Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial.

Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P = .29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration: clinicaltrials.gov Identifier: NCT02139800.

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.

Extracorporeal Cardiopulmonary Resuscitation (E-CPR) During Pediatric In-Hospital Cardiopulmonary Arrest Is Associated With Improved Survival to Discharge: A Report from the American Heart Association's Get With The Guidelines-Resuscitation (GWTG-R) Registry.

BACKGROUND: Although extracorporeal cardiopulmonary resuscitation (E-CPR) can result in survival after failed conventional CPR (C-CPR), no large, systematic comparison of pediatric E-CPR and continued C-CPR has been reported. METHODS AND RESULTS: Consecutive patients <18 years old with CPR events ≥10 minutes in duration reported to the Get With the Guidelines-Resuscitation registry between January 2000 and December 2011 were identified. Hospitals were grouped by teaching status and location. Primary outcome was survival to discharge. Regression modeling was performed, conditioning on hospital groups. A secondary analysis was performed with the use of propensity score matching. Of 3756 evaluable patients, 591 (16%) received E-CPR and 3165 (84%) received C-CPR only. Survival to hospital discharge and survival with favorable neurological outcome (Pediatric Cerebral Performance Category score of 1-3 or unchanged from admission) were greater for E-CPR (40% [237 of 591] and 27% [133 of 496]) versus C-CPR patients (27% [862 of 3165] and 18% [512 of 2840]). Odds ratios (ORs) for survival to hospital discharge and survival with favorable neurological outcome were greater for E-CPR versus C-CPR. After adjustment for covariates, patients receiving E-CPR had higher odds of survival to discharge (OR, 2.80; 95% confidence interval, 2.13-3.69; P<0.001) and survival with favorable neurological outcome (OR, 2.64; 95% confidence interval, 1.91-3.64; P<0.001) than patients who received C-CPR. This association persisted when analyzed by propensity score-matched cohorts (OR, 1.70; 95% confidence interval, 1.33-2.18; P<0.001; and OR, 1.78; 95% confidence interval, 1.31-2.41; P<0.001, respectively]. CONCLUSION: For children with in-hospital CPR of ≥10 minutes duration, E-CPR was associated with improved survival to hospital discharge and survival with favorable neurological outcome compared with C-CPR.

Intravenous Versus Oral Antibiotics for the Prevention of Treatment Failure in Children With Complicated Appendicitis: Has the Abandonment of Peripherally Inserted Catheters Been Justified?

OBJECTIVE: To compare treatment failure leading to hospital readmission in children with complicated appendicitis who received oral versus intravenous antibiotics after discharge. BACKGROUND: Antibiotics are often employed after discharge to prevent treatment failure in children with complicated appendicitis, although existing studies comparing intravenous and oral antibiotics for this purpose are limited. METHODS: We identified all patients aged 3 to 18 years undergoing appendectomy for complicated appendicitis, who received postdischarge antibiotics at 35 childrens hospitals from 2009 to 2012. Discharge codes were used to identify study subjects from the Pediatric Health Information System database, and chart review confirmed eligibility, treatment assignment, and outcomes. Exposure status was based on outpatient antibiotic therapy, and analysis used optimal and full matching methods to adjust for demographic and clinical characteristics. Treatment failure (defined as an organ-space infection) requiring inpatient readmission was the primary outcome. Secondary outcomes included revisits from any cause to either the inpatient or emergency department setting. RESULTS: In all, 4579 patients were included (median: 99/hospital), and utilization of intravenous antibiotics after discharge ranged from 0% to 91.7% across hospitals. In the matched analysis, the rate of treatment failure was significantly higher for the intravenous group than the oral group [odds ratio (OR) 1.74, 95% confidence interval (CI) 1.05-2.88; risk difference: 4.0%, 95% CI 0.4-7.6%], as was the rate of all-cause revisits (OR 2.11, 95% CI 1.44-3.11; risk difference: 9.4%, 95% CI 4.7-14.2%). The rate of peripherally inserted central catheter line complications was 3.2% in the intravenous group, and drug reactions were rare in both groups (intravenous: 0.7%, oral: 0.5%). CONCLUSIONS: Compared with oral antibiotics, use of intravenous antibiotics after discharge in children with complicated appendicitis was associated with higher rates of both treatment failure and all-cause hospital revisits.

A Toddler Parenting Intervention in Primary Care for Caregivers With Depression Symptoms.

Caregiver depression impacts parenting behaviors and has deleterious effects on child behavior. Evidence-based interventions to address parenting have not been adapted for use with depressed caregivers in pediatric primary care settings. Our study examined the feasibility and explored outcomes of an evidence-based parenting program implemented in primary care and adapted for caregivers with depressive symptoms caring for toddlers. We conducted a randomized controlled trial with a wait-list control. Participants were caregivers who screened positive for depressive symptoms in pediatric settings with a toddler. Our study was implemented from July 2011 to June 2012. We adapted the Incredible Years Parents, Babies and Toddlers program with the addition of depression psychoeducation (12 weekly sessions), and assessed caregivers at baseline and immediately post-intervention. We assessed participation rates, depressive symptoms, parenting discipline practices, social support, and parenting stress. Our results revealed that 32 caregivers participating in the intervention group had significantly greater improvement in self-reported parenting discipline practices compared to the 29 wait-list control group caregivers. We found no differences between groups in depressive symptoms, social support, or parenting stress. Our study demonstrated that the average attendance was poor (mean attendance = 3.7 sessions). We adapted an evidence-based parenting intervention for caregivers with depressive symptoms and toddlers in primary care; however, participation was challenging. Alternative intervention strategies are needed to reach and retain low-income caregivers with depression symptoms as they face multiple barriers to participation in groups within center-based services. Trial Registration Clinical Trials.gov identifier NCT01464619.

Association between chronic urticaria and self-reported penicillin allergy.

BACKGROUND: Penicillin allergy is the most commonly reported drug allergy and often presents with cutaneous symptoms. Other common diagnoses, such as chronic urticaria, may be falsely attributed to penicillin allergy. Because chronic urticaria is fairly common in the general population, evaluation of its prevalence in patients with self-reported penicillin allergy was of interest. Similarly, the prevalence of self-reported penicillin allergy in patients with chronic urticaria is not well known and also becomes interesting in light of the high prevalence of self-reported penicillin allergy in the general population. OBJECTIVES: To determine the prevalence of self-reported penicillin allergy in patients with chronic urticaria and the prevalence of chronic urticaria in patients with self-reported penicillin allergy. METHODS: This was a retrospective medical record review of 11,143 patients completed using the electronic health record of the University of Pennsylvania Allergy and Immunology clinic. RESULTS: The prevalence of self-reported penicillin allergy in patients with chronic urticaria was found to be approximately 3 times greater than in the general population. The prevalence of chronic urticaria in patients with self-reported penicillin allergy was also found to be approximately 3 times greater than in the population. CONCLUSION: This link between chronic urticaria and self-reported penicillin allergy highlights the need for clinicians to inquire about self-reported penicillin allergy in patients with chronic urticaria and to consider penicillin skin testing. Furthermore, patients who report penicillin allergy might actually have chronic urticaria, indicating the importance of inquiring about chronic urticaria symptoms in patients with self-reported penicillin allergy.

Random-effects meta-analysis of inconsistent effects: a time for change.

A primary goal of meta-analysis is to improve the estimation of treatment effects by pooling results of similar studies. This article explains how the most widely used method for pooling heterogeneous studies--the Der Simonian-Laird (DL) estimator--can produce biased estimates with falsely high precision. A classic example is presented to show that use of the DL estimator can lead to erroneous conclusions. Particular problems with the DL estimator are discussed, and several alternative methods for summarizing heterogeneous evidence are presented. The authors support replacing universal use of the DL estimator with analyses based on a critical synthesis that recognizes the uncertainty in the evidence,focuses on describing and explaining the probable sources of variation in the evidence, and uses random-effects estimates that provide more accurate confidence limits than the DL estimator.

Prevalence of abuse among young children with femur fractures: a systematic review.

BACKGROUND: Clinical factors that affect the likelihood of abuse in children with femur fractures have not been well elucidated. Consequently, specifying which children with femur fractures warrant an abuse evaluation is difficult. Therefore the purpose of this study is to estimate the proportion of femur fractures in young children attributable to abuse and to identify demographic, injury and presentation characteristics that affect the probability that femur fractures are secondary to abuse. METHODS: We conducted a systematic review of published articles written in English between January 1990 and July 2013 on femur fracture etiology in children less than or equal to 5 years old based on searches in PubMed/MEDLINE and CINAHL databases. Data extraction was based on pre-defined data elements and included study quality indicators. A meta-analysis was not performed due to study population heterogeneity. RESULTS: Across the 24 studies reviewed, there were a total of 10,717 children less than or equal to 60 months old with femur fractures. Among children less than 12 months old with all types of femur fractures, investigators found abuse rates ranging from 16.7% to 35.2%. Among children 12 months old or greater with femur fractures, abuse rates were lower: from 1.5% - 6.0%. In multiple studies, age less than 12 months, non-ambulatory status, a suspicious history, and the presence of additional injuries were associated with findings of abuse. Diaphyseal fractures were associated with a lower abuse incidence in multiple studies. Fracture side and spiral fracture type, however, were not associated with abuse. CONCLUSIONS: Studies commonly find a high proportion of abuse among children less than 12 months old with femur fractures. The reported trauma history, physical examination findings and radiologic results must be examined for characteristics that increase or decrease the likelihood of abuse determination.

Longitudinal association of county-level economic indicators and child maltreatment incidents.

To evaluate the association between economic indicators (unemployment and mortgage foreclosure rates) and volume of investigated and substantiated cases of child maltreatment at the county level from 1990 to 2010 in the Commonwealth of Pennsylvania. County-level investigated reports of child maltreatment and proportion of investigated cases substantiated by child protective services in the Commonwealth of Pennsylvania were compared with county-level unemployment rates from 1990 to 2010, and with county-level mortgage foreclosure rates from 2000 to 2010. We employed fixed-effects Poisson regression modeling to estimate the association between volume of investigated and substantiated cases of maltreatment, and current and prior levels of local economic indicators adjusting for temporal trend. Across Pennsylvania, annual rate of investigated maltreatment reports decreased through the 1990s and rose in the early 2000s before reaching a peak of 9.21 investigated reports per 1,000 children in 2008, during the recent economic recessionary period. The proportion of investigated cases substantiated, however, decreased statewide from 33 % in 1991 to 15 % in 2010. Within counties, current unemployment rate, and current and prior-year foreclosure rates were positively associated with volume of both investigated and substantiated child maltreatment incidents (p < 0.05). Despite recent increases in investigations, the proportion of investigated cases substantiated decreased by more than half from 1990 to 2010 in Pennsylvania. This trend suggests significant changes in substantiation standards and practices during the period of study. Economic indicators demonstrated strong association with investigated and substantiated maltreatment, underscoring the urgent need for directing important prophylactic efforts and resources to communities experiencing economic hardship.

Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children.

BACKGROUND: Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children. METHODS: A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI (propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects. RESULTS: We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2-13 years) for exposed and 8 years (IQR, 3-14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77-12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54-6.56 days) and $18 900 (95% CI, $15 100-$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29-23.90 days) and $93 600 (95% CI, $80 000-$107 200) for HO-CDI. CONCLUSIONS: Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children.

The use of palliative chemotherapy in pediatric oncology patients: a national survey of pediatric oncologists.

BACKGROUND: Many children continue receiving chemotherapy after there is no realistic hope for cure. One factor that influences parental decisions to pursue medical therapies is physician preference. To date, no studies have described pediatric oncologists' perspectives and practices regarding palliative chemotherapy (PC). PROCEDURE: We surveyed via email pediatric oncologists practicing in the U.S who are members of the Children's Oncology Group to achieve the following objectives: (1) Describe pediatric oncologists treatment considerations regarding the use of PC. (2) Assess treatment considerations that influenced pediatric oncologists' therapy recommendations for their most recent patient receiving PC. There were 422 participants (40.8%) who completed the survey. RESULTS: The most important factors considered by pediatric oncologists when prescribing PC were the toxicity of the chemotherapy (4.90 mean SD = 0.36 utilizing 5 point scale with 1 = not important to 5 = very important), the preferences of the family (4.57; SD = 0.60), and the potential to decrease symptoms arising from tumor burden (4.42; SD = 0.65). These treatment considerations were not as important when PC was prescribed for their most recent patient. Similarly, the chief aims in prescribing PC were not achieved for recent patients receiving PC. For their most recent patient who received PC, 40.8% believe this treatment was primarily for parental wishes. CONCLUSION: According to 80.2% of pediatric oncologists completing the survey, some patients receive chemotherapy beyond medical benefit and 40.8% of these oncologists have prescribed PC for the purpose of parental wishes to a recent patient. The chief aims in prescribing palliative chemotherapy were not achieved for recent patients.

A family psychosocial risk questionnaire for use in pediatric practice.

The objective of this study is to develop new methods to better identify psychosocial risk such that children with the greatest risk of poor future outcomes receive more intensive preventive health services. Based on structured literature review and secondary data analysis, a 52-item psychosocial risk questionnaire was administered to 2,083 families of children (<36 months). To quantify the questionnaire's construct validity, developmental concern was assessed with the Ages and Stages Questionnaire version II (ASQ) [n = 1,163]. An iterative model selection process was used to produce the most parsimonious predictive model. Model fit was examined using c-statistics, the Hosmer-Lemeshow test, and a heuristic measure of model overfit based on the fitted log-likelihood values and associated number of degrees of freedom. We found 13 items easily obtained from parental report produced a regression model with a c-statistic of 0.70. Using an integer scoring system derived from the regression model, we calculated stratum specific likelihood ratios to revise a given prior probability of ASQ failure. The posterior probability of ASQ failure was 44.9 % for a child in the highest risk group (score >25) on the questionnaire, more than double our observed average failure rate of 19.5 %, while it was less than 7 % for a child with the lowest possible score on the questionnaire. Thirteen parent-reported items can be compiled into a summary psychosocial risk questionnaire that predicts failure on developmental screening among preschool children. With further validation, this questionnaire could conceivably be used by clinicians to tailor pediatric preventive care to children at varying levels of risk.

Examination of Text Message Plans and Baseline Usage of Families Enrolled in a Text Message Influenza Vaccine Reminder Trial: Survey Study.

BACKGROUND: Mobile health (mHealth) is quickly expanding as a method of health promotion, but some interventions may not be familiar or comfortable for potential users. SMS text messaging has been investigated as a low-cost, accessible way to provide vaccine reminders. Most (97%) US adults own a cellphone and of those adults most use SMS text messaging. However, understanding patterns of SMS text message plan type and use in diverse primary care populations needs more investigation. OBJECTIVE: We sought to use a survey to examine baseline SMS text messaging and data plan patterns among families willing to accept SMS text message vaccine reminders. METHODS: As part of a National Institutes of Health (NIH)-funded national study (Flu2Text) conducted during the 2017-2018 and 2018-2019 influenza seasons, families of children needing a second seasonal influenza vaccine dose were recruited in pediatric primary care offices at the time of their first dose. Practices were from the American Academy of Pediatrics' (AAP) Pediatric Research in Office Settings (PROS) research network, the Children's Hospital of Philadelphia, and Columbia University. A survey was administered via telephone (Season 1) or electronically (Season 2) at enrollment. Standardized (adjusted) proportions for SMS text message plan type and texting frequency were calculated using logistic regression that was adjusted for child and caregiver demographics. RESULTS: Responses were collected from 1439 participants (69% of enrolled). The mean caregiver age was 32 (SD 6) years, and most children (n=1355, 94.2%) were aged 6-23 months. Most (n=1357, 94.3%) families were English-speaking. Most (n=1331, 92.8%) but not all participants had an unlimited SMS text messaging plan and sent or received texts at least once daily (n=1313, 91.5%). SMS text messaging plan type and use at baseline was uniform across most but not all subgroups. However, there were some differences in the study population's SMS text messaging plan type and usage. Caregivers who wanted Spanish SMS text messages were less likely than those who chose English to have an unlimited SMS text messaging plan (n=61, 86.7% vs n=1270, 94%; risk difference -7.2%, 95% CI -27.1 to -1.8). There were no significant differences in having an unlimited plan associated with child's race, ethnicity, age, health status, insurance type, or caregiver education level. SMS text messaging use at baseline was not uniform across all subgroups. Nearly three-quarters (n=1030, 71.9%) of participants had received some form of SMS text message from their doctor's office; most common were appointment reminders (n=1014, 98.4%), prescription (n=300, 29.1%), and laboratory notifications (n=117, 11.4%). Even the majority (n=64, 61.5%) of those who did not have unlimited plans and who texted less than daily (n=72, 59%) reported receipt of these SMS text messages. CONCLUSIONS: In this study, most participants had access to unlimited SMS text messaging plans and texted at least once daily. However, infrequent texting and lack of access to an unlimited SMS text messaging plan did not preclude enrolling to receive SMS text message reminders in pediatric primary care settings.

Pediatric Practices' Perceptions of Text Message Communication with Families: An American Academy of Pediatrics (AAP), Pediatric Research in Office Settings (PROS) Study.

Background: Text messages can be an effective and low-cost mechanism for patient reminders; however, they are yet to be consistently integrated into pediatric primary care. Objective: The aim of this study was to explore pediatric primary care clinician and staff perceptions of pediatric office text message communication with families. Methods: As part of the National Institutes of Health-funded Flu2Text randomized controlled trial of second-dose influenza vaccine text message reminders, we conducted 7 focus groups and 4 individual interviews in July-August 2019 with primary care pediatric clinicians and staff (n = 39). Overall, 10 Pediatric Research in Office Settings (PROS) pediatric practices in 10 states were selected using stratified sampling. Semi-structured discussion guides included perspectives on possible uses, perceived usefulness, and ease of use of text messages; practices' current text messaging infrastructure; and perceived barriers/facilitators to future use of texting. Two investigators independently coded and analyzed transcripts based on the technology acceptance model using NVIVO 12 Plus (intercoder reliability, K = 0.86). Results: Overall, participants were supportive of text reminders for the second-dose influenza vaccine, other vaccines, and appointments and perceived texting as a preferred method of communication for caregivers. Health information privacy and patient confidentiality were the main concerns cited. Only respondents from practices with no internal appointment text message reminder system prior to the study expressed concerns about technology implementation logistics, time, and cost. Conclusion: Text message reminders, for various uses, appear to be well accepted among a group of geographically widespread pediatric practices after participation in a trial of influenza vaccine text message reminders. Privacy, confidentiality, and resource barriers need to be addressed to facilitate successful implementation.

Performance Feedback for Human Papillomavirus Vaccination: A Randomized Trial From the American Academy of Pediatrics Pediatric Research in Office Settings Research Network.

OBJECTIVE: To test the hypothesis that a feedback-based intervention would reduce human papillomavirus (HPV) vaccine missed opportunities. METHODS: In a longitudinal cluster randomized controlled trial of 48 pediatric primary care practices, we allocated half the practices to receive a sequential, multicomponent intervention phased over consecutive periods. In a prior trial (period 1), communication skills training reduced missed opportunities for the initial HPV vaccine dose at well visits but not at acute/chronic visits. The current trial (period 2) evaluated the added value of performance feedback to clinicians after communication training. Performance feedback consisted of an introductory training module, weekly electronic "Quick Tips," and 3 individualized performance feedback reports to clinicians. We fit logistic regression models for the primary outcome of HPV vaccination missed opportunities using generalized estimating equations with independence working correlation, accounting for clustering at the practice level. RESULTS: Performance feedback resulted in a 3.4 (95% confidence interval [CI]: -6.8, 0.0) percentage point greater reduction in missed HPV vaccine opportunities for the intervention versus control group during acute/chronic visits for subsequent HPV vaccinations (dose 2 or 3). However, during well visits for HPV vaccination dose #1, intervention practices increased missed opportunities (worsened) by 4.2 (95% CI: 1.0, 7.4) percentage points more than control practices, reducing the prior period 1 improvements and blunting the overall effect of performance feedback. We did not observe differences for the other visit/dose categories. CONCLUSIONS: Performance feedback improved HPV vaccination for one subset of visits (acute/chronic, subsequent HPV vaccinations due), but not for well visits.

Missed Opportunities for Adolescent Immunizations at Well-Care Visits During the COVID-19 Pandemic.

PURPOSE: The Coronavirus Disease 2019 pandemic disrupted healthcare, but the impact on vaccination missed opportunities (MOs, vaccine-eligible visits without vaccination) is unknown. We evaluated pandemic-related trends in MOs at adolescent well-care visits for three vaccines: human papillomavirus; quadrivalent meningococcal conjugate; and tetanus, diphtheria, and acellular pertussis (Tdap). METHODS: We analyzed electronic health record data from 24 pediatric primary care practices in 13 states from 1/1/2018 to 12/31/2021. Segmented logistic regression estimated risk differences for MOs during the pandemic relative to prepandemic trends. RESULTS: Among 106,605 well-care visits, we observed decreases in MOs prepandemic followed by an increase in MOs during the pandemic for all three vaccines. Relative to prepandemic, MOs increased for human papillomavirus (+15.9%, 95% confidence interval [CI]: 11.7%, 20.1%), meningococcal conjugate (+9.4%, 95% CI: 5.2%, 13.7%), and tetanus, diphtheria, and acellular pertussis (Tdap) (+ 8.2%, 95% CI: 4.3%, 12.1%). DISCUSSION: Increases in vaccine MOs during the pandemic equaled or exceeded pre-pandemic decreases. Reducing MOs in adolescent well-care could raise vaccine coverage.

Clinician Prompts for Human Papillomavirus Vaccination: A Cluster Randomized Trial.

OBJECTIVE: We assessed the impact of an online intervention using clinician prompts for human papillomavirus (HPV) vaccination with a cluster randomized controlled trial. METHODS: The randomized trial occurred July 2021-January 2022 in 48 primary care pediatric practices (24 intervention, 24 control) across the US. We trained clinicians via two online learning modules, plus weekly ''quick tips'' delivered via text or email. The training taught practices to implement a staff prompt to the clinician (e.g., printed reminders placed on the keyboard) plus electronic health record (EHR) prompts (if not already done) at well and acute/chronic visits for initial and subsequent HPV vaccination. We assessed missed opportunities for HPV vaccination using logistic regression models accounting for clustering by practice on an intent to treat basis. Surveys assessed facilitators and barriers to using prompts. RESULTS: During the 6-month intervention, missed opportunities for HPV vaccination increased (worsened) in both intervention and control groups. However, at well child care visits, missed opportunities for the initial HPV vaccine increased by 4.5 (95% CI: -9.0%, -0.1%) percentage points less in intervention versus control practices. Change in missed opportunities for subsequent doses at well child care and non-well child care visits did not differ between trial groups. An end-of trial survey found understaffing as a common challenge. CONCLUSIONS: Clinician prompts reduced missed opportunities for HPV vaccination at well child care visits. Understaffing related to the COVID-19 pandemic may have led to worsening missed opportunities for both groups and likely impeded practices in fully implementing changes.

Home visitation program effectiveness and the influence of community behavioral norms: a propensity score matched analysis of prenatal smoking cessation.

BACKGROUND: The influence of community context on the effectiveness of evidence-based maternal and child home visitation programs following implementation is poorly understood. This study compared prenatal smoking cessation between home visitation program recipients and local-area comparison women across 24 implementation sites within one state, while also estimating the independent effect of community smoking norms on smoking cessation behavior. METHODS: Retrospective cohort design using propensity score matching of Nurse-Family Partnership (NFP) clients and local-area matched comparison women who smoked cigarettes in the first trimester of pregnancy. Birth certificate data were used to classify smoking status. The main outcome measure was smoking cessation in the third trimester of pregnancy. Multivariable logistic regression analysis examined, over two time periods, the association of NFP exposure and the association of baseline county prenatal smoking rate on prenatal smoking cessation. RESULTS: The association of NFP participation and prenatal smoking cessation was stronger in a later implementation period (35.5% for NFP clients vs. 27.5% for comparison women, p < 0.001) than in an earlier implementation period (28.4% vs. 25.8%, p = 0.114). Cessation was also negatively associated with county prenatal smoking rate, controlling for NFP program effect, (OR = 0.84 per 5 percentage point change in county smoking rate, p = 0.002). CONCLUSIONS: Following a statewide implementation, program recipients of NFP demonstrated increased smoking cessation compared to comparison women, with a stronger program effect in later years. The significant association of county smoking rate with cessation suggests that community behavioral norms may present a challenge for evidence-based programs as models are translated into diverse communities.

Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance.

PURPOSE: Impaired incretin secretion may contribute to the defective insulin secretion and abnormal glucose tolerance (AGT) that associate with worse clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). The study objective was to test the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitor-induced increases in intact incretin hormone [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] concentrations augment insulin secretion and glucagon suppression and lower postprandial glycemia in PI-CF with AGT. METHODS: 26 adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT [defined by oral glucose tolerance test glucose (mg/dL): early glucose intolerance (1-h ≥ 155 and 2-h < 140), impaired glucose tolerance (2-h ≥ 140 and < 200 mg/dL), or diabetes (2-h ≥ 200)] were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched placebo; 24 completed the trial (n = 12 sitagliptin; n = 12 placebo). Main outcome measures were mixed-meal tolerance test (MMTT) responses for intact GLP-1 and GIP, insulin secretory rates (ISRs), glucagon suppression, and glycemia and glucose-potentiated arginine (GPA) test-derived measures of ß- and α-cell function. RESULTS: Following 6-months of sitagliptin vs placebo, MMTT intact GLP-1 and GIP responses increased (P < 0.001), ISR dynamics improved (P < 0.05), and glucagon suppression was modestly enhanced (P < 0.05) while GPA test responses for glucagon were lower. No improvements in glucose tolerance or ß-cell sensitivity to glucose, including for second-phase insulin response, were found. CONCLUSIONS: In glucose intolerant PI-CF, sitagliptin intervention augmented meal-related incretin responses with improved early insulin secretion and glucagon suppression without affecting postprandial glycemia.

Effect of Training Pediatric Clinicians in Human Papillomavirus Communication Strategies on Human Papillomavirus Vaccination Rates: A Cluster Randomized Clinical Trial.

Importance: Missed opportunities for human papillomavirus (HPV) vaccination during pediatric health care visits are common. Objectives: To evaluate the effect of online communication training for clinicians on missed opportunities for HPV vaccination rates overall and at well-child care (WCC) visits and visits for acute or chronic illness (hereafter referred to as acute or chronic visits) and on adolescent HPV vaccination rates. Design, Setting, and Participants: From December 26, 2018, to July 30, 2019, a longitudinal cluster randomized clinical trial allocated practices to communication training vs standard of care in staggered 6-month periods. A total of 48 primary care pediatric practices in 19 states were recruited from the American Academy of Pediatrics Pediatric Research in Office Settings network. Participants were clinicians in intervention practices. Outcomes were evaluated for all 11- to 17-year-old adolescents attending 24 intervention practices (188 clinicians) and 24 control practices (177 clinicians). Analyses were as randomized and performed on an intent-to-treat basis, accounting for clustering by practice. Interventions: Three sequential online educational modules were developed to help participating clinicians communicate with parents about the HPV vaccine. Weekly text messages were sent to participating clinicians to reinforce learning. Statisticians were blinded to group assignment. Main Outcomes and Measures: Main outcomes were missed opportunities for HPV vaccination overall and for HPV vaccine initiation and subsequent doses at WCC and acute or chronic visits (visit-level outcome). Secondary outcomes were HPV vaccination rates (person-level outcome). Outcomes were compared during the intervention vs baseline. Results: Altogether, 122 of 188 clinicians in intervention practices participated; of these, 120, 119, and 116 clinicians completed training modules 1, 2, and 3, respectively. During the intervention period, 29 206 adolescents (14 664 girls [50.2%]; mean [SD] age, 14.2 [2.0] years) made 15 888 WCC and 28 123 acute or chronic visits to intervention practices; 33 914 adolescents (17 069 girls [50.3%]; mean [SD] age, 14.2 [2.0] years) made 17 910 WCC and 35 281 acute or chronic visits to control practices. Intervention practices reduced missed opportunities overall by 2.4 percentage points (-2.4%; 95% CI, -3.5% to -1.2%) more than controls. Intervention practices reduced missed opportunities for vaccine initiation during WCC visits by 6.8 percentage points (-6.8%; 95% CI, -9.7% to -3.9%) more than controls. The intervention had no effect on missed opportunities for subsequent doses of the HPV vaccine or at acute or chronic visits. Adolescents in intervention practices had a 3.4-percentage point (95% CI, 0.6%-6.2%) greater improvement in HPV vaccine initiation compared with adolescents in control practices. Conclusions and Relevance: This scalable, online communication training increased HPV vaccination, particularly HPV vaccine initiation at WCC visits. Results support dissemination of this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03599557.