Search

Aim: The serotonergic (5-HT) system functions in central autonomic regulation with homeostatic roles in cardiorespiratory control, thermoregulation, arousal and sleep-wake cycling. Altered function and development of this system in cases of sudden infant death syndrome (SIDS) have been established, but the aetiology of these disturbances remains unclear. The serotonin receptor, HTR2A, functions within this system with roles in the homeostatic response to hypoxia including excitatory effects on respiration, gasping and rhythm generation, all functions potentially compromised in SIDS. The objective of this study was to examine the relationship between SIDS risk and HTR2A variation. Methods: All coding regions, intron-exon boundaries and the promoter region of HTR2A were PCR amplified and analysed by standard sequencing in 96 SIDS cases and 96 matched controls. Results: Twenty-one HTR2A variations were identified in this case-control cohort, including four novel variations (c.C-1185A, c.T-923C, c.T-17C and c.C50T). None of the variations identified showed a significant association with SIDS. Conclusion: This report provides evidence that despite known alterations of the 5-HT system in SIDS, and the logical role for the HTR2A receptor, genetic variation of HTR2A as studied in our cohort is not responsible for these alterations. These results represent a further step in the investigation of the aetiology of the altered serotonin system in SIDS cases. [ABSTRACT FROM AUTHOR]

RATIONALE: Congenital central hypoventilation syndrome (CCHS), a unique disorder of respiratory control associated with Hirschsprung disease (HSCR) and tumors of neural crest origin, results from polyalanine repeat expansion mutations in the paired-like homeobox (PHOX)2B gene in more than 90% of cases, and alternative PHOX2B mutations in remaining cases. OBJECTIVES: To characterize CCHS-associated nonpolyalanine repeat mutations in PHOX2B, evaluate genotype-phenotype relationships, and compare clinical features of CCHS in cases with nonpolyalanine repeat mutations to those with polyalanine expansion mutations. METHODS: DNA from probands was analyzed by polymerase chain reaction for the common polyalanine repeat expansion. If no expansion was present, coding regions and intron-exon boundaries of PHOX2B were sequenced. When possible, parents and siblings were screened for the mutation found in the proband. RESULTS: Fourteen nonpolyalanine repeat mutations, including missense, nonsense, and frameshift mutations, and 170 polyalanine repeat mutations were identified in 184 CCHS probands. Both incomplete penetrance and parental mosaicism were observed within the family members of probands with nonpolyalanine repeat mutations. Increased prevalence of continuous ventilatory dependence, HSCR, and neural crest tumors was seen in the nonpolyalanine repeat group compared to those with polyalanine repeat mutations. CONCLUSIONS: These data suggest that nonpolyalanine repeat mutations produce more severe disruption of PHOX2B function. Patients carrying these mutations should be evaluated for HSCR and neural crest tumors. Because incomplete penetrance can occur in families of CCHS probands with PHOX2B mutations, genetic screening of appropriate family members is indicated to evaluate reproductive risk and because asymptomatic mutation carriers may be at risk for developing alveolar hypoventilation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Medical homes are health care settings that offer continuous, comprehensive, accessible primary care; these settings generally involve pediatric and family physician practices or community health centers but can also involve gynecologists or internists. OBJECTIVES: In this article, we review available evidence on the role of the medical home in optimizing adolescent immunization delivery, particularly with respect to health care utilization patterns and barriers to vaccinations in medical homes, and solutions. METHODS: We conducted a systematic review of the existing immunization and adolescent literature and used a Delphi process to solicit opinions from content experts across the United States. RESULTS: Most adolescents across the United States do have a medical home, and many pay a health care visit to their medical home within any given year. Barriers exist in regards to the receipt of adolescent immunizations, and they are related to the adolescent/family, health care provider, and health care system. Although few studies have evaluated adolescent vaccination delivery, many strategies recommended for childhood or adult vaccinations should be effective for adolescent vaccination delivery as well. These strategies include education of health care providers and adolescents/parents; having appropriate health insurance coverage; tracking and reminder/recall of adolescents who need vaccination; practice-level interventions to ensure that needed vaccinations are provided to eligible adolescents at the time of any health care visit; practice-level audits to measure vaccination coverage; and linkages across health care sites to exchange information about needed vaccinations. Medical homes should perform a quality improvement project to improve their delivery of adolescent vaccinations. Because many adolescents use a variety of health care sites, it is critical to effectively transfer vaccination information across health care settings to identify adolescents who are eligible for vaccinations and to encourage receipt of comprehensive preventive. CONCLUSIONS: Medical homes are integral to both the delivery of adolescent immunizations and comprehensive adolescent preventive health care. Many strategies recommended for childhood and adult vaccinations should work for adolescent vaccinations and should be evaluated and implemented if they are successful. By incorporating evidence-based strategies and coordinating effectively with other health care sites used by adolescents, medical homes will be the pivotal settings for the delivery of adolescent vaccinations. [ABSTRACT FROM AUTHOR]

Objectives: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor., Methods: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls., Results: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples., Discussion: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Objective. Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from>700extremely preterm infants to identify physiologic features that predict respiratory outcomes. Approach . We calculated a subset of 33 HCTSA features on>7 M 10 min windows of oxygen saturation (SPO2) and heart rate (HR) from the Pre-Vent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on>3500HCTSA algorithms. We hypothesized that the best HCTSA algorithms would compare favorably to optimal PreVent physiologic predictor IH90_DPE (duration per event of intermittent hypoxemia events below 90%). Main Results. The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90_DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90_DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850). Significance . These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90_DPE as an optimal predictor of respiratory outcomes., (Creative Commons Attribution license.)

Background: Congenital Central Hypoventilation Syndrome (CCHS) has devastating consequences if not diagnosed promptly. Despite identification of the disease-defining gene PHOX2B and a facial phenotype, CCHS remains underdiagnosed. This study aimed to incorporate automated techniques on facial photos to screen for CCHS in a diverse pediatric cohort to improve early case identification and assess a facial phenotype-PHOX2B genotype relationship., Methods: Facial photos of children and young adults with CCHS were control-matched by age, sex, race/ethnicity. After validating landmarks, principal component analysis (PCA) was applied with logistic regression (LR) for feature attribution and machine learning models for subject classification and assessment by PHOX2B pathovariant., Results: Gradient-based feature attribution confirmed a subtle facial phenotype and models were successful in classifying CCHS: neural network performed best (median sensitivity 90% (IQR 84%, 95%)) on 179 clinical photos (versus LR and XGBoost, both 85% (IQR 75-76%, 90%)). Outcomes were comparable stratified by PHOX2B genotype and with the addition of publicly available CCHS photos (n = 104) using PCA and LR (sensitivity 83-89% (IQR 67-76%, 92-100%)., Conclusions: Utilizing facial features, findings suggest an automated, accessible classifier may be used to screen for CCHS in children with the phenotype and support providers to seek PHOX2B testing to improve the diagnostics., Impact: Facial landmarking and principal component analysis on a diverse pediatric and young adult cohort with PHOX2B pathovariants delineated a distinct, subtle CCHS facial phenotype. Automated, low-cost machine learning models can detect a CCHS facial phenotype with a high sensitivity in screening to ultimately refer for disease-defining PHOX2B testing, potentially addressing gaps in disease underdiagnosis and allow for critical, timely intervention., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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., Competing Interests: Declaration of Competing Interest Dr. Humiston has the following conflicts of interest: until 9/2022, Dr. Humiston’s employer received grant money for her work sponsored by the Pediatric Infectious Diseases Society (PIDS) Foundation, a not-for-profit organization. PIDS is funded for the project through unrestricted joint educational grants from Sanofi US, Merck & Co., Inc., Pfizer, Inc., GlaxoSmithKline, and Seqirus USA, Inc., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: With contemporaneous advances in congenital central hypoventilation syndrome (CCHS), recognition, confirmatory diagnostics with PHOX2B genetic testing, and conservative management to reduce the risk of early morbidity and mortality, the prevalence of identified adolescents and young adults with CCHS and later-onset (LO-) CCHS has increased. Accordingly, there is heightened awareness and need for transitional care of these patients from pediatric medicine into a multidisciplinary adult medical team. Hence, this review summarizes key clinical and management considerations for patients with CCHS and LO-CCHS and emphasizes topics of particular importance for this demographic., Methods: We performed a systematic review of literature on diagnostics, pathophysiology, and clinical management in CCHS and LO-CCHS, and supplemented the review with anecdotal but extensive experiences from large academic pediatric centers with expertise in CCHS., Results: We summarized our findings topically for an overview of the medical care in CCHS and LO-CCHS specifically applicable to adolescents and adults. Care topics include genetic and embryologic basis of the disease, clinical presentation, management, variability in autonomic nervous system dysfunction, and clarity regarding transitional care with unique considerations such as living independently, family planning, exposure to anesthesia, and alcohol and drug use., Conclusions: While a lack of experience and evidence exists in the care of adults with CCHS and LO-CCHS, a review of the relevant literature and expert consensus provides guidance for transitional care areas., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents., Methods: The literature (1965-2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause., Results: ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions., Conclusion: ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare disorders of autonomic regulation with risk for disrupted neurocognitive development. Our aim is to summarize research on neurocognitive outcomes in these conditions, advance understanding of how to best support these individuals throughout development, and facilitate future research., Methods: We conducted a narrative review of literature on neurocognitive outcomes in CCHS and ROHHAD, supplemented with previously unpublished data from patients with CCHS and ROHHAD at our Center for Autonomic Medicine in Pediatrics (CAMP)., Results: Individuals with CCHS and ROHHAD experience a wide range of neurocognitive functioning ranging from above average to below average, but are at particular risk for difficulties with working memory, processing speed, perceptual reasoning, and visuographic skills. An assessment framework emphasizing fluid cognition seems especially appropriate for these conditions. Owing to small cohorts and varied methods of data collection, it has been difficult to identify associations between disease factors (including CCHS PHOX2B genotypes) and cognitive outcomes. However, results suggest that early childhood is a period of particular vulnerability, perhaps due to the disruptive impact of recurrent intermittent hypoxic episodes on brain and cognitive development., Conclusion: Neurocognitive monitoring is recommended as a component of routine clinical care in CCHS and ROHHAD as a marker of disease status and to ensure that educational support and disability accommodations are provided as early as possible. Collaborative efforts will be essential to obtain samples needed to enhance our understanding of neurocognitive outcomes in CCHS and ROHHAD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Disorders of autonomic functions are typically characterized by disturbances in multiple organ systems. These disturbances are often comorbidities of common and rare diseases, such as epilepsy, sleep apnea, Rett syndrome, congenital heart disease or mitochondrial diseases. Characteristic of many autonomic disorders is the association with intermittent hypoxia and oxidative stress, which can cause or exaggerate a variety of other autonomic dysfunctions, making the treatment and management of these syndromes very complex. In this review we discuss the cellular mechanisms by which intermittent hypoxia can trigger a cascade of molecular, cellular and network events that result in the dysregulation of multiple organ systems. We also describe the importance of computational approaches, artificial intelligence and the analysis of big data to better characterize and recognize the interconnectedness of the various autonomic and non-autonomic symptoms. These techniques can lead to a better understanding of the progression of autonomic disorders, ultimately resulting in better care and management., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Children and young adults with congenital central hypoventilation syndrome (CCHS) are at risk of cognitive deficits. They experience autonomic dysfunction and chemoreceptor insensitivity measured during ventilatory and orthostatic challenges, but relationships between these features are undefined., Research Question: Can a biomarker be identified from physiologic responses to ventilatory and orthostatic challenges that is related to neurocognitive outcomes in CCHS?, Study Design and Methods: This retrospective study included 25 children and young adults with CCHS tested over an inpatient stay. Relationships between physiologic measurements during hypercarbic and hypoxic ventilatory challenges, hypoxic ventilatory challenges, and orthostatic challenges and neurocognitive outcomes (by Wechsler intelligence indexes) were examined. Independent variable inclusion was determined by significant associations in Pearson's analyses. Multivariate linear regressions were used to assess relationships between measured physiologic responses to challenges and neurocognitive scores., Results: Significant relationships were identified between areas of fluid intelligence and measures of oxygen saturation (SpO 2 ) and heart rate (HR) during challenges. Specifically, perceptual reasoning was related to HR (adjusted regression [β] coefficient, -0.68; 95% CI, 1.24 to -0.12; P = .02) during orthostasis. Working memory was related to change in HR (β, -1.33; 95% CI, -2.61 to -0.05; P = .042) during the hypoxic ventilatory challenge. Processing speed was related to HR (β, -1.19; 95% CI, -1.93 to -0.46; P = .003) during orthostasis, to baseline SpO 2 (hypercarbic and hypoxic β, 8.57 [95% CI, 1.63-15.51]; hypoxic β, 8.37 [95% CI, 3.65-13.11]; P = .002 for both) during the ventilatory challenges, and to intrachallenge SpO 2 (β, 5.89; 95% CI, 0.71-11.07; P = .028) during the hypoxic ventilatory challenge., Interpretation: In children and young adults with CCHS, SpO 2 and HR-or change in HR-at rest and as a response to hypoxia and orthostasis are related to cognitive outcomes in domains of known risk, particularly fluid reasoning. These findings can guide additional research on the usefulness of these as biomarkers in understanding the impact of daily physical stressors on neurodevelopment in this high-risk group., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is an ultra-rare neurocristopathy with no known genetic or environmental etiology. Rapid-onset obesity over a 3-12 month period with onset between ages 1.5-7 years of age is followed by an unfolding constellation of symptoms including severe hypoventilation that can lead to cardiorespiratory arrest in previously healthy children if not identified early and intervention provided. Congenital Central Hypoventilation syndrome (CCHS) and Prader-Willi syndrome (PWS) have overlapping clinical features with ROHHAD and known genetic etiologies. Here we compare patient neurons from three pediatric syndromes (ROHHAD, CCHS, and PWS) and neurotypical control subjects to identify molecular overlap that may explain the clinical similarities., Methods: Dental pulp stem cells (DPSC) from neurotypical control, ROHHAD, and CCHS subjects were differentiated into neuronal cultures for RNA sequencing (RNAseq). Differential expression analysis identified transcripts variably regulated in ROHHAD and CCHS vs. neurotypical control neurons. In addition, we used previously published PWS transcript data to compare both groups to PWS patient-derived DPSC neurons. Enrichment analysis was performed on RNAseq data and downstream protein expression analysis was performed using immunoblotting., Results: We identified three transcripts differentially regulated in all three syndromes vs. neurotypical control subjects. Gene ontology analysis on the ROHHAD dataset revealed enrichments in several molecular pathways that may contribute to disease pathology. Importantly, we found 58 transcripts differentially expressed in both ROHHAD and CCHS patient neurons vs. control neurons. Finally, we validated transcript level changes in expression of ADORA2A , a gene encoding for an adenosine receptor, at the protein level in CCHS neurons and found variable, although significant, changes in ROHHAD neurons., Conclusions: The molecular overlap between CCHS and ROHHAD neurons suggests that the clinical phenotypes in these syndromes likely arise from or affect similar transcriptional pathways. Further, gene ontology analysis identified enrichments in ATPase transmembrane transporters, acetylglucosaminyltransferases, and phagocytic vesicle membrane proteins that may contribute to the ROHHAD phenotype. Finally, our data imply that the rapid-onset obesity seen in both ROHHAD and PWS likely arise from different molecular mechanisms. The data presented here describes important preliminary findings that warrant further validation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Victor, Hedgecock, Donaldson, Johnson, Rand, Weese-Mayer and Reiter.)

The American College of Obstetrics and Gynecology recommends influenza vaccine annually, Tdap with each pregnancy, and COVID-19 vaccine for those not previously vaccinated or who are due for boosters. The influenza and COVID-19 vaccines are safe during pregnancy and are effective in reducing morbidity in both the pregnant person and infant. The Tdap vaccine is given primarily to protect the newborn from pertussis through transplacental antibody transfer. Methods to enhance vaccination rates include stocking and giving vaccines in the obstetric office, recommending eligible vaccines at each visit, and focusing on the health of the infant in conversations with patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Despite the seriousness of influenza and pertussis, availability of safe and effective vaccines against them, and long-standing maternal vaccination recommendations, US maternal influenza and Tdap vaccination rates have been low. To increase vaccination rates in obstetric offices, it is important to understand clinician perspectives and office processes. We conducted in-depth interviews with nurses and providers on these topics., Methods: Interviewees worked in obstetric offices in one-of-four participating health systems in NY and CA. We audio-recorded and transcribed 20-30-min interviews. We used predetermined categories to code interviews with Dedoose, then iteratively refined codes and identified themes., Results: We conducted 20 interviews between 4/2020 and 9/2020: 13 providers (physician or nurse midwife) (5 NY, 8 CA); 7 office nurses (6 NY, 1 CA). In almost all offices, patient refusal of influenza vaccine was considered the major vaccination barrier; Tdap was often deferred by patients until post-delivery. Nurse-only visits for either vaccine were rare. Vaccination outside the office was uncommon; few offices systematically documented vaccines given elsewhere in a retrievable manner. Participants emphasized patient education as key to prenatal care, but the number of topics left little time for immunizations. Few interviewees could identify an office "immunization champion," knew their office vaccination rates, or had participated in vaccination quality improvement. Several interviewees indicated that they or another provider were good at persuading hesitant patients, but their method had not been shared with other clinicians., Conclusions for Practice: Multiple practical barriers and maternal vaccine hesitancy limit maternal vaccination. Quality improvement strategies are needed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy, caused by mutations in the paired-like homeobox gene PHOX2B, which alters control of breathing and autonomic nervous system regulation, necessitating artificial ventilation as life-support. A broad range of neurocognitive performance has been reported in CCHS, including an array of cognitive deficits. We administered the NIH Toolbox® Cognition Battery (NTCB), a novel technology comprised of seven tasks presented via an interactive computer tablet application, to a CCHS cohort and studied its convergent and divergent validity relative to traditional clinical neurocognitive measures. The NTCB was administered to 51 CCHS participants, including a subcohort of 24 who also received traditional clinical neurocognitive testing (Wechsler Intelligence Scales). Age-corrected NTCB scores from the overall sample and subcohort were compared to population norms. Associations between NTCB indices and Wechsler Intelligence scores were studied to determine the convergent and divergent validity of the NTCB. NTCB test results indicated reduced Fluid Cognition, which measures new learning and speeded information processing (p < 0.001), but intact Crystallized Cognition, which measures past learning, in CCHS relative to population norms. Moderate to strong associations (r > 0.60) were found between age-corrected NTCB Fluid and Crystallized indices and comparable Wechsler indices, supporting the convergent and discriminant validity of the NTCB. Results reveal deficits of Fluid Cognition in individuals with CCHS and indicate that the NTCB is a valid and sensitive measure of cognitive outcomes in this population. Our findings suggest that the NTCB may play a useful role in tracking neurocognition in CCHS., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Although maternal vaccination with influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines improve health outcomes for pregnant individuals and infants, maternal vaccination rates are low. This study assessed obstetric providers' attitudes and practices related to influenza and Tdap vaccination in four large health systems in New York (NY) and California (CA). Methods: We conducted a cross-sectional survey of all obstetric providers within four health systems (two in NY, two in CA) to evaluate provider attitudes and office systems used for Tdap and influenza vaccination. The survey assessed perceptions of influenza and Tdap vaccination based on the Health Belief Model, and assessed office systems (reminders, prompts, standing orders, and patient education) and communication with pregnant patients related to influenza and Tdap vaccines. Results: We had 112 responses (52% response rate) for analyses. Respondents strongly supported vaccination during pregnancy but viewed influenza disease as less of a concern for newborns than for pregnant individuals (40% vs. 67% considered influenza disease to be very significant, p  < 0.001). Only 84% agreed that giving influenza vaccine in the first trimester is very safe. Patient vaccine refusal was the most commonly named barrier for both influenza and Tdap vaccination. Providers frequently used office system prompts, but did not frequently use standing orders, patient educational materials, vaccine champions, and feedback on vaccination rates. Conclusions: While most providers consider influenza and Tdap vaccination important during pregnancy, there is room for improvement in focusing on the importance of maternal vaccination to the health of the infant, and increasing the use of office systems to improve vaccination during pregnancy.

Rationale: Congenital central hypoventilation syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia/hypoxia in CCHS raises the concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment. Objectives: To evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases versus controls. Methods: CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. Fifty CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (regional oxygen saturation) were continuously monitored. The cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated. Measurements and Main Results: HUT resulted in a greater mean BP decrease from baseline in CCHS versus controls (11% vs. 6%; P  < 0.05) and a diminished increase in HR in CCHS versus controls (11% vs. 18%; P  < 0.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx ( P  < 0.01) and a 29% increase in minutes of impaired autoregulation ( P  < 0.02) in CCHS versus controls (4.0 vs. 3.1 min). Conclusions: Cerebral autoregulatory mechanisms appear to be intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx/impaired autoregulation when BP is below the lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.

Purpose: CCHS is an extremely rare congenital disorder requiring artificial ventilation as life support. Typically caused by heterozygous polyalanine repeat expansion mutations (PARMs) in the PHOX2B gene, identification of a relationship between PARM length and phenotype severity has enabled anticipatory management. However, for patients with non-PARMs in PHOX2B (NPARMs, ~10% of CCHS patients), a genotype-phenotype correlation has not been established. This comprehensive report of PHOX2B NPARMs and associated phenotypes, aims at elucidating potential genotype-phenotype correlations that will guide anticipatory management., Methods: An international collaboration (clinical, commercial, and research laboratories) was established to collect/share information on novel and previously published PHOX2B NPARM cases. Variants were categorized by type and gene location. Categorical data were analyzed with chi-square and Fisher's exact test; further pairwise comparisons were made on significant results., Results: Three hundred two individuals with PHOX2B NPARMs were identified, including 139 previously unreported cases. Findings demonstrate significant associations between key phenotypic manifestations of CCHS and variant type, location, and predicted effect on protein function., Conclusion: This study presents the largest cohort of PHOX2B NPARMs and associated phenotype data to date, enabling genotype-phenotype studies that will advance personalized, anticipatory management and help elucidate pathological mechanisms. Further characterization of PHOX2B NPARMs demands longitudinal clinical follow-up through international registries., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Objective: Patients with a new diagnosis of attention-deficit/hyperactivity disorder (ADHD) who are prescribed stimulant medication need regular follow-up. Guidelines recommend follow-up within 30 days of stimulant initiation or change but this goal is seldom achieved. This quality improvement (QI) study in an urban academic outpatient practice aimed to: 1) assess whether use of school-based telemedicine increases rates of follow-up within 30 days and decreases the number of days to follow-up for ADHD, and 2) compare rates of 30-day follow-up via in-person vs telemedicine visits., Methods: We performed three Plan-Do-Study-Act cycles over a 12-month period: QI interventions included clinic wide education, paper prompts for clinicians, and creation of a database to track ADHD patients. We measured days from the index visit to the follow-up visit, and the mode of both visits (in-person or telemedicine). Data were collected for 6 months pre-intervention and 12 months post-intervention., Results: Follow-up within 30 days increased from 19% (of 191 visits) to 33% (of 661 visits) (P < .001). The time to follow-up decreased from 67 to 34 days (P < .001). Follow up visits by telemedicine were more also more likely to be within 30 days (62% vs. 32%, P < .001)., Discussion: A QI intervention for ADHD care increased rates of follow-up within 30 days, particularly when telemedicine was used, and decreased the number of days to follow-up. This intervention could serve as a model to improve follow-up for ADHD in other settings., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Indwelling arterial lines, the clinical gold standard for continuous blood pressure (BP) monitoring in the pediatric intensive care unit (PICU), have significant drawbacks due to their invasive nature, ischemic risk, and impediment to natural body movement. A noninvasive, wireless, and accurate alternative would greatly improve the quality of patient care. Recently introduced classes of wireless, skin-interfaced devices offer capabilities in continuous, precise monitoring of physiologic waveforms and vital signs in pediatric and neonatal patients, but have not yet been employed for continuous tracking of systolic and diastolic BP-critical for guiding clinical decision-making in the PICU. The results presented here focus on materials and mechanics that optimize the system-level properties of these devices to enhance their reliable use in this context, achieving full compatibility with the range of body sizes, skin types, and sterilization schemes typically encountered in the PICU. Systematic analysis of the data from these devices on 23 pediatric patients, yields derived, noninvasive BP values that can be quantitatively validated against direct recordings from arterial lines. The results from this diverse cohort, including those under pharmacological protocols, suggest that wireless, skin-interfaced devices can, in certain circumstances of practical utility, accurately and continuously monitor BP in the PICU patient population., (© 2021 Wiley-VCH GmbH.)

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.

Robust literature supports the positive effects of kangaroo mother care (KMC) on infant physiologic stability and parent-infant bonding in the Neonatal Intensive Care Unit (NICU). Comparatively little is known about kangaroo father care (KFC) in the NICU, and KFC implementation has been limited. Our pilot feasibility study objective was to examine KFC effects on premature infants and fathers as compared to KMC. Parents of preterm NICU infants independently completed a 90-min Kangaroo Care (KC) session on consecutive days. Infant heart rate variability (HRV) and apnea/periodicity measures were compared (pre-KC to KC; KFC to KMC). Additionally, we assessed the feasibility of administering three psychosocial questionnaires to fathers and mothers in the NICU and after discharge. Ten preterm infants completed 20 KC sessions (33 4/7 -37 4/7  weeks post-menstrual age). Results demonstrated similar infant physiologic responses between KMC and KFC, including significant differences in measures of HRV (p < .05) between KC and non-KC periods. Eighty-eight percentage of questionnaires administered were completed, supporting the utilization of these instruments in future research of this population. If confirmed, these preliminary results identify an opportunity to objectively assess KFC effects, supporting the development of empirically based KFC programs benefitting NICU families., (© 2021 Wiley Periodicals LLC.)

The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source-detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

The objectives of this study were to assess the contextual factors, practice strategies, and sustainability of interventions implemented during a national quality improvement (QI) project to raise human papillomavirus (HPV) vaccination rates. We conducted semistructured interviews with positive deviant practices that successfully reduced missed opportunities by ≥20% for HPV vaccination in the prior year. We assessed leadership support, motivators, interventions used, and sustainability. Key themes related to QI teams included strong leadership support, multidisciplinary teams, having a practice champion, and a collaborative environment. Themes related to the interventions included using a presumptive bundled recommendation for all appropriate vaccines at age 11, previsit planning, and reminders for preventive visits, which were sustainable for most practices 1-year postintervention. Both internal practice-level factors (multidisciplinary teams, collaboration, and previsit planning) and organizational factors (institutional support and health system-level reminders for preventive visits) were key to a successful QI intervention to improve HPV vaccination.

Human papillomavirus (HPV) vaccination rates are well below the Healthy People 2020 goal of 80%. Vaccinating in settings other than primary care, such as local health departments (LHDs), may help achieve higher HPV immunization rates. We tested the effect of a quality improvement (QI) collaborative to reduce missed opportunities (MOs) for HPV vaccine in LHDs. Between 2016 and 2019, we conducted four consecutive cohorts of a virtual QI collaborative at 24 LHDs across multiple states. Participants were trained on topics including how to provide an effective recommendation for HPV vaccine, strategies to reduce MOs, and motivational interviewing. Throughout the 6-month project implementation, LHDs tested strategies to reduce MOs through Plan-Do-Study-Act cycles, performed chart reviews to identify and characterize MOs, and received feedback reports to assess progress on MOs. HPV vaccination rates were assessed pre- and post-intervention. LHDs reduced MOs for HPV vaccine in all four cohorts with aggregated data showing a 25.3 percentage point reduction in MOs. Modified Poisson regression analysis found a 44% reduction in the relative risk of missing the opportunity for an HPV vaccine at a visit (RR = 0.56, 0.46-0.68, p < .001). This project shows that strategies effective in reducing MO for HPV vaccine in primary care settings are also effective in LHD settings. Training LHD staff on these strategies may help the U.S. approach national goals for HPV vaccine coverage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: While many clinicians encounter parents or adolescents who refuse HPV vaccine, little is known about the prevalence of hesitancy for HPV vaccine nationally or its association with vaccination., Methods: In April 2019, we surveyed families with adolescents 11-17 years using a national online panel (Knowledge Panel®) as the sampling frame. We assessed the prevalence of HPV vaccine hesitancy with the validated 9-item Vaccine Hesitancy Scale (VHS). We used multivariate analyses to assess demographic factors associated with HPV vaccine hesitancy. We also assessed practical barriers to receipt of HPV vaccine and the relationship between barriers and hesitancy. Finally, we evaluated the association between both HPV vaccine hesitancy and practical barriers on HPV vaccine receipt or refusal., Results: 2,177 parents out of 4,185 sampled (52%) completed the survey, 2,020 qualified (lived with adolescent). Using a VHS cut-off score > 3 out of 5 points, 23% of US parents were hesitant about HPV vaccine. Hesitancy was lower among those with Hispanic ethnicity. At least one out of five parents disagreed that the HPV vaccine is beneficial for their adolescent, that the vaccine is effective, protects against HPV-related cancers, or that they followed their adolescent's health-care provider's recommendation about the vaccine. Many were concerned about vaccine side effects and the novelty of the vaccine. Adolescents living with vaccine-hesitant parents were less than one-third as likely to have received the vaccine (RR = 0.29, 95% CI 0.24, 0.35) or completed the vaccine series (RR = 0.29, 95% CI 0.23, 0.36), and were 6-fold more likely to have refused the vaccine because of parental vaccine-related concerns (RR = 6.09, 95% CI = 5.26, 7.04). Most practical barriers were independently associated with vaccine receipt but not with vaccine refusal., Conclusions: HPV vaccine hesitancy is common nationally and strongly related to both under-vaccination and vaccine refusal., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: G. Zimet has received honoraria and travel support from Merck for consultations related to HPV vaccination and honoraria from Sanofi Pasteur for work on the Adolescent Immunization Initiative. S. Humiston has received an honorarium and travel support from Sanofi Pasteur for work on vaccine hesitancy but not specific to this study or manuscript., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Influenza vaccination rates across the US are low. Because few practices send patient reminders for influenza vaccination, a scalable patient reminder system is needed., Objective: To evaluate the effect of patient reminders sent via a health care system's electronic health record patient portal on influenza vaccination rates., Design, Setting, and Participants: This pragmatic, 4-arm randomized clinical trial was performed from October 1, 2018, to March 31, 2019, across the UCLA (University of California, Los Angeles) health care system. A total of 164 205 patients in 52 primary care practices who had used the patient portal within 12 months were included., Interventions: Patients due for an influenza vaccine were sent a letter via the patient portal of the health care system reminding them about the importance of influenza vaccination, safety of the vaccine, and morbidity associated with influenza. Patients were randomized within primary care practices to 1 of 4 study groups (no reminder [n = 41 070] vs 1 reminder [n = 41 055], 2 reminders [n = 41 046], or 3 reminders [n = 41 034])., Main Outcomes and Measures: The primary outcome was receipt of 1 or more influenza vaccines as documented in the electronic health record, which was supplemented with influenza vaccination data from external sources (eg, pharmacies). Secondary outcomes were influenza vaccination rates among subgroups and influenza vaccinations self-reported by patients in reply to the portal-based query as having been received elsewhere., Results: A total of 164 205 patients (mean [SD] age, 46.2 [19.6] years; 95 779 [58.3%] female) were randomly allocated to 1 of the 4 study arms. In the primary analysis across all ages and not including patient self-reported vaccinations in reply to portal reminders, influenza vaccination rates were 37.5% for those receiving no reminders, 38.0% for those receiving 1 reminder (P = .008 vs no reminder), 38.2% for those receiving 2 reminders (P = .03 vs no reminder), and 38.2% for those receiving 3 reminders (P = .02 vs no reminder). In the secondary analysis not including patient self-reported vaccinations, among adults aged 18 to 64 years (vaccination rates: 32.0% in the control group, 32.8% in the 1-reminder group, 32.8% in the 2-reminder group, and 32.8% in the 3-reminder group; P = .001), male patients (vaccination rates: 37.3% vs 38.3%, 38.6%, and 38.8%; P = .001), non-Hispanic patients (vaccination rates: 37.6% vs 38.2%, 38.3%, and 38.2%; P = .004), and those who were not vaccinated in the prior 2 years (vaccination rates: 15.3% vs 15.9%, 16.3%, and 16.1%; P < .001), vaccination rates were higher in the portal reminder groups than in the control group; the findings in these 3 subgroups mirrored the findings in the entire population. When self-reported vaccinations received elsewhere were included, influenza vaccination rates were 1.4 to 2.9 percentage points higher in the portal reminder groups, with a dose-response effect (0 reminders: 15 537 [37.8%]; 1 reminder: 16 097 [39.2%]; 2 reminders: 16 426 [40.0%]; and 3 reminders: 16 714 [40.7%]; P < .001)., Conclusions and Relevance: Generic patient portal reminders were effective in minimally increasing influenza vaccination rates, but more intensive or more targeted patient motivational strategies appear to be needed., Trial Registration: ClinicalTrials.gov Identifier: NCT03666026.

Objective: To evaluate the effect of different modalities of centralized reminder/recall (autodialer, text, mailed reminders) on increasing childhood influenza vaccination., Study Design: Two simultaneous randomized clinical trials conducted from October 2017 to April 1, 2018, in New York State and Colorado. There were 61 931 children in New York (136 practices) and 23 845 children in Colorado (42 practices) who were randomized to different centralized reminder/recall modalities-4 arms in New York (autodialer, text, mailed, and no reminder control) and 3 arms in Colorado (autodialer, mailed, and no reminder control). The message content was similar across modalities. Up to 3 reminders were sent for intervention arms. The main outcome measure was receipt of ≥1 influenza vaccine., Results: In New York, compared with the control arm (26.6%), postintervention influenza vaccination rates in the autodialer arm (28.0%) were 1.4 percentage points higher (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10), but the rates for text (27.6%) and mail (26.8%) arms were not different from controls. In Colorado, compared with the control arm (29.9%), postintervention influenza vaccination rates for the autodialer (32.9%) and mail (31.5%) arms were 3.0 percentage points (adjusted risk ratio, 1.08; 95% CI, 1.03-1.12) and 1.6 percentage points (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10) higher, respectively. Compared with the control arm, the incremental cost per additional vaccine delivered was $20 (New York) and $16 (Colorado) for autodialer messages., Conclusions: Centralized reminder/recall for childhood influenza vaccine was most effective via autodialer, less effective via mail, and not effective via text messages. The impact of each modality was modest. Compared with no reminders, the incremental cost per additional vaccine delivered was also modest for autodialer messages., Trial Registration: ClinicalTrials.gov: NCT03294473 and NCT03246100., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Standard clinical care in neonatal and pediatric intensive-care units (NICUs and PICUs, respectively) involves continuous monitoring of vital signs with hard-wired devices that adhere to the skin and, in certain instances, can involve catheter-based pressure sensors inserted into the arteries. These systems entail risks of causing iatrogenic skin injuries, complicating clinical care and impeding skin-to-skin contact between parent and child. Here we present a wireless, non-invasive technology that not only offers measurement equivalency to existing clinical standards for heart rate, respiration rate, temperature and blood oxygenation, but also provides a range of important additional features, as supported by data from pilot clinical studies in both the NICU and PICU. These new modalities include tracking movements and body orientation, quantifying the physiological benefits of skin-to-skin care, capturing acoustic signatures of cardiac activity, recording vocal biomarkers associated with tonality and temporal characteristics of crying and monitoring a reliable surrogate for systolic blood pressure. These platforms have the potential to substantially enhance the quality of neonatal and pediatric critical care.

Purpose: To determine if variables of the pupillary light response mature with age and sex in a healthy pediatric cohort and the utility of pupillometry in assessment among pediatric participants., Methods: After 1 min in a dark room to establish baseline, pupillometry was performed on 323 healthy, pediatric participants (646 eyes; 2-21 years; 175 females). Variables included initial pupil diameter, pupil diameter after light stimulus, percent pupillary constriction, latency to onset of constriction, average constriction velocity, maximum constriction velocity, average dilation velocity, and time from light stimulus to 75% of the initial pupil diameter. Data analyses employed ANOVAs and non-linear regressions., Results: Analyses of age group differences revealed that participants 12-21 years old had a larger initial pupil diameter and pupil diameter after light stimulus, with males aged 12-18 years demonstrating a larger pupil diameter than all younger participants (ps < 0.05). Participants 12-18 years old had a slower maximum constriction velocity than participants 6-11 years old, with no sex differences (ps < 0.05). Furthermore, males aged 12-18 years old had a smaller percent constriction than males 6-11 years old (ps < 0.05). Regressions revealed that percent constriction and dilation velocity seemed to mature linearly, initial pupil diameter and ending pupil diameter matured quadratically, and the constriction velocity terms matured cubically., Conclusions: Results revealed maturation of the pupillary light response by age and sex in healthy pediatric participants. Given the value of the pupillary light response as a biomarker, the results provide normative benchmarks for comparison in health and disease, including opiate-exposed and concussion patients.

Background: Only half of US schoolchildren receive influenza vaccine. School-located influenza vaccination (SLIV) might raise vaccination rates but conducting flu vaccine clinics at schools is challenging to implement. We compared 2 school-based programs designed to raise influenza vaccination rates: parent reminder/educational messages sent to parents from schools which is a low-intensity intervention vs the combination of reminder/educational messages plus SLIV clinics which is a high-intensity intervention., Methods: We assigned 36 schools (6 school districts, 2 per group) to 3 groups: (1) control, ie, no SLIV and no parent reminder/education, (2) parent reminder/education emailed by schools, and (3) parent reminder/education plus SLIV clinics. Some schools had SLIV clinics in prior years. Health department nurses conducted SLIV clinics., Results: Among 24,832 children at 36 schools, vaccination rates were control (51.3%), parent reminder/education-only (41.2%), and reminder/education + SLIV (58.7%). On multivariate analyses which controlled for vaccination in prior seasons, children in reminder/education + SLIV schools had higher vaccination rates (OR 1.27, 95% CI 1.10-1.47), but children in reminder/education-only schools had lower rates (OR 0.87, 95% CI 0.75-1.00) than children in control schools., Conclusions: Parent reminder/education combined with SLIV clinics raise vaccination rates, but parent reminder/education alone does not., (© 2019, American School Health Association.)

Background: Studies have noted variations in the cost-effectiveness of school-located influenza vaccination (SLIV), but little is known about how SLIV's cost-effectiveness may vary by targeted age group (e.g., elementary or secondary school students), or vaccine consent process (paper-based or web-based). Further, SLIV's cost-effectiveness may be impacted by its spillover effect on practice-based vaccination; prior studies have not addressed this issue., Methods: We performed a cost-effectiveness analysis on two SLIV programs in upstate New York in 2015-2016: (a) elementary school SLIV using a stepped wedge design with schools as clusters (24 suburban and 18 urban schools) and (b) secondary school SLIV using a cluster randomized trial (16 suburban and 4 urban schools). The cost-per-additionally-vaccinated child (i.e., incremental cost-effectiveness ratio (ICER)) was estimated by dividing the incremental SLIV intervention cost by the incremental effectiveness (i.e., the additional number of vaccinated students in intervention schools compared to control schools). We performed deterministic analyses, one-way sensitivity analyses, and probabilistic analyses., Results: The overall effectiveness measure (proportion of children vaccinated) was 5.7 and 5.5 percentage points higher, respectively, in intervention elementary (52.8%) and secondary schools (48.2%) than grade-matched control schools. SLIV programs vaccinated a small proportion of children in intervention elementary (5.2%) and secondary schools (2.5%). In elementary and secondary schools, the ICER excluding vaccine purchase was $85.71 and $86.51 per-additionally-vaccinated-child, respectively. When additionally accounting for observed spillover impact on practice-based vaccination, the ICER decreased to $80.53 in elementary schools -- decreasing substantially in secondary schools. (to $53.40). These estimates were higher than the published practice-based vaccination cost (median = $25.50, mean = $45.48). Also, these estimates were higher than our 2009-2011 urban SLIV program mean costs ($65) due to additional costs for use of a new web-based consent system ($12.97 per-additionally-vaccinated-child) and higher project coordination costs in 2015-2016. One-way sensitivity analyses showed that ICER estimates were most sensitive to the SLIV effectiveness., Conclusions: SLIV raises vaccination rates and may increase practice-based vaccination in primary care practices. While these SLIV programs are effective, to be as cost-effective as practice-based vaccination our SLIV programs would need to vaccinate more students and/or lower the costs for consent systems and project coordination., Trial Registration: ClinicalTrials.gov NCT02227186 (August 25, 2014), updated NCT03137667 (May 2, 2017).

Half of US school children receive influenza vaccine. In our previous trials, school-located influenza vaccination (SLIV) raised vaccination rates by 5 to 8 percentage points. We assessed whether text message reminders to parents could raise vaccination rates above those observed with SLIV. Within urban elementary schools we randomized families into text message + SLIV (intervention) versus SLIV alone (comparison). All parents were sent 2 backpack notifications plus 2 autodialer phone reminders about SLIV at a single SLIV clinic. Intervention group parents also were sent 3 text messages from the school nurse encouraging flu vaccination via either primary care or SLIV. Among 15 768 children at 32 schools, vaccination rates were text + SLIV (40%) and SLIV control (40%); 4% of students per group received influenza vaccination at SLIV. Text message reminders did not raise influenza vaccination rates above those observed with SLIV alone. More intensive interventions are needed to raise influenza vaccination rates.