Patient preferences for healthcare delivery through community pharmacy settings in the USA: A discrete choice study.

WHAT IS KNOWN AND OBJECTIVE: In order to improve public health, it is necessary to facilitate patients' easy access to affordable high-quality primary health care, and one enhanced approach to do so may be to provide primary healthcare services in the community pharmacy setting. Discrete choice experiments to evaluate patient demand for services in pharmacy are relatively limited and have been hampered by a focus on only a few service alternatives, most focusing on changes in more traditional pharmacy services. The study aim was to gauge patient preferences explicitly for primary healthcare services that could be delivered through community pharmacy settings in the USA, using a very large sample to accommodate multiple service delivery options. METHODS: An online survey was administered to a total of 9202 adult patients from the general population. A subsequent online survey was administered to 50 payer reimbursement decision-makers. The patient survey included a discrete choice experiment (DCE) which showed competing scenarios describing primary care service offerings. The respondents chose which scenario would be most likely to induce them to switch from their current pharmacy, and an optimal patient primary care service model was derived. The likelihood this model would be reimbursed was then determined in the payer survey. RESULTS AND DISCUSSION: The final optimal service configuration that would maximize patient preference included the pharmacy: offering appointments to see a healthcare provider in the pharmacy, having access to their full medical record, provide point-of-care diagnostic testing, offer health preventive screening, provide limited physical examinations such as measuring vital signs, and drug prescribing in the pharmacy. The optimal model had the pharmacist as the provider; however, little change in demand was evident if the provider was a nurse-practitioner or physician's assistant. The demand for this optimal model was 2-fold higher (25.5%; 95% Bayesian precision interval (BPI) 23.5%-27.0%) than for a base pharmacy offering minimal primary care services (12.6%; 95% BPI 12.2%-13.2%), and was highest among Hispanic (30.6%; 95% BPI: 25.7%-34.3%) and African American patients (30.7%; 95% BPI: 27.1%-35.2%). In the second reimbursement decision-maker survey, the majority (66%) indicated their organization would be likely to reimburse the services described in the optimal patient model if provided in the pharmacy setting. WHAT IS NEW AND CONCLUSION: This United States national study provides empirical support for a model of providing primary care services through community pharmacy settings that would increase access, with the potential to improve the public health.

Adherence to controller asthma medications: 6-month prevalence across a US community pharmacy chain.

WHAT IS KNOWN AND OBJECTIVE: Non-adherence to controller asthma medications is an important public health problem. It is estimated to occur in 30-70% of individuals and is a significant risk factor for asthma morbidity and mortality. The aim of this study was to determine the level of adherence, as indicated by refill rates, to controller asthma medications in a community pharmacy setting. METHODS: Secondary analyses of a community pharmacy dispensing database in 15 locations throughout Utah. RESULTS AND DISCUSSION: The dispensing records of 2193 patients who received controller medications for asthma in a 12-month period, and had a minimum of 6-month potential coverage (180 days) from the date of their first receipt of a controller medication in that period, were examined. Using standard metrics to gauge adherence, the proportion of days covered (PDC) and the medication possession ratio (MPR), the average coverage for controller asthma medications across a 6-month period (180 days) was poor, averaging less than 50% of days' availability. Standard cut-offs (≥80% medication availability) indicated that only 14-16% of patients had 'satisfactory' adherence over their 6-month follow-on period. Females and older patients had significantly greater satisfactory adherence. Medication adherence was significantly greater with inhaled corticosteroid (ICS)-long-acting ß2 -agonist (LABA) combinations than with ICS alone. WHAT IS NEW AND CONCLUSION: This study confirms the considerable scope of the asthma therapy non-adherence problem. Therefore, it is imperative to conduct survey-based research linked directly to pharmacy-based dispensing data to derive patient behavioural, attitudinal and environmental factors that may contribute to the issue, and then pilot and evaluate interventions for change.

Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure.

OBJECTIVES: The primary purpose of this study was to determine the acute and long-term hemodynamic and clinical effects of irbesartan in patients with heart failure. BACKGROUND: Inhibition of angiotensin II production by angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients with heart failure. Irbesartan is an orally active antagonist of the angiotensin II AT1 receptor subtype with potential efficacy in heart failure. METHODS: Two hundred eighteen patients with symptomatic heart failure (New York Heart Association [NYHA] class II-IV) and left ventricular ejection fraction < or = 40% participated in the study. Serial hemodynamic measurements were made over 24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study medication, patients receiving placebo were reallocated to one of the four irbesartan doses, treatment was continued for 12 weeks and hemodynamic measurements were repeated. RESULTS: Irbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change -5.9+/-0.9 mm Hg and -5.3+/-0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine. The neurohormonal effects of irbesartan were highly variable and none of the changes was statistically significant. There was a significant dose-related decrease in the percentage of patients discontinuing study medication because of worsening heart failure. Irbesartan was well tolerated without evidence of dose-related cough or azotemia. CONCLUSIONS: Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained hemodynamic improvement and prevented worsening heart failure.

Elucidation of the nifedipine-quinidine interaction.

Four case reports have been published that document a clinically significant drug interaction between nifedipine and quinidine in patients with left ventricular dysfunction. To define the population at risk and the mechanisms involved in manifestations of this interaction, 12 patients currently treated with quinidine for either ventricular or supraventricular arrhythmias were stratified into two groups based on left ventricular ejection fraction (EF) measurements (group A greater than 35%; group B less than 35%). The interaction was conducted through two phases: oral quinidine (Q) and oral quinidine plus nifedipine (N + Q). Pharmacokinetic modeling of total body clearance (CL) and AUC were assessed for each phase. One patient (group A, 70% EF) exhibited the interaction with a 41% decrease in steady-state serum quinidine concentrations. The patient's AUC and CL were 48.2 micrograms/ml.hr (Q) versus 28.6 micrograms/ml.hr (N + Q) and 94.4 ml/min (Q) versus 159.1 ml/min (N + Q), respectively. There was no difference in AUC or CL between the Q and N + Q phases or between groups A and B for the entire population. The N + Q interaction is not hemodynamically mediated. Clinical consideration of the possibility of this low-frequency interaction should be noted.

Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Proinflammatory cytokines are capable of modulating cardiovascular function by a variety of mechanisms. These cytokines are elevated in patients with severe heart failure, but changes in mild or moderate heart failure have not been reported. Therefore, simultaneous arterial and coronary sinus concentrations of interleukin-1alpha, soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha were measured in 78 patients with New York Heart Association functional class II to IV heart failure and compared with 17 healthy volunteers. Concentrations of interleukin-1alpha, soluble interleukin-2 receptor, and interleukin-6 were determined by a "sandwich" enzyme-linked immunosorbent assay and tumor necrosis factor-alpha by tissue culture technique. There were no statistical differences in interleukin-1alpha, soluble interleukin-2 receptor, or tumor necrosis factor-alpha concentrations in mild to moderate heart failure versus control subjects. Interleukin-6 was significantly elevated, 75 +/- 16 versus 0.4 +/- 0.4pg/ml (p = 0.002). Cytokine concentrations did not differ by heart failure etiology. Paired arterial and coronary sinus concentrations were not significantly different. Soluble interleukin-2 receptor concentrations were significantly correlated with New York Heart Association functional class (r = 0.59, p = 0.04) and negatively associated with exercise tolerance time (r = -0.59, p = 0.007). Thus, interleukin-6 is significantly elevated in mild or moderate heart failure.

Assessment of hemodynamic tolerance from a 24-hour intravenous infusion of fenoldopam mesylate in congestive heart failure.

To determine the maintenance of pharmacodynamic effects of fenoldopam mesylate, a dopamine-1 agonist, the invasive hemodynamic profiles of 33 patients with New York Heart Association functional class III to IV congestive heart failure were examined. Fenoldopam mesylate was initiated at 0.1 micrograms/kg/min and titrated to a cardiac index greater than or equal to 25% above baseline. Upon achievement of optimal hemodynamics, maintenance infusion was begun (mean dose 0.6 micrograms/kg/min). Fenoldopam mesylate (baseline vs maximal effect) decreased systemic vascular resistance by 37% (p less than 0.001), left ventricular filling pressure by 16% (p less than 0.05) and mean arterial pressure by 11% (p less than 0.05), with an associated augmentation in cardiac index and stroke volume index by 27% (p less than 0.001). Attenuation of hemodynamic effect (maximal effect vs time) was noted in cardiac index (14% p less than 0.001), systemic vascular resistance (13% p less than 0.05) and stroke volume index (13% p less than 0.05). None of the parameters exhibited complete attenuation to baseline values. Fenoldopam mesylate improves cardiac output and lowers systemic vascular resistance with relative attenuation of pharmacodynamic effect during a 24-hour intravenous infusion.

Arterial oxygen saturation in chronic congestive heart failure.

Continuous, 24-hour, ambulatory pulse oximetry was used in 10 subjects with New York Heart Association functional class II to III heart failure and in 5 age-matched controls to test the prevailing view that arterial oxygen saturation is preserved during wakefulness in chronic mild to moderate heart failure. Subjects with heart failure were stabilized on digitalis and diuretics at the time of the study. All subjects maintained time-activity logs, with an emphasis on self-reported sleep and wakefulness. A desaturation event was defined as a decrease in arterial oxygen saturation > or = 4% from baseline lasting > 5 seconds. Variables assessed included total desaturation events, decrease in arterial oxygen saturation duration/event, nadir of arterial oxygen saturation/event, and desaturation index ([cumulative desaturation time/total monitoring time] x 100). The ratio of self-reported wakefulness:sleep desaturation time was 47:53% for subjects with heart failure versus 64:36% for controls (p = NS). Mean (+/- SEM) time of arterial oxygen saturation < 90% was 123 +/- 67 minutes for subjects with heart failure versus 22 +/- 25 minutes for controls (p < 0.01). Total desaturations were 220 +/- 63 and 76 +/- 35 (p = NS) for the heart failure and control groups, respectively. The heart failure group had a statistically, significantly greater decrease in arterial oxygen saturation, and a longer duration and deeper nadir of the desaturation event than did the age-matched control group. The desaturation index was 21 +/- 3% and 4 +/- 1% for the heart failure and control groups, respectively (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary events during hemodialysis: effects of dialysis membranes and dialysate buffers.

Adverse cardiac and pulmonary events are frequently observed during hemodialysis and contribute to significant morbidity and mortality. The temporal relationship between these events during the intradialytic period has not been well defined. To examine the event rate and timing of silent ischemia, cardiac ectopy, and hypoxemia, we conducted a prospective, single-blind, randomized study of 10 subjects undergoing maintenance hemodialysis with four contiguous combinations of dialysis membranes (cuprammonium or polysulfone) and dialysates (acetate or bicarbonate). The frequency of oxygen desaturation events peaked during the first 2 hours, whereas silent myocardial ischemia and supraventricular ectopies occurred more often in the later hours. Ventricular ectopy occurred steadily throughout the intradialytic period. The combination of acetate dialysis and cuprammonium membrane is associated with the most frequent events. We conclude that cardiopulmonary events can occur frequently during hemodialysis, and the frequency is dependent on the type of dialysis membrane and dialysate buffer used.

Evaluation of quinapril on regional blood flow and cardiac function in patients with congestive heart failure.

Quinapril, a nonsulfhydryl ACE inhibitor, was evaluated in ten New York Heart Association (NYHA) functional class (FC) II-III CHF patients to determine its effects on regional blood flow [effective renal plasma flow (ERPF), renal blood flow (RBF), renal vascular resistance (RVR), hepatic blood flow (HBF), hepatic vascular resistance (HVR), segmental limb pressure (SLP), creatinine clearance (CRCL)] and cardiac function [left ventricular ejection fraction (LVEF)]. Previous vasodilator therapy was withdrawn 2 weeks before baseline measurements. Stable regimens of digoxin and diuretics were continued throughout the study. ERPF was assessed using p-aminohippurate (PAH), HBF by indocyanine green (ICG) clearance, and LVEF by radionuclide scintography. Segmental limb pressures were measured by Doppler flow detection. Measurements were performed at baseline (B) and after 4 weeks of quinapril therapy (10 mg BID). Quinapril increased renal (P less than 0.05) and hepatic blood flow (P = 0.06) and significantly reduced renal and hepatic vascular resistance. Glomerular filtration rate and left ventricular ejection fraction were unchanged. Mean arterial pressure and brachial segmental pressures decreased without change in heart rate. Noninvasive cardiovascular assessments indicate that quinapril improves regional blood flow while exhibiting no change in left ventricular ejection fraction, in patients with NYHA FC II-III CHF.

Candesartan cilexetil: comparison of once-daily versus twice-daily administration for systemic hypertension. Candesartan Cilexetil Study Investigators.

This randomized, double-masked, placebo-controlled, forced-titration, parallel-arm study was designed to compare the blood pressure (BP)-lowering effect of candesartan cilexetil, a potent antagonist of the angiotensin II receptor subtype AT1, administered once daily with that of the same agent administered twice daily at the same total daily dose of 16 mg. After a 4- to 5-week placebo run-in period, 277 patients with a sitting diastolic BP of 95 to 109 mm Hg were randomly allocated to receive placebo (n = 92) or candesartan cilexetil 8 mg once daily for 4 weeks, followed by forced titration to either 16 mg once daily (n = 91) or 8 mg twice daily (n = 94) for 4 weeks. At 8 weeks, mean reductions in trough sitting diastolic BP were similar for the once- and twice-daily treatment groups (9.4 and 10.3 mm Hg, respectively). After 8 weeks of treatment, no statistically significant differences were observed in diastolic or systolic BP, peak or trough BP, or sitting or standing BP between the 2 active-treatment groups. The rates of positive responses (defined as a trough sitting diastolic BP of <90 mm Hg or a decrease in BP of > or =10 mm Hg) were also similar (approximately 60%) in the once- and twice-daily candesartan cilexetil groups. Furthermore, placebo-corrected trough-to-peak ratios for sitting diastolic BP exceeded 75% for both candesartan cilexetil regimens, indicating a persistent 24-hour duration of drug effect. Ambulatory BP monitoring performed in a subset of patients (n = 44) confirmed the consistent 24-hour BP-lowering effect and preservation of diurnal variation with once-daily dosing. No significant between-group differences were observed in the incidence or severity of clinical or laboratory adverse events. The results of this study suggest that identical daily doses of candesartan cilexetil administered once or twice daily have comparable efficacy and tolerability and that no additional clinical benefit is derived from twice-daily administration.

On the fringes.

The expanded training pharmacists now receive in human pharmacotherapy has led to their increased participation in direct patient care. These activities may be global or specific, and can include drug therapy consultation, pharmacokinetic-based dosing recommendations, drug-use review, participation in nutritional support, and clinical pharmacology research. Such a listing of relatively sophisticated roles makes today's pharmacy practitioners almost unidentifiable with their counterparts of 20 years ago. This rapid transition makes pharmacy somewhat different in the health professions, since in comparison, medicine and nursing have been more stable. Despite these hard-fought advancements, there is a disturbing discrepancy between standards of care in pharmacy and the legal definition of pharmacy practice. Continued and future advancements are tenuous secondary to fear generated from noncompliance with state regulations. The entire profession should strive to develop updated pharmacy acts to prevent individuals from practicing "on the fringes."

beta-blocker therapy: a standard of care for heart failure.

beta-Adrenergic-blocking agents underwent extensive research over the past 2 decades and emerged as a proven state-of-art therapy for the failing human heart. Through blockade of chronically elevated cardiac adrenergic stimulation, selective and nonselective agents with vasodilating properties prevent progression of myocardial dysfunction and cardiac remodeling. Most important, beta-adrenergic blockers added to conventional therapy of vasodilators and diuretics significantly increase survival to a 5-year rate similar to that of cardiac transplantation. The agents also significantly reduce hospitalizations, improve quality of life, and are well tolerated in clinical trials. The challenge in treating heart failure is to ensure that every eligible patient receives these life-saving drugs.

Angiotensin II receptor blockers: novel therapy for heart failure?

Heart failure is a severe, disabling disease that portends a short life expectancy. This grave prognosis may be explained by growth-promoting effects of angiotensin II implicated in heart failure that mediate a genetic response called programmed cell death. The effects of angiotensin II are inhibited by angiotensin-converting enzyme (ACE) inhibitors, which improve exercise performance and quality of life, attenuate disease progression, and modestly lengthen survival. Unfortunately, mortality remains exceedingly high and may be partly attributable to augmented production of angiotensin II from a non-ACE chymase pathway. Angiotensin II production may therefore increase despite treatment with ACE inhibitors. The angiotensin II receptor antagonists are a new class of nonpeptide-reversible inhibitors that may offer clinical promise in heart failure through blockade of angiotensin II actions, whether produced from ACE or non-ACE chymase pathways.

Comparison of publication rates for basic sciences versus practice from pharmacy-based grant programs.

The future of a profession in an era of scarce resources depends on maintaining a focus on science. The times demand that pharmacy practice examine its commitment to science. To address this concern, pharmacy practice-based research awards from the American College of Clinical Pharmacy Research Institute Award Program, American Society of Health-System Pharmacists Research and Education Foundation Grant Program, and American Association of Colleges of Pharmacy New Investigator Program were compared with basic sciences awards from the American Association Colleges of Pharmacy New Investigator Program from their inception to 1991 to determine the percentage of awarded grants successfully published (publication rate). Pharmacy practice published awarded grants at 46% (70/154) versus 62% (26/42) for basic sciences (p = 0.09). A significant decline of 37% in pharmacy practice publication rate was observed over the study period. Economically, an average of $11,393 was spent to publish one manuscript in pharmacy practice versus $8077 in basic sciences. The results suggest that pharmacy practice should redefine a paradigm of commitment to scholarship to provide firm evidence for supporting science and sustaining professional growth.

Growth hormone: a promising treatment for the failing heart?

Many pathologic processes that accelerate the progression of heart failure, such as cardiac remodeling and impaired contractility, may be modulated by administration of recombinant growth hormone. The agent improves structural and functional aspects of the failing heart both in the short term and after several months of therapy. However, conflicting clinical results cast doubt on whether it has a clear benefit in all of these patients. In addition, growth hormone therapy may be associated with cardiac and noncardiac adverse effects. Many questions must be addressed before its place in heart failure therapy is established. Optimal patient population, dosing regimen, duration of therapy, and effect on patient survival are unknown. Until larger, blinded studies are completed, growth hormone therapy remains an investigational approach to managing refractory heart failure.

Carvedilol: therapeutic application and practice guidelines.

Current knowledge of the mechanisms contributing to progression of heart failure suggests that therapies that limit or interfere with the consequences of neurohormonal activation and improve myocardial energetics appear to be most beneficial. Carvedilol, a nonselective beta-adrenergic blocker with peripheral vasodilating properties, reduces mortality, slows progression of disease, and improves quality of life in patients with heart failure when added to standard therapy. When administered according to recommended guidelines, carvedilol is well tolerated. Clinical guidelines on the use of carvedilol in heart failure are provided.

Fatality due to intravenous diltiazem for acute ventricular rate control.

Progressive, sustained bradycardia resulting in asystole and subsequent death is reported in a 70-year-old woman with hyperkalemia and suspected digoxin toxicity following a 0.25 mg/kg intravenous diltiazem dose for treatment of atrial fibrillation with a rapid ventricular response. The possible pharmacodynamic and pharmacokinetic interactions between diltiazem, digoxin, and an elevated plasma potassium concentration are discussed and related to the outcome of the case. The routine practice of concomitant administration of diltiazem for rapid ventricular rate control and digoxin for long-term control may be dangerous in a subset of patients.

Effect of intravenous fructose-1,6-diphosphate on myocardial contractility in patients with left ventricular dysfunction.

STUDY OBJECTIVE: To examine the effects of fructose-1,6-diphosphate on myocardial performance using nuclear scintigraphy. DESIGN: Prospective, randomized, single-blind, parallel study. SETTING: Urban teaching hospital clinical research center. PATIENTS: Individuals with New York Heart Association functional class II-III heart failure (mild to moderate). INTERVENTIONS: Subjects received either intravenous fructose-1,6-diphosphate 125 mg/kg or normal saline 1.3 ml/kg every 12 hours over 10 minutes for four consecutive doses. Left ventricular performance was assessed by radionuclide ventriculography at baseline and within 60 minutes after the fourth infusion. Vital signs were monitored throughout the study period. MEASUREMENTS AND MAIN RESULTS: Fructose-1,6-diphosphate resulted in a modest 7% increase in left ventricular ejection fraction (p < 0.05). Peak ejection rate and peak diastolic filling rate did not change significantly. There were no changes in blood pressure or heart rate with either fructose-1,6-diphosphate or placebo. CONCLUSIONS: Fructose-1,6-diphosphate produces a modest but significant increase in left ventricular ejection fraction in patients with mild to moderate heart failure.

Invasive pharmacodynamic characterization of combined ibopamine and calcium blocker therapy for heart failure.

STUDY OBJECTIVE: To determine the acute hemodynamic response of single-dose coadministration of ibopamine plus nifedipine or diltiazem in patients with New York Heart Association functional class (NYHA FC) II-III congestive heart failure. DESIGN: A single-blind, placebo-controlled, two-paired, crossover study. SETTING: Cardiology clinics at two large teaching hospitals. PATIENTS: Eight patients with NYHA FC II-III congestive heart failure who met the inclusion criteria were selected randomly. INTERVENTIONS: All patients underwent right heart catheterization. Day 1 consisted of concomitant calcium channel blocker plus placebo, with cardiac and peripheral hemodynamic recordings from 30 minutes-24 hours. The design was equivalent on day 2, with single-dose administration of ibopamine plus calcium channel blocker. MEASUREMENTS AND MAIN RESULTS: Single-dose nifedipine-diltiazem augmented cardiac output and stroke volume secondary to decreasing systemic vascular resistance. The nifedipine-ibopamine and diltiazem-ibopamine subgroups demonstrated relatively equal hemodynamics, augmenting cardiac index (nifedipine 43%, p < 0.05; diltiazem 40%, p < 0.05 vs baseline) while decreasing systemic vascular resistance (nifedipine 41%, p < 0.05; diltiazem 28%, p NS vs baseline) 30 minutes after the dose. In contrast to single-dose diltiazem, the diltiazem-ibopamine subgroup exhibited an increased left ventricular filling pressure (122%, p < 0.05 vs baseline) and mean pulmonary artery pressure (43%, p < 0.05 vs baseline) at 30 minutes after the dose. One patient experienced a transient episode of chest pain associated with increased heart rate and blood pressure with diltiazem-ibopamine. CONCLUSION: Diltiazem and ibopamine should be coadministered with caution in patients with coronary artery disease and left ventricular dysfunction.

High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy.

STUDY OBJECTIVE: To assess the efficacy of high-dose epinephrine (HDE) compared with standard-dose epinephrine (SDE) in emergency department patients in cardiac arrest after SDE failed to improve asystole or ventricular fibrillation. DESIGN: Prospective, multicenter, blinded, controlled trial. SETTING: Eight academic center emergency departments. PATIENTS: One hundred forty patients treated for cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were either improvement in cardiac rhythm or return of spontaneous circulation (ROSC). Of the 140 patients enrolled, 78 received HDE and 62 received SDE. Of the 34 patients with ventricular fibrillation, 3 were resuscitated with HDE and 2 with SDE (p = 0.60). Of those with asystole, ROSC occurred in 12 of HDE and 5 of SDE recipients (p = 0.11). No patient had return of significant neurologic function and none survived to hospital discharge. Overall, there was no advantage to HDE after failure of SDE. CONCLUSION: Our results are similar to those of controlled clinical trials comparing HDE with SDE in cardiac arrest.