Andrew J Clegg

A case-control study of childhood environmental risk factors for the development of inflammatory bowel disease.

Objective To clarify the relationship between childhood environment and the risk of subsequent development of Crohns disease or ulcerative colitis. Design and outcome measures A case–control study, assessing the risk of inflammatory bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression. Setting District general hospital (secondary care institution). Participants Subjects with Crohns disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control. Results Helicobacter seroprevalence was substantially reduced in Crohns disease (OR 0.18; 95% CI, 0.06–0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38–2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01–0.51). Crohns disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23–6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21–6.91). There was no association between hepatitis A seroprevalence and either disease. Conclusion The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohns disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohns disease.

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation.

BACKGROUND Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. OBJECTIVE To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. SOURCES MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. METHODS Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. RESULTS We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). LIMITATIONS There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. CONCLUSIONS Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). FUNDING The National Institute for Health Research Health Technology Assessment programme.

Systematic Review and Meta-Analysis of Psychosocial Risk Factors for Stroke

Abstract Several studies have assessed the link between psychosocial risk factors and stroke; however, the results were inconsistent. We have conducted a systemic review and meta‐analysis of cohort or case‐control studies to ascertain the association between psychosocial risk factors (psychological, vocational, behavioral, interpersonal, and neuropsychological) and the risk of stroke. Systematic searches were undertaken in MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Database of Systematic Reviews between 2000 and January 2017. Two reviewers independently screened titles, abstracts, and full texts. One reviewer assessed quality and extracted data, which was checked by a second reviewer. For studies that reported risk estimates, a meta‐analysis was performed. We identified 41 cohort studies and 5 case‐control studies. No neuropsychological papers were found. Overall, pooled adjusted estimates showed that all other psychosocial risk factors were independent risk factors for stroke. Psychological factors increased the risk of stroke by 39% (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.27‐1.51), vocational by 35% (HR, 1.35; 95% CI, 1.20‐1.51), and interpersonal by 16% (HR, 1.16; 95% CI, 1.03‐1.31), and the effects of behavioral factors were equivocal (HR, 0.94; 95% CI, 0.20‐4.31). The meta‐analyses were affected by heterogeneity. Psychosocial risk factors are associated with an increased risk of stroke.

Screening for aspiration risk associated with dysphagia in acute stroke

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To determine the diagnostic accuracy of bedside screening tools for detecting dysphagia, which is a predictor of aspiration, in people with acute stroke. To assess the influence of the following potential sources of heterogeneity. • Patient demographics (e.g. age, gender, % of males in study, median age of study by gender). • The time post-stroke that the study was conducted (from admission to 48 hours) to ensure only hyperacute and acute stroke dysphagia screening tools are identified. • Any significant change in the patient’s condition between the index and reference tests being performed. • The definition of dysphagia used by the study. • Level of training of nursing staff, both grade and training in the screening tool. • Low quality studies identified from the methodological quality checklist. • i) Type of the index test and ii) the threshold of the index test • Type of the reference test 1 Screening for aspiration risk associated with dysphagia in acute stroke (Protocol) Copyright

Clinical risk factors for underlying gastrointestinal malignancy in iron deficiency anaemia–prospective validation of the IDIOM score

Abstract Objective: Ten percent of adults presenting with iron deficiency anaemia (IDA) have underlying cancer. This study was undertaken to prospectively validate the observation in a previous retrospective study that three simple clinical parameters can usefully predict the likelihood of gastrointestinal (GI) malignancy on investigation of patients with IDA, and to screen for other potential clinical predictors of risk. Method: Observational study of a cohort of 643 subjects attending an IDA clinic at a District General Hospital between 2012 and 2015, with multivariable analysis of the predictive value of a series of clinical variables including sex, age and haemoglobin concentration ([Hb]) for underlying GI malignancy. Results: Analysis of the validation cohort data confirmed the original observation that sex, age, and Hb were associated with the risk of GI malignancy—the parsimonious model including only these variables yielded odds ratios of 1.9 (95% confidence interval (CI): 1.1, 3.3) for males vs. females; 1.6 (95% CI: 0.9, 2.9) for age >70 vs. ≤70 years; and 2.9 (95% CI: 1.2, 6.9) for [Hb] <90.6 g/l vs. >112 g/l. Combining data from the observation and validation cohorts (total n = 1,363) identified sub-groups with cancer risks ranging from 0% to over 20%. No other predictive clinical variables were identified. Conclusions: Three simple and objective clinical parameters can be combined to provide a clinically useful cancer risk stratification model for subjects with IDA. This may assist with patient counselling and the prioritisation of investigational resources.