Hepatitis B and C co-Infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults

Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV) co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR 800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60–5.90). Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia and CKD

Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice

CD4+ Count–Guided Interruption of Antiretroviral Treatment

BACKGROUND Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). Full Text of Background... METHODS We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352.

Фінанси санаторно-курортних підприємств України

Метою дослідження є аналіз стану санаторно-курортної сфери України як на рівні галузі, так і на рівні окремого санаторно-курортного підприємства

Carotid artery stenosis in patients with peripheral arterial disease: The SMART study

AbstractPurpose: The prevalence of asymptomatic internal carotid artery stenosis (ICAS) in patients with peripheral arterial disease (PAD) and characteristics that are associated with ICAS were studied. Methods: We used data from the first 600 patients enrolled in the Second Manifestations of ARTerial disease (SMART) study, a single-center, prospective cohort study among patients referred with a manifestation of cardiovascular disease, diabetes mellitus, hypertension, or hyperlipidemia. Included in the analysis were 162 patients with PAD or a history of PAD, who were not known to have ICAS at the time of referral and who had no history of cerebrovascular symptoms or previous carotid endarterectomy. ICAS was detected with duplex scanning and defined as a peak systolic velocity more than 150 cm/s (diameter reduction 50% or higher) on at least one side. Cardiovascular risk factors were measured. Logistic regression analysis was performed to investigate associations between these characteristics and ICAS. Results: The prevalence of previously unknown ICAS was 14%. A patient age of 67 years or older, body weight of 68 kg or less, and diastolic blood pressure of 75 mm Hg or lower were independently associated with ICAS. The Prevalence Of Icas In Patients With One Of These Characteristics (38% Of The Patients) Was 8%, In Those With Two Characteristics (21% Of The Patients) Was 32%, And In Those With Three Characteristics (6% Of The Patients) Was 50%. Conclusions: The prevalence of ICAS increases as much as 50% in patients who have PAD and the risk indicators of an age of 67 years or older, a body weight of 68 kg or less, and a diastolic blood pressure of 75 mm Hg or lower, and, therefore, these characteristics may be used as a means of increasing the likelihood of detecting ICAS. (J Vasc Surg 1999;30:519-25.

Association of childhood maltreatment and cortisol with the severity and stability of depression symptoms

Background: Little is known about patterns of depression symptoms over time in older adults. This study aims to assess the association of childhood maltreatment and cortisol levels with latent classes of depression symptoms over ten years in older adults. Methods: A total of 752 participants (mean age 61.7±9.5, female 18%) in the Second Manifestations of ARTerial disease-Memory, depression and aging (SMART-Medea) study provided up to twenty measures of depression symptoms over ten years based on the Patient Health Questionnaire-9 (PHQ-9). At baseline, salivary cortisol was measured, and childhood maltreatment was assessed. Responses to the PHQ-9 were indicators in a latent class analysis. Multinomial regression determined associations between class membership and cortisol and maltreatment, adjusting for age, sex, and education. Results: Four distinct classes were identified; never depressed (n=275, 37%), energy/sleep difficulties (n=237, 32%), mild depression symptoms (n=152, 20%) and fluctuating severe depression (n=88, 12%). Childhood maltreatment was associated with mild depression symptoms (OR=1.95, 95% CI: 1.17-3.25) and fluctuating severe depression (OR=3.50, 95% CI: 1.99-6.15). Blunted morning cortisol was associated with energy/sleep difficulties (OR=0.98, 95% CI: 0.95-1.00) and fluctuating severe depression (OR=0.96, 95% CI: 0.92-0.99). There was no evidence for interaction between maltreatment and cortisol. Limitations: There is limited generalizability due to the cohort consisting of participants with atherosclerosis and being mostly male. This study utilizes retrospective self-reporting of childhood maltreatment. Conclusion: Childhood maltreatment and blunted morning cortisol independently contribute to a worse depression course. Blunted morning cortisol may contribute to sub-clinical depression symptoms, specifically difficulties with energy levels and sleep

В портфеле редакции

OBJECTIVE Our aim is to compare the effect of type 2 diabetes on recurrent major cardiovascular events (MCVE) for patients with symptomatic vascular disease at different locations. RESEARCH DESIGN AND METHODS A total of 6,841 patients from the single-center, prospective Second Manifestations of ARTerial disease (SMART) cohort study from Utrecht, the Netherlands, with clinically manifest vascular disease with (n = 1,155) and without (n = 5,686) type 2 diabetes were monitored between 1996 and 2013. The effect of type 2 diabetes on recurrent MCVE was analyzed with Cox proportional hazards models, stratified for disease location (cerebrovascular disease, peripheral artery disease, abdominal aortic aneurysm, coronary artery disease, or polyvascular disease, defined as >= 2 vascular locations). RESULTS Five-year risks for recurrent MCVE were 9% in cerebrovascular disease, 9% in peripheral artery disease, 20% in those with an abdominal aortic aneurysm, 7% in coronary artery disease, and 21% in polyvascular disease. Type 2 diabetes increased the risk of recurrent MCVE in coronary artery disease (hazard ratio [HR] 1.67; 95% CI 1.25-2.21) and seemed to increase the risk in cerebrovascular disease (HR 1.36; 95% CI 0.90-2.07), while being no risk factor in polyvascular disease (HR 1.12; 95% CI 0.83-1.50). Results for patients with peripheral artery disease (HR 1.42; 95% CI 0.79-2.56) or an abdominal aortic aneurysm (HR 0.93; 95% CI 0.23-3.68) were inconclusive. CONCLUSIONS Type 2 diabetes increased the risk of recurrent MCVE in patients with coronary artery disease, but there is no convincing evidence that it is a major risk factor for subsequent MCVE in all patients with symptomatic vascular disease

Factors associated with D-dimer levels in HIV-infected individuals.

BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels

Factors Associated with D-Dimer Levels in HIV-Infected Individuals

Matti A Ristola on työryhmän jäsen.Peer reviewe