Pharmaceutical policies: effects of policies regulating drug marketing.

BACKGROUND: The costs of developing new treatments and bringing them to the market are substantial. The pharmaceutical industry uses drug promotion to gain a competitive market share, and drive sale volumes and industry profitability. This involves disseminating information about new treatments to relevant targets. However, conflicts of interest can arise when profits are prioritised over patient care and its benefits. Drug promotion regulations are complex interventions that aim to prevent potential harm associated with these activities. OBJECTIVES: To assess the effects of policies that regulate drug promotion on drug utilisation, coverage or access, healthcare utilisation, patient outcomes, adverse events and costs. SEARCH METHODS: We searched Epistemonikos for related reviews and their included studies. To find primary studies we searched MEDLINE, CENTRAL, Embase, EconLit, Global Index Medicus, Virtual Health Library, INRUD Bibliography, two trial registries and two sources of grey literature. All databases and sources were searched in January 2023. SELECTION CRITERIA: We planned to include studies that assessed policies regulating drug promotion to consumers, healthcare professionals or regulators and third-party payers, or any combination of these groups.In this review we defined policies as laws, rules, guidelines, codes of practice, and financial or administrative orders made by governments, non-government organisations or private insurers. One of the following outcomes had to be reported: drug utilisation, coverage or access, healthcare utilisation, patient health outcomes, any adverse effects (unintended consequences), and costs. The study had to be a randomised or non-randomised trial, an interrupted time series analysis (ITS), a repeated measures (RM) study or a controlled before-after (CBA) study. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed eligibility for inclusion of studies. When consensus was not reached, any disagreements were discussed with a third review author.  We planned to use the criteria suggested by Cochrane Effective Practice and Organisation of Care (EPOC) to assess the risk of bias of included studies. For randomised trials, non-randomised trials, and CBA studies, we planned to estimate relative effects, with 95% confidence intervals (CI). For dichotomous outcomes, we planned to report the risk ratio (RR) when possible and adjusted for baseline differences in the outcome measures. For ITS and RM, we planned to compute changes along two dimensions: change in level and change in slope. We planned to undertake a structured synthesis following EPOC guidance.  MAIN RESULTS: The search yielded 4593 citations, and 13 studies were selected for full-text review. No study met the inclusion criteria. AUTHORS' CONCLUSIONS: We sought to assess the effects of policies that regulate drug promotion on drug use, coverage or access, use of health services, patient outcomes, adverse events, and costs, however we did not find studies that met the review's inclusion criteria. As pharmaceutical policies that regulate drug promotion have untested effects, their impact, as well as their positive and negative influences, is currently only a matter of opinion, debate, informal or descriptive reporting. There is an urgent need to assess the effects of pharmaceutical policies that regulate drug promotion using well-conducted studies with high methodological rigour.

Use of second-generation antipsychotics in autism spectrum disorder: a systematic review and meta-analysis protocol.

INTRODUCTION: Atypical antipsychotics have been studied to treat autism spectrum disorder (ASD). However, like little is known about whether these drugs are effective and safe when compared in controlled and non-controlled settings. This study aims to assess the efficacy and safety of second-generation antipsychotics in ASD in randomised controlled trials (RCT) and observational studies. METHODS AND ANALYSIS: This systematic review will include RCT and prospective cohorts evaluating second-generation antipsychotics in people 5 years and older diagnosed with ASD. Searches will be conducted in Medline, Embase, Cochrane Library, Epistemonikos, Lilacs, CINAHL, PsycINFO, trial registries and grey literature databases without restriction on publication status, year of publication and language. The primary outcomes will be symptoms of aggressive behaviour, quality of life for the individual or their careers, and discontinuation or dropouts/withdrawals of antipsychotics due to adverse events. The secondary outcomes are other not serious adverse events and adherence to pharmacotherapy. Selection, data extraction, and quality assessment will be performed by pairs of reviewers, independently. The Risk of Bias 2 (RoB 2) and Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tools will be used to assess the risk of bias in the included studies. If appropriate, a meta-analysis and network meta-analysis will be conducted to synthesise the results. The overall quality of the evidence for each outcome will be determined by the Recommendation, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This study will systematically summarise the existing evidence evaluating the use of second-generation antipsychotics for treating ASD, in controlled and uncontrolled studies. The results of this review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022353795.

Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017.

OBJECTIVE: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. METHODS: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. RESULTS: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. CONCLUSION: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Uso de antipsicóticos atípicos no tratamento da esquizofrenia no Sistema Único de Saúde do Brasil: estudo de coorte, 2008-2017 / Uso de antipsicóticos atípicos en el tratamiento de la esquizofrenia en el Sistema Único de Salud de Brasil: estudio de 2008 a 2017 / Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017

Objective: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. Methods: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. Results: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. Conclusion: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Objetivo: investigar las características sociodemográficas y clínicas de los usuarios de antipsicóticos atípicos, atendidos por el Componente Especializado de Asistencia Farmacéutica (CEAF) para el tratamiento de la esquizofrenia en Brasil, de 2008 a 2017. Métodos: estudio de cohorte retrospectivo utilizando registros de autorizaciones de trámites de alta complejidad del Sistema de Información Ambulatorio del SUS, de todos los estados brasileños. Resultados: de los 759.654 usuários identificados, el 50,5% era del sexo feminino de la región Sudeste (60,2%), diagnosticadas con esquizofrenia paranoide (77,6%). Hubo una mayor prevalencia de risperidona (63,3%) entre niños y adolescentes; de olanzapina (34,0%) en adultos; y quetiapina (47,4%) en ancianos. Alrededor del 40% de los niños/adolescentes estaba bajo uso no autorizado de antipsicóticos según la edad. La adherencia al CEAF fue alta (82%), y la deserción a los seis meses fue del 24%. Conclusión: los hallazgos amplían el conocimiento sobre el perfil sociodemográfico y clínico de los usuarios y destacan la práctica del uso off-label.

Objetivo: investigar características sociodemográficas e clínicas de usuários de antipsicóticos atípicos assistidos pelo Componente Especializado da Assistência Farmacêutica (CEAF), para tratamento da esquizofrenia no Brasil, de 2008 a 2017. Métodos: estudo de coorte retrospectivo utilizando registros das autorizações de procedimentos de alta complexidade do Sistema de Informações Ambulatoriais do Sistema Único de Saúde, de todos os estados brasileiros. Resultados: dos 759.654 usuários, 50,5% eram do sexo feminino, da região Sudeste (60,2%), diagnosticados com esquizofrenia paranoide (77,6%); observou-se maior prevalência de uso da risperidona (63,3%) entre crianças/adolescentes; de olanzapina (34,0%), em adultos; e quetiapina (47,4%), nos idosos; cerca de 40% das crianças/ adolescentes estavam sob uso off-label de antipsicóticos segundo a idade; a adesão ao CEAF foi alta (82%), e o abandono em seis meses foi de 24%. Conclusão: os achados ampliam o conhecimento sobre perfil sociodemográfico e clínico dos usuários e destacam a prática do uso off-label.

Varenicline for Tobacco-Dependent Adults Who Are Not Ready to Discontinue Use: A Systematic Review and Meta-Analysis.

Rationale: Not all individuals with tobacco dependence are ready to give up smoking. Research reveals behavioral differences between adults ready to discontinue tobacco use and those who are not. Thus, the interventions applied to these populations might differ. However, the evidence of using varenicline in individuals who are not ready to discontinue tobacco use is uncertain. Objectives: To determine if, in tobacco-dependent adults who report not being ready to discontinue tobacco use, clinicians should begin treatment with varenicline or wait until subjects are ready to discontinue tobacco use. Methods: We conducted a systematic review to assess the effectiveness and safety of treatment with varenicline in tobacco-dependent adults who are not ready to discontinue tobacco use. We systematically searched the Cumulative Index to Nursing and Allied Health Literature, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials comparing varenicline versus placebo for individuals who were not ready to discontinue tobacco use. Outcomes of interest include point prevalence abstinence during treatment or at six months or longer, smoking reduction, motivation to quit, adverse events, and withdrawal symptoms. Two authors independently extracted data and assessed eligibility and risk of bias using a standardized data collection form. We followed the Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of evidence. Results: Five trials met our inclusion criteria. All 2,616 participants were adults who were not ready to discontinue tobacco use at study entry. For 7-day point prevalence abstinence at six months or longer, high-certainty evidence suggested that varenicline increased abstinence compared with placebo (relative risk, 2.00 [95% confidence interval (CI), 1.70-2.35]; absolute risk reduction, 173 more per 1,000 [95% CI, 121 more to 234 more]). We identified moderate-certainty evidence suggesting that varenicline increased serious adverse events (relative risk, 1.75 [95% CI, 0.98-3.13]; absolute risk reduction, 12 more per 1,000 [95% CI, 0 fewer to 35 more]). For withdrawal, low-certainty evidence suggested that varenicline treatment was associated with a lower symptom score (mean difference, 1.54 points lower; 95% CI, 2.15-0.93 points lower; low certainty) assessed using the Brief Questionnaire of Smoking Urges. Conclusions: In tobacco-dependent adults who are not ready to discontinue tobacco use, initiating varenicline treatment results in a large increase in abstinence and likely results in a slight increase in serious adverse events.

Improving the adherence to COVID-19 preventive measures in the community: Evidence brief for policy.

Objectives: To identify evidence-based strategies to improve adherence to the preventive measures against the coronavirus disease (COVID-19) at the community level. Method: This is an evidence brief for policy, combining research evidence specific to contextual knowledge from stakeholders. A systematic search was performed in 18 electronic databases, gray literature, and a handle search, including only secondary and tertiary studies that focused on the adherence of the general population to COVID-19 preventive measures in the community. Two reviewers, independently, performed the study selection, data extraction, and assessment of the quality of the studies. Relevant evidence has been synthesized to draft evidence-based strategies to improve adherence. These strategies were circulated for external endorsement by stakeholders and final refinement. Endorsement rates >80%, 60-80% and <60% were considered high, moderate, and low respectively. Results: Eleven studies, with varying methodological qualities were included: high (n = 3), moderate (n = 3), low (n = 1), and critically low (n = 4). Three evidence based strategies were identified: i. Risk communication; ii. Health education to the general public, and iii. Financial support and access to essential supplies and services. The rates of endorsement were: 83% for risk communication, 83% for health education, and 92% for financial support and access to essential supplies and services. The evidence showed that an increase in knowledge, transparent communication, and public awareness about the risks of COVID-19 and the benefits of adopting preventive measures results in changes in people's attitudes and behavior, which can increase adherence. In addition, the guarantee of support and assistance provides conditions for people to adopt and sustain such measures. Conclusions: These strategies can guide future actions and the formulation of public policies to improve adherence to preventive measures in the community during the current COVID-19 pandemic and other epidemics.

Extended Duration Treatment of Tobacco Dependence: A Systematic Review and Meta-Analysis.

Rationale: The American Thoracic Society (ATS) developed a clinical practice guideline on initiating pharmacologic treatment in tobacco-dependent adults. Controller pharmacotherapies treat tobacco dependence effectively when taken as prescribed, but relapse after pharmacologic discontinuation is common. Objectives: To evaluate the effectiveness and safety of initiating controller for an extended (>12 wk) versus a standard duration (6-12 wk) in tobacco-dependent adults. Methods: We systematically searched PubMed, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to December 2021 to identify randomized controlled trials comparing extended versus standard duration of controllers for tobacco-dependent adults. We conducted meta-analyses using the Mantel-Haenszel method with random effects model. Outcomes of interest include point-prevalent abstinence at 1-year follow-up or longer, relapse, adverse events, quality of life, and withdrawal symptoms. Subgroup analyses were conducted according to types of treatment and duration of extended therapy when feasible. We assessed the certainty of the estimate following the grading of recommendations, assessment, development and evaluation methodology. Results: We included 13 randomized controlled trials including 8,695 participants that directly compared extended- (>12 wk) versus standard-duration controller therapy with varenicline, bupropion, or nicotine replacement therapy. Compared with standard-duration controller therapy, extended-duration controller therapy probably increased abstinence at 1-year follow-up, measured as 7-day point-prevalence abstinence (relative risk, 1.18; 95% confidence interval [CI], 1.05-1.33; moderate certainty). Extended-duration controller therapy probably reduced relapse compared with standard-duration controller therapy, assessed at 12-18 months after initiation of therapy (hazard ratio, 0.43; 95% CI, 0.29-0.64; moderate certainty). Moderate certainty evidence also suggested that extended-duration controller therapy probably did not increase risk of serious adverse events (relative risk, 1.37; 95% CI, 0.79-2.36). Conclusions: This systematic review supported the recommendation for extended-duration therapy with controllers. Further studies on optimal extended duration are warranted.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Efficacy and safety of repellents marketed in Brazil against bites from Aedes aegypti and Aedes albopictus: A systematic review.

BACKGROUND: Dengue, Zika and Chikungunya viruses represent a serious public health problem. No evidence is available on the efficacy of repellents commercially available in Brazil. This systematic review assessed the efficacy and safety of products containing repellents commercially available in Brazil for protection against bites from Aedes aegypti and Aedes albopictus. METHODS: We performed a systematic review using the CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science, AMED, LILACS and Scopus databases. Randomized clinical trials and non-randomized clinical trials comparing topical repellent products registered with the Brazilian Health Surveillance Agency were included. Main outcomes of interest investigated were adverse effects, percentage repellency and protection time against bites. Pairs of reviewers selected the studies, extracted the data and evaluated the risk of bias. RESULTS: Sixteen studies were included. No adverse effects were reported by the studies. Against Ae. aegypti: protection time using DEET (10% and 20%-spray) was similar to IR3535 (10% and 20%-spray) and longer than citronella (5%-spray). DEET (25%-solution) had longer protection time than eucalyptus (25%-solution), while DEET (20%-lotion) had longer protection time than citronella (10%-lotion). There was no difference in protection time between herbal repellents. DEET (7% and 15%- spray) had higher percentage repellency compared to both icaridin (7%-spray) and IR3535 (20%-spray). Against Ae. albopictus: DEET (15%-spray) had a similar protection time to icaridin (20%-spray), but longer than citronella (10%-spray). CONCLUSION: DEET proved more effective than the other synthetic and natural repellents marketed in Brazil for protecting against bites from the mosquito species investigated. All repellents studied exhibited satisfactory safety profile.

Switching Between Second-Generation Antipsychotics in Patients with Schizophrenia and Schizoaffective Disorder: 10-Year Cohort Study in Brazil.

Objective: Switching between second-generation antipsychotics (SGAs) is a common clinical practice in the treatment of schizophrenia and schizoaffective disorders due to differences in the drugs' tolerability and safety profiles as well as the challenge of obtaining an ideal response. However, the factors associated with SGA switching remain uncertain and related real-world data are scarce. The main objective was to identify the factors associated with the switching of SGAs in patients with schizophrenia or schizoaffective disorder. Methods: We conducted a retrospective cohort study of outpatients with schizophrenia or schizoaffective disorder, who were aged ≥18 years and received a SGA (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a Brazilian pharmaceutical assistance program for at least 3 months. We identified SGA users from 2008 to 2017 by using a national administrative database (Ambulatory Information System-SIA/SUS). The factors associated with the switches were evaluated by Cox proportional hazards regression and adjusted for sex and age; the confidence interval was set at 95% (95% CI). Results: In total, 563,765 patients were included. Female sex, advanced age of ≥70 years, residence in the Brazilian northeast region, and the type of antipsychotic used were associated with an increased risk of switching (p < 0.001). The incidence of switching ranged from 37.6/100 person-years for clozapine users to 58.2/100 person-years for risperidone users. Compared to the adjusted hazard ratio, for clozapine users, the corresponding ratios for risperidone, ziprasidone, quetiapine and olanzapine were 1.59 (95% CI, 1.57-1.61), 1.41 (95% CI, 1.39-1.44), 1.25 (95% CI, 1.23-1.26) and 1.11 (95% CI, 1.10-1.12) respectively. Conclusion: The groups most susceptible to SGA switching in real-life setting were older individuals, women, and those living in the Brazilian northeast region. Risperidone was associated with the highest risk of switching and as expected, clozapine was associated with the lowest risk of switching than that associated with the other SGAs.

Gender differences in the use of atypical antipsychotics in early-onset schizophrenia: a nationwide population-based study in Brazil.

BACKGROUND: The use of atypical antipsychotics for the treatment of schizophrenia and other mental disorders in populations under 18 years of age is increasing worldwide. Little is known about treatment patterns and the influence of gender differences, which may be a predictor of clinical outcomes. The aim of this study was to investigate gender differences in the use of atypical antipsychotics in patients with early-onset schizophrenia (EOS) assisted by the public health system in Brazil. METHODS: We conducted a cross-sectional study of outpatients with EOS aged 10 to 17 years who received at least one provision of atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a large Brazilian pharmaceutical assistance programme. Data were retrieved from a nationwide administrative database from 2008 to 2017. RESULTS: Of the 49,943 patients with EOS, 63.5% were males, and the mean age was 13.6 years old. The patients were using risperidone (62.5%), olanzapine (19.6%), quetiapine (12.4%), ziprasidone (3.3%) and clozapine (2.2%). We found gender differences, especially in the 13-17 year age group (65.1% for males vs. 34.9% for females, p < 0.001), in the use of risperidone (72.1% for males vs. 27.9% for females, p < 0.001) and olanzapine (66.5% for males vs. 33.5% for females, p < 0.001). Only in the 13 to 17 years age group were the prescribed doses of olanzapine (p = 0.012) and quetiapine (p = 0.041) slightly higher for males than for females. CONCLUSIONS: Our findings showed gender differences among patients diagnosed with EOS and who received atypical antipsychotics. More attention should be devoted to gender differences in research and clinical practice.

Improving Care for Deinstitutionalized People With Mental Disorders: Experiences of the Use of Knowledge Translation Tools.

Background: The deinstitutionalization process is complex, long-term and many countries fail to achieve progress and consolidation. Informing decision-makers about appropriate strategies and changes in mental health policies can be a key factor for it. This study aimed to develop an evidence brief to summarize the best available evidence to improve care for deinstitutionalized patients with severe mental disorders in the community. Methods: We used the SUPPORT (Supporting Policy Relevant Reviews and Trials) tools to elaborate the evidence brief and to organize a policy dialogue with 24 stakeholders. A systematic search was performed in 10 electronic databases and the methodological quality of systematic reviews (SRs) was assessed by AMSTAR 2. Results: Fifteen SRs were included (comprising 378 studies and 69,736 participants), of varying methodological quality (3 high-quality SRs, 2 moderate-quality SRs, 7 low-quality SRs, 3 critically low SRs). Six strategies were identified: (i). Psychoeducation; (ii). Anti-stigma programs, (iii). Intensive case management; (iv). Community mental health teams; (v). Assisted living; and (vi). Interventions for acute psychiatric episodes. They were associated with improvements on a global status, satisfaction with the service, reduction on relapse, and hospitalization. Challenges to implementation of any of them included: stigma, the shortage of specialized human resources, limited political and budgetary support. Conclusions: These strategies could guide future actions and policymaking to improve mental health outcomes.

Risks of Adverse Neonatal Outcomes in Early Adolescent Pregnancy Using Group Prenatal Care as a Strategy for Public Health Policies: A Retrospective Cohort Study in Brazil.

Background: Adolescent pregnancy is a public health concern and many studies have evaluated neonatal outcomes, but few have compared younger adolescents with older using adequate prenatal care. Objective: To compare the risks of adverse neonatal outcomes in younger pregnant adolescents who are properly followed through group prenatal care (GPC) delivered by specialized public services. Methods: This retrospective cohort study followed pregnant adolescents (aged 10-17 years) who received GPC from specialized public services in Brazil from 2009 to 2014. Data were obtained from medical records and through interviews with a multidisciplinary team that treated the patients. The neonatal outcomes (low birth weight, prematurity, Apgar scores with 1 and 5 min, and neonatal death) of newborns of adolescents aged 10-13 years were compared to those of adolescents aged 14-15 years and 16-17 years. Incidence was calculated with 95% confidence intervals (CIs) and compared over time using a chi-squared test to observe trends. Poisson Multivariate logistic regression was used to adjust for confounding variables. The results are presented as adjusted relative risks or adjusted mean differences. Results: Of the 1,112 adolescents who were monitored, 758 were included in this study. The overall incidence of adverse neonatal outcomes (low birth weight and prematurity) was measured as 10.2% (95% CI: 9.7-11.5). Apgar scores collected at 1 and 5 min were found to be normal, and no instance of fetal death occurred. The incidence of low birth weight was 16.1% for the 10-13 age group, 8.7% for the 14-15 age group and 12.1% for the 16-17 age group. The incidence of preterm was measured at 12, 8.5, and 12.6% for adolescents who were 10-13, 14-15, and 16-17 years of age, respectively. Neither low birth weight nor prematurity levels significantly differed among the groups (p > 0.05). The infants born to mothers aged 10-13 years presented significantly (p < 0.05) lower Apgar scores than other age groups, but the scores were within the normal range. Conclusions: Our findings showed lower incidence of neonatal adverse outcomes and no risk difference of neonatal outcomes in younger pregnancy adolescents. It potentially suggests that GPC model to care pregnant adolescents is more important than the age of pregnant adolescent, however further research is needed.

Data Sources for Drug Utilization Research in Brazil-DUR-BRA Study.

Background: In Brazil, studies that map electronic healthcare databases in order to assess their suitability for use in pharmacoepidemiologic research are lacking. We aimed to identify, catalogue, and characterize Brazilian data sources for Drug Utilization Research (DUR). Methods: The present study is part of the project entitled, "Publicly Available Data Sources for Drug Utilization Research in Latin American (LatAm) Countries." A network of Brazilian health experts was assembled to map secondary administrative data from healthcare organizations that might provide information related to medication use. A multi-phase approach including internet search of institutional government websites, traditional bibliographic databases, and experts' input was used for mapping the data sources. The reviewers searched, screened and selected the data sources independently; disagreements were resolved by consensus. Data sources were grouped into the following categories: 1) automated databases; 2) Electronic Medical Records (EMR); 3) national surveys or datasets; 4) adverse event reporting systems; and 5) others. Each data source was characterized by accessibility, geographic granularity, setting, type of data (aggregate or individual-level), and years of coverage. We also searched for publications related to each data source. Results: A total of 62 data sources were identified and screened; 38 met the eligibility criteria for inclusion and were fully characterized. We grouped 23 (60%) as automated databases, four (11%) as adverse event reporting systems, four (11%) as EMRs, three (8%) as national surveys or datasets, and four (11%) as other types. Eighteen (47%) were classified as publicly and conveniently accessible online; providing information at national level. Most of them offered more than 5 years of comprehensive data coverage, and presented data at both the individual and aggregated levels. No information about population coverage was found. Drug coding is not uniform; each data source has its own coding system, depending on the purpose of the data. At least one scientific publication was found for each publicly available data source. Conclusions: There are several types of data sources for DUR in Brazil, but a uniform system for drug classification and data quality evaluation does not exist. The extent of population covered by year is unknown. Our comprehensive and structured inventory reveals a need for full characterization of these data sources.

Critical appraisal and comparison of recommendations of clinical practice guidelines for treatment of schizophrenia in children and adolescents: a methodological survey protocol.

INTRODUCTION: The number of clinical practice guidelines (CPGs) have increased substantially mainly in the paediatric area of mental health. However, little is known about the quality or how recommendations for the treatment of disorders such as schizophrenia in children and adolescents have changed over time. The aim of this study will be to assess the quality of the development of CPGs for the treatment and management of schizophrenia in children and adolescents over time using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and to compare the recommendations and interventions described in these documents. METHODS AND ANALYSIS: CPGs will be identified using a prospective protocol through a systematic search of multiple databases (Medline, Embase, Health Systems Evidence, Epistemonikos, Lilacs, etc) and guideline websites from 2004 to December 2020. The quality of the guidelines will be assessed by three reviewers, independently using the AGREE II. CPGs will be considered of high-quality if they scored ≥60% in four or more domains of the AGREE II instrument. Non-parametric tests will be used to test for the change of quality over time. We will summarise the different evidence grading systems and compare the recommendations. ETHICS AND DISSEMINATION: Ethical approval is not required since it is a literature-based study. Future results of the research can be submitted for publication in scientific journals of high impact, peer reviewed and also published in national and international conferences. The results derived from this study will contribute to the improvement of health institutions and policies, informing about existing recommendation guidelines and about deficiencies and qualities found in those. This study may also identify key areas for future research. This study may guide the search and choice for high quality CPGs by health policy makers and health professionals and subsidise future adaptations. PROTOCOL REGISTRATION NUMBER: CRD42020164899.

Factors associated with thrombocytopenia in patients with dengue fever: a retrospective cohort study.

OBJECTIVE: Some patients with dengue fever tend to develop thrombocytopenia during the course of infection and are thus vulnerable to haemorrhagic manifestations and other complications. However, the factors associated with the development of thrombocytopenia are unknown. We aimed to identify factors associated with an increased risk of thrombocytopenia and haematological changes in patients with confirmed dengue fever. DESIGN: Retrospective cohort study. SETTING: Brazilian multicentre primary care databases. PARTICIPANTS: 387 patients had positive laboratory serological confirmation of dengue infection during 2014. The data were identified from two databases: Notification of Injury Information System (SINAN) and Municipal Laboratory. MAIN OUTCOME MEASURE: The presence of thrombocytopenia (platelet count <1 50×109/L). The associations of factors that predisposed patients to thrombocytopenia and haematological changes were analysed using logistic regression. ORs and 95% CIs were calculated. RESULTS: Among 387 patients, 156 had both dengue and thrombocytopenia. The risk factors associated with thrombocytopenia included male sex (OR: 1.77, 95% CI: 1.16 to 2.71, p=0.007), age of 46-64 years (OR: 2.20, 95% CI: 1.15 to 4.21, p=0.009) or ≥65 years (OR: 3.02, 95% CI: 1.40 to 6.50, p=0.002), presence of leucopenia (OR: 6.85, 95% CI: 4.27 to 10.99, p<0.001) and high mean corpuscular haemoglobin (MCH) levels (OR: 2.00, 95% CI: 1.29 to 3.12, p=0.005). CONCLUSION: Older age, male sex, presence of leucopenia and high MCH levels were identified as risk factors associated with the development of thrombocytopenia in this population.

Initiating Pharmacologic Treatment in Tobacco-Dependent Adults. An Official American Thoracic Society Clinical Practice Guideline.

Background: Current tobacco treatment guidelines have established the efficacy of available interventions, but they do not provide detailed guidance for common implementation questions frequently faced in the clinic. An evidence-based guideline was created that addresses several pharmacotherapy-initiation questions that routinely confront treatment teams.Methods: Individuals with diverse expertise related to smoking cessation were empaneled to prioritize questions and outcomes important to clinicians. An evidence-synthesis team conducted systematic reviews, which informed recommendations to answer the questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in the estimated effects and the strength of recommendations.Results: The guideline panel formulated five strong recommendations and two conditional recommendations regarding pharmacotherapy choices. Strong recommendations include using varenicline rather than a nicotine patch, using varenicline rather than bupropion, using varenicline rather than a nicotine patch in adults with a comorbid psychiatric condition, initiating varenicline in adults even if they are unready to quit, and using controller therapy for an extended treatment duration greater than 12 weeks. Conditional recommendations include combining a nicotine patch with varenicline rather than using varenicline alone and using varenicline rather than electronic cigarettes.Conclusions: Seven recommendations are provided, which represent simple practice changes that are likely to increase the effectiveness of tobacco-dependence pharmacotherapy.

Use of IMMPACT domains in clinical trials of acupuncture for chronic pain: A methodological survey.

Acupuncture is one of the therapeutic resources used for the management of chronic pain. Variability in outcome measurements in randomized clinical trials of non-oncologic chronic pain (RCT-NOCP) generates inconsistencies in determining effects of treatments. The objective of this survey was to assess the adherence to the recommendations made by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in the measurement of RCT-NOCP of acupuncture. This methodological research made a systematic search for eligible studies from different sources of information. Eligible studies included those with number of patients ≥100, who randomized and allocated patients with chronic non-oncologic pain to be treated with acupuncture or with "sham" acupuncture, or non-acupuncture. This research included the recommendations for IMMPACT in the measurement of RCT-NOCP: presence of outcomes pain, physical function, emotional state and improvement perception of patient, the source of the outcome information pain and the tools used to measure such domains. From a total of 1,386 studies, 24 were included in this survey. Eleven studies presented low risk of bias. Pain outcome was measured in 23 studies, physical function in 22 studies, emotional state in 14 studies and improvement perception of patient in one study. As for the pain outcome, the patient was the information source in 50% of the studies. The measurement tools recommended for IMMPACT were included in eight studies (35%) that evaluated pain, one study that evaluated the emotional state (7%), and one study that evaluated the improvement perception and satisfaction of patient. It was observed that studies which did not adhere to the recommendations had more favorable results for acupuncture in the outcome pain. This study concludes that randomized clinical trials that used acupuncture to manage chronic pain failed to adhere to IMMPACT recommendations. Clinical societies and IMMPACT do not share the same recommendations. This fact reflects in the diversity of outcomes and instruments adopted in the studies, making it difficult to compare the results.

Adverse Events in Patients With Rheumatoid Arthritis and Psoriatic Arthritis Receiving Long-Term Biological Agents in a Real-Life Setting.

Background: Biological agents used for the treatment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are associated with serious adverse effects (SAEs). Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to a relative lack of long-term safety data. Objective: To determine the frequency and severity of adverse effects associated with the long-term use of biologics in the treatment of PsA and RA, and possible risk factors for such events in a real-life setting. Methods: We conducted a longitudinal study in PsA and RA patients only taking long-term biological agents from 2003 to 2011. Sources of information included dispensing pharmacy data and interviews with patients. Research staff conducted telephone interviews with patients inquiring about any apparent medication-related adverse drug reactions (ADRs) or SAEs. ADR/SAE's data was based on pharmacy reports. We conducted a multivariate analysis to identify the factors associated with the risk of ADRs. Results: Of the 305 patients identified, we interviewed 268 patients. Most of these were taking adalimumab 127 (47.4%), 52 (19.4%) etanercept, 42 (15.7%) infliximab, 25 (9.3%) rituximab, 10 (3.7%) abatacept, 9 (3.4%) efalizumab, and 3 (1.1%) tocilizumab. Of the 268 patients, 116 (43.3%) experienced one or more adverse events related to biological agents with 1.6 events per patient, and of these 29 (25%) experienced one or more SAEs, with majority subjected to hospitalizations. The most frequently reported ADRs were administration site reactions as observed in 73 patients (27.2%), infections in 30 patients (11.2%), effects on nervous system in 22 patients (8.2%), and 15 (5.6%) patients withdrew due to ADRs. The use of rituximab was related with less risk of ADR [PR 0.42, 95% CI 0.18-0.96; p = 0.04] than other agents. No other predisposing factors were associated with risk of ADR. The monitoring of patients (medical consultation and laboratory test) was only completed by 48 patients (30.4%). Conclusion: These data showed the early biological experience in Brazil that were associated with ADRs, withdrawals due to ADRs and SAEs. The quantification of adverse effects (serious or nonserious) considering close monitoring and patients' perceptions are increasingly important for future decision-making.

Knowledge Translation for Improving the Care of Deinstitutionalized People With Severe Mental Illness in Health Policy.

BACKGROUND: Knowledge translation (KT) is an effective strategy that uses the best available research evidence to bring stakeholders together to develop solutions and improve public health policy-making. Despite progress, the process of deinstitutionalization in Brazil is still undergoing consolidation, and the changes and challenges that are involved in this process are complex and necessitate evidence-informed decision-making. Accordingly, this study used KT tools to support efforts that aim to improve the care that is available to deinstitutionalized people with severe mental disorders in Brazil. METHODS: We used the Supporting Policy Relevant Reviews and Trials tools for evidence-informed health policymaking and followed eight steps: 1) capacity building; 2) identification of a priority policy issue within a Brazilian public health system; 3) meetings with policy-makers, researchers and stakeholders; 4) development of an evidence brief (EB) that addresses the problem of deinstitutionalization; 5) facilitating policy dialogue (PD); 6) the evaluation of the EB and PD; 7) post-dialogue mini-interviews; and 8) dissemination of the findings. RESULTS: Capacity building and meetings with key informants promoted awareness about the gap between research and practice. Local findings were used to define the problem and develop the EB. Twenty-four individuals (policy-makers, stakeholders, researchers, representatives of the civil society, and public defense) participated in the PD. They received the EB to subsidise their deliberations during the PD, which in turn were used to validate and improve the EB. The PD achieved the objective of promoting an exhaustive discussion about the problem and proposed options and improved communication and interaction among those who are involved in mental health care. The features of both the EB and PD were considered to be favorable and helpful. CONCLUSIONS: The KT strategy helped participants understand different perspectives and values, the interpersonal tensions that exist among those who are involved in the field of mental health, and the strategies that can bridge the gap between research and policy-making. The present findings suggest that PDs can influence practice by promoting greater engagement among stakeholders who formulate or revise mental health policies.