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Objectives:. Treatment of hypoxemic respiratory failure and acute respiratory distress syndrome is complex. Evidence-based therapies that can improve survival and guidelines advocating their use exist; however, implementation is inconsistent. Our objective was to develop and validate an evidence-based, stakeholder-informed standardized management pathway for hypoxemic respiratory failure and acute respiratory distress syndrome to improve adherence to best practice. Design:. A standardized management pathway was developed using a modified Delphi consensus process with a multidisciplinary group of ICU clinicians. The proposed pathway was externally validated with a survey involving multidisciplinary stakeholders and clinicians. Setting:. In-person meeting and web-based surveys of ICU clinicians from 17 adult ICUs in the province of Alberta, Canada. Intervention:. Not applicable. Measurements and Main Results:. The consensus panel was comprised of 30 ICU clinicians (4 nurses, 10 respiratory therapists, 15 intensivists, 1 nurse practitioner; median years of practice 17 [interquartile range, 13–21]). Ninety-one components were serially rated and revised over two rounds of online and one in-person review. The final pathway included 46 elements. For the validation survey, 692 responses (including 59% nurses, 33% respiratory therapists, 7% intensivists and 1% nurse practitioners) were received. Agreement of greater than 75% was achieved on 43 of 46 pathway elements. Conclusions:. A 46-element evidence-informed hypoxemic respiratory failure and acute respiratory distress syndrome standardized management pathway was developed and demonstrated to have content validity.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent for coronavirus disease 2019 (COVID-19), and its ensuing mitigation measures have negatively affected the Maternal and Child Health (MCH) population. There is currently no surveillance system established to enhance our understanding of SARS-CoV-2 transmission to guide policy decision making to protect the MCH population in this pandemic. Based on reports of community and household spread of this novel infection, we present an approach to a robust family-centered surveillance system for the MCH population. The surveillance system encapsulates data at the individual and community levels to inform stakeholders, policy makers, health officials and the general public about SARS-CoV-2 transmission dynamics within the MCH population. Key words: • COVID-19 • Coronavirus • Maternal and child health • Family-centered • Surveillance system • Individual level data elements • Community level data elements • Community transmission of SARS-CoV-2 Copyright © 2020 Ajewole et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are thought to be the main drivers of insulin secretion in individuals with sulfonylurea (SU)-treated KCNJ11 permanent neonatal diabetes. The aim of this study was to assess for the first time the incretin hormone response to carbohydrate and protein/fat in adults with sulfonylurea-treated KCNJ11 permanent neonatal diabetes compared with that of controls without diabetes. Participants were given a breakfast high in carbohydrate and an isocaloric breakfast high in protein/fat on two different mornings. Incremental area under the curve and total area under the curve (0-240 minutes) for total GLP-1 and GIP were compared between groups, using non-parametric statistical methods. Post-meal GLP-1 and GIP secretion were similar in cases and controls, suggesting this process is adenosine triphosphate-sensitive potassium channel-independent. Future research will investigate whether treatments targeting the incretin pathway are effective in individuals with KCNJ11 permanent neonatal diabetes who do not have good glycemic control on sulfonylurea alone., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

A randomized controlled trial is being conducted in the United States to test the efficacy of a personalized interactive mobile health intervention (iSTEP) designed to increase physical activity (PA) and improve neurocognitive functioning among HIV-positive persons. This article describes an initial qualitative study performed to develop iSTEP for the HIV-positive population, including assessment of PA barriers and facilitators. Two focus groups, with 9 and 12 unique HIV-positive individuals, respectively, were administered to evaluate barriers limiting PA and potential iSTEP content created to encourage greater PA. Group discussions revealed prominent PA barriers, including HIV symptoms (neuropathy, lipoatrophy), antiretroviral medication effects, and fatigue; significant PA facilitators included self-monitoring and family support. Participants provided feedback on strategies to increase PA and expressed positive support for a mobile intervention adapted to personal priorities. These findings will assist the development of novel PA interventions focused on treating the epidemic of HIV-associated neurocognitive disorders.

Background: Cardiopulmonary exercise testing (CPET), and its primary outcome of peak oxygen uptake (VO 2peak ), are acknowledged as biomarkers in the diagnostic and prognostic management of interstitial lung disease (ILD). However, the validity and repeatability of CPET in those with ILD has yet to be fully characterised, and this study fills this evidence gap., Methods: Twenty-six people with ILD were recruited, and 21 successfully completed three CPETs. Of these, 17 completed two valid CPETs within a 3-month window, and 11 completed two valid CPETs within a 6-month window. Technical standards from the European Respiratory Society established validity, and repeatability was determined using mean change, intraclass correlation coefficient and typical error., Results: Every participant (100%) who successfully exercised to volitional exhaustion produced a maximal, and therefore valid, CPET. Approximately 20% of participants presented with a plateau in VO 2 , the primary criteria for establishing a maximal effort. The majority of participants otherwise presented with secondary criteria of respiratory exchange ratios in excess of 1.05, and maximal heart rates in excess of their predicted values. Repeatability analyses identified that the typical error (expressed as percent of coefficient of variation) was 20% over 3-months in those reaching volitional exhaustion., Conclusion: This work has, for the first time, fully characterised how patients with ILD respond to CPET in terms of primary and secondary verification criteria, and generated novel repeatability data that will prove useful in the assessment of disease progression, and future evaluation of therapeutic regimens where VO 2peak is used as an outcome measure., (© 2022. The Author(s).)

Objective: Recent joint American Diabetes Association and European Association for the Study of Diabetes guidelines recommend routine islet autoantibody testing in all adults newly diagnosed with type 1 diabetes. We aimed to assess the impact of routine islet autoantibody testing in this population., Research Design and Methods: We prospectively assessed the relationship between islet autoantibody status (GADA, IA-2A, and ZNT8A), clinical and genetic characteristics, and progression (annual change in urine C-peptide-to-creatinine ratio [UCPCR]) in 722 adults (≥18 years old at diagnosis) with clinically diagnosed type 1 diabetes and diabetes duration <12 months. We also evaluated changes in treatment and glycemia over 2 years after informing participants and their clinicians of autoantibody results., Results: Of 722 participants diagnosed with type 1 diabetes, 24.8% (179) were autoantibody negative. This group had genetic and C-peptide characteristics suggestive of a high prevalence of nonautoimmune diabetes: lower mean type 1 diabetes genetic risk score (islet autoantibody negative vs. positive: 10.85 vs. 13.09 [P < 0.001] [type 2 diabetes 10.12]) and lower annual change in C-peptide (UCPCR), -24% vs. -43% (P < 0.001).After median 24 months of follow-up, treatment change occurred in 36.6% (60 of 164) of autoantibody-negative participants: 22.6% (37 of 164) discontinued insulin, with HbA1c similar to that of participants continuing insulin (57.5 vs. 60.8 mmol/mol [7.4 vs. 7.7%], P = 0.4), and 14.0% (23 of 164) added adjuvant agents to insulin., Conclusions: In adult-onset clinically diagnosed type 1 diabetes, negative islet autoantibodies should prompt careful consideration of other diabetes subtypes. When routinely measured, negative antibodies are associated with successful insulin cessation. These findings support recent recommendations for routine islet autoantibody assessment in adult-onset type 1 diabetes., (© 2022 by the American Diabetes Association.)

Background: Human birthweight is a complex, multifactorial trait. Maternal characteristics contribute to birthweight variation by influencing the intrauterine environment. Variation explained by genetic effects is also important, but their contributions have not been assessed alongside other key determinants. We aimed to investigate variance in birthweight explained by genetic scores in addition to easily-measurable clinical and anthropometric variables., Methods: We analysed 549 European-ancestry parent-offspring trios from a UK community-based birth cohort. We investigated variance explained in birthweight (adjusted for sex and gestational age) in multivariable linear regression models including genetic scores, routinely-measured maternal characteristics, and parental anthropometric variables. We used R-Squared (R 2 ) to estimate variance explained, adjusted R-squared (Adj-R 2 ) to assess improvement in model fit from added predictors, and F-tests to compare nested models., Results: Maternal and fetal genetic scores together explained 6.0% variance in birthweight. A model containing maternal age, weight, smoking, parity and 28-week fasting glucose explained 21.7% variance. Maternal genetic score explained additional variance when added to maternal characteristics (Adj-R 2  = 0.233 vs Adj-R 2  = 0.210, p < 0.001). Fetal genetic score improved variance explained (Adj-R 2  = 0.264 vs 0.248, p < 0.001) when added to maternal characteristics and parental heights., Conclusions: Genetic scores account for variance explained in birthweight in addition to easily measurable clinical variables. Parental heights partially capture fetal genotype and its contribution to birthweight, but genetic scores explain additional variance. While the genetic contribution is modest, it is comparable to that of individual clinical characteristics such as parity, which suggests that genetics could be included in tools aiming to predict risk of high or low birthweights., (© 2022. The Author(s).)

Background: Higher birthweight is associated with higher adult body mass index (BMI). Alleles that predispose to greater adult adiposity might act in fetal life to increase fetal growth and birthweight. Whether there are fetal effects of recently identified adult metabolically favorable adiposity alleles on birthweight is unknown., Aim: We aimed to test the effect on birthweight of fetal genetic predisposition to higher metabolically favorable adult adiposity and compare that with the effect of fetal genetic predisposition to higher adult BMI., Methods: We used published genome wide association study data (n = upto 406 063) to estimate fetal effects on birthweight (adjusting for maternal genotype) of alleles known to raise metabolically favorable adult adiposity or BMI. We combined summary data across single nucleotide polymorphisms (SNPs) with random effects meta-analyses. We performed weighted linear regression of SNP-birthweight effects against SNP-adult adiposity effects to test for a dose-dependent association., Results: Fetal genetic predisposition to higher metabolically favorable adult adiposity and higher adult BMI were both associated with higher birthweight (3 g per effect allele (95% CI: 1-5) averaged over 14 SNPs; P = 0.002; 0.5 g per effect allele (95% CI: 0-1) averaged over 76 SNPs; P = 0.042, respectively). SNPs with greater effects on metabolically favorable adiposity tended to have greater effects on birthweight (R2 = 0.2912, P = 0.027). There was no dose-dependent association for BMI (R2 = -0.0019, P = 0.602)., Conclusions: Fetal genetic predisposition to both higher adult metabolically favorable adiposity and BMI is associated with birthweight. Fetal effects of metabolically favorable adiposity-raising alleles on birthweight are modestly proportional to their effects on future adiposity, but those of BMI-raising alleles are not., (© The Author(s) 2021. Published by Oxford University Press.)

The rs2802292, rs2764264 and rs13217795 variants of FOXO3 have been associated with extreme longevity in multiple human populations, but the mechanisms underpinning this remain unclear. We aimed to characterise potential effects of longevity-associated variation on the expression and mRNA processing of the FOXO3 gene. We performed a comprehensive assessment of FOXO3 isoform usage across a wide variety of human tissues and carried out a bioinformatic analysis of the potential for longevity-associated variants to disrupt regulatory regions involved in isoform choice. We then related the expression of full length and 5' truncated FOXO3 isoforms to rs13217795 genotype in peripheral blood and skeletal muscle from individuals of different rs13217795 genotypes. FOXO3 isoforms displayed considerable tissue specificity. We determined that rs13231195 and its tightly aligned proxy variant rs9400239 may lie in regulatory regions involved in isoform choice. The longevity allele at rs13217795 was associated with increased levels of full length FOXO3 isoforms in peripheral blood and a decrease in truncated FOXO3 isoforms in skeletal muscle RNA. We suggest that the longevity effect of FOXO3 SNPs may in part derive from a shift in isoform usage in skeletal muscle away from the production of 5' truncated FOXO3 isoforms lacking a complete forkhead DNA binding domain, which may have compromised functionality., (© 2021. The Author(s).)

Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians., (© 2022 by the American Diabetes Association.)

Aims/hypothesis: Higher maternal BMI during pregnancy is associated with higher offspring birthweight, but it is not known whether this is solely the result of adverse metabolic consequences of higher maternal adiposity, such as maternal insulin resistance and fetal exposure to higher glucose levels, or whether there is any effect of raised adiposity through non-metabolic (e.g. mechanical) factors. We aimed to use genetic variants known to predispose to higher adiposity, coupled with a favourable metabolic profile, in a Mendelian randomisation (MR) study comparing the effect of maternal 'metabolically favourable adiposity' on offspring birthweight with the effect of maternal general adiposity (as indexed by BMI)., Methods: To test the causal effects of maternal metabolically favourable adiposity or general adiposity on offspring birthweight, we performed two-sample MR. We used variants identified in large, published genetic-association studies as being associated with either higher adiposity and a favourable metabolic profile, or higher BMI (n = 442,278 and n = 322,154 for metabolically favourable adiposity and BMI, respectively). We then extracted data on the metabolically favourable adiposity and BMI variants from a large, published genetic-association study of maternal genotype and offspring birthweight controlling for fetal genetic effects (n = 406,063 with maternal and/or fetal genotype effect estimates). We used several sensitivity analyses to test the reliability of the results. As secondary analyses, we used data from four cohorts (total n = 9323 mother-child pairs) to test the effects of maternal metabolically favourable adiposity or BMI on maternal gestational glucose, anthropometric components of birthweight and cord-blood biomarkers., Results: Higher maternal adiposity with a favourable metabolic profile was associated with lower offspring birthweight (-94 [95% CI -150, -38] g per 1 SD [6.5%] higher maternal metabolically favourable adiposity, p = 0.001). By contrast, higher maternal BMI was associated with higher offspring birthweight (35 [95% CI 16, 53] g per 1 SD [4 kg/m 2 ] higher maternal BMI, p = 0.0002). Sensitivity analyses were broadly consistent with the main results. There was evidence of outlier SNPs for both exposures; their removal slightly strengthened the metabolically favourable adiposity estimate and made no difference to the BMI estimate. Our secondary analyses found evidence to suggest that a higher maternal metabolically favourable adiposity decreases pregnancy fasting glucose levels while a higher maternal BMI increases them. The effects on neonatal anthropometric traits were consistent with the overall effect on birthweight but the smaller sample sizes for these analyses meant that the effects were imprecisely estimated. We also found evidence to suggest that higher maternal metabolically favourable adiposity decreases cord-blood leptin while higher maternal BMI increases it., Conclusions/interpretation: Our results show that higher adiposity in mothers does not necessarily lead to higher offspring birthweight. Higher maternal adiposity can lead to lower offspring birthweight if accompanied by a favourable metabolic profile., Data Availability: The data for the genome-wide association studies (GWAS) of BMI are available at https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT&#95;consortium&#95;data&#95;files . The data for the GWAS of body fat percentage are available at https://walker05.u.hpc.mssm.edu ., (© 2021. The Author(s).)

Aim: To determine the insulin requirement for a high-fat, high-protein breakfast to optimise postprandial glycaemic excursions in children and young people with type 1 diabetes using insulin pumps., Methods: In all, 27 participants aged 10-23 years, BMI <95 th percentile (2-18 years) or BMI <30 kg/m 2 (19-25 years) and HbA 1c ≤64 mmol/mol (≤8.0%) consumed a high-fat, high-protein breakfast (carbohydrate: 30 g, fat: 40 g and protein: 50 g) for 4 days. In this cross-over trial, insulin was administered, based on the insulin-to-carbohydrate ratio (ICR) of 100% (control), 120%, 140% and 160%, in an order defined by a randomisation sequence and delivered in a combination bolus, 60% ¼ hr pre-meal and 40% over 3 hr. Postprandial sensor glucose was assessed for 6 hr., Results: Comparing 100% ICR, 140% ICR and 160% ICR resulted in significantly lower 6-hr areas under the glucose curves: mean (95%CI) (822 mmol/L.min [605,1039] and 567 [350,784] vs 1249 [1042,1457], p ≤ 0.001) and peak glucose excursions (4.0 mmol/L [3.0,4.9] and 2.7 [1.7,3.6] vs 6.0 [5.0,6.9],p < 0.001). Rates of hypoglycaemia for 100%-160% ICR were 7.7%, 7.7%, 12% and 19% respectively (p ≥ 0.139). With increasing insulin dose, a step-wise reduction in mean glucose excursion was observed from 1 to 6 hr (p = 0.008)., Conclusions: Incrementally increasing the insulin dose for a high-fat, high-protein breakfast resulted in a predictable, dose-dependent reduction in postprandial glycaemia: 140% ICR improved postprandial glycaemic excursions without a statistically significant increase in hypoglycaemia. These findings support a safe, practical method for insulin adjustment for high-fat, high-protein meals that can be readily implemented in practice to improve postprandial glycaemia., (© 2021 Diabetes UK.)

Introduction: Patients with neurogenic bladder (NGB) and urinary incontinence (UI) due to low bladder outlet resistance may require bladder neck procedures (BNPs) to achieve continence. These patients may also have reduced bladder capacity and or elevated detrusor storage pressures that require augmentation cystoplasty (AC). AC is not without complications that include risks for bladder rupture, urolithiasis, urinary tract infections and metabolic issues. Avoidance of AC would be helpful in patients with neurogenic urinary incontinence that have safe bladder parameters in the setting of low bladder outlet resistance., Objective: To determine if pre-operative urodynamics could select children with NGBs and UI for isolated BNPs without AC. Additionally we sought to determine the safety of BNPs without AC and future need of AC with long-term follow-up., Study Design: This is an IRB-approved retrospective analysis of all patients undergoing BNPs for management of neurogenic UI over a 17-year period. We separated these BNP patients into two groups: No AC + BNP (Group 1) vs. AC + BNP (Group 2). Our primary analyses focused on postoperative outcomes for patients in Group 1. Outcomes assessed included additional surgical procedures, urodynamic changes, development of CKD, new hydronephrosis (HDN) and vesicoureteral reflux (VUR). Secondary analysis included the timeline for the development of any bladder deterioration that necessitated AC in Group 1., Results: 93 patients underwent BNP at a mean age of 10.8 years. Thirty did not have AC at the time of surgery (Group 1). These children had larger (p < 0.001) and more compliant (p < 0.001) bladders than Group 2 having simultaneous augmentation. At 6 years mean follow-up in Group 1 patients, three developed new reflux and three had new hydronephrosis. Nine (30%) had additional continence procedures. Twelve required (40%) AC at a mean of 23 months after the initial BNP. No patients had AC after 5 years. Detrusor end filling pressure increased 14.8 cm H2O (p = 0.028) and expected bladder capacity decreased 26.1% (p = 0.005) after isolated BNP., Discussion: We found that from our cohort of patients who had normal bladder compliance and normal/near normal expected capacity preoperatively 40% required subsequent AC. We were unable to find pre-operative clinical parameters which predicted failure or conversion to AC. We found that 43.3% of our BNP without AC patients had no subsequent invasive procedures with mean 6-year follow-up. We found that none of our patients developed any degree of CKD. Finally, we found that the majority of patients that converted to AC after their BNP did so within the first 2 years after their initial BNP and no patients required augmentation 5 years post their initial BNP. This data validates that these patients require very strict follow up, particularly in the first 5 years after surgery., Conclusions: BNP without AC is safe in only a few selected patients with NGB. Despite preoperative selection, there are significant changes in bladder dynamics and 40% required subsequent augmentation. Bladder deterioration occurs early and generally in the first 2 years. Since there are no apparent reliable pre-operative variables predicting the need for subsequent AC, parents should be counseled regarding vigilant post-operative follow-up., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Babies born clinically Small- or Large-for-Gestational-Age (SGA or LGA; sex- and gestational age-adjusted birth weight (BW) <10th or >90th percentile, respectively), are at higher risks of complications. SGA and LGA include babies who have experienced environment-related growth-restriction or overgrowth, respectively, and babies who are heritably small or large. However, the relative proportions within each group are unclear. We assessed the extent to which common genetic variants underlying variation in birth weight influence the probability of being SGA or LGA. We calculated independent fetal and maternal genetic scores (GS) for BW in 11,951 babies and 5,182 mothers. These scores capture the direct fetal and indirect maternal (via intrauterine environment) genetic contributions to BW, respectively. We also calculated maternal fasting glucose (FG) and systolic blood pressure (SBP) GS. We tested associations between each GS and probability of SGA or LGA. For the BW GS, we used simulations to assess evidence of deviation from an expected polygenic model. Higher BW GS were strongly associated with lower odds of SGA and higher odds of LGA (ORfetal = 0.75 (0.71,0.80) and 1.32 (1.26,1.39); ORmaternal = 0.81 (0.75,0.88) and 1.17 (1.09,1.25), respectively per 1 decile higher GS). We found evidence that the smallest 3% of babies had a higher BW GS, on average, than expected from their observed birth weight (assuming an additive polygenic model: Pfetal = 0.014, Pmaternal = 0.062). Higher maternal SBP GS was associated with higher odds of SGA P = 0.005. We conclude that common genetic variants contribute to risk of SGA and LGA, but that additional factors become more important for risk of SGA in the smallest 3% of babies., Competing Interests: The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. MMcC has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MMcC is an employee of Genentech, and a holder of Roche stock.

Neonatal diabetes presents <6 months of life but delays in recognition result in presentation with life-threatening hyperglycaemia/diabetic ketoacidosis. Early identification and rapid genetic diagnosis is crucial and ensures correct treatment/management. Adding 'glucose' to newborn bloodspot screening (NBS) could aid prompt detection but requires evidence of parental acceptance., Objectives: Increase understanding of parental experience of presentation/recognition of neonatal diabetes and perceptions of glucose testing within NBS., Setting: UK families confirmed with a genetic diagnosis of neonatal diabetes, November 2014-2018, were invited to participate., Participants: In-depth qualitative interviews were conducted with 10 parents of 14 children. 8 had transient neonatal diabetes: KCNJ11 (n=5), ABCC8 (n=1), 6q24 (n=2), 6 had permanent neonatal diabetes: KCNJ11 (n=4), INS (n=1), homozygous GCK (n=1)., Primary and Secondary Outcome Measures: Interviews audio recorded, transcribed and subjected to thematic content analysis., Results: 3 key themes emerged:Babies were extremely ill at hospital admission, with extended stays in intensive care required.Identification of diabetes was not 'standardised' and perceived a 'chance' finding.Adding glucose to NBS was universally considered extremely positive., Conclusions: Diagnosis of neonatal diabetes is frequently delayed, resulting in critically ill presentation with prolonged intensive care support, additional healthcare costs and familial distress. Potential to detect hyperglycaemia earlier was universally endorsed by parents with no negative consequences identified. Although further study including a larger number of individuals is needed to confirm our findings this study provides the first evidence of acceptability of glucose testing fulfilling Wilson-Jungner criteria for implementation within the NBS programme., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MMcC: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. He serves on advisory panels for Pfizer, NovoNordisk, Zoe Global; has received honoraria from Merck, Pfizer, NovoNordisk and Eli Lilly; has stock options in Zoe Global; has received research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. MS receives funding from Pfizer Inc. for a project not related to this research. IB and spouse own stock in GlaxoSmithKline and Incyte Corp. ZE and CDB currently serve on the editorial board of PLOS Genetics. AC reports personal fees from Novartis, personal fees from Thermo Fisher Scientific, personal fees from Philips, personal fees from Sanofi, personal fees from Stallergenes Greer, outside the submitted work. KC in involved in consultancy for Danone Research, LNC-therapeutic and Confo-therapeutic but no personal funding is received and this activity not linked to the present research.

Study Design: Retrospective cohort study., Objectives: This study investigates postoperative urinary retention (POUR) following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and the effects of postoperative analgesia and mobility on retention. High opioid use and decreased postoperative mobility are proposed risk factors for retention in adults. There is a paucity of literature on POUR in the adolescent population undergoing surgery for AIS. The impact of pain control and mobility on POUR in these patients is unknown., Methods: A retrospective cohort study was conducted of adolescents (11-18 years) undergoing elective PSF for AIS at a single institution (2012-2018). POUR was defined as the inability to void > 8 h after catheter removal. Possible risk factors for retention including opioid usage and ambulatory status at the time of catheter removal were assessed on univariate and binomial logistic regression analyses., Results: One hundred and thirty-six patients were included, with 21 (15.4%) experiencing POUR. On the day of catheter removal, 24 patients had not attempted ambulation; these patients had 2.5 times higher rate of POUR than those who were walking (30% vs. 12%, p = 0.04). Patients who developed retention ambulated a mean threefold shorter distance than those without POUR (45 vs. 136 feet, p = 0.04). On binomial logistic regression, decreased ambulation distance was associated with retention (p = 0.038). While opioid use was not significant on univariate analysis, higher opioid use on the day of catheter removal predicted retention on logistic regression (p = 0.001). POUR resolved in all patients (median duration 0.5 days, range 0-12 days)., Conclusions: The development of POUR after PSF for AIS affects one in six patients but resolves quickly. Non-ambulatory patients and patients who received large doses of opioids on the day of catheter removal were more likely to develop POUR., Level of Evidence: III.

Background: Babies of women with heterozygous pathogenic glucokinase (GCK) variants causing mild fasting hyperglycemia are at risk of macrosomia if they do not inherit the variant. Conversely, babies who inherit a pathogenic hepatocyte nuclear factor 4α (HNF4A) diabetes variant are at increased risk of high birth weight. Noninvasive fetal genotyping for maternal pathogenic variants would inform pregnancy management., Methods: Droplet digital PCR was used to quantify reference and variant alleles in cell-free DNA extracted from blood from 38 pregnant women heterozygous for a GCK or HNF4A variant and to determine fetal fraction by measurement of informative maternal and paternal variants. Droplet numbers positive for the reference/alternate allele together with the fetal fraction were used in a Bayesian analysis to derive probability for the fetal genotype. The babies' genotypes were ascertained postnatally by Sanger sequencing., Results: Droplet digital PCR assays for GCK or HNF4A variants were validated for testing in all 38 pregnancies. Fetal fraction of ≥2% was demonstrated in at least 1 cell-free DNA sample from 33 pregnancies. A threshold of ≥0.95 for calling homozygous reference genotypes and ≤0.05 for heterozygous fetal genotypes allowed correct genotype calls for all 33 pregnancies with no false-positive results. In 30 of 33 pregnancies, a result was obtained from a single blood sample., Conclusions: This assay can be used to identify pregnancies at risk of macrosomia due to maternal monogenic diabetes variants., (© American Association for Clinical Chemistry 2020.)

Background: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight., Methods: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496., Findings: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT 4 ]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT 4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p interaction =0·10). Each 1 SD increase in FT 4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second., Interpretation: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT 4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy., Funding: Netherlands Organization for Scientific Research (grant 401.16.020)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-K ATP -channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. We aimed to assess the physiological response to carbohydrate and protein/fat in people with sulfonylurea-treated KCNJ11 PNDM., Research Design and Methods: 5 adults with sulfonylurea-treated KCNJ11 PNDM and five age, sex and body mass index-matched controls without diabetes had a high-carbohydrate and high-protein/fat meal on two separate mornings. Insulin(i) and glucose(g) were measured at baseline then regularly over 4 hours after the meal. Total area under the curve (tAUC) for insulin and glucose was calculated over 4 hours and compared between meals in controls and KCNJ11 cases., Results: In controls, glucose values after carbohydrate and protein/fat were similar (median glucose tAUC 0-4h 21.4 vs 19.7 mmol/L, p=0.08). In KCNJ11 cases glucose levels were higher after carbohydrate than after protein/fat (median glucose tAUC 0-4h 58.1 vs 31.3 mmol/L, p=0.04). These different glycemic responses reflected different patterns of insulin secretion: in controls, insulin secretion was greatly increased after carbohydrate versus protein/fat (median insulin tAUC 0-4h 727 vs 335 pmol/L, p=0.04), but in KCNJ11 cases insulin secretion was similar after carbohydrate and protein/fat (median insulin tAUC 0-4h 327 vs 378 pmol/L, p=0.50)., Conclusions: Individuals with sulfonylurea-treated KCNJ11 PNDM produce similar levels of insulin in response to both carbohydrate and protein/fat meals despite carbohydrate resulting in much higher glucose levels and protein/fat resulting in relatively low glucose levels. This suggests in an inability to modulate insulin secretion in response to glucose levels, consistent with a dependence on non-K ATP pathways for insulin secretion., Trial Registration Number: NCT02921906., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Self-care is among the emerging types of mental health support which operate outside traditional services, although the meaning and practice of self-care for young people with mental health difficulties are currently unclear. This systematic review was pre-registered with PROSPERO (CRD42021282510) and investigated conceptualizations of self-care in academic publications which investigated or discussed self-care for young people's mental health or wellbeing. A Patient and Public Involvement (PPI) workshop facilitated young people with experience of mental health difficulties to respond to the identified concepts and co-develop a definition of self-care. Searches in PsycINFO, MEDLINE, Embase, CINAHL Plus, Scopus, Cochrane Library of Systematic Reviews, and gray literature sources resulted in 90 included publications. Content analysis indicated little conceptual consistency, with health and wellness promotion most commonly used to define self-care. The PPI workshop co-developed a definition of mental health self-care, which attendees felt should emphasize an individual process of self-awareness, self-compassion, and specific strategies to work toward emotional balance. This study highlights the gap between current academic understandings of young people's mental health self-care and young people's experience. The presented definition will enable future research to begin from an understanding of self-care which is relevant to young people with experience of mental health difficulties., Competing Interests: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there are no conflicting or competing interests. Ethical information: Ethical approval was not required for systematic review research. As Patient and Public Involvement is not considered research, ethical approval was not required for this portion of the submission. Informed consent and consent for publication: Not applicable., (© 2023. The Author(s).)

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10 -14 ). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

Aims: Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA 1c , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA 1c in those with long duration (> 5 years) Type 1 diabetes., Methods: We conducted a cross-sectional case-control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C-peptide after a mixed-meal tolerance test. We compared self-reported hypoglycaemia (n = 160), HbA 1c , insulin dose and microvascular complications (n = 140) in those with preserved and low C-peptide., Results: Stimulated median (IQR) C-peptide was 114 (43, 273) pmol/l and < 3 (< 3, < 3) pmol/l in those with preserved and low C-peptide respectively. Participants with preserved C-peptide had lower reported monthly rates of hypoglycaemia, with 21% fewer symptomatic episodes, 5.9 vs. 7.5 [incidence rate ratio (IRR) 0.79, P = 0.001], and 65% fewer asymptomatic episodes, 1.0 vs. 2.9 (IRR 0.35, P < 0.001). Those with preserved C-peptide had a lower insulin dose (0.68 vs. 0.81 units/kg, P = 0.01) but similar HbA 1c (preserved 69 vs. low 67 mmol/mol, P = 0.06)., Conclusions: Adults with Type 1 diabetes and preserved endogenous insulin production receiving usual care in the UK have lower daily insulin doses and fewer self-reported hypoglycaemic episodes, but no difference in HbA 1c . This is consistent with non-intensive treatment in previous studies, and suggests a need to consider therapy intensification to gain full benefit of preserved endogenous insulin., (© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Public policy across the world is increasingly focusing on the role of mental health promotion in whole of health strategies. There is a growing evidence-base that mental health promotion, delivered by trained facilitators, is effective in promoting self-awareness and self-care to prevent the damaging effects of ongoing stress in one's life and to promote early detection of any possible emerging mental health problems. Within Australia, however, few clinicians or school staff are confident or trained in mental health promotion. Aims: This paper reports the results of a two-day training designed for facilitators of a mental health program for secondary-school students. The goal was to develop facilitators' knowledge and understanding of best practice in youth mental health promotion and to increase their confidence in delivering the program. Design: A mixed methods evaluation assessed the impact that a solution-focused training program had on participating facilitators. Methods: A questionnaire was created and included eight quantitative items and one open ended, qualitative question. Twenty-seven nurses and guidance officers from central Queensland were recruited via convenience sampling and data were analysed using descriptive statistics and thematic analysis. Results: The evaluation revealed that participants' perception of their ability to facilitate a youth mental health program significantly improved after completing the training. Qualitative data indicated that participants found the professional development experience to be valuable, provide useful and transferable skills, and believed it to be necessary for mental health promotion work. Conclusion: By providing detailed description of the program's content and processes, other mental health professionals may be inspired to further develop effective learning experiences.

Background: Systematic reviews of randomised controlled trials (RCTs) have suggested that maternal vitamin D (25[OH]D) and calcium supplementation increase birth weight. However, limitations of many trials were highlighted in the reviews. Our aim was to combine genetic and RCT data to estimate causal effects of these two maternal traits on offspring birth weight., Methods and Findings: We performed two-sample mendelian randomisation (MR) using genetic instrumental variables associated with 25(OH)D and calcium that had been identified in genome-wide association studies (GWAS; sample 1; N = 122,123 for 25[OH]D and N = 61,275 for calcium). Associations between these maternal genetic variants and offspring birth weight were calculated in the UK Biobank (UKB) (sample 2; N = 190,406). We used data on mother-child pairs from two United Kingdom birth cohorts (combined N = 5,223) in sensitivity analyses to check whether results were influenced by fetal genotype, which is correlated with the maternal genotype (r ≈ 0.5). Further sensitivity analyses to test the reliability of the results included MR-Egger, weighted-median estimator, 'leave-one-out', and multivariable MR analyses. We triangulated MR results with those from RCTs, in which we used randomisation to supplementation with vitamin D (24 RCTs, combined N = 5,276) and calcium (6 RCTs, combined N = 543) as an instrumental variable to determine the effects of 25(OH)D and calcium on birth weight. In the main MR analysis, there was no strong evidence of an effect of maternal 25(OH)D on birth weight (difference in mean birth weight -0.03 g [95% CI -2.48 to 2.42 g, p = 0.981] per 10% higher maternal 25[OH]D). The effect estimate was consistent across our MR sensitivity analyses. Instrumental variable analyses applied to RCTs suggested a weak positive causal effect (5.94 g [95% CI 2.15-9.73, p = 0.002] per 10% higher maternal 25[OH]D), but this result may be exaggerated because of risk of bias in the included RCTs. The main MR analysis for maternal calcium also suggested no strong evidence of an effect on birth weight (-20 g [95% CI -44 to 5 g, p = 0.116] per 1 SD higher maternal calcium level). Some sensitivity analyses suggested that the genetic instrument for calcium was associated with birth weight via exposures that are independent of calcium levels (horizontal pleiotropy). Application of instrumental variable analyses to RCTs suggested that calcium has a substantial effect on birth weight (178 g [95% CI 121-236 g, p = 1.43 × 10-9] per 1 SD higher maternal calcium level) that was not consistent with any of the MR results. However, the RCT instrumental variable estimate may have been exaggerated because of risk of bias in the included RCTs. Other study limitations include the low response rate of UK Biobank, which may bias MR estimates, and the lack of suitable data to test whether the effects of genetic instruments on maternal calcium levels during pregnancy were the same as those outside of pregnancy., Conclusions: Our results suggest that maternal circulating 25(OH)D does not influence birth weight in otherwise healthy newborns. However, the effect of maternal circulating calcium on birth weight is unclear and requires further exploration with more research including RCT and/or MR analyses with more valid instruments., Competing Interests: DAL has received support from Medtronic LTD and Roche Diagnostics for biomarker research that is not related to the study presented in this paper. SMR has received funding from the MRC, ESRC, and Wellcome Trust. The other authors report no conflicts.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Objective: Central nervous system (CNS) features in children with permanent neonatal diabetes (PNDM) due to KCNJ11 mutations have a major impact on affected families. Sulfonylurea therapy achieves outstanding metabolic control but only partial improvement in CNS features. The effects of KCNJ11 mutations on the adult brain and their functional impact are not well understood. We aimed to characterize the CNS features in adults with KCNJ11 PNDM compared with adults with INS PNDM., Research Design and Methods: Adults with PNDM due to KCNJ11 mutations ( n = 8) or INS mutations ( n = 4) underwent a neurological examination and completed standardized neuropsychological tests/questionnaires about development/behavior. Four individuals in each group underwent a brain MRI scan. Test scores were converted to Z scores using normative data, and outcomes were compared between groups., Results: In individuals with KCNJ11 mutations, neurological examination was abnormal in seven of eight; predominant features were subtle deficits in coordination/motor sequencing. All had delayed developmental milestones and/or required learning support/special schooling. Half had features and/or a clinical diagnosis of autism spectrum disorder. KCNJ11 mutations were also associated with impaired attention, working memory, and perceptual reasoning and reduced intelligence quotient (IQ) (median IQ KCNJ11 vs. INS mutations 76 vs. 111, respectively; P = 0.02). However, no structural brain abnormalities were noted on MRI. The severity of these features was related to the specific mutation, and they were absent in individuals with INS mutations., Conclusions: KCNJ11 PNDM is associated with specific CNS features that are not due to long-standing diabetes, persist into adulthood despite sulfonylurea therapy, and represent the major burden from KCNJ11 mutations., (© 2018 by the American Diabetes Association.)

Background: Iodine is important for thyroid hormone synthesis, and iodine deficiency in pregnancy may impair fetal neurological development. As perchlorate and thiocyanate inhibit sodium-iodide symporter reducing the transport of iodine from circulation into the thyroid follicular cells, environmental exposure to these substances in pregnancy may impair maternal thyroid hormone synthesis. We aimed to explore the impact of perchlorate and thiocyanate exposure on thyroid status in a cohort of pregnant mothers from South West England., Methods: Urine samples were obtained from 308 women participating in a study of breech presentation in late pregnancy. They had no known thyroid disease and a singleton pregnancy at 36-38 weeks gestation. Samples were analysed for urinary concentrations of iodine (UIC), perchlorate (UPC) and thiocyanate (UTC). Blood samples were taken for free T4 (FT4), thyrotropin (TSH) and thyroid peroxidase antibodies (TPO-Ab). Baseline data included age, parity, smoking status, ethnicity and BMI at booking. Following delivery, data on offspring's sex, gestational age at birth and birthweight were collected., Results: Participants had a mean (SD) age 31 (5) years, median (IQR) BMI 24.4 (22.0, 28.3) kg/m 2 , 42% were primiparous, 10% were smokers, and 96% were Caucasian. Median UIC was 88 μg/l, and 174/308 (57%) women had UIC < 100 μg/l. Log transformed UPC negatively correlated with FT4, but not with TSH, in the whole cohort ( r  = - 0.12, p  = 0.03) and in the subgroup of women with UIC < 100 μg/l ( r  = - 0.15, p  = 0.04). Regression analysis with the potential confounders (TPO-Ab status, UIC and UTC) identified UPC to be negatively associated with FT4 ( p  = 0.01). There was no correlation between UTC and FT4 or TSH. Maternal UPC or UTC was not associated with offspring birthweight., Conclusion: Environmental perchlorate exposure is negatively associated with circulating FT4 levels in third trimester pregnant women. This may have an adverse impact on neurocognitive development of the fetus., Competing Interests: The study was approved by the National Research Ethics Service (NRES) Committee South West – Exeter, and all participants gave informed written consent.All authors provide consent for this publication.LEB and ENP have received research funding from Sociedad Química y Minera de Chile.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Mental health is a leading health issue facing young people today, particularly those living in rural and regional areas. Although public policy supports schools-based health promotion, there is limited evidence of the efficacy of such programmes and the elements that enhance successful implementation in rural and regional areas. A study was designed to evaluate a mental health promotion programme, delivered collaboratively by nurses, guidance officers, and teachers, to 850 young people from 23 rural and regional high schools in Queensland, Australia. The study aims were to determine what effect the intervention had on young peoples' resilience, coping, and self-efficacy, and to understand the implications of delivering the programme in the regional Queensland school setting. Students completed self-report measures of self-efficacy, resilience, and coping strategies pre- and postprogramme, as well as at 8-week follow-up. We found that after programme completion there was a significant increase in self-efficacy and in the number of positive coping strategies used by the participating young people. Qualitative data indicated that participants benefited from the collaboration between health and education sectors; that is, nurses, guidance officers, and teachers delivered the programme together in ways that were perceived to be respectful of young people and effectively discussion-based, and engaging., (© 2017 Australian College of Mental Health Nurses Inc.)

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry ( n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms., (© 2018 by the American Diabetes Association.)

Objective: A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy., Research Design and Methods: We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study; n = 254), with replication for routinely available markers in U.K. electronic health care records (Clinical Practice Research Datalink [CPRD]; n = 23,001). In CPRD, we evaluated associations between baseline markers and 3-year durability of response. To test the specificity of findings, we repeated analyses for glucagon-like peptide 1 (GLP-1) receptor agonists (PRIBA, n = 339; CPRD, n = 4,464)., Results: In PRIBA, markers of higher insulin resistance (higher fasting C-peptide [ P = 0.03], HOMA2 insulin resistance [ P = 0.01], and triglycerides [ P < 0.01]) were associated with reduced 6-month HbA 1c response to DPP-4 inhibitors. In CPRD, higher triglycerides and BMI were associated with reduced HbA 1c response (both P < 0.01). A subgroup defined by obesity (BMI ≥30 kg/m 2 ) and high triglycerides (≥2.3 mmol/L) had reduced 6-month response in both data sets (PRIBA HbA 1c reduction 5.3 [95% CI 1.8, 8.6] mmol/mol [0.5%] [obese and high triglycerides] vs. 11.3 [8.4, 14.1] mmol/mol [1.0%] [nonobese and normal triglycerides]; P = 0.01). In CPRD, the obese, high- triglycerides subgroup also had less durable response (hazard ratio 1.28 [1.16, 1.41]; P < 0.001). There was no association between markers of insulin resistance and response to GLP-1 receptor agonists., Conclusions: Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP-4 inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP-4 inhibitor therapy., (© 2018 by the American Diabetes Association.)