Prescriber adherence to pharmacokinetic monitoring service recommendations for aminoglycoside dosing and the risk of acute kidney injury.

OBJECTIVE: The importance of adherence to aminoglycoside dosing recommendations by a pharmacokinetic monitoring service for preventing acute kidney injury (AKI) is unknown. We aimed to examine the association between AKI and discordance in aminoglycoside dosing between physician orders and recommendations by a pharmacokinetic monitoring service. MATERIALS: We utilized 2000 - 2003 data from a large quaternary care academic medical center, including: hand-written pharmacokinetic monitoring service recommendations; computerized physician order entry inpatient medication orders; and electronic inpatient laboratory orders and results. METHODS: We conducted a case-control study, nested within users of intravenous aminoglycosides. Outcomes of interest were cases of AKI, as determined by changes in serum creatinine. Exposures of interest were discordances between pharmacokinetic monitoring service recommendations and physician orders in the past 2 days with regard to total daily aminoglycoside dose. RESULTS: Most patients received once-daily or less frequent aminoglycoside dosing. In 1,414 evaluable aminoglycoside courses, 220 patients developed AKI, for a cumulative incidence of 15.6%. We identified 690 controls, matched these to 220 cases, and found adjusted odds ratios of 0.72 (95% CI: 0.37 - 1.39) for overdose discordance and of 0.83 (0.51 - 1.34) for underdose discordance, suggesting that discordance in dosing is not associated with AKI. CONCLUSION: Non-adherence to dosing recommendations for aminoglycosides was not associated with risk of AKI in a setting primarily of once-daily aminoglycoside administration.

Pharmacogenetic modulation of combined hormone replacement therapy by progesterone-metabolism genotypes in postmenopausal breast cancer risk.

Combined hormone replacement therapy (CHRT) containing estrogens and progestins is associated with breast cancer risk. The authors evaluated interactions between CHRT use and progestin metabolism genotypes at CYP3A4 and the progesterone receptor (PGR) and their effects on breast cancer risk using the population-based Women's Insights and Shared Experiences (WISE) Study (1999-2002) of postmenopausal Caucasian women (522 breast cancer cases, 708 controls). The authors observed an elevated risk of ductal tumors in women with 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.35, 95% confidence interval (CI): 1.13, 9.99; two-sided p(interaction) = 0.035). They also observed an elevated risk of progesterone receptor-positive tumors in women who had had 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.82, 95% CI: 1.26, 11.55; p = 0.028). Finally, they observed an increased risk of estrogen receptor-negative tumors in women without CHRT exposure and CYP3A4*1B alleles compared with those who had neither factor (odds ratio = 6.46, 95% CI: 2.02, 20.66; p = 0.024), although the biologic interpretation of this result requires further study. When stratified by recency of use, PGR effects were observed only in current CHRT users, while CYP3A4 effects were observed only in former CHRT users. Breast cancer risk in women who have used CHRT may be influenced by genetic factors involved in progestin metabolism.

Defining optic nerve tortuosity.

BACKGROUND AND PURPOSE: Optic nerve tortuosity is one of several nonmalignant abnormalities documented on MR imaging in patients with neurofibromatosis type 1 and may be related to the development of optic pathway gliomas. This study seeks an operational definition for optic nerve tortuosity. MATERIALS AND METHODS: A focus group of 3 pediatric neuroradiologists reviewed 20 MR images of the brain and orbits of patients suspected to have optic nerve tortuosity in the absence of optic pathway glioma and found 6 radiographic factors that occurred frequently. Subsequently, 28 MR images were assessed for the presence of optic nerve tortuosity, using a global assessment question that reflects a neuroradiologist's confidence in the presence of optic nerve tortuosity, and for the presence of the 6 radiographic factors, to identify a combination of these factors that best predicted a diagnosis of optic nerve tortuosity. RESULTS: We found perfect inter-rater agreement between 3 readers on the presence/absence of tortuosity in 75% of cases. Lack of congruity of the optic nerves, in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves, when found together are sensitive (89%) and specific (93%) for a diagnosis of tortuosity on the global scale. The absence of these 2 factors, along with absence of deviation of the optic nerve within the axial plane, provides a reliable test to exclude tortuosity. CONCLUSION: Lack of congruity of the optic nerves in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves together provide an operational radiographic definition of optic nerve tortuosity.

Pathophysiology of tumor progression in human gallbladder: flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease.

Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.

International variations in epidemiology of cancers of the extrahepatic biliary tract.

Previous studies of the descriptive epidemiology of biliary tract cancers have not differentiated among different types of biliary tract cancer because until recently the International Classification of Diseases (ICD) did not classify them separately. Recent versions of the ICD now distinguish cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater. In order to describe more precisely the distribution of these three cancers, we obtained data from nine cancer registries throughout the world which used the eighth or ninth revision of the ICD. Sex-specific, age-adjusted disease rates were calculated for each disease. Log-linear models were used to evaluate the association of age and sex with the risk of acquiring each disease and to assess whether the risk of acquiring disease or the age and sex distribution of the three diseases varied by geographic location. Gallbladder cancer was the most common of the three diseases and occurred more frequently in females. Extrahepatic bile duct cancer was the next most common disease and occurred equally in both sexes. Cancer of the ampulla of Vater was the least common and was more common in males. The incidence of each of the diseases increased with age. The age and sex distributions of the different diseases different among the nine registries. Thus these three neoplasms differ in their descriptive epidemiology and should therefore be considered separately in clinical practice and in future investigations.

Risk factors for infective endocarditis: oral hygiene and nondental exposures.

BACKGROUND: The risks of infective endocarditis (IE) associated with various conditions and procedures are poorly defined. METHODS AND RESULTS: This was a population-based case-control study conducted in 54 Philadelphia, Pa-area hospitals from 1988 to 1990. Community-acquired IE cases unassociated with intravenous drug use were compared with matched community residents. Subjects were interviewed for risk factors. Diagnoses were confirmed by expert review of medical record abstracts with risk factor data removed. Cases were more likely than controls to suffer from prior severe kidney disease (adjusted OR [95% CI]=16.9 [1.5 to 193], P:=0.02) and diabetes mellitus (adjusted OR [95% CI]=2.7 [1.4 to 5.2], P:=0.004). Cases infected with skin flora had received intravenous fluids more often (adjusted OR [95% CI]=6.7 [1.1 to 41], P:=0.04) and had more often had a previous skin infection (adjusted OR [95% CI]=3.5 [0.7 to 17], P:=0.11). No association was seen with pulmonary, gastrointestinal, cardiac, or genitourinary procedures or with surgery. Edentulous patients had a lower risk of IE from dental flora than patients who had teeth but did not floss. Daily flossing was associated with a borderline decreased IE risk. CONCLUSIONS: Within the limits of the available sample size, the data showed that IE patients differ from people without IE with regard to certain important risk factors but not regarding recent procedures.

Invasive pulmonary aspergillosis in adult acute leukemia: clinical clues to its diagnosis.

Invasive pulmonary aspergillosis, a leading cause of morbidity and mortality in patients with acute leukemia, is difficult to diagnose antemortem because its signs and symptoms are ill-defined. To refine the clinical description of this infection, we reviewed our experience with 15 pathologically documented cases of invasive pulmonary aspergillosis in a population of 60 patients treated for acute leukemia. Findings occurring significantly more often (P less than or equal to .001) among cases than controls included pleuritic chest pain; acute sinus tenderness, and nasal discharge, epistaxis and eschar; rales; development of multilobar infiltrates after the 14th hospital day; and presence of nodular or cavitary infiltrates. In addition, patients with invasive pulmonary aspergillosis had a significantly prolonged duration of granulocytopenia, more febrile days and febrile episodes without a fever diagnosis and more febrile days on antibiotics (P less than or equal to .001 in all). This complex of findings should improve the clinician's ability to diagnose invasive pulmonary aspergillosis in patients with acute leukemia.

Development and validation of simplified predictive index for major complications in contemporary percutaneous transluminal coronary angioplasty practice. The Registry Committee of the Society for Cardiac Angiography and Interventions.

OBJECTIVES: This study was designed to determine the preprocedural risk factors for major complications (emergent coronary bypass surgery, myocardial infarction or death) of coronary angioplasty and to derive and validate a simplified index that predicts patients' a priori risk of complications. BACKGROUND: Previous studies of risk factors for complications after coronary angioplasty may not be generalizable to current, broad-based angioplasty practice. Furthermore, to our knowledge a clinically useful predictive index has not been derived and independently validated. METHODS: From data collected prospectively for the Registry of the Society for Cardiac Angiography and Interventions for 1992, multivariable logistic regression was used to determine which variables were independently associated with complications in 10,622 first angioplasty procedures. Stepwise regression and receiver operating characteristic curves then were used in this registry to develop a predictive index for complications that was validated using 5,250 first angioplasty procedures in the 1993 registry. RESULTS: Predictors of major complications were multivessel disease, unstable angina, recent myocardial infarction, type C lesion or left main angioplasty, shock, age, geographic region and absence of previous coronary bypass surgery. The derived predictive index consisted of the first six of these variables plus aortic valve disease and classified patients into four risk groups: low (1.3% complications), moderate (2.8%), high (12.7%) and very high (29.7%) risk. This index demonstrated consistent reliability and discriminatory ability when applied to the 1993 data. CONCLUSIONS: Predictors of major complications identified in selected populations also apply currently in broad-based practice. From these variables, a predictive index can stratify patients into risk groups before angioplasty, thus aiding in risk assessment, resource allocation and risk adjustment.

Risk of major complications from coronary angioplasty performed immediately after diagnostic coronary angiography: results from the Registry of the Society for Cardiac Angiography and Interventions.

OBJECTIVES: This study was designed to determine the risk of performing percutaneous transluminal coronary angioplasty (PTCA) at the time of diagnostic catheterization ("combined procedures"). BACKGROUND: Health care providers are under increasing pressure to combine diagnostic and interventional coronary procedures to reduce costs. However, the risk associated with combined procedures has not been rigorously assessed. METHODS: A multicenter cohort study of 35,700 patients undergoing elective PTCA from 1992 through 1995 was performed to determine the risk of major complications (myocardial infarction, emergency coronary artery bypass graft surgery or death) from combined relative to staged procedures (i.e., performing PTCA at a session subsequent to diagnostic catheterization). RESULTS: The risks of major complications from combined and staged procedures were 2.0% and 1.6%, respectively (unadjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.05 to 1.57). After adjusting for clinical and angiographic differences and clustering by laboratory, the risk from combined procedures was not significantly elevated (multivariable OR 1.18, 95% CI 0.89 to 1.55). However, several subgroups of patients did have an increased risk from combined procedures: patients with multivessel disease (multivariable OR 1.64, 95% CI 1.13 to 2.39); women (multivariable OR 1.64, 95% CI 1.05 to 2.55); patients > 65 years old (multivariable OR 1.40, 5% CI 1.02 to 1.93); and patients undergoing multilesion PTCA (multivariable OR 1.53, 95% CI 1.06 to 2.21). The risk of combined relative to staged procedures decreased over the 4-year period (multivariable p = 0.029). CONCLUSIONS: Combining PTCA with diagnostic catheterization appears to be safe in many patients. However, several subgroups of patients may be at increased risk. Careful patient selection will most likely remain critical to ensuring the safety of combined procedures.

Risk factors for clinically important adverse events after protamine administration following cardiopulmonary bypass.

OBJECTIVES: The purpose of this study was to determine risk factors for adverse events following protamine administration after cardiopulmonary bypass. BACKGROUND: Intravenous protamine administration is associated with a risk of severe systemic reactions. However, risk factors for these events have not been well delineated, thus hampering development of preventive strategies. METHODS: A case-control study nested within a cohort of consecutive patients undergoing surgery requiring cardiopulmonary bypass was performed. The primary case definition included those events (pulmonary hypertensive and systemic hypotensive) occurring within 10 min of protamine administration in the absence of other measurable causes of hemodynamic compromise. RESULTS: Comparing the 53 cases to the 223 control subjects, three risk factors were independently associated with events (multivariable odds ratio [95% confidence interval]): neutral protamine Hagedorn insulin use (8.18 [2.08, 32.2]); fish allergy (24.5 [1.24, 482.3]), and a history of nonprotamine medication allergy (2.97 [1.25, 7.07]). These risk factors demonstrated an increasingly strong association with progressively more specific case definitions. An estimated 39% of cardiopulmonary bypass patients had one or more of these risk factors. Prior intravenous protamine, central venous pressure prior to protamine, preoperative ejection fraction and the need for inotropes when coming off bypass did not exhibit statistically significant associations with events (all p > 0.15). Prior protamine allergy was associated specifically with an increased risk of pulmonary hypertension (multivariable odds ratio 189; 95% confidence interval 13, 2,856). CONCLUSIONS: Immunologic factors are important in predisposing individuals to protamine reactions, and a substantial proportion of patients are at considerably increased risk Strategies to reduce the risk of protamine-associated events are needed.

Risk of acute first myocardial infarction and use of nicotine patches in a general population.

OBJECTIVES: To determine if nicotine patches, both as prescribed and used over-the-counter, increase the risk of first myocardial infarction (MI). BACKGROUND: Although nicotine patches improve smoking cessation rates, case reports have raised the hypothesis that they may increase the risk of MI. METHODS: A population-based case-control study among 68 hospitals in an eight-county region surrounding Philadelphia was performed to determine if nicotine patches increase the risk of first MI. Cases were smokers (current or within the prior year) admitted to all hospitals in the region with a first MI. Controls were smokers (current or within the prior year) without prior MI selected from the same region using random-digit dialing. Data were collected by telephone interviews and chart reviews. The study had 80% power to detect an odds ratio (OR) of 2.5. RESULTS: A total of 653 cases and 2,990 controls were interviewed. There was no association between nicotine patches and MI (OR 0.46; 95% CI: 0.09, 1.47), and the confidence interval (CI) excluded an effect from nicotine patches equal to that from cigarette smoking itself (OR < 2.5). Among those who abstained from smoking, the OR for use of nicotine patches was 0.25 (95% CI: 0.01, 1.67); among those who smoked concomitantly, the OR for patch use was 0.83 (95% CI: 0.09, 3.81). Adjustment for confounding did not alter the study's findings (OR adjusted for confounders that could mask a harmful effect of patches: 0.70; 95% CI: 0.20, 2.46). CONCLUSIONS: Nicotine patches, as used in actual practice, do not appear to be associated with an increased risk of MI.

Frequency and morbidity of invasive procedures: report of a pilot study from two teaching hospitals.

The medical services of two teaching hospitals were assessed for the frequency of and complications from invasive procedures. There were 231 procedures performed on 303 patients. The frequency of procedures was significantly higher at one hospital (62% vs 39%, P less than .01). Twenty-nine complications occurred in 20 cases: 14% of patients who underwent procedures had at least one complication. Left-sided cardiac catheterization was the most common procedure. Procedures with more than one complication included the following: left-sided cardiac catherization (18% probability of complication); arteriovenous shunt (60% probability); thoracentesis (19%); bronchoscopy (25%); and percutaneous liver biopsy (8%). While no permanent damage or deaths were observed, over three fourths of the complications either required specific therapy or prolonged hospitalization or both. This study suggests invasive procedures are common and carry appreciable risks of serious complications. Appropriate clinical decision making and medical-legal protection require accurate estimates of those risks.

Safety of nonsteroidal anti-inflammatory drugs with respect to acute liver disease.

OBJECTIVE: To examine the magnitude of the risk of acute hepatitis associated with the use of nonsteroidal antiinflammatory drugs. METHODS: We calculated the annual incidence rate of hepatitis resulting in hospitalization and then performed a case-control study using 1980 to 1987 Medicaid billing data from Michigan and Florida. The 107 cases included patients with symptomatic acute hepatitis without an identifiable cause of liver disease. Four controls per case were randomly selected and were matched for age, sex, and state. Antecedent drug exposure was assessed 30 days prior to the onset of the disease in the cases and during the same period in the controls. RESULTS: The annual incidence rate (95% confidence interval) of acute idiopathic symptomatic hepatitis resulting in hospitalization was 2.2 (2.0 to 2.4) per 100,000 persons per year. Nine cases (8.4%) and 26 controls (6.1%) were exposed to nonsteroidal anti-inflammatory drugs, yielding an odds ratio of 1.4 (0.6 to 3.1). After adjustment for potential confounding variables, the odds ratio was 1.2 (0.5 to 2.8). CONCLUSIONS: Acute symptomatic idiopathic liver disease severe enough to result in hospitalization is uncommon, and no association was evident between nonsteroidal anti-inflammatory drugs and acute hepatitis. This study was large enough to exclude a relative risk of 2.8. These data suggest that acute symptomatic liver disease from nonsteroidal anti-inflammatory drugs is not a frequent clinical problem.

Risk factors for the development of hyponatremia in psychiatric inpatients.

BACKGROUND: When inpatients who are on psychiatry services develop hyponatremia, medical consultation is usually required for evaluation and management, thus halting or delaying psychiatric treatment. Risk factors for the development of hyponatremia in this population have not been studied. METHODS: A case-control study of psychiatric inpatients in a tertiary care facility was performed. Sixty-four patients who had a serum sodium level of less than 130 mmol/L were identified; three control subjects were chosen from the inpatient psychiatry service for each case. Risk factors investigated included medications, psychiatric diagnoses, basic demographic variables, and medical comorbidities. RESULTS: Univariate and logistic regression analyses revealed that, in addition to diuretic use (adjusted odds ratio, 8.2; 95% confidence intervals, 2.2 to 30.8), use of fluoxetine (adjusted odds ratio, 21.4; 95% confidence interval, 5.3 to 86.9), tricyclic antidepressants (adjusted odds ratio, 4.9; 95% confidence interval, 1.6 to 15.2), and calcium antagonists (adjusted odds ratio, 4.0; 95% confidence interval, 1.1 to 14.2) were all associated with the development of hyponatremia. Important comorbidities included elevated creatinine levels, chronic obstructive pulmonary disease, hypertension, systolic blood pressure, and diabetes. Although age was significantly associated with hyponatremia in univariate analyses, it was not significant in multivariate analyses. CONCLUSIONS: Among psychiatric patients, hyponatremia is often associated with factors other than psychogenic polydipsia, including medications and medical comorbidities. Although elderly psychiatric inpatients seem to develop hyponatremia more often than younger patients, once drugs and comorbidities are taken into account, age does not appear to be a significant risk factor for hyponatremia in this population.

Nonsteroidal anti-inflammatory drugs and neutropenia.

BACKGROUND: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and neutropenia is based primarily on case reports only. METHODS: A population-based, case-control study was performed with Medicaid claims data from six states. Cases were defined as patients hospitalized with neutropenia. Four controls per case were randomly chosen, matched for age, sex, state, and year. The frequency of exposure to NSAIDs in the 30 days before hospital admission in the cases was compared with the frequency in the identical period in the controls. The diagnosis of neutropenia was validated by review of medical records. RESULTS: The crude odds ratio for NSAIDs as a class was 3.3 (90% confidence interval, 1.6 to 6.6). The multivariate adjusted odds ratio was 4.2 (90% confidence interval, 2.0 to 8.7). No single class of NSAID, nor any individual NSAID, was associated with a unique risk, although the data on individual NSAIDs were sparse. Even excluding phenylbutazone and indomethacin, an increased risk was observed (3.5 [1.6 to 7.6]). CONCLUSIONS: Neutropenia is associated with the use of NSAIDs. However, given the low incidence of this disease, the additional number of cases of neutropenia caused by the use of NSAIDs is small. These data do not support the existence of a risk restricted to selected NSAIDs only.

Descriptive epidemiology of agranulocytosis.

BACKGROUND: To determine the incidence of agranulocytosis, a descriptive epidemiologic study was performed. METHODS: With the use of computerized Medicaid billing data from 1980 through 1985 from Minnesota, Michigan, and Florida, the ratio of persons hospitalized with a discharge diagnosis of neutropenia to persons with any claim for medical service was first used as an estimate of the incidence rate of the condition. Patients with cancer and patients receiving cytotoxic and immunosuppressive drugs were excluded. The information provided by a review of medical records for a subset of neutropenia cases was used to determine the proportion with neutropenia after excluding cases with recurrent or chronic neutropenia, and to determine the proportion with agranulocytosis. RESULTS: The incidence rates (95% confidence intervals) of agranulocytosis, excluding recurrent or chronic disease, were 2.3 (1.4 to 3.7), 7.7 (6.6 to 8.9), and 15.4 (11.3 to 20.4) per million per year in each state, respectively. The overall incidence was 7.2 (6.3 to 8.1) per million per year. CONCLUSIONS: Agranulocytosis is an extremely uncommon condition. The excess risk of agranulocytosis due to any drug other than cytotoxic drugs must, therefore, be very low.

The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding.

To evaluate the risk of developing upper gastrointestinal (UGI) bleeding from nonsteroidal anti-inflammatory drugs (NSAIDs), a retrospective (historical) cohort study was performed, using a computerized data base including 1980 billing data from all Medicaid patients in the states of Michigan and Minnesota. Comparing 47,136 exposed patients to 44,634 unexposed patients, the unadjusted relative risk for developing UGI bleeding 30 days after exposure to a NSAID was 1.5 (95% confidence interval 1.2 to 2.0). Univariate analyses demonstrated associations between UGI bleeding and age, sex, state, alcohol-related diagnoses, preexisting abdominal conditions, and use of anticoagulants. This association between NSAIDs and UGI bleeding was unchanged after adjusting for these potential confounding variables using logistic regression. A linear dose-response relationship and a quadratic duration-response relationship were demonstrated. Non-steroidal anti-inflammatory drugs are associated with UGI bleeding, although the magnitude of the increased risk is reassuringly small.

Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen.

BACKGROUND: The risk of gastrointestinal tract bleeding requiring hospitalization associated with naproxen sodium was compared with that with ibuprofen, using a prescription database to approximate over-the-counter dosing. OBJECTIVE: To evaluate the safety of naproxen sodium. METHODS: A claims database containing Ohio Medicaid data from January 1986 through February 1993 and Michigan Medicaid data from April 1983 through July 1993 was used to compare 101,318 patients dispensed naproxen sodium with 277,601 patients dispensed ibuprofen. Using a case-cohort design, all 59 patients from the full cohort who had been hospitalized with upper gastrointestinal tract bleeding (UGIB) that developed within 14 days after the first prescription for the study drugs were compared with a subcohort made up of a 10% random sample of subjects selected from the combined drug cohorts. RESULTS: The incidence of UGIB occurring within 14 days after the first prescription in the naproxen sodium cohort was 26 (0.026%) of 101,318 (95% confidence interval [CI], 0.017%-0.038%), compared with 33 (0.012%) of 277,601 patients (95% CI, 0.008%-0.017%) in the ibuprofen cohort. Overall, the use of naproxen sodium vs ibuprofen was associated with an adjusted relative risk of 2.0 (95% CI, 1.1-3.8). Among people with multiple prescriptions, the crude relative risk for those receiving therapy in a dose typical of over-the-counter use was 4.1 (95% CI, 1.2-13.8). CONCLUSIONS: The overall incidence of UGIB is low with both drugs. There is little additional absolute risk posed by the use of low-dose naproxen sodium, compared with low-dose ibuprofen, despite an increased relative risk. However, given the widespread use of these drugs, a substantial number of additional cases of UGIB could result from use of naproxen sodium. This increased risk should be considered, especially for patients whose baseline risk of UGIB is elevated.

Effects of coronary stents on cardiovascular outcomes in broad-based clinical practice.

BACKGROUND: Although stents have been shown to reduce the need for repeated percutaneous coronary intervention (PCI) in randomized trials, the effects of stents in broad-based, diverse clinical practice have not been well studied, nor has their effect on subsequent myocardial infarction or cardiac death. METHODS: A retrospective cohort study was performed that included all 43 hospitals performing PCI in Pennsylvania in the last quarter of 1995, with the use of the Pennsylvania Health Care Cost Containment Council database. All 5258 patients who underwent PCI, excluding those with previous PCI within the preceding 6 months, were included. The primary outcomes were in-hospital events (death or coronary bypass), 6-month revascularization rates, and 6-month rates of cardiac death or myocardial infarction. RESULTS: A total of 1240 patients (24%) had a stent procedure. Compared with nonstent procedures, stents reduced the risk of in-hospital events (multivariable odds ratio adjusted for patient and hospital level differences, 0.63; 95% confidence interval, 0.41-0.97), primarily because of a 52% reduction in the need for coronary bypass. Stents also reduced the need for follow-up revascularization procedures (multivariable hazard ratio, 0.72; 95% confidence interval, 0.59-0. 87), primarily because of a 31% reduction in repeated PCI. However, stents had no effect on 6-month rate of myocardial infarction or cardiac death (multivariable hazard ratio, 0.97; 95% confidence interval, 0.71-1.33). CONCLUSIONS: Using stents decreases the need for repeated PCI in broad-based clinical practice, confirming results from randomized trials. However, this study did not detect any effect on subsequent myocardial infarction or cardiac death.

Upper gastrointestinal tract bleeding from oral potassium chloride. Comparative risk from microencapsulated vs wax-matrix formulations.

A retrospective cohort study was performed to assess the relative risk of upper gastrointestinal (UGI) tract bleeding from two formulations of potassium chloride. Relevant information was obtained from 1980 through 1984 Medicaid billing data from the states of Michigan, Minnesota, Florida, and Ohio. After patients with a history of UGI tract bleeding prior to their first prescription for either of the two potassium chloride preparations under study were excluded, data were analyzed for 28,790 patients (143,512 patient-months) dispensed a microencapsulated formulation exclusively and 76,118 patients (560,341 patient-months) dispensed a wax-matrix formulation exclusively. The risk of UGI tract bleeding within 30 days after each prescription for the drug of interest was examined. After sampling from the undiseased study subjects and adjusting for multiple potential confounding variables using logistic regression, an odds ratio (95% confidence interval) of 0.67 (0.52 to 0.85) was observed.