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Background: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO. Methods: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies. Results: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06–1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12–1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery. Conclusions: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.

Background: Mendelian randomization studies of systolic blood pressure (SBP) can assess the shape and strength of the associations of genetically predicted differences in SBP with major disease outcomes and are less constrained by biases in observational analyses. This study aimed to compare the associations of usual and genetically predicted SBP with major cardiovascular disease (CVD) outcomes, overall and by levels of SBP, age, and sex. Methods: The China Kadoorie Biobank involved a 12-year follow-up of a prospective study of 489 495 adults aged 40 to 79 years with no prior CVD and 86 060 with genetic data. Outcomes included major vascular events (59 490/23 151 in observational/genetic analyses), and its components (ischemic stroke [n=39 513/12 043], intracerebral hemorrhage [7336/5243], and major coronary events [7871/4187]). Genetically predicted SBP used 460 variants obtained from European ancestry genome-wide studies. Cox regression estimated adjusted hazard ratios for incident CVD outcomes down to usual SBP levels of 120 mm Hg. Results: Both observational and genetic analyses demonstrated log-linear positive associations of SBP with major vascular event and other major CVD types in the range of 120 to 170 mm Hg. Consistent with the observational analyses, the hazard ratios per 10 mm Hg higher genetically predicted SBP were 2-fold greater for intracerebral hemorrhage (1.71 [95% CI, 1.58–1.87]) than for ischemic stroke (1.37 [1.30–1.45]) or major coronary event (1.29 [1.18–1.42]). Genetic analyses also demonstrated 2-fold greater hazard ratios for major vascular event in younger (1.69 [95% CI, 1.54–1.86]) than in older people (1.28 [1.18–1.38]). Conclusions: The findings provide support for initiation of blood pressure-lowering treatment at younger ages and below the conventional cut-offs for hypertension to maximize CVD prevention, albeit the absolute risks of CVD are far greater in older people.

Obesity is common among children and young people, with potential for significant clinical consequences. The physical and psychological comorbidities associated with childhood obesity persist into adult life, but many children do not have access to tailored obesity services. We present a framework for the identification, assessment and management of childhood obesity by the non-specialist. We also offer strategies to initiate discussions about weight and to communicate effectively with patients living with obesity.

Background Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. Methods We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. Findings At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42–1·58] vs 1·25 [1·20–1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. Interpretation Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. Funding British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

ObjectiveTo determine the extent to which the presence of acanthosis nigricans confers additional risk for insulin resistance, in addition to obesity alone (body mass index, BMI) within a young, overweight, UK population.Research design and methodsRetrospective data were collected to compare the degree of insulin resistance within a sample of 94 young people with acanthosis nigricans, and a matched cohort of 94 participants with obesity alone. Insulin resistance was assessed by fasting glucose, fasting insulin and Homeostatic Model Assessment of insulin resistance (HOMA-IR) score (a mathematical model derived to measure insulin resistance).ResultsThe acanthotic and control group were well matched for age, BMI, BMI SDS and sex, although the groups were not matched for ethnicity. The acanthotic group showed a significantly greater median fasting insulin (215 pmol/L), mean fasting glucose (4.7 mmol/L) and median HOMA-IR score (6.4), compared with the control group (126 pmol/L, 4.5 mmol/L and 3.7, respectively). The presence of acanthosis nigricans as an indicator of insulin resistance was found to have a positive predictive value of 81% (within this study population).ConclusionIndividuals with both acanthosis nigricans and obesity had significantly greater degrees of insulin resistance than individuals with obesity alone. The findings support the potential for acanthosis nigricans as a visible marker of type 2 diabetes in young people.

Background Metabolic acidosis is common in sick children. Measurement of anion gap helps to narrow down the cause of high anion gap metabolic acidosis such as DKA/lactic acidosis/renal failure. A rare cause of high anion gap metabolic acidosis is due to accumulation of pyroglutamic acid. Acquired PGA occurs in association with glutathione and cysteine depletion or as a side effect of certain medications.We report a complex case of child with GLIS3 mutation who had high anion gap metabolic acidosis secondary to acquired pyroglutamic aciduria associated with common drugs such as paracetamol. Objectives Methods Results 10 yrs old girl was born at 35 weeks gestation with severe growth retardation with birth weight of 1.17 kg. She developed neonatal diabetes on day 3 and congenital hypothyroidism on day 4. The combination of neonatal diabetes, congenital hypothyroidism and some dysmorphic facial features led to a clinical diagnosis of a GLIS 3 mutation, subsequently confirmed by genetic analysis.Her neonatal diabetes was managed with insulin pump therapy and high dose thyroxine in order to maintain her thyroid function. She was treated for exocrine pancreatic insufficiency, gastro oesophageal reflux with jejunostomy feeds. She also had liver transplantation at the age of 3 yrs for hepatic fibrosis and cirrhosis. She had polycystic kidney disease and deteriorating renal function, hypertension, chronic anaemia, recurrent chest infections and developmental delay. She was admitted with a viral illness and chest infection treated with cefuroxime, paracetamol and salbutamol along with her regular diabetes and thyroid medicines. She was initially managed in HDU, needed high flow oxygen support and strict fluid balance. In the ward, she suddenly became unresponsive and collapsed with an asystolic cardiac arrest. She developed severe metabolic acidosis with very high anion gap. The anion gap suggested the presence of a fixed acid and was not due to ketone production related to diabetes. This was confirmed at post-mortem also. She received prolonged resuscitation with multiple doses of adrenaline and boluses of bicarbonate. But remained in asystole and sadly succumbed.The pathologist noted that the child had a high anion gap metabolic acidosis and subsequent post mortem organic acid profile suggested that it was due to pyroglutamic aciduria. Pyroglutamic acidosis is noted to be a rare phenomenon which can happen in acutely unwell patients who receive antibiotics and paracetamol. The child had received paracetamol at a reduced dose in view of her renal impairment. Conclusions The learning point from the above presentation is that Pyroglutamic acidosis (PGA) should be considered as a differential diagnosis in patients presenting with high anion gap metabolic acidosis with complex co-morbidities and risk factors.The mainstay of treatment of PGA includes cessation of medications that can influence the γ-glutamyl cycle or glutathione levels, N-Acetyl Cysteine (NAC) and the implementation of supportive measures. Unrecognised acidosis due to PGA can contribute to morbidity and mortality in patients with hepatic and renal dysfunction.

Background: Little is known about the contemporary use of hospital treatments for major stroke pathological types in urban and rural areas of China. Methods: The China Kadoorie Biobank recruited >0.5 million adults (mean age 51 years, 59% women) during 2004-08 from ten (five urban, five rural) diverse areas in China. In-hospital medical records were retrieved from 20,229 participants (n=261 hospitals) hospitalised with a first-ever incident stroke over an 11-year follow-up period. Details of hospital management of stroke cases were analysed by sex, age of stroke onset, calendar year, hospital tier, region and other factors. Results: Among the 20,299 first-ever stroke cases, 17,306 (85%) had ischaemic stroke (IS; 7,123 non-lacunar, 6,690 lacunar and 3,493 silent lacunar), 2,623 (13%) had intracerebral haemorrhage (ICH), and 370 (2%) had subarachnoid haemorrhage (SAH). Among IS cases, anti-platelet treatment was used by 64% (65% non-lacunar, 66% lacunar, 56% silent lacunar), lipid-lowering by 50% (52% non-lacunar, 53% lacunar, 43% silent lacunar), blood pressure-lowering by about 42% of all IS subtypes, along with traditional Chinese medicines (TCM) by 59% (50% non-lacunar, 62% lacunar, 74% silent lacunar), with positive trends in use of these treatments by calendar year (Figure 1A), but inverse trends by hospital tier except TCM (Figure 1B). Approximately half of ICH (52.6%) or SAH (50.5%) cases received blood pressure-lowering medication, which did not vary significantly by area. A small proportion of cases with SAH had surgery to insert a coil (7.0%) or clip on aneurysm (5.7%). Interpretation: Among IS cases, use of antiplatelet, lipid-lowering and TCM increased in recent years and exceeded use of blood pressure-lowering treatment. In contrast, about half of all ICH and SAH cases used blood pressure-lowering treatments and there is significant under-use of surgery for SAH cases.

Type 1 diabetes is a self-managed condition. Regular monitoring of blood glucose (BG) levels has been the cornerstone of diabetes management. Finger prick BG testing traditionally has been the standard method employed. More recently, rapid advancements in the development of continuous glucose monitoring devices have led to increased use of technology to help children and young people with diabetes manage their condition. These devices have the potential to improve diabetes control and reduce hypoglycaemia especially if used in conjunction with a pump to automate insulin delivery. This paper aims to provide an update on main CGM devices available and practical considerations for doctors if they come across a child with diabetes who is using one of these devices.

Background and aims Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. Methods and results The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). Conclusions This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

Objectives Measuring testicular volume (TV) by orchidometer is routine in the clinic when staging male puberty. We have developed a simulation model for TV estimation and investigated whether training medical students, using a workshop with simulation models, could improve the accuracy and reliability of TV estimation. Methods All participating medical students watched a video representing standard undergraduate training in male pubertal assessment. Volunteers were then randomised directly to assessment or to attend a workshop consisting of a further video and four stations contextualising and practising the skills required for TV estimation, prior to assessment. Three child mannequins displaying testes of 3 mL, 4 mL (twice), 5, 10 and 20 mL were used for assessment. Participants were asked to return a fortnight later for repeat assessment to assess intra-observer reliability, the effect of repeated examinations on accuracy and time on skill retention. Results Ninety students participated (55F), 46 attended the workshop and were considered “trained”. There was no difference between the groups in numbers of correct estimations (29% trained, 27% untrained, p=0.593). However, the trained group’s estimations were closer to the true volume, with more from the trained group one bead away (p=0.002) and fewer more than three beads away from the true volume (p Conclusions Overall TV estimation accuracy was poor. Workshop-style training improved accuracy, reliability and retention of skill acquisition and could be considered as a useful learning tool.

Objective Copy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal/high GH) or previously in IGF-1 insensitivity (short stature, high/normal GH and IGF-1). Design and methods Array comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (n = 53) and IGF-1 insensitivity (n = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways/novel candidate growth genes within the CNV regions. Results Both cohorts were enriched for class 3–5 CNVs (7/53 (13%) GHI and 3/10 (30%) IGF-1 insensitivity patients). Interestingly, 6/10 (60%) CNV subjects had diagnostic/associated clinical features of SRS. 5/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (n = 2), 12q14 (n = 1) deletions and Xp22 (n = 1), Xq26 (n = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and CLOCK was identified as an upstream regulator in the IGF-1 insensitivity cohorts. Conclusions Our cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified.

Introduction\ud \ud The spontaneous, sporadic and sometimes unpredictable nature of children's physical activity causes fluctuations in blood glucose level and challenges for children with type 1 diabetes. Physical activity monitoring has potential utility. This study aimed to explore the perceptions of physical activity monitoring among healthcare professionals and assess the feasibility and acceptability of using it in the management of paediatric type 1 diabetes.\ud \ud \ud \ud Methods\ud \ud Seven healthcare professionals from one paediatric diabetes centre in the UK were involved in a focus group. Data were analysed thematically. Physical activity monitoring using a wrist-worn monitor was tested for feasibility with thirteen children aged 7-11 years with type 1 diabetes. The primary outcome was feasibility (i.e., recruitment, adherence, data completion, adverse events and acceptability). Secondary measures were glycaemic control, parental self-efficacy for diabetes management and parental fear of hypoglycaemia.\ud \ud \ud \ud Results\ud \ud Healthcare professionals valued having an awareness of the level, type and intensity of children’s physical activity. They identified unmet training and resource needs that would facilitate them being able to give physical activity advice to children and families. Recruitment rate was 20%, adherence to the activity monitoring was good and study completion rate was 62%. No adverse events were reported. Physical activity monitoring was deemed acceptable by parents.\ud \ud \ud \ud Conclusions\ud \ud Physical activity monitoring could be a feasible part of routine clinical practice, but further research is needed to understand whether healthcare professionals are best placed to implement it and what impact it has on health outcomes.

ObjectiveAim to examine the independent and joint associations of physical activity (PA) and sedentary leisure-time (SLT) with risk of diabetes and assess the extent to which these associations were mediated by adiposity.Research design and methodsThe prospective China Kadoorie Biobank recruited ~512 000 adults from 10 diverse areas across China. Self-reported PA was estimated based on type, frequency and duration of specific types of PA, covering four domains (occupation, leisure, household and commuting). SLT was defined as hours per day spent watching television, reading or playing card games. Stratified Cox proportional hazards models were used to estimate adjusted HRs (aHRs) for PA and SLT associated with incident diabetes. Analyses were stratified by age-at-risk (5-year intervals), sex and region and adjusted for household income, education, alcohol consumption, smoking, fresh fruit intake, self-reported general health status, family history of diabetes and body mass index (BMI) status. Analyses of total PA, occupational and non-occupational PA and SLT were mutually adjusted for each other, as appropriate.ResultsAfter ~9 years of follow-up, there were 14 940 incident diabetes cases among 460 736 participants without prior diabetes or cardiovascular diseases at baseline. The mean (SD) age at baseline was 51 (10.6) years, 59% were women and 43% resided in urban areas. Overall, the mean BMI was 23.5 (3.3) kg/m2, which differed by ~0.5 kg/m2 among individuals in the highest compared with the lowest PA and SLT groups. PA was inversely associated the risk of diabetes 16% (aHR: 0.84, 95% CI 0.81 to 0.88) lower in top than bottom fifth. After further adjustment for BMI this was attenuated to 0.99 (95% CI 0.98 to 1.00). SLT was positively associated with diabetes and each 1 hour per day higher usual level was associated with aHR of 1.13 (95% CI 1.09 to 1.17) for diabetes, attenuated to 1.05 (95% CI 1.01 to 1.09) after further adjustment for BMI.ConclusionsAmong Chinese adults, higher levels of PA and lower levels of SLT were associated with lower risks of diabetes with no evidence of effect modification by each other. These associations appeared to arise mainly through adiposity.

ObjectivesTo compare hospital treatments for major stroke types in Chinese adults by stroke pathological types, sex, age, calendar year, hospital tier, region and other factors.DesignCross-sectional analysis of medical records retrieved from 20 229 stroke cases in the China Kadoorie Biobank.SettingTen diverse areas (five urban, five rural) in China.ParticipantsFirst-incident stroke cases who were recruited during an 11-year follow-up of 0.5M participants in the China Kadoorie Biobank.MethodsElectronic copies of medical records of stroke cases were retrieved for clinical adjudication by local neurologists. Stroke cases were classified as ischaemic stroke (IS) (including lacunar infarction (LACI) and non-LACI (non-LACI)), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) and unspecified stroke types.ResultsAmong 20 299 first-ever stroke cases, 17 306 (85%) had IS, 7123 had non-LACI, 6690 had LACI, 3493 had silent LACI, 2623 (13%) had ICH and 370 (2%) had SAH. Among IS cases, antiplatelet treatment was used by 64% (65% non-LACI, 66% LACI, 56% silent LACI), lipid-lowering by 50% (52% non-LACI, 53% LACI, 43% silent LACI) and blood pressure-lowering by ~42% of all IS types, with positive trends in the use of these treatments by calendar year and hospital tier. Among ICH cases, 53% used blood pressure-lowering and 10% used lipid-lowering treatments, respectively. In contrast, traditional Chinese medicines (TCMs) were used by 59% of IS (50% non-LACI, 62% LACI, 74% silent LACI), 38% of ICH and 30% of SAH cases, with positive trends by calendar year and by hospital tier.ConclusionsAmong IS cases, use of antiplatelet and lipid-lowering medications increased in recent years, but use of TCM still exceeded use of blood pressure-lowering treatment. In contrast, blood pressure-lowering treatment was widely used for ICH, but only half of all ICH cases used blood pressure-lowering treatment.

Intragastric Balloons are a temporary, reversible, and safer option compared to bariatric surgery to promote significant weight loss leading to improved metabolic outcomes. However due to subsequent weight regain, alternative procedures are now preferred in adults. In adolescents, more amenable to lifestyle change, balloons may be an alternative to less reversible procedures. Our aim was to assess the tolerability and efficacy of the intragastric balloon in severely obese adolescents and the impact of associated weight loss on biomedical outcomes (glucose metabolism, blood pressure, lipid profiles) and bone density. A 2-year cohort study of 12 adolescents (BMI >3.5 s.d., Tanner stage >4) following 6 months intragastric balloon placement was carried out. Subjects underwent anthropometry, oral glucose tolerance test, and DEXA scans at 0, 6 and 24 months. Results showed clinically relevant improvements in blood pressure, insulin: glucose metabolism, liver function and sleep apnoea at 6 months. Changes were not sustained at 2 years though some parameters (Diastolic BP, HBA1c, insulin AUC) demonstrated longer-term improvement despite weight regain. Despite weight loss, bone mass accrual showed age appropriate increases. In conclusion, the intra-gastric balloon was safe, well tolerated and effective in supporting short-term weight loss and clinically relevant improvement in obesity related complications, which resolved in some individuals. Benefits were not sustained in the majority at 2 years.International Journal of Obesity accepted article preview online, 05 September 2017. doi:10.1038/ijo.2017.215.

Spatio–temporal models of ambient air pollution can be used to predict pollutant levels across a geographical region. These predictions may then be used as estimates of exposure for individuals in analyses of the health effects of air pollution. Integrated nested Laplace approximations is a method for Bayesian inference, and a fast alternative to Markov chain Monte Carlo methods. It also facilitates the SPDE approach to spatial modelling, which has been used for modelling of air pollutant levels, and is available in the R-INLA package for the R statistics software. Covariates such as meteorological variables may be useful predictors in such models, but covariate misalignment must be dealt with. This paper describes a flexible method used to estimate pollutant levels for six pollutants in Suzhou, a city in China with dispersed air pollutant monitors and weather stations. A two-stage approach is used to address misalignment of weather covariate data.

Background: Severe adolescent obesity (body mass index (BMI) >99.6th centile) is a significant public health challenge. Current non-invasive treatments, including community-based lifestyle interventions, are often of limited effectiveness in this population, with NICE guidelines suggesting the use of bariatric surgery as the last line of treatment. Health professionals are understandably reluctant to commission bariatric surgery and as an alternative, the use of an intra-gastric balloon as an adjunct to a lifestyle programme might offer a reversible, potentially safer and less invasive option. Objectives: Explore the use of an intra-gastric balloon as an adjunct to a lifestyle support programme, to promote weight loss in severely obese adolescents. Outcomes included weight loss, waist and hip measurements, psychosocial outcomes including health-related quality of life (HRQoL) and physical self perceptions, physical activity and cardiorespiratory fitness. Method: Non-randomised pilot study. Results: Twelve severely obese adolescents (5 males, 7 females; mean age 15 years; BMI >3.5 s.d.; puberty stage 4 or more) and their families were recruited. Mean weight loss at 12 months (n=9) was 3.05 kg±14.69; d=0.002, P=0.550, and a BMI Z-score (n=12) change of 0.2 s.d.; d=0.7, P=0.002 was observed at 6 months with a large effect, but was not sustained at 12 months (mean change 0.1 s.d.; d=0.3, P=0.146). At 24 months (n=10), there was a weight gain from baseline of +9.9 kg±1.21 (d=0.4; P=0.433). Adolescent and parent HRQoL scores exceeded the minimal clinical important difference between baseline and 12 months for all domains but showed some decline at 24 months. Conclusion: An intra-gastric balloon as an adjunct to a lifestyle support programme represents a safe and well-tolerated treatment approach in severely obese adolescents, with short-term effects on weight change. Improvements in psychosocial health, physical activity and cardiorespiratory fitness were maintained at 12 months, with varying results at 24 months.

Background Lean body mass has been identified as a key determinant of left ventricular mass and wall thickness. However, the importance of lean body mass or other body‐size measures as normative determinants of carotid intima‐media thickness ( cIMT ), a widely used early indicator of atherosclerosis, has not been well established. Methods and Results Carotid artery ultrasound measurements of cIMT and carotid artery plaque burden (derived from plaque number and maximum size) and measurements of body size, including height, body mass index, weight, body fat proportion, and lean body mass ([1−body fat proportion]×weight), were recorded in 25 020 participants from 10 regions of China. Analyses were restricted to a healthy younger subset (n=6617) defined as never or long‐term ex‐regular smokers aged cIMT , but was not associated with plaque burden: overall, each 10 kg higher lean body mass was associated with a 0.03 (95% CI , 0.03–0.04) mm higher cIMT ( P =5×10 −33 ). Fat mass, height, and other body‐size measures were more weakly associated with cIMT . Conclusions The strong association of lean body mass with cIMT, but not with plaque burden, in healthy adults suggests a normative relationship rather than reflecting atherosclerotic pathology. Common mechanisms may underlie the associations of lean body mass with cIMT and with nonatherosclerotic vascular traits.

Context\ud Measuring testicular volume (TV) by orchidometer is the standard method of male pubertal staging. A paucity of evidence exists as to its inter‐ and intra‐observer reliability and the impact of clinicians’ gender, training and experience on accuracy.\ud \ud Objective\ud Prosthetic testicular models were engineered to investigate accuracy and reliability of TV estimation.\ud \ud Design\ud Simulation study.\ud \ud Setting\ud Conducted over three‐day 2015 British Society for Paediatric Endocrinology and Diabetes (BSPED) meeting.\ud \ud Participants\ud 215 meeting delegates (161F, 54M): 50% consultants, 30% trainees, 9% clinical nurse specialists, 11% other professionals.\ud \ud Intervention\ud Three child‐sized mannequins displayed latex scrotum containing prosthetic testicles of 3ml, 4ml, 5ml, 10ml and 20ml. Demographic data, paediatric endocrinology experience, TV examination training, examination technique and TV estimations were collected. Delegates were asked to repeat their measurements later during the meeting. Scrotum order was changed daily.\ud \ud Main outcome measure\ud Accuracy by variance from the simulated TV. Inter‐ and intra‐observer variability.\ud \ud Results\ud 1284 individual estimations were obtained. Eighty‐five participants repeated measurements. Delegates measured TV accurately on 33.4% (±2.6) of occasions: overestimations 37.7% (±2.3), underestimations 28.7% (±1.8) (Fleiss Kappa score 0.04). The accuracy of assessing a 4 ml testis was 36‐39%. Observers underestimated the volume when paired with a 3ml testes and overestimated when paired with a 5 ml testis demonstrating a tendency impose biological symmetry. Intra‐observer reliability was lacking; individuals giving different estimations for the same size testicle on 61% (±4.2) of occasions, 20% (±3.5) of estimations were more than 1 size outside the previous measurement. On only 39% (±4.2) of occasions did individuals agree with their previous estimation (irrespective of whether or not it was initially accurate). Training did not impact on results but experience did improve accuracy.\ud \ud Conclusions\ud Overall TV estimation accuracy was poor. Considerable variation exists between and within subjects. Seniority slightly improved measurement estimation.

In the UK, there have been reports of significant reductions in paediatric emergency attendances and visits to the general practitioners due to COVID-19. A national survey undertaken by the UK Association of Children’s Diabetes Clinicians found that the proportion of new-onset type 1 diabetes (T1D) presenting with diabetes ketoacidosis (DKA) during this COVID-19 pandemic was higher than previously reported, and there has been an increase in presentation of severe DKA at diagnosis in children and young people under the age of 18 years. Delayed presentations of T1D have been documented in up 20% of units with reasons for delayed presentation ranging from fear of contracting COVID-19 to an inability to contact or access a medical provider for timely evaluation. Public health awareness and diabetes education should be disseminated to healthcare providers on the timeliness of referrals of children with T1D.

Approximately 3% of children and adolescents in the UK have severe obesity. The incidence of cardiovascular risk factors such as hypertension, hyperinsulinism and hyperlipidaemia approaches 20% in such individuals. Lifestyle intervention programmes and pharmacotherapy are effective in some individuals, but the relapse rate is high. In exceptional cases, bariatric surgery is effective. This review outlines the scale of the problem, highlights those at risk and discusses referral, current services, appropriate screening and therapeutic interventions.

Rationale Little evidence from large-scale cohort studies exists about the relationship of solid fuel use with hospitalization and mortality from major respiratory diseases. Objectives To examine the associations of solid fuel use and risks of acute and chronic respiratory diseases. Methods A cohort study of 277,838 Chinese never-smokers with no prior major chronic diseases at baseline. During 9 years of follow-up, 19,823 first hospitalization episodes or deaths from major respiratory diseases, including 10,553 chronic lower respiratory disease (CLRD), 4,398 chronic obstructive pulmonary disease (COPD), and 7,324 acute lower respiratory infection (ALRI), were recorded. Cox regression yielded adjusted hazard ratios (HRs) for disease risks associated with self-reported primary cooking fuel use. Measurements and Main Results Overall, 91% of participants reported regular cooking, with 52% using solid fuels. Compared with clean fuel users, solid fuel users had an adjusted HR of 1.36 (95% confidence interval, 1.32–1.40) for major respiratory diseases, whereas those who switched from solid to clean fuels had a weaker HR (1.14, 1.10–1.17). The HRs were higher in wood (1.37, 1.33–1.41) than coal users (1.22, 1.15–1.29) and in those with prolonged use (≥40 yr, 1.54, 1.48–1.60; Conclusions Among Chinese adults, solid fuel use for cooking was associated with higher risks of major respiratory disease admissions and death, and switching to clean fuels or use of ventilated cookstoves had lower risk than not switching.

Background There is an increasing demand by non-commercial funders that trialists should provide access to trial data once the primary analysis is completed. This has to take into account concerns about identifying individual trial participants, and the legal and regulatory requirements. Methods Using the good practice guideline laid out by the work funded by the Medical Research Council Hubs for Trials Methodology Research (MRC HTMR), we anonymised a dataset from a recently completed trial. Using this example, we present practical guidance on how to anonymise a dataset, and describe rules that could be used on other trial datasets. We describe how these might differ if the trial was to be made freely available to all, or if the data could only be accessed with specific permission and data usage agreements in place. Results Following the good practice guidelines, we successfully created a controlled access model for trial data sharing. The data were assessed on a case-by-case basis classifying variables as direct, indirect and superfluous identifiers with differing methods of anonymisation assigned depending on the type of identifier. A final dataset was created and checks of the anonymised dataset were applied. Lastly, a procedure for release of the data was implemented to complete the process. Conclusions We have implemented a practical solution to the data anonymisation process resulting in a bespoke anonymised dataset for a recently completed trial. We have gained useful learnings in terms of efficiency of the process going forward, the need to balance anonymity with data utilisation and future work that should be undertaken. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2382-9) contains supplementary material, which is available to authorized users.

ObjectiveThe short synacthen test (SST) is widely used to assess patients for adrenal insufficiency but the frequency and protocols used across different centres for the low-dose test (LDT) are unknown. This study aimed to survey centres and test the accuracy of ten different synacthen preparation strategies used for the LDT.MethodsMembers of six international endocrine societies were surveyed regarding diagnostic tests used for adrenal insufficiency, and in particular the SST. Synacthen was diluted for the LDT and concentrations measured using a synacthen ELISA.ResultsSurvey responses were received from 766 individuals across 60 countries (52% adult, 45% paediatric endocrinologists). The SST is used by 98% of centres: 92% using high-dose (250 μg), 43% low-dose, and 37% both. Ten low-dose dilution methods were assessed and variation in synacthen concentration was demonstrated with intra-method coefficients of variation (CV) ranging from 2.1% to 109%. The method using 5% dextrose as a diluent was the least variable (CV of 2.1%). The variation in dilution methods means that the dose of synacthen administered in a LDT may vary between 0.16 μg and 0.81 μg.ConclusionsThe high-dose SST is the most popular diagnostic test of adrenal insufficiency but up to 72% of paediatric endocrinologists use a LDT. There is considerable variation observed both within and between low-dose synacthen dilution methods creating considerable risk of inaccurate dosing and thereby invalid results.

Background:Left hand and wrist X-rays are conventionally used to assess skeletal maturity using methods such as Tanner-Whitehouse 3 (TW3). We noted a number were poor quality, caused by difficulty with hand placement. We introduced a simple radiolucent hand template to assist in hand positioning and assessed changes in X-ray quality and repeat X-ray rates.Methods:The position of fingers, thumb and overall clarity of bone age X-rays were prospectively scored. In the absence of a validated tool to assess quality a 1–3 scale (poor, borderline, good) was devised. A radiolucent hand template was introduced for use in the intervention group. Need for repeat X-ray was determined by set criteria.Results:The intervention improved scores. More patients scored 3 (good) for positioning of fingers (89.29% and 85.33%, p=0.38), thumb (98.21% and 89.96%, p=0.06) and overall clarity (76.79% and 70.27%, p=0.41) for the intervention (n=56) and control groups (n=259), respectively. No patient required repeat X-ray from the intervention group, compared with 28 in the control group (p=0.007).Conclusions:Achieving good quality bone age X-rays is more difficult than previously assumed. The use of a radiolucent hand template has been shown to improve hand position and significantly reduce the need for repeat X-ray.

Background Self‐rated health ( SRH ) is a strong predictor of mortality in different populations. However, the associations between SRH measures and risk of ischemic heart disease ( IHD ) have not been extensively explored, especially in a Chinese population. Methods and Results More than 500 000 adults from 10 cities in China were followed from baseline (2004–2008) through December 31, 2013. Global and age‐comparative SRH were reported from baseline questionnaires. Incident IHD cases were identified through links to well‐established disease registry systems and the national health insurance system. During 3 423 542 person‐years of follow‐up, we identified 24 705 incident cases of IHD . In multivariable‐adjusted models, both global and age‐comparative SRH was significantly associated with incident IHD . Compared with excellent SRH , the hazard ratios for good, fair, and poor SRH were 1.02 (95% confidence interval [CI], 0.98–1.07), 1.32 (95% CI, 1.27–1.37), and 1.76 (95% CI, 1.68–1.85), respectively. Compared with better age‐comparative SRH , the hazard ratios for same and worse age‐comparative SRH were 1.23 (95% CI, 1.19–1.27) and 1.78 (95% CI, 1.70–1.86), respectively. The associations persisted in all subgroup analyses, although they were slightly modified by study location, education, and income levels. Conclusions A simple questionnaire for self‐assessment of health status was significantly associated with incident IHD in Chinese adults. Individuals and healthcare providers can use SRH measures as a convenient tool for assessing future IHD risk.

Context Salivary cortisone reflects serum cortisol levels, is more sensitive than salivary cortisol at lower values of serum cortisol and is non-invasive. Objective To investigate the relationship between serum cortisol and salivary cortisol and cortisone following low and high-dose synacthen. Design and Setting Prospective pharmacodynamic studies in clinical research facilities. Participants and Intervention 35 dexamethasone-suppressed, healthy adult males underwent an intravenous synacthen test: N=23 low-dose (1mcg), N=12 high-dose (250mcg). Paired serum and salivary samples were taken at 15 sampling points over 120 minutes. Main outcome measure Serum cortisol and salivary cortisol and cortisone were analyzed for correlations and by a mixed effects model. Results At baseline the correlation between serum cortisol and salivary cortisol was weak with many samples undetectable (r=0.45, NS), but there was a strong correlation with salivary cortisone (r=0.94, p

BACKGROUND Female chronic pelvic pain (CPP) is defined as intermittent or constant pelvic or lower abdominal pain occurring in a woman for at least 6 months. Up to a quarter of women are estimated to be affected by CPP worldwide and it is responsible for one fifth of specialist gynecological referrals in the United Kingdom. Psychological interventions are commonly utilized. As waiting times and funding capacity impede access to face-to-face consultations, supported self-management (SSM) has emerged as a viable alternative. Mindfulness meditation is a potentially valuable SSM tool, and in the era of mobile technology, this can be delivered to the individual user via a smartphone app. OBJECTIVE To assess the feasibility of conducting a trial of a mindfulness meditation intervention delivered by a mobile phone app for patients with CPP. The main feasibility objectives were to assess patient recruitment and app adherence, to obtain information to be used in the sample size estimate of a future trial, and to receive feedback on usability of the app. METHODS Mindfulness Meditation for Women With Chronic Pelvic Pain (MEMPHIS) is a three-arm feasibility trial, that took place in two hospitals in the United Kingdom. Eligible participants were randomized in a 1:1:1 ratio to one of three treatment arms: (1) the intervention arm, consisting of a guided, spoken mindfulness meditation app; (2) an active control arm, consisting of a progressive muscle relaxation app; and (3) usual care (no app). Participants were followed-up for 6 months. Key feasibility outcomes included the time taken to recruit all patients for the study, adherence, and estimates to be used in the sample size calculation for a subsequent full-scale trial. Upon completion of the feasibility trial we will conduct focus groups to explore app usability and reasons for noncompliance. RESULTS Recruitment for MEMPHIS took place between May 2016 and September 2016. The study was closed March 2017 and the report was submitted to the NIHR on October 26, 2017. CONCLUSIONS This feasibility trial will inform the design of a large multicentered trial to assess the clinical effectiveness of mindfulness meditation delivered via a smartphone app for the treatment of CPP. CLINICALTRIAL ClinicalTrials.gov: NCT02721108; https://clinicaltrials.gov/ct2/show/NCT02721108 (Archived by WebCite at http://www.webcitation.org/6wLMAkuaU); BioMed Central: ISRCTN10925965; https://www.isrctn.com/ISRCTN10925965 (Archived by WebCite at http://www.webcitation.org/6wLMVLuys)