Enhancing Genetic Association Power in Endometriosis through Unsupervised Clustering of Clinical Subtypes Identified from Electronic Health Records.

Background: Endometriosis affects 10% of reproductive-age women, and yet, it goes undiagnosed for 3.6 years on average after symptoms onset. Despite large GWAS meta-analyses (N > 750,000), only a few dozen causal loci have been identified. We hypothesized that the challenges in identifying causal genes for endometriosis stem from heterogeneity across clinical and biological factors underlying endometriosis diagnosis. Methods: We extracted known endometriosis risk factors, symptoms, and concomitant conditions from the Penn Medicine Biobank (PMBB) and performed unsupervised spectral clustering on 4,078 women with endometriosis. The 5 clusters were characterized by utilizing additional electronic health record (EHR) variables, such as endometriosis-related comorbidities and confirmed surgical phenotypes. From four EHR-linked genetic datasets, PMBB, eMERGE, AOU, and UKBB, we extracted lead variants and tag variants 39 known endometriosis loci for association testing. We meta-analyzed ancestry-stratified case/control tests for each locus and cluster in addition to a positive control (Total N endometriosis cases = 10,108). Results: We have designated the five subtype clusters as pain comorbidities, uterine disorders, pregnancy complications, cardiometabolic comorbidities, and EHR-asymptomatic based on enriched features from each group. One locus, RNLS , surpassed the genome-wide significant threshold in the positive control. Thirteen more loci reached a Bonferroni threshold of 1.3 x 10 -3 (0.05 / 39) in the positive control. The cluster-stratified tests yielded more significant associations than the positive control for anywhere from 5 to 15 loci depending on the cluster. Bonferroni significant loci were identified for four out of five clusters, including WNT4 and GREB1 for the uterine disorders cluster, RNLS for the cardiometabolic cluster, FSHB for the pregnancy complications cluster, and SYNE1 and CDKN2B-AS1 for the EHR-asymptomatic cluster. This study enhances our understanding of the clinical presentation patterns of endometriosis subtypes, showcasing the innovative approach employed to investigate this complex disease.

Classification and treatment of vaginal strictures at the donor-recipient anastomosis after uterus transplant.

OBJECTIVE: To describe the incidence and management of vaginal stricture after uterus transplantation (UTx) in the US, to propose a grading system to classify stricture severity, and to identify risk factors for stricture formation. DESIGN: Prospective cohort study. SETTING: University Hospital. PATIENTS: Recipients undergoing UTx from 2016-2023 at Baylor University Medical Center in Dallas, Cleveland Clinic, the University of Pennsylvania, and the University of Alabama at Birmingham were monitored postoperatively with regular pelvic examinations. Stricture was defined as vaginal narrowing of <3 cm in patients with graft survival of at least 7 days. INTERVENTION: Demographic and surgery characteristics. MAIN OUTCOME MEASURES: Stricture development and severity (grade 1 for diameter 2-<3 cm, grade 2 for 1-<2 cm, or grade 3 for <1 cm). RESULTS: Of the 45 UTx from 2016-2023 (16 deceased donors and 29 living donors), 3 were excluded from the analysis because of graft loss within 7 days. Of the 42 remaining recipients, 39 (92.9%) had Mayer-Rokitansky-Küster-Hauser syndrome and 3 (7.1%) had a prior hysterectomy. Twenty-eight (66.7%) UTx recipients developed postoperative vaginal strictures with a median time to stricture of 33 days (interquartile range 19-53 days). Most strictures were of moderate severity, with 4 (14.3%) strictures categorized as grade 1, 19 (67.9%) as grade 2, and 5 (17.9%) as grade 3. History of Mayer-Rokitansky-Küster-Hauser syndrome and preoperative recipient vaginal length were significant risk factors for stricture, after adjustment for donor and recipient age and body mass index, anastomosis technique, total ischemia time, center, and year. Patients with longer preoperative vaginal length had a lower risk of stricture (hazard ratio 0.45, 0.29-0.70). The severity grading of the stricture was associated with the effectiveness of a nonoperative treatment approach (grade 1 vs. grade 3). No patients with grade 3 strictures improved with self-dilation alone; all required surgical repair and/or dilation under anesthesia. Conversely, for grade 1 or 2 strictures, self-dilation alone was successful in 47.8% (11/23), and no grade 1 strictures required surgical repair. CONCLUSIONS: Vaginal stricture is a common postoperative complication after UTx, affecting >65% of recipients. Short preoperative vaginal length and history of müllerian agenesis in the recipient are significant risk factors. Vaginal self-dilation was effective for some mild to moderate strictures, although dilation under anesthesia or surgical repair was required in most cases. CLINICAL TRIAL REGISTRATION NUMBERS: Dallas UtErus Transplant Study (DUETS) at Baylor University Medical Center (NCT02656550), Uterine transplantation for the treatment of uterine factor infertility at the Cleveland Clinic (NCT02573415), The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial (UNTIL) (NCT03307356).

Care Models and Discharge Services for Children With Medical Complexity.

BACKGROUND AND OBJECTIVES: Children with medical complexity (CMC) are high health care utilizers prompting hospitals to implement care models focused on this population, yet practices have not been evaluated on a national level. Our objective with this study is to describe the presence and structure of care models and the use of discharge services for CMC admitted to freestanding children's hospitals across the nation. METHODS: We distributed an electronic survey to 48 hospitals within the Pediatric Health Information System exploring the availability of care models and discharge services for CMC. Care models were grouped by type and number present at each institution. Discharge services were grouped by low (never, rarely), medium (sometimes), and high (most of the time, always) frequency use. RESULTS: Of 48 eligible hospitals, 33 completed the survey (69%). There were no significant differences between responders and non-responders for both hospital and patient characteristics. Most participants identified an outpatient care model (67%), whereas 21% had no dedicated care model for CMC in the inpatient or outpatient setting. High-frequency discharge services included durable medical equipment delivery, medication delivery, and communication with outpatient provider before discharge. Low-frequency discharge services included the use of a structured handoff tool for outpatient communication, personalized access plans, inpatient team follow-up with family after discharge, and the use of discharge checklists. CONCLUSIONS: Children's hospitals vary largely in care model structure and discharge services. Future work is needed to evaluate the associations between care models and discharge services for CMC with various health care outcomes.

A Systematic Review and Meta-analysis of Chemical Exposures and Attention-Deficit/Hyperactivity Disorder in Children.

Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a larger set of literature searches conducted to synthesize results from longitudinal studies of potentially modifiable risk factors for childhood ADHD, we present meta-analytic results from 66 studies that examined the associations between early chemical exposures and later ADHD diagnosis or symptoms. Studies were eligible for inclusion if the chemical exposure occurred at least 6 months prior to measurement of ADHD diagnosis or symptomatology. Included papers were published between 1975 and 2019 on exposure to anesthetics (n = 5), cadmium (n = 3), hexachlorobenzene (n = 4), lead (n = 22), mercury (n = 12), organophosphates (n = 7), and polychlorinated biphenyls (n = 13). Analyses are presented for each chemical exposure by type of ADHD outcome reported (categorical vs. continuous), type of ADHD measurement (overall measures of ADHD, ADHD symptoms only, ADHD diagnosis only, inattention only, hyperactivity/impulsivity only), and timing of exposure (prenatal vs. childhood vs. cumulative), whenever at least 3 relevant effect sizes were available. Childhood lead exposure was positively associated with ADHD diagnosis and symptoms in all analyses except for the prenatal analyses (odds ratios (ORs) ranging from 1.60 to 2.62, correlation coefficients (CCs) ranging from 0.14 to 0.16). Other statistically significant associations were limited to organophosphates (CC = 0.11, 95% confidence interval (CI): 0.03-0.19 for continuous measures of ADHD outcomes overall), polychlorinated biphenyls (CC = 0.08, 95% CI: 0.02-0.14 for continuous measures of inattention as the outcome), and both prenatal and childhood mercury exposure (CC = 0.02, 95% CI: 0.00-0.04 for continuous measures of ADHD outcomes overall for either exposure window). Our findings provide further support for negative impacts of prenatal and/or childhood exposure to certain chemicals and raise the possibility that primary prevention and targeted screening could prevent or mitigate ADHD symptomatology. Furthermore, these findings support the need for regular review of regulations as our scientific understanding of the risks posed by these chemicals evolves.

Systematic Review and Meta-analysis of the Relationship Between Exposure to Parental Substance Use and Attention-Deficit/Hyperactivity Disorder in Children.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by persistent patterns of inattention, hyperactivity, and impulsiveness. Among US children and adolescents aged 3-17 years, 9.4% have a diagnosis of ADHD. Previous research suggests possible links between parental substance use and ADHD among children. We conducted a systematic review and meta-analysis of 86 longitudinal or retrospective studies of prenatal or postnatal alcohol, tobacco, or other parental substance use and substance use disorders and childhood ADHD and its related behavioral dimensions of inattention and hyperactivity-impulsivity. Meta-analyses were grouped by drug class and pre- and postnatal periods with combined sample sizes ranging from 789 to 135,732. Prenatal exposure to alcohol or tobacco and parent substance use disorders were consistently and significantly associated with ADHD among children. Other parental drug use exposures resulted in inconsistent or non-significant findings. Prevention and treatment of parental substance use may have potential for impacts on childhood ADHD.

Pediatric COVID-19 Vaccination in the Inpatient Setting.

BACKGROUND AND OBJECTIVES: The inpatient setting is often underutilized as a venue for providing pediatric vaccines. During the 2019 novel coronavirus (COVID-19) pandemic, our hospital began a vaccination program to provide access to COVID-19 vaccines for eligible pediatric inpatients. Our objective was to describe the establishment and assess the impact of a COVID-19 vaccination program for pediatric inpatients. METHODS: All admitted patients were screened for eligibility and interest in inpatient COVID-19 vaccination upon admission from April 27, 2021 until February 12, 2022. For those eligible for vaccination, their interest was recorded and shared with the clinical team. The clinical team completed education and/or vaccination depending on individual case. Interest in inpatient vaccination and ultimate receipt of a vaccine was recorded and analyzed. RESULTS: During the study period, 1615 patients were eligible for inpatient vaccination and 1601 had their interest recorded on hospital admission. Twenty-one percent of these patients were interested, 50% declined, and 28% were unsure. Twenty-nine percent of those initially interested were given vaccine by the clinical team before discharge. Six percent of patients who were unsure and 2% of those who declined vaccine on admission were vaccinated before discharge. CONCLUSIONS: The inpatient setting can be an important venue to allow for education and discussion regarding pediatric COVID-19 vaccine and to improve access to vaccination for a traditionally under-vaccinated population. Challenges remain with consistent vaccine administration even for interested pediatric inpatients.

Increasing Nurse-Physician Family-Centered Rounds Communication: A Quality Improvement Pilot Project.

BACKGROUND: High-quality nurse-physician communication during family-centered rounds (FCRs) can increase patient safety. LOCAL PROBLEM: In our hospital, interdisciplinary team members perceived that nurse-physician communication during FCRs declined during the COVID-19 pandemic. METHODS: Using quality improvement methodology, we measured nurses' perceived awareness of components of the shared mental model, nurses' attendance during FCRs, compliance with completing FCR summaries, and average time spent per FCR encounter. INTERVENTIONS: A structured resident huddle took place prior to an FCR. Residents used a tool to send individualized alerts to bedside nurses to prepare them for an FCR. Residents developed comprehensive summaries after each FCR encounter and sent a summary text to nurses who were unable to attend the FCR. RESULTS: We assessed 40 FCRs over 16 weeks. Nurses' perceived awareness increased from 70% to 87%. Nurse attendance increased from 53% to 75%. CONCLUSIONS: We successfully piloted multiple interventions to improve nurse perceived awareness after an FCR.

Hemoglobin Change after Red Blood Cell Transfusion for Postpartum Anemia: Secondary Analysis of a Randomized, Controlled Trial.

OBJECTIVE: We aimed to describe hemoglobin (Hb) change after transfusion in the nonacute postpartum anemic population in order to provide clinicians with appropriate expectations regarding Hb rise posttransfusion. STUDY DESIGN: We performed a secondary analysis of a randomized controlled trial comparing initial transfusion with 1 unit of packed red blood cells (pRBCs) to 2 units pRBCs for postpartum women requiring nonacute transfusion (n = 66). Inclusion criteria were: age 18 years and older, Hb level either <7 g/dL or >7 g/dL with signs or symptoms of anemia, and > 6 hours postpartum without contraindication to transfusion. Hb assessment was performed 4 to 6 hours after initial transfusion. Hb change (ΔHb) was calculated as posttransfusion Hb minus randomization Hb. Our primary goal was to describe mean ΔHb per pRBC transfused at the 4- to 6-hour posttransfusion blood count. We also compared ΔHb per pRBC transfused by number of units transfused, body mass index (BMI), and symptoms (dizziness and/or fatigue) at time of posttransfusion assessment. RESULTS: Participants were mean age 29, mean BMI of 27, and over 70% self-identified as black, 12% identified as white, and 9% as Asian race. Mean Hb prior to transfusion was 6.9 ± 0.6 g/dL. Mean ΔHb per pRBC transfused was 0.9 ± 0.4g/dL. There was no difference in ΔHb per pRBC by BMI category (normal weight < 25 kg/m2: 1.1 ± 0.2 g/dL; overweight 25-29.9 kg/m2: 0.9 ± 0.5 g/dL; obese ≥ 30 kg/m2: 0.9 ± 0.5 g/dL; p = 0.12). Finally, there was also no significant difference in ΔHb per pRBC by whether or not symptoms of anemia persisted after initial transfusion (1.0 ± 0.7 vs. 0.9 ± 0.4 g/dL, p = 0.39). CONCLUSION: Our data supports the classically accepted rise in Hb after pRBC of approximately 1 g/dL, regardless of BMI category or anemia symptomatology. The study population includes patients at highest risk of postpartum anemia. The results of our study provide important information for clinicians caring for postpartum patients with nonacute anemia. KEY POINTS: · Postpartum anemia is a significant public health issue.. · Providers use hemoglobin change to assess response to blood transfusion.. · The established 1 g/dL change in Hb after transfusion is based on historic surgical populations.. · Our data suggests the 1 g/dL Hb change is applicable to postpartum patients..

Safety of Same-Day Discharge Versus Hospital Admission in Minimally Invasive Myomectomy.

STUDY OBJECTIVE: To compare postoperative complication rates between same-day discharge patients and patients admitted to hospital after minimally invasive myomectomy, stratified by patient demographics and perioperative variables including myoma burden. DESIGN: Retrospective cohort study. Setting Hospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2019. PATIENTS: Female patients aged ≥18 years undergoing minimally invasive myomectomy. INTERVENTIONS: Patients were categorized into either the same-day discharge or admitted patient cohort. Univariate comparisons of demographics, perioperative variables, and 30-day postoperative complications were performed. Multivariate logistic regression was used to 1) identify demographic and perioperative factors associated with admission, and 2) compare postoperative complication rates of same-day discharge patients with those of admitted patients while adjusting for demographic and perioperative factors. MEASUREMENTS AND MAIN RESULTS: Eight thousand one hundred patients were recruited during the study period. The overall rate of same-day discharge was 57.2% in 2015 and 65.0% in 2019. The same-day discharge rate was 64.6% for patients with a smaller myoma burden (1-4 fibroids and ≤250 grams, Current Procedural Terminology 58545) and 56.8% for larger myoma burden (≥5 fibroids or >250 grams, Current Procedural Terminology 58546). Age, race, American Society of Anesthesiologists classification III or IV, preoperative hematocrit <36%, hypertension, diabetes, bleeding disorder, and increasing operative time were associated with admission to hospital. After adjusting for these variables, composite postoperative complication rates were similar between admitted patients and patients who were discharged the same day regardless of myoma burden (adjusted OR [aOR], 0.66; 95% confidence interval [CI] 0.18-2.47 for low myoma burden and aOR, 0.91; 95% CI 0.18-4.63 for high myoma burden). Admitted patients with both low (aOR, 9.1; 95% CI 2.27-37.04) and high (aOR, 8.24; 95% CI 1.59-42.49) myoma burdens were significantly more likely to receive a blood transfusion compared to same-day discharge patients. CONCLUSION: Same-day discharge after minimally invasive myomectomy, regardless of myoma burden, is associated with low complication rates. Our findings may aid in shared decision making on discharge planning.

Length of Stay and Barriers to Discharge for Technology-Dependent Children During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: During the coronavirus disease 2019 pandemic, technology-dependent children are at risk of encountering barriers to hospital discharge because of limits to in-home services. Transition difficulties could increase length of stay (LOS). With this study, we aim to (1) evaluate change in LOS and (2) describe barriers to hospital discharge between prepandemic and early pandemic periods for technology-dependent children. METHODS: A retrospective chart review of technology-dependent children discharged from an acute and specialty pediatric hospital within a single urban area between January 1 and May 28, 2020 was conducted. Technology dependence was defined by using a validated complex chronic condition coding system. Patients discharged prepandemic and during the pandemic were compared. Outcomes included LOS and the number and type of discharge barriers (a factor not related to a medical condition that delays discharge). Multivariate regression modeling and parametric and nonparametric analysis were used to compare cohorts. RESULTS: Prepandemic, 163 patients were discharged, and 119 were discharged during the early stages of the pandemic. The most common technology dependence was a feeding tube. The unadjusted median LOS was 7 days in both groups. After adjusting for patient-level factors, discharge during the pandemic resulted in a 32.2% longer LOS (confidence interval 2.1%-71.2%). The number of discharge barriers was high but unchanged between cohorts. Lack of a trained caregiver was more frequent during the pandemic (P = .03). CONCLUSIONS: Barriers to discharge were frequent for both cohorts. Discharge during the pandemic was associated with longer LOS. It was more difficult to identify a trained caregiver during the pandemic.

Development and Implementation of a Peer Curbside Consult Service for Pediatric Hospitalists.

OBJECTIVE: To describe the development and implementation of a Peer Curbside Consult Service (PCCS) for a pediatric hospital medicine (PHM) division. METHODS: We developed a pilot intervention with hospitalists at a freestanding children's hospital to provide peer consultation services for challenging clinical cases. Postconsultation surveys collected from both the requesting and consulting hospitalists provided feedback about the program. The 12-point Template for Intervention Description and Replication (TIDieR) checklist is used to describe the process for program creation and implementation. RESULTS: The PCCS has provided 60 consultations in the first 2 years since implementation in April 2020 and supports a large PHM division with >75 members who practice at a tertiary care, freestanding children's hospital and 7 affiliate sites. Hospitalists request peer consultation for challenging clinical cases. The consultations were typically conducted in person or via telephone. Currently, 11 PHM faculty members within the division volunteer as consultants, with 2 assigned per week. Electronic postconsultation experience surveys were received from 70% of requesting and 89% of consultant hospitalists. We also provide preliminary data from this pilot intervention in the Supplemental Information. CONCLUSIONS: We successfully established a peer consult service that provided just-in-time clinical decision support across the various practice sites. Through transparent reporting using the TIDieR checklist, other divisions may be able to replicate and adapt their own peer consult program.

Childhood Physical Health and Attention Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Modifiable Factors.

Although neurobiologic and genetic factors figure prominently in the development of attention deficit/hyperactivity disorder (ADHD), adverse physical health experiences and conditions encountered during childhood may also play a role. Poor health is known to impact the developing brain with potential lifelong implications for behavioral issues. In attempt to better understand the relationship between childhood physical health and the onset and presence of ADHD symptoms, we summarized international peer-reviewed articles documenting relationships between a select group of childhood diseases or health events (e.g., illnesses, injuries, syndromes) and subsequent ADHD outcomes among children ages 0-17 years. Drawing on a larger two-phase systematic review, 57 longitudinal or retrospective observational studies (1978-2021) of childhood allergies, asthma, eczema, head injury, infection, or sleep problems and later ADHD diagnosis or symptomatology were identified and subjected to meta-analysis. Significant associations were documented between childhood head injuries, infections, and sleep problems with both dichotomous and continuous measures of ADHD, and between allergies with dichotomous measures of ADHD. We did not observe significant associations between asthma or eczema with ADHD outcomes. Heterogeneity detected for multiple associations, primarily among continuously measured outcomes, underscores the potential value of future subgroup analyses and individual studies. Collectively, these findings shed light on the importance of physical health in understanding childhood ADHD. Possible etiologic links between physical health factors and ADHD are discussed, as are implications for prevention efforts by providers, systems, and communities.

Oncologic outcomes of surgical para-aortic lymph node staging in patients with advanced cervical carcinoma undergoing chemoradiation.

OBJECTIVES: We aimed to evaluate the utilization and impact of surgical para-aortic lymph node staging on the survival of patients with locally advanced stage cervical carcinoma receiving definitive chemoradiation. METHODS: We identified patients in the National Cancer Database diagnosed between January 2010 and December 2015 with locally advanced (FIGO 2009 stage IB2-IVA) cervical carcinoma who did not undergo hysterectomy, received primary chemoradiation and had at least 1 month of follow-up. Two groups of patients were formed based on the assessment method of para-aortic lymph node status - radiologic assessment only versus surgical lymphadenectomy. Overall survival was compared with the log-rank test after Kaplan-Meier curves were generated. A Cox model was constructed to control for a priori selected confounders. RESULTS: We identified a total of 3540 patients who met the inclusion criteria. Para-aortic staging was performed in 333 (9.4%) patients. These patients were younger (median age 46 vs 52 years, p<0.001), less likely to have co-morbidities (8.7% vs 15.6%, p<0.001), more likely to have private insurance (48.9% vs 37.8%, p<0.001) and receive brachytherapy (76.9% vs 70.9%, p=0.022). The rate of para-aortic lymphadenectomy was comparable between patients with stage IB2-II and III-IVA disease (9.4% for both groups, p=0.98). Patients who underwent para-aortic lymphadenectomy were also more likely to have lymph nodes categorized as positive compared with those who had imaging only (27.3% vs 13.2%, p<0.001). There was no difference in overall survival between patients who underwent radiologic only or surgical para-aortic lymph node assessment (p=0.80 from log-rank test); 4 year overall survival rates were 62.9% and 63%. After controlling for confounders, performance of para-aortic lymphadenectomy was not associated with a survival benefit (HR 1.07, 95% CIs: 0.88 to 1.31). CONCLUSIONS: In a large cohort of patients with locally advanced stage cervical carcinoma, para-aortic lymphadenectomy was rarely performed and not associated with a survival benefit.

A Systematic Review and Meta-analysis of Parental Depression, Antidepressant Usage, Antisocial Personality Disorder, and Stress and Anxiety as Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD) in Children.

Poor parental mental health and stress have been associated with children's mental disorders, including attention-deficit/hyperactivity disorder (ADHD), through social, genetic, and neurobiological pathways. To determine the strength of the associations between parental mental health and child ADHD, we conducted a set of meta-analyses to examine the association of parent mental health indicators (e.g., parental depression, antidepressant usage, antisocial personality disorder, and stress and anxiety) with subsequent ADHD outcomes in children. Eligible ADHD outcomes included diagnosis or symptoms. Fifty-eight articles published from 1980 to 2019 were included. We calculated pooled effect sizes, accounting for each study's conditional variance, separately for test statistics based on ADHD as a dichotomous (e.g., diagnosis or clinical cutoffs) or continuous measurement (e.g., symptoms of ADHD subtypes of inattentiveness and hyperactivity/impulsivity). Parental stress and parental depression were significantly associated with increased risk for ADHD overall and both symptoms and diagnosis. Specifically, maternal stress and anxiety, maternal prenatal stress, maternal depression, maternal post-partum depression, and paternal depression were positively associated with ADHD. In addition, parental depression was associated with symptoms of ADHD inattentive and hyperactive/impulsive subtypes. Parental antisocial personality disorder was also positively associated with ADHD overall and specifically ADHD diagnosis. Prenatal antidepressant usage was associated with ADHD when measured dichotomously only. These findings raise the possibility that prevention strategies promoting parental mental health and addressing parental stress could have the potential for positive long-term impacts on child health, well-being, and behavioral outcomes.

All in the Family? A Systematic Review and Meta-analysis of Parenting and Family Environment as Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD) in Children.

Parenting and family environment have significant impact on child development, including development of executive function, attention, and self-regulation, and may affect the risk of developmental disorders including attention-deficit/hyperactivity disorder (ADHD). This paper examines the relationship of parenting and family environment factors with ADHD. A systematic review of the literature was conducted in 2014 and identified 52 longitudinal studies. A follow-up search in 2021 identified 7 additional articles, for a total of 59 studies that examined the association of parenting factors with ADHD outcomes: ADHD overall (diagnosis or symptoms), ADHD diagnosis specifically, or presence of the specific ADHD symptoms of inattention and hyperactivity/impulsivity. For parenting factors that were present in three or more studies, pooled effect sizes were calculated separately for dichotomous or continuous ADHD outcomes, accounting for each study's conditional variance. Factors with sufficient information for analysis were parenting interaction quality (sensitivity/warmth, intrusiveness/reactivity, and negativity/harsh discipline), maltreatment (general maltreatment and physical abuse), parental relationship status (divorce, single parenting), parental incarceration, and child media exposure. All factors showed a significant direct association with ADHD outcomes, except sensitivity/warmth which had an inverse association. Parenting factors predicted diagnosis and overall symptoms as well as inattentive and hyperactive symptoms when measured, but multiple factors showed significant heterogeneity across studies. These findings support the possibility that parenting and family environment influences ADHD symptoms and may affect a child's likelihood of being diagnosed with ADHD. Prevention strategies that support parents, such as decreasing parenting challenges and increasing access to parent training in behavior management, may improve children's long-term developmental health.

A Systematic Review and Meta-analysis of Prenatal, Birth, and Postnatal Factors Associated with Attention-Deficit/Hyperactivity Disorder in Children.

Previous studies have shown mixed results on the relationship between prenatal, birth, and postnatal ("pregnancy-related") risk factors and attention-deficit/hyperactivity disorder (ADHD). We conducted meta-analyses to identify potentially modifiable pregnancy-related factors associated with ADHD. A comprehensive search of PubMed, Web of Science, and EMBASE in 2014, followed by an updated search in January 2021, identified 69 articles published in English on pregnancy-related risk factors and ADHD for inclusion. Risk factors were included in the meta-analysis if at least three effect sizes with clear pregnancy-related risk factor exposure were identified. Pooled effect sizes were calculated for ADHD overall, ADHD diagnosis, inattention, and hyperactivity/impulsivity. Odds ratios (OR) were calculated for dichotomous measures and correlation coefficients (CC) for continuous measures. Prenatal factors (pre-pregnancy weight, preeclampsia, pregnancy complications, elevated testosterone exposure), and postnatal factors (Apgar score, neonatal illness, no breastfeeding) were positively associated with ADHD overall; the findings for ADHD diagnosis were similar with the exception that there were too few effect sizes available to examine pre-pregnancy weight and lack of breastfeeding. Prenatal testosterone was significantly associated with inattention and hyperactivity/impulsivity. Effect sizes were generally small (range 1.1-1.6 ORs, -0.16-0.11 CCs). Risk factors occurring at the time of birth (perinatal asphyxia, labor complications, mode of delivery) were not significantly associated with ADHD. A better understanding of factors that are consistently associated with ADHD may inform future prevention strategies. The findings reported here suggest that prenatal and postnatal factors may serve as potential targets for preventing or mitigating the symptoms of ADHD.

Novel isoforms of influenza virus PA-X and PB1-F2 indicated by automatic annotation.

The influenza A virus genome contains 8 gene segments encoding 10 commonly recognized proteins. Additional protein products have been identified, including PB1-F2 and PA-X. We report the in-silico identification of novel isoforms of PB1-F2 and PA-X in influenza virus genomes sequenced from avian samples. The isoform observed in PA-X includes a mutated stop codon that should extend the protein product by 8 amino acids. The isoform observed in PB1-F2 includes two nonsense mutations that should truncate the N-terminal region of the protein product and remove the entire mitochondrial targeting domain. Both isoforms were uncovered during automatic annotation of CEIRS sequence data. Nominally termed PA-X8 and PB1-F2-Cterm, both predicted isoforms were subsequently found in other annotated influenza genomes previously deposited in GenBank. Both isoforms were noticed due to discrepant annotations output by two annotation engines, indicating a benefit of incorporating multiple algorithms during gene annotation.

Occupational Safety and Health and Illicit Opioids: State of the Research on Protecting Against the Threat of Occupational Exposure.

The nationwide opioid crisis continues to affect not only people who use opioids but also communities at large by increasing the risk of accidental occupational exposure to illicit opioids. In addition, the emergence of highly potent synthetic opioids such as fentanyl and carfentanil increases the need to protect workers who may encounter unknown drug substances during job activities. To support the National Institute for Occupational Safety and Health Opioids Research Gaps Working Group, we examined the state of the literature concerning methods to protect workers against accidental occupational exposure to illicit opioids, and have identified unmet research needs concerning personal protective equipment, decontamination methods, and engineering controls. Additional studies are needed to overcome gaps in technical knowledge about personal protective equipment, decontamination, and control methods, and gaps in understanding how these measures are utilized by workers. Increasing our knowledge of how to protect against exposure to illicit opioids has the potential to improve occupational health across communities.

Development of Novel Video-Based First Responder Opioid Hazard Refresher Training.

First responders encounter many hazards in the execution of their duties, and exposure to hazardous materials such as opioids is a primary safety concern. The ongoing opioid crisis in the United States continues to be a major public health issue, with overdose deaths from opioids reaching epidemic levels. Although responders frequently encounter opioids, available data on safety and risk are not always well-communicated, and we identified a need for refresher and just-in-time training products on this topic. In response, we created a training video series that is informative, concise, and visually appealing. The video series, available on YouTube, was tested with a small initial population, with findings suggesting key questions for a larger study focused on integration of the refresher training with existing programs to optimize retention and adoption of safety practices.

Early Predictors of Performance Deficiencies in Academic Faculty: Pre-Employment Red Flags.

OBJECTIVE: To determine whether faculty who had red flags (unprofessional behavior, delayed response to queries, or delayed submission of required documentation) during pre-employment were more likely to have performance deficiencies than faculty who did not have red flags. METHODS: The study included 187 faculty consecutively hired in a Department of Pediatrics in a large academic health system from 2013 to 2018. Faculty with and without pre-employment red flags were compared to identify the proportion who had subsequent performance deficiencies related to documentation, unprofessional behavior, performance, or premature departure from the faculty. RESULTS: Most of the hired faculty were female (127, 0.68), physicians (136, 0.73), and clinicians or clinician-educators (124, 0.67). Sixteen faculty (0.09) had pre-employment red flags. In the 3 years after hiring, 31 (0.17) of the faculty cohort had at least 1 performance deficiency. Faculty with pre-employment red flags were more than 4 times as likely to experience a performance deficiency during follow-up (0.56 vs 0.13, P < .001). The hazard ratio for performance deficiency comparing faculty with pre-employment red flags to those without was 5.98 (95% confidence interval 2.73-13.1, P < .0001). CONCLUSIONS: Faculty who had pre-employment red flags were significantly more likely to experience subsequent performance deficiencies. Given the substantial investment that individuals and academic medical centers make in recruiting and hiring new faculty, efforts to identify and assist faculty members at risk provide academic departments opportunities to provide the best environment for success for all faculty.