Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS)

Background Women genetically predisposed to breast cancer often develop the disease at a young age when dense breast tissue reduces the sensitivity of X-ray mammography. Our aim was, therefore, to compare contrast enhanced magnetic resonance imaging (CE MRI) with mammography for screening. Methods We did a prospective multicentre cohort study in 649 women aged 35-49 years with a strong family history of breast cancer or a high probability of a BRCA1, BRCA2, or TP53 mutation. We recruited participants from 22 centres in the UK, and offered the women annual screening with CE MRI and mammography for 2-7 years. Findings We diagnosed 35 cancers in the 649 women screened with both mammography and CE MRI (1881 screens): 19 by CE MRI only, six by mammography only, and eight by both, with two interval cases. Sensitivity was significantly higher for CE MRI (77%, 95% CI 60-90) than for mammography (40%, 24-58; p=0.01), and was 94% (81-99) when both methods were used. Specificity was 93% (92-95) for mammography, 81% (80-83) for CE MRI (p

Jane Austen's lifelong health problems and final illness: New evidence points to a fatal Hodgkin's disease and excludes the widely accepted Addison's

Jane Austen is typically described as having excellent health until the age of 40 and the onset of a mysterious and fatal illness, initially identified by Sir Zachary Cope in 1964 as Addison's disease. Her biographers, deceived both by Cassandra Austen's destruction of letters containing medical detail, and the cheerful high spirits of the existing letters, have seriously underestimated the extent to which illness affected Austen's life. A medical history reveals that she was particularly susceptible to infection, and suffered unusually severe infective illnesses, as well as a chronic conjunctivitis that impeded her ability to write. There is evidence that Austen was already suffering from an immune deficiency and fatal lymphoma in January 1813, when her second and most popular novel, Pride and Prejudice, was published. Four more novels would follow, written or revised in the shadow of her increasing illness and debility. Whilst it is impossible now to conclusively establish the cause of her death, the existing medical evidence tends to exclude Addison's disease, and suggests there is a high possibility that Jane Austen's fatal illness was Hodgkin's disease, a form of lymphoma.

The experience of insomnia among older women

Study Objectives: To measure sleeping difficulty and sleep quality among older women, explore experience and attitudes towards sleep, and test for negative association between difficulty sleeping and health-related quality of life. Design: Four-year longitudinal study. Setting: Women were participants in the Australian Longitudinal Study on Women's Health. Participants: Women were sampled according to use of sleeping medication and classified into 4 groups: sleeping badly and using sleeping medications; not sleeping badly, but using sleeping medications; sleeping badly, not using sleeping medications; not sleeping badly, not using sleeping medications. Interventions: None. Measurements and Results: Sleeping difficulty and sleeping-medication use were measured at Survey 1, Survey 2 (3 years later), and Survey 3 (4 years later). Survey 3 included: Nottingham Health Profile Sleep Subscale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Geriatric Depression Scale, Duke Social Support Index, Medical Outcomes Study Short-Form 36-item Health Survey, and a 21-item life events scale. Survey 3 was returned by 1011 women (84%). Sleeping problems were negatively associated with SF-36 subscale scores. Most associations remained significant after comorbid conditions, Geriatric Depression Scale, life events scores, and medication use were added to models. Most women with sleeping problems (72%) sought help from a doctor, and 54% used prescribed sleeping medications in the past month. Conclusions: Sleeping difficulty is a serious symptom for older women and is associated with poorer quality of life. Some of this effect can be explained by comorbidities, depression scores, life events, and use of sleeping medications.

The effect of a reduction in heroin supply on fatal and non-fatal drug overdoses in New South Wales, Australia

Objective: To examine the impact of a sudden and dramatic decrease in heroin availability, concomitant with increases in price and decreases in purity, on fatal and non-fatal drug overdoses in New South Wales, Australia. Design and setting: Time-series analysis was conducted where possible on data on overdoses collected from NSW hospital emergency departments, the NSW Ambulance Service, and all suspected drug-related deaths referred to the NSW Coroner's court. Main outcome measures: The number of suspected drug-related deaths where heroin and other drugs were mentioned; ambulance calls to suspected opioid overdoses; and emergency department admissions for overdoses on heroin and other drugs. Results: Both fatal and non-fatal heroin overdoses decreased significantly after heroin supply reduced; the reductions were greater among younger age groups than older age groups. There were no clear increases in non-fatal overdoses with cocaine, methamphetamines or benzodiazepines recorded at hospital emergency departments after the reduction in heroin supply. Data on drug-related deaths suggested that heroin use was the predominant driver of drug-related deaths in NSW, and that when heroin supply was reduced overdose deaths were more likely to involve a wider combination of drugs. Conclusion: A reduction in heroin supply reduced heroin-related deaths, and did not result in a concomitant increase, to the same degree, in deaths relating to other drugs. Younger people were more affected by the reduction in supply.

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was 28 pound 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to 11 pound 731 (CE MRI vs mammography) and 15 pound 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

Familial aggregation of human infection with Schistosoma japonicum in the Poyang Lake region, China

Despite the success of extensive control measures that have been implemented in China for over 50 years, the number of individuals infected with Schistosoma japonicum remains high in the existing endemic areas. A variance components analysis was undertaken to estimate the heritable and environmental components that contribute to S. japonicum infection in the Poyang Lake region of Jiangxi Province, PR China. The total target population was 3148 from four separate administrative villages. Two thousand seven hundred and five of these comprised 400 families ranging in size from 3 to 188. After adjustments were made for gender, water contact and past history of having had schistosomiasis, the heritable component was estimated to account for as much as 58% of the phenotype variation under the polygenic model. Household was not shown to be an important environmental factor. Incorporating village effects indicated that the results were valid for the total population. We conclude that genetic heritability in this region is high and plays an important role in determining risk of infection with S. japonicum. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Safety behaviors and dysfunctional beliefs about sleep: Testing a cognitive model of the maintenance of insomnia

Objective: Our aim was to determine if insomnia severity, dysfunctional beliefs about sleep, and depression predicted sleep-related safety behaviors. Method: Standard sleep-related measures (such as the Insomnia Severity Index; the Dysfunctional Beliefs About Sleep scale; the Depression, Anxiety, and Stress Scale; and the Sleep-Related Behaviors Questionnaire) were administered. Additionally, 14 days of sleep diary (Pittsburg Sleep Diary) data and actual use of sleep-related behaviors were collected. Results: Regression analysis revealed that dysfunctional beliefs about sleep predicted sleep-related safety behaviors. Insomnia severity did not predict sleep-related safety behaviors. Depression accounted for the greatest amount of unique variance in the prediction of safety behaviors, followed by dysfunctional beliefs. Exploratory analysis revealed that participants with higher levels of depression used more sleep-related behaviors and reported greater dysfunctional beliefs about their sleep. Conclusion: The findings underlie the significant influence that dysfunctional beliefs have on individuals' behaviors. Moreover, the results suggest that depression may need to be considered as an explicit component of cognitive-behavioral models of insomnia. (c) 2006 Elsevier Inc. All rights reserved.