Stigmatization of patients with AIDS : understanding the interrelationships between Thai nurses' attitudes towards HIV/AIDS, drug use and commercial sex

There is currently a scarcity of research on the nature of HIV/AIDS stigma within the Thai health context. This is problematic given the negative role of stigma in hindering the provision of patient care and treatment. This study used a mixed-method approach to investigate the interrelationships between the stigma of HIV/AIDS and the stigmas relating to its various modes of disease transmission including injection drug use (IDU). Twenty interviews were conducted with trainees and qualified nurses from a Bangkok college. Participants were presented with vignettes describing a hypothetical person varying in disease diagnoses (AIDS, leukemia, no disease) and co-characteristics (IDU,  commercial sex (CS), blood transfusion, no co-characteristic). Using a Q-sort task, participants arranged the vignettes along a bipolar scale according to their willingness to interact with the persons, and were asked to explain their decisions. Univariate and multivariate regression analyses showed that IDU, AIDS, and CS were all individually stigmatizing. Strong interactions were found between the stigmas of HIV/AIDS, IDU, and CS. Interview data also showed clear biases toward patients according to their IDU and CS habits. The findings  suggest that addressing these co-stigmas could be vital to the success of efforts aimed at reducing the disease stigma of HIV/AIDS.

Stigmatization of AIDS patients : disentangling Thai nursing students' attitudes towards HIV/AIDS, drug use and commercial sex

This paper analyzes the interrelationships between the stigma of HIV/AIDS stigma and the co-stigmas of commercial sex (CS) and injecting drug use (IDU). Students of a Bangkok nursing college (N = 144) were presented with vignettes describing a person varying in the disease diagnoses (AIDS, leukemia, no disease) and co-characteristics (IDU, CS, blood transfusion, no co-characteristic). For each vignette, participants completed a social distance measure assessing their attitudes towards the hypothetical person portrayed. Multivariate analyses showed strong interactions between the stigmas of AIDS and IDU but not between AIDS and CS. Although AIDS was shown to be stigmatizing in and of itself, it was significantly less stigmatizing than IDU. The findings highlight the need to consider the non-disease-related stigmas associated with HIV as well as the actual stigma of HIV/AIDS in treatment and care settings. Methodological strengths and limitations were evaluated and implications for future research discussed.

Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimers disease, across the blood-brain

Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza (Danshen), is widely used in the treatment of coronary heart disease, stroke and less commonly Alzheimer's disease. Our recent study indicates that CTS is a substrate for Pglycoprotein (PgP/MDR1/ABCB1). This study has investigated the nature of the brain distribution of CTS across the brain-blood barrier (BBB) using several in vitro and in vivo rodent models. A polarized transport of CTS was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with facilitated efflux from the abluminal side to luminal side. Addition of a PgP (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2) inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides attenuated the polarized transport. In a bilateral in situ brain perfusion model, the uptake of CTS into the cerebrum increased from 0.52 ± 0.1% at 1 min to 11.13 ± 2.36 ml/100 g tissue at 30 min and was significantly greater than that of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g. probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%. The brain levels of CTS were only about 21% of those in plasma, and were significantly increased when coadministered with verapamil or probenecid in rats. The brain levels of CTS in rats subjected to middle cerebral artery occlusion and rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-) mice were 10.9- and 1.5-fold higher than those in the wild-type mice, respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit the brain penetration of CTS in rodents, suggesting a possible role of PgP and MRP1 in limiting the brain penetration of CTS in patients and causing drug resistance to Danshen therapy and interactions with conventional drugs that are substrates of PgP and MRP1. Further studies are needed to explore the role of other drug transporters in restricting the brain penetration of CTS and the clinical relevance.

Hormone replacement therapy and cardiovascular disease

The authors examine the most recent research concerning the risks and benefits of oestrogen or combined oestrogen-progestin therapy in postmenopausal women.

Prevalence, detection and drug treatment of hypertension in a rural Australian population : the Greater Green Triangle Risk Factor Study 2004

Background: Hypertension is an important risk factor for cardiovascular disease; however, limited findings are available on its detection and management in rural Australia.

Aim: To assess the prevalence, awareness and treatment of hypertension in a rural South-East Australian population.

Methods: Three cross-sectional surveys in Limestone Coast, Corangamite Shire and Wimmera regions during 2004–2006 using a random population sample (n = 3320, participation rate 49%) aged 25–74 years. Blood pressure was measured by trained nurses. Information on history of hypertension and medication was obtained by questionnaires. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or on antihypertensive drug treatment.

Results: Overall, one-third of participants had hypertension; of these, two-thirds, 54% (95% confidence interval (CI) 47–60) of men and 71% (95% CI 65–77) of women, were aware of their condition. Half of the participants with hypertension were treated and nearly half of these were controlled. Both treatment and control were more common in women (60%, 95% CI 54–67 and 55%, 95% CI 47–64) compared with men (42%, 95% CI 36–49 and 35%, 95% CI 26–44). Monotherapy was used by 55% (95% CI 48–61) of treated hypertensives. Angiotensin-converting enzyme inhibitors were the most frequently used class of antihypertensive drugs in men, whereas angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists and diuretics were all widely used among women.

Conclusion: This study emphasizes suboptimal detection and treatment of hypertension, especially in men, in rural Australia.

Why is type 2 diabetes such a serious risk factor for coronary heart disease in women?

Women with type 2 diabetes were found to display an altered distribution of body fat, higher resistance to the action of insulin, highly increased levels of tryglycerides and significant elevations in the level of plasminogen activator inhibiter. Concludes that interventions which enhance the action of insulin, such as exercise or drug therapy, should lower the risk of coronary heart disease in these women.

Clinical pharmacy input for hospital inpatients according to disease state

This study measured the clinical activities performed and times taken by hospital pharmacists to provide medication monitoring services to individual medical and surgical patients. Linking these data to hospital Patient Administration Systems showed how clinical pharmacy manpower needs are guided by patient partition, disease complexity and Diagnosis Related Group classification.

Economic implications of obesity among people with atherothrombotic disease

Objective: The purpose of this study was to ascertain the impact of obesity on the cost of disease management in people with or at high risk of atherothrombotic disease from a governmental perspective using a bottom-up approach to cost estimation. In addition, the aim was also to explore the causes of any differences found.

Method: The health-care costs of obesity were estimated from 2819 participants recruited into the nationwide Australian REACH Registry with established atherothrombotic disease or at least three risk factors for atherothrombosis. Enrollment was in 2004, through primary care general practices. Information was collected on the use of cardiovascular drugs, hospitalizations and ambulatory care services. Bottom-up costing was undertaken by assigning unit costs to each health-care item, based on Australian Government-reimbursed figures 2006-2007. Linear-mixed models were used to estimate associations between direct medical costs and body mass index (BMI) categories.

Results: Annual pharmaceutical costs per person increased with increasing BMI category, even after adjusting for gender, age, living place, formal education, smoking status, hypertension and diabetes. Adjusted annual pharmaceutical costs of overweight and obese participants were higher (7 (P0.004) and 144 (0.001), respectively) than those of the normal weight participants. This was due to participants in higher BMI categories receiving more pharmaceuticals than normal weight participants. There was no significant change across the BMI categories in annual ambulatory care costs and annual hospital costs.

Conclusion: In these participants with or at high risk of atherothrombotic disease, annual pharmaceutical costs were greater in participants of higher BMI category, but there was not such a gradient in the annual hospital or ambulatory care costs. The greater cardiovascular pharmaceutical costs for participants of higher BMI categories remained even after adjusting for a range of demographic factors and comorbidities. Our results suggest that these costs are explained by the higher number of drugs used among people with atherothrombotic disease. Further investigation is needed to understand the reasons for this level of drug use.

Screening, referral and treatment for depression in patients with coronary heart disease: a consensus statement from the National Heart Foundation of Australia

In 2003, the National Heart Foundation of Australia position statement on “stress” and heart disease found that depression was an important risk factor for coronary heart disease (CHD). This 2013 statement updates the evidence on depression (mild, moderate and severe) in patients with CHD, and provides guidance for health professionals on screening and treatment for depression in patients with CHD.

The prevalence of depression is high in patients with CHD and it has a significant impact on the patient’s quality of life and adherence to therapy, and an independent effect on prognosis. Rates of major depressive disorder of around 15% have been reported in patients after myocardial infarction or coronary artery bypass grafting.

To provide the best possible care, it is important to recognise depression in patients with CHD. Routine screening for depression in all patients with CHD is indicated at first presentation, and again at the next follow-up appointment. A follow-up screen should occur 2–3 months after a CHD event. Screening should then be considered on a yearly basis, as for any other major risk factor for CHD.

A simple tool for initial screening, such as the Patient Health Questionnaire-2 (PHQ-2) or the short-form Cardiac Depression Scale (CDS), can be incorporated into usual clinical practice with minimum interference, and may increase uptake of screening.

Patients with positive screening results may need further evaluation. Appropriate treatment should be commenced, and the patient monitored. If screening is followed by comprehensive care, depression outcomes are likely to be improved.

Patients with CHD and depression respond to cognitive behaviour therapy, collaborative care, exercise and some drug therapies in a similar way to the general population. However, tricyclic antidepressant drugs may worsen CHD outcomes and should be avoided.

Coordination of care between health care providers is essential for optimal outcomes for patients. The benefits of treating depression include improved quality of life, improved adherence to other therapies and, potentially, improved CHD outcomes.

Zebrafish as a genetic model in pre-clinical drug testing and screening

The traditional drug discovery pipeline for the identification and development of compounds that selectively target specific molecules to ameliorate disease remains a major focus for medical research. However, the zebrafish is increasingly providing alternative strategies for various components of this pipeline. Zebrafish and their embryos are small, easily accessible and relatively low cost, making them applicable to high-throughput, small molecule screening. Zebrafish can also be manipulated by a range of forward and reverse genetics techniques to facilitate gene discovery and functional studies. Moreover, their physiological and developmental complexity provides accurate models of human disease to underpin mechanism of action and in vivo validation studies. Finally, several of these biological characteristics make zebrafish eminently suitable for toxicity testing, including eco-toxicology. Here we review the application of zebrafish to preclinical drug development and toxicity testing, including recent advances in mutant generation, drug screening and toxicology that serve to further enhance the capabilities of this valuable model organism in drug discovery.

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation.

The deleterious effects of oxidative and nitrosative stress on palmitoylation, membrane lipid rafts and lipid-based cellular signalling : new drug targets in neuroimmune disorders

Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.

Evolving epidemiology of injecting drug use-associated infective endocarditis: a regional centre experience

INTRODUCTION AND AIMS: Injecting drug use (IDU) is a major risk factor for infective endocarditis (IE). An understanding of the epidemiology of IE and IDU is vital for delivery of health care for this disease. Our aim was to examine the rates of IDU-associated IE (IDU-IE) in a single centre over the last 12 years. DESIGN AND METHODS: Retrospective analysis of two cohorts of consecutive patients (n = 226) admitted with IE from 2002 to 2013. Numbers of cases and rates of IE were compared between two cohorts (2002-2006 and 2009-2013). Rate ratios were calculated using Poisson distributions. Poisson regression was used to examine relationship over time. RESULTS: One hundred thirty cases of endocarditis were seen in the first observation period (6 IDU-IE) and 96 in the second observation period (15 IDU-IE). The estimated incidence rate of IE had fallen from 10.1 to 6.45 per 100, 000 person-years [rate ratio 0.64, 95% confidence interval (CI) 0.48, 0.85]. In contrast, the estimated incidence rate of IDU-E has risen from 0.48 to 0.79 per 100, 000 person-years (rate ratio 1.65, 95% CI 0.59, 4.57). Incidence rate regression suggests that the number of IDU-IE cases is expected to increase by a factor of 1.25 (95%CI 1.09-1.44) for each increase of 1 year. DISCUSSION AND CONCLUSIONS: Over the last decade, there has been a decrease in incidence rate and total number of cases of IE but a rise in rate and number of cases of IDU-IE. This may indicate increasing IDU or increased rates of endocarditis in intravenous drug users in this region. This finding may inform health-care planning in the area.

The Glutathione System: a new drug target in neuroimmune disorders

Glutathione (GSH) has a crucial role in cellular signaling and antioxidant defenses either by reacting directly with reactive oxygen or nitrogen species or by acting as an essential cofactor for GSH S-transferases and glutathione peroxidases. GSH acting in concert with its dependent enzymes, known as the glutathione system, is responsible for the detoxification of reactive oxygen and nitrogen species (ROS/RNS) and electrophiles produced by xenobiotics. Adequate levels of GSH are essential for the optimal functioning of the immune system in general and T cell activation and differentiation in particular. GSH is a ubiquitous regulator of the cell cycle per se. GSH also has crucial functions in the brain as an antioxidant, neuromodulator, neurotransmitter, and enabler of neuron survival. Depletion of GSH leads to exacerbation of damage by oxidative and nitrosative stress; hypernitrosylation; increased levels of proinflammatory mediators and inflammatory potential; dysfunctions of intracellular signaling networks, e.g., p53, nuclear factor-κB, and Janus kinases; decreased cell proliferation and DNA synthesis; inactivation of complex I of the electron transport chain; activation of cytochrome c and the apoptotic machinery; blockade of the methionine cycle; and compromised epigenetic regulation of gene expression. As such, GSH depletion has marked consequences for the homeostatic control of the immune system, oxidative and nitrosative stress (O&NS) pathways, regulation of energy production, and mitochondrial survival as well. GSH depletion and concomitant increase in O&NS and mitochondrial dysfunctions play a role in the pathophysiology of diverse neuroimmune disorders, including depression, myalgic encephalomyelitis/chronic fatigue syndrome and Parkinson’s disease, suggesting that depleted GSH is an integral part of these diseases. Therapeutical interventions that aim to increase GSH concentrations in vivo include N-acetyl cysteine; Nrf-2 activation via hyperbaric oxygen therapy; dimethyl fumarate; phytochemicals, including curcumin, resveratrol, and cinnamon; and folate supplementation.