Polymorphic variation in the androgen receptor gene: association with risk of testicular germ cell cancer and metastatic disease

Increasing incidence of testicular germ cell cancer (TGCC) is most probably related to environment and lifestyle. However, an underlying genetic predisposition may play a role and since sex steroids are assumed to be important for the rise and progression of TGCC, a study of androgen receptor (AR) gene polymorphisms in relation to the risk, histological type and progression of TGCC was undertaken. In 367 TGCC cases and 214 controls, AR CAG and GGN repeat lengths were determined and 11 haplotype-tagging single nucleotide polymorphisms (SNPs) were genotyped. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the risk of TGCC, non-seminoma versus seminoma and metastatic versus localised (stage I) disease. For the non-coding SNP, rs12014709, the minor genotype (G) was found in 10% of the cases and in 5.1% of the controls, conferring an OR of 2.07 (95% CI: 1.03-4.15) for having TGCC. Furthermore, short GGN (<23) was associated with an increased risk of metastatic disease (OR: 2.15; 95% CI: 1.04-4.45). The AR polymorphisms found by us might be involved in gene-environment interaction by increasing the susceptibility to the effect of endocrine disruptors. From a biological point of view, our findings strengthen the hypothesis of the importance of androgen action in the aetiology and pathogenesis of testicular malignancy. Future studies should focus on the impact of sex hormones on foetal germ cell development and the interaction between environmental factors and androgen receptor variants in relation to the risk of testicular malignancy

Decentralised paediatric HIV care in Ethiopia: a comparison between outcomes of patients managed in health centres and in a hospital clinic

Background: In order to increase access to antiretroviral therapy (ART) in HIV-infected children, paediatric HIV care has been introduced in health centres in Ethiopia, where patients are managed by health professionals with limited training. Objective: To compare outcomes of paediatric HIV care in hospital and health centre clinics and to determine risk factors for death and loss to follow-up (LTFU). Design: Retrospective comparison of patient characteristics and outcomes among children managed in a public hospital and all five public health centres in the uptake area. Results: Among 1,960 patients (health centres 572, hospital clinic 1,388), 34% were lost to follow-up, 2% died, 14% were transferred out, and 46% remained in care. Children initiating ART in the hospital clinic had lower median CD4 cell counts (age &#60;1 year: 575 vs. 1,183 cells/mm3, p=0.024; age 1&#x2013;5 years: 370 vs. 598 cells/mm3, p&#60;0.001; age &#x003E;5 years: 186 vs. 259 cells/mm3, p&#60;0.001), and a higher proportion were &#60;1 year of age (22% vs. 15%, p=0.025). ART initiation rates and retention in care were similar between children managed in health centres and in the hospital clinic (36% vs. 37% and 47% vs. 46%, respectively). Among patients starting ART, mortality was associated with age &#60;1 year [hazard ratio (HR) 12.0; 95% confidence interval (CI): 3.5, 41]. LTFU was associated with CD4 cell counts &#60;350 cells/mm3 (HR 1.8; 95% CI: 1.2, 3.0), weight-for-age z-scores below &#x2212;4 (HR 2.8; 95% CI: 1.4, 5.6), and age &#60;5 years (1&#x2013;5 years: HR 1.6; 95% CI: 1.0, 2.5; &#60;1 year: HR 3.3; 95% CI: 1.6, 6.6). Conclusions: Outcomes of HIV care were similar for Ethiopian children managed in a hospital clinic or in health centres. However, patients treated at the hospital clinic had characteristics of more advanced disease. Rates of LTFU were high in both types of health facility