AN ECONOMIC EVALUATION OF AN ALCOHOL REDUCTION INTERVENTION IN THE HIV CLINIC SETTING IN VIETNAM

Introduction: Hazardous alcohol use is a global public health problem disproportionately affecting persons living with HIV (PWH) and is associated with reduced antiretroviral therapy adherence and viral suppression. Competing priorities have limited scale-up of evidence-based alcohol reduction interventions, particularly in resource-constrained settings. In order to help prioritize alcohol reduction programs for PWH, economic evaluations of these programs are needed. Methods: This dissertation’s overall objective was to evaluate the costs from the patient and health care system perspective of implementing and maintaining an alcohol reduction program in a Vietnam HIV clinic setting. I conducted three studies using data from the Reducing Hazardous Alcohol Use & HIV Viral Load (REDART), a randomized control trial conducted with PWH with hazardous drinking. Participants were randomized to one of three trial arms: 1) a combined cognitive-behavioral therapy and motivational interviewing-informed intervention (CoI); 2) a brief alcohol intervention (BI) and 3) the standard of care. In Study 1 I undertook a micro-costing approach to determine the costs of delivering the CoI and BI. In Study 2 I applied the Andersen Model of Behavioral Health Services Use to assess the role of patient cost in attending the CoI. In Study 3 I compared the cost-effectiveness of CoI and BI to the standard of care. Results: In Study 1, implementation, overhead, and counselor had equal proportions of the cost of the BI while counselor costs accounted for the largest proportion of the CoI. In Study 2, despite the relatively high number of sessions involved in the CoI, participants’ attendance was not associated with time, distance, or money spent traveling to the clinic. In Study 3, the BI was less costly and more effective in reducing hazardous drinking and improving viral suppression status as compared to the CoI. Conclusions: Findings from this dissertation demonstrate delivering alcohol reduction interventions to PWH in Vietnam requires up front costs, yet the cost burden for the health care system may be reduced by using a brief intervention format. Future research is needed to explore the cost-effectiveness of scale up of BI in the HIV clinic setting to reduce hazardous alcohol use.Doctor of Philosoph

Le programme de clercs à la Cour suprême du Canada

Le présent article porte sur les clercs et leur rôle à la Cour suprême du Canada. Le but est de renseigner les clercs éventuels sur la nature du poste et de permettre à tous de mieux comprendre le fonctionnement du processus judiciaire à ce niveau. Les auteurs commencent par étudier l'histoire du programme de clercs à la Cour suprême. Bien que les fonctions du clerc aient peu changé depuis la création du poste en 1968, le programme a évolué au même rythme que la Cour. Les auteurs traitent ensuite du programme de clercs actuel. Ils décrivent d'abord le processus de sélection. En s'inspirant d'un questionnaire envoyé aux clercs des années 1991 à 1993, les auteurs tentent également d'établir, de façon générale, le profil des personnes qui ont été employées par la Cour au cours des dernières années. L'article inclut ensuite une description des tâches. Bien que cette catégorie de personnel assume de nombreuses responsabilités, les auteurs réfutent les critiques habituellement adressées à la Cour suprême des États-Unis en affirmant que les clercs de la Cour suprême du Canada ne jouissent pas d'une autorité excessive. Les auteurs concluent qu'un stage à la Cour profite à la fois aux clercs eux-mêmes et aux procédures de la Cour. Ainsi, les clercs font partie intégrante du processus judiciaire à la Cour suprême du Canada.This article takes an in-depth look at law clerks and the role they play at the Supreme Court of Canada. Such an examination both informs prospective clerks on the nature of the position and promotes a better general understanding of how the judicial process operates at this level. The authors begin their analysis by looking at the history of the law clerks at the Supreme Court. Although the functions of the clerks have changed little since their introduction in 1968, the clerkship program has evolved with a changing Supreme Court, contributing to the institution's « coming of age ». The authors then shift their attention to examining the present clerkship program. The article first reveals the manner in which law clerks are selected by the Court. Using data collected by a questionnaire sent to clerks of the 1991-93 terms, the authors also attempt to convey, in a general way, some sense of the people who have served at the Court in recent years. Next, the major functions performed by the clerks are described. While the clerks do have a great deal of responsibility, the authors dispel much of the criticism directed at the United States Supreme Court clerks by stating that law clerks at the Supreme Court of Canada do not have an improper degree of authority. The authors conclude that the clerking experience benefits both the clerks themselves and Court procedures. As such, law clerks are an entrenched and indispensable part of the judicial process at the Supreme Court of Canada

Past-year prevalence of prescription opioid misuse among those 11 to 30

AbstractBackgroundThere are high levels of prescription and consumption of prescription opioids in the US. Misuse of prescription opioids has been shown to be highly correlated with prescription opioid-related morbidity and mortality including fatal and non-fatal overdose. We characterized the past-year prevalence of prescription opioid misuse among those 11–30years of age in the US.MethodsA systematic review and meta-analysis were carried out following a published protocol and PRISMA guidelines. We searched electronic databases; reports were eligible if they were published between 1/1/1990–5/30/2014, and included data on individuals 11–30years of age from the US. Study quality was assessed using the Newcastle-Ottawa Scale.ResultsA total of 3211 abstracts were reviewed for inclusion; after discarding duplicates and identifying non-eligible reports, a total of 19 unique reports, providing 34 estimates, were included in the final systematic review and meta-analysis. The range of past-year prescription opioid misuse prevalence the reports was 0.7%–16.3%. An increase in prevalence of 0.4% was observed over the years of data collection.ConclusionsThis systematic review and meta-analysis found a high prevalence of past-year prescription opioid misuse among individuals 11–30years of age. Importantly, we identified an increase in past-year prevalence 1990–2014. Misuse of prescription opioids has played an important role in national increases of fatal and non-fatal drug overdose, heroin use and injection, and HIV and HCV infection among young people. The observed high and increasing prevalence of prescription opioid misuse is an urgent public health issue

Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease - United States.

The term "chronic Lyme disease" is used by some health care providers as a diagnosis for various constitutional, musculoskeletal, and neuropsychiatric symptoms (1,2). Patients with a diagnosis of chronic Lyme disease have been provided a wide range of medications as treatment, including long courses of intravenous (IV) antibiotics (3,4). Studies have not shown that such treatments lead to substantial long-term improvement for patients, and they can be harmful (1,5). This report describes cases of septic shock, osteomyelitis, Clostridium difficile colitis, and paraspinal abscess resulting from treatments for chronic Lyme disease. Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks

Identification and Characterization of Thymic Epithelial Progenitor Cells

AbstractT cell differentiation and repertoire selection depend critically on several distinct thymic epithelial cell types, whose lineage relationships are unclear. We have investigated these relationships via functional analysis of the epithelial populations within the thymic primordium. Here, we show that mAbs MTS20 and MTS24 identify a population of cells that, when purified and grafted ectopically, can differentiate into all known thymic epithelial cell types, attract lymphoid progenitors, and support CD4+ and CD8+ T cell development in nude mice. In contrast, other epithelial populations in the thymic primordium can fulfill none of these functions. These data establish that the MTS20+24+ population is sufficient to generate a functional thymus in vivo and thus argue strongly that all thymic epithelial cell types derive from a common progenitor cell

Assessing changes to adolescent health-promoting behaviors following the onset of the COVID-19 pandemic: A multi-methods exploration of the role of within-person combinations of trait perfectionism.

The current work provides a multi-methods exploration of how within-person subtypes of self-oriented perfectionism (SOP) and socially prescribed perfectionism (SPP) were related to shifts in health-promoting behaviors among adolescents following the onset of the COVID-19 pandemic. Study One tested the 2 × 2 and tripartite models of perfectionism through a quantitative test of how such subtypes predicted changes in health behaviors pre-pandemic to intra-pandemic among 202 adolescents (M = 17.86, SD = 1.421). Results indicated that the combination of high SOP/high SPP was linked to the most maladaptive changes to health-promoting behaviors, supporting the tripartite model. Study Two aimed to contextualize these findings by analyzing semi-structured interviews with 31 adolescent self-identified perfectionists (M = 15.97, SD = 1.991) during the initial lockdown mandate. Results indicated that participants experienced a welcome break and found more time to engage in health-promoting behaviors. However, those high in SOP - regardless of their level of SPP - had more difficulty relaxing due to a resistance to relenting their perfectionistic standards. Altogether, these findings support the exacerbating role of SOP when combined with SPP posited by the tripartite model of perfectionism with respect to adolescents' health-promoting behaviors during the COVID-19 pandemic.This work was supported by an Ontario Government Early Researcher Award awarded to Danielle S. Molnar (Ministry of Research and Innovation, Government of Ontario)

The Association of Physical Activity Fragmentation with Physical Function in Older Adults: Analysis from the SITLESS Study

The distribution of physical activity bouts through the day may provide useful information for assessing the impacts of interventions on aspects such as physical function. This study aimed to investigate the associations between physical activity fragmentation, tested using different minimum physical activity bout lengths, with physical function in older adults. The SITLESS project recruited 1360 community-dwelling participants from four European countries (≥65 years old). Physical activity fragmentation was represented as the active-to-sedentary transition probability (ASTP), the reciprocal of the average physical activity bout duration measured using ActiGraph wGT3X+ accelerometers. Four minimum bout lengths were utilised to calculate the ASTP: ≥10-s, ≥60-s, ≥120-s and ≥300-s. Physical function was assessed using the 2-min walk test (2MWT) and the composite score from the Short Physical Performance Battery (SPPB) test. Linear regression analyses, after adjusting for relevant covariates, were used to assess cross-sectional associations. After adjustment for relevant covariates, lower ASTP using ≥10-s bouts were associated with longer 2MWT distances and higher SPPB scores. Lower ASTP using ≥120-s bouts and ≥300-s bouts were associated with longer 2MWT distances but not the SPPB. Less fragmented physical activity patterns appeared to be associated with better physical function in community-dwelling older adult

The effect of chair-based exercise on physical function in older adults: a systematic review and meta-analysis

Physical activity is an important determinant of health in later life. The public health restrictions in response to COVID-19 have interrupted habitual physical activity behaviours in older adults. In response, numerous exercise programmes have been developed for older adults, many involving chair-based exercise. The aim of this systematic review was to synthesise the effects of chair-based exercise on the health of older adults. Ovid Medline, EMBASE, CINAHL, AMED, PyscInfo and SPORTDiscus databases were searched from inception to 1 April 2020. Chair-based exercise programmes in adults ≥50 years, lasting for at least 2 weeks and measuring the impact on physical function were included. Risk of bias of included studies were assessed using Cochrane risk of bias tool v2. Intervention content was described using TiDieR Criteria. Where sufficient studies (≥3 studies) reported data on an outcome, a random effects meta-analysis was performed. In total, 25 studies were included, with 19 studies in the meta-analyses. Seventeen studies had a low risk of bias and five had a high risk of bias. In this systematic review including 1388 participants, results demonstrated that chair-based exercise programmes improve upper extremity (handgrip strength: MD = 2.10; 95%CI = 0.76, 3.43 and 30 s arm curl test: MD = 2.82; 95%CI = 1.34, 4.31) and lower extremity function (30 s chair stand: MD 2.25; 95%CI = 0.64, 3.86). The findings suggest that chair-based exercises are effective and should be promoted as simple and easily implemented activities to maintain and develop strength for older adults

The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation

Normal physiology relies on the precise coordination of intracellular signaling pathways that respond to nutrient availability to balance cell growth and cell death. The canonical mitogen-activated protein kinase pathway consists of the RAFMEK- ERK signaling cascade and represents one of the most well-defined axes within eukaryotic cells to promote cell proliferation, which underscores its frequent mutational activation in human cancers. Our recent studies illuminated a function for the redox-active micronutrient copper (Cu) as an intracellular mediator of signaling by connecting Cu to the amplitude of mitogen-activated protein kinase signaling via a direct interaction between Cu and the kinases MEK1 and MEK2. Given the large quantities of molecules such as glutathione and metallothionein that limit cellular toxicity from free Cu ions, evolutionarily conserved Cu chaperones facilitate efficient delivery of Cu to cuproenzymes. Thus, a dedicated cellular delivery mechanism of Cu to MEK1/2 likely exists. Using surface plasmon resonance and proximity-dependent biotin ligase studies, we report here that the Cu chaperone for superoxide dismutase (CCS) selectively bound to and facilitated Cu transfer to MEK1. Mutants of CCS that disrupt Cu(I) acquisition and exchange or a CCS small-molecule inhibitor were used and resulted in reduced Cu-stimulated MEK1 kinase activity. Our findings indicate that the Cu chaperone CCS provides fidelity within a complex biological system to achieve appropriate installation of Cu within the MEK1 kinase active site that in turn modulates kinase activity and supports the development of novel MEK1/2 inhibitors that target the Cu structural interface or blunt dedicated Cu delivery mechanisms via CCS