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Background and Aims: Glucosamine sulphate (GS) can be used as background therapy in people affected by knee osteoarthritis (OA). Knowledge regarding the efficacy and safety of GS is of importance since its use worldwide is increasing. Therefore, the present study aimed to map and grade the diverse health outcomes associated with GS using an umbrella review approach., Methods: Medline, Cinahl and Embase databases were searched until 1 April 2020. An umbrella review of systematic reviews and meta-analyses of randomized controlled trials (RCTs) was carried out. The evidence from the RCTs was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool., Results: From 140 articles returned, 11 systematic reviews, for a total of 21 outcomes (37 RCTs; 3949 participants; almost all using 1500 mg/day), were included. No systematic reviews/meta-analyses of observational studies were included. Regarding the findings of the meta-analyses, 9/17 outcomes were statistically significant, indicating that GS is more effective than placebo. A high certainty of evidence, as assessed by GRADE, supported the use of GS ( versus placebo) in improving the Lequesne Index, joint space width change, joint space width change after 3 years of follow up, joint space narrowing and OA progression. No difference in terms of adverse effects was found between GS and placebo. In systematic reviews, GS was associated with a better glucose profile and a better physical function performance than placebo., Conclusion: GS, when used as a prescription drug (i.e. crystalline glucosamine sulphate) at 1500 mg daily dosage, can positively affect the cartilage structure, reduce pain, improve function and glucose metabolism in people with knee OA, without having a greater incidence of adverse effects than placebo., Competing Interests: Conflict of interest statement: J-YR reports grants and personal fees from IBSA-Genevrier, Mylan, Radius Health and CNIEL, personal fees from Laboratoires Pierre Fabre, Faes Pharma, Rejuvenate Biomed, Samumed, Teva, Theramex, Pfizer, Mithra Pharmaceuticals, Dairy Research Council, Nutricia, Danone and AgNovos, and grants from TRB. GH reports lecture fees and travel support from IBSA. SM reports grants from Sanofi Pasteur, MSD, GlaxoSmithKline, Pfizer and Takeda as organiser of meetings/congresses and as principal investigator of epidemiological studies, for taking part on advisory boards and in expert meetings. OB reports grants from Biophytis, IBSA, Meda, Servier Laboratories and SMB, and personal fees from Amgen, Aptissen, Biophytis, IBSA, Meda, Novartis, Sanofi, Servier Laboratories, SMB and UCB. NV reports personal fees from Mylan, IBSA and Fidia., (© The Author(s), 2020.)

Background: Out-of-hours (OOH) services in Italy provide >10 million consultations every year. To the authors' knowledge, no data on patient safety culture (PSC) have been reported., Aim: To assess PSC in the Italian OOH setting., Design & Setting: National cross-sectional survey using the Safety Attitudes Questionnaire - Ambulatory Version (SAQ-AV)., Method: The SAQ-AV was translated into Italian and distributed in a convenience sample of OOH doctors in 2015. Answers were collected anonymously by Qualtrics. Stata (version 14) was used to estimate Cronbach's alpha, perform exploratory and confirmatory factor analysis, correlate items to doctors' characteristics, and to do item descriptive analysis., Results: Overall, 692 OOH doctors were contacted, with a 71% response rate. In the exploratory factor analysis (EFA), four factors were identified: Communication and Safety Climate (14 items); Perceptions of Management (eight items); Workload and Clinical Risk (six items); and Burnout Risk (four items).These four factors accounted for 68% of the total variance (Kaiser-Meyer-Olkin [KMO] statistic = 0.843). Cronbach's alpha ranged from 0.710-0.917. OOH doctors were often dissatisfied with their job; there is insufficient staff to provide optimal care and there is no training or supervision for new personnel and family medicine trainees. Service managers are perceived as distant, with particular issues concerning the communication between managers and OOH doctors. A large proportion of OOH doctors (56.8%) state that they do not receive adequate support., Conclusion: These findings could be useful for informing policies on how to improve PSC in Italian OOH service., (Copyright © 2020, The Authors.)

Growing evidence reports that obesity might play a role in erectile dysfunction (ED), but limited knowledge is available. We conducted a meta-analysis to estimate the prevalence of ED in overweight men and men with obesity. We performed a systematic review up to 01/04/2019 to investigate the associations between obesity and ED. Applying a random-effect model, we calculated the prevalence of ED, the odds ratio (OR) for the presence of ED by Body Mass Index (BMI) categories and the mean differences between ED and controls in BMI and Waist Circumference (WC). Among 3409 studies, we included 45 articles with 42,489 men (mean age = 55 years). Taking normal weight men as reference, the prevalence of ED was significantly higher in overweight (OR = 1.31; 95%CI: 1.13-1.51; I 2  = 72%) and in men with obesity (OR = 1.60; 95%CI: 1.29-1.98; I 2  = 79%). Adjusting our analyses for potential confounders, the results were confirmed in men with obesity (OR = 1.46; 95%CI: 1.24-1.72; I 2  = 72%). ED was associated with significant higher values of BMI (MD = 0.769; 95%CI: 0.565-0.973 Kg/m 2 ; I 2  = 78%) and WC (MD = 5.251 cm; 95%CI: 1.295-9.208; I 2  = 96%). Considering the high prevalence of ED among men with obesity, clinicians should screen for this clinical condition in this population. Findings from the present study suggest that reducing adiposity is a crucial approach in patients with ED who are affected by obesity.

Objective: To evaluate the precipitating factors for heart failure decompensation in primary care and associations with short-term prognosis. Design Prospective cohort study with a 30-d follow-up from an index consultation. Regression models to determine independent factors associated with hospitalisation or death., Setting: Primary care in ten European countries. Patients Patients with diagnosis of heart failure attended in primary care for a heart failure decompensation (increase of dyspnoea, unexplained weight gain or peripheral oedema)., Main Outcome Measures: Potential precipitating factors for decompensation of heart failure and their association with the event of hospitalisation or mortality 30 d after a decompensation., Results: Of 692 patients 54% were women, mean age 81 (standard deviation [SD] 8.9) years; mean left ventricular ejection fraction (LVEF) 55% (SD 12%). Most frequently identified heart failure precipitation factors were respiratory infections in 194 patients (28%), non-compliance of dietary recommendations in 184 (27%) and non-compliance with pharmacological treatment in 157 (23%). The two strongest precipitating factors to predict 30 d hospitalisation or death were respiratory infections (odds ratio [OR] 2.8, 95% confidence interval [CI] (2.4-3.4)) and atrial fibrillation (AF) > 110 beats/min (OR 2.2, CI 1.5-3.2). Multivariate analysis confirmed the association between the following variables and hospitalisation/death: In relation to precipitating factors: respiratory infection (OR 1.19, 95% CI 1.14-1.25) and AF with heart rate > 110 beats/min (OR 1.22, 95% CI 1.10-1.35); and regarding patient characteristics: New York Heart Association (NYHA) III or IV (OR 1.22, 95% CI 1.15-1.29); previous hospitalisation (OR 1.15, 95% CI 1.11-1.19); and LVEF < 40% (OR 1.14, 95% CI 1.09-1.19)., Conclusions: In primary care, respiratory infections and rapid AF are the most important precipitating factors for hospitalisation and death within 30 d following an episode of heart failure decompensation. Key points Hospitalisation due to heart failure decompensation represents the highest share of healthcare costs for this disease. So far, no primary care studies have analysed the relationship between precipitating factors and short term prognosis of heart failure decompensation episodes. We found that in 692 patients with heart failure decompensation in primary care, the respiratory infection and rapid atrial fibrillation (AF) increased the risk of short-term hospital admission or death. Patients with a hospital admission the previous year and a decompensation episode caused by respiratory infection were even more likely to be hospitalized or die within 30 d.

Objectives: The aim of this umbrella review was to determine the effect of physical activity/exercise on improving cognitive and noncognitive outcomes in people with MCI (mild cognitive impairment) and dementia., Design: Umbrella review of systematic reviews (SR), with or without meta-analyses (MAs), of randomized controlled trials (RCTs) and observational studies., Settings and Participants: People with MCI or dementia, confirmed through validated assessment measures. Any form of physical activity/exercise was included. As controls, we included participants not following any prespecified physical activity/exercise intervention or following the same standard protocol with the intervention group., Methods: The protocol was registered in PROSPERO (CDR 164197). Major databases were searched until December 31, 2019. The certainty of evidence of statistically significant outcomes was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. SRs' findings, without a formal MA, were reported descriptively., Results: Among 1160 articles initially evaluated, 27 SRs (all of RCTs, 9 without MA) for a total of 28,205 participants with MCI/dementia were included. In patients with MCI, mind-body intervention (standardized mean difference [SMD] = 0.36; 95% confidence intervals [CI] 0.20-0.52; low certainty) and mixed physical activity interventions (SMD = 0.30; 95% CI 0.11-0.49; moderate certainty) had a small effect on global cognition, whereas resistance training (SMD = 0.80; 95% CI 0.29-1.31; very low certainty) had a large effect on global cognition. In people affected by dementia, physical activity/exercise was effective in improving global cognition in Alzheimer disease (SMD = 1.10; 95% CI 0.65-1.64; very low certainty) and in all types of dementia (SMD = 0.48; 95% CI 0.22-0.74; low certainty). Finally, physical activity/exercise improved noncognitive outcomes in people with dementia including falls, and neuropsychiatric symptoms., Conclusions and Implications: Supported by very low-to-moderate certainty of evidence, physical activity/exercise has a positive effect on several cognitive and noncognitive outcomes in people with MCI and dementia, but RCTs, with low risk of bias/confounding, are still needed to confirm these relationships., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Vaccination is the main public health intervention to prevent influenza. We aimed to evaluate the efficacy and safety of influenza vaccination including systematic reviews and meta-analyses of observational studies and randomized controlled trials (RCTs). Peer-reviewed systematic reviews with meta-analyses of prospective studies that investigated the association of influenza vaccination with any health-related outcome, as well as RCTs that investigated the efficacy and safety of influenza vaccination, were included. Among 1240 references, 6 meta-analyses were included. In cohort studies of community-dwelling older people influenza vaccination was associated with a lower risk of hospitalization for heart disease and for influenza/pneumonia (strength of evidence: convincing). Evidence in lowering the risk of mortality in community-dwelling older people, of all deaths/severe respiratory diseases in high risk community-dwelling older people and of hospitalization for influenza/pneumonia in case-control studies, was highly suggestive. In RCTs, influenza vaccination, compared to placebo/no intervention, was associated to higher risk of local tenderness/sore arm and to a reduced risk of influenza like-illness. Both these associations showed moderate evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation). In conclusion, influenza vaccination in older people seems safe and effective. Further, the evidence on safety and efficacy of vaccines in this population might benefit by an extension of the follow-up period both in RCTs and in longitudinal studies, beyond the usual 6-month period, in order to be able to evaluate the impact of vaccination on long term outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Aim of this study, part of a European collaborative research project, was to evaluate the "patient safety culture" (PSC) in a primary care out of hours service in order to provide the management with a baseline for improvement interventions., Methods: Cross sectional study with the administration of the Safety Attitude Questionnaire Ambulatory Version (SAQ-AV) administered to all the 56 doctors working out of hours in the ULSS 20 Verona Local Health Trust in April/May 2015. For each item of the questionnaire the average score, standard deviation, non-applicability, percentage of agreement, percentage of disagreement were calculated., Results: Doctors working out of hours appreciate the type of work, feel mutual trust and provide support to each other but only 63.6% would feel safe if they would be a patient; little attention to the rules, protocols and evidence-based practices, poor diffusion of culture to learn from the mistakes of other operators and the difficulty of speaking about the mistakes made were detected. Despite the positive perception of the work provided by the group, the doctors seem to feel that the morale of the operators is not optimal and their overall satisfaction is poor. Workload seems to be perceived as a minor issue, differently from the perception of a lack of attention by the management towards the service, lack of support, feedback and recognition, and the lack of reference points for the operators, risk management procedures, recently graduate staff training, equipment provision, regularity and correctness of drug and prescription supply, lack of and loss of essential information to make decisions and lack of communication leading to dysfunction of care., Conclusions: The questionnaire provides decision-makers with useful information about the patient safety culture, identifying critical areas to address improvement efforts.

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<0.05) from convincing to weak. For narrative systematic reviews, findings were reported descriptively., Results: From 210 studies initially evaluated, 14 publications were included, reporting on 18 outcomes, 795 studies, and 746,706 participants. Highly suggestive evidence (class II) supported the association between loneliness and incident dementia (relative risk, RR=1.26; 95%CI: 1.14-1.40, I 2 23.6%), prevalent paranoia (odds ratio, OR=3.36; 95%CI: 2.51-4.49, I 2 92.8%) and prevalent psychotic symptoms (OR=2.33; 95%CI: 1.68-3.22, I 2 56.5%). Pooled data supported the longitudinal association between loneliness and suicide attempts and depressive symptoms. In narrative systematic reviews, factors cross-sectionally associated with loneliness were age (in a U-shape way), female sex, quality of social contacts, low competence, socio-economic status and medical chronic conditions., Limitations: Low quality of the studies included; mainly cross-sectional evidence., Conclusions: This work is the first meta-evidence synthesis showing that highly suggestive and significant evidence supports the association between loneliness and adverse mental and physical health outcomes. More cohort studies are needed to disentangle the direction of the association between risk factors for loneliness and its related health outcomes., Competing Interests: Declarations of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Inappropriate prescriptions and consumption of antibiotics are the main determinants of the selection of antibiotic resistant bacteria. Italy has a high consumption rate of antibiotics if compared to other European countries and 90% of these drugs are prescribed in an outpatient setting by General Practitioners (GPs). Therefore, as stated by the Italian Medicines Agency (AIFA): «General Practice is [...] a crucial clinical area in which the utilization of these kind of drugs have to be monitored, [...] considering that a relevant quote of prescriptions could be avoided. Achieving a better understanding of the clinical and extra-clinical determinants of GPs prescription habits is, therefore, hugely important to design appropriate interventions to tackle the phenomenon of inappropriate antibiotic use. To the best of our knowledge, there are no published studies measuring GPs knowledge and attitudes on antibiotic resistance and prescriptions in our setting. To fill this lack of knowledge, the aim of our study is the development of a valid and reliable questionnaire in Italian language, able to measure these constructs. In this article, we present the process of cross-cultural adaptation of the KAAR-11 questionnaire from Spanish into Italian language and its preliminary validation.

Purpose: Increased nocturia episodes can be a clinical marker of poor health status. The present study aimed to evaluate patterns and temporal trends in nocturia and sociodemographic and lifestyle correlates in the US population., Methods: Participants, aged 20 years or older, were included in this repeated cross-sectional study. The National Health and Nutrition Examination Survey from 2005 to 2016 was used. Participants were asked "During the past 30 days, how many times per night did you most typically get up to urinate, from the time you went to bed at night until the time you got up in the morning?". Individuals were categorized as either ≥ 1 nocturia episode or ≥ 2 nocturia episodes per night., Results: The estimated prevalence of ≥ 1 nocturia was high among men (20-39 years, 56.8%; 40-59 years, 70.2%; ≥ 60 years, 82.7%) and women (20-39 years, 68.9%; 40-59 years, 74.3%; ≥ 60 years, 84.7%), particularly in Non-Hispanic-blacks. From 2005-2016, the trends in prevalence of ≥ 1 nocturia increased for the age groups 20-39 and 40-59 years among men (p < 0.001 and p = 0.001, respectively) and women 20-39 and 40-59 years (p < 0.001 and p = 0.032, respectively), but a stable trend was observed among men and women who were 60 years and older (p = 0.814, and p = 0.64, respectively). A significant increasing trend of ≥ 2 nocturia episodes was observed among men only aged 40-59 years (p = 0.007)., Conclusions: From 2005 through 2016, the secular trend in the frequency of nocturia increased in both men and women in general, which was significant under the age of 60 years, particularly in Non-Hispanic-blacks.

The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition., (Copyright © 2020 Veronese, Demurtas, Yang, Tonelli, Barbagallo, Lopalco, Lagolio, Celotto, Pizzol, Zou, Tully, Ilie, Trott, López-Sánchez and Smith.)

Background: This paper aims to examine associations between pet ownership and symptoms of depression in a large, population-based sample of older adults. Specifically, we tested whether: (i) people who report more depressive symptoms are more likely to own a pet; (ii) pet ownership protects against an increase in depressive symptoms over time; (iii) associations differ by symptom type., Methods: Data were drawn from the English Longitudinal Study of Ageing, a longitudinal panel study of men and women aged 50 and older (n = 7,617, 52.5% female). Pet ownership (dog/cat/other/none) was self-reported in 2010/11. Depressive symptoms were assessed in 2010/11 and 2016/17 using the 8-item centre for Epidemiologic Studies Depression (CES-D) scale. We analysed total CES-D score and derived symptom subscales (depressed mood, anhedonia, somatic symptoms) in relation to pet ownership, adjusting for sociodemographic and health-related covariates., Results: A one-symptom increase in total CES-D score was associated with 7% increased odds of dog ownership (OR=1.07, 95% CI 1.03-1.11). Significant associations were observed between each subset of depressive symptoms and dog ownership, with models run on z-scores showing a slightly stronger association for symptoms of depressed mood (OR=1.13, 95% CI 1.06-1.21) compared with anhedonia (OR=1.10, 95% CI 1.04-1.17) or somatic symptoms (OR=1.10, 95% CI 1.03-1.18). Prospectively, no significant associations were found., Limitations: Self-reported data; small sample size for some pet categories., Conclusion: Amongst older adults in England, those with more depressive symptoms are more likely to own a dog, but pet ownership is not significantly associated with change in depressive symptoms over time., Competing Interests: Declarations of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To map and grade all health outcomes associated with magnesium (Mg) intake and supplementation using an umbrella review., Methods: Umbrella review of systematic reviews with meta-analyses of observational studies and randomized controlled trials (RCTs) using placebo/no intervention as control group. 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. For meta-analyses of RCTs, outcomes with a random-effect p value < 0.005 and a high-GRADE assessment were classified as strong evidence., Results: From 2048 abstracts, 16 meta-analyses and 55 independent outcomes were included (36 in RCTs and 19 in observational studies). In RCTs of Mg versus placebo/no active treatment, 12 over 36 outcomes reported significant results (p < 0.05). A strong evidence for decreased need for hospitalization in pregnancy and for decreased risk of frequency and intensity of migraine relapses in people with migraine was observed using the GRADE assessment. In observational studies, 9/19 outcomes were significant (p < 0.05). However, only one outcome presented highly suggestive evidence (lower incidence of type 2 diabetes in people with higher Mg intake at baseline) and one suggestive (lower incidence of stroke associated with higher Mg intake at baseline)., Conclusion: Strong evidence according to the GRADE suggests that Mg supplementation can decrease the risk of hospitalization in pregnant women and reduce the intensity/frequency of migraine. Higher Mg intake is associated with a decreased risk of type 2 diabetes and stroke with highly suggestive and suggestive evidence, respectively, in observational studies.

Frailty and cardiovascular disease (CVD) are both highly prevalent in older adults. Cardiovascular disease has been identified as the most frequent cause of death, while frailty has been identified as one of geriatric giants characterized by decreased physiological reserves and increased vulnerability. However, the exact pathobiological links between the two conditions have not been fully elucidated. Consequently, we observe a relevant difficulty not only in accurately defining cardiovascular risk in vulnerable elderly patients (and the other way around), but also a lack of consensus regarding CVD management in the very old. Nowadays, considering the enormous technical innovation, many elderly patients, if appropriately selected, could be eligible even for the most complex treatments, including invasive cardiological procedures. Identification of frail patients at risk of negative outcomes can allow the customization of therapeutic interventions in elderly patients with CVD, allowing the elderly who can benefit from them to undergo even invasive procedures and avoiding futile or dangerous treatments for the most vulnerable patients. A large number of tools and definitions for assessing frailty have been proposed; different scales and assessment tools can be useful for different purposes, but at present there is no clear indication for their use in CVD. In this chapter, we will describe the main geriatric approach to ascertain frailty, the assessment tools used in patients with cardiovascular diseases, and propose an operational strategy to evaluate frailty and identify patients eligible for pharmacologic or surgical interventions.

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., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The 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., Methods: A 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 < 0.05) from class I (convincing) to class IV (weak), according to pre-established criteria., Results: From 358 abstracts, 6 meta-analyses with 14 associations were included. Sarcopenia was associated with higher risk of other comorbidities and mortality in 11 of 14 outcomes explored. However, only 3 outcomes (i.e., association between sarcopenia and increased risk of death in community-dwelling older people [odds ratio, OR = 3.60; 95% CI 2.96-4.37; n = 14,305], disability [OR = 3.04; 95% CI 1.80-5.12; n = 8569], and falls [OR = 1.60; 95% CI 1.31-1.97; n = 12,261]) presented a highly suggestive evidence (class II). Other association was classified as having only a weak evidence., Conclusion: Sarcopenia is associated with several adverse health-related outcomes in older people, and its associations with mortality, disability, and falls are supported by a highly suggestive evidence. The effect of interventions on sarcopenia to improve these outcomes needs to be investigated., (© 2019. European Geriatric Medicine Society.)

Purpose: Orthostatic hypotension (OH) is associated with older age and many negative clinical outcomes in geriatric practice. We aimed to capture the breadth of outcomes that have been associated with the presence of OH and systematically assess the quality, strength and credibility of these associations using an umbrella review with integrated meta-analyses., Methods: We systematically searched several major databases from their commencements through to 16th May 2019 for meta-analyses of observational studies of OH and any health-related outcome. We used these metrics to categorize the strength of evidence of significant outcomes (p < 0.05) from class I (convincing) to class IV (weak), according to the pre-established criteria., Results: From 975 abstracts, seven meta-analyses of 12 outcomes were included. For each outcome, the median number of studies was four, and the median number of participants was 46,493, with a median of 3630 incident cases. There was suggestive (class III) evidence that OH was associated with significantly higher risk of coronary heart disease (HR = 1.32, 95% CI 1.12-1.56), stroke (HR = 1.22, 95% CI 1.08-1.38), congestive heart failure (HR = 1.30, 95% CI 1.09-1.55), all-cause mortality (RR = 1.50, 95% CI 1.24-1.81), falls (OR = 1.84, 95% CI 1.39-2.44), and dementia (HR = 1.22, 95% CI 1.11-1.35)., Conclusion: The current evidence base indicates that OH is significantly associated with a range of adverse cardiovascular, cognitive, and mortality outcomes in older people, although the strength of this evidence remains only suggestive. Further research in larger samples and with lower risk of bias is required to build a fuller picture of the impact of OH on health., (© 2019. European Geriatric Medicine Society.)

Globally, there is increasing usage and legalization of cannabis. In addition to its reported therapeutic effects, cannabis has several health risks which are not clearly defined. Erectile dysfunction (ED) is the most common male sexual disorder and there are plausible mechanisms linking cannabis use to ED. No attempt has been made to collate the literature on this topic. The aim of this review was to summarize the prevalence and risk of ED in cannabis users compared to controls. A systematic review of major databases from inception to January 1, 2019, without language restriction, was undertaken to identify studies investigating cannabis use and presence of ED. The analysis compared the prevalence of ED in cannabis users versus controls. Consequently, the odds ratio (OR) with 95% confidence intervals (CI) was calculated, applying a random-effect model. Five case-control studies were included with data from 3,395 healthy men, 1,035 using cannabis (smoking) and 2,360 nonusers. The overall prevalence of ED in cannabis users was 69.1% (95% CI: 38.0-89.1), whilst the correspondent figure in controls was 34.7% (95% CI: 20.3-52.7). The OR of ED in cannabis users was almost four times that of controls (OR = 3.83; 95% CI: 1.30-11.28; p = .02), even if characterized by high heterogeneity ( I 2 = 90%) and the prediction intervals overlapped 1.00 (95% CI: 0.35-7.26). Data suggest that ED is twice as high in cannabis users compared to controls. Future longitudinal research is needed to confirm/refute this and explore if a dose-response relationship between cannabis and ED may be evident.

Purpose: Sarcopenia and diabetes are two common conditions in older people. Some recent literature has proposed that these two conditions can be associated. However, to date, no attempt has been made to collate this literature. Therefore, we aimed to summarize the prevalence of sarcopenia in diabetes (and vice versa) and the prevalence of sarcopenia in people with diabetes complications, through a systematic review and meta-analysis., Methods: Two authors searched major electronic databases from inception until March 2019 for case control/cross-sectional/longitudinal studies investigating sarcopenia and diabetes. The strength of the reciprocal associations between sarcopenia and diabetes was assessed through odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders, where possible., Results: From 953 potential eligible articles, 20 were included in the systematic review, with 17 providing data for meta-analysis. Overall, 54,676 participants were included (mean age = 65.4 years). Diabetic participants had an increased prevalence of sarcopenia compared to controls (n = 10; OR = 1.635; 95% CI 1.204-2.220; p = 0.002; I 2  = 67%), whilst, after adjusting for potential confounders, sarcopenia was associated with an increased odds of having diabetes (OR = 2.067; 95% CI 1.396-3.624; p < 0.0001; I 2  = 0%). In 1868 diabetic participants with a complication, there was an increased prevalence of sarcopenia (OR = 2.446; 95% CI 1.839-3.254; p < 0.0001; I 2  = 0%), as compared with those with no complication. Very limited data existed regarding studies with a longitudinal design., Conclusions: Our study suggests a bidirectional association between diabetes and sarcopenia, particularly when diabetic complications are present., (© 2019. European Geriatric Medicine Society.)

Objective: To examine associations between chocolate consumption and depressive symptoms in a large, representative sample of US adults., Methods: The data were from 13,626 adults (≥20 years) participating in the National Health and Nutrition Examination Survey between 2007-08 and 2013-14. Daily chocolate consumption was derived from two 24-hr dietary recalls. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9), with scores ≥10 indicating the presence of clinically relevant symptoms. We used multivariable logistic regression to test associations of chocolate consumption (no chocolate, non-dark chocolate, dark chocolate) and amount of chocolate consumption (grams/day, in quartiles) with clinically relevant depressive symptoms. Adults with diabetes were excluded and models controlled for relevant sociodemographic, lifestyle, health-related, and dietary covariates., Results: Overall, 11.1% of the population reported any chocolate consumption, with 1.4% reporting dark chocolate consumption. Although non-dark chocolate consumption was not significantly associated with clinically relevant depressive symptoms, significantly lower odds of clinically relevant depressive symptoms (OR = 0.30, 95%CI 0.21-0.72) were observed among those who reported consuming dark chocolate. Analyses stratified by the amount of chocolate consumption showed participants reporting chocolate consumption in the highest quartile (104-454 g/day) had 57% lower odds of depressive symptoms than those who reported no chocolate consumption (OR = 0.43, 95%CI 0.19-0.96) after adjusting for dark chocolate consumption., Conclusions: These results provide some evidence that consumption of chocolate, particularly dark chocolate, may be associated with reduced odds of clinically relevant depressive symptoms. Further research capturing long-term chocolate consumption and using a longitudinal design are required to confirm these findings and clarify the direction of causation., (© 2019 Wiley Periodicals, Inc.)

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. 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic., Methods: We searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALT- patients as the primary outcome. The secondary outcome was the hazard ratio (HR), adjusted for the maximum number of covariates available, using ALT- patients as reference., Results: Eight articles comprising a total of 551 patients with sarcomas (226 ALT+ and 325 ALT-) were selected. The ALT+ group showed a higher mitotic count and a higher tumor grade compared with the ALT- group (p < 0.01). Furthermore, we demonstrate a strong impact of ALT on survival. In fact, ALT+ patients showed a statistically significant higher risk of death than ALT- patients, when also considering data from multivariate analyses (RR = 1.50; 95% CI: 1.15-1.96; p = 0.003; HR = 2.02; 95% CI: 1.22-3.38; p = 0.007)., Conclusions: Our results indicate that ALT is associated with an increased risk of death in patients with sarcoma. In these neoplasms, ALT should be taken into account for a precise prognostic stratification and design of potential therapeutic strategies.

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 78.2 years; 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; I 2  = 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.)

Extranodal extension (ENE) of nodal metastasis is defined as the extension of metastatic cells through the nodal capsule into the perinodal tissue. This morphological parameter, recently proposed as an important prognostic factor in different types of malignancy, has not been included in the TNM staging system for non-small cell lung cancer (NSCLC). In this systematic review with meta-analysis, we weighted the prognostic role of ENE in patients with lymph node-positive NSCLC. Two independent authors searched SCOPUS and PubMed through 28 February 2017. Prospective and retrospective studies on NSCLC, comparing patients with presence of ENE (ENE+) ENE+) vs. only intranodal extension (ENE-) and including data regarding prognosis, were considered as eligible. Data were summarized using risk ratios (RR) for the number of deaths/recurrences, and hazard ratios (HR) with 95% confidence intervals (CI) for time-dependent risk related to ENE+, adjusted for potential confounders. We identified 13 studies, including 1709 patients (573 ENE+ and 1136 ENE-) with a median follow-up of 60 months. ENE was associated with a significantly increased risk of mortality of all causes (RR = 1.39, 95% CI: 1.18-1.65, P < 0.0001, I 2  = 70%; HR = 1.30, 95% CI: 1.01-1.67, P = 0.04, I 2  = 0%) and of disease recurrence (RR = 1.32, 95% CI: 1.04-1.68, P = 0.02, I 2  = 42%; HR = 1.93, 95% CI: 1.53-2.44, P < 0.0001, I 2  = 0%). We conclude that in NSCLC, requirements for assessment of ENE should be included in gross sampling and ENE status should be included in the pathology report. Inclusion of ENE status in oncology staging systems will allow further assessment of its role as prognostic parameter.

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.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 (sd 9·1) 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.