UO1-AI-35041: To examine the impact of HIV infection and highly active antiretroviral therapy on systolic and diastolic hypertension.
Cohort study with semi-annual assessment of the outcome.
We ...studied 5578 participants of the Multicenter AIDS Cohort Study with blood pressure measurements obtained between 1984 and 2003. The primary outcomes were systolic hypertension (SH; systolic blood pressure > 140 mmHg) and diastolic hypertension (DH; diastolic blood pressure > 90 mmHg). Statistical analyses were performed using multiple logistic regression with robust variance estimation.
Of the 84 813 person-visits available for analysis, 7.3 and 8.0% showed SH and DH, respectively. Controlling for age, race, body mass index, and smoking, HIV positive men not taking antiretroviral therapy were significantly less likely than HIV negative men to have SH odds ratio (OR), 0.79; 95% confidence interval (CI), 0.70-0.89, as were men taking mono/combination therapy (OR, 0.69; 95% CI, 0.59-0.80). The prevalence of SH among men taking highly active antiretroviral therapy (HAART) for less than 2 years was similar to that among HIV negative men (OR, 1.06; 95% CI, 0.87-1.30), but was significantly higher thereafter; for 2 to 5 years of HAART (OR, 1.51; 95% CI, 1.25-1.82) and for more than 5 years of HAART (OR, 1.70; 95% CI, 1.34-2.16). In contrast, DH was not significantly higher among men with prolonged HAART use compared to that among HIV negative controls.
Prolonged HAART use was significantly associated with a higher prevalence of SH. This finding suggests that individuals taking HAART may be at increased risk of developing hypertension-related conditions and underscores the importance of blood pressure monitoring among these individuals.
Background. Prospective characterization of hepatitis C virus (HCV) transmission in both human immunodeficiency virus (HIV)—infected and —uninfected men who have sex with men (MSM) over the entire ...HIV epidemic has not been comprehensively conducted. Methods. To determine the trends in and risk factors associated with incident HCV in MSM since 1984, 5310 HCV antibody (anti-HCV)—negative MSM in the Multicenter AIDS Cohort Study were prospectively followed during 1984–2011 for anti-HCV seroconversion. Results. During 55 343 person-years (PYs) of follow-up, there were 115 incident HCV infections (incidence rate, 2.08/1000 PYs) scattered throughout the study period. In a multivariable analysis with time-varying covariates, older age (incidence rate ratio IRR, 1.40/10 years, P < .001), enrollment in the later (2001–2003) recruitment period (IRR, 3.80, P = .001), HIV infection (IRR, 5.98, P < .001), drinking >13 alcoholic drinks per week (IRR, 1.68, (P < .001), hepatitis B surface antigen positivity (IRR, 1.68, P < .001), syphilis (IRR, 2.95, P < .001), and unprotected receptive anal intercourse with >1 male partner (IRR, 3.37, P < .001) were independently associated with incident HCV. Among HIV-infected subjects, every 100 cell/mm 3 increase in CD4 count was associated with a 7% (P = .002) decrease in the HCV incidence rate up to a CD4 count of 500 cells/mm 3 , whereas there was no association with highly active antiretroviral therapy. Conclusions. The spread of HCV among both HIV-infected and -uninfected MSM in the United States has been ongoing since the beginning of the HIV epidemic. In HIV-infected men with <500 CD4 + T cells, the HCV incidence rate was inversely proportional to CD4 T-cell count.
Although coinfection with HIV-1 and hepatitis B virus (HBV) is common, few long-term studies on liver-disease mortality in coinfected people have been undertaken. Our aim was to examine liver-related ...mortality among people at risk for HIV-1 and HBV infections.
We used data from a multicentre, prospective cohort study to classify 5293 men who had sex with men, according to their HIV-1 antibody status, ascertained semiannually, and their hepatitis-B surface antigen status (HBsAg), which we ascertained at baseline. Mortality rates were estimated in terms of person-years and Poisson regression methods were used to test for signifiance of relative risks.
326 (6%) men were HBsAg positive, of whom 213 (65%) were HIV-1 positive. Of the 4967 HBsAg negative men, 2346 (47%) were infected with HIV-1. The liver-related mortality rate was 1·1/1000 person years, and was higher in men with HIV-1 and HBsAg (14·2/1000) than in those with only HIV-1 infection (1·7/1000, p<0·001) or only HBsAg (0·8/1000, p<0·001). In coinfected individuals, the liver-related mortality rate was highest with lower nadir CD4+ cell counts and was twice as high after 1996, when highly active antiretroviral therapy (HAART) was introduced.
Individuals coinfected with HIV-1 and HBV, especially those with low CD4+ nadir counts, are at increased risk for liver-related mortality, underscoring the importance of prevention, identification, and comprehensive management of hepatitis B in people infected with HIV-1.
Hepatic allograft rejection remains an important problem following liver transplantation, and, indeed, complications related to the administration of immunosuppressive therapy remain a predominant ...cause of posttransplantation morbidity and mortality. The Liver Transplantation Database (LTD) was used to study a cohort of 762 consecutive adult liver transplantation recipients and determined the incidence, timing, and risk factors for acute rejection. We also evaluated the impact of histological severity of rejection on the need for additional immunosuppressive therapy and on patient and graft survival. Four hundred ninety (64%) of the 762 adult liver transplantation recipients developed at least one episode of rejection during a median follow‐up period of 1,042 days (range, 336‐1,896 days), most of which occurred during the first 6 weeks after transplantation. Multivariate analysis revealed that recipient age, serum creatinine, aspartate transaminase (AST) level, presence of edema, donor/recipient HLA‐DR mismatch, cold ischemic time, and donor age were independently associated with the time to acute rejection. An interesting observation was that the histological severity of rejection was an important prognosticator: the use of antilymphocyte preparations was higher, and the time to death or retransplantation was shorter, for patients with severe rejection. Findings from this study will assist in decision‐making for the use of immunosuppressive regimens and call into question whether complete elimination of all rejection or alloreactivity is a desirable goal in liver transplantation.
Inactivating mutations of CDC73 cause Hyperparathyroidism-Jaw Tumour syndrome (HPT-JT), Familial Isolated Hyperparathyroidism (FIHP) and sporadic parathyroid carcinoma. We conducted CDC73 mutation ...analysis in an HPT-JT family and confirm carrier status of the proband's daughter.
The proband had primary hyperparathyroidism (parathyroid carcinoma) and uterine leiomyomata. Her father and daughter had hyperparathyroidism (parathyroid adenoma) but no other manifestations of HPT-JT. CDC73 mutation analysis (sequencing of all 17 exons) and whole-genome copy number variation (CNV) analysis was done on leukocyte DNA of the three affecteds as well as the proband's unaffected sister.
A novel deletion of exons 4 to 10 of CDC73 was detected by CNV analysis in the three affecteds. A novel insertion in the 5'UTR (c.-4_-11insG) that co-segregated with the deletion was identified. By in vitro assay the 5'UTR insertion was shown to significantly impair the expression of the parafibromin protein. Screening for the mutated CDC73 confirmed carrier status in the proband's daughter and the biochemistry and ultrasonography led to pre-emptive surgery and resolution of the hyperparathyroidism.
A novel gross deletion mutation in CDC73 was identified in a three-generation HPT-JT family emphasizing the importance of including screening for large deletions in the molecular diagnostic protocol.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Laser compression has long been used as a method to study solids at high pressure. This is commonly achieved by sandwiching a sample between two diamond anvils and using a ramped laser pulse ...to slowly compress the sample, while keeping it cool enough to stay below the melt curve. We demonstrate a different approach, using a multilayer ‘ring-up’ target whereby laser-ablation pressure compresses Pb up to 150 GPa while keeping it solid, over two times as high in pressure than where it would shock melt on the Hugoniot. We find that the efficiency of this approach compares favourably with the commonly used diamond sandwich technique and could be important for new facilities located at XFELs and synchrotrons which often have higher repetition rate, lower energy lasers which limits the achievable pressures that can be reached.
Chronic hepatitis B (CH-B) is common among HIV-infected individuals and increases liver-related mortality in the absence of HAART. The impact of CH-B on long-term HAART outcomes has not been fully ...characterized.
To address this question, HAART initiators enrolled in the Multicenter AIDS Cohort Study were retrospectively analyzed. Patients were classified by hepatitis B category based on serology at the time of HAART initiation. The association of CH-B with mortality, AIDS-defining illnesses, CD4 cell rise, and HIV suppression was assessed using regression analysis.
Of 816 men followed for a median of 7 years on HAART, 350 were never hepatitis B virus (HBV) infected, 357 had past infection, 45 had CH-B, and 64 were only core-antibody positive. Despite HAART, AIDS-related mortality was the most common cause of death 8.3/1000 person-years (PYs). It was highest in those with CH-B (17/1000 PYs, 95% confidence interval 7.3, 42) and lowest among never HBV infected (2.9/1000 PYs, 95% confidence interval 1.4, 6.4). In a multivariable model, patients with CH-B had a 2.7-fold higher incidence of AIDS-related mortality compared with those never infected (P = 0.08). Non-AIDS-related mortality was also highest among those with CH-B (22/1000 PYs), primarily due to liver disease (compared to never infected, adjusted hazard ratio 4.1, P = 0.04). There was no significant difference in AIDS-defining events, HIV RNA suppression, and CD4 cell increase.
In HIV-infected patients receiving long-term HAART, HBV status did not influence HIV suppression or CD4 cell increase. However, mortality was highest among those with CH-B and was mostly due to liver disease despite HBV-active HAART.
To determine the mortality, hospital stay, and total hospital charges and cost of hospitalization attributable to candidemia by comparing patients with candidemia with control-patients who have ...otherwise similar illnesses. Prior studies lack broad patient and hospital representation or cost-related information that accurately reflects current medical practices.
Our case-control study included case-patients with candidemia and their cost-related data, ascertained from laboratory-based candidemia surveillance conducted among all residents of Connecticut and Baltimore and Baltimore County, Maryland, during 1998 to 2000. Control-patients were matched on age, hospital type, admission year, discharge diagnoses, and duration of hospitalization prior to candidemia onset.
We identified 214 and 529 sets of matched case-patients and control-patients from the two locations, respectively. Mortality attributable to candidemia ranged between 19% and 24%. On multivariable analysis, candidemia was associated with mortality (OR, 5.3 for Connecticut and 8.5 for Baltimore and Baltimore County; P < .05), whereas receiving adequate treatment was protective (OR, 0.5 and 0.4 for the two locations, respectively; P < .05). Candidemia itself did not increase the total hospital charges and cost of hospitalization; when treatment status was accounted for, having received adequate treatment for candidemia significantly increased the total hospital charges and cost of hospitalization ($6,000 to $29,000 and $3,000 to $22,000, respectively) and the length of stay (3 to 13 days).
Our findings underscore the burden of candidemia, particularly regarding the risk of death, length of hospitalization, and cost associated with treatment.
Summary
We examined the characteristics associated with hepatitis C virus (HCV) antibody (anti‐HCV) prevalence and HCV clearance between injection drug using (IDU) and non‐IDU men who have sex with ...men (MSM). Stored serum and plasma samples were tested for anti‐HCV and HCV RNA to determine the HCV status of 6925 MSM at enrolment into the Multicentre AIDS Cohort Study (MACS). Prevalence and clearance ratios were calculated to determine the characteristics associated with HCV prevalence and clearance. Multivariable analyses were performed using Poisson regression methods with robust variance estimation. Anti‐HCV prevalence was significantly higher among IDU than among non‐IDU MSM (42.9% vs 4.0%), while clearance was significantly lower among IDU MSM (11.5% vs 34.5% among non‐IDU MSM). HIV infection, Black race, and older age were independently associated with higher prevalence in both groups, while smoking, transfusion history, and syphilis were significantly associated with prevalence only among non‐IDU MSM. The rs12979860‐C/C genotype was the only characteristic independently associated with HCV clearance in both groups, but the effects of both rs12979860‐C/C genotype clearance ratio (CR) = 4.16 IDUs vs 1.71 non‐IDUs; P = 0.03 and HBsAg positivity (CR = 5.06 IDUs vs 1.62 non‐IDUs; P = 0.03) were significantly larger among IDU MSM. HIV infection was independently associated with lower HCV clearance only among non‐IDU MSM (CR = 0.59, 95% CI = 0.40–0.87). IDU MSM have higher anti‐HCV prevalence and lower HCV clearance than non‐IDU MSM. Differences in the factors associated with HCV clearance suggest that the mechanisms driving the response to HCV may differ according to the mode of acquisition.
OBJECTIVE: To confirm the association between depression and self‐rated general health, independent of demographics, functional disability, physical illness burden, and health services utilization.
...DESIGN: Logistic regression analyses of data obtained in a cross‐sectional epidemiological survey.
SETTING: The mid‐Monongahela Valley, a rural, nonfarm, low SES community.
PARTICIPANTS: Random sample of 880 subjects aged 65 and older.
MEASUREMENTS: The dependent variable was self‐rated overall health, categorized as excellent, good, fair, or poor. The independent variables were demographics (age, gender, education), number of depressive symptoms, number of impaired instrumental activities of daily living (IADLs), measures of physical illness burden (individual medical conditions, number of affected organ systems or disease processes, and number of prescription medications), and measures of health services utilization (number of visits to physicians, and acute hospitalization).
RESULTS: Univariate analyses indicated that poorer self‐rated health was associated with lesser education, higher numbers of depressive symptoms, impaired IADLs, prescription medications, physician visits, hospitalizations, and affected organ systems, and with the presence of several specific conditions. However, multiple logistic regression analyses revealed that only the following variables were associated independently with poorer self‐rated health: age less than 75 years, education less than high school graduation, greater numbers of depressive symptoms, impaired IADLs, prescription medications, and physician visits.
CONCLUSIONS: Even when controlling for physical illness and functional disability, subjective rating of overall health remains strongly and independently associated with depressive symptoms.
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