Search

Background: In recent years, age at liver transplantation (LT) has markedly increased. In the context of organ shortage, we investigated the impact of recipient age on post‐transplantation mortality. Methods: All adult patients who received a first LT between 2007 and 2017 were included in this cross‐sectional study. Recipients' characteristics at the time of listing, donor and surgery data, post‐operative complications and follow‐up of vital status were retrieved from the national transplantation database. The impact of age on 5‐year overall mortality post‐LT was estimated using a flexible multivariable parametric model which was also used to estimate the association between age and 10‐year net survival, accounting for expected age‐ and sex‐related mortality. Results: Among the 7610 patients, 21.4% were aged 60–65 years, and 15.7% over 65. With increasing age, comorbidities increased but severity of liver disease decreased. Older recipient age was associated with decreased observed survival at 5 years after LT (p <.001), with a significant effect particularly during the first 2 years. The linear increase in the risk of death associated with age does not allow any definition of an age's threshold for LT (p =.832). Other covariates associated with an increased risk of 5‐year death were dialysis and mechanical ventilation at transplant, transfusion during LT, hepatocellular carcinoma and donor age. Ten‐year flexible net survival analysis confirmed these results. Conclusion: Although there was a selection process for older recipients, increasing age at LT was associated with an increased risk of death, particularly in the first years after LT. [ABSTRACT FROM AUTHOR]

The article investigates whether rhythm control versus rate control treatment strategies for atrial fibrillation (AF) have similar effectiveness when applied to a general population of patients with AF with longer follow-up. Results reveal little difference in mortality within four years of treatment initiation between patients with AF initiating rhythm control therapy versus those initiating rate control therapy. Rhythm control therapy, however, appears to be superior in the long-term.

Abstract: Objective: The instrumental variable (IV) method can remove bias because of unobserved confounding, but it is unclear to what extent the choice of the IV may affect the results. We compared the estimates obtained with different provider-based IVs in a real-life observational comparative drug effectiveness study. Study Design and Setting: We assessed the effectiveness of rhythm vs. rate control treatment in reducing 5-years mortality in a population-based cohort of patients with atrial fibrillation. We compared the IV treatment effect estimates obtained from two-stage least square regression models using nine alternative provider-based IVs defined at either hospital or physician level. Results: All nine IVs reduced the covariate imbalance between the treatment groups. Yet, there were large variations in both the point estimates and the width of the confidence intervals obtained with alternative IVs. Relative to the physician-based IVs, the hospital-based IVs were stronger, had smaller variance, and produced less extreme point estimates. Conclusions: The IV estimates of treatment effect may vary considerably depending on the IV definition. Choosing the strongest IV could reduce the variance of the IV estimates. [Copyright &y& Elsevier]

Background: Existing clinical trial data do not address whether all angiotensin-converting-enzyme (ACE) inhibitors are similarly beneficial in improving survival and reducing the rate of readmission among patients with congestive heart failure. We sought to answer this question using administrative databases from Canada's 3 most populous provinces. Methods: Using linked hospital discharge and prescription claims databases in Quebec, Ontario and British Columbia, we identified all patients 65 years or older who were admitted to hospital because of congestive heart failure between Jan. 1, 1998, and Mar. 31, 2002, and who had not been admitted for the same reason in the 3 years preceding the study period. We analyzed the association between the type of ACE inhibitor prescribed within 30 days after discharge and subsequent mortality using Cox proportional hazards models. We then adjusted for demographic, clinical, physician and hospital-related variables, with additional time-dependent variables representing current drug use and dosage. We chose ramipril as the reference category for comparison with the other ACE inhibitors because it has increasingly been prescribed to patients with congestive heart failure. Results: A total of 43 316 patients with congestive heart failure filled prescriptions for ACE inhibitors within 30 days after discharge from hospital. Demographic, clinical and prescription-related characteristics were similar among users of each type of ACE inhibitor. In the time-dependent model, the mortality associated with 5 ACE inhibitors was similar to that with ramipril: adjusted hazard ratios (and 95% confidence intervals [CIs]) were 0.95 (0.89-1.02) for lisinopril, 0.92 (0.85-1.00) for fosinopril, 0.99 (0.88-1.11) for quinapril, 0.90 (0.77-1.06) for perindopril and 1.00 (0.80-1.24) for cilazapril. However, use of enalapril or captopril was associated with higher mortality compared with ramipril: adjusted hazard ratios (and 95% CIs) were 1.10 (1.04-1.16) for enalapril and 1.13 (1.01-1.26) for captopril. Interpretation: When prescribing ACE inhibitors to patients, physicians should consider a possible 10%-15% increase in mortality with captopril and enalapril compared with ramipril among patients with congestive heart failure. [ABSTRACT FROM AUTHOR]

Background: Several randomized, controlled trials show that angiotensin-converting enzyme (ACE) inhibitors improve survival in patients who have had an acute myocardial infarction. However, existing data from trials do not address whether all ACE inhibitors benefit patients similarly. Objective: To evaluate whether all ACE inhibitors are associated with similar mortality in patients 65 years of age or older who have had an acute myocardial infarction. Design: Retrospective cohort study that used linked hospital discharge and prescription databases containing information on 18 453 patients 65 years of age or older who were admitted for an acute myocardial infarction between 1 April 1996 and 31 March 2000. Setting: 109 hospitals in Quebec, Canada. Patients: 7512 patients who filled a prescription for an ACE inhibitor within 30 days of discharge and who continued to receive the same drug for at least 1 year. Measurements: The association between the specific drugs and clinical outcomes was measured by using Cox proportional hazards models, with adjustment for demographic, clinical, physician, and hospital variables and dosage categories, represented by time-dependent variables. Results: Enalapril, fosinopril, captopril, quinapril, and lisinopril were associated with higher mortality than was ramipril; the adjusted hazard ratios and 95% CIs were 1.47 (95% CI, 1.14 to 1.89), 1.71 (CI, 1.29 to 2.25), 1.56 (CI, 1.13 to 2.15), 1.58 (CI, 1.10 to 2.82), and 1.28 (CI, 0.98 to 1.67), respectively. The adjusted hazard ratio associated with perindopril was 0.98 (CI, 0.60 to 1.60). Limitations: The administrative databases did not contain detailed clinical information, and unmeasured factors associated with a patient's risk for death may have influenced physicians' prescription choices. Conclusion: Survival benefits in the first year after acute myocardial infarction in patients 65 years of age or older seem to differ according to the specific ACE inhibitor prescribed. Ramipr... [ABSTRACT FROM AUTHOR]

Accurate estimation of the exposure-response relationship between environmental particulate air pollution and mortality is important from both an etiologic and regulatory perspective. However, little is known about the actual shapes of these exposure-response curves. The objective of this studywas to estimate theexposure-response relationshipsbetween mortality and long-term average city-specific levels of sulfates and fine particulate matter (PM 2.5 ). We reanalyzed the data derived from the American Cancer Society (ACS) Cancer Prevention Study II, a large prospective study conducted in the United States between 1982 and 1989. Exposure to particulate air pollution was assessed prior to entry into the cohort. Mean sulfate concentrations for 1980 were available in 151 cities, and median PM 2.5 levels between 1979 and 1983 were available in 50 cities. Two sampling strategies were employed to reduce the computational burden. The modified case-cohort approach combined a random subcohort of 1200 individuals with an additional 1300 cases (i.e., deaths). The second strategy involved pooling the results of separate analyses of 10 disjoint random subsets, each with about 2200 participants. To assess the independent effect of the particulate levels on all-causes mortality, we relied on flexible, nonparametric survival analytical methods. To eliminate potentially restrictive assumptions underlying the conventional models, we employed a flexible regression spline generalization of the Cox proportional-hazards (PH) model. The regression spline method allowed us to model simultaneously the time-dependent changes in the effect of particulate matter on the hazard and a possibly nonlinear exposure-response relationship. The PH and linearity hypotheses were tested using likelihood ratio tests. In all analyses, we stratified by age and 5-yr age groups and adjusted for the subject's age, lifetime smoking exposure, obesity, and education. For both fine particles (PM 2.5 ) and sulfates, there was a statistically significant (at .05 level) departure from the conventional linearity assumption. The adjusted effect of fine particles on mortality indicated a stronger relationship in the lower (up to about 16 μg/m 3 ) than in the higher range of their values. Increasing levels of sulfates in the lower range (up to about 12 μg/m 3 ) had little impact on mortality, suggesting a possible "no-effect threshold." For body mass index (BMI), the risks were lowest in the middle range and increased for both very obese and very lean individuals. It was concluded that flexible modeling yields new insights about the effect of long-term air pollution on mortality. [ABSTRACT FROM AUTHOR]

Background: Delirium has not been found to be a significant predictor of postdischarge mortality, but previous research has methodologic limitations including small sample sizes and inadequate control of confounding. This study aimed to determine the independent effects of presence of delirium, type of delirium (incident vs prevalent), and severity of delirium symptoms on 12-month mortality among older medical inpatients. Methods: A prospective, observational study of 2 cohorts of medical inpatients was conducted with patients 65 years or older: 243 patients had prevalent or incident delirium, and 118 controls had no delirium. Baseline measures included presence of delirium and/or dementia, severity of delirium symptoms, physical function, comorbidity, and physiological and clinical severity of illness. Mortality during the 12 months after enrollment was analyzed with the Cox proportional hazards model with adjustment for covariates. Results: The unadjusted hazard ratio of delirium with mortality was 3.44 (95% confidence interval, 2.05-5.75); the adjusted hazard ratio was 2.11 (95% confidence interval, 1.18-3.77). The effect of delirium was sustained over the entire 12-month period after adjustment for covariates and was stronger among patients without dementia. Among patients with dementia, there was a weak, nonsignificant effect of delirium on survival. After adjustment for covariates, mortality did not differ between patients with incident and prevalent delirium, but among patients with delirium without dementia, greater severity of delirium symptoms was associated with higher mortality. Conclusions: Delirium is an independent marker for increased mortality among older medical inpatients during the 12 months after hospital admission. It is a particularly important prognostic marker among patients without dementia. [ABSTRACT FROM AUTHOR]

Background--Clinical guidelines recommend specialized care for adult congenital heart disease (ACHD) patients. In reality, few patients receive such dedicated care. We sought to examine the impact of specialized care on ACHD patient mortality. Methods and Results--We examined referral rates to specialized ACHD centers and ACHD patient mortality rates between 1990 and 2005 in the population-based Quebec Congenital Heart Disease database (n=71 467). This period covers several years before and after the publication of guidelines endorsing specialized care for ACHD patients. A time-series design, based on Joinpoint and Poisson regression analyses, was used to assess the changes in annual referral and patient mortality rates. The association between specialized ACHD care and all-cause mortality was assessed in both case-control and cohort studies. The time-series analysis demonstrated a significant increase in referral rates to specialized ACHD centers in 1997 (rate ratio, +7.4%; 95% confidence interval [CI], +6.6% to +8.2%). In parallel, a significant reduction in expected ACHD patient mortality was observed after year 2000 (rate ratio, -5.0%;95% CI, -10.8% to -0.8%). In exploratory post hoc cohort and case-control analyses, specialized ACHD care was independently associated with reduced mortality (hazard ratio, 0.78; 95% CI, 0.65-0.94) and a reduced odds of death (adjusted odds ratio, 0.82; 95% CI, 0.08-0.97), respectively. This effect was predominantly driven by patients with severe congenital heart disease (hazard ratio, 0.38; 95% CI, 0.22-0.67). Conclusions--A significant increase in referrals to specialized ACHD centers followed the introduction of the clinical guidelines. Moreover, referral to specialized ACHD care was independently associated with a significant mortality reduction. Our findings support a model of specialized care for all ACHD patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate mortality of ICU patients over a 3-month period after an initial episode of septic shock and to identify factors associated with mortality. Design: Prospective multicenter observational cohort study. Setting: Fourteen ICUs from 10 French nonacademic and university teaching hospitals. Patients: All consecutive adult patients with septic shock admitted between October 2009 and September 2011 were eligible. Intervention: None. Measurements and Main Results: Multivariable analyses were performed using a Cox proportional hazard model and a flexible extension of the Cox model. In total, 1,495 of 10,941 patients (13.7%) had septic shock and 1,488 patients (99.5%) were included. Median age was 68 years (range, 58-78 yr). The majority of admissions (84%) were medical. Median (interquartile range) Simplified Acute Physiological Score II and Sequential Organ Failure Assessment were, respectively, 56 (45-70) and 11 (9-14). ICU and hospital mortality were, respectively, 39.4% and 48.6%. At 3 months, 776 patients (52.2%) had died. Factors significantly associated with increased risk of death in the multivariable Cox model were older age, male sex, comorbidities (immune deficiency, cirrhosis), Knaus C/D score, and high Sequential Organ Failure Assessment score. Flexible analyses indicated that the impact of Sequential Organ Failure Assessment score was greatest early after septic shock, while the onset of the effect of age, nosocomial infection, and cirrhosis was later. Conclusions: This is the most recent large-scale epidemiological study to investigate medium-term mortality in nonselected patients hospitalized in the ICU for septic shock. Advances in early management have improved survival at the initial phase, but risk of death persists in the medium term. Flexible modeling techniques yield insights into the profile of the risk of death in the first 3 months. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to characterize temporal trends in all-cause mortality in patients with congenital heart disease (CHD). Background: Historically, most deaths in patients with CHD occurred in early childhood. Notable advances have since been achieved that may impact on mortality trends. Methods: We conducted a population-based cohort study of patients with CHD in Quebec, Canada, from July 1987 to June 2005. A total of 8,561 deaths occurred in 71,686 patients with CHD followed for 982,363 patient-years. Results: The proportion of infant and childhood deaths markedly declined from 1987 to 2005, with a reduction in mortality that exceeded that of the general population. Distribution of age at death transitioned from a bimodal to unimodal, albeit skewed, pattern, more closely approximating the general population. Overall, mortality decreased by 31% (mortality rate ratio: 0.69, 95% confidence interval [CI]: 0.61 to 0.79) in the last (2002 to 2005) relative to the first (1987 to 1990) period of observation. Mortality rates decreased in all age groups below 65 years, with the largest reduction in infants (mortality rate ratio: 0.23, 95% CI: 0.12 to 0.47). In adults 18 to 64 years, the mortality reduction (mortality rate ratio: 0.84, 95% CI: 0.73 to 0.97) paralleled the general population. Gains in survival were mostly driven by reduced mortality in severe forms of CHD, particularly in children (mortality rate ratio: 0.33, 95% CI: 0.19 to 0.60), and were consistent across most subtypes. Conclusions: Deaths in CHD have shifted away from infants and towards adults, with a steady increase in age at death and decreasing mortality. [ABSTRACT FROM AUTHOR]

This article presents information about a study which examines the relationship between myocardial injury and outcome in selected critically ill patients without acute coronary syndromes or cardiac dysfunction. Over a 6-month period, 217 consecutive patients admitted to the ICU were studied. Cardiac troponin I assays were performed in all patients on admission to the ICU. This study demonstrates the high frequency of myocardial injury (32%) in critically ill patients without acute coronary syndromes or cardiac dysfunction on admission to ICU. Myocardial injury is an independent determinant of hospital mortality. Assessment of myocardial injury on admission to ICU would make it possible to identify patients at increased risk of death.

This article provides an overview of the Reanalysis Study of the Harvard Six Cities and the American Cancer Society (ACS) studies of particulate air pollution and mortality. The previous findings of the studies have been subject to debate. In response, a reanalysis team, comprised of Canadian and Amercian researchers, was invited to participate in an independent reanalysis project to address the concerns. Phase I of the reanalysis involved the design of data audits to determine whether each study conformed to the consistency and accuracy of their data. Phase II of the reanalysis involved conducting a series of comprehensive analyses using alternative statistical methods. Alternative models were also used to identify covariates that may confound or modify the association of particulate air pollution as well as identify sensitive population subgroups. The audit demonstrated that the data in the original analyses were of high quality, as were the risk estimates reported by the original investigators. The sensitivity analysis illustrated that the mortality risk estimates reported in both studies were found to be robust against alternative Cox models. Detailed investigation of the covariate effects found a significant modifying effect of education and a relative risk of mortality associated with fine particles and declining education levels. The study team applied spatial analytic methods to the ACS data, resulting in various levels of spatial autocorrelations supporting the reported association for fine particles mortality of the original investigators as well as demonstrating a significant association between sulfur dioxide and mortality. Collectively, our reanalysis suggest that mortality may be attributable to more than one component of the complex mixture of ambient air pollutants for U.S. urban areas. [ABSTRACT FROM AUTHOR]