Do gastroprotective drugs prevent NSAID toxicity?
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
Jerry Avorn
Publications and source records attributed to Jerry Avorn.
The hidden cost of nonselective nonsteroidal antiinflammatory drugs in older patients.
OBJECTIVE: Nonselective nonsteroidal antiinflammatory drugs (NSAID) are well known to cause an increased risk of gastrointestinal (GI) hemorrhage, congestive heart failure, and hypertension, but the cost of such adverse effects has not been rigorously defined. We calculated the excess risk and costs associated with the major adverse effects of prescription nonselective NSAID. METHODS: This study involved a retrospectively collected random cohort of 41,826 continuously enrolled patients over 65 years old in the New Jersey Pharmaceutical Assistance to the Aged and Disabled or Medicaid programs. We calculated the adjusted rates and costs of major adverse effects associated with nonselective NSAID, including hospitalization for GI hemorrhage, gastroprotective drug use, ambulatory upper GI procedures, antihypertensive drug use, and hospitalization and medication use to treat congestive heart failure. RESULTS: Eighteen percent of patients filled > or = 1 new prescription for a nonselective NSAID during the study year. All adverse effects studied were more common in patients filling prescriptions for nonselective NSAID than in those not. Average annual costs for the adverse effects studied were 1,234 (1998 US dollars) in nonselective NSAID users compared with 1,036 (1998 US dollars) for controls. After adjusting for sociodemographic factors, other health care utilization, and relevant comorbid diseases, the average annual cost for the major nonselective NSAID related adverse effects studied was 117 (1998 US dollars) higher for patients filling a nonselective NSAID prescription than for those who did not. Nonselective NSAID users with > or = 4 risk factors for nonselective NSAID related adverse effects had average excess costs of 316 (1998 US dollars) over controls, whereas those with no risk factors had an average excess cost of only 75 (1998 US dollars) . CONCLUSION: The excess cost of nonselective NSAID related adverse effects is modest in low risk patients, but much higher in patients with specific risk factors. This approach of stratifying patients based on the risk of nonselective NSAID associated adverse effects can help clinicians and policymakers determine which patients might be the most appropriate candidates for treatment options costlier than nonselective NSAID.
Aged↗
Pharmaceutical cost containment with reference-based pricing: time for refinements.
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British Columbia↗
Nephrologist care and mortality in patients with chronic renal insufficiency.
BACKGROUND: For patients with chronic renal insufficiency, rates of referral to nephrologists are highly variable, and little is known about the effect of such consultation on clinical outcomes. We sought to determine whether early or frequent access to nephrologist care prior to the initiation of dialysis was associated with a difference in mortality rates in the first year after dialysis began. METHODS: We identified all patients in the New Jersey Medicaid and Medicare programs who began maintenance dialysis during a 6-year period and who had been diagnosed with renal disease more than 12 months prior to dialysis. Use of nephrologist services was documented during this 1-year period, along with other clinical and sociodemographic variables. The outcome measure of our analysis was mortality in the first year after initiation of dialysis. RESULTS: From multivariate analyses, we found that patients who did not see a nephrologist until 90 days or less before initiation of dialysis had a 37% higher likelihood of death in the first year of dialysis compared with patients with earlier referral (95% confidence interval, 1.22-1.52; P<.001). Similarly, those who saw a nephrologist on fewer than 5 occasions in the year prior to dialysis had a 15% higher mortality rate in the first year of dialysis compared with those who had had 5 or more nephrologist visits (95% confidence interval, 1.03-1.28; P =.01). CONCLUSIONS: For patients with long-standing renal disease, earlier consultation with a nephrologist and more frequent specialist encounters is associated with lower mortality in the first year of dialysis. These findings need to be confirmed in younger and less indigent patients as well.
Adult↗
Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease.
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Anti-Inflammatory Agents, Non-Steroidal↗
Late nephrologist referral and access to renal transplantation.
BACKGROUND: Our aim was to explore a possible association between late nephrologist referral before onset of renal replacement therapy (RRT) and the likelihood of receiving a renal transplant. METHODS: For the period of 1991 to mid-1996 we defined an inception cohort of all patients with new-onset chronic RRT who were New Jersey Medicare and/or Medicaid beneficiaries in the year before RRT and who had been diagnosed with renal disease more than 1 year before RRT. To control for known risk factors and confounders of access to renal transplantation, we conducted a matched case-control study. Using number of days from onset of RRT to transplantation as the index date for cases, we successfully matched 32 transplant recipients (cases) with 197 controls who shared the cases' age (+/-2 years), gender, race (white/black/other), and year of onset of RRT (+/-1 year) but had not received a transplant on index date. Using conditional logistic regression, we evaluated the effects on the likelihood of transplantation of late referral (< or = 90 days vs. >90 days before first RRT) and socioeconomic status (lower socioeconomic status indicated by enrollment in Medicaid or another state program for the poor), further controlling for comorbidity (Charlson score) in the year before index date. RESULTS: In the full multivariate conditional model, late referral was significantly associated with a much lower rate of renal transplantation (odds ratio [OR]=0.22; 95% confidence interval [CI]: 0.05, 0.97), as were socioeconomic status (OR=0.18; 95% CI: 0.04, 0.82) and comorbidity status (OR=0.69; 95% CI: 0.48, 1.00). CONCLUSIONS: Delayed referral of renal patients to a nephrologist before RRT is significantly associated with reduced access to renal transplantation, independent of age, gender, race, socioeconomic and comorbidity status. The validity of our result needs to be confirmed in larger populations.
Adult↗
Admissions caused by adverse drug events to internal medicine and emergency departments in hospitals: a longitudinal population-based study.
OBJECTIVE: To estimate incidence rates of drug-related hospitalizations (DRHs) in a longitudinal population-based study with prospective event assessment. DESIGN: Cohort study and time-trend analysis. SETTING: All departments of internal medicine and emergency departments in the urban regions of Jena and Rostock, Germany, serving about 520,000 residents. PARTICIPANTS: All patients admitted between October 1997 and March 2000. Patients with severe cutaneous reactions were excluded. MAIN OUTCOME MEASURES: Incidence of DRH was defined by symptoms or diagnoses at admission that were very likely, likely, or possibly caused by prescription medications, according to a standardized assessment. RESULTS: The incidence of DRH was 9.4 admissions per 10,000 treated patients [95% confidence interval (CI) 9.0-9.9]. Rates were highest for antithrombotics with 26.9 admissions per 10,000 treated patients (95% CI 23.6, 30.1). Most frequent events were gastroduodenal lesions and bleeding (45%). Digitalis preparations showed a linearly increasing trend from 2/10,000 to 14/10,000 during ten quarters ( P<0.0001), which was exclusively attributable to digitoxin, the major source of digitalis in the study area (93%). The incidence of DRH increased with age (4/10,000 to 20/10,000). The mean length of stays in patients with DRH was 13+/-10.6 days. Cumulative direct costs for hospitalization were Euro 4 million in the two urban study areas. The annual direct costs for Germany were estimated to be Euro 400 million. CONCLUSIONS: DRHs are a considerable public health and economic burden. A longitudinal design can observe changes in population-based incidence over time. This approach can be used for public-health planning or to evaluate outcomes of quality management programs designed to reduce drug-induced illness.
Adolescent↗
Nonsteroidal anti-inflammatory drug use and acute myocardial infarction.
BACKGROUND: Although aspirin has been shown to protect patients from acute myocardial infarction (AMI), the effect of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) is not clear. OBJECTIVE: To determine whether NSAIDs have a similar effect or whether they differ in their effect on the risk of AMI. METHODS: We performed a case-control study of AMI in a large health care database containing information on all filled prescriptions, hospitalizations, diagnoses, and procedures for all patients covered by the New Jersey Medicaid or Medicare and Pharmaceutical Assistance for the Aged and Disabled programs. We identified 4425 patients hospitalized for AMI between January 1, 1991, and December 31, 1995, and 17 700 control subjects. Multivariate models were constructed to control for potential confounders. RESULTS: A quarter of the cases and controls had filled a prescription for an NSAID in the 6 months before theirAMI (cases) or a randomly assigned index date (controls); 9% had filled a prescription for an NSAID that overlapped with their date of AMI or index date. Overall, NSAID users had the same risk of AMI as nonusers, whether such use was measured on the index date (adjusted odds ratio, 1.04; 95% confidence interval, 0.92-1.18; P =.55) or at any time in the prior 6 months (adjusted odds ratio, 1.00; 95% confidence interval, 0.92-1.08; P =.92). However, use of naproxen was associated with a significant reduction in the risk of AMI (adjusted odds ratio, 0.84; 95% confidence interval, 0.72-0.98; P =.03). CONCLUSIONS: Although NSAIDs have anti-inflammatory and antiplatelet effects similar to those of aspirin, we did not find that these drugs confer a protective effect against AMI. However, use of one specific NSAID, naproxen, appeared to be associated with a reduced rate of AMI, an effect recently suggested by a large randomized controlled trial as well.
Adult↗
Adherence to therapy with oral antineoplastic agents.
With the rise in availability and increasing use of oral anticancer agents, concerns about adherence to prescribed regimens will become an increasingly important issue in oncology. Few published studies have focused on adherence to oral antineoplastic therapy, in part because the vast majority of chemotherapy is delivered intravenously in physicians' offices or hospitals. In this article, we review current knowledge of adherence behavior with regard to oral medications in general, including factors associated with adherence and methods for measuring adherence. We also review published studies of adherence to oral antineoplastic agents in adult and pediatric populations and adherence issues in cancer prevention. The available evidence reveals that patient adherence to oral chemotherapy recommendations is variable and not easily predicted. Adherence rates ranging from less than 20% to 100% have been reported, and certain populations, such as adolescents, pose particular challenges. Future efforts should focus on improving measurement and prediction of adherence and on developing interventions to improve adherence for both patients in clinical trials and patients being treated outside of the research setting. Assessment of adherence among individuals with cancer and implementation of interventions in situations of poor adherence should improve clinical outcomes.
Administration, Oral↗
Correction: cost-effectiveness of statins in older patients with myocardial infarction.
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Age Factors↗
Dopamine antagonists and the development of breast cancer.
BACKGROUND: Although animal studies have raised the possibility that prolactin-elevating dopamine antagonists used to treat psychotic disorders may initiate and promote breast cancers, epidemiologic studies in humans have been limited and inconsistent. METHODS: A retrospective cohort study was conducted of 52 819 women exposed and 55 289 not exposed to dopamine antagonists between January 1, 1989, and June 30, 1995. All participants were 20 years or older, initially free of breast cancer, and enrolled in the Medicaid or the Pharmaceutical Assistance to the Aged and Disabled programs of New Jersey. Incident breast cancer cases were identified through the New Jersey Cancer Registry and definitive breast cancer surgeries. Adjusted hazard ratios of breast cancer were calculated from multivariable proportional hazards models. RESULTS: Use of antipsychotic dopamine antagonists was associated with a 16% increase in the risk of breast cancer (adjusted hazard ratio, 1.16; 95% confidence interval, 1.07-1.26), with a dose-response relationship between larger cumulative dosages and greater risk. The increased risk was also seen in women who used prolactin-elevating antiemetic dopamine antagonists despite having different breast cancer risk profiles than antipsychotic dopamine antagonist users. Dopamine antagonist use was not associated with risk of colon cancer, a control condition not related to elevated prolactin levels. The increased risk of breast cancer among dopamine antagonist users was not explained by increased surveillance or protopathic bias. CONCLUSIONS: Antipsychotic dopamine antagonist use may confer a small but significant risk of breast cancer. In light of the small hazards and the possibility of residual confounding, these findings should lead to follow-up investigations but not to changes in treatment strategies.
Adult↗
Measuring the cost-effectiveness of lipid-lowering drugs in the elderly: the outcomes research and economic analysis components of the PROSPER trial.
Little information exists to quantify the functional status and economic consequences of lipid-lowering therapy in elderly patients. We describe the design of the cost-effectiveness component of the first large, randomized, placebo-controlled trial of lipid-lowering therapy in subjects aged 70 years or older. The PROspective Study of Pravastatin in the Elderly at Risk has randomized 5804 men and women 70-82 years old, with existing vascular disease or related risk factors, to receive 40 mg/d of pravastatin or placebo. The cost-effectiveness study will be based on within-trial observations of differences between the two study arms in rates of myocardial infarction, stroke and related vascular disease outcomes (including vascular dementia). In addition to comparing within-trial clinical outcomes, we will model the projected changes in life expectancy and cardiovascular outcome rates that would be seen with lifelong use of the drug, based on the risk reduction rates seen in the trial as well as baseline observational data from the three countries where the trial is being conducted (Scotland, Ireland and the Netherlands). A state transition (Markov) model will be constructed to estimate the likely states of health, functional status and health care resource utilization (including lipid-lowering drug costs) in a cohort of elderly patients with versus without pravastatin therapy over a series of 1-year cycles until death. In addition, a standard measure of utility (the Health Utilities Index) will be administered to all study subjects to permit calculation of quality-adjusted life-years gained with this regimen. This approach will make it possible to go beyond the calculation of a single endpoint for each subject, and to translate the trial findings into definitions of effectiveness and outcomes that will be relevant to the ongoing debate concerning how best to relate the benefits of such medications to their costs.
Aged↗
Which patients with unstable angina or non-Q-wave myocardial infarction should have immediate cardiac catheterization? A clinical decision rule for predicting who will fail medical therapy.
Unstable angina and non-Q-wave myocardial infarction (MI) are common and costly clinical events, but there is considerable uncertainty about optimal clinical management of these syndromes. We developed a prediction rule to help clinicians determine which patients with unstable angina or non-Q-wave MI are likely to "fail" medical therapy and ultimately require cardiac catheterization within 6 weeks of presentation. Subjects were 733 patients presenting with unstable angina or non-Q-wave MI enrolled in the TIMI IIIB trial and randomized to initial medical management. We developed a prediction rule based on logistic regression analysis of baseline data from history, physical examination, electrocardiogram, and blood studies. The outcome of interest was "failure" of medical therapy, defined as need for coronary catheterization within 42 days. Significant predictors of "failing" medical therapy included ST segment depression >or= .1 mV (odds ratio, OR, = 2.7, 95% confidence interval, CI, 1.8-4.1), accelerated angina in the prior 2 months (OR = 1.8, 95% CI 1.2-2.6), nitrate use in the prior week (OR = 1.6, 95% CI 1.1-2.2), exertional angina in the prior 2 months (OR = 1.6, 95% CI 1.1-2.2), and cardiac troponin I (cTnI) >or= 0.4 ng/mL (OR = 1.4, 95% CI 1.1-1.9). We used these variables to build a risk score by assigning point values based on these ORs. The risk score had a moderate ability to predict which patients would subsequently fail medical therapy and undergo cardiac catheterization (c = 0.682). Out of a total risk score of 13, failure of medical therapy occurred in 86% of patients who had a risk score >or= 8 (n = 111), 78% of patients who had a risk score >or= 6 (n = 240), and 72% of patients who had a risk score >or= 4 (n = 438). At scores of < 2 (n = 88), 40% of patients failed medical therapy. Although the management of unstable angina is in constant evolution, clinicians will always be faced with determining which patients should be managed most invasively. The simple prediction rule we present can be applied to patients with unstable angina or non-Q-wave MI at the time of presentation to predict which patients have a high probability of failing medical therapy. Such a rule may be useful for identifying patients who should be considered for early cardiac catheterization.
Adult↗
Delayed nephrologist referral and inadequate vascular access in patients with advanced chronic kidney failure.
We sought to determine whether late referral to a nephrologist in patients with chronic renal failure influences the adequacy of vascular access for hemodialysis. We analyzed data describing all health care encounters for all Medicare and Medicaid patients with end-stage renal failure in New Jersey between January 1991 and June 1996. Patients were required to have been diagnosed with renal disease at least 1 year prior to onset of hemodialysis. In the resulting cohort of 2,398 incident hemodialysis patients, 35% had their first nephrologist consultation < or =90 days prior to initiation of dialysis. After controlling for demographic characteristics, socio-economic status and underlying renal disease, we found that patients who were referred to a nephrologist >90 days prior to onset of hemodialysis were 38% more likely to have undergone predialysis vascular access surgery than those who were referred to a nephrologist < or =90 days before dialysis [OR: 1.38; 95% CI (1.15; 1.64)]. Similarly, patients referred late were 42% more likely to require central venous access for hemodialysis compared to those seen by a nephrologist early [OR: 1.42; 95% CI (1.17; 1.71)]. Inadequate development of vascular access for renal replacement therapy in patients with late nephrologist referral unnecessarily contributes to the burden of disease experienced by this vulnerable patient population.
Adult↗
Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors.
OBJECTIVE: Addressing the epidemic of poor compliance with antihypertensive medications will require identifying factors associated with poor adherence, including modifiable psychosocial and behavioral characteristics of patients. DESIGN: Cross-sectional study, comparing measured utilization of antihypertensive prescriptions with patients' responses to a structured interview. STUDY POPULATION: Four hundred ninety-six treated hypertensive patients drawn from a large HMO and a VA medical center. DATA COLLECTION: We developed a survey instrument to assess patients' psychosocial and behavioral characteristics, including health beliefs, knowledge, and social support regarding blood pressure medications, satisfaction with health care, depression symptom severity, alcohol consumption, tobacco use, and internal versus external locus of control. Other information collected included demographic and clinical characteristics and features of antihypertensive medication regimens. All prescriptions filled for antihypertensive medications were used to calculate actual adherence to prescribed regimens in a 365-day study period. MAIN OUTCOME OF INTEREST: Adjusted odds ratios (ORs) of antihypertensive compliance, based on ordinal logistic regression models. RESULTS: After adjusting for the potential confounding effects of demographic, clinical, and other psychosocial variables, we found that depression was significantly associated with noncompliance (adjusted OR per each point increase on a 14-point scale, 0.93; 95% confidence interval [95% CI], 0.87 to 0.99); in unadjusted analyses, the relationship did not reach statistical significance. There was also a trend toward improved compliance for patients perceiving that their health is controlled by external factors (adjusted OR per point increase, 1.14; 95% CI, 0.99 to 1.33). There was no association between compliance and knowledge of hypertension, health beliefs and behaviors, social supports, or satisfaction with care. CONCLUSIONS: Depressive symptoms may be an underrecognized but modifiable risk factor for poor compliance with antihypertensive medications. Surprisingly, patient knowledge of hypertension, health beliefs, satisfaction with care, and other psychosocial variables did not appear to consistently affect adherence to prescribed regimens.
Aged↗
Preventive health care measures before and after start of renal replacement therapy.
OBJECTIVE: To describe utilization of preventive health care measures in patients with chronic kidney disease (CKD), both in the year prior to onset of renal replacement therapy (RRT), and in the first year of RRT. METHODS: We identified a large cohort of patients with CKD in the New Jersey Medicaid and Medicare programs with fixed enrollment into the cohort at 1 year prior to RRT. We applied commonly used quality assurance instruments (Health Plan Employer Data and Information Set measures) and defined levels and correlates of use of preventive care measures before and after RRT. These included mammography, Pap smear testing, prostate cancer screening, diabetic eye exams, and glycosylated hemoglobin testing (HbA1c). We employed logistic regression models with adjustment for age, race, gender, comorbidity, timing of first nephrologist contact, socioeconomic status, and calendar year of first RRT. RESULTS: Overall, screening rates were low with the exception of diabetic eye exams. Prostate cancer screening, diabetic eye exams, and HbA1c testing were performed less often after onset of RRT compared to the year before (P < .05). Although screening rates before RRT improved considerably over the period of observation for these measures (P < .05), this was not the case once patients were on RRT. CONCLUSIONS: Preventive health care interventions remain underutilized among RRT patients. Greater attention to such preventive measures could lead to significant improvements in the health status of such vulnerable patients. Thus, quality improvement of the general health care for patients on RRT should become a priority in renal health policy.
Cohort Studies↗
Urinary antispasmodic use and the risks of ventricular arrhythmia and sudden death in older patients.
OBJECTIVES: The introduction of new medications to treat overactive bladder has resulted in a significant increase in the number of individuals with this condition who use medications for symptoms. Formal epidemiological studies of the safety of these medications in typical patient populations are lacking, particularly studies of serious events. We sought to determine whether the use of urinary antispasmodics increases the risk of ventricular arrhythmias or sudden death. DESIGN: Retrospective cohort study. SETTING: Retrospective analysis of data of participants in community, hospital or nursing home setting. PARTICIPANTS: Fourteen thousand six hundred thirty-eight subjects with a diagnosis of urinary incontinence made between January 1, 1991, and June 30, 1995; all were aged 65 and older and enrolled in Medicare and Medicaid or the Pharmacy Assistance for the Aged and Disabled programs of New Jersey. MEASUREMENTS: Filled prescriptions for oxybutynin (Ditropan), flavoxate (Urispas), hyoscyamine (Cystospas), and hyoscyamine sulfate (Cystospas-M) were used to define days of exposure to these drugs. We also identified all use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors, and their concurrent use, to serve as a positive control exposure. Two outcomes were then defined: a new diagnosis of ventricular arrhythmia combined with initiation of an antiarrhythmic medication and sudden death. Other covariates, including clinical, demographic, medication use, and healthcare utilization variables, were also assessed. Adjusted risk ratios of ventricular arrhythmia and sudden death were derived from multivariable Cox proportional hazards models. RESULTS: There was no significant association between periods of use of urinary antispasmodics and the development of ventricular arrhythmias (adjusted risk ratio (RR) = 1.23, 95 confidence interval (CI) = 0.87-1.75) or sudden death (adjusted RR = 0.70, 95% CI = 0.28-1.74). A significantly increased risk of ventricular arrhythmia was observed for the positive control regimen, concurrent use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors (adjusted RR = 5.47; 95% CI = 1.34-22.26), but not for use of either drug group alone. Concurrent use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors was also associated with a significant increase in the risk of sudden death (adjusted RR = 21.50, 95% CI = 5.23-88.37). Other variables significantly associated with ventricular arrhythmia included ischemic heart disease and congestive heart failure, whereas nursing home use before the index date was associated with a decreased likelihood of receiving a diagnosis of and treatment for ventricular arrhythmia. Other variables significantly associated with sudden death included male gender, black race, and congestive heart failure. CONCLUSIONS: Antimuscarinic urinary antispasmodics available before 1996 were not associated with an increased risk of ventricular arrhythmias and sudden death. Additional study will be required to confirm these results, exclude the possibility of unmeasured confounders contributing to any lack of an observed relationship, and extend these findings to newer agents such as tolterodine.
Aged↗
Clozapine use and risk of diabetes mellitus.
Recent reports have raised the concern that clozapine increases the risk for diabetes mellitus. Accurate pharmacoepidemiologic data on whether such a hazard exists and its magnitude are needed to enable clinicians and patients to make proper treatment decisions about clozapine. The authors performed a case-control study involving 7,227 cases of newly treated diabetes and 6,780 controls, all with psychiatric disorders. Cases and controls were older than 20 years and enrolled in government-sponsored drug benefit programs in New Jersey. The authors measured the use of clozapine or other antipsychotic medications and additional covariates. They developed logistic regression models adjusted for demographic, clinical, and health care use characteristics to identify whether clozapine users were at increased risk to begin treatment for diabetes. Clozapine use was not significantly associated with developing diabetes (adjusted odds ratio [OR], 0.98; 95% confidence interval [CI], 0.74-1.31). There was no suggestion of relationships between larger dosages or longer durations of clozapine use and increasing risks of diabetes. On the other hand, nonclozapine antipsychotic medication use was associated with a modest but significantly increased risk of developing diabetes (adjusted OR, 1.13; 95% CI, 1.05-1.22). Among individual nonclozapine antipsychotics, significantly elevated risks were observed for two phenothiazine agents: chlorpromazine (adjusted OR, 1.31; 95% CI, 1.09-1.56) and perphenazine (adjusted OR, 1.34; 95% CI, 1.11- 1.62). In contrast to earlier reports, these results provide some reassurance that clozapine does not increase the risk of developing diabetes. Additional data from pharmacoepidemiologic studies and randomized controlled trials are needed to exclude the possibility of residual confounding and ensure the appropriate use of this agent.
Adult↗