Genetically elevated gamma-glutamyltransferase and Alzheimer’s disease

Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer’ disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer’s Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associated with GGT in a previous genome-wide association study on liver enzymes as instruments. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR. The odds ratio of AD was 1.09 (95% confidence interval, 0.98 to 1.22; p = 0.10) per one standard deviation genetically elevated GGT based on all 26 SNPs. The results were similar in both MR-Egger and weighted median MR methods. Overall, our findings cannot confirm a strong causal effect of GGT on AD risk. Further MR investigations using individual-level data are warranted to confirm or rule out causality.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Dr. Setor Kunutsor acknowledges support from the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol ... Dr. Stephen Burgess is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 204623/Z/16/Z)

Paying for Performance to Improve the Delivery and Uptake of Family Planning in Low and Middle Income Countries: A Systematic Review

Paying for performance is a strategy to meet the unmet need for family planning in low and middle income countries; however, rigorous evidence on effectiveness is lacking. Scientific databases and grey literature were searched from 1994 to May 2016. Thirteen studies were included. Payments were linked to units of targeted services, usually modified by quality indicators. Ancillary components and payment indicators differed between studies. Results were mixed for family planning outcome measures. Paying for performance was associated with improved modern family planning use in one study, and increased user and coverage rates in two more. Paying for performance with conditional cash transfers increased family planning use in another. One study found increased use in the upper wealth group only. However, eight studies reported no impact on modern family planning use or prevalence. Secondary outcomes of equity, financial risk protection, satisfaction, quality, and service organization were mixed. Available evidence is inconclusive and limited by the scarcity of studies and by variation in intervention, study design, and outcome measures. Further studies are warranted

Aspirin for primary prevention of cardiovascular and all-cause mortality events in diabetes:Updated meta-analysis of randomized controlled trials

AIMS: To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta-analysis. METHODS: Randomized controlled trials of aspirin compared with placebo (or no treatment) in people with diabetes with no history of cardiovascular disease were identified from MEDLINE, EMBASE, Web of Science, the Cochrane Library and a manual search of bibliographies to November 2015. Study-specific relative risks with 95% CIs were aggregated using random effects models. RESULTS: A total of 10 randomized trials were included in the review. There was a significant reduction in risk of major adverse cardiovascular events: relative risk of 0.90 (95% CI 0.81-0.99) in groups taking aspirin compared with placebo or no treatment. Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk, medication compliance and sex (P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infarction, coronary heart disease, stroke, cardiovascular mortality or all-cause mortality. Aspirin significantly reduced the risk of myocardial infarction for a treatment duration of ≤ 5 years. There were differences in the effect of aspirin by dosage and treatment duration on overall stroke outcomes (P for interaction for all < 0.05). There was an increase in risk of major or gastrointestinal bleeding events, but estimates were imprecise and not significant. CONCLUSIONS: The emerging data do not clearly support guidelines that encourage the use of aspirin for the primary prevention of cardiovascular disease in adults with diabetes who are at increased cardiovascular disease risk

Systematic review of risk prediction scores for surgical site infection or periprosthetic joint infection following joint arthroplasty

Accurate identification of individuals at high risk of surgical site infections (SSIs) or periprosthetic joint infections (PJIs) influences clinical decisions and development of preventive strategies. We aimed to determine progress in the development and validation of risk prediction models for SSI or PJI using a systematic review. We searched for studies that have developed or validated a risk prediction tool for SSI or PJI following joint replacement in MEDLINE, EMBASE, Web of Science and Cochrane databases; trial registers and reference lists of studies up to September 2016. Nine studies describing 16 risk scores for SSI or PJI were identified. The number of component variables in a risk score ranged from 4 to 45. The C-index ranged from 0·56 to 0·74, with only three risk scores reporting a discriminative ability of >0·70. Five risk scores were validated internally. The National Healthcare Safety Network SSIs risk models for hip and knee arthroplasties (HPRO and KPRO) were the only scores to be externally validated. Except for HPRO which shows some promise for use in a clinical setting (based on predictive performance and external validation), none of the identified risk scores can be considered ready for use. Further research is urgently warranted within the field

GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality:results from the PREVEND study and meta-analysis

BACKGROUND: Chronic diseases are associated with an inflammatory response. We determined the association of two inflammatory markers, GlycA and high-sensitivity C-reactive protein (hsCRP), with overall and cause-specific mortality in a cohort of men and women.METHODS: Cox regression analyses were used to examine associations of GlycA and hsCRP with all-cause, cancer and cardiovascular mortality in 5526 subjects (PREVEND cohort; average follow-up 12.6 years).RESULTS: GlycA was associated with all-cause mortality (n = 838), independent of clinical risk factors and hsCRP (hazard ratio 1.43 [95% confidence interval (CI): 1.09-1.87] for top versus bottom quartiles). For hsCRP, the association with all-cause mortality was nonsignificant after adjustment for GlycA. GlycA and hsCRP were associated with cancer mortality in men (n = 248), but not in women (n = 132). Neither GlycA nor hsCRP was independently associated with cardiovascular mortality (n = 201). In a meta-analysis of seven population-based studies, including 8153 deaths, the pooled multivariable-adjusted relative risk of GlycA for all-cause mortality was 1.74 (95% CI: 1.40-2.17) for top versus bottom quartiles. The association of GlycA with all-cause mortality was somewhat stronger than that of hsCRP. GlycA and hsCRP were not independently associated with cardiovascular mortality. The associations of GlycA and hsCRP with cancer mortality were present in men, but not in women.CONCLUSIONS: GlycA is significantly associated with all-cause mortality. GlycA and hsCRP were each not independently associated with cardiovascular mortality. The association of GlycA and hsCRP with cancer mortality appears to be driven by men.</p

Association of Vasomotor and Other Menopausal Symptoms with Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis

$\textbf{IMPORTANCE}$: Vasomotor symptoms (hot flushes and night sweats) and other symptoms, including depression, anxiety and panic attacks, are commonly experienced by menopausal women and have been associated with an unfavourable cardiovascular risk profile. $\textbf{OBJECTIVE}$: To investigate whether presence of menopausal symptoms is associated with the development of cardiovascular disease (CVD). $\textbf{METHODS}$: Five electronic databases (Medline, EMBASE and Web of Science) were search until February 17th, 2015 to identify relevant studies. Observational cohort studies or randomised intervention studies were eligible for inclusion if they followed participants prospectively (at least 1 year of follow-up), and reported relevant estimates on the association of any vasomotor symptoms, or other menopausal symptoms, with risk of CVD, coronary heart disease (CHD), or stroke in perimenopausal, menopausal, or postmenopausal women. Data were extracted by two independent reviewers using a pre-designed data collection form. Separate pooled relative risks (RRs) for age and non-established cardiovascular risk factors (e.g., education, ethnicity) adjusted data and for established cardiovascular risk factors and potential mediators-adjusted data (e.g., smoking, body mass index, and hypertension) were calculated. $\textbf{RESULTS}$: Out of 9,987 initially identified references, ten studies were selected, including 213,976 women with a total of 10,037 cardiovascular disease outcomes. The age and non-established cardiovascular risk factors adjusted RRs) [95% confidence intervals] for development of CHD, Stroke and CVD comparing women with and without any menopausal symptoms were 1.34 [1.13-1.58], 1.30 [0.99-1.70], 1.48 [1.21-1.80] respectively, and the corresponding RRs adjusted for cardiovascular risk factors and potential mediators were 1.18 [1.03-1.35], 1.08 [0.89-1.32], 1.29 [0.98-1.71]. However, these analyses were limited by potential unmeasured confounding and the small number of studies on this topic. $\textbf{CONCLUSION}$: Presence of vasomotor symptoms and other menopausal symptoms are generally associated with an increased risk of cardiovascular disease, which is mainly explained by cardiovascular risk factors.This study was sponsored and funded by Metagenics Inc. Role of the Funder/Sponsor: Metagenics Inc. had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript. The funder/sponsor did not have the ability to veto publication of study results. Disclosure statement: TM and OHF work in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc. and AXA. MK is supported by the AXA Research Fund. Nestlé Nutrition (Nestec Ltd.), Metagenics Inc

Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis

$\textbf{Importance}$ Between 40% and 50% of women in Western countries use complementary therapies to manage menopausal symptoms. $\textbf{Objective}$ To determine the association of plant-based therapies with menopausal symptoms, including hot flashes, night sweats, and vaginal dryness. $\textbf{Data Sources}$ The electronic databases Ovid MEDLINE, EMBASE, and Cochrane Central were systematically searched to identify eligible studies published before March 27, 2016. Reference lists of the included studies were searched for further identification of relevant studies. $\textbf{Study Selection}$ Randomized clinical trials that assessed plant-based therapies and the presence of hot flashes, night sweats, and vaginal dryness. $\textbf{Data Extraction}$ Data were extracted by 2 independent reviewers using a predesigned data collection form. $\textbf{Main Outcomes and Measures}$ Hot flashes, night sweats, and vaginal dryness. $\textbf{Results}$ In total, 62 studies were identified, including 6653 individual women. Use of phytoestrogens was associated with a decrease in the number of daily hot flashes (pooled mean difference of changes, −1.31 [95% CI, −2.02 to −0.61]) and vaginal dryness score (pooled mean difference of changes, −0.31 [95% CI, −0.52 to −0.10]) between the treatment groups but not in the number of night sweats (pooled mean difference of changes, −2.14 [95% CI, −5.57 to 1.29]). Individual phytoestrogen interventions such as dietary and supplemental soy isoflavones were associated with improvement in daily hot flashes (pooled mean difference of changes, −0.79 [−1.35 to −0.23]) and vaginal dryness score (pooled mean difference of changes, −0.26 [−0.48 to −0.04]). Several herbal remedies, but not Chinese medicinal herbs, were associated with an overall decrease in the frequency of vasomotor symptoms. There was substantial heterogeneity in quality across the available studies, and 46 (74%) of the included randomized clinical trials demonstrated a high risk of bias within 3 or more areas of study quality. $\textbf{Conclusions and Relevance}$ This meta-analysis of clinical trials suggests that composite and specific phytoestrogen supplementations were associated with modest reductions in the frequency of hot flashes and vaginal dryness but no significant reduction in night sweats. However, because of general suboptimal quality and the heterogeneous nature of the current evidence, further rigorous studies are needed to determine the association of plant-based and natural therapies with menopausal health.This study was sponsored by Metagenics Inc