Impact of frailty on all-cause mortality or major amputation in patients with lower extremity peripheral artery disease: A meta-analysis

BackgroundFrailty has been increasingly identified as a risk factor of adverse outcomes in vascular disease. However, its impact on the survival and amputation in patients with lower extremity peripheral artery disease (PAD) remains controversial. This meta-analysis aimed to examine the value of frailty in predicting all-cause mortality or major amputation in patients with lower extremity PAD.MethodsPubMed, Embase, Web of Sciences, and Scopus databases (up to April 7, 2022) were comprehensively searched to identify relevant studies that investigated the association between frailty and all-cause mortality or major amputation in patients with lower extremity PAD. The impact of frailty on adverse outcomes was summarized by pooling the fully adjusted hazard ratio (HR) with 95% confidence intervals (CI) using a random effect (DerSimonian-Laird) model.ResultsSeven studies reporting on eight articles that involved 122,892 patients were included. The prevalence of frailty ranged from 42% to 80% based on the frailty tool used. Meta-analysis showed that frailty was associated with an increased risk of 30-day all-cause mortality (HR 2.11; 95% CI 1.41–3.15; I² =47.6%, p = 0.148, Tau-squared=0.058) and long-term all-cause mortality (HR 1.86; 95% CI 1.25–2.76; I² =76.1%, p = 0.002, Tau-squared=0.118). However, no clear association was observed between frailty and major amputation (HR 1.07; 95% CI 0.83–1.36; I² =23.0%, p = 0.273, Tau-squared=0.019).ConclusionFrailty independently predicts short and long-term all-cause mortality but not major amputation in patients with lower extremity PAD. Frailty status may play an important role in risk stratification of lower extremity PAD.     

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.     

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.     

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.     

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.     

Frailty and mortality,disability and mobility loss in a Spanish cohort of older adults: The FRADEA Study

BackgroundOriginal Fried's frailty criteria have not demonstrated their prognostic validity of mortality, disability and mobility loss in European cohorts.ObjectivesTo analyze whether frailty implies increased risk of death, incident disability in basic (BADL) or instrumental (IADL) activities of daily living, or mobility impairment.DesignConcurrent cohort study.SettingAlbacete City, Spain.Participants993 participants over age 70 from the FRADEA Study.MeasurementsMortality, BADL and mobility using the Barthel Index, and IADL using the Lawton IADL Index, were recorded. BADL disability was defined as loss of the ability to perform bathing, grooming, dressing, toilet use, or feeding, while deterioration of mobility was defined as loss of ability to perform transfers, walk, or use stairs, and IADL disability as losing any of the activities included in the Lawton Index. The risk of presenting adverse events was determined by Cox and Kaplan–Meier proportional hazard analysis and logistic regression adjusted for age, sex, function, and comorbidity.ResultsMean follow-up was 534 days (SD 153), during which 105 participants (10.6%) died. Mean time to death was 363 days (SD 218), while 192 (25.4%) lost at least one BADL, 492 (60%) at least one IADL, and 222 (28.9%) lost mobility. Frail subjects had a greater adjusted risk of death (HR 5.5, CI 95% 1.5–20.2), of losing BADL (HR 2.5, CI 95% 1.3–4.8), of losing mobility (HR 2.7, CI 95% 1.5–5.0), and of losing IADL (HR 1.9, CI 95% 1.1–3.3) than non-frail patients.ConclusionFried's frailty criteria are associated with death, incident disability, and mobility impairment in a Spanish cohort of older adults.     

Clinical characteristics,management and in-hospital mortality of patients with coronavirus disease 2019 in Genoa,Italy

ObjectivesTo describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality.MethodsThis retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020.ResultsOverall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An ‘atypical’ presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04–1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07–6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004–1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality.ConclusionsCOVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.     

Survival trends from the Prader–Willi Syndrome Association (USA) 40-year mortality survey

PurposePrader–Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia and morbid obesity with increased cardiopulmonary and hyperphagia-related mortality. Survival trends in PWS were evaluated to assess the impact of modern interventions on mortality risk.MethodsThe Prader–Willi Syndrome Association (USA) 40-year mortality syndrome-specific database of 486 death reports was utilized to examine survival trends in PWS and cohort effects for recent deaths (years 2000–2015, N=331) relative to deaths prior to 2000 (N=94). Cox proportional hazards regression modeling was applied to generate log rank statistics and Kaplan–Meier curves examining sex, cause of death, and cohort.ResultsRisk for all-cause mortality in PWS was 1.5 (95% confidence interval (CI)=1.2–1.9) times higher for the Early than the Recent era cohort reflected in female cardiac failure (hazard ratio (HR)=1.8; 95% CI=1.3–2.6), pulmonary embolism (HR=6.1; 95% CI=1.7–22), and gastrointestinal-related (HR=3.2; 95% CI=1.1–7.4) causes. Accidental deaths in males increased in the Recent era cohort (HR=5.7; 95% CI=1.2–27.1), possibly due to enhanced weight management and mobility. Risk of death from respiratory failure was unchanged.ConclusionWe report measurable increases in survival effecting cardiovascular and gastrointestinal-related causes in PWS most likely attributable to earlier diagnosis and proactive interventions to prevent morbid obesity. More research is needed to address underlying vulnerability to respiratory failure, an unchanged mortality risk in PWS.     

Comparative safety of bedaquiline and delamanid in patients with multidrug resistant tuberculosis: A nationwide retrospective cohort study

Background/Purpose(s)Bedaquiline and delamanid were recently approved for multidrug resistant tuberculosis (MDR-TB). Bedaquiline carries a black box warning of increased risk of death compared to the placebo arm, and there is a need to establish the risks of QT prolongation and hepatotoxicity for bedaquiline and delamanid.MethodsWe retrospectively analyzed data of MDR-TB patients retrieved from the South Korea national health insurance system database (2014–2020) to assess the risks of all-cause death, long QT-related cardiac event, and acute liver injury associated with bedaquiline or delamanid, compared with conventional regimen. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Stabilized inverse probability of treatment weighting based on propensity score was used to balance characteristics between the treatment groups.ResultsOf 1998 patients, 315 (15.8%) and 292 (14.6%) received bedaquiline and delamanid, respectively. Compared with conventional regimen, bedaquiline and delamanid did not increase risk of all-cause death at 24-month (HR 0.73 [95% CI, 0.42–1.27] and 0.89 [0.50–1.60], respectively). Bedaquiline-containing regimen increased risk of acute liver injury (1.76 [1.31–2.36]), while delamanid-containing regimen increased risk of long QT-related cardiac events (2.38 [1.05–3.57]) within 6 months of treatment.ConclusionThis study adds to the emerging evidence refuting the higher mortality rate observed in the bedaquiline trial population. Association between bedaquiline and acute liver injury needs careful interpretation considering for other background hepatotoxic anti-TB drugs. Our finding on delamanid and long QT-related cardiac events suggest careful risk-benefit assessment in patients with pre-existing cardiovascular disease.     

Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: A meta-analysis

Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients.     

Primary care organisational interventions for secondary prevention of ischaemic heart disease: a systematic review and meta-analysis

BackgroundIschaemic heart disease (IHD) is the most common cause of death worldwide.AimTo determine the long-term impact of organisational interventions for secondary prevention of IHD.MethodSearches were conducted for randomised controlled trials of patients with established IHD, with long-term follow-up, of cardiac secondary prevention programmes targeting organisational change in primary care or community settings. A random-effects model was used and risk ratios were calculated.ResultsFive studies were included with 4005 participants. Meta-analysis of four studies with mortality data at 4.7–6 years showed that organisational interventions were associated with approximately 20% reduced mortality, with a risk ratio (RR) for all-cause mortality of 0.79 (95% confidence interval [CI] = 0.66 to 0.93), and a RR for cardiac-related mortality of 0.74 (95% CI = 0.58 to 0.94). Two studies reported mortality data at 10 years. Analysis of these data showed no significant differences between groups. There were insufficient data to conduct a meta-analysis on the effect of interventions on hospital admissions. Additional analyses showed no significant association between organisational interventions and risk factor management or appropriate prescribing at 4.7–6 years.ConclusionCardiac secondary prevention programmes targeting organisational change are associated with a reduced risk of death for at least 4–6 years. There is insufficient evidence to conclude whether this beneficial effect is maintained indefinitely.     

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.     

Accuracy of quick Sequential Organ Failure Assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for predicting mortality in hospitalized patients with suspected infection: a meta-analysis of observational studies

ObjectiveTo identify sensitivity, specificity and predictive accuracy of quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria to predict in-hospital mortality in hospitalized patients with suspected infection.MethodsThis meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group consensus statement for conducting and reporting the results of systematic review. PubMed and EMBASE were searched for the observational studies which reported predictive utility of qSOFA score for predicting mortality in patients with suspected or proven infection with the following search words: ‘qSOFA’, ‘q-SOFA’, ‘quick-SOFA’, ‘Quick Sequential Organ Failure Assessment’, ‘quick SOFA’. Sensitivity, specificity, area under receiver operating characteristic (ROC) curves with 95% confidence interval (CI) of qSOFA and SIRS criteria for predicting in-hospital mortality was collected for each study and a 2 × 2 table was created for each study.ResultsData of 406 802 patients from 45 observational studies were included in this meta-analysis. Pooled sensitivity (95% CI) and specificity (95% CI) of qSOFA ≥2 for predicting mortality in patients who were not in an intensive care unit (ICU) was 0.48 (0.41–0.55) and 0.83 (0.78–0.87), respectively. Pooled sensitivity (95% CI) of qSOFA ≥2 for predicting mortality in patients (both ICU and non-ICU settings) with suspected infection was 0.56 (0.47–0.65) and pooled specificity (95% CI) was 0.78 (0.71–0.83).ConclusionqSOFA has been found to be a poorly sensitive predictive marker for in-hospital mortality in hospitalized patients with suspected infection. It is reasonable to recommend developing another scoring system with higher sensitivity to identify high-risk patients with infection.     

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.     

Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies

ObjectiveTo provide a systematic review and meta-analysis of prospective, population-based cohort studies on the association of serum 25-hydroxyvitamin D (25(OH)D) and all-cause mortality.MethodsRelevant studies were identified by systematically searching Medline, EMBASE and ISI Web of Knowledge. Reported hazard ratios (HRs) for 25(OH)D categories were recalculated employing comprehensive trend estimation from summarized dose-response data and pooled in a random effects model meta-analysis.ResultsOverall, 12 original studies were included in the review and meta-analysis comprising 32,142 mainly elderly study participants with measured 25(OH)D of whom 6921 died during follow-up. An inverse association between 25(OH)D levels and all-cause mortality was found in all but two studies that was statistically significant in several of the individual studies. In meta-analysis, 25(OH)D levels were significantly inversely associated with all-cause mortality with a pooled HR of 0.92 (95% confidence interval: 0.89–0.95) for a 20 nmol/l increase in 25(OH)D levels.ConclusionIn this meta-analysis of prospective, population-based cohort studies, a 20 nmol/l increase in 25(OH)D levels was associated with an 8% lower mortality in the general elderly population. This agrees with results from meta-analyses on randomized controlled trials that found a decrease in mortality with vitamin D₃ supplementation of a comparable magnitude.     

Associations between loneliness and physical frailty in community-dwelling older adults: A systematic review and meta-analysis

ObjectivesOlder adults may be at increased risk of loneliness. Frailty is also common in older adults, however, associations between loneliness and frailty have been understudied. This systematic review and meta-analysis aimed to explore evidence on how loneliness and frailty are correlated.MethodsA systematic search of the literature was conducted using 4 electronic databases in February 2022 for any studies published in 2000 or later that provided cross-sectional or longitudinal associations between loneliness and physical frailty in community-dwelling older adults. A meta-analysis was attempted to combine data when possible.ResultsFrom 1386 studies identified by the initial search, 16 studies were included for this review. Standardized mean difference (SMD) meta-analysis based on mean loneliness score across 3 frailty groups provided by 6 cross-sectional studies showed that worse frailty status was significantly associated with a higher degree of loneliness (SMD between frail and robust, frail and prefrail, and prefrail and robust were 0.77 (95% confidence interval (CI)= 0.57–0.96), 0.37 (95%CI=0.25–0.50), and 0.30 (95%CI=0.20–0.40), respectively.) Meta-analyses combining cross-sectional data from 6 studies revealed that frailty was significantly associated with a higher risk of loneliness compared with robustness (3 studies: pooled OR=3.51, 95%CI=2.70–4.56 for frailty, pooled OR=1.88, 95%CI=1.57–2.25 for prefrailty) and compared with non-frailty (4 studies: pooled OR=2.05, 95%CI=1.76–2.39). A meta-analysis involving two longitudinal studies showed that baseline loneliness was associated with a significantly higher risk of worsening frailty (2 studies: pooled OR=1.41, 95%CI=1.16–1.72).ConclusionsThis systematic review and meta-analysis was the first, to our knowledge, to quantitatively demonstrate significant cross-sectional and longitudinal associations between loneliness and frailty in community-dwelling older adults.     

Current in-hospital management for patients with tuberculosis in a high-income country: a retrospective cohort study

ObjectivesIn Japan, most cases of tuberculosis (TB) occur among individuals aged 65 years or older. However, data on in-hospital adverse events (AEs) associated with TB management, especially in high-income nations with an ageing population, are scarce. The present study aimed to scrutinize the current TB unit practices, incidence of in-hospital AEs and predictors of in-hospital mortality.MethodsThis retrospective cohort study was conducted at a tertiary care centre in Tokyo, Japan from 2012 to 2017. Inpatients with the diagnosis of TB and aged >18 years were included. Quality of in-hospital care and factors associated with in-hospital mortality were investigated using multivariate logistic regression analysis.ResultsIn total, 448 patients were enrolled. The in-hospital mortality rate was 16.7% (75/448). Miliary/disseminated TB was common (59/448, 13.2%), especially in those who died (17/75, 22.7%). Factors independently associated with in-hospital mortality were a low Karnofsky performance status score on admission (score: 40-10, adjusted odds ratio (aOR) 25.65, 95% CI 5.63–116.92 and score: 70-50, aOR 9.47, 95% CI 2.07–43.3), age over 89 years (aOR 3.68, 95% CI 1.08–12.46), Charlson Co-morbidity Index >5 (aOR 3.56, 95% CI 1.37–9.21), development of any health-care-associated infection (aOR 2.95, 95% CI 1.35–6.41), and development of any drug-related AE leading to discontinuation of anti-TB agents (seven patients were unable to resume treatment with anti-TB agents before death) (aOR 2.29, 95% CI 1.02–5.11).ConclusionsIn-hospital AEs (i.e. health-care-associated infection and drug-related AEs), as well as patient-related variables, were associated with in-hospital mortality among TB patients.     

Changes in Cardiovascular Health Status and Risk of Sudden Cardiac Death in Older Adults

PurposeCardiovascular health (CVH) status is associated with several cardiovascular outcomes; however, correlations between changes in CVH status and risk of sudden cardiac death (SCD) are unknown. We aimed to evaluate associations between changes in CVH status and risk of SCD and all-cause death in older adults.Materials and MethodsWe used data from the Korea National Health Insurance Service-Senior cohort database (2005–2012). Six metrics from the American Heart Association (smoking, body mass index, physical activity, blood pressure, total cholesterol, and fasting blood glucose) were used to calculate CVH scores. Changes in CVH status between two health checkups were categorized as low to low, low to high, high to low, and high to high.ResultsWe included 105200 patients whose CVH status for an initial and follow-up health checkup (2-year interval) was available. During a median of 5.2 years of follow-up after a second health checkup, 688 SCDs occurred. Compared to patients with a persistent low CVH status, those with a consistently high CVH status had a reduced risk of SCD [adjusted hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.56–0.86] and all-cause death (adjusted HR, 0.74; 95% CI, 0.69–0.78). The risk of all-cause death followed similar trends. However, an inconsistent linear relationship was observed for changes in CVH status and the risk of SCD, but not of all-cause death.ConclusionMaintaining a high CVH status was associated with future risks of SCD and all-cause death among an older adult population.     

Is obesity associated with short-term revision after total knee arthroplasty? An analysis of 121,819 primary procedures from the Dutch Arthroplasty Register

BackgroundThe prevalence of obesity is increasing. The association with knee osteoarthritis is well documented, resulting in the population requesting total knee arthroplasty (TKA) for invalidating symptoms to be heavier in nature. The purpose of the current analysis was to assess the association between preoperative body mass index (BMI) and short-term revision rate after TKA. The secondary aim was to investigate the influence of implant fixation method on the association between BMI and survivorship.MethodsThis is a retrospective analysis of prospectively collected registry data (Dutch Arthroplasty Register; LROI). All primary TKA procedures in patients >18 years of age with registered BMI were selected (n = 121,819). Non-obese patients (BMI 18–25) were compared with overweight (BMI 25–30) and class I–III obese (BMI >30, >35, >40) patients. Crude all-cause revision rates were calculated using competing risk analysis. Adjusted hazard ratios (HRs) were determined with Cox multivariable regression analyses for all-cause, septic and aseptic revision and secondary patellar resurfacing.ResultsRevision rates were 3.3% for non-obese patients, 3.5% for overweight patients, 3.7% for class I obese patients, 3.6% for class II obese patients and 3.7% for class III obese patients. Class III obese patients had a significant higher risk for septic revision compared with non-obese patients (HR 1.53, 95% confidence interval (CI) 1.06–2.22). Class I obese patients had a higher risk for secondary patellar resurfacing (HR 1.52, 95% CI 1.12–2.08). All-cause and aseptic revision rates were similar between BMI groups.ConclusionsObesity appeared to be associated with some short-term revision risks after TKA, but was not associated with an overall increase in revision rate.     

Good glycaemic control is associated with a better prognosis in breast cancer patients with type 2 diabetes mellitus

Although diabetes mellitus (DM) is one of the risk factors associated with increased breast cancer (BC) mortality, the effects of glycaemic control on the prognosis of BC have not been thoroughly evaluated. This retrospective study aimed to evaluate the relationship between glycaemic control and BC prognosis and to determine an optimal target of glycaemic control for BC patients with diabetes. We included 2812 stage 0–3 BC women, of whom 145 were diabetic and were 2667 non-diabetic. In those with diabetes, a mean haemoglobin A1C (HbA1C) <?7% (n?=?77) was defined as well-controlled diabetes, while a mean HbA1C >?9% (n?=?16) was defined as poorly controlled diabetes. All of the BC populations were followed from the date on which BC was diagnosed until 31 December 2015. Cox regression analysis was performed to estimate the adjusted hazards for all-cause mortality and BC-specific mortality. After controlling for the baseline and BC-related confounders, the adjusted hazard ratio (HR) for all-cause mortality and the HR for BC-specific mortality were 3.65 (95% confidence interval [95% CI] 1.13–11.82) and 8.37 (95% CI 1.90–36.91), respectively, for poorly controlled diabetic women and non-DM women. However, for the diabetic women with good glycaemic control, the HRs of all-cause mortality and BC-specific mortality were not significantly different (HR 0.91, 95% CI 0.42–1.01; HR 0.77, 95% CI 0.18–3.32, respectively) from those for both mortalities in non-DM patients. For moderate controlled diabetic women, the HRs for all-cause mortality and BC-specific mortality were 1.95 (95% CI 0.89–4.27) and 3.55 (95% CI 1.369–9.30), respectively. This pilot and retrospective cohort study reveals a relationship between glycaemic control and BC prognosis in diabetic women. In addition, well-controlled HbA1C, with maintained mean HbA1C values under 7%, may be associated with a better progression outcome of BC.