Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Conduta para o melanoma cutâneo

A incidência do melanoma cutâneo vem aumentando significativamente de 1:1500 em 1935 para cerca de 1:75 no ano 2000. Contudo, atribuído a um diagnóstico cada vez mais precoce, têm-se observado uma melhora da sobrevida em cinco anos com diminuição da taxa de mortalidade geral entre 70 a 80% desde a década de 30. É o câncer mais prevalente na faixa etária entre 25 e 35 anos nos EUA. O Brasil ocupa a 15º posição com relação à incidência do tumor no mundo. O estadiamento inicial é baseado na pesquisa de sinais e sintomas que podem indicar doença metastática. Especial atenção deve ser dada à palpação de linfonodos regionais. A espessura e a ulceração são os principais fatores de risco independentes, em pacientes com melanoma primário com linfonodos livres. Já naqueles com metástases linfonodais, a presença de ulceração, de metástase detectada macroscopicamente e o número de linfonodos acometidos, são os principais índices de impacto na sobrevida. Pacientes com metástases para o pulmão possuem melhor prognóstico no primeiro ano de sobrevida em comparação àqueles com metástases para outros órgãos. A dosagem de DHL é fator prognóstico poderoso, sendo incluída no último estadiamento publicado, em pacientes com estádio IV da doença. A pesquisa do linfonodo sentinela já é técnica incorporada à conduta de pacientes com melanoma com reconhecido impacto no estadiamento, prognóstico e programação terapêutica. Devido à falta de padronização para o tratamento do melanoma, muitos pacientes ainda evoluem com um prognóstico reservado devido a uma conduta inicial inadequada. Os tratamentos vêm mudando significativamente e a proposta deste trabalho visa apresentar uma revisão com ênfase nas condutas preconizadas para o melanoma

Ultrasound energy and endothelial cell loss with stop-and-chop and nuclear preslice phacoemulsification

PURPOSE: To evaluate ultrasound (US) energy and endothelial cell loss in cataract surgery using the stop-and-chop and nuclear preslice techniques.SETTING: Vision Institute, Federal University of São Paulo, São Paulo, Brazil.METHODS: This prospective clinical trial comprised 43 patients (50 eyes) with senile nuclear cataract who were randomly assigned to 1 of 2 groups: stop-and-chop (n=26) or nuclear preslice (n=24). the groups were divided according to nuclear density (NO3 NC3 and NO4 NC4) using the Lens Opacity Classification System III. A full ophthalmic examination including biometry, specular microscopy, and pachymetry was performed preoperatively and postoperatively. the following parameters were evaluated: age, anterior chamber depth, lens thickness, axial length, phaco time and power, effective phaco time (EPT), infusion volume, ocular inflammation, endothelial cell loss, and best corrected visual acuity (BCVA).RESULTS: Phacoemulsification time, power, and EPT were significantly higher in the stop-and-chop group. Infusion volumes did not vary significantly between the groups. A significant decrease in endothelial cell density occurred postoperatively and was similar with both techniques (stop-and-chop 8.70%; nuclear preslice, 8.72%). the BCVA improved significantly in both groups. No significant correlations were found between endothelial cell loss and either technique.CONCLUSIONS: Ultrasound energy consumption was lower with the nuclear preslice technique. Both techniques had similar results including endothelial cell loss.Universidade Federal de São Paulo, Vis Inst, São Paulo, BrazilSanta Casa & UNIDERP, Campo Grande, BrazilUniversidade Federal de São Paulo, Vis Inst, São Paulo, BrazilWeb of Scienc

Distribuição espacial do baixo peso ao nascer em Sergipe, Brasil, 1995/1998 Space distribution of low birth weight in Sergipe, Brazil, 1995/1998

O estudo analisa a distribuição espacial do baixo peso ao nascer em Sergipe, Brasil, avaliando o evento como indicador de saúde. A análise foi feita a partir de 166.312 nascimentos vivos dos 75 municípios, numa abordagem ecológica. Foram utilizados quatro métodos: clusters analysis, análise de correlação, análise de regressão múltipla e multiple comparisons (Tukey). O estudo evidencia homogeneidade interna dos municípios nos distritos de saúde e nos grupos resultantes do dendrograma. Considerando 10,00% de perda de informação, identifica-se a presença de sete grupos, sendo dois resíduos (Aracaju e Porto da Folha). A evolução do baixo peso ao nascer, em Sergipe, é declinante (média de 6,97% no período) e reflete tímida melhoria da qualidade de vida. As suas causas indicam relações com o ambiente e são influenciadas pelos padrões de ocupação do espaço. O percentual do baixo peso ao nascer é útil como indicador de risco individual, porém, como indicador coletivo de saúde, não parece ser capaz de expressar diferenças entre regiões que não apresentam variabilidade acentuada entre si.<br>This study analyzes the spatial distribution of low birth weight (LBW) in the State of Sergipe, Brazil, evaluating the event as a health indicator. The analysis was based on 166,312 live births in the 75 municipalities in the State, using an ecological approach. Four methods were used: cluster analysis, correlation analysis, multiple regression analysis, and multiple comparisons (Tukey). The study shows internal homogeneity in the municipalities' health districts and in the groups resulting from the cluster analysis. Considering a 10% loss of information, seven groups were identified, two of which were residues (Aracaju and Porto da Folha). There is a downward trend in LBW in Sergipe (with a mean of 6.97% during the period), reflecting a slight improvement in quality of life. The causes suggest relations with the environment and are influenced by spatial occupation patterns. The percentage of LBW is a useful indicator of individual risk, but as a collective health indicator it does not appear capable of expressing differences between regions that do not display strong inter-variability

Pesquisa do linfonodo sentinela em pacientes com melanoma: experiência com fitato marcado com Tecnécio-99m e revisão da literatura The role of sentinel node mapping in malignant melanoma: experience with 99mTc-phytate and a review of the literature

FUNDAMENTOS: A progressão linfática do melanoma maligno habitualmente se inicia pelo linfonodo sentinela (LNS), cuja análise histopatológica permite predizer o acometimento de toda a cadeia. OBJETIVO: O trabalho tem por objetivo descrever a utilização do 99mTc-Fitato na detecção do LNS em pacientes com melanoma maligno, revisando as indicações e informações fornecidas por sua biópsia. MÉTODO: A pesquisa de LNS foi realizada por meio da linfocintilografia com 99mTc-Fitato em 92 pacientes com melanoma (54,0±14,3 anos). Após 18-24 horas, 88 pacientes foram submetidos à localização intra-operatória com detector portátil, seguida da ressecção e análise histopatológica do LNS. RESULTADOS: A linfocintilografia permitiu a identificação do LNS em todos os estudos, havendo detecção intra-operatória em 98,8% dos casos. O LNS estava acometido em 23 pacientes (26%). O valor preditivo negativo foi de 100% e não se observaram reações adversas pelo uso do 99mTc-Fitato. CONCLUSÃO: A detecção do LNS pode ser realizada com diferentes radiofármacos, incluindo o 99mTc-Fitato, que apresenta vantagens de custo e disponibilidade no Brasil. A pesquisa de LNS resulta em maior acurácia e menor morbidade no estadiamento de pacientes com melanoma maligno<br>BACKGROUND: Sentinel lymph node (SLN), corresponding to the first lymph node draining the tumor, is usually the first one to receive its metastasis, and its biopsy is used to define the status of the whole lymphatic basin. OBJECTIVE: The aim of this paper is to describe the use 99mTc-Fitato in SLN localization in malignant melanoma patients, and to review the main indications and information provided by SLN biopsy. METHOD: A total of 92 patients with malignant melanoma was studied. Lymph node scintigraphy was carried out after the subdermal injection of 99mTc-Phytate. After 18-24 hours, intra-operative SLN localization was carried out using the gamma-probe and lymph node dissection was then performed. RESULTS: Lymphoscintigraphy identified the sentinel node in all studies and intra-operative detection using gamma-probe was reached in 98.8% of the cases. The SLN was involved in 23 patients (26%). The method's negative predictive value was 100%, and there were no side effects related to 99mTc-Phytate. CONCLUSION: Scintigraphic and intra-operative sentinel node detection was satisfactorily performed using 99mTc-Phytate, an easily available and low cost radiopharmaceutical. SLN mapping allows the use of more accurate tumor staging techniques and reduces surgical morbidity