Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa

Introduction The universal test‐and‐treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa. Methods The TasP cluster‐randomized trial (2012 to 2016) implemented six‐monthly repeat home‐based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 × 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level. Results 8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited. Conclusions PVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART‐initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90‐90‐90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context‐specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH‐27‐0512‐3974 (South African National Clinical Trials Register)

Development and use of a computer program to detect potentially inappropriate prescribing in older adults residing in Canadian long-term care facilities

BACKGROUND: Inappropriate prescribing has been estimated to be as high as 40% in long-term care. The purpose of this study was to develop a computer program that identifies potentially inappropriate drug prescriptions and to test its reliability. METHODS: Potentially inappropriate prescriptions were identified based on modified McLeod guidelines. A database from one pharmacy servicing long-term care facilities in Ontario was utilized for this cross-sectional study. Prescription information was available for the 356 long-term care residents and included: the date the prescription was filled, the quantity of drug prescribed and the eight-digit drug identification number. The pharmacy database was linked to the computer-based program for targeting potential inappropriate prescriptions. The computer program's reliability was assessed by comparing its results to a manual search conducted by two independent research assistants. RESULTS: There was complete agreement between the computer and manual abstraction for the total number of potentially inappropriate prescriptions detected. In total, 83 potentially inappropriate prescriptions were identified. Fifty-three residents (14.9%) received at least one potentially inappropriate prescription. Of those, twenty (37.7%) received two potential inappropriate prescriptions and eight (15.1%) received 3 or more potential inappropriate prescriptions. The most common potential inappropriate prescriptions were identified as long-term use of non-steroidal anti-inflammatory agents and tricyclic antidepressants with active metabolites. CONCLUSION: A computer program can accurately and automatically detect inappropriate prescribing in residents of long-term care facilities. This tool may be used to identify potentially inappropriate drug combinations and educate health care professionals

Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

<p>Abstract</p> <p>Background</p> <p>Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD.</p> <p>Methods</p> <p>A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1) for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia) and 22, 23, 24 (hypersomnia) of the Hamilton Depression Rating Scale (HDRS). Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse.</p> <p>Results</p> <p>The severities of early (<it>P </it>> 0.05), middle (<it>P </it>> 0.05), late (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (<it>P </it>> 0.05), oversleeping (<it>P </it>> 0.05), napping (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment.</p> <p>Conclusion</p> <p>The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT00427128</p

Engineering challenges of intrafirm technology reuse

Companies derive additional value from technological investments by repeatedly applying them across different product lines in their portfolios. Technology reuse strategies have helped to increase efficiency in leveraging research and development investments, but the attempts to explain how to duplicate such results for technology reuse at the engineering level are missing. While there are synergetic effects to the reuse of technologies, there are also transaction costs that limit the benefits in practice. This paper presents a model, along with three examples, of technology reuse to help account for these transaction costs and mitigate the fallacy of perceiving technologies as reusable “off‐the‐shelf” elements

Nanoparticles in cigarette smoke; real-time undiluted measurements by a scanning mobility particle sizer

Cigarette smoke is a complex mixture of smoke constituents, often characterised by size-resolved particle distributions. Since descriptions of ultrafine particles <50 nm are absent, our aim was to explore the existence of these nanoparticles in fresh and undiluted cigarette smoke. We measured undiluted smoke particles real-time by a scanning mobility particle sizer with Faraday cup electrometer, integrated in our custom-made smoking machine. Cigarettes were smoked by 2 s puffs, 30 s puff intervals and 50 ml puff volume. We tested six different cigarettes (1–10 mg tar per cigarette) at ten particle size-ranges between 6 and 50 nm, and repeated measurements five times. The formation of nanoparticles in fresh cigarette smoke was observed over the entire range between 6 and 50 nm, and reproduced in all cigarettes. The highest mean yield was 8.8 × 109 (SD = 1.1 × 109) particles per cigarette at the largest particle size range by high-tar cigarettes. Nanoparticle counts appear to increase with particle size, claimed tar values and blocking of filter ventilation holes, and inversely with butt length. Fresh undiluted cigarette smoke contains large amounts of potentially toxic nanoparticles <50 nm. We recommend to further study nanoparticles in the characterisation of cigarette smoke

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Regional variation and determinants of vitamin D status in sunshine-abundant Thailand

<p>Abstract</p> <p>Background</p> <p>Vitamin D insufficiency is highly prevalent. Most of the studies concerning vitamin D status were generated from countries situated at temperate latitudes. It is less clear what the extent of vitamin D insufficiency is in countries situated in the tropics and how geographical regions within country would affect vitamin D status. In the present study, we investigated vitamin D status in Thais according to geographical regions and other risk factors.</p> <p>Methods</p> <p>Subjects consisted of 2,641 adults, aged 15 - 98 years, randomly selected from the Thai 4th National Health Examination Survey (2008-9) cohort. Serum 25 hydroxyvitamin D were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean ± SE.</p> <p>Results</p> <p>Subjects residing in Bangkok, the capital city of Thailand, had lower 25(OH)D levels than other parts of the country (Bangkok, central, northern, northeastern and southern regions: 64.8 ± 0.7, 79.5 ± 1.1, 81.7 ± 1.2, 82.2 ± 0.8 and 78.3 ± 1.3 nmol/L, respectively; <it>p </it>< 0.001). Within each region, except for the northeastern part of the country, subjects living inside municipal areas had lower circulating 25(OH)D (central, 77.0 ± 20.9 nmol/L vs 85.0 ± 22.1 nmol/L, <it>p </it>< 0.001; north 79.3 ± 22.1 nmol/L vs 86.8 ± 21.8 nmol/L, <it>p </it>< 0.001; northeast 84.1 ± 23.3 nmol/L vs 87.3 ± 20.9 nmol/L, <it>p </it>= 0.001; south, 76.6 ± 20.5 nmol/L vs 85.2 ± 24.7 nmol/L, <it>p </it>< 0.001). Overall, the prevalence of vitamin D insufficiency was 64.6%, 46.7%, and 33.5% in Bangkok, municipal areas except Bangkok, and outside municipal area in other parts of the country, respectively. In addition, the prevalence of vitamin D insufficiency according to geographical regions was 43.1%, 39.1%, 34.2% and 43.8% in the central, north, northeast and south, respectively. After controlling for covariates in multiple linear regression analysis, the results showed that low serum 25(OH)D levels were associated with being female, younger age, living in urban and Bangkok.</p> <p>Conclusions</p> <p>Vitamin D insufficiency is common and varies across geographical regions in Thailand.</p

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets