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Rick M Gardner Department of Psychology, University of Colorado Denver, Denver, CO, USA Abstract: Understanding the role of body size in relation to the accuracy of body image perception in men is an important topic because of the implications for avoiding and treating obesity, and it may serve as a potential diagnostic criterion for eating disorders. The early research on this topic produced mixed findings. About one-half of the early studies showed that obese men overestimated their body size, with the remaining half providing accurate estimates. Later, improvements in research technology and methodology provided a clearer indication of the role of weight status in body image perception. Research in our laboratory has also produced diverse findings, including that obese subjects sometimes overestimate their body size. However, when examining our findings across several studies, obese subjects had about the same level of accuracy in estimating their body size as normal-weight subjects. Studies in our laboratory also permitted the separation of sensory and nonsensory factors in body image perception. In all but one instance, no differences were found overall between the ability of obese and normal-weight subjects to detect overall changes in body size. Importantly, however, obese subjects are better at detecting changes in their body size when the image is distorted to be too thin as compared to too wide. Both obese and normal-weight men require about a 3%–7% change in the width of their body size in order to detect the change reliably. Correlations between a range of body mass index values and body size estimation accuracy indicated no relationship between these variables. Numerous studies in other laboratories asked men to place their body size into discrete categorizes, ranging from thin to obese. Researchers found that overweight and obese men underestimate their weight status, and that men are less accurate in their categorizations than are women. Cultural influences have been found to be important, with body size underestimations occurring in cultures where a larger body is found to be desirable. Methodological issues are reviewed with recommendations for future studies. Keywords: body size, men, weight status, body image, body perception, literature review

Objective: To evaluate the data quality of ventilator settings recorded by respiratory therapists using a computer charting application and assess the impact of incorrect data on computerized ventilator management protocols. DESIGN An analysis of 29,054 charting events gathered over 12 months from 678 ventilated patients (1,736 ventilator days) in four intensive care units at a tertiary care hospital.Measurements: Ten ventilator settings were examined, including fraction of inspired oxygen (Fio (2)), positive end-expiratory pressure (PEEP), tidal volume, respiratory rate, peak inspiratory flow, and pressure support. Respiratory therapists entered values for each setting approximately every two hours using a computer charting application. Manually entered values were compared with data acquired automatically from ventilators using an implementation of the ISO/IEEE 11073 Medical Information Bus (MIB). Data quality was assessed by measuring the percentage of time that the two sources matched. Charting delay, defined as the interval between data observation and data entry, also was measured.Results: The percentage of time that settings matched ranged from 99.0% (PEEP) to 75.9% (low tidal volume alarm setting). The average charting delay for each charting event was 6.1 minutes, including an average of 1.8 minutes spent entering data in the charting application. In 559 (3.9%) of 14,263 suggestions generated by computerized ventilator management protocols, one or more manually charted setting values did not match the MIB data.Conclusion: Even at institutions where manual charting of ventilator settings is performed well, automatic data collection can eliminate delays, improve charting efficiency, and reduce errors caused by incorrect data. [ABSTRACT FROM AUTHOR]

Objective: To assess the acceptability and usage of a standalone personal digital assistant (PDA)-based clinical decision-support system (CDSS) for the diagnosis and management of acute respiratory tract infections (RTIs) in the outpatient setting.Design: Observational study performed as part of a larger randomized trial in six rural communities in Utah and Idaho from January 2002 to March 2004. Ninety-nine primary care providers received a PDA-based CDSS for use at the point-of-care, and were asked to use the tool with at least 200 patients with suspected RTIs.Measurements: Clinical data were collected electronically from the devices at periodic intervals. Providers also completed an exit questionnaire at the end of the study period.Results: Providers logged 14,393 cases using the CDSS, the majority of which (n=7624; 53%) were from family practitioners. Overall adherence with CDSS recommendations for the five most common diagnoses (pharyngitis, otitis media, sinusitis, bronchitis, and upper respiratory tract infection) was 82%. When antibiotics were prescribed (53% of cases), adherence with the CDSS-recommended antibiotic was high (76%). By logistic regression analysis, the odds of adherence with CDSS recommendations increased significantly with each ten cases completed (P=0.001). Questionnaire respondents believed the CDSS was easy to use, and most (44/65; 68%) did not believe it increased their encounter time with patients, regardless of prior experience with PDAs.Conclusion: A standalone PDA-based CDSS for acute RTIs used at the point-of-care can encourage better outpatient antimicrobial prescribing practices and easily gather a rich set of clinical data. [ABSTRACT FROM AUTHOR]

Providing quality health care requires access to continuous patient data that developing countries often lack. A panel of medical informatics specialists, clinical human immunodeficiency virus (HIV) specialists, and program managers suggests a minimum data set for supporting the management and monitoring of patients with HIV and their care programs in developing countries. The proposed minimum data set consists of data for registration and scheduling, monitoring and improving practice management, and describing clinical encounters and clinical care. Data should be numeric or coded using standard definitions and minimal free text. To enhance accuracy, efficiency, and availability, data should be recorded electronically by those generating them. Data elements must be sufficiently detailed to support clinical algorithms/guidelines and aggregation into broader categories for consumption by higher level users (e.g., national and international health care agencies). The proposed minimum data set will evolve over time as funding increases, care protocols change, and additional tests and treatments become available for HIV-infected patients in developing countries. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Charting systems with decision support have been developed to assist with medication charting, but many of the features of these programs are not properly used in their clinical application. An analysis of medication error reports at LDS Hospital revealed the occurrence of errors that should have been detected and prevented by decision support features if real-time entry at the bedside had taken place. The aim of this study was to increase the real-time bedside charting behavior of nurses. DESIGN: A quasiexperimental before and after design was used. The study took place in two 40-bed surgical units, one of which served as the study unit, the other as control unit. The study unit received educational intervention about error avoidance through real-time bedside charting, and 12 weeks of monitoring and performance feedback. The real-time and bedside charting rates for the study and control units were measured before and after the intervention. RESULTS: Before the intervention on the study unit, the real-time charting rate was 59% and the bedside rate was 40%. At the conclusion of a 12-week intervention period, the real-time rate increased to 73% and the bedside rate increased to 63%. Postintervention real-time rates were 75% after eight weeks and remained at 75% after one year. Equivalent control unit real-time rates varied from 53% to 57%, and bedside rates varied from 34% to 44% during the same intervals. CONCLUSION: Targeted educational intervention and monitored feedback yielded measurable improvements in the effective use of the computerized medication charting system and must be an ongoing process. [ABSTRACT FROM AUTHOR]

Context: Although adverse drug events have been extensively evaluated by computer-based surveillance, medical device errors have no comparable surveillance techniques.Objectives: To determine whether computer-based surveillance can reliably identify medical device-related hazards (no known harm to patient) and adverse medical device events (AMDEs; patient experienced harm) and to compare alternative methods of detection of device-related problems.Design, Setting, and Participants: This descriptive study was conducted from January through September 2000 at a 520-bed tertiary teaching institution in the United States with experience in using computer tools to detect and prevent adverse drug events. All 20 441 regular and short-stay patients (excluding obstetric and newborn patients) were included.Main Outcome Measures: Medical device events as detected by computer-based flags, telemetry problem checklists, International Classification of Diseases, Ninth Revision (ICD-9) discharge code (which could include AMDEs present at admission), clinical engineering work logs, and patient survey results were compared with each other and with routine voluntary incident reports to determine frequencies, proportions, positive predictive values, and incidence rates by each technique.Results: Of the 7059 flags triggered, 552 (7.8%) indicate a device-related hazard or AMDE. The estimated 9-month incidence rates (number per 1000 admissions [95% confidence intervals]) for AMDEs were 1.6 (0.9-2.5) for incident reports, 27.7 (24.9-30.7) for computer flags, and 64.6 (60.4-69.1) for ICD-9 discharge codes. Few of these events were detected by more than 1 surveillance method, giving an overall incidence of AMDE detected by at least 1 of these methods of 83.7 per 1000 (95% confidence interval, 78.8-88.6) admissions. The positive predictive value of computer flags for detecting device-related hazards and AMDEs ranged from 0% to 38%.Conclusions: More intensive surveillance methods yielded higher rates of medical device problems than found with traditional voluntary reporting, with little overlap between methods. Several detection methods had low efficiency in detecting AMDEs. The high rate of AMDEs suggests that AMDEs are an important patient safety issue, but additional research is necessary to identify optimal AMDE detection strategies. [ABSTRACT FROM AUTHOR]

The 2002 Olympic Winter Games were held in Utah from February 8 to March 16, 2002. Following the terrorist attacks on September 11, 2001, and the anthrax release in October 2001, the need for bioterrorism surveillance during the Games was paramount. A team of informaticists and public health specialists from Utah and Pittsburgh implemented the Real-time Outbreak and Disease Surveillance (RODS) system in Utah for the Games in just seven weeks. The strategies and challenges of implementing such a system in such a short time are discussed. The motivation and cooperation inspired by the 2002 Olympic Winter Games were a powerful driver in overcoming the organizational issues. Over 114,000 acute care encounters were monitored between February 8 and March 31, 2002. No outbreaks of public health significance were detected. The system was implemented successfully and operational for the 2002 Olympic Winter Games and remains operational today. [ABSTRACT FROM AUTHOR]

Background: Based on the technologies of applied behavior analysis and person-centered planning, positive behavior support is a process for designing and implementing proactive behavioral interventions with the goal of positive lifestyle changes. Participants: The two adolescents who received the intensive, longitudinal, multicomponent intervention had experienced escalating behavior challenges over several years after brain injury in early childhood. Main Outcome Measures: Quantitative data included episodes of aggression and property destruction. Qualitative data included intensity of supports, family involvement, peer relationships, medication regime, vocational status, educational status, community access, and self-help skills. Research Design: A long-term, natural-environment, case-study method was used. Results: The targeted challenging behaviors were reduced to zero. In addition, the participants' domains of activity increased and self-management improved even as supports were systematically withdrawn. Conclusions: These results illustrate the potential for successfully treating extreme chronic behavior disorders after childhood brain injury. [ABSTRACT FROM AUTHOR]

Objective: To analyze whether computer-generated reminders about infections could influence clinicians' practice patterns and consequently improve the detection and management of nosocomial infections.Design: The conclusions produced by an expert system developed to detect and manage infections were presented to the attending clinicians in a pediatric hospital to determine whether this information could improve detection and management. Clinician interventions were compared before and after the implementation of the system.Measurements: The responses of the clinicians (staff physicians, physician assistants, and nurse practitioners) to the reminders were determined by review of paper medical charts. Main outcome measures were the number of suggestions to treat and manage infections that were followed before and after the implementation of COMPISS (Computerized Pediatric Infection Surveillance System). The clinicians' opinions about the system were assessed by means of a paper questionnaire distributed following the experiment.Results: The results failed to show a statistical difference between the clinicians' treatment strategies before and after implementation of the system (P: > 0.33 for clinicians working in the emergency room and P: > 0.45 for clinicians working in the pediatric intensive care unit). The questionnaire results showed that the respondents appreciated the information presented by the system.Conclusion: The computer-generated reminders about infections were unable to influence the practice patterns of clinicians. The methodologic problems that may have contributed to this negative result are discussed. [ABSTRACT FROM AUTHOR]

Background: A role for prenatal steroid hormones in the etiology of autism has been proposed, but evidence is conflicting., Methods: Here, we examined serum levels of maternal estradiol, testosterone, 17-hydroxyprogesterone (OHP), and cortisol from the first trimester of gestation (mean = 10.1 weeks) in relation to the odds of diagnosed autism with and without co-occurring intellectual disability (ID) in the offspring (n = 118 autism with ID, n = 249 autism without ID, n = 477 control). Levels of maternal hormones were measured using highly sensitive liquid chromatography tandem mass spectrometry, standardized according to gestational timing of sample collection, and analyzed with restricted cubic spline logistic regression models adjusting for child's sex and maternal health, demographic, and socioeconomic factors., Results: We observed significant nonlinear associations between maternal estradiol, 17-OHP, and cortisol with autism, which varied with the presence of co-occurring ID. Compared to mean levels, lower levels of estradiol were associated with higher odds of autism with ID (odds ratio for concentrations 1 SD below the mean = 1.66; 95% CI, 1.24-2.11), while higher cortisol levels were associated with lower odds (odds ratio for 1 SD above the mean = 0.55; 95% CI, 0.36-0.88). In contrast, higher 17-OHP was associated with increased odds of autism without ID (odds ratio for 1 SD above the mean = 1.49; 95% CI, 1.11-1.99). We observed no evidence for interaction with sex of the child., Conclusions: These findings support the notion that the maternal steroid hormonal environment in early pregnancy may contribute to autism, but also emphasize the complex relationship between early-life steroid exposure and autism., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy., Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability., Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021., Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records., Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers., Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively., Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

Hypoxia inducible factor (HIF) is a heterodimeric transcription factor composed of an oxygen-regulated α subunit and a constitutively expressed β subunit that serves as the master regulator of the cellular response to low oxygen concentrations. The HIF transcription factor senses and responds to hypoxia by significantly altering transcription and reprogramming cells to enable adaptation to a hypoxic microenvironment. Given the central role played by HIF in the survival and growth of tumors in hypoxia, inhibition of this transcription factor serves as a potential therapeutic approach for treating a variety of cancers. Here, we report the identification, optimization, and characterization of a series of cyclic peptides that disrupt the function of HIF-1 and HIF-2 transcription factors by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1β. These compounds are shown to bind to HIF-α and disrupt the protein-protein interaction between the α and β subunits of the transcription factor, resulting in disruption of hypoxia-response signaling by our lead molecule in several cancer cell lines.

Objective: To measure pediatrician adherence to evidence-based guidelines in the treatment of young children with attention-deficit/hyperactivity disorder (ADHD) in a diverse healthcare system using natural language processing (NLP) techniques., Materials and Methods: We extracted structured and free-text data from electronic health records (EHRs) of all office visits (2015-2019) of children aged 4-6 years in a community-based primary healthcare network in California, who had ≥1 visits with an ICD-10 diagnosis of ADHD. Two pediatricians annotated clinical notes of the first ADHD visit for 423 patients. Inter-annotator agreement (IAA) was assessed for the recommendation for the first-line behavioral treatment (F-measure = 0.89). Four pre-trained language models, including BioClinical Bidirectional Encoder Representations from Transformers (BioClinicalBERT), were used to identify behavioral treatment recommendations using a 70/30 train/test split. For temporal validation, we deployed BioClinicalBERT on 1,020 unannotated notes from other ADHD visits and well-care visits; all positively classified notes (n = 53) and 5% of negatively classified notes (n = 50) were manually reviewed., Results: Of 423 patients, 313 (74%) were male; 298 (70%) were privately insured; 138 (33%) were White; 61 (14%) were Hispanic. The BioClinicalBERT model trained on the first ADHD visits achieved F1 = 0.76, precision = 0.81, recall = 0.72, and AUC = 0.81 [0.72-0.89]. Temporal validation achieved F1 = 0.77, precision = 0.68, and recall = 0.88. Fairness analysis revealed low model performance in publicly insured patients (F1 = 0.53)., Conclusion: Deploying pre-trained language models on a variable set of clinical notes accurately captured pediatrician adherence to guidelines in the treatment of children with ADHD. Validating this approach in other patient populations is needed to achieve equitable measurement of quality of care at scale and improve clinical care for mental health conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Psychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood., Aim: We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions., Methods: Using nationwide Swedish health registries, we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy. We then used summary data from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression. Finally, we assessed the potential bidirectional relationships using two-sample Mendelian randomisation., Results: In a cohort of 7 628 495 individuals, we found that almost half of the 94 435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime (adjusted lifetime prevalence, 44.09%; 95% confidence interval (CI) 43.78% to 44.39%). We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions. For example, we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder (r g =0.18, 95% CI 0.09 to 0.27, p<0.001)-a correlation that was more pronounced in focal epilepsy (r g =0.23, 95% CI 0.09 to 0.36, p<0.001). Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions., Conclusions: Psychiatric comorbidities are common in patients with epilepsy. Genetic correlations may partially explain some comorbidities; however, there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions. These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy., Competing Interests: Competing interests: TT has received support from Eisai, GSK, UCB, Bial, Sanofi, GW Pharma, Teva, Angelini Pharma, and personal fees from Eisai, Sanofi, Sun Pharma, UCB and Angelini Pharma outside the submitted work. The remaining authors have no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions., Methods and Findings: In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins. A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child's sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term (≥37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures., Conclusions: In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Maternal pre-gestational diabetes (PGDM), gestational diabetes mellitus (GDM), and overweight/obesity have been associated with increased risks of offspring neurodevelopmental conditions (NDCs) including autism, intellectual disability (ID), and attention deficit/hyperactivity disorder (ADHD). Less is known about whether and how obstetric and neonatal complications (e.g., preterm birth, neonatal asphyxia) could mediate these associations., Methods: In this Swedish register-based cohort study, we examined complications during pregnancy, delivery, and the neonatal period as potential mediators of the relationships between maternal metabolic conditions and offspring NDCs. We quantified the extent to which these obstetric and neonatal factors could mediate the associations of maternal metabolic conditions with offspring NDCs by applying parametric regression models for single mediation analyses and weighting-based methods for multiple mediation analyses under counterfactual frameworks., Results: The study sample included 2,352,969 singleton children born to 1,299,692 mothers from 1987-2010 who were followed up until December 31, 2016, of whom 135,832 children (5.8%) were diagnosed with at least one NDC. A substantial portion of the association between maternal PGDM and children's odds of NDCs could be explained by the combined group of obstetric and neonatal complications in the multiple mediation analysis. For instance, these complications explained 44.4% of the relationship between maternal PGDM and offspring ID risk. The proportion of the relationship between maternal overweight/obesity and children's risk of NDCs that could be explained by obstetric and neonatal complications was considerably smaller, ranging from 1.5 to 8.1%. Some complications considered on their own, including pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities, could explain at least 10% of the associations between maternal PGDM and offspring NDCs. Complications during the neonatal period showed a stronger joint mediating effect for the relationship between PGDM and offspring NDCs than those during pregnancy or delivery., Conclusions: Obstetric and neonatal complications could explain nearly half of the association between maternal PGDM and offspring risk of NDCs. The mediating effects were more pronounced for complications during the neonatal period and for specific complications such as pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities. Effective preventive strategies for offspring NDCs should holistically address both the primary metabolic issues related to PGDM and the wide array of potential complications, especially those in the neonatal period., (© 2023. The Author(s).)

Background: Gestational diabetes mellitus (GDM) is associated with both short- and long-term risks, although it is unknown if risks vary by severity, timing, and duration of gestational hyperglycemia. We aimed to identify trajectories of random capillary glucose (RCG) levels throughout pregnancy and assess their associations with both obstetric/neonatal outcomes and children's risk of neurodevelopmental conditions (NDCs) (i.e., autism, intellectual disability, and attention-deficit/hyperactivity disorders [ADHD])., Methods: A population-based cohort study was conducted involving 76,228 children born to 68,768 mothers without pregestational diabetes. Group-based trajectory modeling was utilized to identify distinct glucose trajectories across RCG values throughout the course of pregnancy. The associations between these trajectory groups and obstetric/neonatal outcomes as well as children's NDCs were then assessed using generalized estimating equation models with a logit link. The Benjamini-Hochberg (BH) procedure was employed to adjust P-values for multiple comparisons, controlling the false discovery rate (FDR)., Results: Five distinct glucose trajectory groups were identified, each with varying percentages diagnosed with GDM. Their associations with obstetric/neonatal outcomes as well as children's NDCs varied. For example, when compared to the "Persistently Low" group, other groups exhibited varying degrees of increased risk for large-for-gestational-age babies, with the exception of the "High in Early Pregnancy" group. Compared to the "Persistently Low" group, all other trajectory groups were associated with NDC outcomes, except the "High in Mid-Pregnancy" group. However, none of the associations with offspring NDCs remained significant after accounting for the FDR correction., Conclusions: Persistent high glucose levels or moderately elevated glucose levels throughout pregnancy, as well as transient states of hyperglycemia in early or mid-pregnancy, were found to be associated with increased risks of specific obstetric and neonatal complications, and potentially offspring NDCs. These risks varied depending on the severity, timing, duration, and management of hyperglycemia. The findings underscore the need for continuous surveillance and individualized management strategies for women displaying different glucose trajectories during pregnancy. Limitations such as potential residual confounding, the role of mediators, and small sample size should be addressed in future studies., (© 2023. The Author(s).)

Background and Objectives: Primary care pediatricians (PCP) are often called on to manage child and adolescent anxiety and depression. The objective of this study was to describe PCP care practices around prescription of selective serotonin reuptake inhibitors (SSRI) for patients with anxiety and/or depression by using medical record review., Methods: We identified 1685 patients who had at least 1 visit with a diagnosis of anxiety and/or depression in a large primary care network and were prescribed an SSRI by a network PCP. We randomly selected 110 for chart review. We reviewed the visit when the SSRI was first prescribed (medication visit), immediately previous visit, and immediately subsequent visit. We abstracted rationale for prescribing medication, subspecialist involvement, referral for psychotherapy, and medication monitoring practices., Results: At the medication visit, in 82% (n = 90) of cases, PCPs documented reasons for starting an SSRI, most commonly clinical change (57%, n = 63). Thirty percent (n = 33) of patients had documented involvement of developmental-behavioral pediatrics or psychiatry subspecialists at 1 of the 3 visits reviewed. Thirty-three percent (n = 37) were referred to unspecified psychotherapy; 4% (n = 4) were referred specifically for cognitive behavioral therapy. Of 69 patients with a subsequent visit, 48% (n = 33) had documentation of monitoring for side effects., Conclusions: When prescribing SSRIs for children with anxiety and/or depression, PCPs in this network documented appropriate indications for starting medication and prescribed without subspecialist involvement. Continuing medical education for PCPs who care for children with these conditions should include information about evidence-based psychotherapy and strategies for monitoring potential side effects., (Copyright © 2023 by the American Academy of Pediatrics.)

Purpose: To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos., Methods: This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m 2 ) category: normal weight (18.5-24.9), overweight (25-29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes., Results: 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4% normal weight, 61.2% overweight, and 64.2% obese). There was also no difference for the secondary outcome, CPR, across all categories (58.5%, 65.5%, and 66.7%, respectively). This was confirmed in GEE analysis when adjusting for confounders., Conclusion: While increased weight has commonly been implicated in poor pregnancy outcomes, the effect of BMI on the success of mNC-FET remains debated. Across five years of data from a single institution using euploid embryos in mNC-FET cycles, elevated BMI was not associated with reduced LBR or CPR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Frontline providers frequently make time-sensitive antibiotic choices, but many feel poorly equipped to handle antibiotic allergies., Objective: We hypothesized that a digital decision support tool could improve antibiotic selection and confidence when managing β-lactam allergies., Methods: A digital decision support tool was designed to guide non-allergist providers in managing patients with β-lactam allergy labels. Non-allergists were asked to make decisions in clinical test cases without the tool, and then with it. These decisions were compared using paired t tests. Users also completed surveys assessing their confidence in managing antibiotic allergies., Results: The tool's algorithm was validated by confirming its recommendations aligned with that of five allergists. Non-allergist providers (n = 102) made antibiotic management decisions in test cases, both with and without the tool. Use of the tool increased the proportion of correct decisions from 0.41 to 0.67, a difference of 0.26 (95% CI, 0.22-0.30; P < .001). Users were more likely to give full-dose antibiotics in low-risk situations, give challenge doses in medium-risk situations, and avoid the antibiotic and/or consult allergy departments in high-risk situations. A total of 98 users (96%) said the tool would increase their confidence when choosing antibiotics for patients with allergies., Conclusions: A point-of-care clinical decision tool provides allergist-designed guidance for non-allergists and is a scalable system for addressing antibiotic allergies, irrespective of allergist availability. This tool encouraged appropriate antibiotic use in low- and medium-risk situations and increased caution in high-risk situations. A digital support tool should be considered in quality improvement and antibiotic stewardship efforts., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET)., Methods: Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5 mg of daily letrozole for 5 days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness., Results: The demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7 days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38 weeks and 1 day for LTZ; 39 weeks and 0 day for NC) were full term., Conclusion: There were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6 days does not appear to be clinically significant, this warrants larger studies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The purpose of this study is to determine the rate and age at first identification of speech-language delay in relation to child sociodemographic variables among a pediatric primary care network., Methods: We analyzed a deidentified data set of electronic health records of children aged 1- to 5-years-old seen between 2015 and 2019 at 10 practices of a community-based pediatric primary health care network. Primary outcomes were numbers (proportions) of patients with relevant ICD-10 visit-diagnosis codes and patient age (months) at first documentation of speech-language delay. Regression models estimated associations between outcomes and patient characteristics, adjusting for practice affiliation., Results: Of 14,559 included patients, 2063 (14.1%) had speech-language delay: 68.4% males, 74.4% with private insurance, and 96.1% with English as a primary household language. Most patients (60%) were first identified at the 18- or 24-month well-child visit. The mean age at first documentation was 25.4 months (SD = 9.3), which did not differ between practices reporting the use of standardized developmental screener and those using surveillance questionnaires. Regression models showed that males were more than twice as likely than females to be identified with speech-language delay (adjusted odds ratio [aOR] = 2.05, 95% CI: [1.86-2.25]); publicly insured were more likely than privately insured patients to be identified with speech-language delay (aOR = 1.48, 95% CI: [1.30-1.68]). Females were older than males at first identification (+1.2 months, 95% CI: [0.3-2.1]); privately insured were older than military insured patients (private +3.3 months, 95% CI: [2.2-4.4])., Conclusion: Pediatricians in this network identified speech-language delays at similar rates to national prevalence. Further investigation is needed to understand differences in speech-language delay detection across patient subgroups in practices that use developmental screening and/or surveillance., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous studies have suggested that gestational weight gain (GWG) outside an optimal range increases the risks of neurodevelopmental disorders (NDDs) in offspring including autism spectrum disorder (ASD), intellectual disability (ID), and attention deficit/hyperactivity disorder (ADHD). The sequential development of the fetal brain suggests that its vulnerability may vary depending on the timing of exposure. Therefore, we aimed to investigate the associations of not only gestational age-standardized total GWG (GWG z-scores) but also the rate of GWG (RGWG) in the second and third trimesters with risks of NDDs in offspring., Methods: In this population-based cohort study, we used maternal weight data from antenatal care records collected for 57,822 children born to 53,516 mothers between 2007 and 2010 in the Stockholm Youth Cohort. Children were followed from 2 years of age to December 31, 2016. GWG z-scores and RGWG (kg/week) in the second and third trimesters were considered as continuous variables in cox regression models, clustered on maternal identification numbers. Nonlinear relationships were accommodated using restricted cubic splines with 3 knots. RGWG were also categorized according to the 2009 US Institute of Medicine (IOM) guidelines for optimal GWG. According to the IOM guidelines, the optimal rate of GWG for the second and third trimesters for underweight, normal weight, overweight, and obese categories were 0.44-0.58, 0.35-0.50, 0.23-0.33, and 0.17-0.27 kg/week, respectively., Results: During a mean follow-up of 5.4 years (until children were on average 7.4 years old), 2205 (3.8%) children were diagnosed with NDDs, of which 1119 (1.9%) received a diagnosis of ASD, 1353 (2.3%) ADHD, and 270 (0.5%) ID. We observed a J-shaped association between total GWG z-score and offspring risk of NDDs, with higher total GWG (GWG z-score = 2) associated with 19% increased risk of any NDD (95% CI = 3-37%) and lower total GWG (GWG z-score = - 2) associated with 12% increased risk of any NDDs (95% CI = 2-23%), compared to the reference (GWG z-score = 0). In the second trimester, lower RGWG (0.25 kg/week) was associated with a 9% increased risk of any NDD diagnosis (95% CI = 4-15%) compared to the median of 0.57 kg/week, with no apparent relationship between higher RGWG and risk of NDDs. In the third trimester, there was no apparent association between lower RGWG and risk of NDDs, though higher RGWG (1 kg/week) was associated with a 28% increased risk of NDD diagnosis (95% CI = 16-40%), compared to the median (0.51 kg/week). When considering categorized RGWG, we found that slow weight gain in the second trimester followed by rapid weight gain in the third trimester most significantly increased the risk of ADHD (HR adjusted = 1.55, 1.13-2.13) and ID (HR adjusted = 2.53, 1.15-5.55) in offspring. The main limitations of our study are the relatively few years for which detailed GWG data were available and the relatively short follow-up for the outcomes, limiting power to detect associations and misclassifying children who receive an NDD diagnosis later in childhood., Conclusions: The relationship between maternal weight gain and children's risk of NDDs varied according to timing in pregnancy, with the greatest risks associated with slow weight gain in the second trimester and rapid weight gain in the third trimester., (© 2023. The Author(s).)

Objectives: 1) To assess continuity of care (CoC) within primary-care practices for children with asthma and autism spectrum disorder (ASD) compared to children without chronic conditions, and 2) to determine patient and clinical-care factors associated with CoC., Methods: Retrospective cohort study of electronic health records from office visits of children <9 years, seen ≥4 times between 2015 and 2019 in 10 practices of a community-based primary health care network in California. Three cohorts were constructed: 1) Asthma: ≥2 visits with asthma visit diagnoses; 2) ASD: same method; 3) Controls: no chronic conditions. CoC, using Usual Provider of Care measure (range > 0-1), was calculated for 1) all visits (overall) and 2) well-care visits. Fractional regression models examined CoC adjusting for patient age, medical insurance, practice affiliation, and number of visits., Results: Of 30,678 children, 1875 (6.1%) were classified with Asthma, 294 (1.0%) with ASD, and 15,465 (50.4%) as Controls. Overall CoC was lower for Asthma (Mean = 0.58, SD 0.21) and ASD (M = 0.57, SD = 0.20) than Controls (M = 0.66, SD = 0.21); differences in well-care CoC were minimal. In regression models, lower overall CoC was found for Asthma (aOR = 0.90, 95% CI, 0.85-0.94). Lower overall and well-care CoC were associated with public insurance (aOR = 0.77, CI, 0.74-0.81; aOR = 0.64, CI, 0.59-0.69)., Conclusion: After accounting for patient and clinical-care factors, children with asthma, but not with ASD, in this primary-care network had significantly lower CoC compared to children without chronic conditions. Public insurance was the most prominent patient factor associated with low CoC, emphasizing the need to address disparities in CoC., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To provide an updated systematic review on the use of extracorporeal cardiopulmonary resuscitation (ECPR) compared with manual or mechanical cardiopulmonary resuscitation during cardiac arrest., Methods: This was an update of a systematic review published in 2018. OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized trials and observational studies between January 1, 2018, and June 21, 2022. The population included adults and children with out-of-hospital or in-hospital cardiac arrest. Two investigators reviewed studies for relevance, extracted data, and assessed bias. The certainty of evidence was evaluated using GRADE., Results: The search identified 3 trials, 27 observational studies, and 6 cost-effectiveness studies. All trials included adults with out-of-hospital cardiac arrest and were terminated before enrolling the intended number of subjects. One trial found a benefit of ECPR in survival and favorable neurological status, whereas two trials found no statistically significant differences in outcomes. There were 23 observational studies in adults with out-of-hospital cardiac arrest or in combination with in-hospital cardiac arrest, and 4 observational studies in children with in-hospital cardiac arrest. Results of individual studies were inconsistent, although many studies favored ECPR. The risk of bias was intermediate for trials and critical for observational studies. The certainty of evidence was very low to low. Study heterogeneity precluded meta-analyses. The cost-effectiveness varied depending on the setting and the analysis assumptions., Conclusions: Recent randomized trials suggest potential benefit of ECPR, but the certainty of evidence remains low. It is unclear which patients might benefit from ECPR., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study aims to compare endometrial growth before and after the addition of human growth hormone (hGH) in controlled ovarian hyperstimulation (COH) cycles. A 5-year retrospective cohort study of patients treated with hGH to improve oocyte development during COH cycles was conducted. Each patient’s cycle without hGH immediately preceding cycle(s) with hGH was used for patients to serve as their own controls. Primary outcome was absolute growth in endometrial thickness from pre-stimulation start to day of hCG trigger. Mixed-model regression analysis controlled for patient correlation over repeat cycles and potential confounders. 80 patients were included. Mean age was 39.7 years; mean BMI was 23.8 kg/m2. Majority of patients were nulliparous, non-smoking, and White or Asian. Most common diagnosis was diminished ovarian reserve. Endometrial growth was compared between 159 COH cycles with hGH and 80 COH control cycles; mean increase was 4.5 mm and 3.9 mm, respectively-an unadjusted difference of 0.6 mm (95% CI: 0.2−1.1, p = 0.01). After adjusting for demographic/clinical factors, hGH was associated with 0.9 mm greater endometrial growth (0.4−1.4, p < 0.01). Absolute increase in endometrial thickness was higher in COH cycles that included hGH. Further prospective studies in embryo transfer cycles are needed.

Background: Maternal infections during pregnancy are associated with intellectual disability and autism in exposed children. Whether these associations are causal, and therefore should be targets of preventive strategies, remains unknown. We aimed to investigate these associations, to determine whether there is a causal role of maternal infection during pregnancy for children's risk of autism and intellectual disability, by accounting for unmeasured familial factors., Methods: We used a register-based cohort study design, and included children living in Stockholm County, Sweden, who were born in 1987-2010. We excluded children not born in Sweden, adopted children, and children with unknown biological mothers or fathers. Maternal infections during pregnancy, defined by ICD-8, ICD-9, and ICD-10 codes, were identified in the National Patient Register and Medical Birth Register. Children were followed up from birth to an outcome or a censoring event (death, migration from Stockholm, age 18 years, or Dec 31, 2016, whichever occurred first). The primary outcomes were diagnosis of autism or diagnosis of intellectual disability. We did a survival analysis to examine the association between inpatient and outpatient specialised care for any infection during pregnancy and likelihood of autism or intellectual disability in the child. To address potential residual confounding, we also estimated the relationship between maternal infection in the year preceding pregnancy as a negative control exposure and conducted a matched sibling analysis of sibling pairs who were discordant for autism or intellectual disability., Findings: 647 947 children living in Stockholm County were identified and, after excluding 97 980 children, we included 549 967 in the study (267 995 [48·7%] were female and 281 972 [51·3%] were male; mean age at censoring 13·5 years [SD 5·0; range <1 to 18]; 142 597 [25·9%] had a mother who was not born in Sweden). 445 (1·3%) of 34 013 children exposed to maternal infection during pregnancy were diagnosed with intellectual disability and 1123 (3·3%) with autism. 5087 (1·0%) of 515 954 unexposed children were diagnosed with intellectual disability and 13 035 (2·5%) with autism. Maternal infection during pregnancy was associated with autism (hazard ratio [HR] 1·16, 95% CI 1·09-1·23) and intellectual disability (1·37, 1·23-1·51) in exposed children compared with unexposed children. Maternal infection in the year before pregnancy (negative control exposure) was also associated with autism (HR 1·25, 95% CI 1·14-1·36), but was not associated with intellectual disability (1·09, 0·94-1·27). In sibling comparisons, the associations with maternal infection during pregnancy were attenuated for autism (HR 0·94, 95% CI 0·82-1·08; n=21 864), but not to the same extent for intellectual disability (1·15, 0·95-1·40; n=9275)., Interpretation: Although infections in pregnant women are associated with both autism and intellectual disability in their children, the association with autism does not appear to reflect a causal relationship, but is more likely to be explained by factors shared between family members such as genetic variation or aspects of the shared environment. Thus, infection prevention is not expected to reduce autism incidence. For intellectual disability, unmeasured familial factors might not fully explain the observed associations, and a causal role of maternal infections cannot be excluded. Causal effects of specific but rare infections or infections not requiring health care contact cannot be excluded in either autism or intellectual disability., Funding: Swedish Research Council, Stanley Medical Research Institute, and Autism Speaks., Translation: For the Swedish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Magnetic resonance imaging (MRI) is safe for most patients with cardiovascular implantable electronic devices (CIEDs). However, patients presenting with acute ischemic stroke or transient ischemic attack (AIS/TIA) who have CIEDs may undergo MRI less frequently than patients without devices. We assessed contemporary use of MRI for patients with AIS/TIA and the effect of a recent coverage revision by the Center for Medicare and Medicaid Services (CMS) on MRI utilization., Methods: Using Optum ® claims data from January 2012 to June 2019, we performed an interrupted time series analysis of MRI utilization during AIS/TIA hospitalizations with the April 2018 CMS coverage revision serving as the intervention. For patients treated after the coverage revision, we used multivariable logistic regression to determine the association between lack of CIED and MRI utilization for AIS/TIA., Results: We identified 417,899 patient hospitalizations for AIS/TIA, of which 30,425 (7%) had a CIED present (CIED vs non-CIED patients: age 77.6 ± 9.8 vs 72.7 ± 12.3 years; 45.5% vs 54.3% female). From 2012 to 2019, annual MRI utilization increased from 3% to 20% for CIED patients and 58% to 66% for non-CIED patients. The CMS coverage revision was associated with a 4.2% absolute additional increase in MRI utilization for CIED patients. Non-CIED patients treated after the CMS coverage revision were substantially more likely than CIED patients to undergo MRI (adjusted OR 6.7, 95% CI: 6.3-7.1, P<.001)., Conclusions: MRI utilization has increased for stroke patients with CIEDs but remains far lower than in similar patients without devices., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Culbertson CJ: nothing to disclose. Perino AC: research support from the American Heart Association and Bristol-Myers Squibb/Pfizer; consultant services for Bristol-Myers Squibb/Pfizer. Gardner RM: nothing to disclose. Balasubramanian V: nothing to disclose. Vora N: nothing to disclose., (© The Author(s) 2022.)

Evidence linking parental inflammatory bowel disease (IBD) with autism in children is inconclusive. We conducted four complementary studies to investigate associations between parental IBD and autism in children, and elucidated their underlying etiology. Conducting a nationwide population-based cohort study using Swedish registers, we found evidence of associations between parental diagnoses of IBD and autism in children. Polygenic risk score analyses of the Avon Longitudinal Study of Parents and Children suggested associations between maternal genetic liability to IBD and autistic traits in children. Two-sample Mendelian randomization analyses provided evidence of a potential causal effect of genetic liability to IBD, especially ulcerative colitis, on autism. Linkage disequilibrium score regression did not indicate a genetic correlation between IBD and autism. Triangulating evidence from these four complementary approaches, we found evidence of a potential causal link between parental, particularly maternal, IBD and autism in children. Perinatal immune dysregulation, micronutrient malabsorption and anemia may be implicated., (© 2022. The Author(s).)

Previous studies indicate a role of immune disturbances during early development in the etiology of autism spectrum disorders (ASD). Any potential disturbances during fetal development are best addressed by prospective evaluation of maternal markers of inflammation. Previous studies have investigated maternal cytokines, a group of powerful effectors of the immune system, with inconsistent results. In this study, we aimed to clarify the relationship between maternal cytokines and ASD by evaluating levels of 17 cytokines in first trimester maternal serum samples, from 318 mothers to ASD-cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. Overall, we observed no consistent associations between levels of maternal cytokines and ASD. While we observed a number of individual associations, the patterns varied across the diagnostic sub-groups. Levels above the 90th percentile of IL-1β (OR = 2.31, 95% CI 1.16-4.60), IL-7 (OR = 2.28, 95% CI 1.20-4.33), IL-13 (OR = 2.42, 95% CI 1.29-4.55), and MCP-1 (OR = 2.09, 95% CI 1.03-4.24) were associated with increased odds of ASD with co-occurring intellectual disability (ID), whereas GMCSF (OR = 2.06, 95% CI 1.03-4.11) and TNF-α (OR = 2.31, 95% CI 1.18-4.50) were associated with increased odds of ASD with ADHD but none survived correction for multiple comparisons. Also, none of the measured maternal cytokines were associated with ASD without co-occurring ID or ADHD. Implementing a data-driven approach using machine learning (Random Forest's Variable Importance measurement), we found no evidence to suggest that adding these cytokines and other markers of maternal immunity, to register-based maternal factors (e.g., psychiatric history) improves prediction of ASD. In summary, we found no robust evidence of an association between maternal immune markers during early pregnancy and ASD., 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., (Copyright © 2022 Brynge, Gardner, Sjöqvist, Lee, Dalman and Karlsson.)

Introduction: Patients with EGFR-mutant lung cancer who have had disease progression on osimertinib commonly receive platinum doublet chemotherapy, but whether adding immunotherapy or bevacizumab provides additional benefit is unknown., Materials and Methods: This was a retrospective analysis at 2 university-affiliated institutions. Patients with EGFR-mutant lung cancer who had progression on osimertinib and received next-line therapy with platinum doublet chemotherapy (chemo), platinum doublet chemotherapy plus immunotherapy (chemo-IO), or platinum doublet chemotherapy plus bevacizumab (chemo-bev), were identified; patients who continued osimertinib with these regimens were included. Efficacy outcomes including duration on treatment (DOT) and overall survival (OS) from the start of chemotherapy were assessed. Associations of treatment regimen with outcomes were evaluated using adjusted Cox regression models, using pairwise comparisons between groups., Results: 104 patients were included: 57 received chemo, 12 received chemo-IO, and 35 received chemo-bev. In adjusted models, patients who received chemo-IO had worse OS than did those who received chemo (hazard ratio (HR) 2.66, 95% CI 1.25-5.65; P= .011) or those who received chemo-bev (HR 2.37, 95% CI 1.09-5.65; P= .030). A statistically significant difference in OS could not be detected in patients who received chemo-bev versus those who received chemo (HR 1.50, 95% CI 0.84-2.69; P= .17)., Conclusion: In this retrospective study, giving immunotherapy with platinum doublet chemotherapy after progression on osimertinib was associated with a worse OS compared with platinum doublet chemotherapy alone. Platinum doublet chemotherapy without immunotherapy (with consideration of continuation of osimertinib, in selected cases) is a reasonable choice in this setting, while we await results of clinical trials examining optimal next-line chemotherapy-based regimens in EGFR-mutant lung cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In most studies, patients with EGFR L858R mutant non-small cell lung cancer (NSCLC) have a shorter duration of response to EGFR tyrosine kinase inhibitor (TKI) therapy than do patients with EGFR exon 19 deletion NSCLC. The role that co-mutations play in this observation is unknown., Methods: We performed a single-institution retrospective analysis of patients with EGFR-mutant NSCLC (exon 19 deletion or L858R mutation) who received frontline EGFR TKI for metastatic disease between 2014 and 2019, and who had STAMP next-generation sequencing (NGS), a 130-gene platform. Time to treatment failure (TTF) and overall survival were calculated using Cox models adjusted for age, race, and brain metastases. Co-mutations in key tumor suppressor genes (TP53, RB1, KEAP1, CDKN2A, or CTNNB1) were identified and their effects on outcomes were evaluated. Analyses were stratified according to receipt of osimertinib versus nonosimertinib as frontline EGFR TKI., Results: Of 137 patients, 72 (57%) had EGFR exon 19 deletions and 65 (43%) had EGFR L858R mutations. Median TTF and OS on frontline TKI was shorter for the L858R cohort versus the exon 19 deletion cohort in univariate analysis. In adjusted models, this difference persisted for TTF but was no longer significant for OS. The difference in TTF in L858R mutant tumors was driven by the presence of co-mutations in key tumor suppressor genes., Conclusion: Patients with metastatic NSCLC with mutations in EGFR L858R had shorter TTF on frontline TKI compared to patients with EGFR exon 19 deletions. Co-mutations in tumor suppressor genes may play an important role in the differential response to TKI therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To describe medication management of children diagnosed with anxiety and/or depression by primary care providers within a primary care network., Study Design/methods: We performed a retrospective cross-sectional analysis of electronic health record (EHR) structured data from all children seen at least twice in a 4-year observation period within a network of primary care clinics in Northern California. For children who had visit diagnoses of anxiety, depression, anxiety+depression or symptoms characteristic of these conditions, we analyzed the rates and types of medications prescribed. A logistic regression model considered patient variables for the combined sample., Results: Of all patients 6-18 years old ( N = 59,484), 4.4% ( n = 2,635) had a diagnosis of anxiety only, 2.4% ( n = 1,433) depression only, and 1.2% ( n = 737) both anxiety and depression (anxiety + depression); 18% of children with anxiety and/or depression had comorbid ADHD. A total of 15.0% with anxiety only ( n = 357), 20.5% with depression only ( n = 285), and 47.4% with anxiety+depression (n=343) were prescribed a psychoactive non-stimulant medication. For anxiety and depression only, the top three medications prescribed were sertraline, fluoxetine, and citalopram. For anxiety + depression, the top three medications prescribed were citalopram, sertraline, and escitalopram. Frequently prescribed medications also included benzodiazepines. Logistic regression modeling showed that the depression only and anxety + depression categories had increased likelihood of medication prescription. Older age and mental health comorbidities were independently associated with increased likelihood of medication prescription., Conclusions: In this network, ~8% of children carried a diagnosis of anxiety and/or depression. Medication choices generally aligned with current recommendations with the exception of use of benzodiazepines., 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., (Copyright © 2022 Lester, Bannett, Gardner, Feldman and Huffman.)

To characterize the population of children diagnosed with small intestinal bacterial overgrowth (SIBO) based on breath test (BT), correlate symptomatology, and describe SIBO treatments and treatment efficacy., Methods: A retrospective cohort study of pediatric patients seen at Stanford Children's Health Gastroenterology Clinics from 2012 to 2018 who had a positive BT, defined by a rise in hydrogen by ≥20 ppm, a baseline hydrogen level ≥20 ppm, or a methane value ≥10 ppm. The main outcome was symptom resolution, defined as complete or partial improvement after a course of treatment. Absolute standardized differences and Chi-square tests were used to assess associations., Results: From 98 children, 54 met inclusion and did not meet exclusion criteria (53.7% female). Lactulose substrate was used for 41 (75.9%) patients, whereas glucose was used for 13 (24.1%). Complete or partial resolution of symptoms was achieved in 13 of 16 (81.2%) patients who received probiotics with or without antibiotics versus 21 of 31 (67.7%) patients treated with antibiotics alone ( P = 0.524). Metronidazole versus rifaximin versus other antibiotics showed no significant difference in symptom resolution (12 (63.2%), 13 (76.5%), 7 (77.8%), respectively, P = 0.601)., Conclusion: Seventy-two percent of patients experienced at least partial symptom relief after treatment. We did not find a strong correlation between specific symptoms and analyte elevation. There was no difference in effectiveness between metronidazole and rifaximin to treat SIBO symptoms. Further research needs to be done to determine effective treatments for SIBO in pediatrics., Competing Interests: Dr. Peinado Fabregat is Ernest and Amelia Gallo Endowed Postdoctoral Fellow and Child Health Research Institute. The remaining authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: To evaluate whether morphology impacts the pregnancy and neonatal outcomes of euploid blastocysts, and whether maternal age still affects outcomes when top-graded, euploid blastocysts are used., Methods: This retrospective cohort study included all natural-cycle frozen embryo transfers (NC-FET) using an autologous, euploid blastocyst from June 2016 to June 2020 (n = 610). There were five groups based on embryo grade: AA, AB, BA, BB, and "any C". For analysis of only AA-graded embryos, there were three maternal age groups: < 35, 35-39, and 40 + years. The main outcomes measured were clinical pregnancy and live birth rates, while the secondary outcomes included neonatal outcomes such as gestational age at delivery and birthweight. Multivariable logistic regression models were performed to adjust for confounders., Results: Euploid blastocysts with poorer morphology had lower odds of pregnancy and live birth; specifically, embryos with inner cell mass (ICM) graded as "C" had statistically significant decreased odds of pregnancy (aOR 0.33, p = 0.04) and live birth (aOR 0.32, p = 0.03) compared with ICM grade "A". The differences in pregnancy rate between trophectoderm grades were not statistically significant. Even in cycles that transferred a top-graded (AA) euploid embryo, maternal age at transfer was independently associated with outcomes. Embryo grade and maternal age, however, did not significantly impact neonatal outcomes such as prematurity and birthweight., Conclusion: The morphology of euploid blastocysts and maternal age at NC-FET both independently impact pregnancy outcomes. Neonatal outcomes were similar across embryo morphology and maternal age groups, suggesting that lower morphology euploid embryos not be discounted as viable options for transfer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: With advancing therapeutics, lung cancer (LC) survivors are rapidly increasing in number. Although mounting evidence suggests LC survivors have high risk of second primary lung cancer (SPLC), there is no validated prediction model available for clinical use to identify high-risk LC survivors for SPLC., Methods: Using data from 6325 ever-smokers in the Multiethnic Cohort (MEC) study diagnosed with initial primary lung cancer (IPLC) in 1993-2017, we developed a prediction model for 10-year SPLC risk after IPLC diagnosis using cause-specific Cox regression. We evaluated the model's clinical utility using decision curve analysis and externally validated it using 2 population-based data-Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Screening Trial (NLST)-that included 2963 and 2844 IPLC (101 and 93 SPLC cases), respectively., Results: Over 14 063 person-years, 145 (2.3%) ever-smoking IPLC patients developed SPLC in MEC. Our prediction model demonstrated a high predictive accuracy (Brier score = 2.9, 95% confidence interval [CI] = 2.4 to 3.3) and discrimination (area under the receiver operating characteristics [AUC] = 81.9%, 95% CI = 78.2% to 85.5%) based on bootstrap validation in MEC. Stratification by the estimated risk quartiles showed that the observed SPLC incidence was statistically significantly higher in the 4th vs 1st quartile (9.5% vs 0.2%; P < .001). Decision curve analysis indicated that in a wide range of 10-year risk thresholds from 1% to 20%, the model yielded a larger net-benefit vs hypothetical all-screening or no-screening scenarios. External validation using PLCO and NLST showed an AUC of 78.8% (95% CI = 74.6% to 82.9%) and 72.7% (95% CI = 67.7% to 77.7%), respectively., Conclusions: We developed and validated a SPLC prediction model based on large population-based cohorts. The proposed prediction model can help identify high-risk LC patients for SPLC and can be incorporated into clinical decision making for SPLC surveillance and screening., (© The Author(s) 2021. Published by Oxford University Press.)

Objectives: This report describes a model of training and performance management that was designed for and implemented with care providers at a residential school for children with neurodevelopmental and intellectual disabilities in response to the COVID-19 pandemic. The model focused on health and safety concerns, risk mitigation, and intervention integrity., Methods: Procedures followed an applied behavior analysis (ABA) and organizational behavior management (OBM) framework. Action plans addressed (a) critical COVID-19 protocols, (b) behavior-specific implementation guidelines, (c) remote and in-person training formats, (d) in vivo supervision, and (e) knowledge and performance assessments., Results: A competency evaluation (field study) revealed that participant care providers ( N  = 25) acquired and maintained COVID-19 protocols at near 100% proficiency immediately following and 1-month post-training. Supervisors had uniformly positive approval and acceptance ratings of school responsiveness to the COVID-19 pandemic., Conclusions: Integrated and evidence-based care provider training and supervisory practices can promote risk mitigation and performance effectiveness during health crises such as the COVID-19 pandemic. More controlled research that includes multiple dependent measures is needed to replicate and extend our findings to similar human services settings., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)