Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

BACKGROUND: Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage. OBJECTIVES: To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 µg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 µg (DRSP/EE30). METHODS: Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current). RESULTS: The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41). CONCLUSIONS: We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected.

Is antiepileptic drug use related to depression and suicidal ideation among patients with epilepsy?

Depression and suicide are increased in patients with epilepsy. The U.S. Food and Drug Administration warns that antiepileptic drugs (AEDs) are associated with increased risk of suicidality. This study examines the relationship among depression, suicidal ideation, and AEDs in a prospective cohort of 163 patients with epilepsy from a registry at the University of Florida (January 2006 to August 2008). The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was used to measure mood and suicidal ideation across two time points (median = 154 days). Groups included: (1) No AED Change, (2) New AED Added, (3) AED Dose Increased, (4) AED Reduced/Stopped, (5) Multiple AED Changes, and (6) Combined Any AED Change (groups 2-5 combined). No group had worsening mood or suicidal ideation. Significant improvements in proportions of depression and suicidal ideation were seen only for the No AED Change group, which differed only with the AED Dose Increased group with respect to suicidal ideation.

Asthma self-management: the perspective of children.

This qualitative study explored the knowledge, perceptions, and autonomy of 7- and 12-year-old children relative to the management of their asthma. A total of 32 children with moderate to severe asthma were interviewed using an open-ended drawing interview and a semi-structured interview. The triangulation of results from these two methods revealed developmental differences. Younger children identified medicines by shape, color, or lay terms, relied on adults to manage their asthma, and did not recognize warning symptoms of an attack. Older children mastered biomedical terminology and used medicines independently, although they sometimes asked for the assistance of an adult. All children perceived benefits and non-monetary costs of asthma medicines. However, they lacked understanding of the categories and role of asthma medicines. This study suggests that long-term control and quick-relief metered dose inhalers should be identifiable by consistent color-coding, and that professionals should tailor asthma education and information to children's stages of cognitive development.

Effect of vaccination by community pharmacists among adult prescription recipients.

BACKGROUND: Millions of doses of influenza vaccine are administered each year in the United States at nontraditional sites and by nontraditional vaccine providers. Pharmacists are increasingly becoming vaccine providers. OBJECTIVES: To measure association between availability of pharmacist-immunizers and immunization delivery to adult prescription recipients, and the relative contributions of various types of vaccine providers. RESEARCH DESIGN: Mailed survey in spring 1999, contrasting adults in urban Washington State, where pharmacists administer vaccines, to adults in urban Oregon, where pharmacists did not. SUBJECTS: Cluster sample based on October 1998 prescription records suggesting need for influenza vaccine, derived from 24 community pharmacies belonging to one pharmacy chain. MEASURES: Vaccination status and choice of vaccine provider. RESULTS: Influenza vaccination rates among respondents 65 years or older increased 4.7% more in Washington than in Oregon between 1997 and 1998 (P = 0.20). The net increase in influenza vaccination rate among younger respondents taking indicator medications for chronic diseases for which influenza vaccination is recommended was 10.6% (P = 0.05). Among respondents unvaccinated against influenza in 1997, the 1998 influenza vaccination rate was 34.7% in Washington, compared with 23.9% in Oregon (P = 0.01). CONCLUSIONS: Vaccine delivery by pharmacists is associated with higher rates of vaccination among those younger than 65 taking indicator medications medications for chronic diseases, as well as prescription recipients unvaccinated against influenza in the previous year.

People vaccinated by pharmacists: descriptive epidemiology.

OBJECTIVE: To describe the demographic, clinical, and attitudinal characteristics of people vaccinated by pharmacists, using a multistate sample of pharmacists and a more extensive set of parameters than previous studies. DESIGN: Cross-sectional survey. PATIENTS AND OTHER PARTICIPANTS: 1,730 adults vaccinated at 21 community pharmacies in 17 cities in 10 states. MAIN OUTCOME MEASURES: Vaccinees' age, sex, and selected demographic characteristics; current medications and prescription use patterns; distance traveled to pharmacy; and opinions about vaccine providers. RESULTS: 60% of respondents were women; average age was 54 +/- 15 years. One-quarter were age 65 years or older. About 9% were younger than 65 and took medication for chronic heart or lung disease or diabetes. Almost half took prescribed medications chronically, and 84% came to the pharmacy intending to be vaccinated. All of the respondents believed they were treated respectfully. Many respondents considered the pharmacy advantageous, compared with other vaccine providers, based on access, proximity, trust, convenience, and/or cost. CONCLUSION: Respondents vaccinated by a community pharmacist were satisfied with the experience and would recommend it to others.

Economic assessment of three antimicrobial therapies for uncomplicated urinary tract infection in women.

This retrospective cohort study used North Carolina Medicaid paid-claims data to assess clinical and economic outcomes of treatments for urinary tract infection (UTI). The study population comprised female Medicaid recipients, between 15 and 64 years of age, with a paid claim filed for a primary diagnosis of UTI or acute UTI from January 1 to June 30, 1994, who were treated with ciprofloxacin, nitrofurantoin, or trimethoprim/sulfamethoxazole (TMP/SMZ). Patients had follow-up for 6 months after the primary diagnosis. Patients who did not receive further treatment for UTI with 1 of the 3 drugs within 30 days after initial treatment were assumed to be cured. Costs were measured as the sum of reimbursements for UTI-related medical services and drug treatments. Outcomes for 409 patients were assessed. Cure rates of initial treatment with ciprofloxacin, nitrofurantoin, and TMP/SMZ were 81%, 88%, and 93%, respectively. Cost-effectiveness ratios of initial treatment with the 3 drugs were $150.80, $81.20, and $69.00, respectively. When efficacy rates generated from published randomized clinical studies were applied, cost-effectiveness ratios for the 3 drugs were $130.96, $86.17, and $72.00, respectively. A decision model of treatment pattern and associated costs is presented. Several patient variables indicate that the ciprofloxacin group included more severe cases of UTI than did the other groups. Study limitations, confounders, and future research suggestions are discussed. Our results show that treatment for >7 days results in a better cure rate regardless of the drug used than does treatment for < or =7 days and that TMP/SMZ is the most cost-effective of the 3 drugs for UTI or acute UTI.

Physician over-the-counter drug prescribing patterns: an analysis of the National Ambulatory Medical Care Survey.

OBJECTIVE: To describe the prevalence of physician over-the-counter (OTC) drug prescribing in relation to selected physician, patient, and drug characteristics. DATA SOURCE AND METHODS: Data from the 1990 National Ambulatory Medical Care Survey, a multistage probability clustered sample, were analyzed. Physician drug utilization was expressed in drug mentions defined as "the physician's entry of a pharmaceutical agent ordered or provided, by any route of administration, for prevention, diagnosis, or treatment." Sampling weights were used to obtain unbiased national estimates. Cross tabulations of the drug prescription status (OTC or prescription [Rx]) with independent variables were performed, overall and by therapeutic class. The overall OTC/Rx ratio (0.11) was used as the cutoff point for distinguishing high- from low-level OTC drug prescribing. RESULTS: In 1990, 9.7% of physician drug mentions were of OTC drugs. Women between 16 and 34 years, Asian/Pacific Islanders, white Hispanics, and African-Americans experienced high OTC drug mentions (OTC/Rx > or = 0.11). After stratification by drug therapeutic class, physicians in general practice, family practice, internal medicine, obstetrics/gynecology, and pediatrics highly mentioned OTC drugs. CONCLUSIONS: OTC drug prescribing by physicians is substantial, and primary care specialties, patient gender, age, and race should be considered by those interested in evaluating OTC drug utilization in the ambulatory care setting.

Demographics, health behaviors, and past drug use as predictors of recall accuracy for previous prescription medication use.

Drug data for pharmacoepidemiologic studies are often ascertained by self-report, but little research has addressed the factors influencing its accuracy. Stratified random sampling was used to select individuals for a study comparing interview data on past prescription drug use with dispensation information from the Group Health Cooperative of Puget Sound pharmacy database. The strata included age, gender, and recency of use. Recall accuracy and its determinants were evaluated for repetitively used non-steroidal anti-inflammatory drugs (NSAIDs), short-term NSAIDs (only a single dispensation), and post-menopausal estrogens. We investigated whether recall accuracy was influenced by education, marital status, race, smoking, alcohol consumption, cumulative drug history, the number of different NSAIDs or estrogens dispensed (both by name and dosage), and the number of dispensations of the drug in question. For repetitively used NSAIDs, recall accuracy was positively associated with the number of NSAID dispensations (the odds of recall were 1.7 [95% confidence interval {CL}: 1.3-2.2] times greater for each additional four dispensations of the NSAID), the total number of drugs dispensed and the number of different NSAIDs dispensed. For estrogen and short-term NSAID use, only higher educational attainment improved recall accuracy: the odds of recall were 4.1 (95% CI: 1.4-11.7) and 2.1 (95% CI: 1.0-4.7) times greater for those with some college compared with those with only a high school degree, respectively. This study demonstrates that predictors of recall accuracy for previous medication use differ by the type of drug and the repetitiveness of its use.

Self-initiated modification of hypertension treatment in response to perceived problems.

OBJECTIVE: To assess the prevalence of patient-initiated modification of drug instructions and the association between different classes of problems and the modification of hypertension therapy. DESIGN AND METHODS: In this cross-sectional study, all patients (n = 1215) who had been examined at a hypertension clinic during a 1-year period were surveyed. The response rate to the questionnaire was 85%. Of the 1035 respondents, 623 currently taking antihypertensive medication (self-report) were included in the study. RESULTS: Of the patients taking antihypertensive drugs, 36% admitted that they had tried to manage their condition with a lower dosage and/or fewer drugs than prescribed. The percentage of patients who modified their drug regimen decreased with increasing age. One or more problems with the treatment of hypertension were reported by 79% of the respondents. The odds ratio (95% confidence interval) for modification among patients who reported 1 or more problems compared with those not reporting any problem was 3.5 (2.12 to 5.67). The prevalence of modification increased with the number of problems; this was seen in all age groups and among men and women. CONCLUSIONS: Perceived problems in drug taking in the treatment of hypertension have an important impact on the prevalence of modifying drug instructions.

Pharmacoepidemiology of bleeding events after use of r-alteplase or streptokinase in acute myocardial infarction.

OBJECTIVE: To determine in nonresearch, general medical practice conditions the comparative incidence and types of bleeding complications after the use of streptokinase (SK) and r-alteplase (recombinant tissue plasminogen activator, rt-PA) to treat acute myocardial infarction (AMI). DESIGN: Retrospective medical record review of concurrently treated patients (96-hour observation posttreatment) in 32 participating hospitals in the US. MAIN OUTCOME MEASURES: The medical record description of all bleeding events regarding the body site affected, changes in hemoglobin concentrations, blood products administered, and clinical outcome (permanent sequelae or death). Bleeding severity was determined by defined criteria. CONTROL DATA: Comorbidity and concomitant medications (e.g., aspirin, heparin, warfarin) likely to predispose or contribute to bleeding events were analyzed. DATA ANALYSIS: Logistic regression analysis. RESULTS: Data from 419 patients who received rt-PA and 207 who received SK were evaluated. In the 96-hour period after initiation of thrombolytic therapy, 30.5 and 31.9 percent of rt-PA and SK patients, respectively, experienced one or more bleeding events (crude risk ratio [CRR] = 1.04; 95 percent confidence interval [CI] 0.91-1.14; p = 0.73). In the first 24-hour period, 21.5 percent of rt-PA and 15.9 percent of SK patients experienced bleeding events (CRR = 0.74; 95 percent CI 0.42-1.15; p = 0.08). The leading types of bleeding and percents of all patients affected were: perivascular access site (18.4 percent), gastrointestinal (6.4 percent), skin/soft tissue/muscle (5.0 percent), urinary (3.4 percent), pulmonary (2.2 percent), systemic (1.9 percent), and oral (1.4 percent). Intracranial bleeding occurred in 4 rt-PA and 2 SK patients; 4 of these patients died. Events deemed clinically significant occurred in 15 rt-PA and 9 SK patients (3.8 percent of all patients). Ten patients likely died from these events, 6 within the first 24 hours. Three rt-PA patients and 1 who received SK (0.6 percent) died of cerebrovascular events within the first 24 hours. After controlling for demographic factors and therapeutic variables, using logistic regression analyses, no thrombolytic-related differences were found in the incidence or severity of bleeding following use of the two thrombolytics. CONCLUSIONS: These clinical data do not support a theoretical advantage of rt-PA to cause less bleeding propensity than SK.

Computerized monitoring protocols as a pharmaceutical care practice enhancement: a conceptual illustration using diabetes mellitus.

OBJECTIVE: To illustrate how a computer system used in an ambulatory care pharmacy setting might enhance care of patients with diabetes by prospectively monitoring and prompting them to seek routine medical care. DATA SOURCES: A MEDLINE search to identify existing works on informatics was conducted. An epidemiology and general medical literature review of diabetes mellitus was also performed via MEDLINE. Additionally, known textbooks on the disease were consulted. CONCLUSIONS: Programming a computer system to prompt pharmacists to remind their patients of necessary medical interventions could save medical resources by warning chronically ill patients not to ignore routine medical care. Also, this would allow the pharmacist to prospectively monitor patient outcomes. By knowing when medical interventions are due and obtaining feedback from patients on the results of the medical contact, pharmacists increase their knowledge about patient outcomes and the rationale behind changes in pharmacotherapy. It is expected that such a system would prevent the inconspicuous development of chronic complications.

Community pharmacists as immunization advocates. Cost-effectiveness of a cue to influenza vaccination.

To assess the cost-effectiveness of a cue to influenza vaccination provided by community pharmacists, a decision tree was constructed of the consequences of implementing a pharmacy-based vaccine-advocacy program, based on experience gained in an experiment involving three community pharmacies in Durham County, North Carolina. The model used morbidity and mortality assumptions derived from the infectious-disease literature and cost assumptions based on 1990-91 Medicare Part A and Part B reimbursement costs. This analysis suggests that if Medicare reimbursed pharmacists for advising 100,000 patients at risk to accept influenza vaccine through vaccine-advocacy messages, for an apparent expenditure of $110,000, the increased rate of influenza vaccinations would avert 139 hospitalizations and 63 deaths, and actually yield Medicare a net savings of $280,588. These calculations probably underestimate the benefit to society of a pharmacy-based vaccine-advocacy program, because only direct costs to the single government agency were computed and no cost was attributed to death or lost earnings.

Pharmacoepidemiology and military medical automation: opportunity for excellence.

Fielding of the Composite Health Care System (CHCS) brings an unparalleled opportunity for medical research. This sophisticated automated medical record system promises pharmacoepidemiologic research of a quality and quantity never before possible. Pharmacoepidemiology provides answers about the validity of beneficial and adverse drug events and aids in individualizing drug therapy. When CHCS eventually encompasses an estimated 9.1 million patients at 166 military hospitals and 588 clinics around the world, it will provide a database capable of supporting sophisticated automated research. In addition to the unprecedented size of this resource, advantages of pharmacoepidemiology performed with the CHCS database include integration of inpatient and outpatient care records, the completeness of prescription and medical records, and the wide socioeconomic spectrum covered in a defined population. Limitations and potential biases of such a database include separate drug formularies at each medical treatment facility, only limited information about nonprescription drug use and single-dose drug orders in clinics, and the mobility of military service members and their families. Pharmacoepidemiology is a tool that will benefit individual members of the military family, as well as advancing the sciences of pharmacy and medicine. Using the CHCS database for this form of research is in the best tradition of military medical research.

Guide to interpreting and evaluating the pharmacoepidemiologic literature.

The purpose of this guide is to provide review criteria for the pharmacoepidemiologic literature. Case-control and cohort studies are the major methodologies used in pharmacoepidemiologic analysis. Evaluation criteria for case-control and cohort studies address proper sample-frame definition, compatibility of cases and controls, drug-exposure validations, unintended-effect ascertainment procedures, and considerations for confounding. Moreover, interpretation of the statistics used in reporting cohort and case-control studies is provided. Further review criteria are given for meta-analysis, an approach to integrating the pharmacoepidemiologic literature.

Pharmaceutical sciences' manpower supply and internal rate of return.

A pharmacy student has many career options upon graduation. These options include graduate education in one of the pharmaceutical sciences and a retail pharmacy position. The attractive salaries offered by chain pharmacies play an important role in the recent graduate's career decision-making process. The purpose of this study is to provide a comparative assessment of the internal rate of return (IRR) for different pharmaceutical science career options as related to chain-store pharmacist earnings. Additionally, this study analyzes the effect of the IRR on the applicant pool size and composition for graduate study in pharmaceutical sciences. Income/age profiles were developed using public domain income data derived from salary surveys sponsored by professional associations. Based on these income/age profiles, IRRs were estimated for the pharmaceutical science disciplines, clinical pharmacy, pharmaceutics, medicinal chemistry, and pharmacy administration, and further differentiated for industry versus academic careers. The IRRs are the highest for Pharm.D.'s in academic careers (16.0%), followed by pharmaceutical scientists employed by pharmaceutical industry (8.13%). The IRR of pharmaceutical scientists in academia is lower than the return of other financial investment vehicles. Other authors have established a relationship between the IRR of a profession and a rise or decline in the applicant pool. The IRRs calculated here imply that this association can also be observed for the pharmaceutical scientist applicant pool. Low IRRs should result in a declining applicant pool. However, the last decade has shown an increase of 66% in the number of Ph.D.'s granted, while the percentage of Ph.D.'s granted to nonpharmacists or non-Americans has not increased significantly over the same time period.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical education for hospital pharmacists in The Netherlands and the United States of America: some observations.

Three parameters for the quality of clinical education for hospital pharmacists are postulated: the number of pharmacists who can serve as preceptors, the depth and scope of clinical pharmacy services, and the structure of the training. Dutch hospital pharmacies exhibit consistently lower pharmacist staffing ratios than their American counterparts. For the scope of services provided in Dutch (as compared to American) hospitals, the emphasis is on pharmacokinetic consultation and handling of radiopharmaceuticals, services which require less patient involvement and are consequently less labour intensive than services, such as patient profile and drug interaction monitoring services, which are more prevalent in American hospital pharmacies. 17% of Dutch respondents were not exposed to patient profile monitoring during their training, 16% were not exposed to drug interactions monitoring, 9.8% were not exposed to pharmacokinetic services and 8.9% were not exposed to drug information services, although these services are provided at the current worksite. Dutch hospital pharmacists are often solo practitioners maintaining a high standard of practice by focusing on core tasks and activities.

Drug utilization study methodologies: national and international perspectives.

This paper in the series on pharmacoepidemiology describes the history, development, and present status of drug utilization activities. The various methodologies employed in drug utilization studies are evaluated and presented along with a listing of the principal drug databases available for drug utilization research. An analysis is presented comparing the validity of drug consumption rates based on individual patient usage or drug cost data as adopted in North America and the defined daily dose unit as developed in Europe. Drug utilization derives its importance in pharmacoepidemiology from the fact that it provides the methodological rigor for defining the denominator data needed in pharmacoepidemiological research.