| AimsRevealing and retest the autoimmune theory of MG using systematic review of qualitative and quantitative analysis methods with the principles of evidenced-based medicine. Specifically, we wanted to gain insight into the level of evidence of each main point of theory, and explorded the relevant factors if available. We end each of our review with recommendations for further reserch.Methods and ResultsFirstly, a reintegrate theory was conducted based on different research type using clinical epidemiology methods. Then we proposed five testable hypothesis listed below:The patients with MG have a higher frequency of other autoimmue diseases compared with population-based data based on general diseases (hypothesis one); The patients with MG have a higher frequency of thymoma compared with population-based data based on general diseases (hypothesis two); AChR antibodies yielded high sensitivity and specitivity in adult and neonate MG patients (hypothesis three); immunosuppressive therapy, plasma exchange and thymectomy benefit patients of MG; MG was a female predominance disease and the course of MG was typical relapse-remission phases (hypothesis four). The tests of these hypothesises were divided into following five parts:Part one. Frequency of autoimmune diseases in myasthenia gravis:a systematic reviewTo test hypotheis one, a systematic search for English language studies was conducted MEDLINE and EMBASE from 1960 through 2010. Incidence studies and case series of unselected MG patients with information about autoimmune diseases were included.28 studies met the inclusion criteria. Although there was considerable heterogeneity, the pooled estimate of coexisting autoimmune diseases in MG was 13%(95%confidence interval, 12%-14%). Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients. Heterogeneity in study estimates could be explained by ascertainment bias and case mix. Furthermore, autoimmune diseases occured significantly more often in females and anti-Acetylcholine receptor seropositive MG patients. Patients with MG have an increased frequency of coexisting autoimmune diseases. Autoimmune diseases seem to occur more often in female and seropositive MG patients.Part two. Frequency of thymoma in myasthenia gravis:a systematic reviewTo test hypothesis two, a systematic review search was conducted in MEDLINE and EMBASE for English language studies from 1960 through 2010. We identified additional studies by reviewing bibliographies of retrieved articles and hand search main journal of neurology. Incidence studies and case series of unselected MG patients in who information about thymoma had to be present were included.49 studies met the inclusion criteria. Although considerable heterogeneity, the pooled estimate of thymoma in MG was 21%(95% confidence interval,20%-22%). Surgery-based studies yielded significantly higher pooled frequency than population-based and hospital-based studies. Higher frequency of thymoma was related to noninvasive thymoma. Further more, thymoma occured significantly higher among those male and late-onset MG patients.thymoma in MG patients is common. Thymoma seems to occur more often in male and late-onset MG patients.Part three. Diagnostic Accuracy of Anti-AChR Antibodies Test for Myasthenia Gravis:A Systematic ReviewTo test hypothesis three, we conducted a diagnostic systematic review to assess the diagnostic accuracy of anti-AChR antibodies test for myasthenia gravis (MG) using bivariate model. Twenty-seven studies met the inclusion criteria. The included studies were heterogeneous with respect to sample size, study design, antigen sources, and assays. The pooled sensitivity of the anti-AChR antibodies test was 0.56 (95% confidence interval, CI,0.47-0.64) in ocular MG (OMG) and 0.85 (95%CI,0.81-0.89) in generalized MG (GMG). The specificity of the anti-AChR antibodies test for both OMG and GMG was consistently high. Furthermore, we found that sensitivity of the anti-AChR antibodies test is higher in cohort studies and in studies using the radioimmunosorbent assay (RIA) instead of enzyme-linked immunosorbent assay (ELISA). The anti-AChR antibodies test has a good diagnostic performance in GMG and less in OMG. Our findings should be interpreted with caution because of the methodological weaknesses of included studies.Part four. Treatment of myasthenia gravis:a systematic reviewTo test hypothesis four and evaluate the effects of other common therapy, we conducted in MEDLINE and EMBASE for systematic review, meta analysis, or those randomised controlled studies have not been covered by published evidence-based review. We synthesized the evidence by using Oxford Centre for Evidence-based Medicine Levels of Evidence and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) classification. Overall, limited evidence suggests that monotherapy or with corticosteroids, ciclosporin, tacrolimus, plasma exchange and intravenous immunoglobulin, significantly improve MG. Limited evidence shows no significant benefit from azathioprine (as monotherapy or with steroids), mycophenolate mofetil (as monotherapy or with either corticosteroids or ciclosporin). No RCTs focus on thymectomy and acetylcholinesterase inhibitors.Part five. Course and prognosis of MG:a systematic reviewTo test hypothesis five, and identified prognostic factors of MG at the same time, a systematic review search was conducted in MEDLINE and EMBASE for English language studies from 1985 through 2009. Studies evaluating variables associated with or predictive of remission in adults MG patients were included. Due to methodological heterogeneity, we refrained from statistical pooling, instead, a best evidence synthesis was used for summarizing the results. 17 cohort studies met the inclusion criteria. The included studies were heterogeneous considerably in sample size, disease duration, follow-up years, definition of remission, and analysis. Study quality was limited by retrospective design in most studies and lack of multivariate analysis. A remitting and relapsing course was noted in 48%,46% had no major fluctuations and progressive worsening was seen in the remaining 6%. Time of diagnosis from onset (<1 year) showed strong evidence of predicting a better remission. In studies using completely stable remission (CSR) outcomes, there was strong evidence that age at onset (<40 years) was of prognostic importance. Furthermore, gender showed no association with remission. Time of diagnosis from onset and age at onset were found to be predictors of remission. Gender do not seem to predict the course of MG.ConclusionBy using evidence-based methods, the (1) Patients with MG seems to have an increased frequency of coexisting autoimmune diseases. Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients; (2) Strong evidence suggests MG patients have a high requency of thymoma, higher frequency of thymoma was related to noninvasive thymoma. (3) AChR antibodies only yielded high diagnostic accuracy in GMG, while limited accuracy in OMG; (4) Limited evidence suggests significant benefit about corticosteroids, ciclosporin, tacrolimus, plasma exchange and intravenous immunoglobulin; (5) strong evidence shows MG is a female pridominance disease, however, gender do not seem to predict the course of MG. Excepts relapse-remission course, it is possible that still exist other type of course. However, this hypothesis need further research to test.Overall, we providen three first-time evidence-based proof for the research of MG, furthermore, this research provide a new evidence based on evidence-based methods, and bettter understand this classical therory in a new horizon.
|
PDF Full Text Request