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Biomedical subjects

J L Bauman

Publications and source records attributed to J L Bauman.

At least 19 recordsLinked to original sources

Impact of the cost of prescription drugs on clinical outcomes in indigent patients with heart disease.

STUDY OBJECTIVE: To measure the impact that economic relief for prescription drugs to indigent patients with cardiovascular disease has on indicators of disease control. DESIGN: Prospective cohort study. SETTING: University inner-city outpatient clinic. PATIENTS: One hundred sixty-three indigent patients with heart disease who were uninsured or whose insurance plan did not provide prescription drug coverage and who had baseline data. INTERVENTION: Patients were assisted in obtaining prescription drugs, free of charge, in an attempt to improve adherence to their drug regimens. MEASUREMENTS AND MAIN RESULTS: The primary end point was to determine if cardiovascular outcome measures (i.e., international normalized ratio [INR], blood pressure, low-density lipoprotein [LDL] cholesterol, and hospitalizations) and drug adherence improved in all patients after 6 months of prescription assistance compared with a 6-month baseline period. In patients receiving warfarin, mean INR increased from 2.44 +/- 0.64 at baseline to 2.61 +/- 0.53 at 6 months (p<0.05). In patients with hypertension, mean blood pressure decreased from 138 +/- 20/80 +/- 11 mm Hg at baseline to 138 +/- 19/78 +/- 12 mm Hg at 6 months (p<0.05 for diastolic blood pressure only). The mean LDL level for patients on lipid-lowering drugs significantly decreased from 126 +/- 39 mg/dl at baseline to 108 +/- 38 mg/dl at 6 months (p<0.001). For each disease measure, the improved disease control seen at 6 months persisted throughout 24 months of follow-up. Hospitalizations for the entire cohort decreased from 85 at baseline to 49 at 6 months. Patient drug adherence improved from 48.5% at baseline to 72.7% at 6 months (p<0.001). CONCLUSIONS: Drug adherence and clinical outcomes improved, and the number of hospitalizations declined when cardiovascular drugs were obtained for patients who could not afford to pay for them. Health care insurance plans that do not provide coverage for cardiovascular prescription drugs may be more costly secondary to poor disease control and increased hospitalizations.

Cholesterol, LDL↗

Analysis of the use of digoxin immune fab for the treatment of non-life-threatening digoxin toxicity.

BACKGROUND: Studies indicate that digoxin toxicity often results in lengthy hospitalizations and considerable costs, both of which may be decreased through the routine use of digoxin immune Fab (FAB). METHODS: A computer-based decision analysis model was developed to compare the treatment of non-life-threatening digoxin toxicity with either FAB or standard therapy from the hospital perspective. A cost-minimization analysis was then performed to compare overall total costs (primary endpoint) for each treatment branch. A secondary endpoint of length of hospital stay (LOS) was also compared between the 2 groups. Clinical variables (serum digoxin concentration [SDC], creatinine clearance [Clcr], and body weight), event probabilities, and other model-specific variables were varied in univariate and multivariate sensitivity analyses. RESULTS: FAB was associated with an incremental cost of $54 compared with standard therapy ($2,784 vs. $2,730, respectively) but reduced LOS by 1.5 days (1.5 days vs. 3.0 days, respectively). Sensitivity analyses show that FAB is less costly at SDC > 3.5 ng/mL and Clcr < 22 mL/min. FAB reduced LOS at SDC > 2.3 ng/mL. Monte Carlo simulation revealed that FAB was less costly in 37% of the cases and reduced LOS 72% of the time compared with standard therapy. CONCLUSIONS: The abbreviated LOS associated with the use of FAB in patients with non-life-threatening digoxin toxicity may translate into lower treatment costs in many clinical scenarios, making it a cost-saving alternative to standard therapy in patients with high SDC and renal dysfunction.

Cardiotonic Agents↗

Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients.

The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily doses for 14 days. Blood pressures, heart rates, P-R intervals; and serum concentrations of R-/S-verapamil and norverapamil were measured multiple times in patients during the last day of each therapy. Median blood pressure decreased more with generic verapamil than with the brand-name drug, with the largest difference occurring at 0.5 hours (137/74 mmHg versus 144.5/80.5 mmHg; P = 0.05 and 0.091, respectively). Pharmacokinetic parameters were not different for the two products (P < 0.01). However, the generic product, compared with the brand-name drug, had mean area under the concentration-time curve (time 0 to 12 hours) ratios (90% CI) of 1.09 (0.78-1.52), 1.16 (0.87-1.55) and 1.11 (0.81-1.52) for R-, S-, and total verapamil. Seventy concentration peaks (31 with the brand-name drug, 39 with the generic drug) appeared between 8 and 24 hours. Median percentages of increase of these peaks, compared with those of previous concentrations, were 48.3% and 36.3% for brand-name and generic drugs, respectively. Fifty of the 70 peaks (71%) were associated with a stereospecific concentration peak of norverapamil and, temporally, with meals. Our findings suggest that whereas the two verapamil products may not be bioequivalent by Food and Drug Administration criteria, the observed differences in effects were not clinically significant in this elderly population. Multiple concentration peaks after absorption were observed in all patients with both verapamil products and were perhaps related to enterohepatic recirculation.

Aged↗

Evaluation of two forms of sustained release nifedipine using 24 h ambulatory blood pressure monitoring.

Therapeutic interchange between the available forms of sustained release nifedipine (osmotic-pump and coat-core forms of nifedipine) is a matter of controversy. This study was initiated to determine whether there is a difference in clinical outcomes when there is interchange between the two forms of sustained release nifedipine when used for the treatment of hypertension. A total of 43 patients with a history of stage I hypertension who were receiving stable doses of the osmotic-pump form of nifedipine for > 3 months with controlled blood pressures (< 150/90 mm Hg) were enrolled. Patients were then switched to the same dose of the coat-core form of nifedipine and were followed for 3 months. In the 36 patients who completed the study, mean trough serum nifedipine concentrations were significantly higher with the osmotic-pump from (46.5 +/- 35.0 ng/mL) of nifedipine compared with the coat-core form (27.2 +/- 20.4 ng/mL) (P < .05). However, blood pressure control as determined by the indices of 24 h ambulatory blood pressure monitoring, trough blood pressures and load blood pressures were similar between the osmotic-pump and coat-core forms of nifedipine. The coat-core form of nifedipine was discontinued in four patients for possible side effects. In this group of patients with mild hypertension, there were no clinically relevant differences in blood pressure control between the two forms of nifedipine. Some patients on the coat-core form of nifedipine may need to discontinue therapy due to intolerable side effects.

Aged↗

Economic impact of digoxin toxicity.

The costs of digoxin toxicity to the US healthcare system have not been previously reported. Therefore, the 1994 database of US University Health-System Consortium (UHC) was searched for cases of digoxin toxicity using the International Classification of Diseases (9th edition) [ICD-9] codes. In addition, the medical records of 17 patients admitted to the University of Illinois Hospital from September 1994 to July 1995 with a diagnosis of digoxin toxicity were also reviewed. Of the 17 patients, 14 were admitted with a primary diagnosis of digoxin toxicity. Causes of digoxin toxicity were worsening renal function (6 patients), excessive dosage prescribed (4 patients), excessive dosage self-administered (2 patients), multiple prescriptions (2 patients), accidental ingestion (1 patient), drug-drug interaction (1 patient) and unknown (1 patient). Digoxin toxicity could have been prevented in 9 (53%) of the 17 patients. The mean length of stay in the hospital as a result of digoxin toxicity was 3.3 +/- 1.2 days. The mean laboratory cost associated with digoxin toxicity was $US275.54 +/- $US106.57 and the mean hospital bed cost was $US3781.92 +/- $US2572.22. The mean overall cost associated with digoxin toxicity was $US4087.05 +/- $US2659.76. There was a significant correlation between the total cost associated with digoxin toxicity and the serum digoxin concentration on admission (r = 0.73, p < 0.01). From the UHC database, a total of 836 cases of digoxin toxicity in 56 hospitals were identified. This represented the occurrence of digoxin toxicity in 0.07% of all patients admitted to these US academic hospitals. Digoxin toxicity results in considerable costs to the healthcare system. Most cases can be considered readily preventable with proper patient counselling and education.

Adolescent↗

Serum nifedipine concentrations and response of patients with pulmonary hypertension.

In patients with primary pulmonary hypertension who respond to nifedipine during acute drug testing, there is a significant linear correlation of serum nifedipine concentration with pulmonary artery pressure and resistance. Although most demonstrate an initial response at readily attainable nifedipine concentrations with conventional dosages, a subset of patients seem to display delayed or incomplete oral absorption; these results may facilitate the clinical use of nifedipine in patients with primary pulmonary hypertension.

Adult↗

Pharmacologic profile of survivors of acute myocardial infarction at United States academic hospitals.

Optimal drug therapy for patients with acute myocardial infarction (AMI) is well described in the medical literature. However, data on the actual pharmacologic management of patients surviving AMI at academic hospitals is unavailable. The purpose of this study was to document treatment profiles in 500 patients surviving AMI at 12 academic hospitals in the United States. These profiles were compared with established guidelines and were evaluated for trends. Overall, thrombolytics (streptokinase > or = tissue-type plasminogen activator) were administered in 29% of the patients, with a greater proportion of patients receiving beta-blockers than calcium channel antagonists in the initial 72 hours (61% vs 40%; p < 0.005) and at discharge (51% vs 35%; p < 0.005). Further, women were less likely than men to receive thrombolytic therapy (odds ratio [OR] = 0.61; confidence interval [CI], 0.54 to 0.69) or beta-blocker therapy within the first 72 hours (OR = 0.61; CI, 0.55 to 0.67) or at hospital discharge (OR = 0.53; CI, 0.48 to 0.58). Overall, improvements could still be made in the number of patients who receive thrombolytic and acute and chronic beta-blocker therapies after AMI, particularly in women. Changes in treatment profiles may be a reflection of the publication of large clinical trials.

Adrenergic beta-Antagonists↗

Cocaine concentration-effect relationship in the presence and absence of lidocaine: evidence of competitive binding between cocaine and lidocaine.

UNLABELLED: To better understand the interaction between cocaine and lidocaine, we studied the cocaine's concentration-effect relationship for action potential duration (APD) and the rate of rise of phase 0 of the action potential (Vmax) of canine papillary muscle in the presence and absence of lidocaine. We measured APD and Vmax during programmed stimulation and superfusion with normal Tyrode's, 30 microM cocaine and 30 microM cocaine + 30 microM lidocaine. Using two microelectrodes, we simultaneously recorded action potentials from two sites during programmed stimulation and measured the conduction velocity and effective refractory period during exposure to normal Tyrode's, cocaine and cocaine + lidocaine. Cocaine with or without lidocaine delayed the plateau of the APD restitution curve. At 1000 msec cycle length, the addition of 30 microM lidocaine to the superfusate containing 30 microM cocaine shortened the time constant for reactivation of Vmax from 514 +/- 63 to 234 +/- 28 msec (P < .01). Lidocaine also improved the conduction velocity decreased by cocaine, but did not significantly change the effective refractory period. The configuration of cocaine concentration-effect curve for APD was biphasic. For cocaine concentrations < 100 microM, APD progressively shortened prolonged with increasing concentrations. As cocaine concentrations increased > 100 microM, APD progressively shortened. The addition of lidocaine to the superfusate with cocaine > 100 microM tended to attenuate the progressive APD shortening due to cocaine. Lidocaine shifted the curve correlating cocaine concentration and reduction of Vmax rightward, but preserved Emax at cocaine concentration > 225 microM. These findings suggest competitive antagonism between cocaine and lidocaine at a single sodium channel receptor. CONCLUSION: lidocaine displaces cocaine from the sodium channel receptor through competitive binding. Lidocaine may prove to be beneficial in reversing cocaine-induced slowing of ventricular conduction.

Action Potentials↗

Prescribing trends and pharmacoeconomic considerations in the treatment of arrhythmias. Focus on atrial fibrillation and flutter.

Considerable progress has been made regarding the treatment of atrial fibrillation and atrial flutter. However, controversies still exist with respect to the therapy of choice for ventricular rate control, requirements for long term preventive therapy, and the place of surgical and ablation alternatives. Surrounding these controversies also lies a paucity of pharmacoeconomic studies, which limits delineation of the most cost-effective therapy for patients with atrial fibrillation and atrial flutter. This article reviews prescribing trends in the US for antiarrhythmic agents, and the available pharmacoeconomic studies that have specifically addressed the treatment of atrial fibrillation and atrial flutter.

Arrhythmias, Cardiac↗

Bioavailability of total and unbound disopyramide: implications for clinical use of the immediate and controlled-release dosage forms.

This study further characterized the impact of concentration-dependent protein binding on the bioavailability and clinical use of the immediate-release (IR) and controlled-release (CR) dosage forms of disopyramide after single doses and during steady-state conditions in ten healthy volunteers. Consistent with the clinical use of these products, steady state has incorporated an IR to CR conversion step. Side effects and electrocardiographic actions were quantitated using a visual analog scale and serial Holter monitor recordings, respectively. Significant decreases resulted in area under the curve for total disopyramide between single dose and steady state: IR, 47.8 +/- 13.6 versus 33.0 +/- 6.4 mg/Lxh (P < .05); and CR, 46.9 +/- 9.5 versus 31.7 +/- 5.9 mg/Lxh (P < .05). In contrast, there were no differences in area under the curve for unbound disopyramide between phases or products. During conversion, the mean IR peak significantly decreased (P < .05) to the nadir before the first CR dose for total (37%) and unbound (60%) concentrations. There were no major differences in change in QT interval or side effects detected between products or phases. These findings indicate that, because of concentration-dependent protein binding, unbound, not total, concentrations should be used to estimate the bioavailability of disopyramide. Also, although the previously recommended conversion method (first CR dose 6 hours after the last IR dose) should provide an adequate transition in most, an alternative method (combined first CR with last IR dose) is indicated in select patients.

Adolescent↗

Cocaine-related sudden cardiac death: a hypothesis correlating basic science and clinical observations.

Sudden, unexpected death due to cocaine in young otherwise healthy individuals occurs in an idiosyncratic manner and is commonly felt to be arrhythmogenic in nature, although the exact cause of death is rarely documented. In addition to indirect sympathomimetic actions, cocaine is a potent sodium channel blocking drug and, in this regard, most closely resembles agents such as flecainide. We suggest that sudden death due to cocaine is proarrhythmic in nature, occurring under similar circumstances as that due to specific antiarrhythmic drugs.

Adult↗

Invasive and noninvasive methods to predict the long-term efficacy of amiodarone: a compilation of clinical observations using meta-analysis.

BACKGROUND: The method of choice to predict the long-term efficacy of amiodarone in the treatment of complex ventricular arrhythmias is unknown. Whether electrophysiological testing or Holter monitoring better predicts long-term outcome is controversial. METHODS AND RESULTS: We performed a meta-analysis of trials using electrophysiological testing or electrocardiographic monitoring to predict the efficacy of amiodarone in patients with sustained ventricular tachycardia. Arrhythmia recurrence data were combined after homogeneity testing across trials. Bayesian estimates and 95% credibility intervals were constructed to compare the arrhythmia-free probability among groups. Nine studies using electrophysiological testing (351 patients) and three using Holter monitoring (167 patients) met criteria for inclusion determined a priori. The combined arrhythmia-free probability estimate and credibility intervals were 0.86 (0.78-0.92) for patients rendered noninducible and 0.81 (0.73-0.87) for patients with abolition of ventricular tachycardia during Holter monitoring on amiodarone. With this primary analysis, there was no significant difference between the predictive value of noninducibility during electrophysiological testing and abolition of ventricular tachycardia with Holter. However, if only those electrophysiological studies using at least triple extrastimuli were included, arrhythmia-free probability for patients rendered noninducible increased to 0.96 (0.88-0.99), significantly better than noninvasive testing. CONCLUSIONS: Noninducible ventricular tachycardia during electrophysiological testing and abolition of ventricular tachycardia during electrocardiographic monitoring on amiodarone appear equally predictive of long-term amiodarone success, but this conclusion seems dependent on the stimulation protocol used. Although the yield is lower (compared to Holter monitoring), ventricular tachycardia rendered noninducible with a stimulation protocol using triple extrastimuli is the most highly predictive test of long-term amiodarone efficacy.

Aged↗

Effectiveness and costs of digoxin treatment for atrial fibrillation and flutter.

Clinical outcomes and costs associated with the use of digoxin in atrial fibrillation and flutter were evaluated in a prospective, observational study at 18 academic medical centers in the United States. Data were collected on 115 patients (aged > 18 years) with atrial fibrillation or flutter who were treated with digoxin for rapid ventricular rate (> or = 120 beats/min). The median time to ventricular rate control (i.e., resting ventricular rate < 100 beats/min, decrease in ventricular rate of > 20%, or sinus rhythm) was 11.6 hours from the first dose of digoxin for all evaluable patients (n = 105) and 9.5 hours for those only receiving digoxin (n = 64). Before ventricular rate control, the mean +/- SD dose of digoxin administered was 0.80 +/- 0.74 mg, and a mean of 1.4 +/- 1.8 serum digoxin concentrations were ordered per patient. Concomitant beta-blocker or calcium antagonist therapy was instituted in 47 patients (41%); in 19 of these, combination therapy was initiated within 2 hours. Adenosine was administered to 13 patients (11%). Patients spent a median of 4 days (range 1 to 25) in the hospital; 28% spent time in a coronary/intensive care unit and 79% in a telemetry bed. Loss of control (i.e., resting ventricular rate returned to > 120 beats/min) occurred at least once in 50% of patients and was associated with a longer hospital stay (p < 0.05). Based on 1991 data, the estimated mean hospital bed cost for patients with atrial fibrillation or flutter was $3,169 +/- $3,174.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Variability in plasma lipoprotein profiles when comparing diltiazem and propranolol.

OBJECTIVE: To examine the effects of diltiazem and propranolol on plasma lipoproteins in a double-blind, comparative trial. PATIENTS: Twenty-one mild-to-moderate hypertensive patients. METHODS: Following discontinuation of previous antihypertensive treatments, and a 4-week, single-blind, placebo run-in, subjects were randomized to receive sustained-release diltiazem or propranolol. Total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) were measured during placebo administration and after 12-16 weeks of treatment. RESULTS: No significant changes in plasma lipoprotein concentrations were noted in either the diltiazem or propranolol group compared with baseline values or each other. Marked variation in HDL, LDL, and VLDL were noted following drug treatment and in eight subjects whose lipoprotein concentrations were remeasured prior to drug treatment during the placebo period. The alterations were bidirectional, and similar in magnitude to those found following drug treatment. CONCLUSIONS: In many cases, changes in plasma lipoproteins reported to be a consequence of antihypertensive treatment may merely reflect normal intrapatient variability.

Adult↗

Impact of food on the pharmacokinetics and electrocardiographic effects of sustained release verapamil in normal subjects.

To evaluate the impact of food on the pharmacokinetics and electrocardiographic effects of sustained release (SR) verapamil tablets, 9 healthy men each received 3 single doses of verapamil in a randomized, crossover manner: 10 mg of intravenous verapamil, 240 mg SR verapamil on an empty stomach, and 240 mg SR verapamil with a standardized meal. PR intervals and racemic verapamil serum concentrations were measured serially over 30 hours after administration. The time to peak concentration was longer (7.5 +/- 3.0 vs 4.4 +/- 2.3 hours), resulting in a lower peak verapamil serum concentration (118 +/- 43 vs 175 +/- 50 ng/ml) when SR verapamil was administered with food (p < 0.05). Food tended to decrease the bioavailability of SR verapamil (34 +/- 12 vs 49 +/- 14%), although this difference did not reach statistical significance (p = 0.065). Precipitous or exaggerated release of verapamil from the SR tablet was not observed in any subject during the fasting state. Prolongation of the PR interval paralleled these alterations in serum concentration. The maximal change in the PR interval was greater (21 +/- 8 vs 14 +/- 5%; p < 0.05) when SR verapamil was given in the fasting state. Although an exaggerated verapamil release or effect was not observed, food significantly altered the absorption and electrocardiographic effects of a single dose of SR verapamil. Manipulation of the administration condition may be helpful in achieving desired outcomes.

Administration, Oral↗