Risk Reducing Salpingectomy and Delayed Oophorectomy in high risk women: views of cancer geneticists, genetic counsellors and gynaecological oncologists in the UK

Risk-reducing-salpingectomy and Delayed-Oophorectomy (RRSDO) is being proposed as a two-staged approach in place of RRSO to reduce the risks associated with premature menopause in high-risk women. We report on the acceptability/attitude of UK health professionals towards RRSDO. An anonymised web-based survey was sent to UK Cancer Genetics Group (CGG) and British Gynaecological Cancer Society (BGCS) members to assess attitudes towards RRSDO. Baseline characteristics were described using descriptive statistics. A Chi square test was used to compare categorical, Kendal-tau-b test for ordinal and Mann–Whitney test for continuous variables between two groups. 173/708 (24.4 %) of invitees responded. 71 % respondents (CGG = 57 %/BGCS = 83 %, p = 0.005) agreed with the tubal hypothesis for OC, 55 % (CGG = 42 %/BGCS = 66 %, p = 0.003) had heard of RRSDO and 48 % (CGG = 46 %/BGCS = 50 %) felt evidence was not currently strong enough for introduction into clinical practice. However, 60 % respondents’ (CGG = 48 %/BGCS = 71 %, p = 0.009) favoured offering RRSDO to high-risk women declining RRSO, 77 % only supported RRSDO within a clinical trial (CGG = 78 %/BGCS = 76 %) and 81 % (CGG = 76 %/BGCS = 86 %) advocated a UK-wide registry. Vasomotor symptoms (72 %), impact on sexual function (63 %), osteoporosis (59 %), hormonal-therapy (55 %) and subfertility (48 %) related to premature menopause influenced their choice of RRSDO. Potential barriers to offering the two-stage procedure included lack of data on precise level of benefit (83 %), increased surgical morbidity (79 %), loss of breast cancer risk reduction associated with oophorectomy (68 %), need for long-term follow-up (61 %) and a proportion not undergoing DO (66 %). There were variations in perception between BGCS/CGG members which are probably attributable to differences in clinical focus/expertise between these two groups. Despite concerns, there is reasonable support amongst UK clinicians to offering RRSDO to premenopausal high-risk women wishing to avoid RRSO, within a prospective clinical trial.This work has not been directly funded by any commercial organisation, or charity

A common genetic factor for Parkinson disease in ethnic Chinese population in Taiwan

BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized clinically by resting tremor, bradykinesia, postural instability and rigidity. The prevalence of PD is approximately 2% of the population over 65 years of age and 1.7 million PD patients (age ≥ 55 years) live in China. Recently, a common LRRK2 variant Gly2385Arg was reported in ethnic Chinese PD population in Taiwan. We analyzed the frequency of this variant in our independent PD case-control population of Han Chinese from Taiwan. METHODS: 305 patients and 176 genetically unrelated healthy controls were examined by neurologists and the diagnosis of PD was based on the published criteria. The region of interest was amplified with standard polymerase chain reaction (PCR). PCR fragments then were directly sequenced in both forward and reverse directions. Differences in genotype frequencies between groups were assessed by the X(2 )test, while X(2 )analysis was used to test for the Hardy-Weinberg equilibrium. RESULTS: Of the 305 patients screened we identified 27 (9%) with heterozygous G2385R variant. This mutation was only found in 1 (0.5%) in our healthy control samples (odds ratio = 16.99, 95% CI: 2.29 to 126.21, p = 0.0002). Sequencing of the entire open reading frame of LRRK2 in G2385R carriers revealed no other variants. CONCLUSION: These data suggest that the G2385R variant contributes significantly to the etiology of PD in ethnic Han Chinese individuals. With consideration of the enormous and expanding aging Chinese population in mainland China and in Taiwan, this variant is probably the most common known genetic factor for PD worldwide

Using Basic Science to Design a Clinical Trial: Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)

Observational and epidemiological studies suggest that menopausal hormone therapy (MHT) reduces cardiovascular disease (CVD) risk. However, results from prospective trials showed neutral or adverse effects most likely due to differences in participant demographics, such as age, timing of initiation of treatment, and preexisting cardiovascular disease, which reflected in part the lack of basic science information on mechanisms of action of hormones on the vasculature at the time clinical trials were designed. The Kronos Early Estrogen Replacement Study (KEEPS) is a prospective, randomized, controlled trial designed, using findings from basic science studies, to test the hypothesis that MHT when initiated early in menopause reduces progression of atherosclerosis. KEEPS participants are younger, healthier, and within 3 years of menopause thus matching more closely demographics of women in prior observational and epidemiological studies than women in the Women’s Health Initiative hormone trials. KEEPS will provide information relevant to the critical timing hypothesis for MHT use in reducing risk for CVD

Health status in older hospitalized patients with cancer or non-neoplastic chronic diseases

BACKGROUND: Whether cancer is more disabling than other highly prevalent chronic diseases in the elderly is not well understood, and represents the objective of the present study. METHODS: We used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study, a large collaborative observational study based in community and university hospitals located throughout Italy. Our series consisted of three groups of patients with non-neoplastic chronic disease (congestive heart failure, CHF, N = 832; diabetes mellitus, N = 939; chronic obstructive pulmonary disease, COPD, N = 399), and three groups of patients with cancer (solid tumors without metastasis, N = 813; solid tumors with metastasis, N = 259; leukemia/lymphoma, N = 326). Functional capabilities were ascertained using the activities of daily living (ADL) scale, and categorical variables for dependency in at least 1 ADL or dependency in 3 or more ADLs were considered in the analysis. Cognitive status was evaluated by the 10-items Hodgkinson Abbreviated Mental Test (AMT). RESULTS: Cognitive impairment was more prevalent in patients with CHF (28.0%) or COPD (25.8%) than in those with cancer (solid tumors = 22.9%; leukemia/lymphoma = 19.6%; metastatic cancer = 22.8%). Dependency in at least 1 ADL was highly prevalent in patients with metastatic cancer (31.3% vs. 24% for patients with CHF and 22.4% for those with non-metastatic solid tumors, p < 0.001). In people aged 80 years or more, metastatic cancer was not associated with increased prevalence of physical disability. In multivariable analysis, metastatic cancer was associated with a greater prevalence of physical (OR 2.09, 95%CI 1.51–2.90) but not cognitive impairment (OR 1.34, 95%CI 0.94–1.91) with respect to CHF patients. Finally, diabetes was significantly associated with cognitive impairment (OR 1.40, 95%CI 1.11–1.78). CONCLUSION: Cancer should not be considered as an ineluctable cause of severe cognitive and physical impairment, at least not more than other chronic conditions highly prevalent in older people, such as CHF and diabetes mellitus

PECAM-Independent Thioglycollate Peritonitis Is Associated With a Locus on Murine Chromosome 2

Background: Previous studies have demonstrated that knockout or inhibition of Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine strains results in impaired inflammatory responses, but that no such phenotype is seen in the C57BL/6 (B6) murine background. Methodology/Principal Findings: We have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible for this unique feature of B6 mice. We have identified a locus on murine chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score = 9.0) with inflammatory responses in the absence of PECAM. Conclusions/Significance: These data potentiate further study of the diapedesis machinery, as well as potential identification of new components of this machinery. As such, this study is an important step to better understanding the processes of inflammation

Characteristics of Nondisabled Older Patients Developing New Disability Associated with Medical Illnesses and Hospitalization

OBJECTIVE: To identify demographic, clinical, and biological characteristics of older nondisabled patients who develop new disability in basic activities of daily living (BADL) during medical illnesses requiring hospitalization. DESIGN: Longitudinal observational study. SETTING: Geriatric and Internal Medicine acute care units. PARTICIPANTS: Data are from 1,686 patients aged 65 and older who independent in BADL 2 weeks before hospital admission, enrolled in the 1998 survey of the Italian Group of Pharmacoepidemiology in the Elderly Study. MEASUREMENTS: Study outcome was new BADL disability at time of hospital discharge. Sociodemographic, functional status, and clinical characteristics were collected at hospital admission; acute and chronic conditions were classified according to the International Classification of Disease, ninth revision; fasting blood samples were obtained and processed with standard methods. RESULTS: At the time of hospital discharge 113 patients (6.7%) presented new BADL disability. Functional decline was strongly related to patients’ age and preadmission instrumental activities of daily living status. In a multivariate analysis, older age, nursing home residency, low body mass index, elevated erythrocyte sedimentation rate, acute stroke, high level of comorbidity expressed as Cumulative Illness Rating Scale score, polypharmacotherapy, cognitive decline, and history of fall in the previous year were independent and significant predictors of BADL disability. CONCLUSION: Several factors might contribute to loss of physical independence in hospitalized older persons. Preexisting conditions associated with the frailty syndrome, including physical and cognitive function, comorbidity, body composition, and inflammatory markers, characterize patients at high risk of functional decline

Occupational risk factors for Parkinson's disease: a case-control study in Japan

<p>Abstract</p> <p>Background</p> <p>The evidence for associations between occupational factors and the risk of Parkinson's disease (PD) is inconsistent. We assessed the risk of PD associated with various occupational factors in Japan.</p> <p>Methods</p> <p>We examined 249 cases within 6 years of onset of PD. Control subjects were 369 inpatients and outpatients without neurodegenerative disease. Information on occupational factors was obtained from a self-administered questionnaire. Relative risks of PD were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) based on logistic regression. Adjustments were made for gender, age, region of residence, educational level, and pack-years of smoking.</p> <p>Results</p> <p>Working in a professional or technical occupation tended to be inversely related to the risk of PD: adjusted OR was 0.59 (95% CI: 0.32-1.06, <it>P </it>= 0.08). According to a stratified analysis by gender, the decreased risk of PD for persons in professional or technical occupations was statistically significant only for men. Adjusted ORs for a professional or technical occupation among men and women were 0.22 (95% CI: 0.06-0.67) and 0.99 (0.47-2.07), respectively, and significant interaction was observed (<it>P </it>= 0.048 for homogeneity of OR). In contrast, risk estimates for protective service occupations and transport or communications were increased, although the results were not statistically significant: adjusted ORs were 2.73 (95% CI: 0.56-14.86) and 1.74 (95% CI: 0.65-4.74), respectively. No statistical significance was seen in data concerning exposure to occupational agents and the risk of PD, although roughly a 2-fold increase in OR was observed for workers exposed to stone or sand.</p> <p>Conclusion</p> <p>The results of our study suggest that occupational factors do not play a substantial etiologic role in this population. However, among men, professional or technical occupations may decrease the risk of PD.</p