A joint model for interval‐censored functional decline trajectories under informative observation

Multi‐state models are useful for modelling disease progression where the state space of the process is used to represent the discrete disease status of subjects. Often, the disease process is only observed at clinical visits, and the schedule of these visits can depend on the disease status of patients. In such situations, the frequency and timing of observations may depend on transition times that are themselves unobserved in an interval‐censored setting. There is a potential for bias if we model a disease process with informative observation times as a non‐informative observation scheme with pre‐specified examination times. In this paper, we develop a joint model for the disease and observation processes to ensure valid inference because the follow‐up process may itself contain information about the disease process. The transitions for each subject are modelled using a Markov process, where bivariate subject‐specific random effects are used to link the disease and observation models. Inference is based on a Bayesian framework, and we apply our joint model to the analysis of a large study examining functional decline trajectories of palliative care patients. Copyright © 2015 John Wiley & Sons, Ltd.     

New perspectives in cardio-oncology

Journal of Thrombosis and Thrombolysis -     

Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function?

Early clinical studies investigating the role of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure unexpectedly demonstrated a possible reduction in coronary heart disease endpoints. Two large scale clinical trials, HOPE and EUROPA, both studies in patients with coronary artery disease (CAD) but without clinical evidence of heart failure, showed a highly significant improvement in coronary heart disease outcomes on treatment with ramipril and perindopril, respectively, in contrast, in a similar population, PEACE was unable to demonstrate such benefit with trandolapril. Meta-analyses of all trials involving ACE-inhibitors showed a highly significant improvement in coronary heart disease endpoints. Current ESC guidelines recommend ACE-inhibitor therapy in CAD patients with co-existing indications for ACE-inhibitors, such as hypertension, heart failure, left ventricular dysfunction, prior MI was left ventricular dysfunction, or diabetes (class I, level of evidence A). These guidelines also recommend ACE-inhibitor therapy in all patients with angina and proven coronary disease (class IIa, level of evidence B). However, in angina patients without independent indication for ACE-inhibitor treatment, the anticipated benefit should be weighted against the costs and risks of side effects; in these patients, only agents and doses of proven efficacy for secondary prevention should be employed.     

Association of NT-ProBNP,Blood Pressure,and Cardiovascular Events: The ARIC Study

BackgroundAlthough intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.ObjectivesThis study examined whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.MethodsParticipants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.ResultsThere were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.ConclusionsElevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.     

Mixed gynecomastia

Gynecomastia is an enlargement of male breast resulting from a proliferation of its glandular component, and it is usually due to an altered estrogen-androgen balance. It should be differentiated from pseudogynecomastia, which is characterized by fat deposition without glandular proliferation and from breast carcinoma. Gynecomastia could be physiological in neonates and pubertal or pathological due to drug intake, chronic liver, or renal disease, hyperthyroidism, testicular or adrenal neoplasms, and hypogonadism whether primary, or secondary. Properly organized work-up is needed to reach the cause of gynecomastia. Here, we reported a case of a young Omani man with gynecomastia with the aim of creating awareness of the occurrence of Klinefelter’s syndrome (KS) in patients with gynecomastia, to observe any differences in clinical presentation of KS from those reported in the literature, and highlight the needed diagnostic work-up and treatment.Gynecomastia is an enlargement of male breast resulting from a proliferation of its glandular component. It is usually benign, bilateral, and characterized by the presence of a rubbery or firm mass around the nipples. It usually results from either increased estrogen level, increased breast sensitivity to estrogen,1 or low testosterone level. The highest incidence of gynecomastia is reported during neonatal period, puberty, and aging due to physiological disturbances. Pseudogynecomastia, which is often seen in obese men, refers to fat deposition without glandular proliferation and should be differentiated from gynecomastia. Therefore, male breast enlargement can be fatty (pseudogynecomastia or lipomastia), pure gynecomastia, or mixed. Our objective in presenting this particular case is to create awareness of the occurrence of Klinefelter’s syndrome (KS) in patients with gynecomastia, to observe any differences in clinical presentation of KS from those reported in the literature, and highlight the needed diagnostic work-up and treatment.     

Correlation between apoptotic endothelial microparticles and serum interleukin-6 and C-reactive protein in healthy men

Inflammation has been associated with increased cardiovascular risk, and endothelial cell (EC) apoptosis has been implicated in atherogenesis. The correlation between circulating concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and endothelial microparticles (EMPs) expressing an apoptotic (EMP31) or activation (EMP62E) phenotype in 20 middle-aged healthy men was investigated. IL-6 was significantly correlated with EMP31 (r = 0.6, p = 0.004), which persisted after adjusting for body mass index and CRP. CRP was significantly correlated with body mass index (r = 0.49, p = 0.02) but not with EMP31 or EMP62E. EC apoptosis is associated with IL-6 levels in men and might be partially responsible for the increased cardiovascular risk associated with subclinical inflammation.