All-cause Mortality In People Research Articles

The association between disability and all-cause mortality in low-income and middle-income countries: a systematic review and meta-analysis

There are 1·3 billion people with disabilities globally. On average, they have poorer health than their non-disabled peers, but the extent of increased risk of premature mortality is unknown. We aimed to systematically review the association between disability and mortality in low-income and middle-income countries (LMICs). We searched MEDLINE, Global Health, PsycINFO, and EMBASE from Jan 1, 1990 to Nov 14, 2022. Longitudinal epidemiological studies in any language with a comparator group that measured the association between disability and all-cause mortality in people of any age were eligible for inclusion. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to calculate the pooled hazard ratio (HR) for all-cause mortality by disability status. We then conducted meta-analyses separately for different impairment and age groups. We identified 6146 unique articles, of which 70 studies (81 cohorts) were included in the systematic review, from 22 countries. There was variability in the methods used to assess and report disability and mortality. The meta-analysis included 54 studies, representing 62 cohorts (comprising 270 571 people with disabilities). Pooled HRs for all-cause mortality were 2·02 (95% CI 1·77-2·30) for people with disabilities versus those without disabilities, with high heterogeneity between studies (τ2=0·23, I2=98%). This association varied by impairment type: from 1·36 (1·17-1·57) for visual impairment to 3·95 (1·60-9·74) for multiple impairments. The association was highest for children younger than 18 years (4·46, [3·01-6·59]) and lower in people aged 15-49 years (2·45 [1·21-4·97]) and people older than 60 years (1·97 [1·65-2·36]). People with disabilities had a two-fold higher mortality rate than people without disabilities in LMICs. Interventions are needed to improve the health of people with disabilities and reduce their higher mortality rate. UK National Institute for Health and Care Research; and UK Foreign, Commonwealth and Development Office.

Real-world Use and Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors in Adults With Diabetes and Heart Failure: A Population-level Cohort Study in Alberta, Canada

ObjectivesSince 2016, clinical guidelines have recommended sodium-glucose cotransporter-2 inhibitors (SGLT2is) for people with type 2 diabetes with heart failure. We examined SGLT2i dispensation, factors associated with dispensation, and heart failure hospitalization and all-cause mortality in people with diabetes and heart failure. MethodsThis retrospective, population-based cohort study identified people with diabetes and heart failure between January 1, 2014, and December 31, 2017, in Alberta, Canada, and followed them for a minimum of 3 years for SGLT2i dispensation and outcomes. Multivariate logistic regression assessed the factors associated with SGTL2i dispensation. Propensity scores were used with regression adjustment to estimate the effect of SGLT2i treatment on heart failure hospitalization. ResultsAmong 22,025 individuals with diabetes and heart failure (43.4% women, mean age 74.7±11.8 years), only 10.2% were dispensed an SGLT2i. Male sex, age <65 years, a higher baseline glycated hemoglobin, no chronic kidney disease, presence of atherosclerotic cardiovascular disease, and urban residence were associated with SGLT2i dispensation. Lower heart failure hospitalization rates were observed in those with SGLT2i dispensation (548.1 per 100 person-years) vs those without (813.5 per 1,000 person-years; p<0.001) and lower all-cause mortality in those with an SGLT2i than in those without (48.5 per 1,000 person-years vs 206.1 per 1,000 person-years; p<0.001). Regression adjustment found SGLT2i therapy was associated with a 23% reduction in hospitalization. ConclusionsSGLT2is were dispensed to only 10% of people with diabetes and established heart failure, underscoring a significant care gap. SGLT2i use was associated with a real-world reduction in heart failure hospitalization and all-cause death. This study highlights an important opportunity to optimize SGLT2i use.

Exercise-based cardiac rehabilitation for adults with heart failure.

People with heart failure experience substantial disease burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous 2018 Cochrane review reported that exercise-based cardiac rehabilitation (ExCR) compared to no exercise control shows improvement in HRQoL and hospital admission amongst people with heart failure, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane review include the following: (1) most trials were undertaken in patients with heart failure with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with heart failure with preserved (≥ 45%) ejection fraction (HFpEF) were under-represented; and (2) most trials were undertaken in a hospital or centre-based setting. To assess the effects of ExCR on mortality, hospital admission, and health-related quality of life of adults with heart failure. We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and Web of Science without language restriction on 13 December 2021. We also checked the bibliographies of included studies, identified relevant systematic reviews, and two clinical trials registers. We included randomised controlled trials (RCTs) that compared ExCR interventions (either exercise only or exercise as part of a comprehensive cardiac rehabilitation) with a follow-up of six months or longer versus a no-exercise control (e.g. usual medical care). The study population comprised adults (≥ 18 years) with heart failure - either HFrEF or HFpEF. We used standard Cochrane methods. Our primary outcomes were all-cause mortality, mortality due to heart failure, all-cause hospital admissions, heart failure-related hospital admissions, and HRQoL. Secondary outcomes were costs and cost-effectiveness. We used GRADE to assess the certainty of the evidence. We included 60 trials (8728 participants) with a median of six months' follow-up. For this latest update, we identified 16 new trials (2945 new participants), in addition to the previously identified 44 trials (5783 existing participants). Although the existing evidence base predominantly includes patients with HFrEF, with New York Heart Association (NYHA) classes II and III receiving centre-based ExCR programmes, a growing body of trials includes patients with HFpEF with ExCR undertaken in a home-based setting. All included trials employed a usual care comparator with a formal no-exercise intervention as well as a wide range of active comparators, such as education, psychological intervention, or medical management. The overall risk of bias in the included trials was low or unclear, and we mostly downgraded the certainty of evidence of outcomes upon GRADE assessment. There was no evidence of a difference in the short term (up to 12 months' follow-up) in the pooled risk of all-cause mortality when comparing ExCR versus usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.71 to 1.21; absolute effects 5.0% versus 5.8%; 34 trials, 36 comparisons, 3941 participants; low-certainty evidence). Only a few trials reported information on whether participants died due to heart failure. Participation in ExCR versus usual care likely reduced the risk of all-cause hospital admissions (RR 0.69, 95% CI 0.56 to 0.86; absolute effects 15.9% versus 23.8%; 23 trials, 24 comparisons, 2283 participants; moderate-certainty evidence) and heart failure-related hospital admissions (RR 0.82, 95% CI 0.49 to 1.35; absolute effects 5.6% versus 6.4%; 10 trials; 10 comparisons, 911 participants; moderate-certainty evidence) in the short term. Participation in ExCR likely improved short-term HRQoL as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire (lower scores indicate better HRQoL and a difference of 5 points or more indicates clinical importance; mean difference (MD) -7.39 points, 95% CI -10.30 to -4.77; 21 trials, 22 comparisons, 2699 participants; moderate-certainty evidence). When pooling HRQoL data measured by any questionnaire/scale, we found that ExCR may improve HRQoL in the short term, but the evidence is very uncertain (33 trials, 37 comparisons, 4769 participants; standardised mean difference (SMD) -0.52, 95% CI -0.70 to -0.34; very-low certainty evidence). ExCR effects appeared to be consistent across different models of ExCR delivery: centre- versus home-based, exercise dose, exercise only versus comprehensive programmes, and aerobic training alone versus aerobic plus resistance programmes. This updated Cochrane review provides additional randomised evidence (16 trials) to support the conclusions of the previous 2018 version of the review. Compared to no exercise control, whilst there was no evidence of a difference in all-cause mortality in people with heart failure, ExCR participation likely reduces the risk of all-cause hospital admissions and heart failure-related hospital admissions, and may result in important improvements in HRQoL. Importantly, this updated review provides additional evidence supporting the use of alternative modes of ExCR delivery, including home-based and digitally-supported programmes. Future ExCR trials need to focus on the recruitment of traditionally less represented heart failure patient groups including older patients, women, and those with HFpEF.

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non-AIDS-related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long-term follow-up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all-cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug-based combination therapy and with medical follow-up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T-cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3 ). Primary outcomes included all-cause mortality, AIDS-defining events and non-communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T-cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow-up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T-cell count) and older age were risk factors for all-cause mortality. We also found that older age, male sex and higher baseline CD4 T-cell count were associated with lower CD4 count increase following therapy initiation. Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow-up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

Weight Loss Induced by Antiobesity Medications and All-Cause Mortality Among Patients With Knee or Hip Osteoarthritis.

The current guidelines recommend weight loss for patients with overweight or obesity and knee or hip osteoarthritis (OA); however, there is a paucity of data on the relation of weight loss to death among patients with OA. We aimed to examine the relation of the rate of weight loss induced by antiobesity medications over one year to all-cause mortality among patients with overweight or obesity and knee or hip OA. Using the IQVIA Medical Research Database, we identified people with overweight or obesity and knee or hip OA. We emulated analyses of a hypothetical target trial to assess the effect of slow-to-moderate (2%-10%) or fast (≥10%) weight loss induced by the initiation of antiobesity medications within one year on all-cause mortality and secondary outcomes over five years' follow-up. Among 6,524 participants, the five-year all-cause mortality rates were 5.3%, 4.0%, and 5.4% for weight gain or stable, slow-to-moderate weight loss, and fast weight loss arms, respectively. Compared with the weight gain or stable arm, hazard ratios of all-cause mortality were 0.72 (95% confidence interval [CI] 0.56-0.92) for the slow-to-moderate weight loss arm and 0.99 (95% CI 0.67-1.44) for the fast weight loss arm. We found dose-response protective effects of weight loss on incident hypertension, type 2 diabetes, and venous thromboembolism but a slightly higher risk of cardiovascular disease, albeit not statistically significant, in the fast rate of weight loss arm than in the weight gain or stable arm and no significant relations of weight loss to the risk of cancer. In this population-based study, a slow-to-moderate, but not fast, rate of weight loss induced by antiobesity medications is associated with a lower risk of all-cause mortality in people with overweight or obesity and knee or hip OA.

Severe mental illness, race/ethnicity, multimorbidity and mortality following COVID-19 infection: nationally representative cohort study.

The association of COVID-19 with death in people with severe mental illness (SMI), and associations with multimorbidity and ethnicity, are unclear. To determine all-cause mortality in people with SMI following COVID-19 infection, and assess whether excess mortality is affected by multimorbidity or ethnicity. This was a retrospective cohort study using primary care data from the Clinical Practice Research Database, from February 2020 to April 2021. Cox proportional hazards regression was used to estimate the effect of SMI on all-cause mortality during the first two waves of the COVID-19 pandemic. Among 7146 people with SMI (56% female), there was a higher prevalence of multimorbidity compared with the non-SMI control group (n = 653 024, 55% female). Following COVID-19 infection, the SMI group experienced a greater risk of death compared with controls (adjusted hazard ratio (aHR) 1.53, 95% CI 1.39-1.68). Black Caribbean/Black African people were more likely to die from COVID-19 compared with White people (aHR = 1.22, 95% CI 1.12-1.34), with similar associations in the SMI group and non-SMI group (P for interaction = 0.73). Following infection with COVID-19, for every additional multimorbidity condition, the aHR for death was 1.06 (95% CI 1.01-1.10) in the SMI stratum and 1.16 (95% CI 1.15-1.17) in the non-SMI stratum (P for interaction = 0.001). Following COVID-19 infection, patients with SMI were at an elevated risk of death, further magnified by multimorbidity. Black Caribbean/Black African people had a higher risk of death from COVID-19 than White people, and this inequity was similar for the SMI group and the control group.

Adherence to the Mediterranean diet regulates the association between osteopenia and the risk of all-cause mortality in general population

BackgroundThis study aimed to explore the association of adherence to the Mediterranean diet (MD), osteopenia and the risk of all-cause mortality in general population.MethodsThis retrospective cohort study included 5452 participants ≥ 50 years from the National Health and Nutrition Examination Survey (NHANES). The associations of osteopenia and adherence to the MD with all-cause mortality, as well as the interaction and moderating effects between the osteopenia and adherence to the MD on the all-cause mortality, were explored via univariate and multivariable Cox proportional hazards models.ResultsThe follow-up was from October 1, 2006, to December 31, 2019. The median survival time of patients was 81 months. In total, 4724 people were survived and 728 were dead. Osteopenia was associated with increased risk of all-cause mortality in people [hazards ratio (HR) = 1.57, 95% confidence interval (CI) 1.23–1.99]. No significant risk of all-cause mortality was found in people with high adherence to the MD compared with those with low adherence to the MD (P > 0.05). Compared to subjects with no osteopenia who had high adherence to the MD, osteopenia people who had high adherence to the MD (HR = 1.52, 95% CI 1.17–1.98) or low adherence to the MD (HR = 1.81, 95% CI 1.23–2.66) were at increased risk of all-cause mortality after adjusting for confounding factors. The relationship between osteopenia and the risk of all-cause mortality was decreased in those with high adherence to the MD (HR = 1.57, 95% CI 1.17–2.11) compared with those with low adherence to the MD (HR = 1.62, 95% CI 1.08–2.41) after adjusting for confounding factors.ConclusionThe adherence to the MD regulated the association between osteopenia and the risk of all-cause mortality, which suggested the importance of adherence to the MD in those with osteopenia, and the MD could be advocated in general people.

Associations of modern initial antiretroviral therapy regimens with all-cause mortality in people living with HIV in resource-limited settings: a retrospective multicenter cohort study in China

Despite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others [including darunavir, raltegravie, elvitegravir and rilpivirine]) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.

Association of retinopathy with risk of all-cause and specific-cause mortality in the National Health and Nutrition Examination Survey, 2005 to 2008.

This study aimed to elucidate the relationship between retinopathy status or severity and the all-cause and specific-cause mortality risk based on the updated National Health and Nutrition Examination Survey (NHANES) database and 2019 Public Access Link mortality file. In this prospective cohort study, a total of 6,797 participants aged over 40 years based on NHANES 2005-2008 were analyzed. The severity of retinopathy was classified into 4 grades-no retinopathy, mild non-proliferative retinopathy (NPR), moderate to severe NPR, and proliferative retinopathy (PR). Multiple covariate-adjusted Cox proportional hazards regression models and Fine and Gray competing risk regression models were used to assess the all-cause and cause-specific mortality risks, respectively. The propensity score matching (PSM) approach was also applied additionally to adequately balance between-group covariates to validate our findings. A final total of 4,808 participants representing 18,282,772 United States (US) non-hospitalized participants were included for analysis, 50.27% were male (n = 2,417), 55.32% were non-hispanic white (n = 2,660), and mean [SE] age, 56.10 [0.40] years. After a median follow-up of 12.24 years (interquartile range, 11.16-13.49 years), 1,164 participants died of all-cause mortality, of which 941 (80.84%) died without retinopathy and 223 (19.16%) died with retinopathy at baseline. The presence of retinopathy was associated with increased all-cause mortality, cardiovascular disease (CVD), and diabetes mellitus (DM)-specific mortality, and the results remain consistent after PSM. Severity analysis showed that only mild NPR was associated with an increased all-cause mortality risk (hazard ratio (HR) = 2.01; 95% confidence interval (CI), 1.00-4.03), while increased CVD and DM-specific mortality risk were associated with all grades of retinopathy and were exponentially greater with increasing retinopathy severity, and the trend test was also significant (P for trend 0.004 and 0.04, respectively). Our findings suggest that the diagnosis of retinopathy is an independent risk factor for all-cause mortality in people over 40 years old. Retinopathy grading is significantly associated with the survival risk of patients with CVD or DM, it can be a valuable predictor in the stratified management and risk warning of CVD or DM patients, as well as in the monitoring of systemic vasculopathy status.

Ceramides as risk markers for future cardiovascular events and all-cause mortality in long-standing type 1 diabetes.

Ceramides are lipid molecules involved in inflammation-related signaling. Recent studies have shown that higher amounts of specific circulating ceramides and their ratios are associated with future development of cardiovascular (CV) disease (CVD). We examined the associations between serum ceramide levels with CVD, kidney failure, and all-cause mortality in individuals with longstanding type 1 diabetes (T1D). We included 662 participants with T1D and 6-year follow-up, with a mean age of 55 years and mean diabetes duration of 33 years. Baseline serum samples were analyzed using liquid chromatography-mass spectrometry. Six predefined ceramide levels were measured, and predefined ratios were calculated. Adjusted Cox regression analyses on ceramide levels in relation to future CV events (CVE), kidney failure and all-cause mortality were performed, with and without adjustment for age, sex, BMI, LDL, triglycerides, systolic blood pressure, HbA1C, history of CVD, smoking status, statin use, eGFR and UAER. The ceramide ratio cer(d18:1/18:0)/cer(d18:1/24:0) was significantly associated with risk of CVE (HR = 1.33, P = 0.01) and all-cause mortality (HR = 1,48, P = 0.01) before and after adjustments. All five investigated ceramide ratios were associated with kidney failure, before adjusting for the kidney markers eGFR and UAER. In this study we demonstrate specific ceramides and ratios associated with 6-year cardiovascular risk and all-cause mortality in a T1D cohort. This highlights the strength of ceramide association with vascular complications and presents a new potential tool for early risk assessment if validated in other cohorts.

Pre- and post-diagnostic dairy intake in relation to recurrence and all-cause mortality in people with stage I-III colorectal cancer.

Higher dairy consumption is associated with a lower risk of colorectal cancer (CRC), but no studies thus far have investigated its relation with recurrence in CRC. Few studies have investigated total dairy in relation to mortality in CRC, and yielded inconsistent results. In this prospective cohort study, people newly diagnosed with stage I-III CRC filled out a food frequency questionnaire at diagnosis (n = 1812) and six months after diagnosis (n = 1672). We examined associations between pre- and post-diagnostic intake of total dairy, low-fat dairy, high-fat dairy, milk, yoghurt, and cheese with recurrence and all-cause mortality using multivariable Cox proportional hazard models and restricted cubic splines (RCS). A total of 176 recurrences and 301 deaths occurred during a median follow-up of 3.0 and 5.9years, respectively. Before diagnosis, a higher low-fat dairy intake was associated with a lower risk of recurrence (HRQ4vsQ1: 0.42, 95% CI 0.26-0.67; PRCS: 0.008) and all-cause mortality (HRQ4vsQ1: 0.58, 95% CI 0.41-0.81; PRCS < 0.001), whereas a higher high-fat dairy consumption tended to be associated with an increased all-cause mortality risk (HRQ4vsQ1: 1.41, 95% CI 0.98-2.01; PRCS: 0.030). After diagnosis, only the associations between low- and high-fat dairy in relation to all-cause mortality remained. This study demonstrated that higher pre- and post-diagnostic intakes of low-fat dairy were associated with a reduced all-cause mortality risk in people with stage I-III CRC, whereas higher intakes of high-fat dairy were associated with an increased all-cause mortality risk. Also, a higher pre-diagnostic low-fat dairy intake was associated with a reduced risk of recurrence. Clinical Trials.gov identifier: NCT03191110.

489-P: Abnormal Combined Point-of-Care-Device DPN-Check and SUDOSCAN Results Predict All-Cause Mortality in People with Diabetes

Aims: Diabetic peripheral neuropathy (DPN) has been associated with increased mortality; however, data is not available for objectively diagnosed DPN using point-of-care-devices (POCDs). We therefore examined the predictive validity of POCD-diagnosed DPN for increased mortality in a prospective study. Methods: A total of 245 consecutive people with diabetes (17 type 1 diabetes, age 62.3+14.3) attending retinal-screening had all annual review health checks in a One-stop Screening Service. DPN assessments included Toronto Clinical Neuropathy Score (TCNS) evaluation, 10g-monofilament test(10g-MFT) and two validated, objective POCDs, DPN-Check (handheld device measuring sural nerve conduction velocity/amplitude), and SUDOSCAN (measuring sudomotor function). Mortality data was collected at 7-year follow-up. Kaplan-Meier survival curves and Cox-proportional hazards models were generated to assess associations of DPN measures with all-cause mortality. Results: At follow-up, 52 [21.2% (SE 6.8%)] had died. Those who died were older at screening [72.4 (10.9) vs 59.6 (13.9) years; (p&amp;lt;0.001)]. The prevalence of screen-detected DPN was 12.6% (SE 4.4%) for 10g-MFT, 27.7% (SE 8.2%) for TCNS and 33.4% (SE 9.1%) for combined POCDs. In crude Kaplan-Meier analyses all-cause mortality risk was greater in patients with abnormal TCNS (p&amp;lt;0.001) and POCDs (p&amp;lt;0.001) but was equivalent in patients with normal or abnormal 10g-MFT (p=0.21). After adjusting for age, HbA1c and Total Cholesterol, only abnormal POCDs was significantly associated with all-cause mortality [HR 1.18 (p=0.04, 95%CI 1.00:1.39) vs TCNS [HR 1.33 (p=0.06, 95%CI 0.99:1.78)]. Conclusions: This is the first prospective study showing abnormal combined DPN-Check and SUDOSCAN results predict all-cause mortality after adjusting for other risk factors. However, 10g-MFT and TCNS that diagnose DPN late did not predict all-cause mortality. Disclosure M.Goonoo: None. D.Selvarajah: None. G.P.Sloan: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH &amp; Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter &amp; Gamble, Novo Nordisk, Berlin-Chemie AG.

Liver fibrosis markers and all cause mortality in people with type 2 diabetes: A population based study (The Ayrshire Diabetes Outcomes Cohort (ADOC) Study).

To describe the distribution of the biomarker scores Fibrosis-4 (FIB4), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI), and the associations between risk categories and all-cause mortality. This was a retrospective cohort study of 12 589 patients, with follow-up from January 2012 until November 2021. The cut-off points used to identify low risk were: FIB4 <1.3 if aged <65 years or <2.0 if aged ≥65 years; NFS < -1.455 if aged <65 years or <0.12 if aged ≥ 65 years; APRI <1 (independent of age). High-risk cut-off points were FIB4 >2.67, NFS >0.676 and APRI ≥1 (all independent of age). Multivariable Cox regression analysis was performed to assess the association between liver fibrosis scores and all-cause mortality. The mean ± standard deviation age was 65.2 ± 12.1 years, 54.5% were men and the median (interquartile range) diabetes duration was 5.8 (2.8-9.3) years. The prevalence of high-risk categories was 6.1% for FIB4, 23.5% for NFS and 1.6% for APRI. During a median follow-up of 9.8 years, 3925 patients (31.1%) died, resulting in a crude mortality rate of 40.4 per 1000 person-years. The overall adjusted all-cause mortality hazard ratios (95% confidence intervals [CIs]) in the high- compared with low-fibrosis-risk groups were 3.69 (1.95-2.75) for FIB4, 2.32 (2.88-4.70) for NFS, and 3.92 (2.88-5.34) for APRI. Stratified adjusted all-cause mortality hazard ratios for individuals under 65 years and people over 65 years of age at cohort entry were 3.89 (95% CI 2.99-5.05) and 1.44 (95% CI 1.28-1.61) for FIB4, 2.50 (95% CI 1.89-3.18) and 1.35 (95% CI 1.24-1.48) for NFS and 3.74 (95% CI 2.73-5.14) and 1.64 (95% CI 1.24-2.17) for APRI. All three fibrosis risk scores were positively associated with all-cause mortality in people with type 2 diabetes, with higher relative risks in younger than older people. Effective interventions are required to minimize excess mortality in people at high risk of liver fibrosis.

Efficacy and safety of N-acetylcysteine for preventing post-intravenous contrast acute kidney injury in patients with kidney impairment: a systematic review and meta-analysis.

N-Acetylcysteine (NAC) may confer protection against post-contrast acute kidney injury (PC-AKI), although evidence is sparse and conflicting. The objective was to analyse the evidence on the efficacy and safety of NAC vs no administration of NAC in preventing PC-AKI in patients with pre-existing kidney impairment undergoing a non-interventional radiological examination requiring intravenous (IV) contrast media (CM) administration. We carried out a systematic review including randomised controlled trials (RCTs) published in MEDLINE, EMBASE, and Clinicaltrials.gov up to May 2022. The primary outcome was PC-AKI. Secondary outcomes included the requirement of renal replacement therapy, all-cause mortality, serious adverse events, and length of hospital stay. We conducted the meta-analyses using the Mantel-Haenszel method and following a random-effects model. NAC was not associated with a significant reduction in PC-AKI (RR 0.47, 95%CI 0.20 to 1.11; 8 studies; 545 participants; I2: 56%; low certainty), all-cause mortality (RR 0.67, 95%CI 0.29 to 1.54; 2 studies; 129 participants; very low certainty), or length of hospital stay (mean difference 9.2days, 95%CI - 20.08 to 38.48; 1 study; 42 participants; very low certainty). The impact on other outcomes could not be determined. NAC may not reduce the risk of PC-AKI or all-cause mortality in people with kidney impairment who receive an IV CM prior to radiological imaging, although the certainty of the evidence is very low or low. Our review concludes that prophylactic administration of N-acetylcysteine may not significantly reduce the risk of acute kidney injury in patients with kidney impairment receiving an intravenous contrast media prior to non-interventional radiological imaging, which may support decision making in this common clinical scenario. • N-Acetylcysteine may not significantly reduce the risk of acute kidney injury in patients with kidney impairment receiving an intravenous contrast media prior to non-interventional radiological imaging. • All-cause mortality and length of hospital stay would not be decreased with the administration of N-Acetylcysteine in this setting.

All-cause and cause-specific mortality among people with and without intellectual disabilities during the COVID-19 pandemic in the Netherlands: a population-based cohort study

Although high rates of COVID-19-related deaths have been reported for people with intellectual disabilities during the first 2 years of the pandemic, it is unknown to what extent the pandemic has impacted existing mortality disparities for people with intellectual disabilities. In this study, we linked a Dutch population-based cohort that contained information about intellectual disability statuses with the national mortality registry to analyse both cause-specific and all-cause mortality in people with and without intellectual disabilities, and to make comparisons with pre-pandemic mortality patterns. This population-based cohort study used a pre-existing cohort that included the entire Dutch adult population (everyone aged ≥18 years) on Jan 1, 2015, and identified people with presumed intellectual disabilities through data linkage. For all individuals within the cohort who died up to and including Dec 31, 2021, mortality data were obtained from the Dutch mortality register. Therefore, for each individual in the cohort, information was available about demographics (sex and date of birth), indicators of intellectual disability, if any, based on chronic care and (social) services use, and in case of death, the date and underlying cause of death. We compared the first 2 years of the COVID-19 pandemic (2020 and 2021) with the pre-pandemic period (2015-19). The primary outcomes in this study were all-cause and cause-specific mortality. We calculated rates of death and generated hazard ratios (HRs) using Cox regression analysis. At the start of follow-up in 2015, 187 149 Dutch adults with indicators of intellectual disability were enrolled and 12·6 million adults from the general population were included. Mortality from COVID-19 was significantly higher in the population with intellectual disabilities than in the general population (HR 4·92, 95% CI 4·58-5·29), with a particularly large disparity at younger ages that declined with increasing age. The overall mortality disparity during the COVID-19 pandemic (HR 3·38, 95% CI 3·29-3·47) was wider than before the pandemic (3·23, 3·17-3·29). For five disease groups (neoplasms; mental, behavioural, and nervous system; circulatory system; external causes; and other natural causes) higher mortality rates were observed in the population with intellectual disabilities during the pandemic than before the pandemic, and the pre-pandemic to during the pandemic difference in mortality rates was greater in the population with intellectual disabilities than in the general population, although relative mortality risks for most other causes remained within similar ranges compared with pre-pandemic years. The impact of the COVID-19 pandemic on people with intellectual disabilities has been greater than reflected by COVID-19-related deaths alone. Not only was the mortality risk from COVID-19 higher in people with intellectual disabilities than in the general population, but overall mortality disparities were also further exacerbated during the first 2 years of the pandemic. For disability-inclusive future pandemic preparedness this excess mortality risk for people with intellectual disabilities should be addressed. Dutch Ministry of Health, Welfare, and Sport and Netherlands Organization for Health Research and Development.

Emerging healthy lifestyle factors and all-cause mortality among people with metabolic syndrome and metabolic syndrome-like characteristics in NHANES

BackgroundThe impact of integrated lifestyles on health has attracted a lot of attention. It remains unclear whether adherence to low-risk healthy lifestyle factors is protective in individuals with metabolic syndrome and metabolic syndrome-like characteristics. We aimed to explore whether and to what extent overall lifestyle scores mitigate the risk of all-cause mortality in individuals with metabolic syndrome and metabolic syndrome-like characteristics.MethodsIn total, 6934 participants from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) were included. The weighted healthy lifestyle score was constructed based on smoking, alcohol consumption, physical activity, diet, sleep duration, and sedentary behavior information. Generalized linear regression models and restricted cubic splines were used to analyze the association between healthy lifestyle scores and all-cause mortality. ​ResultsCompared to participants with relatively low healthy lifestyle scores, the risk ratio (RR) in the middle healthy lifestyle score group was 0.51 (RR = 0.51, 95% CI 0.30–0.88), and the high score group was 0.26 (RR = 0.26, 95% CI 0.15–0.48) in the population with metabolic syndrome. The difference in gender persists. In females, the RRs of the middle and high score groups were 0.47 (RR = 0.47, 95% CI 0.23–0.96) and 0.21 (RR = 0.21, 95% CI 0.09–0.46), respectively. In males, by contrast, the protective effect of a healthy lifestyle was more pronounced in the high score group (RR = 0.33, 95% CI 0.13–0.83) and in females, the protective effects were found to be more likely. The protective effect of a healthy lifestyle on mortality was more pronounced in those aged < 65 years. Higher lifestyle scores were associated with more prominent protective effects, regardless of the presence of one metabolic syndrome factor or a combination of several factors in 15 groups. What's more, the protective effect of an emerging healthy lifestyle was more pronounced than that of a conventional lifestyle.ConclusionsAdherence to an emerging healthy lifestyle can reduce the risk of all-cause mortality in people with metabolic syndrome and metabolic syndrome-like characteristics; the higher the score, the more obvious the protective effect. Our study highlights lifestyle modification as a highly effective nonpharmacological approach that deserves further generalization.

The association between distal symmetric polyneuropathy in diabetes with all-cause mortality - a meta-analysis.

Distal symmetric polyneuropathy (DSPN) is a common microvascular complication of both type 1 and 2 diabetes with substantial morbidity burden and reduced quality of life. Its association with mortality is equivocal. To describe the association between DSPN and all-cause mortality in people with diabetes and further stratify by the type of diabetes based on a meta-analysis of published observational studies. We searched Medline from inception to May 2021. Original data were collected from case-control and cohort studies that reported on diabetes and DSPN status at baseline and all-cause mortality during follow-up. was completed by diabetes specialists with clinical experience in neuropathy assessment. Data was synthesized using random-effects meta-analysis. The difference between type 1 and 2 diabetes was investigated using meta-regression. A total of 31 cohorts (n=155,934 participants, median 27.4% with DSPN at baseline, all-cause mortality 12.3%) were included. Diabetes patients with DSPN had an almost twofold mortality (HR: 1.96, 95%CI: 1.68-2.27, I2 = 91.7%), I2 = 91.7%) compared to those without DSPN that was partly explained by baseline risk factors (adjusted HR: 1.60, 95%CI: 1.37-1.87, I2 = 78.86%). The association was stronger in type 1 compared to type 2 diabetes (HR: 2.22, 95%CI: 1.43-3.45). Findings were robust in sensitivity analyses without significant publication bias. Not all papers reported multiple adjusted estimates. The definition of DSPN was heterogeneous. DSPN is associated with an almost twofold risk of death. If this association is causal, targeted therapy for DSPN could improve life expectancy of diabetic patients.

Targeting Diabetes Prevention to More Disadvantaged Groups Improves Cost-Effectiveness: Implications of Inequality in Type 2 Diabetes From Theoretical Interventions

ObjectivesTo determine the effect of socioeconomic status on efficacy and cost thresholds at which theoretical diabetes prevention policies become cost-effective. MethodsWe designed a life table model using real-world data that captured diabetes incidence and all-cause mortality in people with and without diabetes by socioeconomic disadvantage. The model used data from the Australian diabetes registry for people with diabetes and the Australian Institute of Health and Welfare for the general population. We simulated theoretical diabetes prevention policies and estimated the threshold at which they would be cost-effective and cost saving, overall, and by socioeconomic disadvantage, from the public healthcare perspective. ResultsFrom 2020 to 2029, 653 980 people were projected to develop type 2 diabetes, 101 583 in the least disadvantaged quintile and 166 744 in the most. Theoretical diabetes prevention policies that reduce diabetes incidence by 10% and 25% would be cost-effective in the total population at a maximum per person cost of Australian dollar (AU$) 74 (95% uncertainty interval: 53-99) and AU$187 (133-249) and cost saving at AU$26 (20-33) and AU$65 (50-84). Theoretical diabetes prevention policies remained cost-effective at a higher cost in the most versus least disadvantaged quintile (eg, a policy that reduces type 2 diabetes incidence by 25% would be cost-effective at AU$238 [169-319] per person in the most disadvantaged quintile vs AU$144 [103-192] in the least). ConclusionsPolicies targeted at more disadvantaged populations will likely be cost-effective at higher costs and lower efficacy compared to untargeted policies. Future health economic models should incorporate measures of socioeconomic disadvantage to improve targeting of interventions.

Lower serum FT3 within the reference range is associated with mortality for older adults over 80 years of age with sarcopenia

ObjectiveThyroid hormones stimulate myogenesis and muscle contraction and regulate skeletal muscle cell metabolism. However, the association between thyroid hormone levels and mortality in sarcopenic older adults remains elusive. The aim of this study was to investigate the relationship between thyroid hormones and all-cause mortality in people over 80 years of age with sarcopenia.MethodsThis study was performed on 264 sarcopenic patients aged 80 years and older. Serum levels of thyroid hormone, including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were tested to evaluate thyroid status. Sarcopenia was defined using the criteria of the European Working Group on Sarcopenia in Older People. Mortality data were available for up to 38 months of follow-up. The correlation between FT3 and calf circumference (CC) or handgrip strength (HGS) was determined by Pearson correlation analysis. Kaplan-Meier analysis was used to compare the differences between FT3 tertile groups. Cox regression was used to analyze the mortality risk ratio of patients with different FT3 tertiles.ResultsDuring the follow-up period, 88 older adults died. Non-Survivors had lower serum FT3 levels (3.7 ± 0.5 vs. 3.9 ± 0.7, P = 0.001) than the Survivor. Serum FT3 was positively associated with CC and HGS (r = 0.29, P < 0.001, r = 0.21, P = 0.002, respectively). The Kaplan-Meier curve analysis demonstrated a difference in mortality among the FT3 tertile groups (log-rank test, χ2 = 11.83, P = 0.003). The high FT3 group had lower mortality compared with the low FT3 group (the adjusted HRs were 0.63 (95%CI: 0.41–0.96 P = 0.031).ConclusionLower FT3 within the reference range is associated with higher mortality in adults over 80 years with sarcopenia and euthyroid. Routine assessment of FT3 may be an easy way to identify high-risk older adults with sarcopenia.

Relationship between serum sodium levels and all-cause mortality in congestive heart failure patients: A retrospective cohort study based on the Mimic-III database.

The relationship between serum sodium levels and mortality in congestive heart failure (CHF) patients has not been well-studied previously. The non-linear correlation between serum sodium levels and mortality in patients with heart failure is currently controversial, and the relationship between different serum sodium levels and mortality is disputed. The goal of this study is to look into the relationship between serum sodium levels and all-cause mortality in people with CHF after controlling for other factors. The publicly accessible Mimic III database was the source of data for our study. We use the ICU Admission Scoring System to collect demographic data, laboratory findings, comorbidities, vital signs, and scoring information for each patient. Cox proportional risk analysis, smooth curve fitting, and the Kaplan-Meier survival curve were used to assess the relationship between baseline sodium levels and all-cause mortality in CHF patients. The segmentation regression model discovered a turning point value of serum sodium levels (137.5 mmol/L) between serum sodium levels and all-cause mortality. According to the results of the fully adjusted Cox proportional hazard model, lower serum sodium levels (<137.5 mmol/L) were associated with an increased risk of 30, 90, 365-day, and 4-year all-cause deaths. The HRs and 95th confidence intervals were 0.96 (0.94, 0.99), 0.96 (0.94, 0.99), 0.96 (0.94, 0.98), and 0.96 (0.95, 0.98), respectively; the higher serum sodium levels (≥137.5 mmol/L) were related to an associated multiplied risk of 30, 90, 365-day, and 4-year all-cause deaths; the HRs and 95th confidence intervals were 1.02 (1.00, 1.05), 1.02 (1.00, 1.04), 1.02 (1.00, 1.03), and 1.02 (1.00, 1.03), respectively. Serum sodium levels were u-shaped about all-cause mortality. In individuals with CHF, serum sodium levels are linked to an elevated risk of short-, medium-, and long-term all-cause mortality.