Aboriginal Status is a Prognostic Factor for Mortality among Antiretroviral Naive HIV-Positive Individuals First Initiating HAART

Background: Although the impact of Aboriginal status on HIV incidence, HIV disease progression, and accessto treatment has been investigated previously, little is known about the relationship between Aboriginal ethnicityand outcomes associated with highly active antiretroviral therapy (HAART). We undertook the present analysisto determine if Aboriginal and non-Aboriginal persons respond differently to HAART by measuring HIV plasmaviral load response, CD4 cell response and time to all-cause mortality.Methods: A population-based analysis of a cohort of antiretroviral therapy naïve HIV-positive Aboriginal menand women 18 years or older in British Columbia, Canada. Participants were antiretroviral therapy naïve, initiatedtriple combination therapy between August 1, 1996 and September 30, 1999. Participants had to complete abaseline questionnaire as well as have at least two follow-up CD4 and HIV plasma viral load measures. Theprimary endpoints were CD4 and HIV plasma viral load response and all cause mortality. Cox proportionalhazards models were used to determine the association between Aboriginal status and CD4 cell response, HIVplasma viral load response and all-cause mortality while controlling for several confounder variables.Results: A total of 622 participants met the study criteria. Aboriginal status was significantly associated with noAIDS diagnosis at baseline (p = 0.0296), having protease inhibitor in the first therapy (p = 0.0209), lower baselineHIV plasma viral load (p < 0.001), less experienced HIV physicians (P = 0.0133), history of IDU (p < 0.001), notcompleting high school (p = 0.0046), and an income of less than $10,000 per year (p = 0.0115). Cox proportionalhazards models controlling for clinical characteristics found that Aboriginal status had an increased hazard ofmortality (HR = 3.12, 95% CI: 1.77–5.48) but did not with HIV plasma viral load response (HR = 1.15, 95% CI:0.89–1.48) or CD4 cell response (HR = 0.95, 95% CI: 0.73–1.23).Conclusion: Our study demonstrates that HIV-infected Aboriginal persons accessing HAART had similar HIVtreatment response as non-Aboriginal persons but have a shorter survival. This study highlights the need forcontinued research on medical interventions and behavioural changes among HIV-infected Aboriginal and othermarginalized populations

Unwinding of primer-templates by archaeal family-B DNA polymerases in response to template-strand uracil

Archaeal family-B DNA polymerases bind tightly to deaminated bases and stall replication on encountering uracil in template strands, four bases ahead of the primer-template junction. Should the polymerase progress further towards the uracil, for example, to position uracil only two bases in front of the junction, 3′–5′ proof-reading exonuclease activity becomes stimulated, trimming the primer and re-setting uracil to the +4 position. Uracil sensing prevents copying of the deaminated base and permanent mutation in 50% of the progeny. This publication uses both steady-state and time-resolved 2-aminopurine fluorescence to show pronounced unwinding of primer-templates with Pyrococcus furiosus (Pfu) polymerase–DNA complexes containing uracil at +2; much less strand separation is seen with uracil at +4. DNA unwinding has long been recognized as necessary for proof-reading exonuclease activity. The roles of M247 and Y261, amino acids suggested by structural studies to play a role in primer-template unwinding, have been probed. M247 appears to be unimportant, but 2-aminopurine fluorescence measurements show that Y261 plays a role in primer-template strand separation. Y261 is also required for full exonuclease activity and contributes to the fidelity of the polymerase

Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes

Clinical pharmacy as an area of practice, education and research started developing around the 1960s when pharmacists across the globe gradually identified the need to focus more on ensuring the appropriate use of medicines to improve patient outcomes rather than being engaged in manufacturing and supply. Since that time numerous studies have shown the positive impact of clinical pharmacy services (CPS). The need for wider adoption of CPS worldwide becomes urgent, as the global population ages, and the prevalence of polypharmacy as well as shortage of healthcare professionals is rising. At the same time, there is great pressure to provide both high-quality and cost-effective health services. All these challenges urgently require the adoption of a new paradigm of healthcare system architecture. One of the most appropriate answers to these challenges is to increase the utilization of the potential of highly educated and skilled professionals widely available in these countries, i.e., pharmacists, who are well positioned to prevent and manage drug-related problems together with ensuring safe and effective use of medications with further care relating to medication adherence. Unfortunately, CPS are still underdeveloped and underutilized in some parts of Europe, namely, in most of the Central and Eastern European (CEE) countries. This paper reviews current situation of CPS development in CEE countries and the prospects for the future of CPS in that region

CD4 count at presentation for HIV care in the United States and Canada: Are those over 50 years more likely to have a delayed presentation?

We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in 13 US and Canadian clinical cohorts and compared to <50-year-olds. 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included in our study. Trends in mean CD4 count (measured as cells/mm3) and 95% confidence intervals ([,]) were determined using linear regression stratified by age category and adjusted for gender, race/ethnicity, HIV transmission risk and cohort. From 1997-2007, the proportion of individuals presenting for HIV care who were ≥50-years-old increased from 17% to 27% (p-value < 0.01). The median CD4 count among ≥50 year-olds was consistently lower than younger adults. The interaction of age group and calendar year was significant (p-value <0.01) with both age groups experiencing modest annual improvements over time (< 50-year-olds: 5 [4 , 6] cells/mm3; ≥50-year-olds: 7 [5 , 9] cells/mm3), after adjusting for sex, race/ethnicity, HIV transmission risk group and cohort; however, increases in the two groups were similar after 2000. A greater proportion of older individuals had an AIDS-defining diagnosis at, or within three months prior to, first presentation for HIV care compared to younger individuals (13% vs. 10%, respectively). Due to the increasing proportion, consistently lower CD4 counts, and more advanced HIV disease in adults ≥50-year-old at first presentation for HIV care, renewed HIV testing efforts are needed

Bacterial Causes of Empyema in Children, Australia, 2007–2009

Most infections were caused by non–7-valent pneumococcal conjugate vaccine serotypes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000–2010

Background. There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)–infected patients in care in the United States and Canada

Development of a workplace intervention for sick-listed employees with stress-related mental disorders: Intervention Mapping as a useful tool

Background. To date, mental health problems and mental workload have been increasingly related to long-term sick leave and disability. However, there is, as yet, no structured protocol available for the identification and application of an intervention for stress-related mental health problems at the workplace. This paper describes the structured development, implementation and planning for the evaluation of a return-to-work intervention for sick-listed employees with stress-related mental disorders (SMDs). The intervention is based on an existing successful return-to-work intervention for sick-listed employees with low back pain. Methods. The principles of Intervention Mapping were applied to combine theory and evidence in the development, implementation and planning for the evaluation of a participatory workplace intervention, aimed at an early return-to-work for sick-listed employees with SMDs. All stakeholders were involved in focus group interviews: i.e. employees recently sick-listed with SMDs, supervisors and occupational health professionals. Results. The development of the participatory workplace intervention according to the Intervention Mapping principles resulted in a structured return-to-work intervention, specifically tailored to the needs of sick-listed employees with SMDs. Return-to-work was proposed as a behavioural change, and the Attitude - Social influence - self-Efficacy model was identified as a theoretical framework. Stakeholder involvement in focus group interviews served to enhance the implementation. The cost-effectiveness of the intervention will be evaluated in a randomised controlled trial. Conclusion. Intervention Mapping was found to be a promising method to develop interventions tailored to a specific target group in the field of occupational health. Trial registration. ISRCTN92307123. © 2007 van Oostrom et al; licensee BioMed Central Ltd

Missing Data on the Estimation of the Prevalence of Accumulated Human Immunodeficiency Virus Drug Resistance in Patients Treated With Antiretroviral Drugs in North America

Determination of the prevalence of accumulated antiretroviral drug resistance among persons infected with human immunodeficiency virus (HIV) is complicated by the lack of routine measurement in clinical care. By using data from 8 clinic-based cohorts from the North American AIDS Cohort Collaboration on Research and Design, drug-resistance mutations from those with genotype tests were determined and scored using the Genotypic Resistance Interpretation Algorithm developed at Stanford University. For each year from 2000 through 2005, the prevalence was calculated using data from the tested subset, assumptions that incorporated clinical knowledge, and multiple imputation methods to yield a complete data set. A total of 9,289 patients contributed data to the analysis; 3,959 had at least 1 viral load above 1,000 copies/mL, of whom 2,962 (75%) had undergone at least 1 genotype test. Using these methods, the authors estimated that the prevalence of accumulated resistance to 2 or more antiretroviral drug classes had increased from 14% in 2000 to 17% in 2005 (P < 0.001). In contrast, the prevalence of resistance in the tested subset declined from 57% to 36% for 2 or more classes. The authors’ use of clinical knowledge and multiple imputation methods revealed trends in HIV drug resistance among patients in care that were markedly different from those observed using only data from patients who had undergone genotype tests

Predictive Accuracy of the Veterans Aging Cohort Study Index for Mortality With HIV Infection: A North American Cross Cohort Analysis

By supplementing an index composed of HIV biomarkers and age (Restricted Index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) Index more completely reflects risk of mortality. We compare the accuracy of the VACS and Restricted Indices 1) among subjects outside the Veterans Healthcare System (VA), 2) over 1–5 years of prior exposure to antiretroviral therapy (ART), and 3) within important patient subgroups