A Symptom-Checker for Adult Patients Visiting an Interdisciplinary Emergency Care Center and the Safety of Patient Self-Triage: Real-Life Prospective Evaluation.

BACKGROUND: Symptom-checkers have become important tools for self-triage, assisting patients to determine the urgency of medical care. To be safe and effective, these tools must be validated, particularly to avoid potentially hazardous undertriage without leading to inefficient overtriage. Only limited safety data from studies including small sample sizes have been available so far. OBJECTIVE: The objective of our study was to prospectively investigate the safety of patients' self-triage in a large patient sample. We used SMASS (Swiss Medical Assessment System; in4medicine, Inc) pathfinder, a symptom-checker based on a computerized transparent neural network. METHODS: We recruited 2543 patients into this single-center, prospective clinical trial conducted at the cantonal hospital of Baden, Switzerland. Patients with an Emergency Severity Index of 1-2 were treated by the team of the emergency department, while those with an index of 3-5 were seen at the walk-in clinic by general physicians. We compared the triage recommendation obtained by the patients' self-triage with the assessment of clinical urgency made by 3 successive interdisciplinary panels of physicians (panels A, B, and C). Using the Clopper-Pearson CI, we assumed that to confirm the symptom-checkers' safety, the upper confidence bound for the probability of a potentially hazardous undertriage should lie below 1%. A potentially hazardous undertriage was defined as a triage in which either all (consensus criterion) or the majority (majority criterion) of the experts of the last panel (panel C) rated the triage of the symptom-checker to be "rather likely" or "likely" life-threatening or harmful. RESULTS: Of the 2543 patients, 1227 (48.25%) were female and 1316 (51.75%) male. None of the patients reached the prespecified consensus criterion for a potentially hazardous undertriage. This resulted in an upper 95% confidence bound of 0.1184%. Further, 4 cases met the majority criterion. This resulted in an upper 95% confidence bound for the probability of a potentially hazardous undertriage of 0.3616%. The 2-sided 95% Clopper-Pearson CI for the probability of overtriage (n=450 cases,17.69%) was 16.23% to 19.24%, which is considerably lower than the figures reported in the literature. CONCLUSIONS: The symptom-checker proved to be a safe triage tool, avoiding potentially hazardous undertriage in a real-life clinical setting of emergency consultations at a walk-in clinic or emergency department without causing undesirable overtriage. Our data suggest the symptom-checker may be safely used in clinical routine. TRIAL REGISTRATION: ClinicalTrials.gov NCT04055298; https://clinicaltrials.gov/study/NCT04055298.

Essential steps in primary care management of older people with Type 2 diabetes: an executive summary on behalf of the European geriatric medicine society (EuGMS) and the European diabetes working party for older people (EDWPOP) collaboration.

We present an executive summary of a guideline for management of type 2 diabetes mellitus in primary care written by the European Geriatric Medicine Society, the European Diabetes Working Party for Older People with contributions from primary care practitioners and participation of a patient's advocate. This consensus document relies where possible on evidence-based recommendations and expert opinions in the fields where evidences are lacking. The full text includes 4 parts: a general strategy based on comprehensive assessment to enhance quality and individualised care plan, treatments decision guidance, management of complications, and care in case of special conditions. Screening for frailty and cognitive impairment is recommended as well as a comprehensive assessment all health conditions are concerned, including end of life situations. The full text is available online at the following address: essential_steps_inprimary_care_in_older_people_with_diabetes_-_EuGMS-EDWPOP___3_.pdf.

Comprehensive geriatric assessment in older people: an umbrella review of health outcomes.

BACKGROUND: Comprehensive geriatric assessment (CGA) has been in use for the last three decades. However, some doubts remain regarding its clinical use. Therefore, we aimed to capture the breadth of outcomes reported and assess the strength of evidence of the use of comprehensive geriatric assessment (CGA) for health outcomes in older persons. METHODS: Umbrella review of systematic reviews of the use of CGA in older adults searching in Pubmed, Embase, Scopus, Cochrane library and CINHAL until 05 November 2021. All possible health outcomes were eligible. Two independent reviewers extracted key data. The grading of evidence was carried out using the GRADE for intervention studies, whilst data regarding systematic reviews were reported as narrative findings. RESULTS: Among 1,683 papers, 31 systematic reviews (19 with meta-analysis) were considered, including 279,744 subjects. Overall, 13/53 outcomes were statistically significant (P < 0.05). There was high certainty of evidence that CGA reduces nursing home admission (risk ratio [RR] = 0.86; 95% confidence interval [CI]: 0.75-0.89), risk of falls (RR = 0.51; 95%CI: 0.29-0.89), and pressure sores (RR = 0.46; 95%CI: 0.24-0.89) in hospital medical setting; decreases the risk of delirium (OR = 0.71; 95%CI: 0.54-0.92) in hip fracture; decreases the risk of physical frailty in community-dwelling older adults (RR = 0.77; 95%CI: 0.64-0.93). Systematic reviews without meta-analysis indicate that CGA improves clinical outcomes in oncology, haematology, and in emergency department. CONCLUSIONS: CGA seems to be beneficial in the hospital medical setting for multiple health outcomes, with a high certainty of evidence. The evidence of benefits is less strong for the use of CGA in other settings.

Sleep duration and sarcopenia in adults aged ≥ 65 years from low and middle-income countries.

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 ≥ 65 years 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 ≥ 9 h/day. Multivariable logistic regression analysis was conducted. RESULTS: Data on 13,210 adults aged ≥ 65 years [mean (SD) age 72.6 (11.3) years; 55.0% females] were analyzed. In the overall sample, compared to > 6 to ≤ 9 h/day of sleep duration, > 9 h/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.

Dietary acrylamide and incident osteoporotic fractures: an 8-year prospective cohort study.

BACKGROUND: Acrylamide, a component of fried foods, has been associated with several negative health outcomes. However, the relationship between dietary acrylamide and osteoporotic fractures has been explored by a few cross-sectional studies. AIMS: To investigate if dietary acrylamide is associated with the onset of fractures in North American participants at high risk/having knee osteoarthritis (OA), over 8 years of follow-up. METHODS: A Cox's regression analysis, adjusted for baseline confounders was run and the data were reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Dietary acrylamide intake was assessed at the baseline using a food frequency questionnaire and categorized in tertiles (T), whilst fractures' history was recorded using self-reported information. RESULTS: Altogether, 4,436 participants were included. Compared to participants with lower acrylamide intake (T1; < 3,313 µg), those with a higher acrylamide intake (T3; > 10,180 µg) reported a significantly higher risk of any fracture (HR = 1.37; 95% CI 1.12-1.68; p for trend = 0.009), forearm (HR = 1.73; 95% CI 1.09-2.77; p for trend = 0.04), spine (HR = 2.21; 95% CI 1.14-4.31; p for trend = 0.04), and hip fracture (HR = 4.09; 95% CI 1.29-12.96; p for trend = 0.046). CONCLUSIONS: Our study is the first to report that high dietary acrylamide may be associated with an increased risk of osteoporotic fractures.

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.

Pulmonary Stretch and Lung Mechanotransduction: Implications for Progression in the Fibrotic Lung.

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, which is followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of the extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress-strain curve but follows the mechano-elastic models of "squishy balls", where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity that are surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with associated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review, we aim to summarize the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.

Human Immunodeficiency Virus Infection and Diverse Physical Health Outcomes: An Umbrella Review of Meta-analyses of Observational Studies.

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 (<10-6). None of the unique outcomes presented convincing evidence (Class I), yet 3 outcomes presented highly suggestive evidence, 5 outcomes presented suggestive evidence, and 37 outcomes presented weak evidence. CONCLUSIONS: Results show highly suggestive and suggestive evidence for HIV and the presence of a cough, COPD, ischemic heart disease, pregnancy-related mortality, maternal sepsis, and bone fractures. Public health policies should reflect and accommodate these changes, especially in light of the increases in the life expectancy and the incidence of comorbidities in this population.

Associations between body mass index, waist circumference and erectile dysfunction: a systematic review and META-analysis.

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; I2 = 72%) and in men with obesity (OR = 1.60; 95%CI: 1.29-1.98; I2 = 79%). Adjusting our analyses for potential confounders, the results were confirmed in men with obesity (OR = 1.46; 95%CI: 1.24-1.72; I2 = 72%). ED was associated with significant higher values of BMI (MD = 0.769; 95%CI: 0.565-0.973 Kg/m2; I2 = 78%) and WC (MD = 5.251 cm; 95%CI: 1.295-9.208; I2 = 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.

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.

Comprehensive Geriatric Assessment in Cardiovascular Disease.

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.

Precipitating factors of heart failure decompensation, short-term morbidity and mortality in patients attended in primary care.

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.

Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis.

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.

Is there a relationship between chocolate consumption and symptoms of depression? A cross-sectional survey of 13,626 US adults.

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.

The Activation Status of the TGF-ß Transducer Smad2 Is Associated with a Reduced Survival in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.

Aberrant function of Smad2, a crucial member of transforming growth factor beta (TGF-ß) 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-ß 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.

Dietary magnesium intake and fracture risk: data from a large prospective study.

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.

Efficacy of deprescribing on health outcomes: An umbrella review of systematic reviews with meta-analysis of randomized controlled trials.

BACKGROUND: Deprescribing is an important intervention across different settings in medicine, but the literature supporting such a practice is still conflicting. Therefore, we aimed to capture the breadth of outcomes reported and assess the strength of evidence of the use of deprescribing for health outcomes. METHODS: Umbrella review of systematic reviews of the use of deprescribing searching in Medline, Scopus, and Web of Science until 01 November 2023. The grading of evidence was carried out using the GRADE for intervention studies, whilst data regarding systematic reviews were reported as narrative findings. RESULTS: Among 456 papers, 12 systematic reviews (six with meta-analysis) for a total of 231 RCTs and 44,193 patients were included. In any setting, deprescribing was able to significantly reduce the number of total and of potentially inappropriate medications (PIMs) in older patients (low certainty of evidence) and to reduce the proportion of participants potentially having several or PIMs (moderate certainty of evidence). In community, supported by a high certainty of evidence, deprescribing was not more effective than standard care in decreasing injurious falls, any falls or number of fallers. In nursing home, deprescribing was associated with a significantly lower PIMs than standard care (very low certainty of evidence). In end-of-life situations, deprescribing significantly reduced mortality rate of approximately 41% (high certainty of evidence). CONCLUSIONS: Deprescribing is a promising intervention across different settings and situations, but a notable gap in the literature concerning its effects on substantial outcomes still exists.