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BACKGROUND: This is the first update of this review first published in 2009. When treating elevated blood pressure, doctors usually try to achieve a blood pressure target. That target is the blood pressure value below which the optimal clinical benefit is supposedly obtained. "The lower the better" approach that guided the treatment of elevated blood pressure for many years was challenged during the last decade due to lack of evidence from randomised trials supporting that strategy. For that reason, the standard blood pressure target in clinical practice during the last years has been less than 140/90 mm Hg for the general population of patients with elevated blood pressure. However, new trials published in recent years have reintroduced the idea of trying to achieve lower blood pressure targets. Therefore, it is important to know whether the benefits outweigh harms when attempting to achieve targets lower than the standard target. OBJECTIVES: The primary objective was to determine if lower blood pressure targets (any target less than or equal to 135/85 mm Hg) are associated with reduction in mortality and morbidity as compared with standard blood pressure targets (less than or equal to 140/ 90 mm Hg) for the treatment of patients with chronic arterial hypertension. The secondary objectives were: to determine if there is a change in mean achieved systolic blood pressure (SBP) and diastolic blood pressure (DBP associated with "lower targets" as compared with "standard targets" in patients with chronic arterial hypertension; and to determine if there is a change in withdrawals due to adverse events with "lower targets" as compared with "standard targets", in patients with elevated blood pressure. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to May 2019: the Cochrane Hypertension Specialised Register, CENTRAL (2019, Issue 4), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing patients allocated to lower or to standard blood pressure targets (see above). DATA COLLECTION AND ANALYSIS: Two review authors (JAA, VL) independently assessed the included trials and extracted data. Primary outcomes were total mortality; total serious adverse events; myocardial infarction, stroke, congestive heart failure, end stage renal disease, and other serious adverse events. Secondary outcomes were achieved mean SBP and DBP, withdrawals due to adverse effects, and mean number of antihypertensive drugs used. We assessed the risk of bias of each trial using the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach.  MAIN RESULTS: This update includes 11 RCTs involving 38,688 participants with a mean follow-up of 3.7 years. This represents 7 new RCTs compared with the original version. At baseline the mean weighted age was 63.1 years and the mean weighted blood pressure was 155/91 mm Hg. Lower targets do not reduce total mortality (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.05; 11 trials, 38,688 participants; high-certainty evidence) and do not reduce total serious adverse events (RR 1.04, 95% CI 0.99 to 1.08; 6 trials, 18,165 participants; moderate-certainty evidence). This means that the benefits of lower targets do not outweigh the harms as compared to standard blood pressure targets. Lower targets may reduce myocardial infarction (RR 0.84, 95% CI 0.73 to 0.96; 6 trials, 18,938 participants, absolute risk reduction (ARR) 0.4%, number needed to treat to benefit (NNTB) 250 over 3.7 years) and congestive heart failure (RR 0.75, 95% CI 0.60 to 0.92; 5 trials, 15,859 participants, ARR 0.6%, NNTB  167 over 3.7 years) (low-certainty for both outcomes). Reduction in myocardial infarction and congestive heart failure was not reflected in total serious adverse events. This may be due to an increase in other serious adverse events (RR 1.44, 95% CI 1.32 to 1.59; 6 trials. 18,938 participants, absolute risk increase (ARI) 3%,  number needed to treat to harm (NNTH) 33 over four years) (low-certainty evidence). Participants assigned to a "lower" target received one additional antihypertensive medication and achieved a significantly lower mean SBP (122.8 mm Hg versus 135.0 mm Hg, and a lower mean DBP (82.0 mm Hg versus 85.2 mm Hg, than those assigned to "standard target". AUTHORS' CONCLUSIONS: For the general population of persons with elevated blood pressure, the benefits of trying to achieve a lower blood pressure target rather than a standard target (≤ 140/90 mm Hg) do not outweigh the harms associated with that intervention. Further research is needed to see if some groups of patients would benefit or be harmed by lower targets. The results of this review are primarily applicable to older people with moderate to high cardiovascular risk. They may not be applicable to other populations.

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Introdução: O melanoma cutâneo é uma neoplasia que apresenta comportamento agressivo quando em estágio de evolução avançado, de forma que o sucesso no tratamento depende do diagnóstico precoce. A utilização da microscopia confocal in vivo (MC) como técnica complementar à dermatoscopia digital tem se mostrado útil para aumentar a acurácia diagnóstica dessa neoplasia. Semelhante à dermatoscopia, a MC revela detalhes morfológicos da arquitetura tecidual no plano paralelo à pele e, além disso, fornece imagens instantâneas com alta magnificação e resolução celular. Objetivo: Determinar como a utilização da microscopia confocal in vivo como técnica complementar à dermatoscopia digital pode melhorar a acurácia no diagnóstico do melanoma e reduzir o número de excisões cirúrgicas desnecessárias em um hospital referência de oncologia cutânea. Demonstrar por meio do cálculo do Número necessário para tratar (NNT), o impacto da associação dos métodos de imagem na rotina de um hospital referência em oncologia cutânea. Material e método: Trata-se de um estudo, retrospectivo observacional a ser realizado no Departamento de Oncologia Cutânea do A.C.Camargo Cancer Center. Foram incluídas 209 lesões melanocíticas duvidosas, divididas em dois grupos de análise: as lesões que sofreram modificações no seguimento dermatoscópico, sugestivas de melanoma, encaminhadas para excisão cirúrgica, após realização da MC (Grupo de lesões excisadas) e outro grupo em que os achados de benignidade da MC indicaram o seguimento da lesão (Grupo de lesões em seguimento). Todos os casos foram analisados em 3 etapas distintas: dermatoscopia isolada da lesão a ser analisada antes do exame de MC, utilizando-se o método de Análise de Padrão; dermatoscopia digital comparativa: análise das mudanças que levaram a indicação da MC; análise da Microscopia confocal, utilizando protocolo do Departamento. Para o cáculo do NNT da dermatoscopia de seguimento, foram analisadas mais 300 lesões melanocíticas de pacientes que estavam em acompanhamento digital. Resultados: Por meio da regressão logística simples e múltipla, foram criados dois nomogramas de análise para predizer a chance de uma dada lesão ser um melanoma. Posteriormente, de forma inédita, foi calculado valores de NNT em 3 cenários distintos. Os valores obtidos foram de 7,89 para dermatoscopia digital de seguimento, 5,8 para MC e um NNT hipotético de 3,09 quando aplicado aos nomogramas criados, aplicados na amostra. Conclusão: O presente estudo comprova a importância da MC como método de avaliação complementar no seguimento dos nevos melanocíticos em pacientes com alto risco para câncer de pele, aumentando a detecção do melanoma no seu estágio inicial, por meio da criação de dois nomogramas e a criação de uma aplicativo para a sua aplicabilidade.Comprovou-se a redução significativa do NNT quando associado o exame de microscopia confocal à dermatoscopia digital na rotina ambulatorial de seguimento dos pacientes de alto risco num hospital oncológico de referência (AU)

Introduction: Cutaneous melanoma is a neoplasm that presents aggressive behavior when in advanced stage of evolution, so success in treatment depends on early diagnosis. The use of in vivo confocal microscopy (CM) as a complementary technique to digital dermatoscopy has been shown to be useful to increase the diagnostic accuracy of this neoplasm. Similar to dermoscopy, CM reveals morphological details of tissue architecture in the plane parallel to the skin and, in addition, provides instant images with high magnification and cellular resolution. Objective: To determine how the use of in vivo confocal microscopy as a complementary technique to digital dermatoscopy can improve the accuracy of melanoma diagnosis and reduce the number of unnecessary surgical excisions in a cutaneous oncology referral hospital. Demonstrate by calculating the Number Needed to Treat (NNT) the impact of combining imaging methods on the routine of a referral cutaneous oncology hospital. Material and method: This is a retrospective observational study to be performed at the Department of Cutaneous Oncology, Hospital A.C.Camargo Cancer Center. We included 209 dubious melanocytic lesions divided into two groups of analysis: lesions that underwent changes in the dermoscopic follow-up, suggestive of melanoma, which were referred for surgical excision after MC (Excised lesions group) and another group in which the findings of benignity of the MC indicated follow-up of the lesion (Group of injuries in follow-up). All cases were analyzed in 3 distinct stages: isolated dermatoscopy of the lesion to be analyzed before the MC examination, using the Pattern Analysis method; Comparative digital dermatoscopy: analysis of changes that led to the indication of MC, analysis of confocal microscopy, using MC protocol of the Department. For the NNT calculation of the follow up dermatoscopy, it was analysed more than 300 melanocytic lesions from patients that were under digital follow up. Results: Through simple and multiple logistic regression, two analysis nomograms were created to predict the chance of a given lesion being a melanoma. Subsequently, unpublished, NNT values were calculated in 3 different scenarios. The values obtained were 7.89 for follow-up digital dermatoscopy, 5.8 for MC and a hypothetical NNT of 3.09 when applying the nomograms applied to the sample. Conclusion: The current study proves the importance of the MC as complementar evaluation method in the follow up of the melanocytic nevi in patients with high risk for skin cancer, increasing the melanoma detection in its early stage. Through the creation of two new nomograms and its applicability by the creation of an app, it was proven a significative reduction of the NNT when the confocal microscopy examination is associate to the digital dermoscopic in the ambulatory routine of high risk patients follow up in an oncologic reference hospital (AU)

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OBJECTIVE: Multiple sclerosis (MS) is a complex autoimmune and neurodegenerative disease of the central nervous system. Since MS affects mostly fertile women, pregnancy issues often arise in daily practice. The present study assessed the use of postpartum intravenous immunoglobulin (IVIG) in MS. METHODS: The authors individually searched for records using PubMed, Medline, EMBASE, Cochrane, SciELO, LILACS, and Google Scholar, using the terms "multiple sclerosis" OR "MS" AND "pregnancy" OR "gestation" OR "partum" OR "post-partum" OR "puerperium" AND "immunoglobulin". RESULTS: The initial search returned 321 papers. There were 11 eligible articles selected for the review. In total, 380 patients had received post-natal IVIG to reduce the number of postpartum relapses. The unadjusted number needed to treat was 6.3 for the quantitative and 5.8 for the qualitative analyses. CONCLUSION: The therapeutic effect of IVIG for prevention of postnatal relapses in MS could not clearly be established in this meta-analysis.

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ABSTRACT Multiple sclerosis (MS) is a complex autoimmune and neurodegenerative disease of the central nervous system. Since MS affects mostly fertile women, pregnancy issues often arise in daily practice. The present study assessed the use of postpartum intravenous immunoglobulin (IVIG) in MS. Methods The authors individually searched for records using PubMed, Medline, EMBASE, Cochrane, SciELO, LILACS, and Google Scholar, using the terms "multiple sclerosis" OR "MS" AND "pregnancy" OR "gestation" OR "partum" OR "post-partum" OR "puerperium" AND "immunoglobulin". Results The initial search returned 321 papers. There were 11 eligible articles selected for the review. In total, 380 patients had received post-natal IVIG to reduce the number of postpartum relapses. The unadjusted number needed to treat was 6.3 for the quantitative and 5.8 for the qualitative analyses. Conclusion The therapeutic effect of IVIG for prevention of postnatal relapses in MS could not clearly be established in this meta-analysis.

RESUMO Esclerose múltipla (EM) é uma complexa doença autoimune e neurodegenerativa do sistema nervoso central. Uma vez que EM afeta principalmente mulheres em idade fértil, assuntos relacionados à gravidez frequentemente surgem na prática diária. O presente estudo avaliou o uso pós-parto de imunoglobulina (IVIG) na EM. Métodos Os autores individualmente pesquisaram as bases de dados PubMed, Medline, EMBASE, Cochrane, SciELO, LILACS, e Google Scholar usando os termos "multiple sclerosis" OR "MS" AND "pregnancy" OR "gestation" OR "partum" OR "post-partum" OR "puerperium" AND "immunoglobulin". Resultados A pesquisa inicial retornou 321 artigos. Havia 11 artigos elegíveis para a revisão. No total, havia relato de 380 pacientes que receberam IVIG após a gravidez visando reduzir o número de surtos. O número necessário para tratar não ajustado foi 6,3 para análise quantitativa e 5,8 para análise qualitativa. Conclusão O efeito terapêutico da IVIG para prevenção dos surtos pós-parto na EM não pôde ser claramente estabelecida nesta meta-análise.

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Objetivo: O objetivo do estudo foi estimar e comparar o número necessário para tratar (NNT) entre a associação de cobimetinibe + vemurafenibe e outras opções terapêuticas no tratamento de melanoma metastático BRAFV600 mutado em primeira linha. Métodos: O NNT foi calculado como o inverso do risco absoluto de um medicamento em um ponto específico de tempo (12 meses). Os comparadores considerados foram o vemurafenibe monoterapia, dabrafenibe monoterapia, dabrafenibe + trametinibe, nivolumabe e ipilimumabe. O desfecho considerado foi a sobrevida livre de progressão (SLP), cujas curvas foram obtidas dos estudos coBRIM, BRIM-3, Robert, 2015, BREAK-3 e Checkmate 67. Resultados: Em 12 meses, os resultados de NNT foram: cobimetinibe + vemurafenibe = 1,92, vemurafenibe = 3,33; dabrafenibe = 4,67; dabrafenibe + trametinibe = 2,04; nivolumabe = 4,39 e ipilimumabe = 7,84. Conclusão: A associação de cobimetinibe e vemurafenibe no tratamento de pacientes com melanoma irressecável ou metastático, positivo para mutação BRAFV600 sem tratamento sistêmico prévio para a doença, apresenta resultados favoráveis em termos de NNT quando comparada a todas as outras opções terapêuticas disponíveis no mercado brasileiro para essa mesma indicação.

Objective: The objective of the study was to estimate and compare the number needed to treat (NNT) between the association of cobimetinib + vemurafenib and other therapeutic options in the first line treatment of metastatic melanoma with BRAFV600 mutation. Methods: The NNT was calculated as the inverse of absolute risk of a drug in a specific time point (12 months). The considered comparators were vemurafenib (monotherapy), dabrafenib (monotherapy), dabrafenib + trametinib, nivolumab and ipilumumab. Progression free survival (PFS) was the defined outcome, and its curves were obtained from coBRIM, BRIM-3, BREAK-3, Robert, 2015 and Checkmate 67 studies. Results: In 12 months, the NNT results were: cobimetinib + vemurafenib = 1.92; vemurafenib = 3.33; dabrafenib = 4.67; dabrafenib + trametinib = 2.04; nivolumab = 4.39 and ipilimumab = 7.84. Conclusion: The association of cobimetinib and vemurafenib in the treatment of patients with unresectable or metastatic melanoma, BRAFV600 mutated without previous systemic treatment, showed favorable results in terms of NNT when compared to the other therapeutic options available in the Brazilian market for the same indication.

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Objetivo: O objetivo deste estudo foi estimar o número necessário a tratar (NNT) e custo por evento evitado (COPE) de enzalutamida (ENZ) em comparação com abiraterona+prednisona (AA+P) em 12 e 24 meses sob perspectiva do sistema de saúde suplementar em pacientes com câncer de próstata resistente à castração metastático (CPRCM) sem quimioterapia prévia. Métodos: O NNT é calculado pelo inverso da diferença do risco absoluto de uma intervenção versus placebo; adicionalmente, o COPE representa o NNT multiplicado pelo custo de tratamento total de um período determinado. O risco absoluto de ENZ e AA+P e seus respectivos controles foram obtidos das curvas de sobrevida livre de progressão radiográfica (SLPr) e sobrevida global (SG) dos estudos PREVAIL e COU-AA-302, respectivamente. A duração de tratamento média no horizonte de 24 meses foi estimada utilizando a área sob a curva das respectivas curvas de SLPr. Os resultados foram a comparação entre ENZ e AA+P versus seus respectivos placebos em 12 e 24 meses para NNT e COPE. O custo total de tratamento consistiu em custos de medicamento, monitoramento, e manejo de eventos adversos (≥1%, eventos de interesses especiais). Resultados: A análise de 12 meses resultou em NNTSG/ENZ= 12,79; NNTSLPr/ENZ= 2,59; NNTSG/AA+P= 116,28; NNTSLPr/AA+P= 4,72 e COPESG/ENZ= BRL 1.626.583; COPESLPr/ENZ= BRL 329.701; COPESG/AA+P= BRL 15.144.886; COPESLPr/AA+P= BRL 614.368. Para a análise de 24 meses, os resultados foram: NNTSG/ENZ= 11,00; NNTSLPr/ENZ= 3,58; NNTSG/AA+P= 16,56; NNTSLPr/AA+P= 5,00 e COPESG/ENZ= BRL 1.965.454; COPESLPr/ENZ= BRL 639.327; COPESG/AA+P= BRL 2.833.580; COPESLPr/AA+P= BRL 855.741. Conclusão: Para ambos horizontes de tempo, os resultados foram favoráveis para ENZ vs. AA+P em pacientes com CPRCM.

Objective: The aim of this study was to estimate the NNT and COPE of enzalutamide (ENZ) in comparison with abiraterone acetate+prednisone (AA+P) over a 12-month and 24-month period from the Supplementary Health System perspective in metastatic castration-resistant prostate cancer patients who are chemotherapy naïve (MCRPC). Methods: The NNT is calculated by the inverse of the absolute risk reduction of an intervention vs. control; additionally, COPE represents the NNT multiplied by total cost of treatment in a pre-defined period. The absolute risk of ENZ and AA+P, and their respective control treatments, were obtained from the Kaplan Meier curves for the co-primary end points of radiographic progression free survival (rPFS) and overall survival (OS) from the clinical studies PREVAIL and COU-AA-302, respectively. Mean treatment duration was estimated utilizing the area under curve (AUC) technique from the respective intervention rPFS curves. The results analyzed ENZ or AA+P versus its respective placebo at 12 and 24 months for NNT and COPE. Total treatment cost consisted of drug cost, monitoring cost and adverse event (>=1% incidence and special interest adverse events) related cost. Results: The 12 month analysis resulted in NNTOS/ENZ= 12.79; NNTrPFS/ENZ= 2.59; NNTOS/AA+P= 116.28; NNTrPFS/AA+P= 4.72 and COPEOS/ENZ= BRL 1,626,583; COPErPFS/ENZ= BRL 329,701; COPEOS/AA+P= BRL 15,144,886; COPErPFS/AA+P= BRL 614,368. For the 24-month analysis, the results were: NNTOS/ENZ= 11.00; NNTrPFS/ENZ= 3.58; NNTOS/AA+P=16.56; NNTrPFS/AA+P= 5.00 and COPEOS/ENZ= BRL 1,965,454; COPErPFS/ENZ= BRL 639,327; COPEOS/ AA+P= BRL 2,833,580; COPErPFS/AA+P= BRL 855,741. Conclusion: Across the 12- and 24-month time horizons, the NNT and COPE was favorable for ENZ vs. AA+P in patients with MCRPC.

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The occurrence of leprosy has decreased in the world but the perspective of its elimination has been questioned. A proposed control measure is the use of post-exposure chemoprophylaxis (PEP) among contacts, but there are still questions about its operational aspects. In this text we discuss the evidence available in literature, explain some concepts in epidemiology commonly used in the research on this topic, analyze the appropriateness of implementing PEP in the context of Brazil, and answer a set of key questions. We argue some points: (1) the number of contacts that need to receive PEP in order to prevent one additional case of disease is not easy to be generalized from the studies; (2) areas covered by the family health program are the priority settings where PEP could be implemented; (3) there is no need for a second dose; (4) risk for drug resistance seems to be very small; (5) the usefulness of a serological test to identify a higher risk group of individuals among contacts is questionable. Given that, we recommend that, if it is decided to start PEP in Brazil, it should start on a small scale and, as new evidence can be generated in terms of feasibility, sustainability and impact, it could move up a scale, or not, for a wider intervention.

A ocorrência de hanseníase tem diminuído no mundo apesar de que a perspectiva de sua eliminação tem sido questionada. Uma proposta para o controle da endemia é a quimioprofilaxia pós-exposição entre contatos (post-exposure chemoprophylaxis, PEP), embora ainda existam dúvidas quanto aos seus aspectos operacionais e generalização de resultados. Nesse texto nós discutimos as evidências disponíveis na literatura, explicamos alguns conceitos epidemiológicos comumente encontrados em pesquisa sobre PEP e a implantação da PEP no contexto brasileiro. Nós argumentamos que: (1) a estimativa em diferentes estudos do numero de contatos necessário para receber PEP para prevenir um novo caso de hanseníase (number needed to treat, NNT) não é facilmente generalizável; (2) áreas cobertas pelo programa de saúde da família são as áreas prioritárias onde PEP poderia ser implantado; (3) não existe necessidade de segunda dose da quimioprofilaxia; (4) o risco de resistência à droga usada na PEP parece ser muito pequeno; (5) questionamos a necessidade de teste sorológico para identificar indivíduos entre os contatos que tenham maior risco de doença. Nós opinamos que, se houver uma decisão para se iniciar PEP no Brasil, essa intervenção deveria ser iniciada em pequena escala e, à proporção que novas evidências são geradas sobre a factibilidade, sustentabilidade e impacto da intervenção, a intervenção com PEP poderia ou não ser usada em larga escala.

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