A pathway to a stronger research culture in health policy

Background

There are currently limited pathways into a career in health policy research in Australia, due in part to a serious absence of health policy research capability in Australian universities.

Discussion

We define what we consider health policy research and education should comprise. We then examine what is currently on offer and propose ways to strengthen health policy research in Australia.

Summary

This paper, which is part analysis and part commentary, is offered to provoke wider debate about how health policy research can be nurtured in Australia.

     

Sex dependent influence of a functional polymorphism in steroid 5‐α‐reductase type 2 (SRD5A2) on post‐traumatic stress symptoms

A non‐synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5‐α‐reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post‐traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African‐American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post‐traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex‐dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex‐specific way, the severity of post‐traumatic stress symptoms and risk for diagnosis of PTSD. © 2013 Wiley Periodicals, Inc.     

Effect of preexisting immunity to Salmonella on the immune response to recombinant Salmonella enterica serovar typhimurium expressing a Porphyromonas gingivalis hemagglutinin

Recombinant Salmonella strains expressing foreign heterologous genes have been extensively studied as live oral vaccine delivery vectors. We have investigated the mucosal and systemic immune responses following oral immunization with a recombinant Salmonella enterica serovar Typhimurium expressing the hemagglutinin HagB from Porphyromonas gingivalis, a suspected etiological agent of adult periodontal disease. We have previously shown a primary mucosal and systemic response following oral immunization with chi4072/pDMD1 and recall responses following boosting at 14 weeks after primary immunization. In this study, we examined the effects of earlier boosting as well as the effects of deliberately induced immunity to the Salmonella carrier strain on subsequent immune responses. Mice boosted at week 7 following immunization, a point which corresponded to the peak of the primary response, generally showed lower responses than those boosted at week 14. When mice were preimmunized with the Salmonella carrier alone and then immunized with the recombinant strain 7 or 14 weeks later, significant reductions were seen for serum immunoglobulin G (IgG) antibodies at week 14 and for salivary IgA at week 7. No reductions were seen in serum IgA or vaginal wash IgA antibodies. Mice appear to be refractory to boosting with orally administered salmonellae at 7 weeks. Deliberate immunization with the carrier strain did not appreciably affect recall responses at 14 weeks, with the exception of the serum IgG responses, nor did it affect colonization of the Peyer's patches.     

Role of beta1 and beta2 subunits of the interleukin-12 receptor in determining T helper 1/T helper 2 responses in vivo in the rat

Interleukin-12 (IL-12) responsiveness, and hence capacity to mount a T helper type 1(Th1) immune response, may be regulated via differential expression of the IL-12 receptor beta2 subunit at least in vitro in human and murine cells. To test whether a similar phenomenon operates in vivo in the rat we cloned and sequenced partial cDNAs for rat IL-12Rbeta1 and IL-12Rbeta2 subunits and analysed expression of these genes in vivo in two rat strains with different Th1/Th2 bias. After treatment with mercuric chloride (HgCl2), Brown-Norway rats develop Th2-biased autoimmunity whereas Lewis rats do not develop autoimmunity, instead becoming resistant to Th1-biased diseases to which they are normally susceptible. We report close sequence homology between the segments of the rat IL-12R genes sequenced and corresponding mouse genes (95.6% and 92% for IL-12Rbeta1 and IL-12Rbeta2, respectively). Both Brown-Norway and Lewis rats express both beta1 and beta2 subunits of IL-12 receptor in vivo in spleen; Brown-Norway rats express the beta2 subunit at a lower level than Lewis rats. After HgCl2 treatment, IL-12Rbeta1 expression was not altered but there was down-regulation of IL-12Rbeta2 expression in both strains. We conclude that relative under-expression of IL-12Rbeta2 by Brown-Norway rats contributes to their Th2 bias, and that down-regulation of IL-12Rbeta2 after HgCl2 administration in Lewis rats underlies subsequent resistance to induction of Th1-biased diseases.     

The genetic aetiology of somatic distress

BACKGROUND: Somatoform disorders such as neurasthenia and chronic fatigue syndrome are characterized by a combination of prolonged mental and physical fatigue. This study aimed to investigate the heritability of somatic distress and determine whether this dimension is aetiologically distinct from measures of depression and anxiety. METHOD: Measures of anxiety, depression, phobic anxiety, somatic distress and sleep difficulty were administered in a self-report questionnaire to a community-based sample of 3469 Australian twin individuals aged 18 to 28 years. Factor analysis using a Promax rotation, produced four factors: depression, phobic anxiety, somatic distress and sleep disturbance. Multivariate and univariate genetic analyses of the raw categorical data scores for depression, phobic anxiety and depression were then analysed in Mx1.47. RESULTS: Univariate genetic analysis revealed that an additive genetic and non-shared environmental (AE) model best explained individual differences in depression and phobic anxiety scores, for male and female twins alike, but could not resolve whether additive genes or shared environment were responsible for significant familial aggregation in somatic distress. However, multivariate genetic analysis showed that an additive genetic and non-shared environment (AE) model best explained the covariation between the three factors. Furthermore, 33 % of the genetic variance in somatic distress was due to specific gene action unrelated to depression or phobic anxiety. In addition, 74% of the individual environmental influence on somatic distress was also unrelated to depression or phobic anxiety. CONCLUSION: These results support previous findings that somatic symptoms are relatively aetiologically distinct both genetically and environmentally from symptoms of anxiety and depression.     

Comparison of renal function after open radical cystectomy,extracorporeal robot assisted radical cystectomy,and intracorporeal robot assisted radical cystectomy

PurposeRenal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution.Materials and MethodsWe retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m². Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m². Renal function decline was defined as a ≥10 ml/min/1.73m² drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B.ResultsSix hundred and forty four patients were included with median follow-up of 32 months (IQR 12–56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m², P = 0.15). Median postoperative eGFR on follow up was not different between groups (P = 0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001).ConclusionRenal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline.     

Visual contrast enhancement with a patterned overlay

A dot-screen pattern was devised and superimposed on computed tomography images to improve contrast at a viewbox. The phenomenon is believed to be probably related to lateral inhibition. To evaluate its usefulness, the device was used on 12 images (eight showed metastatic liver lesions, and four were normal); each image was viewed without the device by ten observers. Three control images were viewed a second time without the device. The remaining nine images were viewed a second time with the device. The overlay improved diagnostic performance in nine observers. Sensitivity improved by 12%, and confidence in true-positive findings increased by 41.6%. Forty-five percent of false-negative findings were converted to true positive with the use of the overlay.