Crotalidae Polyvalent Immune Fab and Cost-Effective Management of Hospital Admissions for Snakebites.

BACKGROUND: Venomous snakebites are a common clinical scenario in the Southeastern United States. CroFab® (Crotalidae Polyvalent Immune Fab (Ovine), BTG, Wales, UK) antivenom is indicated in cases involving pit vipers and is known to be expensive. The treatment protocol for snakebites is based on clinically subjective measures triggering the application, or escalation of, antivenom administration. The purpose of this study is to characterize the use of CroFab at our institution and to evaluate the impact of its use regarding cost and overall outcomes. We suspect that it is often used but potentially less often needed. We hypothesized that CroFab use was associated with increased length of stay (LOS) without an observed difference in patient outcomes. MATERIALS AND METHODS: A retrospective chart review of snakebite patients at our level-1 trauma center from 2000 to 2016 was performed. Snakebite location, snake species, number of vials of CroFab administered, hospital LOS, intensive care unit (ICU) LOS, and complications were identified for each patient. Patients were divided into CroFab (C) and no CroFab (NC) groups. RESULTS: One hundred ninety patients with venomous snakebites were included. 53.7% of patients received CroFab. There was no difference in the complication rate of C versus NC groups, (P = .1118). CroFab use was associated with longer hospital LOS (P < .0001) and ICU LOS (P < .0001). DISCUSSION: CroFab use was associated with increased LOS in our patient population. There was no difference in observed outcomes between the C and NC groups. These findings imply that CroFab is potentially over-used in our patient population.

FabAV antivenin use after copperhead snakebite: clinically indicated or knee-jerk reaction?

Abstract Background Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) antivenin is commonly recommended after pit viper snakebites. Because copperhead envenomations are usually self-limited, some physicians are reluctant to use this costly treatment routinely, while others follow a more liberal approach. We hypothesized that, in practice, only patients with evidence of significant (moderate or severe) copperhead envenomation [those with snakebite severity score (SSS) > 3] receive FabAV and examined a large cohort to determine the relationship between clinical findings and FabAV administration. Methods All data from patients evaluated for copperhead snakebite at a rural tertiary referral center from 5/2002 to 10/2013 were compiled. Demographics, transfer status, antivenin use, and clinical findings were collected; SSS was calculated. The relationships among FabAV use, clinical findings, and SSS were analyzed using t-test, chi-square, and Pearson’s coefficient (p < 0.05 was significant). Results During the study period, 318 patients were treated for copperhead snakebite; 44 (13.8 %) received antivenin. Median dose was four vials (range: 1–10; IQR: 4,6). There were no deaths. Most patients receiving FabAV (63.6 %) were admitted. With regard to demographics and symptoms, only the degree of swelling (moderate vs. none/mild; p < 0.01) and bite location (hand/arm vs. leg: p < 0.0001) were associated with FabAV use. A SSS > 3, indicating moderate or severe envenomation, was only very weakly correlated with antivenin use (r = 0.217;p < 0.0001). The majority of patients with SSS > 3 (65.8 %) did not receive antivenin while most patients who did receive antivenin (70.5 %) had SSS ≤ 3 (indicating mild envenomation). Conclusions Considerable variation occurs in antivenin administration after copperhead snakebite. Use of FabAV appears poorly correlated with patients’ symptoms. This practice may expose patients to the risks of antivenin and increasing costs of medical care without improving outcomes. Guidelines used for treating other pit viper strikes, such as rattlesnake or cottonmouth snakebite may be too liberal for copperhead envenomations. Our data suggests that most patients with mild or moderate envenomation appear to do well independent of FabAV use. We suggest, for patients with copperhead snakebite, that consideration be given to withholding FabAV for those without clinical evidence of severe envenomation until prospective randomized data are available.

Health outcomes and cost-effectiveness of certolizumab pegol in the treatment of Crohn's disease.

Crohn's disease (CD) causes chronic inflammation of the gastrointestinal tract and leads to fluctuations between active disease and remission. Certolizumab pegol is one of the newer biological treatments for patients with moderate-to-severe CD. Certolizumab pegol was shown to be effective in CD patients achieving response and remission in both randomized and non-randomized studies, and is an alternative biological treatment for CD. The available data show that certolizumab pegol achieves similar therapeutic efficacy and health-related quality of life scores in CD patients as the other biological agents, but at a higher cost, if dose escalation of other biologics is not considered. Considering subcutaneous self-administration, and lower number and frequency of injections, patients may prefer certolizumab pegol over the other biological treatments.

Abciximab bolus with optional infusion in intervention for ST-elevation myocardial infarction.

OBJECTIVES: The standard abciximab regimen is a bolus dose followed by a 12-h infusion. Whether the bolus dose alone is sufficient for ST-elevation myocardial infarction patients receiving a high loading dose of clopidogrel is unknown. DESIGN: In an observational study, 693 consecutive patients were treated with abciximab during percutaneous coronary intervention for ST-elevation myocardial infarction. Totally 354 patients received standard strategy of abciximab bolus and infusion followed by 339 patients that recieved abciximab bolus only (271 patients) or bolus and infusion if suboptimal result (68 patients) in combination with a higher loading dose of clopidogrel (600 mg) - the modified strategy. RESULTS: The two groups were similar regarding baseline characteristics and in hospital bleeding events. At 30 days, the composite of death, re-infarction or target vessel revascularization was 9.1% in the standard and 7.5% in the modified strategy (p = 0.45). The rate of stent thrombosis was lower in the modified strategy group with 0% and 2.3% in the standard group (p < 0.001) and the mean total medical cost was lower in the modified strategy group with €8032 and €8665 in the standard group (p < 0.001). CONCLUSIONS: In primary percutaneous coronary intervention with a loading dose of 600 mg clopidogrel, it seems safe and cost-saving to give abciximab bolus with optional infusion.

Certolizumab pegol compared to natalizumab in patients with moderate to severe Crohn's disease: results of a decision analysis.

INTRODUCTION: A significant proportion of patients with Crohn's disease (CD) lose response to antibodies directed against tumor necrosis factor α (TNF). Prior TNF-antagonist failure is associated with lower rates of response to subsequent TNF-antagonist therapy. In patients failing two anti-TNF agents, a choice exists between using a third-anti-TNF therapy or natalizumab (NAT), an α-4 integrin inhibitor. A cost-effectiveness analysis comparing these competing strategies has not been performed. METHODS: A decision analytic model was constructed to compare the performance of certolizumab pegol (CZP) versus NAT in patients with moderate to severe CD. Previously published estimates of efficacy of third-line anti-TNF therapy and NAT were used to inform the model. Costs were expressed in 2010 US dollars. A 1-year time frame was used for the analysis. RESULTS: In the base case estimate, use of NAT was only marginally more effective [0.71 vs. 0.70 quality adjusted life-years (QALYs)] than CZP but was expensive with an incremental cost-effectiveness ratio (ICER) of $381,678 per QALY gained. For CZP 2 months response rate of at least 24%, NAT had an ICER above the willingness-to-pay (WTP) threshold. The model was sensitive to the costs of both therapies; for all CZP costs below $2,300 per dose, NAT had higher ICER than the WTP threshold. Substituting adalimumab for CZP resulted in similar ICER estimates and thresholds for NAT use. CONCLUSIONS: In patients with moderate to severe CD failing two TNF-antagonists, using a third TNF-antagonist therapy appears to be a cost-effective strategy without significantly compromising treatment efficacy.

Sensitivity analysis for causal inference using inverse probability weighting.

Evaluation of impact of potential uncontrolled confounding is an important component for causal inference based on observational studies. In this article, we introduce a general framework of sensitivity analysis that is based on inverse probability weighting. We propose a general methodology that allows both non-parametric and parametric analyses, which are driven by two parameters that govern the magnitude of the variation of the multiplicative errors of the propensity score and their correlations with the potential outcomes. We also introduce a specific parametric model that offers a mechanistic view on how the uncontrolled confounding may bias the inference through these parameters. Our method can be readily applied to both binary and continuous outcomes and depends on the covariates only through the propensity score that can be estimated by any parametric or non-parametric method. We illustrate our method with two medical data sets.

Certolizumab pegol (CIMZIA®) for the treatment of rheumatoid arthritis.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of certolizumab pegol (CZP) for adults with active rheumatoid arthritis (RA) that have not responded adequately to treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX), in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcome measures included American College of Rheumatology (ACR) 20, 50 and 70 response rates and quality of life measures after 3 months and 6 months of treatment. The ERG examined the submission's search strategies and considered they appeared comprehensive and that it was unlikely that relevant studies would have been missed. Only English language studies were considered in the submission and non-English language studies relevant to the decision problem may possibly have been ignored. The ERG analysed the first submitted economic model so as to itemise in detail clarification points that were brought to the attention of the manufacturer. In response the manufacturer submitted a modified cost-effectiveness analysis. The ERG undertook further analysis of this second model and other additional submitted evidence. The clinical evidence was derived from two multicentre blinded randomised controlled trials (RCTs) comparing CZP + MTX to placebo + MTX (the RAPID 1 and RAPID 2 trials). RAPID 1 lasted 52 weeks with 982 patients and RAPID 2 24 weeks with 619 patients. Evidence for clinical effectiveness of CZP in mono-therapy came from the 24-week FAST4WARD trial with 220 patients that compared CZP (400 mg every 4 weeks) versus placebo. The three key RCTs demonstrated statistically significant superiority of CZP + MTX versus placebo + MTX and of CZP versus placebo with respect to a variety of outcomes including ACR 20, ACR 50 and ACR 70 measures and quality of life measures at 3 and 6 months. On the basis of results from the indirect comparison meta-analyses, the manufacturer suggested that CZP may be at least as effective as other 'biological' DMARD (bDMARD) comparators and, in a few ACR measures at 3 and 6 months, more effective. CZP is an effective therapy for adult RA patients whose disease has failed to respond adequately to cDMARDs including MTX or who are intolerant of MTX. The cost-effectiveness of CZP relative to other bDMARDs is unclear because the economic modelling undertaken may have ignored relevant effectiveness data and potential differences between trial populations, and so may have included effectiveness results that were biased in favour of CZP; underestimated uncertainty in the relative effectiveness of compared DMARDs; and ignored the potential influence of differences between bDMARDs with regard to adverse events and their related costs and health impacts. The NICE guidance issued in October 2009 states that: the Committee is minded not to recommend certolizumab pegol as a treatment option for people with RA; and the Committee recommends that NICE asks the manufacturer of CZP for more information on the clinical effectiveness and cost-effectiveness of CZP for the treatment of people with RA. On receipt of this information and details of a patient access scheme NICE issued final guidance recommending CZP, under certain criteria, as a treatment option for people with RA.

Long-term results following switch from abciximab to eptifibatide during percutaneous coronary intervention.

BACKGROUND: The usage of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors improves the outcome during high-risk percutaneous coronary interventions (PCI). The aim of this study was to evaluate the long-term effects after a planned switch from abciximab to eptifibatide during PCI. HYPOTHESIS: A switch from the general use of abciximab to eptifibatide as a GP IIb/IIIa in connection with PCI would not have any negative effects on long-term clinical outcomes. METHODS: To reduce costs, a general switch from abciximab to eptifibatide was instituted in 2004 in 2 university hospitals in Sweden. All patients treated 6 months before and 6 months after the switch were followed for 30 months. During the study period, 1038 patients underwent PCI and received a GP IIb/IIIa receptor inhibitor, 481 (46%) before the switch (Group A) and 557 (54%) after the switch (Group B). The 2 groups had similar baseline characteristics. The primary endpoint was the composite of death, myocardial infarction, stroke, or new coronary revascularization (percutaneous or surgical); secondary endpoints were the individual components of this composite. A separate analysis was performed on patients treated for ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction/unstable angina, and diabetes, respectively. Data were collected from the Swedish Coronary Angiography and Angioplasty Registry. RESULTS: There were no differences between the groups in the primary endpoint (29.7% in Group A vs 29.3% in Group B; P = 0.48) or in any of the secondary endpoints. CONCLUSIONS: A switch from the general usage of abciximab to eptifibatide as a GP IIb/IIIa receptor inhibitor in connection with PCI did not seem to have any negative effects on long-term clinical outcomes.

Economic impact of same-day home discharge after uncomplicated transradial percutaneous coronary intervention and bolus-only abciximab regimen.

OBJECTIVES: This study sought to estimate the economic impact of same-day home discharge compared with overnight hospitalization after transradial percutaneous coronary intervention (PCI). BACKGROUND: Same-day home discharge after transradial PCI and a bolus-only abciximab regimen was found to be clinically noninferior to the abciximab standard therapy and overnight hospitalization in patients with various forms of acute coronary syndromes. METHODS: In the EASY (Early Discharge After Transradial Stenting of Coronary Arteries) trial, 1,005 patients were randomized after a bolus of abciximab and uncomplicated transradial coronary stenting, either to same-day home discharge and no infusion (outpatient group) or to overnight hospitalization and 12-h abciximab infusion (overnight-stay group). We estimated post-PCI health care cost (in Canadian dollars) of trial subjects and short-term economic impact of same-day home discharge. As randomization was done after the procedure, outcomes were similar, and PCI resource use showed minimal and nonsignificant differences, a post-PCI cost-minimization analysis was conducted. Detailed per-patient information of health care resources used immediately after PCI up to 30 days was collected. RESULTS: Mean post-PCI hospital stay was 8.9 h for outpatients versus 26.5 h for overnight-stay patients (p < 0.001). At 30-day follow-up, the mean cumulative medical cost per outpatient was $1,117 ± $1,554 versus $2,258 ± $1,328 for overnight-stay patients. The mean difference of $1,141 (95% confidence interval: $962 to $1,320) was mainly due to the extra night for overnight hospital stay. CONCLUSIONS: In a real-world setting, same-day home discharge after uncomplicated transradial PCI and a bolus-only abciximab regimen resulted in a 50% relative reduction in medical costs. Extension of this outpatient strategy would be welcomed by the hospitals and reimbursement systems in a context of increasing demand for health care cost reduction. (Early Discharge After Transradial Stenting of Coronary Arteries [EASY]; NCT00169819).

Bolus-only versus bolus + infusion of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention.

BACKGROUND: The present study was done to analyze if glycoprotein IIb/IIIa inhibitors (GPI) bolus-only will reduce vascular/bleeding complications and cost with similar major adverse cardiac events (MACE) when compared with GPI bolus + infusion. Evidence-based therapy of GPI inhibitors during percutaneous coronary intervention (PCI) incorporates intravenous bolus followed by 12 to 18 hours of infusion. However, GPI bolus + infusion may increase vascular/bleeding complications and may not reduce MACE when compared with GPI bolus-only. METHODS: From January 1, 2003, to December 31, 2004, 2,629 consecutive patients received GPI during PCI at a single center. Of these, 1,064 patients received GPI bolus + infusion in 2003 and were compared with 1,565 patients that received GPI bolus-only in 2004. Baseline characteristics were similar in both groups. RESULTS: Patients receiving GPI bolus-only had reduced vascular/bleeding complications when compared with bolus + infusion (4.9% vs 7%, P < .05, odds ratio 0.62, 95% confidence interval 0.45-0.89). Furthermore, ischemic complications were similar in both groups, including periprocedural creatine kinase-MB enzyme release (12.8% vs 15.3%, P = NS), MACE at 30 days (3.2% vs 3%, P = NS), and death and myocardial infarction at 1 year (7.1% vs 7.8%, P = NS). In addition, GPI bolus-only reduced cost in US dollars ($323 vs $706, P < .001) and increased ambulatory PCI (13.1% vs 3.2%, P < .01), with reduced length of stay (1.1 vs 1.6 days, P < .01), when compared with GPI bolus + infusion. CONCLUSIONS: Glycoprotein inhibitor bolus-only reduces vascular/bleeding complications with similar MACE and reduced cost when compared with GPI bolus + infusion. In addition, GPI bolus-only improved ambulatory PCI and reduced length of stay. These results are consistent with a safer and cost-effective strategy for bolus-only when GPI therapy is considered during PCI.

A longitudinal analysis of outcomes associated with abciximab and eptifibatide in a consecutive series of 3074 percutaneous coronary interventions.

BACKGROUND: Although the efficacy of platelet glycoprotein IIb/IIIa inhibitors (GPIIb/IIIa) in reducing complication rates during percutaneous coronary intervention (PCI) is well established, comparative studies assessing currently approved agents as administered in current practice are limited. We studied the clinical and length of stay (LOS) outcomes of patients undergoing PCI who received either abciximab or eptifibatide. METHODS: All patients undergoing elective, urgent, or emergency PCI at Mayo Clinic Rochester between November 17, 2000 and August 31, 2004 who received either abciximab or eptifibatide were included. Clinical, angiographic, and follow-up data were prospectively recorded in the Mayo Clinic PCI Registry; administrative data recorded LOS. We used logistic and Cox proportional hazard models to estimate the risk of adverse events and generalized linear modeling to predict LOS. Propensity score and standard risk adjustments were used to account for baseline differences. RESULTS: A total of 2123 PCI patients received eptifibatide and 951 received abciximab. The adjusted odds ratio for in-hospital death and myocardial infarction (MI) with eptifibatide was 0.80 (95% CI 0.56-1.14, P = 0.21) versus abciximab. Adjusted hazard ratios for death and MI and for death, MI, or target vessel revascularization during a median follow-up of 24.6 months were 0.84 (95% CI 0.68-1.02, P = 0.08) and 0.95 (95% CI 0.81-1.11, P = 0.53), respectively. Adjusted postprocedural LOS was similar at 3.4 days. CONCLUSION: This large observational study found no evidence of a clinical or LOS advantage to physician choice of either abciximab or eptifibatide during PCI in contemporary practice.

Resource allocation among cardiovascular specialists and trainees: a pilot survey.

OBJECTIVE: To assess the relative importance that cardiovascular specialists assign to new technologies. METHODS: A pilot survey of practising cardiologists in one tertiary hospital and cardiology trainees from two university programs. Respondents were asked to distribute a hypothetical budget among several new technologies. RESULTS: A total of 28 responses (response rate of 62%) were analyzed. In the hypothetical situation described, doctors appeared willing to spend approximately equal amounts on implantable cardiac defibrillators (median 25%, interquartile range 5% to 30%) and bare metal coronary stents (median 28%, interquartile range 20% to 40%). Physicians were more restrained in their allocation for refinements of these two technologies, including drug-eluting stents and biventricular pacing. Wide individual variations in technology use were noted. CONCLUSIONS: There is considerable uncertainty among cardiovascular specialists regarding the relative value of new technologies. Further work is required to better quantify this uncertainty and its determinants.

A strategy to offset the extra cost of sirolimus-eluting stent in patients undergoing intervention for acute myocardial infarction.

OBJECTIVE: To obtain a quantitative estimate of the overall costs and cost effectiveness ratio of sirolimus-eluting stents (SES) implantation and tirofiban infusion compared to abciximab and bare metal stent (BMS) in patients undergoing primary intervention for acute ST segment elevation myocardial infarction (STEMI). METHODS: In the attempt to make the unrestricted use of SES in STEMI patients affordable under the current European reimbursement system, between March 6, 2003, and April 23, 2004, 175 patients with STEMI were randomized to receive tirofiban infusion and SES versus abciximab and BMS as part of the STRATEGY trial. Costs and outcome were monitored for 2 years. RESULTS: The cost of the index procedure was 9345 euros +/-2573 and 9657+/-2114 for the tirofiban+SES and abciximab+BMS group, respectively (P=0.048). At follow-up, the composite of death or myocardial infarction and the costs not related to target vessel revascularisation (TVR) did not differ in the two groups while the rate of TVR and the costs related to it were lower in the tirofiban+SES group. The overall 2-year cost of treating a patient in the tirofiban+SES group was 10,971 euros +/-4185 compared to 12,066 euros +/-4636 for the abciximab+BMS group (P=0.006). Halving the cost of abciximab resulted in higher initial hospital costs for the tirofiban+SES but overall cost neutrality over a 24-month time horizon. CONCLUSIONS: Compared to abciximab+BMS, tirofiban infusion+SES implantation in STEMI patients was an economically dominant strategy, with an improved composite outcome and lower overall costs.

Bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors in drug-eluting stent implantations in the absence of acute myocardial infarction: clinical and economic results.

BACKGROUND: The use of bivalirudin in percutaneous coronary interventions has been shown to be clinically safe and effective, and may be associated with shorter hospital stays and lower costs than heparin + glycoprotein (GP) IIb/IIIa inhibition. This study compared the utilization, clinical outcomes and costs associated with the planned use of bivalirudin versus heparin + GP IIb/IIIa inhibition in drug-eluting stent (DES) patients without acute myocardial infarction (MI). METHODS: We retrospectively studied 1,842 patients who underwent DES placement between May 2003 and December 2004. Planned treatment with heparin + GP IIb/IIIa inhibition was administered to 1,305 and planned bivalirudin alone was administered to 537 patients. Clinical follow ups (mean = 782 +/- 204 days) were obtained via telephone or mailed surveys in 1,813 patients (98.4%). Propensity analysis was utilized to adjust for between-groups baseline differences. RESULTS: The unadjusted data revealed similar in-hospital outcomes in both groups. After propensity adjustment, the rate of vascular complications was significantly lower in the bivalirudin-treated group (0.2% vs. 1.2%; p = 0.04). At 1 year, clinical outcomes were similar in both groups. The overall unadjusted and adjusted cost analysis revealed similar mean hospital costs (11,384 U.S. dollars vs. 11,018 U.S. dollars; p = ns) and length of stay (2.9 days vs. 2.8 days; p = ns) in both groups. The unadjusted and adjusted mean hospital costs were significantly lower in patients treated with bivalirudin versus patients who received heparin + abciximab. CONCLUSIONS: These observations suggest that bivalirudin is a safe, cost-effective alternative to heparin + GP IIb/IIIa inhibition in patients undergoing DES in the absence of acute MI.

The role of risk stratification in the decision to provide upstream versus selective glycoprotein IIb/IIIa inhibitors for acute coronary syndromes: a cost-effectiveness analysis.

OBJECTIVES: We endeavored to determine under what conditions a strategy of upstream use of small molecule platelet glycoprotein (GP) IIb/IIIa inhibitors for all acute coronary syndromes (ACS) patients is cost effective compared to that of selective use of abciximab in only those patients requiring percutaneous coronary intervention (PCI). BACKGROUND: Small molecule GP IIb/IIIa inhibitors have shown benefit in ACS, but abciximab, the more expensive GP IIb/IIIa inhibitor, may be more effective during PCI. However, abciximab does not have proven efficacy in medical management. No prior study has attempted to balance these competing benefits. METHODS: A decision analysis was performed to examine two strategies: 1) treat all ACS patients upstream with a small molecule GP IIb/IIIa inhibitor and continue through medical management and PCI, if performed; or 2) wait, and selectively use abciximab only in patients who ultimately undergo PCI. Applicable randomized controlled trial data were used for the principal analysis. RESULTS: The strategy of upstream use of a small molecule GP IIb/IIIa inhibitor was superior to selective use, and economically acceptable, with a cost-effectiveness ratio of 18,000 dollars per year of life gained. The superiority of the upstream use strategy persisted over the majority of sensitivity analyses. When stratified by risk according to Thrombolysis in Myocardial Infarction risk score, a strategy of upstream use was only cost effective in those patients with moderate or high risk. CONCLUSIONS: Upstream use of small molecule GP IIb/IIIa inhibition in ACS patients with moderate or high risk for cardiovascular events is a cost-effective approach that should be considered in this subset of patients.