Are the Cochrane group registers comprehensive? A case study of Japanese psychiatry trials

BACKGROUND: Language bias is a form of publication bias and constitutes a serious threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt to remedy this and now contains more than 300,000 citations. However we are still unsure if it provides comprehensive coverage, particularly for non-English trials. METHODS: We have recently established a comprehensive register of Japanese trials of psychotropic drugs through extensive personal contacts, electronic searches and handsearches. We examined two Cochrane psychiatry group registers against this Japanese database. RESULTS: The Japanese register contained 56 reports of randomized controlled trials (RCTs) of antidepressants for depression but the Cochrane Depression, Anxiety and Neurosis group register contained 18, with an overlap of only nine. The Japanese register contained 61 reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia group register contained 36, with an overlap of only six. Taking account of some duplicate publications, only a quarter to a third of all relevant Japanese RCTs were retrievable from the Cochrane group registers. CONCLUSIONS: Similar, or worse, yields may be expected with RCTs conducted in other East Asian countries, and in other fields of medicine. What evidence there is suggests that this situation may lead to a systematic over estimate of treatment effect

The cost of schizophrenia in Japan

Schizophrenia is a disorder that produces considerable burdens due to its often relapsing/remitting or chronic longitudinal course. This burden is felt not only by patients themselves, but also by their families and health care systems. Although the societal burden caused by this disorder has been evaluated in several countries, the magnitude of the societal cost of schizophrenia in Japan has never been estimated. The aim of this study is to clarify the societal burden of schizophrenia by estimating the cost of schizophrenia in Japan in 2008. Methods: A human capital approach was adopted to estimate the cost of schizophrenia. The total cost of schizophrenia was calculated as the sum of the direct, morbidity, and mortality costs. Schizophrenia was defined as disorders coded as F20.0-F20.9 according to the International Classification of Diseases-10. The data required to estimate the total cost was collected from publicly available statistics or previously reported studies. Results: The total cost of schizophrenia in Japan in 2008 was JPY 2.77 trillion (USD 23.8 billion). While the direct cost was JPY 0.770 trillion (USD 6.59 billion), the morbidity and mortality costs were JPY 1.85 trillion (USD 15.8 billion) and JPY 0.155 trillion (USD 1.33 billion), respectively. Conclusion: The societal burden caused by schizophrenia is tremendous in Japan, similar to that in other developed countries where published data exist. Compared with other disorders, such as depression or anxiety disorders, the direct cost accounted for a relatively high proportion of the total cost. Furthermore, absolute costs arising from unemployment were larger, while the prevalence rate was smaller, than the corresponding results for depression or anxiety in Japan

Lipopolysaccharide inhibits hepatic gluconeogenesis in rats: The role of immune cell

Aims/Introduction: Bacterial septicemia has diverse clinical symptoms including severe hypoglycemia. However, sepsis‐induced hypoglycemia has not yet been examined in detail. The aim of the present study was to investigate the mechanisms underlying hypoglycemia in sepsis.Materials and Methods: We induced endotoxin shock in rats using lipopolysaccharide (LPS). After an intraperitoneal injection of LPS, we measured gluconeogenesis using the pyruvate tolerance test. The effects of LPS on glucose metabolism were investigated in perfused livers and isolated hepatocytes. Furthermore, its effects on the production of inflammatory cytokines were examined in isolated splenocytes. The interaction between splenocytes and hepatocytes in response to LPS was investigated in vitro using a co‐culture of splenocytes and hepatocytes.Results: In the pyruvate tolerance test, the pretreatment with LPS decreased gluconeogenesis. The in vivo pretreatment of rats with LPS did not inhibit glucose production in perfused livers. The in vitro treatment of isolated hepatocytes with LPS did not decrease hepatic gluconeogenesis. Although LPS increased the production of inflammatory cytokines (tumor necrosis factor‐α, interferon‐γ, interleukin‐1β, interleukin‐6 and interleukin‐10) and nitric oxide in isolated splenocytes, only nitric oxide significantly inhibited gluconeogenesis in isolated hepatocytes. When splenocytes and hepatocytes were co‐cultured in medium containing LPS, the messenger ribonucleic acid expression of glucose‐6‐phosphatase in hepatocytes was suppressed.Conclusions: LPS reduced hepatic gluconeogenesis, at least in part, by stimulating the production of nitric oxide in splenocytes. This effect could contribute to the mechanisms responsible for septicemia‐induced hypoglycemia

Insulin secretory defect and insulin resistance in isolated impaired fasting glucose and isolated impaired glucose tolerance

Objective. To investigate the characteristics of isolated impaired glucose tolerance (IGT) and isolated impaired fasting glucose (IFG), we analyzed the factors responsible for elevation of 2-hour postchallenge plasma glucose (2 h PG) and fasting plasma glucose (FPG) levels. Methods. We investigated the relationship between 2 h PG and FPG levels who underwent 75 g OGTT in 5620 Japanese subjects at initial examination for medical check-up. We compared clinical characteristics between isolated IGT and isolated IFG and analyzed the relationships of 2 h PG and FPG with clinical characteristics, the indices of insulin secretory capacity, and insulin sensitivity. Results. In a comparison between isolated IGT and isolated IFG, insulinogenic index was lower in isolated IGT than that of isolated IFG (0.43 ± 0.34 versus 0.50 ± 0.47, resp.; p < 0.01). ISI composite was lower in isolated IFG than that of isolated IGT (6.87 ± 3.38 versus 7.98 ± 4.03, resp.; p < 0.0001). In isolated IGT group, insulinogenic index showed a significant correlation with 2 h PG (r = - 0.245, p < 0.0001) and had the strongest correlation with 2 h PG (β = - 0.290). In isolated IFG group, ISI composite showed a significant correlation with FPG (r = - 0.162, p < 0.0001) and had the strongest correlation with FPG (β = - 0.214). Conclusions. We have elucidated that decreased early-phase insulin secretion is the most important factor responsible for elevation of 2 h PG levels in isolated IGT subjects, and decreased insulin sensitivity is the most important factor responsible for elevation of FPG levels in isolated IFG subjects