Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201).

OBJECTIVES: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. METHODS: Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD\u27s 38/69/94/95/158/279). RESULTS: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) \u3e50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL \u3e50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. CONCLUSIONS: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT00084019

Supporting patient-clinician interaction in chronic HIV care: Design and development of a patient-reported outcomes software application

Background: The consideration of health-related quality of life (HRQL) is a hallmark of best practice in HIV care. Information technology offers an opportunity to more closely engage patients with chronic HIV infection in their long-term management and support a focus on HRQL. However, the implementation of patient-reported outcome (PRO) measures, such as HRQL in routine care, is challenged by the need to synthesize data generated by questionnaires, the complexity of collecting data between patient visits, and the integration of results into clinical decision-making processes. Objective: Our aim is to design and pilot-test a multimedia software platform to overcome these challenges and provide a vehicle to increase focus on HRQL issues in HIV management. Methods: A multidisciplinary team in France and Australia conducted the study with 120 patients and 16 doctors contributing to the design and development of the software. We used agile development principles, user-centered design, and qualitative research methods to develop and pilot the software platform. We developed a prototype application to determine the acceptability of the software and piloted the final version with 41 Australian and 19 French residents using 2 validated electronic questionnaires, the Depression, Anxiety and Stress Scale-21 Items, and the Patient Reported Outcomes Quality of Life-HIV. Results: Testing of the prototype demonstrated that patients wanted an application that was intuitive and without excessive instruction, so it felt effortless to use, as well as secure and discreet. Clinicians wanted the PRO data synthesized, presented clearly and succinctly, and clinically actionable. Safety concerns for patients and clinicians included confidentiality, and the potential for breakdown in communication if insufficient user training was not provided. The final product, piloted with patients from both countries, showed that most respondents found the application easy to use and comprehend. The usability testing survey administered found that older Australians had reduced scores for understanding the visual interface (P=.004) and finding the buttons organized (P=.02). Three-fourths of the respondents were concerned with confidentiality (P=.007), and this result was more prevalent in participants with higher anxiety and stress scores (P=.01), as measured by the Depression, Anxiety and Stress Scale-21 Items. These statistical associations were not observed in 15 French patients who completed the same questionnaire. Conclusions: Digital applications in health care should be safe and fit for purpose. Our software was acceptable to patients and shows potential to overcome some barriers to the implementation of PROs in routine care. The design of the clinicians’ interface presents a solution to the problem of voluminous data, both synthesizing and providing a snapshot of longitudinal data. The next stage is to conduct a randomized controlled trial to determine whether patients experience increased satisfaction with care and whether doctors perceive that they deliver better clinical care without compromising efficiency

Preoperative falls predict postoperative falls, functional decline, and surgical complications

AbstractBackgroundFalls are common and linked to morbidity. Our objectives were to characterize postoperative falls, and determine whether preoperative falls independently predicted postoperative falls (primary outcome), functional dependence, quality of life, complications, and readmission.MethodsThis prospective cohort study included 7982 unselected patients undergoing elective surgery. Data were collected from the medical record, a baseline survey, and follow-up surveys approximately 30days and one year after surgery.ResultsFall rates (per 100 person-years) peaked at 175 (hospitalization), declined to 140 (30-day survey), and then to 97 (one-year survey). After controlling for confounders, a history of one, two, and ≥three preoperative falls predicted postoperative falls at 30days (adjusted odds ratios [aOR] 2.3, 3.6, 5.5) and one year (aOR 2.3, 3.4, 6.9). One, two, and ≥three falls predicted functional decline at 30days (aOR 1.2, 2.4, 2.4) and one year (aOR 1.3, 1.5, 3.2), along with in-hospital complications (aOR 1.2, 1.3, 2.0). Fall history predicted adverse outcomes better than commonly-used metrics, but did not predict quality of life deterioration or readmission.ConclusionsFalls are common after surgery, and preoperative falls herald postoperative falls and other adverse outcomes. A history of preoperative falls should be routinely ascertained

Rapid progression of prostate cancer in men with a BRCA2 mutation.

Men with BRCA2 mutations have been found to be at increased risk of developing prostate cancer. There is a recent report that BRCA2 carriers with prostate cancer have poorer survival than noncarrier prostate cancer patients. In this study, we compared survival of men with a BRCA2 mutation and prostate cancer with that of men with a BRCA1 mutation and prostate cancer. We obtained the age at diagnosis, age at death or current age from 182 men with prostate cancer from families with a BRCA2 mutation and from 119 men with prostate cancer from families with a BRCA1 mutation. The median survival from diagnosis was 4.0 years for men with a BRCA2 mutation vs 8.0 years for men with a BRCA1 mutation, and the difference was highly significant (P<0.01). It may be important to develop targeted chemotherapies to treat prostate cancer in men with a BRCA2 mutation

Programme Impact Assessment in Micro?Finance: The Need for Analysis of Real Markets

summary Impact assessment in micro?finance has focused on the impact of services on users and the ability of the organisation delivering those services to sustain its operations into the future. However, a focus on building organisations capable of long?term provision assumes that they will have a positive impact on the efficiency of the financial market. This is an assumption which impact assessment should also test but which has so far been neglected. Moreover, the search for a framework within which to undertake such an assessment must incorporate the complex array of social and political, as well as economic, relationships which financial markets embody. A fourfold analytical approach is proposed which can incorporate gender relations and which focuses on state involvement, market organisation, market structure and social embeddedness

Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials

OBJECTIVE: We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed and EMBASE databases were searched to identify randomised trials studying HCQ. STUDY SELECTION: Ten RCTs were identified (n=5079 participants). DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written. MAIN OUTCOMES: The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection. RESULTS: Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73). CONCLUSIONS AND RELEVANCE: Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events. PROSPERO REGISTRATION NUMBER: CRD42021285093

Genetic variation in the endocannabinoid system and response to cognitive behavioural therapy for child anxiety disorders

Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre- and post-treatment and during the follow-up period in the full sample and a subset with fear-based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow-up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear-based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility