Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type ii (hunter syndrome)

Background Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X-linked disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase, which catalyses a step in the catabolism of glycosaminoglycans. The glycosaminoglycans accumulate within tissues affecting multiple organs and physiologic systems. The clinical manifestations include neurologic involvement, severe airways obstruction, skeletal deformities and cardiomyopathy. The disease has a variable age of onset and variable rate of progression. In those with severe disease, death usually occurs in the second decade of life, whereas those individuals with less severe disease may survive into adulthood. Enzyme replacement therapy with intravenous infusions of idursulfase has emerged as a new treatment for mucopolysaccharidosis type II. This is an update of a previously published version of this review. Objectives To evaluate the effectiveness and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo or no intervention, for treating mucopolysaccharidosis type II. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 23 November 2015). We also searched Embase, PubMed and the Literature Latino-Americana e do Caribe em Ciencias da Saude (LILACS) (date of last search 28 November 2015). Selection criteria Randomised and quasi-randomised controlled trials of enzyme replacement therapy with idursulfase compared to no intervention, placebo or other options (e.g. behavioral strategies, transplantation). Data collection and analysis Two authors independently screened the trials identified, appraised quality of papers and extracted data. Main results One study (96 male participants) met the inclusion criteria, although the primary outcome of this review -z score for height and weight, was not assessed in the study. This trial was considered to be of overall good quality. Following 53 weeks of treatment, participants in the weekly idursulfase 0.5 mg/kg group demonstrated a significant improvement rate compared with placebo for the primary outcome: distance walked in sixminutes on the basis of the sum of ranks of change from baseline, mean difference 37.00 (95% confidence interval 6.52 to 67.48). The every-other-week idursulfase 0.5 mg/kg group also showed an improvement, which was not significant compared with placebo, mean difference 23.00 (95% confidence interval -4.49 to 50.49). After 53 weeks, there was no statistical significance difference in per cent predicted forced vital capacity between the three groups and absolute forced vital capacity was significantly increased from baseline in the weekly dosing group compared to placebo, mean difference 0.16 (95% confidence interval CI 0.05 to 0.27). No difference was observed between the every-other-week idursulfase 0.5 mg/kg group and placebo. In addition, liver and spleen volumes and urine glycosaminoglycan excretion were significantly reduced from baseline by both idursulfase dosing regimens. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 31.7% of participants at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels. Authors' conclusions The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in people with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy.National Institute for Health Research, UKNational Institute for Health ResearchEmergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilDepartment of Public Health, Universidade do Estado do Pará, Belém, BrazilDepartment of Urology,Universidade Federal de São Paulo, São Paulo, BrazilEmergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, Rua Borges Lagoa 564 Cj 64, BR-04038000 Sao Paulo, SP, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilDepartment of Urology,Universidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Mortalidade brasileira por neoplasia maligna de próstata: uma comparação com o cenário internacional (2015 a 2019)

Introduction: Prostate cancer progresses silently and many individuals are asymptomatic at first. Method: This study aims to measure the incidence of deaths from prostate cancer in Brazil and compare it with the international scenario. Method: Cross-sectional, descriptive and quantitative study, which included 76,360 deaths from prostate cancer in Brazil, which occurred between 2015 and 2019. The Welch’s ANOVA, chi-square and Kruskal-Wallis tests were applied to compare the Dice. Results: Brazil had a mean age-standardized mortality of 16.26 (SD = ±3.11); Canada, 8.84 (SD = ±0.17); Japan, 4.28 (SD = ±0.06); Australia, 6.03 (SD = ±0.22); Italy, 4.94 (SD = ±0.05); and USA, 8.33 (SD = ±0.11). Conclusion: further studies are needed to identify the impact of culture and diet on mortality across countries. Screening significantly influences mortality.Introdução: o câncer de próstata evolui silenciosamente e muitos indivíduos são assintomáticos no começo. Método: Trata-se de um estudo transversal, descritivo e quantitativo, que incluiu 76.360 óbitos por neoplasia de próstata no Brasil, entre 2015 e 2019. Os testes de ANOVA de Welch, qui-quadrado e Kruskal-Wallis foram aplicados para comparação dos dados. Resultados: O Brasil apresentou uma mortalidade padronizada por idade média de 16,26 (DP = ±3,11); Canadá, 8,84 (DP = ±0,17); Japão, 4,28 (DP = ±0,06); Austrália, 6,03 (DP = ±0,22); Itália, 4,94 (DP = ±0,05); e EUA, 8,33 (DP = ±0,11).  Conclusão: necessita-se de novos estudos para identificar o impacto da cultura e dieta na mortalidade entre os países. O rastreamento influencia significativamente na mortalidade

Bevacizumab for ocular neovascular diseases: a systematic review

CONTEXT AND OBJECTIVE: Many eye diseases involve increased local levels of vascular endothelial growth factor (VEGF), and there are several therapeutic strategies for them. Thus, the aim of this study was to evaluate the effectiveness and safety of bevacizumab for treating eye diseases involving increased local levels of VEGF, as the assumed pathophysiological mechanism. DATA SOURCES: The following databases were systematically searched for evidence: PubMed, CENTRAL (Cochrane Library), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) and reference lists, without language restrictions. Only randomized controlled trials were included. The primary outcome of interest was visual acuity, irrespective of the evaluation method. DATA SYNTHESIS: A total of 667 eyes in nine randomized trials were included. Meta-analysis showed that the proportion of patients with age-related macular degeneration who presented improvements from baseline regarding best-corrected visual acuity was higher among those treated with bevacizumab than among those in the photodynamic therapy group (risk ratio, RR, 0.49; 95% confidence interval, CI, 0.31 to 0.78; P = 0.01). CONCLUSIONS: The evidence available demonstrates that bevacizumab alone or combined with other treatments is more effective than other options, including photodynamic therapy, focal photocoagulation and triamcinolone. The use of bevacizumab instead of photodynamic therapy could reduce treatment costs by more than 99% and could significantly increase access to treatment. However, long-term studies are still needed in order to reduce uncertainty concerning the safety of this medication for all ocular neovascular diseases in which bevacizumab has the potential to improve visual acuity

De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock

BackgroundMortality rates among patients with sepsis, severe sepsis or septic shock are highly variable throughout different regions or services and can be upwards of 50%. Empirical broad-spectrum antimicrobial treatment is aimed at achieving adequate antimicrobial therapy, thus reducing mortality; however, there is a risk that empirical broad-spectrum antimicrobial treatment can expose patients to overuse of antimicrobials. De-escalation has been proposed as a strategy to replace empirical broad-spectrum antimicrobial treatment by using a narrower antimicrobial therapy. This is done by reviewing the patient's microbial culture results and then making changes to the pharmacological agent or discontinuing a pharmacological combination.ObjectivesTo evaluate the effectiveness and safety of de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock caused by any micro-organism.Search methodsIn this updated version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); MEDLINE via PubMed (from inception to October 2012); EMBASE (from inception to October 2012); LILACS (from inception to October 2012); Current Controlled Trials; bibliographic references of relevant studies; and specialists in the area. We applied no language restriction. We had previously searched the databases to August 2010.Selection criteriaWe planned to include randomized controlled trials (RCTs) comparing de-escalation (based on culture results) versus standard therapy for adults with sepsis, severe sepsis or septic shock. the primary outcome was mortality (at 28 days, hospital discharge or at the end of the follow-up period). Studies including patients initially treated with an empirical but not adequate antimicrobial therapy were not considered for inclusion.Data collection and analysisTwo authors planned to independently select and extract data and to evaluate methodological quality of all studies. We planned to use relative risk (risk ratio) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals. We planned to use the random-effects statistical model when the estimate effects of two or more studies could be combined in a meta-analysis.Main resultsOur search strategy retrieved 493 studies. No published RCTs testing de-escalation of antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic were included in this review. We found one ongoing RCT.Authors' conclusionsThere is no adequate, direct evidence as to whether de-escalation of antimicrobial agents is effective and safe for adults with sepsis, severe sepsis or septic shock. This uncertainty warrants further research via RCTs and the authors are awaiting the results of an ongoing RCT testing the de-escalation of empirical antimicrobial therapy for severe sepsis.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Ctr Estudos Med Baseada Evidencias & Avaliacao Te, Brazilian Cochrane Ctr, BR-04038000 São Paulo, BrazilUniv Estado Para, Dept Publ Hlth, Belem, Para, BrazilUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilWeb of Scienc

The Effect of A Programmed Hydration Strategy in the Physical Performance of Soccer Referees During An Amateur Championship

UNIFESP EPM, São Paulo, BrazilUNIFESP EPM, São Paulo, BrazilWeb of Scienc