All-cause mortality and serious cardiovascular events in people with hip and knee osteoarthritis: a population based cohort study

BACKGROUND: Because individuals with osteoarthritis (OA) avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD) and death, we assessed the relationship between OA disability and these outcomes. METHODS: In a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC) OA scores; Health Assessment Questionnaire (HAQ) walking score; use of walking aids) and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack) over a median follow-up of 13.2 and 9.2 years, respectively. RESULTS: Of 2156 participants, 1,236 (57.3%) died and 822 (38.1%) experienced a CVD outcome during follow-up. Higher (worse) baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01–1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22–1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34–1.70, p<0.001). In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid  = 1.27, 95% CI 1.10–1.47, p = 0.001; aHR per unit increase in HAQ walking score  = 1.17, 95% CI 1.08–1.27, p<0.001). CONCLUSIONS: Among individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders. Research is needed to elucidate modifiable mechanisms

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Interpreting polymorphic FPC into domain theoretic models of parametric polymorphism

Abstract. This paper shows how parametric PILLY (Polymorphic Intuitionistic / Linear Lambda calculus with a fixed point combinator Y) can be used as a metalanguage for domain theory, as originally suggested by Plotkin more than a decade ago. Using recent results about solutions to recursive domain equations in parametric models of PILLY, we show how to interpret FPC in these. Of particular interest is a model based on “admissible ” pers over a reflexive domain, the theory of which can be seen as a domain theory for (impredicative) polymorphism. We show how this model gives rise to a parametric and computationally adequate model of PolyFPC, an extension of FPC with impredicative polymorphism. This is the first model of a language with parametric polymorphism, recursive terms and recursive types in a non-linear setting.