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.

Time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drug: A one-stage network meta-analysis.

AIMS: To assess the time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drugs. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, and Cochrane Library up to 18 November 2021, for randomized controlled trials (RCTs) and propensity-score-matched non-randomized studies (NRSs) comparing all anti-diabetic drugs with standard treatment or with each other on fracture in adults with type 2 diabetes. The study performed a one-stage network meta-analysis using discrete-time hazard regression with reconstructed individual time-to-event data. RESULTS: This network meta-analysis involved seven RCTs (65,051 adults with type 2 diabetes) with a median follow-up of 36 months and three propensity-score-based NRSs (17,954 participants) with a median follow-up of 27.3 months. Among anti-diabetic drugs, thiazolidinediones increased the overall hazard of fracture by 42% (95% credible interval [CrI], 3%-97%) and almost tripled the risk after 4 years (hazard ratio [HR], 2.74; 95% CrI, 1.53-4.80). Credible subgroup analysis suggested that thiazolidinediones increased the hazard of fracture only in females (HR, 2.19; 95% CrI, 1.26-3.74) but not among males (HR, 0.81; 95% CrI, 0.45-1.40). Moderate certainty evidence established that thiazolidinediones increase 92 fractures in five years per 1000 female patients. We did not find the risk of fractures with other anti-diabetic drugs including metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. CONCLUSIONS: Long-term use of thiazolidinediones elevates the risk of fracture among females with type 2 diabetes. There is no evidence eliciting fracture risk associated with other anti-diabetic drugs.

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.

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.

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.

Analysis of Risk Factors for Cognitive Dysfunction in Disabled Elderly Patients in Chengdu, China.

BACKGROUND With the aging population comes an increase in functional disability that leads to dependency and institutionalization, as well as social, medical, and economic challenges. This study aimed to classify and assess the factors affecting cognitive deficits in disabled elderly people. MATERIAL AND METHODS Disabled patients ≥60 years old were assessed by face-to-face cross-sectional surveys, which were conducted using advanced peer-to-peer software. The ability to perform daily life tasks was assessed using the Modified Barthel Index. Cognitive function was evaluated with the Mini-cognitive assessment instrument. Using these surveys, 9471 individuals were included in this study. The rank-sum test was used to investigate differences between groups. Disordered multi-class logistic regression was used to correct related confounding factors for multivariate analysis. RESULTS The ratios of normal cognitive function, cognitive impairment, and dementia were 3.71%, 38.59%, and 57.70%, respectively. The univariate analysis and multivariate analysis showed that older individuals (≥80 years), women, illiterate individuals, and lonely persons were more prone to dementia. Moreover, a history of hypertension, diabetes, osteoporosis, and fractures were significantly associated with dementia. CONCLUSIONS The proportion of dementia in the elderly disabled patients is very high (57.7%) in Chengdu City. Age (≥80 years), female sex, education level (illiterate individuals), living conditions, and chronic disease were closely correlated with cognitive functions.

The impact of functional status on LOS and readmission in older patients in geriatrics department: a cohort study.

BACKGROUND: Length of hospital stay (LOS) and readmission are important outcomes for older inpatients. The association between functional status on admission and outcomes has not been well investigated in Chinese elderly. OBJECTIVES: To detect the impact of function impairments on LOS and 90-day readmission in a population of Chinese elderly inpatients. METHODS: This is a prospective cohort study. All new patients over 60 years in geriatrics department of a university hospital in Western China from June to August 2016 were enrolled. Activities of daily living (ADL) and Instrumental ADL (IADL) on admission were evaluated with Barthel Index and Lawton IADL. Outcomes were LOS and 90-day readmission. LOS was calculated as the total days of hospital stay. Readmission was investigated through telephone interviews after discharge. Pearson Chi-square test was used to detect the associations. Binary logistic regression was used to detect the association of function status on admission with LOS and readmission. RESULTS: A total of 225 patients were enrolled. Mean age 82.41 (± 7.316; 63-99), 31.1% were females. Overall, 64.9% of the patients were hospitalized longer than 14 days and 33.30% experienced a 90-day readmission. Following an adjustment for age, gender, marital status, education level, smoking, alcohol, nutrition status, and admission location, the binary logistic regression models showed that both ADL impairment (OR 2.03; 95% CI 1.06-3.87) and IADL impairment (OR 2.54; 95% CI 1.28-5.01) were independent predictors for LOS. ADL impairment was an independent predictor for 90-day readmission (OR 2.26; 95% CI 1.14-4.47), while IADL impairment was not associated with readmission (OR 1.43; 95% CI 0.68-3.02). CONCLUSION: Functional status on admission is the predictor of LOS and 90-day readmission in Chinese older inpatients from the geriatric department of a university hospital.

Comparison of procalcitonin, a potentially new inflammatory biomarker of frailty, to interleukin-6 and C-reactive protein among older Chinese hospitalized patients.

AIM: Procalcitonin (PCT) has predictive value for patients with infectious diseases, but has not been studied in frailty. The purpose of this study was to compare PCT to two other inflammatory biomarkers [interleukin-6 (IL-6)] and C-reactive protein (CRP) in their association with frailty among older hospitalized patients. METHODS: Retrospective study of inpatients (June-December, 2016), who had all three biomarkers measured within 24 h of admission. Frailty was defined according to the Chinese version of a validated frailty scale. Due to the association of biomarkers with infection, we divided patients into "non-infected" (no pneumonia or other infections) and "pneumonia" (using standard criteria) groups. RESULTS: Of 435 patients (mean age 81.6 ± 8.6 years), 181 (41.6%) were designated the non-infected group and 254 (58.4%) the pneumonia group. Prevalence of frailty in the non-infected group was 32.0% (58/181) and frailty (univariate analysis) was associated with higher PCT and IL-6 levels but not CRP. Prevalence of frailty in the pneumonia group was 40.2% (102/254) and frailty was associated with all three biomarkers. In multivariable analysis adjusting for age, gender, smoking, alcohol use, hemoglobin, albumin, neutrophils and creatinine, PCT (not IL-6 and CRP) was associated with frailty in the non-infected group (OR = 5.244; 95% CI, 1.622-16.947; P = 0.006) and none of the biomarkers were associated with frailty in the pneumonia group. CONCLUSIONS: Although the study is limited due to the retrospective methods, PCT but not IL-6 or CRP, was associated with frailty among older inpatients without infection. None of these biomarkers were associated with frailty among patients with pneumonia.

The impact of frailty and sarcopenia on postoperative outcomes in older patients undergoing gastrectomy surgery: a systematic review and meta-analysis.

BACKGROUND: Gastric cancer is a major health problem, and frailty and sarcopenia will affect the postoperative outcomes in older people. However, there is still no systematic review to determine the role of frailty and sarcopenia in predicting postoperative outcomes among older patients with gastric cancer who undergo gastrectomy surgery. METHODS: We searched Embase, Medline through the Ovid interface and PubMed websites to identify potential studies. All the search strategies were run on August 24, 2016. We searched the Google website for unpublished studies on June 1, 2017. The data related to the endpoints of gastrectomy surgery were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the association between sarcopenia and adverse postoperative outcomes by using Stata version 11.0. PRISMA guidelines for systematic reviews were followed. RESULTS: After screening 500 records, we identified eight studies, including three prospective cohort studies and five retrospective cohort studies. Only one study described frailty, and the remaining seven studies described sarcopenia. Frailty was statistically significant for predicting hospital mortality (OR 3.96; 95% CI: 1.12-14.09, P = 0.03). Sarcopenia was also associated with postoperative outcomes (pooled OR 3.12; 95% CI: 2.23-4.37). No significant heterogeneity was observed across these pooled studies (Chi2 = 3.10, I2 = 0%, P = 0.685). CONCLUSION: Sarcopenia and frailty seem to have significant adverse impacts on the occurrence of postoperative outcomes. Well-designed prospective cohort studies focusing on frailty and quality of life with a sufficient sample are needed.

Sex differences in rapid eye movement sleep behavior disorder: A systematic review and meta-analysis.

Although rapid eye movement (REM) sleep behavior disorder (RBD) has been widely considered as a male-predominant parasomnia, the existing evidence for the sex difference in the risk of RBD in the general population was conflicting. The present study conducted a systematic review to explore the sex differences in the prevalence, comorbidities, clinical characteristics, and phenoconversion of RBD. One hundred thirty-five eligible studies were identified for the systematic review, and 133 were finally included in the meta-analysis. Males in the general population showed a trend for a higher risk of probable/possible RBD (pRBD), especially among the male older adults (aged ≥60). In the clinical populations, males showed a significantly higher risk of confirmed RBD, but not of pRBD. Among idiopathic RBD (iRBD) patients, males had a significantly earlier age onset of RBD compared with females. Male patients with Parkinson's disease (PD) had a higher risk of comorbid RBD. There was no significant sex difference in the risk of developing neurodegenerative diseases in iRBD patients. Large scale and prospective studies utilizing stringent diagnostic criteria for RBD are recommended to further verify the sex differences in RBD and to investigate the mechanism underlying the sex difference.

Exercise for sarcopenia in older people: A systematic review and network meta-analysis.

BACKGROUND: Sarcopenia is a serious public health concern among older adults worldwide. Exercise is the most common intervention for sarcopenia. This study aimed to compare the effectiveness of different exercise types for older adults with sarcopenia. METHODS: Randomized controlled trials (RCTs) that examined the effectiveness of exercise interventions on patient-important outcomes for older adults with sarcopenia were eligible. We systematically searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials via Ovid until 3 June 2022. We used frequentist random-effects network meta-analyses to summarize the evidence and applied the Grading of Recommendations, Assessment, Development, and Evaluations framework to rate the certainty of evidence. RESULTS: Our search identified 5988 citations, of which 42 RCTs proved eligible with 3728 participants with sarcopenia (median age: 72.9 years, female: 73.3%) with a median follow-up of 12 weeks. We are interested in patient-important outcomes that include mortality, quality of life, muscle strength and physical function measures. High or moderate certainty evidence suggested that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life compared to usual care (standardized mean difference from 0.68 to 1.11). Moderate certainty evidence showed that resistance and balance exercise plus nutrition (mean difference [MD]: 4.19 kg) was the most effective for improving handgrip strength (minimally important difference [MID]: 5 kg). Resistance and balance exercise with or without nutrition (MD: 0.16 m/s, moderate) were the most effective for improving physical function measured by usual gait speed (MID: 0.1 m/s). Moderate certainty evidence showed that resistance and balance exercise (MD: 1.85 s) was intermediately effective for improving physical function measured by timed up and go test (MID: 2.1 s). High certainty evidence showed that resistance and aerobic, or resistance and balance, or resistance and aerobic exercise plus nutrition (MD from 1.72 to 2.28 s) were intermediately effective for improving physical function measured by the five-repetition chair stand test (MID: 2.3 s). CONCLUSIONS: In older adults with sarcopenia, high or moderate certainty evidence showed that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life. Adding nutritional interventions to exercise had a larger effect on handgrip strength than exercise alone while showing a similar effect on other physical function measures.

Chest computed tomography-derived muscle mass and quality indicators, in-hospital outcomes, and costs in older inpatients.

BACKGROUND: Muscle mass and muscle quality assessed by computed tomography (CT) have been associated with poor prognosis in oncology and surgery patients, but the relevant evidence was limited in older patients. We hypothesized that muscle mass and muscle quality indicators derived from opportunistic chest CT images at the 12th thorax vertebra level (T12) could predict in-hospital death, length of hospital stay (hospital LOS), and hospital costs among older patients in acute care wards. METHODS: We conducted a prospective cohort study. Older patients admitted to the acute geriatric wards of a teaching hospital were continuously recruited. Chest CT images were analysed using SliceOmatic software. The skeletal muscle area, skeletal muscle radiodensity, and intermuscular adipose tissue (IMAT) at the T12 level were measured. Skeletal muscle index (SMI) was calculated using skeletal muscle area divided by body height squared. RESULTS: We included 1135 older patients with a median age of 80 years (interquartile range, 73 to 85 years), 498 (44%) were women, 148 (13%) patients died during hospitalization. The SMI and SMD were negatively correlated to age (ρ = -0.11, P < 0.001, ρ = -0.30, P < 0.001, respectively), whereas the IMAT was positively correlated to age (ρ = 0.27, P < 0.001). Compared with survivors, dead patients had significantly lower SMI in men (P < 0.001) but not in women (P = 0.760). After adjusting for sex and other potential confounders, the SMI [increased per 1 cm2 /m2 , odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93 to 0.99] and SMD (increased per 1 Hounsfield unit, OR 0.93, 95% CI 0.90 to 0.96) were negatively and independently associated with in-hospital death, whereas the IMAT (increased per 1 cm2 , OR 1.09, 95% CI 1.05 to 1.14) was independently and positively associated with in-hospital death. None of the SMI, SMD, or IMAT was significantly related to long hospital LOS or increased hospital costs. CONCLUSIONS: Chest CT-derived muscle mass indicator (T12 SMI) and muscle quality indicators (T12 SMD and T12 IMAT) may serve as prognostic factors for predicting in-hospital death among older inpatients. Opportunistic chest CT images might be an overlooked resource for measuring muscle mass and muscle quality and for predicting short-term prognosis in older inpatients.

Visit-to-visit glycated hemoglobin A1c variability in adults with type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Current practice uses the latest measure of glycated hemoglobin (HbAlc) to facilitate clinical decision-making. Studies have demonstrated that HbAlc variability links the risk of death and complications of diabetes. However, the role of HbAlc variability is unclear in clinical practice. This systematic review summarized the evidence of visit-to-visit HbAlc variability regarding different metrics in micro- and macro-vascular complications and death in people with type 2 diabetes. METHODS: We searched PubMed, EMBASE (via OVID), and Cochrane Central Register (CENTRAL, via OVID) for studies investigating the association between HbAlc variability and adverse outcomes in patients with type 2 diabetes and performed random-effects meta-analysis stratified by HbAlc variability metrics in terms of standard deviation (SD), coefficient of variation (CV), and HbAlc variability score (HVS). RESULTS: In people with type 2 diabetes, the highest quantile of all three HbAlc variability metrics (HbAlc-standard deviation [HbAlc-SD], HbAlc-coefficient of variance [HbAlc-CV], and HVS) is associated with increased risks of all-cause mortality, cardiovascular events, progression to chronic kidney disease, amputation, and peripheral neuropathy. For example, the hazard ratio of HbAlc-SD on all-cause mortality was l.89 with 95% confidence interval (95% CI) l.46-2.45 (HbAlc-CV l.47, 95% CI l.26-l.72; HVS l.67, 95% CI l.34-2.09). CONCLUSIONS: High HbAlc variability leads to micro- and macro-vascular complications of type 2 diabetes and related death. People with type 2 diabetes and high HbAlc variability need additional attention and care for the potential adverse outcomes.

Effects of Exercise on Patients Important Outcomes in Older People With Sarcopenia: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials.

BACKGROUND: Many clinical practice guidelines strongly recommend exercise as an intervention for patients with sarcopenia. However, the significance of exercise on patient-important outcomes in older adults with sarcopenia is inconsistent when considering available minimal important differences. To synthesize current systematic review and meta-analyses evidence on the efficacy of exercise on patient-important outcomes in the treatment of sarcopenia in older adults. METHODS: We searched MEDLINE, EMBASE, Cochrane Library (Cochrane database of systematic review, CDSR) via OvidSP and Web of science until April 2021 and reference lists. Two independent investigators performed abstracted and title screening, assessed the full text and quality of evidence. This umbrella review included systematic reviews and meta-analyses of randomized controlled trials (RCTs). Eligible reviews aim to evaluate the effect of exercise on patient-important sarcopenic outcomes (muscle or physical function, mortality, and quality of life) in treating sarcopenia in older people. We used the minimally important differences (MIDs) of these outcomes to assess if the effects of exercise matter to patients. RESULTS: This umbrella review provided a broad overview of the existing evidence and evaluated the systematic reviews' methodological quality and evidence for all these associations. In older patients with sarcopenia, moderate- to high-quality evidence showed that exercise intervention probably increases walking speed and improved physical performance (measured by TUG test); exercise may increase the muscle strength (grip strength, keen extension strength); but the effect size for grip strength probably too small to achieve patients important changes. Evidence for older people with sarcopenic obesity is limited, and we found the consistent effect of exercise interventions on grip strength and usual walking speed. CONCLUSION: Exercise has a positive and important effect on physical performance for older adults with sarcopenia, which supports leaving the current recommendations unchanged. New systematic reviews to summarize the effect of exercise on the quality of life are warranted to fill the current evidence gap.

Association of Serum Homocysteine with Cardiovascular and All-Cause Mortality in Adults with Diabetes: A Prospective Cohort Study.

Background: Homocysteine (Hcy) was implicated in oxidative stress and diabetes biologically. However, the clinical evidence on the link between Hcy level and diabetes is limited and controversial. This study is aimed at investigating the association of serum Hcy with all-cause and cardiovascular mortality in diabetic patients. Methods: Serum Hcy was measured among 2,286 adults with type 2 diabetes in NHANES 1999-2006. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CIs for the association of Hcy with all-cause and cause-specific mortality. Results: Over a median follow-up of 11.0 (interquartile range, 8.9-13.4) years, 952 of the 2286 patients with diabetes died, covering 269 (28.3%) cardiovascular deaths and 144 (15.2%) cancer deaths. Restricted cubic spline showed the linear relationship between Hcy and all-cause mortality risk. After multivariate adjustment, higher serum Hcy levels were independently associated with increased risk of all-cause and cardiovascular mortality. Compared with participants in the bottom tertile of Hcy, the multivariate-adjusted HRs and 95% CI for participants in the top quartile were 2.33 (1.64-3.30) for all-cause mortality (p trend < 0.001), 2.24 (1.22-4.10) for CVD mortality (p trend = 0.017), and 2.05 (0.90-4.69) for cancer mortality (p trend = 0.096). The association with total mortality was especially stronger among patients with albuminuria. Serum Hcy significantly improved reclassification for 10-year mortality in diabetic patients (net reclassification index = 0.253 and integrated discrimination improvement = 0.011). Conclusions: Serum Hcy was associated with risks of all-cause and cardiovascular mortality in diabetic adults. Our results suggested that Hcy was a promising biomarker in risk stratification among diabetic patients.

Safety of proprotein convertase subtilisin/kexin 9 inhibitors: a systematic review and meta-analysis.

OBJECTIVE: To determine the harms of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in people who need lipid-lowering therapy. METHODS: This systematic review included randomised controlled trials that compared PCSK9 inhibitors with placebo, standard care or active lipid-lowering comparators in people who need lipid-lowering therapy with the follow-up duration of at least 24 weeks. We summarised the relative effects for potential harms from PCSK9 inhibitors using random-effect pairwise meta-analyses and assessed the certainty of evidence using GRADE (Grading of Recommendation Assessment, Development and Evaluation) for each outcome. RESULTS: We included 32 trials with 65 861 participants (with the median follow-up duration of 40 weeks, ranging from 24 to 146 weeks). The meta-analysis showed an incidence of injection-site reaction leading to discontinuation (absolute incidence of 15 events (95% CI 11 to 20) per 1000 persons in a 5-year time frame, high certainty evidence). PCSK9 inhibitors do not increase the risk of new-onset diabetes mellitus, neurocognitive events, cataracts or gastrointestinal haemorrhage with high certainty evidence. PCSK9 inhibitors probably do not increase the risks of myalgia or muscular pain leading to discontinuation or any adverse events leading to discontinuation with moderate evidence certainty. Given very limited evidence, PCSK9 inhibitors might not increase influenza-like symptoms leading to discontinuation (risk ratio 1.5; 95% CI 0.06 to 36.58). We did not identify credible subgroup analyses results, including shorter versus longer follow-up duration of trials. CONCLUSIONS: PCSK9 inhibitors slightly increase the risk of severe injection-site reaction but not cataracts, gastrointestinal haemorrhage, neurocognitive events, new-onset diabetes or severe myalgia or muscular pain.

The Electronic Frailty Index is Associated with Increased Infection and All-Cause Mortality Among Older Patients with Primary Lung Cancer: A Cohort Study.

INTRODUCTION: To assess whether the electronic frailty index (eFI) is independently associated with all-cause mortality and chemotherapy adverse reactions among older Chinese patients with lung cancer. METHODS: This is a retrospective, single-institution, chart review, and not a prospective cohort study. All patients ≥60 years with primary lung cancer in the West China Hospital from 2010 to 2017 were included in this cohort. The eFI was established using 35 frailty-related variables in the electronic medical record (EMR) system and was cut by a value of 0.2 to classify the patients into frail (eFI ≥0.2) and robust/non-frail groups (eFI<0.2). The long-term outcome was all-cause mortality identified by government databases and telephone interviews. Short-term outcomes were any infection, bone suppression, chemotherapy discontinuation, impaired liver function, any gastrointestinal reactions and length of hospitalization. An inverse probability weighting method was used to eliminate the potential confounders. An adjusted Kaplan-Meier estimator and a weighted Cox model were used to calculate the survival and hazard ratio. A weighted logistic model was used to calculate the odds of short-term outcomes. RESULTS: A total of 997 patients were included in this study with a median follow-up of 34 months. Compared with non-frail patients, frail patients had an increased risk of mortality and shortened overall survival (hazard ratio [HR] of mortality, 1.29; 95% confidence interval [CI], 1.05 to 1.60; adjusted restricted mean survival time [aRMST] difference, -5.68 months; 95% CI, -10.15 to -1.21 months). For short-term outcomes, frail patients had increased odds of infection compared to non-frail patients (odds ratio, 1.83; 95% CI, 1.09 to 3.06). No other outcome showed a significant result. CONCLUSION: This study of older Chinese patients with primary lung cancer suggests that eFI-based frail patients had worse prognoses with increased risk of all-cause mortality and shortened survival times.

Prognostic Value of Sarcopenia in Lung Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence regarding the association between sarcopenia (skeletal muscle depletion) and outcomes in patients with lung cancer varies across studies. We aimed to systematically review the prognostic value of sarcopenia in lung cancer. METHODS: We searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials through July 23, 2018 to identify retrospective or prospective cohort studies. We applied the Quality in Prognostic Studies instrument to assess the risk of bias in individual studies. We examined the heterogeneity and publication bias and performed subgroup analyses and sensitivity analyses. RESULTS: We included 13 studies (1,810 participants). The pooled prevalence of sarcopenia was 43% in patients with non-small cell lung cancer (NSCLC) and 52% in patients with small cell lung cancer (SCLC). Sarcopenia was associated with a shorter overall survival (OS) in patients with lung cancer (hazard ratio [HR], 2.23; 95% CI, 1.68-2.94). This association existed for both NSCLC (HR, 2.57; 95% CI, 1.79-3.68) and SCLC (HR, 1.59; 95% CI, 1.17-2.14). Sarcopenia was an independent predictor of shorter OS in both stage I-II NSCLC (HR, 3.23; 95% CI, 1.68-6.23) and stage III-IV NSCLC (HR, 2.19; 95% CI, 1.14-4.24). However, sarcopenia was not an independent predictor of disease-free survival in patients with NSCLC (HR, 1.28; 95% CI, 0.44-3.69). CONCLUSIONS: Sarcopenia is highly prevalent in patients with lung cancer (approximately one in two) and an important predictor of impaired OS in patients with SCLC or with different stages of NSCLC.

Prevalence and Associated Factors of Sarcopenia in Nursing Home Residents: A Systematic Review and Meta-analysis.

OBJECTIVE: To review the prevalence and associated factors of sarcopenia in nursing homes. DESIGN: A systematic review and meta-analysis of published studies in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. SETTING: Nursing homes. PARTICIPANTS: Older adults aged ≥60 years. MEASUREMENTS: Sarcopenia was defined according to various validated diagnostic criteria, such as the European Working Group on Sarcopenia in Older People (EWGSOP) criteria and skeletal muscle index (SMI). We performed meta-analyses with random effects models to calculate the pooled prevalence of sarcopenia. The risk of bias of the included studies was evaluated using a 10-item tool explicitly designed for prevalence studies. RESULTS: We included 16 studies with a total of 3585 participants from 129 nursing homes. The included studies were of low to moderate risk of bias. The pooled prevalences of EWGSOP-defined sarcopenia and SMI-defined sarcopenia were 41% [95% confidence interval (CI) 32%-51%, 12 studies, 2685 cases] and 59% (95% CI 24%-93%, 3 studies, 643 cases), respectively. The pooled prevalences of EWGSOP-defined sarcopenia in women and men were 46% (8 studies, 1332 cases) and 43% (8 studies, 739 cases), respectively. The pooled data showed that malnutrition was an independent associated factor of EWGSOP-defined sarcopenia (odds ratio [OR] 1.74, 95% CI 1.36-2.24; 3 studies, 718 cases), but malnutrition risk (OR 1.01, 95% CI 0.53-1.94; 2 studies, 379 cases) and female gender were not (OR 1.14, 95% CI 0.11-11.66; 3 studies, 827 cases). The association between age and body mass index with sarcopenia was inconsistent across studies. Limited evidence indicated that smoking might be related to sarcopenia. CONCLUSIONS/IMPLICATIONS: Sarcopenia is highly prevalent in older nursing home residents. Malnutrition may be an associated factor of sarcopenia. More prospective studies are needed to clarify the association between age, gender, malnutrition, and smoking with sarcopenia.