Gary David Rogers

No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial

BACKGROUND Lipodystrophy commonly complicates antiretroviral therapy of HIV-1 infection. Thiazolidinediones such as rosiglitazone promote subcutaneous fat growth in type 2 diabetics and adults with congenital lipodystrophy, and can prevent HIV-1 protease inhibitor toxicity to adipocytes in vitro. We postulated that rosiglitazone would improve HIV lipoatrophy. METHODS 108 HIV-1-infected lipoatrophic adults on antiretroviral therapy were randomised to rosiglitazone 4 mg twice daily (n=53) or matching placebo (n=55) for 48 weeks. The study had 80% power to detect a 0.5 kg difference in changes in limb fat (using dual-energy X-ray absorptiometry) between groups at week 48 by intention-to-treat analysis, and a 0.7 kg difference within each protease inhibitor stratum. FINDINGS Limb fat increased by 0.14 kg in the rosiglitazone group and 0.18 kg in the placebo group (mean difference -0.04 kg [95%CI -0.29 to 0.21]; p=0.74 by t test), with three participants (one on rosiglitazone and two controls), lost to follow-up. Rosiglitazone had no significant benefit on any other measure of lipodystrophy, despite large relative increases in plasma adiponectin (4.2 mmol/L [102%]; p<0.0001) and in three markers of insulin sensitivity (p=0.01 to 0.02). Six participants ceased study drug in each group, four participants (three on rosiglitazone and one control) for related adverse events. The main adverse effects, which seem to be almost unique to this population, were asymptomatic hypertriglyceridaemia (mean relative increase 0.9 mmol/L at week 48; p=0.04) and hypercholesterolaemia (1.5 mmol/L; p=0.001). INTERPRETATION Rosiglitazone for 48 weeks did not improve lipoatrophy in HIV-1-infected adults receiving antiretroviral therapy. Use of less toxic antiretroviral treatment is necessary to prevent lipoatrophy.

Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care

To examine the relationship between depressive disorders and unprotected anal intercourse with casual partners, among homosexually active men attending for primary care.

Social factors associated with Major Depressive Disorder in homosexually active, gay men attending general practices in urban Australia

Objectives : Social factors associated with Major Depressive Disorder (MDD) were identified among gay men attending high HIV caseload general practices in Sydney and Adelaide.

Competencies and frameworks in interprofessional education: a comparative analysis.

Health professionals need preparation and support to work in collaborative practice teams, a requirement brought about by an aging population and increases in chronic and complex diseases. Therefore, health professions education has seen the introduction of interprofessional education (IPE) competency frameworks to provide a common lens through which disciplines can understand, describe, and implement team-based practices. Whilst an admirable aim, often this has resulted in more confusion with the introduction of varying definitions about similar constructs, particularly in relation to what IPE actually means. The authors explore the nature of the terms competency and framework, while critically appraising the concept of competency frameworks and competency-based education. They distinguish between competencies for health professions that are profession specific, those that are generic, and those that may be achieved only through IPE. Four IPE frameworks are compared to consider their similarities and differences, which ultimately influence how IPE is implemented. They are the Interprofessional Capability Framework (United Kingdom), the National Interprofessional Competency Framework (Canada), the Core Competencies for Interprofessional Collaborative Practice (United States), and the Curtin University Interprofessional Capability Framework (Australia). The authors highlight the need for further discussion about establishing a common language, strengthening ways in which academic environments work with practice environments, and improving the assessment of interprofessional competencies and teamwork, including the development of assessment tools for collaborative practice. They also argue that for IPE frameworks to be genuinely useful, they need to augment existing curricula by emphasizing outcomes that might be attained only through interprofessional activity.

A randomized, multicenter, open-label study of poly-L-lactic acid for HIV-1 facial lipoatrophy.

Background:Facial lipoatrophy can stigmatize and can reduce quality of life, self esteem, and antiretroviral adherence. Poly-L-lactic acid (PLA) injections seem safe and effective, but no randomized study has included objective endpoints. Methods:HIV-positive adults with moderate/severe facial lipoatrophy were randomized to 4 open-label PLA treatments administered every 2 weeks from week 0 (immediate group, n = 51) or after week 24 (deferred group, n = 50). The primary endpoint was mean change in facial soft tissue volume (FSTV), as assessed by spiral computed tomography. Analyses were by intention to treat. Results:At week 24, mean changes in FSTV were 0 cm3 in the intermediate group and −10 cm3 in the deferred group (between-group difference of 10 [95% confidence interval (CI): −7 to 28] cm3; P = 0.24). The immediate group had a greater mean change in soft tissue depth at the maxilla (2.2 mm [95% CI: 1.6 to 2.9]; P < 0.0001) and base of the nasal septum (1.0 mm [95% CI: 0.3 to 1.6]; P = 0.003) levels. PLA did not have an impact on peripheral fat mass, viral load, or antiretroviral adherence. Patient and physician subjectively assessed facial lipoatrophy severity (P < 0.0001), 2 of 8 Short Form-36 Health Survey and 2 of 5 Multidimensional Body-Self Relations Questionnaire-Appearance Scales, scores improved significantly. The median duration of treatment-related adverse events was 2 (interquartile range: 1 to 3) days. Conclusions:PLA did not increase FSTV, although tissue thickness in injection planes increased modestly, an improvement observed by patients. PLA was safe and well tolerated. Facial lipoatrophy severity and some quality-of-life domains improved.

Effect of Rosiglitazone on Peroxisome Proliferator-Activated Receptor γ Gene Expression in Human Adipose Tissue Is Limited by Antiretroviral Drug-Induced Mitochondrial Dysfunction

BACKGROUND Treatment of human immunodeficiency virus (HIV)-1 with thymidine-analogue nucleoside reverse-transcriptase inhibitors (tNRTIs) causes lipoatrophy, mitochondrial toxicity, and lower adipose tissue expression of peroxisome proliferator-activated receptor gamma (PPARgamma [PPARG gene]). Rosiglitazone (RSG), a PPARgamma agonist, improves congenital lipoatrophy but not HIV lipoatrophy. METHODS Serial fat biopsies were taken from HIV-infected, lipoatrophic men randomized to receive RSG or placebo for 48 weeks. Adipose tissue mitochondrial and nuclear gene expression and mitochondrial DNA content were quantified by real-time polymerase chain reaction. Nonparametric analyses were applied. RESULTS Subjects receiving tNRTI-containing antiretroviral therapy had lower baseline mitochondrial RNA expression and DNA content. In subjects receiving tNRTIs, exposure to RSG did not affect PPARG expression at either week 2 or 48. At week 2, RSG increased PPARG expression only in subjects not treated with tNRTIs, whereas at week 48, increased PPARG expression was observed in subjects not treated with tNRTIs, regardless of RSG use. Similar findings were observed for the PPARG-responsive gene fatty acid-binding protein 4. Changes in PPARG expression were associated with increases in limb fat mass. CONCLUSIONS These data suggest that in HIV-infected, lipoatrophic men, adipose PPARG expression and function are dependent on intact mitochondrial function. These data support a direct link between mitochondrial toxicity and adipose tissue PPARG expression and help explain the poor clinical response to RSG observed in clinical trials.

International consensus statement on the assessment of interprofessional learning outcomes.

Abstract Regulatory frameworks around the world mandate that health and social care professional education programs graduate practitioners who have the competence and capability to practice effectively in interprofessional collaborative teams. Academic institutions are responding by offering interprofessional education (IPE); however, there is as yet no consensus regarding optimal strategies for the assessment of interprofessional learning (IPL). The Program Committee for the 17th Ottawa Conference in Perth, Australia in March, 2016, invited IPE champions to debate and discuss the current status of the assessment of IPL. A draft statement from this workshop was further discussed at the global All Together Better Health VIII conference in Oxford, UK in September, 2016. The outcomes of these deliberations and a final round of electronic consultation informed the work of a core group of international IPE leaders to develop this document. The consensus statement we present here is the result of the synthesized views of experts and global colleagues. It outlines the challenges and difficulties but endorses a set of desired learning outcome categories and methods of assessment that can be adapted to individual contexts and resources. The points of consensus focus on pre-qualification (pre-licensure) health professional students but may be transferable into post-qualification arenas.

Poly-L-lactic acid for HIV-1 facial lipoatrophy: 48-week follow-up

Poly‐l‐lactic acid (PLA) injections modestly increase objectively assessed facial thickness but not facial soft tissue volume (FSTV) over 24 weeks. The durability of this response has not been well defined objectively.

Simulated death can be an appropriate training tool for medical students.

Editor – In their recent letter, Bruppacher, Chen and Lachapelle expressed concern about the potential dangers of using simulated death in scenario-based teaching for health professionals in training, suggesting that such a strategy ‘would be best directed towards senior trainees whose scope of practice and responsibilities are commensurate with managing such complex scenarios’. Given that the death of the patient is by far the most common outcome in the resuscitation of real patients who experience cardiac arrest in hospitals and that such emergencies are managed by teams that often include practitioners at all levels of experience, this seems a surprising assertion.

Features of the management of depression in gay men and men with HIV from the perspective of Australian GPs

BACKGROUND In contrast to the broad literature on depression in the general population, little is known about the management of depression affecting gay men and HIV-positive men attending general practice clinics. OBJECTIVE This paper explores qualitative descriptions of how depression in gay men and HIV-positive men is managed by GPs. METHODS As part of the qualitative component of a mixed method study on HIV and depression, semi-structured interviews were conducted with 16 GPs in three geographical settings in Australia: Sydney, Adelaide and a rural coastal town. RESULTS GPs identified a range of features in their experience of managing depression in gay men and in HIV-positive men. Some were common to the care of other groups with depression, but this paper reports on features unique to this patient group. These include capitalizing on the high frequency of contact with this patient group, taking advantage of the specialist multidisciplinary teams who provide support, building upon the unusual willingness of this patient group to take medication, appreciating the central importance to many gay men of sexual functioning, and recreational drug use, responding to social isolation in this patient group and coping with increasing challenges for the HIV general practice workforce. CONCLUSIONS Despite the identification of several key strengths in working with this patient group, the ability of GPs to develop their capacity to manage depression in gay men and men with HIV is uncertain in the context of a growing range of challenges for GPs in both mental health and HIV care.