Philosophiae Doctor - PhD / Overweight/obesity is a risk factor for non-communicable diseases such as cardiovascular diseases, diabetes, and some cancers. Obesity in childhood is known to predict later obesity in adolescence and adulthood. Understanding the factors associated with overweight/obesity among children may present an opportunity for timely and appropriate interventions in the African setting.

Abstract Aim: It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC. Methods: We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by NewcastleeOttawa scale. Randomeffects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC. Results: Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n Z 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confi- dence interval [CI] 15.04e52.85, p Z 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n Z 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08e0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n Z 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20e2.06, p Z 0.02). There was moderate-to-high heterogeneity among the included studies. Conclusion: Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMAIR values. / Revisión por pares

Objective: To review evidence on the efficacy of HPV vaccines in the prevention of non-cancer lesions (anogenital warts [AGW], recurrent laryngeal papillomatosis and oral papillomatosis). Materials and methods: We conducted a systematic review of randomized trials. We performed random effect models and effects were reported as relative risks (RR) and their confidence intervals (95%CI) following both intention to treat (ITT) and per protocol (PP) analyses. Results: We included six studies (n=27 078). One study was rated as high risk of bias. One study could not be included in the meta-analysis because it provided combined results. We found that quadrivalent vaccine reduced the risk of AGW by 62% (RR: 0.38, 95%CI:0.32-0.45, I2:0%) in the ITT analysis and by 95% (RR: 0.05, 95%CI:0.01-0.25, I2:66%) in the PP analysis. Subgroup analyses of studies in women or with low-risk of bias provided similar results. Conclusion: HPV quadrivalent vaccine is efficacious in preventing AGW in men and women. / HPV quadrivalent vaccine is efficacious in preventing AGW in men and women. / Revisión por pares

Orientador: Edison Iglesias de Oliveira Vidal / Resumo: A síndrome de fragilidade é definida como uma síndrome clínica de origem multicausal caracterizada por redução de reservas fisiológicas que aumentam a vulnerabilidade de um indivíduo a desfechos adversos como quedas, hospitalização, desenvolvimento de dependência funcional e morte. Acredita-se que a síndrome da fragilidade pode ser potencialmente modificável ou reversível mediante intervenções apropriadas. Esta é a primeira revisão sistemática com metanálise de ensaios clínicos randomizados para avaliar a eficácia de intervenções nutricionais para o tratamento da síndrome da fragilidade em idosos. Foram incluídos 11 ensaios clínicos randomizados com idosos de 60 anos ou mais com diagnóstico de síndrome da fragilidade ou pré-fragilidade. Metanálises bayesianas de efeitos randômicos não revelaram diferenças estatisticamente significativas ao comparar a suplementação nutricional isolada com grupos controle que receberam placebo ou nenhum tratamento em relação ao escore de síndrome da fragilidade (MD: 0,09 pontos, IC 95%: -0,45 a 0,62), Bateria de Desempenho Físico Breve (SMD: 0,29, IC 95%: -0,55 a 1,40), força muscular (SMD: -0,14, IC 95%: -0,38 a 0,09), velocidade da marcha (SMD: 0,06, IC 95%: -0,04 a 0,17), massa magra apendicular (MD: 0,60kg, IC 95%: -0,82 a 2,01), massa gorda (MD: 1,67kg, IC 95%: -0,63 a 3,96), memória declarativa (SMD: 0,11, IC 95%: -0,31 a 0,53), linguagem e função executiva (MD: 0,21 pontos, IC 95%: -0,99 a 1,42) e outros resultados. Estudo único de inter... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Frailty is a clinical syndrome of multicausal origin characterized by a reduction of physiological reserves that increase the vulnerability of an individual to adverse outcomes such as falls, hospital admission, disability and death. It has been suggested that frailty can be potentially modifiable or even reversible with appropriate interventions. This is the first systematic review with meta-analysis or Randomized Clinical Trials (RCTs) to appraise the effectiveness of nutritional interventions for the treatment of frailty in older adults. We included 11 RCTs of people aged 60 years and older with a diagnosis of frailty or pre-frailty. Bayesian random effects meta-analyses found no statistically significant differences when comparing nutritional supplementation alone with control groups receiving placebo or no treatment regarding frailty score (MD: 0.09 points, 95%CI: -0.45 to 0.62), Short Physical Performance Battery (SMD: 0.29, 95%CI: -0.55 to 1.40), muscle strength (SMD: -0.14, 95%CI: -0.38 to 0.09), gait speed (SMD: 0.06, 95%CI: -0.04 to 0.17), appendicular lean mass (MD: 0.60kg, 95%CI: -0.82 to 2.01), fat mass (MD: 1.67kg, 95%CI: -0.63 to 3.96), declarative memory (SMD: 0.11, 95%CI: -0.31 to 0.53), language & executive function (MD: 0.21 points, 95%CI: -0.99 to 1.42) and other outcomes. Single study of nutritional education interventions also did not show any significant improvements in comparison with general health advice. The overall quality of evidence assessed usin... (Complete abstract click electronic access below) / Mestre

Meta-analysis is frequently used in the analysis of safety data. In dealing with rare events, the commonly used risk measures, such as the odds ratio, or risk difference, or their variance, can become undefined when no events are observed in studies. The use of an arcsine transformation and arcsine difference (AD) as treatment effect were shown to have desirable statistical properties (Rucker, 2009). However, the interpretation of the AD remains challenging and this may hamper its utility. To convert the AD to a risk measure similar to the risk difference, two previously proposed linear approximation methods, along with new linear and non-linear methods were discussed and evaluated. The existing approximation methods generally provide satisfactory approximation when the event proportions are between 0.15 and 0.85. We propose a new linear approximation method, the modified rationalized arcsine unit (MRAU) which improves the approximation when proportions fall outside the range from 0.15 to 0.85. However, the MRAU can still lead to under- or over-estimation depending on the underlying proportion. We then proposed a non-linear approximation method, based on a Taylor series expansion (TRAUD), which shows the best approximation across the full range of risk levels. However, the variance for TRAUD is less easily estimated and requires bootstrap estimation. Results from simulation studies confirm these findings under a wide array of scenarios. In the second section, heterogeneity in meta-analysis is discussed along with current methods that address the issue. To provide an exploration of the nature of heterogeneity, finite mixture model methods (FMM) were presented, and their application in meta-analysis discussed. The estimates derived from the components in FMM indicate that even with a pre-specified protocol, the studies included in a meta-analysis may come from different distributions that can cause heterogeneity. The estimated number of components may suggest the existence of multiple sub-populations that a simple overall effect estimate will neglect. We propose that in the analysis of safety data, the estimates of the number of components and their respective means can provide valuable information for better patient care. In the final section, the application of the approximation methods and the use of FMM are demonstrated in the analysis of two published meta-analysis examples from the medical literature.

NR 20140805

Background The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. Methods We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. Results Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure. / Revisión por pares

BACKGROUND: Hypoalbuminemia (HA) is common in HF, however, its pathophysiology and clinical implications are poorly understood. While multiple studies have been published in the past decade investigating the role of serum albumin in HF, there is still no consensus on the prognostic value of this widely available measure. The objective of this study is to assess the prognostic role of albumin in heart failure (HF) patient. METHODS: Unrestricted searches of MEDLINE, EMBASE, Cochrane databases were performed. The results were screened for relevance and eligibility criteria. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The Begg and Mazumdar rank correlation test was utilized to evaluate for publication bias. RESULTS: A total of 48 studies examining 44,048 patients with HF were analyzed. HA was found in 32% (95% confidence interval [CI] 28.4%-37.4%) HF patients with marked heterogeneity (I2 = 98%). In 10 studies evaluating acute HF, in-hospital mortality was almost 4 times more likely in HA with an odds ratios (OR) of 3.77 (95% CI 1.96-7.23). HA was also associated with a significant increase in long-term mortality (OR: 1.5; 95% CI: 1.36-1.64) especially at 1-year post-discharge (OR: 2.44; 95% CI: 2.05-2.91; I2 = 11%). Pooled area under the curve (AUC 0.73; 95% CI 0.67-0.78) was comparable to serum brain natriuretic peptide (BNP) in predicting mortality in HF patients. CONCLUSION: Our results suggest that HA is associated with significantly higher in-hospital mortality as well as long-term mortality with a predictive accuracy comparable to that reported for serum BNP. These findings suggest that serum albumin may be useful in determining high-risk patients.

Objective: Several studies have demonstrated that end-stage renal disease (ESRD) patients on dialysis are at higher risk for cerebrovascular events, especially those on hemodialysis. However, the risk of stroke in patients on peritoneal dialysis (PD) compared to those on hemodialysis (HD) remains unclear. We performed this meta-analysis to assess the risks of stroke in ESRD patients on PD compared to HD. Methods: A systematic review was conducted using MEDLINE, EMBASE, Cochrane databases from inception through January 2018 to identify studies that evaluated the risks of stroke (all types of stroke, ischemic stroke or hemorrhagic stroke) in ESRD patients on different dialysis modalities. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Results: Fifteen cohort studies with a total of 1 289 572 ESRD patients (over 1 140 942 on HD and 122 534 on PD) were enrolled. Compared with HD, PD was associated with a significantly decreased risk of hemorrhagic stroke with pooled OR of 0.84 (95% CI: 0.76-0.92). However, there were no differences in risks of all types of stroke or ischemic stroke in those on PD compared to HD with pooled ORs of 1.06 (95% CI: 0.91-1.22) and 1.01 (95% CI: 0.80-1.18,), respectively. Conclusions: PD status is associated with 16% lower risk of hemorrhagic stroke compared to HD, but the risks of all types of stroke and hemorrhagic stroke are not statistically different in PD patients when compared to HD patients.

Background/Objectives: The possible relationship between smoking and risk of colonic diverticulosis has been suggested by recent epidemiological studies, although the results were inconsistent. This meta-analysis was conducted to summarize all available data. Methods: A comprehensive literature review was conducted using the MEDLINE and EMBASE databases through May 2017 to identify all studies that compared the risk of colonic diverticulosis among current and former smokers versus nonsmokers. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. Results: Of 465 potentially eligible articles, three prospective cohort studies with 130,520 participants met the eligibility criteria and were included in the meta-analysis. The risk of colonic diverticulosis in current smokers was significantly higher than nonsmokers with the pooled risks ratio of 1.46 (95% confidence interval [CI], 1.13-1.89). However, the risk of colonic diverticulosis in former smokers was not significantly higher than nonsmokers with the pooled risk ratio of 1.13 (95% CI, 0.88-1.44). Conclusions: A significantly increased risk of colonic diverticulosis among current smokers is demonstrated in this study.