Relationship between systolic blood pressure and mortality in older vs younger trauma patients - a retrospective multicentre observational study.

BACKGROUND: The population of older trauma patients is increasing. Those patients have heterogeneous presentations and need senior-friendly triaging tools. Systolic blood pressure (SBP) is commonly used to assess injury severity, and some authors advocated adjusting SBP threshold for older patients. We aimed to describe and compare the relationship between mortality and SBP in older trauma patients and their younger counterparts. METHODS: We included patients admitted to three level-I trauma centres and performed logistic regressions with age and SBP to obtain mortality curves. Multivariable Logistic regressions were performed to measure the association between age and mortality at different SBP ranges. Subgroup analyses were conducted for major trauma and severe traumatic brain injury admissions. RESULTS: A total of 47,661 patients were included, among which 12.9% were aged 65-74 years and 27.3% were ≥ 75 years. Overall mortality rates were 3.9%, 8.1%, and 11.7% in the groups aged 16-64, 65-74, and ≥ 75 years, respectively. The relationship between prehospital SBP and mortality was nonlinear (U-shape), mortality increased with each 10 mmHg SBP decrement from 130 to 50 mmHg and each 10-mmHg increment from 150 to 220 mmHg across all age groups. Older patients were at higher odd for mortality in all ranges of SBP. The highest OR in patients aged 65-74 years was 3.67 [95% CI: 2.08-6.45] in the 90-99 mmHg SBP range and 7.92 [95% CI: 5.13-12.23] for those aged ≥ 75 years in the 100-109 mmHg SBP range. CONCLUSION: The relationship between SBP and mortality is nonlinear, regardless of trauma severity and age. Older age was associated with a higher odd of mortality at all SBP points. Future triage tools should therefore consider SBP as a continuous rather than a dichotomized predictor.

Technical note: Extrapolation of hepatic glycogen concentration of the whole organ by performing a liver biopsy.

Glycogen, a complex polysaccharide, is the form of storage of glucose in mammals that can be released rapidly when needed. Recent studies have mainly reported hepatic glycogen concentration for early-lactating cows, when the energy demand is higher than the energy supply from dry matter intake, driving the cow to use the energy stored as hepatic glycogen. Generally, liver samples are obtained through percutaneous needle biopsies in the right lobe of the liver. Our objective was to analyze the variation of glycogen concentration in the livers of Holstein and Jersey cows among different liver locations representing all lobes, to evaluate whether samples obtained by liver biopsies are representative of the whole organ. Liver from 10 culled lactating cows (5 Holstein and 5 Jersey cows) from 30 to 113 mo of age at slaughter were obtained. Each liver was sampled no more than 3 h after death on the following sites: 3 sites in the right lobe (1 to 3), 2 in the diaphragmatic surface of the left lobe (4 and 5), 3 in the visceral surface of the left lobe (6 to 8), 1 in the quadrate lobe (9), and 1 in the caudate lobe (10). Samples were snap frozen in liquid N2 and were then analyzed for glucose concentration after conversion of glycogen to glucose using amyloglucosidase (EC 3.2.1.3). Glycogen results are reported as grams of glucose per 100 g of wet weight of liver (i.e., percent of wet weight of liver). Liver weights averaged 5.1 [standard deviation (SD) 1.2, minimum 3.3, maximum 6.2] kg for Holstein and 6.0 (SD 1.8, minimum 4.7, maximum 8.9) kg for Jersey cows. Holstein cows [1.31, standard error of the mean (SEM) 0.05% of wet weight] had greater liver glycogen concentration than did Jersey cows (0.75, SEM 0.05% of wet weight). No significant difference was noted among the 10 liver locations regarding glycogen concentration and averaged, for both breeds, 1.03% of wet weight (SEM 0.10). These results suggest that, in dairy cows, percutaneous needle liver biopsy in the right lobe is an accurate technique to fairly extrapolate glycogen concentration of the whole organ.

Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study.

OBJECTIVE: The objective was to compare, in a real-world setting, the risk of mental and physical health events associated with different antipsychotic drugs (clozapine, olanzapine, risperidone, quetiapine and first-generation antipsychotics) in patients with SZ. METHODS: This is a retrospective cohort study using administrative data. Outcome measures included any mental health event (suicide, hospitalization or emergency visit for mental disorders) and physical health event (death other than suicide, hospitalization or emergency visit for physical disorders). Cox proportional hazard models were used to estimate the hazard ratios of the events associated with the use of the different antipsychotic drugs. RESULTS: The cohort included 18 869 adult patients living in the province of Quebec (Canada) with SZ and starting antipsychotic drugs between January 1998 and December 2005. Results show that quetiapine and not using any antipsychotics were associated with an increased risk of mental and physical health events as compared to other drugs. The second finding is the confirmation of better performance of clozapine. The results were robust across sensitivity analyses. CONCLUSION: Both findings call for an international public health and drug agencies surveillance of 'real-world' antipsychotic medication to ensure the optimal choices in treatment guidelines for SZ.

Patterns of oral anticoagulants use in atrial fibrillation.

BACKGROUND: Novel oral anticoagulants are available for the management of atrial fibrillation and are considered more convenient to use than warfarin. OBJECTIVE: The main objective of this study was to describe patterns of oral anticoagulant use in the 6 months period following the availability of dabigatran at our hospital. METHODS: A cross-sectional study was conducted in a single University hospital in the province of Québec, Canada. Medical records of subjects on oral anticoagulants for atrial fibrillation that were hospitalized between October 1st, 2011 and March 31th, 2012 were reviewed. Type of use (prevalent, incident and switch) and patient's characteristics of warfarin and dabigatran users were compared using Chi-squared and T-tests. RESULTS: In the 6-month period following dabigatran availability in the hospital, 59 patients (13%) were on dabigatran and 388 (87%) on warfarin. Mean CHADS2 score, mean age and mean number of chronic medications were lower in the dabigatran group. The percentage of patients with coronary artery disease was lower and renal function was higher in the dabigatran group. CONCLUSION: Dabigatran use remained low in the first 6 months period following the approval of dabigatran at our hospital, which could be explained by limited data on the efficacy and safety of this agent in subjects with multiple comorbidities.

Impact of a primary care physician workshop on osteoporosis medical practices.

SUMMARY: Attendance at a fragility-fractures-prevention workshop by primary care physicians was associated with higher rates of osteoporosis screening and treatment initiation in elderly female patients and higher rates of treatment initiation in high-risk male and female patients. However, osteoporosis management remained sub-optimal, particularly in men. INTRODUCTION: Rates of osteoporosis-related medical practices of primary care physicians exposed to a fragility-fractures-prevention workshop were compared with those of unexposed physicians. METHODS: In a cluster cohort study, 26 physicians exposed to a workshop were matched with 260 unexposed physicians by sex and year of graduation. For each physician, rates of bone mineral density (BMD) testing and osteoporosis treatment initiation among his/her elderly patients 1 year following the workshop were computed. Rates were compared using multilevel logistic regression models controlling for potential patient- and physician-level confounders. RESULTS: Twenty-five exposed physicians (1,124 patients) and 209 unexposed physicians (9,663 patients) followed at least one eligible patient. In women, followed by exposed physicians, higher rates of BMD testing [8.5% versus 4.2%, adjusted OR (aOR) = 2.81, 95% CI 1.60-4.94] and treatment initiation with bone-specific drugs (BSDs; 4.8% vs. 2.4%, aOR = 1.95, 1.06-3.60) were observed. In men, no differences were detected. In patients on long-term glucocorticoid therapy or with a previous osteoporotic fracture, higher rates of treatment initiation with BSDs were observed in women (12.0% vs. 1.9%, aOR = 7.38, 1.55-35.26), and men were more likely to initiate calcium/vitamin D (5.3% vs. 0.8%, aOR = 7.14, 1.16-44.06). CONCLUSIONS: Attendance at a primary care physician workshop was associated with higher rates of osteoporosis medical practices for elderly women and high-risk men and women. However, osteoporosis detection and treatment remained sub-optimal, particularly in men.

Better adherence to antihypertensive agents and risk reduction of chronic heart failure.

AIMS: Antihypertensive (AH) agents have been shown to reduce the risk of major cardiovascular events including chronic heart failure (CHF). However, the impact of changes in patterns of AH agents use on CHF is unknown. Our objective was to estimate to which different patterns of AH agent use is associated with the occurrence of CHF in a population-based study. METHOD AND RESULTS: A cohort of 82 320 patients was reconstructed using the Régie de l'assurance maladie du Québec's databases. Patients were eligible if they were between 45 to 85 years of age, had no indication of cardiovascular disease and were newly treated with AH therapy between 1999 and 2004. A nested case-control design was used to study the occurrence of CHF. Every case of CHF was matched for age and duration of follow-up to a maximum of 15 randomly selected controls. Adherence level was reported as a medication possession ratio. Conditional logistic regression models were used to estimate the rate ratio (RR) of CHF adjusting for different covariables. The mean patient age was 65 years, 37% were male, 8% had diabetes, 19% had dyslipidaemia and mean time of follow-up at 2.7 years. High adherence level (95%) to AH therapy compared with lower adherence level (60%) was associated with an additional reduction of CHF events (RR: 0.89; 0.80-0.99). Risk factors for CHF were being on social assistance, diabetes, dyslipidaemia, higher chronic disease score and developing a cardiovascular condition during follow-up. CONCLUSION: Our study suggests that a better adherence is associated with a significant risk reduction of CHF. Adherence to AH therapy needs to be improved to optimize benefits.

Control and severity of asthma during pregnancy are associated with asthma incidence in offspring: two-stage case-control study.

The extent to which childhood asthma incidence is influenced by asthma control and severity during pregnancy is unknown. We have studied this association during the child's first 10 yrs of life. A two-stage, case-control study, nested in a cohort of 8,226 children of asthmatic mothers, was conducted using three interlinked databases of Quebec, Canada, and mailed questionnaires. A total of 2,681 asthmatic children and 30,318 age-matched controls were selected (< or =20 controls.case(-1); stage 1), and 3,254 selected mothers were mailed questionnaires to obtain additional information (stage 2). Asthma control and severity was defined using validated indexes and childhood asthma incidence based on at least one asthma-related diagnosis and prescription received within 2 yrs. A total of 44 confounders were considered. Compared with children of mild controlled asthmatic mothers, children whose mothers had moderate-to-severe uncontrolled asthma during pregnancy had an increased risk of asthma (adjusted OR 1.27, 95% CI 1.06-1.52). No increased risk was observed for children of mild uncontrolled and moderate-to-severe controlled mothers. Based on one of the largest studies of children of asthmatic mothers, a significant increase in asthma risk was demonstrated among children whose mothers had poor control and increased severity of asthma during pregnancy, indicating that this element should be added to the expanding list of determinants of childhood asthma. As it constitutes a risk factor where pregnant asthmatic females can intervene, it is of great importance for physicians to optimally treat asthmatic females during pregnancy and to encourage females to be adherent to the prescribed asthma medications.

Risk of perinatal mortality associated with asthma during pregnancy.

BACKGROUND: Thirteen studies investigating the association between asthma during pregnancy and perinatal mortality reported generally no increased risk. Most of these studies should be interpreted with caution because they were limited in terms of statistical power. A study was therefore undertaken to evaluate whether maternal asthma during pregnancy increases the risk of perinatal mortality. METHODS: Through three administrative databases from Québec (Canada), a cohort of women with and without asthma who had at least one pregnancy between 1990 and 2002 was formed. Perinatal mortality was identified by diagnostic codes. The adjusted odds ratio (OR) of perinatal mortality in women with and without asthma was compared using Generalised Estimation Equation (GEE) models. The first model included all potential confounders (except small for gestational age, SGA), the second model excluded birth weight, gestational age at birth and SGA and the third model excluded birth weight, gestational age at birth but included only SGA. This analysis was also stratified for birth weight and gestational age at birth. RESULTS: The cohort was formed of 13 100 and 28 042 single pregnancies in women with and without asthma. The crude OR of perinatal mortality was 1.35 (95% CI 1.08 to 1.67), which decreased to 0.93 (95% CI 0.75 to 1.17) after adjustment for birth weight and gestational age at birth. Women with asthma had a higher rate of low birthweight babies and preterm delivery than those without asthma. CONCLUSION: The increased risk of low birthweight babies and premature delivery in women with asthma may partly explain the association between maternal asthma and the increased risk of perinatal mortality.

Prevalence and predictors of antidepressant use in a cohort of pregnant women.

OBJECTIVE: (1) To determine the prevalence of antidepressant utilisation before, during, and after pregnancy, (2) to determine switches, dosages, and classes of antidepressant used during pregnancy, and (3) to identify factors associated with their use at the beginning and at the end of pregnancy. DESIGN: Retrospective longitudinal cohort. SETTING: The 'Medication and Pregnancy' cohort was used for this study. This cohort was built by the linkage of three administrative databases (Régie de l'Assurance Maladie du Québec [RAMQ], Med-Echo, and l'Institut de la Statistique du Québec). POPULATION: All pregnancies occuring in Quebec between January 1 1998 and December 31 2002. METHODS: Date of entry in the cohort was the first day of gestation. To be eligible for this study, women had to be (1) 15-45 years old at cohort entry and (2) covered by the RAMQ drug plan for at least 12 months before, during, and at least 12 months after pregnancy. Antidepressant users were defined as those receiving at least one antidepressant before, during, or after pregnancy, depending on the time period analysed. Logistic regression models were used to identify factors associated with receiving an antidepressant either at the beginning or at the end of pregnancy. MAIN OUTCOME MEASURES: To determine the prevalence and predictors associated with the use of antidepressants. RESULTS: A total of 97,680 women met inclusion criteria. The prevalence rates significantly declined during the first trimester compared with before pregnancy (3.7 versus 6.6%, P < 0.01). During pregnancy, antidepressants were used under the recommended daily dosage 7.7% of the time, and 4.7% of women switched to another class of antidepressant. Factors significantly associated with antidepressant utilisation on the first day of gestation (P < 0.05) were older maternal age, being on welfare, and calendar year; receiving at least six different types of medications other than antidepressants, having at least two different prescribers, having at least three visits to the physician, and having at least one diagnosis of depression in the year before pregnancy also increased the odds of having an antidepressant. Similar predictors were found at the end of pregnancy. CONCLUSIONS: Our findings indicate that antidepressant utilisation declines once pregnancy is diagnosed.

Persistence and determinants of statin therapy among middle-aged patients for primary and secondary prevention.

AIMS: Statins have been shown to significantly reduce morbidity and mortality in patients with coronary artery disease (CAD), and also in patients with dyslipidaemia when statins are taken regularly. Middle-aged patients have the highest level of forecasting benefit and little is known about persistence rate of these therapies in a real-life setting. The objective was to evaluate the persistence rate of middle-aged patients initiating a statin therapy and its relation with several determinants for primary and secondary prevention. METHODS: A cohort was reconstructed using the RAMQ databases. All patients aged 50-64 years-old who received at least one statin prescription between 1 January, 1998 and 31 December, 2000 for a new intention of treatment for dyslipidaemia were included in the cohort and followed up until 30 June, 2001. The date of the first prescription of statin was defined as the index date. There were 4316 patients in the secondary prevention (CAD diagnosis) and 13,642 patients in primary prevention cohort. The cumulative persistence rate was estimated using Kaplan-Meier, and Cox regression models were used to estimate the hazard ratio of ceasing statins. RESULTS: We found that persistence with statins had fallen to 71% after 6 months of treatment, and had declined to 45% after 3 years in the secondary prevention cohort; the corresponding figures were 65% and 35% in the primary prevention cohort. Our results suggest that patients with dyslipidaemia in primary prevention compared with those in secondary prevention (HR: 1.18; 1.11-1.25) are less likely to be persistent. Patients with other cardiovascular risk factors such as age (HR: 0.99; 0.98-0.99), diabetes (HR: 0.84; 0.79-0.90), hypertension (HR: 0.76; 0.72-0.80) were most likely to be persistent with statins. We observed lower persistence in patients who have used the greatest number of pharmacies and prescribing physicians. CONCLUSION: This analysis indicates that barriers to persistence occur early in the therapeutic course. Overall persistence with statins is low, and particularly among patients with few other cardiovascular risk factors.

Use of inhaled corticosteroids following discharge from an emergency department for an acute exacerbation of asthma.

BACKGROUND: Most patients who have an asthma exacerbation leading to a visit to an emergency department (ED) will benefit from treatment with inhaled corticosteroids (ICS) at discharge. We investigated whether asthmatic children and adolescents were receiving ICS after discharge from the ED and identified the characteristics of patients and physicians associated with their use. METHODS: A cohort of 4042 asthmatic patients aged 5-17 years was selected from the administrative database of the Regie de l'assurance maladie du Quebec between 1997 and 1999. The proportion of patients using ICS 1, 3, and 6 months after ED discharge was estimated. Using GEE models the independent contribution of sociodemographic variables, markers of asthma severity, prior use of healthcare services and ICS, and physician characteristics was investigated on the likelihood of using ICS after ED discharge. RESULTS: 68% of children and 51% of adolescents had a valid prescription for ICS in the month following discharge. At 6 months after discharge the corresponding figures were 77% and 60%. The strongest predictors of ICS use were age, with adolescents being less likely to use ICS than children (OR 0.49; 95% CI 0.43 to 0.56), prior use of ICS (OR 2.28; 95% CI 2.00 to 2.61), and filling a prescription for oral corticosteroids in the month following discharge (OR 2.29; 95% CI 2.03 to 2.58). However, patients who had an ED visit or a hospital admission for asthma during the 6 months before discharge were not more likely to use ICS after discharge. CONCLUSION: A large proportion of patients with clear markers of uncontrolled or severe asthma did not have a valid prescription for an ICS after discharge from the ED.

Impact of a cost-sharing drug insurance plan on drug utilization among older people.

OBJECTIVES: In August 1996, the Régie de l'assurance-maladie du QuEbec (RAMQ), the government body responsible for medical insurance in the Canadian province of Quebec, introduced a cost-sharing drug insurance plan. Before this plan, individuals age 65 years and older had to pay Canadian (CDN)$2 per prescription, with the remaining cost paid by the RAMQ. With the new plan, beneficiaries may have to pay an amount between CDN$200 and CDN$925 per year, depending on their income. Concerned that this financial constraint imposed on older people might have an impact on the use of medications, we investigated whether the consumption of four classes of medications, antihypertensive agents, anticoagulants, nitrates, and benzodiazepines, was affected by the drug plan implementation. DESIGN: Time series models with pre/post comparison group. SETTING: Administrative computerized databases of the RAMQ. PARTICIPANTS: Random sample of Quebec residents age 65 years and older registered in the provincial drug plan between August 1992 and June 1997: 54,771 users of nitrates, 133,146 users of antihypertensive agents, 45,534 users of anti-coagulants, and 26,165 users of benzodiazepines. MEASUREMENTS: We modeled the monthly consumption of the medications under study between August 1992 and June 1996. Monthly drug consumptions predicted from the models were compared with those observed for the 13 months (August 1996 to August 1997) following the implementation of the new drug plan using 95% confidence intervals. The number of prescriptions dispensed served as an indicator for drug consumption. RESULTS: During the study period we observed a nonstatistically significant decrease in number of prescriptions of 5.1% for nitrates, 1.1% for antihypertensive agents, and 0.8% for benzodiazepines, and a nonstatistically significant increase of 1.6% for anticoagulants. CONCLUSION: Residents of Quebec age 65 years and older were not found to have reduced significantly their consumption of nitrates, antihypertensive agents, anticoagulants, and benzodiazepines during the 13 months that followed the implementation of a cost-sharing drug insurance plan.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of cancer: a nested case-control study.

BACKGROUND: During the past 15 years there has been an exponential increase in the number of prescriptions for lipid-lowering drugs. Uncertainties remain about the long-term impact of these medications on cancer, which is particularly bothersome given that the duration of these treatments may extend for several decades. OBJECTIVE: To explore the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence. METHODS: Using the administrative health databases of the Régie de l'Assurance-Maladie du Québec we performed a nested case-control study. We selected a cohort of 6721 beneficiaries of the health care plan of Quebec who were free of cancer for at least 1 year at cohort entry, 65 years and older, and treated with lipid-modifying agents. Cohort members were selected between 1988 and 1994 and were followed up for a median period of 2.7 years. From the cohort, 542 cases of first malignant neoplasm were identified, and 5420 controls were randomly selected. Users of HMG-CoA reductase inhibitors were compared with users of bile acid-binding resins as to their risk of cancer. Specific cancer sites were also considered. RESULTS: Users of HMG-CoA reductase inhibitors were found to be 28% less likely than users of bile acid-binding resins to be diagnosed as having any cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific cancer sites under study were found to be not or inversely associated with the use of HMG-CoA reductase inhibitors. CONCLUSION: The results of our study provide some degree of reassurance about the safety of HMG-CoA reductase inhibitors.

Inhaled corticosteroids and the prevention of readmission to hospital for asthma.

Despite the proven efficacy of inhaled corticosteroids in reducing airway inflammation and their increasing use for the treatment of asthma since the mid 1980s, hospitalization for asthma has been increasing in frequency in several countries. Only few studies, reporting contradictory results, have investigated the role of inhaled corticosteroids in the prevention of hospitalizations for asthma. Using a cohort of 2,059 hospitalized asthmatic patients between 5 and 54 yr of age, we estimated the effectiveness of inhaled corticosteroids in preventing a readmission to hospital for asthma as a function of the duration of therapy. The cohort was selected from the databases of Saskatchewan Health from 1977 to 1993. The rate ratio (RR) of a readmission for asthma varied with duration of regular therapy with inhaled corticosteroids. During the first 15 d of regular therapy, users of inhaled corticosteroids were as likely as nonusers of these medications to be readmitted for asthma with a RR of 1.2 (95% CI: 0.8-1.8). Subjects treated regularly with inhaled corticosteroids for at least 16 d and as long as 6 mo were 40% less likely to be readmitted for asthma (RR = 0.6; 95% CI: 0.4-0.9), while after 6 mo of regular treatment the protective effect disappeared (RR = 1.3; 95% CI: 0.7-2.4). We conclude that regular therapy with inhaled corticosteroids can substantially reduce the risk of a readmission for asthma after only 15 d of use. Confounding by severity appears as the most likely explanation for the disappearance of the beneficial effect after 6 mo of regular therapy.

First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma.

BACKGROUND: Early treatment with inhaled corticosteroids appears to improve clinical symptoms in asthma. Whether a first treatment initiated in the year following the recognition of asthma can prevent major outcomes such as admission to hospital has yet to be studied. METHODS: A case-control study nested within a cohort of 13,563 newly treated asthmatic subjects selected from the databases of Saskatchewan Health (1977-1993) was undertaken to investigate the effectiveness of a first treatment with inhaled corticosteroids in preventing admissions to hospital for asthma. Study subjects were aged between five and 44 years at cohort entry. First time users of inhaled corticosteroids were compared with first time users of theophylline for a maximum of 12 months of treatment. The two treatments under study were further classified into initial and subsequent therapy to minimize selection bias and confounding by indication. Odds ratios associated with hospital admissions for asthma were estimated using conditional logistic regression. Markers of asthma severity, as well as age and sex, were considered as potential confounders. RESULTS: Three hundred and three patients admitted to hospital with asthma were identified and 2636 matched controls were selected. subjects initially treated with regular inhaled corticosteroids were 40% less likely to be admitted to hospital for asthma than regular users of theophylline (odds ratio 0.6; 95% CI 0.4 to 1.0). The odds ratio decreased to 0.2 (95% CI 0.1 to 0.5) when inhaled corticosteroids and theophylline were given subsequently. CONCLUSION: The first regular treatment with inhaled corticosteroids initiated in the year following the recognition of asthma can reduce the risk of admission to hospital for asthma by up to 80% compared with regular treatment with theophylline. This is probably due, at least in part, to reducing the likelihood of a worsening in the severity of asthma.

First-time use of newer oral contraceptives and the risk of venous thromboembolism.

Recent epidemiologic studies reported that the risk of venous thromboembolism (VTE) was higher with the use of the newer third generation oral contraceptives than with second generation agents. Although the overall findings of these studies are similar, the results, as they relate to patterns and duration of oral contraceptive use particularly among first-time users, are inconsistent. We reanalyzed data from the Transnational case-control study to assess the risk of VTE associated with first-time use of oral contraceptives as a function of its duration of use. Over the period 1993 to 1995, 471 cases of venous thromboembolism were identified in Germany and the United Kingdom. For each case, up to four controls were obtained, for a total of 1772 controls. Data on oral contraceptive use and confounding variables, including data on sociodemographic, lifestyle, medical history, and family history of disease, were obtained by interview. Data analysis was based on the 105 cases and 422 controls who were first-time users of second or third generation agents, or never users of oral contraception. Rate ratios, adjusted for confounders and approximated by odds ratios, were estimated as a continuous function of duration of oral contraceptive use by logistic regression and quadratic spline models. We found, for first-time users, that the adjusted rate ratio of VTE as a function of the duration of oral contraceptive use is essentially identical for second and third generation pills relative to never users. This rate ratio increases to around 10 in the first year of use and decreases to around two after 2 years of use, remaining at this risk level thereafter for both second and third generation agents. We conclude that second and third generation agents are associated with identical risks of venous thromboembolism when they are prescribed to women who are using oral contraceptives for the first time ever.

PIP: Recent epidemiologic studies reported that the risk of venous thromboembolism (VTE) was higher with the use of the newer third-generation oral contraceptives (OCs) than with second-generation agents. Although the overall findings of these studies are similar, the results, as they relate to patterns and duration of OC use, particularly among first-time users, are inconsistent. The authors reanalyzed data from the transnational case-control study to assess the risk of VTE associated with first-time use of OCs as a function of its duration of use. Over the period 1993-95, 471 cases of VTE were identified in Germany and the UK. For each case, up to 4 controls were obtained, for a total of 1772 controls. Data on OC use and confounding variables, including data on sociodemographic, lifestyle, medical history, and family history of disease, were obtained by interview. Data analysis was based on the 105 cases and 422 controls who were first-time users of second- or third-generation agents or never-users of OCs. Rate ratios, adjusted for confounders and approximated by odds ratios, were estimated as a continuous function of duration of OC use by logistic regression and quadratic spline models. The authors found, for first-time users, that the adjusted rate ratio of VTE as a function of the duration of OC use is essentially identical for second- and third-generation pills relative to never-users. This rate ratio increases to about 10 in the first year of use and decreases to about 2 after 2 years of use, remaining at this risk level thereafter for both second- and third-generation agents. The authors conclude that second- and third-generation agents are associated with identical risks of VTE when they are prescribed to women who are using OCs for the first time ever.

A rapid method for the determination of vitamin E forms in tissues and diet by high-performance liquid chromatography using a normal-phase diol column.

This paper describes a simple method for the analysis of tocopherols in tissues by which frozen tissues-70 degrees C were pulverized at dry ice temperatures (-70 degrees C) and immediately extracted with hexane. There was no need to remove the coeluting lipids from tissues by saponification, since at that level of neutral lipids in the sample, there was no reduction in fluorescence response. For the analysis of oil, in which large amounts of neutral lipids were coextracted, a 20% reduction of fluorescence response was observed, but the response was equal for all tocopherol forms, and was appropriately corrected. Saponification was used only when tocopherol esters were present, and only after an initial hexane extraction to remove the free tocopherols in order to avoid their loss by saponification, particularly non alpha-tocopherol and tocotrienols. All the tocopherols and tocotrienols were separated on a normal-phase diol (epoxide) column that gave consistent and reproducible results, without the disadvantages of nonreproducibility with silica columns, or the lack of separation with reversed-phase columns. The tocopherols were quantitated by using a tocopherol form not present in the sample as an internal tocopherol standard, or using an external tocopherol standard if all forms were present, or when the sample was saponified. Piglet heart and liver samples showed the presence of mainly alpha-tocopherol, with minor amounts of beta- and gamma-tocopherol and alpha-tocotrienol, but no delta-tocopherol. Only small amounts of tocopherol esters were present in the liver but not in the heart.

Confounding by indication and channeling over time: the risks of beta 2-agonists.

A previously published nested case-control study, the Saskatchewan Asthma Epidemiologic Project (SAEP) spanning 1980-1987, investigated the risk of fatal or near fatal asthma and found different risks for two inhaled beta 2-agonists, fenoterol and salbutamol. The authors assessed whether this comparison was confounded by indication because of channeling of inhaled fenoterol to more severely afflicted asthmatics. Using three subcohorts selected from a cohort of 12,301 asthmatics assembled from the computerized databases of Saskatchewan Health and followed over 7 years, the authors studied two forms of channeling and investigated whether greater asthma severity and less well-controlled disease were associated with preferential prescribing of a first prescription of inhaled fenoterol, as opposed to inhaled salbutamol, and whether they were associated with the likelihood of a switch from inhaled salbutamol to fenoterol as well as a switch from inhaled fenoterol to salbutamol. The authors found that the initial choice between fenoterol and salbutamol was independent of the severity of the asthma and disease control, but that preferential prescribing of fenoterol occurred among users of salbutamol who showed signs of increased severity or uncontrolled asthma. The switch from inhaled fenoterol to salbutamol was, however, minimally related to asthma severity. They conclude that the comparison between inhaled fenoterol and salbutamol in the SAEP may have been biased by indication. This study demonstrates that long-term information on medication use is essential to ensure that the results of such case-control studies are not biased by indication.