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Aims Clinical experience suggests that atherosclerotic disease is common in individuals with coeliac disease, but epidemiological studies have had contradicting findings. To summarise the currently available evidence, we systematically reviewed and analysed observational studies of the association of coeliac disease or dermatitis herpetiformis with coronary heart disease (CHD) or stroke. Data synthesis We searched for studies comparing CHD or stroke outcomes with individuals with and without coeliac disease or dermatitis herpetiformis. Three investigators independently searched electronic databases, identified relevant studies and extracted data. Study-specific results were combined in random-effects meta-analyses, and heterogeneity was quantified using the I 2 statistic and meta-regression. Twenty-one studies were included in our systematic review and 18 in the meta-analyses. For CHD, the pooled hazard ratio for incident disease was 1.05 (95% confidence interval (CI): 0.93, 1.19) and the overall standardised mortality ratio was 1.21 (0.99, 1.49). For stroke and brain haemorrhage, the corresponding estimates were 1.10 (95% CI: 1.00, 1.21) and 1.43 (0.97, 2.10), respectively. There was moderate to considerable heterogeneity among the study-specific estimates. In addition, many estimates were based on small numbers of outcomes and they had limitations in terms of adjustment for potential confounders. Conclusion Our meta-analyses lend some support to an association between coeliac disease and CHD or cerebrovascular disease, but the evidence base was heterogeneous and had limitations. Our systematic review highlighted a need in this area for adequately powered prospective studies with appropriate adjustment for potentially confounding factors.

Background It has been suggested that antibodies against transglutaminase (TG) 6 could serve as a biomarker to identify a subgroup of gluten-sensitive patients who may be at risk of developing neurological disease. We here investigated whether TG6-targeted autoantibodies are a characteristic feature of celiac patients, especially those with neurological symptoms, and further, whether such antibodies are gluten-dependent. Methods Serum IgA-class TG6 autoantibodies were measured in untreated and treated celiac patients with and without neurological manifestions and in non-celiac controls. The results were compared to TG2 autoantibody levels. Results During a gluten-containing diet the number of TG6 autoantibody-positive celiac patients with neurological problems (25%) did not significantly differ from that of TG6-seropositive patients without neurological impairment (16%) or from non-celiac controls (15%). This was in contrast to our finding in TG2 autoantibody-positive individuals, whose numbers differed significantly between all three study groups. On a gluten-free diet the levels of TG6 autoantibodies remained unchanged. Conclusions We conclude that the serum IgA-class TG6 autoantibody assay is not able to distinguish gluten-sensitive patients with neurological manifestations from celiac patients without neurological problems or from control subjects, and further, that TG6 autoantibodies are not gluten-dependent.

Background and aims The diagnosis of coeliac disease is problematic in individuals not responding to a gluten-free diet. Small-bowel villous atrophy occurs in other enteropathies and non-responsive patients are often seronegative. We investigated whether small-bowel mucosal transglutaminase-2 specific autoantibody deposits distinguish non-responsive coeliac disease from other enteropathies. Methods Small-bowel mucosal autoantibody deposits were determined in 27 non-responsive, 28 responsive coeliac patients and 10 controls with other enteropathies. Of the non-responsive coeliac patients six were adhering poorly and 21 strictly to the diet; six of the 21 had enteropathy-associated lymphoma, five refractory coeliac disease and 10 otherwise persistent villous atrophy. The presence of mucosal autoantibody deposits was compared to serology, villous morphology, densities of intraepithelial lymphocytes (IELs) and markers of refractory coeliac disease. Results Twenty out of 21 well-adhering, all six poorly adhering non-responsive and all 28 untreated responsive coeliac patients had small-bowel mucosal autoantibody deposits present, while controls with other enteropathies were negative. Small-bowel mucosal autoantibody deposits were more accurate in detecting coeliac disease than serology or IEL densities. Refractory coeliac markers revealed only cases with the most severe condition. Conclusions Small-bowel mucosal autoantibody deposits differentiate coeliac disease from other enteropathies, enabling the design of appropriate therapeutic strategies.

Background: The seasonality of suicide rates and methods of suicide may be related to changes in weather and conditions of employment. Particularly the amount of occupational outdoor exposure could show differences in the distribution of suicides by season and the selection of suicide method, in addition to age at the time of death. Methods: The data consisted of all death certificates ( n =1359) of completed suicides in the province of Oulu, Finland, during the years 1988–1999. For male subjects included in this study, four occupational groups were identified according to decreasing occupational outdoor exposure. The mean ages, the distribution of suicide methods and the seasonal variation in suicides for each occupational group were analyzed. Results: Farmers were significantly older at the time of suicide than construction or indoor workers, and farmers employed significantly more violent methods than the other occupational groups. In the spring, farmers had a significant peak in the rate of suicides. In the winter, forest workers had a significant trough in the rate of suicides. In the summer, indoor workers had a significant peak in the rate of suicides. Limitations: The analyses were restricted to males due to the low number of females in the study population. Conclusions: The novel finding in this study was that the seasonality of violent suicides was most strongly seen as a spring peak and a winter trough among outdoor workers. The recognition of typical risk factors of different occupations, such as outdoor exposure, and occupational-related susceptibility towards certain suicide methods could benefit in the prevention of suicides.

Objective To establish whether children who are endomysial antibody (EmA) positive and have normal small-bowel mucosal villous morphology are truly gluten-sensitive and may benefit from early treatment with a gluten-free diet. Study design Children who were EmA positive with normal small-bowel mucosal villi were compared with children who were seropositive with villous atrophy by using several markers of untreated celiac disease. Thereafter, children with normal villous structure either continued on a normal diet or were placed on a gluten-free diet and re-investigated after 1 year. Seventeen children who were seronegative served as control subjects for baseline investigations. Results Normal villous morphology was noted in 17 children who were EmA positive, and villous atrophy was noted in 42 children who were EmA positive. These children were comparable in all measured variables regardless of the degree of enteropathy, but differed significantly from the seronegative control subjects. During the dietary intervention, in children who were EmA positive with normal villi, the disease was exacerbated in children who continued gluten consumption, whereas in all children who started the gluten-free diet, both the gastrointestinal symptoms and abnormal antibodies disappeared. Conclusions The study provided evidence that children who are EmA positive have a celiac-type disorder and benefit from early treatment despite normal mucosal structure, indicating that the diagnostic criteria for celiac disease should be re-evaluated.