Mapping the extent of the literature and psychometric properties for the Physical Activity Scale for the Elderly (PASE) in community-dwelling older adults: a scoping review.

BACKGROUND: Identifying valid and accessible tools for monitoring and improving physical activity levels is essential for promoting functional ability and healthy aging. The Physical Activity Scale for the Elderly (PASE) is a commonly used and recommended self-report measure of physical activity in older adults. The objective of this scoping review was to map the nature and extent to which the PASE has been used in the literature on community-dwelling older adults, including the evidence for its psychometric properties. METHODS: Seven electronic databases (MEDLINE (Ovid), Embase (Ovid), AMED (Ovid), Emcare (Ovid), CINAHL (EBSCO), Ageline (EBSCO)) were searched from inception to January 25, 2023. Studies were included if physical activity was part of the aim(s) and measured using the PASE, participants had a mean age of 60 years or older and lived in the community, and papers were peer-reviewed journal articles published in English. Pairs of independent reviewers screened abstracts, full-texts, and extracted data. Where possible, weighted mean PASE scores were calculated for different subgroups based on age, sex, and clinical population. RESULTS: From 4,124 studies screened, 232 articles from 35 countries met the inclusion criteria. Most studies were cross-sectional (60.78%), completed in high-income countries (86.4%) and in North America (49.57%). A variety of clinical conditions were included (n = 21), with the most common populations being osteoarthritis (n = 13), Parkinson's disease (n = 11), and cognitive impairment (n = 7). Psychometric properties of ten versions of the PASE were found. All versions demonstrated acceptable test-retest reliability. Evidence for construct validity showed moderate correlations with self-reported physical activity, fair to moderate with accelerometry derived activity and fair relationships with physical function and self-reported health. Pooled means were reported in graphs and forest plots for males, females, age groups, and several clinical populations. CONCLUSION: The PASE was widely used in a variety of clinical populations and geographical locations. The PASE has been culturally adapted to several populations and evaluated for its reliability and convergent validity; however, further research is required to examine responsiveness and predictive validity. Researchers can use the weighted mean PASE scores presented in this study to help interpret PASE scores in similar populations. OSF REGISTRATION: osf.io/7bvhx.

Pulmonary rehabilitation with balance training for fall reduction in chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Available evidence suggests that adults with chronic obstructive pulmonary disease (COPD) performed substantially worse than healthy controls on many balance measures and balance training can improve the balance measures in this population. We conducted this study to determine the effects of incorporating balance training into pulmonary rehabilitation (PR) on the incidence of falls at 12 months follow-up in high fall risk adults with COPD. METHODS: We conducted a prospective international multi-center randomized controlled trial. Eligible participants were adults with COPD at a high risk of future falls and were randomly assigned (1:1) to the intervention or control group. The intervention included personalized balance training for a targeted total of 90 min per week. Both the intervention and control groups received usual PR (2-3 times per week for 8-12 weeks). The primary outcome was the incidence of falls at 12-month follow-up using monthly fall diary calendars. Negative binomial regression or recurrent events models were used to examine the effects of the intervention on fall events. Multiple imputations were performed to deal with missing values. RESULTS: Of 258 participants who were enrolled in the trial, 178 provided falls information (intervention group = 91, control group = 87) and were included in the main analysis. Forty-one participants (45%) experienced at least one fall event in the intervention group and 33 (38%) in the control group (p = 0.34). The mean incidence of falls at 12 months was similar between the two groups (128 versus 128 per 100 person-years; mean difference: 0.30, 95% CI: -0.76 to 1.36 per 100 person-years). The results are robust after multiple imputations for missing data (n = 67). CONCLUSIONS: PR incorporating balance training compared to PR alone did not reduce the incidence of falls over the 12-month period in high fall risk adults with COPD. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT02995681) on 14/12/2016.

Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis.

BACKGROUND: Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. FINDINGS: Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. INTERPRETATION: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. FUNDING: World Health Organization.

Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023, that enrolled hospitalised patients with suspected or laboratory-confirmed influenza and compared direct-acting influenza antivirals against placebo, standard care, or another antiviral. Pairs of coauthors independently extracted data on study characteristics, patient characteristics, antiviral characteristics, and outcomes, with discrepancies resolved by discussion or by a third coauthor. Key outcomes of interest were time to alleviation of symptoms, duration of hospitalisation, admission to intensive care unit, progression to invasive mechanical ventilation, duration of mechanical ventilation, mortality, hospital discharge destination, emergence of antiviral resistance, adverse events, adverse events related to treatments, and serious adverse events. We conducted frequentist network meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. This study is registered with PROSPERO, CRD42023456650. FINDINGS: Of 11 878 records identified by our search, eight trials with 1424 participants (mean age 36-60 years for trials that reported mean or median age; 43-78% male patients) were included in this systematic review, of which six were included in the network meta-analysis. The effects of oseltamivir, peramivir, or zanamivir on mortality compared with placebo or standard care without placebo for seasonal and zoonotic influenza were of very low certainty. Compared with placebo or standard care, we found low certainty evidence that duration of hospitalisation for seasonal influenza was reduced with oseltamivir (mean difference -1·63 days, 95% CI -2·81 to -0·45) and peramivir (-1·73 days, -3·33 to -0·13). Compared with standard care, there was little or no difference in time to alleviation of symptoms with oseltamivir (0·34 days, -0·86 to 1·54; low certainty evidence) or peramivir (-0·05 days, -0·69 to 0·59; low certainty evidence). There were no differences in adverse events or serious adverse events with oseltamivir, peramivir, and zanamivir (very low certainty evidence). Uncertainty remains about the effects of antivirals on other outcomes for patients with severe influenza. Due to the small number of eligible trials, we could not test for publication bias. INTERPRETATION: In hospitalised patients with severe influenza, oseltamivir and peramivir might reduce duration of hospitalisation compared with standard care or placebo, although the certainty of evidence is low. The effects of all antivirals on mortality and other important patient outcomes are very uncertain due to scarce data from randomised controlled trials. FUNDING: World Health Organization.

Comprehensive geriatric assessment of older patients with renal disease: a cross-sectional survey.

Multidimensional health function impairments are common in older patients with chronic kidney disease (CKD). The purpose of this study was to explore whether the risk or severity of geriatric syndrome increased with a decline in renal function. This survey was conducted for CKD patients aged ≥ 60 years and hospitalized at West China Hospital of Sichuan University (Center of Gerontology and Geriatrics, Nephrology, and Endocrinology) and Chengdu Kangfu Kidney Disease Hospital from September 01, 2013 to June 30, 2014. Patients underwent multidimensional individualized assessments by trained doctors. Logistic regression analysis found that the risk of assisted walking (P = 0.001) and urinary incontinence (P = 0.039) increased with a decline in renal function. Regression analysis revealed that the scores of activities of daily living (P = 0.024), nutritional status (P = 0.000), total social support (P = 0.014), and objective support (P = 0.000) decreased with a decline in renal function.

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.

Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis.

Background: Chronic fatigue syndrome (CFS) is a global public health concern. We performed this systematic review of randomised controlled trials (RCTs) to evaluate the effects and safety of traditional Chinese mind-body exercises (TCME) for patients with CFS. Methods: We comprehensively searched MEDLINE, Embase, Web of Science, PsycINFO, Cochrane Library, CNKI, VIP databases, and Wanfang Data from inception to October 2022 for eligible RCTs of TCME for CFS management. We used Cochran's Q statistic and I2 to assess heterogeneity and conducted subgroup analyses based on different types of TCME, background therapy, and types of fatigue. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results: We included 13 studies (n = 1187) with a maximal follow-up of 12 weeks. TCME included Qigong and Tai Chi. At the end of the treatment, compared with passive control, TCME probably reduces the severity of fatigue (standardised mean differences (SMD) = 0.85; 95% confidence interval (CI) = 0.64, 1.07, moderate certainty), depression (SMD = 0.53; 95% CI = 0.34, 0.72, moderate certainty), anxiety (SMD = 0.29; 95% CI = 0.11, 0.48, moderate certainty), sleep quality (SMD = 0.34; 95% CI = 0.10, 0.57, low certainty) and mental functioning (SMD = 0.90; 95% CI = 0.50, 1.29, low certainty). Compared with other active control therapies, TCME results in little to no difference in the severity of fatigue (SMD = 0.08; 95% CI = -0.18, 0.34, low certainty). For long-term outcomes, TCME may improve anxiety (SMD = 1.74; 95% CI = 0.44, 3.03, low certainty) compared to passive control. We did not identify TCME-related serious adverse events. Conclusions: In patients with CFS, TCME probably reduces post-intervention fatigue, depression, and anxiety and may improve sleep quality and mental function compared with passive control, but has limited long-term effects. These findings will help health professionals and patients with better clinical decision-making. Registration: PROSPERO: CRD42022329157.

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.

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.

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.

GRADE concept 6: a novel application of external indirect evidence into GRADE ratings of evidence certainty in network meta-analysis.

OBJECTIVES: We describe how consideration of external evidence may play an important role in judging certainty in the process of establishing the certainty of the evidence. Our example is a network meta-analysis (NMA) addressing treatment for Ebola virus disease, which informed a World Health Organization guideline. STUDY DESIGN AND SETTING: Through Grading of Recommendations Assessment, Development, and Evaluations (GRADE) project group iterative online, in-person and email discussions, we developed this GRADE concept and obtained approval from the GRADE working group. Using the null as a threshold, we rated our certainty for network estimates in mortality, including consideration of evidence external to the NMA (i.e., did not meet eligibility criteria) and formal logical construction. RESULTS: Based on the existing GRADE guidance, we rated the network estimate for one indirect comparison as low certainty. The formal logical construction that lead us reevaluate the certainty of the evidence is as follows: if A is superior to B, and B is not inferior to C, then A must be superior to C. After considering the logic and the external indirect evidence, we concluded at least moderate certainty for the comparison. CONCLUSION: Systematic review authors and guideline developers should apply the fundamental logical construction for indirect comparisons and consider compelling external evidence in NMA certainty ratings.

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.

Comparing SARS-CoV-2 testing positivity rates and COVID-19 impact among different isolation strategies: a rapid systematic review and a modelling study.

Background: The optimal isolation duration for patients with COVID-19 remains unclear. To support an update of World Health Organization (WHO)'s Living Clinical management guidelines for COVID-19 (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2022.2), this rapid systematic review and modelling study addresses the effects of different isolation periods for preventing onward transmission leading to hospitalisation and death among secondary cases. Methods: We searched the WHO COVID-19 database for studies up to Feb 27, 2023. We included clinical studies of any design with COVID-19 patients confirmed by PCR test or rapid antigen test addressing the impact of any isolation strategy on preventing the spread of COVID-19. There were no restrictions on publication language, publication status, age of patients, severity of COVID-19, variants of SARS-COV-2, comorbidity of patients, isolation location, or co-interventions. We performed random-effects meta-analyses to summarise testing rates of persistent test positivity rates after COVID-19 infection. We performed pre-specified subgroup analyses by symptom status and meta-regression analyses for the proportion of fully vaccinated patients. We developed a model to compare the effects of three isolation strategies on onward transmission leading to hospitalisation and death. The three isolation strategies were (1) 5-day isolation, with no test to release; (2) removal of isolation based on a negative test; and (3) 10-day isolation, with no test to release. The model incorporates estimates of test positivity rates, effective reproduction number, isolation adherence, false negative rate, and hospitalisation rates or case fatality rates. To assess the impact of varying isolation adherence and false negative rates on rapid antigen testing, we conducted some sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess certainty of evidence. The protocol is registered with PROSPERO (CRD42022348626). Findings: Fifteen studies addressing persistent test positivity rates including 4188 patients proved eligible. Asymptomatic patients (27.1%, 95% CI: 15.8%-40.0%) had a significantly lower rapid antigen test positive rate than symptomatic patients (68.1%, 95% CI: 40.6%-90.3%) on day 5. The rapid antigen test positive rate was 21.5% (95% CI: 0-64.1%; moderate certainty) on day 10. Our modelling study suggested that the risk difference (RD) for asymptomatic patients between 5-day isolation and 10-day isolation in hospitalisations (23 more hospitalisations of secondary cases per 10,000 patients isolated, 95% uncertainty interval (UI) 14 more to 33 more) and mortality (5 more per 10,000 patients, 95% UI 1 to 9 more) of secondary cases proved very small (very low certainty). For symptomatic patients, the potential impact of 5- versus 10-day isolation was much greater in hospitalisations (RD 186 more per 10,000 patients, 95% UI 113 more to 276 more; very low certainty) and mortality (RD 41 more per 10,000 patients, 95% UI 11 more to 73 more; very low certainty). There may be little or no difference between removing isolation based on a negative antigen test and 10-day isolation in the onward transmission leading to hospitalisation or death, but the average isolation period (mean difference -3 days) will be shorter for the removal of isolation based on a negative antigen test (moderate certainty). Interpretation: 5 days versus 10 days of isolation in asymptomatic patients may result in a small amount of onward transmission and negligible hospitalisation and mortality; however, in symptomatic patients, the level of onward transmission is concerning and may lead to high hospitalisation and death rates. The evidence is, however, very uncertain. Funding: This work was done in collaboration with WHO.

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.

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.

Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022325948.

Acupuncture for treatment of knee osteoarthritis: A clinical practice guideline.

CLINICAL QUESTION: Is acupuncture effective in treating knee osteoarthritis (KOA)? CURRENT PRACTICE: Although increasingly used in the clinical setting, acupuncture is not mentioned or weakly recommended in guidelines for the treatment of KOA. RECOMMENDATIONS: We suggest acupuncture rather than no treatment in adult KOA (weak recommendation, moderate certainty evidence), and acupuncture combined with nonsteroidal anti-inflammatory drugs (NSAIDs) rather than acupuncture alone when KOA symptoms are severe (weak recommendation, moderate certainty evidence), with duration of acupuncture for 4-8 weeks depending on KOA severity and treatment response (weak recommendation, moderate certainty evidence), and discussing with patients in shared decision-making. HOW THIS GUIDELINE WAS CREATED: This rapid recommendation was developed following the Making GRADE the Irresistible Choice (MAGIC) methodological framework. First, the clinical specialist identified the topic of recommendation and demand for evidence. Then the independent evidence synthesis group performed a systematic review to summarize available evidence and evaluate the evidence using the GRADE approach. Finally, the clinical specialist group produced recommendations for practice through a consensus procedure. THE EVIDENCE: The linked systematic review and meta-analysis included 9422 KOA patients, 61.1% of whom were women. The median mean age was 61.8 years. Compared with no treatment, acupuncture had beneficial effect on KOA in improving the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (moderate certainty evidence), and WOMAC pain (very low certainty evidence), WOMAC stiffness (low certainty evidence), and WOMAC function (low certainty evidence) subscale scores. Compared with usual care, acupuncture improved WOMAC stiffness subscale score (moderate certainty evidence). Subgroup analyses showed different effects in the improvement of WOMAC total scores by different durations of acupuncture and whether acupuncture combined with NSAIDs, but no difference between manual acupuncture and electroacupuncture was found. UNDERSTANDING THE RECOMMENDATIONS: Compared with no treatment, acupuncture is suggested to reduce pain, stiffness, and disfunction in KOA patients, ultimately improving the patient's health status. Acupuncture can be used as an alternative therapy when usual care is ineffective or there are adverse reactions so that patients can no longer continue the treatment. Manual acupuncture or electroacupuncture is suggested for 4-8 weeks to improve the health status of KOA. The patient's values and preferences should be considered when selecting acupuncture for KOA treatment.

The prognostic and clinicopathological significance of SLC7A11 in human cancers: a systematic review and meta-analysis.

Objective: It is of great importance to recognize bio-markers for cancer prognosis. However, the association between solute carrier family 7 member 11 (SLC7A11) and prognosis is still controversial. Therefore, we conducted this systematic review and meta-analysis to identify the prognostic and clinicopathological significance of SLC7A11 in human cancers. Methods: PubMed, Web of Science, Scopus, the Cochrane Library and Embase database were searched from database inceptions to March 19th 2022. Hand searches were also conducted in references. Prognosis and clinicopathological data were extracted and analyzed. Results: A total of 12 eligible studies with 1,955 patients were included. The results indicated that SLC7A11 expression is associated with unfavorable overall survival (OS), unfavorable recurrence-free survival (RFS) and unfavorable progression free survival (PFS). And SLC7A11 expression is also associated with more advanced tumor stage. Conclusions: SLC7A11 expression is associated with more unfavorable prognosis and more advanced tumor stage. Therefore, SLC7A11 could be a potential biomarker for human cancer prognosis.

An extension minimal important difference credibility item addressing construct proximity is a reliable alternative to the correlation item.

OBJECTIVES: Minimal important difference (MID), the smallest change or difference that patients perceive as important, aids interpretation of change in patient-reported outcome measure (PROM) scores. A credibility instrument that assesses the methodological rigor of an anchor-based MID includes one core item addressing the correlation between the PROM and the anchor. However, the majority of MID studies in the literature fail to report the correlation. To address this issue, we extended the anchor-based MID credibility instrument by adding an item addressing construct proximity as an alternative to the correlation item. STUDY DESIGN AND SETTING: Informed by an MID methodological survey, we added an alternative item-a subjective assessment of similarity of the constructs (i.e., construct proximity) between PROM and anchor-to the correlation item and generated principles for the assessment. We sampled 101 MIDs and analyzed the assessments performed by each pair of raters. By calculating weighted Cohen's kappa, we assessed the reliability of the assessments. RESULTS: Construct proximity assessment is based on the anticipated association between the anchor and PROM constructs: the closer the anticipated association, the higher the rating. Our detailed principles address the most frequently used anchors: transition ratings, measures of satisfaction, other PROMs, and clinical measures. The assessments showed acceptable agreement (weighted kappa 0.74, 95% CI 0.55-0.94) between raters. CONCLUSION: In the absence of a reported correlation coefficient, construct proximity assessment provides a useful alternative in the credibility assessment of anchor-based MID estimates.