Comparing the Prevalence of Psychiatric Disorders in Cohorts of Children Born Extremely Preterm in 1995 and 2006: The EPICure Studies.

Objective: This study aimed to identify the prevalence of psychiatric disorders in 2 population-based cohorts of children born extremely preterm (EP) 11 years apart to ascertain whether psychiatric outcomes have changed over time following improved survival of EP children. Method: In the EPICure2 study, 200 children born EP (22-26 weeks' gestation) in England in 2006 were assessed at 11 years of age alongside 143 term-born children. Children were assessed using the Developmental and Wellbeing Assessment (DAWBA). DSM-IV diagnoses were assigned by clinical psychiatrists for 145 EP and 98 term-born children. Outcomes were compared between a subsample of children from the EPICure2 cohort (2006, n = 76) and the earlier-born EPICure (1995, n = 161) cohort born at 22 to 25 weeks' gestation in England. Results: EP children in EPICure2 were significantly more likely than term-born children to have any psychiatric disorder (39.3% vs 3.1%; adjusted odds ratio [OR] = 15.1, 95% CI = 4.4-51.1), emotional disorders (14.6% vs 2.0%; OR = 7.3, 95% CI = 1.6-32.7), conduct disorders (6.3% vs 0.0%, p = .01), attention-deficit/hyperactivity disorder (ADHD, 21.9% vs 2.6%; OR = 7.2; 95% CI = 1.5-33.6), and autism spectrum disorder (ASD, 18.9%; vs 0.0%, p < .001). There was no significant difference in the rates of any psychiatric disorder between EP children in the EPICure2 and EPICure cohorts. Conclusion: EP children remain at increased risk for psychiatric disorders at 11 years of age compared with term-born peers. Increased survival has not translated into improved psychiatric outcomes. Health care professionals need to be aware of this ongoing risk when caring for children born preterm.

Medical advances have improved the survival of extremely preterm children, but whether long-term outcomes have also improved is unclear. This study compared rates of psychiatric disorders at age 11 years among 76 children born extremely preterm in 1995 and 161 children born extremely preterm in 2006, to identify trends in psychiatric outcomes. Results showed that children born extremely preterm in 2006 were more likely than term children to have psychiatric disorders (39.3% vs 3.1%). There was no difference in rates of disorders between children born extremely preterm in 2006 and 1995. These results suggest that there has been no improvement in psychological outcomes for extremely preterm children, and healthcare professionals should continue to monitor for psychiatric disorders in this population.

Romantic and sexual relationships of young adults born very preterm: An individual participant data meta-analysis.

AIM: To compare romantic and sexual relationships between adults born very preterm (VP; <32 weeks of gestation) or with very low birth weight (VLBW; <1500 g) and at term, and to evaluate potential biological and environmental explanatory factors among VP/VLBW participants. METHODS: This individual participant data (IPD) meta-analysis included longitudinal studies assessing romantic and sexual relationships in adults (mean sample age ≥ 18 years) born VP/VLBW compared with term-born controls. Following PRISMA-IPD guidelines, 11 of the 13 identified cohorts provided IPD from 1606 VP/VLBW adults and 1659 term-born controls. IPD meta-analyses were performed using one-stage approach. RESULTS: Individuals born VP/VLBW were less likely to be in a romantic relationship (OR 0.49; 95% CI 0.31-0.76), to be married/cohabiting (OR 0.70, 95% CI 0.53-0.92), or to have had sexual intercourse (OR 0.21, 95% CI 0.09-0.36) than term-born adults. If sexually active, VP/VLBW participants were more likely to experience their first sexual intercourse after the age of 18 years (OR 1.93, 95% CI 1.24-3.01) than term-born adults. Among VP/VLBW adults, males, and those with neurosensory impairment were least likely to experience romantic relationships. CONCLUSIONS: These findings reflect less optimal social functioning and may have implications for socioeconomic and health outcomes of adults born VP/VLBW.

Genomic Analysis Aids in the Management of Dermoscopically Atypical Pigmented Lesions.

BACKGROUND: Numerous melanoma-specific dermoscopic features have been described in invasive melanomas, while fewer features are found in melanoma in situ (MIS) and atypical nevi (ATN). Consensus regarding which features are critical for the differentiation of MIS from ATN has not been reached. PURPOSE: Determine 1) whether there are dermoscopic features that differentiate early MIS from ATN, and 2) whether non-invasive assessment of genomic biomarkers (LINC00518 and PRAME) can aid in patient management. METHODS: From 2018 to 2023, 56 melanomas were evaluated for 5 clinical and 13 dermoscopic features and melanoma-associated genomic biomarkers. Two groups of ATN with positive and negative genomic biomarkers were randomly selected for comparison. RESULTS: All melanomas in this study expressed one or both melanoma-associated genomic markers. MIS had an average of 3.90 (range, 2-7) of the 13 dermoscopic features, while invasive melanomas had an average of 4.44 (range, 3-6). Sixteen of 40 (40%) MIS and 3 of 16 (18.8%) invasive melanomas had 3 or fewer dermoscopic features. These findings were comparable to those observed in both ATN groups. The most common dermoscopic features were absent or diminished pigment network, regression structures, and granularity. This combination of features was most helpful in identifying lesions for genomic testing. CONCLUSIONS: Clinical and dermoscopic features alone could not differentiate MIS from ATN. Non-invasive genomic testing helped differentiate lower from higher-risk lesions and aid in clinical management decisions. Genomic testing was particularly helpful in patients with large numbers of lesions with several being considered for biopsy based on clinical and dermoscopic examination. J Drugs Dermatol. 2024;23(9):717-723. doi:10.36849/JDD.8454.

Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers.

To identify cancer-associated gene regulatory changes, we generated single-cell chromatin accessibility landscapes across eight tumor types as part of The Cancer Genome Atlas. Tumor chromatin accessibility is strongly influenced by copy number alterations that can be used to identify subclones, yet underlying cis-regulatory landscapes retain cancer type-specific features. Using organ-matched healthy tissues, we identified the "nearest healthy" cell types in diverse cancers, demonstrating that the chromatin signature of basal-like-subtype breast cancer is most similar to secretory-type luminal epithelial cells. Neural network models trained to learn regulatory programs in cancer revealed enrichment of model-prioritized somatic noncoding mutations near cancer-associated genes, suggesting that dispersed, nonrecurrent, noncoding mutations in cancer are functional. Overall, these data and interpretable gene regulatory models for cancer and healthy tissue provide a framework for understanding cancer-specific gene regulation.

Anthropogenic, environmental and temporal associations with vertebrate road mortality in a wildland-urban interface of a biodiverse desert ecoregion.

Road mortality adversely affects wildlife populations. As urbanization and infrastructure densities expand, transportation and wildlife management aim to mitigate wildlife-vehicle conflicts while conserving biodiversity. Roadways in aridland ecosystems can invariably and adversely impact wildlife differently from temperate and other biomes, yet these rapidly urbanizing regions are understudied as are urban-rural gradients. We conducted road-cruise surveys (n = 204; 2018-2023) to assess anthropogenic, environmental, and temporal factors associated with vertebrate roadkill across the wildland-urban interface of Arizona's biodiverse Sonoran Desert ecoregion-already subjected to increased human development and climate change. Of n = 2019 vertebrates observed, 28.5% were roadkill. Increasing urbanization levels were associated with reduced vertebrate abundance on roads and increased road-killed endothermic vertebrates. Traffic volume was strongly associated with reduced vertebrate abundance and increased roadkill; additive effects on roadkill began at approximately 20 vehicles. Daily low temperature and/or relative humidity were also associated with roadkill across vertebrate groups. We provide empirical evidence to understand wildlife-roadkill associations across expanding wildland-urban interfaces to inform effective roadkill mitigation and wildlife conservation management strategies in biodiverse aridland regions. We recommend that managers mitigate or avoid development in rural areas that possess high biodiversity, valuable waterways or migration corridors, and populations of vulnerable species.

Demographic, Environmental, and Psychosocial Influences on Resilience Toward Chronic Stress.

As studied previously, chronic stress environments lead to the formation of distinctive resilience groupings when related to individual outcomes among participants. The majority of the population has decreased mental and physical strength during prolonged periods of mental distress but returns to baseline status when those stressors are removed. Others have increased and decreased mental fortitude despite the removal of stressors. Our hypothesis is that certain demographic, environmental, and/or transgenerational aspects are associated with resilience or lack thereof in populations with a history of chronic stress. The end goal is the early identification of at-risk populations to decrease adverse outcomes and improve quality of life. In this review, we looked at 17 studies to gain a greater understanding of which factors influence individual resilience. The factors found to have a positive relationship with resilience were religion, cognitive function, socioeconomic status, marriage, psychological functioning, positive coping mechanisms, and relationships; the negative were medical diagnoses, violence exposure, female sex, stressors/trauma, disaster exposure, and negative coping mechanisms. During our research, we found that transgenerational aspects such as race/ethnicity, occupation, education, age, substance use, and physical location had mixed results across multiple studies. These findings suggest the need for future original research to allow for a definitive understanding of populations resilient to chronic stress.

Oxidation of Ammonia Catalyzed by a Molecular Iron Complex: Translating Chemical Catalysis to Mediated Electrocatalysis.

Ammonia is a promising candidate in the quest for sustainable, clean energy. With its capacity to serve as an energy carrier, the oxidation of ammonia opens avenues for carbon-neutral approaches to address worldwide growing energy needs. We report the catalytic chemical oxidation of ammonia by an Earth-abundant transition metal complex, trans-[LFeII(MeCN)2][PF6]2, where L is a macrocyclic ligand bearing four N-heterocyclic carbene (NHC) donors. Using triarylaminium radical cations in MeCN, up to 182 turnovers of N2 per Fe were obtained from chemical catalysis with an extremely low loading of the Fe catalyst (0.043 mM, 0.004 mol % catalyst). This chemical catalysis was successfully transitioned to mediated electrocatalysis for the oxidation of ammonia. Molecular electrocatalysis by the Fe catalyst and the mediator (p-MeOC6H4)3N exhibited a catalytic half-wave potential (Ecat/2) of 0.18 V vs [Cp2Fe]+/0 in MeCN, and achieved 9.3 turnovers of N2 at an applied potential of 0.20 V vs [Cp2Fe]+/0 at -20 °C in controlled-potential electrolysis, with a Faradaic efficiency of 75%. Based on computational results, the catalyst undergoes sequential oxidation and deprotonation steps to form [LFeIV(NH2)2]2+, and thereafter bimetallic coupling to form an N-N bond.

The impact of Chatbot-Assisted Self Assessment (CASA) on intentions for sexual health screening in people from minoritised ethnic groups at risk of sexually transmitted infections.

Background Sexually transmitted infections (STIs) present a significant global public health issue, with disparities in STI rates often observed across ethnic groups. The study investigates the impact of Chatbot-Assisted Self Assessment (CASA) on the intentions for sexual health screening within minoritised ethnic groups (MEGs) at risk of STIs as well as the subsequent use of a chatbot for booking STI screening. Methods A simulation within-subject design was utilised to evaluate the effect of CASA on intentions for STI/HIV screening, concern about STIs, and attitudes towards STI screening. Screening intentions served as the dependent variable, while demographic and behavioural factors related to STI/HIV risk were the independent variables. ANCOVA tests were conducted to measure the impact of CASA on these perceptions. Results Involving 548 participants (54% women, 66% black, average age=30years), the study found that CASA positively influenced screening intentions t (547)=-10.3, P t (544)=-4.96, P t (543)=-4.36, P Conclusion CASA increased motivations for STI screening intentions among ethnically diverse communities. The intervention's non-judgemental nature and the chatbot's ability to emulate sexual history-taking were critical in fostering an environment conducive to behavioural intention change. The study's high acceptability indicates the potential for broader application in digital health interventions. However, the limitation of not tracking actual post-intervention behaviour warrants further investigation into CASA's real-world efficacy.

Termination of Resuscitation Rules and Survival Among Patients With Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.

Importance: Termination of resuscitation (TOR) rules may help guide prehospital decisions to stop resuscitation, with potential effects on patient outcomes and health resource use. Rules with high sensitivity risk increasing inappropriate transport of nonsurvivors, while rules without excellent specificity risk missed survivors. Further examination of the performance of TOR rules in estimating survival of out-of-hospital cardiac arrest (OHCA) is needed. Objective: To determine whether TOR rules can accurately identify patients who will not survive an OHCA. Data Sources: For this systematic review and meta-analysis, the MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science databases were searched from database inception up to January 11, 2024. There were no restrictions on language, publication date, or time frame of the study. Study Selection: Two reviewers independently screened records, first by title and abstract and then by full text. Randomized clinical trials, case-control studies, cohort studies, cross-sectional studies, retrospective analyses, and modeling studies were included. Systematic reviews and meta-analyses were reviewed to identify primary studies. Studies predicting outcomes other than death, in-hospital studies, animal studies, and non-peer-reviewed studies were excluded. Data Extraction and Synthesis: Data were extracted by one reviewer and checked by a second. Two reviewers assessed risk of bias using the Revised Quality Assessment Tool for Diagnostic Accuracy Studies. Cochrane Screening and Diagnostic Tests Methods Group recommendations were followed when conducting a bivariate random-effects meta-analysis. This review followed the Preferred Reporting Items for a Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) statement and is registered with the International Prospective Register of Systematic Reviews (CRD42019131010). Main Outcomes and Measures: Sensitivity and specificity tables with 95% CIs and bivariate summary receiver operating characteristic (SROC) curves were produced. Estimates of effects at different prevalence levels were calculated. These estimates were used to evaluate the practical implications of TOR rule use at different prevalence levels. Results: This review included 43 nonrandomized studies published between 1993 and 2023, addressing 29 TOR rules and involving 1 125 587 cases. Fifteen studies reported the derivation of 20 TOR rules. Thirty-three studies reported external data validations of 17 TOR rules. Seven TOR rules had data to facilitate meta-analysis. One clinical study was identified. The universal termination of resuscitation rule had the best performance, with pooled sensitivity of 0.62 (95% CI, 0.54-0.71), pooled specificity of 0.88 (95% CI, 0.82-0.94), and a diagnostic odds ratio of 20.45 (95% CI, 13.15-31.83). Conclusions and Relevance: In this review, there was insufficient robust evidence to support widespread implementation of TOR rules in clinical practice. These findings suggest that adoption of TOR rules may lead to missed survivors and increased resource utilization.

Sex differences in the association between short sleep duration and obesity: A systematic-review and meta-analysis.

AIMS: Obesity is a leading contributor to global morbidity and mortality. Short sleep duration is significantly associated with the incidence of obesity, however, it remains unclear whether this relationship is influenced by sex. The purpose of this meta-analysis was to systematically evaluate the evidence of whether the association between short sleep duration and obesity differs between males and females. DATA SYNTHESIS: The protocol was registered with PROSPERO (CRD42023374205). From inception through June 2023, Medline, Embase and Web of Science databases were searched for longitudinal cohort studies with minimum 12 months of observation. The quality of studies was assessed using the Newcastle-Ottawa Quality Assessment for Cohort Studies. Results were pooled using a random effects model. Results are expressed as ratio of odds ratios (ROR) with 95% confidence interval (CI). ROR directly estimates the relative strength of the association of interest (measured as odds ratio [OR] between females and males). Sensitivity analysis was performed and inconsistency between studies was assessed using I2 statistics. A total of 4582 articles were retrieved with the search strategy, of which 6 were included. The meta-analysis indicated that the association between short sleep duration and obesity incidence was statistically significant in both men [OR 1.26 (95% CI 1.13-1.40)] and women [OR 1.36 (95% CI 1.16-1.59)]. However, it did not differ significantly between sexes ROR (women/men) 1.04 (95%CI 0.79-1.36; I2 20.1%). CONCLUSIONS: This meta-analysis indicates that women and men who subjectively report short sleep duration have similarly increased risks of incident obesity.

Whole-body hypothermia in mild neonatal encephalopathy: protocol for a multicentre phase III randomised controlled trial.

BACKGROUND: Mild hypoxic ischemic encephalopathy is associated with sub optimal cognition and learning difficulties at school age. Although whole-body hypothermia reduces death and disability after moderate or severe encephalopathy in high-income countries, the safety and efficacy of hypothermia in mild encephalopathy is not known. The cooling in mild encephalopathy (COMET) trial will examine if whole-body hypothermia improves cognitive development of neonates with mild encephalopathy. METHODS: The COMET trial is a phase III multicentre open label two-arm randomised controlled trial with masked outcome assessments. A total of 426 neonates with mild encephalopathy will be recruited from 50 to 60 NHS hospitals over 2 ½ years following parental consent. The neonates will be randomised to 72 h of whole-body hypothermia (33.5 ± 0.5 C) or normothermia (37.0 ± 0.5 C) within six hours or age. Prior to the recruitment front line clinical staff will be trained and certified on expanded modified Sarnat staging for encephalopathy. The neurological assessment of all screened and recruited cases will be video recorded and centrally assessed for quality assurance. If recruitment occurs at a non-cooling centre, neonates in both arms will be transferred to a cooling centre for continued care, after randomisation. All neonates will have continuous amplitude integrated electroencephalography (aEEG) at least for the first 48 h to monitor for seizures. Predefined safety outcomes will be documented, and data collected to assess resource utilization of health care. A central team masked to trial group allocation will assess neurodevelopmental outcomes at 2 years of age. The primary outcome is mean difference in composite cognitive scores on Bayley scales of Infant and Toddler development 4th Edition. DISCUSSION: The COMET trial will establish the safety and efficacy of whole-body hypothermia for mild hypoxic ischaemic encephalopathy and inform national and international guidelines in high income countries. It will also provide an economic assessment of whole-body hypothermia therapy for mild encephalopathy in the NHS on cost-effectiveness grounds. TRIAL REGISTRATION NUMBER: NCT05889507 June 5, 2023.

Recommendations for data collection in cohort studies of preterm born individuals - The RECAP Preterm Core Dataset.

BACKGROUND: Preterm birth (before 37 completed weeks of gestation) is associated with an increased risk of adverse health and developmental outcomes relative to birth at term. Existing guidelines for data collection in cohort studies of individuals born preterm are either limited in scope, have not been developed using formal consensus methodology, or did not involve a range of stakeholders in their development. Recommendations meeting these criteria would facilitate data pooling and harmonisation across studies. OBJECTIVES: To develop a Core Dataset for use in longitudinal cohort studies of individuals born preterm. METHODS: This work was carried out as part of the RECAP Preterm project. A systematic review of variables included in existing core outcome sets was combined with a scoping exercise conducted with experts on preterm birth. The results were used to generate a draft core dataset. A modified Delphi process was implemented using two stages with three rounds each. Three stakeholder groups participated: RECAP Preterm project partners; external experts in the field; people with lived experience of preterm birth. The Delphi used a 9-point Likert scale. Higher values indicated greater importance for inclusion. Participants also suggested additional variables they considered important for inclusion which were voted on in later rounds. RESULTS: An initial list of 140 data items was generated. Ninety-six participants across 22 countries participated in the Delphi, of which 29% were individuals with lived experience of preterm birth. Consensus was reached on 160 data items covering Antenatal and Birth Information, Neonatal Care, Mortality, Administrative Information, Organisational Level Information, Socio-economic and Demographic information, Physical Health, Education and Learning, Neurodevelopmental Outcomes, Social, Lifestyle and Leisure, Healthcare Utilisation and Quality of Life. CONCLUSIONS: This core dataset includes 160 data items covering antenatal care through outcomes in adulthood. Its use will guide data collection in new studies and facilitate pooling and harmonisation of existing data internationally.

Emergency front-of-neck access in cardiac arrest: A scoping review.

Background: Airway management is a core component of the treatment of cardiac arrest. Where a rescuer cannot establish a patent airway to provide oxygenation and ventilation using standard basic and advanced airway techniques, there may be a need to consider emergency front-of-neck airway access (eFONA, e.g., cricothyroidotomy), but there is limited evidence to inform this approach. Objectives: This scoping review aims to identify the evidence for the use of eFONA techniques in patients with cardiac arrest. Methods: In November 2023, we searched Medline, Embase, and Cochrane Central to identify studies on eFONA in adults. We included randomised controlled trials, non-randomised studies, and case series with at least five cases that described any use of eFONA. We extracted data, including study setting, population characteristics, intervention characteristics, and outcomes. Our analysis focused on four key areas: incidence of eFONA, eFONA success rates, clinical outcomes, and complications. Results: The search identified 21,565 papers, of which 18,934 remained after de-duplication. After screening, we included 69 studies (53 reported incidence, 40 reported success rate, 38 reported clinical outcomes; 36 studies reported complications). We identified only one randomised controlled trial. Across studies, there was a total of 4,457 eFONA attempts, with a median of 31 attempts (interquartile range 16-56.5) per study. There was marked heterogeneity across studies that precluded any pooling of data. There were no studies that included only patients in cardiac arrest. Conclusion: The available evidence for eFONA is extremely heterogeneous, with no studies specifically focusing on its use in adults with cardiac arrest.

The early educational environment at five years of age in a European cohort of children born very preterm: challenges and opportunities for research.

BACKGROUND: Early childhood education offers opportunities for stimulation in multiple developmental domains and its positive impact on long-term outcomes and wellbeing for children is well documented. Few studies have explored early education in children born very preterm (VPT; <32 weeks of gestation) who are at higher risk of neurodevelopmental disorders and poor educational outcomes than their term-born peers. The purpose of the study is to describe and compare the educational environment of children born VPT in European countries at 5 years of age according to the degree of perinatal risk. METHODS: Data originated from the population-based Screening to Improve Health In very Preterm infants (SHIPS) cohort of children born VPT in 2011/2012 in 19 regions from 11 European countries. Perinatal data were collected from medical records and the 5-year follow-up was conducted using parental questionnaires. Outcomes at 5 years were participation in early education (any, type, intensity of participation) and receipt of special educational support, which were harmonized across countries. RESULTS: Out of 6,759 eligible children, 3,687 (54.6%) were followed up at 5 years (mean gestational age 29.3 weeks). At 5 years, almost all children (98.6%) were in an educational program, but type (preschool/primary), attendance (full-time/part-time) and use and type of school support/services differed by country. In some countries, children with high perinatal risk were more likely to be in full-time education than those with low risk (e.g. Estonia: 97.9% vs. 87.1%), while the inverse pattern was observed elsewhere (e.g. Poland: 78.5% vs. 92.8%). Overall, 22.8% of children received special educational support (country range: 12.4-34.4%) with more support received by children with higher perinatal risk. Large variations between countries remained after adjustment for socio-demographic characteristics. CONCLUSIONS: There are marked variations in approaches to early education for children born VPT in Europe, raising opportunities to explore its impact on their neurodevelopment and well-being.

Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study.

Background: Perinatal exposure to SARS-CoV-2 may affect neurodevelopment before 12 months of age, but longer-term outcomes remain unknown. We examined whether antenatal or neonatal SARS-CoV-2 exposure compared with non-exposure is associated with neurodevelopment, respiratory symptoms, and health care usage in early childhood. Methods: This prospective national population-based cohort study was conducted in England and Wales, United Kingdom. We enrolled term-born children (≥37 weeks' gestation) with and without antenatal or neonatal exposure to SARS-CoV-2 infection by approaching parents of eligible children who were cared for in 87 NHS hospitals. Potential participants were identified through the national active surveillance studies of pregnant women and newborn infants hospitalised with confirmed SARS-CoV-2 infection conducted through the UK Obstetric Surveillance System and the British Paediatric Surveillance Unit. We defined antenatal and neonatal SARS-CoV-2 exposure as infants born to mothers hospitalised with confirmed SARS-CoV-2 infection between 14 + 0 and 36 + 6 weeks gestation and infants admitted to hospital with confirmed SARS-CoV-2 infection within the first 28 days after birth. Children born preterm or with major congenital anomaly or who were not residing in the UK were excluded. We assessed children's development (Ages and Stages Questionnaire 3rd Edition (ASQ-3); Ages and Stages Questionnaire Social-Emotional 2nd Edition (ASQ:SE-2)), respiratory symptoms (Liverpool Respiratory Symptom Questionnaire (LRSQ)) and health care usage (parent-completed questionnaire) at 21-32 months of age. Primary outcome: total ASQ-3 score, converted to z-scores. Secondary outcomes: ASQ:SE-2 z-scores; risk of delay in ASQ-3 domains; total LRSQ scores, converted to z-scores. Analyses were adjusted for children's age, sex, maternal ethnicity, parental education, and index of multiple deprivation. Findings: Between October 20, 2021 and January 27, 2023, we approached 668 and 1877 families out of 712 and 1917 potentially eligible participants in the exposed and comparison cohort. Of the 125 and 306 participants who were enrolled to the exposed and comparison cohort 121 and 301 participants completed the questionnaires and 96 and 243 participants were included in the analysis. In the age adjusted analysis, the mean total ASQ-3 z-score was lower in the exposed than the comparison cohort (-0.3, 95% CI: -0.6 to -0.05), however, when adjusted for sex, parental education, ethnicity and IMD quintile, there was no significant difference (difference in mean z-score = -0.2 95% CI: -0.5 to 0.03). SARS-CoV-2 exposure was associated with increased risk of delayed personal-social skills (odds ratio = 3.81; 95% CI: 1.07-13.66), higher ASQ:SE-2 total z-scores (difference in mean z-score = 0.4; 95% CI: 0.2-0.6) and increased risk of delayed social-emotional development (OR = 3.58, 95% CI: 1.30-9.83), after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. The exposed cohort had a higher mean total LRSQ z-score than the comparison cohort (0.3 95% CI: 0-0.6) and higher inpatient (38% vs. 21%, p = 0.0001), outpatient (38% vs. 30%, p = 0.0090), and General Practitioner appointments (60% vs. 50%, p = 0.021) than the comparison cohort, after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. No differences in other secondary outcomes between the exposed and comparison cohorts were found. Interpretation: Although the exposed cohort did not differ from the comparison cohort on the primary outcome, total ASQ-3 score, the exposed cohort were at greater risk of delayed social-emotional development, had a greater prevalence of respiratory symptoms and increased health care usage relative to the comparison cohort. The study is limited by the smaller sample size due to the low response rate and lack of clinical developmental assessments. Given the association of poor social-emotional development with antenatal or neonatal SARS-CoV-2 exposure, developmental screening, and follow-up of children with confirmed antenatal or neonatal SARS-CoV-2 infection may be warranted to identify those in need of early intervention. Funding: Action Medical Research for Children.

Long-Acting Injectable ART in Practice: A Mixed Methods Implementation Study Assessing the Feasibility of Using LAI ART in High Risk Populations and At Alternative Low Barrier Care Sites.

Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to change the lives of people living with HIV (PLWH). To ensure equitable access to new treatment modalities, we examined the feasibility and acceptability of administering Cabotegravir Rilpivirine Long Acting (CAB/RPV LA) to individuals who experience challenging social determinants of health (SDoH) and struggle with adherence to traditional oral ART. Quantitative and qualitative data were used to assess feasibility of utilizing ART at alternative clinic. Data were collected on individuals eligible to receive CAB/RPV LA at an alternative street-based clinic and on individuals receiving CAB/RPV LA at a traditional HIV clinic. After 6 months, participants were interviewed about their experience. Providers involved in the implementation were also interviewed about their experiences. Only one participant (out of 5) who received CAB/RPV LA at the alternative clinic received consistent treatment, whereas 17 out of 18 participants receiving CAB/RPV LA at the traditional clinic site were adherent. Participants and providers believed that LAI had potential for making treatment adherence easier, but identified several barriers, including discrepancies between patients' desires and their lifestyles, impact of LAI on interactions with the medical system, risk of resistance accompanying sub-optimal adherence, and need for a very high level of resources. While LAI has major potential benefits for high-risk patients, these benefits must be balanced with the complexities of implementation. Despite challenges that impacted study outcomes, improving treatment outcomes for PLWH requires addressing SDoH and substance use.

Mental health, pain and tiredness in adults born very preterm or with very low birthweight.

AIM: Adults born preterm have increased risk of mental health problems and other neurodevelopmental conditions. We aimed to investigate associations of mental health with pain and tiredness in adults born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) and at term, and whether these associations are influenced by physical activity. METHODS: As part of an EU Horizon 2020 project, individual participant data from six prospective cohort studies were harmonised for 617 VP/VLBW and 1122 term-born participants. Mental health was assessed by the Achenbach System of Empirically Based Assessment Adult Self-Report. Pain and tiredness were harmonised based on specific items from self-reported questionnaires. Associations between mental health and pain or tiredness were explored by linear regression. RESULTS: An increase in the mental health scales internalising, externalising and total problems was associated with increased pain and tiredness in the preterm and term group alike. Results were maintained when adjusting for physical activity. CONCLUSION: The findings indicate that associations between mental health, pain and tiredness in adults are independent of gestation or birthweight. Future research should explore other potential mechanisms that may underlie the increased risk of mental health problems in the preterm population.

Antenatal and neonatal exposure to SARS-CoV-2 and children's development: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review of the impact of antenatal and neonatal exposure to SARS-CoV-2 on developmental outcomes in preterm and term-born infants. METHODS: We searched Embase, Emcare, MEDLINE, PsycINFO, Web of Science and grey literature on May 27, 2022 and updated on May 8, 2023. Studies defining exposure with a positive SARS-CoV-2 protein or genetic material, used a contemporaneous non-exposed cohort, and reported developmental outcomes up to 2 years of age were included. RESULTS: Four out of 828 screened studies were included. Meta-analysis included 815 infants screened for developmental delay (n = 306 exposed; n = 509 non-exposed) between 3- and 11-months of age. Among term-born infants, we did not find an increased risk of delay in communication (odd's ratio: 0.73 (95% CI: 0.24-2.24)), gross motor (1.50 (0.62, 3.62)), fine motor (2.90 (0.58, 14.43)), problem-solving (1.19 (0.54, 2.66)) or personal-social development (1.93 (0.78, 4.75)) in exposed infants. The number of preterm-born infants in the exposed (n = 37) and comparison cohorts (n = 41) were too few to report meaningful comparisons. CONCLUSION: Evidence regarding the potential impact of antenatal or neonatal exposure to SARS-CoV-2 infection on developmental outcomes in early infancy is limited and inconsistent. Larger cohorts with outcomes beyond the first year of life are needed. IMPACT: The current evidence examining associations between SARS-CoV-2 exposure during the neonatal period and developmental outcomes in infancy is limited by there being few studies with extremely small sample sizes. Based on sparse data there was no consistent association between antenatal or neonatal exposure to SARS-CoV-2 infection and an adverse impact on developmental outcomes below 12 months of age for babies born preterm or at term. This study highlights that larger cohorts with outcomes assessed beyond the first year are needed to determine the potential longer-term impact of SARS-CoV-2 infection exposure on child development.

Prediction of movement difficulties at 5 years from parent report at 2 years in children born extremely preterm.

AIM: To assess the predictive validity of parent-reported gross motor impairment (GMI) at age 2 years to detect significant movement difficulties at age 5 years in children born extremely preterm. METHOD: Data were from 556 children (270 males, 286 females) born at less than 28 weeks' gestation in 2011 to 2012 in 10 European countries. Parent report of moderate/severe GMI was defined as walking unsteadily or unable to walk unassisted at 2 years corrected age. Examiners assessed significant movement difficulties (score ≤ 5th centile on the Movement Assessment Battery for Children, Second Edition) and diagnoses of cerebral palsy (CP) were collected by parent report at 5 years chronological age. RESULTS: At 2 years, 66 (11.9%) children had moderate/severe GMI. At 5 years, 212 (38.1%) had significant movement difficulties. Parent reports of GMI at age 2 years accurately classified CP at age 5 years in 91.0% to 93.2% of children. Classification of moderate/severe GMI at age 2 years had high specificity (96.2%; 95% confidence interval 93.6-98.0) and positive predictive value (80.3%; 68.7-89.1) for significant movement difficulties at age 5 years. However, 74.5% of children with significant movement difficulties at 5 years were not identified with moderate/severe GMI at age 2 years, resulting in low sensitivity (25.1%; 19.4-31.5). INTERPRETATION: This questionnaire may be used to identify children born extremely preterm who at age 2 years have a diagnosis of CP or movement difficulties that are likely to have a significant impact on their functional outcomes at age 5 years.

Higher level domain specific skills in mathematics; The relationship between algebra, geometry, executive function skills and mathematics achievement.

Algebra and geometry are important components of mathematics that are often considered gatekeepers for future success. However, most studies that have researched the cognitive skills required for success in mathematics have only considered the domain of arithmetic. We extended models of mathematical skills to consider how executive function skills play both a direct role in secondary-school-level mathematical achievement as well as an indirect role via algebra and geometry, alongside arithmetic. We found that verbal and visuospatial working memory were indirectly associated with mathematical achievement via number fact knowledge, calculation skills, algebra and geometry. Inhibition was also indirectly associated with mathematical achievement via number fact knowledge and calculation skills. These findings highlight that there are multiple mechanisms by which executive function skills may be involved in mathematics outcomes. Therefore, using specific measures of mathematical processes as well as context-rich assessments of mathematical achievement is important to understand these mechanisms.