Cost of adverse drug events related to potentially inappropriate medication use: A systematic review.

BACKGROUND: The use of potentially inappropriate medications (PIMs) for older people is associated with worse health outcomes owing to the occurrence of adverse drug events (ADEs) and drug interactions, leading to increased health care costs. OBJECTIVES: Identify the costs of ADEs related to PIMs use, in addition to the costs predictors. METHODS: A systematic review was conducted in the PubMed and Scopus databases (until February, 2022), and the report of this study was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Interventional and observational studies that reported costs of ADEs regardless of perspective (i.e., payer) were considered. Reporting and methodological quality were assessed using the tool proposed by Larg and Moss for evaluating cost-of-illness studies. RESULTS: A total of 20 (21 publications), published between 2001 and 2020, were included (236,888,744 older people). The ADEs costs related to PIMs use were mostly related to the use of health services (hospitalization [n = 7], health care expenses [n = 7], and emergency department visits [n = 3]). Among the 8 studies that reported P value, 7 identified higher costs for PIM users than non-PIM users. Three studies reported cost predictors, being highest number of PIMs in use, age older than 75 years, male gender, general health status in older people in use of benzodiazepines, and drug interactions in older people diagnosed as having dementia. Regarding to assessment of reporting and methodological quality, all studies had at least one limitation (answer "no"). CONCLUSIONS: Our findings suggest that PIMs use is associated with higher costs of hospitalization, health care expenses, and visits to emergency department owing to ADEs, regardless of PIMs in use, health service, perspective, and screening tools used for PIMs identification. However, these findings should be interpreted with caution because all studies had at least one methodological limitation.

Methodological standards for conducting and reporting meta-analyses: Ensuring the replicability of meta-analyses of pharmacist-led medication review.

BACKGROUND: Meta-analyses of clinical pharmacy services are frequently criticized for restricted data transparency and reproducibility. OBJECTIVES: To describe the methodological characteristics of meta-analyses of pharmacist-led medication reviews, to identify the elements that limit their replicability and robustness, and to propose recommendations for an appropriate conduction and reporting. METHODS: A meta-research study was conducted. Systematic searches of the PubMed, Scopus, and Web of Science databases were performed to identify meta-analyses of pharmacist services. Meta-analyses assessing the effect of pharmacist-led medication reviews were selected for data extraction, analysis and replication. Two replication exercises were performed for the two most common outcomes: (i) considering the data provided by authors to construct the meta-analysis and (ii) considering the raw data available in the primary studies included. Prediction intervals (PI), fragility index (FI), and number needed to treat (NNT) were also calculated for each replicated meta-analysis. RESULTS: Nine studies reporting meta-analyses about pharmacist-led medication review were found comprising 30 different outcomes. Eleven meta-analyses, including six for hospital admission and five for mortality, were replicated. In five meta-analyses, the pooled effect sizes of the replicated meta-analyses differed from the original ones. Only four meta-analyses mentioned the statistical method used. Other meta-analytic parameters (e.g., q-value, tau2) were omitted in all studies. In nine meta-analyses, the data from primary studies had been incorrectly extracted for at least one variable. The PI demonstrated that the uncertainty intervals of the effect sizes were always underestimated by the authors. NNTs showed wide intervals, ranging from benefit to harm, in almost all meta-analyses. Nine recommendations to facilitate the replication of a meta-analysis were proposed: providing all original data needed to build the analysis; informing about the imputed data or data obtained from different sources; performing sensitivity analyses for imputed or unpublished data; inform about all the statistical methods used; providing all statistical results; and reporting the PI, FI and NNT. CONCLUSION: Errors in data extraction and poor reporting of meta-analytic parameters are common in the pharmacy literature. We proposed nine recommendations to enhance data reproducibility and interpretability. Journal editors and peer reviewers should ensure that authors strictly comply with minimum standards for conduction and reporting of meta-analyses.

Methodological quality and risk of bias of meta-analyses of pharmacy services: A systematic review.

BACKGROUND: A suboptimal meta-analysis with misleading conclusions, frequently published in the healthcare journals, can compromise decision making in clinical practice. OBJECTIVE: To evaluate the reporting quality, methodological quality, and risk of bias of meta-analyses of pharmacy services. METHODS: Systematic searches to identify all the meta-analyses reporting the effect of pharmacy services were performed in PubMed, Scopus, and Web of Science. The reporting quality, the methodological quality, and the risk of bias of the included meta-analyses were evaluated using PRISMA checklist, R-AMSTAR, and ROBIS, respectively. RESULTS: A total of 109 meta-analyses were eligible for the study. The heterogeneity, the quality of evidence, and the quality analyses were poorly reported on authors' conclusions (14.3%, 14.7%, and 17.4%, respectively). The median scores of PRISMA and R-AMSTAR tolls were 24 (IQR 21.75-25), and 30 (IQR 27-32.5), respectively. Additionally, most of the studies were considered as high risk of bias (n = 83, 76.1%). No association between the date of publication and guideline compliance exists. PRISMA score was higher in studies published in high impact factor journals (rho = 0.313; p = 0.002), in articles that reported the quality of evidence obtained (p = 0.018), and in those that stated the need for future studies in their conclusions (p = 0.011). R-AMSTAR score was higher in studies published in high impact factor journals (rho = 0.338; p = 0.001), in those which reported the quality of evidence (p = 0.002), and in articles that described the quality analyses in their conclusions (p = 0.046). An association between the risk of bias and the recognition of the need for further studies in their conclusions (p = 0.041) was also found. CONCLUSION: The rapid increase of the meta-analyses of pharmacy services was not associated with higher quality. Mechanistic meta-analyses with poor conclusions are commonly published. Quality of the analyses, strength of evidence, heterogeneity, and absence of confrontation with current guidelines are rarely considered when synthetizing evidence and making recommendations.

Cost-Effectiveness of Molecular Method Diagnostic for Rapid Detection of Antibiotic-Resistant Bacteria.

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.

Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial.

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.

Analysis of completeness for spontaneous reporting of disease-modifying therapies in multiple sclerosis.

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.

Outcome measures for disease-modifying therapies in relapsing multiple sclerosis randomized clinical trials: a scoping review protocol.

OBJECTIVE: The objective of the review is to explore randomized controlled trials on disease-modifying therapies for relapsing multiple sclerosis to identify and quantify the different outcome measures, instruments and definitions of efficacy, safety outcomes, health-related quality of life instruments and population subgroups. INTRODUCTION: A wide range of therapies are available for relapsing multiple sclerosis, as well as a wide range of outcome measures and definitions, which can be explained by the absence of a core outcome set for this disease. Establishing a core outcome set is fundamental for guiding future studies as they improve the consistency and relevance of new findings and enable the results of trials to be compared and combined. These features are especially important for relapsing multiple sclerosis due to the limited number of head-to-head studies on this disease. Although many systematic reviews and meta-analyses have focused on the efficacy and safety of disease-modifying therapies in relapsing multiple sclerosis, none have had the specific objective of mapping outcome measures. INCLUSION CRITERIA: This review will consider randomized controlled trials that explore populational subgroups, efficacy, safety outcomes, health-related quality of life instruments and their definitions in the context of disease-modifying therapies for adults with relapsing multiple sclerosis. METHODS: Electronic searches will be performed in PubMed, Scopus, the Cochrane Library, ClinicalTrials.gov, and JBI Evidence Synthesis with no time limit. Two researchers will independently select registries (screening and eligibility steps) and extract data on study characteristics, outcome measures, definitions and population subgroups. Data will be presented in graphical or tabular form, accompanied by a narrative summary.

Clinical pharmacy services in Brazil, particularly cardiometabolic diseases: a systematic scoping review and meta-analyses.

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.

Mapping the characteristics of meta-analyses of pharmacy services: a systematic review.

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.

Reliability in long-term clinical studies of disease-modifying therapies for relapsing-remitting multiple sclerosis: A systematic review.

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.

Efficacy and safety of the pharmacotherapy used in the management of hyperkalemia: a systematic review.

BACKGROUND: Although the management of hyperkalemia follows expert guidelines, treatment approaches are based on traditionally accepted practice standards. New drugs have been assessed such as sodium zirconium cyclosilicate and patiromer; however, their safety and efficacy or effectiveness have not yet been compared to traditional pharmacotherapy. OBJECTIVE: The present systematic review had the purpose to evaluate the efficacy, effectiveness, and safety of hyperkalemia pharmacotherapies. METHODS: PubMed, LILACS, Cochrane Library, and ClinicalTrials were searched through November 2018. Clinical trial, cohort and case-control were searched. The risk of bias (RoB v2.0 and ROBINS-I) and quality of evidence (GRADE) at the level of outcomes were assessed. RESULTS: Sixteen clinical trials and one retrospective cohort were identified regarding efficacy and safety of 24 different alternatives. The management of hyperkalemia remains empirical and off-label, since sodium zirconium cyclosilicate and patiromer are not available in several countries and further studies are required to assess efficacy, effectiveness and safety. Sodium or calcium polystyrene sulfonate (moderate confidence), sodium zirconium cyclosilicate (moderate confidence), and insulin plus dextrose (moderate confidence) showed superior efficacy to, respectively, placebo, no treatment, placebo, and dextrose. Other therapies (low confidence) showed similar efficacy compared to active or inactive alternatives. Most of the adverse events reported were nonspecific, so it was not possible to assign the cause and to classify as defined or probable. CONCLUSIONS: Comparative cohort and case-control studies are need to evaluate the safety and effectiveness of new and traditional pharmacotherapies to support the development of guidelines about acute and chronic hyperkalemia, with high-quality evidence.

Safety outcomes of disease-modifying therapies for relapsing-remitting multiple sclerosis: A network meta-analysis.

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.

Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: A Network Meta-Analysis.

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).

Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review protocol

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)

Pharmacist-led interventions in Brazil: a scoping review protocol

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)