Opioid Prescribing After Implementation of Single Click Access to a State Prescription Drug Monitoring Program Database in a Health System's Electronic Health Record.

OBJECTIVES: To determine the effect of one-click integration of a state's prescription drug monitoring program (PDMP) on the number of PDMP searches and opioid prescriptions, stratified by specialty. METHODS: Our large health system worked with the state department of public health to integrate the PDMP with the electronic health record (EHR), which enabled providers to query the data with a single click inside the EHR environment. We evaluated Schedule II or III opioid prescriptions reported to the Massachusetts PDMP 6 months before (November 15, 2017-May 15, 2018) and 6 months after (May 16, 2018, to November 16, 2018) integration. Search counts, prescriptions, patients, morphine milligram equivalents, as well as prescriber specialty were compared. RESULTS: There were 3,185 unique prescribers with a record of a Schedule II and/or III opioid prescription in both study periods that met inclusion criteria. After integration, the number of PDMP searches increased from 208,684 in the pre-integration phase to 298,478 searches in the post-integration phase (+43.0%). The number of opioid prescriptions dispensed decreased by 4.8%, the number of patients receiving a prescription decreased by 5.1%, and the mean morphine milligram equivalents (MMEs) per prescriber decreased by 5.4%. There were some notable specialty-specific differences in these measures. CONCLUSIONS: Integration of the PDMP into the EHR markedly increased the number of searches but was associated with modest decreases in opioids prescribed and patients receiving a prescription. Single click EHR integration of the PDMP, if implemented broadly, may be a way for states to significantly increase PDMP utilization.

Racial and social inequities in medication use: A review of articles responding to the Journal of Managed Care + Specialty Pharmacy's Call to Action.

This article provides a summary of Viewpoint and Research articles responding to the 2020 Journal of Managed Care + Specialty Pharmacy Call to Action to address racial and social inequities in medication use. We find great heterogeneity in terms of topic, clinical condition examined, and health disparity addressed. Common recommendations across Viewpoint articles include the need to increase racial and ethnic diversity in clinical trial participants, the need to address drug affordability and health insurance literacy, and the need to incentivize providers and plans to participate in diversity initiatives, such as the better capture of information on social determinants of health (SDOH) in claims data to be able to address SDOH needs. Across research articles, we also find a large range of approaches and study designs, spanning from randomized controlled trials to surveys to observational studies. These articles identify disparities in which minoritized beneficiaries are shown to be less likely to receive medications and vaccines, as well as less likely to be adherent to medications, across a variety of conditions. Finally, we discuss Healthy People 2030 as a potential framework for future health disparity researchers.

Comparison of healthcare resource use between patients receiving ondansetron or palonosetron as prophylaxis for chemotherapy-induced nausea and vomiting.

OBJECTIVE: To analyze the differences between ondansetron and palonosetron in healthcare resource use (i.e., inpatient/ outpatient encounters) among patients receiving intraperitoneal cisplatin. METHOD: A medical record review was performed. Intraperitoneal cisplatin administrations for gynecological cancers from January through June 2006 and from October 2007 through June 2008 were divided into two groups based on the serotonin-receptor antagonist used. The occurrence of chemotherapy-induced nausea and vomiting (CINV)-related hospital readmissions, emergency department visits, and outpatient encounters occurring within 7 days after cisplatin administration was compared. CINV-related resource use was defined as events associated with dehydration, hypovolemia, nausea/vomiting, hypokalemia, constipation, shortness of breath, or syncope/collapse. RESULTS: Ondansetron or palonosetron was used in 39 and 89 cisplatin administrations, respectively. The baseline characteristics were similar between the groups with mean age of 59 years and ovarian cancer being the most common cancer. Length of stay was approximately 2 days. Palonosetron was always administered as a single-day therapy while one- or multi-day ondansetron therapy was administered in 27% and 73% of cycles, respectively. A trend towards more CINV-related hospitalizations with ondansetron versus palonosetron was observed (5.1% vs. 0%, p = 0.09) with no significant difference in other CINV-related encounters. CONCLUSION: Palonosetron was associated with a trend to a lower risk of CINV-related hospital readmission than ondansetron in patients receiving intraperitoneal cisplatin for gynecological cancers, although not statistically significant. The duration of ondansetron therapy might be suboptimal with 27% of patients receiving only 1 day of therapy during hospital stay. These findings need to be confirmed in future studies.

Pharmacologic options to prevent postoperative ileus.

OBJECTIVE: To summarize the evidence on pharmacologic options in preventing postoperative ileus (POI). DATA SOURCES: The Cochrane Database of Reviews and OVID databases and Food and Drug Administration (FDA) Web site were searched (1950-April 2009) using the term postoperative ileus. STUDY SELECTION AND DATA EXTRACTION: Meta-analyses and randomized controlled trials were included for review. The FDA Web site was searched for clinical reviews and label information for drugs indicated for the prevention of POI. DATA SYNTHESIS: Three meta-analyses, 2 on gum-chewing and 1 on alvimopan, and 18 clinical trials were identified. Only gum chewing and alvimopan were effective in preventing POI. Gum chewing reduced the time to first flatus and bowel movement (weighted mean difference 21h; p = 0.0006 and 33h; p = 0.0002, respectively). In one meta-analysis, gum chewing significantly reduced length of stay (LOS) by 2.4 days (p < 0.00001) but this was not replicated in the second meta-analysis. Alvimopan shortened the time to reach a composite endpoint of solid food intake, plus/minus flatus, and bowel movement (93 vs 105 h; p < 0.001). A higher incidence of myocardial infarction was observed in a 12-month study of alvimopan for the treatment of opioid-induced bowel dysfunction, but not in studies in patients undergoing bowel resection. Alvimopan decreased the time to written hospital discharge order (hazard ratio 1.35; p < 0.01), while the significance of a reduction in LOS (0.2-1.3 days) was not reported. CONCLUSIONS: Gum chewing and alvimopan are effective in preventing POI, but given safety concerns and higher cost with alvimopan, gum chewing may be preferred.

Andexanet Alfa (Andexxa) Formulary Review.

Andexanet alfa, a recombinant modified human "decoy" factor Xa (FXa) protein, is the first and only available antidote approved by the Food and Drug Administration to manage life-threatening or uncontrolled bleeding associated with the anti-Xa agents. It binds to direct and indirect anti-Xa oral anticoagulants with high specificity to reverse their inhibitory effects and restore the activity of FXa. Andexanet alfa is administered via two different dosing regimens, standard and high dose, based on the specific FXa inhibitor, dose, and time since the patient's last dose of FXa inhibitor. The approval for andexanet alfa is supported by data from two phase 3 studies (ANNEXA-A, ANNEXA-R) and preliminary data from the phase 3b/4 ANNEXA-4 trial. The first study found that andexanet alfa rapidly reduced anti-Xa activity by 92%-94% in healthy volunteers taking apixaban or rivaroxaban. The ANNEXA-4 study found that the median anti-Xa activity decreased by 89%-93% in patients with major bleeding taking apixaban or rivaroxaban. However, thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up in ANNEXA-4. Additionally, only 40% of patients had restarted anticoagulation and, in this group, the rate of thrombotic events was 12%. Four patients had a thrombotic event within 3 days after andexanet alfa treatment. The wholesale acquisition cost of the standard dose regimen is $24,750, and the high-dose regimen is $49,500. The estimated annual drug budget of treating 10-100 patients ranges from $248K to $495M. Effective October 1, 2018, Medicare will provide an add-on payment for andexanet alfa of up to $14,063 per qualifying case to Inpatient Prospective Payment System-participating acute care hospitals. In this formulary review for a health system's pharmacy and therapeutics committee, andexanet alfa clinical trials and medication package insert were summarized and, after consulting with clinical experts from our institutions, practical recommendations for use were generated to ensure appropriate and safe use of this agent.

Guidelines for pharmacoeconomic and outcomes research fellowship training programs: joint guidelines from the american college of clinical pharmacy and the international society of pharmacoeconomics and outcomes research.

Abstract Pharmacoeconomics and outcomes research (PEOR) demonstrates the added value of health services and treatments and is used by a variety of individuals in numerous settings to optimize patient care. Currently, 51 PEOR fellowship programs are publicized on Web sites from organizations such as the American College of Clinical Pharmacy (ACCP), the International Society of Pharmacoeconomics and Outcomes Research (ISPOR), and the Academy of Managed Care Pharmacy. These programs demonstrate the diversity of PEOR fellowships, as they are offered by sponsors in a variety of environments (e.g., academia, industry, consulting services, United States managed care, and government). Although the program sponsors vary, all fellowships should have the common goal of providing directed, highly individualized postgraduate training designed to prepare participants to become independent PEOR researchers. Like any health discipline, advancements in knowledge and technology along with changes in health care systems require refinement of existing training programs, including PEOR fellowships. Members of ACCP and ISPOR developed a survey instrument to assess structure, educational objectives, and outcome measures of PEOR fellowship programs. The survey objectives were to determine PEOR researchers' beliefs regarding qualifications of the training site, program, and preceptors(s) as well as fellowship applicant requirements, research commitment, didactic coursework and evaluation of fellows' research skills; and to develop PEOR fellowship guidelines based on data obtained from the survey. Pharmacoeconomics and outcomes research fellowship guidelines were originally published in 1999; this document outlines the revised PEOR fellowship guidelines based on recent literature and results of the ACCP-ISPOR survey described above. These guidelines are intended to assist PEOR researchers design, refine, and self-assess their fellowship program and to serve as a tool for prospective PEOR fellowship candidates to evaluate programs.

Conversion from Filgrastim to Tbo-filgrastim: Experience of a Large Health Care System.

BACKGROUND: In 2008, tbo-filgrastim was approved as a biosimilar in Europe and then approved in the United States by the FDA in 2012 as a biologic product with 1 similar indication to filgrastim. Because tbo-filgrastim was less expensive than filgrastim, and clinical information and expert opinion supported similarity, the Pharmacy & Therapeutics Committee of a large health care system approved tbo-filgrastim as the preferred granulocyte-colony stimulating factor (G-CSF) product in March 2014. OBJECTIVES: To (a) assess the use of filgrastim and tbo-filgrastim products by comparing baseline characteristics, setting of care, indication for use, and payer type and (b) understand potential barriers of conversion to tbo-filgrastim. METHODS: A retrospective evaluation of filgrastim and tbo-filgrastim use was conducted on all patients (N = 204) who received the drugs between July 2015 and December 2015 at the 2 largest hospitals in the health system. Baseline characteristics, indication requiring use of filgrastim or tbo-filgrastim, setting of care, and payer information were collected from electronic medical records, and descriptive analyses were conducted. RESULTS: Overall, G-CSFs were administered to 204 patients for 261 episodes of care (filgrastim and tbo-filgrastim were used in 65 and 196 episodes of care, respectively). Baseline characteristics were similar between the 59 patients who received filgrastim and the 174 patients who received tbo-filgrastim. G-CSF was primarily used in the inpatient setting (163 episodes of care, 63%) with 90% of patients using tbo-filgrastim. In the outpatient setting (98 episodes of care, 38%), filgrastim and tbo-filgrastim were each used by 50% of patients. Tbo-filgrastim was the preferred G-CSF by clinical providers for all indications, except for stem cell mobilization, where filgrastim use was higher (55% vs. 45% of 71 episodes of care). In the outpatient setting, analysis by payers showed that the majority of patients on commercial plans were using filgrastim (58%), while half of Medicare patients were using filgrastim (50%, n = 12). Twelve patients were self-paid, and all were using tbo-filgrastim. Subgroup analysis by hospital showed differences in utilization patterns. CONCLUSIONS: Although tbo-filgrastim was the preferred G-CSF in our formulary, 29% of patients continued to receive filgrastim. Conversion to tbo-filgrastim has been largely successful, but extra steps may be needed to achieve full conversion to biosimilars. DISCLOSURES: No outside funding supported this study. Agboola was employed by Partners Healthcare at the time of the study. The authors have nothing to disclose. Study concept and design were contributed equally by Agboola and Reddy. Agboola collected the data, and data interpretation was performed by both authors. The manuscript was written primarily by Agboola, with assistance from Reddy. Both authors revised the manuscript.

Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

The economic impact of blue-light filtering intraocular lenses on age-related macular degeneration associated with cataract surgery: a third-party payer's perspective.

OBJECTIVES: Epidemiological data support an association between age-related macular degeneration (AMD) and cataract surgery that may be attributed to post-operative blue light exposure. By limiting the retina's blue light exposure, new blue-light filtering intraocular lenses (BLF IOLs) have the potential to reduce the development of AMD following cataract surgery. In the current economic healthcare environment, there is increased interest in the cost impact of new medical technologies. The objective of this analysis was to evaluate the cost impact of a BLF IOL versus a non-BLF IOL in cataract surgery. METHODS: An economic model was developed to emulate three age-specific cohorts and to assess the clinical and economic outcomes over 5 years. Data from the published literature was supplemented with clinical expert opinion. Key literature inputs involved the risk of AMD after cataract surgery as well as laboratory and animal data on the effectiveness of the BLF IOL in reducing the risk of AMD. Clinical experts provided information on the management of AMD. Direct medical costs including the cost of the IOL, monitoring, and AMD prophylaxis and treatment were incorporated into the model. All costs were standardized to 2004 US dollars. Age-stratified sensitivity analyses were conducted. RESULTS: In the BLF IOL group, the 5-year age-stratified incidence of AMD ranged from 0.58 to 9.23 per 100 eyes, compared with 1.69 to 24.55 per 100 eyes in the non-BLF IOL group. The incremental cost of the BLF was offset by reduced costs associated with averted AMD treatment. Estimated savings with BLF IOLs per 100 eyes were $4275, $29 997, and $111 734 in the 55 to 64 year-old, 65 to 74 year-old, and >or= 75-year-old cohorts, respectively; these findings remained robust throughout the sensitivity analyses. CONCLUSION: Limitations of this analysis include the lack of prospective clinical trial data that definitively demonstrate the efficacy of a BLF IOL in preventing AMD. Moreover, the efficacy data used to populate the model were derived from laboratory and animal studies. Thus, based on preliminary data, this study suggests that the economic benefits of implanting BLF IOLs during cataract surgery are observed in all patients over a 5-year timeframe although cost savings are greatest in patients >or= 75 years.

Idarucizumab (Praxbind) Formulary Review.

Idarucizumab (Praxbind), a humanized monoclonal antibody fragment was granted accelerated approval from the Food and Drug Administration in October 2015 as the first agent to reverse the effects of a novel oral anticoagulant. The drug is indicated for dabigatran reversal in patients requiring emergency surgery/urgent procedures or with life-threatening or uncontrolled bleeding. In a randomized study with healthy volunteers, compared with placebo, idarucizumab reduced the clotting times for all tests assays (assessed pre-, end of-, and 24 hours after infusion), while the results for the placebo group remained unchanged. Another randomized clinical trial assessed the safety and efficacy of idarucizumab in patients with either overt bleeding or undergoing emergency surgery where hemostasis was required. This study is ongoing, but preliminary results showed reversal efficacy demonstrated a reasonable safety profile from the time of the infusion to 90 days after. The wholesale acquisition cost of two 2.5 g vials of idarucizumab is currently $3482.50. To treat 10 or 20 patients per year with a single 5 g dose is estimated to cost $34,825 and $69,650, respectively. In the clinical trial described above, approximately 20% of patients required a second dose, which would further increase the cost of use. In this formulary review for a health system's pharmacy and therapeutics committee, idarucizumab clinical trials and medication package insert were summarized and, after consulting with clinical experts from our institutions, practical recommendations for use were generated to ensure appropriate and safe use of this agent.

Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: the Atrial Fibrillation Suppression Trial II (AFIST II).

BACKGROUND: The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown. METHODS AND RESULTS: Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2x2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (P=0.037 and P=0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P=0.047 and P=0.040, respectively). CONCLUSIONS: Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.

A comparison of two individual amiodarone regimens to placebo in open heart surgery patients.

BACKGROUND: This study compares the ability of two oral amiodarone regimens to reduce the risk of atrial fibrillation (AF) as compared with the placebo among elderly open heart surgery (OHS) patients receiving beta blockade. METHODS: This is a randomized, double-blinded, placebo-controlled trial of 220 patients undergoing OHS. Patients (average age, 73 years) received 7 g of oral amiodarone more than 10 days starting 5 days before OHS (slow load; n = 56), a 6 g oral amiodarone regimen more than 6 days starting 1 day before OHS (fast load; n = 64), or matching placebo in one of the two previously mentioned regimens (n = 100). RESULTS: Patients receiving the slow load amiodarone regimen had a significant reduction in the risk of AF (48.4%; p = 0.013), AF lasting more than 24 hours (76.5%; p = 0.003), symptomatic AF (90.0%; p = 0.002), and recurrent AF (64.5%; p = 0.025) as compared with the placebo. Patients receiving the fast load amiodarone regimen had significant reductions in the risk of AF lasting more than 24 hours (52.6%; p = 0.038) and symptomatic AF (65.0%; p = 0.024), but the incidence of any AF or any recurrence of AF only showed a trend toward significance (34.0% and 45.5%; p = 0.054 and 0.09, respectively). CONCLUSIONS: Oral amiodarone in a slow loading regimen provides significant suppression of all AF factors and can be used when a patient has started it at least 5 days before OHS. If a patient has less than 5 days before OHS, the fast loading regimen is an efficacious alternative as it provides significant benefits in preventing AF from lasting more than 24 hours and for preventing symptomatic AF. Both regimens were well tolerated and safe in elderly patients receiving beta blockade according to the hospital's standard protocol.

Direct medical costs associated with using vancomycin in methicillin-resistant Staphylococcus aureus infections: an economic model.

OBJECTIVES: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP). RESEARCH DESIGN AND METHODS: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario. MAIN OUTCOME MEASURES: The cost of using vancomycin in the four indications, including and excluding hospital cost. RESULTS: Whereas the drug acquisition price of vancomycin 1g is US dollars 9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to US dollars 29-US dollars 43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP,US dollars 779, US dollars 749, US dollars 2261, and US dollars 768, respectively. Total costs, including hospital length of stay, were for SSTI US dollars 23616, bacteremia US dollars 26446, IE US dollars 48925, and HAP US dollars 22493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications. CONCLUSIONS: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.

The effect of phytosterols on quality of life in the treatment of benign prostatic hyperplasia.

In the United States, phytosterols are available as over-the-counter dietary supplements and are promoted as a safe and natural way to maintain a healthy prostate. In men with benign prostatic hyperplasia (BPH), evidence suggests that the agents improve urologic symptoms and flow measures to a greater extent than placebo and to a similar extent as finasteride. The primary goal for treating men with BPH is to reduce lower urinary tract symptoms and increase quality of life (QOL). Therefore, QOL has become an increasingly important end point in clinical trials. We reviewed all seven studies that determined the effect of phytosterols on QOL in patients with BPH. All trials assessed QOL with international prostate symptom score questions. Six studies found phytosterols to have beneficial effects on QOL; however, poor study design limits what can be learned from these evaluations. Most studies included a limited number of patients, and many were not placebo controlled. Since few of them evaluated the effect of phytosterols beyond 6 months, little evidence exists of the agents' long-term efficacy in reducing symptomatology or increasing QOL. Finally, phytosterols have not been adequately compared with alpha-blocking agents, one of the most widely administered and effective pharmacologic treatments of BPH. Larger studies comparing phytosterols with other treatments of BPH such as alpha-blockers should be conducted. In addition, a consensus should be reached as to which questionnaires are best to evaluate potential changes in QOL after treatment of BPH.

An economic analysis of amiodarone versus placebo for the prevention of atrial fibrillation after open heart surgery.

STUDY OBJECTIVE: To determine if the additional costs of oral amiodarone in patients undergoing open heart surgery would be offset by reductions in the frequency of atrial fibrillation. DESIGN: Piggyback cost analysis of the data from a randomized, double-blind, placebo-controlled trial. SETTING: Urban academic hospital. PATIENTS: Two hundred twenty elderly patients (> or = 60 yrs old) undergoing open heart surgery. INTERVENTION: Hospital costs of open heart surgery in patients given amiodarone for the prevention of atrial fibrillation and in prespecified subgroups were compared with those for patients given placebo (i.e., standard care with beta-blockers alone). MEASUREMENTS AND MAIN RESULTS: Total hospital costs incurred were $15,565 +/- $9832 and $16,126 +/- $8043 in the amiodarone and placebo groups, respectively (p=0.12). General ward, intensive care unit, operating room, pharmacy, and costs in all other departments were similar between the groups (p>0.05 for all comparisons). Because costs were similar but amiodarone was more effective than placebo, amiodarone was cost-effective compared with placebo. Amiodarone remained cost-effective compared with placebo regardless of the following subgroup characteristics: rapid or slow loading strategy, no history of atrial fibrillation or heart failure, age older than 70 years, and no tolerance to preoperative beta-blockers. Moreover, in the one-way sensitivity analysis, the findings remained robust to changes in effectiveness and cost of amiodarone. CONCLUSION: Routine prophylaxis with amiodarone is cost-effective compared with placebo. Future studies should examine the cost-effectiveness of selective prophylaxis, and primary cost-effectiveness studies should be conducted to validate these findings.

Economic analysis of intravenous plus oral amiodarone, atrial septal pacing, and both strategies to prevent atrial fibrillation after open heart surgery.

STUDY OBJECTIVES: To compare the cost-effectiveness of intravenous plus oral amiodarone, atrial septal pacing, and both strategies combined to prevent atrial fibrillation after open heart surgery. Secondary objectives were to compare the cost-effectiveness of amiodarone versus no amiodarone and of pacing versus no pacing, and to compare hospitalization costs of the various strategies. DESIGN: Piggyback cost analysis of a randomized, 2 x 2 factorial trial. SETTING: Urban academic hospital. PATIENTS: One hundred and sixty patients with coronary artery and/or valvular disease. INTERVENTION: Patients were randomized to receive amiodarone or matching placebo and then further randomized to receive atrial septal pacing or no pacing. MEASUREMENTS AND MAIN RESULTS: The economic analysis was conducted from a hospital perspective. Charges were converted to costs using cost:charge ratios. For the cost-effectiveness analysis, a joint distribution of costs and effectiveness was performed using the nonparametric bootstrap method. Amiodarone plus pacing significantly decreased the frequency of atrial fibrillation after open heart surgery, compared with amiodarone alone, pacing alone, and placebo. Total costs (mean+/-SD) were $27,026+/-30,226 for the placebo group, $22,725+/-17,661 for the amiodarone group, $33,868+/-60,309 for the pacing group, and $18,697+/-8174 for the amiodarone plus pacing group (p=0.27). In the joint distribution cost-effectiveness analysis, when compared with placebo, the probability of lower cost but higher effect (superiority) was 67% for amiodarone, 15% for pacing, and 97% for amiodarone plus pacing. In the multivariate analysis, preoperative beta-blockers and amiodarone were negatively associated with hospital costs (p<0.05). CONCLUSIONS: Data suggest that both amiodarone alone and the combination of amiodarone plus pacing are cost-effective compared with placebo. Additional comparative studies of these strategies are warranted to confirm these findings.

Cost comparisons of pharmacological strategies in open-heart surgery.

Open-heart surgery (OHS) is performed to bypass occluded arteries, replace malfunctioning cardiac valves or correct congenital abnormalities. The average cost of OHS varies from $US25 057-$US79 795 (1997 values). The objective of this paper was to review economic studies of pharmacological strategies in open-heart surgery. Pharmacological strategies studied include the prevention of postoperative complications such as atrial fibrillation (AF), bleeding and infection. Modifications in anaesthetic technique have been attempted by using agents that promote early extubation. In addition, strategies for postoperative management of sedation, analgesia and AF and use of neuromuscular blockers have also been compared. The majority of studies in this area have been cost analyses with few cost-effectiveness studies performed. Prophylaxis against AF with amiodarone is associated with a reduction in AF and was cost-neutral compared with placebo. Compared with placebo, prevention of bleeding with antifibrinolytics reduces transfusion costs. In direct comparative studies, lysine analogues, due to lower drug acquisition costs, offset transfusion costs to a greater extent than aprotinin. However, safety concerns with the lysine analogues remain. Erythropoietin decreases transfusion requirements and is cost effective compared with no intervention when the cost of postoperative bacterial complications is included. First- and second-generation cephalosporins prevent postoperative infections. Based on drug acquisition cost, the first-generation agents are less expensive although when administration costs are included, both classes have similar costs. Modifications in anaesthetic technique with short-acting anaesthetic agents, results in higher drug costs although nursing and total hospital costs are typically reduced. For neuromuscular blockers, drug acquisition costs are lowest with pancuronium but administration costs and the cost of adverse events have not been included in existing analyses. Midazolam provides an equivalent level of postoperative sedation to propofol but the acquisition cost is lower. The combined use of propofol and midazolam warrants further investigation, as its use is associated with lower sedative agent costs compared with either agent alone. There is limited data on the economics of postoperative analgesia and the management of AF. As the majority of studies to date are partial cost analyses, additional studies that include length of stay and other hospitalisation data are warranted. In future, cost-effectiveness and cost-utility studies, which incorporate quality of life and the cost of adverse effects and other longer term costs, should be undertaken.

Cost effectiveness of ibutilide with prophylactic magnesium in the treatment of atrial fibrillation.

BACKGROUND: In the Treatment with Ibutilide and Magnesium Evaluation (TIME) study, a retrospective multicentre cohort trial, prophylactic magnesium was found to improve the antiarrhythmic efficacy of ibutilide as demonstrated by an increase in the rate of successful chemical conversion and reduction in the need for direct current cardioversion (DCC). OBJECTIVE: The primary objective of this piggyback cost-effectiveness analysis of the TIME study was to compare the cost per successful conversion of atrial fibrillation (AF) for ibutilide in the presence and absence of magnesium prophylaxis. A secondary objective was to determine whether specific factors predict costs in the conversion of AF. METHOD: The study was conducted from the US hospital-payer perspective. Direct medical costs (USD, 2002 values) including drugs, intravenous admixture and administration, DCC, electrocardiographs and physicians' fees were obtained directly from the provider. Nonparametric bootstrapping was conducted to calculate confidence intervals for the incremental cost-effectiveness ratios. One-way sensitivity analysis was conducted varying efficacy, and drug, hospital and physician costs. Multivariate analysis was conducted to determine whether specific baseline factors were predictors of total cost. RESULTS: Total costs per patient were lower in the ibutilide plus magnesium group compared with ibutilide alone (USD1075 vs USD1201); however, the difference was not statistically significant (p = 0.116). Patients receiving ibutilide plus magnesium had lower DCC costs compared with those receiving ibutilide alone (USD261 vs USD399; p = 0.036), but higher magnesium-associated costs (USD0.50 vs USD0; p < 0.001). Bootstrapping revealed that the ibutilide plus magnesium strategy would result in lower costs and greater efficacy 93.4% of the time. These results remained robust to changes in both cost and efficacy. No baseline factors were found to be independent predictors of total costs. CONCLUSION: Our data suggest that adding prophylactic magnesium to ibutilide may be cost effective, from a US hospital-payer perspective, for the acute conversion of patients in AF or flutter compared with ibutilide alone.

The economic burden of dry eye: a conceptual framework and preliminary assessment.

PURPOSE: To develop a conceptual framework for analyzing the economic burden of dry eye and a preliminary assessment of key factors that contribute to that burden. METHODS: The MEDLINE database was searched from 1966 to May 2003 combining the term "dry eye" with various economic terms. In addition, individual interviews with a panel of clinicians were conducted to provide additional insight on resource use. RESULTS: Direct resource utilization among dry eye sufferers includes healthcare professional visits, nonpharmacological therapies, pharmacological treatments, and surgical procedures, with the latter 2 categories being the major cost drivers. Complementary and alternative medicine (CAM) therapies are a newly recognized component of the dry eye economic burden. There is wide variation in patterns of diagnosis and treatment, but current therapies are not universally effective. Given the prevalence of the condition, indirect costs may be large. Utilization of pharmacological therapies, especially those other than tear replacements, the extent of CAM use, cost of complications of surgical procedures, and indirect costs are unknown. The natural history and probability that patients will transition between therapies, based on underlying disease severity, need to be elucidated. CONCLUSIONS: Dry eye is a prevalent condition with the potential for a high economic burden; additional studies are needed to further characterize the economic impact.