United Kingdom Cohort Research Articles

Differences in Pregnancy Metabolic Profiles and Their Determinants between White European and South Asian Women: Findings from the Born in Bradford Cohort.

There is widespread metabolic disruption in women upon becoming pregnant. South Asians (SA) compared to White Europeans (WE) have more fat mass and are more insulin-resistant at a given body mass index (BMI). Whether these are reflected in other gestational metabolomic differences is unclear. Our aim was to compare gestational metabolic profiles and their determinants between WE and SA women. We used data from a United Kingdom (UK) cohort to compare metabolic profiles and associations of maternal age, education, parity, height, BMI, tricep skinfold thickness, gestational diabetes (GD), pre-eclampsia, and gestational hypertension with 156 metabolic measurements in WE (n = 4072) and SA (n = 4702) women. Metabolic profiles, measured in fasting serum taken between 26–28 weeks gestation, were quantified by nuclear magnetic resonance. Distributions of most metabolic measures differed by ethnicity. WE women had higher levels of most lipoprotein subclasses, cholesterol, glycerides and phospholipids, monosaturated fatty acids, and creatinine but lower levels of glucose, linoleic acid, omega-6 and polyunsaturated fatty acids, and most amino acids. Higher BMI and having GD were associated with higher levels of several lipoprotein subclasses, triglycerides, and other metabolites, mostly with stronger associations in WEs. We have shown differences in gestational metabolic profiles between WE and SA women and demonstrated that associations of exposures with these metabolites differ by ethnicity.

Beta-lactam allergy in Chinese patients and factors predicting genuine allergy

IntroductionBeta-lactams (BL) are the most frequently reported drug allergy, but the vast majority of patients are found not to be genuinely allergic after evaluation. Few studies have investigated the clinical predictors of genuine BL allergy, and the prevalence in hospitalized Chinese patients is unknown. MethodsPatients admitted to a tertiary hospital in Hong Kong (HK) were analyzed to identify the prevalence and factors associated with the presence of BL allergy labels among hospitalized Chinese patients. A combined cohort of patients having completed allergy investigation for suspected BL allergies in the United Kingdom (UK) and HK were analyzed to identify predictors of genuine allergy. ResultsThe prevalence of BL allergy labels in hospitalized HK Chinese was 5%, which was associated with female gender and concomitant non-BL antibiotic allergy labels. The rate of genuine BL allergy patients referred for suspected allergies in the UK and HK cohort was only 14%. History of anaphylaxis and interval of less than a year since the index reaction were independent clinical predictors of genuine BL allergy. The negative predictive value of penicillin skin testing was 90%, confirming the need for drug provocation testing after negative skin testing. There was a high rate of confirmed piperacillin-tazobactam allergy. DiscussionThe estimated true prevalence of genuine BL allergy in hospitalized HK Chinese is around 0.5%. This high rate of BL mislabeling highlights the need for comprehensive allergy evaluation and screening. History of anaphylaxis and duration since the index reaction are important predictors of genuine allergy. Piperacillin-tazobactam allergy may pose a unique challenge in this population with a high prevalence of suspected allergies, surging antibiotic resistance, and lack of testing available.

Characterisation of the Serum Metabolic Signature of Cholangiocarcinoma in a United Kingdom Cohort

A distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers. Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures)and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics. The serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma. The serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies.

Multicentre validation of a clinical prognostic score integrating the systemic inflammatory response to the host for patients treated with curative-intent for colorectal liver metastases: The Liverpool score

BackgroundThis study aimed to create a new prognostic score integrating the systemic inflammatory response to predict survival in patients treated with curative intent for colorectal liver metastases (CLM). MethodsWe identified independent prognostic factors in patients who underwent liver surgery for CLM in a tertiary centre in the United Kingdom (UK) between 2010 and 2015. A pre- and a postoperative score (Liverpool score) were created by combining these factors to stratify patients into different risk groups. These new scores were validated in an international cohort of 219 patients from China and France. ResultsMultivariate cox regression analysis of the 364 patients of the UK cohort identified 6 preoperative and 1 postoperative prognostic factors for overall survival (OS): American society of anaesthesiologists (ASA) score, location and node status of the primary tumour, number and size of CLM, neutrophil-to-lymphocyte ratio (NLR) and resection margin. Both pre- and postoperative scores can be calculated with an online calculator at https://jscalc.io/calc/PXatrmjfrEFpYy2t. Using the pre-operative model on the UK cohort, median OS was 61.22 (50.23, not reached) months in the low-risk group (n = 162) and 30.36 (23.68, 35.95) months in the high-risk group (n = 162, p < 0.0001). The same difference was observed in the validation cohort. The Liverpool score outperformed previously published scoring system with a c-index of 0.619 pre-operatively and of 0.637 post-operatively. ConclusionWe developed a new prognostic score based on clinicopathologic characteristics including the site of the primary tumour location and on measurement of the systemic inflammatory response which could help to tailor patients’ management.

Associated factors that influenced persistence with basal analog insulin therapy among people with type 2 diabetes: An exploratory analysis from a UK real-world sample

AimReal-world effectiveness of insulin therapy is affected by poor treatment persistence, often occurring soon after initiation. An international cross-sectional survey of people with type 2 diabetes mellitus (T2DM) has been conducted to describe reasons for non-persistence with insulin therapy. MethodsResponders to an online survey in 7 countries were classified as continuers (no gap of ≥7days), interrupters (interrupted therapy for ≥7days within first 6 months, then restarted), and discontinuers (terminated therapy for ≥7days within first 6 months, no restart before survey). We present the results from the United Kingdom (UK) cohort. ResultsOf 942 global respondents, 131 were from the UK, having a mean age of 37years and a mean of 7years since first T2DM diagnosis. Reasons contributing to insulin continuation (n=50) were improved physical feeling (52.0%) and improved glycemic control (48.0%). Common reasons for interruption (n=50) or discontinuation (n=31), respectively were weight gain (50.0%, 48.4%) and hypoglycemia (38.0%, 25.8%). Most important reason for possible re-initiation for interrupters and discontinuers, respectively was persuasion by physician/healthcare professional (74.0%, 64.5%). ConclusionThe benefits of basal insulin therapy motivated continuers to persist with the treatment; experienced or anticipated side effects contributed to interruption and discontinuation.

Cross-sectional study of a United Kingdom cohort of neonatal vein of galen malformation.

ObjectiveDescribe the course and outcomes in a UK national cohort of neonates with vein of Galen malformation identified before 28 days of life.MethodsNeonates with angiographically confirmed vein of Galen malformation presenting to 1 of 2 UK treatment centers (2006–2016) were included; those surviving were invited to participate in neurocognitive assessment. Results in each domain were dichotomized into “good” and “poor” categories. Cross‐sectional and angiographic brain imaging studies were systematically interrogated. Logistic regression was used to explore potential outcome predictors.ResultsOf 85 children with neonatal vein of Galen malformation, 51 had survived. Thirty‐four participated in neurocognitive assessment. Outcomes were approximately evenly split between “good” and “poor” categories across all domains, namely, neurological status, general cognition, neuromotor skills, adaptive behavior, and emotional and behavioral development. Important predictors of poor cognitive outcome were initial Bicêtre score ≤ 12 and presence of brain injury, specifically white matter injury, on initial imaging; in multivariate analysis, only Bicêtre score ≤ 12 remained significant.InterpretationDespite modern supportive and endovascular treatment, more than one‐third of unselected newborns with vein of Galen malformation did not survive. Outcome was good in around half of survivors. The importance of white matter injury suggests that abnormalities of venous as well as arterial circulation are important in the pathophysiology of brain injury. Ann Neurol 2018;84:547–555

A multicentre development and evaluation of a dietetic referral score for nutritional risk in sick infants

Unrecognized nutritional issues may delay recovery in hospitalized infants. It has been proposed that nutritional risk screening should be performed at hospital admission, but few tools include infants. The aim of this study was to develop and test a tool to identify sick infants in need of dietetic input. Hospitalised infants were recruited from hospitals in the United Kingdom (UK), Greece and Iran. Weight, skinfold thickness and mid upper arm circumference (MUAC) were measured, with detailed dietetic assessment in the UK and Greece. Simple screening questions were used in the UK cohort to formulate a score (infant early nutrition warning score-iNEWS) which was then validated in the Greek and Iranian groups. After dietetic assessment, 20 (9.6%) UK and 22 (22%) Greek infants were rated as needing dietetic input. Underweight, poor weight gain/loss and reduced intake were all independent predictors of perceived need for dietetic input in stepwise multivariate regression analysis. The score based on these items (iNEWS), had 84% sensitivity, 91% specificity and 49% positive predictive value to predict need for dietetic input in the UK cohort. In the Greek cohort this was 86%, 78% and 53% respectively. In all three countries, infants with high iNEWS had significantly lower average skinfold thickness (between-1 and-1.8 SD, p<0.0001) and MUAC (between-1.8 and-2 SD, p<0.0001) than those at low risk. iNEWS, a simple nutritional risk tool, identifies most hospitalised infants who need dieteticinput. https://clinicaltrials.gov/ct2/show/NCT03323957.

One-year risks of stroke and mortality in patients with atrial fibrillation from different clinical settings: The Gulf SAFE registry and Darlington AF registry

BackgroundDifferences exist in oral anticoagulation (OAC) use between different populations with atrial fibrillation (AF), which may be associated with varying outcomes. PurposeWe aimed to provide patient level comparisons of two cohorts of patients with AF, from the United Kingdom (UK) and Middle East (ME). MethodsThe clinical characteristics, prescription of OAC, one-year risk of stroke and mortality were compared between individual patients with AF included into the Darlington AF registry (UK, n = 2258) and the Gulf SAFE (Survey of atrial fibrillation events) registry (ME, n = 1740). ResultsA high percentage of patients from the Darlington registry were candidates for OAC (i.e., CHA2DS2-VASc score ≥2 in males or ≥3 in females; 82.0% in Darlington and 57.1% in Gulf SAFE). OAC use was suboptimal (52.0% in Darlington vs 58.4% in Gulf SAFE).One-year rates of stroke and mortality were high in both populations, especially in those with CHA2DS2-VASc score ≥2 in males and ≥3 in females (Darlington vs. Gulf SAFE: 3.51% vs. 5.63 for stroke; 11.4% vs. 16.8% for mortality). On multivariate analyses, female sex and previous stroke were independently associated with stroke events; while elderly age, female sex, vascular disease and heart failure were independent risk factors for mortality (all p < 0.05). Patients from Gulf SAFE registry had higher risk of stroke (odds ratio, 2.18 [1.47–3.23]) and mortality (odds ratio, 1.67 [1.31–2.14]) compared with those from Darlington registry. The CHA2DS2-VASc score showed good discrimination in predicting one-year risk of stroke (area under curve, 0.71 [0.65–0.76] in non-anticoagulated patients) and mortality (area under curve, 0.70 [0.68–0.72]) in the whole study population, as well as in Darlington or Gulf SAFE registry separately. ConclusionsStroke prevention was generally suboptimal in patient cohorts from the two registries, which was associated with high one-year risks of stroke and mortality, particularly so among patients from the Gulf SAFE registry. The higher risks for stroke and mortality in AF patients from the Gulf SAFE registry (compared to a UK cohort) merit further implementation of cardiovascular prevention strategies.

Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis. Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. Weanalyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM). In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34-0.57; P<.001). In a multivariable analysis, BE with IM was associated with longersurvival independent of patient age or sex, tumor stage or location, and BE length (adjusted HR, 0.66; 95% CI, 0.5-0.88; P=.005). In the United Kingdom cohort, patients BE and IM had a reduced risk of death compared with those without (HR, 0.59; 95% CI, 0.5-0.69; P<.001), with continued significance in multivariable analysis that included patient age and sex and tumor stage and tumor location (adjusted HR, 0.77; 95% CI, 0.64-0.93; P=.006). Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis ofpatients.

Genome-Wide Association Study Identifies a Susceptibility Locus for Comitant Esotropia and Suggests a Parent-of-Origin Effect.

PurposeTo identify genetic variants conferring susceptibility to esotropia. Esotropia is the most common form of comitant strabismus, has its highest incidence in European ancestry populations, and is believed to be inherited as a complex trait.MethodsWhite European American discovery cohorts with nonaccommodative (826 cases and 2991 controls) or accommodative (224 cases and 749 controls) esotropia were investigated. White European Australian and United Kingdom cohorts with nonaccommodative (689 cases and 1448 controls) or accommodative (66 cases and 264 controls) esotropia were tested for replication. We performed a genome-wide case–control association study using a mixed linear additive model. Meta-analyses of discovery and replication cohorts were then conducted.ResultsA significant association with nonaccommodative esotropia was discovered (odds ratio [OR] = 1.41, P = 2.84 × 10−09) and replicated (OR = 1.23, P = 0.01) at rs2244352 [T] located within intron 1 of the WRB (tryptophan rich basic protein) gene on chromosome 21 (meta-analysis OR = 1.33, P = 9.58 × 10−11). This single nucleotide polymorphism (SNP) is differentially methylated, and there is a statistically significant skew toward paternal inheritance in the discovery cohort. Meta-analysis of the accommodative discovery and replication cohorts identified an association with rs912759 [T] (OR = 0.59, P = 1.89 × 10−08), an intergenic SNP on chromosome 1p31.1.ConclusionsThis is the first genome-wide association study (GWAS) to identify significant associations in esotropia and suggests a parent-of-origin effect. Additional cohorts will permit replication and extension of these findings. Future studies of rs2244352 and WRB should provide insight into pathophysiological mechanisms underlying comitant strabismus.

Visual outcomes after chemotherapy for optic pathway glioma in children with and without neurofibromatosis type 1: results of the International Society of Paediatric Oncology (SIOP) Low-Grade Glioma 2004 trial United Kingdom (UK) cohort

To report visual acuity (VA) outcomes following chemotherapy for optic pathway glioma (OPG) in children with or without neurofibromatosis type-1 (NF1) and to analyse associated risk factors.

One-Year Consumption of a Mediterranean-Like Dietary Pattern With Vitamin D3 Supplements Induced Small Scale but Extensive Changes of Immune Cell Phenotype, Co-receptor Expression and Innate Immune Responses in Healthy Elderly Subjects: Results From the United Kingdom Arm of the NU-AGE Trial.

Amongst the major features of aging are chronic low grade inflammation and a decline in immune function. The Mediterranean diet (MedDiet) is considered to be a valuable tool to improve health status, and although beneficial effects have been reported, to date, immunological outcomes have not been extensively studied. We aimed to test the hypothesis that 1 year of a tailored intervention based on the MedDiet with vitamin D (10 μg/day) would improve innate immune responses in healthy elderly subjects (65–79 years) from the English cohort (272 subjects recruited) of the NU-AGE randomized, controlled study (clinicaltrials.gov, NCT01754012). Of the 272 subjects forming the United Kingdom cohort a subgroup of 122 subjects (61 in the intervention group and 61 in the control group) was used to evaluate ex vivo innate immune response, phenotype of circulating immune cells, and levels of pro- and anti-inflammatory markers. Odds Ratio (OR) was calculated for all the parameters analyzed. After adjustment by gender, MedDiet-females with a BMI < 31 kg/m2 had a significant upregulation of circulating CD40+CD86+ cells (OR 3.44, 95% CI 1.01–11.75, P = 0.0437). Furthermore, in all MedDiet subjects, regardless of gender, we observed a MedDiet-dependent changes, although not statistically significant of immune-critical parameters including T cell degranulation, cytokine production and co-receptor expression. Overall, our study showed that adherence to an individually tailored Mediterranean-like dietary pattern with a daily low dose of vitamin D3 supplements for 1 year modified a large variety of parameters of immune function in healthy, elderly subjects. We interpreted these data as showing that the MedDiet in later life could improve aspects of innate immunity and thus it could aid the design of strategies to counteract age-associated disturbances.Clinical Trial Registration: clinicaltrials.gov, NCT01754012.

Comment on: Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis-findings from a United Kingdom cohort: reply.

Objectives. To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort. Methods. All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug. Results. Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (S.D.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (S.D.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05). Conclusion. We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

Comment on: Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis-findings from a United Kingdom cohort.

Objectives. To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort. Methods. All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug. Results. Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (S.D.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (S.D.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05). Conclusion. We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

Sex and area differences in the association between adiposity and lipid profile in Sub-Saharan Africa: A comparison with a European population

Introduction Sub-Saharan African (SSA) countries are facing a rising epidemic of non-communicable diseases (NCDs) alongside a persistent burden from undernutrition and infectious diseases. Mendelian randomization (using genetic variants as instrumental variables) and randomised controlled trial (RCT) evidence show that high levels of total (TC) and low-density lipoprotein-cholesterol (LDL-C) and of triglycerides (TG) are key causal risk factors for coronary heart diseases (CHD), that can be effectively modified to prevent CHD. Studies in high-income countries show that higher adiposity results in an adverse lipid profile, but whether this association is similar in SSA populations is unclear. One previous small study from Cameroon suggested higher adiposity increased dyslipidaemia in urban dwelling SSA populations but not in those in rural areas, but to our knowledge previous studies have not sought to replicate this. This study aimed to (i) assess the association between total and central adiposity measures and lipid profile in Malawi, exploring differences by sex and area of residence and (ii) compare the associations with observations from a predominantly white European-origin population cohort from the United Kingdom (UK). Methods Baseline data from the Malawi Epidemiology and Intervention Research Unit Non-Communicable Disease study (MEIRU NCD) were used. The study assessed adults in a rural (Karonga, Northern Malawi; n = 12,153) and an urban (area 25 of Lilongwe, the capital city; n= 12,869) of Malawi. The association of body mass index (BMI) and waist-hip ratio (WHR) with fasting lipids [TC, LDL-C, high density lipoprotein-cholesterol (HDL-C) and TG] was assessed by area and sex. Data from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) were used for the comparison with a population from a high-income European setting, and included 3286 adolescents (mean age 17.8), 4107 mothers (mean age 47.9), and 1933 fathers (mean age 53.3). Multiple linear regression was used to examine the association of both BMI and WHR with each lipid measure, adjusted initially for age and then for potential confounding by household assets, education, marital status, number of children, smoking, alcohol, physical activity, lipid-lowering medication, and HIV status. As the UK data were taken from largely urban/sub-urban dwelling adolescents and middle-aged females and males, we selected two age groups of participants from the urban group of the Malawi cohort that had similar age distributions to the UK cohorts to compare associations between Malawians and UK residents. Results We observed positive linear associations of BMI and WHR with TC, LDL-C and TG and inverse association with HDL-C. Associations between BMI/WHR and serum lipids were in general similar in females and males, however, differed by area, with the associations between BMI and all serum lipids being stronger in rural than urban females, except for HDL-C, which was stronger in urban females. Associations did not differ consistently between rural and urban male residents. Associations of BMI and WHR with lipids were mostly similar or weaker in Malawi than the UK urban residents in both sexes and age groups. However, in middle-aged males, there was some evidence that associations of BMI and WHR with TC and LDL-C were stronger in Malawians. Conclusions The consistent associations observed of higher adiposity with adverse lipid profiles in females and males living in rural and urban areas of Malawi highlight the emerging adverse cardio-metabolic epidemic in this poor population. The similarity (or even stronger) associations between the Malawian and UK population highlight the importance of early interventions to control the emerging obesity epidemic in SSA populations.

Prevalence and clinical challenges among adults with primary immunodeficiency and recombination-activating gene deficiency

Prevalence and clinical challenges among adults with primary immunodeficiency and recombination-activating gene deficiency

Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis-findings from a United Kingdom cohort.

To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort. All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug. Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (s.d.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (s.d.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05). We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

Adverse Childhood Experiences (ACEs) and Adiposity in Adolescents: A Cross-Cohort Comparison.

ObjectiveThis study aimed to assess the association between adverse childhood experiences (ACEs) and adiposity in adolescents from two cohorts in different socioeconomic contexts.MethodsData from the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom) and the 1993 Pelotas Cohort (Brazil) were used. Six ACEs were assessed in both cohorts up to age 15. At 15 years, body mass index (BMI) and waist circumference (WC) were measured, and at 18 years, BMI, fat mass index, and android fat percentage were assessed.ResultsFew associations were observed between ACEs and adiposity at 15 years, and they were not consistent across cohorts. For adiposity at age 15 in ALSPAC, physical abuse had a positive association with WC, and domestic violence had a positive association with both WC and BMI. A dose‐response relationship between the ACE score and both WC and BMI at 15 years was observed in ALSPAC. In the 1993 Pelotas Cohort, the associations found in crude analysis were no longer evident after adjustment.ConclusionsThis study found some evidence of an association between an ACE score and adiposity in adolescence in a United Kingdom cohort but no evidence of association in a Brazilian cohort. Residual confounding or context‐specific relationships could explain the different pattern of associations.

A multi-national comparison of antipsychotic drug use in children and adolescents, 2005\u20132012

Over the last decades, an increase in antipsychotic (AP) prescribing and a shift from first-generation antipsychotics (FGA) to second-generation antipsychotics (SGA) among youth have been reported. However, most AP prescriptions for youth are off-label, and there are worrying long-term safety data in youth. The objective of this study was to assess multinational trends in AP use among children and adolescents. A repeated cross-sectional design was applied to cohorts from varied sources from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006–2012. The annual prevalence of AP use was assessed, stratified by age group, sex and subclass (FGA/SGA). The prevalence of AP use increased from 0.78 to 1.03% in the Netherlands’ data, from 0.26 to 0.48% in the Danish cohort, from 0.23 to 0.32% in the German cohort, and from 0.1 to 0.14% in the UK cohort. In the US cohort, AP use decreased from 0.94 to 0.79%. In the US cohort, nearly all ATP dispensings were for SGA, while among the European cohorts the proportion of SGA dispensings grew to nearly 75% of all AP dispensings. With the exception of the Netherlands, AP use prevalence was highest in 15–19 year-olds. So, from 2005/6 to 2012, AP use prevalence increased in all youth cohorts from European countries and decreased in the US cohort. SGA were favoured in all countries’ cohorts.

Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients.

Von Hippel‐Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age‐related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age‐related risks for the five major VHL‐associated tumors were evaluated using Kaplan–Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age‐adjusted telomere length ≤ 0.44) suffered higher age‐related risks for VHL‐associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age‐related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL‐associated tumors.