SummaryBackgroundKCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients.MethodsIn this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817.Findings90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3–10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA1c and sulfonylurea at all time points (ie, pre-transfer [for HbA1c], year 1, and most recent follow-up; n=64)—median HbA1c was 8·1% (IQR 7·2–9·2; 65·0 mmol/mol [55·2–77·1]) before transfer to sulfonylureas, 5·9% (5·4–6·5; 41·0 mmol/mol [35·5–47·5]; p<0·0001 vs pre-transfer) at 1 year, and 6·4% (5·9–7·3; 46·4 mmol/mol [41·0–56·3]; p<0·0001 vs year 1) at most recent follow-up (median 10·3 years [IQR 9·2–10·9]). In the same patients, median sulfonylurea dose at 1 year was 0·30 mg/kg per day (0·14–0·53) and at most recent follow-up visit was 0·23 mg/kg per day (0·12–0·41; p=0·03). No reports of severe hypoglycaemia were recorded in 809 patient-years of follow-up for the whole cohort (n=81). 11 (14%) patients reported mild, transient side-effects, but did not need to stop sulfonylurea therapy. Seven (9%) patients had microvascular complications; these patients had been taking insulin longer than those without complications (median age at transfer to sulfonylureas 20·5 years [IQR 10·5–24·0] vs 4·1 years [1·3–10·2]; p=0·0005). Initial improvement was noted following transfer to sulfo...

Background: The high volume and pace of research has posed challenges to researchers, policymakers and practitioners wanting to understand the overall impact of the pandemic on children and young people's mental health. We aimed to search for and review the evidence from epidemiological studies to answer the question: how has mental health changed in the general population of children and young people? Methods: Four databases (Medline, CINAHL, EMBASE and PsychINFO) were searched in October 2021, with searches updated in February 2022. We aimed to identify studies of children or adolescents with a mean age of 18 years or younger at baseline, that reported change on a validated mental health measure from prepandemic to during the pandemic. Abstracts and full texts were double-screened against inclusion criteria and quality assessed using a risk of bias tool. Studies were narratively synthesised, and meta-analyses were performed where studies were sufficiently similar. Results: 6917 records were identified, and 51 studies included in the review. Only four studies had a rating of high quality. Studies were highly diverse in terms of design, setting, timing in relation to the pandemic, population, length of follow-up and choice of measure. Methodological heterogeneity limited the potential to conduct meta-analyses across studies. Whilst the evidence suggested a slight deterioration on some measures, overall, the findings were mixed, with no clear pattern emerging. Conclusions: Our findings highlight the need for a more harmonised approach to research in this field. Despite the sometimes-inconsistent results of our included studies, the evidence supports existing concerns about the impact of Covid-19 on children's mental health and on services for this group, given that even small changes can have a significant impact on provision at population level. Children and young people must be prioritised in pandemic recovery, and explicitly considered in planning for any future pandemic response.

Background Adolescent self‐harm is a major public health concern. To date there is a limited evidence‐base for prevention or intervention, particularly within the school setting. To develop effective approaches, it is important to first understand the school context, including existing provision, barriers to implementation, and the acceptability of different approaches. Methods A convenience sample of 222 secondary schools in England and Wales were invited to participate in a survey, with a 68.9% (n = 153) response rate. One member of staff completed the survey on behalf of each school. Participants responded to questions on the existing provision of adolescent self‐harm prevention and intervention, barriers to delivery, and future needs. Results Adolescent self‐harm is an important concern for senior management and teachers. However, emotional health and well‐being is the primary health priority for schools. Health services, such as Child and Adolescent Mental Health Services, and on‐site counselling are the main approaches schools currently use to address adolescent self‐harm, with counselling cited as the most useful provision. Fifty‐two per cent of schools have received some staff training on adolescent self‐harm, although only 22% rated the adequacy of this training as high. Where schools do not have existing provision, respondents stated that they would like staff training, specialist student training, external speakers, posters and assemblies, although the latter four options were infrequently ranked as the most useful approaches. Key barriers to addressing adolescent self‐harm were: lack of time in the curriculum; lack of resources; lack of staff training and time; and fear of encouraging self‐harm amongst adolescents. Conclusions Adolescent self‐harm is a priority for schools. Intervention might focus on increasing the availability of training to teaching staff.

<b>Objective </b><br><p> <i>ABCC8</i> mutations cause neonatal diabetes that can be transient (TNDM) or less commonly permanent (PNDM); ~90% individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with <i>ABCC8-</i>PNDM require lower sulfonylurea doses and have milder neurological features than those with <i>KCNJ11-</i>PNDM. However, these studies were short-term and included combinations of permanent and transient forms of <i>ABCC8</i>-NDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated <i>ABCC8</i>-PNDM. <b><br> Research Design and Methods </b><br> We studied all 24 individuals with <i>ABCC8-</i>PNDM diagnosed in the UK, Italy, France or USA known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analysed using non-parametric statistical methods. <b><br> Results </b><br> Long-term data were obtained for 21/24 individuals (median follow-up 10.0 (4.1-13.2) years). 18/21 remained on sulfonylureas without insulin at most recent follow-up. Glycemic control improved on sulfonylureas (pre-sulfonylurea vs 1-year post-transfer HbA1c 7.2% vs 5.7%, p=0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, p=0.04), n=16. Relatively high doses were used (1-year vs 10-year dose 0.37 vs 0.25mg/kg/day glyburide, p=0.50), without any severe hypoglycemia. Neurological features were reported in 13/21 individuals: these improved following sulfonylurea transfer in 7/13. The commonest features were learning difficulties (52%), developmental delay (48%), and ADHD (38%).<b><br> Conclusions </b><br> Sulfonylurea treatment of <i>ABCC8</i>-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment. </p>

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