Increased Hazard Of Mortality Research Articles

Sickle Cell Trait and Mortality Risk: California Newborn Screening Longitudinal Follow up of Births 1991-2013

Sickle cell trait (SCT) represents a significant global public health issue with approximately three million carriers in United States and over 300 million worldwide. Yet, the mortality risk of sickle cell trait is unknown. Early anecdotal research on SCT led to social bias and stigmatization of individuals with the trait, which unfortunately hindered the conduct of well-designed morbidity and mortality studies in this population. This resulted in SCT being perceived as a benign asymptomatic condition that protects against malaria and its importance confined to the genetic risk for sickle cell disease. As research in SCT gradually increased, it became evident that SCT is indeed a risk factor for several complications including exertional related rhabdomyolysis, chronic kidney disease, venous thromboembolism, and other morbidities. SCT red cells in abnormal physiologic conditions sickle and can cause morbidity and mortality. Additionally, SCT could potentially influence the severity of various illnesses. Individuals with SCT commonly experience hyposthenuria and are at risk for dehydration which could further exacerbate the severity of many medical problems. It is essential to determine if SCT is a risk factor for overall mortality. This study is the first population-level investigation of all-cause mortality risk for individuals with SCT. This longitudinal analysis included all live births with SCT identified by the California newborn screening (NBS) program between 1991 and 2013. For each newborn with SCT, three matched controls with hemoglobin AA were randomly selected from the NBS cohort. Controls were matched to SCT cases on year of birth, sex, race/ethnicity, and city of birth. SCT records with incomplete data for the matched variables or those with fewer than three matching controls were excluded from the analysis. SCT cases and controls were linked to all deaths within the state of California for the years 1991-2013 using statewide death data files. Cox proportional hazard ratios and 95% confidence intervals were calculated to compare mortality between individuals with SCT and controls with hemoglobin AA, including stratified by age (<1, 1-4, 5-14, 15-22). The study identified 94,240 live births with SCT (Table 1), which represents 96% of all SCT live births identified by the California NBS program in 1991-2013, and 282,720 matched controls. Between 1991 to 2013, there were 693 (0.74%) SCT deaths and 1,910 (0.68%) control deaths. Those with SCT had an increased mortality hazard rate compared to those with hemoglobin AA (11% higher, p=0.015). When stratified by age, mortality hazard rates in the age strata 1-4 years (44% higher, p= .0009) and 5-14 years (48% higher, p=.0047) were higher than those with hemoglobin AA (Table 2). These age strata describe periods of follow up time, and an individual may appear in more than one stratum. Mortality hazard ratios calculated for each age stratum are conditional to individuals surviving to the starting age of that stratum. This analysis of mortality risk for a cohort of over 94,000 infants identified with SCT is the first of its kind and adds important information to the assessment of health risk for the condition. This is the first study that reports a higher risk of mortality for children and young adults with SCT compared to those with hemoglobin AA. These findings highlight the need for comprehensive research, including confirming the study results in other longitudinal sickle cell trait population-level studies and investigation into underlying causes of death, to inform clinical management and counseling for individuals with SCT.

Impact of eGFR slope upon mortality in a real world heart failure cohort

Abstract Background Heart failure (HF) frequently causes an imbalance in heart and kidney functions, and the prognosis of heart and kidney disease can worsen one another. In addition to the prognostic role of chronic kidney disease (CKD), dynamic changes in renal function have been recognized to portend a poor prognosis in HF patients. Purpose This study aimed to investigate the prevalence of impaired renal function at HF diagnosis and its association with short and long-term outcomes in a real-world cohort of HF patients. In addition, we assessed how dynamic changes in renal function after HF diagnosis might predict HF prognosis. Methods Using a natural language processing algorithm, clinical data of patients with at least one diagnosis of HF (index event) were retrospectively collected. Patients for which the most recent estimated glomerular filtration rate (eGFR) value prior to the index date was ≤ 60 mL/min/1.73m2 and/or had a documented medical history of CKD (including dialysis) were considered as having CKD. A linear mixed effects model was used to show the longitudinal eGFR trajectories during the follow-up period (after index). A Cox proportional hazard model was used to analyse the association between baseline variables and mortality. Finally, joint modelling was used to combine the linear mixed eGFR sub-model with the survival sub-model, to estimate the effect of the current eGFR value and the eGFR slope of the year prior on mortality. Results The study population consisted of 1992 patients with a mean (±SD) age of 74.8 ± 11.7 years and 58% males. In total, 17% had HF with preserved ejection fraction (HFpEF, n = 339) and 70% (n = 1156) presented CKD at the index event. The median follow-up time was 3.16 years and 13% (n = 198) of the patients were deceased after two years. The group of 2-year survivors had significantly lower proportion of CKD at index (55 vs 76%, p < 0.001). The calculated mean yearly decrease of the eGFR value was 4.2 mL/min/1.73m². The multivariate Cox PH model identified age, CVA, diastolic blood pressure, HDL, and log10proBNP as baseline predictors of mortality. Joint modelling showed that a 10 mL/min/1.73m2 lower current eGFR value amongst patients was associated with an increased mortality hazard of 1.30 ± 0.06 (p < 0.001). Additionally, a decrease of 10 mL/min/1.73m2 in eGFR during the year prior indicated an increased mortality hazard of 1.87 ± 0.19 (p < 0.001). Conclusion In a real-world cohort of HF patients, the prevalence of CKD is high and CKD is an independent predictor of mortality. The current eGFR value and the year prior’s eGFR slope adds additional prognostic information and helps to better fine tune the individual mortality hazard. Based on the findings of this analysis, patients with worse prognosis might benefit from a closer and more vigilant follow-up.

Evaluating the viability of the use of T‐bar and radiotelemetry tags on prespawn Arctic Lampreys

AbstractObjectiveArctic Lampreys Lethenteron camtschaticum are harvested by subsistence and commercial fisheries in the Yukon–Kuskokwim River region of Alaska; however, baseline population data are deficient. For mark–recapture and telemetry studies to be effectively implemented to assess Arctic Lamprey abundance, migratory and dispersal patterns, and spawning locations, tags must not impact fish survival, physiology, or behavior.MethodsFor this laboratory evaluation, we examined survival, tag retention, swim endurance at short‐term (1 day posttreatment) and long‐term (43 days [~6 weeks] posttreatment) intervals, and incision healing for T‐bar‐tagged and radio‐tagged prespawn Yukon River Arctic Lampreys (N = 216). Six treatment groups were evaluated: control; sham surgery; external T‐bar anchor tag; and small (0.30 g; 0.1–0.4% tag burden [ratio of tag weight to fish body weight]), medium (0.57 g; 0.2–0.8% tag burden), and large (1.50 g; 0.6–1.9% tag burden) internal dummy radio transmitter tags.ResultAlthough all lampreys survived tagging and surgical procedures through the first 4 weeks of the experiment, a higher tag burden was associated with an increased mortality hazard up to 35 weeks postsurgery. Over the 14‐week experimental period, one T‐bar tag and one small radio tag were shed by lampreys. Although treatment was not a significant predictor of swim endurance, a higher tag burden led to reductions in swim endurance at 1 day posttreatment but not at 43 days posttreatment. Healing did not differ among surgical treatment groups, but persistent inflammation was observed at incision sites and skin erosion was observed at antenna protrusion locations.ConclusionThese results indicate that T‐bar anchor tags and internal radio tags are acceptable for Arctic Lamprey tagging studies if the radio tag burden is ≤1.3% for short‐term (≤14‐week) studies and ≤0.5% for long‐term (≥14‐week) studies.

Long-term outcomes of patients bridged to recovery with venoarterial extracorporeal life support.

Our study examines the long-term outcomes of patients discharged from the hospital without heart replacement therapy (HRT) after recovery from cardiogenic shock using venoarterial extracorporeal life support (VA-ECLS). We retrospectively reviewed 615 cardiogenic shock patients who recovered from VA-ECLS at our institution between January 2015 and July 2021. Of those, 166 patients (27.0%) who recovered from VA-ECLS without HRT were included in this study. Baseline characteristics, discharge labs, vitals, electrocardiograms and echocardiograms were assessed. Patients were contacted to determine vital status. The primary outcome was post-discharge mortality. Of 166 patients, 158 patients (95.2%) had post-discharge follow-up, with a median time of follow-up of 2years (IQR: [1 year, 4 years]). At discharge, the median ejection fraction (EF) was 52.5% (IQR: [32.5, 57.5]). At discharge, 92 patients (56%) were prescribed β-blockers, 28 (17%) were prescribed an ACE inhibitor, ARB or ARNI, and 50 (30%) were prescribed loop diuretics. Kaplan-Meier analysis showed a 1-year survival rate of 85.6% (95% CI: [80.1%, 91.2%]) and a 5-year survival rate of 60.6% (95% CI: [49.9%, 71.3%]). A Cox regression model demonstrated that a history of congestive heart failure (CHF) was strongly predictive of increased mortality hazard (HR = 1.929; p = 0.036), while neither discharge EF nor etiology of VA-ECLS were associated with increased post-discharge mortality. Patients discharged from the hospital after full myocardial recovery from VA-ECLS support without HRT should have close outpatient follow-up due to the risk of recurrent heart failure and increased mortality in these patients.

A prospective, observational study of frailty, quality of life and dialysis in older people with advanced chronic kidney disease

BackgroundFrailty is prevalent in older people with chronic kidney disease (CKD) and robust evidence supporting the benefit of dialysis in this setting is lacking. We aimed to measure frailty and quality of life (QOL) longitudinally in older people with advanced CKD and assess the impact of dialysis initiation on frailty, QOL and mortality.MethodsOutpatients aged ≥65 with an eGFR ≤ 20ml/minute/1.73m2 were enrolled in a prospective observational study and followed up four years later. Frailty status was measured using a Frailty Index (FI), and QOL was evaluated using the EuroQol 5D-5L instrument. Mortality and dialysis status were determined through inspection of electronic records.ResultsNinety-eight participants were enrolled. Between enrolment and follow-up, 36% of participants commenced dialysis and 59% died. Frailty prevalence increased from 47% at baseline to 86% at follow-up (change in median FI = 0.22, p < 0.001). Initiating dialysis was not significantly associated with change in FI. QOL declined from baseline to follow-up (mean EQ-5D-5L visual analogue score of 70 vs 63, p = 0.034), though commencing dialysis was associated with less decline in QOL. Each 0.1 increment in baseline FI was associated with 59% increased mortality hazard (HR = 1.59, 95%CI = 1.20 to 2.12, p = 0.001), and commencing dialysis was associated with 59% reduction in mortality hazard (HR = 0.41, 95%CI = 0.20 to 0.87, p = 0.020) irrespective of baseline FI.ConclusionsFrailty increased substantially over four years, and higher baseline frailty was associated with greater mortality. Commencing dialysis did not affect the trajectory of FI but positively influenced the trajectory of QOL from baseline to follow-up. Within the limitations of small sample size, our data suggests that frail participants received similar survival benefit from dialysis as non-frail participants.

Autonomic nervous system and postural control regulation during orthostatic test as putative markers of physical resilience among community-dwelling older adults

IntroductionWe examined whether autonomic nervous system (ANS) and postural control regulation during orthostatic test reflect physical resilience by studying their associations with maximal walking speed and mortality. MethodsThe participants were community-dwelling Finnish men (n = 303) and women (n = 386) aged 75, 80, and 85 years at baseline. Systolic and diastolic blood pressure (BP), heart rate, heart rate variability (HRV), respiratory rate, and postural sway were obtained using a digital sphygmomanometer, a single-channel ECG, and thigh- and chest-worn accelerometers. Linear and Cox regression models were used to estimate the associations of the physiological indices with maximal 10-m walking speed and 5-year mortality separately for sexes. ResultsBetter maintenance of BP under orthostatic stress was associated with faster walking speed in women and lower mortality hazard in men. Greater HRV in terms of low frequency power and lower respiration rate in supine position and smaller orthostatic changes in these were associated with faster walking speed especially in women. Less postural sway after standing up was associated with faster walking speed in women (−0.057, SE 0.022, p = 0.011) and more postural sway with increased mortality hazard in men (HR 1.71, 95 % CI 1.20–2.43) even after controlling for BP responses. ConclusionsIn addition to ANS regulation at rest and under stress, adaptation of postural control system to orthostasis may be used in quantifying older adults' physical resilience. Wearable sensors capturing stimulus-response patterns and natural fluctuations of body functions may provide opportunities to monitor and incorporate different subsystems' resilience also in free-living conditions.

Prognostic value of high-sensitivity C-reactive protein among chronic kidney disease patients undergoing percutaneous coronary intervention

BackgroundData on the prognostic value of high-sensitivity C-reactive protein (hs-CRP) levels in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) are limited. MethodsPatients undergoing PCI at a tertiary center from January 2012 to December 2019 were included. CKD was defined as a glomerular filtration rate (GFR) <60 mL/min/1.73m2 and elevated hs-CRP was defined as >3 mg/L. Acute myocardial infarction (MI), acute heart failure, neoplastic disease, patients undergoing hemodialysis, or hs-CRP >10 mg/L were exclusion criteria. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, MI, and target vessel revascularization at 1-year after PCI. ResultsOut of 12,410 patients, 3029 (24.4 %) had CKD. Elevated hs-CRP levels were found in 31.8 % of CKD and 25.8 % of no-CKD patients. At 1 year, MACE occurred in 87 (11.0 %) CKD patients with elevated hs-CRP and 163 (9.5 %) with low hs-CRP (adj. HR 1.26, 95 % CI 0.94–1.68); among no-CKD patients, in 200 (10 %) and 470 (8.1 %), respectively (adj. HR 1.21, 95 % CI 1.00–1.45). Hs-CRP was associated with an increased risk of all-cause death in both CKD (Adj. HR 1.92, 95 % CI 1.07–3.44) and no-CKD patients (adj. HR 3.02, 95 % CI 1.74–5.22). There was no interaction between hs-CRP and CKD status. ConclusionsAmong patients undergoing PCI without acute MI, elevated hs-CRP values were not associated with a higher risk of MACE at 1 year, but with increased mortality hazards consistently in patients with or without CKD.

Low Grip Strength and Increased Mortality Hazard among Middle-Aged and Older Chinese Adults with Chronic Diseases

ObjectiveThis study aims to evaluate the association between lower grip strength and mortality hazard. MethodsWe selected 10,280 adults aged 45 to 96 years old from the China Health and Retirement Longitudinal Study and used multivariate Cox proportional hazard models to assess the association of grip strength with mortality hazard. In addition, we explored the possibility of a nonlinear relationship using a 4-knot restricted spline regression. ResultsWe found that elevated grip strength was associated with lower mortality up to a certain threshold. The baseline quartile values of grip strength were 30, 37, and 44 kg for males and 25, 30, and 35 kg for females. After adjusting for confounders, with category 1 as the reference group, the adjusted HRs were 0.58 (0.42–0.79) in males and 0.70 (0.48–0.99) in females (category 4). We also found a linear association between grip strength values and all-cause death risk (males, P = 0.274; females, P = 0.883) using restricted spline regression. For males with a grip strength < 37 kg and females with a grip strength < 30 kg, grip strength and death were negatively associated. ConclusionGrip strength below a sex-specific threshold is inversely associated with mortality hazard among middle-aged and older Chinese adults with chronic diseases.

Emergency Department Utilization Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Longitudinal Analysis of 557 Patients

Allogeneic HSCT recipients are at risk of various complications during post-transplant follow-up. Some patients may refer to an emergency department (ED) for medical attention, but data on ED visits by HSCT recipients are lacking. 1) Assess ED utilization in HSCT recipients and associated risk factors during post-transplant follow-up. 2) Identify subgroups of HSCT patients presenting to the ED. 3) Analyze outcomes and prognostic factors for hospitalization and 30-day mortality after ED visits. 4) Assess mortality hazards following an ED presentation. A retrospective single-center longitudinal analysis including 557 consecutive recipients of allogeneic HSCT at the Medical University of Vienna, Austria, between 01/2010 and 01/2020. Descriptive statistics, event estimates accounting for censored data with competing risks, latent class analysis, and multivariate regression models were used for data analysis. Out of 557 patients (median age at HSCT: 49 [interquartile range: 39-58] years; f:m = 233:324), 137 (25%) presented to our center's ED at least once during post-HSCT follow-up (median individual follow-up: 2.66 [0.72-5.59] years). Cumulative incidence estimates of a first ED visit in the overall cohort were: 19% at two years, 25% at 5 years, and 28% at 10 years from HSCT. These numbers increased to 34%, 41%, and 43% in patients resident in Vienna. Chronic GVHD was the only risk factor showing a statistically significant association with ED presentation in multivariate analysis (HR 2.34, 95% CI 1.63-3.35). Patients presented with various and often multiple symptoms to the ED. We identified three latent patient groups in the ED, mainly characterized by the time from HSCT, chronic GVHD, and documented pulmonary infection. Hospitalization was required in 132/216 (61%) of all analyzed ED visits; in-hospital mortality and 30-day mortality rates were 13% and 7%, respectively. Active acute GVHD, systemic steroids, documented infection, pulmonary infiltrates, and oxygen supplementation were statistically significant predictors of hospitalization; shorter time from HSCT, pulmonary infiltrates, and hemodynamic instability were independent risk factors for 30-day mortality. ED presentation during the last 30 days increased mortality hazards in the overall cohort (HR 4.56, 95% CI 2.68-7.76) after adjustment for relevant confounders. Every fourth patient sought the ED for medical attention at least once during post-HSCT follow-up. Depending on the presence of identified risk factors, a significant proportion of patients may require hospitalization and be at risk for adverse outcomes. Screening for these risk factors and specialist consultation should be part of managing most HSCT patients presenting to the ED.

Associations among cardiorespiratory fitness, C-reactive protein, and all-cause mortality in men and women.

We examined individual and joint associations among high-sensitivity C-reactive protein (CRP), cardiorespiratory fitness (fitness), and mortality in healthy men and women. Between January 1, 2000 and December 31, 2016, 30,077 adults (31.3% women) received a comprehensive physical examination. Fitness was determined from maximal treadmill exercise test duration. Participants were categorized as unfit (Quintile 1) and fit (Quintiles 2-5), and by normal (<2 mg/L) and elevated (≥2 mg/L) CRP categories. Adjusted hazard ratios (HRs) with 95% confidence interval (CI) for all-cause mortality were computed with Cox regression. During an average of 10.1 years of follow-up, 576 deaths occurred. Following adjustment for age, smoking status, sex, exam year, body mass index, systolic blood pressure, total cholesterol, triglyceride:high-density lipoprotein ratio, and fasting glucose, HR (95% CI) for all-cause mortality were 1.0 (referent) and 1.52 (1.14-2.02) for fit and unfit categories, respectively. Corresponding values for normal and elevated CRP categories were 1.0 and 1.50 (1.20-1.89), respectively. When grouped by fitness and CRP category, there was significantly greater mortality risk in the unfit than the fit category within the elevated CRP category (HR = 1.77 (1.14-2.75)), but not in the normal CRP category (HR = 1.38 (0.96-1.98)). Each 1 metabolic equivalent increment in fitness and 1 mg/L increment in CRP were associated with 10.0% (95% CI: 5.1-14.8%) decreased and 7.3% (95% CI: 2.0%-12.9%) increased mortality hazard, respectively. Compared to the unfit, fit individuals have an attenuated mortality risk within each CRP category. Thus, higher fitness appears to provide some protection against all-cause mortality, particularly among those with elevated levels of inflammation.

Sedation‐associated medications at dementia diagnosis, their receptor activity, and associations with adverse outcomes in a large clinical cohort

AbstractBackgroundWe aimed to investigate whether sedative medications are associated with adverse outcomes in people with dementia, and whether specific characteristics of these medications predict a higher risk of harm.MethodA retrospective cohort study was carried out of 15,210 patients diagnosed with dementia between 2008 and 2017 in South London. From recorded medications at dementia diagnosis, we ascertained those with drowsiness listed as a side effect (termed ‘sedative’ hereafter) and subdivided them by frequency and strength of sedation, receptor profile, half‐life and whether they were psychotropics. Multivariable Cox regression models were applied to determine risk of mortality and emergency hospitalisation, and generalised estimating equations to investigate cognitive decline. Final models were adjusted for 19 potential confounders, including measures of physical and mental health, functioning and central anticholinergic burden.ResultAt diagnosis 70.4% of patients with dementia were receiving at least one sedative medication. Median survival time was 4.0 years and median time to first hospitalisation 1.4 years. After controlling for potential confounders, receipt of any sedative medication at dementia diagnosis was associated with accelerated cognitive decline and a higher hospitalisation risk, but only medications with a cautionary warning yielded an increased mortality hazard. Medications acting through gamma‐aminobutyric acid agonism, psychotropic sedatives and those with a short half‐life were associated with a higher risk of mortality. Gamma‐aminobutyric acid agonists, N‐methyl‐D‐aspartate receptor antagonists and non‐psychotropic sedatives were associated with an increased hospitalisation risk. Alpha‐1 antagonist, antihistamines, N‐methyl‐D‐aspartate receptor antagonists, psychotropic sedatives, and those with shortest or longest half‐life were associated with accelerated cognitive decline.ConclusionReceipt of any sedative agent was associated with hospitalisation and accelerated cognitive decline. Differences in hazard appear to exist between frequency/strength of sedation, receptor profiles, half‐life, and prescribing indication. These differences should be taken into consideration in medication reviews at the time of dementia diagnosis.

Depression, Diabetes Mellitus and Mortality in Older Adults: A National Cohort Study in Taiwan.

Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period. A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of ≥8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups. During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval [CI]: 2.02-3.03), 1.95 (95% CI: 1.63-2.32), and 1.23 (95% CI: 1.09-1.39), respectively. The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex.

Self-reported health change in haemodialysis recipients modulates the effect of frailty upon mortality and hospital admissions: outcomes from a large prospective UK cohort.

Frailty among haemodialysis patients is associated with hospitalization and mortality, but high frailty prevalence suggests further discrimination of risk is required. We hypothesized that incorporation of self-reported health with frailty measurement may aid risk stratification. Prospective cohort study of 485 prevalent haemodialysis recipients linked to English national datasets. Frailty Phenotype (FP), Frailty Index (FI), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS) and self-reported health change were assessed. Mortality was explored using Fine and Gray regression, and admissions by negative binomial regression. Over a median 678 (interquartile range 531-812) days, there were 111 deaths, and 1241 hospitalizations. Increasing frailty was associated with mortality on adjusted analyses for FP [subdistribution hazard ratio (SHR) 1.26, 95% confidence interval (CI) 1.05-1.53, P=.01], FI (SHR 1.21, 95% CI 1.09-1.35, P=.001) and CFS (SHR 1.32, 95% CI 1.11-1.58, P=.002), but not EFS (HR 1.08, 95% CI 0.99-1.18, P=.1). Health change interacted with frailty tools to modify association with mortality; only those who rated their health as the same or worse experienced increased mortality hazard associated with frailty by FP (Pinteraction=.001 and 0.035, respectively), FI (Pinteraction=.002 and .007, respectively) and CFS (Pinteraction=.009 and 0.02, respectively). CFS was the only frailty tool associated with hospitalization (incidence rate ratio 1.12, 95% CI 1.02-1.23, P=.02). We confirm the high burden of hospitalization and mortality associated with haemodialysis patients regardless of frailty tool utilized and introduce the discriminatory ability of self-reported health to identify the most at-risk frail individuals.

Long-term mortality in ischemic stroke patients with concomitant chronic obstructive pulmonary disease

BackgroundLong-term mortality in ischemic stroke patients with concomitant COPD has been largely unexplored. This study aimed to compare long-term all-cause mortality in ischemic stroke patients with and without COPD. MethodsThis was a retrospective cohort study of ischemic stroke patients with and without COPD in the Geisinger Neuroscience Ischemic Stroke database to examine all-cause mortality up to 3 years using Kaplan-Meier estimator and Cox proportional hazards model. ResultsOf the 6,589 ischemic stroke patients included in this study, 5,525 (83.9%) did not have COPD (group A). Group B (n=1,006) consisted of patients with COPD diagnosis by ICD-9/10-CM codes. COPD patients in Group C (n=233) were diagnosed by spirometry, and in Group D (n=175) by both ICD-9/10-CM codes and spirometry confirmation. The survival probabilities at three years in Group B, C, and D were significantly lower than in Group A. Group B (HR=1.262, 95% CI 1.122–1.42, p<0.001) and group C (HR=1.251, 95% CI 1.01–1.55, p=0.041) had significantly lower hazard of mortality compared to group A. There was no significant difference in survival between COPD subtypes of chronic bronchitis and emphysema. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 stage had an increased mortality hazard compared to the GOLD 1 stage. ConclusionsWhile ischemic stroke patients with preexisting COPD have worse long-term survival than those without COPD, the results largely depended on the definition of COPD used. These results suggest that ischemic stroke patients with COPD need more personalized medical care to decrease long-term mortality.

Hypo- and Hyperphosphatemia at Admission as Independent Factors of Mortality of COVID-19 Patients: Findings from a Retrospective Cohort Study.

Electrolyte imbalances are common in COVID-19 infection and are associated with poor outcomes in hospitalized patients. This study examined whether serum phosphate imbalances at admission are associated with mortality in hospitalized COVID-19 patients. In this registry-based single-center retrospective cohort study, 1349 inpatients with COVID-19 were included from March 2020 to March 2021 in an academic hospital in Ilam (southwest Iran). The Cox proportional hazard (PH) regression model was applied to the data set of COVID-19. The in-hospital median survival time for patients with low, normal, and high serum phosphate levels was 14, 25, and 8 days, respectively. In a multivariate model, adjusted for the other variables, patients with hypophosphatemia (adjusted hazard ratio [HR], 2.53; 95% CI, 1.15 - 5.58; P = 0.02) and hyperphosphatemia (adjusted HR, 1.77; 95% CI, 1.00 - 3.14; P = 0.05) had an increased mortality hazard compared with those who had normal levels of serum phosphate. Our results demonstrate associations of hypophosphatemia and hyperphosphatemia with increased in-hospital mortality in COVID-19 patients. Intensive medical care and more attention must be paid to COVID-19 patients with serum phosphate imbalances at admission.

O-086 Assisted reproductive technology does not influence body mass index (BMI) in a cohort of 606 children aged 6-9 years

Abstract Study question Is BMI in children conceived after frozen embryo transfer different from children conceived after fresh embryo transfer and after natural conception? Summary answer BMI in children conceived after frozen embryo transfer was similar to BMI in children conceived after fresh embryo transfer or children born after natural conception. What is known already Children conceived after frozen embryo transfer (FET) have higher risk of being born large for gestational age (LGA) than children conceived after natural conception (NC). Generally, being born LGA increases the risk of obesity in childhood. Childhood BMI is strongly associated with obesity and cardiometabolic disease and mortality in adulthood. The long-term effects of ART on the metabolic health of the offspring and the underlying mechanisms are scarcely explored. However, it has been proposed that ART may induce epigenetic variations around fertilization, implantation, and early embryonic stages that may influence size at birth. Study design, size, duration The study “Health in Childhood following Assisted Reproductive Technology” (HiCART) includes 606 singletons (292 boys, 314 girls) – 200 conceived after FET; 203 after fresh-ET; and a random sample of 203 naturally conceived children matched for age and sex. All children were born in Eastern Denmark from 2009-2013 and had a clinical examination performed at the Copenhagen University Hospital - Rigshospitalet when they were 6-9 years of age. Participants/materials, setting, methods The children underwent a clinical examination with anthropometric measurements, whole-body dual-energy x-ray absorptiometry-scan (DXA), pubertal staging, and a blood sample. All anthropometric measurements were converted to standard deviation scores (SDS) using a Danish reference. Parents filled in a questionnaire regarding the pregnancy and the current health of the child and themselves. Maternal, obstetric and neonatal data from the national ART and birth registry were obtained. Main results and the role of chance Children conceived after FET had higher birthweight SDS (0.20SDS, 1.09SD) than children conceived after fresh-ET (-0.22SDS, 1.00SD), p &amp;lt; 0.001 and children conceived naturally (-0.16SDS, 1.09SD), p = 0.001. Mothers conceiving naturally were younger and had higher parity than mothers conceiving after ART. The three groups were similar regarding pregestational maternal BMI and gestational age. Puberty had started in 57 children (54 girls), evenly distributed among the groups. There were no differences in height SDS between FET (0.25SDS, 1.00SD) compared to fresh-ET (0.17SDS, 0.96SD), p = 0.50 and compared to NC (0.07 SDS, 1.06SD), p = 0.11 or in weight SDS between FET (0.22SDS, 1.07SD) compared to fresh-ET (0.10 SDS, 1.06SD), p = 0.22 and compared to NC (0.14SDS, 1.00SD), p = 0.43. Similarly, no differences were found in BMI SDS between FET (0.16SDS, 1.16SD) compared to fresh-ET (0.04SDS, 1.10SD), p = 0.25 and compared to NC (0.20SDS, 1.01SD), p = 0.80. Our primary endpoint BMI SDS remained non-significant after adjustment for child sex, age and birthweight SDS, parity, maternal BMI and smoking in pregnancy. Limitations, reasons for caution The sample size was decided to be able to detect a difference of 0.3 SDS in childhood BMI, corresponding to a 3.4% increased mortality hazard. Thus, smaller differences in BMI SDS may be overlooked. As the participation rate was between 18-42% in the three groups, selection bias cannot be excluded. Wider implications of the findings The increased birth weight in children conceived after FET did not translate into a difference in BMI in this large cohort. Since BMI in childhood is a strong biomarker of cardiometabolic disease later in life, the findings are reassuring and may reduce concerns associated with the long-term consequences of FET. Trial registration number NCT03719703

Pattern and Trends in Adult Hospitalization/Admission and Mortality Among Medical Ward Inpatients at Gadarif Hospital in Eastern Sudan: A Four-Year Retrospective Study.

PurposeSub-Saharan Africa suffers from a dual impact of communicable (CDs) and non-communicable diseases (NCDs). There is scarce data on causes, trends of admission, and deaths among patients in Sudan. We aimed to determine the causes, trends of admission, and mortality among adult patients admitted to Gadarif Hospital in Eastern Sudan.Patients and MethodsThe medical records of adult patients admitted to Gadarif medical wards from January 2017 to December 2020 were reviewed for age, gender, causes of admission, and outcomes. Multivariate Cox regression analysis was used to analysis factors (age, sex, years, and disease) associated with the mortality.ResultsOf the 7230 patients who were admitted, 2221 (34.7%) were females and 5009 (69.3%) were males. The median age (interquartile range, IQR) was 47.0 (35.0) years. Of these 7230 patients, 3167 (43.8%) and 4063 (56.2%) patients were admitted with CDs and NCDs, respectively. Cardiovascular diseases (18.4%), snakebites (12.9%), and visceral leishmaniasis (12.0%) were the most common causes of admission. The overall in-patient adult deaths were 674 (9.3%). Cardiovascular diseases (22.3%), neurological diseases (16.9%), sepsis (15.9%), renal diseases (13.9%), and snakebites (8.3%) were the most common causes of inpatient mortality. Malignancy (20.7%), sepsis (20.9%), neurological diseases (17.4%), and cardiovascular diseases (13.8%) comprised the highest case fatality rates among the admitted patients. Using a Cox regression model (adjusted), age (adjusted hazard ratio = 1.02, 95% confidence interval = 1.01‒1.03) was associated with increased mortality hazard. However, the gender and years of admission were not associated with increased mortality hazard.ConclusionAdmissions and mortality rates for CDs and NCDs are high compared with other African countries. Preventive measures are required to avert the high burden of these diseases. Health care systems in Sudan need to be prepared to deal with the dual burden of the diseases.

Deficit Accumulation Frailty Index (DAFI) scores and acute myeloid leukemia outcomes.

12040 Background: Novel strategies are needed to assess frailty in the context of therapy decisions for older adults with acute myeloid leukemia (AML). Our objectives were to describe pre-treatment DAFI scores for older AML patients treated on clinical trials and explore their relationship with treatment outcomes. Methods: We conducted a exploratory analysis utilizing data from two clinical trials of adults aged ≥60 years with newly diagnosed AML (Alliance/CALGB 11001 [intensive therapy] and Alliance/CALGB 11002 [non-intensive therapy]). We included the subset of patients in each trial enrolled on geriatric assessment companion studies (Alliance/CALGB 361006, 361101). A DAFI score was calculated for each patient using 51 variables including demographic, geriatric assessment, and laboratory data derived from the geriatric assessment. Individuals with ≥90% items were included (consistent with other studies); DAFI scores ranged from 0 to 1 and were evaluated using established categories (0- &lt;.2 [robust]; 0.2-&lt;.35 [pre-frail]; 0.35+ [frail]) and as a continuous score. Associations between DAFI scores and toxicity and overall survival (OS) were evaluated with Fisher’s exact-testing and Kaplan Meier/cox proportional hazards, respectively. Results: The median age was 68 years (range 61, 82) and 72 years (range 61, 92) for those getting intensive (N=31) and less intensive therapy (N= 75), respectively. Individuals in the intensive study had a median pre-treatment DAFI score of 0.15 (range 0.05, 0.31) and were all categorized as robust (75%) or pre-frail (25%). There was no significant difference in median OS (14.6 vs. 14.7 months) or non-hematological grade 3+ adverse events (AEs; 85% vs. 89%) between robust vs. pre-frail individuals in this trial, respectively. However, pre-frail adults experienced a trend towards greater grade 4 non-hematological toxicity than robust individuals (67% vs 26%, p=0.05). In the non-intensive trial, the median DAFI score was 0.24 (range 0.04, 0.48) and most individuals were pre-frail (49.3%) or frail (17.3%). Non-hematologic grade 3+ AEs did not vary by DAFI group, 88% robust, 95% pre-frail, and 77% frail (p=0.15). Median OS was 7.4, 10.8, and 6.3 months for robust, pre-frail, and frail respectively (p=0.17). Adjusting for age, each 0.1 increase in DAFI score was associated with increased mortality hazard (HR 1.8, 95% CI 1.0-3.2). Conclusions: DAFI score calculation provides a potential novel strategy for categorization of frailty in AML. In our assessment, higher DAFI scores were associated with toxicity during intensive induction and mortality in the less intensive setting. This method should be studied in larger samples randomized by treatment intensity. Support: UG1CA189823; Bayer Healthcare/Berlex (CALGB 11001); NCT01253070 (CALGB 11001). Clinical trial information: NCT01253070, NCT01420926.

Sedation-Associated Medications at Dementia Diagnosis, Their Receptor Activity, and Associations With Adverse Outcomes in a Large Clinical Cohort.

We aimed to investigate whether sedative medications are associated with adverse outcomes in people with dementia, and whether specific characteristics of these medications predict a higher risk of harm. Retrospective cohort study. 15,210 patients diagnosed with dementia between 2008 and 2017 in South London. From recorded medications at dementia diagnosis, we ascertained those with drowsiness listed as a side effect (termed "sedative" hereafter) and subdivided them by frequency and strength of sedation, receptor profile, half-life, and whether they were psychotropics. Multivariable Cox regression models were applied to determine risk of mortality and emergency hospitalization, and generalized estimating equations to investigate cognitive decline. Final models were adjusted for 19 potential confounders, including measures of physical and mental health, functioning, and central anticholinergic burden. At diagnosis, 70.4% of patients with dementia were receiving at least 1 sedative medication. Median survival time was 4.0years and median time to first hospitalization 1.4years. After controlling for potential confounders, receipt of any sedative medication at dementia diagnosis was associated with accelerated cognitive decline and a higher hospitalization risk, but only medications with a cautionary warning yielded an increased mortality hazard. Medications acting through γ-aminobutyric acid agonism, psychotropic sedatives, and those with a short half-life were associated with a higher risk of mortality. γ-aminobutyric acid agonists, N-methyl-d-aspartate receptor antagonists, and nonpsychotropic sedatives were associated with an increased hospitalization risk. α1 antagonist, antihistamines, N-methyl-d-aspartate receptor antagonists, psychotropic sedatives, and those with the shortest or longest half-life were associated with accelerated cognitive decline. Receipt of any sedative agent was associated with hospitalization and accelerated cognitive decline. Differences in hazard appear to exist between frequency and strength of sedation, receptor profiles, half-life, and prescribing indication. These differences should be taken into consideration in medication reviews at the time of dementia diagnosis.

Determinants of hospital outcomes for patients with COVID-19 in the University of Pennsylvania Health System.

There is growing evidence that racial and ethnic minorities bear a disproportionate burden from COVID-19. Temporal changes in the pandemic epidemiology and diversity in the clinical course require careful study to identify determinants of poor outcomes. We analyzed 6255 hospitalized individuals with PCR-confirmed SARS-CoV-2 infection from one of 5 hospitals in the University of Pennsylvania Health System between March 2020 and March 2021, using electronic health records to assess risk factors and outcomes through 8 weeks post-admission. Discharge, readmission and mortality outcomes were analyzed in a multi-state model with multivariable Cox models for each transition. Mortality varied markedly over time, with cumulative incidence (95% CI) 30 days post-admission of 19.1% (16.9, 21.3) in March-April 2020, 5.7% (4.2, 7.5) in July-October 2020 and 10.5% (9.1,12.0) in January-March 2021; 26% of deaths occurred after discharge. Average age (SD) at admission varied from 62.7 (17.6) to 54.8 (19.9) to 60.5 (18.1); mechanical ventilation use declined from 21.3% to 9–11%. Compared to Caucasian, Black race was associated with more severe disease at admission, higher rates of co-morbidities and residing in a low-income zip code. Between-race risk differences in mortality risk diminished in multivariable models; while admitting hospital, increasing age, admission early in the pandemic, and severe disease and low blood pressure at admission were associated with increased mortality hazard. Hispanic ethnicity was associated with fewer baseline co-morbidities and lower mortality hazard (0.57, 95% CI: 0.37, .087). Multi-state modeling allows for a unified framework to analyze multiple outcomes throughout the disease course. Morbidity and mortality for hospitalized COVID-19 patients varied over time but post-discharge mortality remained non-trivial. Black race was associated with more risk factors for morbidity and with treatment at hospitals with lower mortality. Multivariable models suggest there are not between-race differences in outcomes. Future work is needed to better understand the identified between-hospital differences in mortality.