. J Hosp Med. 2006;1(4):257–266.
- , . Patient handoffs: standardized and reliable measurement tools remain elusive. Jt Comm J Qual Patient Saf. 2010;36(2):52–61.
- , , , , . Improving measurement in clinical handover. Qual Saf Health Care. 2009;18(4):272–276.
- , , , . Adequacy of information transferred at resident sign‐out (inhospital handover of care): a prospective survey. Qual Saf Health Care. 2008;17(1):6–10.
- , , . Standardized Sign‐out reduces intern perception of medical errors on the general internal medicine ward. Teach Learn Med. 2009;21(2):121–126.
- , , , et al. Hand‐off education and evaluation: piloting the observed simulated hand‐off experience (OSHE). J Gen Intern Med. 2009;25(2):129–134.
- , , , , . Assessing the quality of patient handoffs at care transitions. Qual Saf Health Care. 2010;19(6):1–5.
- , , , , . Implementing peer evaluation of handoffs: associations with experience and workload. J Hosp Med. 2013;8(3):132–136.
- , , , et al. Development of a handoff evaluation tool for shift‐to‐shift physician handoffs: the handoff CEX. J Hosp Med. 2013;8(4):191–200.
- , . The effects of patient handoff characteristics on subsequent care: a systematic review and areas for future research. Acad Med. 2012;87(8):1105–1124.
- . Construct validity in organizational behavior. In: Cummings LL, Stawe BM, eds. Research in Organizational Behavior. Vol 2. Greenwich, CT: JAI Press; 1980:3–43.
- , , , , . Development and validation of the medication regimen complexity index. Ann Pharmacother. 2004;38(9):1369–1376.
- , , . A chronic disease score from automated pharmacy data. J Clin Epidemiol. 1992;45(2):197–203.
- , , , , , . Research electronic data capture (REDCap)—a metadata‐driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381.
- . A Wilcoxon‐type test for trend. Stat Med. 1985;4(1):87–90.
© 2014 Society of Hospital Medicine
Percutaneous closure
Editor’s Note: I urge readers unfamiliar with the Perclose Proglide® device to pay special attention to the instructions for use and to follow them carefully. The device is relatively simple to use but it is a complex piece of equipment and so it is also easy to misuse it with dire consequences. I suggest that one at least read the section on "Troubleshooting," since preventing some of these problems can be lifesaving.
The key to successful percutaneous closure is selecting the appropriate site of entry into the common femoral artery (CFA). Using ultrasound (in transverse and longitudinal planes) and fluoroscopy, I gain access at a noncalcified spot 1 cm above the bifurcation of the CFA (Fig. 1). This is immediately confirmed with an oblique angiogram while pulling the 5F sheath to the ipsilateral side (Fig. 2). This small last maneuver allows me to see exactly where the puncture was and confirms that I will be able to use a closure device.
If using a sheath larger than 12F, I would dilate the track and cut any skin bridges within the puncture site using 11 blade. Doing this maneuver at the end of the procedure could result in inadvertently cutting the sutures. The Proglide device is then inserted and the sutures deployed as per the instructions for use.
At the end of the case, the sheath is pulled over a nonstiff wire while pulling on the nonrail (blue end) wire in a coaxial fashion. I can’t stress enough the need to be calm and not to pull too hard on the suture. This can result in the suture breaking or being pulled out of the artery. The knot pusher is then used on each suture sequentially. At this point, I tug on the wire to make sure it is "snug" within the arteriotomy. This signifies adequate closure but I also check briefly to ensure that there is no significant bleeding. Then I can go ahead and remove the wire and slide the knot pusher again.
The final step is to advance the knot pusher over the two sutures and cut the suture just under the skin. There is no need to slide the knot pusher all the way down to cut the suture as this may inadvertently cut the knot. Steristrips and Band-Aid are applied and I reverse the heparin after confirming the status of distal pulses
Dr. Mussa is an assistant professor of surgery at New York University School of Medicine and Langone Medical Center.
Editor’s Note: I urge readers unfamiliar with the Perclose Proglide® device to pay special attention to the instructions for use and to follow them carefully. The device is relatively simple to use but it is a complex piece of equipment and so it is also easy to misuse it with dire consequences. I suggest that one at least read the section on "Troubleshooting," since preventing some of these problems can be lifesaving.
The key to successful percutaneous closure is selecting the appropriate site of entry into the common femoral artery (CFA). Using ultrasound (in transverse and longitudinal planes) and fluoroscopy, I gain access at a noncalcified spot 1 cm above the bifurcation of the CFA (Fig. 1). This is immediately confirmed with an oblique angiogram while pulling the 5F sheath to the ipsilateral side (Fig. 2). This small last maneuver allows me to see exactly where the puncture was and confirms that I will be able to use a closure device.
If using a sheath larger than 12F, I would dilate the track and cut any skin bridges within the puncture site using 11 blade. Doing this maneuver at the end of the procedure could result in inadvertently cutting the sutures. The Proglide device is then inserted and the sutures deployed as per the instructions for use.
At the end of the case, the sheath is pulled over a nonstiff wire while pulling on the nonrail (blue end) wire in a coaxial fashion. I can’t stress enough the need to be calm and not to pull too hard on the suture. This can result in the suture breaking or being pulled out of the artery. The knot pusher is then used on each suture sequentially. At this point, I tug on the wire to make sure it is "snug" within the arteriotomy. This signifies adequate closure but I also check briefly to ensure that there is no significant bleeding. Then I can go ahead and remove the wire and slide the knot pusher again.
The final step is to advance the knot pusher over the two sutures and cut the suture just under the skin. There is no need to slide the knot pusher all the way down to cut the suture as this may inadvertently cut the knot. Steristrips and Band-Aid are applied and I reverse the heparin after confirming the status of distal pulses
Dr. Mussa is an assistant professor of surgery at New York University School of Medicine and Langone Medical Center.
Editor’s Note: I urge readers unfamiliar with the Perclose Proglide® device to pay special attention to the instructions for use and to follow them carefully. The device is relatively simple to use but it is a complex piece of equipment and so it is also easy to misuse it with dire consequences. I suggest that one at least read the section on "Troubleshooting," since preventing some of these problems can be lifesaving.
The key to successful percutaneous closure is selecting the appropriate site of entry into the common femoral artery (CFA). Using ultrasound (in transverse and longitudinal planes) and fluoroscopy, I gain access at a noncalcified spot 1 cm above the bifurcation of the CFA (Fig. 1). This is immediately confirmed with an oblique angiogram while pulling the 5F sheath to the ipsilateral side (Fig. 2). This small last maneuver allows me to see exactly where the puncture was and confirms that I will be able to use a closure device.
If using a sheath larger than 12F, I would dilate the track and cut any skin bridges within the puncture site using 11 blade. Doing this maneuver at the end of the procedure could result in inadvertently cutting the sutures. The Proglide device is then inserted and the sutures deployed as per the instructions for use.
At the end of the case, the sheath is pulled over a nonstiff wire while pulling on the nonrail (blue end) wire in a coaxial fashion. I can’t stress enough the need to be calm and not to pull too hard on the suture. This can result in the suture breaking or being pulled out of the artery. The knot pusher is then used on each suture sequentially. At this point, I tug on the wire to make sure it is "snug" within the arteriotomy. This signifies adequate closure but I also check briefly to ensure that there is no significant bleeding. Then I can go ahead and remove the wire and slide the knot pusher again.
The final step is to advance the knot pusher over the two sutures and cut the suture just under the skin. There is no need to slide the knot pusher all the way down to cut the suture as this may inadvertently cut the knot. Steristrips and Band-Aid are applied and I reverse the heparin after confirming the status of distal pulses
Dr. Mussa is an assistant professor of surgery at New York University School of Medicine and Langone Medical Center.
Predictions for 2014
Are you prepared to manage the infectious disease challenges you’ll be facing in 2014? Here are my Top 5 predictions for what lies ahead in infectious diseases for the next year with pearls to help you in your practice. The first addresses a series of concerns around influenza. Others target diagnoses you might not have encountered or considered in the past. The last will hopefully improve HPV vaccination rates in your practice.
1. Expect an especially busy influenza season and the possibility that you may encounter patients with life-threatening influenza. We’ve already detected influenza in over 1,000 children at my institution, almost all 2009 pandemic H1N1 influenza A viruses, which is consistent with the national data from the Centers for Disease Control and Prevention. We are really just a month into influenza season, and we are seeing a significant number of children admitted to our pediatric intensive care unit with life-threatening disease presentations, and we’ve also seen unusual influenza complications. Talk to your ID colleagues about the potential for intravenous zanamivir in critically ill children who do not respond to oseltamivir. While pulmonary complications of influenza are most common, unusual presentations you may encounter include influenza encephalopathy (altered mental status, seizures, and mutism) and bacterial superinfection (when fever recurs or recrudesces after initial improvement, often 3-5 days into the course, think Staphylococcus aureus or Group A streptococcal disease). The CDC is alerting practitioners to the potential for increased morbidity and mortality in young/middle aged adults so the parents of your patients are at increased risk this year.
• False-negative testing can happen if the sensitivity of the rapid test is low, but a false-negative test can occur if the specimen is collected late in the clinical course. (This is especially true in the adult population in which testing may be negative at just 4-5 days into the course of disease.)
• Recognize that all hospitalized children should be treated with oseltamivir, as well as children who are immunocompromised; have chronic cardiopulmonary conditions, including hemodynamically significant heart disease and asthma; renal disease; metabolic disease, including diabetes; pregnant teens; morbidly obese patients; patients with neuromuscular/neurodevelopmental conditions (especially those with difficulty controlling airway secretions); and children under 2 years of age.
• I predict you may be hearing about oseltamivir shortages, but for now this relates to the sporadic difficulty in finding the oseltamivir suspension, in part, because of the lack of early season availability of this product at retail pharmacies, many of which are just getting in their stock. Prescribe the suspension for children aged younger than 1 year and be explicit about the mL dosage that should be dispensed. For children over 1 year of age, capsules can be opened and placed in pudding for those who cannot swallow capsules. Lexicomp Online offers guidelines for easy use of 30-mg, 45-mg and 75-mg capsules for different weight categories. If the suspension is necessary for an infant and is not available, the drug can be compounded by your pharmacy using capsules. You may find some pharmacies are reluctant to compound, so be prepared to contact your local children’s hospital for help. And keep offering vaccine throughout the season to healthy patients!
2. Most practitioners are aware of the importance of methicillin-resistant S. aureus (MRSA) as a pathogen that causes bacteremia and musculoskeletal and pulmonary disease in otherwise healthy children. I suspect there is less awareness that, in many locales, methicillin-sensitive S. aureus (MSSA) is being seen just as often, if not slightly more often than MRSA, as a bloodstream pathogen. The inclusion of vancomycin (which covers MRSA) with cefepime should be considered for empiric coverage in the otherwise healthy child with suspected sepsis. Cefepime is a fourth-generation cephalosporin with good gram-negative and gram-positive coverage and also has bactericidal activity against MSSA strains. Clindamycin should be considered as an adjunct to vancomycin and cefepime in those with toxin-mediated disease/toxic shock syndrome. Of course, modification of the empiric regimen should follow identification of the specific pathogen and the site(s) of infection.
3. E. coli remains the most common cause of urinary tract infections in children, but infections caused by multiple drug resistant (MDR) Escherichia coli strains are increasingly being seen. Consider infection caused by extended spectrum beta-lactamase–producing organisms in children with underlying renal anomalies, especially if they have been previously exposed to third-generation cephalosporins. Most strains are also resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides as well as to non–carbapenem beta-lactams. Speaking of antibiotic resistance, look for many hospital microbiology laboratories to begin using advanced molecular detection methodology to more quickly identify bacterial and fungal isolates; such methods could reduce the time of identification from over 24 hours with conventional techniques to less than one hour. The use of newer systems to identify microbes and confirm susceptibility testing has the potential to transform care and improve outcomes.
4. Consider the diagnosis of human parechovirus (HPeV) infection in young febrile infants with sepsis/meningitis presentation but negative bacterial cultures. Detection of HPeV by polymerase chain reaction testing in serum or cerebrospinal fluid is diagnostic. Exclusion of herpes simplex virus and enterovirus disease is key, as similar clinical presentations may be seen. HPeV infections are more commonly noted in late spring and early summer in contrast to enteroviral infections, which tend to occur from July to September.
5. The strength of your vaccine recommendation continues to be the most important factor affecting the parental decision to vaccinate a child. Nowhere is this more obvious than with human papillomavirus vaccine (HPV), where practitioners often simply offer the vaccine rather than recommend it. In terms of teenage vaccines, when practitioners recommend Tdap (tetanus, diphtheria, and pertussis vaccine) and meningococcal conjugate vaccine as standard for their patients ("Today your child will receive whooping cough vaccine and the meningitis vaccine."), vaccine uptake is very high. But when it comes to the HPV vaccine, some practitioners feel they first must establish whether the parents are aware of HPV vaccine; then discuss their questions regarding the safety of the vaccine; and finally, explain that the vaccine prevents cancer. Some practitioners offer the option of "thinking about" the vaccine for the next visit, but in such cases, the patient generally leaves without receiving the vaccine. Add HPV vaccine into your standard teen vaccine recommendation and make it a goal to get the first vaccine initiated in all eligible patients. The three-dose HPV vaccine schedule is still recommended, but I predict that simplification of the schedule may occur as early as 2014 in the United States. We’ll keep you posted.
Dr. Jackson is director of the division of infectious disease and associate director of the infectious disease fellowship program at the University of Missouri, Kansas City.
Are you prepared to manage the infectious disease challenges you’ll be facing in 2014? Here are my Top 5 predictions for what lies ahead in infectious diseases for the next year with pearls to help you in your practice. The first addresses a series of concerns around influenza. Others target diagnoses you might not have encountered or considered in the past. The last will hopefully improve HPV vaccination rates in your practice.
1. Expect an especially busy influenza season and the possibility that you may encounter patients with life-threatening influenza. We’ve already detected influenza in over 1,000 children at my institution, almost all 2009 pandemic H1N1 influenza A viruses, which is consistent with the national data from the Centers for Disease Control and Prevention. We are really just a month into influenza season, and we are seeing a significant number of children admitted to our pediatric intensive care unit with life-threatening disease presentations, and we’ve also seen unusual influenza complications. Talk to your ID colleagues about the potential for intravenous zanamivir in critically ill children who do not respond to oseltamivir. While pulmonary complications of influenza are most common, unusual presentations you may encounter include influenza encephalopathy (altered mental status, seizures, and mutism) and bacterial superinfection (when fever recurs or recrudesces after initial improvement, often 3-5 days into the course, think Staphylococcus aureus or Group A streptococcal disease). The CDC is alerting practitioners to the potential for increased morbidity and mortality in young/middle aged adults so the parents of your patients are at increased risk this year.
• False-negative testing can happen if the sensitivity of the rapid test is low, but a false-negative test can occur if the specimen is collected late in the clinical course. (This is especially true in the adult population in which testing may be negative at just 4-5 days into the course of disease.)
• Recognize that all hospitalized children should be treated with oseltamivir, as well as children who are immunocompromised; have chronic cardiopulmonary conditions, including hemodynamically significant heart disease and asthma; renal disease; metabolic disease, including diabetes; pregnant teens; morbidly obese patients; patients with neuromuscular/neurodevelopmental conditions (especially those with difficulty controlling airway secretions); and children under 2 years of age.
• I predict you may be hearing about oseltamivir shortages, but for now this relates to the sporadic difficulty in finding the oseltamivir suspension, in part, because of the lack of early season availability of this product at retail pharmacies, many of which are just getting in their stock. Prescribe the suspension for children aged younger than 1 year and be explicit about the mL dosage that should be dispensed. For children over 1 year of age, capsules can be opened and placed in pudding for those who cannot swallow capsules. Lexicomp Online offers guidelines for easy use of 30-mg, 45-mg and 75-mg capsules for different weight categories. If the suspension is necessary for an infant and is not available, the drug can be compounded by your pharmacy using capsules. You may find some pharmacies are reluctant to compound, so be prepared to contact your local children’s hospital for help. And keep offering vaccine throughout the season to healthy patients!
2. Most practitioners are aware of the importance of methicillin-resistant S. aureus (MRSA) as a pathogen that causes bacteremia and musculoskeletal and pulmonary disease in otherwise healthy children. I suspect there is less awareness that, in many locales, methicillin-sensitive S. aureus (MSSA) is being seen just as often, if not slightly more often than MRSA, as a bloodstream pathogen. The inclusion of vancomycin (which covers MRSA) with cefepime should be considered for empiric coverage in the otherwise healthy child with suspected sepsis. Cefepime is a fourth-generation cephalosporin with good gram-negative and gram-positive coverage and also has bactericidal activity against MSSA strains. Clindamycin should be considered as an adjunct to vancomycin and cefepime in those with toxin-mediated disease/toxic shock syndrome. Of course, modification of the empiric regimen should follow identification of the specific pathogen and the site(s) of infection.
3. E. coli remains the most common cause of urinary tract infections in children, but infections caused by multiple drug resistant (MDR) Escherichia coli strains are increasingly being seen. Consider infection caused by extended spectrum beta-lactamase–producing organisms in children with underlying renal anomalies, especially if they have been previously exposed to third-generation cephalosporins. Most strains are also resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides as well as to non–carbapenem beta-lactams. Speaking of antibiotic resistance, look for many hospital microbiology laboratories to begin using advanced molecular detection methodology to more quickly identify bacterial and fungal isolates; such methods could reduce the time of identification from over 24 hours with conventional techniques to less than one hour. The use of newer systems to identify microbes and confirm susceptibility testing has the potential to transform care and improve outcomes.
4. Consider the diagnosis of human parechovirus (HPeV) infection in young febrile infants with sepsis/meningitis presentation but negative bacterial cultures. Detection of HPeV by polymerase chain reaction testing in serum or cerebrospinal fluid is diagnostic. Exclusion of herpes simplex virus and enterovirus disease is key, as similar clinical presentations may be seen. HPeV infections are more commonly noted in late spring and early summer in contrast to enteroviral infections, which tend to occur from July to September.
5. The strength of your vaccine recommendation continues to be the most important factor affecting the parental decision to vaccinate a child. Nowhere is this more obvious than with human papillomavirus vaccine (HPV), where practitioners often simply offer the vaccine rather than recommend it. In terms of teenage vaccines, when practitioners recommend Tdap (tetanus, diphtheria, and pertussis vaccine) and meningococcal conjugate vaccine as standard for their patients ("Today your child will receive whooping cough vaccine and the meningitis vaccine."), vaccine uptake is very high. But when it comes to the HPV vaccine, some practitioners feel they first must establish whether the parents are aware of HPV vaccine; then discuss their questions regarding the safety of the vaccine; and finally, explain that the vaccine prevents cancer. Some practitioners offer the option of "thinking about" the vaccine for the next visit, but in such cases, the patient generally leaves without receiving the vaccine. Add HPV vaccine into your standard teen vaccine recommendation and make it a goal to get the first vaccine initiated in all eligible patients. The three-dose HPV vaccine schedule is still recommended, but I predict that simplification of the schedule may occur as early as 2014 in the United States. We’ll keep you posted.
Dr. Jackson is director of the division of infectious disease and associate director of the infectious disease fellowship program at the University of Missouri, Kansas City.
Are you prepared to manage the infectious disease challenges you’ll be facing in 2014? Here are my Top 5 predictions for what lies ahead in infectious diseases for the next year with pearls to help you in your practice. The first addresses a series of concerns around influenza. Others target diagnoses you might not have encountered or considered in the past. The last will hopefully improve HPV vaccination rates in your practice.
1. Expect an especially busy influenza season and the possibility that you may encounter patients with life-threatening influenza. We’ve already detected influenza in over 1,000 children at my institution, almost all 2009 pandemic H1N1 influenza A viruses, which is consistent with the national data from the Centers for Disease Control and Prevention. We are really just a month into influenza season, and we are seeing a significant number of children admitted to our pediatric intensive care unit with life-threatening disease presentations, and we’ve also seen unusual influenza complications. Talk to your ID colleagues about the potential for intravenous zanamivir in critically ill children who do not respond to oseltamivir. While pulmonary complications of influenza are most common, unusual presentations you may encounter include influenza encephalopathy (altered mental status, seizures, and mutism) and bacterial superinfection (when fever recurs or recrudesces after initial improvement, often 3-5 days into the course, think Staphylococcus aureus or Group A streptococcal disease). The CDC is alerting practitioners to the potential for increased morbidity and mortality in young/middle aged adults so the parents of your patients are at increased risk this year.
• False-negative testing can happen if the sensitivity of the rapid test is low, but a false-negative test can occur if the specimen is collected late in the clinical course. (This is especially true in the adult population in which testing may be negative at just 4-5 days into the course of disease.)
• Recognize that all hospitalized children should be treated with oseltamivir, as well as children who are immunocompromised; have chronic cardiopulmonary conditions, including hemodynamically significant heart disease and asthma; renal disease; metabolic disease, including diabetes; pregnant teens; morbidly obese patients; patients with neuromuscular/neurodevelopmental conditions (especially those with difficulty controlling airway secretions); and children under 2 years of age.
• I predict you may be hearing about oseltamivir shortages, but for now this relates to the sporadic difficulty in finding the oseltamivir suspension, in part, because of the lack of early season availability of this product at retail pharmacies, many of which are just getting in their stock. Prescribe the suspension for children aged younger than 1 year and be explicit about the mL dosage that should be dispensed. For children over 1 year of age, capsules can be opened and placed in pudding for those who cannot swallow capsules. Lexicomp Online offers guidelines for easy use of 30-mg, 45-mg and 75-mg capsules for different weight categories. If the suspension is necessary for an infant and is not available, the drug can be compounded by your pharmacy using capsules. You may find some pharmacies are reluctant to compound, so be prepared to contact your local children’s hospital for help. And keep offering vaccine throughout the season to healthy patients!
2. Most practitioners are aware of the importance of methicillin-resistant S. aureus (MRSA) as a pathogen that causes bacteremia and musculoskeletal and pulmonary disease in otherwise healthy children. I suspect there is less awareness that, in many locales, methicillin-sensitive S. aureus (MSSA) is being seen just as often, if not slightly more often than MRSA, as a bloodstream pathogen. The inclusion of vancomycin (which covers MRSA) with cefepime should be considered for empiric coverage in the otherwise healthy child with suspected sepsis. Cefepime is a fourth-generation cephalosporin with good gram-negative and gram-positive coverage and also has bactericidal activity against MSSA strains. Clindamycin should be considered as an adjunct to vancomycin and cefepime in those with toxin-mediated disease/toxic shock syndrome. Of course, modification of the empiric regimen should follow identification of the specific pathogen and the site(s) of infection.
3. E. coli remains the most common cause of urinary tract infections in children, but infections caused by multiple drug resistant (MDR) Escherichia coli strains are increasingly being seen. Consider infection caused by extended spectrum beta-lactamase–producing organisms in children with underlying renal anomalies, especially if they have been previously exposed to third-generation cephalosporins. Most strains are also resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides as well as to non–carbapenem beta-lactams. Speaking of antibiotic resistance, look for many hospital microbiology laboratories to begin using advanced molecular detection methodology to more quickly identify bacterial and fungal isolates; such methods could reduce the time of identification from over 24 hours with conventional techniques to less than one hour. The use of newer systems to identify microbes and confirm susceptibility testing has the potential to transform care and improve outcomes.
4. Consider the diagnosis of human parechovirus (HPeV) infection in young febrile infants with sepsis/meningitis presentation but negative bacterial cultures. Detection of HPeV by polymerase chain reaction testing in serum or cerebrospinal fluid is diagnostic. Exclusion of herpes simplex virus and enterovirus disease is key, as similar clinical presentations may be seen. HPeV infections are more commonly noted in late spring and early summer in contrast to enteroviral infections, which tend to occur from July to September.
5. The strength of your vaccine recommendation continues to be the most important factor affecting the parental decision to vaccinate a child. Nowhere is this more obvious than with human papillomavirus vaccine (HPV), where practitioners often simply offer the vaccine rather than recommend it. In terms of teenage vaccines, when practitioners recommend Tdap (tetanus, diphtheria, and pertussis vaccine) and meningococcal conjugate vaccine as standard for their patients ("Today your child will receive whooping cough vaccine and the meningitis vaccine."), vaccine uptake is very high. But when it comes to the HPV vaccine, some practitioners feel they first must establish whether the parents are aware of HPV vaccine; then discuss their questions regarding the safety of the vaccine; and finally, explain that the vaccine prevents cancer. Some practitioners offer the option of "thinking about" the vaccine for the next visit, but in such cases, the patient generally leaves without receiving the vaccine. Add HPV vaccine into your standard teen vaccine recommendation and make it a goal to get the first vaccine initiated in all eligible patients. The three-dose HPV vaccine schedule is still recommended, but I predict that simplification of the schedule may occur as early as 2014 in the United States. We’ll keep you posted.
Dr. Jackson is director of the division of infectious disease and associate director of the infectious disease fellowship program at the University of Missouri, Kansas City.
Random acts of readiness in unpredictable times
My little girl had outgrown most of her Sunday dresses, so I recently took her to the mall down the street in my quiet, award-winning family-friendly city, just miles outside of Baltimore. She stocked up on a few frilly dresses, then played for a while at the indoor playground. On our way out, we stopped and bought frozen yogurt and greeted friends we knew as they walked by – a typical, uneventful day in Columbia, Md.
Just a few days later, a seemingly ordinary young man entered the mall through the same door I had used, and strolled around unnoticed, lost in a sea of eager shoppers. The rest is history. He entered a store, rifle in hand, and shot and killed two young employees, viciously robbing them, and their loved ones of decades of precious hopes, dreams, and memories. This nightmare occurred right around the time my granddaughter arrived at the Columbia Mall to begin her shift at a children’s clothing store. Fortunately, she was not injured, at least not physically.
The week before, I was saddened to learn that a teaching assistant at my alma mater, Purdue University, ruthlessly slaughtered a fellow student.
Then, I learned that a college student a couple of hours away in Pennsylvania was arrested for possession of weapons of mass destruction.
When will the madness end? It won’t. People seem to be getting more cruel and violent with each passing day.
Whether a mall in the suburbs, a marathon, a movie theater, or a university campus, the number of senseless acts of violence are skyrocketing and, one day, some of us may be called upon to provide emergency care, when we least expect it. Sure, we function well in a hospital environment when the code team, anesthesiologist, and surgeon can be summoned in a matter of seconds, but how many of us are prepared to meet the challenges of a catastrophe in our communities, in our schools, and in our social settings?
If faced with a catastrophic situation, our medical instincts would likely kick in, and we would do whatever is needed to help those in need – stabilize the spine or control the bleeding in trauma victims – but what if we are not sure what to do? What if the 911 operators are overwhelmed by terrified callers fearing for their lives?
The Centers for Disease Control maintains an Emergency Operations Center that can assist health care providers with emergency patient care: 770-488-7100. The CDC’s Clinician Outreach Communication Activity (COCA) works to ensure that clinicians have the up-to-date information they need about emerging health threats. It has posted "Emergency Preparedness: Understanding Physicians’ Concerns and Readiness to Respond," a very informative page full of resources to learn about a variety of scenarios and what we can do. (Some COCA information sessions qualify for continuing education credits.)
Local poison control centers may be of benefit in certain emergency situations as well. The National Capital Poison Center help line – 800-222-1222 – is the telephone number for every poison center in the United States.
This time, the chaos was in my backyard. Next month, God forbid, it may be in yours. No one expects unforeseen emergencies to happen, but knowing where to turn may just make a seemingly impossible situation a little more doable.
Dr. Hester is a hospitalist with Baltimore-Washington Medical Center who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.
My little girl had outgrown most of her Sunday dresses, so I recently took her to the mall down the street in my quiet, award-winning family-friendly city, just miles outside of Baltimore. She stocked up on a few frilly dresses, then played for a while at the indoor playground. On our way out, we stopped and bought frozen yogurt and greeted friends we knew as they walked by – a typical, uneventful day in Columbia, Md.
Just a few days later, a seemingly ordinary young man entered the mall through the same door I had used, and strolled around unnoticed, lost in a sea of eager shoppers. The rest is history. He entered a store, rifle in hand, and shot and killed two young employees, viciously robbing them, and their loved ones of decades of precious hopes, dreams, and memories. This nightmare occurred right around the time my granddaughter arrived at the Columbia Mall to begin her shift at a children’s clothing store. Fortunately, she was not injured, at least not physically.
The week before, I was saddened to learn that a teaching assistant at my alma mater, Purdue University, ruthlessly slaughtered a fellow student.
Then, I learned that a college student a couple of hours away in Pennsylvania was arrested for possession of weapons of mass destruction.
When will the madness end? It won’t. People seem to be getting more cruel and violent with each passing day.
Whether a mall in the suburbs, a marathon, a movie theater, or a university campus, the number of senseless acts of violence are skyrocketing and, one day, some of us may be called upon to provide emergency care, when we least expect it. Sure, we function well in a hospital environment when the code team, anesthesiologist, and surgeon can be summoned in a matter of seconds, but how many of us are prepared to meet the challenges of a catastrophe in our communities, in our schools, and in our social settings?
If faced with a catastrophic situation, our medical instincts would likely kick in, and we would do whatever is needed to help those in need – stabilize the spine or control the bleeding in trauma victims – but what if we are not sure what to do? What if the 911 operators are overwhelmed by terrified callers fearing for their lives?
The Centers for Disease Control maintains an Emergency Operations Center that can assist health care providers with emergency patient care: 770-488-7100. The CDC’s Clinician Outreach Communication Activity (COCA) works to ensure that clinicians have the up-to-date information they need about emerging health threats. It has posted "Emergency Preparedness: Understanding Physicians’ Concerns and Readiness to Respond," a very informative page full of resources to learn about a variety of scenarios and what we can do. (Some COCA information sessions qualify for continuing education credits.)
Local poison control centers may be of benefit in certain emergency situations as well. The National Capital Poison Center help line – 800-222-1222 – is the telephone number for every poison center in the United States.
This time, the chaos was in my backyard. Next month, God forbid, it may be in yours. No one expects unforeseen emergencies to happen, but knowing where to turn may just make a seemingly impossible situation a little more doable.
Dr. Hester is a hospitalist with Baltimore-Washington Medical Center who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.
My little girl had outgrown most of her Sunday dresses, so I recently took her to the mall down the street in my quiet, award-winning family-friendly city, just miles outside of Baltimore. She stocked up on a few frilly dresses, then played for a while at the indoor playground. On our way out, we stopped and bought frozen yogurt and greeted friends we knew as they walked by – a typical, uneventful day in Columbia, Md.
Just a few days later, a seemingly ordinary young man entered the mall through the same door I had used, and strolled around unnoticed, lost in a sea of eager shoppers. The rest is history. He entered a store, rifle in hand, and shot and killed two young employees, viciously robbing them, and their loved ones of decades of precious hopes, dreams, and memories. This nightmare occurred right around the time my granddaughter arrived at the Columbia Mall to begin her shift at a children’s clothing store. Fortunately, she was not injured, at least not physically.
The week before, I was saddened to learn that a teaching assistant at my alma mater, Purdue University, ruthlessly slaughtered a fellow student.
Then, I learned that a college student a couple of hours away in Pennsylvania was arrested for possession of weapons of mass destruction.
When will the madness end? It won’t. People seem to be getting more cruel and violent with each passing day.
Whether a mall in the suburbs, a marathon, a movie theater, or a university campus, the number of senseless acts of violence are skyrocketing and, one day, some of us may be called upon to provide emergency care, when we least expect it. Sure, we function well in a hospital environment when the code team, anesthesiologist, and surgeon can be summoned in a matter of seconds, but how many of us are prepared to meet the challenges of a catastrophe in our communities, in our schools, and in our social settings?
If faced with a catastrophic situation, our medical instincts would likely kick in, and we would do whatever is needed to help those in need – stabilize the spine or control the bleeding in trauma victims – but what if we are not sure what to do? What if the 911 operators are overwhelmed by terrified callers fearing for their lives?
The Centers for Disease Control maintains an Emergency Operations Center that can assist health care providers with emergency patient care: 770-488-7100. The CDC’s Clinician Outreach Communication Activity (COCA) works to ensure that clinicians have the up-to-date information they need about emerging health threats. It has posted "Emergency Preparedness: Understanding Physicians’ Concerns and Readiness to Respond," a very informative page full of resources to learn about a variety of scenarios and what we can do. (Some COCA information sessions qualify for continuing education credits.)
Local poison control centers may be of benefit in certain emergency situations as well. The National Capital Poison Center help line – 800-222-1222 – is the telephone number for every poison center in the United States.
This time, the chaos was in my backyard. Next month, God forbid, it may be in yours. No one expects unforeseen emergencies to happen, but knowing where to turn may just make a seemingly impossible situation a little more doable.
Dr. Hester is a hospitalist with Baltimore-Washington Medical Center who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.
Yes, give more patients statins
The question of whether or not to give more healthy patients statin drugs is one of considerable interest to the public and much debate in both the medical community and the lay press.
In Nov. 12, 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) released their long-awaited new guideline on the treatment of blood cholesterol to reduce the risk of adult atherosclerosis.
This guideline, among other recommendations, guided physicians to expand the number of patients being treated with statin drugs. This ACC/AHA guideline was greeted with many objections in both the medical community and the lay press. Most notable was a Nov. 14 New York Times Op Ed by two respected experts, Dr. John Abramson and Dr. Rita Redberg, entitled "Don’t Give More Patients Statins."
Other New York Times articles by Gina Kolata on Nov. 18 and 26 (citing Dr. Paul Ridker, Dr. Nancy Cook, and others) expressed similar reservations about the ACC/AHA guideline recommendation to broaden statin administration. Thus, this guideline and its recommendations are controversial and of great interest and importance to physicians and the public.
The Op Ed by Dr. Abramson and Dr. Redberg makes the case that the recent ACC/AHA cholesterol guideline is incorrect to advocate expansion of statin usage to more patients because such expansion "will benefit the pharmaceutical industry more than anyone else." They state that the guideline’s authors were not "free of conflicts of interest." In addition, they claim that "18% or more" of statin recipients "experience side effects" and that the increase in statin administration will largely be in "healthy people" who do not benefit and who would be better served by an improved diet and lifestyle.
While the latter is true for everyone, Dr. Abramson and Dr. Redberg convey the wrong message. Statins are the miracle drug of our era. They have proven repeatedly and dramatically to lower the disabling and common consequences of arteriosclerosis – most prominently heart attacks, strokes, and deaths in patients at risk. Statins avoid these vascular catastrophes not only by lowering bad blood lipids but also by a number of other beneficial effects that stabilize arterial plaques.
They have minimal side effects, most of which are benign. In several controlled studies, the patients who did not receive statins had an incidence of "side effects" equal to those who received them. Serious side effects are rare and manageable. Moreover, healthy patients are healthy only until they get sick. Many individuals over 40 take a daily aspirin. Statins are far more effective than aspirin in preventing heart attacks and strokes which often occur unexpectedly in previously "healthy people."
Clearly it would be worthwhile for such healthy people to take a daily statin pill with few side effects if it would lower their risk of such vascular catastrophes and premature death. In contrast to what is implied in the Abramson–Redberg Op Ed, these drugs are an easy way for people to live longer and live better, and statins cannot be replaced with a healthy life style and diet – although combining the latter with statins is a good thing.
Lastly, regarding the comments about the pharmaceutical industry benefitting and guideline authors’ conflicts of interest, both are less important than patient benefit, which has been demonstrated dramatically and consistently in many controlled statin trials. Moreover, most statins are now generic so the cost for obtaining these miraculous drugs need not be prohibitive, and the guideline’s authors are experts who are eminently qualified to write them.
More patients should be on statin medication.
Dr. Veith is professor of vascular surgery, Langone New York University Medical Center and The Cleveland Clinic. He is an associate medical editor for VASCULAR SPECIALIST. He has no financial conflicts of interest.
The ideas and opinions expressed in VASCULAR SPECIALIST do not necessarily reflect those of the Society or Publisher.
The question of whether or not to give more healthy patients statin drugs is one of considerable interest to the public and much debate in both the medical community and the lay press.
In Nov. 12, 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) released their long-awaited new guideline on the treatment of blood cholesterol to reduce the risk of adult atherosclerosis.
This guideline, among other recommendations, guided physicians to expand the number of patients being treated with statin drugs. This ACC/AHA guideline was greeted with many objections in both the medical community and the lay press. Most notable was a Nov. 14 New York Times Op Ed by two respected experts, Dr. John Abramson and Dr. Rita Redberg, entitled "Don’t Give More Patients Statins."
Other New York Times articles by Gina Kolata on Nov. 18 and 26 (citing Dr. Paul Ridker, Dr. Nancy Cook, and others) expressed similar reservations about the ACC/AHA guideline recommendation to broaden statin administration. Thus, this guideline and its recommendations are controversial and of great interest and importance to physicians and the public.
The Op Ed by Dr. Abramson and Dr. Redberg makes the case that the recent ACC/AHA cholesterol guideline is incorrect to advocate expansion of statin usage to more patients because such expansion "will benefit the pharmaceutical industry more than anyone else." They state that the guideline’s authors were not "free of conflicts of interest." In addition, they claim that "18% or more" of statin recipients "experience side effects" and that the increase in statin administration will largely be in "healthy people" who do not benefit and who would be better served by an improved diet and lifestyle.
While the latter is true for everyone, Dr. Abramson and Dr. Redberg convey the wrong message. Statins are the miracle drug of our era. They have proven repeatedly and dramatically to lower the disabling and common consequences of arteriosclerosis – most prominently heart attacks, strokes, and deaths in patients at risk. Statins avoid these vascular catastrophes not only by lowering bad blood lipids but also by a number of other beneficial effects that stabilize arterial plaques.
They have minimal side effects, most of which are benign. In several controlled studies, the patients who did not receive statins had an incidence of "side effects" equal to those who received them. Serious side effects are rare and manageable. Moreover, healthy patients are healthy only until they get sick. Many individuals over 40 take a daily aspirin. Statins are far more effective than aspirin in preventing heart attacks and strokes which often occur unexpectedly in previously "healthy people."
Clearly it would be worthwhile for such healthy people to take a daily statin pill with few side effects if it would lower their risk of such vascular catastrophes and premature death. In contrast to what is implied in the Abramson–Redberg Op Ed, these drugs are an easy way for people to live longer and live better, and statins cannot be replaced with a healthy life style and diet – although combining the latter with statins is a good thing.
Lastly, regarding the comments about the pharmaceutical industry benefitting and guideline authors’ conflicts of interest, both are less important than patient benefit, which has been demonstrated dramatically and consistently in many controlled statin trials. Moreover, most statins are now generic so the cost for obtaining these miraculous drugs need not be prohibitive, and the guideline’s authors are experts who are eminently qualified to write them.
More patients should be on statin medication.
Dr. Veith is professor of vascular surgery, Langone New York University Medical Center and The Cleveland Clinic. He is an associate medical editor for VASCULAR SPECIALIST. He has no financial conflicts of interest.
The ideas and opinions expressed in VASCULAR SPECIALIST do not necessarily reflect those of the Society or Publisher.
The question of whether or not to give more healthy patients statin drugs is one of considerable interest to the public and much debate in both the medical community and the lay press.
In Nov. 12, 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) released their long-awaited new guideline on the treatment of blood cholesterol to reduce the risk of adult atherosclerosis.
This guideline, among other recommendations, guided physicians to expand the number of patients being treated with statin drugs. This ACC/AHA guideline was greeted with many objections in both the medical community and the lay press. Most notable was a Nov. 14 New York Times Op Ed by two respected experts, Dr. John Abramson and Dr. Rita Redberg, entitled "Don’t Give More Patients Statins."
Other New York Times articles by Gina Kolata on Nov. 18 and 26 (citing Dr. Paul Ridker, Dr. Nancy Cook, and others) expressed similar reservations about the ACC/AHA guideline recommendation to broaden statin administration. Thus, this guideline and its recommendations are controversial and of great interest and importance to physicians and the public.
The Op Ed by Dr. Abramson and Dr. Redberg makes the case that the recent ACC/AHA cholesterol guideline is incorrect to advocate expansion of statin usage to more patients because such expansion "will benefit the pharmaceutical industry more than anyone else." They state that the guideline’s authors were not "free of conflicts of interest." In addition, they claim that "18% or more" of statin recipients "experience side effects" and that the increase in statin administration will largely be in "healthy people" who do not benefit and who would be better served by an improved diet and lifestyle.
While the latter is true for everyone, Dr. Abramson and Dr. Redberg convey the wrong message. Statins are the miracle drug of our era. They have proven repeatedly and dramatically to lower the disabling and common consequences of arteriosclerosis – most prominently heart attacks, strokes, and deaths in patients at risk. Statins avoid these vascular catastrophes not only by lowering bad blood lipids but also by a number of other beneficial effects that stabilize arterial plaques.
They have minimal side effects, most of which are benign. In several controlled studies, the patients who did not receive statins had an incidence of "side effects" equal to those who received them. Serious side effects are rare and manageable. Moreover, healthy patients are healthy only until they get sick. Many individuals over 40 take a daily aspirin. Statins are far more effective than aspirin in preventing heart attacks and strokes which often occur unexpectedly in previously "healthy people."
Clearly it would be worthwhile for such healthy people to take a daily statin pill with few side effects if it would lower their risk of such vascular catastrophes and premature death. In contrast to what is implied in the Abramson–Redberg Op Ed, these drugs are an easy way for people to live longer and live better, and statins cannot be replaced with a healthy life style and diet – although combining the latter with statins is a good thing.
Lastly, regarding the comments about the pharmaceutical industry benefitting and guideline authors’ conflicts of interest, both are less important than patient benefit, which has been demonstrated dramatically and consistently in many controlled statin trials. Moreover, most statins are now generic so the cost for obtaining these miraculous drugs need not be prohibitive, and the guideline’s authors are experts who are eminently qualified to write them.
More patients should be on statin medication.
Dr. Veith is professor of vascular surgery, Langone New York University Medical Center and The Cleveland Clinic. He is an associate medical editor for VASCULAR SPECIALIST. He has no financial conflicts of interest.
The ideas and opinions expressed in VASCULAR SPECIALIST do not necessarily reflect those of the Society or Publisher.
Hyperprolactinemia: Causes and Treatments
A 31-year-old woman is referred by her Ob-Gyn for elevated prolactin. She initially presented with a three-month history of amenorrhea, a negative home pregnancy test, and 100% compliance with condom use. She denies hirsutism and acne but admits to thin milky nipple discharge upon squeezing (but not spontaneous).
Two weeks ago, her Ob-Gyn ordered labs; results were negative for serum beta human chorionic gonadotropin and within normal ranges for thyroid-stimulating hormone (TSH), luteinizing hormone, follicle-stimulating hormone, estradiol, free and total testosterone, dehydroepiandrosterone sulfate (DHEAs), complete chemistry panel, and complete blood count. Her serum prolactin level was 110 ng/mL (normal, 3 to 27 ng/mL).
Q: How is prolactin physiologically regulated?
The primary role of prolactin, which is produced by lactotroph cells in the anterior pituitary gland, is to stimulate lactation and breast development. Prolactin is regulated by dopamine (also known as prolactin inhibitory hormone), which is secreted from the hypothalamus via an inhibitory pathway unique to the hypothalamus-pituitary hormone system. Dopamine essentially suppresses prolactin.
Other hormones can have a stimulatory effect on the anterior pituitary gland and thus increase prolactin levels. Estrogen can induce lactotroph hyperplasia and elevated prolactin; however, this is only clinically relevant in the context of estrogen surge during pregnancy. (Estrogen therapy, such as oral contraception or hormone replacement therapy, on the other hand, is targeted to “normal” estrogen levels.) Thyrotropin-releasing hormone (TRH) from the hypothalamus also stimulates the anterior pituitary gland, so patients with inadequately treated or untreated primary hypothyroidism will have mildly elevated prolactin.
Neurogenic stimuli of the chest wall, through nipple suckling or varicella zoster infection (shingles), can also increase prolactin secretion. And since prolactin is eliminated by the liver (75%) and the kidney (25%), significant liver disease and/or renal insufficiency can raise prolactin levels, due to decreased clearance.
What are the possible etiologies for elevated prolactin? See answer on the next page...
Q: What are the possible etiologies for elevated prolactin?
The causes of hyperprolactinemia fall into three categories: physiologic, pharmacologic, and pathologic.2 The table provides examples from each category.
A nonsecretory pituitary adenoma or any lesion in the brain that would disrupt the hypophyseal stalk may interfere with dopamine’s inhibitory control and thereby increase prolactin. This is called the stalk effect. It is important to note that not all MRI-proven pituitary adenomas are prolactin secreting, even in the presence of hyperprolactinemia. According to an autopsy series, about 12% of the general population had pituitary microadenoma.3
There is rough correlation between prolactinoma size and level of prolactin. Large nonsecretory pituitary adenomas have prolactin levels less than 150 ng/mL. Microprolactinomas (< 1 cm) are usually in the range of 100 to 250 ng/mL, while macroprolactinomas (> 1 cm) are generally
≥ 250 ng/mL. If the tumor is very large and invades the cavernous sinus, prolactin can measure in the 1,000s.3
Polycystic ovarian syndrome (PCOS) is a common disorder affecting women of reproductive age and the most common cause of underlying ovulatory problems. Patients with PCOS can have mildly elevated prolactin; the exact mechanism of hyperprolactinemia in PCOS is unknown. One theory is that constant high levels of estrogen experienced in PCOS would stimulate prolactin production. It is important to rule out other causes of hyperprolactinemia before making the diagnosis of PCOS.
What is the clinical significance of elevated prolactin? Why do we have to work up and treat it? See answer on the next page...
Q: What is the clinical significance of elevated prolactin? Why do we have to work up and treat it?
By physiologic mechanisms not completely understood, hyperprolactinemia can interrupt the gonadal axis, leading to hypogonadism. In women, it can cause irregular menstrual cycles, oligomenorrhea, amenorrhea, and infertility. In men, it can lower testosterone levels. Long-term effects include declining bone mineral density due to insufficient estrogen in women or testosterone in men.
With macroadenoma, the size of the tumor can have a mass effect such as headache and visual defect by compressing the optic chiasm (bitemporal hemianopsia), which may lead to permanent vision loss if left untreated. Referral to an ophthalmologist may be necessary for formal visual field examination.
How is hyperprolactinemia treated? See answer on the next page...
Q: How is hyperprolactinemia treated?
There are three options for treatment: medication, surgery, and radiation.
Dopamine agonists (bromocriptine, cabergoline) are effective in normalizing prolactin and reducing the size of the tumor in the majority of cases. However, some patients may require long-term treatment. Bromocriptine has been used since the late 1970s, but, due to better tolerance and less frequent dosing, cabergoline is the preferred agent.3
Transsphenoidal surgery is indicated for patients who are intolerant to medication, who have a medication-resistant tumor or significant mass effect, or who prefer definitive treatment. Women of childbearing age with a macroadenoma might consider surgery due to the risk for tumor expansion during pregnancy (estrogen effect) and risk for pituitary apoplexy (hemorrhage or infarct of the pituitary gland). Surgical risk is usually low with a neurosurgeon who has extensive experience.
Radiation can be considered for large tumors that are resistant to medication. It can be used as adjunctive therapy to surgery, since reducing the size of the tumor can make the surgical field smaller. In some medication-resistant tumors, radiation can raise sensitivity to medication.
What does follow-up entail? See next page for answer...
Q: What does follow-up entail?
Once medication is initiated or dosage is adjusted, have the patient follow up in one month and recheck the prolactin level to assess responsiveness to medication (as well as medication adherence). When a therapeutic prolactin level is achieved, recheck the prolactin and have the patient follow up at three and six months and then every six months thereafter.3
MRI of the pituitary gland should be performed at baseline, then in six months to assess tumor response to medication, and then at 12 and 24 months.3 If tumor regression has stabilized or if the tumor has shrunk to a nondetectable size, consider discontinuing the dopamine agonist. If medication is discontinued, recheck prolactin every three months for the first year; if it remains in normal reference range, simply check serum prolactin annually.3
See next page for summary.
See next page for references.
REFERENCES
1. Jameson JL. Harrison’s Endocrinology. 18th ed. China: McGraw-Hill; 2010.
2. Gardner D, Shoback D. Greenspan’s Basic & Clinical Endocrinology. 9th ed. China: McGraw-Hill; 2011.
3. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(2):273-288.
A 31-year-old woman is referred by her Ob-Gyn for elevated prolactin. She initially presented with a three-month history of amenorrhea, a negative home pregnancy test, and 100% compliance with condom use. She denies hirsutism and acne but admits to thin milky nipple discharge upon squeezing (but not spontaneous).
Two weeks ago, her Ob-Gyn ordered labs; results were negative for serum beta human chorionic gonadotropin and within normal ranges for thyroid-stimulating hormone (TSH), luteinizing hormone, follicle-stimulating hormone, estradiol, free and total testosterone, dehydroepiandrosterone sulfate (DHEAs), complete chemistry panel, and complete blood count. Her serum prolactin level was 110 ng/mL (normal, 3 to 27 ng/mL).
Q: How is prolactin physiologically regulated?
The primary role of prolactin, which is produced by lactotroph cells in the anterior pituitary gland, is to stimulate lactation and breast development. Prolactin is regulated by dopamine (also known as prolactin inhibitory hormone), which is secreted from the hypothalamus via an inhibitory pathway unique to the hypothalamus-pituitary hormone system. Dopamine essentially suppresses prolactin.
Other hormones can have a stimulatory effect on the anterior pituitary gland and thus increase prolactin levels. Estrogen can induce lactotroph hyperplasia and elevated prolactin; however, this is only clinically relevant in the context of estrogen surge during pregnancy. (Estrogen therapy, such as oral contraception or hormone replacement therapy, on the other hand, is targeted to “normal” estrogen levels.) Thyrotropin-releasing hormone (TRH) from the hypothalamus also stimulates the anterior pituitary gland, so patients with inadequately treated or untreated primary hypothyroidism will have mildly elevated prolactin.
Neurogenic stimuli of the chest wall, through nipple suckling or varicella zoster infection (shingles), can also increase prolactin secretion. And since prolactin is eliminated by the liver (75%) and the kidney (25%), significant liver disease and/or renal insufficiency can raise prolactin levels, due to decreased clearance.
What are the possible etiologies for elevated prolactin? See answer on the next page...
Q: What are the possible etiologies for elevated prolactin?
The causes of hyperprolactinemia fall into three categories: physiologic, pharmacologic, and pathologic.2 The table provides examples from each category.
A nonsecretory pituitary adenoma or any lesion in the brain that would disrupt the hypophyseal stalk may interfere with dopamine’s inhibitory control and thereby increase prolactin. This is called the stalk effect. It is important to note that not all MRI-proven pituitary adenomas are prolactin secreting, even in the presence of hyperprolactinemia. According to an autopsy series, about 12% of the general population had pituitary microadenoma.3
There is rough correlation between prolactinoma size and level of prolactin. Large nonsecretory pituitary adenomas have prolactin levels less than 150 ng/mL. Microprolactinomas (< 1 cm) are usually in the range of 100 to 250 ng/mL, while macroprolactinomas (> 1 cm) are generally
≥ 250 ng/mL. If the tumor is very large and invades the cavernous sinus, prolactin can measure in the 1,000s.3
Polycystic ovarian syndrome (PCOS) is a common disorder affecting women of reproductive age and the most common cause of underlying ovulatory problems. Patients with PCOS can have mildly elevated prolactin; the exact mechanism of hyperprolactinemia in PCOS is unknown. One theory is that constant high levels of estrogen experienced in PCOS would stimulate prolactin production. It is important to rule out other causes of hyperprolactinemia before making the diagnosis of PCOS.
What is the clinical significance of elevated prolactin? Why do we have to work up and treat it? See answer on the next page...
Q: What is the clinical significance of elevated prolactin? Why do we have to work up and treat it?
By physiologic mechanisms not completely understood, hyperprolactinemia can interrupt the gonadal axis, leading to hypogonadism. In women, it can cause irregular menstrual cycles, oligomenorrhea, amenorrhea, and infertility. In men, it can lower testosterone levels. Long-term effects include declining bone mineral density due to insufficient estrogen in women or testosterone in men.
With macroadenoma, the size of the tumor can have a mass effect such as headache and visual defect by compressing the optic chiasm (bitemporal hemianopsia), which may lead to permanent vision loss if left untreated. Referral to an ophthalmologist may be necessary for formal visual field examination.
How is hyperprolactinemia treated? See answer on the next page...
Q: How is hyperprolactinemia treated?
There are three options for treatment: medication, surgery, and radiation.
Dopamine agonists (bromocriptine, cabergoline) are effective in normalizing prolactin and reducing the size of the tumor in the majority of cases. However, some patients may require long-term treatment. Bromocriptine has been used since the late 1970s, but, due to better tolerance and less frequent dosing, cabergoline is the preferred agent.3
Transsphenoidal surgery is indicated for patients who are intolerant to medication, who have a medication-resistant tumor or significant mass effect, or who prefer definitive treatment. Women of childbearing age with a macroadenoma might consider surgery due to the risk for tumor expansion during pregnancy (estrogen effect) and risk for pituitary apoplexy (hemorrhage or infarct of the pituitary gland). Surgical risk is usually low with a neurosurgeon who has extensive experience.
Radiation can be considered for large tumors that are resistant to medication. It can be used as adjunctive therapy to surgery, since reducing the size of the tumor can make the surgical field smaller. In some medication-resistant tumors, radiation can raise sensitivity to medication.
What does follow-up entail? See next page for answer...
Q: What does follow-up entail?
Once medication is initiated or dosage is adjusted, have the patient follow up in one month and recheck the prolactin level to assess responsiveness to medication (as well as medication adherence). When a therapeutic prolactin level is achieved, recheck the prolactin and have the patient follow up at three and six months and then every six months thereafter.3
MRI of the pituitary gland should be performed at baseline, then in six months to assess tumor response to medication, and then at 12 and 24 months.3 If tumor regression has stabilized or if the tumor has shrunk to a nondetectable size, consider discontinuing the dopamine agonist. If medication is discontinued, recheck prolactin every three months for the first year; if it remains in normal reference range, simply check serum prolactin annually.3
See next page for summary.
See next page for references.
REFERENCES
1. Jameson JL. Harrison’s Endocrinology. 18th ed. China: McGraw-Hill; 2010.
2. Gardner D, Shoback D. Greenspan’s Basic & Clinical Endocrinology. 9th ed. China: McGraw-Hill; 2011.
3. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(2):273-288.
A 31-year-old woman is referred by her Ob-Gyn for elevated prolactin. She initially presented with a three-month history of amenorrhea, a negative home pregnancy test, and 100% compliance with condom use. She denies hirsutism and acne but admits to thin milky nipple discharge upon squeezing (but not spontaneous).
Two weeks ago, her Ob-Gyn ordered labs; results were negative for serum beta human chorionic gonadotropin and within normal ranges for thyroid-stimulating hormone (TSH), luteinizing hormone, follicle-stimulating hormone, estradiol, free and total testosterone, dehydroepiandrosterone sulfate (DHEAs), complete chemistry panel, and complete blood count. Her serum prolactin level was 110 ng/mL (normal, 3 to 27 ng/mL).
Q: How is prolactin physiologically regulated?
The primary role of prolactin, which is produced by lactotroph cells in the anterior pituitary gland, is to stimulate lactation and breast development. Prolactin is regulated by dopamine (also known as prolactin inhibitory hormone), which is secreted from the hypothalamus via an inhibitory pathway unique to the hypothalamus-pituitary hormone system. Dopamine essentially suppresses prolactin.
Other hormones can have a stimulatory effect on the anterior pituitary gland and thus increase prolactin levels. Estrogen can induce lactotroph hyperplasia and elevated prolactin; however, this is only clinically relevant in the context of estrogen surge during pregnancy. (Estrogen therapy, such as oral contraception or hormone replacement therapy, on the other hand, is targeted to “normal” estrogen levels.) Thyrotropin-releasing hormone (TRH) from the hypothalamus also stimulates the anterior pituitary gland, so patients with inadequately treated or untreated primary hypothyroidism will have mildly elevated prolactin.
Neurogenic stimuli of the chest wall, through nipple suckling or varicella zoster infection (shingles), can also increase prolactin secretion. And since prolactin is eliminated by the liver (75%) and the kidney (25%), significant liver disease and/or renal insufficiency can raise prolactin levels, due to decreased clearance.
What are the possible etiologies for elevated prolactin? See answer on the next page...
Q: What are the possible etiologies for elevated prolactin?
The causes of hyperprolactinemia fall into three categories: physiologic, pharmacologic, and pathologic.2 The table provides examples from each category.
A nonsecretory pituitary adenoma or any lesion in the brain that would disrupt the hypophyseal stalk may interfere with dopamine’s inhibitory control and thereby increase prolactin. This is called the stalk effect. It is important to note that not all MRI-proven pituitary adenomas are prolactin secreting, even in the presence of hyperprolactinemia. According to an autopsy series, about 12% of the general population had pituitary microadenoma.3
There is rough correlation between prolactinoma size and level of prolactin. Large nonsecretory pituitary adenomas have prolactin levels less than 150 ng/mL. Microprolactinomas (< 1 cm) are usually in the range of 100 to 250 ng/mL, while macroprolactinomas (> 1 cm) are generally
≥ 250 ng/mL. If the tumor is very large and invades the cavernous sinus, prolactin can measure in the 1,000s.3
Polycystic ovarian syndrome (PCOS) is a common disorder affecting women of reproductive age and the most common cause of underlying ovulatory problems. Patients with PCOS can have mildly elevated prolactin; the exact mechanism of hyperprolactinemia in PCOS is unknown. One theory is that constant high levels of estrogen experienced in PCOS would stimulate prolactin production. It is important to rule out other causes of hyperprolactinemia before making the diagnosis of PCOS.
What is the clinical significance of elevated prolactin? Why do we have to work up and treat it? See answer on the next page...
Q: What is the clinical significance of elevated prolactin? Why do we have to work up and treat it?
By physiologic mechanisms not completely understood, hyperprolactinemia can interrupt the gonadal axis, leading to hypogonadism. In women, it can cause irregular menstrual cycles, oligomenorrhea, amenorrhea, and infertility. In men, it can lower testosterone levels. Long-term effects include declining bone mineral density due to insufficient estrogen in women or testosterone in men.
With macroadenoma, the size of the tumor can have a mass effect such as headache and visual defect by compressing the optic chiasm (bitemporal hemianopsia), which may lead to permanent vision loss if left untreated. Referral to an ophthalmologist may be necessary for formal visual field examination.
How is hyperprolactinemia treated? See answer on the next page...
Q: How is hyperprolactinemia treated?
There are three options for treatment: medication, surgery, and radiation.
Dopamine agonists (bromocriptine, cabergoline) are effective in normalizing prolactin and reducing the size of the tumor in the majority of cases. However, some patients may require long-term treatment. Bromocriptine has been used since the late 1970s, but, due to better tolerance and less frequent dosing, cabergoline is the preferred agent.3
Transsphenoidal surgery is indicated for patients who are intolerant to medication, who have a medication-resistant tumor or significant mass effect, or who prefer definitive treatment. Women of childbearing age with a macroadenoma might consider surgery due to the risk for tumor expansion during pregnancy (estrogen effect) and risk for pituitary apoplexy (hemorrhage or infarct of the pituitary gland). Surgical risk is usually low with a neurosurgeon who has extensive experience.
Radiation can be considered for large tumors that are resistant to medication. It can be used as adjunctive therapy to surgery, since reducing the size of the tumor can make the surgical field smaller. In some medication-resistant tumors, radiation can raise sensitivity to medication.
What does follow-up entail? See next page for answer...
Q: What does follow-up entail?
Once medication is initiated or dosage is adjusted, have the patient follow up in one month and recheck the prolactin level to assess responsiveness to medication (as well as medication adherence). When a therapeutic prolactin level is achieved, recheck the prolactin and have the patient follow up at three and six months and then every six months thereafter.3
MRI of the pituitary gland should be performed at baseline, then in six months to assess tumor response to medication, and then at 12 and 24 months.3 If tumor regression has stabilized or if the tumor has shrunk to a nondetectable size, consider discontinuing the dopamine agonist. If medication is discontinued, recheck prolactin every three months for the first year; if it remains in normal reference range, simply check serum prolactin annually.3
See next page for summary.
See next page for references.
REFERENCES
1. Jameson JL. Harrison’s Endocrinology. 18th ed. China: McGraw-Hill; 2010.
2. Gardner D, Shoback D. Greenspan’s Basic & Clinical Endocrinology. 9th ed. China: McGraw-Hill; 2011.
3. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(2):273-288.
What Caused Patient’s Palpitations?
ANSWER
This ECG shows atrial flutter with 2:1 atrioventricular conduction. Additionally, ST depressions are seen in the anterior leads.
Typical sinus node P waves are absent, and atrial conduction at a rate of 310 beats/min is indicated by the sawtooth pattern in leads II and aVF. The ventricular rate is half that of the atrial rate (hence the 2:1 ratio). The ST depressions seen in the anterior leads, thought to be rate related, resolved upon cardioversion to terminate the atrial flutter.
Atrial flutter is uncommon in patients with structurally normal hearts and occurs far less frequently than atrial fibrillation. The etiology of this man’s arrhythmia may be due to pericarditis, based on his history and physical examination.
ANSWER
This ECG shows atrial flutter with 2:1 atrioventricular conduction. Additionally, ST depressions are seen in the anterior leads.
Typical sinus node P waves are absent, and atrial conduction at a rate of 310 beats/min is indicated by the sawtooth pattern in leads II and aVF. The ventricular rate is half that of the atrial rate (hence the 2:1 ratio). The ST depressions seen in the anterior leads, thought to be rate related, resolved upon cardioversion to terminate the atrial flutter.
Atrial flutter is uncommon in patients with structurally normal hearts and occurs far less frequently than atrial fibrillation. The etiology of this man’s arrhythmia may be due to pericarditis, based on his history and physical examination.
ANSWER
This ECG shows atrial flutter with 2:1 atrioventricular conduction. Additionally, ST depressions are seen in the anterior leads.
Typical sinus node P waves are absent, and atrial conduction at a rate of 310 beats/min is indicated by the sawtooth pattern in leads II and aVF. The ventricular rate is half that of the atrial rate (hence the 2:1 ratio). The ST depressions seen in the anterior leads, thought to be rate related, resolved upon cardioversion to terminate the atrial flutter.
Atrial flutter is uncommon in patients with structurally normal hearts and occurs far less frequently than atrial fibrillation. The etiology of this man’s arrhythmia may be due to pericarditis, based on his history and physical examination.
A 52-year-old man developed acute-onset palpitations, shortness of breath, and lightheadedness while sitting at his desk at work. He noticed his heart rate was rapid and asked a coworker to take his pulse for confirmation. He did not experience chest pain, syncope, or near syncope, but if he stood up and tried to walk, he very quickly became fatigued. His coworker tried to call 911; however, the patient asked to be driven to the urgent care center six blocks from their office instead. The patient’s heart rate and symptoms did not change en route. There is no previous history of heart disease. Although the patient works in an office, he is very active. He played hockey in high school and college and continues to play in an amateur league as well as coaching a youth group at the local ice rink. He is also an active member of a local bicycling club and recently completed a 150-mile recreational ride. He has no history of hypertension, diabetes, or pulmonary disease. Surgical history is remarkable for a medial meniscus repair of his right knee and a laparoscopic cholecystectomy, both performed more than 10 years ago. He works as a certified public accountant, does not smoke, and drinks one or two glasses of wine in the evening with meals. He is married and has two adult children. He denies using recreational drugs or herbal medicines. The only medication he uses is ibuprofen as needed for musculoskeletal aches and pains associated with his active lifestyle. He has no known drug allergies, and his immunizations are current. The review of systems is positive for a recent viral upper respiratory illness. He reports having vague, nonspecific substernal chest discomfort, but no pain, at the time of his illness. Symptoms have resolved. There are no other complaints. On arrival, the patient appears anxious and in mild distress, but without pain. Vital signs include a heart rate of 160 beats/min; blood pressure, 100/64 mm Hg; respiratory rate, 18 breaths/min-1; and temperature, 98.4°F. The HEENT exam is unremarkable except for corrective lenses. The chest is clear in all lung fields. There is no jugular venous distention, and carotid upstrokes are brisk. The cardiac exam reveals a regular rhythm at a rate of 150 beats/min with no murmurs or gallops; however, a rub is noted. The abdomen is soft and nontender with no organomegaly. Well-healed scars from his laparoscopic ports are present. The lower extremities show no evidence of edema. Peripheral pulses are strong and equal in both upper and lower extremities, and the neurologic exam is normal. Laboratory studies including a metabolic panel, complete blood count, and cardiac enzymes all yield normal results. An ECG reveals the following: a ventricular rate of 155 beats/min; PR interval, not measured; QRS duration, 78 ms; QT/QTc interval, 272/437 ms; P axis, unmeasurable; R axis, 34°; and T axis, –50°. What is your interpretation of this ECG?
Man Seeks Treatment for Periodic “Eruptions”
The correct answer is benign familial pemphigus (choice “b”). Also known as Hailey-Hailey disease, this is an unusual autosomally inherited blistering disease.
Benign familial pemphigus (BFP) is often mistaken for bacterial infection, such as pyoderma (choice “a”) or impetigo (choice “c”). Although it can become secondarily infected, its origins are entirely different.
Contact dermatitis (choice “d”) in its more severe forms can present in a similar manner. However, it would have shown entirely different changes (acute inflammation and spongiosis) on biopsy.
See next page for the discussion...
DISCUSSION
In 1939, two dermatologist-brothers in Georgia saw a patient with this previously unreported condition. They uncovered the family history and worked out the histologic basis, which they then described in the literature. They named the condition benign familial pemphigus, but it is now more commonly known as Hailey-Hailey disease in their honor.
Pemphigus vulgaris (PV), a serious blistering disease, was more common and far more feared at the time of the Hailey brothers’ discovery. Nearly 100% of PV patients died from the condition in that pre-steroid, pre-antibiotic era (most from secondary bacterial infection).
Fortunately, BFP is more benign, though it shares some features with PV. Both are said to be Nikolsky-positive, meaning the initial blisters can be extended with digital pressure. But BFP, unlike PV, does not involve deposition of immunoglobulins (IgA in the case of PV), nor is it accompanied by circulating auto-antibodies. BFP patients typically have no systemic symptoms, whereas in those with PV, the oral mucosae are often affected.
Herpes simplex virus, which was the primary care provider’s initial suspected diagnosis, can cause somewhat similar outbreaks, even in this area. However, it was effectively ruled out by the lack of response to treatment and by the biopsy results.
Although BFP is an inherited condition, it demonstrates variable penetrance, as in our case. It is rare enough that diagnosis is almost invariably delayed while other diagnoses are considered and treated. The actual “lesion” of BFP is still debated, but appears to involve the quality and quantity of desmosomes (microscopic structures that act as connecting fibers between layers of tissue) breaking down, often because of heat and friction, eventuating in blistering. This theory is bolstered by considerable research and by the fact that most cases present in intertriginous areas, such as the neck, axillae, and groin. Appearing episodically, it typically begins in the third to fourth decade of life, tending to diminish with age.
Biopsy is often necessary to confirm the diagnosis of BFP, with the sample best taken from perilesional skin to avoid separation of friable sample fragments. Additional specimens can be taken for special handling (Michel’s media) to detect immunoglobulins that might be seen in other blistering diseases.
See next page for treatment...
TREATMENT
BFP can be treated empirically with application of a soothing solution of aluminum acetate, or more specifically with topical corticosteroids (class III to IV) and topical antibiotics (eg, clindamycin 2% solution), plus/minus oral minocycline, which has potent anti-inflammatory as well as antimicrobial effects.
Difficult cases should be referred to dermatology, which has a number of treatments at its disposal. This includes diaminodiphenyl sulfone (dapsone), systemic glucocorticoids, methotrexate, systemic retinoids, and even local injection of botulinum toxin to decrease local hidrosis.
This patient is responding well to a regimen of oral minocycline 100 mg bid, topical clindamycin 2% bid application, and topical tacrolimus.
The correct answer is benign familial pemphigus (choice “b”). Also known as Hailey-Hailey disease, this is an unusual autosomally inherited blistering disease.
Benign familial pemphigus (BFP) is often mistaken for bacterial infection, such as pyoderma (choice “a”) or impetigo (choice “c”). Although it can become secondarily infected, its origins are entirely different.
Contact dermatitis (choice “d”) in its more severe forms can present in a similar manner. However, it would have shown entirely different changes (acute inflammation and spongiosis) on biopsy.
See next page for the discussion...
DISCUSSION
In 1939, two dermatologist-brothers in Georgia saw a patient with this previously unreported condition. They uncovered the family history and worked out the histologic basis, which they then described in the literature. They named the condition benign familial pemphigus, but it is now more commonly known as Hailey-Hailey disease in their honor.
Pemphigus vulgaris (PV), a serious blistering disease, was more common and far more feared at the time of the Hailey brothers’ discovery. Nearly 100% of PV patients died from the condition in that pre-steroid, pre-antibiotic era (most from secondary bacterial infection).
Fortunately, BFP is more benign, though it shares some features with PV. Both are said to be Nikolsky-positive, meaning the initial blisters can be extended with digital pressure. But BFP, unlike PV, does not involve deposition of immunoglobulins (IgA in the case of PV), nor is it accompanied by circulating auto-antibodies. BFP patients typically have no systemic symptoms, whereas in those with PV, the oral mucosae are often affected.
Herpes simplex virus, which was the primary care provider’s initial suspected diagnosis, can cause somewhat similar outbreaks, even in this area. However, it was effectively ruled out by the lack of response to treatment and by the biopsy results.
Although BFP is an inherited condition, it demonstrates variable penetrance, as in our case. It is rare enough that diagnosis is almost invariably delayed while other diagnoses are considered and treated. The actual “lesion” of BFP is still debated, but appears to involve the quality and quantity of desmosomes (microscopic structures that act as connecting fibers between layers of tissue) breaking down, often because of heat and friction, eventuating in blistering. This theory is bolstered by considerable research and by the fact that most cases present in intertriginous areas, such as the neck, axillae, and groin. Appearing episodically, it typically begins in the third to fourth decade of life, tending to diminish with age.
Biopsy is often necessary to confirm the diagnosis of BFP, with the sample best taken from perilesional skin to avoid separation of friable sample fragments. Additional specimens can be taken for special handling (Michel’s media) to detect immunoglobulins that might be seen in other blistering diseases.
See next page for treatment...
TREATMENT
BFP can be treated empirically with application of a soothing solution of aluminum acetate, or more specifically with topical corticosteroids (class III to IV) and topical antibiotics (eg, clindamycin 2% solution), plus/minus oral minocycline, which has potent anti-inflammatory as well as antimicrobial effects.
Difficult cases should be referred to dermatology, which has a number of treatments at its disposal. This includes diaminodiphenyl sulfone (dapsone), systemic glucocorticoids, methotrexate, systemic retinoids, and even local injection of botulinum toxin to decrease local hidrosis.
This patient is responding well to a regimen of oral minocycline 100 mg bid, topical clindamycin 2% bid application, and topical tacrolimus.
The correct answer is benign familial pemphigus (choice “b”). Also known as Hailey-Hailey disease, this is an unusual autosomally inherited blistering disease.
Benign familial pemphigus (BFP) is often mistaken for bacterial infection, such as pyoderma (choice “a”) or impetigo (choice “c”). Although it can become secondarily infected, its origins are entirely different.
Contact dermatitis (choice “d”) in its more severe forms can present in a similar manner. However, it would have shown entirely different changes (acute inflammation and spongiosis) on biopsy.
See next page for the discussion...
DISCUSSION
In 1939, two dermatologist-brothers in Georgia saw a patient with this previously unreported condition. They uncovered the family history and worked out the histologic basis, which they then described in the literature. They named the condition benign familial pemphigus, but it is now more commonly known as Hailey-Hailey disease in their honor.
Pemphigus vulgaris (PV), a serious blistering disease, was more common and far more feared at the time of the Hailey brothers’ discovery. Nearly 100% of PV patients died from the condition in that pre-steroid, pre-antibiotic era (most from secondary bacterial infection).
Fortunately, BFP is more benign, though it shares some features with PV. Both are said to be Nikolsky-positive, meaning the initial blisters can be extended with digital pressure. But BFP, unlike PV, does not involve deposition of immunoglobulins (IgA in the case of PV), nor is it accompanied by circulating auto-antibodies. BFP patients typically have no systemic symptoms, whereas in those with PV, the oral mucosae are often affected.
Herpes simplex virus, which was the primary care provider’s initial suspected diagnosis, can cause somewhat similar outbreaks, even in this area. However, it was effectively ruled out by the lack of response to treatment and by the biopsy results.
Although BFP is an inherited condition, it demonstrates variable penetrance, as in our case. It is rare enough that diagnosis is almost invariably delayed while other diagnoses are considered and treated. The actual “lesion” of BFP is still debated, but appears to involve the quality and quantity of desmosomes (microscopic structures that act as connecting fibers between layers of tissue) breaking down, often because of heat and friction, eventuating in blistering. This theory is bolstered by considerable research and by the fact that most cases present in intertriginous areas, such as the neck, axillae, and groin. Appearing episodically, it typically begins in the third to fourth decade of life, tending to diminish with age.
Biopsy is often necessary to confirm the diagnosis of BFP, with the sample best taken from perilesional skin to avoid separation of friable sample fragments. Additional specimens can be taken for special handling (Michel’s media) to detect immunoglobulins that might be seen in other blistering diseases.
See next page for treatment...
TREATMENT
BFP can be treated empirically with application of a soothing solution of aluminum acetate, or more specifically with topical corticosteroids (class III to IV) and topical antibiotics (eg, clindamycin 2% solution), plus/minus oral minocycline, which has potent anti-inflammatory as well as antimicrobial effects.
Difficult cases should be referred to dermatology, which has a number of treatments at its disposal. This includes diaminodiphenyl sulfone (dapsone), systemic glucocorticoids, methotrexate, systemic retinoids, and even local injection of botulinum toxin to decrease local hidrosis.
This patient is responding well to a regimen of oral minocycline 100 mg bid, topical clindamycin 2% bid application, and topical tacrolimus.
For three months, a 38-year-old man has been trying to resolve an “eruption” on his neck. The rash burns and itches, though only mildly, and produces clear fluid. His primary care provider initially prescribed acyclovir, then valacyclovir; neither helped. Subsequent courses of oral antibiotics (cephalexin 500 mg qid for three weeks, then ciprofloxacin 500 mg bid for two weeks) also had no beneficial effect. There is no family history of similar outbreaks. The patient, however, has had several of these eruptions—on the face as well as the neck—since his 20s. They typically last two to four weeks, then disappear completely for months or years. The eruptions tend to occur in the summer. He denies any history of cold sores and does not recall any premonitory symptoms prior to this eruption. He further denies any history of atopy or immunosuppression. His health is otherwise excellent, and he is taking no prescription medications. The denuded area measures about 8 x 4 cm, from his nuchal scalp down to the C6 area of the posterior neck. Discrete ruptured vesicles are seen on the periphery of the site. A layer of peeling skin, resembling wet toilet tissue, covers the partially denuded central portion, at the base of which is distinctly erythematous underlying raw tissue. There is no erythema surrounding the lesion, and no nodes are palpable in the area. A 4-mm punch biopsy is performed, with a sample taken from the periphery of the lesion and submitted for routine handling. It shows a hyperplastic epithelium, as well as intradermal and suprabasilar acantholysis extending focally into the spinous layer.
Stimulants for kids with ADHD—how to proceed safely
› Complete a thorough, cardiac-focused history and physical examination before starting stimulants for attention deficit hyperactivity disorder (ADHD) in a child or adolescent. C
› Avoid using stimulants in children or adolescents with comorbid conditions associated with sudden cardiac death, including hypertrophic cardiomyopathy, long QT interval syndrome, and preexcitation syndromes such as Wolff-Parkinson-White syndrome. C
› Monitor all children and adolescents who are taking stimulants for tachycardia, hypertension, palpitations, and chest pain. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
CASE › A young patient has been struggling in school. His worried mother, having had several conferences with the child’s teachers, brings him to the family physician (FP), where he is given a diagnosis of attention deficit hyperactivity disorder (ADHD). The FP considers prescribing a stimulant medication, but first plans on conducting a more thorough family history and exam. She also debates the merits of ordering an electrocardiogram (EKG) to screen for conditions that could lead to sudden cardiac death.
If you were caring for this patient, how would you proceed?
That’s a good question, given the debate that has surrounded this subject since the US Food and Drug Administration (FDA) first learned of 25 cases of sudden death that were linked to stimulant medications.1 The majority of the cases, which were reported to the FDA’s Adverse Event Reporting System between 1999 and 2003, involved amphetamines or methylphenidate in patients under the age of 19.1 In 2008, the American Heart Association (AHA) issued a scientific statement advocating that physicians perform a proper family history and physical exam that includes blood pressure (BP) and an EKG before prescribing a stimulant for children and adolescents.2 The inclusion of EKG screening was intended to increase the likelihood of identifying patients with potentially life-threatening conditions that could lead to sudden cardiac death (SCD).2
Not everyone, however, agreed.
Later that year, the American Academy of Pediatrics (AAP) challenged the routine use of EKGs in this screening process, citing a lack of evidence between stimulant use and the induction of potentially lethal arrhythmias.3 And in 2011, the European Guideline Group also concluded that there was no evidence to suggest an incremental benefit for routine EKG assessment of ADHD patients before initiation of medication.4
Underscoring the uncertainty surrounding the subject are the findings of a 2012 survey of 525 randomly selected US pediatricians.5 Nearly a quarter of the respondents expressed concerns over the risk for SCD in children receiving stimulants for ADHD, and a slightly higher number—30%—worried that the risks for legal liability were high enough to warrant cardiac assessment.5
So how should the prudent FP proceed? In this review, we will describe how to thoroughly screen children and adolescents for their risk of SCD before prescribing stimulants for ADHD. We’ll also summarize what the evidence tells us about whether—and when—you should order an EKG. But first, a word about the pharmacology of stimulants.
How stimulants might increase SCD risk
Stimulants have been used to treat ADHD for more than 40 years6 and are a first-line of therapy for children with ADHD. Stimulants increase attention span by releasing dopamine and norepinephrine at synapses in the frontal cortex, brain stem, and midbrain.
The effect on heart rate and BP. In clinical trials with small samples sizes, children and adolescents receiving stimulants to treat ADHD experienced a minimal rise in heart rate and BP. As measured by 24-hour ambulatory BP monitoring, 13 subjects in a double-blind, randomized, placebo/stimulant crossover trial had slightly elevated total diastolic BP (69.7 vs 65.8 mm Hg; P=.02), waking diastolic BP (75.5 vs 72.3 mm Hg; P=.03), and total heart rate (85.5 vs 79.9 beats per minutes [bpm]; P=.004) while receiving stimulants.7 Other investigators noted similar findings among 17 boys ages 7 to 11 years.8
Whether prolonged childhood exposure to stimulants increases the risk for developing hypertension or tachycardia is unknown. A 10-year follow-up study of 579 children between the ages of 7 to 9 years found stimulants had no effect on systolic or diastolic BP.9 Stimulants use did, however, lead to a higher heart rate (84.2±12.4 vs 79.1±12.0 bpm) during treatment.9 No stimulant-related QT interval changes—which some have proposed might explain SCD in ADHD patients—have been reported in pediatric patients.10 Researchers have noted small increases in mean QTc intervals in adults treated with stimulants for ADHD, but none were >480 msec.11
Steps you should always take before prescribing a stimulant
Before prescribing stimulants to children or adolescents with ADHD, complete an in-depth cardiac history and physical examination, as recommended by the AHA and AAP (TABLE),2,3 to identify conditions that increase the likelihood of SCD, such as hypertrophic cardiomyopathy (HCM), long QT interval syndrome (LQTS), and preexcitation syndromes such as Wolff-Parkinson-White syndrome (WPW).
Confirm, for instance, that your patient has a normal heart rate, rhythm, and BP, and no pathological murmurs. In a survey of families with a child or young adult who had sudden cardiac arrest, 72% reported the patient had at least one cardiovascular symptom within 19 to 71 months of SCD, and 27% reported having a family member with a history of SCD before age 50.12 For patients with no such complaints or family history, the news is good. Two large studies found that in the absence of any suspected or overt cardiac disease, children with ADHD who were receiving stimulant therapy had no increased risk of SCD.13,14
What about patients with this common heart problem? Physicians face a dilemma when a stimulant is needed and the patient has a common acyanotic congenital heart lesion, such as a small atrial or ventricular septal defect, which is considered nonlethal. Based on limited data, there is no evidence that the risk of SCD is higher when these patients take stimulants.15
Should you order that EKG—or not?
Currently, the AHA still favors an EKG, though in a correction to its original statement, it adjusted the language to say that EKG could be “useful,” in addition to an in-depth cardiac history and physical examination.16
Opposition to routine EKG screening in these patients stems from the procedure’s extremely low yield and relatively high false positive findings, which may result in higher financial and psychological burdens for patients and families. Thomas et al17 reported that at a single center, the number of EKGs ordered with an indication of “stimulant medication screening” quadrupled during 2009, the year after the AHA published its recommendations. Of 372 patients referred for EKG, 24 (6.4%) had abnormal findings and 18 were referred for further evaluation, but none were found to have cardiac disease. ADHD therapy was delayed in 6 patients because of the EKG.
In a similar evaluation of 1470 ADHD patients ages 21 years and younger, Mahle et al18 noted that 119 patients (8.1%) had an abnormal EKG, 78 of whom (65%) were already receiving stimulants. Five patients had cardiac disease, including 2 who had a preexcitation syndrome. Overall, the positive predictive value was low (4.2%).18 Other research, including a study lead by one of this article’s authors (SKM), has found similar increases in the number of EKGs ordered for patients with ADHD.19
Cost vs benefit. In the Mahle et al18 study described above, the mean cost of EKG screening, including further testing for patients with abnormal initial results, was $58 per child. The mean cost to identify a true-positive result was $17,162.18
In 2012, Leslie et al20 used simulation models to estimate the societal cost of routine EKG screening to prevent SCD in children with ADHD. Their findings: The cost would be high relative to its health benefits—approximately $91,000 to $204,000 per life year saved. Furthermore, these researchers found that ordering an EKG to screen for 3 common cardiac conditions linked to SCD (HCM, WPW, and LQTS) would add <2 days to a patient’s projected life expectancy.20
Our recommendations
We believe stimulants can safely be used in the treatment of children and adolescents with ADHD, given the evidence that suggests a low risk of SCD. That said, it is prudent to avoid prescribing stimulants for children who have an underlying condition that may deteriorate secondary to increased blood pressure or heart rate.
We agree with the current AHA and AAP recommendations that physicians should obtain an in-depth cardiac history and physical examination, with emphasis on screening for cardiac disorders that may put a child at risk for SCD, such as HCM, LQTS, and preexcitation syndromes. For instance, a history of a family member with palpitations should prompt an EKG, which may reveal familial preexcitation syndrome. Similarly, an EKG is in order if you suspect LQTS based on a parent’s description of a family member’s death after hearing a loud noise, such as fireworks.
It often takes active probing to uncover a history of sudden death in the family that a parent may not consider relevant. For example, one of the authors (SKM) cared for a 6-year-old boy who presented with a history of syncope after his hand got caught in a door jam. On further probing, his mother revealed that her father had died at age 30 while he was taking astemizole, an allergy drug known to prolong the QT interval. Subsequent EKGs revealed that both the boy and his mother had LQTS.
For patients already taking stimulants, we recommend monitoring BP and heart rate and ordering an EKG only if the patient exhibits cardiac symptoms or there are concerns based on follow-up history and physical examination. Should a patient develop palpitations while taking a therapeutic dose of stimulants, a detailed history of the onset and duration of symptoms is important. For example, tachycardia that has a gradual onset and occurs with exercise is suggestive of physiological sinus tachycardia. In our judgment, most patients who experience symptoms that suggest sinus tachycardia simply require downward readjustment of their medication or a switch to a nonstimulant.
However, if the patient or family history prompts you to suspect other arrhythmias such as ectopic beats or supraventricular tachycardia, immediate assessment either in an emergency department or in the physician’s office may be required, because obtaining an EKG during symptoms is crucial for the diagnosis. Similarly, unexplained exercise intolerance or the onset of chest pain associated with exercise, dizziness, syncope, seizures, or dyspnea requires immediate cardiovascular assessment.
And finally, whether your patient has just started taking medication for his or her ADHD or has been on the medication for some time, it’s important to periodically reassess the need to continue the stimulant therapy; ADHD symptoms may decrease during mid- to late adolescence and into adulthood.21
CASE › The FP completed a thorough physical exam and found no evidence of any conditions that would increase the likelihood of SCD in the young patient. There was no history of SCD in the boy’s family, either. Based on these findings, the FP opted to forgo an EKG. She prescribed lisdexamfetamine, starting with 20 mg/d (the lowest dose available) and then monitored his course by telephone. Eventually, 30 mg was found to be an effective dose. At a 6-week follow-up visit, the boy’s ADHD symptoms were substantially reduced, without any adverse effects—cardiac or otherwise.
CORRESPONDENCE
Sudhir Ken Mehta, Cleveland Clinic Children’s Hospital, 9500 Euclid Avenue, Cleveland, OH 44111; [email protected]
1. Safety review: Follow up review of AERS search identifying cases of sudden death occurring with drugs used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). US Food and Drug Administration Web site. Available at: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_07_01_safetyreview.pdf. Accessed January 17, 2014.
2. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation. 2008;117:2407-2423.
3. Perrin JM, Friedman RA, Knilans TK; Black Box Working Group; Section on Cardiology and Cardiac Surgery. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics. 2008;122:451-453.
4. Graham J, Banaschewski T, Buitelaar J, et al; European Guidelines Group. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011;20:17-37.
5. Leslie LK, Rodday AM, Saunders TS, et al. Cardiac screening prior to stimulant treatment of ADHD: a survey of US-based pediatricians. Pediatrics. 2012;129:222-230.
6. Conners CK. Symposium: behavior modification by drugs. II. Psychological effects of stimulant drugs in children with minimal brain dysfunction. Pediatrics. 1972;49:702-708.
7. Samuels JA, Franco K, Wan F, et al. Effect of stimulants on 24-h ambulatory blood pressure in children with ADHD: a double-blind, randomized, cross-over trial. Pediatr Nephrol. 2006;21:92-95.
8. Stowe CD, Gardner SF, Gist CC, et al. 24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy. Ann Pharmacother. 2002;36:1142-1149.
9. Vitiello B, Elliott GR, Swanson JM, et al. Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD. Am J Psychiatry. 2012;169:167-177.
10. Hammerness P, Wilens T, Mick E, et al. Cardiovascular effects of longer-term, high-dose OROS methylphenidate in adolescents with attention deficit hyperactivity disorder. J Pediatr. 2009;155:84-89,89.e1.
11. Weisler RH, Biederman J, Spencer TJ, et al. Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr. 2005;10(suppl 20):35-43.
12. Drezner JA, Fudge J, Harmon KG, et al. Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med. 2012;25:408-415.
13. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med. 2011;365:1896-1904.
14. Schelleman H, Bilker WB, Strom BL, et al. Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics. 2011;127:1102-1110.
15. Winterstein AG, Gerhard T, Kubilis P, et al. Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study. BMJ. 2012;345:e4627.
16. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing [published correction appears in Circulation. 2009;120:e55-e59]. Circulation. 2008;117:2407-2423.
17. Thomas PE, Carlo WF, Decker JA, et al. Impact of the American Heart Association scientific statement on screening electrocardiograms and stimulant medications. Arch Pediatr Adolesc Med. 2011;165:166-170.
18. Mahle WT, Hebson C, Strieper MJ. Electrocardiographic screening in children with attention-deficit hyperactivity disorder. Am J Cardiol. 2009;104:1296-1299.
19. Mehta SK, Richards N, Jacobs I. Children and adolescents with attention deficit hyperactivity disorder in a pediatric cardiology office. Cardiol Young. 2010;20(suppl 3):167.
20. Leslie LK, Cohen JT, Newburger JW, et al. Costs and benefits of targeted screening for causes of sudden cardiac death in children and adolescents. Circulation. 2012;125:2621-2629.
21. Mannuzza S, Klein RG, Bessler A, et al. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry. 1998;155:493-488.
› Complete a thorough, cardiac-focused history and physical examination before starting stimulants for attention deficit hyperactivity disorder (ADHD) in a child or adolescent. C
› Avoid using stimulants in children or adolescents with comorbid conditions associated with sudden cardiac death, including hypertrophic cardiomyopathy, long QT interval syndrome, and preexcitation syndromes such as Wolff-Parkinson-White syndrome. C
› Monitor all children and adolescents who are taking stimulants for tachycardia, hypertension, palpitations, and chest pain. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
CASE › A young patient has been struggling in school. His worried mother, having had several conferences with the child’s teachers, brings him to the family physician (FP), where he is given a diagnosis of attention deficit hyperactivity disorder (ADHD). The FP considers prescribing a stimulant medication, but first plans on conducting a more thorough family history and exam. She also debates the merits of ordering an electrocardiogram (EKG) to screen for conditions that could lead to sudden cardiac death.
If you were caring for this patient, how would you proceed?
That’s a good question, given the debate that has surrounded this subject since the US Food and Drug Administration (FDA) first learned of 25 cases of sudden death that were linked to stimulant medications.1 The majority of the cases, which were reported to the FDA’s Adverse Event Reporting System between 1999 and 2003, involved amphetamines or methylphenidate in patients under the age of 19.1 In 2008, the American Heart Association (AHA) issued a scientific statement advocating that physicians perform a proper family history and physical exam that includes blood pressure (BP) and an EKG before prescribing a stimulant for children and adolescents.2 The inclusion of EKG screening was intended to increase the likelihood of identifying patients with potentially life-threatening conditions that could lead to sudden cardiac death (SCD).2
Not everyone, however, agreed.
Later that year, the American Academy of Pediatrics (AAP) challenged the routine use of EKGs in this screening process, citing a lack of evidence between stimulant use and the induction of potentially lethal arrhythmias.3 And in 2011, the European Guideline Group also concluded that there was no evidence to suggest an incremental benefit for routine EKG assessment of ADHD patients before initiation of medication.4
Underscoring the uncertainty surrounding the subject are the findings of a 2012 survey of 525 randomly selected US pediatricians.5 Nearly a quarter of the respondents expressed concerns over the risk for SCD in children receiving stimulants for ADHD, and a slightly higher number—30%—worried that the risks for legal liability were high enough to warrant cardiac assessment.5
So how should the prudent FP proceed? In this review, we will describe how to thoroughly screen children and adolescents for their risk of SCD before prescribing stimulants for ADHD. We’ll also summarize what the evidence tells us about whether—and when—you should order an EKG. But first, a word about the pharmacology of stimulants.
How stimulants might increase SCD risk
Stimulants have been used to treat ADHD for more than 40 years6 and are a first-line of therapy for children with ADHD. Stimulants increase attention span by releasing dopamine and norepinephrine at synapses in the frontal cortex, brain stem, and midbrain.
The effect on heart rate and BP. In clinical trials with small samples sizes, children and adolescents receiving stimulants to treat ADHD experienced a minimal rise in heart rate and BP. As measured by 24-hour ambulatory BP monitoring, 13 subjects in a double-blind, randomized, placebo/stimulant crossover trial had slightly elevated total diastolic BP (69.7 vs 65.8 mm Hg; P=.02), waking diastolic BP (75.5 vs 72.3 mm Hg; P=.03), and total heart rate (85.5 vs 79.9 beats per minutes [bpm]; P=.004) while receiving stimulants.7 Other investigators noted similar findings among 17 boys ages 7 to 11 years.8
Whether prolonged childhood exposure to stimulants increases the risk for developing hypertension or tachycardia is unknown. A 10-year follow-up study of 579 children between the ages of 7 to 9 years found stimulants had no effect on systolic or diastolic BP.9 Stimulants use did, however, lead to a higher heart rate (84.2±12.4 vs 79.1±12.0 bpm) during treatment.9 No stimulant-related QT interval changes—which some have proposed might explain SCD in ADHD patients—have been reported in pediatric patients.10 Researchers have noted small increases in mean QTc intervals in adults treated with stimulants for ADHD, but none were >480 msec.11
Steps you should always take before prescribing a stimulant
Before prescribing stimulants to children or adolescents with ADHD, complete an in-depth cardiac history and physical examination, as recommended by the AHA and AAP (TABLE),2,3 to identify conditions that increase the likelihood of SCD, such as hypertrophic cardiomyopathy (HCM), long QT interval syndrome (LQTS), and preexcitation syndromes such as Wolff-Parkinson-White syndrome (WPW).
Confirm, for instance, that your patient has a normal heart rate, rhythm, and BP, and no pathological murmurs. In a survey of families with a child or young adult who had sudden cardiac arrest, 72% reported the patient had at least one cardiovascular symptom within 19 to 71 months of SCD, and 27% reported having a family member with a history of SCD before age 50.12 For patients with no such complaints or family history, the news is good. Two large studies found that in the absence of any suspected or overt cardiac disease, children with ADHD who were receiving stimulant therapy had no increased risk of SCD.13,14
What about patients with this common heart problem? Physicians face a dilemma when a stimulant is needed and the patient has a common acyanotic congenital heart lesion, such as a small atrial or ventricular septal defect, which is considered nonlethal. Based on limited data, there is no evidence that the risk of SCD is higher when these patients take stimulants.15
Should you order that EKG—or not?
Currently, the AHA still favors an EKG, though in a correction to its original statement, it adjusted the language to say that EKG could be “useful,” in addition to an in-depth cardiac history and physical examination.16
Opposition to routine EKG screening in these patients stems from the procedure’s extremely low yield and relatively high false positive findings, which may result in higher financial and psychological burdens for patients and families. Thomas et al17 reported that at a single center, the number of EKGs ordered with an indication of “stimulant medication screening” quadrupled during 2009, the year after the AHA published its recommendations. Of 372 patients referred for EKG, 24 (6.4%) had abnormal findings and 18 were referred for further evaluation, but none were found to have cardiac disease. ADHD therapy was delayed in 6 patients because of the EKG.
In a similar evaluation of 1470 ADHD patients ages 21 years and younger, Mahle et al18 noted that 119 patients (8.1%) had an abnormal EKG, 78 of whom (65%) were already receiving stimulants. Five patients had cardiac disease, including 2 who had a preexcitation syndrome. Overall, the positive predictive value was low (4.2%).18 Other research, including a study lead by one of this article’s authors (SKM), has found similar increases in the number of EKGs ordered for patients with ADHD.19
Cost vs benefit. In the Mahle et al18 study described above, the mean cost of EKG screening, including further testing for patients with abnormal initial results, was $58 per child. The mean cost to identify a true-positive result was $17,162.18
In 2012, Leslie et al20 used simulation models to estimate the societal cost of routine EKG screening to prevent SCD in children with ADHD. Their findings: The cost would be high relative to its health benefits—approximately $91,000 to $204,000 per life year saved. Furthermore, these researchers found that ordering an EKG to screen for 3 common cardiac conditions linked to SCD (HCM, WPW, and LQTS) would add <2 days to a patient’s projected life expectancy.20
Our recommendations
We believe stimulants can safely be used in the treatment of children and adolescents with ADHD, given the evidence that suggests a low risk of SCD. That said, it is prudent to avoid prescribing stimulants for children who have an underlying condition that may deteriorate secondary to increased blood pressure or heart rate.
We agree with the current AHA and AAP recommendations that physicians should obtain an in-depth cardiac history and physical examination, with emphasis on screening for cardiac disorders that may put a child at risk for SCD, such as HCM, LQTS, and preexcitation syndromes. For instance, a history of a family member with palpitations should prompt an EKG, which may reveal familial preexcitation syndrome. Similarly, an EKG is in order if you suspect LQTS based on a parent’s description of a family member’s death after hearing a loud noise, such as fireworks.
It often takes active probing to uncover a history of sudden death in the family that a parent may not consider relevant. For example, one of the authors (SKM) cared for a 6-year-old boy who presented with a history of syncope after his hand got caught in a door jam. On further probing, his mother revealed that her father had died at age 30 while he was taking astemizole, an allergy drug known to prolong the QT interval. Subsequent EKGs revealed that both the boy and his mother had LQTS.
For patients already taking stimulants, we recommend monitoring BP and heart rate and ordering an EKG only if the patient exhibits cardiac symptoms or there are concerns based on follow-up history and physical examination. Should a patient develop palpitations while taking a therapeutic dose of stimulants, a detailed history of the onset and duration of symptoms is important. For example, tachycardia that has a gradual onset and occurs with exercise is suggestive of physiological sinus tachycardia. In our judgment, most patients who experience symptoms that suggest sinus tachycardia simply require downward readjustment of their medication or a switch to a nonstimulant.
However, if the patient or family history prompts you to suspect other arrhythmias such as ectopic beats or supraventricular tachycardia, immediate assessment either in an emergency department or in the physician’s office may be required, because obtaining an EKG during symptoms is crucial for the diagnosis. Similarly, unexplained exercise intolerance or the onset of chest pain associated with exercise, dizziness, syncope, seizures, or dyspnea requires immediate cardiovascular assessment.
And finally, whether your patient has just started taking medication for his or her ADHD or has been on the medication for some time, it’s important to periodically reassess the need to continue the stimulant therapy; ADHD symptoms may decrease during mid- to late adolescence and into adulthood.21
CASE › The FP completed a thorough physical exam and found no evidence of any conditions that would increase the likelihood of SCD in the young patient. There was no history of SCD in the boy’s family, either. Based on these findings, the FP opted to forgo an EKG. She prescribed lisdexamfetamine, starting with 20 mg/d (the lowest dose available) and then monitored his course by telephone. Eventually, 30 mg was found to be an effective dose. At a 6-week follow-up visit, the boy’s ADHD symptoms were substantially reduced, without any adverse effects—cardiac or otherwise.
CORRESPONDENCE
Sudhir Ken Mehta, Cleveland Clinic Children’s Hospital, 9500 Euclid Avenue, Cleveland, OH 44111; [email protected]
› Complete a thorough, cardiac-focused history and physical examination before starting stimulants for attention deficit hyperactivity disorder (ADHD) in a child or adolescent. C
› Avoid using stimulants in children or adolescents with comorbid conditions associated with sudden cardiac death, including hypertrophic cardiomyopathy, long QT interval syndrome, and preexcitation syndromes such as Wolff-Parkinson-White syndrome. C
› Monitor all children and adolescents who are taking stimulants for tachycardia, hypertension, palpitations, and chest pain. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
CASE › A young patient has been struggling in school. His worried mother, having had several conferences with the child’s teachers, brings him to the family physician (FP), where he is given a diagnosis of attention deficit hyperactivity disorder (ADHD). The FP considers prescribing a stimulant medication, but first plans on conducting a more thorough family history and exam. She also debates the merits of ordering an electrocardiogram (EKG) to screen for conditions that could lead to sudden cardiac death.
If you were caring for this patient, how would you proceed?
That’s a good question, given the debate that has surrounded this subject since the US Food and Drug Administration (FDA) first learned of 25 cases of sudden death that were linked to stimulant medications.1 The majority of the cases, which were reported to the FDA’s Adverse Event Reporting System between 1999 and 2003, involved amphetamines or methylphenidate in patients under the age of 19.1 In 2008, the American Heart Association (AHA) issued a scientific statement advocating that physicians perform a proper family history and physical exam that includes blood pressure (BP) and an EKG before prescribing a stimulant for children and adolescents.2 The inclusion of EKG screening was intended to increase the likelihood of identifying patients with potentially life-threatening conditions that could lead to sudden cardiac death (SCD).2
Not everyone, however, agreed.
Later that year, the American Academy of Pediatrics (AAP) challenged the routine use of EKGs in this screening process, citing a lack of evidence between stimulant use and the induction of potentially lethal arrhythmias.3 And in 2011, the European Guideline Group also concluded that there was no evidence to suggest an incremental benefit for routine EKG assessment of ADHD patients before initiation of medication.4
Underscoring the uncertainty surrounding the subject are the findings of a 2012 survey of 525 randomly selected US pediatricians.5 Nearly a quarter of the respondents expressed concerns over the risk for SCD in children receiving stimulants for ADHD, and a slightly higher number—30%—worried that the risks for legal liability were high enough to warrant cardiac assessment.5
So how should the prudent FP proceed? In this review, we will describe how to thoroughly screen children and adolescents for their risk of SCD before prescribing stimulants for ADHD. We’ll also summarize what the evidence tells us about whether—and when—you should order an EKG. But first, a word about the pharmacology of stimulants.
How stimulants might increase SCD risk
Stimulants have been used to treat ADHD for more than 40 years6 and are a first-line of therapy for children with ADHD. Stimulants increase attention span by releasing dopamine and norepinephrine at synapses in the frontal cortex, brain stem, and midbrain.
The effect on heart rate and BP. In clinical trials with small samples sizes, children and adolescents receiving stimulants to treat ADHD experienced a minimal rise in heart rate and BP. As measured by 24-hour ambulatory BP monitoring, 13 subjects in a double-blind, randomized, placebo/stimulant crossover trial had slightly elevated total diastolic BP (69.7 vs 65.8 mm Hg; P=.02), waking diastolic BP (75.5 vs 72.3 mm Hg; P=.03), and total heart rate (85.5 vs 79.9 beats per minutes [bpm]; P=.004) while receiving stimulants.7 Other investigators noted similar findings among 17 boys ages 7 to 11 years.8
Whether prolonged childhood exposure to stimulants increases the risk for developing hypertension or tachycardia is unknown. A 10-year follow-up study of 579 children between the ages of 7 to 9 years found stimulants had no effect on systolic or diastolic BP.9 Stimulants use did, however, lead to a higher heart rate (84.2±12.4 vs 79.1±12.0 bpm) during treatment.9 No stimulant-related QT interval changes—which some have proposed might explain SCD in ADHD patients—have been reported in pediatric patients.10 Researchers have noted small increases in mean QTc intervals in adults treated with stimulants for ADHD, but none were >480 msec.11
Steps you should always take before prescribing a stimulant
Before prescribing stimulants to children or adolescents with ADHD, complete an in-depth cardiac history and physical examination, as recommended by the AHA and AAP (TABLE),2,3 to identify conditions that increase the likelihood of SCD, such as hypertrophic cardiomyopathy (HCM), long QT interval syndrome (LQTS), and preexcitation syndromes such as Wolff-Parkinson-White syndrome (WPW).
Confirm, for instance, that your patient has a normal heart rate, rhythm, and BP, and no pathological murmurs. In a survey of families with a child or young adult who had sudden cardiac arrest, 72% reported the patient had at least one cardiovascular symptom within 19 to 71 months of SCD, and 27% reported having a family member with a history of SCD before age 50.12 For patients with no such complaints or family history, the news is good. Two large studies found that in the absence of any suspected or overt cardiac disease, children with ADHD who were receiving stimulant therapy had no increased risk of SCD.13,14
What about patients with this common heart problem? Physicians face a dilemma when a stimulant is needed and the patient has a common acyanotic congenital heart lesion, such as a small atrial or ventricular septal defect, which is considered nonlethal. Based on limited data, there is no evidence that the risk of SCD is higher when these patients take stimulants.15
Should you order that EKG—or not?
Currently, the AHA still favors an EKG, though in a correction to its original statement, it adjusted the language to say that EKG could be “useful,” in addition to an in-depth cardiac history and physical examination.16
Opposition to routine EKG screening in these patients stems from the procedure’s extremely low yield and relatively high false positive findings, which may result in higher financial and psychological burdens for patients and families. Thomas et al17 reported that at a single center, the number of EKGs ordered with an indication of “stimulant medication screening” quadrupled during 2009, the year after the AHA published its recommendations. Of 372 patients referred for EKG, 24 (6.4%) had abnormal findings and 18 were referred for further evaluation, but none were found to have cardiac disease. ADHD therapy was delayed in 6 patients because of the EKG.
In a similar evaluation of 1470 ADHD patients ages 21 years and younger, Mahle et al18 noted that 119 patients (8.1%) had an abnormal EKG, 78 of whom (65%) were already receiving stimulants. Five patients had cardiac disease, including 2 who had a preexcitation syndrome. Overall, the positive predictive value was low (4.2%).18 Other research, including a study lead by one of this article’s authors (SKM), has found similar increases in the number of EKGs ordered for patients with ADHD.19
Cost vs benefit. In the Mahle et al18 study described above, the mean cost of EKG screening, including further testing for patients with abnormal initial results, was $58 per child. The mean cost to identify a true-positive result was $17,162.18
In 2012, Leslie et al20 used simulation models to estimate the societal cost of routine EKG screening to prevent SCD in children with ADHD. Their findings: The cost would be high relative to its health benefits—approximately $91,000 to $204,000 per life year saved. Furthermore, these researchers found that ordering an EKG to screen for 3 common cardiac conditions linked to SCD (HCM, WPW, and LQTS) would add <2 days to a patient’s projected life expectancy.20
Our recommendations
We believe stimulants can safely be used in the treatment of children and adolescents with ADHD, given the evidence that suggests a low risk of SCD. That said, it is prudent to avoid prescribing stimulants for children who have an underlying condition that may deteriorate secondary to increased blood pressure or heart rate.
We agree with the current AHA and AAP recommendations that physicians should obtain an in-depth cardiac history and physical examination, with emphasis on screening for cardiac disorders that may put a child at risk for SCD, such as HCM, LQTS, and preexcitation syndromes. For instance, a history of a family member with palpitations should prompt an EKG, which may reveal familial preexcitation syndrome. Similarly, an EKG is in order if you suspect LQTS based on a parent’s description of a family member’s death after hearing a loud noise, such as fireworks.
It often takes active probing to uncover a history of sudden death in the family that a parent may not consider relevant. For example, one of the authors (SKM) cared for a 6-year-old boy who presented with a history of syncope after his hand got caught in a door jam. On further probing, his mother revealed that her father had died at age 30 while he was taking astemizole, an allergy drug known to prolong the QT interval. Subsequent EKGs revealed that both the boy and his mother had LQTS.
For patients already taking stimulants, we recommend monitoring BP and heart rate and ordering an EKG only if the patient exhibits cardiac symptoms or there are concerns based on follow-up history and physical examination. Should a patient develop palpitations while taking a therapeutic dose of stimulants, a detailed history of the onset and duration of symptoms is important. For example, tachycardia that has a gradual onset and occurs with exercise is suggestive of physiological sinus tachycardia. In our judgment, most patients who experience symptoms that suggest sinus tachycardia simply require downward readjustment of their medication or a switch to a nonstimulant.
However, if the patient or family history prompts you to suspect other arrhythmias such as ectopic beats or supraventricular tachycardia, immediate assessment either in an emergency department or in the physician’s office may be required, because obtaining an EKG during symptoms is crucial for the diagnosis. Similarly, unexplained exercise intolerance or the onset of chest pain associated with exercise, dizziness, syncope, seizures, or dyspnea requires immediate cardiovascular assessment.
And finally, whether your patient has just started taking medication for his or her ADHD or has been on the medication for some time, it’s important to periodically reassess the need to continue the stimulant therapy; ADHD symptoms may decrease during mid- to late adolescence and into adulthood.21
CASE › The FP completed a thorough physical exam and found no evidence of any conditions that would increase the likelihood of SCD in the young patient. There was no history of SCD in the boy’s family, either. Based on these findings, the FP opted to forgo an EKG. She prescribed lisdexamfetamine, starting with 20 mg/d (the lowest dose available) and then monitored his course by telephone. Eventually, 30 mg was found to be an effective dose. At a 6-week follow-up visit, the boy’s ADHD symptoms were substantially reduced, without any adverse effects—cardiac or otherwise.
CORRESPONDENCE
Sudhir Ken Mehta, Cleveland Clinic Children’s Hospital, 9500 Euclid Avenue, Cleveland, OH 44111; [email protected]
1. Safety review: Follow up review of AERS search identifying cases of sudden death occurring with drugs used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). US Food and Drug Administration Web site. Available at: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_07_01_safetyreview.pdf. Accessed January 17, 2014.
2. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation. 2008;117:2407-2423.
3. Perrin JM, Friedman RA, Knilans TK; Black Box Working Group; Section on Cardiology and Cardiac Surgery. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics. 2008;122:451-453.
4. Graham J, Banaschewski T, Buitelaar J, et al; European Guidelines Group. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011;20:17-37.
5. Leslie LK, Rodday AM, Saunders TS, et al. Cardiac screening prior to stimulant treatment of ADHD: a survey of US-based pediatricians. Pediatrics. 2012;129:222-230.
6. Conners CK. Symposium: behavior modification by drugs. II. Psychological effects of stimulant drugs in children with minimal brain dysfunction. Pediatrics. 1972;49:702-708.
7. Samuels JA, Franco K, Wan F, et al. Effect of stimulants on 24-h ambulatory blood pressure in children with ADHD: a double-blind, randomized, cross-over trial. Pediatr Nephrol. 2006;21:92-95.
8. Stowe CD, Gardner SF, Gist CC, et al. 24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy. Ann Pharmacother. 2002;36:1142-1149.
9. Vitiello B, Elliott GR, Swanson JM, et al. Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD. Am J Psychiatry. 2012;169:167-177.
10. Hammerness P, Wilens T, Mick E, et al. Cardiovascular effects of longer-term, high-dose OROS methylphenidate in adolescents with attention deficit hyperactivity disorder. J Pediatr. 2009;155:84-89,89.e1.
11. Weisler RH, Biederman J, Spencer TJ, et al. Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr. 2005;10(suppl 20):35-43.
12. Drezner JA, Fudge J, Harmon KG, et al. Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med. 2012;25:408-415.
13. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med. 2011;365:1896-1904.
14. Schelleman H, Bilker WB, Strom BL, et al. Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics. 2011;127:1102-1110.
15. Winterstein AG, Gerhard T, Kubilis P, et al. Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study. BMJ. 2012;345:e4627.
16. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing [published correction appears in Circulation. 2009;120:e55-e59]. Circulation. 2008;117:2407-2423.
17. Thomas PE, Carlo WF, Decker JA, et al. Impact of the American Heart Association scientific statement on screening electrocardiograms and stimulant medications. Arch Pediatr Adolesc Med. 2011;165:166-170.
18. Mahle WT, Hebson C, Strieper MJ. Electrocardiographic screening in children with attention-deficit hyperactivity disorder. Am J Cardiol. 2009;104:1296-1299.
19. Mehta SK, Richards N, Jacobs I. Children and adolescents with attention deficit hyperactivity disorder in a pediatric cardiology office. Cardiol Young. 2010;20(suppl 3):167.
20. Leslie LK, Cohen JT, Newburger JW, et al. Costs and benefits of targeted screening for causes of sudden cardiac death in children and adolescents. Circulation. 2012;125:2621-2629.
21. Mannuzza S, Klein RG, Bessler A, et al. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry. 1998;155:493-488.
1. Safety review: Follow up review of AERS search identifying cases of sudden death occurring with drugs used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). US Food and Drug Administration Web site. Available at: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_07_01_safetyreview.pdf. Accessed January 17, 2014.
2. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation. 2008;117:2407-2423.
3. Perrin JM, Friedman RA, Knilans TK; Black Box Working Group; Section on Cardiology and Cardiac Surgery. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics. 2008;122:451-453.
4. Graham J, Banaschewski T, Buitelaar J, et al; European Guidelines Group. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011;20:17-37.
5. Leslie LK, Rodday AM, Saunders TS, et al. Cardiac screening prior to stimulant treatment of ADHD: a survey of US-based pediatricians. Pediatrics. 2012;129:222-230.
6. Conners CK. Symposium: behavior modification by drugs. II. Psychological effects of stimulant drugs in children with minimal brain dysfunction. Pediatrics. 1972;49:702-708.
7. Samuels JA, Franco K, Wan F, et al. Effect of stimulants on 24-h ambulatory blood pressure in children with ADHD: a double-blind, randomized, cross-over trial. Pediatr Nephrol. 2006;21:92-95.
8. Stowe CD, Gardner SF, Gist CC, et al. 24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy. Ann Pharmacother. 2002;36:1142-1149.
9. Vitiello B, Elliott GR, Swanson JM, et al. Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD. Am J Psychiatry. 2012;169:167-177.
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