Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta-analysis.

INTRODUCTION: Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta-analysis to assess the effectiveness and safety of progestogens for these patients. MATERIAL AND METHODS: We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk-of-bias tool and the certainty of evidence using the GRADE approach. RESULTS: Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99-1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97-1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96-1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98-1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01-1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76-1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83-1.40, absolute increase 0.2%, moderate certainty). CONCLUSIONS: In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages.

Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

A unified framework for the measurement of mobility in older persons.

Mobility is often referred to as a 'sixth vital sign' because of its ability to predict critical health outcomes in later adulthood. In the World Health Organization (WHO) World Report on Aging and Health, mobility is described as movement in all its forms whether powered by the body or a vehicle. As such, mobility encompasses basic physical actions such as getting up from a chair and walking, as well as activities such as exercising, driving and using public transportation. A plethora of measurement tools have been developed to assess various aspects of mobility; however, there is wide variability in the mobility constructs being measured which limits standardisation and meaningful comparison across studies. In this paper, we propose a comprehensive framework for measuring mobility that considers three distinct facets of mobility: perceived mobility ability ('what can you do'), actual mobility ability ('what you actually do') and locomotor capacity for mobility ('what could you do'). These three facets of mobility are rooted in the three components of healthy aging endorsed by the WHO: functional ability, intrinsic capacity and environments. By proposing a unified framework for measuring mobility based on theory and empirical evidence, we can advance the science of monitoring and managing mobility to ensure functional ability in older age.

Measures of perceived mobility ability in community-dwelling older adults: a systematic review of psychometric properties.

OBJECTIVES: The objective of this systematic review was to synthesise the psychometric properties of measures of perceived mobility ability and related frameworks used to define and operationalise mobility in community-dwelling older adults. METHODS: We registered the review protocol with PROSPERO (CRD42022306689) and included studies that examined the psychometric properties of perceived mobility measures in community-dwelling older adults. Five databases were searched to identify potentially relevant primary studies. We qualitatively summarised psychometric property estimates and related operational frameworks. We conducted risk of bias and overall quality assessments, and meta-analyses when at least three studies were included for a particular outcome. The synthesised results were compared against the Consensus-based Standards for the Selection of Health Measurement Instruments criteria for good measurement properties. RESULTS: A total of 36 studies and 17 measures were included in the review. The Late-Life Function and Disability Index: function component (LLFDI-FC), lower extremity functional scale (LEFS), Mobility Assessment Tool (MAT)-short form (MAT-SF) or MAT-Walking, and Perceived Driving Abilities (PDA) Scale were identified with three or more eligible studies. Most measures showed sufficient test-retest reliability (moderate or high), while the PDA scale showed insufficient reliability (low). Most measures had sufficient or inconsistent convergent validity (low or moderate) or known-groups validity (low or very low), but their predictive validity and responsiveness were insufficient or inconsistent (low or very low). Few studies used a conceptual model. CONCLUSION: The LLFDI-FC, LEFS, PDA and MAT-SF/Walking can be used in community-dwelling older adults by considering the summarised psychometric properties. No available comprehensive mobility measure was identified that covered all mobility domains.

Assessing the measurement properties of life-space mobility measures in community-dwelling older adults: a systematic review.

BACKGROUND: Preserving and enhancing mobility is an important part of healthy ageing. Life-space mobility is a construct that captures actual mobility within the home and the community. The objective of this systematic review was to synthesise the measurement properties and interpretability of scores produced by life-space mobility measures in community-dwelling older adults. METHODS: This systematic review followed Consensus-based Standards for the selection of health Measurement Instruments (COSMIN). Multiple databases were searched to identify potentially relevant articles. Data extraction and assessment of methodological quality was conducted by two independent reviewers. When possible, results were quantitatively pooled for each measurement property. If studies could not be combined quantitatively, then findings were summarised qualitatively using means and percentage of confirmed hypothesis. Synthesised results were assessed against the COSMIN criteria for good measurement properties. RESULTS: A total of 21 full text articles were included in the review. The University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA) was the most evaluated life-space mobility measure. The LSA demonstrated content validity, internal consistency (Cronbach's alpha 0.80-0.92), reliability [intra-class correlation value 0.89 (95% confidence interval (CI): 0.80, 0.94)] and convergent validity with measures of physical function in community-dwelling older adults. CONCLUSION: This systematic review summarised the measurement properties of life-space mobility measures in community-dwelling older adults following COSMIN guidelines. The LSA has been translated into multiple languages and has sufficient measurement properties for assessing life-space mobility among community-dwelling older adults.

Associations between transitions of intrinsic capacity and frailty status, and 3-year disability.

BACKGROUND: The trajectory of frailty and intrinsic capacity (IC) often overlap in older adults. Longitudinal analyses of transitions of frailty and IC, and their associations with incident functional decline are limited. The present study aimed to identify transitions of frailty status and IC, and explore associations between transitions of frailty and IC, and future disability among community-dwelling older adults. METHODS: In the West China and Aging Trend Study, 808 participants aged ≥ 60 years completed baseline and three years follow-up (frailty, IC and disability assessments). Physical frailty was measured based on Fried phenotype. IC was evaluated by five domains (cognition, locomotion, sensory, psychological, and vitality). Disability was defined as a need for assistance in any items in activity of daily living (ADL) or the instrumental activity of daily living (IADL). Logistic regressions were performed to examine their relationships. RESULTS: Four transitions of IC status (kept well: 27.4%, improved: 8.4%, worsened: 35.4%, and kept poor: 28.8%), and two transitions of frailty status (kept not-frail/improved: 93.2%, kept frail/worsened: 6.8%) were identified. Impaired locomotion and vitality at baseline were significantly associated with kept frail or worsened frail. However, impaired sensory and vitality at baseline not frailty status was significantly associated with transitions of IC. Adjusted for covariates and transitions of frailty, kept poor IC was associated with ADL (OR = 2.26, 95%CI = 1.17,4.34) and IADL disability (OR = 3.74, 95%CI = 1.79, 7.82). CONCLUSIONS: Transitions of IC, but not frailty were associated with higher risk of incident disability. Baseline locomotion and vitality impairment were associated with worsened or kept frail. Our findings support the WHO's notion of monitoring and optimizing IC to delay deterioration of IC and preventing frailty and disability. CLINICAL TRIAL NUMBER: ChiCTR1800018895.

Cost-effectiveness of adding ezetimibe and/or PCSK9 inhibitors to high-dose statins for secondary prevention of cardiovascular disease in Chinese adults.

OBJECTIVES: The latest international guideline recommended the add-on therapy of ezetimibe and PCSK9 inhibitors in selected people for the secondary prevention of cardiovascular diseases (CVDs). However, it remains unclear whether these regimens fit the Chinese healthcare system economically. METHODS: Based on the Chinese context, this simulation study evaluated four therapeutic strategies including the high-dose statin-only group, ezetimibe plus statin group, PCSK9 inhibitors plus statin group, and PCSK9 inhibitors plus ezetimibe plus statin group. The team developed a Markov model to estimate the incremental cost-effectiveness ratio (ICER). With each 1-yr cycle, the simulation subjects could have nonfatal cardiovascular events (stroke and/or myocardial infarction) or death (vascular or nonvascular death event) with a follow-up duration of 20 yr. Cardiovascular risk reduction was gathered from a network meta-analysis, and cost and utility data were gathered from hospital databases and published research. RESULTS: For Chinese adults receiving high-dose statins for secondary prevention of CVDs, the ICER was US$68,910 per quality-adjusted life year (QALY) for adding PCSK9 inhibitors, US$20,242 per QALY for adding ezetimibe, US$51,552 per QALY for adding both drugs. Given a threshold of US$37,655 (three times of Chinese GDP), the probability of cost-effectiveness is 2.9 percent for adding PCSK9 inhibitors, 53.1 percent for adding ezetimibe, and 16.8 percent for adding both drugs. To meet the cost-effectiveness, an acquisition price reduction of PCSK9 inhibitors of 33.6 percent is necessary. CONCLUSION: In Chinese adults receiving high-dose statins for the secondary prevention of CVDs, adding ezetimibe is cost-effective compared to adding PCSK9 inhibitors and adding both drugs.

Measuring physical performance in later life: reliability of protocol variations for common performance-based mobility tests.

BACKGROUND AND AIMS: Performance-based tests of mobility or physical function such as the Timed Up and Go (TUG), gait speed, chair-rise, and single-leg stance (SLS) are often administered using different protocols in aging populations, however, the reliability of their assessment protocols is not often considered. The purpose of this study was to examine the reliabilities of frequently used assessment protocols for the TUG, gait speed, chair-rise, and SLS in different age groups. METHODS: We administered the following assessment protocols in an age-stratified (50-64, 65-74, 75+ years) sample of participants (N = 147) from the Canadian Longitudinal Study on Aging (CLSA): TUG fast pace and TUG normal pace: TUG-cognitive counting backwards by ones and counting back by threes, gait speed with 3-m and 4-m course, chair-rise with arms crossed and allowing the use of arms, and SLS using preferred leg or both legs-on two occasions within 1 week. We assessed the relative (intra-class correlation) and absolute reliability (standard error of measurement, SEM and minimal detectable change, MDC) for each protocol variation and provided recommendations based on relative reliability. RESULTS: For participants aged 50-64 years, our results suggest better reliability for TUG fast-pace compared with normal-pace (ICC and 95% CI 0.70; 0.41-0.85 versus 0.38; 0.12-0.59). The reliability values for 3-m gait speed were potentially higher than for 4-m gait speed (ICC 0.75; 0.67-0.82 versus 0.64; 0.54-0.73) and values for chair-rise suggested better reliability allowing participants to use their arms than with arms crossed (ICC 0.79; 0.66-0.86 versus 0.64; 0.45-0.77) for participants overall. For participants aged 75+ years, ICCs for SLS with the preferred leg showed better reliability than for both legs (ICC = 0.62-0.79 versus 0.30-0.39). CONCLUSIONS AND DISCUSSION: These reliability data and the recommendations can help guide the selection of the most appropriate performance-based test protocols for measuring mobility in middle-aged and older community-dwelling adults.

Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To determine the safety and efficacy of probiotics or synbiotics on morbidity and mortality in critically ill adults and children. DATA SOURCES: We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021. STUDY SELECTION: We performed a systematic search for randomized controlled trials (RCTs) that compared enteral probiotics or synbiotics to placebo or no treatment in critically ill patients. We screened studies independently and in duplicate. DATA EXTRACTION: Independent reviewers extracted data in duplicate. A random-effects model was used to pool data. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Sixty-five RCTs enrolled 8,483 patients. Probiotics may reduce ventilator-associated pneumonia (VAP) (relative risk [RR], 0.72; 95% CI, 0.59 to 0.89 and risk difference [RD], 6.9% reduction; 95% CI, 2.7-10.2% fewer; low certainty), healthcare-associated pneumonia (HAP) (RR, 0.70; 95% CI, 0.55-0.89; RD, 5.5% reduction; 95% CI, 8.2-2.0% fewer; low certainty), ICU length of stay (LOS) (mean difference [MD], 1.38 days fewer; 95% CI, 0.57-2.19 d fewer; low certainty), hospital LOS (MD, 2.21 d fewer; 95% CI, 1.18-3.24 d fewer; low certainty), and duration of invasive mechanical ventilation (MD, 2.53 d fewer; 95% CI, 1.31-3.74 d fewer; low certainty). Probiotics probably have no effect on mortality (RR, 0.95; 95% CI, 0.87-1.04 and RD, 1.1% reduction; 95% CI, 2.8% reduction to 0.8% increase; moderate certainty). Post hoc sensitivity analyses without high risk of bias studies negated the effect of probiotics on VAP, HAP, and hospital LOS. CONCLUSIONS: Low certainty RCT evidence suggests that probiotics or synbiotics during critical illness may reduce VAP, HAP, ICU and hospital LOS but probably have no effect on mortality.

The prevalence and associated factors of motoric cognitive risk syndrome in multiple ethnic middle-aged to older adults in west China: a cross-sectional study.

BACKGROUND AND PURPOSE: Motoric cognitive risk (MCR) syndrome characterized by subjective cognitive complaints and slow gait has been proposed and validated as a pre-dementia syndrome. The overall and specific ethnic prevalence of MCR and the associated factors are poorly understood in middle-aged to older community-dwelling residents in west China. METHODS: The present study included 6091 samples from the prospective cohort study, West China Health and Aging Trend (WCHAT). Multidimensional factors of demography, lifestyle, social support, anthropometrics and body components, and clinical status were investigated and analyzed by univariate and multivariate logistic regression models. Lasso regression and K-fold cross-validation were conducted to construct the most predictive model with fitted factors. RESULTS: The overall prevalence of MCR was 9.74%, and ethnically the prevalence was 14.25% in Tibetan, 11.03% in Yi, 10.72% in Han, 5.18% in Uighur and 4.55% in Qiang, respectively. In the adjusted models, the positively associated risk factors included diabetes mellitus (odds ratio [OR] = 1.51, p = 0.007), osteoarthritis (OR = 1.50, p = 0.002), depression (OR = 1.36, p = 0.005), poor sleep (OR = 1.21, p = 0.045), comorbidity (OR = 1.49, p = 0.001) and falls in the last 12 months (OR = 1.34, p = 0.031). Of note, every 1-unit increase of value in stroke was associated with an approximate 3-fold higher risk of having MCR, whilst in high-density lipoprotein with a 30% lower risk of MCR,respectively. CONCLUSIONS: Profiles of MCR from the aspects of ethnicity and the presenium stage need further exploration. It is a promising strategy to apply MCR as a primary prevention tool to prevent dementia.

Probiotics for preventing acute upper respiratory tract infections.

BACKGROUND: Probiotics are live micro-organisms that may give a beneficial physiological effect when administered in adequate amounts. Some trials show that probiotic strains can prevent respiratory infections. Even though our previously published review showed the benefits of probiotics for acute upper respiratory tract infections (URTIs), several new studies have been published. This is an update of a review first published in 2011 and updated in 2015. OBJECTIVES: To assess the effectiveness and safety of probiotics (any specified strain or dose), compared with placebo or no treatment, in the prevention of acute URTIs in people of all ages, at risk of acute URTIs. SEARCH METHODS: We searched CENTRAL (2022, Issue 6), MEDLINE (1950 to May week 2, 2022), Embase (1974 to 10 May 2022), Web of Science (1900 to 10 May 2022), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to 10 May 2022), the Chinese Medicine Popular Science Literature Database (from 2000 to 10 May 2022), and the Master's Degree Dissertation of Beijing Union Medical College Database (from 1981 to 10 May 2022). We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials on 10 May 2022. SELECTION CRITERIA: We included individual randomised controlled trials (RCTs) and cluster-RCTs comparing probiotics with placebo or no treatment to prevent acute URTIs. The participants were children, adults, or the elderly in the community, care facilities, schools, or hospitals. Our main outcomes were the number of participants diagnosed with URTIs (at least one event and at least three events), the incidence rate (number of cases/person year) of acute URTIs, and the mean duration of an episode of URTIs. Our secondary outcomes were the number of participants who were absent from childcare centre, school, or work due to acute URTIs; the number of participants who used prescribed antibiotics for acute URTIs; and the number of participants who experienced at least one adverse event from probiotics. We excluded studies if they did not specify acute respiratory infections as 'upper'; studies with more than 50% of participants vaccinated against influenza or other acute URTIs within the last 12 months; and studies with significantly different proportions of vaccinated participants between the probiotics arm and the placebo or no treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of trials and extracted data using standard Cochrane methodological procedures. We analysed both intention-to-treat and per-protocol data and used a random-effects model. We expressed results as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 23 individual RCTs and one cluster-RCT. As one of the individual RCTs did not report outcomes in a usable way, we could only meta-analyse data from 23 trials, involving a total of 6950 participants including children (aged from one month to 11 years old), adults (mean age 37.3), and older people (mean age 84.6 years). One trial reported 22.5% flu-vaccine participants within the last 12 months, and 25.4% flu-vaccine participants during the intervention. Probiotics were more likely to be given with milk-based food in children; administered in powder form in adults; and given with milk-based food or in capsules in the elderly. Most of the studies used one or two strains (e.g. Lactobacillus plantarum HEAL9, Lactobacillus paracasei (8700:2 or N1115)) and 109 or 1011 colony-forming units (CFU)/day of probiotics for more than three months. We found that probiotics may reduce the number of participants diagnosed with URTIs (at least one event) (RR 0.76, 95% CI 0.67 to 0.87; P < 0.001; 16 studies, 4798 participants; low-certainty evidence); likely reduce the number of participants diagnosed with URTIs (at least three events) (RR 0.59, 95% CI 0.38 to 0.91; P = 0.02; 4 studies, 763 participants; moderate-certainty evidence); may reduce the incidence rate (number of cases/person year) of URTIs (rate ratio 0.82, 95% CI 0.73 to 0.92, P = 0.001; 12 studies, 4364 participants; low-certainty evidence); may reduce the mean duration of an episode of acute URTIs (MD -1.22 days, 95% CI -2.12 to -0.33; P = 0.007; 6 studies, 2406 participants; low-certainty evidence); likely reduce the number of participants who used prescribed antibiotics for acute URTIs (RR 0.58, 95% CI 0.42 to 0.81; P = 0.001; 6 studies, 1548 participants; moderate-certainty evidence); and may not increase the number of participants who experienced at least one adverse event (RR 1.02, 95% CI 0.90 to 1.15; P = 0.79; 8 studies, 2456 participants; low-certainty evidence). Evidence showing a decrease in the number of people absent from childcare centre, school, or work due to acute URTIs with probiotics is very uncertain (RR 0.14, 95% CI 0.03 to 0.59; 1 study, 80 participants; very low-certainty evidence). Adverse events from probiotics were minor, and most commonly gastrointestinal symptoms, such as vomiting, flatulence, diarrhoea, and bowel pain.  AUTHORS' CONCLUSIONS: Overall, we found that probiotics were better than placebo or no treatment in preventing acute URTIs.

The mediation role of sleep quality in the relationship between cognitive decline and depression.

OBJECTIVES: Associations between cognitive decline and depression have been inconclusive. We examined 1) whether sleep quality mediates these relationships and 2) which factor of sleep quality mediates these relationships. METHODS: This study utilized baseline data from the 2018 West China Health and Aging Trend study (WCHAT), a large cohort data-set that including participants aged over 50 years old. We defined depression using the 15-item Geriatric Depression Scale (GDS-15). Cognitive status was measured using the Short Portable Mental Status Questionnaire (SPMSQ) and sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Direct relationships between cognitive decline, sleep quality and depression were assessed using multiple linear regression. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of specific aspects of sleep (e.g., quality, duration) in the relationship between cognitive decline and depression. RESULTS: Of 6828 participants aged 50 years old or older, the proportion of depression was 17.4%. Regression analysis indicated a total association between cognitive scores (ß = 0.251, 95% CI 0.211 to 0.290, p < 0.001) and depression status. After adjusted PSQI scores, the association between cognitive scores and depression status was still significant (ß = 0.242, 95% CI 0.203 to 0.281, p < 0.001), indicating a partial mediation effect of sleep quality. Mediation analysis verified sleep quality partially mediate the associations between cognitive decline and depression (indirect effect estimate = 0.0308, bootstrap 95% CI 0.023 to 0.040; direct effect estimate = 0.3124, bootstrap 95% CI 0.269 to 0.350). And daytime dysfunction had a highest mediation effect with a proportion of mediation up to 14.6%. CONCLUSIONS: Sleep quality partially mediated the relationship between cognitive decline and depression. Daytime dysfunction had a highest mediation effect. Further research is necessary to examine the effects of sleep quality on the relationship of cognitive decline and depression.

Newly prescribed canagliflozin vs. GLP-1 agonists was linked to amputation in older adults with type 2 DM and CVD.

SOURCE CITATION: Fralick M, Kim SC, Schneeweiss S, et al. Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study. BMJ. 2020;370:m2812. 32843476.

Efficacy and safety of dapagliflozin were similar in patients with type 2 DM and atherosclerotic CVD, regardless of PAD.

SOURCE CITATION: Bonaca MP, Wiviott SD, Zelniker TA, et al. Dapagliflozin and cardiac, kidney, and limb outcomes in patients with and without peripheral artery disease in DECLARE-TIMI 58. Circulation. 2020;142:734-47. 32795086.

Thrombolytic therapy for pulmonary embolism.

BACKGROUND: Thrombolytic therapy is usually reserved for people with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and may reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhage. This is the fourth update of the Cochrane review first published in 2006. OBJECTIVES: To assess the effects of thrombolytic therapy for acute pulmonary embolism. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 August 2020. We undertook reference checking to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for people with acute PE (massive/submassive). We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. DATA COLLECTION AND ANALYSIS: Two review authors (ZZ, QH) assessed the eligibility and risk of bias of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with a 95% confidence interval (CI) or the mean difference (MD) with a 95% CI. The primary outcomes of interest were death, recurrence of PE and haemorrhagic events. We assessed the certainty of the evidence using GRADE criteria. MAIN RESULTS: We identified three new studies for inclusion in this update. We included 21 trials in the review, with a total of 2401 participants. No studies compared thrombolytics versus surgical intervention. We were not able to include one study in the meta-analysis because it provided no extractable data. Most studies carried a high or unclear risk of bias related to randomisation and blinding. Meta-analysis showed that, compared to control (heparin alone or heparin plus placebo), thrombolytics plus heparin probably reduce both the odds of death (OR 0.58, 95% CI 0.38 to 0.88; 19 studies, 2319 participants; low-certainty evidence), and recurrence of PE (OR 0.54, 95% CI 0.32 to 0.91; 12 studies, 2050 participants; low-certainty evidence). Effects on mortality weakened when six studies at high risk of bias were excluded from analysis (OR 0.71, 95% CI 0.45 to 1.13; 13 studies, 2046 participants) and in the analysis of submassive PE participants (OR 0.61, 95% CI 0.37 to 1.02; 1993 participants). Effects on recurrence of PE also weakened after removing one study at high risk of bias for sensitivity analysis (OR 0.60, 95% CI 0.35 to 1.04; 11 studies, 1949 participants). We downgraded the certainty of evidence to low because of 'Risk of bias' concerns. Major haemorrhagic events were probably more common in the thrombolytics group than in the control group (OR 2.84, 95% CI 1.92 to 4.20; 15 studies, 2101 participants; moderate-certainty evidence), as were minor haemorrhagic events (OR 2.97, 95% CI 1.66 to 5.30; 13 studies,1757 participants; low-certainty evidence). We downgraded the certainty of the evidence to moderate or low because of 'Risk of bias' concerns and inconsistency. Haemorrhagic stroke may occur more often in the thrombolytics group than in the control group (OR 7.59, 95% CI 1.38 to 41.72; 2 studies, 1091 participants). Limited data indicated that thrombolytics may benefit haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, composite clinical outcomes, need for escalation and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and the small number of participants involved warrant caution when interpreting results. The length of hospital stay was shorter in the thrombolytics group than in the control group (mean difference (MD) -1.40 days, 95% CI -2.69 to -0.11; 5 studies, 368 participants). Haemodynamic decompensation may occur less in the thrombolytics group than in the control group (OR 0.36, 95% CI 0.20 to 0.66; 3 studies, 1157 participants). Quality of life was similar between the two treatment groups. None of the included studies provided data on post-thrombotic syndrome or on cost comparison. AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that thrombolytics may reduce death following acute pulmonary embolism compared with heparin (the effectiveness was mainly driven by one trial with massive PE). Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events, including haemorrhagic stroke. More studies of high methodological quality are needed to assess safety and cost effectiveness of thrombolytic therapy for people with pulmonary embolism.

The Comparison of Sarcopenia Diagnostic Criteria using AWGS 2019 with the Other Five Criteria in West China.

INTRODUCTION: The aim of this study was to investigate the prevalence and associated factors of sarcopenia defined by different criteria in community-dwelling adults of west China using the baseline data of West-China Health and Aging Trend (WCHAT) study. METHODS: Adults aged 50 years or older in communities of Yunnan, Guizhou, Sichuan, and Xinjiang provinces were enrolled in this study. We applied 6 -diagnostic criteria (AWGS 2019, AWGS 2014, EWGSOP1, -EWGSOP2, IWGS, and FNIH) to define sarcopenia. Muscle mass was measured based on bioimpedance analysis. Handgrip strength and walking speed were recorded, respectively. Different variables like anthropometry measures, lifestyles, chronic disease, and blood test were collected. RESULTS: We included 4,500 participants. The prevalence of sarcopenia was 22.8, 19.3, 57.1, 11.8, 24.1, and 18.1% according to the AWGS 2019, AWGS 2014, EWGSOP 1, EWGSOP 2, IWGS, and FNIH criteria, respectively. We found that serum albumin level was independently associated with sarcopenia using AWGS 2019 and IWGS. And vitamin D level was independently associated with sarcopenia using AWGS 2014, -EWGSOP2, and FNIH. While age, depressive status, BMI, hemoglobin, vitamin D, and insulin level were all significantly associated with sarcopenia using AWGS 2014, but all of these factors were not significant using AWGS 2019. CONCLUSIONS: Sarcopenia was highly prevalent in west China regardless of the diagnostic criteria. Serum albumin and vitamin D level were mostly associated with sarcopenia defined by different criteria. While most risk factors associated with the AWGS 2014-defined sarcopenia exhibited no consistent pattern with AWGS 2019, the validity of the AWGS 2019 consensus needs to be confirmed in further prospective studies.

Sarcopenia index based on serum creatinine and cystatin C predicts the risk of postoperative complications following hip fracture surgery in older adults.

OBJECTIVE: To assess the utility of the preoperative Sarcopenia index (SI) as a predictive marker of the risk of postoperative complications following hip fracture surgery in older adults. STUDY DESIGN: This observational study enrolled older adults with hip fracture who were hospitalized in the Department of Orthopedics of West China Hospital, Sichuan University, from December 7, 2010 - June 14, 2017, and who underwent hip fracture surgery. PRIMARY OUTCOME AND MEASURES: Clinical data were collected from medical records and serum creatinine and cystatin C were measured before surgery. Outcomes included postoperative complications such as pneumonia, urinary tract infection, respiratory failure, heart failure, and non-grade A healing. Binary logistic regression analyses were used to analyze association between SI and postoperative complications. RESULTS: A total of 897 patients aged 60 years and over were enrolled in this study (age range: 60 - 100 years), of whom 306(34.1%)were male, and 591(65.9%)were female. Postoperative complications included pneumonia (12%), urinary tract infections (1.8%), respiratory failure (1.5%), heart failure (1.6%), and non-A- grade healing (3.6%). In the patient group that received joint replacements, the incidence of pneumonia was negatively associated with SI values. After adjusting for potential confounding factors, binary logistic regression analyses showed that a higher SI was independently associated with a lower risk of pneumonia after joint replacement surgery (OR:0.39, 95% CI:0.18-0.89, P<0.05). However, we did not find statistically significant association between SI and the risk of postoperative complications other than pneumonia among patients with two types of hip fracture surgery. CONCLUSION: The SI based on serum creatinine and cystatin C can predict pneumonia rather than other postoperative complications among older patients with hip fracture after joint replacement surgery.

The association between preoperative modified frailty index and postoperative complications in Chinese elderly patients with hip fractures.

OBJECTIVES: To investigate the role of a preoperative modified frailty index (mFI) based on data from medical records in predicting postoperative complications among older Chinese patients with hip fractures. METHODS: This retrospective cohort study included consecutive older patients with hip fracture admitted to the Department of Orthopaedics, West China Hospital, Sichuan University, from December 2010 to June 2017 who underwent surgical repair. We selected 33 variables, including characteristics of hip fracture, to construct a mFI. Each variable was coded with a value of 0 when a deficit was absent or 1 when it was present. We calculated the mFI as the proportion of positive items and defined frailty as mFI value greater than or equal to 0.21 according to threshold proposed by Hoover et al. We examined the relationship between mFI and severity of postoperative complications and the occurrence of in-hospital pneumonia including statistical adjustment for several demographics (e.g. age, gender, and marital status) and habits (smoking and alcohol intake), time from fracture to surgery in the multivariable model. RESULTS: We included 965 patients (34% male; mean age: 76.77 years; range: 60 to 100 years) with a prevalence of frailty of 13.06%. The presence of frailty was associated with a higher severity of complications (OR: 2.07; 95% CI: 1.40 to 3.05). Frail patients were more likely to develop in-hospital pneumonia than non-frail patients (OR: 2.08; 95% CI: 1.28 to 3.39). CONCLUSION: The preoperative modified frailty index based on data from medical records proved significantly associated with postoperative complications among older patients with hip fractures undergoing hip surgery.

Vitamin D status and obesity markers in older adults: results from West China Health and Aging Trends study.

BACKGROUNDS: Vitamin D deficiency and insufficiency in older adults seems to be common, but the prevalence estimates are lacking in West China. Previous studies suggested that low vitamin D status was associated with obesity. However, most of them evaluated obesity based on body mass index (BMI) and there are no studies at present exploring the association between vitamin D status and different obesity markers. The present study aims to investigate the prevalence of low vitamin D status and evaluate the association between the vitamin D status and different obesity markers among older adults in West China. METHODS: Data was based on the baseline of West China Health and Aging Trends study (WCHAT). All of the participants were older than 60 years old in the present study. Vitamin D status was based on laboratory data, and obesity markers were assessed by bioelectrical impedance analysis (BIA) using the InBody 770 analyzer. Multiple linear regression was performed to find the association between the vitamin D status and various obesity markers. RESULTS: The study included 2661 individuals (mean age: 67.7 ± 6.0 years; males: 41 %). The mean vitamin D level was 18.8 ± 6.3 ng/ml (range: 5 to 59 ng/ml); 5.2 % of participants had a sufficient level of vitamin D, 31.8 % had vitamin D insufficiency, and 63.0 % had vitamin D deficiency. Our results showed that vitamin D status was negatively associated with fat mass index (FMI), visceral fat area (VFA), and waist-hip ratio (WHR) in both sexes. Comparing to other obesity markers, WHR had the strongest correlation with vitamin D status in both sexes (ß = -6.090, P = 0.046 in males; ß = -11.253, P < 0.001 in females). No significant association was found between vitamin D status and BMI in males. CONCLUSION: The prevalence of vitamin D insufficiency and deficiency among older adults in West China was high. Among the older adults in west China, WHR showed stronger association with vitamin D status and was better for the prediction of vitamin D insufficiency or deficiency in both sexes, compared to BMI. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800018895 .