Sinead Brophy

The bath ankylosing spondylitis radiology index (BASRI): A new, validated approach to disease assessment

OBJECTIVE To develop a reproducible and simple radiologic scoring system for the spine in patients with ankylosing spondylitis (AS): the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s). METHODS Radiographs of 470 patients with AS were scored using the New York criteria for the sacroiliac joints and, similarly, grading the lumbar and cervical spine on a scale of 0-4 (for normal, suspicious, mild, moderate, and severe). These 3 scores were added together to produce the BASRI-s score (scored 2-12). Radiographs of 188 patients were used to test reproducibility. Blinded radiographs of 89 non-AS patients were included, randomly, to assess disease specificity. Sensitivity to change was assessed using 177 radiographs from 58 AS patients. RESULTS Intra- and interobserver variation showed 75-86% and 73-79% complete agreement at all sites, respectively. Specificities of 0.83-0.89 suggested that the lumbar and cervical spine BASRI scores were disease specific. Sensitivity to change became apparent at 2 years (P < 0.001). Using a lateral view and an anteroposterior view of the lumbar spine was more sensitive than using a lateral view alone. Grading a set of radiographs (sacroiliac joints, lumbar spine, and cervical spine) took 30 seconds. CONCLUSION BASRI is a reliable method for grading radiographic changes in patients with AS. It is disease specific, sensitive to change, valid, simple, and rapid to perform.

Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis

OBJECTIVES It has long been suspected that susceptibility to ankylosing spondylitis (AS) is influenced by genes lying distant to the major histocompatibility complex. This study compares genetic models of AS to assess the most likely mode of inheritance, using recurrence risk ratios in relatives of affected subjects. METHODS Recurrence risk ratios in different degrees of relatives were determined using published data from studies specifically designed to address the question. The methods of Risch were used to determine the expected recurrence risk ratios in different degrees of relatives, assuming equal first degree relative recurrence risk between models. Goodness of fit was determined by χ2 comparison of the expected number of affected subjects with the observed number, given equal numbers of each type of relative studied. RESULTS The recurrence risks in different degrees of relatives were: monozygotic (MZ) twins 63% (17/27), first degree relatives 8.2% (441/5390), second degree relatives 1.0% (8/834), and third degree relatives 0.7% (7/997). Parent-child recurrence risk (7.9%, 37/466) was not significantly different from the sibling recurrence risk (8.2%, 404/4924), excluding a significant dominance genetic component to susceptibility. Poor fitting models included single gene, genetic heterogeneity, additive, two locus multiplicative, and one locus and residual polygenes (χ2 >32 (two degrees of freedom), p<10−6for all models). The best fitting model studied was a five locus model with multiplicative interaction between loci (χ2=1.4 (two degrees of freedom), p=0.5). Oligogenic multiplicative models were the best fitting over a range of population prevalences and first degree recurrence risk rates. CONCLUSIONS This study suggests that of the genetic models tested, the most likely model operating in AS is an oligogenic model with predominantly multiplicative interaction between loci.

Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype: Action LADA 7

OBJECTIVE Specific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non–insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes. RESEARCH DESIGN AND METHODS We consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30–70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A). RESULTS Of 6,156 patients, 541 (8.8%) had GADA and only 57 (0.9%) IA-2A or ZnT8A alone. More autoantibody-positive than autoantibody-negative patients were younger, leaner, on insulin (49.5 vs. 13.2%), and female (P < 0.0001 for each), though LADA patients (9.7% of total) did not show categorically distinct clinical features from autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (>200 World Health Organization IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P < 0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than type 1 autoimmune diabetes (odds ratio 3.3). CONCLUSIONS Adult-onset autoimmune diabetes emerges as a prevalent form of autoimmune diabetes. Our results indicate that adult-onset autoimmune diabetes in Europe encompasses type 1 diabetes and LADA in the same broad clinical and autoantibody-positive spectrum. At diagnosis, patients with adult-onset autoimmune diabetes are usually non–insulin requiring and clinically indistinguishable from patients with type 2 diabetes, though they tend to be younger and leaner. Only with screening for autoantibodies, especially GADA, can they be identified with certainty.

Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype Action LADA 7

OBJECTIVE Specific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non–insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes. RESEARCH DESIGN AND METHODS We consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30–70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A). RESULTS Of 6,156 patients, 541 (8.8%) had GADA and only 57 (0.9%) IA-2A or ZnT8A alone. More autoantibody-positive than autoantibody-negative patients were younger, leaner, on insulin (49.5 vs. 13.2%), and female (P < 0.0001 for each), though LADA patients (9.7% of total) did not show categorically distinct clinical features from autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (>200 World Health Organization IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P < 0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than type 1 autoimmune diabetes (odds ratio 3.3). CONCLUSIONS Adult-onset autoimmune diabetes emerges as a prevalent form of autoimmune diabetes. Our results indicate that adult-onset autoimmune diabetes in Europe encompasses type 1 diabetes and LADA in the same broad clinical and autoantibody-positive spectrum. At diagnosis, patients with adult-onset autoimmune diabetes are usually non–insulin requiring and clinically indistinguishable from patients with type 2 diabetes, though they tend to be younger and leaner. Only with screening for autoantibodies, especially GADA, can they be identified with certainty.

Risk factors for childhood obesity at age 5: Analysis of the Millennium Cohort Study

BackgroundWeight at age 5 is a predictor for future health of the individual. This study examines risk factors for childhood obesity with a focus on ethnicity.MethodsData from the Millennium Cohort study were used. 17,561 singleton children of White/European (n = 15,062), Asian (n = 1,845) or African (n = 654) background were selected. Logistic regression and likelihood ratio tests were used to examine factors associated with obesity at age 5. All participants were interviewed in their own homes. The main exposures examined included; Birth weight, sedentary lifestyle, family health behaviours, ethnicity, education and income.ResultsChildren with a sedentary lifestyle, large at birth, with high risk family health behaviours (overweight mothers, smoking near the child, missing breakfast) and from a family with low income or low educational attainment, were more likely to be obese regardless of ethnicity. Feeding solid food before 3 months was associated with obesity in higher income White/European families. Even when controlling for socioeconomic status, ethnic background is an important independent risk factor for childhood obesity [Odds ratio of obesity; was 1.7 (95%CI: 1.2-2.3) for Asian and 2.7 (95%CI: 1.9-3.9) for African children, compared to White/European]. The final adjusted model suggests that increasing income does not have a great impact on lowering obesity levels, but that higher academic qualifications are associated with lower obesity levels [Odds of obesity: 0.63 (95%CI: 0.52-0.77) if primary carer leaves school after age 16 compared at age 16].ConclusionsEducation of the primary carer is an important modifiable factor which can be targeted to address rising obesity levels in children. Interventions should be family centred supporting and showing people how they can implement lifestyle changes in their family.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Impact of sex on inheritance of ankylosing spondylitis: a cohort study.

Summary Background Ankylosing spondylitis is a genetically determined and commonly familial disorder. Men and women differ in their susceptibility to ankylosing spondylitis, with about 2·5 men affected for every woman with the disease. We investigated the influence of the sex of the index case on disease penetrance within families. Methods The ages at which 50% and 75% of patients were diagnosed with ankylosing spondylitis were ascertained from a database of 4400 cases. Index patients with children or siblings who were old enough to have obtained a diagnosis (50% and 75% rates) were assessed for prevalence of disease among relatives. Confirmation of diagnosis for affected relatives was sought for all offspring and a random 25% selection of siblings. Findings Ankylosing spondylitis was more prevalent among children (odds ratio 1·9 [95% CI 1·2–3·0], p Interpretation The influence of female sex is greater than that of male sex in determining increased susceptibility to ankylosing spondylitis in children. The striking maternal effect is greatest for women with young age at onset, which is not seen in men. The sex ratio of affected children depends on the sex of the affected parent.

No Increased Rate of Acute Myocardial Infarction or Stroke Among Patients with Ankylosing Spondylitis—A Retrospective Cohort Study Using Routine Data

OBJECTIVES To examine if people with ankylosing spondylitis (AS) are at higher risk of acute myocardial infarction (MI) or stroke compared to those without AS. METHODS Primary care records were linked with all hospital admissions and deaths caused by MI or stroke in Wales for the years 1999-2010. The linked data were then stratified by AS diagnosis and survival analysis was used to obtain the incidence rate of MI and separately cerebrovascular disease (CVD)/stroke. Cox regression was used to adjust for gender and age. Logistic regression was used to examine prevalence of diabetes, hypertension, or hyperlipidemia for those with AS compared to those without. RESULTS There were 1686 AS patients (75.9% male, average age 46.1 years) compared to 1,206,621 controls (48.9% male, average age 35.9 years). Age- and gender-adjusted hazard ratios for MI were 1.28 (95% CI: 0.93 to 1.74) P = 0.12, and for CVD/stroke 1.0 (95% CI: 0.73 to 1.39) P = 0.9, in AS compared to controls. The prevalence of diabetes and hypertension, but not hyperlipidemia/hypercholesterolemia, was higher in AS. CONCLUSIONS There is no increase in the MI or CVD/stroke rates in patients with AS compared to those without AS, despite higher rates of hypertension, which may be related to nonsteroidal anti-inflammatory drug use.

ROC Generated Thresholds for Field-Assessed Aerobic Fitness Related to Body Size and Cardiometabolic Risk in Schoolchildren

Objectives 1. to investigate whether 20 m multi-stage shuttle run performance (20mSRT), an indirect measure of aerobic fitness, could discriminate between healthy and overweight status in 9–10.9 yr old schoolchildren using Receiver Operating Characteristic (ROC) analysis; 2. Investigate if cardiometabolic risk differed by aerobic fitness group by applying the ROC cut point to a second, cross-sectional cohort. Design Analysis of cross-sectional data. Participants 16,619 9–10.9 year old participants from SportsLinx project and 300 11–13.9 year old participants from the Welsh Schools Health and Fitness Study. Outcome Measures SportsLinx; 20mSRT, body mass index (BMI), waist circumference, subscapular and superilliac skinfold thicknesses. Welsh Schools Health and Fitness Study; 20mSRT performance, waist circumference, and clustered cardiometabolic risk. Analyses Three ROC curve analyses were completed, each using 20mSRT performance with ROC curve 1 related to BMI, curve 2 was related to waist circumference and 3 was related to skinfolds (estimated % body fat). These were repeated for both girls and boys. The mean of the three aerobic fitness thresholds was retained for analysis. The thresholds were subsequently applied to clustered cardiometabolic risk data from the Welsh Schools study to assess whether risk differed by aerobic fitness group. Results The diagnostic accuracy of the ROC generated thresholds was higher than would be expected by chance (all models AUC >0.7). The mean thresholds were 33 and 25 shuttles for boys and girls respectively. Participants classified as ‘fit’ had significantly lower cardiometabolic risk scores in comparison to those classed as unfit (p<0.001). Conclusion The use of the ROC generated cut points by health professionals, teachers and coaches may provide the opportunity to apply population level ‘risk identification and stratification’ processes and plan for “at-risk” children to be referred onto intervention services.

Incidence of Campylobacter and Salmonella infections following first prescription for PPI– a cohort study using routine data.

OBJECTIVES:To examine the incidence of Campylobacter and Salmonella infection in patients prescribed proton pump inhibitors (PPIs) compared with controls.METHODS:Retrospective cohort study using anonymous general practitioner (GP) data. Anonymised individual-level records from the Secure Anonymised Information Linkage (SAIL) system between 1990 and 2010 in Wales were selected. Data were available from 1,913,925 individuals including 358,938 prescribed a PPI. The main outcome measures examined included incidence of Campylobacter or Salmonella infection following a prescription for PPI.RESULTS:The rate of Campylobacter and Salmonella infections was already at 3.1–6.9 times that of non-PPI patients even before PPI prescription. The PPI group had an increased hazard rate of infection (after prescription for PPI) of 1.46 for Campylobacter and 1.2 for Salmonella, compared with baseline. However, the non-PPI patients also had an increased hazard ratio with time. In fact, the ratio of events in the PPI group compared with the non-PPI group using the prior event rate ratio was 1.17 (95% CI 0.74–1.61) for Campylobacter and 1.00 (0.5–1.5) for Salmonella.CONCLUSIONS:People who go on to be prescribed PPIs have a greater underlying risk of gastrointestinal (GI) infection beforehand and they have a higher prevalence of risk factors before PPI prescription. The rate of diagnosis of infection is increasing with time regardless of PPI use, and there is no evidence that PPI is associated with an increase in diagnosed GI infection. It is likely that factors associated with the demographic profile of the patient are the main contributors to increased rate of GI infection for patients prescribed PPIs.