Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Metabolomics and cancer preventive behaviors in the BC Generations Project.

Metabolomics can detect metabolic shifts resulting from lifestyle behaviors and may provide insight on the relevance of changes to carcinogenesis. We used non-targeted nuclear magnetic resonance to examine associations between metabolic measures and cancer preventive behaviors in 1319 participants (50% male, mean age 54 years) from the BC Generations Project. Behaviors were dichotomized: BMI < 25 kg/m2, ≥ 5 servings of fruits or vegetables/day, ≤ 2 alcoholic drinks/day for men or 1 drink/day for women and ≥ 30 min of moderate or vigorous physical activity/day. Linear regression was used to estimate coefficients and 95% confidence intervals with a false discovery rate (FDR) of 0.10. Of the 218 metabolic measures, 173, 103, 71 and 6 were associated with BMI, fruits and vegetables, alcohol consumption and physical activity. Notable findings included negative associations between glycoprotein acetyls, an inflammation-related metabolite with lower BMI and greater fruit and vegetable consumption, a positive association between polyunsaturated fatty acids and fruit and vegetable consumption and positive associations between high-density lipoprotein subclasses with lower BMI. These findings provide insight into metabolic alterations in the context of cancer prevention and the diverse biological pathways they are involved in. In particular, behaviors related to BMI, fruit and vegetable and alcohol consumption had a large metabolic impact.

Utilization of bone mineral density testing among breast cancer survivors in British Columbia, Canada.

Breast cancer survivors are at high osteoporosis risk. Bone mineral density testing plays a key role in osteoporosis management. We analyzed a historical utilization of bone mineral density testing in breast cancer survivors. The utilization remained low in the 1995-2008 period. Lower socio-economic status and rural residency were associated with lower utilization. INTRODUCTION: To evaluate the utilization of bone mineral density (BMD) testing for female breast cancer survivors aged 65+ surviving ≥ 3 years in British Columbia, Canada. METHODS: A retrospecitve population-based data linkage study. Trends in proportion of survivors with ≥ 1 BMD test for each calendar year from 1995 to 2008 were evaluated with a serial cross-sectional analysis. Associations between factors (socio-demographic and clinical) and BMD testing rates over the period 2006-2008 for 7625 survivors were evaluated with a cross-sectional analysis and estimated as adjusted prevalence ratios (PRadj) using log-binomial models. RESULTS: Proportions of survivors with ≥ 1 BMD test increased from 1.0% in 1995 to 10.1% in 2008. The BMD testing rate in 2006-2008 was 26.5%. Socio-economic status (SES) and urban/rural residence were associated with BMD testing rates in a dose-dependent relationship (p for trend< 0.01). Survivors with lower SES (PRadj = 0.66-0.78) or rural residence (PRadj = 0.70) were 20-30% less likely to have BMD tests, compared with survivors with the highest SES or urban residence. BMD testing rates were also negatively associated with older age (75+) (PRadj = 0.47; 95% CI = 0.42, 0.52), nursing home residency (0.05; 0.01, 0.39), recent osteoporotic fractures (0.21; 0.14, 0.32), and no previous BMD tests (0.26; 0.23, 0.29). CONCLUSION: Utilization of BMD testing was low for breast cancer survivors in BC, Canada. Lower SES and rural residence were associated with lower BMD testing rates. IMPLICATION FOR CANCER SURVIVORS: Female breast cancer survivors, especially those with lower SES or rural residence, should be encouraged to receive BMD tests as recommended by Canadian guidelines.

Fluid intake and hydration status in obese vs normal weight children.

BACKGROUND/OBJECTIVES: Little is known on the relationship between obesity and hydration levels in children. This study assessed whether and by which mechanisms hydration status differs between obese and non-obese children. SUBJECTS/METHODS: Hydration levels of 86 obese and 89 normal weight children (age: 7-11 years) were compared. Hydration was measured as the average free water reserve (FWR=urine output/24 h minus the obligatory urine output [total 24 h excreted solutes/97th percentile of urine osmolality of children with adequate water intake, that is, 830 mOsm/kg]) over 2 days. Three days of weighed dietary and fluid intakes were recorded. Non-parametric tests were used to compare variables that were skewed and to assess which variables correlated with hydration. Variables mediating the different hydration levels of obese and normal weight children were assessed by co-variance analysis. RESULTS: Obese children were less hydrated than normal weight peers [FWR=median (IQR): 0.80 (-0.80-2.80) hg/day vs 2.10 (0.10-4.45) hg/day, P<0.02; 32% of obese children vs 20% of non-obese peers had negative FWR, P<0.001]. Body mass index (BMI) z-score (z-BMI) and water intake from fluids correlated with FWR (ρ=-0.18 and 0.45, respectively, both P<0.05). Water intake from fluids completely explained the different hydration between obese and normal weight children [FWR adjusted for water from fluids and z-BMI=2.44 (0.44) hg vs 2.10 (0.50) hg, P=NS; B coefficient of co-variation between FWR (hg/day) and water intake from fluids (hg/day)=0.47, P<0.001]. CONCLUSIONS: Obese children were less hydrated than normal weight ones because, taking into account their z-BMI, they drank less. Future prospective studies are needed to explore possible causal relationships between hydration and obesity.

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph).

BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of InterLymph case-control studies.

BACKGROUND: Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. DESIGN: Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. RESULTS: Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69-0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54-0.80) and FL (pooled OR = 0.82, 95% CI 0.66-1.01). CONCLUSION: Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL.

Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case-control studies.

BACKGROUND: The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. MATERIALS AND METHODS: Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. RESULTS: Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled OR(trend) = 0.88, 95% CI 0.81-0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04-1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65-1.16). CONCLUSIONS: Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.

From expert-based to quantitative retrospective exposure assessment at a Soderberg aluminum smelter.

OBJECTIVES: Expert judgement of exposure levels is often only poorly or moderately correlated with directly measured levels. For a follow-up of a historical cohort study at a Söderberg aluminum smelter we updated an expert-based semiquantitative job exposure matrix of coal tar pitch volatiles (CTPV) to quantitative estimates of CTPV and benzo(a)pyrene (BaP). METHODS: Mixed effects models to predict exposure for potroom operation and maintenance jobs were constructed from personal CTPV and BaP measurements. Mean exposures of jobs in non-potroom locations were directly calculated when measurements were available. Exposure estimates for jobs/time periods with no measurements were based on proportion of time spent in exposed areas compared to jobs where exposure was modeled or measured. For pre-1977, the original expert exposure assignments were calibrated using the updated 1977 estimates. RESULTS: The rate of change in exposure levels varied by time period and was accounted for in mixed models with a linear spline time trend. Other variables significant in the models were job, potroom group and season as fixed effects, and worker as a random effect. The models for potroom operations explained 45 and 27% of the variability in the CTPV and BaP measurements, respectively. The models for maintenance jobs explained 40 and 19% of the variability in the CTPV and BaP measurements, respectively. For 1977-2000 model estimates, direct calculation of means and extrapolation from modeled/measured exposures accounted for 57, 6 and 37% of the exposed person-years, respectively. CONCLUSIONS: The above methodology maximized the use of exposure measurements and largely replaced the original expert-based estimates. Finer discrimination between exposure levels was possible with the updated exposure assessment. The new estimates are expected to reduce exposure misclassification and help better assess the exposure-response relationships.

Validation of a semi-quantitative job exposure matrix at a Söderberg aluminum smelter.

OBJECTIVES: We tested the validity of a job exposure matrix (JEM) for coal tar pitch volatiles (CTPV) at a Söderberg aluminum smelter. The JEM had been developed by a committee of company hygienists and union representatives for an earlier study of cancer incidence and mortality. Our aim was to test the validity and reliability of the expert-based assignments. METHODS: Personal CTPV exposure measurements (n = 1879) overlapped 11 yr of the JEM. The arithmetic mean was calculated for 35 job/time period combinations (35% of the exposed work history), categorized using the original exposure intervals, and compared with the expert-based assignments. RESULTS: The expert-based and the measurement-based exposure assignments were only moderately correlated (Spearman's rho = 0.42; weighted kappa = 0.39, CI 0.10-0.69). Only 40% of the expert-based medium category assignments were correctly assigned, with better agreement in the low (84%) and high (100%) categories. Pot operation jobs exhibited better agreement (rho = 0.60) than the maintenance and pot shell repair jobs (rho = 0.25). The mid-point value of the medium category was overestimated by 0.3 mg/m(3). CONCLUSIONS: The expert-based exposure assignments may be improved by better characterizing the transitions between exposure categories, by accounting for exposure differences between pot lines and by re-examining the category mid-point values used in calculating the cumulative exposure. Lack of historical exposure measurements often requires reliance on expert knowledge to assess exposure levels. Validating the experts' estimates against available exposure measurements may help to identify weaknesses in the exposure assessment where improvements may be possible, as was shown here.

Canadian male farm residents, pesticide safety handling practices, exposure to animals and non-Hodgkin's lymphoma (NHL).

BACKGROUND: A majority of published studies indicate that farmers have an elevated risk of developing non-Hodgkin's lymphoma (NHL) compared to other workers. METHODS: We evaluated accidental exposure to pesticides, the use of personal protective equipment, and exposure to animals among male farm residents in a Canadian population-based, multi-centre, NHL-control questionnaire study. RESULTS: In a multivariate model, the following variables had statistically significant adjusted odds ratios (OR) using 95% confidence intervals (95% CI) (a) higher risk: having more than 13 head of swine, raising bison, elk or ostriches, a personal history of cancer, > 4 and < or = 15 years of farm residence and occupational exposure to diesel fuel and exhaust; (b) lower risk: raising cattle and a personal history of measles. CONCLUSIONS: Future multidisciplinary studies of NHL should include a comprehensive review of exposure to animals in sufficient detail to assess etiological mechanisms to explain the putative associations between exposure to farm animals and NHL.

Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances.

OBJECTIVES: We sought to investigate the impact of six months of cardiac resynchronization therapy (CRT) on echocardiographic variables of left ventricular (LV) function. BACKGROUND: Cardiac resynchronization therapy has recently been introduced as a new therapeutic modality in patients with advanced heart failure (HF) and conduction abnormalities. However, most studies have only investigated the early hemodynamic effects of CRT. METHODS: Twenty-five patients (12 women and 13 men; 59.8 +/- 5.1 years old) with advanced HF caused by ischemic (n = 7) or idiopathic dilated cardiomyopathy (n = 18) and a prolonged QRS complex were analyzed. All patients underwent early hemodynamic testing with a randomized testing protocol; echocardiographic measurements were compared before implantation and after six months of CRT. RESULTS: Left ventricular end-diastolic and end-systolic diameters (LVEDD and LVESD, respectively) were significantly reduced after six months (LVEDD from 71 +/- 10 to 68 +/- 11 mm, p = 0.027; LVESD from 63 +/- 11 to 58 +/- 11 mm, p = 0.007), as were LV end-diastolic and end-systolic volumes (LVEDV from 253 +/- 83 to 227 +/- 112 ml, p = 0.017; LVESV from 202 +/- 79 to 174 +/- 101 ml, p = 0.009). Ejection fraction was significantly increased (from 22 +/- 7% to 26 +/- 9%, p = 0.03). "Nonresponders," with regard to LV volume reduction, had significantly higher baseline LVEDV, compared with "responders" (351 +/- 52 vs. 234 +/- 74 ml, p = 0.018). Overall, there was only mild mitral regurgitation at baseline, with a minor reduction by semiquantitative analysis. The results of early hemodynamic testing did not predict the volume response. CONCLUSIONS: Cardiac resynchronization therapy may lead to a reduction in LV volumes in patients with advanced HF and conduction disturbances. Volume nonresponders have significantly higher baseline LVEDV.

Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves systolic function in heart failure patients with ventricular conduction delay by stimulating the left ventricle (LV) or both ventricles (biventricular, BV). Optimal LV site selection is of major clinical interest for CRT device implantation; however, the dependence of hemodynamics on LV stimulation site has not been established. Thus, the objective of this study was to compare the hemodynamic response to CRT for 2 LV coronary vein sites: the free wall and anterior wall. Methods and Results- A total of 30 patients (mean NYHA class, 2.7; mean QRS interval, 152 ms; mean PR interval, 194 ms) enrolled in the PATH-CHF-II trial were studied. CRT was administered with LV and BV stimulation in VDD mode at 4 AV delays. LV stimulation was at the lateral free wall or anterior wall, whereas right ventricular stimulation was fixed near the apex. LV+dP/dt(max) and aortic pulse pressure changes from baseline during CRT were compared for LV sites. Free wall sites with LV and BV stimulation yielded significantly larger LV+dP/dt(max) (14% versus 6%, P<0.001 for LV; 12% versus 5%, P<0.001 for BV) and pulse pressure (8% versus 4%, P<0.001 for LV; 9% versus 5%, P<0.001 for BV) compared with anterior sites. In one third of patients, CRT at free wall sites increased LV+dP/dt(max), whereas it decreased at anterior sites over most AV delays. CONCLUSION: CRT with LV free wall stimulation produced significantly better LV systolic performance compared with anterior stimulation. Further studies are warranted to prove the clinical superiority of the LV free wall as a site for long-term CRT.

Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health.

Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% CI, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40-2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49-3.29) and to aldrin (OR, 3.42; 95% CI, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.

HER-2/neu in breast cancer: interobserver variability and performance of immunohistochemistry with 4 antibodies compared with fluorescent in situ hybridization.

The immunohistochemistry (IHC) performance of 4 anti-HER-2/neu antibodies was compared with fluorescent in situ hybridization (FISH) analysis of HER-2/neu gene expression in breast cancer patients considered for Herceptin (Trastuzumab) therapy. Interobserver variability in IHC interpretation was measured. Formalin-fixed tissue was received from 24 provincial hospital laboratories. The following anti-Her-2 antibodies were used: DAKO A0485 (polyclonal), Novacastra CB11 (monoclonal), Zymed TAB250 (monoclonal), and DAKO HercepTest (polyclonal). Additional sections were analyzed by FISH (Vysis). Three pathologists blinded to FISH results independently interpreted invasive tumor cell membranous staining on a scale of 0 to +3. The HER-2/neu gene was considered amplified when the FISH signal ratio of HER-2/CEP-17 was > or =2.0. Blocks from all hospitals and of all ages were suitable for IHC and FISH analysis. No interlaboratory analysis variability was noted. The interobserver agreement (kappa) for stain intensity for each antibody was good for 0 and +3 but poor for +1 and +2. Reasonable concordance between IHC and FISH was found with three of the four antibodies. TAB250 was the most sensitive antibody. For the three pathologists, the IHC sensitivities and specificities compared with FISH using 0/+1 as negative and +2/+3 as positive were as follows: A0485, 63-84/95-98; CB11, 63-66/97-98; TAB-250, 82-100/94-95; HercepTest, 59-77/91-93. The positive and negative predictive values varied by stain intensity. Stain scores of 0 and +3 were highly predictive of gene status. Stain scores of +1 and +2 were not sufficiently predictive to classify cases as amplified versus nonamplified. IHC is a reasonable first test to assess HER-2/neu status in patients with breast cancer. For most cases, DAKO A0485, TAB250, and HercepTest adequately predicted gene status. In cases with stain intensity of +1 or +2, the interobserver agreement is poor, and the predictive value is unsatisfactory for clinical use. Additional testing, preferably with FISH, is recommended.

Parity and carotid artery atherosclerosis in elderly women: The Rotterdam Study.

BACKGROUND AND PURPOSE: It has been postulated that physiological changes in the cardiovascular system, lipids, and glucose metabolism during pregnancy may increase subsequent risk of cardiovascular disease. Examination of the association between parity and risk factors for atherosclerosis may contribute information regarding possible mechanisms. METHODS: The relationship of parity with cardiovascular risk factors and the presence of carotid atherosclerosis was examined in the Rotterdam Study, a population-based study comprising 4878 women aged 55 years and older. Carotid atherosclerosis was assessed by ultrasonographic detection of plaques in the common carotid artery and bifurcation. Logistic regression models were used to compute odds ratios and 95% confidence intervals, adjusted for confounding factors. RESULTS: Parity was inversely associated with high-density lipoprotein cholesterol, and alcohol intake. Parity was positively associated with body mass index, total/HDL cholesterol ratio, insulin resistance, age at menopause, and socioeconomic status. Relative to nulliparous women, parous women had 36% (9% to 71%) greater risk of carotid atherosclerosis, rising to 64% in women with >/=4 children (19% to 127%). Adjustment for known cardiovascular risk factors, including insulin resistance and current lipid levels, did not diminish the magnitude of this association. CONCLUSIONS: Data demonstrated that there is a positive association between parity and risk of carotid artery plaques in elderly women and, further, that high parity is associated with lower HDL cholesterol levels and higher glucose/insulin ratios long after childbearing has ceased.

Simultaneous modelling of operative mortality and long-term survival after coronary artery bypass surgery.

Typical analyses of lifetime data treat the time to death or failure as the response variable and use a variety of modelling strategies such as proportional hazards or fully parametric, to investigate the relationship between the response and covariates. In certain circumstances it may be more natural to view the distribution of the response variable as consisting of two or more parts since the survival curve appears segmented. This article addresses such a scenario and we propose a model for simultaneously investigating the effects of covariates over the two segments. The model is an analogue of that proposed by Lambert for zero-inflated Poisson regression. The application is central to the model development and is concerned with survival after coronary artery bypass surgery. Here operative mortality, defined as death within 30 days after surgery, and long-term mortality, are viewed as distinct outcomes. For the application considered, the survivor function displays much steeper descent during the first 30 days after surgery, that is, for operative mortality, than after this period. An investigation of the effects of covariates on operative and long-term mortality after coronary artery bypass surgery illustrates the usefulness of the proposed model.

Underutilization of acute care settings in a tertiary care hospital.

OBJECTIVE: To estimate underutilization of acute care settings in a tertiary care hospital. DESIGN: A retrospective and concurrent cohort study using chart reviews and the Intensity of service, Severity of illness, Discharge screen for Acute Care (ISD-AC(R)) tool to measure appropriateness of acute care for patients who were receiving care in a less acute setting, as an indicator of underutilization. SETTING: A 450-bed tertiary care teaching hospital. STUDY PARTICIPANTS: Patients discharged from the emergency department, patients discharged from acute care inpatient units and patients in acute, non-critical care settings. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The percentage of patients discharged from the emergency department who did not meet the criteria for acute care discharge screens; the percentage of patients discharged from an acute care inpatient unit who did not meet the criteria for discharge screens; and the percentage of patients who were in acute, non-critical care beds and who met the criteria for critical care. RESULTS: It was found that six out of 168 patients [3.57%; 95% confidence interval (CI), 1.32-7.61%] did not meet the discharge screens at the time of discharge from the emergency department. Four out of 156 patients (2.56%; 95% CI, 0.70-6.43%) did not meet the discharge screens at the time of discharge from an acute care inpatient service and two out of 156 acute care patients (1.33%; 95% CI, 0.02-4.73%) who were in non-critical care beds met the criteria for critical care. CONCLUSION: These findings of underutilization may help to quantitate an unmet need in health care.

Double trouble: impact of inappropriate use of asthma medication on the use of health care resources.

BACKGROUND: There is considerable controversy about the regular use of short-acting beta-agonists for the treatment of asthma. Although case-control studies have suggested that excessive use of these drugs may worsen asthma control and increase the risk of fatal or near-fatal asthma, the controversy remains unresolved because of the confounding that exists among disease control, disease severity and the use of short-acting beta-agonists. Whatever the cause-and-effect relation between the use of short-acting beta-agonists and disease severity, we hypothesized that their excessive use, in conjunction with underuse of inhaled corticosteroids, would be a marker for poorly controlled asthma and excessive use of health care resources. METHODS: To characterize the pattern of health services utilization among asthmatic patients taking various doses of inhaled beta-agonists and corticosteroids in British Columbia, we linked the relevant health administrative databases. All patients between 5 and 50 years of age for whom a prescription for a short-acting beta-agonist was filled in 1995 and whose prescription data were captured through the provincial drug plan were included in a retrospective analysis of prescriptions for asthma drugs, physician prescribing patterns and health services utilization. Patients' use of asthma medication was classified as appropriate (low doses of short-acting beta-agonist and high doses of inhaled corticosteroid) or inappropriate (high doses of short-acting beta-agonist and low doses of inhaled corticosteroid), and the 2 resulting groups were compared, by means of logistic, Poisson and gamma regression, for differences in prescribing patterns, physician visits and use of hospital resources. RESULTS: A total of 23,986 patients were identified as having filled a prescription for a short-acting beta-agonist (for inhalation) in 1995. Of these, 3069 (12.8%) filled prescriptions for 9 or more canisters of beta-agonist, and of this group of high-dose beta-agonist users, 763 (24.9%) used no more than 100 micrograms/day of inhaled beclomethasone. On average, those with inappropriate use of beta-agonists visited significantly more physicians for their prescriptions (1.8 v. 1.4), and each of these physicians on average wrote significantly more prescriptions for asthma medications per patient than the physicians who prescribed to appropriate users (5.2 v. 2.5 prescriptions). Patients with inappropriate use were more likely to be admitted to hospital (adjusted relative risk [RR] 1.68, 95% confidence interval [CI] 1.25-2.26), were admitted to hospital more frequently (adjusted RR 1.81, 95% CI 1.41-2.32) and were more likely to require emergency admission (adjusted RR 1.93, 95% CI 1.35-2.77). INTERPRETATION: Despite the widespread distribution of guidelines for asthma pharmacotherapy, inappropriate use of asthma medications persists (specifically excessive use of inhaled short-acting beta-agonists combined with underuse of inhaled corticosteroids). Not only are patients who use medication inappropriately at higher risk for fatal or near-fatal asthma attacks, but, as shown in this study, they use significantly more health care resources than patients with appropriate medication use.

Value of ST elevation in lead III greater than lead II in inferior wall acute myocardial infarction for predicting in-hospital mortality and diagnosing right ventricular infarction.

ST elevation in lead III > II has a higher sensitivity than lead V4R in diagnosing right ventricular myocardial infarction. Lead III > II is also predictive of in-hospital mortality.