1,3-Butadiene has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to 1,3-butadiene primarily through ambient air. Inhaled 1,3-butadiene is carcinogenic in both mice and rats, inducing tumors at multiple sites at all concentrations tested in all identified studies. In addition, 1,3-butadiene is genotoxic in both somatic and germ cells of rodents. It also induces adverse effects in the reproductive organs of female mice at relatively low concentrations. The greater sensitivity in mice than in rats to induction of these effects by 1,3-butadiene is likely related to species differences in metabolism to active epoxide metabolites. Exposure to 1,3-butadiene in the occupational environment has been associated with the induction of leukemia; there is also some limited evidence that 1,3-butadiene is genotoxic in exposed workers. Therefore, in view of the weight of evidence of available epidemiological and toxicological data, 1,3-butadiene is considered highly likely to be carcinogenic, and likely to be genotoxic, in humans. Estimates of the potency of butadiene to induce cancer have been derived on the basis of both epidemiological investigation and bioassays in mice and rats. Potencies to induce ovarian effects have been estimated on the basis of studies in mice. Uncertainties have been delineated, and, while there are clear species differences in metabolism, estimates of potency to induce effects are considered justifiably conservative in view of the likely variability in metabolism across the population related to genetic polymorphism for enzymes for the critical metabolic pathway.
This quality assurance project was designed to determine the reliability, completeness and comprehensiveness of the data entered into Niday Perinatal Database.
Quality of the data was measured by comparing data re-abstracted from the patient record to the original data entered into the Niday Perinatal Database. A representative sample of hospitals in Ontario was selected and a random sample of 100 linked mother and newborn charts were audited for each site. A subset of 33 variables (representing 96 data fields) from the Niday dataset was chosen for re-abstraction.
Of the data fields for which Cohen's kappa statistic or intraclass correlation coefficient (ICC) was calculated, 44% showed substantial or almost perfect agreement (beyond chance). However, about 17% showed less than 95% agreement and a kappa or ICC value of less than 60% indicating only slight, fair or moderate agreement (beyond chance).
Recommendations to improve the quality of these data fields are presented.
It has been proposed that type 1 and 2 diabetes might share common pathophysiological pathways and, to some extent, genetic background. However, to date there has been no convincing data to establish a molecular genetic link between them. We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly972Arg in the insulin receptor substrate 1 (IRS1) gene, Glu23Lys in the potassium inwardly-rectifying channel gene (KCNJ11), and Pro12Ala in the peroxisome proliferative-activated receptor gamma2 gene (PPARG2). We were unable to confirm a recently published association of the IRS1 Gly972Arg variant with type 1 diabetes. Moreover, KCNJ11 Glu23Lys showed no association with type 1 diabetes (P > 0.05). However, the PPARG2 Pro12Ala variant showed evidence of association (RR 1.15, 95% CI 1.04-1.28, P = 0.008). Additional studies need to be conducted to confirm this result.
Juvenile Diabetes Research Foundation/Wellcome Trust DiabetesInflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, WT/MRC building, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK. email@example.com
Vitamin D is known to modulate the immune system, and its administration has been associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been commonly studied, and evidence of association with type 1 diabetes has been reported previously. We sequenced the VDR gene region and developed its SNP map. Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with two affected offspring. We further tested eight SNPs, including four SNPs associated with P
To describe the Computerized Obstetrics and Gynecology Automated Learning Anaalysis (KOALAtrade mark), a multicentre, Internet-based learning portfolio and to determine its effects on residents' perception of their self-directed learning abilities.
The KOALA programme allows residents to record their obstetrical, surgical, ultrasound, and ambulatory patient encounters and to document critical incidents of learning or elements of surprise that arose during these encounters. By prompting the student to reflect on these learning experiences, KOALA encourages residents to articulate questions which can be directly pursued through hypertext links to evidence-based literature. Four Canadian residency training programmes participated in the pilot project, from February to May 1997, using a dynamic relational database with a central server. All participants completed the Self-directed Learning Readiness Scale and a learning habits questionnaire. The impact of the KOALA programme on residents' perception of their self-directed learning abilities was measured by comparing KOALA-naive schools (schools 2, 3, and 4) with school 1 (exposed to the KOALA prototype for 1 year). Ordered variables were compared using the Mann-Whitney U test and continuous variables with the Student t test (statistical significance P
The use of appetite suppressants in Europe has been associated with the development of primary pulmonary hypertension (PPH). Recently, fenfluramine appetite suppressants became widely used in the United States but were withdrawn in September 1997 because of concerns over adverse effects.
We conducted a prospective surveillance study on patients diagnosed with pulmonary hypertension at 12 large referral centers in North America. Data collected on patients seen from September 1, 1996, to December 31, 1997, included the cause of the pulmonary hypertension and its severity. Patients with no identifiable cause of pulmonary hypertension were classed as PPH. A history of drug exposure also was taken with special attention on the use of antidepressants, anorexigens, and amphetamines.
Five hundred seventy-nine patients were studied, 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension [SPH]). The use of anorexigens was common in both groups. However, of the medications surveyed, only the fenfluramines had a significant preferential association with PPH as compared with SPH (adjusted odds ratio for use > 6 months, 7.5; 95% confidence interval, 1.7 to 32.4). The association was stronger with longer duration of use when compared to shorter duration of use and was more pronounced in recent users than in remote users. An unexpectedly high (11.4%) number of patients with SPH had used anorexigens.
The magnitude of the association with PPH, the increase of association with increasing duration of use, and the specificity for fenfluramines are consistent with previous studies indicating that fenfluramines are causally related to PPH. The high prevalence of anorexigen use in patients with SPH also raises the possibility that these drugs precipitate pulmonary hypertension in patients with underlying conditions associated with SPH.
A cluster of four cases of surgical and burn wound aspergillosis occurred in a 900-bed, adult, tertiary-care hospital. The source was traced to the outside packages of dressing supplies, which had become contaminated during construction in the central Inventory Control area. This resulted in patients with large exposed surface areas being inoculated directly with Aspergillus spores.
Increasing numbers of health care users may be confronted with new genetic knowledge and discoveries that offer new types of medical decision-making. How people use these new insights and make decisions about genetic risk depends, at least in part, on their knowledge and attitudes about human genetics.
A postal survey administered to 560 women who had been offered prenatal screening in Ontario measured knowledge about, and attitudes toward, genetic testing and the uses of genetic information.
Respondents strongly supported the use of genetic information to improve disease diagnosis and to help understand disease causes; however, people also held a more critical attitude towards certain aspects of testing and genetic information. Relatively high levels of knowledge about genetics were also observed in this sample, although there were deficits in specific areas (e.g., transmission patterns).
Despite overall positive attitudes towards genetics, participants held more critical attitudes towards certain aspects of testing and the uses of genetic information. It would be unwise for genetics policy-makers and stakeholders to assume that a better-informed public would automatically be more supportive of all genetics research and new genetic discoveries.
To explore intention to breastfeed and breastfeeding rates in hospital and on discharge across women with pre-gestational or gestational diabetes mellitus, or no diabetes.
A retrospective cohort analysis was conducted using data from four Ontario hospitals. Women who delivered a viable infant between 1 April 2008 and 31 March 2010 were included in the study. Unadjusted and adjusted odds ratios were calculated for each outcome measure and were used to compare the breastfeeding rates among women with and without diabetes.
After controlling for potential confounders, women with insulin-treated diabetes were less likely to intend to breastfeed, when compared with women without diabetes (adjusted odds ratio 0.49, 95% CI 0.27-0.89). In hospital, women with insulin-treated diabetes were least likely to breastfeed (odds ratio 0.42, 95% CI 0.26-0.67), followed by women with non-insulin-treated diabetes (odds ratio 0.50, 95% CI 0.26-0.96) and women with gestational diabetes (odds ratio 0.77, 95% CI 0.68-0.87) when compared with women without diabetes. On discharge, women with insulin-treated diabetes were least likely to breastfeed (odds ratio 0.38, 95% CI 0.24-0.60), followed by women with gestational diabetes (odds ratio 0.75, 95% CI 0.66-0.85); rates of breastfeeding among women with non-insulin-treated diabetes were comparable on discharge with those of women without diabetes. Women seeking care from an antenatal provider other than a physician were 2-3 times more likely to breastfeed in hospital and on discharge.
Women with insulin-treated diabetes had the poorest outcomes with respect to breastfeeding rates. Gestational and non-insulin-treated diabetes were associated with lower rates of breastfeeding in hospital, while gestational diabetes was additionally associated with lower breastfeeding rates on discharge.