Analysis of Nausea in Clinical Studies of Lubiprostone for the Treatment of Constipation Disorders

Digestive Diseases and Sciences - Lubiprostone is a ClC-2 chloride channel activator approved for the treatment of chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC) in...     

Age, period and birth cohort effects on prevalence of overweight and obesity in Australian adults from 1990 to 2000

OBJECTIVE: To assess the individual contributions of age, period and birth cohort to prevalence of overweight and obesity in the Australian population during 1990 to 2000. DESIGN: Age-period-cohort Poisson regression modelling of data from National Health Surveys conducted in Australia in 1990, 1995 and 2000. SUBJECTS: Adults aged 20 years and over. Weightings were applied to account for differences in sampling and participation rates so that the sample is representative of the entire Australian adult population. METHODS: Twelve age groups, based on 5-year intervals from 20 to 24 years to greater than 75 years, three survey periods and 14 cohorts, also based on 5-year intervals from pre-1915 up to 1976-1980, were used in the analysis. The data were age-standardized to the 2000 population and body mass index (BMI) was calculated. Log-linear models, for the prevalence rates of overall overweight (BMI > or =25) and of obesity (BMI > or =30) were fitted to the data. RESULTS: Age (P<0.001), period (P<0.001) and cohort (P=0.002) all showed significant independent effects on prevalence of overall overweight in the Australian population such that prevalence rises with increasing age, recency of period and cohorts born since 1960. Age (P<0.001) and period (P<0.001) demonstrated strong effects on prevalence of obesity but birth cohort (P=0.07) was not significant. The effects were similar for men and women except that the overall effect of birth cohort on overall overweight was significant in women (P<0.05) but not men (P=0.09). CONCLUSION: The prevalence of overweight and obesity in Australian adults continued to rise during the 1990s. The obesogenic environment seems to have worsened and more recently born cohorts may be at increased risk of overweight.     

Patch testing with carbamazepine and its main metabolite carbamazepine epoxide in cutaneous adverse drug reactions to carbamazepine

The value of skin tests in the diagnosis of adverse drug reactions (ADRs) has been limited. Lack of knowledge as to the nature of drug allergens has contributed to these limitations. Several reports have addressed the roles of metabolites in cutaneous ADRs and skin testing. We evaluated the role of a carbamazepine (CBZ) metabolite on the results obtained from patch tests, using CBZ and its main metabolite 10, 11-epoxide of CBZ (CBZ-epoxide), on 13 patients with CBZ-induced drug eruptions and 39 controls with no CBZ-induced cutaneous ADRs. 10 of the 13 patients showed a positive reaction, and 2 of the 10 patients had a reaction to the CBZ-epoxide only and 1 to both CBZ and CBZ-epoxide. None of the 39 controls displayed any reactions to either CBZ or CBZ-epoxide. Patch testing of suspected drugs, as well as their available metabolites, would be helpful in improving the results.     

Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian women with breast cancer

The frequency of BRCA1 and BRCA2 mutations in women with breast cancer varies according to the age at diagnosis, family history of cancer, and ethnicity/country of origin. We set out to estimate the frequency of seven previously described founder mutations in BRCA1 and BRCA2 in all eligible French Canadian women diagnosed with invasive breast cancer at one Montreal hospital over a 20-month period. One hundred and ninety-two patients were eligible and 127 (66.2%) provided blood for genetic testing. We identified 4 women who carried a founder mutation (3.1%, 95% confidence interval 0.9-7.9%) in this population. Interestingly, all the mutations were in BRCA2. The mean age at diagnosis for mutation carriers was 51.2 years (range 49.1-53.5). Two of these 4 cases were lobular invasive carcinomas and 2 were ductal carcinomas, histological grade 1 or 2. Despite a small tumor size (< or =20 mm), axillary nodal involvement was present in 3 women. Estrogen receptors were strongly expressed in all cases. Two of the 4 cases reported a strong family history of breast cancer, but a family history of site-specific breast cancer was a relatively poor indicator of the presence of BRCA2 mutations. The absence of BRCA1 mutations may be a result of chance, but may also reflect different geographical origins of the most common BRCA1 mutations within the French Canadian population.     

卡托普利对大鼠t-PA和PAI-1活性的作用

目的评价卡托普利对大鼠血浆t-PA和PAI-1活性水平的影响。方法给大鼠应用三种剂量的卡托普利,观察其对大鼠血浆t-PA和PAI-1活性水平的作用。结果卡托普利治疗后使大鼠血浆t-PA活性升高,PAI-1活性及PAI-1/t-PA活性比值显著降低,这种作用呈某种程度的剂量依赖性。结论卡托普利能增强大鼠纤溶系统的活性,这种作用呈某种程度的剂量依赖性。     

Validation of a predictive model for asthma admission in children: how accurate is it for predicting admissions?

We studied 364 index presentations to the Emergency Department of a children's hospital with a diagnosis of asthma. The admission rate for this group of children was about 31%. We developed a parsimonious multiple logistic regression model to predict asthma hospital admission based on asthma severity indicators. We then evaluated the model's predictive ability using two methods of cross-validation, using the same sample that was used for the predictive model, and using data from a split sample. The logistic regression model had a predictive accuracy of 90% (95% confidence interval 85–95%). The sensitivity and specificity were 86% and 88%, respectively. Cross-validation models confirmed that the predictive ability of the model was stable. In studies with limited sample sizes, it is possible to validate a model without setting aside a split sample for cross-validation.