Ambiguity in a masculine world: Being a BRCA1/2 mutation carrier and a man with prostate cancer.

OBJECTIVE: Increased risk of prostate cancer (PCa) is observed in men with BRCA1/BRCA2 mutations. Sex and gender are key determinants of health and disease although unequal care exists between the sexes. Stereotypical male attitudes are shown to lead to poor health outcomes. METHODS: Men with BRCA1/2 mutations and diagnosed with PCa were identified and invited to participate in a qualitative interview study. Data were analysed using a framework approach. "Masculinity theory" was used to report the impact of having both a BRCA1/2 mutation and PCa. RESULTS: Eleven of 15 eligible men were interviewed. The umbrella concept of "Ambiguity in a Masculine World" was evident. Men's responses often matched those of women in a genetic context. Men's BRCA experience was described, as "on the back burner" but "a bonus" enabling familial detection and early diagnosis of PCa. Embodiment of PCa took precedence as men revealed stereotypical "ideal" masculine responses such as stoicism and control while creating new "masculinities" when faced with the vicissitudes of having 2 gendered conditions. CONCLUSION: Health workers are urged to take a reflexive approach, void of masculine ideals, a belief in which obfuscates men's experience. Research is required regarding men's support needs in the name of equality of care.

Hospitalizations due to hepatitis C in Los Angeles County, 2007-2009: case characteristics and factors associated with mortality.

Morbidity and mortality due to hepatitis C (HCV) infection are rising in the United States as the highest risk cohort (those born between 1945 and 1965) ages. It is important for governments and healthcare providers to have timely, readily obtainable data to estimate the burden of HCV locally. Demographic factors, hospital charges and comorbid conditions were summarized for Los Angeles County (LAC) residents who had at least one hospitalization in California during 2007-2009 with HCV as a primary or secondary diagnosis using statewide hospital discharge data. Logistic regression was used to estimate odds ratios for factors associated with dying during hospitalization. A total of 19 907 unique patients were hospitalized with HCV during the 3-year study period; 63.0% were aged 45-65 years; 1874 (9.4%) died. Hospitalizations for HCV doubled during this time period. Total charges for hospitalizations for which HCV was coded as the principal diagnosis increased from $18 million to $58 million, with over 70% charged to government sources. After adjusting for demographic factors, human immunodeficiency virus (HIV) and hepatitis B (HBV), current alcohol abuse and kidney disease were associated with dying during hospitalization. Based on statewide hospital discharge data, morbidity and mortality from HCV infections increased in LAC from 2007-2009, and pose an economic burden to government. To lower mortality risk, HCV patients should be referred for follow-up. The expected increase in HCV hospitalizations as infected patients' age poses an increasing burden to healthcare systems.

Reproductive decision-making in young female carriers of a BRCA mutation.

STUDY QUESTION: How do young women, who were identified as carrying a BRCA gene mutation before they had children, approach reproductive decision-making and what are their attitudes towards reproductive genetic testing? SUMMARY ANSWER: Reproductive decision-making within the context of cancer risk is complex and influenced by personal experiences of cancer. Younger women were not concerned with reproductive decision-making at the time of their genetic test; however, the impact on subsequent reproductive decision-making was considerable and left them with unanticipated dilemmas, such as having children who would be at risk of inheriting cancer predisposition, timing risk-reducing surgery and changing perceptions of responsibility. WHAT IS KNOWN ALREADY: Individuals carrying gene mutations predisposing to hereditary breast/ovarian cancer have concerns about passing on the gene mutation to children. STUDY DESIGN, SIZE, DURATION: Qualitative methodology and thematic analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected through semi-structured interviews with 25 women aged 18-45 who had received a positive result for a BRCA1 or BRCA2 gene mutation while childless. MAIN RESULTS AND THE ROLE OF CHANCE: Analysis revealed four central themes: (i) the impact of cancer on reproductive decision-making; (ii) motivation for genetic testing; (iii) risk management and timing of planning children; and (iv) optimism for future medical advancements. LIMITATIONS, REASONS FOR CAUTION: This study explores the views of female BRCA carriers. Further research should explore the views of couples, men, and include samples with greater ethnic and social diversity. WIDER IMPLICATIONS OF THE FINDINGS: This evidence highlights the need for reproductive decision-making to be addressed at the time of pretest genetic counselling. More information should be provided on reproductive options as well as counselling/support to guide women's reproductive decision-making and prenatal testing options at the time they undertake genetic testing. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Cancer Research UK (Number C1226 A7920) and NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and RMH. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Beyond prostate-specific antigen - future biomarkers for the early detection and management of prostate cancer.

Prostate-specific antigen is currently commonly used as a screening biomarker for prostate cancer, but it has limitations in both sensitivity and specificity. The development of novel biomarkers for early cancer detection has the potential to improve survival, reduce unnecessary investigations and benefit the health economy. Here we review the use and limitations of prostate-specific antigen and its subtypes, urinary biomarkers including PCA3, alpha-methylacyl-CoA racemase, the TMPRSS2-ERG fusion gene and microseminoprotein-beta, and other novel markers in both serum and urine. Many of these biomarkers are at early stages of development and require evaluation in prospective trials to determine their potential usefulness in clinical practice. Genetic profiling may allow for the targeting of high-risk populations for screening and may offer the opportunity to combine biomarker results with genotype to aid risk assessment.

The carrier clinic: an evaluation of a novel clinic dedicated to the follow-up of BRCA1 and BRCA2 carriers--implications for oncogenetics practice.

BACKGROUND: A novel oncogenetic clinic was established in 2002 at the Royal Marsden NHS Foundation Trust offering advice and specialist follow-up for families with a germline mutation in BRCA1 or BRCA2. The remit of this multidisciplinary clinic, staffed by individuals in both oncology and genetics, is to provide individualised screening recommendations, support in decision making, risk reducing strategies, cascade testing, and an extensive research portfolio. METHODS: A retrospective analysis was performed to evaluate uptake of genetic testing, risk reducing surgery and cancer prevalence in 346 BRCA1/BRCA2 families seen between January 1996 and December 2006. RESULTS: 661 individuals attended the clinic and 406 mutation carriers were identified; 85.8% mutation carriers have chosen to attend for annual follow-up. 70% of mutation carriers elected for risk reducing bilateral salpingo-oophorectomy (RRBSO). 32% of unaffected women chose risk reducing bilateral mastectomy. 32% of women with breast cancer chose contralateral risk reducing mastectomy at time of diagnosis. Some women took over 8 years to decide to have surgery. 91% of individuals approached agreed to participate in research programmes. INTERPRETATION: A novel specialist clinic for BRCA1/2 mutation carriers has been successfully established. The number of mutation positive families is increasing. This, and the high demand for RRBSO in women over 40, is inevitably going to place an increasing demand on existing health resources. Our clinic model has subsequently been adopted in other centres and this will greatly facilitate translational studies and provide a healthcare structure for management and follow-up of such people who are at a high cancer risk.

Elevated expression of Ki-67 identifies aggressive prostate cancers but does not distinguish BRCA1 or BRCA2 mutation carriers.

Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more aggressive than morphologically similar cancers in men without these mutations. This study was performed to test the hypothesis that enhanced expression of Ki-67, as a surrogate of cell proliferation, is a characteristic feature of prostate cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised 20 cases of prostate cancer in mutation carriers and 126 control sporadic prostate cancers. Of the combined sample cohort, 65.7% stained only within malignant tissues while 0.7% stained in both malignant and benign tissues (p<0.001). Significantly increased expression of Ki-67 occurred in prostate cancers with higher Gleason score (p<0.001). Elevated Ki-67 expression was identified in 71% of prostate cancers in BRCA1 or BRCA2 mutation carriers and in 67% of the sporadic controls (p>0.5). Similar results were obtained when the data were analysed using a threshold set at 3.5 and 7.1%. This study shows that elevated expression of Ki-67 is associated both with aggressive prostate cancers and with high Gleason score irrespective of whether their occurrence is against a background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest that, since elevated Ki-67 does not distinguish prostate cancers occurring in BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the effects of these genetic mutations are probably independent. While all prostate cancers occurring in the presence of BRCA germline mutations are clinically aggressive, their potentially different phenotypes consistently involve maximal rates of cell proliferation.

Hospitalization of paediatric patients for methicillin-resistant Staphylococcus aureus skin and soft-tissue infection, 1998-2006.

Hospital discharge reports have provided data for studies of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infection (SSTI) studies. This analysis determined the sensitivity and positive predictive value of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code combinations to calculate hospitalization incidence rates, representativeness of a set of three ICD-9-CM codes to define MRSA SSTI, and hospitalization incidence rate trends for paediatric MRSA SSTIs in Los Angeles County (LAC). Using 133 cases from 31 hospitals, we found that the set of three ICD-9-CM codes used to define laboratory-confirmed cases had one of the highest positive predictive values (49%). There was no difference in age and race between those categorized using three codes vs. other code combinations. A dramatic increase in paediatric MRSA SSTI cases occurred in LAC during 1998-2006. We conclude that this combination of codes may be used to determine the rise of MRSA SSTIs in paediatric populations.

Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype.

There is a high and rising prevalence of prostate cancer (PRCA) within the male population of the United Kingdom. Although the relative risk of PRCA is higher in male BRCA2 and BRCA1 mutation carriers, the histological characteristics of this malignancy in these groups have not been clearly defined. We present the histopathological findings in the first UK series of BRCA1 and BRCA2 mutation carriers with PRCA. The archived histopathological tissue sections of 20 BRCA1/2 mutation carriers with PRCA were collected from histopathology laboratories in England, Ireland and Scotland. The cases were matched to a control group by age, stage and serum PSA level of PRCA cases diagnosed in the general population. Following histopathological evaluation and re-grading according to current conventional criteria, Gleason scores of PRCA developed by BRCA1/2 mutation carriers were identified to be significantly higher (Gleason scores 8, 9 or 10, P=0.012) than those in the control group. Since BRCA1/2 mutation carrier status is associated with more aggressive disease, it is a prognostic factor for PRCA outcome. Targeting screening to this population may detect disease at an earlier clinical stage which may therefore be beneficial.

AIDIT and IMPACT: building research collaborations in targeted prostate cancer screening.

AIDIT (Advancing International Co-operation and Developing Infrastructure for Targeted Screening of Prostate Cancer in Men with Genetic Predisposition) is a project funded by the Sixth Framework Programme of the European Community which is endeavouring to facilitate co-operation between European countries in the field of cancer research. The project also aims to raise awareness of familial prostate cancer among health professionals and the public within the associated candidate countries (ACCs) and new member states of the European Union (EU). AIDIT will focus on linking clinical and research teams in the ACCs and new member states with the IMPACT Consortium (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), an international team investigating screening and diagnosis for men with a genetic risk of prostate cancer predisposition genes BRCA1 or BRCA2). Cancer research has been targeted as a high priority for the European Community; however, research is most successful when centralised and well coordinated, avoiding the duplication and fragmentation associated with smaller, isolated studies. AIDIT will consolidate the current IMPACT consortium and allow research partners from across the world to benefit from shared knowledge and experience. To date, the AIDIT team has established a website to facilitate communication between project collaborators (www.impact-study.co.uk), has been represented at several international meetings and has facilitated a conference for the IMPACT study to bring together international research teams, clinicians and policy makers.

Survey of patients attending the eye clinic during the month of March; 1992

An audit survey was carried out during the month of March 1992 of patients attending the eye clinic. The number of patients; age and sex distribution; diagnosis; treatment modality and disposal were recorded. A total of 1166 patients were seen. The commonest diagnosis seen by the Ophthalmologist was non specific; and the commonest by the optometrist was presbyopia. Diseases required treatment included cataract; glaucoma and pterygium. Conditions that require screening included glaucoma and diabetic retinopathy. Prevention could be instituted in reducing other common conditions such trauma; pterygium and toxoplasma chorioretinitis