Metformin and health outcomes: An umbrella review of systematic reviews with meta-analyses.

BACKGROUND: The objective was to capture the breadth of outcomes that have been associated with metformin use and to systematically assess the quality, strength and credibility of these associations using the umbrella review methodology. METHODS: Four major databases were searched until 31 May 2020. Meta-analyses of observational studies and meta-analyses of randomized controlled trials (RCTs) (including active and placebo control arms) were included. RESULTS: From 175 eligible publications, we identified 427 different meta-analyses, including 167 meta-analyses of observational studies, 147 meta-analyses of RCTs for metformin vs placebo/no treatment and 113 meta-analyses of RCTs for metformin vs active medications. There was no association classified as convincing or highly suggestive from meta-analyses of observational studies, but some suggestive/weak associations of metformin use with a lower mortality risk of CVD and cancer. In meta-analyses of RCTs, metformin was associated with a lower incidence of diabetes in people with prediabetes or no diabetes at baseline; lower ovarian hyperstimulation syndrome incidence (in women in controlled ovarian stimulation); higher success for clinical pregnancy rate in poly-cystic ovary syndrome (PCOS); and significant reduction in body mass index in people with type 1 diabetes mellitus, in women who have obesity/overweight with PCOS and in obese/overweight women. Of 175 publications, 166 scored as low or critically low quality per AMSTAR 2 criteria. CONCLUSIONS: Observational evidence on metformin seems largely unreliable. Randomized evidence shows benefits for preventing diabetes and in some gynaecological and obstetrical settings. However, almost all meta-analyses are of low or critically low quality according to AMSTAR 2 criteria.

Urinary incontinence and quality of life: a systematic review and meta-analysis.

BACKGROUND: Urinary incontinence (UI) and low quality of life (QoL) are two common conditions. Some recent literature proposed that these two entities can be associated. However, no attempt was made to collate this literature. Therefore, the aim of this study was to conduct a systematic review and meta-analysis of existing data to estimate the strength of the association between UI and QoL. METHODS: An electronic search of major databases up to 18th April 2020 was carried out. Meta-analysis of cross-sectional and case-control studies comparing mean values in QoL between patients with UI and controls was performed, reporting random-effects standardized mean differences (SMDs) ± 95% confidence intervals (CIs) as the effect size. Heterogeneity was assessed with the I2. RESULTS: Out of 8279 articles initially screened, 23 were finally included for a total of 24,983 participants, mainly women. The mean age was ≥ 50 years in 12/23 studies. UI was significantly associated with poor QoL as assessed by the short-form 36 (SF-36) total score (n = 6 studies; UI: 473 vs. 2971 controls; SMD = - 0.89; 95% CI - 1.3 to - 0.42; I2 = 93.5) and by the sub-scales of SF-36 and 5/8 of the domains included in the SF-36. Similar results were found using other QoL tools. The risk of bias of the studies included was generally high. CONCLUSIONS: UI is associated with a poor QoL, with a strong level of certainty. This work, however, mainly based on cross-sectional and case-control studies, highlights the necessity of future longitudinal studies for better understanding the importance of UI on QoL.

Effect of low-dose aspirin on health outcomes: An umbrella review of systematic reviews and meta-analyses.

AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies.

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.

[COVID-Guide: an app for covid-19 triage and self-assessment.] / COVID-Guide: una app per il triage e l'autovalutazione della covid-19.

INTRODUCTION: The unprecedented covid-19 pandemic has shown the weaknesses of health systems and opened new spaces for e-health and telemedicine. Recent literature states that chatbots, if implemented effectively, could be useful tools for quickly sharing information, promoting healthy behaviors, and helping reduce the psychological burden of isolation. The aim of this project is to develop and test a secure and reliable computerized decision support system (CDSS) in web-app and evaluate its use, usability and its outputs in a pre-specified way. METHODS: A multidisciplinary team was recruited to plan and design, based on the SMASS medical CDSS, the scenarios of the COVID-Guide web-app, a self-triage system for patients with suspected covid-19. The output data for the period May-September 2020 from Germany were analyzed. RESULTS: During the period under review, the total number of consultations in Germany was 96,012. 3,415 (3.56%) consultations indicated the need for immediate evaluation, by activating the emergency service (calling an ambulance) - 1,942, equal to 2.02% - or by advising the patient to go to hospital - 1,743, equal to 1.54%. CONCLUSIONS: Data seems to show good usability and a consistent number of consultations carried out. Regular use of COVID-Guide could help collect epidemiological data on the spread of (suspected) covid-19 cases, easily and quickly available in all countries where the tool will be used. Using the SSDC could help reduce the load on operators. Furthermore, the use of anonymous and geolocatable clinical data together with the generation of alerts and indicators produced by COVID-Guide could become a useful tool for epidemiological surveillance in the future phases of the pandemic (Telemedical Syndromic Surveillance).

An umbrella review of systematic reviews with meta-analyses evaluating positive and negative outcomes of Hydroxychloroquine and chloroquine therapy.

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.

Patient safety culture in Italian out-of-hours primary care service: a national cross-sectional survey study.

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.

Pet ownership and symptoms of depression: A prospective study of older adults.

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.

Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature.

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.

The efficacy and safety of influenza vaccination in older people: An umbrella review of evidence from meta-analyses of both observational and randomized controlled studies.

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.

Angiotensin-Converting Enzyme Inhibitor Use and Incident Frailty: A Longitudinal Cohort Study.

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 8 years 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 61.2 years, 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.

Is chocolate consumption associated with health outcomes? An umbrella review of systematic reviews and meta-analyses.

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.

Dietary Protein Intake and Falls in Older People: Longitudinal Analyses From the Osteoarthritis Initiative.

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.

The Relationship between Dietary Vitamin K and Depressive Symptoms in Late Adulthood: A Cross-Sectional Analysis from a Large Cohort Study.

Few studies assessed the associations between dietary vitamin K and depressive symptoms. We aimed to investigate the association between dietary vitamin K and depressive symptoms in a large cohort of North American People. In this cross-sectional analysis, 4,375 participants that were aged 45⁻79 years from the Osteoarthritis Initiative were included. Dietary vitamin K intake was collected through a semi-quantitative food frequency questionnaire and categorized in quartiles. Depressive symptoms were diagnosed using the 20-item Center for Epidemiologic Studies-Depression (CES-D) ≥ 16. To investigate the associations between vitamin K intake and depressive symptoms, logistic regression analysis were run, which adjusted for potential confounders. Overall, 437 (=10%) subjects had depressive symptoms. After adjusting for 11 confounders, people with the highest dietary vitamin K intake had lower odds of having depressive symptoms (OR = 0.58; 95%CI: 0.43⁻0.80). This effect was only present in people not taking vitamin D supplementation. In conclusion, higher dietary vitamin K intake was significantly associated with a lower presence of depressive symptoms, also after accounting for potential confounders. Future longitudinal research is required to explore the directionality of the association.

Low-dose vitamin D supplementation and incident frailty in older people: An eight year longitudinal study.

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.

[#1 Word for Family Medicine: ideas beyond words]. / #1WordforFamilyMedicine: idee oltre le parole.

Social media has proven to be a powerful method in which ideas can be formed and shared publicly. Within the global family medicine community, the #1 Word for Family Medicine project has gained widespread popularity with participation in over 30 countries on 5 continents. With over 3000 responses - and counting - this idea has crossed the globe to engage both the general public and medical community at an exponential rate. Further exploration into the use of social media for the benefit of our profession should continue as patients and physicians become increasing connected to the internet.