Environmental pollutants as risk factors for autism spectrum disorders: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition affecting communication, social interaction, and behavior. Evidence suggests that environmental pollutants are associated with ASD incidence. This review aimed to analyze the effect of environmental pollutants on ASD. METHODS: Systematic review and meta-analysis of cohort studies evaluated the association between exposure to environmental pollutants and ASD. We searched COCHRANE CENTRAL, MEDLINE, CINAHL, LILACS, EMBASE, PsycINFO, Web of Science, SciELO, and gray literature from inception to January 2023. The model used for meta-analysis was inverse variance heterogeneity (IVhet). The effect measures were the beta coefficient (ß) and the relative risk (RR) with their 95% confidence intervals (95% CI). Sensitivity analyses were carried out using an instrument to screen or diagnose autism. RESULTS: A total of 5,780 studies were identified; 27 were included in the systematic review, and 22 were included in the meta-analysis. These studies included 1,289,183 participants and 129 environmental pollutants. Individual meta-analyses found a significant association between nitrogen dioxide RR = 1.20 (95% CI: 1.03 to 1.38; I2: 91%), copper RR = 1.08 (95% CI: 1.03 to 1.13; I2: 0%), mono-3-carboxy propyl phthalate ß = 0.45 (95% CI: 0.20 to 0.70; I2: 0%), monobutyl phthalate ß = 0.43 (95% CI: 0.13 to 0.73; I2: 0%) and polychlorinated biphenyl (PCB) 138 RR = 1.84 (95% CI: 1.14 to 2.96; I2:0%) with ASD. Subgroup meta-analyses found a significant association with carbon monoxide RR = 1.57 (95% CI: 1.25 to 1.97; I2: 0%), nitrogen oxides RR = 1.09 (95% CI: 1.04 to 1.15; I2: 34%) and metals RR = 1.13 (95% CI: 1.01 to 1.27; I2:24%). CONCLUSION: This study found positive associations nitrogen dioxide, copper, mono-3-carboxypropyl phthalate, monobutyl phthalate, and PCB 138, and the development of ASD, likewise, with subgroups of pollutants carbon monoxide, nitrogen oxides, and metals. Therefore, it is important to identify these risk factors in children and adolescents to contribute to ASD and identify prevention strategies effectively.

Systems approach in planetary health education for medical students: a mixed methods study.

BACKGROUND: Introducing students to the "planetary health lenses" perspective is crucial. Comprehensive strategies for teaching this perspective are lacking, especially in the domains of "interconnection within nature (IWN)" and "systems thinking/complexity." There is also a scarcity of studies assessing medical students' opinions on planetary health and evaluating teaching strategies. OBJECTIVE: To understand Brazilian medical students' perceptions and knowledge of planetary health (PH) and evaluate the application of the educational material "Patient and Clinic through the Lens of Planetary Health," which addresses "IWN" and "complexity" through the sociological lens of Actor-Network Theory, in an integrative course at a medical school in Brazil. METHODS: A mixed-methods, quasi-experimental design involving two medical student classes during 2022/2023. Participants completed a questionnaire on sociodemographic data; pre- and post-intervention closed-ended questions about perceptions related to PH, and an open-ended questionnaire on experience and learning. Each student group presented a portfolio under the planetary health lenses regarding a real patient, developing a network diagram that described the social network involving both human and non-human actors with which this person is interconnected. The cohorts participated in "IWN" activities: a contemplative trail or reflection on belonging to the planet. RESULTS: Ninety-six students and 9 professors participated. The majority of students (66.7%) reported significant or extremely significant learning from the sessions. There was an increase in perception of the need for physicians to incorporate PH into their clinical practice (p = 0.002; r = 0.46) and an intensification of the sense of interconnection with the environment (p = 0.003; r = 0.46). There was a gain in knowledge about how many diseases were related to PH (p < 0.02 for all 13 listed diseases). The majority (83%) found the sessions relevant or highly relevant and commented on their impact, both professionally and personally. CONCLUSIONS: Teaching PH in a medical school allowed students to learn from the patient's perspective, considering psychosocial and environmental determinants, about the intrinsic interdependence between population's health and PH. This strategy made a significant contribution by proposing pioneering didactics and offering valuable insights into the challenges and nuances of teaching PH.

Effect of oral exercises and photobiomodulation therapy in the rehabilitation of patients with mandible fractures: randomized double-blind clinical trial.

Mandible fractures compromise stomatognathic functions, requiring rehabilitation. Evaluate the effectiveness of photobiomodulation (PBM) associated with oral exercises for rehabilitation of patients with mandible fractures. In this randomized clinical trial, we compared PBM with PBM sham in 14 adults with mandibular fractures who underwent surgical intervention. The sessions were performed 24 h and 48 h after surgical procedure, and weekly for 4 weeks after hospital discharge. Both groups performed oral exercises after each PBM session. Restriction of food consistencies, mandibular mobility, pain, and facial sensitivity measured before and after the surgical procedure were the outcomes evaluated, one and 3 months after surgery. Maximum interincisal distances (MID), exercise pain, and restriction of food consistencies were also evaluated during each week of intervention. Both groups showed normal MID (> 35 mm) and food consistencies consumed 1 month after the surgical procedure, with no significant differences between them. Individuals in the PBM group had less pain response to exercise during all the weeks of intervention than the sham group (p < 0.05). The patients presented a reduction in the painful response in MID and mandibular laterality movements 1 month after surgery compared to the preoperative period. In contrast, there was an improvement in laterality in the sham group only 3 months postoperatively and persistent pain in MID. There was no significant difference in facial sensitivity within and between groups during follow-up. The performance of oral exercises associated with PBM effectively facilitated the early rehabilitation of oral functions, with significant gains in pain management.

Clinical practice guidelines in Brazil - developing a national programme.

In Brazil, governmental and non-governmental organisations develop practice guidelines (PGs) in order to optimise patient care. Although important improvements have been made over the past years, many of these documents still lack transparency and methodological rigour. In order to conduct a critical analysis and define future steps in PG development in Brazil, we carried out a structured assessment of strengths, weaknesses, opportunities and threats (SWOT analysis) for the development of a national guideline programme. Participants consisted of academia, methodologists, medical societies and healthcare system representatives. In summary, the PG development process has improved in Brazil and current investments in methodological research and capacity-building are ongoing. Despite the centralised processes for public PGs, standardised procedures for their development are not well established and human resources are insufficient in number and capacity to develop the amount of trustworthy documents needed. Brazil's capacity could be strengthened and initial efforts have been made such as the adoption of standards proposed by world-renowned institutions in PG development and enhancement of the involvement of key stakeholders. Further steps involve the alignment between health technology assessment and PG processes for synergy and the development of a national network to promote the interaction between groups involved in the development of PGs. The lessons learned from this paper could be used to foster debate on guideline development, especially for countries facing similar threats on this topic.

Efficacy of low-level laser for treatment of cancer oral mucositis: a systematic review and meta-analysis.

Review effectiveness of low-level laser therapy (LLLT) in the curative treatment of oral mucositis (OM) in patients receiving cancer therapy. A systematic review with meta-analysis was performed using Medline, Embase, and Cochrane Library databases according to PRISMA guidelines, to identify randomized controlled trials (RCT) on OM in patients during and/or after cancer therapy and in which the therapeutic approach was LLLT, with wavelengths between 632 and 970 nm. We considered grade of OM as a dichotomous variable (such as an improvement or not in severe OM on the seventh day of therapy), with the analysis of subgroups of adult patients or children and adolescents and as a continuous variable with determination of the time for the complete resolution and the subgroup analysis occurred with the strata of the samples by treatment only with chemotherapy or chemotherapy and radiotherapy. This paper's protocol was registered a priori at https://www.crd.york.ac.uk/PROSPERO . We found five RCT (total of 315 patients) with adequate methodology. LLLT was effective, presenting a 62% risk reduction of severe mucositis on the seventh day of evaluation (RR = 0.38 [95% CI, 0.19-0.75]). When we analyzed subgroups, RR was 0.28 (95% CI 0.17-0.46) in the adult studies and 0.90 (95% CI, 0.46-1.78) in the studies with children and adolescents. We demonstrated a mean reduction of 4.21 days in the time of complete resolution of OM (CI - 5.65 to - 2.76) in favor of LLLT. There is moderate evidence that LLLT is effective in resolving OM lesions in adult patients undergoing cancer therapy. LLLT demonstrates potential for decreasing the resolution time of OM lesions by approximately 4.21 days.

Efficacious Cefazolin Prophylactic Dose for Morbidly Obese Women Undergoing Bariatric Surgery Based on Evidence from Subcutaneous Microdialysis and Populational Pharmacokinetic Modeling.

PURPOSE: To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling. METHODS: A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously describe plasma and tissue data sets. The outcomes was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and 6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo simulation. RESULTS: CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with MICs ≤1 mg/L such as Escherichia coli and Staphylococcus aureus. For species such as Klebsiella pneumoniae, which present MIC distribution frequency of 2 mg/L, the maintenance of PTA ≥ 90% occurs with a 3 g dose for surgeries lasting up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%). CONCLUSIONS: Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.

Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals.

Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals owing to alterations in drug tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need for cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin lower limit of quantitation was 5 µg/mL in human plasma, 2 µg/mL in rat plasma, and 0.5 and 0.025 µg/mL in human and rat microdialysate samples, respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%, respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and inaccuracy were < 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations.

Analysis of the Association of Nonsynonymous Polymorphisms in ADH Genes with Hazardous Drinking in HIV-1-Positive Individuals.

BACKGROUND: Hazardous drinking (HD) is a serious health problem in people infected with human immunodeficiency virus type 1 (HIV-1). Single nucleotide polymorphisms (SNPs) in alcohol dehydrogenase (ADH) genes have been associated with HD in different populations, but there were no data about this in HIV-1-positive individuals. This study investigated the association of 4 nonsynonymous SNPs in ADH genes (Arg48His and Arg370Cys in ADH1B gene; Arg272Gln and Ile350Val in ADH1C gene) with HD in people living with HIV-1. METHODS: This case-control study included 365 HIV-1-positive individuals (121 with HD and 244 without HD). Sociodemographic variables were collected with a standardized individual questionnaire. HD (score ≥8) and binge drinking (BD) (drinks on the same occasion ≥5) were detected with the Alcohol Use Disorders Identification Test. The 4 SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. The Bonferroni correction was used (considering the 4 SNPs studied). RESULTS: There were no significant differences in the frequencies of Arg370Cys, Arg272Gln, and Ile350Val polymorphisms between HD cases and controls. Otherwise, Arg/His genotype (rs1229984) in ADH1B gene showed a protective effect against HD (aOR = 0.36; 95% CI: 0.14 to 0.90) and BD (aOR = 0.49; 95% CI: 0.21 to 0.95). Nevertheless, these differences were no longer significant after Bonferroni correction. CONCLUSIONS: The results of this study suggest a possible effect of the Arg48His genotype on the protection against HD in HIV-1-positive individuals.

Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients.

Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

Estimating an EQ-5D-Y-3L Value Set for Brazil.

INTRODUCTION: The EQ-5D-Y-3L is a generic measure of health-related quality of life in children and adolescents. Although the Brazilian-Portuguese EQ-5D-Y-3L version is available, there is no value set for it, hampering its use in economic evaluations. This study aimed to elicit a Brazilian EQ-5D-Y-3L value set based on preferences of the general adult population. METHODS: Two independent samples of adults participated in an online discrete choice experiment (DCE) survey and a composite time trade-off (cTTO) face-to-face interview. The framing was "considering your views for a 10-year-old child". DCE data were analyzed using a mixed-logit model. The 243 DCE predicted values were mapped into the observed 28 cTTO values using linear and non-linear mapping approaches with and without intercept. Mapping approaches' performance was assessed to estimate the most valid method to rescale DCE predicted values using the model fit (R2), Akaike Information Criteria (AIC), root mean squared error (RMSE), and mean absolute error (MAE). RESULTS: A representative sample of 1376 Brazilian adults participated (DCE, 1152; cTTO, 211). The linear mapping without intercept (R2 = 96%; AIC, - 44; RMSE, 0.0803; MAE, - 0.0479) outperformed the non-linear without intercept (R2 = 98%; AIC, - 63; RMSE, 0.1385; MAE, - 0.1320). Utilities ranged from 1 (full health) to - 0.0059 (the worst health state). Highest weights were assigned to having pain or discomfort (pain/discomfort), followed by walking about (mobility), looking after myself (self-care), doing usual activities (usual activities), and feeling worried, sad, or unhappy (anxiety/depression). CONCLUSION: This study elicited the Brazilian EQ-5D-Y-3L value set using a mixed-logit DCE model with a power parameter based on a linear mapping without intercept, which can be used to estimate the quality-adjusted life-years for economic evaluations of health technologies targeting the Brazilian youth population.

GRADE guidance 39: using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses.

BACKGROUND AND OBJECTIVE: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-ADOLOPMENT methodology has been widely used to adopt, adapt, or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. The objective of this guidance is to refine the operationalization for applying GRADE-ADOLOPMENT. METHODS: Through iterative discussions, online meetings, and email communications, the GRADE-ADOLOPMENT project group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE working group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people), and twice in September 2023 (approximately 60 and 90 people) for approval. RESULTS: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by doing the following: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing evidence-to-decision (EtDs), when available or developing new EtDs, if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. CONCLUSION: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over 6 years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources.

Guidelines' recommendations for the treatment-resistant depression: A systematic review of their quality.

INTRODUCTION: Depression is a serious and widespread mental health disorder. A significant proportion of patients with depression fail to remit after two antidepressant treatment trials, a condition named treatment-resistant depression (TRD). Clinical practice guidelines (CPGs) are instruments aimed to improve diagnosis and treatment. This study objective is to systematically appraise the quality and elaborate a comparison of high-quality CPGs with high-quality recommendations aimed at TRD. METHODS AND ANALYSIS: We searched several specialized databases and organizations that develop CPGs. Independent researchers assessed the quality of the CPGs and their recommendations using AGREE II and AGREE-REX instruments, respectively. We selected only high-quality CPGs that included definition and recommendations for TRD. We investigated their divergencies and convergencies as well as weak and strong points. RESULTS: Among seven high-quality CPGs with high-quality recommendations only two (Germany's Nationale Versorgungs Leitlinie-NVL and US Department of Veterans Affairs and Department of Defense-VA/DoD) included specific TRD definition and were selected. We found no convergent therapeutic strategy among these two CPGs. Electroconvulsive therapy is recommended by the NVL but not by the VA/DoD, while repetitive transcranial magnetic stimulation is recommended by the VA/DoD but not by the NVL. While the NVL recommends the use of lithium, and a non-routine use of thyroid or other hormones, psychostimulants, and dopaminergic agents the VA/DoD does not even include these drugs among augmentation strategies. Instead, the VA/DoD recommends ketamine or esketamine as augmentation strategies, while the NVL does not mention these drugs. Other differences between these CPGs include antidepressant combination, psychotherapy as a therapeutic augmentation, and evaluation of the need for hospitalization all of which are only recommended by the NVL. CONCLUSIONS: High-quality CPGs for the treatment of depression diverge regarding the definition and use of the term TRD. There is also no convergent approach to TRD from currently high-quality CPGs.

Factors associated with higher quality of clinical practice guidelines and their recommendations for the pharmacological treatment of depression: a systematic review.

OBJECTIVE: The objective of this study was to assess the quality of clinical practice guidelines (CPGs) for the pharmacological treatment of depression along with their recommendations and factors associated with higher quality. DESIGN: We conducted a systematic review that included CPGs for the pharmacological treatment of depression in adults. DATA SOURCES: We searched for publications from 1 January 2011 to 31 December 2021, in MEDLINE, Cochrane Library, Embase, PsycINFO, BVS and 12 other databases and guideline repositories. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included CPGs containing recommendations for the pharmacological treatment of depression in adults at outpatient care setting, regardless of whether it met the U.S. National Academy of Medicine criteria, or not. If a CPG included recommendations for both children and adults, they were considered. No language restriction was applied. DATA EXTRACTION AND SYNTHESIS: Data extraction was also conducted independently and in duplicate, a process that was validated in a previous project. The quality of the CPGs and their recommendations were assessed by three independent reviewers using Appraisal of Guidelines for Research and Evaluation (AGREE II) and Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX). A CPG was considered to be of high quality if AGREE II Domain 3 was ≥60%; while their recommendations were considered high if AGREE-REX Domain 1 was ≥60%. RESULTS: Seventeen out of 63 (27%) CPGs were classified as high quality, while 7 (11.1%) had high-quality recommendations. The factors associated with higher-scoring CPGs and recommendations in the multiple linear regression analyses were 'Handling of conflicts of interest', 'Multiprofessional team' and 'Type of institution'. 'Inclusion of patient representative in the team' was also associated with higher-quality recommendations. CONCLUSIONS: The involvement of professionals from diverse backgrounds, the handling of conflicts of interest, and the inclusion of patients' perspectives should be prioritised by developers aiming for high-quality CPGs for the treatment of depression.

Low-Risk Antenatal Care Enhanced by Telemedicine: A Practical Guideline Model.

OBJECTIVE: To develop a protocol for hybrid low-risk prenatal care adapted to Brazilian guidelines, merging reduced face-to-face consultations and remote monitoring. METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched on telemedicine and antenatal care perspectives and adaptation of the low-risk prenatal care protocols recommended by the Ministry of Health and by the Brazilian Federation of Gynecology and Obstetrics Associations. RESULTS: Five relevant articles and three manuals were included in the review, for presented criteria to develop this clinical guideline. We identified, in these studies, that the schedule of consultations is unevenly distributed among the gestational trimesters, and ranges from 7 to 14 appointments. In general, the authors propose one to two appointments in the first trimester, two to three appointments in the second trimester, and two to six appointments in the third trimester. Only three studies included puerperal evaluations. The routine exams recommended show minimal variations among authors. To date, there are no validated Brazilian protocols for prenatal care by telemedicine. The included studies showed that pregnant women were satisfied with this form of care, and the outcomes of interest, except for hypertensive diseases, were similar between the groups exposed to traditional and hybrid prenatal care. CONCLUSION: The presented guideline comprises the Ministry of Health recommendations for low-risk prenatal care and reduces exposure to the hospital environment and care costs. A randomized clinical trial, to be developed by this group, will provide real-world data on safety, effectiveness, satisfaction, and costs.

OBJETIVO: Desenvolver uma diretriz clínica híbrida para atendimento pré-natal de baixo risco, mesclando consultas presenciais e remotas por telemedicina, adapta às recomendações brasileiras. MéTODOS: Revisão sistemática da literatura nas bases de dados PubMed, Embase e Cochrane e adaptação dos protocolos de atenção ao pré-natal de baixo risco preconizados pelo Ministério da Saúde e pela Federação Brasileira das Associações de Ginecologia e Obstetrícia. RESULTADOS: Cinco artigos relevantes e três manuais foram incluídos na revisão por preencherem critérios para o desenvolvimento desta diretriz clínica. Nos estudos incluídos, identificou-se que o cronograma de consultas se distribui de forma desigual entre os trimestres gestacionais, variando entre 07 e 14 encontros. De forma geral, os autores propõem uma a duas consultas no primeiro trimestre, duas a três consultas no segundo trimestre e duas a seis consultas no terceiro trimestre. Somente três estudos incluíram avaliações puerperais. A rotina de exames preconizada apresenta mínimas variações entre os autores. Até o momento, não existem protocolos brasileiros validados para atendimento pré-natal por telemedicina. Os estudos incluídos evidenciaram a satisfação das gestantes em relação a esta forma de atendimento, e os desfechos de interesse, excetuando doenças hipertensivas, foi semelhante entre os grupos expostos ao pré-natal tradicional e ao pré-natal híbrido. CONCLUSãO: A diretriz apresentada contempla as recomendações do Ministério da Saúde para atendimento pré-natal de gestantes de baixo risco, reduz a exposição ao ambiente hospitalar e os custos de atendimento. Seu emprego em um ensaio clínico randomizado, a ser desenvolvido por este grupo, proporcionará dados de mundo real, relativos à segurança, efetividade, satisfação e custos.

Recommendations for the pharmacological treatment of treatment-resistant depression: A systematic review protocol.

INTRODUCTION: Depression is a serious and widespread mental health disorder. Although effective treatment does exist, a significant proportion of patients with depression fail to respond to antidepressant treatment trials, a condition named treatment-resistant depression. Efficient approach should be given this condition in order to revert the burden caused by depression. Clinical practice guidelines (CPGs) are evidence-based health promotion instruments to improve diagnosis and treatment. CPGs recommendations for treatment-resistant depression must be trustworthy. The objective of the proposed study is to systematically identify, appraise the quality of CPGs for the treatment of depression and elaborate a synthesis of recommendations for treatment-resistant depression of CPGs considered to be of high quality and with high quality recommendations. METHODS AND ANALYSIS: We will search the databases of organizations, such as PubMed, Embase, Cochrane Library, PsycInfo, and the Virtual Health Library, and organizations that develop CPGs. Three independent researchers will assess the quality of the CPGs and their recommendations using the AGREE II and AGREE-REX instruments, respectively. Given the identification of divergences and convergences as well as weak and strong points among high quality CPGs, our work may help developers, clinicians and eventually patients. ETHICS AND DISSEMINATION: No ethical approval is required for a systematic review, as no patient data will be used. The research results will be disseminated in conferences and submitted to a peer reviewed journal.

Quality of clinical practice guidelines for inadequate response to first-line treatment for depression according to AGREE II checklist and comparison of recommendations: a systematic review.

OBJECTIVE: To assess similarities and differences in the recommended sequence of strategies among the most relevant clinical practice guidelines (CPGs) for the treatment of depression in adults with inadequate response to first-line treatment. DATA SOURCES: We performed a systematic review of the literature spanning January 2011 to August 2020 in Medline, Embase, Cochrane Library and 12 databases recognised as CPGs repositories. CPGs quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). STUDY SELECTION: The eligibility criteria were CPGs that described pharmacological recommendations for treating depression for individuals aged 18 years or older in outpatient care setting. We included CPGs considered of high-quality (≥80% in domain 3 of AGREE II) or recognised as clinically relevant. DATA EXTRACTION: Two independent researchers extracted recommendations for patients who did not respond to first-line pharmacological treatment from the selected CPGs. RESULTS: We included 46 CPGs and selected 8, of which 5 were considered high quality (≥80% in domain 3 of AGREE II) and 3 were recognised as clinically relevant. Three CPGs did not define inadequate response to treatment and 3 did not establish a clear sequence of strategies. The duration of treatment needed to determine that a patient had not responded was not explicit in 3 CPGs and was discordant in 5 CPGs. Most CPGs agree in reassessing the diagnosis, assessing the presence of comorbidities, adherence to treatment, and increase dosage as first steps. All CPGs recommend psychotherapy, switching antidepressants, and considering augmentation/combining antidepressants. CONCLUSION: Relevant CPGs present shortcomings in recommendations for non-responders to first-line antidepressant treatment including absence and divergencies in definition of inadequate response and sequence of recommended strategies. Overall, most relevant CPGs recommend reassessing the diagnosis, evaluate comorbidities, adherence to treatment, increase dosage of antidepressants, and psychotherapy as first steps. PROSPERO REGISTRATION NUMBER: CRD42016043364.

Adult patients admitted to a tertiary hospital for COVID-19 and risk factors associated with severity: a retrospective cohort study.

COVID-19 is a disease whose knowledge is still under construction, high transmissibility, with no consensual treatment available to everyone. Therefore, the identification of patients at higher risk of evolving to the critical form of the disease is fundamental. The study aimed to determine risk factors associated with the severity of COVID-19 in adults patients. This is an observational, retrospective study from a cohort of adult patients with COVID-19 admitted to a public hospital from March to August 2020, whose medical records were evaluated. For the association of possible severity predictors, a Poisson regression was used. The primary outcome was the critical form of the disease (need for admission to the Intensive Care Unit and/or invasive mechanical ventilation). We included 565 patients: mostly men; 55.5% of those who progressed to the critical form of the disease were over sixty years old. Hypertension, diabetes mellitus and obesity were the most frequent comorbidities. There were 39.8% of patients who progressed to the critical form of the disease. The hospital mortality rate was 22.1%, and that of critical patients was 46.7%. The independent factors associated with the severity of the disease were obesity [RR = 1.33 (95% CI 1.07 to 1.66; p = 0.011)], SpO2/FiO2 ratio ≤ 315 [RR = 2.20 (95% CI 1.79 to 2.71; p = 0.000)], C-reactive protein > 100 mg/L [RR = 1.65 (95% CI 1.33 to 2.06; p = 0.000)], and lymphocytes < 1,000/µL [RR = 1.44 (95% CI 1.18 to 1.75; p = 0.000)]. Advanced age and comorbidities were dependent factors strongly associated with the critical form of the disease.

Prediction of all-cause and cardiovascular mortality using central hemodynamic indices among elderly people: systematic review and meta-analysis.

BACKGROUND: Despite widespread usage of central blood pressure assessment its predictive value among elderly people remains unclear. OBJECTIVE: To ascertain the capacity of central hemodynamic indices for predicting future all-cause and cardiovascular hard outcomes among elderly people. DESIGN AND SETTING: Systematic review and meta-analysis developed at the Del Cuore cardiology clinic, in Antonio Prado, Rio Grande do Sul, Brazil. METHODS: 312 full-text articles were analyzed, from which 35 studies were included for systematic review. The studies included needed to report at least one central hemodynamic index among patients aged 60 years or over. RESULTS: For all-cause mortality, aortic pulse wave velocity (aPWV) and central systolic blood pressure (SBP) were significant, respectively with standardized mean difference (SMD) 0.85 (95% confidence interval, CI 0.69-1.01; I2 96%; P < 0.001); and SMD 0.27 (95% CI 0.15-0.39; I2 77%; P 0.012). For cardiovascular mortality brachial-ankle PWV (baPWV), central SBP and carotid-femoral PWV (cfPWV) were significant, respectively SMD 0.67 (95% CI 0.40-0.93; I2 0%; P 0.610); SMD 0.65 (95% CI 0.48- 0.82; I2 80%; P 0.023); and SMD 0.51 (95% CI 0.32-0.69; I2 85%; P 0.010). CONCLUSIONS: The meta-analysis results showed that aPWV was promising for predicting all-cause mortality, while baPWV and central SBP demonstrated consistent results in evaluating cardiovascular mortality outcomes. Thus, the findings support usage of central blood pressure as a risk predictor for hard outcomes among elderly people. REGISTRATION NUMBER IN PROSPERO: RD42018085264.

Evaluation of the initial response in clinical trial efforts for COVID-19 in Brazil. / Avaliação da resposta inicial de desenvolvimento de ensaios clínicos para COVID-19 no Brasil.

OBJECTIVE: To describe the methodological characteristics and good research practices of COVID-19 interventional studies developed in Brazil in the first months of the pandemic. METHODS: We reviewed the bulletin of the National Research Ethics Committee - Coronavirus Special Edition (Comissão Nacional de Ética em Pesquisa - CONEP-COVID) (May 28, 2020) and the databases of the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC) to identify interventional studies registered in Brazil that assessed drug type, biological therapy, or vaccines. We described their methodological characteristics and calculated their power for different effect magnitudes. RESULTS: A total of 62 studies were included, 55 retrieved from the CONEP website, and 7 from registry databases. The most tested pharmacological interventions in these studies were: chloroquine/hydroxychloroquine, azithromycin, convalescent plasma, tocilizumab, sarilumab, eculizumab, vaccine, corticosteroids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, and lopinavir/ritonavir. Out of 22 protocols published on registry databases until May 2020, 18 (82%) were randomized clinical trials, and 13 (59%) had an appropriate control group. However, 9 (41%) of them were masked, and only 5 (24%) included patients diagnosed with a specific laboratory test (for example, reverse transcription polymerase chain reaction - RT-PCR). Most of these studies had power > 80% only to identify large effect sizes. In the prospective follow-up, 60% of the studies available at CONEP until May 2020 had not been published on any registry platform (ICTRP/ReBEC/ClinicalTrials) by July 21, 2020. CONCLUSION: The interventions evaluated during the Brazilian research response reflect those of international initiatives, but with a different distribution and a large number of studies assessing hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.

OBJETIVO: Descrever as características metodológicas e de boas práticas em pesquisa dos estudos de intervenção para COVID-19 desenvolvidos no Brasil nos primeiros meses da pandemia. MÉTODOS: Revisamos o boletim da Comissão Nacional de Ética em Pesquisa - edição especial Coronavírus (CONEP-COVID) (28 de maio de 2020) e as bases International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov e Registro Brasileiro de Ensaios Clínicos (ReBEC) para identificar estudos registrados no Brasil que avaliassem intervenções de tipo de medicamento, terapia biológica ou vacinas. Descrevemos as características metodológicas e calculamos o poder para diferentes magnitudes de efeito. RESULTADOS: Foram incluídos 62 estudos, 55 identificados no site da CONEP e mais sete nas bases de registro. As intervenções medicamentosas mais frequentemente testadas nesses estudos foram: cloroquina/hidroxicloroquina, azitromicina, plasma convalescente, tocilizumabe, sarilumabe, eculizumabe, vacina, corticoides, anticoagulantes, n-acetilcisteína, nitazoxanida, ivermectina e lopinavir/ritonavir. De 22 protocolos publicados até maio de 2020 nas bases de registro, 18 (82%) eram ensaios clínicos randomizados e 13 (59%) tinham grupo controle adequado. Entretanto, nove (41%) eram mascarados e somente cinco (24%) incluíam pacientes diagnosticados com teste de laboratório específico (por exemplo, transcrição reversa seguida de reação em cadeia da polimerase - RT-PCR). A maioria desses trabalhos teria poder > 80% apenas para identificar grandes tamanhos de efeito. Em seguimento prospectivo, observamos que 60% dos estudos disponíveis na CONEP até maio de 2020 não estavam em nenhuma das plataformas de registro (ICTRP/ReBEC/ClinicalTrials) até o dia 21 de julho de 2020. CONCLUSÃO: As intervenções avaliadas durante a resposta brasileira em pesquisa refletem iniciativas internacionais, porém com distribuição diferente, tendo número elevado de estudos que avaliam hidroxicloroquina/cloroquina. Limitações no delineamento metodológico e planejamento amostral representam desafios que podem afetar o alcance dos trabalhos.

Pay for performance in primary care: the contribution of the Programme for Improving Access and Quality of Primary Care (PMAQ) on avoidable hospitalisations in Brazil, 2009-2018.

BACKGROUND: Evidence on the effect of pay-for-performance (P4P) schemes on provider performance is mixed in low-income and middle-income countries. Brazil introduced its first national-level P4P scheme in 2011 (PMAQ-Brazilian National Programme for Improving Primary Care Access and Quality). PMAQ is likely one of the largest P4P schemes in the world. We estimate the association between PMAQ and hospitalisations for ambulatory care sensitive conditions (ACSCs) based on a panel of 5564 municipalities. METHODS: We conducted a fixed effect panel data analysis over the period of 2009-2018, controlling for coverage of primary healthcare, hospital beds per 10 000 population, education, real gross domestic product per capita and population density. The outcome is the hospitalisation rate for ACSCs among people aged 64 years and under per 10 000 population. Our exposure variable is defined as the percentage of family health teams participating in PMAQ, which captures the roll-out of PMAQ over time. We also provided several sensitivity analyses, by using alternative measures of the exposure and outcome variables, and a placebo test using transport accident hospitalisations instead of ACSCs. RESULTS: The results show a negative and statistically significant association between the rollout of PMAQ and ACSC rates for all age groups. An increase in PMAQ participating of one percentage point decreased the hospitalisation rate for ACSC by 0.0356 (SE 0.0123, p=0.004) per 10 000 population (aged 0-64 years). This corresponds to a reduction of approximately 60 829 hospitalisations in 2018. The impact is stronger for children under 5 years (-0.0940, SE 0.0375, p=0.012), representing a reduction of around 11 936 hospitalisations. Our placebo test shows that the association of PMAQ on the hospitalisation rate for transport accidents is not statistically significant, as expected. CONCLUSION: We find that PMAQ was associated with a modest reduction in hospitalisation for ACSCs.