What Powers Trastuzumab's Cardiotoxicity? Decoding Mitochondrial-Related Gene Expression Through Integrative Review and Meta-Analysis in Cardiomyocytes.

Trastuzumab is a monoclonal antibody used in oncotherapy for HER2-positive tumors. However, as an adverse effect, trastuzumab elevates the risk of heart failure, implying the involvement of energy production and mitochondrial processes. Past studies with transcriptome analysis have offered insights on pathways related to trastuzumab safety and toxicity but limited study sizes hinder conclusive findings. Therefore, we meta-analyzed mitochondria-related gene expression data in trastuzumab-treated cardiomyocytes. We searched the transcriptome databases for trastuzumab-treated cardiomyocytes in the ArrayExpress, DDBJ Omics Archive, Gene Expression Omnibus, Google Scholar, PubMed, and Web of Science repositories. A subset of 1270 genes related to mitochondrial functions (biogenesis, organization, mitophagy, and autophagy) was selected from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology Resource databases to conduct the present meta-analysis using the Metagen package (Study register at PROSPERO: CRD42021270645). Three datasets met the inclusion criteria and 1243 genes were meta-analyzed. We observed 69 upregulated genes after trastuzumab treatment which were related mainly to autophagy (28 genes) and mitochondrial organization (28 genes). We also found 37 downregulated genes which were related mainly to mitochondrial biogenesis (11 genes) and mitochondrial organization (24 genes). The present meta-analysis indicates that trastuzumab therapy causes an unbalance in mitochondrial functions, which could, in part, help explain the development of heart failure and yields a list of potential molecular targets. These findings contribute to our understanding of the molecular mechanisms underlying the cardiotoxic effects of trastuzumab and may have implications for the development of targeted therapies to mitigate such effects.

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

INTRODUCTION: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). METHODS: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. RESULTS: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. CONCLUSION: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

The role of colonoscopy in young patients with rectal bleeding: a systematic review and meta-analysis.

PURPOSE: Anal bleeding is a frequent complaint in the coloproctological practice. Although usually associated with common anorectal disorders, it may represent a sign of an occult colorectal carcinoma. Our purpose was to evaluate the accuracy of the colonoscopy for detection of neoplastic lesions in patients under 50 years of age with rectal bleeding. METHODS: This systematic review and meta-analysis searched publications in PubMed, Web of Science, and Cochrane Library databases up to August, 2023. Cross-sectional and case-control studies including patients under 50 years with rectal bleeding evaluated by colonoscopy were included. Primary outcome was prevalence of neoplastic lesions (adenomas and adenocarcinomas). Secondary outcomes were prevalence of those lesions according to age and anatomic location. The study was registered on PROSPERO (CRD42021257859) on July 5, 2021. RESULTS: Nine studies comprising 4162 patients were analyzed. A total of 398 patients with adenomas and 40 patients with adenocarcinoma were identified. Prevalence of neoplastic lesions (adenomas and carcinomas) was 10%. In patients under 40 years, the prevalence of neoplastic lesions was 7% (6% of adenomas, 1% of carcinomas). Among patients aged 40-50 years the prevalence was 15%, 14%, and 1%, respectively. Most lesions (71%) were located distally to splenic flexure. CONCLUSION: About 10% of patients under 50 years with anal bleeding will have a neoplastic lesion detected through colonoscopy. The greatest benefit of the procedure is observed between 40 and 50 years. Almost 30% of the neoplastic lesions were found in the proximal colon and could not be detected without the performance of a complete colonoscopy.

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. METHODS: A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. RESULTS: Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. CONCLUSION: Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

Efficacy of six exercise-based interventions for individuals undergoing hemodialysis: a network meta-analysis of randomized clinical trials.

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.

Mortalidade Hospitalar Por Infarto do Miocárdio na América Latina e no Caribe: Revisão Sistemática e Metanálise / Hospital Mortality from Myocardial Infarction in Latin America and the Caribbean: Systematic Review and Meta-Analysis

Resumo Fundamento: A maioria das mortes por doenças cardiovasculares ocorrem em países de renda baixa e média, e o infarto do miocárdio é uma das condições com maior risco de morte. Objetivos: Avaliar a mortalidade hospitalar por todas as causas em pacientes admitidos por infarto do miocárdio (IAMCSST e IAMSSST) na América Latina e no Caribe no ano de 2000 em diante. Métodos: Realizamos uma busca sistemática em bancos de dados eletrônicos por estudos do tipo coorte que relataram morte hospitalar por IAMCSST e IAMSSST. Foi realizada uma metanálise e um valor de p<0,05 foi considerado estatisticamente significativo. Resultados: Identificamos 38 estudos (29 com pacientes com IAMCSST, 3 com IAMSSST e 6 com IAMCSST e IAMSSST). A mortalidade por IAMCSST agrupada foi de 9,9% (IC95%: 9,1 - 10,7). Observou-se importante heterogeneidade (I2 = 74% e o intervalo de predição foi de 6,6 - 14.5). A porcentagem de terapia de reperfusão e a década em que os estudos foram conduzidos explicam parte dessa heterogeneidade (I2 = 54%). Quanto maior a taxa de terapia de reperfusão, menor a mortalidade hospitalar (coeficiente = −0,009, IC95%: −0,013 a −0,006, p<0,001). A mortalidade foi maior na primeira década em comparação com a mortalidade na segunda década (coeficiente = −0,14, IC95%: −0,27 a −0,02, p=0,047). A mortalidade hospitalar por IAMSSST foi de 6,3% (IC95%: 5,4 - 7,4) e a heterogeneidade foi nula. Conclusão: A mortalidade por IAMCSST em países de renda baixa e média foi maior em comparação com as taxas relatadas em outros países. Para melhorar essas estimativas, deve-se buscar um maior uso de terapia de reperfusão. A mortalidade hospitalar por IAMSSST agrupada foi similar às taxas descritas em países de alta renda. Contudo, esse dado foi baseado em poucos estudos, cuja maioria foi conduzida em dois países.

Abstract Background: Most cardiovascular deaths occur in low- and middle-income countries and myocardial infarction is one of the main life-threatening conditions. Objective: We assessed all-cause in-hospital mortality in patients admitted for myocardial infarction (STEMI and NSTEMI) in Latin America and the Caribbean from 2000 onward. Methods: We systematically searched in electronic bibliographic databases for cohort studies which reported in-hospital mortality due to STEMI and NSTEMI. A meta-analysis was performed and a p-value < 0.05 was considered significant. Results: We identified 38 studies (29 STEMI, 3 NSTEMI and 6 both). Pooled STEMI in-hospital mortality was 9.9% (95% CI: 9.1 - 10.7). Heterogeneity was not trivial (I2 = 74% and prediction interval = 6.6 - 14.5). The percentage of reperfusion therapy and decade explain part of the heterogeneity (I2 = 54%). The higher the rate of reperfusion therapy, the lower the in-hospital mortality (coefficient = −0.009, 95% CI: −0.013 to −0.006, p<0.001). This mortality was higher in the first decade as compared with the second (coefficient = −0.14, 95% CI: −0.27 to −0.02, p=0.047). Pooled NSTEMI in-hospital mortality was 6.3% (95% CI: 5.4 - 7.4) and heterogeneity was null. Conclusion: Pooled STEMI in-hospital mortality in low- and middle-income countries was high in comparison with rates reported in high income countries. To improve these estimates, higher use of reperfusion therapy must be pursued. Pooled NSTEMI in-hospital mortality was similar to the ones found in high-income countries; however, it was based on few studies and most of them were carried out in two countries.

Thiazide diuretics alone or in combination with a potassium-sparing diuretic on blood pressure-lowering in patients with primary hypertension: protocol for a systematic review and network meta-analysis.

BACKGROUND: The use of thiazide (T) diuretics for the treatment of hypertension may be associated with adverse metabolic effects, which can be minimized by combining thiazides with potassium-sparing (PS) diuretics. The additional blood pressure (BP)-lowering effect provided by the addition of a PS diuretic is unclear. Due to a large number of drugs in the T diuretics class, and the possible difference between them, there is a need to identify the best available evidence for health decision-making. This systematic review with network meta-analysis aims to compare the antihypertensive efficacy of T diuretics alone or in combination with a PS diuretic in patients with primary hypertension, as well as the safety of such drugs through the measurement of drug-related adverse events. METHODS: A comprehensive electronic search will be conducted in six electronic bibliographic databases (PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, Scopus, Lilacs), a registration database ( ClinicalTrials.gov ), and Educational Resources Information Center (ERIC [ProQuest]), published from inception to the date of the search. The search will be updated towards the end of the review. A hand search of the reference sections of the included studies and cited studies will also be performed. In case of missing data, authors will be contacted by e-mail or academic social networking sites whenever possible. To be included in the review, studies must be double-blind randomized controlled trials evaluating T diuretics alone or in combination with PS diuretics in patients with primary hypertension. The primary outcome measure will be office BP. Ambulatory BP monitoring (ABPM), non-melanoma skin cancer, major adverse cardiovascular events, laboratory parameters, and the number of withdrawals will be included as secondary outcomes. The results will be quantitatively summarized using differences between the mean change from baseline or differences between means for quantitative outcomes and relative risk for dichotomous outcomes. Results will be presented as mean or relative risk with credible intervals through a league table. The treatments will also be ranked using the surface under the cumulative ranking curve method. The risk of bias will be assessed through the RoB 1.0 tool. DISCUSSION: To the best of our knowledge, this review will be the first to synthesize currently available evidence on the antihypertensive efficacy of different T diuretics alone or in combination with PS diuretics in adults with hypertension. The goals of hypertension treatment are to control high BP and to reduce associated cardiovascular morbidity and mortality, using the most appropriate therapy. Thiazides are widely used for pharmacological treatment due to their demonstrated effectiveness in reducing BP, favorable safety profile, and low cost. The results of this study will provide evidence regarding the best therapeutic strategies with T and PS diuretics, evidencing interventions with better antihypertensive efficacy and safety profile. TRIAL REGISTRATION: This systematic review and network meta-analysis was prospectively registered at the PROSPERO database ( CRD42018118492 ).

First-line Treatment of Metastatic Renal Cell Carcinoma in the Immuno-oncology Era: Systematic Review and Network Meta-analysis.

Combination treatments with immuno-oncology (IO) agents and IO agents plus a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) have been approved for first-line treatment of patients with metastatic renal cell carcinoma (mRCC). No direct comparisons have been performed among these treatment options. We performed a systematic review and network meta-analysis to compare and rank the available regimens for first-line treatment in terms of survival benefit and efficacy. In accordance with the Preferred Reporting Items for Systematic Review statement, a systematic search of reported studies was performed in MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE up to May 31, 2019. Network meta-analysis models were adjusted using the Bayesian method. Four randomized clinical trials, with a total of 3758 patients, met the inclusion criteria. Considering systemic therapy, 1880 patients had received sunitinib and 550, 432, 442, and 454 patients had received ipilimumab plus nivolumab (ipi + nivo), pembrolizumab plus axitinib (pembro + axi), avelumab plus axitinib (avelu + axi), and atezolizumab plus bevacizumab (atezo + bev). No difference was found in overall survival between ipi + nivo and pembro + axi for the intention to treat population (hazard ratio [HR], 1.34; 95% credible interval [CrI], 0.92-1.97). No difference was found in progression-free survival among the treatments. The overall response rate (ORR) was superior with pembro + axi and avelu + axi compared with the ORR with the other treatments (atezo + bev vs. pembro + axi: HR, 0.66; 95% CrI, 0.52-0.84; ipi + nivo vs. pembro + axi: HR, 0.73; 95% CrI, 0.59-0.90; atezo + bev vs. avelu + axi: HR, 0.55; 95% CrI, 0.43-0.71; avelu + axi vs. ipi + nivo: HR, 1.66; 95% CrI, 1.31-2.12), with no differences across them (HR, 1.21; 95% CrI, 0.95-1.53). In the present indirect comparison, for an intention to treat population, we found no survival differences between pembro + axi and ipi + nivo. All treatments showed better progression-free survival compared with sunitinib that was similar among them. The combination of an IO agent (pembrolizumab or avelumab) and axitinib seemed to be the most effective therapy for the ORR.

Splenic flexure mobilization in sigmoid and rectal cancer resections: a meta-analysis of surgical outcomes. / Mobilização da flexura esplênica nas ressecções dos tumores de reto e sigmoide: meta-análise dos resultados cirúrgicos.

OBJECTIVE: to evaluate the influence of the splenic flexure mobilization for the main surgical outcomes of patients submitted to resection of sigmoid and rectal cancer. METHODS: we searched the MEDLINE, Cochrane Central Register of Controlled Trials and LILACS, using the terms "splenic flexure mobilization", "colorectal surgery", "rectal cancer", "anterior resection", "sigmoid colon cancer", and "sigmoid resection". The main outcome was anastomotic dehiscence. Other outcomes analyzed were mortality, bleeding, infection and general complications. We estimated the effect sizes by grouping data from six case-control studies (1,433 patients) published until January 2018. RESULTS: our meta-analysis showed that patients undergoing complete mobilization of the splenic flexure had a higher risk of anastomotic dehiscence (RR=2.27, 95%CI: 1.22-4.23) compared with those not submitted to this procedure. There was no difference between the groups in terms of mortality, bleeding, infection and general complications. CONCLUSION: splenic flexure mobilization is associated with a higher risk of anastomotic dehiscence in resections of sigmoid and rectal cancer. This surgical maneuver should be used with caution in the surgical management of sigmoid or rectal cancers.

OBJETIVO: avaliar a influência da mobilização da flexura esplênica nos principais resultados cirúrgicos de pacientes submetidos à ressecção de câncer do cólon sigmoide ou reto. MÉTODOS: os bancos de dados MEDLINE, Cochrane Central Register de Ensaios Controlados e LILACS foram pesquisados usando os termos "mobilização da flexura esplênica", "cirurgia colorretal", "câncer retal", "ressecção anterior", "câncer de cólon sigmoide", "ressecção de sigmoide". O desfecho principal foi a deiscência da anastomose. Outros desfechos analisados foram mortalidade, sangramento, infecção e complicações gerais. Os tamanhos dos efeitos foram estimados por meio do agrupamento dos dados de seis estudos de caso-controle (1.433 pacientes) publicados até janeiro de 2018. RESULTADOS: nossa meta-análise revelou que pacientes submetidos à mobilização completa da flexura esplênica tinham um risco maior de deiscência anastomótica (RR=2,27, IC95%: 1,22-4,23) em comparação àqueles não submetidos a esse procedimento. Nenhuma diferença pôde ser demonstrada entre os grupos em termos de mortalidade, sangramento, infecção e complicações gerais. CONCLUSÃO: a mobilização da flexura esplênica está associada a um maior risco de deiscência anastomótica nas ressecções de câncer de reto ou cólon sigmoide. Esta manobra cirúrgica deve ser utilizada com cautela no manejo cirúrgico dos tumores colorretais.

Mobilização da flexura esplênica nas ressecções dos tumores de reto e sigmoide: meta-análise dos resultados cirúrgicos / Splenic flexure mobilization in sigmoid and rectal cancer resections: a meta-analysis of surgical outcomes

RESUMO Objetivo: avaliar a influência da mobilização da flexura esplênica nos principais resultados cirúrgicos de pacientes submetidos à ressecção de câncer do cólon sigmoide ou reto. Métodos: os bancos de dados MEDLINE, Cochrane Central Register de Ensaios Controlados e LILACS foram pesquisados usando os termos "mobilização da flexura esplênica", "cirurgia colorretal", "câncer retal", "ressecção anterior", "câncer de cólon sigmoide", "ressecção de sigmoide". O desfecho principal foi a deiscência da anastomose. Outros desfechos analisados foram mortalidade, sangramento, infecção e complicações gerais. Os tamanhos dos efeitos foram estimados por meio do agrupamento dos dados de seis estudos de caso-controle (1.433 pacientes) publicados até janeiro de 2018. Resultados: nossa meta-análise revelou que pacientes submetidos à mobilização completa da flexura esplênica tinham um risco maior de deiscência anastomótica (RR=2,27, IC95%: 1,22-4,23) em comparação àqueles não submetidos a esse procedimento. Nenhuma diferença pôde ser demonstrada entre os grupos em termos de mortalidade, sangramento, infecção e complicações gerais. Conclusão: a mobilização da flexura esplênica está associada a um maior risco de deiscência anastomótica nas ressecções de câncer de reto ou cólon sigmoide. Esta manobra cirúrgica deve ser utilizada com cautela no manejo cirúrgico dos tumores colorretais.

ABSTRACT Objective: to evaluate the influence of the splenic flexure mobilization for the main surgical outcomes of patients submitted to resection of sigmoid and rectal cancer. Methods: we searched the MEDLINE, Cochrane Central Register of Controlled Trials and LILACS, using the terms "splenic flexure mobilization", "colorectal surgery", "rectal cancer", "anterior resection", "sigmoid colon cancer", and "sigmoid resection". The main outcome was anastomotic dehiscence. Other outcomes analyzed were mortality, bleeding, infection and general complications. We estimated the effect sizes by grouping data from six case-control studies (1,433 patients) published until January 2018. Results: our meta-analysis showed that patients undergoing complete mobilization of the splenic flexure had a higher risk of anastomotic dehiscence (RR=2.27, 95%CI: 1.22-4.23) compared with those not submitted to this procedure. There was no difference between the groups in terms of mortality, bleeding, infection and general complications. Conclusion: splenic flexure mobilization is associated with a higher risk of anastomotic dehiscence in resections of sigmoid and rectal cancer. This surgical maneuver should be used with caution in the surgical management of sigmoid or rectal cancers.

Effectiveness evaluation of mood disorder treatment algorithms in Brazilian public healthcare patients

Objective: To assess the effectiveness of three mood disorder treatment algorithms in a sample of patients seeking care in the Brazilian public healthcare system. Methods: A randomized pragmatic trial was conducted with an algorithm developed for treating episodes of major depressive disorder (MDD), bipolar depressive episodes and mixed episodes of bipolar disorder (BD). Results: The sample consisted of 259 subjects diagnosed with BD or MDD (DSM-IV-TR). After the onset of symptoms, the first treatment occurred ∼6 years and the use of mood stabilizers began ∼12 years. All proposed algorithms were effective, with response rates around 80%. The majority of the subjects took 20 weeks to obtain a therapeutic response. Conclusions: The algorithms were effective with the medications available through the Brazilian Unified Health System. Because therapeutic response was achieved in most subjects by 20 weeks, a follow-up period longer than 12 weeks may be required to confirm adequate response to treatment. Remission of symptoms is still the main desired outcome. Subjects who achieved remission recovered more rapidly and remained more stable over time. Clinical trial registration: NCT02901249, NCT02870283, NCT02918097

Effectiveness evaluation of mood disorder treatment algorithms in Brazilian public healthcare patients.

OBJECTIVE: To assess the effectiveness of three mood disorder treatment algorithms in a sample of patients seeking care in the Brazilian public healthcare system. METHODS: A randomized pragmatic trial was conducted with an algorithm developed for treating episodes of major depressive disorder (MDD), bipolar depressive episodes and mixed episodes of bipolar disorder (BD). RESULTS: The sample consisted of 259 subjects diagnosed with BD or MDD (DSM-IV-TR). After the onset of symptoms, the first treatment occurred ∼6 years and the use of mood stabilizers began ∼12 years. All proposed algorithms were effective, with response rates around 80%. The majority of the subjects took 20 weeks to obtain a therapeutic response. CONCLUSIONS: The algorithms were effective with the medications available through the Brazilian Unified Health System. Because therapeutic response was achieved in most subjects by 20 weeks, a follow-up period longer than 12 weeks may be required to confirm adequate response to treatment. Remission of symptoms is still the main desired outcome. Subjects who achieved remission recovered more rapidly and remained more stable over time. CLINICAL TRIAL REGISTRATION: NCT02901249, NCT02870283, NCT02918097.