Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1

Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy strategies. Such approaches could form an important alternative to current anti-HIV-1 drug regimens, especially if combined with strategies to eradicate HIV reservoirs. Autologous CD4⁺ T cells or their haematopoietic stem cell precursors engineered to express TRIMCyp restriction factors, and provided in a single therapeutic intervention could then be used to restore functional immunity with a pool of cells protected against HIV. We consider the challenges ahead and consider how early clinical phase testing may best be achieved.     

Clinical Evaluation of the Cook Advance Enforcer 35 Focal-Force PTA Balloon Catheter for Treatment of Hemodialysis Fistula Stenoses: A Feasibility Study

Purpose

A prospective, single-center, single-arm feasibility study evaluated procedural and short-term performance of the Advance Enforcer 35 focal-force percutaneous transluminal angioplasty (PTA) balloon catheter in treating stenoses of mature native arteriovenous (AV) hemodialysis access circuits.

Anabolic steroids in the UK: an increasing issue for public health

Aim: The aim of the paper was to identify changes in the extent and patterns of anabolic steroid use in the United Kingdom to better understand the public health implications within the context of the current health-related evidence base. Methods: Using the two time points between 1995 (prior to legislation changes in the United Kingdom) and 2015, a review of the evidence related to health harms was conducted, in conjunction with needle and syringe programme (NSP) data in Cheshire & Merseyside (UK) relating to anabolic steroid users. Findings: Dramatic increase in the number of anabolic steroid users accessing NSPs, 553 in 1995 to 2446 in 2015, now accounting for 54.9% of clients. With the inclusion of pharmacy NSPs, this rose to 5336 individual anabolic steroid users. Conclusions: Key changes in our knowledge during the 20 years, in particular, in relation to HIV prevalence, changes in the market and patterns of use make anabolic steroid use a public health concern. In the context of increasing numbers of injectors, there is a need for comprehensive interventions.     

Is the UK NICE “Reference Case” Influencing the Practice of Pediatric Quality-Adjusted Life-Year Measurement within Economic Evaluations?

ObjectivesTo report findings from a systematic review, this article sought to address two related questions. First, how has the practice of UK pediatric cost-utility analyses evolved over time, in particular how are health-related outcomes assessed and valued? Second, how do the methods compare to the limited guidance available, in particular, the National Institute for Health and Care Excellence (NICE) reference case(s)?MethodsElectronic searches of MEDLINE, Embase, and Cochrane databases were conducted for the period May 2004 to April 2012 and the Paediatric Economic Database Evaluation database for the period May 2004 to December 2010. Identified studies were screened by three independent reviewers.ResultsForty-three studies were identified, 11 of which elicit utility values through primary research. A discrepancy was identified between the methods used for outcome measurement and valuation and the methods advocated within the NICE reference case. Despite NICE recommending the use of preference-based instruments designed specifically for children, most studies that were identified had used adult measures. In fact, the measurement of quality-adjusted life-years is the aspect of economic evaluation with the greatest amount of variability and the area that most digressed from the NICE reference case.ConclusionsRecommendations stemming from the review are that all studies should specify the age range of childhood and include separate statements of perspective for costs and effects as well as the reallocation of research funding away from systematic review studies toward good quality primary research measuring utilities in children.