Maria de Fátima Moreira Martins

Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World

Pentavalent antimonials are first-line drugs for the treatment of the cutaneous form of American tegumentary leishmaniasis. Second-line drugs include amphotericin B and pentamidine. Although these drugs have been used for decades, there are no systematic reviews about their safety. The objective of this review was to identify and classify the main adverse effects associated with these drugs and to estimate the frequency of these effects, whenever possible. Intervention studies, case series and case reports containing information regarding clinical, laboratory or electrocardiographic adverse effects of drugs used for the treatment of cutaneous leishmaniasis were systematically retrieved from 10 databases searched between August 13, 2008 and March 31, 2009. The 65 studies included in this review had treated a total of 4359 patients from 12 countries infected with eight different Leishmania species. Despite the small number of drugs used in these studies, a wide variability in the therapeutic regimens was observed. As a consequence, the adverse effects of pentavalent antimonials and pentamidine needed to be classified jointly according to system, irrespective of formulation, daily dose, duration of treatment, and route of administration. The frequencies of adverse effects were calculated based on the data of 32 articles involving 1866 patients. The most frequently reported clinical adverse effects of pentavalent antimonials and pentamidine were musculoskeletal pain, gastrointestinal disturbances, and mild to moderate headache. Electrocardiographic QTc interval prolongation and a mild to moderate increase in liver and pancreatic enzymes were additional adverse effects of pentavalent antimonials. Patients treated with liposomal amphotericin B had mild dyspnea and erythema. The adverse effects associated with miltefosine were vomiting, nausea, kinetosis, headache, diarrhea, and a mild to moderate increase in aminotransferases and creatinine. Although closer surveillance is needed for the treatment of cutaneous leishmaniasis, antileishmanial drugs are basically safe and severe side effects requiring the discontinuation of treatment are relatively uncommon.

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies

A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs.

Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus

The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohns disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.

Systematic Review With Meta-Analyses and Critical Appraisal of Clinical Prediction Rules for Pulmonary Tuberculosis in Hospitals

OBJECTIVE To systematically review studies evaluating clinical prediction rules (CPRs) for adult inpatients suspected to have pulmonary tuberculosis. DESIGN Systematic review with meta-analyses. SETTING Hospitals. Patients Inpatients at least 15 years of age admitted to acute care. METHODS A search was conducted in 5 indexed electronic databases with no language or year of publication restrictions. We performed a meta-analysis for those CPRs with at least 2 validation studies. Results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS Of the 461 abstracts selected, 36 articles were fully analyzed and 11 articles were included, yielding 8 CPRs derived in 4 countries. Broad validation studies were identified for 2 CPRs. The most frequent clinical predictors were fever and weight loss. All CPRs included chest imaging signs. Most CPRs were derived in countries with a low prevalence of pulmonary tuberculosis and included homeless, immigrants, and those who reacted to the purified protein derivative test. Both of the CPRs derived in countries with a high prevalence of pulmonary tuberculosis strongly relied on chest radiograph predictors. Accuracy of the different CPRs was high (area under receiver operating characteristic curve, 0.79-0.91). Meta-analysis of 4 validation studies for Wisniveskys CPR indicates optimistic pooled results: sensitivity, 94.1% (95% CI, 89.7%-96.7%); negative likelihood ratio, 0.22 (95% CI, 0.12-0.40). CONCLUSION On the basis of a critical appraisal of the 2 best validated CPRs, the presence of weight loss and/or fever in inpatients warrants obtaining a chest radiograph, regardless of the presence of productive cough. If the chest radiograph is abnormal, the patient should be placed in isolation until more specific test results are available. Validation in different settings is required to maximize external generalization of existing CPRs.

Revisão sistemática da indução de autoanticorpos e lúpus eritematoso pelo infliximabe

The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohns disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.