Optimizing therapeutic decision-making for off-label medicines use: A scoping review and consensus recommendations for improving practice and research.

PURPOSE: Off-label medicines use is a common and sometimes necessary practice in many populations, with important clinical, ethical and financial consequences, including potential unintended harm or lack of effectiveness. No internationally recognized guidelines exist to aid decision-makers in applying research evidence to inform off-label medicines use. We aimed to critically evaluate current evidence informing decision-making for off-label use and to develop consensus recommendations to improve future practice and research. METHODS: We conducted a scoping review to summarize the literature on available off-label use guidance, including types, extent and scientific rigor of evidence incorporated. Findings informed the development of consensus recommendations by an international multidisciplinary Expert Panel using a modified Delphi process. Our target audience includes clinicians, patients and caregivers, researchers, regulators, sponsors, health technology assessment bodies, payers and policy makers. RESULTS: We found 31 published guidance documents on therapeutic decision-making for off-label use. Of 20 guidances with general recommendations, only 35% detailed the types and quality of evidence needed and the processes for its evaluation to reach sound, ethical decisions about appropriate use. There was no globally recognized guidance. To optimize future therapeutic decision-making, we recommend: (1) seeking rigorous scientific evidence; (2) utilizing diverse expertise in evidence evaluation and synthesis; (3) using rigorous processes to formulate recommendations for appropriate use; (4) linking off-label use with timely conduct of clinically meaningful research (including real-world evidence) to address knowledge gaps quickly; and (5) fostering partnerships between clinical decision-makers, researchers, regulators, policy makers, and sponsors to facilitate cohesive implementation and evaluation of these recommendations. CONCLUSIONS: We provide comprehensive consensus recommendations to optimize therapeutic decision-making for off-label medicines use and concurrently drive clinically relevant research. Successful implementation requires appropriate funding and infrastructure support to engage necessary stakeholders and foster relevant partnerships, representing significant challenges that policy makers must urgently address.

Clinical competency committee perceptions of entrustable professional activities and their value in assessing fellows: A qualitative study of pediatric subspecialty program directors.

OBJECTIVES: To examine the composition and processes of Clinical Competency Committees (CCCs) assigning entrustable professional activity (EPA) levels of supervision for pediatric subspecialty fellows and to examine fellowship program director (FPD) perspectives about using EPAs to determine fellows' graduation readiness. METHODS: A qualitative study was performed using one-on-one interviews with a purposeful sample of pediatric subspecialty FPDs to yield a thematic analysis. Semi-structured interview guides were used for participants who self-identified as EPA users or non-users. Inductive analysis and coding were performed on transcripts until theoretical sufficiency was attained. RESULTS: Twenty-eight FPDs were interviewed. There was significant variability in the composition and processes of CCCs across subspecialties. FPDs felt that CCCs intuitively understand what entrustment means, allowing for ease of application of level of supervision (LOS) scales and consensus. FPDs perceived that EPAs provided a global assessment of fellows and are one tool to determine graduation readiness. CONCLUSIONS: Although there was variability in the makeup and processes of CCCs across subspecialties, FPDs believe EPAs are intuitive and relatively easy to implement. Consensus can be reached easily using EPA-specific LOS scales focusing on entrustment. FPDs desire a better understanding of how EPAs should be used for graduation.

Transport Medical Control Education for Pediatric Critical Care Fellows: A National Needs Assessment Study.

OBJECTIVES: Characterize transport medical control education in Pediatric Critical Care Medicine fellowship. DESIGN: Cross-sectional survey study. SETTING: Pediatric Critical Care Medicine fellowship programs in the United States. SUBJECTS: Pediatric Critical Care Medicine fellowship program directors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We achieved a 74% (53/72) response rate. A majority of programs (85%) require fellows to serve as transport medical control, usually while carrying out other clinical responsibilities and sometimes without supervision. Fellows at most programs (80%) also accompany the transport team on patient retrievals. Most respondents (72%) reported formalized transport medical control teaching, primarily in a didactic format (76%). Few programs (25%) use a standardized assessment tool. Transport medical control was identified as requiring all six Accreditation Council for Graduate Medical Education competencies, with emphasis on professionalism and interpersonal and communication skills. CONCLUSIONS: Transport medical control responsibilities are common for Pediatric Critical Care Medicine fellows, but training is inconsistent, assessment is not standardized, and supervision may be lacking. Fellow performance in transport medical control may help inform assessment in multiple domains of competencies. Further study is needed to identify effective methods for transport medical control education.

Health Resource Use in Survivors of Pediatric Septic Shock in the United States.

OBJECTIVES: To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use. DESIGN: Secondary analyses of a multicenter prospective observational cohort study. SETTING: Twelve academic PICUs. PATIENTS: Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2-13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%). CONCLUSIONS: Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients' preexisting conditions.

The impact of the COVID-19 pandemic on family medicine residency training.

BACKGROUND: Family physicians have played a unique clinical role during the COVID-19 pandemic. We hypothesized that the pandemic would be associated with significant deleterious effects on clinical activity, educational training, personal safety and well-being. OBJECTIVE: We conducted a national survey to obtain preliminary data that would assist in future targeted data collection and subsequent evaluation of the impact of the pandemic on family medicine residents and teaching faculty. METHODS: An anonymous online survey of residents and faculty was distributed via the Association of Family Medicine Residency Directors list serve between 5/21/2020 and 6/18/2020. Survey questions focused on clinical and educational activities, safety and well-being. RESULTS: One hundred and fifty-three residents and 151 teaching faculty participated in the survey. Decreased clinical activity was noted by 81.5% of residents and 80.9% of faculty and the majority began conducting telehealth visits (97.9% of residents, 91.0% of faculty). Distance learning platforms were used by all residents (100%) and 39.6% noted an overall positive impact on their education. Higher levels of burnout did not significantly correlate with reassignment of clinical duties (residents P = 0.164; faculty P = 0.064). Residents who showed significantly higher burnout scores (P = 0.035) and a decline in levels of well-being (P = 0.031) were more likely to participate in institutional well-being support activities. CONCLUSIONS: Our preliminary data indicate that family medicine residents and teaching faculty were profoundly affected by the COVID-19 pandemic. Future studies can be directed by current findings with focus on mitigation factors in addressing globally disruptive events such as COVID-19.

Family physicians have played a unique clinical role during the COVID-19 pandemic. We hypothesized that the pandemic would be associated with significant deleterious effects on clinical activity, educational training, personal safety and well-being. Towards setting a foundation for further studies, we conducted a national survey to obtain preliminary data that would assist in future targeted data collection and subsequent evaluation of the impact of the pandemic on family medicine residents and teaching faculty. Our preliminary data indicate that family medicine residents and teaching faculty were profoundly affected by the COVID-19 pandemic in all domains studied. Future studies can be directed by current findings with focus on mitigation factors in addressing globally disruptive events such as COVID-19.

Variation in Pediatric Palliative Care Allocation Among Critically Ill Children in the United States.

OBJECTIVES: The objectives are as follows: 1) estimate palliative care consult rates and trends among critically ill children and 2) characterize which children receive palliative care consults, including those meeting previously proposed ICU-specific palliative care screening criteria. DESIGN: Retrospective cohort. SETTING: Fifty-two United States children's hospitals participating in the Pediatric Health Information Systems database. PATIENTS: Hospitalized children with nonneonatal ICU admissions from 2007 to 2018. MEASUREMENTS AND MAIN RESULTS: The primary outcome was palliative care consultation, as identified by the palliative care International Classification of Disease code. Patient characteristics and outcomes were compared between those with and without palliative care. We used a mixed-effects multivariable model to estimate the independent association between the palliative care and patient characteristics accounting for institution and subject clustering. Hospitalizations were categorized into three mutually exclusive groups for comparative analyses: 1) meeting ICU-specific palliative care criteria, 2) presence of a complex chronic condition not in ICU-specific palliative care criteria, or 3) not meeting ICU-specific palliative care or complex chronic condition criteria. Rates and trends of palliative care consultation were estimated including variation among institutions and variation among subcategories of ICU-specific palliative care criteria. The study cohort included 740,890 subjects with 1,024,666 hospitalizations. About 1.36% of hospitalizations had a palliative care consultation. Palliative care consult was independently associated with older age, female sex, government insurance, inhospital mortality, and ICU-specific palliative care or complex chronic condition criteria. Among the hospitalizations, 30% met ICU-specific palliative care criteria, 40% complex chronic condition criteria, and 30% neither. ICU-specific palliative care patients received more mechanical ventilation and cardiopulmonary resuscitation, had longer hospital and ICU lengths of stay, and had higher inhospital mortality (p < 0.001). Palliative care utilization increased over the study period with considerable variation between the institutions especially in the ICU-specific palliative care cohort and its subgroups. CONCLUSIONS: Palliative care consultation for critically ill children in the United States is low. Palliative care utilization is increasing but considerable variation exists across institutions, suggesting inequity in palliative care allocation among this vulnerable population. Future studies should evaluate factors influencing allocation of palliative care among critically ill children in the United States and the drivers of differences between the institutional practices.

Increased Odds of Ventricular Arrhythmias Associated with Selective Serotonin Reuptake Inhibitor Use among the Pediatric and Young Adult Population: A Case-Control Study.

OBJECTIVE: To measure the association between selective serotonin reuptake inhibitor (SSRI) use and out-of-hospital ventricular arrhythmia among the pediatric and young adult population. STUDY DESIGN: Case-control study using US claims data from 2007 to 2018. Cases were subjects with at least 1 event between ages 2 and 24 years. Controls (matched 10:1 on index date, age, sex, and continuous enrollment) had no events during study period. Independent association between current SSRI use (prescription fill with continuous exposure ending on, or after, the index date) and incident out-of-hospital ventricular arrhythmia (hospitalization or emergency room encounter with primary diagnostic code for ventricular arrhythmia) was estimated using multivariable conditional logistic regression. Separate analyses were performed for pediatric (2-17 years of age) vs young adult (18-24 years of age) subjects and between citalopram/escitalopram vs other SSRIs. RESULTS: During the study period, 237 eligible cases were identified with 2370 matched controls. Cases were more likely to have government insurance and have a mental health, cardiac, or other complex chronic condition. Thirteen cases (5%) and 15 controls (<1%) had current SSRI exposure. After adjustment for mental health and chronic conditions, there was an increased odds of current SSRI use among cases compared with controls (OR 5.11, 95% CI 1.22-21.37). No difference was observed between pediatric and young adult ages, nor between citalopram/escitalopram and other SSRIs. CONCLUSIONS: These findings demonstrate increased odds of out-of-hospital ventricular arrhythmia associated with SSRI use in the pediatric and young adult population, suggesting a need for heightened awareness and ongoing monitoring of this potential adverse effect.

Validity of administrative claims-based algorithms for ventricular arrhythmia and cardiac arrest in the pediatric population.

PURPOSE: Identify administrative claims-based algorithms for capturing out-of-hospital ventricular arrhythmias (VA) and cardiac arrests (CA) due to cardiac causes in the pediatric population with high positive-predictive value (PPV). METHODS: Within a single pediatric center, a retrospective cohort of patients hospitalized or seen in the emergency room for VA or CA were identified from the electronic health records. Eligible encounters were blindly reviewed and linked to administrative data, including ICD-9/ICD-10 codes. Test characteristics, including PPV, for different diagnostic and procedure codes were generated using a 50% training sample. The gold standard was definite or suspected out-of-hospital VA or CA due to cardiac cause verified based on clinical criteria. Algorithms with the highest PPV were then applied to a 50% validation sample to validate performance. RESULTS: From 2004-2017, 598 encounters met eligibility criteria. 174 (29%) had an outcome of interest, with remainder being an inpatient event or CA due to other cause. Within the training sample (n = 263), VA codes in primary position had a PPV 94% (95%CI 81%-99%) with low sensitivity (44%, 95%CI 33%-56%). CA codes in any position or VA codes in nonprimary positions had low PPV (18%-19%, 31% respectively). Applying the top three performing algorithms to the validation sample (n = 252) yielded similar PPV values. CONCLUSIONS: Contrary to adults, algorithms including a CA code do not perform well for identifying out-of-hospital VA and CA due to cardiac cause in the pediatric populations. Researchers should be aware of the potential implications for future pediatric drug safety studies for these outcomes.

Expanding Faculty Development of Teaching Skills: A National Needs Assessment of Pediatric Critical Care Medicine Faculty.

OBJECTIVES: High-quality clinical teaching is an essential element in preparing trainees to become independently competent clinicians. In order to better understand the context-specific faculty development needs of teaching faculty in a specific community, we sought to determine the self-reported teaching skill deficits of pediatric critical care medicine faculty and their preferences and motivations regarding faculty development to enhance their teaching. DESIGN: Modified Delphi technique was used to create an online survey in which respondents rated their need for education on a variety of teaching skills, their preferred learning modalities, and factors that motivate their participation in faculty development. SETTING: Pediatric Critical Care Medicine divisions at the 64 sites in the United States with fellowship programs. SUBJECTS: Five-hundred forty-five Pediatric Critical Care Medicine faculty who teach fellows and other trainees. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Response rate was 40%. Respondents reported a median of 8.5 years (interquartile range, 4-16 yr) as teaching faculty. The median age of faculty was 44.6 years (interquartile range, 38-50 yr). Only 20% of respondents indicated that improving their teaching was a low priority. Thirty-six percent of respondents had not participated in any formal teaching skill development as faculty. The most frequently cited factors motivating engagement in faculty development were education being included as part of regularly attended conferences, resources readily available when needed, and participation promoted by a supervisor. Preferred learning modalities included a brief discussion with a colleague, a 10-minute video, and a regular conference series. CONCLUSIONS: Pediatric Critical Care Medicine faculty reported they experience challenges in teaching and would benefit from faculty development training aimed at improving their knowledge and skills about being an educator. Preferred learning methods and motivating factors highlight the importance of efficiency in content delivery and endorsement by faculty supervisors. Consideration of these needs and preferences may be useful in creating context-focused, community of practice-based faculty development programs.

Accuracy of Bedside Ultrasound Femoral Vein Diameter Measurement by PICU Providers.

OBJECTIVES: Perform a needs assessment by evaluating accuracy of PICU provider bedside ultrasound measurement of femoral vein diameter prior to utilization of the catheter-to-vein ratio for central venous catheter size selection. DESIGN: Prospective observational cohort study. SETTING: PICU within a quaternary care children's hospital. PATIENTS: PICU patients greater than 30 days and less than 6 years without a femoral central venous catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gold-standard femoral vein diameter measurements were made by a radiologist, sonographer, or bedside ultrasound expert. PICU providers then repeated the femoral vein diameter measurements, and results were compared by Bland-Altman analysis with a priori accuracy goal of limits of agreement ± 15%. Among recruited patients (n = 27), the median age was 1.1 years (interquartile range 0.5-2.3 yr), weight was 9.0 kg (interquartile range 7.0-11.5 kg), and reference femoral vein diameter was 0.36 cm (interquartile range 0.28-0.45 cm). Providers performed 148 femoral vein diameter measurements and did not meet goal accuracy when compared with the reference measurement with a bias of 4% (95% of limits of agreement -62% to 70%). A majority of patients would have a catheter-to-vein ratio greater than 0.5 using either age-based central venous catheter size selection criterion (14/27) or the provider bedside ultrasound femoral vein diameter measurement (18/27). CONCLUSIONS: PICU provider measurement of femoral vein diameter by bedside ultrasound is inaccurate when compared with expert reference measurement. Central venous catheter size selection based on age or PICU provider femoral vein diameter measurement can lead to a catheter-to-vein ratio greater than 0.5 and potentially increase the risk of catheter-associated venous thromboembolism. Structured bedside ultrasound training with assessment of accuracy is necessary prior to implementation of venous thromboembolism reduction efforts based on catheter-to-vein ratio recommendations.

Establishing the Knowledge and Skills Necessary in Pediatric Critical Care Medicine: A Systematic Approach to Practice Analysis.

OBJECTIVES: To describe the practice analysis undertaken by a task force convened by the American Board of Pediatrics Pediatric Critical Care Medicine Sub-board to create a comprehensive document to guide learning and assessment within Pediatric Critical Care Medicine. DESIGN: An in-depth practice analysis with a mixed-methods design involving a descriptive review of practice, a modified Delphi process, and a survey. SETTING: Not applicable. SUBJECTS: Seventy-five Pediatric Critical Care Medicine program directors and 2,535 American Board of Pediatrics Pediatric Critical Care Medicine diplomates. INTERVENTIONS: A practice analysis document, which identifies the full breadth of knowledge and skill required for the practice of Pediatric Critical Care Medicine, was developed by a task force made up of seven pediatric intensivists and a psychometrician. The document was circulated to all 75 Pediatric Critical Care Medicine fellowship program directors for review and comment and their feedback informed modifications to the draft document. Concurrently, data from creation of the practice analysis draft document were also used to update the Pediatric Critical Care Medicine, was developed by a task force made up of seven pediatric intensivists and a psychometrician. The document was circulated to all 75 Pediatrics Pediatric Critical Care Medicine fellowship program directors for review and comment and their feedback informed modifications to the draft document. Concurrently, data from creation of the practice analysis draft document were also used to update the Pediatric Critical Care Medicine content outline, which was sent to all 2,535 American Board of Pediatrics Pediatric Critical Care Medicine diplomates for review during an open-comment period between January 2019 and February 2019, and diplomate feedback was used to make updates to both the content outline and the practice analysis document. MEASUREMENTS AND MAIN RESULTS: After review and comment by 25 Pediatric Critical Care Medicine program directors (33.3%) and 619 board-certified diplomates (24.4%), a comprehensive practice analysis document was created through a two-stage process. The final practice analysis includes 10 performance domains which parallel previously published Entrustable Professional Activities in Pediatric Critical Care Medicine. These performance domains are made up of between three and eight specific tasks, with each task including the critical knowledge and skills that are necessary for successful completion. The final practice analysis document was also used by the American Board of Pediatrics Pediatric Critical Care Medicine Sub-board to update the Pediatric Critical Care Medicine content outline. CONCLUSIONS: A systematic approach to practice analysis, with stakeholder engagement, is essential for an accurate definition of Pediatric Critical Care Medicine practice in its totality. This collaborative process resulted in a dynamic document useful in guiding curriculum development for training programs, maintenance of certification, and lifetime professional development to enable safe and efficient patient care.

Left ventricular dysfunction in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction. METHODS AND RESULTS: Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate. CONCLUSIONS: In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.

Delirium is a Common and Early Finding in Patients in the Pediatric Cardiac Intensive Care Unit.

OBJECTIVE: To determine incidence, associated risk factors, and characteristics of delirium in a pediatric cardiac intensive care unit (CICU). Delirium is a frequent and serious complication in adults after cardiac surgery, but there is limited understanding of its impact in children with critical cardiac disease. STUDY DESIGN: Single-center prospective observational study of CICU patients ≤21 years old. All were screened for delirium using the Cornell Assessment for Pediatric Delirium each 12-hour shift. RESULTS: Ninety-nine patients were included. Incidence of delirium was 57%. Median time to development of delirium was 1 day (95% CI 0, 1 days). Children with delirium were younger (geometric mean age 4 vs 46 months; P < .001), had longer periods of mechanical ventilation (mean 35.9 vs 8.8 hours; P = .002) and had longer cardiopulmonary bypass times (geometric mean 126 vs 81 minutes; P = .001). Delirious patients had longer length of CICU stay than those without delirium (median 3 (IQR 2, 12.5) vs 1 (IQR1, 2) days; P < .0001). A multivariable generalized linear mixed model showed a significant association between delirium and younger age (OR 0.35 for each additional month, 95% CI 0.19, 0.64), need for mechanical ventilation (OR 4.1, 95% CI 1.7, 9.89), and receipt of benzodiazepines (OR 3.78, 95% CI 1.46, 9.79). CONCLUSIONS: Delirium is common in patients in the pediatric CICU and is associated with longer length of stay. There may be opportunities for prevention of delirium by targeting modifiable risk factors, such as use of benzodiazepines.

Electronic health record (EHR) based postmarketing surveillance of adverse events associated with pediatric off-label medication use: A case study of short-acting beta-2 agonists and arrhythmias.

PURPOSE: Use electronic health record (EHR) data to (1) estimate the risk of arrhythmia associated with inhaled short-acting beta-2 agonists (SABA) in pediatric patients and (2) determine whether risk varied by on-label versus off-label prescribing. METHODS: Retrospective cohort study of 335 041 children ≤18 years using EHR primary care data from 2 pediatric health systems (2011-2013). A series of monthly pseudotrials were created, using propensity score methodology to balance baseline characteristics between SABA-exposed (identified by prescription) and SABA-unexposed children. Association between SABA and subsequent arrhythmia for each health system was estimated through pooled logistic regression with separate estimates for children initiating under and over 4 years old (off-label and on-label, respectively). RESULTS: Eleven percent of the cohort received a SABA prescription, 57% occurred under the age of 4 years (off-label). During the follow-up period, there were 283 first arrhythmia events, most commonly atrial tachyarrhythmias and premature ventricular/atrial contractions. In 1 health system, adjusted risk for arrhythmia was increased among exposed children (OR 1.89, 95% CI 1.31-2.73) without evidence of interaction between label status and risk. The absolute adjusted rate difference was 3.6/10 000 person-years of SABA exposure. The association between SABA exposure and arrhythmias was less strong in the second system (OR 1.26, 95% CI 0.30-5.33). CONCLUSION: Using EHR data, we could estimate the risk of a rare event associated with medication use and determine difference in risk related to on-label versus off-label status. These findings support the value of EHR-based data for postmarketing drug studies in the pediatric population.

Enteral Nutrition Practices in Critically Ill Children Requiring Noninvasive Positive Pressure Ventilation.

OBJECTIVES: Evaluate the practice of providing enteral nutrition in critically ill children requiring noninvasive positive pressure ventilation. DESIGN: Retrospective cohort study. SETTING: PICU within a quaternary care children's hospital. PATIENTS: PICU patients older than 30 days requiring noninvasive positive pressure ventilation for greater than or equal to 24 hours from August 2014 to June 2015. Invasive mechanical ventilation prior to noninvasive positive pressure ventilation and inability to receive enteral nutrition at baseline were additional exclusionary criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was enteral nutrition initiation within 24 hours of admission. Secondary outcomes included time to goal enteral nutrition rate, adequacy of nutrition, adverse events (pneumonia not present at admission, intubation after enteral nutrition initiation, feeding tube misplacement), and lengths of noninvasive positive pressure ventilation and PICU stay. Among those included (n = 562), the median age was 2 years (interquartile range, 39 d to 6.8 yr), 54% had at least one chronic condition, and 43% had malnutrition at baseline. The most common primary diagnosis was bronchiolitis/viral pneumonia. The median length of time on noninvasive positive pressure ventilation was 2 days (interquartile range, 2.0-4.0). Most (83%) required continuous positive airway pressure or bi-level support during their PICU course. Sixty-four percent started enteral nutrition within 24 hours, with 72% achieving goal enteral nutrition rate within 72 hours. Forty-nine percent and 44% received an adequate cumulative calorie and protein intake, respectively, during their PICU admission. Oral feeding was the most common delivery method. On multivariable analysis, use of bi-level noninvasive positive pressure ventilation (odds ratio, 0.40; 95% CI, 0.25-0.63) and continuous dexmedetomidine (odds ratio, 0.59; 95% CI, 0.35-0.97) were independently associated with decreased likelihood of early enteral nutrition. Twelve percent of patients had at least one adverse event. CONCLUSIONS: A majority of patients requiring noninvasive positive pressure ventilation received enteral nutrition within 24 hours. However, less than half achieved caloric and protein goals during their PICU admission. Further investigation is warranted to determine the safety and effectiveness of early enteral nutrition in this population.

Current needs in pediatric pharmacoepidemiology.

PURPOSE: We report on a needs assessment conducted by the International Society of Pharmacoepidemiology (ISPE) Pediatric Special Interest Group (SIG) to identify critical needs in pediatric pharmacoepidemiology and directions for future activities. METHODS: A mixed methods survey using a structured interview was conducted in the SIG and ISPE membership to elicit information about current activities in pediatric pharmacoepidemiology and identify critical methodologic issues. The interviews were conducted in two phases over 2013 and 2014, beginning with interviews of SIG members and expanding to the wider ISPE membership. Members of the SIG conducted the interviews and summarized the responses. RESULTS: Twenty-nine ISPE members participated in the needs assessment The respondents reported working with a total of 59 distinct databases, with only eight databases used by more than one respondent. Seventeen respondents (57%) reported issues of limited sample sizes, noting that the problem intensifies when studying age sub-groups or specific genetic populations. Missing data elements were a problem in three main areas: lack of detailed medication information, inability to link to parental data, and lack of detailed information about age. Respondents reported the need for data elements not typically required in studies of adults, such as birthweight and current height and weight, as well as school performance and mental health status. CONCLUSIONS: Our needs assessment describes a preliminary picture of the emerging sub-specialty of pediatric pharmacoepidemiology encompassing a range of age sub-groups, disease areas, and medical specialties. The assessment also documents a body of methodologic challenges unique to pharmacoepidemiologic research in children. Copyright © 2016 John Wiley & Sons, Ltd.

Exploring Factors for Implementation of EPAs in Pediatric Subspecialty Fellowships: A Qualitative Study of Program Directors.

OBJECTIVE: To understand fellowship program directors' (FPDs) perspectives on facilitators and barriers to using entrustable professional activities (EPAs) in pediatric subspecialty training. METHODS: We performed a qualitative study of FPDs, balancing subspecialty, program size, geographic region and current uses of EPAs. A study coordinator conducted 1-on-1 interviews using a semistructured approach to explore EPA use or nonuse and factors supporting or preventing their use. Investigators independently coded transcribed interviews using an inductive approach and the constant comparative method. Group discussion informed code structure development and refinement. Iterative data collection and analysis continued until theoretical sufficiency was achieved, yielding a thematic analysis. RESULTS: Twenty-eight FPDs representing 11 pediatric subspecialties were interviewed, of whom 16 (57%) reported current EPA use. Five major themes emerged: (1) facilitators including the intuitive nature and simple wording of EPAs; (2) barriers such as workload burden and lack of a regulatory requirement; (2) variable knowledge and training surrounding EPAs, leading to differing levels of understanding; (3) limited current use of EPAs, even among self-reported users; and (4) complementary nature of EPAs and milestones. FPDs acknowledged the differing strengths of both EPAs and milestones but sought additional knowledge about the value added by EPAs for assessing trainees, including the impact on outcomes. CONCLUSIONS: Identified themes can inform effective and meaningful EPA implementation strategies: Supporting and educating FPDs, ongoing assessment of the value of EPAs in training, and practical integration with current workflow. Generating additional data and engaging stakeholders is critical for successful implementation for the pediatric subspecialties.

Implementing Entrustable Professional Activities in Pediatric Fellowships: Facilitating the Process.

BACKGROUND AND OBJECTIVES: Entrustable professional activities (EPAs) will be used for initial certification by the American Board of Pediatrics by 2028. Less than half of pediatric fellowships currently use EPAs for assessment, yet all will need to adopt them. Our objectives were to identify facilitators and barriers to the implementation of EPAs to assess pediatric fellows and to determine fellowship program directors' (FPD) perceptions of EPAs and Milestones. METHODS: We conducted a survey of FPDs from 15 pediatric subspecialties. EPA users were asked about their implementation of EPAs, barriers encountered, and perceptions of EPAs. Nonusers were queried about deterrents to using EPAs. Both groups were asked about potential facilitators of implementation and their perceptions of Milestones. RESULTS: The response rate was 65% (575/883). Of these, 344 (59.8%) were EPA users and 231 (40.2%) were nonusers. Both groups indicated work burden as a barrier to implementation. Nonusers reported more barriers than users (mean [SD]: 7 [3.8] vs 5.8 [3.4], P < .001). Both groups identified training materials and premade assessment forms as facilitators to implementation. Users felt that EPAs were easier to understand than Milestones (89%) and better reflected what it meant to be a practicing subspecialty physician (90%). In contrast, nonusers felt that Milestones were easy to understand (57%) and reflected what it meant to be a practicing subspecialist (58%). CONCLUSIONS: Implementing EPA-based assessment will require a substantial investment by FPDs, facilitated by guidance and easily accessible resources provided by multiple organizations. Perceived barriers to be addressed include FPD time constraints, a need for additional assessment tools, and outcomes data.

Comparative safety of selective serotonin reuptake inhibitors among pediatric users with respect to adverse cardiac events.

PURPOSE: This study aims to perform a comparative safety study assessing the risk of ventricular arrhythmia, cardiac arrest, or sudden death among pediatric selective serotonin reuptake inhibitor (SSRI) users. METHODS: Using US claims data from 1997 to 2009, new pediatric (age < 18 years) users of SSRI monotherapy were identified. Adverse cardiac outcomes occurring within 12 months of SSRI initiation were identified using a previously validated International Classification of Disease, ninth edition algorithm. Cox proportional hazard analysis was used to estimate the risk for each SSRI, using fluoxetine as the referent group, adjusting for the propensity to receive an individual SSRI, demographics, and exposure covariates. RESULTS: Over the study period, 113,714 subjects met the inclusion criteria and contributed 40,639 person-years of SSRI exposure time. Sertraline (33%) and fluoxetine (29%) were the most commonly prescribed SSRIs. Forty events occurred within 12 months of SSRI initiation. The crude incidence rate was highest for escitalopram (19.5/10,000 person-years) and lowest for fluoxetine (4.2/10,000 person-years). The median time to event ranged from 45 to 86 days. The adjusted risk of adverse event, relative to fluoxetine, was highest for citalopram Hazard Ratio (HR) = 3.53, 95% confidence interval [CI] = 1.09­11.46) and escitalopram (HR = 3.30, 95%CI = 1.08­10.14) and lowest for paroxetine (HR = 1.34, 95%CI = 0.30­5.99) and sertraline (HR = 2.14, 95%CI = 0.75­6.16). CONCLUSIONS: The incidence of adverse cardiac events among pediatric SSRI users was low. However, the risk of an adverse outcome was higher for citalopram and escitalopram users as compared with fluoxetine users. Future studies should focus on confirming these findings and identifying modifying risk factors to optimize medication selection for this population.