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Existing literature on the association between influenza vaccination and COVID-19 infection/outcomes is conflicting. Therefore, we aimed to investigate the association between influenza vaccination and COVID-19 outcomes in a large cohort of adults who participated in the SHARE (Survey of Health, Ageing, and Retirement in Europe). Information regarding influenza vaccination in the previous year, and medical and demographic characteristics, were self-reported. Positivity for COVID-19, symptomatology, and hospitalization were also ascertained using self-reported information. An adjusted logistic regression analysis (including 15 baseline factors or propensity score) was used to assess the association between influenza vaccination and COVID-19 outcomes. A total of 48,408 participants (mean age 67 years; 54.1% females) were included. The prevalence of influenza vaccination was 38.3%. After adjusting for 15 potential confounders, influenza vaccination was significantly associated with a lower risk of positivity for COVID-19 (OR = 0.95; p < 0.0001), symptomatic forms (OR = 0.87; p < 0.0001), and hospitalization for COVID-19 (OR = 0.95; p < 0.0001). The results were similar when using a propensity score approach. In conclusion, influenza vaccination may be beneficial for the prevention of COVID-19, as the present study found that influenza vaccination was associated with a small/moderate lower risk of COVID-19 infection and adverse outcomes.

Purpose: Urinary incontinence (UI) and frailty are common geriatric syndromes. Although literature increasingly supports a relationship between these two conditions, no systematic review and meta-analysis has been performed on this topic. Therefore, we aimed to investigate the potential association between UI and frailty, through a meta-analytic approach. Methods: A systematic search in major databases was undertaken until 15th March 2018 for studies reporting the association between UI and frailty. The prevalence of UI in people with frailty (vs. those without) was pooled through an odds ratio (OR) and 95% confidence intervals (CIs), with a random-effects model. The other outcomes were summarized descriptively. Results: Among 828 papers, 11 articles were eligible, including 3784 participants (mean age 78.2years; 55.1% women). The prevalence of UI was 39.1% in people with frailty and 19.4% in those without. A meta-analysis with five studies (1540 participants) demonstrated that UI was over twice as likely in frail people versus those without (OR 2.28; 95% CI 1.35–3.86; I2 = 61%). One cross-sectional study, adjusting for potential confounders and one longitudinal study confirmed that UI is significantly associated with frailty. In two cross-sectional studies, using adjusted analyses, frailty was more common in people with UI. Conclusion: Urinary incontinence is twice as common in older people with frailty compared to older people without frailty. Screening and the development of interventions for UI and frailty could prove useful for this common comorbidity. © 2018, European Geriatric Medicine Society.

Magnesium plays a crucial role in hundreds of bodily processes relevant to aging, but consumption of dietary magnesium intake has been shown to be inadequate in a large proportion of older adults. Identifying groups at risk of low magnesium intake is important for informing targeted advice. Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2016, we examined the association between ethnicity (Caucasian/African American/Hispanic/other) and magnesium intake in a large representative sample of U.S. older adults (65 y, n = 5682, mean (SD) 72.9 (0.10) y). Analyses adjusted for total energy intake and a range of relevant covariates. Overall, 83.3% of participants were not meeting the recommended level of dietary magnesium intake, ranging from 78.1% of other ethnic groups to 90.6% of African Americans. In the fully adjusted model, magnesium intake was lower among African American older adults (-13.0 mg/d, 95% CI: -18.8 to -7.2), and higher among Hispanics (14.0 mg/d, 95% CI: 7.5 to 20.5) and those from other ethnic groups (17.2, 95% CI: 3.8 to 30.5) compared with Caucasian older adults. These results highlight the need for targeted interventions to increase magnesium intake in U.S. older adults, with a focus on African Americans, in order to reduce the burden of morbidity and ethnic inequalities in health in later life.

Background: Sleep duration may influence risk for sarcopenia but studies on this topic are scarce, especially from low and- middle-income countries (LMICs). Thus, the aim of the present study was to investigate the association between sleep duration and sarcopenia among adults aged ≥ 65years from five LMICs (China, Ghana, India, Russia, South Africa). Methods: Cross-sectional, community-based data from the WHO study on global ageing and adult health (SAGE) were analysed. Sarcopenia was defined as having low skeletal muscle mass (SMM) and weak handgrip strength, while severe sarcopenia was defined as having low SMM, weak handgrip strength, and slow gait speed. Self-reported sleep duration in the past two nights were averaged and classified as ≤ 6, > 6 to ≤ 9, and ≥ 9h/day. Multivariable logistic regression analysis was conducted. Results: Data on 13,210 adults aged ≥ 65years [mean (SD) age 72.6 (11.3) years; 55.0% females] were analyzed. In the overall sample, compared to > 6 to ≤ 9h/day of sleep duration, > 9h/day was associated with 1.70 (95% CI 1.15–2.51) and 1.75 (95% CI 1.08–2.84) times higher odds for sarcopenia and severe sarcopenia, respectively. No significant associations were observed among males, but associations were particularly pronounced among females [i.e., OR = 2.19 (95% CI 1.26–3.81) for sarcopenia, and OR = 2.26 (95% CI 1.20–4.23) for severe sarcopenia]. Conclusions: Long sleep duration was associated with an increased odds of sarcopenia and severe sarcopenia in LMICs, particularly in females. Future studies should investigate whether addressing long sleep duration among females can lead to lower risk for sarcopenia onset in LMICs. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Background: Hand osteoarthritis (OA) is common, but the efficacy/safety of treatment interventions aimed to improve health outcomes in this population are not well understood. Therefore, the aim of this study was to map and grade the effect of interventions for health outcomes in hand OA. Methods: Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For outcomes with ap-value

Background: Literature regarding cardiovascular disease (CVD) and incident physical performance limitations and disability in older people is equivocal. Aims: This study aimed to investigate whether CVD is longitudinally associated with incident physical performance limitations and disability in alarge population-based sample. Methods: This was an 8‑year prospective study using data collected as part of the Osteoarthritis Initiative. Participants were community-dwelling adults with knee osteoarthritis or at high risk for this condition. Diagnosed CVD was self-reported. Physical performance was assessed with measures of chair stand time and gait speed, whereas disability was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Longitudinal associations between CVD and changes in physical performance tests (chair stand time and gait speed) and disability score were analyzed using generalized linear models with repeated measurements. Results: The analyzed sample comprised 4796 adults (mean age 61.2 years, 58.5% female), of whom 313 people (6.5%) reported CVD at baseline. During 8years of follow-up, after adjustment for 11 potential confounders measured at baseline, those with CVD experienced aworse profile in chair stand time over the 8‑year follow-up period than those without CVD (p = 0.006). Conclusion: In acohort of middle-aged and older adults with knee osteoarthritis or at high risk for this condition those with CVD experienced aworse profile in chair stand time over the 8‑year follow-up period than those without CVD; however, CVD was not significantly associated with an increased incidence of poor gait speed and disability over 8years of follow-up. Importantly, no associations were observed when utilizing propensity score matching. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.

The coronavirus disease 2019 (COVID-19) has been shown to have more severe health outcomes in older people specifically in relation to mortality and disability. Vaccination seems to be efficacious and safe for preventing the negative consequences of COVID-19, but vaccine hesitancy seems to be high in older adults. We therefore aimed to investigate the prevalence of unwillingness and the uncertainty to vaccinate against COVID-19 in older people and the factors that can be associated with the unwillingness to vaccinate. For this work, we searched several databases until 18th June 2021 for studies reporting the prevalence of unwillingness and the uncertainty to vaccinate against COVID-19 in people aged >60 years. A meta-analysis of the prevalence, with the correspondent 95% confidence intervals (CIs), was proposed. Factors that can be associated with the unwillingness to vaccinate against COVID-19 were explored through multivariable analyses and reported as odds ratios (ORs). Among 662 papers initially screened, we included 15 studies for a total of 9753 older adults. The prevalence of unwillingness to vaccinate against COVID-19 in older people was 27.03% (95%CI: 15.10–38.95%), whilst the correspondent figure of uncertainty was 19.33% (95%CI: 12.28–26.39). The risk of being unvaccinated was significantly higher in Hispanics (OR=1.197; 95%CI: 1.010–1.418) and in case of low education (OR=1.678; 95%CI: 1.170–2.408) and low income (OR=1.287; 95%CI: 1.127–1.469). In conclusion, the hesitancy for COVID-19 vaccination is a relevant problem in older people, particularly in those with a low income, a low level of education, and in Hispanics living in the United States. © 2021 Elsevier B.V.

Frailty is a common condition in older people. The epidemiological data available, however, are mainly based on the physical frailty phenotype. An extensive literature has suggested that frailty should be identified using a multidimensional approach. Based on these recommendations, we estimated the prevalence of frailty and pre-frailty in the older population, using the multidimensional prognostic index (MPI), a common tool for defining multidimensional frailty. We searched several databases until 10th May 2021 for studies reporting the prevalence of frailty according to MPI values. MPI was categorized, where possible, in < 0.33 (robustness), 0.33–0.66 (pre-frailty) and > 0.66 (frailty) or using a RECursive Partition and AMalgamation approach. A meta-analysis of the prevalence, with the correspondent 95% confidence intervals (CIs) of pre-frailty and frailty was performed stratified by setting (population-based, ambulatory, nursing home, and hospital). Among 177 papers initially screened, we included 57 studies for a total of 56,407 older people. The mean age was 78.6 years, with a slight prevalence of women (58%). The overall prevalence of multidimensional frailty (MPI-3) was 26.8% (95%CI: 22.1–31.5), being higher in nursing home setting (51.5%) and lower in population-based studies (13.3%). The prevalence of pre-frailty (MPI-2) was 36.4% (95%CI: 33.1–39.7), being higher in hospital setting (39.3%) and lower in nursing home (20%). In conclusion, frailty and pre-frailty, according to a multidimensional definition, are common in older people affecting, respectively, one person over four and one over three. Our work further strengths the importance of screening frailty in older people using a multidimensional approach. © 2021 Elsevier B.V.

In March 2020, the World Health Organization declared the coronavirus disease 19 (COVID‐19) outbreak as global pandemic. Nursing homes were particularly struck by the COVID‐19 outbreak, with some authors considering the COVID‐19 pandemic as the “ground zero” for these structures.

Highlights • We carried out an umbrella review of systematic reviews with meta-analyses of observational studies on handgrip strength and all health outcomes. • Three outcomes (lower all-cause mortality, lower cardiovascular mortality, and lower risk of disability) were found to have highly suggestive evidence. • One outcome (chair rise performance over time) was found to have suggestive evidence. • Five outcomes (walking speed, inability to balance, hospital admissions, cardiac death, and mortality in those with chronic kidney disease) were found to have weak evidence., Purpose The aim of the present study was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies on handgrip strength and health outcomes. Methods An umbrella review of systematic reviews with meta-analyses of observational studies was conducted. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). Results From 504 articles returned in a search of the literature, 8 systematic reviews were included in our review, with a total of 11 outcomes. Overall, nine of the 11 of the outcomes reported nominally significant summary results (p < 0.05), with 4 associations surviving the application of the more stringent p value (p, Graphical Abstract Image, graphical abstract

Background & aims: Hydroxychloroquine (HCQ) and chloroquine (CQ) are anti-malarial drugs frequently used in the rheumatologic field. They were recently identified as potential therapeutic options for Coronavirus Disease (COVID-19). The present study aims to map and grade the diverse health outcomes associated with HCQ/CQ using an umbrella review approach. Methods: Umbrella review of systematic reviews of observational and intervention studies. For observational studies, random-effects summary effect size, 95% confidence interval, and 95% prediction interval were estimated. We also assessed heterogeneity, evidence for small-study effect, and evidence for excess significance bias. The quality of evidence was then graded using validated criteria from highly convincing to weak. The evidence from randomized controlled trials (RCTs) was graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. Results: From 313 articles returned in the literature search, six meta-analyses were included (n = 25 outcomes). Among meta-analyses (MAs) of observational studies, HCQ/CQ are weakly associated with a reduced risk for cardiovascular events and diabetes when used for autoimmune diseases and with spontaneous abortion; they are also associated with a higher risk of death in COVID-19 patients. Among MAs of RCTs, HCQ/CQ are associated with an improvement of articular manifestations of rheumatic diseases. Conclusions: There is high evidence of the efficacy of HCQ/CQ in the rheumatologic field. The lack of evidence for efficacy and the risk of death associated with the use of HCQ/CQ for COVID-19 indicate the inappropriateness of their inclusion in recent COVID-19 therapy guidelines and the urgent need for RCTs to determine eventual appropriateness as a COVID-19 therapy. Keywords: COVID-19; Chloroquine; Hydroxychloroquine; umbrella review. https://www.sciencedirect.com/science/article/pii/S1201971220325418?via%3Dihub

Introduction: Angiotensin-converting enzyme inhibitors (ACEI) may have several pleiotropic effects, but the literature regarding a possible relationship between ACEI use and frailty is limited. We investigated whether ACEI use is associated with lower risk of frailty in a cohort of North American individuals. Methods: Data from the Osteoarthritis Initiative, a cohort study with 8years of follow-up including community-dwelling adults with knee osteoarthritis or at high risk for this condition, were analyzed. ACEI use was defined through self-reported information and confirmed by a trained interviewer. Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of at least two of the following criteria: (1) weight loss ≥ 5% between baseline and any subsequent follow-up visit; (2) inability to do five chair stands; and (3) low energy level according to the SOF definition. A multivariable Poisson regression analysis was used to assess the association between ACEI use at baseline and incident frailty. The data were reported as relative risks (RRs) with their 95% confidence intervals (CIs). Results: The final sample consisted of 4295 adults (mean age 61.2years, females 58.1%). At baseline, 551 participants (12.8%) used ACEI. After adjusting for 15 potential confounders, the use of ACEI was associated with a lower risk of frailty (RR 0.72; 95% CI 0.53–0.99). The adjustment for the propensity score substantially confirmed these findings (RR 0.75; 95% CI 0.54–0.996). Conclusion: ACEI use may be associated with a reduced risk of frailty in individuals with/at risk of knee osteoarthritis, suggesting a potential role for ACI in the prevention of frailty. © 2019, Springer Nature Switzerland AG.

Background: Few studies have assessed the association between potato consumption and mortality. Objective: We investigated whether potato consumption (including fried and unfried potatoes) is associated with increased premature mortality risk in a North American cohort. Design: A longitudinal analysis included 4440 participants aged 45-79 y at baseline with an 8-y follow-up from the Osteoarthritis Initiative cohort study. Potato consumption (including fried and unfried potatoes) was analyzed by using a Block Brief 2000 food-frequency questionnaire and categorized as ≤1 time/mo, 2-3 times/mo, 1 time/wk, 2 times/wk, or ≥3 times/wk. Mortality was ascertained through validated cases of death. To investigate the association between potato consumption and mortality, Cox regression models were constructed to estimate HRs with 95% CIs, with adjustment for potential confounders. Results: Of the 4400 participants, 2551 (57.9%) were women with a mean ± SD age of 61.3 ± 9.2 y. During the 8-y followup, 236 participants died. After adjustment for 14 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not show an increased risk of overall mortality (HR: 1.11; 95% CI: 0.65, 1.91). However, subgroup analyses indicated that participants who consumed fried potatoes 2-3 times/wk (HR: 1.95; 95% CI: 1.11, 3.41) and ≥3 times/wk (HR: 2.26; 95% CI: 1.15, 4.47) were at an increased risk of mortality. The consumption of unfried potatoes was not associated with an increased mortality risk. Conclusions: The frequent consumption of fried potatoes appears to be associated with an increased mortality risk. Additional studies in larger sample sizes should be performed to confirm if overall potato consumption is associated with higher mortality risk. This trial was registered at clinicaltrials.gov as NCT00080171. Am J Clin Nutr 2017;106:162-7. © 2017 American Society for Nutrition.

Research considering the relationship between dietary Mg and osteoporosis as well as fractures are sparse and conflicting. We therefore aimed to investigate Mg intake and the onset of fractures in a large cohort of American men and women involved in the Osteoarthritis Initiative over a follow-up period of 8 years. Dietary Mg intake (including that derived from supplementation) was evaluated through a FFQ at baseline and categorised using sex-specific quintiles (Q); osteoporotic fractures were evaluated through self-reported history. Overall, 3765 participants (1577 men; 2071 women) with a mean age of 60·6 (sd9·1) years were included. During follow-up, 560 individuals (198 men and 368 women) developed a new fracture. After adjusting for fourteen potential confounders at baseline and taking those with lower Mg intake as reference (Q1), men (hazard ratio (HR) 0·47; 95 % CI 0·21, 1·00,P=0·05) and women (HR 0·38; 95 % CI 0·17, 0·82,P=0·01) in the highest quintile reported a significantly lower risk for fracture. Women meeting the recommended Mg intake were at a 27 % decreased risk for future fractures. In conclusion, higher dietary Mg intake has a protective effect on future osteoporotic fractures, especially in women with a high risk for knee osteoarthritis. Those women meeting the recommended Mg intake appear to be at a lower risk for fractures.

Background: Evidence provides inconsistent findings on risk factors and health outcomes associated with loneliness. The aim of this work was to grade the evidence on risk factors and health outcomes associated with loneliness, using an umbrella review approach. Methods: For each meta-analytic association, random-effects summary effect size, 95% confidence intervals (CIs), heterogeneity, evidence for small-study effect, excess significance bias and 95% prediction intervals were calculated, and used to grade significant evidence (p

Aims:\ud \ud This study aimed to use an umbrella review methodology to capture the range of outcomes that were associated with low‐dose aspirin and to systematically assess the credibility of this evidence.\ud \ud Methods:\ud \ud Aspirin is associated with several health outcomes, but the overall benefit/risk balance related to aspirin use is unclear. We searched three major databases up to 15 August 2019 for meta‐analyses of observational studies and randomized controlled trials (RCTs) including low‐dose aspirin compared to placebo or other treatments. Based on random‐effects summary effect sizes, 95% prediction intervals, heterogeneity, small‐study effects and excess significance, significant meta‐analyses of observational studies were classified from convincing (class I) to weak (class IV). For meta‐analyses of RCTs, outcomes with random effects P ‐value < .005 and a moderate/high GRADE assessment, were classified as strong evidence. From 6802 hits, 67 meta‐analyses (156 outcomes) were eligible.\ud \ud Results:\ud \ud Observational data showed highly suggestive evidence for aspirin use and increased risk of upper gastrointestinal bleeding (RR = 2.28, 95% CI: 1.97–2.64). In RCTs of low‐dose aspirin, we observed strong evidence for lower risk of CVD in people without CVD (RR = 0.83; 95% CI: 0.79–0.87) and in general population (RR = 0.83; 95% CI: 0.79–0.89), higher risk of major gastrointestinal (RR = 1.47; 95% CI: 1.26–1.72) and intracranial bleeding (RR = 1.34; 95% CI: 1.18–1.53), and of major bleedings in people without CVD (RR = 1.62; 95% CI: 1.26–2.08).\ud \ud Conclusion:\ud \ud Compared to other active medications, low‐dose aspirin had strong evidence for lower risk of bleeding, but also lower comparative efficacy. Low‐dose aspirin significantly lowers CVD risk and increases risk of bleeding. Evidence for multiple other health outcomes is limited.

Growing evidence reports that chronic kidney diseases (CKD) might play a role in erectile dysfunction (ED), but limited knowledge is available. Therefore, we performed a systematic review up to 21/08/2019 to investigate the associations between CKD and ED. The main analysis reported the prevalence of ED as absolute estimates (in %) with their 95% confidence intervals (CIs) and across CKD stages (when specified), hemodialysis and transplant, calculating the p for interaction across strata. Among 291 studies, we included 34 articles with 5986 men. We found an overall prevalence of 76% (95%CI: 72–79) with a high degree of heterogeneity (I2 = 84.2%; p < 0.0001). Analyzing the data by CKD stage, we found a significant higher prevalence of ED in CKD (78%; 95%CI: 75–81%; I2 = not possible) compared with hemodialysis stage (prevalence = 77%; 95%CI: 73–80%; I2 = 84.5) or to patients undergoing transplant (prevalence = 64%; 95%CI: 54–74%; I2 = 54%) (p across strata = 0.036). Considering the high prevalence of ED in men with CKD, health care practitioners should focus on issues of sexual health in men with CKD. Given the advancements in dialysis and therapy and the associated advancements in survival and life expectancy, maintaining the patients’ sexual function is important for their well-being and quality of life. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Key summary pointsAimTo investigate associations of sarcopenia with adverse health-related outcomes, through an umbrella review method.FindingsSarcopenia appears to be significantly associated with several adverse outcomes in older people, with a strong evidence for increased risk of mortality, disability, and falls.MessageSarcopenia is associated with several adverse health-related outcomes in older people, indicating the need of assessing this condition in daily practice. AbstractBackgroundThe clinical relevance of sarcopenia has increasingly been recognized. However, whether it is associated with the development of other medical conditions is still unclear. Therefore, we aimed to capture the scale of outcomes that have been associated with the presence of sarcopenia and systematically assess the quality, strength, and credibility of these associations using an umbrella review methodology.MethodsA systematic review in several databases was carried out, until 20th February 2019. For each association, random-effects summary effect size, 95% confidence intervals (CIs), heterogeneity (I-2), evidence for small-study effect, evidence for excess significance bias, and 95%-prediction intervals were estimated. We used these metrics to categorize the evidence of significant outcomes (p

Background Our aim was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies and physical health outcomes associated with human immunodeficiency virus (HIV) but not acquired immunodeficiency syndrome. Methods We performed an umbrella review of observational studies. Evidence was graded as convincing, highly suggestive, suggestive, weak, or nonsignificant. Results From 3413 studies returned, 20 were included, covering 55 health outcomes. Median number of participants was 18 743 (range 403–225 000 000). Overall, 45 (81.8%) of the 55 unique outcomes reported nominally significant summary results (P < .05). Only 5 outcomes (9.0%; higher likelihood of presence of breathlessness, higher chronic obstructive pulmonary disease [COPD] prevalence, maternal sepsis, higher risk of anemia, and higher risk of all fractures among people living with HIV [PLWHIV]) showed suggestive evidence, with P values < 10–3; only 3 (5.5%; higher prevalence of cough in cross-sectional studies, higher incidence of pregnancy-related mortality, and higher incidence of ischemic heart disease among PLWHIV in cohort studies) outcomes showed stronger evidence using a stringent P value (, This umbrella review captures the complexities and variety of physical outcomes associated with human immunodeficiency virus. It reports on 55 unique outcomes: 3 (higher prevalence of cough and higher incidences of pregnancy-related mortality and ischemic heart disease) had strong evidence.

Background & aims: The literature regarding the potential health benefits of chocolate consumption are unclear and the epidemiological credibility has not been systematically scrutinized, while the strength of the evidence is undetermined. We therefore aimed to map and grade the diverse health outcomes associated with chocolate consumption using an umbrella review of systematic reviews. Methods: Umbrella review of systematic reviews of observational and intervention studies (randomized placebo-controlled trials, RCTs). For each association, random-effects summary effect size, 95% confidence interval, and 95% prediction interval were estimated. We also assessed heterogeneity, evidence for small-study effect and evidence for excess significance bias. For significant outcomes of the RCTs, the GRADE assessment was furtherly used. Results: From 240 articles returned, 10 systematic reviews were included (8 of which included a meta-analysis), including a total of 84 studies (36 prospective observational studies and 48 interventional). Nineteen different outcomes were included. Among observational studies, including a total of 1,061,637 participants, the best available evidence suggests that chocolate consumption is associated with reduced risk of cardiovascular disease (CVD) death (n = 4 studies), acute myocardial infarction (n = 6), stroke (n = 5) and diabetes (n = 6), although this was based on a weak evidence of credibility. Across meta-analyses of intervention studies, chocolate consumption was positively associated with flow-mediated dilatation at 90–150 min (n = 3) and at 2–18 weeks (n = 3), and insulin resistance markers (n = 2). However, using the GRADE assessment, the evidence for these outcomes was low or very low. Data from two systematic reviews, reported that chocolate consumption was not associated with better depressive mood or cognitive function. Conclusions: There is weak evidence to suggest that chocolate consumption may be associated with favorable health outcomes. © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

Objectives: Literature regarding dietary protein intake and risk of falls is limited to a few studies with relatively small sample sizes and short follow-ups, which have reported contrasting findings. Thus, we investigated whether dietary protein intake is associated with risk of falls in a large cohort of North American adults. Design: Data were drawn from the Osteoarthritis Initiative, a cohort study, with 8 years of follow-up. Setting and participants: Community-dwelling adults with knee osteoarthritis or at high risk for this condition. Methods: Dietary protein intake was recorded using the Block Brief 2000 food frequency questionnaire and categorized using gender-specific quartiles (Q). Falls were self-reported in response to the question “Did you fall during the past year?” categorized as yes vs no and made during the 6 visits over 8 years of follow-up. Results are reported as relative risks (RRs), with their 95% confidence intervals (CIs), using a multivariable Poisson regression. Results: The final sample consisted of 4450 adults (mean age 61.2 years, females = 59.6%). Higher dietary protein intake was significantly associated with higher frequency of falls during the year before baseline. After adjusting for 17 potential confounders, people with the greatest amount of protein intake (Q4) had a significantly higher risk of falling over the 8-year follow-up period (RR 1.112, 95% CI 1.027-1.211, P = .009) than those with the lowest protein intake (Q1). Conclusions/Implications: In this cohort of people affected by knee osteoarthritis or at high risk for this condition, high dietary protein intake may increase the risk of falls in older people, but further research is needed to confirm or refute these findings. © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine

The aim of the present study was to map and grade evidence for the relationships between telomere length with a diverse range of health outcomes, using an umbrella review of systematic reviews with meta-analyses. We searched for meta-analyses of observational studies reporting on the association of telomere length with any health outcome (clinical disease outcomes and intermediate traits). For each association, random-effects summary effect size, 95% confidence interval (CI), and 95% prediction interval were calculated. To evaluate the credibility of the identified evidence, we assessed also heterogeneity, evidence for small-study effect and evidence for excess significance bias. Twenty-one relevant meta-analyses were identified reporting on 50 different outcomes and including a total of 326 observational studies. The level of evidence was high only for the association of short telomeres with higher risk of gastric cancer in the general population (relative risk, RR=1.95, 95%CI: 1.68-2.26), and moderate for the association of shorter telomeres with diabetes or with Alzheimer’s disease, even if limited to meta-analyses of case-control studies. There was weak evidence for twenty outcomes and not significant association for 27 health outcomes. The present umbrella review demonstrates that shorter telomere length may have an important role in incidence gastric cancer and, probably, diabetes and Alzheimer’s disease. At the same time, conversely to general assumptions, it does not find strong evidence supporting the notion that shorter telomere length plays an important role in many health outcomes that have been studied thus far.

Background/Objectives: A small number of case-control studies have suggested that mitochondrial haplogroups could be associated with obesity. We examined whether obesity risk was influenced by mitochondrial haplogroup in a large North American cohort across an 8-year period. We conducted a longitudinal cohort study including individuals from the Osteoarthritis Initiative. Subjects/Methods: Mitochondrial haplogroups were determined by sequencing and PCR-RFLP techniques using this nomenclature: HV, JT, KU, IWX, and super HV/others. The strength of the association between mitochondrial haplogroups and incident obesity was quantified with hazard ratios (HRs), adjusted for potential confounders using a Cox's regression analysis. Results: Overall, 2342 non-obese Caucasian participants (56.7% women) with a mean ± SD age of 62.0 ± 9.5 years at baseline were included. During a median follow-up of 8 years, 334 individuals (= 14.3% of baseline population) became obese. After adjusting for nine potential confounders, the haplogroups IWX carried a significant 48% higher risk of obesity (HR = 1.48; 95% CI: 1.02-2.39) compared to the HV haplotype (the most frequent type). Conclusion: Only the presence of the IWX haplogroups appears to be linked to increased obesity risk, independent of potential baseline confounders. Future cohort studies are needed to confirm these findings and to determine potential underlying mechanisms. © 2018 Macmillan Publishers Limited, part of Springer Nature.

Hypovitaminosis D is associated with frailty, but if vitamin D supplementation may prevent the onset of frailty is poorly known. Therefore, we aimed to investigate whether vitamin D supplementation is associated with a lower risk of frailty. In this longitudinal study, 4,421 individuals at high risk or having knee osteoarthritis free from frailty at baseline (mean age: 61.3, females = 58.0%) were followed for 8 years. Details regarding vitamin D supplementation were captured by asking whether the participant took vitamin D during the previous year, at least once per month. Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of at least two of the following criteria: (i) weight loss ≥ 5% between baseline and any subsequent follow-up visit; (ii) inability to do five chair stands; (iii) low energy level according to the SOF definition. Multivariable Cox's regression analyses, calculating hazard ratios (HRs) with 95% confidence intervals (CIs), were undertaken. At baseline 69.7% took vitamin D supplements in the previous year, with a mean dose of 384 ± 157 IU per day. During the 8-year follow-up, no difference in the incidence of frailty was evident by vitamin D supplementation status at baseline, even after adjusting for 13 baseline confounders (HR = 0.95; 95% CI: 0.72–1.25). Similar results were obtained using the propensity score (HR = 0.95; 95% CI: 0.71–1.25) or age- and sex-matched controls (HR = 1.00; 95% CI: 0.75–1.33). In conclusion, low-dose vitamin D supplementation was not associated with any decreased risk of frailty during eight years of follow-up in a large cohort of North American people. Future large-scale trials with high doses of oral vitamin D and longer follow-up are needed to confirm/refute our findings. © 2017 Elsevier Inc.

Aberrant function of Smad2, a crucial member of transforming growth factor beta (TGF-β) signaling, is associated with the development of malignancies, particularly in the gastrointestinal district. However, little is known about its possible prognostic role in such tumor types. With the first meta-analysis on this topic, we demonstrated that the lack of the activated form of Smad2 (phosphor-Smad2 or pSmad2), which was meant to be the C-terminally phosphorylated form, showed a statistically significant association with an increased risk of all-cause mortality in patients with gastrointestinal cancers (RR, 1.58; 95% CI, 1.05–2.37, p = 0.029, I2 = 84%), also after having adjusted for potential confounders (RR, 1.65; 95% CI, 1.24–2.18; p < 0.001; I2 = 4%). This finding highlights the importance of the TGF-β signaling in this type of cancer. In this line, further studies are needed to explore more in depth this important molecular pathway, focusing also on potential therapeutic strategies based on its effectors or molecular targets. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Background Some case-control studies reported that mitochondrial haplogroups could be associated with the onset of cardiovascular diseases (CVD), but the literature regarding this topic is limited. We aimed to investigate whether any mitochondrial haplogroup carried a higher or lower risk of CVD in a large cohort of North American people affected by knee osteoarthritis or at high risk for this condition. Materials and methods A longitudinal cohort study including individuals from the Osteoarthritis Initiative was done. Haplogroups were assigned through a combination of sequencing and PCR-RFLP techniques. All the mitochondrial haplogroups have been named following this nomenclature: HV, JT, UK, IWX, and superHV/others. The strength of the association between mitochondrial haplogroups and incident CVD was evaluated through a Cox’s regression analysis, adjusted for potential confounders, and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). Results Overall, 3,288 Caucasian participants (56.8% women) with a mean age of 61.3±9.2 years without CVD at baseline were included. During a median follow-up of 8 years, 322 individuals (= 9.8% of baseline population) developed a CVD. After adjusting for 11 potential confounders at baseline and taking those with the HV haplotype as reference (the most frequent), those with JT carried a significant lower risk of CVD (HR = 0.75; 95%CI: 0.54–0.96; p = 0.03). Participants with the J haplogroup had the lowest risk of CVD (HR = 0.71; 95%CI: 0.46–0.95; p = 0.02). Conclusions The presence of JT haplogroups (particularly J) may be associated with a reduced risk of CVD. However, this result was not based on a high level of statistical significance. Thus, future research with larger sample size is needed to assess whether our results can be corroborated. © 2019 Veronese et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background:\ud A possible relationship between mitochondrial haplogroups and psychiatric diseases (e.g. schizophrenia and bipolar disorder) has been postulated, but data regarding depression is still limited. We investigated whether any mitochondrial haplogroup carried a significant higher risk of depressive symptoms in a large prospective cohort of North American people included in the Osteoarthritis Initiative.\ud \ud Methods:\ud Cross sectional data was derived from the Osteoarthritis Initiative. The haplogroup was assigned through a combination of sequencing and PCR-RFLP techniques. All the mitochondrial haplogroups were named following this nomenclature: H, U, K, J, T, V, SuperHV, I, W, X or Others. Depression was ascertained through the 20-item Center for Epidemiologic Studies- Depression (CES-D), with >16 indicating depressive symptoms.\ud \ud Results:\ud Overall, 3,601 Caucasian participants (55.9% women), mean age of 61.7±9.3 years were included. No difference was observed in mitochondrial haplogroups frequency among those with depressive symptoms (n=285, =7.9% of the baseline population) compared to participants with no depressive symptoms (N=3,316) (chi-square test=0.53). Using a logistic regression analysis, adjusted for eight potential confounders, with those having the haplogroup H as the reference group (the most common haplogroup), no significant mitochondrial haplogroup was associated with prevalent depressive symptoms. The same results were evident in secondary analysis in which we matched depressed and non-depressed participants for age and sex.\ud \ud Limitations:\ud cross-sectional design; only CES-D for evaluating mood; participants not totally representative of general population.\ud \ud Conclusions:\ud We found no evidence of any relationship between specific mitochondrial haplogroups and depressive symptoms. Future longitudinal research is required to confirm/ refute these findings.

This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13-1.88, p = 0.004; HR, 2.65; 95% CI, 1.79-3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05-2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that EMT is a central process in determining the presence of TB in PDAC. Thanks to this meta-analysis, we demonstrate the potential clinical significance of high-grade TB for prognostic stratification of PDAC. TB also shows a clear association with the process of EMT. Based on the results of the present study, TB should be conveyed in pathology reports and taken into account by future oncologic staging systems. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.