Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders

Objectives The aims of the study were to describe the prevalence and associations of mental health disorder (MHD) among a cohort of HIV-infected patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to examine whether antiretroviral therapy use or mortality was influenced by MHD (defined as a record of service provision by psychiatric services on the Victorian Psychiatric Case Register). It was hypothesized that HIV-positive individuals with MHD would have poorer treatment outcomes, reduced responses to highly active antiretroviral therapy (HAART) and increased mortality compared with those without MHD. Methods This is a retrospective cohort of 2981 individuals (73% of the Victorian population diagnosed with HIV infection) captured on an HIV database which was electronically matched with the public Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system psychiatry service provision). The prevalence, dates and recorded specifics of mental health disorders at the time of the electronic match on 1 June 2000 are described. The association with recorded MHD, gender, age, AIDS illness, HIV exposure category, duration and type of antiviral therapy, treatment era (prior to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and mortality at 1 September 2001 was assessed. Results Five hundred and twenty-five individuals (17.6% of the Victorian HIV-positive population) were recorded with MHD, most frequently coded as attributable to substance dependence/abuse or affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis. Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for both psychiatric and nonpsychiatric illness were more frequent in those with MHD (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. Conclusions MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.

Principles and clinical application of assessing alterations in renal elimination pathways

Drugs and metabolites are eliminated from the body by metabolism and excretion. The kidney makes the major contribution to excretion of unchanged drug and also to excretion of metabolites. Net renal excretion is a combination of three processes - glomerular filtration, tubular secretion and tubular reabsorption. Renal function has traditionally been determined by measuring plasma creatinine and estimating creatinine clearance. However, estimated creatinine clearance measures only glomerular filtration with a small contribution from active secretion. There is accumulating evidence of poor correlation between estimated creatinine clearance and renal drug clearance in different clinical settings, challenging the 'intact nephron hypothesis' and suggesting that renal drug handling pathways may not decline in parallel. Furthermore, it is evident that renal drug handling is altered to a clinically significant extent in a number of disease states, necessitating dosage adjustment not just based on filtration. These observations suggest that a re-evaluation of markers of renal function is required. Methods that measure all renal handling pathways would allow informed dosage individualisation using an understanding of renal excretion pathways and patient characteristics. Methodologies have been described to determine individually each of the renal elimination pathways. However, their simultaneous assessment has only recently been investigated. A cocktail of markers to measure simultaneously the individual renal handling pathways have now been developed, and evaluated in healthy volunteers. This review outlines the different renal elimination pathways and the possible markers that can be used for their measurement. Diseases and other physiological conditions causing altered renal drug elimination are presented, and the potential application of a cocktail of markers for the simultaneous measurement of drug handling is evaluated. Further investigation of the effects of disease processes on renal drug handling should include people with HIV infection, transplant recipients (renal and liver) and people with rheumatoid arthritis. Furthermore, changes in renal function in the elderly, the effect of sex on renal function, assessment of living kidney donors prior to transplantation and the investigation of renal drug interactions would also be potential applications. Once renal drug handling pathways are characterised in a patient population, the implications for accurate dosage individualisation can be assessed. The simultaneous measurement of renal function elimination pathways of drugs and metabolites has the potential to assist in understanding how renal function changes with different disease states or physiological conditions. In addition, it will further our understanding of fundamental aspects of the renal elimination of drugs.

A major quantitative trait locus for CD4-CD8 ratio is located on chromosome 11

CD4-CD8 ratio is an important diagnostic measure of immune system functioning. In particular, CD4-CD8 ratio predicts the time taken for progression of HIV infection to acquired immune deficiency syndrome (AIDS) and the long-term survival of AIDS patients. To map genes that regulate differences between healthy individuals in CD4-CD8 ratio, we typed 757 highly polymorphic microsatellite markers at an average spacing of similar to5 cM across the genome in 405 pairs of dizygotic twins at ages 12, 14 and 16. We used multipoint variance components linkage analysis to test for linkage between marker loci and CD4-CD8 ratio at each age. We found suggestive evidence of linkage on chromosome 11p in 12-year-old twins (LOD=2.55, P=0.00031) and even stronger evidence of linkage in the same region at age 14 (LOD 3.51, P=0.00003). Possible candidate genes include CD5 and CD6, which encode cell membrane proteins involved in the positive selection of thymocytes. We also found suggestive evidence of linkage at other areas of the genome including regions on chromosomes 1, 3, 4, 5, 6, 12, 13, 15, 17 and 22.

Nutrient partitioning during treatment of tuberculosis: gain in body fat mass but not in protein mass

Background: Tuberculosis is an important cause of wasting. The functional consequences of wasting and recovery may depend on the distribution of lost and gained nutrient stores between protein and fat masses. Objective: The goal was to study nutrient partitioning, ie, the proportion of weight change attributable to changes in fat mass (FM) versus protein mass (PM), during anti mycobacterial treatment. Design: Body-composition measures were made of 21 men and 9 women with pulmonary tuberculosis at baseline and after 1 and 6 mo of treatment. All subjects underwent dual-energy X-ray absorptiometry and deuterium bromide dilution tests, and a four-compartment model of FM, total body water (TBW), bone minerals (BM), and PM was derived. The ratio of PM to FM at any time was expressed as the energy content (p-ratio). Changes in the p-ratio were related to disease severity as measured by radiologic criteria. Results: Patients gained 10% in body weight (P < 0.001) from baseline to month 6. This was mainly due to a 44% gain in FM (P < 0.001); PM, BM, and TBW did not change significantly. Results were similar in men and women. The p-ratio decreased from baseline to month 1 and then fell further by month 6. Radiologic disease severity was not correlated with changes in the p-ratio. Conclusions: Microbiological cure of tuberculosis does not restore PM within 6 mo, despite a strong anabolic response. Change in the p-ratio is a suitable parameter for use in studying the effect of disease on body composition because it allows transformation of such effects into a normal distribution across a wide range of baseline proportion between fat and protein mass.

Clinical practice guidelines for the psychosocial care of adults with cancer

Clinical practice guidelines are increasingly being developed in medical settings to provide evidence-based recommendations to guide the clinical care of patients. The development of Clinical practice guidelines for the psychosocial care of patients with medical illness is a newer initiative, and more complex as the target audience includes health care professionals from diverse backgrounds. In Australia, the National Breast Cancer Centre and National Cancer Control Initiative have collaborated to develop Clinical practice guidelines for the psychosocial care of adults with cancer, funded by the Australian Government Department of Health and Ageing. This paper outlines the development of these guidelines in the international context, gives an overview of their content, and describes strategies for their implementation and evaluation. Copyright (c) 2005 John Wiley C Sons, Ltd.

Prevalence of injecting drug use and associated risk behavior among regular ecstasy users in Australia

Background: The aim of the study was to investigate the prevalence of injecting drug use and associated risk behaviour among a sentinel sample of ecstasy users. Methods: Cross-sectional surveys were conducted with regular ecstasy users as part of an annual monitoring study of ecstasy and related drug markets in all Australian capital cities. Results: Twenty-three percent of the sample reported having ever injected a drug and 15% reported injecting in the 6 months preceding interview. Independent predictors of lifetime injection were older age, unemployment and having ever been in prison. Completion of secondary school and identifying as heterosexual was associated with a lower likelihood of having ever injected. Participants who had recently injected typically did so infrequently; only 9% reported daily injecting. Methamphetamine was the most commonly injected drug. Prevalence of needle sharing was low (6%), although half (47%) reported sharing other injecting equipment in the preceding 6 months. Conclusions: Ecstasy users who report having injected a drug at some time appear to be demographically different to ecstasy users who have not injected although neither are they typical of other drug injectors. The current investigation suggests that ongoing monitoring of injecting among regular ecstasy users is warranted. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Using cohort studies to estimate mortality among injecting drug users that is not attributable to AIDS

Background: Injecting drug use (IDU) and associated mortality appear to be increasing in many parts of the world. IDU is an important factor in HIV transmission. In estimating AIDS mortality attributable to IDU, it is important to take account of premature mortality rates from other causes to ensure that AIDS related mortality among injecting drug users (IDUs) is not overestimated. The current review provides estimates of the excess non-AIDS mortality among IDUs. Method: Searches were conducted with Medline, PsycINFO, and the Web of Science. The authors also searched reference lists of identified papers and an earlier literature review by English et al (1995). Crude. mortality rates (CMRs) were derived from data on the number of deaths, period of follow UP, and number of participants. In estimating the all-cause mortality, two rates were calculated: one that included all cohort studies identified in the search, and one that only included studies that reported on AIDS deaths in their cohort. This provided lower and upper mortality rates, respectively. Results: The current paper derived weighted mortality rates based upon cohort studies that included 179 885 participants, 1 219 422 person-years of observation, and 16 593 deaths. The weighted crude AIDS mortality rate from studies that reported AIDS deaths was approximately 0.78% per annum. The median estimated non-AIDS mortality rate was 1.08% per annum. Conclusions: Illicit drug users have a greatly increased risk of premature death and mortality due to AIDS forms a significant part of that increased risk; it is, however, only part of that risk. Future work needs to examine mortality rates among IDUs in developing countries, and collect data on the relation between HIV and increased mortality due to all causes among this group.

HIV LTR-dependent expression of Bax selectively induces apoptosis in Tat-positive cells

HIV integrates into the host cell genome where it persists for the life of the cell. One approach to reducing viral burden is to selectively eliminate cells containing integrated provirus early following infection. We have used the HIV LTR promoter to selectively express transgenes in human cells positive for the HIV transactivator protein Tat. Transient transfection of Jurkat cells, or Jurkat cells stably expressing Tat (Jurkat-Tat), with a LTR construct containing luciferase reporter gene resulted in a 37-fold increase in gene expression when Tat was present. We have demonstrated that when pro-apoptotic Bax was used as the transgene, cytotoxicity was seen only in the Jurkat-Tat cells. Annexin-V staining indicated that Bax induced cell death by apoptosis. In mixed populations of Jurkat and Jurkat-Tat cells, the LTR-Bax construct was selectively cytotoxic to the Tat-positive cells. These results suggest that Bax under the control of the HIV LTR can be used to destroy cells harbouring HIV without affecting uninfected cells. (C) 2004 Published by Elsevier Inc.

Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy

Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here. (C) 2002 Elsevier Science Inc. All rights reserved.