Launching a Journal About and Through Students as Partners

Editorial of first issue of the International Journal for Student as Partners

The androgen receptor CAG repeat polymorphism and modification of breast cancer risk in BRCA1 and BRCA2 mutation carriers.

INTRODUCTION: The androgen receptor (AR) gene exon 1 CAG repeat polymorphism encodes a string of 9-32 glutamines. Women with germline BRCA1 mutations who carry at least one AR allele with 28 or more repeats have been reported to have an earlier age at onset of breast cancer. METHODS: A total of 604 living female Australian and British BRCA1 and/or BRCA2 mutation carriers from 376 families were genotyped for the AR CAG repeat polymorphism. The association between AR genotype and disease risk was assessed using Cox regression. AR genotype was analyzed as a dichotomous covariate using cut-points previously reported to be associated with increased risk among BRCA1 mutation carriers, and as a continuous variable considering smaller allele, larger allele and average allele size. RESULTS: There was no evidence that the AR CAG repeat polymorphism modified disease risk in the 376 BRCA1 or 219 BRCA2 mutation carriers screened successfully. The rate ratio associated with possession of at least one allele with 28 or more CAG repeats was 0.74 (95% confidence interval 0.42-1.29; P = 0.3) for BRCA1 carriers, and 1.12 (95% confidence interval 0.55-2.25; P = 0.8) for BRCA2 carriers. CONCLUSION: The AR exon 1 CAG repeat polymorphism does not appear to have an effect on breast cancer risk in BRCA1 or BRCA2 mutation carriers

Prevalence and demographics of methicillin resistant Staphylococcus aureus in culturable skin and soft tissue infections in an urban emergency department

<p>Abstract</p> <p>Background</p> <p>The rising incidence of methicillin resistant <it>Staph. aureus </it>(MRSA) infections is a concern for emergency practitioners. While studies have examined MRSA in inpatients, few have focused on emergency department populations. We sought to describe predictors of MRSA skin infections in an emergency department population.</p> <p>Methods</p> <p>This was a prospective observational cohort study conducted over three months in 2005. A convenience sample of patients with culturable skin infections presenting to a busy, urban emergency department was enrolled. Demographic and risk factor information was collected by structured interview. The predictive value of each risk factor for MRSA, as identified by culture, was tested using univariable logistic regression, and a multivariable predictive model was developed.</p> <p>Results</p> <p>Patients were 43% black, 40% female and mean age was 39 years (SD 14 years). Of the 182 patients with cultures, prevalence of MRSA was 58% (95%CI 50% to 65%). Significant predictors of MRSA were youth, lower body mass index, sexual contact in the past month, presence of an abscess cavity, spontaneous infection, and incarceration. The multivariable model had a C-statistic of 0.73 (95%CI 0.67 to 0.79) with four significant variables: age, group living, abscess cavity, and sexual contact within one month.</p> <p>Conclusion</p> <p>In this population of emergency department patients, MRSA skin infection was related to youth, recent sexual contact, presence of abscess, low body mass index, spontaneity of infection, incarceration or contact with an inmate, and group home living.</p

Secondary Outcomes of a Pilot Randomized Trial of Azithromycin Treatment for Asthma

OBJECTIVES: The respiratory pathogen Chlamydia pneumoniae (C. pneumoniae) produces acute and chronic lung infections and is associated with asthma. Evidence for effectiveness of antichlamydial antibiotics in asthma is limited. The primary objective of this pilot study was to investigate the feasibility of performing an asthma clinical trial in practice settings where most asthma is encountered and managed. The secondary objectives were to investigate (1) whether azithromycin treatment would affect any asthma outcomes and (2) whether C. pneumoniae serology would be related to outcomes. This report presents the secondary results. DESIGN: Randomized, placebo-controlled, blinded (participants, physicians, study personnel, data analysts), allocation-concealed parallel group clinical trial. SETTING: Community-based health-care settings located in four states and one Canadian province. PARTICIPANTS: Adults with stable, persistent asthma. INTERVENTIONS: Azithromycin (six weekly doses) or identical matching placebo, plus usual community care. OUTCOME MEASURES: Juniper Asthma Quality of Life Questionnaire (Juniper AQLQ), symptom, and medication changes from baseline (pretreatment) to 3 mo posttreatment (follow-up); C. pneumoniae IgG and IgA antibodies at baseline and follow-up. RESULTS: Juniper AQLQ improved by 0.25 (95% confidence interval; −0.3, 0.8) units, overall asthma symptoms improved by 0.68 (0.1, 1.3) units, and rescue inhaler use decreased by 0.59 (−0.5, 1.6) daily administrations in azithromycin-treated compared to placebo-treated participants. Baseline IgA antibodies were positively associated with worsening overall asthma symptoms at follow-up (p = 0.04), but IgG was not (p = 0.63). Overall asthma symptom improvement attributable to azithromycin was 28% in high IgA participants versus 12% in low IgA participants (p for interaction = 0.27). CONCLUSIONS: Azithromycin did not improve Juniper AQLQ but appeared to improve overall asthma symptoms. Larger community-based trials of antichlamydial antibiotics for asthma are warranted

Making it work for me: beliefs about making a personal health record relevant and useable.

BACKGROUND: A Personal Health Record (PHR) is an electronic record that individuals use to manage and share their health information, e.g. data from their medical records and data collected by apps. However, engagement with their record can be low if people do not find it beneficial to their health, wellbeing or interactions with health and other services. We have explored the beliefs potential users have about a PHR, how it could be made personally relevant, and barriers to its use. METHODS: A qualitative design comprising eight focus groups, each with 6-8 participants. Groups included adults with long-term health conditions, young people, physically active adults, data experts, and members of the voluntary sector. Each group lasted 60-90 min, was audio recorded and transcribed verbatim. We analysed the data using thematic analysis to address the question "What are people's beliefs about making a Personal Health Record have relevance and impact?" RESULTS: We found four themes. Making it work for me is about how to encourage individuals to actively engage with their PHR. I control my information is about individuals deciding what to share and who to share it with. My concerns is about individuals' concerns about information security and if and how their information will be acted upon. Potential impact shows the potential benefits of a PHR such as increasing self-efficacy, uptake of health-protective behaviours, and professionals taking a more holistic approach to providing care and facilitating behaviour change. CONCLUSIONS: Our research shows the functionality that a PHR requires in order for people to engage with it. Interactive functions and integration with lifestyle and health apps are particularly important. A PHR could increase the effectiveness of behaviour change apps by specifying evidence-based behaviour change techniques that apps should incorporate. A PHR has the potential to increase health-protective behaviours and facilitate a more person-driven health and social care system. It could support patients to take responsibility for self-managing their health and treatment regimens, as well as helping patients to play a more active role when care transfers across boundaries of responsibility

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations