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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.

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.

Despite universal vaccination of newborns, the prevalence of chronic hepatitis virus B (HBV) infection and the associated disease burden remain high among adults in China. We investigated risk factors for chronic HBV infection in a community-based study of 512,726 individuals aged 30–79 years recruited from ten diverse areas during 2004–2008. Multivariable logistic regression was used to estimate odds ratios (ORs) of hepatitis B surface antigen (HBsAg) positivity recorded at baseline by sociodemographic and lifestyle factors, and medical history. In a random subset (n = 69,898) we further assessed the association of 18 single nucleotide polymorphisms (SNPs) previously shown to be associated with HBsAg positivity and development of chronic liver disease (CLD) (1600 cases). Several factors showed strong associations with HBsAg positivity, particularly younger age (HLA-DPB1 were most strongly associated with both outcomes. In Chinese adults a range of genetic and non-genetic factors were associated with chronic HBV infection and CLD, which can inform targeted screening to help prevent disease progression.

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.

Summary Background Stroke is a leading cause of death and disability worldwide. Despite considerable improvements in diagnosis and treatment, little is known about the short-term and long-term prognosis after a first stroke in low-income and middle-income countries, including China. We aimed to assess the short-term and long-term risk of recurrent stroke and mortality after a first stroke for each of the major pathological stroke types. Methods This population-based cohort study included adults aged 35–74 years without disability who were recruited to the China Kadoorie Biobank (CKB). A baseline survey was conducted in ten geographical areas (five urban, five rural) in China, and participants had clinical measurements recorded. Participants were followed up by monitoring death registries and by electronic linkage to health registries and health insurance claims databases, with follow-up until Jan 1, 2017. Participants were excluded from analyses if they had a previous history of stroke, transient ischaemic attack, or ischaemic heart disease at baseline. All incidences of fatal and non-fatal stroke during the study period were recorded by type (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and unspecified type). Primary outcome measures were 28-day mortality, recurrent stroke, major vascular events (recurrent stroke, myocardial infarction, or vascular death), vascular mortality, and all-cause mortality. Findings Of 512 715 individuals in the CKB, 489 586 participants without previous ischaemic heart disease and stroke at recruitment were included, of whom 45 732 (42 073 [92%] confirmed by brain imaging) had a stroke during the study period. The mean age was 59·3 years (SD 9·8) for participants who had a stroke (54% women) and 50·8 years (10·3) for participants with no stroke (60% women). 36 588 (80%) of the incident cases of stroke were ischaemic stroke, 7440 (16%) were intracerebral haemorrhage, 702 (2%) were subarachnoid haemorrhage, and 1002 (2%) were an unspecified stroke type. 28-day mortality was 3% (95% CI 3–4) for ischaemic stroke, 47% (46–48)for intracerebral haemorrhage, 19% (17–22; 52% for rural areas and 32% for urban areas) subarachnoid haemorrhage, and 24% (22–27) for unspecified stroke. Among participants who survived stroke at 28 days, 41% (41–42) had recurrent stroke at 5 years (ischaemic stroke 41% [41–42], intracerebral haemorrhage 44% [42–46], subarachnoid haemorrhage 22% [18–27], unspecified stroke type 40% [35–44]) and mortality at 5 years was 17% ([17–18] ischaemic stroke 16% [15–16], intracerebral haemorrhage 28% [26–29], subarachnoid haemorrhage 16% [12–20], unspecified stroke type 15% [12–19]). After a first ischaemic stroke, 91% of recurrent strokes were also ischaemic stroke; after an intracerebral haemorrhage, 56% of recurrent strokes were intracerebral haemorrhage, and 41% of recurrent strokes were ischaemic stroke. Interpretation After a first stroke, the risk of recurrence or death within 5 years was high among this population of Chinese adults. Urgent improvements to secondary prevention of stroke in China are needed to reduce these risks. Funding Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, National Natural Science Foundation of China. Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background: Cooking practice has transitioned from use of solid fuels to use of clean fuels, with addition of better ventilation facilities. However, the change in mortality risk associated with such a transition remains unclear. Methods: The China Kadoorie Biobank (CKB) Study enrolled participants (aged 30–79 years) from ten areas across China; we chose to study participants from five urban areas where transition from use of solid fuels to clean fuels for cooking was prevalent. Participants who reported regular cooking (weekly or more frequently) at baseline were categorised as persistent clean fuel users, previous solid fuel users, or persistent solid fuel users, according to self-reported fuel use histories. All-cause and cardiopulmonary mortality were identified through linkage to China's Disease Surveillance Point system and local mortality records. Findings: Between June 24, 2004, and July 15, 2008, 226 186 participants living in five urban areas of China were enrolled in the CKB Study. Among 171 677 participants who reported cooking regularly (weekly or more frequently), 75 785 (44%) were persistent clean fuel users, 80 511 (47%) were previous solid fuel users, and 15 381 (9%) were persistent solid fuel users. During a mean of 9·8 (SD 1·7) years of follow-up, 10 831 deaths were documented, including 3819 cardiovascular deaths and 761 respiratory deaths. Compared with persistent clean fuel users, persistent solid fuel users had significantly higher risks of all-cause mortality (hazard ratio [HR] 1·19, 95% CI 1·10–1·28), cardiovascular mortality (1·24, 1·10–1·39), and respiratory mortality (1·43, 1·10–1·85). The excess risk of all-cause and cardiopulmonary mortality fell by more than 60% in 5 years after cessation of solid fuel use and continued to decrease afterwards. Use of ventilation was associated with lower all-cause mortality risk, even among persistent clean fuel users (HR 0·78, 0·69–0·89). Interpretation: Solid fuel use for cooking is associated with a higher risk of mortality, and cessation of solid fuel use cuts excess mortality risks swiftly and substantially within 5 years. Ventilation use also lowers the risk of mortality, even among people who persistently use clean fuels. It is of prime importance for both policy makers and the public to accelerate the transition from solid fuels to clean fuels and promote efficient ventilation to minimise further adverse health effects.

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.

Background Health-related quality of life (HRQOL) may improve as an additional benefit of the growth hormone treatment (GHT) in children with short stature, but this effect has not been conclusively proven. Objectives To explore the direct effect of GHT on HRQOL in children starting GHT due to isolated or multiple GH deficiency (IGHD), acquired GH deficiency (AGHD) and Turner syndrome (TS), in comparison with untreated short stature controls in 18 UK centres. Methods We used recognized measures of HRQOL, the PedsQL, the Strengths and Difficulties Questionnaire and Youth Life Optimism Test scales to investigate the effect of GHT at 0, 6 and 12 months in children and adolescents 6-16 years with IGHD (n = 73) and AGHD (n = 45), and 22 girls with TS. 49 children with non-GHD short stature served as the controls. Results Children rated their HRQOL better than their parents. Those with IGHD and TS rated their overall HRQOL lower than the controls at baseline, psychosocial scores significantly lower in IGHD. After 12 months, the control and TS groups scored higher than UK norms. Those with AGHD had lowest HRQOL scores at all time points, due to poorer physical functioning. The controls showed the greatest improvement in the strength and difficulties scale. All measures evaluated, whether from child, parent or teacher showed an equal improvement over the year of GHT with no discernible direct treatment effect, despite reduced numbers in some patient groups. Conclusions Children with short stature resulting from GHD have lower functioning than controls but HRQOL appears to improve with GHT, most likely on account of greater attention and as a result of the retest phenomenon. We were not able to demonstrate an absolute and independent effect of GHT in itself. HRQOL should not be used as a primary measure, as in adults, to determine whether children should receive GHT.

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.

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.

We write to report on the Association of Children’s Diabetes Clinicians’ (ACDC) national survey on access to continuous glucose monitoring (CGM) and Freestyle Libre Flash Glucose Sensors (FGS) for children and young people (CYP) with type 1 diabetes (T1DM) in England and Wales. CGM and FGS allow continuous blood glucose monitoring for patients with T1DM, therefore reducing the need for finger-prick blood testing. CGM provides a continuous interstitial glucose reading, whereas FGS requires 8 hourly scans to provide data with no alarms. Funding pathways for such devices are complex. While there is clear guidance from The National Institute of Health and Care Excellence (NICE) with regards to whom CGM should be prescribed,1 access is determined locally by Clinical Commissioning Groups (CCGs). Some CCGs require individual funding applications (IFAs), whereas others have local policies on who should access devices. The recently published National Health Service (NHS) Long-Term Plan, advises that all individuals meeting published clinical criteria should be able to access FGS devices from April …

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.

Aim Adequate sick-day management at home can reduce the risk of progression to diabetic ketoacidosis and admission to hospital. The aim of this project was to review the management of diabetes during illness. Method The Association of Children's Diabetes Clinicians (ACDC) carried out a questionnaire survey of all paediatric diabetes units. In addition, parents of children with type 1 diabetes completed an online questionnaire. Results The survey of 127 units had a 73% response rate. Sick-day management guidelines were in place in 93%. All guidelines advised giving extra insulin during illness. In 67%, the extra dose was based on a fraction of total daily dose. 22% used units per kg body weight (U/kg). 21% used locally derived formulae to calculate extra dose of insulin. 3% of units advised only blood ketone monitoring. Although all units had an out-of-hours access policy for the families, 45% received advice from the general paediatric registrar. Only in 15%, the advice was directly from a member of the paediatric diabetes team. 680 parents completed the questionnaire. 86% reported receiving training on managing sick days. The majority (52.2%) receiving an informal session at diagnosis. 40% did not know what to do in the presence of raised blood glucose and high blood ketones. Conclusions There was a wide variation in the practice of monitoring and advice given during illness. Both surveys highlight need for national guidance as well and to improve quality of sick-day rule education programmes for parents of children with type 1 diabetes.

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: Cluster randomised trials (CRTs) are commonly analysed using mixed-effects models or generalised estimating equations (GEEs). However, these analyses do not always perform well with the small number of clusters typical of most CRTs. They can lead to increased risk of a type I error (finding a statistically significant treatment effect when it does not exist) if appropriate corrections are not used.\ud \ud Methods: We conducted a small simulation study to evaluate the impact of using small-sample corrections for mixed-effects models or GEEs in CRTs with a small number of clusters. We then reanalysed data from TRIGGER, a CRT with six clusters, to determine the effect of using an inappropriate analysis method in practice. Finally, we reviewed 100 CRTs previously identified by a search on PubMed in order to assess whether trials were using appropriate methods of analysis. Trials were classified as at risk of an increased type I error rate if they did not report using an analysis method which accounted for clustering, or if they had fewer than 40 clusters and performed an individual-level analysis without reporting the use of an appropriate small-sample correction.\ud \ud Results: Our simulation study found that using mixed-effects models or GEEs without an appropriate correction led to inflated type I error rates, even for as many as 70 clusters. Conversely, using small-sample corrections provided correct type I error rates across all scenarios. Reanalysis of the TRIGGER trial found that inappropriate methods of analysis gave much smaller P values (P ≤ 0.01) than appropriate methods (P = 0.04–0.15). In our review, of the 99 trials that reported the number of clusters, 64 (65 %) were at risk of an increased type I error rate; 14 trials did not report using an analysis method which accounted for clustering, and 50 trials with fewer than 40 clusters performed an individual-level analysis without reporting the use of an appropriate correction.\ud \ud Conclusions: CRTs with a small or medium number of clusters are at risk of an inflated type I error rate unless appropriate analysis methods are used. Investigators should consider using small-sample corrections with mixed-effects models or GEEs to ensure valid results.\ud \ud Abbreviations: CRT, Cluster randomised trial; CI, Confidence interval; GEE, Generalised estimating equations; TRIGGER, Trial in Gastrointestinal Transfusion

BackgroundMany infants born prematurely experience growth failure following delivery, with subsequent catch-up growth. Traditionally catch-up was thought to be complete in the first few years of life. Most studies have focused on groups of infants defined by birth weight, for example MethodologyThis UK based prospective longitudinal cohort study recruited 204 preterm children born at a tertiary neonatal unit during 1994 and 50 matched controls. Growth parameters have been assessed annually until the completion of growth.ResultsThere was no significant difference in the final height SD score (SDS) of children born at term (n=30) and those born prematurely and AGA (n=70) (0.45 term vs 0.22 preterm). Catch-up growth however, continued throughout the whole of childhood. When the difference between final height SDS and mid-parental height SDS were compared, there were again no significant differences (0.13 term vs 0.03 preterm).ConclusionsThose born prematurely with an AGA achieve a comparable adult height to children born at term, however, catch-up growth continues for much longer than traditionally thought.

BackgroundSupported by meta-analyses, the low-dose Synacthen test (LDST) has gained in popularity, with many believing it to be more sensitive than the supraphysiological standard (250 µg) short ST (SSST), particularly when assessing children prescribed high-dose inhaled corticosteroids (HDICS). However, consensus is lacking about its specific clinical application, what is considered ‘low dose’ and how that dose is made up.MethodsTo ascertain current use of the short Synacthen test (SST), a questionnaire was emailed to members of the British Society of Paediatric Endocrinology and Diabetes in the UK and Ireland (N=257), requesting a response from each department (N=92). A reminder was sent a month later to members of departments which had not responded.ResultsThe authors received 39 replies, giving a response rate of 42%. All departments use the SST: 82% use an LDST, 87% use the SSST and 69% use both. The 1 µg dose was used by 44% of hospitals, with the other 56% using seven different doses based on age, weight and body surface area. There were 14 different methods of preparing the low dose test. Additionally, variations in the timings of cortisol sampling and the diagnostic cut-offs for adrenal insufficiency were found. Increased requests for SSTs in children with asthma prescribed HDICS were noted by 44% of respondents, with 67% reporting the detection of adrenal suppression in this group.ConclusionStandardisation of the SST is required to address the considerable variation in the methodology and application of this test in the UK and Ireland.

A qualitative study nested within a randomized controlled trial explored obese adolescents' experiences of participation in an exercise therapy intervention. Semi-structured interviews were conducted with participants assigned to exercise therapy. Participants' reported feeling more energetic during and after exercise, than before. Many participants reported feeling happy/happier and expressed feeling better about themselves as individuals after the intervention. Most participants felt more confident in their ability to exercise regularly. Greater emphasis needs to be placed upon educating obese adolescents about the wide range of health benefits that exercise can provide, and that weight loss, while important, is only one such benefit.

OBJECTIVE. We conducted a proof-of-concept, randomized, controlled trial to investigate the effects of a supervised exercise therapy intervention on psychopathologic outcomes in obese adolescents. METHODS. The participant sample consisted of 81 adolescents (age: 11–16 years) who had been referred to a children's hospital for evaluation of obesity or who responded to a community advertisement. Participants were assigned randomly to exercise therapy, an equal-contact exercise placebo intervention, or usual care. Intervention participants attended 3 one-on-one sessions per week for 8 weeks and then completed a home program for another 6 weeks. Outcomes included self-perceptions (self-esteem), depression, affect, physical activity, aerobic fitness, and BMI. RESULTS. A total of 18 of 81 participants were categorized as morbidly obese (BMI SD score: >3.5; adult equivalent BMI: ≥40). At baseline, 30.3% of participants had a Children's Depression Inventory score of ≥13, and 27% reported recent suicidal ideation. Repeated-measures mixed analysis of covariance (controlling for baseline scores) revealed significant changes in physical self-worth, associated measures of self-esteem, and physical activity over time, consistently favoring exercise therapy. There were no significant changes in BMI. CONCLUSIONS. Findings confirmed psychopathologic conditions as a serious health concern in obese and morbidly obese adolescents. Our study is the first randomized, controlled trial to demonstrate that a brief supervised exercise therapy intervention has the potential to improve psychopathologic outcomes significantly and to increase physical activity in obese adolescents, relative to usual care.

Background/Aims: The effects of growth hormone deficiency (GHD) on linear growth in children are well documented, but there is less convincing evidence regarding the impact on health-related quality of life (QOL). We examined QOL in children aged 8–16 years with acquired GHD following treatment for malignancy (AGHD) or idiopathic GHD (IGHD) on commencing growth hormone treatment (GHT) over 6 months. We adopted a longitudinal design involving consecutive patients and their families attending clinic over an 18-month period. Mothers and children were invited to complete questionnaires before GHT (T1) and 6 months later (T2). Methods: Mothers of 22 children (AGHD n = 14; IGHD n = 8) completed standardized measures of child QOL and behaviour. Children completed parallel measures of QOL, short-term memory tasks and fitness either in clinic or at the family home. Results: For children with AGHD, QOL was significantly below population norms at T1 and improved over time. For children diagnosed with IGHD, QOL at T1 was below, but comparable with population norms. QOL improved over time, though not significantly. Conclusion: GHT is potentially valuable for improving QOL in children, especially in cases of AGHD. We conclude that benefits of GHT for QOL need to be evaluated independent of different diagnostic groups.

Measurement of newborn babies is widely regarded as being too inaccurate to justify its regular practice. It is common for infants to be weighed at birth and for no other measurements to be made. Although such assumptions are superficially correct, it is possible to train people to perform accurate measurements and for improved performance to be sustained. Accurate sequential measurements are possible and provide more information than single measurements. Detailed measurements show that postnatal growth may change rapidly and dramatically, particularly in preterm infants. Postnatal growth impairment is common in such infants and may be sustained. Limited evidence suggests that there may be a significant reduction in final stature. Preliminary data also suggest that many preterm infants may also show evidence of alterations in biochemical and physiological variables consistent with early programming and the potential for altered disease susceptibility in adult life.

Background. With the development of pharmacological treatments for Alzheimer's disease there will be an increase in the numbers of patients requiring assessment from specialist services. Could the role of the specialist clinician be supported by other health professionals screening those who might benefit from treatment? Method. Sixty-four consecutive referrals to the Leicester University Memory Clinic were assessed at home by a community psychiatric nurse using a semi-structured interview. The nurse then reported her findings to a psychiatrist and a diagnosis was agreed. This diagnosis was then compared to the Memory Clinic diagnosis and a standardized (ICD-10) diagnosis recorded by another psychiatrist examining the clinic records. Results. The nurse assessment procedure performed well in detecting dementia, with a kappa statistic (κ) of 0·75 when compared to the standardized and Memory Clinic diagnoses. There was, however, only moderate concordance between the ICD-10 diagnosis and nurse (κ=0·46) and the Memory Clinic and nurse (κ=0·60) for Alzheimer's disease. The relatively low κ value for Alzheimer's disease was principally a result of difficult in differentiating vascular dementia. Conclusions. A single supervised community psychiatric nurse, using a structured assessment instrument, can adequately detect early dementia in a sample of patients referred with memory problems. Subtypes of dementia are not, however, accurately differentiated. © 1998 John Wiley & Sons, Ltd.

Varicose veins are a common condition. Presentations can range from those that are noticed incidentally to those causing significant symptoms. Management options range from conservative to surgical approaches, with many alternatives available that offer different advantages, disadvantages and long term outcomes.To describe the natural history, assessment and management of varicose veins.Surgical or other intervention is only necessary in a small percentage of patients, and is seldom urgent, perhaps only in the setting of progressive thrombophlebitis. Duplex ultrasound has become an essential modality for diagnosis, treatment and follow up. All the current modalities of endoluminal and open surgical treatment have similar short term outcomes and risks. Appropriate surgical treatment has the best long term outcomes and evidence base. Treatment of choice, however, depends on many factors, including local expertise.

Childhood overweight and obesity are increasingly common management problems for clinicians. This review focuses on the pharmacological management of obesity in children. It considers historical treatments, the options currently available (principally orlistat and metformin) and some potential future therapeutic interventions. The short term psychological effect of obesity and longer term health impact are discussed. The clinical settings in which drug treatment may be appropriate, the importance of lifestyle interventions, and the evidence and clinical guidance that underpin their use are discussed.

Context: Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduces the risk for T2D in adult obese nondiabetic patients, but the evidence in obese children and young people is inconclusive. Objective: The objective of the study was to assess the effect of metformin on body mass index sd score (BMI-SDS), metabolic risk factors, and adipokines. Design: This was a prospective, randomized, double-blind, placebo-controlled trial. Setting: The study was conducted at six pediatric endocrine centers in the United Kingdom. Participants: One hundred fifty-one obese children and young people with hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance (metformin: 74, placebo: 77). The study was comprised of 67.5% females, 65.6% postpubertal individuals, and 23.8% British Asian or Afro-Caribbean participants. The age range was 8–18 yr, the mean age was 13.7 (sd 2.3) yr, and the mean BMI-SDS was +3.4 (sd 0.5). Interventions: The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months. Main Outcome Measure: The main outcome measure was a reduction in BMI-SDS at 6 months. Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests, alanine aminotransferase (ALT), and adiponectin to leptin ratio (ALR) at 3 and 6 months. Results: Metformin was associated with a significant reduction in BMI-SDS compared with placebo at 6 months [mean difference −0.1 sd (95% confidence interval −0.18 to −0.02), P = 0.02]. Significant improvements at 3 months were found in the metformin group: fasting glucose, −0.16 mmol/liter (−0.31 to −0.00), P = 0.047; ALT, 19% (5–36%), P = 0.008; and ALR, 32% (4–67%), P = 0.02. Conclusions: Metformin therapy has a beneficial treatment effect over placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with changes in BMI-SDS sustained at 6 months.

What you need to know Thyroid function tests are often requested when investigating obese or overweight children. Slightly raised thyrotropin (TSH) with normal free thyroxine—subclinical hypothyroidism (hyperthyrotropinaemia)—is a common finding. An isolated raised thyrotropin is best described as hyperthyrotropinaemia rather than subclinical hypothyroidism and by definition excludes people with clinical symptoms, positive thyroid antibodies, goitre, or associated thyroidal illness.1 2 The adult consensus guideline defines it as a thyrotropin value between the upper limit of the local normal range and 10 mIU/L.1 Paediatric reviews have adopted a similar definition and thresholds.3 Reference ranges vary with the laboratory but are typically 0.45-4.5 mIU/L.1 In paediatric practice, as in adults, thyrotropin >10 mIU/L is potentially indicative of overt hypothyroidism.4 An isolated increase in thyrotropin is more common in overweight children, with a reported prevalence of 7-23% in obese children compared with only 2% in normal weight children.4 5 Thus it is unclear whether raised thyrotropin is a cause or consequence of obesity and whether thyroxine should be used to help manage these children’s weight. To ascertain the association between obesity and hyperthyrotropinaemia in children, we searched the Medline, Embase, and Cochrane databases until February 2015 …

Summary Context Increasing numbers of very low birth weight (VLBW) infants are surviving into adulthood because of improvements in neonatal intensive care. Adverse events in early life can have long-term effects through reprogramming of metabolic systems. Objective To determine whether young adult VLBW survivors have abnormalities of skeletal development or endocrine function. Design Cross-sectional, observational, case-control study. Participants Thirty-seven VLBW subjects and 27 healthy controls at peak bone mass (mean age 23). Measurements Differences between cases and controls in body size, body composition, bone mass and bone geometry [assessed by dual-energy X-ray absorptiometry (DXA), hip structure analysis and peripheral quantitative computed tomography (pQCT)], bone turnover [urine N-terminal telopeptide of type I collagen (NTX), serum C-terminal telopeptide of type I collagen (CTX)], aminoterminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase), hormones (sex steroids, IGF-1, PTH and 25-OH vitamin D) and insulin sensitivity (HOMA-IR and oral glucose tolerance testing). Results VLBW subjects had lower bone density at the lumbar spine (5.7%) and femoral neck (8.6%), which persisted after correction for bone size by the estimation of volumetric density (bone mineral apparent density). Urine NTX was higher in VLBW subjects than in controls, but there were no significant differences in other bone turnover markers. VLBW survivors had lower insulin sensitivity (mean INS-30 controls = 57.0, VLBW subjects = 94.3, P

We prospectively studied 124 consecutive hypoglycaemia screens performed on children attending our emergency department over a 27-month period (March 2006 to May 2008). In keeping with most other paediatric services in the UK, we routinely collect a number of samples to permit investigation of low blood sugar, including metabolic investigations, and a random cortisol and growth hormone. Most of these patients have an intercurrent illness and are subsequently thought to have had an episode of “physiological hypoglycaemia”. There is a paucity of published data examining how cortisol and growth hormone respond to hypoglycaemia and no previous work looking at …

Background: There are few data in the paediatric literature on the normal cortisol response to stimulation during the low dose synacthen test (LDST) (1 μg). Aim: To examine the cortisol responses in children, subsequently presumed to be normal, who had an LDST during anterior pituitary function tests (APFTs). Methods: A retrospective review of results in children with short stature and normal growth hormone levels. Results: Of 33 children tested, seven had suboptimal cortisol responses based on accepted criteria (peak

Personality status is seldom assessed in community mental health teams except at a rudimentary level. This study challenges the assumption that this policy is either prudent or wise. To measure the prevalence of personality disorder within community mental health teams and to investigate its relationship to mental state disorders and overall pathology. A cross-sectional survey of 2,528 of 2,567 psychiatric patients (98.5%) managed by community mental health teams in four urban settings in the UK in which diagnoses of personality and mental state pathology were assessed separately. Of these, a sample of 400 was interviewed, with a 70.5% completion rate for more in depth information. In total, 40% of all patients in secondary care suffered from at least one personality disorder. Regression modelling showed personality pathology accounted for a greater degree of global psychopathology than psychosis, alcohol or drug dependence, but was associated with anxiety disorders. Comorbid personality pathology contributes greatly to overall psychopathology in secondary psychiatric care. It should be both recognised and managed.

Background: Phytosterolaemia (sitosterolaemia) is a rare autosomal recessive condition caused by mutations on the ABCG5 and ABCG8 gut transporter proteins. This leads to accumulation of plant-derived cholesterol-like molecules in blood and tissues.Case: We describe a family of Bangladesh origin, where three siblings (two males and one female) have homozygous mutations for phytosterolaemia, and exhibit short stature and adrenal failure with the female having ovarian failure.Findings: The index case (18-year-old female) and her sibling (16 years) have adrenal insufficiency with hyperpigmentation and raised levels of ACTH, at 367 and 690 ng/l respectively. The youngest child at 7 years has normal adrenal function. In addition, the index case has ovarian failure and sibling 2 has partial growth hormone deficiency.Conclusion: Although short stature is a recognised phenomenon, no previous association has been made between phytosterolaemia and other endocrine abnormalities. We postulate that the elevated plant sterol levels in phytosterolaemia may interfere with endocrine hormone synthesis; in particular, we present evidence that adrenal cholesterol metabolism may be preferentially affected, accounting for the adrenal insufficiency.

A 6-month-old girl was referred with breast and pubic hair development. Investigations excluded an adrenal or central cause for her precocity. Ovarian ultrasound scans showed bilaterally enlarged ovaries with both solid and cystic changes. A follow-up examination suggested progression of the precocity and in view of the young age of the child, and concerns regarding underlying malignancy, she underwent laparotomy. Histology showed no evidence of neoplasia but there was stromal oedema consistent with a diagnosis of massive ovarian oedema. This entity is poorly recognised in the paediatric literature as a cause of sexual precocity, and has never previously been described in such a young patient. This is an unusual cause of precocity in a young child and its recognition and management are reviewed.

A diploid/triploid karyotype is an uncommon but important cause of true hermaphroditism and ambiguous genitalia. Individuals have a recognisable phenotype and characteristic hydatidiform placental changes. We report a 46,XX/69,XXY chimeric hermaphrodite. This case highlights the typical features (large placenta, intrauterine growth retardation, asymmetric growth, cranio-facial anomalies, syndactyly and pigmentary dysplasia). It illustrates the importance of obtaining skin and gonadal karyotypes in the case of genital ambiguity, as the venous lymphocytic karyotype is usually diploid.

AIMS: To investigate whether treatment of coexisting asthma has any effect on the incidence of hypoglycaemia and on glycaemic control in children with type 1 diabetes. \ud \ud METHODS: An observational study of children attending the paediatric diabetes clinics of five hospitals in the North Trent Region. Information on the frequency of hypoglycaemia in the preceding three months, treatment for asthma, and the individual’s latest HbA1c, was recorded when they attended for review. \ud \ud RESULTS: Data were collected on 226 children, of whom 27 (12%) had treated asthma. Only 11/27 children with asthma were taking their prescribed inhaled steroids. All used ß agonists at least once a week. There was a reduction of 20% in the incidence of hypoglycaemia in the diabetic children with treated asthma. Of the children with diabetes and treated asthma, 52% reported an episode of hypoglycaemia in the previous three months compared to 72% of those with only diabetes. There was no difference in the proportion of children experiencing nocturnal or severe hypoglycaemia. Although not significant, those with asthma and diabetes also had better overall control (HbA1c 8.8%) compared to those with diabetes alone (HbA1c 9.3%). \ud \ud CONCLUSIONS: Diabetic children with treated asthma have significantly fewer episodes of hypoglycaemia and better glycaemic control compared to children with diabetes alone. This observation needs further investigation but raises an interesting question. Do the drugs used to treat asthma, in particular ß agonists, have the therapeutic potential to reduce hypoglycaemia and facilitate an improvement in glycaemic control? \ud