RESUMEN

Background: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. Methods: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. Findings: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]). Interpretation: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. Funding: COALITION COVID-19 Brazil and EMS.

RESUMEN

OBJECTIVES: This study aimed to perform a cost-effectiveness analysis (CEA) of the molecular diagnostic method (MM) associated with conventional diagnostic method (CM) compared with the CM alone, for the detection of resistant profile in bacteremia, from the perspective of the Brazilian Public Health System, in intensive care units setting. METHODS: The clinical parameters regarding methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) infections were collected from searches on PubMed, Scopus, and SciELO, using specific keywords. Data on direct medical costs to treat these infections were collected according to Brazilian Public Health System perspective from Brazilian databases, in tables of 2018 to 2019. CEA was performed after building a dynamic model, which was calibrated and validated according to international recommendations. The incremental cost-effectiveness ratio of the MM + CM compared with the CM was calculated using the outcomes "avoided death" and "avoided resistant infections." One-way sensitivity analyses were performed. RESULTS: This CEA demonstrated that the MM + CM was dominant in all scenarios. Estimates showed that for MRSA, CRGNB, and VRE infections, every avoided death would lead to savings of Brazilian real (R$) 4.9 million ($937 301), R$2.2 million ($419 899), and R$1.3 million ($248 919), respectively. The same infections assessed by avoided resistant infections savings were projected to be R$24 964 ($4686), R$40 260 ($7558), and R$23 867 ($4480). CONCLUSIONS: MM leads to cost reduction and increased benefits, optimizing the use of financial resources on the health system in the intensive care unit setting, in bacteremia caused by MRSA, CRGNB, and VRE.

Asunto(s)

RESUMEN

Introduction: Considering the need for effective postmarketing surveillance of disease-modifying therapies (DMTs) in multiple sclerosis (MS), we analyzed the potential of the spontaneous reports for safety signal detection, verifying the completeness of the reports in the FDA Adverse Event Reporting System (FAERS).Methods: All reports with DMTs for MS considered the primary suspect cause of ADRs and registered between January 2004 and June 2019 were selected. The vigiGrade completeness score was applied and reports with a score greater than 0.80 were considered well documented. Descriptive statistical analysis and comparisons of well-documented reports by DMTs were performed.Results: A total of 297,926 reports were analyzed. The lowest completeness rates were observed for type of report (13.5%), dose (62.7%), and time from treatment start to the ADR (79.0%). Overall, 80.8% of reports were classified as well documented and those related to natalizumab had the highest proportion (92.4%, p < 0.001), while the lowest was observed for reports sent in 2017 (53.1%, p < 0.001) and for teriflunomide (48.5%, p < 0.001).Conclusions: The high proportion of well-documented reports for DMTs indicates that they can be a valuable source for safety signal detection. A more careful analysis should be performed for data from the groups identified with low completeness to avoid the disclosure of spurious results.

Asunto(s)

RESUMEN

OBJECTIVE: To map the clinical pharmacy services conducted in Brazil, their characteristics, outcomes, and process measures in general population, as well as the assessment of the clinical impact on people with cardiometabolic diseases (cardiovascular diseases and metabolic diseases). METHODS: A systematic scoping review and meta-analysis were conducted. The electronic searches were re-run in March 2020. To the clinical impact assessment, meta-analyses of cardiometabolic outcomes (i.e., change of systolic (SBP) and diastolic blood pressure (DBP), triglycerides, total cholesterol, glycated hemoglobin (HbA1c), fasting glycemia, LDL-, and HDL-cholesterol) were led. The risk of bias was assessed with the Cochrane Collaboration tools. RESULTS: 71 studies were identified (7,402 patients), being the majority quasi-experimental studies (n=41) and published by research groups of Southeast Brazil (n=33). Medication therapy management (n=62) was the most frequent clinical pharmacy service, performed on outpatient setting (n=45), with adults or elderly people (n=58) with hypertension (n=18) or diabetes (n=10). Process measures (n=58) (e.g. resolution of drug related-problem) were widely used as indicator, followed by clinical (n=44) (e.g. change in SBP), humanistic (n=12) (e.g. change in quality-of-life score assessed by Short-Form 36 Health Survey Questionnaire), and economic outcomes (n=3) (incremental cost-effectiveness ratio for reduction in HbA1c). Regarding the assessment of clinical impact of the services, 20 studies were included in meta-analyses, showing improvement in most cardiometabolic outcomes when considered individual studies. However, the evidence presents high risk of bias, high heterogeneity (median 67-90%) and imprecision, contributing to wide prediction intervals and low reliability. CONCLUSIONS: A predominance of studies on cardiometabolic diseases, process measures, and clinical outcomes were identified. Considering the assessment of the clinical impact of clinical pharmacy services in cardiometabolic diseases, an improvement in most cardiometabolic outcomes was showed, however, with low confidence and wide prediction interval. Therefore, development of larger studies with low risk of bias and major homogeneity is necessary for a better comprehension of clinical pharmacy service characteristics, benefits, and the population groups most benefited.

RESUMEN

BACKGROUND: Although relapsing-remitting multiple sclerosis (RRMS) has a chronic course, little information is known about the comparison between the disease-modifying therapies (DMT) for long-term outcomes. We aimed to conduct a systematic review of randomized clinical trial (RCT) extension and observational studies to examine the efficacy and safety of all available DMT for RRMS, compare the evidence with that derived from mid-term studies, and investigate whether the published long-term data are robust and reliable enough to inform clinical decision-making concerning RRMS treatment. METHOD: PubMed, Scopus, and manual searches were performed until October 2019. The clinical outcomes of long- and mid-term studies were compared. ROBINS-I was used to assess the methodological qualities of the long-term studies. PROSPERO number CRD42019123361. RESULTS: Nineteen long-term studies (9,018 participants) were included in the systematic review. All studies presented serious or critical risks of bias that were mainly due to confounding, selection, and missing data biases. The annualised relapse rates (ARR) observed in the long-term studies are lower (better) than those from the mid-term studies for most treatments. The main reason for this ARR decrease could be a selection bias for good responders in the long-term studies, since many studies show a loss of patients between the mid- and long-term phases. The safety profiles depend on the study, follow-up, report, and outcome (i.e., discontinuation or number of patients with at least one serious adverse event). CONCLUSION: The currently available long-term data for patients with RRMS exhibit serious or critical risks of bias that preclude robust comparisons between long-term studies. High quality comparative observational studies with long-term follow-ups or RCT extensions with intention-to-treat analyses are needed to support clinical and regulatory practice. Until reliable long-term evidence is available, neurologists should continue to base their conduct on mid-term studies, patient`s experience and, most importantly, patient`s needs and predictor factors, according to personalized medicine.

Asunto(s)

RESUMEN

BACKGROUND: Suboptimal meta-analyses with misleading conclusions are frequently published in the health areas, and they can compromise decision making in clinical practice. AIM OF THE REVIEW: This systematic review aimed to map the characteristics of published meta-analyses of pharmacy services and their association with the study conclusions. METHOD: We searched electronic databases (PubMed, Scopus, and Web of Science) to identify published meta-analyses of pharmacy services up to January 2019. Components of meta-analyses were extracted (i.e. studies' metadata; methods used in the systematic review; description of the statistical model used for the meta-analysis; main results; conflict of interest and funding source). The methodological quality was evaluated using the R-AMSTAR tool. RESULTS: A total of 85 meta-analyses were included, with 2016 as the median publication year. Overall, the methodological quality of meta-analyses of pharmacy services was considered suboptimal. Only one-third of authors registered a protocol; complete search strategy and raw data were provided by 55.3% and 9.4% of studies, respectively. Evidence strength (GRADE) was evaluated in only 19.2% of studies. PRISMA and Cochrane recommendations were stated to be followed in 60% and 27.4% of articles, respectively. Around half of studies performed sensitivity analysis, however, the prediction interval was presented by only one meta-analysis. Studies that favoured the pharmacists' interventions poorly discussed the methodological quality and heterogeneity of primary trials. CONCLUSION: Poor conduction and reporting were observed in meta-analyses of pharmacy services, especially in those that favoured the pharmacist's interventions. Reproducibility and transparency should be rigorously ensured by journal editors and peer-reviewers.

Asunto(s)

RESUMEN

BACKGROUND: Randomised clinical trials (RCTs) and observational studies have reported adverse events that preclude the use of disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) in the long term or in specific populations, however, little is known about the relationship between the use of DMTs and frequency of undesirable events. We aimed to conduct a systematic review and network meta-analyses (NMAs) of RCTs and observational studies to synthesise the evidence on the safety of all available DMTs for patients with RRMS. METHODS: PubMed, Scopus and a manual search were performed. Bayesian NMAs of safety outcomes reported in RCTs and observational studies assessing DMTs as monotherapies were conducted. RESULTS: Forty-seven studies were included in the systematic review. Considering all studies, 368 and 149 different safety outcomes were reported for at least one study and two studies, respectively. Considering clinical trials, 22 NMAs were conducted for 16 outcomes. Regarding geometry metrics, the median number of studies, DMTs, common comparator, strong edge, and patients were 5 (IQR 5-9), 5 (IQR 4-8), 44%, 33%, and 3998 (IQR 3380-6761). In summary, most comparisons showed similar risk of safety events for DMTs and placebo for all outcomes. Considering cohort studies, only three meta-analyses were conducted. CONCLUSION: Safety outcomes are poorly reported in primary studies of DMTs in RRMS, precluding the conduction of robust meta-analyses. Therefore, the current available data on safety of these drugs is not contributing to regulatory and clinical decision making, with adverse event reports underbalanced compared to efficacy outcomes.

Asunto(s)

RESUMEN

Gastrointestinal bleedings (GIB) are one of the most frequent adverse drug reactions. Among the GIB upper gastrointestinal bleeding (UGIB) stands out due to their high mortality. The different idiosyncratic responses related to UGIB ​​in medication users may be due to the presence of genetic variants in the genes that encode enzymes that are targets of pharmacokinetic and pharmacodynamic activity of the metabolism of the drugs, such as cyclooxygenase 1, endothelial nitric oxide synthase, cytochrome P450, among others. Although a review has focused on assessment whether the presence of CYP2C9*2 and CYP2C9*3 could increase UGIB diagnosis, the search is outdated, and more evidence can be identified regarding both CYP polymorphisms and other genes potentially involved with UGIB. The objective of the systematic review is to explore case-control or case-case studies to assess the epidemiological association between genetic polymorphisms and UGIB. This review will consider genetic polymorphisms of case-control and case-case studies and their association with the UGIB, in the presence or absence of drugs exposure. Electronic searches will be performed in PubMed, Scopus and the Cochrane Library with no time limit. Two researchers will select registries and extract data on study and population characteristics, exposure, covariates, and outcomes. Critical appraisal will consider Joanna Briggs tool for case-control studies. Studies will, where possible, be pooled with statistical meta-analysis. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation, where appropriate.(AU)

Asunto(s)

RESUMEN

BACKGROUND: A broad range of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) is available. However, the efficacy and safety of traditional DMTs compared with the recently developed DMTs remain unclear. OBJECTIVE: Therefore, we have synthesised available evidence of clinical outcomes for DMTs in adults with RRMS. METHODS: PubMed, Scopus and a manual search were performed. Bayesian network meta-analyses of randomised clinical trials assessing DMTs as monotherapies were conducted. SUCRA and GRADE were used to rank therapies and to assess quality of general evidence, respectively. RESULTS: Thirty-three studies were included in the meta-analyses. The most effective therapies for the outcome of annualised relapse rate were alemtuzumab (96% probability), natalizumab (96%) and ocrelizumab (85%), compared with all other therapies (hazard ratio versus placebo, 0.31, 0.31 and 0.37, respectively; p < 0.05 for all comparisons) (high-quality evidence). However, no significant differences among these three therapies were found. Discontinuation due to adverse events revealed similarity across all therapies, except for alemtuzumab, which showed less discontinuation when compared with interferon-1a intramuscular (relative risk 0.37; p < 0.05). CONCLUSION: High-quality evidence shows that alemtuzumab, natalizumab and ocrelizumab present the highest efficacy among DMTs, and other meta-analyses are required regarding adverse events frequency, to better understand the safety of therapies. Based on efficacy profile, guidelines should consider a three-category classification (i.e. high, intermediate and low efficacy).

Asunto(s)

RESUMEN

Drug-related problems consist an important avoidable risk factor to the hospitalization in the general population. The increase of technologies to promote and recovery health and their use makes the design of services aimed at preventing health and drug problems, as well as their adequate management, a priority for public health. Pharmacist-led interventions are capable to optimize the use of medicines. However, it is important to know the characteristics and assessed outcomes of interventions, since, as a complex intervention, the variability between services can explain different performances. The objective of the scoping review is to explore randomized and non-randomized clinical trial, quasi-experimental and cohort studies to explore characteristics and assessed outcome of pharmacist-led interventions conducted in Brazil. This review will consider studies about pharmacist-led interventions, regardless of patient profile or health setting. Electronic searches will be performed in PubMed, Scopus, and LILACS databases with no time limit of publication. Two researchers, independently, will select registries and extract data of study and service characteristics, and outcomes measures. The findings will be presented in a narrative form including tables and figures to aid in data presentation, where appropriate.(AU)

Asunto(s)