Withdrawal symptoms as a predictor of mortality in patients HIV-infected through drug use and receiving highly active antiretroviral therapy (HAART)

Even in the highly active antiretroviral therapy (HAART) era, individuals HIV-infected through injecting drug use (IDUs) are at increased risk of death due to the burden of competing events such as liver disease, overdose and suicide. The objective of this study was to explore the role which life events' experience, in particular drug-related events such as detoxification or withdrawal symptoms, may play on the risk of death in HIV-infected IDUs. Our analysis was based on longitudinal data of 296 HIV-infected IDUs from when they started HAART. Data collection included medical records and patient's self-reports detailing, among other information, life events including drug-related problems. Multiple imputations for missing data in the explanatory variables together with Cox models were used to identify predictors of death. During HAART follow-up, 26 deaths occurred, corresponding to 1.8 deaths per 100 person-years. The majority (N=8) were attributable to liver disease while 5 were from unknown causes (found deceased at home or in a car). After adjustment for age and time-dependent viral load (>10,000 cp/ml) individuals experiencing withdrawal symptoms had a fivefold increased risk of death with respect to the others. Withdrawal symptoms in IDUs living with HIV reflect physicians' difficulties in managing their patients' opioid dependence. Early detection and increasing substitution dosages or switching to a more adequate treatment could prevent possible drug-related deaths.     

Factors associated with nonadherence to highly active antiretroviral therapy: a 5-year follow-up analysis with correction for the bias induced by missing data in the treatment maintenance phase

This study aimed to identify factors associated with nonadherence during the maintenance phase of highly active antiretroviral therapy (months 12-60) in the Anti PROtease Cohort (APROCO) cohort after correcting for the bias due to missing outcome data. A Heckman 2-stage approach (generalized estimating equations probit model) was used to compare visits with moderate or poor adherence and visits with high adherence. Between months 12 and 60, at least 1 self-reported adherence measure was available for 970 of the 1110 patients with at least 12 months of follow-up (3889 visits with adherence assessments). Adherence was rated as high at 2466 visits, moderate at 1125, and poor at 298. After adjustment for "missingness," moderate and poor adherence were independently associated with age (younger), perceived treatment side effects, dosing frequency different from twice daily, and a protease inhibitor-based regimen. They were also associated with depression and lack of support from the main partner. High adherence was most likely among patients born outside the European Union. A comparison restricted to poor-adherence and high-adherence visits yielded a similar pattern of predictors. Adjusting for missing outcome data changed the predictor set. Reasons for nonadherence are multifactorial. Psychosocial interventions and the selection of the best-tolerated regimens are needed to improve long-term adherence of HIV-infected patients to their lifelong treatment.     

Predicting pulmonary adenocarcinoma outcome based on a cytology grading system

BACKGROUND:

Pulmonary adenocarcinoma (AD) has a variety of architectural patterns. Recently, a 3‐tiered histological pattern‐based grading system was developed for stage I lung AD, stratifying patients into low, intermediate, and high risk for recurrence. However, cytology may serve as the primary method for diagnosis in patients with inoperable disease. Attempts to correlate architecture between parallel cytological and histological preparations have not been successful. Therefore, we evaluated cytomorphologic features of previously histologically graded AD to identify features of potential prognostic significance.

METHODS:

One hundred and thirteen fine‐needle aspirations with excised adenocarcinomas were reviewed. In the liquid‐based preparation, we evaluated cell arrangements (flat sheets vs 3‐D clusters vs single cells), nuclear features (size variability, shape, and contour), nucleoli (prominent or inconspicuous), presence of nuclear inclusions, chromatin (fine, coarse, or clumped), and quality of background. The features were tested by multivariate analysis to identify associations with histological grade and disease‐free survival (DFS), and a cytological score was generated.

RESULTS:

Nuclear size, chromatin pattern, and nuclear contours showed a significant association with histological grade and DFS. These features were included in the composite cytological score (range, 0‐5). By grouping the cytological scores, we stratified the tumors into low (median DFS, 100%), intermediate (median DFS, 78%), and high (median DFS, 55%) rate of recurrence (P = .008). There was a good correlation with the histological grading system.

CONCLUSIONS:

In liquid‐based preparations, distinctive cytological features of pulmonary adenocarcinoma correlate with levels of histological differentiation and can be combined into a score with prognostic significance. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society.     

Hereditary hemochromatosis in north-eastern Romania

Hereditary hemochromatosis is a genetic disturbance of iron metabolism resulting in iron overload in several organs and their functional failure. Early diagnosis is necessary to start a simple and effective therapy: bleeding. It is the most frequent genetic disease in some populations. Our objectives were 1. An estimate of the expectancy of the disease in the population of our geographic region, and 2. To diagnose the disease by applying the established methods and estimate the efficiency of our diagnosis. METHODS: 1.To estimate the expectancy, we genotyped 200 persons for the most frequent mutations causing the disease: HFE-C282Y and HFE-H63D by PCR-RFLP. 2. To diagnose the disease phenotypically we determined plasma iron level, ferritin level and transferrin saturation index in 549 patients previously diagnosed as chronic hepatitis or cirrhosis and genotyped those with hemochromatosis phenotype. RESULTS: 1. We found allelic frequencies of 1.75% and 13.25% for the HFE-C282Y and H63D mutant alleles respectively. From these frequencies we calculated that a severe case caused by a C282Y/C282Y homozygote can arise in 816 people and a mild case caused by a C282Y/H63D compound heterozygote can arise in 100 people 2. Among 549 patients we found 10 to have the phenotype of hemochromatosis and 3 out of the 10 were found to carry mutations: two in the HFE gene (one homozygous C282Y and one compound heterozygous C282Y/H63D) and one in the hemojuvelin (HJV) gene (a G320V).     

Adherence to antiretroviral therapy in patients enrolled in a comprehensive care program in Cambodia: a 24-month follow-up assessment

BACKGROUND: The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence. METHODS: Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence. RESULTS: A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence. CONCLUSIONS: At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members.     

Pegylated-interferon alpha 2a treatment for chronic hepatitis C in patients on chronic haemodialysis

AIM: To evaluate the response to pegylated-interferon alpha 2a in chronic hepatitis C patients on chronic haemodialysis. METHODS: Ten patients with chronic C hepatitis were enrolled in this study. All had increased aminotransferases for more than 6 mo, positive antiHCV antibodies and positive PCR HCV-RNA. We administrated Peg-Interferon alpha 2a 180μg/wk for 48 wk. After 12 wk of treatment we evaluated the biochemical and early virological response (EVR). At the end of the treatment we evaluated the biochemical response and 24 wk after the end of the treatment we evaluated the sustained virological response (SVR). We monitored the side-effects during the treatment. RESULTS: Two patients dropped out in the first 12 wk of treatment and 2 after the first 12 wk of treatment. After 12 wk of treatment, 7 out of 8 patients had biochemical response and EVR and 1 had biochemical response but persistent viremia. We had to reduce the dose of pegylated-interferon to 135μg/wk in 2 cases. Three out of 6 (50%) patients had SVR 24 wk after the end of the treatment. Intention-to-treat analysis showed that 3 out of 10 patients (30%) had SVR. Side-effects occurred in most of the patients (flu-like syndrome, thrombocytopenia or leucopoenia), but they did not impose the discontinuation of treatment. CONCLUSION: After 12 wk of treatment with Peg-Interferon alpha 2a (40 ku) in patients on chronic haemodialysis with chronic C hepatitis, EVR was obtained in 87.5% (7/8) of the cases. SVR was achieved in 50% of the cases (3/6 patients) that finished the 48 wk of treatment.