Publications

OBJECTIVES: We sought to examine the impact of direct-to-consumer advertising (DTCA) and pharmaceutical promotion to physicians on the likelihood that (1) an individual diagnosed with depression received antidepressant medication and that (2) antidepressant medication was used for the appropriate duration.

RESEARCH DESIGN AND SUBJECTS: A quasiexperimental design was used to examine treatment patterns of 30,621 depressed individuals whose insurance claims were included in the MarketScan database from 1997 through 2000. The main explanatory variables were spending on DTCA, detailing to physicians, and free samples for 6 antidepressant medications.

RESULTS: Individuals diagnosed with depression during periods when class-level antidepressant DTCA spending was highest (cumulative spending more than US 18.5 million dollars) had 32% higher relative odds of initiating medication therapy compared with those diagnosed during periods when DTCA spending was lowest (P < 0.0001). Free samples of medications dispensed to physicians had no effect on odds of initiating antidepressant use. Class-level DTCA spending on antidepressants had a small positive effect on the duration of antidepressant use, whereas DTCA spending for the specific medication taken by an individual had no effect on treatment duration. Detailing spending at the class or product level had no significant effect on duration of treatment with an antidepressant medication.

CONCLUSIONS: Our results suggest that DTCA of antidepressants was associated with an increase in the number of people diagnosed with depression who initiated medication therapy. DTCA was associated with a small increase in the number of individuals treated with antidepressants who received the appropriate duration of therapy. Promotion to physicians was not associated with either the initiation of treatment with an antidepressant or with the duration of therapy.

OBJECTIVE: To determine the incidence of clinically relevant potential drug-drug interactions (DDIs) in a large population of ambulatory patients utilizing a computerized, retrospective drug utilization review (DUR) program followed by clinical pharmacist audit.

METHODS: The drug claims database included approximately 2.9 million patients with more than 30 million prescriptions dispensed in the 12-month period from September 2001 through August 2002. Cases were identified by a computerized, retrospective DUR program with embedded triggers to detect 69 prespecified potentially serious DDIs, with "serious" defined as an interaction that would likely require a change in therapy or use of additional clinical or laboratory monitoring. Two types of automated, computerized assessments were conducted: the first simply detected coprescribed drug pairs, and the second assessment used more sophisticated filters to reduce false positive alerts for coprescribed drug pairs. Clinical pharmacist audit then determined the final incidence of clinically relevant warnings; in this audit, coprescribed drug pairs were defined as clinically relevant if they could cause potentially serious DDIs.

RESULTS: Eighteen drug pairs had insufficient cases for inclusion, leaving 51 drug pairs for evaluation. A total of 244,703 cases of potential DDIs were identified (0.8% of total prescription claims) by simple automated screens. More sophisticated DDI filters reduced the 244,703 potential DDIs by 70.8%, to a total of 65,544 pairs (0.2% of total prescription claims). Clinical pharmacist review reduced the number of potential DDIs by an additional 80.6%, to 12,722 drug pairs (0.04% of total prescription claims) deemed clinically relevant. The combination of sophisticated DDI filters and clinical pharmacist review reduced the incidence of potentially serious DDIs by 94.3%.

CONCLUSION: The incidence of potentially serious DDIs is relatively low (less than 1%) among ambulatory patients; however, the incidence depends on the method of case finding. Retrospective DUR programs, especially those with additional automated filters or that utilize additional pharmacist review, appear to be important screening tools in determining true rates of coprescribed drug pairs that can lead to potentially serious DDIs.

BACKGROUND: Choice of antibiotic therapy for acute exacerbations of chronic bronchitis (AECB) is important because of cost and concerns about development of resistance.

METHODS: A retrospective cohort study was conducted in outpatients with chronic obstructive pulmonary disease and documented AECB treated with antibiotics.

RESULTS: We compared outcomes and costs of AECB treated with first-line antibiotics having partial coverage against organisms associated with AECB (eg, amoxicillin), first-line antibiotics with full coverage against organisms associated with AECB (eg, sulfamethoxazole-trimethoprim), and newer broad-spectrum antibiotics (eg, azithromycin). There were no significant differences among the three antibiotic groups in failure rate, hospitalization rate, or time until subsequent AECB. Pharmacy costs were significantly less with first-line antibiotics (3.18 dollars +/- 0.64, 3.00 dollars +/- 0.48, and 36.70 dollars +/- 16.29, respectively; P < 0.0001), but there was no significant difference among all three groups with regard to total costs.

CONCLUSION: We found no difference in outcome between older traditional antibiotics with adequate coverage against organisms associated with AECB and newer broad-spectrum antibiotics.

OBJECTIVE: To identify the documented indications for long-term therapy with lansoprazole 30 mg twice daily at the Veterans Affairs Pittsburgh Healthcare System, assess compliance with appropriate use criteria, evaluate patients eligible for step-down therapy, and recommend appropriate step-down therapy in order to improve patient care, decrease overprescribing, and reduce medication costs.

STUDY DESIGN: Prospective intervention.

METHODS: The records of all patients with prescriptions for lansoprazole 30 mg twice daily as of June 2000 were reviewed. Patients were interviewed to assess medication compliance and symptom control and to provide education on lifestyle modifications. Interventions with the providers were completed to encourage step-down therapy in appropriate patients.

RESULTS: Two hundred forty-eight patients with active prescriptions for twice-daily lansoprazole were reviewed. Of these patients, 66% (n = 163) did not have an indication compliant with the medical center's guidelines for use of lansoprazole 30 mg twice daily. Of these, 88% (n = 143) had no documented attempt at step-down therapy and 49% (n = 80) had no documented gastrointestinal workup. Interventions for step-down therapy were recommended for 48% (n = 120) of the 248 patients. Forty-six percent (n = 60) of recommendations were accepted, resulting in a cost savings of dollars 85000 per year.

CONCLUSIONS: A high rate of clinician noncompliance with the guidelines for appropriate use of lansoprazole 30 mg twice daily was found. These prescribing patterns resulted in significant cost concerns. Our review and interventions led to step-down therapy for almost half of the patients receiving twice-daily lansoprazole. This review of patient records and intervention with primary care providers resulted in cost reduction and offered an opportunity to educate patients on beneficial lifestyle modifications.

OBJECTIVE: To determine whether there are racial differences in adherence to cardiac medications.

DESIGN: Retrospective analysis.

PATIENTS: African-American and white male veterans aged 45 years or older who had received any of four groups of drugs: angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), calcium channel blockers (CCBs,) or HMG CoA (hydroxymethyl glutaryl coenzyme A) reductase inhibitors (statins).

DATA: Administrative records were used to identify eligible veterans and their demographic characteristics, medical diagnoses, and medication use. We used a standard measure of adherence to medications based on whether the veteran obtained enough drug to take it as prescribed on 80% of the days.

RESULTS: We identified 833 eligible African-American and 4436 eligible white veterans. In univariable analysis, African Americans were less likely to be adherent to medications than whites for ACEIs (81.4% versus 87.6%, P = 0.004), CCBs (75.3% versus 81.7%, P = 0.003), and statins (59.9% versus 74.1%, P < 0.001) but not BBs (84.8% versus 83.5%, P = 0.6). In multivariable analysis, racial differences in adherence to medications were found primarily among veterans younger than 55 years old.

CONCLUSIONS: Younger African Americans were less adherent to medications than whites in a setting where financial barriers are minimized. Although the reason for this finding is unclear, it may contribute to high cardiovascular morbidity among African Americans.

In elongating pollen tubes of the conifer Picea abies (Norway spruce), microtubules form a radial array beneath the plasma membrane only at the elongating tip and an array parallel with elongation throughout the tube. Tips specifically swell following microtubule disruption. Here we test whether these radial microtubules coordinate cell wall deposition and maintain tip integrity as tubes elongate. Control pollen tubes contain cellulose throughout the walls, including the tip. Pollen tubes grown in the presence of isoxaben, which disrupts cellulose synthesis, are significantly shorter with a decrease in cellulose throughout the walls. Isoxaben also significantly increases the frequency of tip swelling, with no effect on tube width outside of the swollen tip. The decrease in cellulose is more pronounced in pollen tubes with swollen tips. The effects of isoxaben are reversible. Following isoxaben treatment, the radial array of microtubules persists beneath the plasma membrane of nonswollen tips, while this array is specifically disrupted in swollen tips. Microtubules instead form a random network throughout the tip. Growth in these pollen tubes is turgor driven, but the morphological changes due to isoxaben are not just the result of weakened cell walls since pollen tubes grown in hypoosmotic media are not significantly shorter but do have swollen tips and tubes are wider along their entire length. We conclude that the radial microtubules in the tip do maintain tip integrity and that the specific inhibition of cellulose microfibril deposition leads to the disorganization of these microtubules. This supports the emerging model that there is bidirectional communication across the plasma membrane between cortical microtubules and cellulose microfibrils.

BACKGROUND: Carcinoma of the urinary bladder accounts for approximately 2% of all malignant tumors and usually spreads through both local invasion and hematogenous dissemination. In the current study, the authors reviewed a large series of patients to determine the nature and frequency of neurologic complications.

METHODS: In the current study, the authors reviewed the records of 359 patients with bladder carcinoma who were treated at the study institution between 1962-2001.

RESULTS: Fifty-two patients (14%) were reported to have neurologic complications. Complications resulting from neurologic metastases were relatively infrequent (5%). Seven patients (2%) had lumbosacral plexopathies and 6 patients (2%) had metastatic epidural spinal cord compression. Brain metastases were present in only 4 patients (1%). Nonmetastatic complications were more common than metastatic complications and were comprised of metabolic encephalopathies in 24 patients (7%), peripheral neuropathies in 9 patients (2.5%), cerebral infarctions in 6 patients (2%), and seizures in 5 patients (1%). No cases of neurologic infection or carcinomatous meningitis were reported.

CONCLUSIONS: The results of the current study demonstrate that neurologic complications are relatively uncommon in patients with bladder carcinoma and that local extension into peripheral nerves or bone, rather than hematogenous dissemination, is the most common cause of neurologic complications resulting from bladder carcinoma.

OBJECTIVE: To determine whether the extent of coronary obstructive disease is similar among black and white patients with acute coronary syndromes.

DESIGN: Retrospective chart review.

PATIENTS: We used administrative discharge data to identify white and black male patients, 30 years of age or older, who were discharged between October 1, 1989 and September 30, 1995 from 1 of 6 Department of Veterans Affairs (VA) hospitals with a primary diagnosis of acute myocardial infarction (AMI) or unstable angina (UnA) and who underwent coronary angiography during the admission. We excluded patients if they did not meet standard clinical criteria for AMI or UnA or if they had had prior percutaneous transluminal coronary angioplasty or coronary artery bypass grafting.

MEASUREMENTS AND MAIN RESULTS: Physician reviewers classified the degree of coronary obstruction from blinded coronary angiography reports. Obstruction was considered significant if there was at least 50% obstruction of the left main coronary artery, or if there was 70% obstruction in 1 of the 3 major epicardial vessels or their main branches. Of the 628 eligible patients, 300 (48%) had AMI. Among patients with AMI, blacks were more likely than whites to have no significant coronary obstructions (28/145, or 19%, vs 10/155 or 7%, P =.001). Similarly, among patients with UnA, 33% (56/168) of blacks but just 17% (27/160) of whites had no significant stenoses (P =.012). There were no racial differences in severity of coronary disease among veterans with at least 1 significant obstruction. Racial differences in coronary obstructions remained after correcting for coronary disease risk factors and characteristics of the AMI.

CONCLUSIONS: Black veterans who present with acute coronary insufficiency are less likely than whites to have significant coronary obstruction. Current understanding of coronary disease does not provide an explanation for these differences.

The detection of adverse drug reactions (ADRs) by a traditional passive reporting system and by a method involving patient and provider interviews was studied. The study sample consisted of randomly selected outpatients seen by their primary care provider during scheduled appointments in January and February 2001 at a Veterans Affairs medical center. After ambulatory care clinic sessions, patients and providers were asked (by telephone and in person, respectively) to identify potential ADRs. Also obtained were demographic data, information about drug regimens, and the severity and management of each ADR. A standardized ADR-assessment tool was used to determine the severity of each reported reaction and its causal relationship with the medication. A total of 198 patients were included. Of these, 51 (26%) had one or more ADRs. The patient and provider interviews identified a total of 83 ADRs, compared with 1 ADR identified by the passive reporting system. When providers were made aware of the ADRs they had not identified, changes were made to the patient's medication regimen in 34% of cases. The risk of an ADR was not associated with age, number of medications, or provider type. Direct patient and provider interviews yielded a significantly higher rate of ADR detection in an ambulatory care setting than did a passive ADR-reporting system.

BACKGROUND: Racial differences exist in the management of coronary artery disease. One hypothesis is that black patients delay seeking care and that this delay may influence the management of coronary artery disease.

OBJECTIVES: To assess delay in seeking care for heart disease.

RESEARCH DESIGN: Cross-sectional survey.

SUBJECTS: One thousand six hundred and fifty-two patients awaiting coronary angiography at three VA and one non-VA Medical Center.

MEASURES: Patients were asked to retrospectively report the time between symptom onset and presentation for medical care and what if any were the reasons for delay.

RESULTS: One thousand five hundred eleven patients (12% VA & 43% non-VA) answered questions regarding delay in treatment. Overall, 73% reported delaying 1 month or more and 16% reported delaying more than 6 months. Black patients and white patients were equally likely to delay as were older persons (> or = 65) compared with younger. Patients at the VA hospitals reported longer delays and patients with prior revascularization were less likely to report delays. We used ordinal logistic regression to predict delay using site type and prior revascularization as covariates. VA site of care independently predicted longer delays whereas prior revascularization predicted less delay. Among patients who reported at least a 1 month delay, patients at the non-VA hospital were more likely to cite ignoring symptoms as their reason for delay (72% vs. 61%; P = 0.03) as were those with at least a high school education 69% versus 50%; P = 0.003). Black patients reported that they ignored their symptom more often but this was marginally significant (77% vs. 63%; P = 0.053).

CONCLUSIONS: Race was not associated with delay in seeking care among patients awaiting coronary angiography. Non-VA patients, and those with past revascularization, were less likely to delay. Ignoring symptoms was the most common reason for delays greater than 1 month. Further study of the sequence of patient and provider decisions that ultimately lead to revascularization is needed.