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.

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.

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.

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.

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.

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Resilient pedagogy: experiences of kinesiology faculty during COVID-19.

The COVID-19 pandemic required an emergency shift to remote teaching. Despite their limited previous experience with online or hybrid teaching, our cohort of kinesiology faculty (n = 112) had high confidence in their ability to deliver quality educational experiences for their students during the pandemic. With support from their institutions, technology departments, and teaching and learning centers, faculty developed new skills and organizational strategies. To achieve this, 81% of faculty reported needing extra course preparation time to deliver high-quality remote teaching, with 51% needing up to 5 extra hours per week per course. There is a fraction of faculty from this study excited about the prospect of teaching online in the future. These newfound online teaching skills should be leveraged to modernize course offerings in kinesiology departments, supporting student recruitment, retention, and success.NEW & NOTEWORTHY The COVID-19 pandemic caused temporary and permanent changes to higher education, specifically kinesiology programs. This article highlights the resiliency of faculty in kinesiology programs, how they adapted, where they felt supported, and what they hope to bring with them into their future pedagogy practices.

A systematic review of interventions for resuscitation following drowning.

Objectives: The International Liaison Committee on Resuscitation, in collaboration with drowning researchers from around the world, aimed to review the evidence addressing seven key resuscitation interventions: 1) immediate versus delayed resuscitation; (2) compression first versus ventilation first strategy; (3) compression-only CPR versus standard CPR (compressions and ventilations); (4) ventilation with and without equipment; (5) oxygen administration prior to hospital arrival; (6) automated external defibrillation first versus cardiopulmonary resuscitation first strategy; (7) public access defibrillation programmes. Methods: The review included studies relating to adults and children who had sustained a cardiac arrest following drowning with control groups and reported patient outcomes. Searches were run from database inception through to April 2023. The following databases were searched Ovid MEDLINE, Pre-Medline, Embase, Cochrane Central Register of Controlled Trials. Risk of bias was assessed using the ROBINS-I tool and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. The findings are reported as a narrative synthesis. Results: Three studies were included for two of the seven interventions (2,451 patients). No randomised controlled trials were identified. A retrospective observational study reported in-water resuscitation with rescue breaths improved patient outcomes compared to delayed resuscitation on land (n = 46 patients, very low certainty of evidence). The two observational studies (n = 2,405 patients), comparing compression-only with standard resuscitation, reported no difference for most outcomes. A statistically higher rate of survival to hospital discharge was reported for the standard resuscitation group in one of these studies (29.7% versus 18.1%, adjusted odds ratio 1.54 (95% confidence interval 1.01-2.36) (very low certainty of evidence). Conclusion: The key finding of this systematic review is the paucity of evidence, with control groups, to inform treatment guidelines for resuscitation in drowning.

Comparing behavioural outcomes in children born extremely preterm between 2006 and 1995: the EPICure studies.

BACKGROUND: Children born extremely preterm (EP) are at increased risk of neurocognitive and behavioural morbidity. Here, we investigate whether behavioural outcomes have changed over time concomitant with increasing survival following EP birth. METHODS: Comparison of outcomes at 11 years of age for two prospective national cohorts of children born EP in 1995 (EPICure) and 2006 (EPICure2), assessed alongside term-born children. Behavioural outcomes were assessed using the parent-completed Strengths and Difficulties Questionnaire (SDQ), DuPaul Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), and Social Communication Questionnaire (SCQ). RESULTS: In EPICure, 176 EP and 153 term-born children were assessed (mean age: 10.9 years); in EPICure2, 112 EP and 143 term-born children were assessed (mean age: 11.8 years). In both cohorts, EP children had higher mean scores and more clinically significant difficulties than term-born children on almost all measures. Comparing outcomes for EP children in the two cohorts, there were no significant differences in mean scores or in the proportion of children with clinically significant difficulties after adjustment for confounders. Using term-born children as reference, EP children in EPICure2 had significantly higher SDQ total difficulties and ADHD-RS hyperactivity impulsivity z-scores than EP children in EPICure. CONCLUSIONS: Behavioural outcomes have not improved for EP children born in 2006 compared with those born in 1995. Relative to term-born peers, EP children born in 2006 had worse outcomes than those born in 1995. There is an ongoing need for long-term clinical follow-up and psychological support for children born EP.

Effects of disturbances and environmental changes on an aridland riparian generalist.

Anthropogenic climate change and ecosystem disturbances can detrimentally affect habitats and species. Areas with concentrated biodiversity, such as aridland riparian zones, often yield the greatest number of vulnerable species. A better understanding of ecological and environmental relationships can guide more effective conservation strategies. We used both visual transects and external (tape) radio telemetry to study the behavioral and spatial ecology of black-necked gartersnakes (Thamnophis cyrtopsis; n = 81)-a dietary generalist yet aquatic habitat specialist-in a heterogenous aridland riparian zone of lower Sabino Canyon, Tucson, Arizona, between 2018 and 2021. Our objectives were to (1) understand how extrinsic conditions influence population ecology dynamics, including immediately prior to and after major disturbances and environmental extremes; (2) analyze behavioral activity and microhabitat usage in relation to environmental factors; and (3) assess the efficacy of a less-invasive telemetry strategy. Between late spring 2020 and early summer 2021, ecosystem disturbances included near-record heat and drought, wildfire, and low overwinter precipitation. Many aquatic habitats either completely dried or were spatially disjunct; gartersnake prey species were noticeably sparse. Extreme drought rapidly shifted to excessive flooding during the 2021 monsoon that brought above-average streamflow magnitude and duration. Between 2019 and 2021, we observed a dramatic decline in T. cyrtopsis; odds of detection reduced by 92.8% (CI [56.0-99.1%]). Strong spatiotemporal links relative to the extent and timing of available surface water appear important. Prior to the onset of monsoonal stream recharge in early summer, shallow and drying aquatic habitats are used as parturition sites and foraging grounds; all age classes took advantage to corral fishes trapped in isolated and shrinking pools. Ambient conditions had varying effects on gartersnake behaviors. Variation in microhabitat assemblages occurred with distance from water, activity level, and developmental age class. Interestingly, associations remained consistent across seasons and years, which suggests a reliance on heterogenous habitat structure. Sampling techniques complemented each other, however, bioclimatic parameters rendered limitations and should be considered in methodological decisions. Overall, disadvantageous responses to major disturbances and climatic extremes by a presumably adaptable generalist like T. cyrtopsis are concerning. Insights from long-term monitoring of responses by common yet environmentally sensitive species such as T. cyrtopsis may serve to more broadly highlight demographic challenges that other taxa with similar semi-aquatic life histories may face in changing systems. Such information could inform more effective conservation management strategies in warming and drying ecosystems.

Pilot feasibility study of a digital technology approach to the systematic electronic capture of parent-reported data on cognitive and language development in children aged 2 years.

BACKGROUND: The assessment of language and cognition in children at risk of impaired neurodevelopment following neonatal care is a UK standard of care but there is no national, systematic approach for obtaining these data. To overcome these challenges, we developed and evaluated a digital version of a validated parent questionnaire to assess cognitive and language development at age 2 years, the Parent Report of Children's Abilities-Revised (PARCA-R). METHODS: We involved clinicians and parents of babies born very preterm who received care in north-west London neonatal units. We developed a digital version of the PARCA-R questionnaire using standard software. Following informed consent, parents received automated notifications and an invitation to complete the questionnaire on a mobile phone, tablet or computer when their child approached the appropriate age window. Parents could save and print a copy of the results. We evaluated ease of use, parent acceptability, consent for data sharing through integration into a research database and making results available to the clinical team. RESULTS: Clinical staff approached the parents of 41 infants; 38 completed the e-registration form and 30 signed the e-consent. The digital version of the PARCA-R was completed by the parents of 21 of 23 children who reached the appropriate age window. Clinicians and parents found the system easy to use. Only one parent declined permission to integrate data into the National Neonatal Research Database for approved secondary purposes. DISCUSSION: This electronic data collection system and associated automated processes enabled efficient systematic capture of data on language and cognitive development in high-risk children, suitable for national delivery at scale.

Consequences of depleting TNRC6, AGO, and DROSHA proteins on expression of microRNAs.

The potential for microRNAs (miRNAs) to regulate gene expression remains incompletely understood. DROSHA initiates the biogenesis of miRNAs while variants of Argonaute (AGO) and trinucleotide repeat containing six (TNRC6) family proteins form complexes with miRNAs to facilitate RNA recognition and gene regulation. Here we investigate the fate of miRNAs in the absence of these critical RNAi protein factors. Knockout of DROSHA expression reduces levels of some miRNAs annotated in miRBase but not others. The identity of miRNAs with reduced expression matches the identity of miRNAs previously identified by experimental approaches. The MirGeneDB resource offers the closest alignment with experimental results. In contrast, the loss of TNRC6 proteins had much smaller effects on miRNA levels. Knocking out AGO proteins, which directly contact the mature miRNA, decreased expression of the miRNAs most strongly associated with AGO2 as determined from enhanced crosslinking immunoprecipitation (AGO2-eCLIP). Evaluation of miRNA binding to endogenously expressed AGO proteins revealed that miRNA:AGO association was similar for AGO1, AGO2, AGO3, and AGO4. Our data emphasize the need to evaluate annotated miRNAs based on approximate cellular abundance, DROSHA-dependence, and physical association with AGO when forming hypotheses related to their function.

Developmental motor problems and health-related quality of life in 5-year-old children born extremely preterm: A European cohort study.

AIM: To measure the association between cerebral palsy (CP) and non-CP-related movement difficulties and health-related quality of life (HRQoL) among 5-year-old children born extremely preterm (<28 weeks gestational age). METHOD: We included 5-year-old children from a multi-country, population-based cohort of children born extremely preterm in 2011 to 2012 in 11 European countries (n = 1021). Children without CP were classified using the Movement Assessment Battery for Children, Second Edition as having significant movement difficulties (≤5th centile of standardized norms) or being at risk of movement difficulties (6th-15th centile). Parents reported on a clinical CP diagnosis and HRQoL using the Pediatric Quality of Life Inventory. Associations were assessed using linear and quantile regressions. RESULTS: Compared to children without movement difficulties, children at risk of movement difficulties, with significant movement difficulties, and CP had lower adjusted HRQoL total scores (ß [95% confidence interval] = -5.0 [-7.7 to -2.3], -9.1 [-12.0 to -6.1], and - 26.1 [-31.0 to -21.2]). Quantile regression analyses showed similar decreases in HRQoL for all children with CP, whereas for children with non-CP-related movement difficulties, reductions in HRQoL were more pronounced at lower centiles. INTERPRETATION: CP and non-CP-related movement difficulties were associated with lower HRQoL, even for children with less severe difficulties. Heterogeneous associations for non-CP-related movement difficulties raise questions for research about mitigating and protective factors.

The TCF4 Trinucleotide Repeat Expansion of Fuchs' Endothelial Corneal Dystrophy: Implications for the Anterior Segment of the Eye.

Purpose: In the United States, 70% of Fuchs' endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the TCF4 gene. CUG repeat RNA transcripts from this expansion accumulate as nuclear foci in the corneal endothelium. In this study, we sought to detect foci in other anterior segment cell types and assess their molecular impact. Methods: We examined CUG repeat RNA foci appearance, expression of downstream affected genes, gene splicing, and TCF4 RNA expression in corneal endothelium, corneal stromal keratocytes, corneal epithelium, trabecular meshwork cells, and lens epithelium. Results: CUG repeat RNA foci, the hallmark of FECD in corneal endothelium (found in 84% of endothelial cells), are less detectable in trabecular meshwork cells (41%), much less prevalent in stromal keratocytes (11%) or corneal epithelium (4%), and absent in lens epithelium. With few exceptions including mis-splicing in the trabecular meshwork, differential gene expression and splicing changes associated with the expanded repeat in corneal endothelial cells are not observed in other cell types. Expression of the TCF4 transcripts including full-length isoforms containing the repeat sequence at the 5' end is much higher in the corneal endothelium or trabecular meshwork than in the corneal stroma or corneal epithelium. Conclusions: Expression of the CUG repeat containing TCF4 transcripts is higher in the corneal endothelium, likely contributing to foci formation and the large molecular and pathologic impact on those cells. Further studies are warranted to examine any glaucoma risk and impact of the observed foci in the trabecular meshwork of these patients.

Person-centred Approaches to Psychopathology in the ABCD Study: Phenotypes and Neurocognitive Correlates.

Issues with classifying psychopathology using narrow diagnostic categories have prompted calls for the use of dimensional approaches. Yet questions remain about how closely dimensional approaches reflect the way symptoms cluster in individuals, whether known risk factors (e.g. preterm birth) produce distinct symptom phenotypes, and whether profiles reflecting symptom clusters are associated with neurocognitive factors. To identify distinct profiles of psychopathology, latent class analysis was applied to the syndrome scales of the parent-reported Child Behaviour Checklist for 11,381 9- and 10- year-olds from the Adolescent Brain Cognitive Development study. Four classes were identified, reflecting different profiles, to which children were assigned probabilistically; Class 1 (88.6%) reflected optimal functioning; Class 2 (7.1%), predominantly internalising; Class 3 (2.4%), predominantly externalising; and Class 4 (1.9%), universal difficulties. To investigate the presence of a possible preterm behavioural phenotype, the proportion of participants allocated to each class was cross-tabulated with gestational age category. No profile was specific to preterm birth. Finally, to assess the neurocognitive factors associated with class membership, elastic net regressions were conducted revealing a relatively distinct set of neurocognitive factors associated with each class. Findings support the use of large datasets to identify psychopathological profiles, explore phenotypes, and identify associated neurocognitive factors.

Postnatal growth restriction and neurodevelopment at 5 years of age: a European extremely preterm birth cohort study.

OBJECTIVE: To investigate whether extrauterine growth restriction (EUGR) during the neonatal hospitalisation by sex among extremely preterm (EPT) infants is associated with cerebral palsy (CP) and cognitive and motor abilities at 5 years of age. STUDY DESIGN: Population-based cohort of births <28 weeks of gestation with data from obstetric and neonatal records and parental questionnaires and clinical assessments at 5 years of age. SETTING: 11 European countries. PATIENTS: 957 EPT infants born in 2011-2012. MAIN OUTCOMES: EUGR at discharge from the neonatal unit was defined as (1) the difference between Z-scores at birth and discharge with <-2 SD as severe, -2 to -1 SD as moderate using Fenton's growth charts (Fenton) and (2) average weight-gain velocity using Patel's formula in grams (g) per kilogram per day (Patel) with <11.2 g (first quartile) as severe, 11.2-12.5 g (median) as moderate. Five-year outcomes were: a CP diagnosis, intelligence quotient (IQ) using the Wechsler Preschool and Primary Scales of Intelligence tests and motor function using the Movement Assessment Battery for Children, second edition. RESULTS: 40.1% and 33.9% children were classified as having moderate and severe EUGR, respectively, by Fenton and 23.8% and 26.3% by Patel. Among children without CP, those with severe EUGR had lower IQ than children without EUGR (-3.9 points, 95% Confidence Interval (CI)=-7.2 to -0.6 for Fenton and -5.0 points, 95% CI=-8.2 to -1.8 for Patel), with no interaction by sex. No significant associations were observed between motor function and CP. CONCLUSIONS: Severe EUGR among EPT infants was associated with decreased IQ at 5 years of age.

Heterogeneity of design features in studies included in systematic reviews with meta-analysis of cognitive outcomes in children born very preterm.

BACKGROUND: Meta-analyses of the voluminous scientific literature on the impact of very preterm (VPT, <32 weeks' gestation) birth on cognition find a marked deficit in intelligence quotient (IQ) among children born VPT relative to term-born peers, but with unexplained between-study heterogeneity in effect size. OBJECTIVES: To conduct an umbrella review to describe the design and methodology of primary studies and to assess whether methodological heterogeneity affects the results of meta-analyses. DATA SOURCES: Primary studies from five systematic reviews with meta-analysis on VPT birth and childhood IQ. STUDY SELECTION AND DATA EXTRACTION: Information on study design, sample characteristics and results was extracted from studies. Study features covered study type, sample size, follow-up rates, adjustment for social context, management of severe impairments and test type. SYNTHESIS: We used random-effects subgroup meta-analyses and meta-regressions to investigate the contribution of study features to between-study variance in standardised mean differences (SMD) in IQ between groups. RESULTS: In 58 cohorts (56%), children with severe impairments were excluded, while 23 (22%) cohorts accounted for social factors. The least reported feature was the follow-up rate (missing in 38 cohorts). The largest difference in SMDs was between studies using full scale IQ tests (61 cohorts, SMD -0.89, 95% CI -0.96, -0.82) versus short-form tests (27 cohorts, SMD -0.68, 95% CI -0.79, -0.57). The proportion of between-study variance explained by the type of test was 14%; the other features explained less than 1% of the variance. CONCLUSIONS: Study design and methodology varied across studies, but most of them did not affect the variance in effect size, except the type of cognitive test. Key features, such as the follow-up rate, were not consistently reported limiting the evaluation of their potential contribution. Incomplete reporting limited the evaluation of the full impact of this methodological diversity.

Gestational age and hospital admission costs from birth to childhood: a population-based record linkage study in England.

OBJECTIVE: To examine the association between gestational age at birth and hospital admission costs from birth to 8 years of age. DESIGN: Population-based, record linkage, cohort study in England. SETTING: National Health Service (NHS) hospitals in England, UK. PARTICIPANTS: 1 018 136 live, singleton births in NHS hospitals in England between 1 January 2005 and 31 December 2006. MAIN OUTCOME MEASURES: Hospital admission costs from birth to age 8 years, estimated by gestational age at birth (<28, 28-29, 30-31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42 weeks). RESULTS: Both birth admission and subsequent admission hospital costs decreased with increasing gestational age at birth. Differences in hospital admission costs between gestational age groups diminished with increasing age, particularly after the first 2 years following birth. Children born extremely preterm (<28 weeks) and very preterm (28-31 weeks) still had higher average hospital admission costs (£699 (95% CI £419 to £919) for <28 weeks; £434 (95% CI £305 to £563) for 28-31 weeks) during the eighth year of life compared with children born at 40 weeks (£109, 95% CI £104 to £114). Children born extremely preterm had the highest 8-year cumulative hospital admission costs per child (£80 559 (95% CI £79 238 to £82 019)), a large proportion of which was incurred during the first year after birth (£71 997 (95% CI £70 866 to £73 097)). CONCLUSIONS: The association between gestational age at birth and hospital admission costs persists into mid-childhood. The study results provide a useful costing resource for future economic evaluations focusing on preventive and treatment strategies for babies born preterm.