Prevalence of parent-reported ASD and ADHD in the UK: Findings from the millennium cohort study

The final publication is available at Springer via http://dx.doi.org/10.1007/s10803-013-1849-0The UK prevalence of parent-reported autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) were estimated from the Millennium Cohort Study. Case definition was if a doctor or health care professional had ever told parents that their child had ASD and/or ADHD. Data were collected in 2008/2009 for 14,043 children. 1.7 % of children were reported as having ASD (95 % CI 1.4-2.0) at mean age 7.2 years (SD = 0.2; range = 6.3-8.2). 1.4 % reportedly had ADHD (95 % CI 1.2-1.7), and 0.3 % had both ASD and ADHD (95 % CI 0.2-0.5). After adjusting for socio-economic disadvantage, only male sex (p < 0.001 for both conditions) and cognitive ability, p = 0.004 (ASD); p = 0.01 (ADHD) remained strongly associated. The observed prevalence of parent-reported ASD is high compared to earlier UK and US estimates. Parent-reported ADHD is low compared to US estimates using the same measure. © 2013 Springer Science+Business Media New York.National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul

The Quality of Life scale for Children (QoL-C)

This is the author's version of the article, which has been published in final form at http://dx.doi.org/10.1108/JCS-05-2013-0019Purpose – There is a lack of valid and reliable generic measures of Health-Related Quality of Life (HRQoL) for children under eight. The purpose of this paper is to assess the psychometric properties of the newly formulated Quality of Life Scale for Children (QoL-C), which uses a pictorial response format. Design/methodology/approach – In total, 335 primary school children completed the QoL-C on two occasions, two weeks apart. Children aged four to seven were interviewed one-to-one while children aged eight to nine completed the measure as a class activity. Test-re-test reliability, convergent validity and child-parent concordance were assessed. Findings – Only one child refused to complete the QoL-C, which suggests the measure is user-friendly. Test-re-test reliability was moderate for the measure's total score (intraclass correlation coefficient =0.48, 95 percent CI 0.39, 0.57) but low to fair for individual items (K from 0.13 to 0.37). Internal consistency was moderate (α=0.42 time one, 0.53 time two). A small significant correlation was found between the QoL-C and Child Health Meter in the expected direction (r=−0.32), suggesting convergent validity. There was low concordance between the children's QoL-C responses and parent's responses (r=0.19) to a parallel measure. Research limitations/implications – The results suggest that further development of this measure is needed. However, the findings indicate that one-to-one support increases the reliability of very young children's responses. The use of pictures, emoticons and minimal text used in the QoL-C should be investigated further. Originality/value – Low parent-child concordance underscores the importance of younger children getting the opportunity to share their views about their HRQoL

Prior event rate ratio adjustment produced estimates consistent with randomized trial: a diabetes case study

Objectives: Electronic health records (EHR) provide a valuable resource for assessing drug side-effects, but treatments are not randomly allocated in routine care creating the potential for bias. We conduct a case study using the Prior Event Rate Ratio (PERR) Pairwise method to reduce unmeasured confounding bias in side-effect estimates for two second-line therapies for type 2 diabetes, thiazolidinediones, and sulfonylureas. Study design and settings: Primary care data were extracted from the Clinical Practice Research Datalink (n = 41,871). We utilized outcomes from the period when patients took first-line metformin to adjust for unmeasured confounding. Estimates for known side-effects and a negative control outcome were compared with the A Diabetes Outcome Progression Trial (ADOPT) trial (n = 2,545). Results: When on metformin, patients later prescribed thiazolidinediones had greater risks of edema, HR 95% CI 1.38 (1.13, 1.68) and gastrointestinal side-effects (GI) 1.47 (1.28, 1.68), suggesting the presence of unmeasured confounding. Conventional Cox regression overestimated the risk of edema on thiazolidinediones and identified a false association with GI. The PERR Pairwise estimates were consistent with ADOPT: 1.43 (1.10, 1.83) vs. 1.39 (1.04, 1.86), respectively, for edema, and 0.91 (0.79, 1.05) vs. 0.94 (0.80, 1.10) for GI. Conclusion: The PERR Pairwise approach offers potential for enhancing postmarketing surveillance of side-effects from EHRs but requires careful consideration of assumptions.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The MASTERMIND (MRC APBI Stratification and Extreme Response Mechanism IN Diabetes) consortium is funded by the U.K Medical Research Council funded study grant number MR/N00633X/1. The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. IQVIA provided some funding for this project.published version, accepted version (12 month embargo), submitted versio

Are the new drugs better? Changing UK prescribing of Type 2 diabetes medications and effects on HbA1c and weight, 2010 to 2016

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Aim: The availability of new glucose‐lowering drugs has changed UK National Institute of Clinical Excellence Type 2 diabetes guidelines, but there has been little evaluation of real‐world use of these drugs, or of the population‐level impact of their use. We examined changes in UK prescribing for patients starting second‐ and third‐line medications, and population‐level trends in glycaemic response and weight change. Methods: We extracted incident second‐ and third‐line oral prescription records for patients with Type 2 diabetes in the UK‐representative Clinical Practice Research Datalink, 2010 to 2016 (n = 68,902). Each year we calculated the proportion of each drug prescribed as the percentage of the total prescribed. We estimated annual mean six‐month HbA1c response and weight change using linear regression, standardised for clinical characteristics. Results: Use of Dipeptidyl peptidase‐4 (DPP4) inhibitors has increased markedly to overtake sulfonylureas as the most commonly prescribed second‐line drug in 2016 (43% vs 34% of total prescriptions compared with 18% v 59% in 2010). Use of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors has increased rapidly to 14% of second‐line and 27% of third‐line prescriptions in 2016. Mean HbA1c response at six months was stable over time (2016: 13.5 (95% confidence interval 12.8, 14.1) mmol/mol vs 2010: 13.9 (13.6;14.2) mmol/mol, p = 0.21). We found mean weight loss at six months in 2016, in contrast to 2010 where there was mean weight gain (2016: −1.2 (−0.9; −1.5) kg vs 2010: +0.4 (+0.3; +0.5) kg, p < 0.001). Conclusion: The pattern of drug prescribing to manage patients with Type 2 diabetes has changed rapidly in the United Kingdom. Increasing use of DPP4 inhibitors and SGLT2 inhibitors has not resulted in improved glycaemic control but has improved the body weight of patients starting second‐ and third‐line therapy. Acknowledgement: This abstract is submitted on behalf of the MASTERMIND consortium

Adherence to oral glucose-lowering therapies and associations with 1-year HbA_1c:A retrospective cohort analysis in a large primary care database

JOURNAL ARTICLEOBJECTIVE: The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K. clinical data (Clinical Practice Research Database [CPRD] and GoDARTS database) to examine the prevalence of nonadherence to treatment for type 2 diabetes and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication. RESEARCH DESIGN AND METHODS: Data were extracted for patients treated between 2004 and 2014 who were newly-prescribed metformin, sulfonylurea, thiazolidinedione, or dipeptidyl peptidase-4 inhibitors and who continued to obtain prescriptions over 1 year. Cohorts were defined by prescribed medication type, and good adherence was defined as a medication possession ratio ≥0.8. Linear regression was used to determine potential associations between adherence and 1-year baseline-adjusted HbA1c reduction. RESULTS: In CPRD and GoDARTS, 13% and 15% of patients, respectively, were nonadherent. Proportions of nonadherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% [thiazolidinedione] to 18.8% [metformin]). Nonadherent, compared with adherent, patients had a smaller HbA1c reduction (0.4% [4.4mmmol/mol] and 0.46% [5.0 mmol/mol] for CPRD and GoDARTs, respectively). Difference in HbA1c response for adherent compared with nonadherent patients varied by drug (range 0.38% [4.1 mmol/mol] to 0.75% [8.2 mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c. CONCLUSIONS: Reduced medication adherence for commonly used glucose-lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose-lowering treatments may be explained in part by their intermittent use.A.J.F. and R.R.H. are National Institute for Health Research (NIHR) Senior Investigators and receive additional support from the Oxford NIHR Biomedical Research Centre. M.N.W. was supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF). E.R.P. holds a Wellcome Trust New Investigator award. The MASTERMIND consortium is funded by the U.K. Medical Research Council MR-K005707-1. The funder of the trial had no role in study design, data collection, data analysis, data interpretation, or writing of the report

The increase of the functional entropy of the human brain with age

We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy

Continuous glucose monitoring demonstrates low risk of clinically significant hypoglycemia associated with sulphonylurea treatment in an African type 2 diabetes population: results from the OPTIMAL observational multicenter study

This is the final version. Available from BMJ Publishing via the DOI in this record. Data availability statement: Data are available on reasonable request. Data analyzed in this study are available to researchers on reasonable request from the corresponding author.INTRODUCTION: People living with diabetes in low-resource settings may be at increased hypoglycemia risk due to food insecurity and limited access to glucose monitoring. We aimed to assess hypoglycemia risk associated with sulphonylurea (SU) and insulin therapy in people living with type 2 diabetes in a low-resource sub-Saharan African setting. RESEARCH DESIGN AND METHODS: This study was conducted in the outpatients' diabetes clinics of two hospitals (one rural and one urban) in Uganda. We used blinded continuous glucose monitoring (CGM) and self-report to compare hypoglycemia rates and duration in 179 type 2 diabetes patients treated with sulphonylureas (n=100) and insulin (n=51) in comparison with those treated with metformin only (n=28). CGM-assessed hypoglycemia was defined as minutes per week below 3mmol/L (54mg/dL) and number of hypoglycemic events below 3.0 mmol/L (54 mg/dL) for at least 15 minutes. RESULTS: CGM recorded hypoglycemia was infrequent in SU-treated participants and did not differ from metformin: median minutes/week of glucose <3 mmol/L were 39.2, 17.0 and 127.5 for metformin, sulphonylurea and insulin, respectively (metformin vs sulphonylurea, p=0.6). Hypoglycemia risk was strongly related to glycated haemoglobin (HbA1c) and fasting glucose, with most episodes occurring in those with tight glycemic control. After adjusting for HbA1c, time <3 mmol/L was 2.1 (95% CI 0.9 to 4.7) and 5.5 (95% CI 2.4 to 12.6) times greater with sulphonylurea and insulin, respectively, than metformin alone. CONCLUSIONS: In a low-resource sub-Saharan African setting, hypoglycemia is infrequent among people with type 2 diabetes receiving sulphonylurea treatment, and the modest excess occurs predominantly in those with tight glycemic control.National Institute for Health Research (NIHR