Recruitment of men to a multi-centre diabetes prevention trial: an evaluation of traditional and online promotional strategies

Background: Effective interventions are required to prevent the current rapid increase in the prevalence of Type 2 diabetes. Clinical trials of large-scale interventions to prevent Type 2 diabetes are essential but recruitment is challenging and expensive, and there are limited data regarding the most cost-effective and efficient approaches to recruitment. This paper aims to evaluate the cost and effectiveness of a range of promotional strategies used to recruit men to a large Type 2 diabetes prevention trial. Methods: An observational study was conducted nested within the Testosterone for the Prevention of Type 2 Diabetes (T4DM) study, a large, multi-centre randomised controlled trial (RCT) of testosterone treatment for the prevention of Type 2 diabetes in men aged 50–74 years at high risk of developing diabetes. Study participation was promoted via mainstream media—television, newspaper and radio; direct marketing using mass mail-outs, publicly displayed posters and attendance at local events; digital platforms, including Facebook and Google; and online promotions by community organisations and businesses. For each strategy, the resulting number of participants and the direct cost involved were recorded. The staff effort required for each strategy was estimated based on feedback from staff. Results: Of 19,022 men screened for the study, 1007 (5%) were enrolled. The most effective recruitment strategies were targeted radio advertising (accounting for 42% of participants), television news coverage (20%) and mass mail-outs (17%). Other strategies, including radio news, publicly displayed posters, attendance at local events, newspaper advertising, online promotions and Google and Facebook advertising, each accounted for no more than 4% of enrolled participants. Recruitment promotions cost an average of AU$594 per randomised participant. The most cost-effective paid strategy was mass mail-outs by a government health agency (AU$745 per participant). Other paid strategies were more expensive: mail-out by general practitioners (GPs) (AU$1104 per participant), radio advertising (AU$1081) and newspaper advertising (AU$1941). Conclusion: Radio advertising, television news coverage and mass mail-outs by a government health agency were the most effective recruitment strategies. Close monitoring of recruitment outcomes and ongoing enhancement of recruitment activities played a central role in recruitment to this RCT.Karen Bracken, Wendy Hague, Anthony Keech, Ann Conway, David J. Handelsman, Mathis Grossmann, David Jesudason, Bronwyn Stuckey, Bu B. Yeap, Warrick Inder, Carolyn Allan, Robert McLachlan, Kristy P. Robledo and Gary Witter

Mutations in HPCA cause autosomal-recessive primary isolated dystonia

Reports of primary isolated dystonia inherited in an autosomal-recessive (AR) manner, often lumped together as "DYT2 dystonia," have appeared in the scientific literature for several decades, but no genetic cause has been identified to date. Using a combination of homozygosity mapping and whole-exome sequencing in a consanguineous kindred affected by AR isolated dystonia, we identified homozygous mutations in HPCA, a gene encoding a neuronal calcium sensor protein found almost exclusively in the brain and at particularly high levels in the striatum, as the cause of disease in this family. Subsequently, compound-heterozygous mutations in HPCA were also identified in a second independent kindred affected by AR isolated dystonia. Functional studies suggest that hippocalcin might play a role in regulating voltage-dependent calcium channels. The identification of mutations in HPCA as a cause of AR primary isolated dystonia paves the way for further studies to assess whether "DYT2 dystonia" is a genetically homogeneous condition or not. © 2015 The American Society of Human Genetics

Mediation analysis of the testosterone treatment effect to prevent type 2 diabetes in the Testosterone for Prevention of Type 2 Diabetes Mellitus trial

OBJECTIVE: To determine if testosterone treatment effect on glycaemia is mediated through changes in total fat mass, abdominal fat mass, skeletal muscle mass, non-dominant handgrip, oestradiol (E2), and sex hormone-binding globulin (SHBG). DESIGN: Mediation analysis of a randomised placebo-controlled trial of testosterone. METHODS: Six Australian tertiary care centres recruited 1007 males, aged 50-74 years, with waist circumference ≥ 95 cm, serum total testosterone ≤ 14 nmol/L (immunoassay) and either impaired glucose tolerance or newly diagnosed type 2 diabetes on an oral glucose tolerance test (OGTT). Participants were enrolled in a lifestyle program and randomised 1:1 to 3 monthly injections of 1000 mg testosterone undecanoate or placebo for 2 years. Complete data were available for 709 participants (70%). Mediation analyses for the primary outcomes of type 2 diabetes at 2-years (OGTT ≥ 11.1 mmol/L and change in 2-hour glucose from baseline), incorporating potential mediators: changes in fat mass, % abdominal fat, skeletal muscle mass, non-dominant hand-grip strength, E2, and SHBG was performed. RESULTS: For type 2 diabetes at 2-years, the unadjusted OR for treatment was 0.53 (95% CI:0.35-0.79), which became 0.48 (95% CI:0.30-0.76) after adjustment for covariates. Including potential mediators attenuated the treatment effect (OR 0.77; 95% CI:0.44-1.35; direct effect) with 65% mediated. Only fat mass remained prognostic in the full model (OR: 1.23; 95% CI: 1.09-1.39; p < 0.001). CONCLUSION: At least part of the testosterone treatment effect was found to be mediated by changes in fat mass, abdominal fat, skeletal muscle mass, grip strength, SHBG, and E2, but predominantly by changes in fat mass.Kristy P. Robledo, Ian C. Marschner, David J. Handelsman, Karen Bracken, Bronwyn G.A. Stuckey, Bu B. Yeap, Warrick Inder, Mathis Grossmann, David Jesudason, Carolyn A. Allan, and Gary Witter

Effect of Testosterone treatment on bone microarchitecture and bone mineral density in men: a two-year RCT

CONTEXT: Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. OBJECTIVE: Determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT). DESIGN, SETTING, PARTICIPANTS: Men>50 years were recruited from six Australian centres. INTERVENTIONS: Injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. MAIN OUTCOMES: Primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (one centre). Secondary endpoints included other HR-pQCT parameters and bone remodelling markers. Areal BMD (aBMD) was measured by dual energy X-ray absorptiometry (DXA) in 601 men (five centres). Using a linear mixed model for repeated measures, the mean adjusted differences (MAD) [95% CI] at 12 and 24 months between groups are reported as treatment effect. RESULTS: Over 24 months, testosterone treatment, compared to placebo, increased tibial cortical vBMD), 9.33mgHA/cm 3[3.96;14.71],p50 years, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.Mark Ng Tang Fui, Rudolf Hoermann, Karen Bracken, David J Handelsman, Warrick J Inder, Bronwyn G A Stuckey ... et al

Modelos de regressão aleatória para avaliação da curva de crescimento em matrizes de codorna de corte Random regression models for growth evaluation of meat-type quail hens

Objetivou-se comparar diferentes modelos de regressão aleatória por meio de funções polinomiais de Legendre de diferentes ordens, para avaliar o que melhor se ajusta ao estudo genético da curva de crescimento de codornas de corte. Foram avaliados dados de 2136 matrizes de codorna de corte, dos quais 1026 pertenciam ao grupo genético UFV1 e 1110 ao grupo UFV2. As codornas foram pesadas nos 1°, 7°, 14°, 21°, 28°, 35°, 42°, 77°, 112° e 147° dias de idade e seus pesos utilizados para a análise. Foram testadas duas possíveis modelagens de variância residual heterogênea, sendo agrupadas em 3 e 5 classes de idade. Após, foi realizado o estudo do modelo de regressão aleatória que melhor aplica-se à curva de crescimento das codornas. A comparação entre os modelos foi feita pelo Critério de Informação de Akaike (AIC), Critério de Informação Bayesiano de Schwarz (BIC), Logaritmo da função de verossimilhança (Log e L) e teste da razão de verossimilhança (LRT), ao nível de 1%. O modelo que considerou a heterogeneidade de variância residual CL3 mostrou-se adequado à linhagem UFV1, e o modelo CL5 à linhagem UFV2. Uma função polinomial de Legendre com ordem 5, para efeito genético aditivo direto e 5 para efeito permanente de animal, para a linhagem UFV1 e, com ordem 3, para efeito genético aditivo direto e 5 para efeito permanente de animal para a linhagem UFV2, deve ser utilizada na avaliação genética da curva de crescimento das codornas de corte.<br>The objective was to compare different random regression models using Legendre polynomial functions of different orders, to evaluate what best fits the genetic study of the growth curve of meat quails. It was evaluated data from 2136 cut dies quail, of which 1026 belonged to genetic group UFV1 and 1110 the group UFV2. Quail were weighed at 10, 70, 140, 210, 280, 350, 420, 770, 1120 and 1470 days of age, and weights used for the analysis. It was tested two possible modeling of heterogeneous residual variance, which was grouped into three five age classes. After, it was studied the random regression mode, which is better applied to the growth curve quail. The comparison between models was made by the Akaike Information Criterion (AIC), Bayesian Information Criterion of Schwarz (BIC), logarithm of the likelihood function (Loge L) and the likelihood ratio test (LRT), at 1%. The model which considered the heterogeneity of residual variance CL3 was adequate to UFV1 lineage and the lineage model CL5 UFV2. A Legendre polynomial with order 5, for direct genetic effect and 5 for the permanent animal to UFV1 bloodline and order 3 for direct genetic effect and 5 for the permanent animal for UFV2 bloodline should be used in genetic evaluation of the growth curve of meat quails