The use of blue dye alone for sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initially node-positive breast cancer.

INTRODUCTION: False-negative sentinel lymph node biopsy (SLNB) rates following neoadjuvant chemotherapy (NACT) in initially node-positive (cN1/2) breast cancer patients are high, but decrease when lymph nodes are clipped, ≥3 sentinel lymph nodes (SLN) are removed or dual-tracer localization (radioisotope and blue dye) is used. Radiotracer, however, is often unavailable and outcomes with blue dye alone are unknown. MATERIALS AND METHODS: Initially cT1-4, cN1/2 patients treated with NACT in 2013-2023 who underwent SLNB using blue dye alone were evaluated regarding SLN identification, axillary recurrence, disease-free and overall survival rates. RESULTS: Of 119 patients included, 19 remained cN1/2 after NACT. SLNB was performed using blue dye alone in 100 ycN0 cases (84%), with an identification rate of 96%. The SLN was negative in 70/119 cases (i.e. 59% avoided axillary dissection). The number of SLN detected was ≥3 in 55/70 cases (78%) (median 3.1; 1-6). Median age was 49 years (25-84). Most were T2 (n = 40, 57.1%), N1 (n = 64, 91.4%). Predominant subtypes were ERBB2 (52.9%) and triple-negative (20%). No axillary recurrence occurred over a median 36-month period. Five-year disease-free and overall survival were, respectively, 85.9% (95%CI: 74-99.8) and 96.3% (95%CI: 89.4-100). The ERBB2 subtype (1.99, 95%CI: 1.02-3.85, p = 0.04) and N1 lymph node status (2.58, 95%CI: 1.54-9.10, p = 0.03) were associated with a greater likelihood of undergoing SLNB alone without axillary dissection. CONCLUSIONS: SLNB with blue dye alone following NACT in initially cN1/2 patients avoided axillary dissection in almost 60% of cases, with no recurrences during the period evaluated. Longer follow-up studies are necessary.

Cancer Risk Factors in Southern Brazil: Report of a Comprehensive, Matched Case-Control Study.

PURPOSE: To evaluate cancer risk factors among cancer cases and controls from Southern Brazil, to analyze a multigene hereditary panel testing (MGPT, 26 genes) for breast cancer (BC) and colorectal cancer (CCR) cases diagnosed age younger than 50 years and to characterize them for hereditary cancer syndrome (HCS) phenotypes. METHODS: A case-control (matched by age group and sex) study was conducted on regional cancer. Data on exposure factors and first-/second-degree family history of cancer (1/2FHC) were collected. The MGPT was performed using Illumina next-generation sequencing technology. RESULTS: A total of 1,007 cases and 1,007 controls were included. The most frequent cancers were BC (n = 311), CCR (n = 147), prostate (n = 132), and lung cancers (n = 89). It was independently associated with cancer, 1/2FHC, tobacco consumption (TC), pesticide exposure (PE), solvent/glue exposure, and BMI <24. BC was associated with 1/2FHC, TC, and hormone replacement therapy use; CCR with 1/2FHC, TC, and BMI <24; prostate cancer with 1/2FHC, TC, and alcohol consumption; and lung cancer with 1/2FHC, TC, PE, and BMI <24. MGPT identified pathogenic/likely pathogenic mutations in 24 (32%) women with BC and in three (18%) women and four (24%) men diagnosed with CCR at under 50 years. Among the tested patients under 50 years with diagnosed BC and CCR, 98.6% and 97% present criteria for HCS, respectively. CONCLUSION: This study confirmed the association of several factors associated with BC, CCR, prostate, and lung cancers and reinforced the importance of evaluating FHC and genetic testing, especially for patients under 50 years with diagnosed BC or CCR. A better understanding of population-specific cancer risk factors builds on sustainable data for developing prevention strategies. These efforts increase the commitment to early detection and surveillance.

Clinical characteristics and outcomes of hospital-manifested COVID-19 among Brazilians.

OBJECTIVES: To analyze the clinical characteristics and outcomes of admitted patients with the hospital- versus community-manifested COVID-19 and to evaluate the risk factors related to mortality in the first population. METHODS: This retrospective cohort included consecutive adult patients with COVID-19, hospitalized between March and September 2020. The demographic data, clinical characteristics, and outcomes were extracted from medical records. Patients with hospital-manifested COVID-19 (study group) and those with community-manifested COVID-19 (control group) were matched by the propensity score model. Logistic regression models were used to verify the risk factors for mortality in the study group. RESULTS: Among 7,710 hospitalized patients who had COVID-19, 7.2% developed symptoms while admitted for other reasons. Patients with hospital-manifested COVID-19 had a higher prevalence of cancer (19.2% vs 10.8%) and alcoholism (8.8% vs 2.8%) than patients with community-manifested COVID-19 and also had a higher rate of intensive care unit requirement (45.1% vs 35.2%), sepsis (23.8% vs 14.5%), and death (35.8% vs 22.5%) (P <0.05 for all). The factors independently associated with increased mortality in the study group were increasing age, male sex, number of comorbidities, and cancer. CONCLUSION: Hospital-manifested COVID-19 was associated with increased mortality. Increasing age, male sex, number of comorbidities, and cancer were independent predictors of mortality among those with hospital-manifested COVID-19 disease.

COVID-19 outcomes in people living with HIV: Peering through the waves

Abstract Objective To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. Methods This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. Results Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). Conclusions Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group.

Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil / Real-Life Data on Hydroxychloroquine or Chloroquine with or Without Azithromycin in COVID-19 Patients: A Retrospective Analysis in Brazil

Resumo Fundamento Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. Objetivos Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. Métodos Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). Conclusão Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.

Abstract Background Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. Objectives To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. Methods A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. Results From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). Conclusion COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.

Pressure injury prevention measures: overview of systematic reviews / Medidas de prevención de las lesiones por presión: overview de revisiones sistemáticas / Medidas de prevenção de lesão por pressão: overview derevisões sistemáticas

ABSTRACT Objective: Summarizing the evidence from systematic reviews regarding the comparison the effectiveness of interventions to prevent pressure injuries. Method: Overview of systematic reviews conducted in accordance with Cochrane guidelines. A search was performed in databases, repositories and systematic review registration sites. Results: 15 reviews were included in this overview. The sensitivity analysis showed a reduction in the incidence of pressure injuries with nutritional supplementation compared to the standard hospital diet (Relative Risk (RR) = 0.83; 95% Confidence Interval (CI): 0.72-0.95). There was evidence of the superiority of constant low-pressure surfaces (RR = 0.38; 95% CI;0.24-0.61), alternating pressure devices (RR = 0.31; 95% CI:0.17-0.58) and alternative foams (RR = 0.40; 95% CI:0.21-0.74) when compared to the standard hospital mattress or standard foam. The use of a silicone cover reduced the incidence of pressure injuries by 75% (RR = 0.25; 95%CI:0.16-0.41) when compared to no cover. Conclusion: Although some interventions have been shown to be effective in reducing the incidence of pressure injury, the evidence is limited or very limited and subject to change. Registration CRD42017064586.

RESUMEN Objetivo: Resumir las pruebas de las revisiones sistemáticas sobre la comparación de la efectividad de las intervenciones para prevenir las lesiones por presión. Método: Resumen de las revisiones sistemáticas realizadas de acuerdo con las recomendaciones Cochrane. Se realizó una búsqueda en bases de datos, repositorios y sitios de registro de revisiones sistemáticas. Resultados: Se incluyeron 15 revisiones en esta revisión. El análisis de sensibilidad mostró una reducción de la incidencia de lesiones por presión con la suplementación nutricional en comparación con la dieta hospitalaria estándar (riesgo relativo [RR] = 0,83; intervalo de confianza [IC] del 95%: 0,72-0,95). Hubo pruebas de la superioridad de las superficies de baja presión constante (RR=0,38; IC del 95%:0,24-0,61), los dispositivos de presión alternante (RR = 0,31; IC del 95%:0,17-0,58) y las espumas alternativas (RR = 0,40; IC del 95%:0,21-0,74) en comparación con el colchón hospitalario estándar o la espuma estándar. El uso de una funda de silicona redujo la incidencia de lesiones por presión en un 75% (RR = 0,25; IC del 95%:0,16-0,41) en comparación con la ausencia de funda. Conclusión: Aunque algunas intervenciones han demostrado ser eficaces para reducir la incidencia de lesiones por presión, las pruebas son limitadas o muy limitadas y están sujetas a cambios. Registro CRD42017064586.

RESUMO Objetivo: Sumarizar as evidências de revisões sistemáticas sobre a comparação da efetividade de intervenções para prevenção de lesão por pressão. Método: Overview de revisões sistemáticas conduzida de acordo com as recomendações Cochrane. Realizou-se busca em bases de dados, repositórios e site de registro de revisões sistemáticas. Resultados: Foram incluídas 15 revisões nesta overview. A análise de sensibilidade demonstrou redução na incidência de lesão por pressão com a suplementação nutricional comparada a dieta hospitalar padrão (Risco Relativo (RR) = 0,83; Intervalo de Confiança(IC) 95%:0,72-0,95). Evidenciaram-se superioridade das superfícies de baixa pressão constante (RR = 0,38; IC 95%;0,24-0,61), dos dispositivos de pressão alternada (RR = 0,31; IC95%:0,17-0,58) e das espumas alternativas (RR = 0,40; IC95%:0,21-0,74) quando comparadas ao colchão hospitalar padrão ou de espuma padrão. O uso de cobertura de silicone reduziu em 75% a incidência de lesão por pressão (RR = 0,25; IC95%:0,16-0,41) quando comparada a nenhuma cobertura. Conclusão: Embora algumas intervenções demonstrem-se efetivas na redução da incidência da lesão por pressão, as evidências são limitadas ou muito limitadas e sujeitas a alteração. Registro CRD42017064586.

Net Survival in Survival Analyses for Patients with Cancer: A Scoping Review.

Population-based net survival is an important tool for assessing prognostic advances. The unbiased Pohar Perme Estimator (PPE) was suggested in 2012 and soon established itself as the gold standard for estimating net survival. This scoping review aims to know in which context this estimator is being used in the oncology area, what the authors point out as a justification for its use, and the limitations found. We searched PubMed, and the grey literature to answer the question: Have studies involving patients diagnosed with cancer used the PPE to estimate cancer-specific survival? How do they justify the use of the PPE and what are the limitations pointed out? Out of 295 screened, 85 studies were included in this review. The two main characteristics of the PPE mentioned by the studies as justification were the fact that it is an unbiased estimator (83.5%) and that it produces comparable estimates among populations with different mortality rates from causes other than cancer (36.47%). No study pointed to a limitation due to the use of PPE. As a conclusion, the Pohar Perme Estimator is the gold standard for estimating net survival and should be more used in oncology, especially when dealing with population-based studies where the follow-up time is long, making high the probability of death from causes other than cancer.

Comparative efficacy of amitriptyline, duloxetine and pregabalin for treating fibromyalgia in adults: an overview with network meta-analysis.

Treatment recommendations for fibromyalgia (FM) include a range of predominantly pharmacological treatment options designed to ensure the maintenance of symptoms and improvement in the quality of life of these patients. Our aim is to identify and compare the efficacy of amitriptyline (AMT), duloxetine (DLX), and pregabalin (PGB) for reducing pain intensity by 30% (R30%) and 50% (R50%) in adult patients with fibromyalgia. The review was conducted in the Medline/PubMed, Cochrane Library, and Embase databases up to February 2022. This study included systematic reviews (SR) of randomized clinical trials (RCTs) targeting adult patients over 18 years of age diagnosed with fibromyalgia according to the criteria of scientific societies, which include the basic clinical diagnosis characterized by the presence of pressure sensitivity in at least 11 of the 18 tender points, in addition to the presence of widespread musculoskeletal pain for a period longer than 3 months and a general assessment of the patient's health status. Pregnant women and children or adolescents were excluded. The Rob 2.0 tool from the Cochrane Collaboration was used to assess the risk of bias in RCTs. The quality of evidence of the reviews included was assessed according to the Grading of Recommendations Assessment, Development and Evaluation-GRADE. A meta-analysis for the evidence network was performed using the Bayesian approach, which allows simultaneous comparison of all treatment options (medication and dose). The different treatments were ranked according to the response rate according to the surface under the curve (SUCRA), which was expressed as a percentage. The results were presented in tables and figures. The protocol with the detailed methods was registered in PROSPERO (CRD42021229264). Eight systematic reviews were identified, and, from these, 15 clinical trials comparing AMT (n = 273), DLX (n = 2595), and PGB (n = 3,506) against placebo were selected. For the outcome R30%, PGB 450 mg was superior to DLX 30 mg and PGB 150 mg, while DLX 20 mg and 30 mg were not superior to placebo. For the outcome R50%, AMT 25 mg was superior to all other alternatives evaluated. The calculation of the SUCRA indicated that PGB 450 mg was the best performance option for R30% and AMT 25 mg for R50%. PGB 150 mg was the drug with the worst performance in the two outcomes evaluated. The drugs evaluated showed benefits for pain reduction in patients with fibromyalgia. In the absence of direct comparison studies, indirect comparison meta-analyses are an important resource for assisting in clinical decision-making. Our data only provide an indicator of the effectiveness of the three drugs evaluated, but as with other health conditions, tolerability and safety are important for the decision-making process and clinical management. In this regard, we encourage caution in interpreting our data.

Is there a better interceptive treatment for unerupted palatally displaced canines? A network meta-analysis

Abstract This systematic review aimed to investigate if there is a better interceptive treatment for palatally displaced canines (PDC) in the mixed dentition stage. The PubMed/MEDLINE, CENTRAL, Scopus, and EMBASE databases were searched for randomized clinical trials related to the research topic. The gray literature and reference lists were also assessed. Network meta-analysis was conducted to analyze the effects of different approaches on PDC eruption. The surface under the cumulative ranking area was calculated to rank the treatments. The certainty of the evidence was evaluated using the GRADE approach. Of the 892 eligible studies, 18 were selected for full-text analysis and 9 for meta-analysis, involving 506 participants and 730 PDC, to compare 9 approaches. The proportion of erupted PDC was significantly higher for all interceptive treatments compared with control (no intervention). Furthermore, the proportion of erupted PDC was higher in patients subjected to rapid maxillary expansion (RME) than those who underwent double extraction of primary canine and primary molar (relative risk (RR) = 2.68 ICr95%: 1.12-9.35). A higher proportion of erupted PDC was found for RME (RR = 3.07 ICr95%: 1.31-10.67), RME plus use of transpalatal arch (TA) plus extraction of primary canine(s) (EC) (RR = 1.43 ICr95%: 1.09-1.95), EC plus use of cervical pull headgear (RR = 1.38 ICr95%: 1.11-1.79), and EC plus use of TA (RR = 1.36 ICr95%: 1.00-1.9) than for EC. RME was most likely to be considered as the best interceptive treatment. Overall, the certainty of the evidence was considered low due to imprecision and indirectness. In conclusion, no intervention in the mixed dentition stage is the worst choice for PDC.

Fatores associados à satisfação das mulheres com a atenção pré-natal em Porto Alegre, Rio Grande do Sul, Brasil / Factors associated with women's satisfaction with prenatal care in Porto Alegre, Rio Grande do Sul, Brazil

Resumo O objetivo deste artigo é identificar fatores associados à plena satisfação com a atenção pré-natal em serviços de saúde de Porto Alegre, Rio Grande do Sul. Estudo transversal, com 287 mulheres que realizaram pré-natal na capital gaúcha. As mulheres foram selecionadas aleatoriamente em duas maternidades de grande porte (pública e privada) e entrevistadas nos seus domicílios, cerca de 30 dias após o parto, entre janeiro e agosto de 2016. A satisfação foi aferida por meio de escala Likert (muito satisfeita a muito insatisfeita). Foram estimadas razões de prevalência (RP) por regressão de Poisson com estimação robusta da variância, utilizando modelo hierarquizado. Os fatores associados à plena satisfação foram: ingresso no ensino superior (RP=1,49; IC95%:1,08-2,06); atendimento multiprofissional (RP=1,29; IC95%:1,00-1,66); recebimento de orientações sobre amamentação (RP=1,33; IC95%:1,05-1,68) e sobre local do parto (RP=1,56; IC95%:1,12-2,17); e sentimento da mulher de estar à vontade para fazer perguntas e participar das decisões (RP=5,17; IC95%:1,79-14,96). Os achados sugerem que serviços de pré-natal que oferecem cuidado multiprofissional, que dão orientações, e que oportunizam às gestantes o sentimento de estar à vontade para questionar e decidir sobre seu cuidado, proporcionam maior satisfação.

Abstract This article aims to identify factors associated with full satisfaction with prenatal care in health services in Porto Alegre (RS), Brazil. This is a cross-sectional study with 287 women that attended prenatal care in the state capital. Women were randomly selected at two large maternity hospitals (public and private) and interviewed at their homes around 30 days after delivery, from January to August 2016. Satisfaction was measured by a Likert scale (very satisfied to very unsatisfied). Prevalence ratios (PR) were estimated by Poisson regression with robust variance, using a hierarchical model. Factors associated with greater satisfaction were higher education (PR=1.49; 95% CI: 1.08-2.06); multiprofessional care (PR=1.29; 95% CI: 1.00-1.66); receiving information about breastfeeding (PR=1.33; 95% CI: 1.05-1.68) and place of delivery (PR=1.56; 95% CI: 1.12-2.17); and women feeling comfortable asking questions and participating in decisions (PR=5.17; 95% CI: 1.79-14.96). The findings suggest that prenatal care services that offer multiprofessional care, provide guidance, and make pregnant women feel comfortable asking and deciding about their care may generate greater satisfaction.

Perioperative Troponin Screening Identifies Patients at Higher Risk for Major Cardiovascular Events in Noncardiac Surgery.

Myocardial injury after noncardiac surgery (MINS) includes patients with traditional myocardial infarction and those with ischemic myocardial injury after surgery. This study evaluated the prognostic value of MINS on major cardiovascular events and 30-day mortality, and determined independent preoperative predictors of MINS in patients after noncardiac surgery. This multicenter prospective cohort study was part of the VISION Study. The sample consisted of 2504 patients who underwent noncardiac surgery at 2 tertiary hospitals in Brazil between September 2008 and July 2012. Troponin Ts were measured 6-12 hours, and on days 1-3 after surgery. Cox regression analyses were performed to identify independent variables of major outcomes. A total of 314 (13%) patients were diagnosed with MINS, of which 26 (8%) died. Length-of-hospital stay of MINS patients was 3 times higher (18 ± 22 days vs 5.8 ± 11 days). In multivariate analysis, 30-day mortality was significantly higher among patients with MINS (hazard ratio [HR] 3.17 (95% confidence interval [CI] 1.56-6.41)), and major bleeding (HR 5.76 (95% CI 2.75-12.05)), sepsis (HR 5.08 (95% CI 2.25-11.46)), active cancer (HR 4.22 (95% CI 1.98-8.98)), and general surgery (HR 3.11 (95% CI 1.51-6.41)). Multivariable analysis indicated a higher chance of MINS in patients ≥75 years of age, history of diabetes mellitus, hypertension, heart failure, coronary disease, and end-stage renal failure. The incidence of MINS within 30 days after noncardiac surgery is related to higher mortality. Postoperative troponin monitoring in elder patients and with risk factors for atherosclerotic disease may help reduce postoperative cardiovascular events.

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis.

BACKGROUND: Several endocrine therapy (ET)-based treatments are available for patients with advanced breast cancer. We assessed the efficacy of different ET-based treatments in patients with hormone receptor-positive/HER2-negative advanced breast cancer with endocrine-sensitive or endocrine-resistant disease. METHODS: We searched Medline and Cochrane Central Register of Controlled Trials up to 15 October 2019 and abstracts from major conferences from 2016 to October 2019. We included phase II/III randomised trials, comparing ≥2 ET-based treatments. Progression-free survival (PFS) and overall survival (OS) were analysed by network meta-analyses using MTC Bayesian models based on both fixed-effect and random-effect models; relative treatment effects were measured as HRs and 95% credibility intervals (CrI). All statistical tests were two-sided. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and this systematic review is registered in the PROSPERO database. RESULTS: 55 publications reporting on 32 trials (n=12 293 patients) were included. Regarding PFS in the endocrine sensitive setting (n=5200; 12 trials), the combination of cyclin-dependent kinases (CDK)4/6-inhibitors (CDK4/6i)+fulvestrant 500 mg (F500) was likely the most effective treatment (surface under the cumulative ranking curve (SUCRA)=97.3%), followed by CDK4/6i+aromatase inhibitor ±goserelin; there was no significant difference between them (HR 0.82; 95% CrI 0.54-1.25). Regarding OS (n=2157; five trials), the most effective treatment was probably CDK4/6i+F500 (SUCRA=97.3%); comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.63-0.95). Regarding PFS in the endocrine-resistant setting (n=6635; 20 trials), CDK4/6i+F500 was likely the most effective treatment (SUCRA=95.7%), followed by capivasertib+F500, without significant difference between them (HR 0.91; 95% CrI 0.60-1.36). For OS (n=4377; 11 trials), the most effective treatments were capivasertib+F500 (SUCRA=84.7%) and CDK4/6i+F500 (SUCRA=69.9%). Comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.67-0.89). CONCLUSIONS: CDK4/6i+F500 is likely the best treatment option in both endocrine-sensitive and endocrine-resistant diseases for PFS, and in endocrine-sensitive patients for OS. Concerning OS in endocrine-resistant patients, capivasertib+F500 and CDK4/6i+F500 are likely the best treatments. PROSPERO REGISTRATION NUMBER: CRD42018104628.

Upfront treatment for newly diagnosed transplant-ineligible multiple myeloma patients: A systematic review and network meta-analysis of 14,533 patients over 29 randomized clinical trials.

Choice of treatment for newly diagnosed transplant-ineligible multiple myeloma poses a difficult task due to an ever-increasing plethora of different regimens. Attempting to clarify this subject, we performed a systematic review and Bayesian network meta-analysis of 29 randomized clinical trials, enrolling 14,533 patients, and comparing 25 different treatment regimens regarding overall survival(OS), progression-free survival(PFS), complete response(CR), overall response rate(ORR) and toxicity. Head-to-head comparisons for all regimens and ranking of best treatments are reported. OS analysis showed superiority of lenalidomide(R) and bortezomib(V) containing regimens over thalidomide(T) protocols (e.g. Rd/CTD-HR:0.7;95%CrI:0.53-0.93, VMP/TD-HR:95%0.45;CrI:0.29-0.69). Concerning PFS, daratumumab(D) plus V (Dara-VMP) showed superior results over R (e.g. Dara-VMP/MPR-HR:0.52;95%CrI:0.34-0.77), V plus T (Dara-VMP/VTd-HR:0.56;95%CrI:0.37-0.65) and T (Dara-VMP/CTD-HR:0.34;95%CrI:0.23-0.49) containing regimens. Also, VRd and VMPT-VT performed well over other regimens. Dara-VMP showed superior response rates over R (ORR Dara-VMP/MPR-RR:6.27;95%CrI:2.18-18.95, CR Dara-VMP/MPR-RR:1.53;95%CrI:1.21-1.96) and T (ORR Dara-VMP/MPT-T-RR:4.05;95%CrI:1.19-13.26, CR Dara-VMP/MPT-T-RR:1.42;95%CrI:1.09-1.85; ORR Dara-VMP/CTD-RR:2.72;95%CrI:1.2-6.31, CR Dara-VMP/CTD-RR:1.2;95%CrI:1.05-1.36) including a higher rate of complete remission even when compared to VRd (RR:1.29;95%CrI:1.01-1.66). A higher rate of grade 3-4 adverse events was found for RD and CPR (thrombotic); VTd, VTP and VMPT-VT (neurological); RD and VAD (infectious); MPR-R and VAD (hematological); Vd and VTd (gastrointestinal); VAD, VMPCc and RD (cardiovascular). These results confirm obsolescence of classical regimens (such as VAD and MP) while pointing out benefits in efficacy resulting from incorporation of quadruplets and triplets combining new agents (Dara-VMP, VRd and VMPT-VT) and supports current rational of treatment until progression or prohibitive toxicity, especially when including lenalidomide. Based on this data, we would recommended incorporation of strategies combining novel agents (monoclonal antibodies, immunomodulatory imide drugs and proteasome inhibitors) in triplets or quadruplets and/or those comprising long term use of lenalidomide as standard frontline treatments. Moreover, this study settles daratumumab's place as an attractive alternative for upfront treatment.

Prevalência de fluorose dental em regiões abastecidas com água sem suplementação de flúor no território brasileiro: uma revisão sistemática e metanálise / Prevalence of dental fluorosis in regions supplied with non-fluoridated water in the Brazilian territory: a systematic review and meta-analysis

Resumo Trata-se de uma revisão sistemática e metanálise para estimar e comparar as prevalências de fluorose dental em localidades brasileiras abastecidas com água tratada sem suplementação de flúor e em localidades que utilizam de água de origem subterrânea. Em dezembro de 2016 foram buscados estudos transversais em 8 bases de dados incluindo a "literatura cinzenta". As prevalências foram estimadas utilizando modelo misto de efeitos aleatórios considerando as localidades como subgrupo. A heterogeneidade entre os estudos foi avaliada através da estatística I2 e do teste Q de Cochran. Foram encontrados 1.038 registros, dos quais apenas 18 artigos preencheram os critérios de inclusão, sendo submetidos para análise. O modelo metanalítico estimou em 8,92% (IC95%:5,41% até 14,36%) a prevalência de fluorose dental em municípios com água tratada sem suplementação de flúor e em 51,96% (IC95%: 31,03% até 72,22%) em municípios abastecidos por poços artesianos. A heterogeneidade entre os estudos foi alta, I2 = 95% (p < 0,01) no primeiro subgrupo de municípios e I2 = 98% (p < 0,01) no segundo subgrupo. A prevalência foi significativamente maior (p < 0,001) em populações expostas à água de poços artesianos, indicando que a presença de flúor natural em concentrações elevadas representa um fator de risco para a ocorrência de fluorose dental.

Abstract This systematic review and meta-analysis aimed to estimate and compare the prevalences of dental fluorosis in Brazilian cities supplied with non-fluoridated water and in locations that uses groundwater. In December of 2016, cross-sectional studies were searched in eight databases, including the "grey literature". The prevalences were estimated through a mixed random effects model considering the locations as subgroups. The heterogeneity among the studies was assessed with I2 statistics and the Cochran's Q test. A total of 1038 records were found, from which only 18 articles met the inclusion criteria and were subjected to analysis. The meta-analytic model estimated a prevalence of dental fluorosis of 8.92 % (95 % CI: 5.41 % to 14.36 %) in cities supplied with non-fluoridated water, and of 51.96 % (95 % CI: 31.03 % to 72.22 %) in cities supplied by artesian wells. The heterogeneity among the studies was high: I2 = 95 % (p < 0.01) in the first subgroup of cities and I2 = 98 % (p < 0.01) in the second subgroup. The prevalence was significantly higher (p < 0.001) in populations exposed to artesian well water, indicating that the presence of natural fluoride at high concentrations represents a risk factor for the occurrence of dental fluorosis.

Association between phase angle from bioelectrical impedance analysis and level of physical activity: Systematic review and meta-analysis.

OBJECTIVE: To evaluate the relationship between physical activity and phase angle. DESIGN: Systematic Review and Meta-analysis. DATA SOURCES: Electronic searches of MEDLINE (via PUBMED), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), SciELO, LILACS, SPORTDiscus, Scopus, and Web of Science from inception to December 10th, 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The PICOS strategy was defined, in which "P" corresponded to participants of any age, sex or ethnicity, "I" indicated any type of physical activity program, "C" denoted lack of exercise or irregular physical activity, "O" corresponded to the phase angle obtained by bio-impedance, and "S" indicated longitudinal or cross-sectional studies. RESULTS: In cross-sectional studies the phase angle was higher among the active individuals (MD = 0.70; 95% CI: 0.48, 0.92, P < 0.001), with low heterogeneity (I2 = 0%; P = 0.619). In longitudinal studies, the mean of the difference of phase angles from the baseline was significantly higher for the active group than the control group (MD = 0.30; 95% CI: 0.11, 0.49, P = 0.001), with low heterogeneity (I2 = 13%, P = 0.331). No evidence of publication bias was found and the overall risk of bias was moderate to high. SUMMARY/CONCLUSION: The positive association of physical activity with phase angle reinforces the importance of routinely including exercise in health care. We also identified the need for further studies to define with different types, intensities and frequencies of exercises should be conducted in order to find the best dose-effect relationship.

Frontline treatment for transplant-eligible multiple myeloma: A 6474 patients network meta-analysis.

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post-transplant results. Therefore, best frontline treatment for transplant-eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta-analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide-lenalidomide-dexamethasone) over TD-based (thalidomide-dexamethasone, HR = 0.76,0.62-0.90), VAD-based (HR = 0.71,0.52-0.90), and Z-Dex (idarubicin-dexamethasone, HR = 0.37,0.17-0.76) regimens. Concerning PFS, VTD (bortezomib-thalidomide-dexametasone) showed superior results when compared with TD-based (HR = 0.66,0.51-0.84), VAD-based (HR = 0.61,0.46-0.82), Z-Dex (HR = 0.42,0.22-0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41-0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide-only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide-doxorubicin-dexamethasone), neurological with PAD (bortezomib-doxorubicin-dexamethasone), infectious with Dex, hematological with Z-Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant-eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression-free survival, when compared with bortezomib/thalidomide protocols.

Cross-border healthcare and prognosis of HIV infection in the triple border Brazil-Paraguay-Argentina / A assistência à saúde transfronteira e o prognóstico da infecção pelo HIV na tríplice fronteira Brasil-Paraguai-Argentina / Atención sanitaria fronteriza y pronóstico de infección por VIH en la triple frontera Brasil-Paraguay-Argentina

Abstract: The act of crossing an international border for healthcare is a reality in border areas and the flow is in the direction of the city with more human and healthcare resources. Although several prognostic factors related to HIV+ patients are known, the prognostic value of this type of mobility for long term care is still neglected. This study compares the prognosis of HIV patients from three groups, one involved in regional mobility, another in cross-border mobility in search for healthcare and the reference group which is composed by patients living in the same city of the health facility. This is a retrospective cohort study using medical records from a healthcare service in Brazil. Following survival analysis with log-rank test and Cox proportional hazard models, overall survival had no significant difference between patients who were involved in regional (HR = 1.03; 95%CI: 0.69-1.54; p = 0.89) or international (HR = 1.07; 95%CI: 0.58-1.97; p = 0.83) mobility and those who were not. This lack of difference was kept when adjusted for known prognostic factors. In this retrospective cohort study, exposure to both regional and international migration did not have a significant association with the risk of death by any cause in crude or adjusted analyses for already known prognostic factors. This is the first study to consider the prognostic role of cross-border healthcare for HIV patients. Despite these findings, the need of monitoring the extent and the clinical and demographic characteristics of healthcare demand originated in the other side of the border and the use of these data for decision making in health management is emphasized.

Resumo: O ato de atravessar uma fronteira internacional para receber cuidados de saúde é uma realidade nas áreas fronteiriças. O fluxo tende a ser em direção à cidade com os melhores recursos humanos e melhor infraestrutura em saúde. Embora sejam conhecidos os fatores prognósticos relacionados à infecção pelo HIV, o valor prognóstico desse tipo de migração a longo prazo tem recebido menos atenção. Este estudo divide e compara o prognóstico em três grupos de pacientes com HIV: um envolvido em mobilidade regional, outro em mobilidade transfronteira em busca de assistência e o terceiro constituído de pacientes que residem na mesma cidade onde o serviço de saúde está localizado. Este estudo de coorte retrospectiva utiliza dados de prontuários de um serviço de saúde no Brasil. Ao analisar a sobrevida com o teste de log-rank e modelos riscos proporcionais de Cox, a sobrevida geral não mostrou diferença significativa entre pacientes que recebiam cuidados através da mobilidade regional (HR = 1,03; IC95%: 0,69-1,54; p = 0,89) ou transfronteira (HR = 1,07; IC95%: 0,58-1,97; p = 0,83) e aqueles que recebiam atendimento na cidade onde residiam. Essa falta de diferença se manteve quando a análise foi ajustada para os fatores prognósticos conhecidos. Neste estudo de coorte retrospectiva, a exposição à migração regional ou internacional não mostrou associação significativa com o risco de óbito por qualquer causa, de acordo com a análise bruta e as análises ajustadas para os fatores prognósticos já conhecidos. Este foi o primeiro estudo a considerar o papel prognóstico da assistência transfronteira para pacientes com HIV. Apesar desses achados, enfatiza-se a necessidade de monitorar o grau e as características clínicas e demográficas da demanda por assistência com origem do lado oposto da fronteira, além de utilizar esses dados no processo decisório na gestão da saúde.

Resumen: El hecho de cruzar una frontera internacional en búsqueda de asistencia sanitaria es una realidad en las áreas fronterizas y el flujo migratorio se dirige hacia la ciudad con más recursos humanos y sanitarios. A pesar de que se conocen los diferentes factores pronósticos relacionados con el VIH, el valor pronóstico de este tipo de movilidad continúa todavía olvidado durante mucho tiempo. Este estudio compara los pronósticos de pacientes de VIH de tres grupos, uno implicado en la movilidad regional, otro en la movilidad fronteriza en búsqueda de asistencia sanitaria y el grupo de referencia que estaba compuesto por pacientes viviendo en la misma ciudad donde se encontraban los servicios sanitarios. Este es un estudio retrospectivo de cohorte, usando expedientes médicos de un servicio de salud en Brasil. En los siguientes análisis de supervivencia con prueba log-rank y modelos de Cox de riesgo proporcional, en cuanto a la supervivencia general no hubo una diferencia significativa entre pacientes que estaban implicados en la movilidad regional (HR = 1,03; 95%CI: 0,69-1,54; p = 0,89) o internacional (HR = 1,07; 95%CI: 0,58-1,97; p = 0,83) y aquellos que no lo estuvieron. Esta falta de diferencia se mantuvo cuando se ajustó para los factores pronósticos conocidos. En este estudio retrospectivo de cohorte, la exposición tanto a la migración regional como la internacional no tuvo una asociación significativa con el riesgo de muerte por alguna causa en los análisis crudos o ajustados para los factores pronósticos ya conocidos. Se trata del primer estudio en considerar el papel pronóstico de la asistencia sanitaria transfronteriza en pacientes con VIH. A pesar de estos resultados, existe la necesidad de un monitoreo sobre la extensión y las características clínicas y demográficas de la demanda de servicios sanitarios al otro lado de la frontera, así como el énfasis del uso de estos datos para la toma de decisiones en la gestión de salud.

Predictors of In-Hospital Mortality among Patients with Pulmonary Tuberculosis: A Systematic Review and Meta-analysis.

BACKGROUND: There is uncertainty regarding which factors are associated with in-hospital mortality among patients with pulmonary TB (PTB). The aim of this systematic review and meta-analysis is to identify predictors of in-hospital mortality among patients with PTB. METHODS: We searched MEDLINE, EMBASE, and Global Health, for cohort and case-control studies that reported risk factors for in-hospital mortality in PTB. We pooled all factors that were assessed for an association, and presented relative associations as pooled odds ratios (ORs). RESULTS: We identified 2,969 records, of which we retrieved 51 in full text; 11 cohort studies that evaluated 5,468 patients proved eligible. Moderate quality evidence suggested an association with co-morbid malignancy and in-hospital mortality (OR 1.85; 95% CI 1.01-3.40). Low quality evidence showed no association with positive sputum smear (OR 0.99; 95% CI 0.40-2.48), or male sex (OR 1.09, 95% CI 0.84-1.41), and very low quality evidence showed no association with diabetes mellitus (OR 1.31, 95% IC 0.38-4.46), and previous TB infection (OR 2.66, 95% CI 0.48-14.87). CONCLUSION: Co-morbid malignancy was associated with increased risk of in-hospital death among pulmonary TB patients. There is insufficient evidence to confirm positive sputum smear, male sex, diabetes mellitus, and previous TB infection as predictors of in-hospital mortality in TB patients.

Is there a best conventional material for restoring posterior primary teeth? A network meta-analysis

Abstract This study aimed to compare the longevity of different conventional restorative materials placed in posterior primary teeth. This systematic review was conducted following the PRISMA statement and registered in PROSPERO (CRD42016035775). A comprehensive electronic search without date or language restrictions was performed in PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, Turning Research Into Practice (TRIP) and Clinical Trials databases up to January 2017, selecting randomized clinical trials that assessed the longevity of at least two different conventional restorative materials performed in primary molars. Seventeen studies were included in this systematic review. Pairwise and network meta-analyses were performed and relative risks and 95% confidence intervals (CI) calculated. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Restorations of primary molars with conventional glass ionomer cement showed increased risk of failure than compomer, resin-modified glass ionomer cement, amalgam, and composite resin. Risk of bias was low in most studies (45.38% of all items across studies). Pediatric dentists should avoid conventional glass ionomer cement for restoring primary molars.

Blood Trace Element Concentrations in Polycystic Ovary Syndrome: Systematic Review and Meta-analysis.

Polycystic ovary syndrome (PCOS) is a prevalent condition in women of reproductive age. PCOS is characterized by androgen excess and chronic anovulation and associated with low-grade inflammation and metabolic comorbidities. Some trace elements have been linked to pathophysiological mechanisms of oxidative stress and inflammation in different disorders. Therefore, we conducted a systematic review and meta-analysis of the available evidence regarding trace element concentrations in PCOS. We reviewed MEDLINE and EMBASE in search of case-control, cross-sectional, and cohort studies published until September 2015. Of 183 studies identified, six were selected for systematic review. All used the Rotterdam criteria for the diagnosis of PCOS. Two studies evaluating chromium and one assessing cobalt levels did not observe differences between PCOS and controls. Another study recorded similar nickel and vanadium levels between the groups, but lower selenium concentrations in women with PCOS compared to controls. Four studies were included in the random effects model meta-analysis, for a total of 264 PCOS and 151 control women. Copper levels were found to be higher in women with PCOS than in controls [mean difference 0.12 ppm (95 % CI 0.07; 0.17 ppm); I 2 = 0 %]. Manganese [mean difference 0.04 ppm (95 % CI -0.05; 0.13 ppm); I 2 = 94.4 %] and zinc concentrations [mean difference 0.02 ppm (95 % CI -0.12; 0.16 ppm); I 2 = 92.4 %] were similar between the groups. The present results suggest a relationship between increased copper concentration and PCOS. This systematic review and meta-analysis is registered in PROSPERO under number CRD42016034036.