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Biomedical subjects

Adrian R Levy

Publications and source records attributed to Adrian R Levy.

31 records · Page 2Linked to original sources

Antiretroviral resistance among HIV-infected persons who have died in British Columbia, in the era of modern antiretroviral therapy.

BACKGROUND: The prevalence of antiretroviral resistance among persons enrolled in the centralized HIV/AIDS Drug Treatment Program in British Columbia, Canada, who had died between July 1997 and December 2001, was investigated, to determine the degree to which antiretroviral resistance contributed to mortality. METHODS: During this period, 637 deaths had occurred. The last plasma sample obtained during therapy was genotyped retrospectively for treated individuals who had died of a nonaccidental cause. Samples with plasma human immunodeficiency virus (HIV) loads <500 copies/mL were not genotyped. Drug resistance among 1220 living HIV-infected persons who had experienced virologic therapy failure during the study period also was examined. RESULTS: Of 554 individuals who had died of nonaccidental causes, 58 (10.4%) were antiretroviral naive, and 99 (17.9%) had very brief exposure to antiretroviral therapy (median, 2 months). The majority of isolates from the remaining 397 individuals harbored either no major resistance mutations or represented samples with plasma HIV suppression of <500 copies/mL. Resistance to >/=1, >/=2, or 3 drug classes was observed in 76%, 42%, and 11% of individuals, respectively, in the group of 1220 living individuals experiencing virologic therapy failure, compared with only 44%, 23%, and 5% of individuals, respectively, who had died (P<.001). CONCLUSION: Only a relatively low prevalence of multidrug resistance was observed in this cohort, indicating that the exhaustion of treatment options because of drug resistance was not a significant contributor to mortality.

Adult↗

Use of time-dependent measures to estimate benefits of beta-blockers after myocardial infarction.

PURPOSE: To estimate the reduction in all-cause mortality conferred by beta-blockers in a population-based cohort of elderly survivors of myocardial infarction during the year following hospital discharge. METHODS: A dynamic retrospective cohort was assembled from persons aged 66 years and over surviving myocardial infarction in Quebec between 1990 and 1993. Information on hospitalizations was linked to medication and physician claims, demographic characteristics and vital status. Subjects prescribed beta-blockers at hospital discharge had fewer comorbid medical conditions, less pre-existing cardiovascular disease and less severe infarcts. To control for these differences, analyzes were restricted to subjects receiving at least one beta-blocker and mortality was compared between periods with and without beta-blocker exposure using Cox proportional hazard models. RESULTS: Among 14,547 survivors of myocardial infarction, 41% were dispensed at least one beta-blocker. Among those subjects, the risk of dying during periods of beta-blocker use was reduced 40% (hazard ratio = 0.6; 95% CI: 0.5, 0.7). CONCLUSION: Confounding by indication threatens the validity of observational studies of intended effects of medications. For elderly survivors of myocardial infarction, the estimated benefit of beta-blockers from observational studies is greater than the estimate from randomized trials. Greater benefits do not seem to be an artifact arising from systematically prescribing beta-blockers to subjects with better prognosis. Reducing confounding by indication can enhance the validity of observational studies of medications and widen research applications of administrative health databases. While the actual benefits of medications are never truly known these studies can provide a credible range that brackets the truth.

Adrenergic beta-Antagonists↗

Interventional cardiovascular procedures among HIV-infected individuals on antiretroviral therapy 1995-2000.

OBJECTIVE: To calculate the rate of interventional cardiac procedures (ICP) among HIV-infected individuals ever treated with antiretroviral therapy (ART) and to describe clinical and sociodemographic characteristics associated with ICP. METHODS: Since 1992, ART in British Columbia (BC) has been centrally distributed by the BC Centre for Excellence in HIV/AIDS. The BC Cardiac Registry maintains information regarding all cardiac procedures performed in BC. The two databases were linked to determine the number of HIV-positive individuals on ART who underwent ICP. Age-adjusted analyses were conducted using direct standardization, and linear regression to test for trend over time. Logistic regression was used to identify patient and treatment characteristics independently associated with having an interventional cardiac procedure. RESULTS: Of the 5082 individuals who have ever received ART, 63 (< 1%) were captured in the Cardiac Registry. There were 97 events: 70 (72%) since 1999. The age-adjusted event rate per 1000 HIV-positive individuals on ART increased significantly over time (P = 0.015) whereas that for the general BC population did not increase over time (P = 0.191). In multivariate analysis, age at baseline per 10 year increase [adjusted odds ratio (AOR) 2.5; 95% confidence interval (CI), 1.8-3.2), and months on ART (AOR 1.3; 95% CI, 1.1-1.4) remained significant. CONCLUSIONS: The rate of ICP among HIV-positive individuals on ART appears to be increasing; in addition, the duration of time on ART is independently associated with ICP after adjustment for patient demographic characteristics.

Adult↗

A simple approach to fitting Bayesian survival models.

There has been much recent work on Bayesian approaches to survival analysis, incorporating features such as flexible baseline hazards, time-dependent covariate effects, and random effects. Some of the proposed methods are quite complicated to implement, and we argue that as good or better results can be obtained via simpler methods. In particular, the normal approximation to the log-gamma distribution yields easy and efficient computational methods in the face of simple multivariate normal priors for baseline log-hazards and time-dependent covariate effects. While the basic method applies to piecewise-constant hazards and covariate effects, it is easy to apply importance sampling to consider smoother functions.

Bayes Theorem↗

Rapid increase in statins newly dispensed to Ontario seniors between 1994 and 2000.

BACKGROUND: The Ontario government spent approximately 10% (CDN $148 million) of the provincial medication budget on statins in 1998. This number can be expected to grow in light of new guidelines from the United States recommending that three times as many patients should be receiving antihyperlipidemic therapy. There is scant population-based information on the age and sex distributions of patients receiving these medications. OBJECTIVES: To estimate the rates of new use of statin medications among community-dwelling elderly adults in Ontario between 1994 and 2000. METHODS: Data from the Ontario Drug Benefit program were used on all medications dispensed to noninstitutionalized Ontarians over 65 years of age to estimate age- and sex-specific annual rates of patients newly dispensed a statin. Changes in rates were estimated using Poisson regression. RESULTS: The number of elderly Ontarians newly dispensed a statin increased rapidly between 1994 and 2000, with age-standardized rates rising from approximately 840 to 2600/100,000 women and from 810 to about 3100/100,000 men. The highest rates of new use were observed among patients of both sexes aged 65 to 74 years. However, the rate of change increased with advancing age so that the biggest increase was observed among those aged 85 years and above, among whom there was an 8.5-fold increase among women and a 12-fold increase among men. CONCLUSIONS: Statins have been shown to be safe, efficacious and cost effective in reducing the risk of sudden cardiac death and other acute coronary events among middle-aged patients with pre-existing cardiovascular disease. The present study showed that there was a rapid increase in the rate of statins newly dispensed to elderly patients in Ontario, among whom estimates of safety, efficacy and cost effectiveness are not well quantified. Better estimates of these parameters in the elderly are required because of the high costs and benefits and potential unintended beneficial and harmful effects of statins.

Aged↗

Coding accuracy of administrative drug claims in the Ontario Drug Benefit database.

BACKGROUND: Every year in Ontario, the records of over 42 million prescriptions dispensed to persons eligible for Ontario Drug Benefit (ODB) benefits are transmitted to a central database. The ODB database is the second largest database of medications in Canada, containing records on almost half of all medications dispensed in Ontario. There is no information about the reliability of the coding on the ODB drug claims database and, therefore, the objective of this study was to estimate the reliability of coding of the Drug Identification Number, and the date, quantity and duration of the dispensation on claims sent to the ODB. METHODS: To meet this objective, approximately 100 randomly selected prescriptions dispensed from each of 50 pharmacies in southern Ontario between July 1, 1998 and December 31, 1999 were audited. For each claim, the written information on the prescription was compared with the electronic information submitted to the ODB database. Logistic regression was used to test the association between coding errors and the location, owner affiliation, and productivity of each pharmacy (defined as the annual volume of dispensations divided by the annual number of hours worked by all pharmacists and pharmacy assistants). RESULTS: Of the 183 pharmacies owners invited to participate, consent to abstract information was obtained in 50, yielding a participation rate of 27%. Of the 5155 dispensed prescriptions, 37 errors were found, yielding an overall error rate of 0.7% (95% CI 0.5% to 0.9%). None of the characteristics of pharmacies that were examined (location, owner affiliation, productivity) was associated with coding errors. CONCLUSIONS: Pharmacists almost always dispense the medication that is prescribed and this information is reliably transmitted to the ODB drug claims database. This means that any conclusions drawn by researchers using these data are not likely to be compromised by low coding reliability.

Clinical Pharmacy Information Systems↗

Impact of reference-based pricing for histamine-2 receptor antagonists and restricted access for proton pump inhibitors in British Columbia.

BACKGROUND: Two programs to reduce expenditures for common gastrointestinal drugs were introduced simultaneously by British Columbia (BC) Pharmacare in 1995. Reference-based pricing restricted reimbursement for all histamine-2 receptor antagonists (H2RAs) to the cost of the least expensive H2RA available, generic cimetidine. Special authority restricted reimbursement for proton pump inhibitors (PPIs) to patients who met certain eligibility criteria. We evaluated the effect of reference-based pricing for H2RAs and special authority for PPIs on dispensing and reimbursement for senior citizen beneficiaries of BC Pharmacare. METHODS: Itemized monthly claims data for upper gastrointestinal drugs were obtained from BC Pharmacare for all beneficiaries 65 years of age or older. Periods before and after implementation of reference-based pricing and special authority were compared with respect to defined daily doses dispensed per 100,000 beneficiaries, BC Pharmacare reimbursement per 100,000 beneficiaries, BC Pharmacare reimbursement per defined daily dose and beneficiary contributions per defined daily dose. We used regression models to project forward trends in expenditures observed before implementation of the new policies and hence to estimate accrued cost savings. RESULTS: Before reference-based pricing and special authority, the numbers of defined daily doses that were dispensed and total BC Pharmacare reimbursements for H2RAs appeared to be declining gradually, whereas those for PPIs were rising. With reference-based pricing, the monthly defined daily dose of cimetidine dispensed increased more than 4-fold, to 116,257 per 100,000 beneficiaries, while those of other restricted H2RAs decreased by more than half, to 50,927 per 100,000 beneficiaries. Special authority immediately reduced the dispensed volumes of PPIs by one-fourth, but growth in volume then appeared to resume at its previous rate. The estimated annualized cost savings achieved by reference-based pricing and special authority were $1.8 million to $3.2 million for H2RAs (depending on the estimation method used) and $5.5 million for PPIs. However, beneficiary contributions for H2RAs increased from negligible amounts to approximately 16% of total drug expenditures. INTERPRETATION: Reference-based pricing and special authority appear to have been successful in altering prescribing habits and reducing provincial expenditures for upper gastrointestinal drugs, but they have increased the financial burden on senior citizen beneficiaries.

Aged↗

The effect of physicians' training on prescribing beta-blockers for secondary prevention of myocardial infarction in the elderly.

PURPOSE: The objective was to determine whether the year and medical school of graduation, the medical specialty and the sex of the treating physician was associated with prescribing beta-blockers after hospital discharge among survivors of myocardial infarction (MI), after adjusting for patient characteristics. METHODS: We carried out a dynamic retrospective cohort study using data from a longitudinal database that contained information on Quebec residents over the age of 65 years sent home from hospital after MI between 1990 and 1993. The outcome was a beta-blocker being dispensed after hospital discharge. Logistic regression was used to estimate the association between training characteristics and beta-blocker dispensation and clustering of patients within physicians was accounted for using Generalized Estimating Equations. RESULTS: The cohort consisted of 14,334 MI survivors who were treated by 3209 physicians, yielding a mean of about 4.5 patients per physician [standard deviation (SD) = 8.2]. Beta-blockers were prescribed to approximately one-third of subjects. After adjusting for patients' demographic characteristics, comorbid medical conditions, and markers of MI severity, physicians who were more likely to prescribe a beta-blocker included cardiologists and the most recent graduates (graduating after 1989). Systematic differences were also observed between graduates of different medical schools. CONCLUSIONS: After adjusting for differences between patients', the sex of the physician was largely unrelated to prescribing beta-blockers for secondary prevention of MI. However, prescribing differed by training characteristics such as medical specialty and year and medical school of graduation.

Adrenergic beta-Antagonists↗

Getting the cat back in the bag: reforming the way provinces manage drug expenditures to make them manageable.

The fiscal "cat" of healthcare spending - drug expenditures - is out of the bag: drug costs are now the fastest rising component of healthcare expenditures in Canada. Laupacis, Anderson and O'Brien describe the current process of listing drugs on the provincial drug formulary in Ontario, identify factors that may contribute to the rapid growth in drug expenditures, and make a number of recommendations for controlling drug expenditures, including (1) improving the evidence on cost-effectiveness; (2) disseminating the evidence to prescribers; (3) re-evaluating the evidence; and (4) increasing the transparency about the acquisition costs of drugs. These are recommendations that, if implemented, would theoretically help decision-makers make more rational decisions about which drugs to list on provincial formularies. The question of how to implement the recommendations remains to be elucidated, as does an evaluation of the trade-offs between costs and benefits of obtaining better information on cost-effectiveness.

Canada↗

Effect of number of medications on cardiovascular therapy adherence.

OBJECTIVE: Increasing regimen complexity is generally assumed to result in lower medication adherence, but there is conflicting evidence. This study determined the relationship between the number of medications dispensed and adherence with chronic cardiovascular regimens. METHODS: A survey was administered to 367 patients who had taken an angiotensin-converting enzyme inhibitor or lipid-lowering medication for at least 3 consecutive months. Information was collected on nonprescription drug use, demographics, adverse effects, and use of adherence aids. Prescription drug use data over the previous 12 months were obtained for each subject from the British Columbia prescription claims database. Adherence for each prescription medication was calculated based on prescription fill dates and number of days supplied. Univariate and multivariate analyses were used to identify predictors of nonadherence (<80%) with cardiovascular medications. RESULTS: Forty-five subjects (12%) were categorized as nonadherent. Nonadherent subjects took fewer regularly scheduled prescription medications per day (4.1 +/- 2.7 vs. 5.9 +/- 3.4; p = 0.001), fewer pills per day (5.3 +/- 3.6 vs. 9.2 +/- 7.1; p < 0.001), and had fewer administration times per day (1.8 +/- 0.7 vs. 2.4 +/- 0.9; p = 0.001). A multivariate logistic regression model adjusting for age, gender, reported adverse effects, reported nonprescription drug use, and use of adherence aids identified fewer regularly scheduled prescription drugs as an independent predictor of nonadherence with chronic cardiovascular medications (OR = 0.85 per medication, 95% CI 0.74 to 0.94; p = 0.01). CONCLUSIONS: Contrary to popular belief, taking fewer medications was associated with lower adherence with chronic cardiovascular regimens.

Aged↗

Cost implications of administering intravenous proton pump inhibitors to all patients presenting to the emergency department with peptic ulcer bleeding.

OBJECTIVES: Administering proton pump inhibitors (PPI) intravenously (iv) after endoscopic treatment of bleeding peptic ulcers reduces the incidence of rebleeding, the need for operative procedures, and hospitalizations. We assessed the cost implications of iv PPI initiated in all patients presenting to the emergency department (ED) with signs of upper gastrointestinal (UGI) bleeding. METHODS: From a third-party payer perspective with a time horizon of 60 days, we built a decision analytic model comparing standard endoscopic therapy to a strategy in which all patients presenting to the ED with UGI bleeding would start iv PPI before endoscopy. After endoscopy, only those with peptic ulcers would be kept on iv PPI added to standard therapy. Probabilities of health events were extracted from published literature. Resource utilization profiles and costs (iv PPI, hospital stay for medical and operative procedures, and professional fees) were based on Medicare reimbursement data from a large hospital in Alabama. All costs were expressed in 2000 US dollars. Uncertainty was investigated through one-way sensitivity analyses and probabilistic analyses using Monte Carlo simulations. RESULTS: In a hypothetical group of 1000 individuals, routine use of iv PPI prevented 40 rebleeds, 9 surgical procedures, and 223 hospital days, and led to incremental savings of dollars 920 per subject. Probabilistic sensitivity analyses indicated that the strategy of using iv PPI was likely to be dominant even when accounting for uncertainty. CONCLUSIONS: Based on available evidence, routine administration of iv PPI to all persons presenting with UGI bleeding represents good value for money and merits consideration as standard hospital policy.

Anti-Ulcer Agents↗

Treatment costs in Canada of health conditions resulting from chronic hepatitis B infection.

GOALS: To estimate resource use and expected annual cost of care for subjects with chronic hepatitis B and resulting complications in Canada. BACKGROUND: Patients chronically infected with hepatitis B virus are at an increased risk of progressing to complications from deteriorating liver function. STUDY: The direct medical costs for six disease states associated with chronic hepatitis B virus infection were estimated for the year 2001. METHODS: Information on resource utilization patterns was obtained from: 1) a questionnaire administered to eight specialists with experience treating hepatitis B patients, and 2) a data set on hospitalizations in nine Canadian provinces for specific diagnostic codes. Unit costs were collected from published literature and provincial physician payment schedules and lists of reimbursed medications. All sources of information were combined to calculate expected annual costs. Uncertainty analysis was performed using Monte Carlo simulations. Costs are reported in 2001 Canadian dollars. RESULTS: The expected annual per-person costs of care and their 95% confidence intervals (CIs) were: 2191 dollars (CI, 1997 dollars-2556 dollars) for chronic hepatitis B, 2987 dollars (CI, 2389 dollars-4462 dollars) for compensated cirrhosis, 11,228 dollars (CI, 8309 dollars-16,388 dollars) for decompensated cirrhosis, 13,350 dollars (CI, 10,608 dollars-17,187 dollars) for hepatocellular carcinoma, 99,066 dollars (CI, 94,328 dollars-106,833 dollars) for liver transplant, and 38,242 dollars (CI, 33,443 dollars-46,087 dollars) for transplant care after the first year. Main cost drivers were hospitalizations and medications. CONCLUSION: The cost of treating Canadian subjects with hepatitis B-related conditions increases substantially with deteriorating liver function. Any new therapy that proves to be more effective at slowing or preventing the course of liver disease progression would be cost-effective.

Canada↗

Psychological distress and cancer survival: a follow-up 10 years after diagnosis.

OBJECTIVE: This study tested the predictive role of psychological distress in cancer survival, while attempting to overcome several important methodological and statistical limitations that have clouded the issue. METHODS: Measures collected on a range of emotional and cognitive factors in the early postdiagnostic period and at 4-month intervals up to 15 months after diagnosis were used to predict survival time up to 10 years among 205 cancer patients heterogeneous in disease site, status, and progression. RESULTS: With the use of both baseline and repeated measures, depressive symptomology was the most consistent psychological predictor of shortened survival time, after controlling for several known demographic and medical risk factors. CONCLUSIONS: Given the importance of depressive symptoms to cancer survival, discussion focuses on the possible mechanisms mediating this relationship, the importance of psychological screening of cancer patients, and need for further research.

Adult↗