Abstract: A recent supplement article by Talbird, Taylor, Knoll, Frostad, and GarcÃa Martà reported estimates of public health impact and cost-effectiveness of the 10-valent pneumococcal conjugate vaccine compared with the 7-valent vaccine. Although the analysis applies a decision analytic model and modeling methodologies that are scientifically sound, many of the assumptions presented in the paper are inconsistent with the current evidence.
Abstract: ABSTRACT: BACKGROUND: Prior studies have found that patients taking single-pill amlodipine/atorvastatin (SPAA) have greater likelihood of adherence at 6 months than those taking 2-pill calcium-channel blocker and statin combinations (CCB/statin). This study examines whether this adherence benefit results in fewer cardiovascular (CV) events. METHODS: A retrospective cohort study was conducted using administrative claims data from the IMS LifeLink: US Health Plan Claims database, identifying adults already taking CCB or statin (but not both) who had an index event of either initiating treatment with SPAA or adding CCB to statin (or vice versa) between April 1, 2004 to August 31, 2005. Inclusion criteria included age 18+ years, continuously enrolled for minimum of 6 months prior and 18 months following treatment initiation, >1 diagnosis of hypertension, and no prescription claims for SPAA or added CCB or statin for 6 months prior. Exclusion criteria included >1 claim with missing or invalid days supplied, age 65+ years and not enrolled in Medicare Advantage, or history of prior CV events, cancer diagnosis, or chronic renal failure. The primary outcome measure was the rate of CV events (myocardial infarction, heart failure, angina, other ischemic heart disease, stroke, peripheral vascular disease, or revascularization procedure) from 6 to 18 months following index date, analyzed at three levels: 1) all adherent vs. non-adherent patients, 2) SPAA vs. dual-pill patients (regardless of adherence level), and 3) adherent SPAA, adherent dual-pill, and non-adherent SPAA patients vs. non-adherent dual-pill patients. RESULTS: Of 1,537 SPAA patients, 56.5% were adherent at 6 months, compared with 21.4% of the 17,910 CCB/statin patients (p<0.001). Logistic regression found SPAA patients more likely to be adherent (OR = 4.7, p<0.001) than CCB/statin patients. In Cox proportional hazards models, being adherent to either regimen was associated with significantly lower risk of CV event (HR=0.77, p=0.003). A similar effect was seen for SPAA vs. CCB/statin patients (HR=0.68, p =0.02). In a combined model, the risk of CV events was significantly lower for adherent CCB/statin patients (HR=0.79, p=0.01) and adherent SPAA patients (HR=0.61, p=0.03) compared to non-adherent CCB/statin patients. CONCLUSIONS: Patients receiving SPAA rather than a 2-pill CCB/statin regimen are more likely to be adherent. In turn, adherence to CCB and statin medications is associated with lower risk of CV events in primary prevention patients.
Abstract: The use of aldosterone blockers in the pharmacologic therapy for heart failure (HF) in patients with left ventricular systolic dysfunction has been shown to significantly reduce overall mortality, sudden cardiac death, and hospitalization. Patient adherence to polypharmaceutical regimens including aldosterone blockade and other key medication components is a concern for clinicians and their patients. A retrospective cohort study was conducted using integrated US pharmacy/medical claims covering 44.5 million lives. Inclusion criteria included the following: age at least 50 years, newly prescribed spironolactone or eplerenone from 2002 to 2006, with HF diagnosis within 12 months of prescription initiation and follow-up of at least 6 months to assess outcomes (12 months for adherence). Compliance was measured as the proportion of days covered (prescription days supply in the first year postindex for 365 days), and persistence was measured as days from the first to the last prescription. Of 388,523 patients with HF, 60,183 patients (15.5%) received an aldosterone blocker (n = 2024 for eplerenone, n = 58,159 for spironolactone), from which a newly treated subset was studied (n = 568 eplerenone, n = 11,982 spironolactone). Proportion of days covered was significantly greater for eplerenone (79% ± 42%) than for spironolactone (66% ± 42%, P < 0.01). Persistence was significantly higher for eplerenone than for spironolactone (P < 0.01) with discontinuation before 1 year at 49.5% and 73.7%, respectively. This analysis shows that a majority of patients did not receive an aldosterone blocker after HF diagnosis despite cardiovascular event risks and raises the hypothesis that eplerenone is associated with higher compliance and persistence as compared with spironolactone.
Abstract: Objective:  We sought to compare the cost-effectiveness of different interventions that have been shown to improve adherence with antihypertensive and lipid-lowering therapy, by combining a burden of nonadherence model framework with literature-based data on adherence-improving interventions. Methods:  MEDLINE was reviewed for studies that evaluated ≥1 adherence intervention compared with a control, used an adherence measure other than self-report, and followed patients for ≥6 months. Effectiveness was assessed as Relative Improvement, ratio of adherence with an intervention versus control. Costs, standardized to 12 months and adjusted to 2007 US$, and effectiveness estimates for each intervention were entered into a previously published model designed to measure the burden of nonadherence with antihypertensive and lipid-lowering medications, in a hypertensive population. Outputs included direct medical costs and incremental costs per quality-adjusted life-year (QALY) gained. Results:  After screening, 23 eligible adherence-improving interventions were identified from 18 studies. Relative Improvement ranged from 1.13 to 3.60. After eliminating more costly/less effective interventions, two remained. Self-monitoring, reminders, and educational materials incurred total health-care costs of $17,520, and compared with no adherence intervention, had an incremental cost-effectiveness ratio (ICER) of $4984 per QALY gained. Pharmacist/nurse management incurred total health-care costs of $17,896, and versus self-monitoring, reminders, and education had an ICER of $6358 per QALY gained. Conclusions:  Of published interventions shown to improve adherence, reminders and educational materials, and a pharmacist/nurse management program, appear to be cost-effective and should be considered before other interventions. Understanding relative cost-effectiveness of adherence interventions may guide design and implementation of efficient adherence-improving programs.
Abstract: Fluconazole is a standard first-line therapy for candidemia/invasive candidiasis (C/IC), based on its efficacy, safety profile, and comparatively low acquisition cost. However, little is known about the total costs associated with fluconazole treatment for this indication, particularly in cases of clinical failure.
Abstract: AIMS: Adherence to cardiovascular medications is poor. Accordingly, interventions have been proposed to improve adherence. However, as intervention-associated costs are rarely considered in full, we sought to review the effectiveness and costs associated with different adherence-improving interventions for cardiovascular disease therapies. METHODS: We reviewed MEDLINE to update a prior review of interventions to improve adherence with antihypertensive and/or lipid-lowering therapy covering January 1972 to June 2002, to add studies published from July 2002 to October 2007. Eligible studies evaluated > or = 1 intervention compared with a control, used measures other than self-report, reported significant improvement in adherence and followed patients for > or = 6 months. Effectiveness was measured as relative improvement (RI), the ratio of adherence in the intervention group to the control group. Costs were calculated based on those reported in the analysis, if available or estimated based on resource use described. All costs were truncated to 6 months and adjusted to 2007 US$. RESULTS: Of 755 new articles, five met all eligibility criteria. Combining with the prior review gave 23 interventions from 18 studies. RI in adherence ranged from 1.11 to 4.65. Six-month intervention costs ranged from $10 to $142 per patient. Reminders had the lowest effectiveness (RI: 1.11-1.14), but were least costly ($10/6 months). Case management was most effective (RI: 1.23-4.65), but the most costly ($90-$130/6 months). CONCLUSIONS: Generally, we found a positive association between intervention costs and effectiveness. Therefore, consideration of intervention costs, along with the benefits afforded to adherence, may help guide the design and implementation of adherence-improving programs.
Abstract: OBJECTIVE: The aim of the study was to compare early symptom resolution with a single 2-g dose of azithromycin extended release or 10 days of amoxicillin/clavulanate 875 mg/125 mg every 12 hours in patients with acute sinusitis. MATERIALS AND METHODS: This was a prospective, randomized, open-label, observational study to mimic "real-world" conditions, including patients with symptoms of acute bacterial sinusitis lasting between 7 and 30 days. Key symptoms were assessed twice daily by patient diary, and patients were interviewed by telephone at 12 and 28 days. The primary end point was symptom resolution at 5 days, defined as reporting "no problem" with at least 3 of 4 diary symptoms in 2 consecutive measures in the per-protocol population. Secondary end points included additional antibiotic use, sinusitis-related quality of life, and treatment satisfaction. RESULTS: Three hundred seventy-eight patients were randomized to a single dose of azithromycin extended release and 371 to 10 days of amoxicillin/clavulanate. In the per-protocol population at day 5, 70/236 patients (29.7%) in the azithromycin extended release arm and 45/238 patients (18.9%) in the amoxicillin/clavulanate arm had resolution of symptoms (difference = 10.8%; 95% confidence interval [CI], 3.1-18.4%). By day 28, 26/236 patients (11.0%) in the azithromycin extended release arm and 27/238 patients (11.3%) in the amoxicillin/clavulanate arm had used additional antibiotics (difference = -0.4%; 95% CI: -6.1% to 5.3%). Additional physician visits, quality of life, and overall satisfaction were similar between groups. CONCLUSIONS: More patients randomized to azithromycin extended release experienced symptom resolution at day 5 than those randomized to amoxicillin/clavulanate, without experiencing differences in second antibiotic use at 28 days.
Abstract: BackgroundHypertension and dyslipidemia are highly prevalent in the elderly. We studied the combined impact of both conditions on cardiovascular disease (CVD) events.MethodsWe studied 4,311 participants aged 65-98 (61.2% female) from the Cardiovascular Health Study (CHS), a longitudinal epidemiologic study, with no prior CVD. We evaluated the relation of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or non-HDL-cholesterol combined with blood pressure (BP) categories to incident CVD-including coronary heart disease (CHD) (angina, myocardial infarction (MI), angioplasty, coronary bypass surgery, or CHD death), stroke, claudication, and CVD death over 15 years.ResultsCVD incidence (per 1,000 person years) ranged from 38.4 when BP <120/80 mm Hg and LDL-C <100 mg/dl to 94.8 when BP >/=160/100 mm Hg and LDL-C >/=160 mg/dl, and from 28.9 when BP <120/80 mm Hg and HDL >60 mg/dl to 87.1 for a BP >/=160/100 and HDL-C <40 mg/dl. Compared with those with BP <120/80 mm Hg with either LDL-C <100 mg/dl or HDL-C >60 mg/dl, hazard ratios (HRs) for CVD events were 2.1 when BP >/=160/100 mm Hg and LDL-C >/=160 mg/dl and 2.1 when BP >/=160/100 and HDL-C <40 mg/dl (all P < 0.01), with similar results for non-HDL-C. Elevated BP was associated with increased risk across all lipid levels. Increased LDL-C added risk mainly when BP <140/90 mm Hg, but lower HDL-C also predicted CVD in those with higher BP.ConclusionIncreased BP confers increased risks for CVD in elderly persons across all lipid levels. Although increased LDL-C added risk mainly when BP <140/90 mm Hg, low HDL-C added risk also in those with hypertension. These results document the importance of combined hypertension and dyslipidemia.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.216.
Abstract: OBJECTIVE: To compare adherence with statin therapy in patients switching to single-pill amlodipine besylate/atorvastatin calcium with patients adding a separate statin to their amlodipine regimen. METHODS: We identified hypertensive patients prescribed amlodipine who switched to amlodipine/atorvastatin (switch) or added a statin to their amlodipine regimen (add-on) from July 2004 to June 2007. Propensity score matching (1 switch:3 add-on) was applied based on 'nearest neighbor' approach. The primary adherence measure was patients with proportion of days covered (PDC) >/=0.80 at 180 days; secondary measures included mean PDC and persistence. A sensitivity analysis was performed, accounting for total statin/amlodipine exposure. RESULTS: Among 4556 matched patients (n = 1139 switch; n = 3417 add-on), mean age was 53.9 years and 52.1% were male. After 180 days, adherence with statin therapy was higher for the switch vs add-on cohort (50.8% vs 44.3%; P < 0.001). After adjusting for pre-index amlodipine adherence, the switch cohort was more likely to be adherent than the add-on cohort (odds ratio: 1.64 [95% confidence interval: 1.42 to 1.89]). Persistence was higher in the switch than the add-on cohort (127.6 vs 117 days; P < 0.001). CONCLUSION: Hypertensive patients taking amlodipine who initiated statin therapy via single-pill amlodipine/atorvastatin were more likely to remain adherent to their statin than patients adding a separate statin to their antihypertensive regimen.
Abstract: AIMS AND OBJECTIVES: To compare the nursing time and cost required for preparation and administration of liposomal amphotericin B, amphotericin B deoxycholate and voriconazole. DESIGN: Cost comparison study. METHODS: Nurse activities associated with the preparation and administration of the three study drugs were divided into 11 tasks and timed by observers at five hospitals. Target tasks were defined as those likely to be affected by the differences between drugs and excluded those tasks likely to differ owing to site-specific factors. Mean times for administration of a single day of therapy for each study drug were compared. Costs of preparation and administration of a 14-day regimen were estimated. RESULTS: Sixty-nine patients were observed receiving a total of 256 doses of study medications. Labour times were 20, 16, 14 and 3 minutes per day for liposomal amphotericin B, amphotericin B deoxycholate, intravenous voriconazole and oral voriconazole, respectively. Administration time was significantly lower for intravenous voriconazole compared with liposomal amphotericin B (p < 0.05), and for oral voriconazole compared with all intravenous regimens (p < 0.05). Preparation of medications took the longest time for intravenous formulations and was longer for liposomal amphotericin B than for the other drugs by 3-5 minutes. Average non-drug costs associated with preparation and administration of a 14-day regimen were greatest in the amphotericin B deoxycholate arm at US$ 335, followed by liposomal amphotericin B (US$ 310) and voriconazole (US$ 180). CONCLUSION: Intravenous voriconazole required less time to prepare and administer on a daily basis than liposomal amphotericin B, and was similar to amphotericin B deoxycholate. Measurements of intravenous vs. oral voriconazole administration suggest the opportunity to save 10-17 minutes per day with the oral formulation. RELEVANCE TO CLINICAL PRACTICE: Oral voriconazole may provide significant savings in terms of nursing time compared with intravenous antifungal drugs.
Abstract: BACKGROUND AND PURPOSE: Prior stroke confers an increased risk of future cardiovascular events. Because the incremental economic impact of this added risk is unknown, we assessed the additional cardiovascular costs and hospitalizations associated with ischemic stroke. METHODS: Patients hospitalized for ischemic stroke during 2002 to 2005 were identified from a large US managed-care plan and matched to control patients hospitalized for a noncardiovascular acute event. Cumulative stroke-related and non-stroke-related cardiovascular medical costs were determined for each group. Stroke and nonstroke cardiovascular hospitalization rates were calculated with the Kaplan-Meier method; risk of hospitalization was estimated with a Cox regression model. RESULTS: Stroke patients and matched controls (N=11 883) were identified (mean age approximately 58 years; 47.8% female). Compared with controls, patients hospitalized for ischemic stroke had higher stroke and nonstroke cardiovascular medical costs at 6 months (stroke: $1756 vs $50, P<0.01; nonstroke cardiovascular: $1437 vs $658, P<0.01) and 12 months (stroke: $2109 vs $68, P<0.01; nonstroke cardiovascular: $2203 vs $1167, P<0.01) of follow-up. Among stroke patients, cumulative stroke and nonstroke cardiovascular hospitalization rates were 9.06% and 5.63% at 6 months, respectively, and 21.09% and 22.05% at 36 months, respectively. Stroke patients were at significantly increased risk of repeat stroke hospitalization (hazard ratio=12.55; 95% CI, 10.50 to 15.01) and nonstroke cardiovascular hospitalization (hazard ratio=1.95; 95% CI, 1.77 to 2.14). CONCLUSIONS: After ischemic stroke, patients have significantly greater stroke and nonstroke cardiovascular costs and hospitalizations than do matched controls. Attention to total cardiovascular risk reduction in this population could potentially reduce downstream costs.
Abstract: OBJECTIVES: This study evaluated the economic implications of results obtained by the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. METHODS: To enable long-term projection of the trial results, a discrete event simulation of the course of clinical care after a recent stroke or transient ischemic attack (TIA) was developed. It generates pairs of identical patients; both receive usual care, one receives atorvastatin in addition. Their clinical course is simulated based on their risk of stroke, cardiovascular events, and case fatality rates taken from SPARCL, life expectancy from Saskatchewan Health data, and utility weights from literature. Costs, from a US health-care payer perspective in 2005 US dollars, were estimated for a within-trial 5-year period; survival and quality-adjusted life-years (QALYs) were extrapolated over a patient's lifetime; all discounted at 3%/year. RESULTS: The prevention of stroke, coronary, and other cardiovascular events expected with atorvastatin translates to mean gains of 0.155 life-years gained and 0.172 QALYs per patient over their lifetime. Reducing associated medical costs ($8405 vs. $11,237) but increasing drug costs ($13,984 vs. $8752) results in net $2400/patient, or $13,916/QALY gained. Probabilistic sensitivity analysis indicates no simulations yield ratios above $50,000/QALY. CONCLUSION: Prescribing atorvastatin for patients with prior stroke or TIA is expected to provide health benefits at an acceptable cost in the United States.
Abstract: PURPOSE: To examine the effect of antihypertensive adherence on blood pressure and barriers to adherence in racially diverse elderly patients. METHODS: Telephone survey of a representative sample of 300 of all 3416 hypertensive patients aged >70 from four urban primary care practices. From electronic records, we calculated subjects' annual mean systolic blood pressure. We asked about the last missed antihypertensive dose in six time intervals. Based on association with blood pressure control, non-adherence was defined as missing any dose in the past 3 months. Subjects were also asked about six domains of adherence barriers: health, personal support, drug coverage, medication filling and use, doctor-patient interaction and knowledge. All models adjust for demographics, treatment regimen and sampling weights. RESULTS: The 202 subjects (67% response rate) were: female (65.9%), black (64.8%), mean age 77.4 years (5.49) and on mean 2.4 (SD 1.3) antihypertensive drugs. Mean annual systolic pressure for non-adherent subjects (22% of the cohort) was higher than adherent subjects (137.7 vs.133.4 mmHg, p = 0.065). After adjustment, the association between adherence and blood pressure was stronger in black than white patients (p = 0.007). In an initial model, being unaware of Medicare Part D had a lower adjusted odds ratio (AOR) of adherence (p < 0.05). In the final model, adherence barriers were: medication filling/use (run out of pills [AOR 0.25, CI 0.09-0.66] and 28% reduction per each of eight barriers); doctor-patient interaction (less important to discuss hypertension [AOR 0.32, CI 0.12-0.84]); and knowledge (38% lower AOR per incorrect answer about diseases unrelated to hypertension). CONCLUSION: Self-reported adherence was associated with a higher blood pressure, especially in elderly black patients. To promote adherence, our data suggest targeting: filling prescriptions, prioritizing hypertension care and educating about effects of hypertension.
Abstract: OBJECTIVE: To quantify the impact of non-adherence on the clinical effectiveness of antibiotics for acute exacerbations of chronic bronchitis (AECB) and to estimate the economic consequences for Spain, Italy and the United States. METHODS: Standard systematic reviewing procedures were followed to identify randomised controlled clinical trials of antibiotic treatment for acute respiratory tract infection for which adherence was reported. A decision-analytic model was then constructed to evaluate the impact of non-adherence to antibiotic treatment on clinical effectiveness and costs per AECB episode. The model compared the total treatment costs, cure rates and incremental costs per cure for a poor compliance group (PCG) against a good compliance group (GCG). Clinical and resource use estimates were from the published literature and physician surveys. RESULTS: Twenty-five articles met the criteria of the systematic review, although only one reported treatment success by adherence status. The relative risk of clinical effectiveness if non-adherent was 0.75 (95%CI 0.73-0.78). Based on this single study, the model predicted that 16-29% more patients would be cured in the GCG vs. the PCG, and payers would save up to euro122, euro179 and US$141 per AECB episode in Spain, Italy and the United States, respectively. CONCLUSIONS: Non-adherence to antibiotics for AECB may have an impact on clinical effectiveness, which is associated with increased costs.
Abstract: OBJECTIVE: We examine the prevalence, treatment, and control of hypertension, dyslipidemia, and concomitant hypertension and dyslipidemia among Hispanics in four US communities. METHODS: This was a cross-sectional study of Hispanics who participated in health screening programs from 2004 to 2006. We enrolled 5288 Hispanics in Miami (n=372), New York (n=254), Los Angeles (n=4037), and Houston (n=625). The main outcome measures were prevalence, treatment and control rates of hypertension, dyslipidemia, and concomitant hypertension and dyslipidemia. RESULTS: Overall prevalence rates of hypertension, dyslipidemia, and concomitant hypertension and dyslipidemia were 37.5%, 26.6%, and 15.3%, respectively. Hypertension treatment rates ranged from 30.9% (Houston) to 68.2% (Miami) (P<.05); control was achieved in 34.7% (Los Angeles) to 47.8% (New York, P<.05). Dyslipidemia treatment rates were lowest in Houston (36.5%) and highest in New York (75.3%, P<.05); control rates were 62.3% (Houston) to 75.1% (Los Angeles P<.05). Dual treatment of hypertension/dyslipidemia ranged from 24.4% (Houston) to 69.4% (New York, P<.05), dual control was achieved in 4.5% (Houston) to 35.3% (New York, P<.05). Multivariable logistic regression analyses showed the odds of having each condition did not to differ by region, but regional differences existed for treatment and control. CONCLUSIONS: A high prevalence of hypertension, dyslipidemia, and combined hypertension and dyslipidemia and low control rates for hypertension and concomitant hypertension and dyslipidemia exist among US Hispanic adults in different communities.
Abstract: OBJECTIVE: The CARDS trial, a multicentre, randomized, controlled trial, found that atorvastatin 10 mg/day for patients with type 2 diabetes mellitus and normal low-density lipoprotein (LDL)-cholesterol significantly reduced cardiovascular (CV) events, including stroke. We estimated the cost effectiveness of atorvastatin as primary prevention against CV disease from the short-term and lifetime US payer perspectives. RESEARCH DESIGN AND METHODS: We constructed a decision analytic (Markov) model to evaluate long-term costs and outcomes for atorvastatin 10 mg/day versus no HMG-CoA reductase inhibitor (statin) therapy for patients with type 2 diabetes and no history of a CV event. CV event rates and survival were based on risk equations calibrated to CARDS and applied to a US type 2 diabetes population; the atorvastatin effect on CV events was based on hazard ratios from CARDS; direct medical care costs were based on US treatment patterns and published costs analyses of patients with diabetes. Costs were valued in $US, year 2005 values; costs and benefits were discounted at 3% per annum. RESULTS: Within the time horizon of the trial (5 years), the cost effectiveness of atorvastatin was $US137 276 per QALY. At 10 years, the incremental cost per QALY improved to $US3640 per QALY. At 25 years, overall costs were lower and QALYs higher in the atorvastatin arm. Costs of managing CV events were lower after 5 years for patients treated with atorvastatin. CONCLUSIONS: For patients with type 2 diabetes and one additional risk factor for CV disease, normal LDL-cholesterol and no history of a CV event, primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years, although it is costly from a short-term US payer perspective. From both a medical and an economic viewpoint, primary prevention is desirable in this patient population.
Abstract: BACKGROUND: Candidemia is a common cause of nosocomial bloodstream infection. When selecting therapeutic treatments for candidemia, cost-effectiveness is an important consideration. The present study assessed the cost-effectiveness of voriconazole for the treatment of candidemia. METHODS: A decision-analytical model was used for evaluating the cost-effectiveness of voriconazole compared with a regimen of conventional amphotericin B (CAB) followed by fluconazole (FLU) in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting, based on the Global Candidemia Study. The time frame of the model was 98 days (14 weeks). Model parameters were based primarily on clinical outcome, and resource use data collected from the clinical trial were used. Supplemental data were obtained from an independent panel of 12 Canadian experts for parameters not available from the clinical trial. Unit costs were collected from Canadian sources. The outcome variables selected in the study were the number of patients cured within 98 days, the number of patients surviving at 98 days and the number of patients avoiding toxicity. Incremental costs per outcome were calculated to compare the cost-effectiveness analyses (both probabilistic and one-way sensitivity analyses were performed). RESULTS: The cost-effectiveness analysis demonstrated a difference of $1,121 in the total average cost of treatment with voriconazole ($70,489) versus CAB/FLU ($69,368). While the costs of voriconazole exceeded the costs of CAB/FLU, these costs were almost completely offset by lower hospitalization costs. While patients in both treatment arms experienced cure rates of 41%, both the percentage of patients surviving at day 98 (64.5% versus 58.2%) and the percentage of patients avoiding toxicity (64.5% versus 52.5%) were higher in the voriconazole arm. Accounting for differences in total costs and clinical outcomes, this analysis estimated an incremental cost per patient surviving at day 98 of $17,739, and an incremental cost per patient avoiding toxicity of $9,298. In the case of cost per patient cured, voriconazole had a higher cost ($1,121) than CAB/FLU. The results of the deterministic and probabilistic sensitivity analyses indicated that the model was robust. CONCLUSIONS: Results of the decision-analytical model provided evidence to support the cost-effectiveness of voriconazole relative to a regimen of CAB/FLU in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting.
Abstract: BACKGROUND: Voriconazole, a broad-spectrum triazole, has demonstrated significantly improved survival compared with conventional amphotericin B (CAB) as initial therapy for invasive aspergillosis (IA). OBJECTIVE: To compare health care resource use and cost at 12 weeks following first-line treatment with voriconazole compared with CAB for IA using resource use data collected during a clinical trial. METHODS: Days of hospitalization, intensive care, antifungal drug use, and outpatient care were collected during a large randomized, controlled trial of patients with IA receiving initial treatment with voriconazole or CAB. Unit costs based on published data sources were applied to healthcare use to estimate 12-week costs following initiation of therapy. Resource use and costs were compared for each treatment arm overall and by survival. The sensitivity of total costs to changes in healthcare use and unit costs was examined. RESULTS: Total hospital days and intensive care unit (ICU) days were similar for voriconazole and CAB (total: 27.8 vs. 27.7, P=0.97 and ICU: 5.6 vs. 8.1, P=0.11). Among survivors, voriconazole was associated with similar numbers of total hospital days (29.8 vs. 32.0 days, P=0.54) to CAB, but fewer ICU days (3.9 vs. 8.2, P=0.03). For non-survivors, those treated with voriconazole had a similar number of total hospital days (23.0 vs. 21.8, P=0.73) and ICU days (9.8 vs. 7.9, P=0.44). Patients treated with voriconazole had significantly more days alive and out of the hospital than with CAB at 12 weeks (40.3 vs. 28.4 days, P<0.001). Total costs were similar with voriconazole compared with CAB ($78,860 vs. $83,857, P=0.51). Differences in cost were not sensitive to changes in the input parameter values. CONCLUSIONS: Using voriconazole first-line for treatment of IA resulted in significantly fewer deaths and similar treatment costs. Hospital-free survival was significantly greater for patients initially treated with voriconazole.
Abstract: BACKGROUND: A previous study found that a single 2-g dose of azithromycin extended release (AZ-ER) was as efficacious as 10 days of levofloxacin (LFX) 500 mg QD in adults with acute bacterial rhinosinusitis (ABRS). The speed with which patients experience resolution of ABRS symptoms has not been reported. OBJECTIVE: The purpose of this study was to evaluate the resolution of ABRS symptoms after a single 2-g dose of AZ-ER compared with 10 days of LFX. METHODS: This was a retrospective analysis of data from a published international, randomized, double-blind, double-dummy clinical trial conducted between January 21, 2003, and February 20, 2004, that included 534 adult (age >or=18 years) outpatients with ABRS. All patients entering the study were required to have purulent nasal discharge, purulent drainage in the posterior pharynx, or purulent discharge from the maxillary sinus orifice and at least 1 of 3 other protocol-defined cardinal symptoms of ABRS (sinus pain, pressure, or tenderness) for >or=7 days. In addition, they were required to have at least 2 of the following 6 noncardinal symptoms at baseline: cough, fever, headache, nasal congestion, postnasal discharge, and leukocytosis. All patients who received medication were assessed for the occurrence of adverse events at study visits during and after therapy. At the ontreatment visit (between days 3 and 5), baseline symptoms were reassessed as resolved, improved, same, new, or worse. Resolution of symptoms was calculated as the proportion of patients with 3 or 4 cardinal symptoms either resolved (if present at baseline) or not new (if absent at baseline). Concomitant medications other than antibiotics were allowed as needed for symptomatic treatment. RESULTS: Demographic characteristics were similar at baseline between the AZ-ER and LFX treatment arms (mean age, 38.4 and 39.5 years, respectively), although more women were randomized to receive LFX (62.9%) than AZ-ER (53.3%) (P = 0.025). More than 90% of patients in both arms had >or=3 ABRS symptoms at baseline. At the on-treatment visit, resolution of >or=3 ABRS symptoms was achieved in 88 of 270 AZ-ER patients (32.6%) and 61 of 261 LFX patients (23.4%) (P = 0.018). Resolution of individual symptoms in the AZ-ER and LFX groups at 3 to 5 days was as follows: sinus pain (92/253[36.4%] and 77/251 [30.7%]; P = NS), sinus pressure (97/243 [39.9%] and 68/244 [27.9%]; P = 0.005), sinus tenderness (83/218 [38.1%] and 73/214 [34.1%]; P = NS), and nasal discharge (57/270 [21.0%] and 49/264 [18.6%]; P = NS). Treatment-related adverse events were reported by 63 of 270 AZ-ER patients (23.3%) and 41 of 268 LFX patients (15.3%). Gastrointestinal disturbances were the most common adverse events, including nausea (4.4% and 3.4%) and abdominal pain (2.6% and 0.4%).
Abstract: This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) added to diuretics or beta-blockers. Adults with hypertension treated with diuretic or beta-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP) > or =140/90 mmHg (> or =130/80 mmHg for diabetes mellitus) and recorded BP measurements within 6 months before and 1-12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort) were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were -17.5/-8.8, -15.7/-6.3, and -13.0/-8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients' beta-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.
Abstract: PURPOSE: The comparative cost-effectiveness of voriconazole and amphotericin B in the treatment of invasive pulmonary aspergillosis (IPA) was examined. METHODS: A decision-tree model was constructed comparing 12-week treatment outcomes in a subset of patients enrolled in a clinical trial comparing initial treatment of IPA with amphotericin B versus voriconazole. Patients included those with IPA who underwent a thoracic computed tomographic (CT) scan at baseline. Cost and survival were estimated for those with and without a halo sign at baseline. Incremental cost-effectiveness ratios comparing voriconazole with amphotericin B were calculated for both patient subgroups. RESULTS: Patients with a halo sign had similar costs and better survival rates than those without the sign. Within the subgroup of patients with the sign, total costs were lower and survival rates higher for those treated with voriconazole than for those treated with amphotericin B. For patients without a halo sign, total costs and survival rates were higher for those treated with voriconazole versus amphotericin B. CONCLUSION: Among patients treated for IPA, those with a baseline CT halo sign, an early indicator of the condition, appeared to have better survival rates and lower health care costs compared with patients without the sign. In patients with the halo sign, survival rates were higher and costs were lower when voriconazole rather than amphotericin B was used as first-line treatment; survival was better with voriconazole than with amphotericin B when the halo sign was not present. Voriconazole was cost-effective compared with amphotericin B when the halo sign was present, but voriconazole's cost-effectiveness when the sign was not present depended on the cost per life saved.
Abstract: BACKGROUND: Voriconazole for the treatment of invasive aspergillosis (IA) shows superior clinical outcome and tolerability compared to conventional amphotericin B. However, the latter is often used as initial treatment due to lower drug acquisition costs. Therefore we performed a cost-effectiveness analysis. METHODS: A decision analytic model was designed to compare the cost-effectiveness of a regimen of voriconazole followed by conventional amphotericin B to a regimen of conventional amphotericin B followed by voriconazole. Patients initiated on treatment either completed initial therapy or switched to second line therapy due to toxicity or non-response. Probability of a switch was based on clinical trial data and local rates of renal toxicity. Resource use in the hospital was taken from the Global Comparative Aspergillosis (GCA) study. Costs were based on local drug acquisition costs, local cost estimates for hospitalisation and adjusted additional costs of amphotericin B-induced acute renal failure from the literature. Effectiveness was defined as survival at 12 weeks from the GCA study. An incremental cost-effectiveness ratio was estimated as the incremental cost per life saved comparing voriconazole to conventional amphotericin B. RESULTS: Based on this model, initial therapy of IA with voriconazole reduced total costs when compared to initial therapy with conventional amphotericin B (CHF 37 878/patient vs CHF 49 861/patient) and resulted in better survival at 12 weeks, making it the dominant treatment in terms of incremental cost-effectiveness. Results were most sensitive to alternative assumptions of the incidence of acute renal failure, but cost savings were sustained for voriconazole over a wide range of values. CONCLUSION: Considering that initial therapy with voriconazole is both cost-saving and results in better clinical outcomes, voriconazole is the dominant cost-effective option for initial therapy of IA, despite very low drug acquisition costs of conventional amphotericin B.
Abstract: BACKGROUND: The burden of asthma is substantial, and the overall cost of its management is growing. OBJECTIVE: To compare asthma-related charges and resource utilization across disease severity levels in the year after initial asthma treatment with any inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA). METHODS: This was a longitudinal, retrospective cohort study of claims data from managed care plans in the United States. All patients had a new prescription for an ICS or an LTRA between January 1999 and December 2000 and were enrolled in a managed care plan for at least 12 months before (preindex) and 12 months after (postindex) the initial claim. Asthma-related charges, hospitalizations, emergency department (ED) visits, physician visits, and asthma medication use were compared between the 2 cohorts. Propensity scores were calculated to control for baseline differences in patient characteristics and types of health care coverage. RESULTS: Claims from 31,860 patients were evaluated. Total postindex asthma-related charges were significantly lower in the ICS cohort than in the LTRA cohort (dollars 613 vs dollars 902, respectively; P < .001), as were asthma-related pharmacy charges (dollars 305 vs dollars 564, respectively; P < .001). Results were consistent for all propensity subclasses and all age groups. CONCLUSIONS: Results from this cohort study suggest that, across varying disease severities, treating asthma with an ICS as initial controller therapy leads to less health care resource utilization than does using an LTRA as initial therapy.
Abstract: Misuse of antibiotic therapy can have a profound negative impact both on individuals and on the community. The objective of this meta-analysis was to estimate the prevalence of antibiotic misuse in terms of non-compliance with therapy or reuse of leftover antibiotics in the community. Of 2848 screened articles, 46 contained the required information on the number of participants, the number compliant/using leftovers and the measurement technique. Mean compliance with antibiotics was 62.2% (95% confidence interval (CI), 56.4-68.0%) and mean use of leftover antibiotics was 28.6% (95% CI, 21.8-35.4%). Although variation in the methods resulted in substantial heterogeneity in the estimates, results were generally consistent by region and measurement technique. Patient education and simpler antibiotic regimens should be encouraged to promote responsible use of antibiotic therapy.
Abstract: BACKGROUND: The objective of this retrospective observational analysis is to examine the clinical effectiveness of amlodipine besylate as monotherapy or in combination with other antihypertensive drugs (AHDs) in systolic blood pressure (BP) control and BP goal attainment, according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 6, JNC 7, and American Diabetes Association (ADA)recommendations, within a multicenter ambulatory care setting. METHODS: Hypertensive adults (n = 1175) were identified during a 4-year period (1998 to 2001) from a large commercially available electronic medical record (EMR) database. Patients were required to have initiated therapy with amlodipine and have at least one BP measurement within 6 months before, and 12 months after, the medication start date. Patients were divided into cohorts based on the number of AHDs used before, and continued through, the initiation of amlodipine. Mean change in systolic BP was compared from pre- to post-amlodipine, and adjusted change in systolic BP was calculated using multivariate regression. The percentage of patients attaining BP goal was also calculated. RESULTS: In the order of increasing number of AHDs before initiation of amlodipine (0, 1, 2, > or = 3 previous AHDs): adjusted systolic BP change in mm Hg was -16.1 (95% confidence interval [CI]: -17.9, -14.3), -17.6 (95% CI: -19.6, -15.5), -16.7 (95% CI: -19.0, -14.5), and -15.7 (95% CI: -18.7, -12.8), respectively; BP goal attainment was 39%, 45%, 41%, and 45%, respectively. Amlodipine initiation in all regimens showed statistically significant incremental systolic BP reduction and BP goal attainment from baseline (P < .001). CONCLUSIONS: This study suggests that amlodipine besylate is effective alone or as an add-on therapy to diverse classes of agents.
Abstract: BACKGROUND: There are 2 million asthma-related emergency department (ED) events each year in the United States. The underrecognition and undertreatment of asthma is believed to be associated with this high level of morbidity. This study was designed to describe the treatment patterns in the year prior to the ED event and for 2 months after the event. METHODS: This retrospective observational study utilized an integrated managed care database that contained administrative claims from > 20 managed care plans across the United States. All patients with at least one ED visit for asthma during 2001 were included. Patients were required to have data available 12 months prior to and 2 months following the ED visit of interest, and were excluded if they had made an asthma-related ED visit within 12 months of the identified event. RESULTS: There were 12,636 patients identified with an asthma-related ED visit. In the year prior to the ED event, 25.1% of the patients received an inhaled corticosteroid (ICS), 29.9% received an oral corticosteroid (OCS), and 53.5% received a short-acting beta-agonist (SABA). Overall, there were three albuterol units dispensed for every ICS unit dispensed in the 12-month period prior to the ED event. Ninety-four percent of patients had made an office visit in the prior year, but only 13.3% underwent spirometry testing. Prescriptions dispensed for ICSs and OCSs increased 2.6-fold and 7.5-fold, respectively, in the month after the ED event, and dispensing rates reverted approximately to baseline rates by the second month after the index ED event. CONCLUSION: This study demonstrates the dependence of this population on the use of rescue medications, including SABA and OCS, to treat their asthma. Furthermore, the ED event resulted in only an incremental short-term improvement in ICS-containing controller treatment.
Abstract: BACKGROUND: A life-threatening attack of asthma that leads to intensive care unit (ICU) admission, intubation, or both identifies patients at high risk of subsequent morbidity and mortality and represents a major cost burden. OBJECTIVE: To assess the rates, characteristics, and costs of ICU admissions and intubations among asthma-related hospitalizations. METHODS: This analysis was performed using a database of 215 hospitals representing more than 3 million annual inpatient visits. Asthma-related hospital admissions were identified by a primary diagnosis code for asthma during 2000. Logistic regression was used to estimate the odds ratios (ORs) for predictors of ICU admission, intubation, and in-hospital mortality. Ordinary least squares regression was used to estimate adjusted mean costs and length of stay. RESULTS: Of 29,430 admissions with a primary diagnosis of asthma, 10.1% were admitted to the ICU and 2.1% were intubated. The risk of in-hospital death was significantly greater in patients who were intubated but not admitted to the ICU (OR, 96.20; 95% confidence interval [CI], 50.24-184.20), those who were admitted to the ICU and intubated (OR, 62.69; 95% CI, 38.17-102.96), and patients with more severe comorbidities (OR, 1.53; 95% CI, 1.38-1.70). On average, intubated patients stayed in the hospital 4.5 days longer and incurred more than $11,000 in additional costs; patients admitted to the ICU stayed 1 day longer and accounted for $3,000 in additional costs vs standard admissions. CONCLUSIONS: The inpatient mortality, morbidity, and cost burden of life-threatening asthma in the United States is considerable. This study characterizes patients with asthma at risk of ICU admissions and intubations. Appropriate recognition and treatment are needed to prevent these severe and potentially life-threatening events.
