Competing Risks Cox Proportional Hazards Research Articles

Analysis of Bankruptcy Factors in Presale Projects and Their Policy Implications

ABSTRACT In this study, we suggest policy implications for managing the risk of bankruptcy in housing presale projects in Korea. In conclusion, we find that the competing risk Cox proportional hazard model (PHM) is the best model for explaining the bankruptcy factors of projects and the banks that lend construction funds and policy authorities need to manage presale projects by considering bankruptcy factors (the initial presale rate, regional factor, the credit rating of the developers, the housing common factor). This study differs from previous studies in that it uses the competing risk Cox proportional hazard model and single-index model methodologies for empirical analysis, distinguishes the causes of business failure as default and the default of repurchase agreement options that are similar to actual defaults, and suggests policy implications based on the analysis.

Does changes in unicompartmental knee arthroplasty practice pattern influence reasons for revision?

The aim of this study was to describe the pattern of revision indications for unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) and any change to this pattern for UKA patients over the last 20 years, and to investigate potential associations to changes in surgical practice over time. All primary knee arthroplasty surgeries performed due to primary osteoarthritis and their revisions reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were included. Complex surgeries were excluded. The data was linked to the National Patient Register and the Civil Registration System for comorbidity, mortality, and emigration status. TKAs were propensity score matched 4:1 to UKAs. Revision risks were compared using competing risk Cox proportional hazard regression with a shared γ frailty component. Aseptic loosening (loosening) was the most common revision indication for both UKA (26.7%) and TKA (29.5%). Pain and disease progression accounted for 54.6% of the remaining UKA revisions. Infections and instability accounted for 56.1% of the remaining TKA revision. The incidence of revision due to loosening or pain decreased over the last decade, being the second and third least common indications in 2017. There was a decrease associated with fixation method for pain (hazard ratio (HR) 0.40; 95% confidence interval (CI) 0.17 to 0.94) and loosening (HR 0.29; 95% CI 0.10 to 0.81) for cementless compared to cemented, and units UKA usage for pain (HR 0.67, 95% CI 0.50 to 0.91), and loosening (HR 0.51; 95% CI 0.37 to 0.70) for high usage. The overall revision patterns for UKA and TKA for the last 20 years are comparable to previous published patterns. We found large changes to UKA revision patterns in the last decade, and with the current surgical practice, revision due to pain or loosening are significantly less likely.

Unique cognitive trajectories associated with inflammatory markers of blood‐brain barrier permeability in atrial fibrillation: An analysis of the Cardiovascular Health Study Cohort

AbstractBackgroundAtrial fibrillation (AF) increases risk of cognitive decline independent of stroke, but mechanisms remain unclear. Elevated levels of peripheral inflammatory markers common in AF are associated with increased blood‐brain barrier (BBB) permeability and may contribute to neuroinflammation and degeneration. To examine the role of these markers in dementia risk, we estimated associations of plasma C‐reactive protein (CRP), interleukin‐6 (IL‐6), and fibrinogen with dementia and cognitive decline in aging adults with and without AF.MethodDementia free adults aged ≥ 65 years were identified from the Cardiovascular Health Cognition Study. Exposures were plasma CRP, IL‐6, and fibrinogen at baseline and follow‐up and primary outcomes were dementia and cognitive function, measured and adjudicated annually with the Modified Mini‐Mental State Examination (3MS). Competing risks Cox proportional hazards regression was used to estimate associations between time‐varying exposures and dementia. Latent class growth models were used to identify cognitive trajectories adjusted binomial logistic regression to test associations between these trajectories and baseline markers. All models were stratified by AF status, with interaction terms for sex and apolipoprotein E (APOE) ε4 status.ResultAmong 3,375 adults (505 with AF and 2,870 without), 480 developed dementia over a median follow‐up of 9.3 years. No associations between inflammatory markers and dementia hazard were observed, but latent class analyses identified two unique cognitive trajectories, with 82% showing a stable trajectory and 18% showing rapidly progressing decline. Among those with AF, elevated CRP and IL‐6 increased the odds of cognitive decline by 10% (95% CI 1.05 – 1.15) and 32% (95% CI 1.22 – 1.44), respectively. Sex‐specific models indicated that a 1g/L increase in fibrinogen increased the odds of cognitive decline by 57% among females with AF only (95% CI 1.36‐1.81). Among those with AF, inflammatory markers were more positively associated with cognitive decline in the presence of the APOE ε4 allele.ConclusionElevated IL‐6 was associated with cognitive decline in aging adults both with and without AF and elevated CRP and fibrinogen were associated with cognitive decline in those with AF only. Critically, sex and APOE genotype significantly modified these associations. Future work using more sensitive markers of central inflammation is needed.

Time to Extubation Among ARDS Subjects With and Without COVID-19 Pneumonia.

Pneumonia from COVID-19 that results in ARDS may require invasive mechanical ventilation. This retrospective study assessed the characteristics and outcomes of subjects with COVID-19-associated ARDS versus ARDS (non-COVID) during the first 6 months of the COVID-19 pandemic in 2020. The primary objective was to determine whether mechanical ventilation duration differed between these cohorts and identify other potential contributory factors. We retrospectively identified 73 subjects admitted between March 1 and August 12, 2020, with either COVID-19-associated ARDS (37) or ARDS (36) who were managed with the lung protective ventilator protocol and required >48 h of mechanical ventilation. Exclusion criteria were the following: <18 years old or the patient required tracheostomy or interfacility transfer. Demographic and baseline clinical data were collected at ARDS onset (ARDS day 0), with subsequent data collected on ARDS days 1-3, 5, 7, 10, 14, and 21. Comparisons were made by using the Wilcoxon rank-sum test (continuous variables) and chi-square test (categorical variables) stratified by COVID-19 status. A Cox proportional hazards model assessed the cause-specific hazard ratio for extubation. The median (interquartile range) mechanical ventilation duration among the subjects who survived to extubation was longer in those with COVID-19-ARDS versus the subjects with non-COVID ARDS: 10 (6-20) d versus 4 (2-8) d; P < .001. Hospital mortality was not different between the two groups (22% vs 39%; P = .11). The competing risks Cox proportional hazard analysis (fit among the total sample, including non-survivors) revealed that improved compliance of the respiratory system and oxygenation were associated with the probability of extubation. Oxygenation improved at a lower rate in the subjects with COVID-19-associated ARDS than in the subjects with non-COVID ARDS. Mechanical ventilation duration was longer in subjects with COVID-19-associated ARDS compared with the subjects with non-COVID ARDS, which may be explained by a lower rate of improvement in oxygenation status.

Physiologic dead space is independently associated with mortality and discharge of mechanically ventilated patients with COVID-19 ARDS: a retrospective study

Physiologic dead space is a well-established independent predictor of death in patients with acute respiratory distress syndrome (ARDS). Here, we explore the association between a surrogate measure of dead space (DS) and early outcomes of mechanically ventilated patients admitted to Intensive Care Unit (ICU) because of COVID-19-associated ARDS. Retrospective cohort study on data derived from Italian ICUs during the first year of the COVID-19 epidemic. A competing risk Cox proportional hazard model was applied to test for the association of DS with two competing outcomes (death or discharge from the ICU) while adjusting for confounders. The final population consisted of 401 patients from seven ICUs. A significant association of DS with both death (HR 1.204; CI 1.019–1.423; p = 0.029) and discharge (HR 0.434; CI 0.414–0.456; p< 0.001) was noticed even when correcting for confounding factors (age, sex, chronic obstructive pulmonary disease, diabetes, PaO_{2}/FiO_{2}, tidal volume, positive end-expiratory pressure, and systolic blood pressure). These results confirm the important association between DS and death or ICU discharge in mechanically ventilated patients with COVID-19-associated ARDS. Further work is needed to identify the optimal role of DS monitoring in this setting and to understand the physiological mechanisms underlying these associations.

Early childhood lower respiratory tract infection and premature adult death from respiratory disease in Great Britain: a national birth cohort study

Lower respiratory tract infections (LRTIs) in early childhood are known to influence lung development and lifelong lung health, but their link to premature adult death from respiratory disease is unclear. We aimed to estimate the association between early childhood LRTI and the risk and burden of premature adult mortality from respiratory disease. This longitudinal observational cohort study used data collected prospectively by the Medical Research Council National Survey of Health and Development in a nationally representative cohort recruited at birth in March, 1946, in England, Scotland, and Wales. We evaluated the association between LRTI during early childhood (age <2 years) and death from respiratory disease from age 26 through 73 years. Early childhood LRTI occurrence was reported by parents or guardians. Cause and date of death were obtained from the National Health Service Central Register. Hazard ratios (HRs) and population attributable risk associated with early childhood LRTI were estimated using competing risks Cox proportional hazards models, adjusted for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and smoking at age 20-25 years. We compared mortality within the cohort studied with national mortality patterns and estimated corresponding excess deaths occurring nationally during the study period. 5362 participants were enrolled in March, 1946, and 4032 (75%) continued participating in the study at age 20-25 years. 443 participants with incomplete data on early childhood (368 [9%] of 4032), smoking (57 [1%]), or mortality (18 [<1%]) were excluded. 3589 participants aged 26 years (1840 [51%] male and 1749 [49%] female) were included in the survival analyses from 1972 onwards. The maximum follow-up time was 47·9 years. Among 3589 participants, 913 (25%) who had an LRTI during early childhood were at greater risk of dying from respiratory disease by age 73 years than those with no LRTI during early childhood (HR 1·93, 95% CI 1·10-3·37; p=0·021), after adjustment for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and adult smoking. This finding corresponded to a population attributable risk of 20·4% (95% CI 3·8-29·8) and 179 188 (95% CI 33 806-261 519) excess deaths across England and Wales between 1972 and 2019. In this prospective, life-spanning, nationally representative cohort study, LRTI during early childhood was associated with almost a two times increased risk of premature adult death from respiratory disease, and accounted for one-fifth of these deaths. National Institute for Health and Care Research Imperial Biomedical Research Centre, Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Royal Brompton and Harefield Hospitals Charity and Imperial College Healthcare NHS Trust, UK Medical Research Council.

EDITORIAL COMMENT

The authors retrospectively evaluated 6319 patients with renal tumors from 1980 to 2018 of whom 56% were treated with radical nephrectomy (RN) and 44% with partial nephrectomy (PN). They utilized multivariable linear and competing risk Cox proportional hazards models for increase in chronic kidney disease (CKD) staging to determine if there was a significant interaction between type of operation and preoperative CKD stage. They reported 12 months eGFR calculations in 3046 (48%) of the patients. Of note, 2055 patients (33%) had significant preexisting CKD (eGFR<60), 3466 patients (54%) had hypertension, 843 patients (13%) were diabetic, and 3440 patients (54%) were former or current smokers.

T083: The Effect of Heart Failure on Management and Outcomes of Older Patients with Hodgkin Lymphoma

Figure 1: Cumulative incidence of lymphoma mortality (blue), cardiovascular mortality (red) and all-cause mortality (black). Dashed line represents patients with heart failure at the time of lymphoma diagnosis and solid lines patients without heart failure Background: Anthracycline-containing regimens are recommended as first-line treatment for Hodgkin lymphoma (HL); however, the management and outcomes of patients with cardiomyopathy or heart failure (HF) at the time of lymphoma diagnosis is not known. Methods: US Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1999–2016 were used to identify newly diagnosed HL in patients 66 years and older with one year of Medicare A and B prior to lymphoma diagnosis. Prevalent HF and comorbidities in the year prior to lymphoma diagnosis were identified using International Classification of Diseases codes. Cancer treatment, including doxorubicin and cardioprotective medications (i.e., liposomal doxorubicin and dexrazoxane) were assessed using Healthcare Common Procedure Coding Systems codes. Cause of death was defined using the SEER Cause of Death Recodes. The association between prevalent HF and cancer treatment was estimated using logistic regression with adjustment for comorbidities, social determinants of health and hospital level variables. The association between prevalent HF and cause specific mortality was evaluated using competing risk Cox proportional hazards models with sequential adjustment for comorbidities and cancer treatment. Results: Among 3,348 individuals with newly diagnosed HL, prevalent HF was present in 13.1%. Patients with prevalent HF were less likely to be treated with an anthracycline in the first year after diagnosis (OR 0.42, 95% CI 0.29, 0.60). Among patients with HF who received an anthracycline, dexrazoxane or liposomal doxorubicin was used in only 4.5%. For those with prevalent HF, 1-year lymphoma mortality was 37.4% (95% CI 35.5, 39.5%) [Fig]. In multivariable models adjusting for clinical covariates, prevalent HF was associated with higher lymphoma mortality (HR 1.21, 95% CI 1.03, 1.41); however, the effect of prevalent HF on lymphoma mortality was no longer significant when adding cancer treatment variables to the model (HR 1.05, 95% CI 0.71, 1.56) [Fig]. Prevalent HF was also associated with cardiovascular mortality in fully adjusted models (HR 1.77, 95% CI 1.34, 2.32). Conclusion: HF is common in older patients with HL and is associated with less anthracycline use and higher lymphoma mortality. Dexrazoxane and liposomal doxorubicin are used infrequently. Future randomized trials are needed to determine strategies to decrease lymphoma and cardiac mortality in this high-risk population.

Progression of Chronic Kidney Disease Following Radical and Partial Nephrectomy

ObjectiveTo compare renal functional outcomes, as determined by percent decline in estimated glomerular filtration rate (eGFR) and CKD stage progression following radical (RN) and partial nephrectomy (PN) stratified by preoperative CKD stage. Materials and MethodsWe retrospectively evaluated adults treated with RN or PN between 1980 and 2018 for unilateral, sporadic, solid renal masses. Multivariable linear models for percent change in eGFR (n = 3046) and competing-risk Cox proportional hazards models for increase in CKD staging (n = 5805) were used to determine if there was a significant interaction between type of surgery (RN vs PN) and preoperative CKD stage. ResultsPercent change in eGFR at 1 year was significantly worse for RN (n = 1724; 57%) compared with PN (n = 1322; 43%) for all preoperative CKD stages. RN (n = 3227; 56%) was more likely to result in CKD stage progression compared with PN (n = 2578; 44%) for preoperative CKD stages I-IIIb (P <.001) but not for CKD stage IV (P = .8). ConclusionRN was more likely to result in decline in eGFR and CKD stage progression compared to PN for patients with preoperative CKD stage IIIb or less. Additionally, RN was associated with a significantly greater decline in eGFR at 1 year relative to PN in the CKD stage IV subset. Our data support performing PN for renal preservation when feasible.

Risk factors for severe lower extremity ischemia following venoarterial extracorporeal membrane oxygenation: an analysis using a nationwide inpatient database

ObjectivesVenoarterial extracorporeal membrane oxygenation is increasingly being used as a life-saving modality in critically ill patients. Despite its necessity, severe lower extremity ischemia associated with venoarterial extracorporeal membrane oxygenation remains...

Associations of long-term exposure to fine particulate matter and its constituents with cardiovascular mortality: A prospective cohort study in China.

Few studies have evaluated long-term cardiovascular effects of fine particulate matter (PM2.5) and its constituents in countries with high air pollution levels. We aimed to investigate the associations of long-term exposure to PM2.5 and constituents with cardiovascular mortality in China. We conducted a prospective cohort study of 90,672 adults≥18years from 2010 to 2017 in 161 districts/counties across China. The residential annual-average exposure to PM2.5 and 6 main components from 2011 to 2017 were estimated by satellite-based and chemical transport models. Associations of PM2.5 and constituents with cardiovascular mortality were analyzed by competing-risk Cox proportional hazards regression. The average PM2.5 exposure throughout the whole period was 46±22μg/m3. The hazard ratios of mortality (95% confidence intervals) per 10μg/m3 increase in PM2.5 concentrations were 1.02 (1.00, 1.05) for overall cardiovascular disease, 1.05 (1.01, 1.09) for ischemic heart disease, 1.03 (1.00, 1.06) for overall stroke, 0.99 (0.94, 1.04) for hemorrhagic stroke, and 1.11 (1.04, 1.19) for ischemic stroke. PM2.5 constituents from fossil fuel combustion (i.e., black carbon, organic matter, nitrate, ammonium, and sulfate) showed larger hazard ratios than PM2.5 total mass, while soil dust showed no risks. This nationwide cohort study demonstrated associations of long-term exposure to PM2.5 and its constituents with increased risks of cardiovascular mortality in the general population of China. Our study highlighted the importance of PM2.5 constituents from fossil fuel combustion in the long-term cardiovascular effects of PM2.5 in China.

The Effect of Low-Dose Aspirin on Frailty in Older Adults in the Aspirin in Reducing Events in the Elderly Study

There are no widely accepted pharmacologic treatments for frailty prevention. Since frailty is associated with inflammation, aspirin has the potential to reduce frailty. We investigated whether low-dose aspirin reduces incident frailty in participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. In the U.S and Australia, 19,114 healthy community-dwelling individuals aged ≥70 years (U.S. minorities ≥65 years) were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100mg daily low-dose aspirin vs. placebo. Frailty was defined according to a modified Fried frailty definition, and a frailty index which used a deficit accumulation model. Competing risk Cox proportional hazards models were used to compare time to incident frailty for aspirin vs. placebo. At baseline, 2.2% and 8.1% met criteria for frailty by Fried and frailty index criteria, respectively. Over a median of 4.7 years of follow-up, 2252 participants developed incident frailty according to Fried classification, and 4376 according to the frailty deficit accumulation index. There was no difference in the risk of incident frailty between individuals randomized to aspirin versus placebo according to either criteria (Fried frailty HR: 1.03, 95% CI 0.97-1.09, p=0.41; frailty index HR: 1.03, 95% CI 0.97-1.10, p=0.29). Change in frailty over time was not different between the aspirin and placebo treatment arms. The results were consistent across a series of sub-groups, including baseline frailty status. Based on these results, aspirin use in healthy older adults does not reduce incident frailty.

The Effect of Low-Dose Aspirin on Frailty Phenotype and Frailty Index in Community-Dwelling Older Adults in the ASPirin in Reducing Events in the Elderly Study.

Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data. Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96-1.13; frailty index HR: 1.03, 95% CI 0.97-1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups. Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty.

Factors associated with time to independent walking recovery post-stroke

BackgroundPast studies have inconsistently identified factors associated with independent walking post-stroke. We investigated the relationship between pre-stroke factors and factors collected acutely after stroke and number of days to walking...

Association of Sepsis Mortality with Specific Cancer Sites and Treatment Type: The Multiethnic Cohort Study

Sepsis is a severe dysregulated immune response to infection. Sepsis deaths represent 9% of cancer deaths in the U.S. Evidence of the effect of specific cancer sites on sepsis mortality risk remains limited, and no research has evaluated the effect of cancer treatment on the risk of sepsis death. We examined whether cancer sites and treatments differentially affect the risk of sepsis death compared to other-cause mortality, among the 94,784 Hawaii participants in the Multiethnic Cohort, including 29,255 cancer cases, using competing risk Cox proportional hazards regression. Cancer diagnosis at any site was associated with similar increases in sepsis and non-sepsis mortality risk (HR: 3.39 and 3.51, resp.). Colorectal cancer differentially affected the risk of sepsis and non-sepsis mortality with a 40% higher effect on the risk of sepsis death compared with non-sepsis mortality (RRR: 1.40; 95% CI: 1.14–1.72). Lung cancer was associated with a significantly lower increase in sepsis compared to non-sepsis mortality (HR: 1.22 and 3.0, resp.; RRR: 0.39). Radiation therapy had no effect on sepsis mortality but was associated with higher risk of non-sepsis mortality (HR: 0.90 and 1.16, resp.; RRR: 0.76), whereas chemotherapy was associated with higher risk of both sepsis and non-sepsis mortality (HR: 1.31 and 1.21, resp.). We conclude that the risk of sepsis-related mortality is differentially affected by cancer sites and treatments. These associations were consistent across sexes and ethnic groups.

Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium.

Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

Co-consumption of Vegetables and Fruit, Whole Grains, and Fiber Reduces the Cancer Risk of Red and Processed Meat in a Large Prospective Cohort of Adults from Alberta's Tomorrow Project.

We examined whether co-consumption of red and processed meat with key foods items and food constituents recommended for cancer prevention (vegetables and fruit, whole grains, and fiber) mitigates cancer incidence. In a prospective cohort of 26,218 adults aged 35–69 years at baseline, dietary intake was collected through 124-item past-year food frequency questionnaire. Incidence of all-cause and 15 cancers previously linked to red and processed meat intake was obtained through data linkage with a cancer registry (average follow-up 13.5 years). Competing risk Cox Proportional Hazard models estimated cancer risk and Accelerated Failure Time models estimated time-to-cancer occurrence for different combinations of intake levels while considering mortality from vital statistics and established confounders. Co-consumption of low vegetables and fruit intake with high processed meat was associated with higher incidence of all-cause and 15 cancers (men: HR = 1.85, 1.91; women: HR = 1.44, 1.49) and accelerated time-to-cancer occurrence (men: 6.5 and 7.1 years and women: 5.6 and 6.3 years, respectively), compared to high vegetables and fruit with low processed meat intake. Less pronounced and less consistent associations were observed for whole grains and fiber and for red meat. The findings provide initial evidence toward refining existing cancer prevention recommendations to optimize the intake and combination of foods in the general adult population.

Comparison of clinical outcomes and impact of SVR in American and Chinese patients with chronic hepatitis C

Background & AimsChronic HCV infection is an important cause of hepatocellular carcinoma (HCC) and liver failure in the US but limited data are available in China. We compared the incidence of clinical outcomes among adults with chronic HCV infection in the US and China and examined factors associated with outcomes.MethodsA parallel prospective study of 2 cohorts of patients with HCV RNA+ recruited in 1 site in the US (UMHS) and 3 sites (PUHSC) in China between September 2011 and July 2015 was carried out. Composite liver outcomes (liver-related deaths, HCC, liver transplantation or liver decompensation), were analysed using competing-risk Cox proportional hazards model to determine incidence and associated factors.ResultsA total of 795 UMHS and 854 PUHSC patients were followed for a median of 3.06 and 3.99 years, respectively. At enrolment, a significantly higher percentage of UMHS patients had cirrhosis (45.4% vs. 16.2%). The 5-year cumulative incidence of composite liver outcomes was significantly higher in UMHS than in PUHSC patients (25.3% vs. 6.6%, p <0.0001). Stratification by stage of liver disease at enrolment showed this difference persisted only in the subgroup without cirrhosis due to higher aspartate aminotransferase to platelet ratio index (APRI) in the UMHS cohort. A total of 493 UMHS and 502 PUHSC patients received HCV treatment, and sustained virologic response (SVR) was achieved in 88.0% UMHS and 86.8% PUHSC treated-patients. SVR as time-dependent variable was associated with 80% lower risk of composite liver outcomes among patients with decompensated cirrhosis but not the overall cohorts.ConclusionsWhen accounting for disease severity at entry, the incidence of composite liver outcomes was similar in patients with HCV in the US and China. Achievement of SVR had the greatest short-term impact on patients with decompensated cirrhosis.Lay summaryPatients with chronic hepatitis C virus infection were recruited from centres in the United States and China. During follow-up, a higher percentage of the American patients had clinical outcomes: liver failure, liver cancer, liver transplant or liver-related deaths than the Chinese patients, mainly because more American patients had cirrhosis at enrolment. Older age and more advanced liver disease were associated with higher incidence of outcomes overall and viral clearance after hepatitis C treatment was associated with a lower incidence of outcomes in patients with advanced cirrhosis. Our findings highlight the importance of improving diagnosis and treatment of hepatitis C before advanced liver disease develops.

Atrial Cardiopathy in the Absence of Atrial Fibrillation Increases Risk of Ischemic Stroke, Incident Atrial Fibrillation, and Mortality and Improves Stroke Risk Prediction

BackgroundAtrial fibrillation (AF) is a major, often undetected, cardiac cause of stroke. Markers of atrial cardiopathy, including left atrial enlargement (LAE) or excessive atrial ectopy (EAE) increase the risk of AF and have shown associations with stroke. We sought to determine whether these markers improve stroke risk prediction beyond traditional vascular risk factors (eg CHA 2 DS 2‐VASc score).Methods and ResultsRetrospective longitudinal cohort of 32 454 consecutive community‐dwelling adults aged ≥65 years referred for outpatient echocardiogram or Holter in Ontario, Canada (2010–2017). Moderate‐severe LAE was defined as men >47 mm and women >43 mm, and EAE was defined as >30 APBs per hour. Cause‐specific competing risks Cox proportional hazards used to estimate risk of ischemic stroke (primary), incident AF, and death (secondary). C‐statistics, incremental discrimination improvement and net reclassification were used to compare CHA 2 DS 2‐VASc with LAE and EAE to CHA 2 DS 2‐VASc alone. Each 10 mm increase in left atrial diameter increased 2‐ and 5‐year adjusted cause‐specific stroke hazard almost 2‐fold (LAE: 2‐year hazard ratio (HR), 1.72; P=0.007; 5‐year HR, 1.87; P<0.0001), while EAE showed no significant associations with stroke (2‐year HR, 1.00; P=0.99; 5‐year HR, 1.08, P=0.70), adjusting for incident AF. Stroke risk estimation improved significantly at 2 (C‐statistics=0.68–0.75, P=0.008) and 5 years (C‐statistics=0.70–0.76, P=0.003) with LAE and EAE.Conclusions LAE was independently associated with an increased risk of ischemic stroke in the absence of AF and both LAE and EAE improved stroke risk prediction. These findings have implications for stroke risk stratification, AF screening, and stroke prevention before the onset of AF.

Anticholinergic drug exposure at intensive care unit admission affects the occurrence of delirium. A prospective cohort study

BackgroundAnticholinergic drugs may increase the risk of delirium in non-critically ill patients, but it is unclear whether exposure to these drugs is also a risk factor for Intensive Care Unit (ICU) delirium. In this study the hypothesis was tested that anticholinergic drug exposure at ICU admission increases the risk to develop delirium during ICU stay, particularly in patients with advanced age and severe sepsis. MethodsA prospective cohort study was performed in the mixed 32-bed medical-surgical ICU of the University Medical Center Utrecht, the Netherlands in the period from January 2011 till June 2013. Included were nonneurological patients that were consecutively admitted for more than 24 hours. The presence of delirium was evaluated each day using a validated algorithm based on the Confusion Assessment Method for the ICU (CAM-ICU), the initiation of delirium treatment as well as chart review by researchers. Anticholinergic drug exposure at ICU admission was assessed using the Anticholinergic Drug Scale (ADS). To evaluate the association between anticholinergic drug exposure at ICU admission and the risk of developing delirium, we performed multivariable competing risk Cox proportional hazard analysis corrected for confounding factors. ResultsApproximately half (47%, n=513) of the 1090 included patients developed delirium during ICU admission. The absolute risk for delirium development increased with more anticholinergic drug exposure: 42% in patients with ADS score=0, 49% in patients with ADS score=1, and 53% in patients with ADS higher than 1. Taking competing events (death and discharge) and potential confounding factors into account, the subdistribution hazard ratio (SHR) was 1.13 (95% CI: 0.91-1.40) for ADS score=1 point and 1.35 (95% CI: 1.09-1.68) for ADS ≥2 compared with an ADS score=0 (no anticholinergic drug exposure). The effect was strongest during the first days of ICU admittance and was strongest in patients above 65 year without severe sepsis and/or septic shock (SHR 2.15, 95% CI 1.43-3.25). ConclusionsAnticholinergic drug exposure at ICU admission increases the risk of delirium in critically ill patients. This effect was most pronounced in patients older than 65 years without severe sepsis and/or septic shock, and declining over time.