Prevalence of frailty in patients with lower extremity peripheral arterial disease: A systematic review and meta-analysis

BackgroundIncreasing studies have reported on the prevalence of frailty in patients with peripheral artery disease (PAD). The aim of this systematic review and meta-analysis was to estimate the pooled prevalence of frailty in patients with lower extremity PAD.MethodsTwo authors systematically searched PubMed and Embase databases from their inception to August 8, 2022. Original articles that reported the prevalence of frailty in patients with lower extremity PAD were included. The prevalence of frailty in patients with lower extremity PAD was pooled using a random-effect model. Meta-regression, subgroup, and sensitivity analyses were conducted to explore the heterogeneity.ResultsEighteen studies reported on 17 articles involving 1,726,343 patients with lower extremity PAD were identified. The pooled prevalence of frailty in patients with lower extremity PAD was 49 % (95 % confidence interval [CI] 37–61 %), with significant heterogeneity between studies (I ² = 100 %, p < 0.001). Multivariable meta-regression showed that only the severity of PAD (coefficient 0.270; 95 % CI 0.017–0.523, p = 0.039) was significantly associated with the heterogeneity. In subgroup analysis, the pooled prevalence of frailty was higher in critical limb ischemia or chronic limb-threatening ischemia (54 %) than all PAD (48 %); the pooled prevalence of frailty was 64 %, 51 %, and 54 % for Modified Frailty Index-5, Modified Frailty Index-11, and Clinical Frailty Scale, respectively. The pooled prevalence of frailty appeared to be lower in male (39 %) than the female patients (47 %).ConclusionsThe prevalence of frailty was higher in patients with lower extremity PAD, suggesting frailty is a common condition. This finding highlights the significance of assessing frailty in patients with lower extremity PAD.     

Frailty for predicting all-cause mortality in elderly acute coronary syndrome patients: A meta-analysis

BackgroundFrailty has been identified as a risk factor for mortality in patients with acute coronary syndrome (ACS). This meta-analysis aimed to evaluate the association between frailty and all-cause mortality outcome in patients with ACS.MethodsPubmed and Embase databases were searched up to September 26, 2018 for the observational studies evaluating the association between frailty and all-cause mortality in elderly ACS patients. Outcome measures were in-hospital death, short-term all-cause mortality (≤6 months),and long-term all-cause mortality (≥12 months).The impact of frailty on all-cause mortality was summarized as hazard ratios (HR) with 95% confidence intervals (CI) for the frail versus nonfrail patients.ResultsA total of 9 cohort studies involving 2475 elderly ACS patients were included. Meta-analysis showed that ACS patients with frailty had an increased risk of in-hospital death (HR 5.49; 95% CI 2.19–13.77), short-term all-cause mortality (HR 3.56; 95% CI 1.96–6.48), and long-term all-cause mortality (HR 2.44; 95% CI 1.92–3.12) after adjustment for confounding factors. In addition, prefrailty was also associated with an increased all-cause mortality (HR 1.65; 95% CI 1.01–2.69).ConclusionsThis meta-analysis demonstrates that frailty independently predicts all-cause mortality in elderly ACS patients. Elderly ACS patients should be assessed the frailty status for improving risk stratification.     

Impact of frailty on all-cause mortality and major bleeding in patients with atrial fibrillation: A meta-analysis

BackgroundConflicting results have been reported on the impact of frailty on adverse outcomes in patients with atrial fibrillation (AF). The aim of this meta-analysis was to evaluate the impact of frailty on death and major bleeding in patients with AF.MethodsWe comprehensively searched PubMed and Embase databases until June 30, 2021 for the relevant studies that investigated the impact of frailty on all-cause mortality and major bleeding in AF patients. Pooled multivariable-adjusted risk ratio (RR) and 95% confidence intervals (CI) was estimated for the frail vs. nonfrail patients using a random-effect model.ResultsTen studies involving 97,413 patients with AF satisfied the inclusion criteria. The prevalence of frailty in patients with AF ranged between 5.9% and 89.5%. Meta-analysis indicated that frailty was associated with higher risk of all-cause mortality (RR 2.77; 95% CI 1.68–4.57) and major bleeding (RR 1.83; 95% CI 1.24–2.71). Subgroup analysis showed that the impact of frailty on all-cause mortality was consistently found in each subgroup.ConclusionFrailty independently predicts all-cause mortality and major bleeding in patients with AF. Determination of frailty status may play an important role in risk classification of AF patients. However. lack of standardized definition of frailty is the most important limitations of this meta-analysis.     

Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia

ObjectivesThe role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk.MethodsAn observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture.ResultsAmong 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p < 0.0001). Propensity score–weighted Cox proportional hazards models revealed that obtaining FUBCs was associated with reductions in all-cause (hazard ratio (HR) 0.629; 95% confidence interval (CI), 0.511–0.772; p < 0.0001) and attributable mortality (HR 0.628; 95% CI, 0.480–0.820; p 0.0007). Positive FUBCs were associated with increased all-cause mortality (49/228, 21%, vs. 110/885, 11%; p 0.0005) and attributable mortality (27/228, 12%, vs. 61/885, 7%; p 0.01) relative to negative FUBCs. Propensity score–weighted Cox proportional hazards models revealed that positive FUBCs were associated with increased all-cause (HR 2.099; 95% CI, 1.567–2.811; p < 0.0001) and attributable mortality (HR 1.800; 95% CI, 1.245–2.603; p 0.002). In a calibration analysis, a scoring system accurately identified patients at high risk of positive FUBCs.ConclusionsRates of positive FUBCs were high and identified patients at increased risk for mortality. Clinical variables can identify patients at high risk for positive FUBCs. FUBCs should be considered in the management of GNB.     

Association of objectively measured sleep with frailty and 5-year mortality in community-dwelling older adults

Study ObjectivesTo determine whether actigraphy-measured sleep was independently associated with risk of frailty and mortality over a 5-year period among older adults.MethodsWe used data from Waves 2 (W2) and 3 (W3) (2010–2015) of the National Social Life, Health and Aging Project, a prospective cohort of community-dwelling older adults born between 1920 and 1947. One-third of W2 respondents were randomly selected to participate in a sleep study, of whom N = 727 consented and N = 615 were included in the analytic sample. Participants were instructed to wear a wrist actigraph for 72 h (2.93 ± 0.01 nights). Actigraphic sleep parameters were averaged across nights and included total sleep time, percent sleep, sleep fragmentation index, and wake after sleep onset. Subjective sleep was collected via questionnaire. Frailty was assessed using modified Fried Frailty Index. Vital status was ascertained at the time of the W3 interview. W3 frailty/mortality status was analyzed jointly with a four-level variable: robust, pre-frail, frail, and deceased. Associations were modeled per 10-unit increase.ResultsAfter controlling for baseline frailty (robust and pre-frail categories), age, sex, education, body mass index, and sleep time preference, a higher sleep fragmentation index was associated with frailty (OR = 1.70, 95% CI: 1.02–2.84) and mortality (OR = 2.12, 95% CI: 1.09–4.09). Greater wake after sleep onset (OR = 1.24, 95% CI: 1.02–1.50) and lower percent sleep (OR = 0.41, 95% CI: 0.17–0.97) were associated with mortality.ConclusionsAmong community-dwelling older adults, actigraphic sleep is associated with frailty and all-cause mortality over a 5-year period. Further investigation is warranted to elucidate the physiological mechanisms underlying these associations.     

Dietary intakes of monounsaturated fatty acids and risk of mortality from all causes,cardiovascular disease and cancer: A systematic review and dose-response meta-analysis of prospective cohort studies

BackgroundFindings on the link between dietary intakes of monounsaturated fatty acids (MUFA) and risk of mortality are conflicting. This study aimed to summarize existing literature regarding the association between MUFA intake and risk of mortality from all causes, cardiovascular diseases (CVDs), and cancer.MethodsPubMed, Scopus, and ISI Web of Science was systematically searched up to December 2020. Prospective cohort studies which investigated MUFA intake in relation to mortality from all causes, CVD, or cancer were eligible for this systematic review. Publications that had reported risk ratios (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) as effect size, were considered.ResultsA total of 17 prospective cohort studies were included. These studies included 1022,321 participants aged ≥ 20 years in total, and 191,283 all-cause deaths, 55,437 CVD deaths, and 64,448 cancer deaths were totally reported. Combining 15 effect sizes from 11 studies, MUFA intake was inversely associated with risk of all-cause mortality (RR: 0.94; 95% CI: 0.90, 0.98; I² =55.5; P = 0.005). Based on 17 effect sizes from 11 studies, we found no significant association between MUFA intake and risk of CVD mortality (RR: 0.95; 95% CI: 0.89, 1.01; I² =37.0; P = 0.06). Combining 10 effect sizes from 6 studies, MUFA intake was not significantly associated with cancer mortality (RR: 0.99; 95% CI: 0.96, 1.03, I² =13.3%, P = 0.32). Also, an additional 5% of energy from MUFA was associated with a 3% reduced risk of all-cause mortality (RR: 0.97; 95%CI: 0.96, 0.98), but not with CVD (RR: 0.98; 95%CI: 0.95, 1.01) and cancer mortality (RR: 0.99; 95%CI: 0.97, 1.01).ConclusionsMUFA intake was found to be inversely associated with risk of all-cause mortality. However, no link was found between MUFA consumption and mortality from CVD or cancer.     

Anti-herpesvirus prophylaxis,pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis

BackgroundHerpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients.ObjectivesTo study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT.Data sourcesCochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries.Study eligibility criteriaRandomized controlled trials (RCTs).ParticipantsAdults with haematological malignancy undergoing allo-HCT.InterventionsAntiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent.MethodsRandom-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I²). The certainty of the evidence was appraised by GRADE.ResultsWe included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7–0.99; 15 trials, I² = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34–0.85; n = 15, I² = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2–0.43; n = 13, I² = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/– pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6–1.02; n = 8, I² = 0%), CMV disease (RR 0.47, 95% CI 0.23–0.97; n = 9, I² = 30%) and HSV disease (RR 0.41, 95% CI 0.24–0.67; n = 4, I² = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events.ConclusionsAntiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.     

A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients

ObjectivesTo describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance.MethodsCirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model.ResultsWe enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure–SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29–18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93–5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28–1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73–4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48–4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12–0.73; p 0.008).ConclusionsMDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.     

Long-Term Aspirin Use and 5-Year Survival in Healthy Adults: A Population-Based Cohort Study in South Korea

PurposeWe investigated whether long-term aspirin use is associated with 5-year all-cause mortality.Materials and MethodsParticipants were individuals aged ≥40 years who were registered in the 2010 sample cohort database of the National Health Insurance Service in South Korea. Aspirin users were divided into three groups: continuous users (2006–2010), previous users (2006–2009), and new users (2010). Individuals with a history of coronary artery disease and cerebrovascular disease were excluded. Five-year all-cause mortality was defined as mortality due to any cause from January 1, 2011 to December 31, 2015. Data were analyzed by multivariable Cox regression.ResultsIn total, 424444 individuals were included. Five-year all-cause mortality was 9% lower in continuous aspirin users than in unexposed individuals [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86–0.97; p=0.003]. Five-year all-cause mortality rates in the new aspirin users (HR: 1.00, 95% CI: 0.90–1.11; p=0.995) and previous aspirin users (HR: 1.01, 95% CI: 0.94–1.09; p=0.776) were not significantly different from that in unexposed individuals. In the 40–60-year age group, 5-year all-cause mortality in the continuous aspirin users was 24% lower (HR: 0.76, 95% CI: 0.64–0.90; p=0.002) than that in unexposed individuals. However, in the >60-year age group, there was no significant association between aspirin use and 5-year all-cause mortality (HR: 0.96, 95% CI: 0.90–1.02; p=0.199).ConclusionLong-term aspirin use is associated with reduced 5-year all-cause mortality in healthy adults, especially those aged <60 years.     

Comparison of influenza hospitalization outcomes among adults,older adults,and octogenarians: a US national population-based study

ObjectivesThis study sought to more fully elucidate the age-related trends in influenza mortality with a secondary goal of uncovering implications for treatment and prevention.MethodsIn this retrospective cohort analysis of data from the Nationwide Readmission Database, patients with influenza as a primary or secondary discharge diagnosis were separated into three age groups: 55 638 adults aged 20–64 years, 36 862 adults aged 65–79 years and 41 806 octogenarians aged ≥80 years. Propensity score (PS) weighting was performed to isolate age from other baseline differences. Crude and PS-weighted hazard ratios (HR) were calculated from the in-hospital all-cause 30-day mortality rate. Admission threshold bias was minimized by comparison of influenza with bacterial pneumonia mortality.ResultsAdults aged 20–64 years experienced higher in-hospital 30-day mortality compared with older adults aged 65–79 years (HR 0.66; 95% CI 0.55–0.79). Octogenarians had the highest mortality rate, but this was statistically insignificant compared with the adult cohort (HR 1.09; 95% CI 0.94–1.27). This trend was not explained by admission threshold bias: the 30-day mortality rate due to in-hospital bacterial pneumonia increased consistently with age (older adult HR 1.45; 95% CI 1.32–1.59; octogenarian HR 1.99; 95% CI 1.82–2.18).ConclusionsAdults aged 20–64 years and octogenarians were more likely to experience all-cause 30-day mortality during influenza hospitalization compared with older adults aged 65–79 years. These data emphasize the importance of prevention and suggest the need for more tailored treatment interventions based on risk stratification that includes age.     

Physical activity and all-cause mortality in Korean older adults

Background: The association between physical activity (PA) and all-cause mortality may be modulated by potential confounders.

Aim: To investigate the association between weekly PA and all-cause mortality in a population-based prospective study.

Subjects and methods: The study sample included Korean older adults aged 60?years and older who participated in baseline assessments (n?=?15 416) in 2008 and completed follow-up visits in 2011 (n?=?14,976). Primary outcome was 3-year all-cause mortality.

Results: Compared with sufficiently active individuals (with Hazard Ratio (HR)?=?1), completely inactive and insufficiently active individuals had a significantly higher risk of all-cause mortality (HR?=?2.086, 95% CI?=?1.639–2.655, p?<?0.00 and HR?=?1.644, 95% CI?=?1.013–2.668, p?=?0.044, respectively), even after adjustments for age and sex, health-related behaviour factors (i.e. smoking, alcohol intake and nutritional risk), cognitive impairment and components of frailty phenotype (i.e. involuntary weight loss, exhaustion and slowness). In addition, the inverse association between PA and all-cause mortality is differently modulated by potential confounders, including age, sex, smoking, depressive symptoms, cognitive impairment and involuntary weight loss.

Conclusion: PA was inversely and independently associated with all-cause mortality in Korean older adults.     

Impact of Statin Treatment Intensity after Endovascular Revascularization on Lower Extremity Peripheral Artery Disease

PurposeOnly a few Asian studies have discussed the impact of statin intensity on clinical outcomes in patients with peripheral artery disease (PAD). We aimed to investigate the clinical impact of statin intensity in patients with PAD after endovascular revascularization.Materials and MethodsFrom April 2009 to June 2019, 376 patients with lower extremity PAD treated with endovascular revascularization were enrolled. They were classified into three groups according to statin intensity: no-statin, low-to-moderate intensity (LMI), and high-intensity (HI). The primary outcomes were major adverse cardiovascular events (MACE) and major adverse limb events (MALE).ResultsDuring the 40-month follow-up, MACE occurred less frequently in the HI and LMI groups than the no-statin group (11.4% vs. 16.0% vs. 39%, p<0.001). In adjusted Cox models, the HI group had the fewest MACE [hazard ratio (HR): 0.447; 95% confidence interval (CI): 0.244–0.834; p=0.018] and MALE (HR: 0.360; 95% CI: 0.129–1.006; p=0.051) events, while the LMI group had fewer MACE (HR: 0.571; 95% CI: 0.326–1.0; p=0.050) events than the no-statin group. HI statin therapy was associated with better outcomes in terms of MALE (HR: 0.432; 95% CI: 0.223–0.837; p=0.003) than LMI statin therapy after inverse probability treatment weighting analysis.ConclusionHI and LMI statin use is associated with a significant reduction in MACE events than no-statin use. HI statin use was associated with better MALE outcomes than no-statin or LMI statin use.     

Mortality and clinical cure rates for pneumonia: a systematic review,meta-analysis,and trial sequential analysis of randomized control trials comparing bactericidal and bacteriostatic antibiotic treatments

BackgroundBactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia.ObjectivesWe performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome. Secondary outcomes included all-cause mortality, microbiological eradication, treatment failure, and relapse rates.Data sourcesPubMed, Cochrane Library, Embase, and MedRxivStudy eligibility criteriaRandomized control trials.ParticiapantsAdult patients with bacterial pneumonia treated with antibiotics in the community or in-hospital.InterventionsBacteriostatic versus bactericidal antibiotics.Assessment of risk of biasThe Cochrane Collaboration assessing risk of bias 2 tool.Methods of data synthesisData on dichotomous outcomes are presented as risk ratio (RR). A random-effects model with the generic Mantel–Haenszel method was used for integrating RRs for generalizability of findings. The I² method was used to assess the magnitude of variation secondary to heterogeneity.ResultsForty-three RCTs involving 10 752 patients met the eligibility criteria. The clinical cure rate (42 studies, 10 312 patients; RR: 1.02; 95% CI, 0.99–1.05; I²: 37%; TSA-adjusted CI, 0.99–1.05), all-cause mortality (25 studies, 8302 patients; RR: 1.07; 95% CI, 0.81–1.42; I²: 57%), microbiological eradication (24 studies, 2776 patients; RR: 1.00; 95% CI, 0.97–1.03; I²: 0%), treatment failure (31 studies, 7296 patients; RR: 0.96; 95% CI, 0.83–1.11; I²: 42%), and relapse rate (5 studies, 1111 patients; RR: 1.15; 95% CI, 0.50–2.63; I²: 0%) were similar between bactericidal and bacteriostatic antibiotic treatments.ConclusionsBactericidal agents are not associated with any statistical difference in clinical cure rates, mortality, microbiological eradication, treatment failure, or relapse rates compared with bacteriostatic antibiotics in the treatment of pneumonia.     

Comparison between frail and non-frail older adults’ gut microbiota: A systematic review and meta-analysis

BackgroundEmerging evidence suggests that the intestinal microbiota (IM) undergoes remodelling as we age, and this impacts the ageing trajectory and mortality in older adults. The aim was to investigate IM diversity differences between frail and non-frail older adults by meta-analysing previous studies.MethodsThe protocol of this systematic review with meta-analysis was registered on PROSPERO (CRD42021276733). We searched for studies comparing IM diversity of frail and non-frail older adults indexed on PubMed, Embase, Cochrane, and Web of Science in November 2021.ResultsWe included 11 studies with 1239 participants, of which 340 were meta-analysed. Frailty was defined by a variety of criteria (i.e. Fried Scale, European Consensus on Sarcopenia). There were no differences in the meta-analyses between the frail and non-frail groups for species richness index (SMD = −0.147; 95% CI = −0.394, 0.100; p = 0.243) and species diversity index (SMD = −0.033; 95% CI = −0.315, 0.250; p = 0.820). However, we identified almost 50 differences between frail and non-frail within the relative abundance of bacteria phyla, families, genera, and species in the primary studies.ConclusionsThe evidence to prove that there are differences between frail and non-frail IM diversity by meta-analysis is still lacking. The present results suggest that further investigation into the role of specific bacteria, their function, and their influence on the physiopathology of frailty is needed.     

Efficacy of early treatment with hydroxychloroquine in people with mild to moderate COVID-19: a systematic review and meta-analysis

IntroductionNo early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.Material and methodsRandomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.ResultsFive RCTs (n = 1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow-up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR = 0.80, 95% CI: 0.47–1.36, I² = 2%, 5 RCTs, low QoE), all-cause mortality (RR = 0.77, 95% CI: 0.16–3.68, I² = 0%, 5 RCTs, very low QoE), symptom resolution (RR = 0.94, 95% CI: 0.77–1.16, I² = 71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR = 1.02, 95% CI: 0.82–1.27, I² = 65%, 2 RCTs, low QoE). There was a larger non-significant increase of adverse events with hydroxychloroquine vs. controls (RR = 2.17, 95% CI: 0.86–5.45, I² = 92%, 5 RCTs, very low QoE).ConclusionsHydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.     

Thresholds of handgrip strength for all-cause,cancer, and cardiovascular mortality: A systematic review with dose-response meta-analysis

BackgroundWhile handgrip strength is associated with all-cause and cause-specific mortality, whether such associations are dose-dependent is largely unknown. Therefore, we conducted a systematic review on the dose-response relationship of handgrip strength with all-cause mortality, cancer, and cardiovascular mortality.MethodsThe data source included three electronic databases (PubMed/MEDLINE, Web of Science and Scopus) from inception to 8 February 2022. Prospective cohort studies of healthy adults with objective measures of handgrip strength were included. Two researchers independently screened studies, extracted data, and assessed risk of bias. We used estimates regarding handgrip strength categories to conduct a random forest model, and a two-stage random-effects hierarchical meta-regression model pooling study-specific estimates for dose-response relationship. Outcomes included all-cause, cancer, and cardiovascular mortality.ReultsForty-eight studies comprising 3,135,473 participants (49.6% women, age range 35–85 years) were included. Random forest models showed a significant inverse association between handgrip strength and all-cause and cause-specific mortality. Dose-response meta-analyses showed that higher levels of handgrip strength significantly reduced the risk of all-cause mortality within 26–50 kg (Higgin´s I² =45.7%) in a close-to-linear inverse fashion. Cancer and cardiovascular mortality displayed a trend towards a U-shaped association with a significant risk reduction between 16 and 33 kg (Higgin´s I² =77.4%), and a close-to-linear inverse shaped and significant risk reduction ranging from 24 to 40 kg (Higgin´s I² =79.7%) respectively.ConclusionThere is strong evidence for an association between lower handgrip strength with higher all-cause, cancer, and cardiovascular mortality risk. The dose-response relationship of handgrip strength substantially varies depending on the cause of mortality.     

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

AimDepression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta- analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty.MethodsTwo authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders.ResultsFrom 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07–47.10, I² = 94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66–7.35, k = 11), also after adjusting for potential confounders (OR = 2.64; 95%CI: 1.59–4.37, I² = 55%, k = 4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00–55.30, I² = 97%). People with depression were at increased odds of having frailty (OR = 4.07, 95%CI 1.93–8.55, k = 8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95–7.08, I² = 98%, k = 4), whilst in two studies frailty increased the risk of incident depression with an OR = 1.90 (95%CI 1.55–2.32, I² = 0%).ConclusionThis meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.     

Efficacy and harms of convalescent plasma for treatment of hospitalized COVID-19 patients: a systematic review and meta-analysis

IntroductionWe systematically reviewed benefits and harms of convalescent plasma (CP) in hospitalized COVID-19 patients.Material and methodsRandomized controlled trials (RCTs) and observational studies assessing CP effects on hospitalized, adult COVID-19 patients were searched until November 24, 2020. We assessed risk of bias (RoB) using Cochrane RoB 2.0 and ROBINS-I tools. Inverse variance random effect meta-analyses were performed. Quality of evidence was evaluated using GRADE methodology. Primary outcomes were all-cause mortality, clinical improvement, and adverse events.ResultsFive RCTs (n = 1067) and 6 cohorts (n = 881) were included. Three and 1 RCTs had some concerns and high RoB, respectively; and there was serious RoB in all cohorts. Convalescent plasma did not reduce all-cause mortality in RCTs of severe (RR = 0.60, 95% CI: 0.33–1.10) or moderate (RR = 0.60, 95% CI: 0.09–3.86) COVID-19 vs. standard of care (SOC); CP reduced all-cause mortality vs. SOC in cohorts (RR = 0.66, 95% CI: 0.49–0.91). Convalescent plasma did not reduce invasive ventilation vs. SOC in moderate disease (RR = 0.85, 95% CI: 0.47–1.55). In comparison to placebo + SOC, CP did not affect all-cause mortality (RR = 0.75, 95% CI: 0.48–1.16) or clinical improvement (HR = 1.07, 95% CI: 0.82–1.40) in severe patients. Adverse and serious adverse events were scarce, similar between CP and controls. Quality of evidence was low or very low for most outcomes.ConclusionsIn comparison to SOC or placebo + SOC, CP did not reduce all-cause mortality in RCTs of hospitalized COVID-19 patients. Convalescent plasma did not have an effect on other clinical or safety outcomes. Until now there is no good quality evidence to recommend CP for hospitalized COVID-19 patients.