A systematic review of new advances in the management of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): focus on galsulfase

Regina P El Dib1, Gregory M Pastores21Department of Surgery, McMaster University, McMaster Institute of Urology, Hamilton, Ontario, Canada; 2Department of Neurology and Pediatrics, New York University School of Medicine, New York, NY, USAIntroduction: Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal storage disorder, characterized primarily by skeletal dysplasia and joint contracture. It is caused by a deficiency of N-acetylgalactosamine-4-sulfatase (arylsulfatase B), for which a recombinant formulation (galsulfase) is available as replacement therapy. Objective: To evaluate the effectiveness and safety of galsulfase compared to placebo or no interventions, for treating MPS VI. We also considered studies evaluating different doses of galsulfase.Methods: A systematic review of the literature was conducted. A computerized electronic search in MEDLINE, EMBASE, CENTRAL, SciELO, and LILACS was carried on to identify any randomized trials that met our inclusion criteria.Results: Two studies were included in the review. Because the number of studies was small, our analysis probably did not find any statistically significant difference. Long-term follow-up will be required to ascertain full clinical benefit, on both event-free survival and quality of life measures.Conclusions: There is some evidence to support the use of galsulfase in the treatment of MPS VI; however due to the very low quantity of included studies we could not analyze it in an appropriate way. This review highlights the need for continued research into the use of enzyme replacement therapy for MPS VI.Keywords: mucopolysaccharidosis VI, Maroteaux-Lamy syndrome, galsulfase, naglazyme, systematic revie

Prevalence of high frequency hearing loss consistent with noise exposure among people working with sound systems and general population in Brazil: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Music is ever present in our daily lives, establishing a link between humans and the arts through the senses and pleasure. Sound technicians are the link between musicians and audiences or consumers. Recently, general concern has arisen regarding occurrences of hearing loss induced by noise from excessively amplified sound-producing activities within leisure and professional environments. Sound technicians' activities expose them to the risk of hearing loss, and consequently put at risk their quality of life, the quality of the musical product and consumers' hearing. The aim of this study was to measure the prevalence of high frequency hearing loss consistent with noise exposure among sound technicians in Brazil and compare this with a control group without occupational noise exposure.</p> <p>Methods</p> <p>This was a cross-sectional study comparing 177 participants in two groups: 82 sound technicians and 95 controls (non-sound technicians). A questionnaire on music listening habits and associated complaints was applied, and data were gathered regarding the professionals' numbers of working hours per day and both groups' hearing complaint and presence of tinnitus. The participants' ear canals were visually inspected using an otoscope. Hearing assessments were performed (tonal and speech audiometry) using a portable digital AD 229 E audiometer funded by FAPESP.</p> <p>Results</p> <p>There was no statistically significant difference between the sound technicians and controls regarding age and gender. Thus, the study sample was homogenous and would be unlikely to lead to bias in the results. A statistically significant difference in hearing loss was observed between the groups: 50% among the sound technicians and 10.5% among the controls. The difference could be addressed to high sound levels.</p> <p>Conclusion</p> <p>The sound technicians presented a higher prevalence of high frequency hearing loss consistent with noise exposure than did the general population, although the possibility of residual confounding due to unmeasured factors such as socioeconomic status cannot be ruled out.</p

Systematic survey of randomized trials evaluating the impact of alternative diagnostic strategies on patient-important outcomes

Objectives: To provide a perspective on the current practice of randomized clinical trials (RCTs) of diagnostic strategies focusing on patient-important outcomes. Study Design and Setting: We conducted a comprehensive search of MEDLINE and included RCTs published in full-text reports that evaluated alternative diagnostic strategies. Results: Of 56,912 unique citations, we sampled 7,500 and included 103 eligible RCTs, therefore suggesting that MEDLINE includes approximately 781 diagnostic RCTs. The 103 eligible trials reported on: mortality (n = 41; 39.8%); morbidities (n = 63; 61.2%); symptoms/quality of life/functional status (n = 14; 13.6%); and on composite end points (n = 10; 9.7%). Of the studies that reported statistically significant results (n = 12; 11.6%), we judged 7 (58.3%) as at low risk of bias with respect to missing outcome data and 4 (33.3%) as at low risk of bias regarding blinding. Of the 41 RCTs that reported on mortality, only one (2.4%) reported statistically significant results. Of 63 RCTs addressing morbidity outcomes, 11 (17.5%) reported statistically significant results, all of which reported relative effects of greater than 20%. Conclusion: RCTs of diagnostic tests are not uncommon, and sometimes suggest benefits on patient-important outcomes but often suffer from limitations in sample size and conduct. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Mapping the Cochrane evidence for decision making in health care

Rationale and aim Over the past 12 years, thousands of authors working with the Cochrane Collaboration around the world have produced systematic reviews to reduce uncertainty in health care decision making. We evaluated the conclusions from Cochrane systematic reviews of randomized controlled trials in terms of their recommendations for clinical practice and research.Methods in our cross-sectional study of systematic reviews published in the Cochrane Library, we randomly selected and analysed completed systematic reviews published across all 50 Cochrane Collaborative Review Groups.Results We analysed 1016 completed systematic reviews. of these, 44% concluded that the interventions studied were likely to be beneficial, of which 1% recommended no further research and 43% recommended additional research. Also, 7% of the reviews concluded that the interventions were likely to be harmful, of which 2% did not recommend further studies and 5% recommended additional studies. in total, 49% of the reviews reported that the evidence did not support either benefit or harm, of which 1% did not recommend further studies and 48% recommended additional studies. Overall, 96% of the reviews recornmended further research.Conclusions Cochrane systematic reviews were about evenly split between those in which the authors concluded that at least one of the interventions was beneficial and those ill which the evidence neither supported nor refuted the intervention tested. the Cochrane Collaboration needs to include clinical trial protocol summaries with a study design optimized to answer the relevant research questions.Universidade Federal de São Paulo, Brazilian Cochrane Ctr, BR-04039001 São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, BR-04039001 São Paulo, BrazilWeb of Scienc

Intravenous versus inhalation anaesthesia for one-lung ventilation

Background the technique called one-lung ventilation can confine bleeding or infection to one lung, prevent rupture of a lung cyst or, more commonly, facilitate surgical exposure of the unventilated lung. During one- lung ventilation, anaesthesia is maintained either by delivering a volatile anaesthetic to the ventilated lung or by infusing an intravenous anaesthetic. It is possible that the method chosen to maintain anaesthesia may affect patient outcomes.Objectives the objective of this review was to evaluate the effectiveness and safety of intravenous versus inhalation anaesthesia for one- lung ventilation.Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( the Cochrane Library 2006, Issue 3), MEDLINE, LILACS, EMBASE ( from inception to June 2006), ISI web of Science ( 1945 to June 2006), reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. There were no language restrictions.Selection criteria We included randomized controlled trials and quasi- randomized controlled trials of intravenous versus inhalation anaesthesia for one-lung ventilation.Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main results We included nine studies that enrolled 291 participants. We could not perform meta-analyses as the included studies did not report the outcomes listed in the protocol for this review.Authors' conclusions There is no evidence from randomized controlled trials of differences in patient outcomes for anaesthesia maintained by intravenous versus inhalational anaesthesia during one- lung ventilation. This review highlights the need for continued research into the use of intravenous versus inhalation anaesthesia for one- lung ventilation. Future trials should have standardized outcome measures such as death, adverse postoperative outcomes and intraoperative awareness. Dropouts and losses to follow up should be reported.Hosp Sirio Libanes, Dept Anesthesiol, BR-05011040 São Paulo, BrazilMcMaster Univ, Toronto, ON, CanadaUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, São Paulo, BrazilWeb of Scienc

Aerobic exercise training programmes for improving physical and psychosocial health in adults with Down syndrome

BackgroundAlthough physical fitness has been suggested to improve physical and psychosocial health for a variety of population profiles, there is a lack of information about the safety and effectiveness of aerobic exercise for adults with Down syndrome.ObjectivesTo evaluate the effectiveness and safety of aerobic exercise training programmes for physiological and psychosocial outcomes in adults with Down syndrome.Search strategyThe following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (2009, Issue 1); MEDLINE (1966 to August 2009); EMBASE (1980 to August 2009); CINAHL (1982 to August 2009); LILACS (1982 to August 2009); PsycINFO (1887 to August 2009); ERIC (1966 to August 2009); Current Controlled Trials (August 2009); and Campbell Collaboration's Social, Psychological, Educational and Criminological Register (C2-SPECTR) (to August 2009). Information about ongoing clinical trials was sought by searching ClinicalTrials.gov (http://clinicaltrials.gov) (accessed August 2009), and the National Research Register (NRR) (2009 Issue 1).Selection criteriaRandomised or quasi-randomised controlled trials using supervised aerobic exercise training programmes with behavioral components accepted as co-interventions.Data collection and analysisTwo reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, data were pooled using meta-analysis with a random-effects model. Positive values favour the intervention group, while negative values favour the control group.Main resultsThree studies included in this systematic review used different kinds of aerobic activity: walking/jogging and rowing training and included participants with a broad age range (17 to 65 years). They were conducted in the USA, Portugal and Israel. in the meta-analyses, only maximal treadmill grade was improved after aerobic exercise training programmes (4.26 grades (%) [ 95% CI 2.06, 6.45]). Other variables relative to work performance that could not be combined in a meta-analysis were also improved in the intervention group (maximal test time P=0.0003), total turns of fan wheel (P=0.02), resistance of ergometer (p=0.003), power knee extension and flexion (p<0.00001), and timed up and go test (p=0.008). Thirty other outcomes measured in this review including, oxidative stress and body composition variables, could not be combined in the meta-analysis. Apart from work performance, trials reported no statistically significant improvements.Authors' conclusionsThere is insufficient evidence to demonstrate that there is improvement in physical or psychosocial outcomes of aerobic exercise in adults with Down syndrome. Although evidence exists to support improvements in physiological and psychological aspects from strategies using mixed physical activity programmes, well-conducted research examining long-term physical outcomes, adverse effects, psychosocial outcomes and costs is required before informed practice decisions can be made.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, BR-04039001 São Paulo, BrazilMcMaster Univ, St Josephs Healthcare Hamilton, Dept Surg, Hamilton, ON, CanadaUniversidade Federal de São Paulo, Discipline Prevent Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, BR-04039001 São Paulo, BrazilUniversidade Federal de São Paulo, Discipline Prevent Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Brazilian Cochrane Ctr, São Paulo, BrazilWeb of Scienc

Zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance

BackgroundDiabetes is associated with long-term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. The risk of developing type 2 diabetes increases with age, obesity and lack of physical activity. Insulin resistance is a fundamental aspect of the aetiology of type 2 diabetes. Insulin resistance has been shown to be associated with atherosclerosis, dyslipidaemia, glucose intolerance, hyperuricaemia, hypertension and polycystic ovary syndrome. The mineral zinc plays a key role in the synthesis and action of insulin, both physiologically and in diabetes mellitus. Zinc seems to stimulate insulin action and insulin receptor tyrosine kinase activity.ObjectivesTo assess the effects of zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance.Search methodsThis review is an update of a previous Cochrane systematic review published in 2007. We searched the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, LILACS and the ICTRP trial register (frominception toMarch 2015). There were no language restrictions. We conducted citation searches and screened reference lists of included studies.Selection criteriaWe included studies if they had a randomised or quasi-randomised design and if they investigated zinc supplementation compared with placebo or no intervention in adults with insulin resistance living in the community.Data collection and analysisTwo review authors selected relevant trials, assessed risk of bias and extracted data.Main resultsWe included three trials with a total of 128 participants in this review. The duration of zinc supplementation ranged between four and 12 weeks. Risk of bias was unclear for most studies regarding selection bias (random sequence generation, allocation concealment) and detection bias (blinding of outcome assessment). No study reported on our key outcome measures (incidence of type 2 diabetes mellitus, adverse events, health-related quality of life, all-cause mortality, diabetic complications, socioeconomic effects). Evaluation of insulin resistance as measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) showed neutral effects when comparing zinc supplementation with control (two trials; 114 participants). There were neutral effects for trials comparing zinc supplementation with placebo for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (2 studies, 70 participants). The one trial comparing zinc supplementation with exercise also showed neutral effects for total cholesterol, HDL and LDL cholesterol, and a mean difference in triglycerides of -30 mg/dL (95% confidence interval (CI) -49 to -10) in favour of zinc supplementation (53 participants). Various surrogate laboratory parameters were also analysed in the included trials.Authors'conclusionsThere is currently no evidence on which to base the use of zinc supplementation for the prevention of type 2 diabetes mellitus. Future trials should investigate patient-important outcome measures such as incidence of type 2 diabetes mellitus, health-related quality of life, diabetic complications, all-cause mortality and socioeconomic effects