Cost Effectiveness of Inhaled Mannitol (Bronchitol®) in Patients with Cystic Fibrosis.

BACKGROUND: Inhaled mannitol (Bronchitol®) is licensed in Australia as a safe and efficacious addition to best supportive care in patients with cystic fibrosis. OBJECTIVE: The objective of this study was to assess the cost effectiveness of inhaled mannitol (in addition to best supportive care) in the Australian setting from the perspective of a government-funded national healthcare system. METHODS: A probabilistic patient-level simulation Markov model estimated life-time costs and outcomes of mannitol when added to best supportive care, compared with best supportive care alone in patients aged 6 years and older. We estimated treatment-related inputs (initial change in percentage of predicted forced expiratory volume, relative reduction in severe pulmonary exacerbations, and treatment discontinuations) from two phase III trials. Longer term natural history rates of predicted forced expiratory volume decline over time and severe pulmonary exacerbation rates for best supportive care were taken from Australian CF registries. The utility value for the cystic fibrosis health state was as measured in the trials using the Health Utility Index, whereas the impact of pulmonary exacerbations and lung transplantation on utility was ascertained from the published literature. The underlying cost of managing cystic fibrosis, and the cost associated with pulmonary exacerbations and transplantations was taken from published Australian sources. RESULTS: The addition of inhaled mannitol to best supportive care resulted in a discounted cost per quality-adjusted life-year of AU$39,165. The result was robust with 77% of probabilistic sensitivity analysis samples below a willingness-to-pay threshold of AU$45,000/quality-adjusted life-year. CONCLUSION: Benchmarked against an implicit Australian willingness-to-pay threshold for life-threatening diseases, our model suggests inhaled mannitol provides a cost-effective addition to best supportive care in patients with cystic fibrosis, irrespective of concomitant dornase alfa use.

Myocardial Protection and Financial Considerations of Custodiol Cardioplegia in Minimally Invasive and Open Valve Surgery.

OBJECTIVE: Single-dose antegrade crystalloid cardioplegia with Custodiol-HTK (histidine-tryptophan-ketoglutarate) has been used for many years. Its safety and efficacy were established in experimental and clinical studies. It is beneficial in complex valve surgery because it provides a long period of myocardial protection with a single dose. Thus, valve procedures (minimally invasive or open) can be performed with limited interruption. The aim of this study is to compare the use of Custodiol-HTK cardioplegia with traditional blood cardioplegia in patients undergoing minimally invasive and open valve surgery. METHODS: A single-institution, retrospective case-control review was performed on patients who underwent valve surgery in Lee Memorial Health System at either HealthPark Medical Center or Gulf Coast Medical Center from July 1, 2011, through March 7, 2015. A total of 181 valve cases (aortic or mitral) performed using Custodiol-HTK cardioplegia were compared with 181 cases performed with traditional blood cardioplegia. Each group had an equal distribution of minimally invasive and open valve cases. Right chest thoracotomy or partial sternotomy was performed on minimally invasive valve cases. Demographics, perioperative data, clinical outcomes, and financial data were collected and analyzed. RESULTS: Patient outcomes were superior in the Custodiol-HTK cardioplegia group for blood transfusion, stroke, and hospital readmission within 30 days (P < 0.05). No statistical differences were observed in the other outcomes categories. Hospital charges were reduced on average by $3013 per patient when using Custodiol-HTK cardioplegia. CONCLUSIONS: Use of Custodiol-HTK cardioplegia is safe and cost-effective when compared with traditional repetitive blood cardioplegia in patients undergoing minimally invasive and open valve surgery.

Comparative analysis of clinical efficacy and cost between University of Wisconsin solution and histidine-tryptophan-ketoglutarate.

OBJECTIVE: To compare University of Wisconsin solution (Viaspan), the universal standard for organ preservation, with histidine-tryptophan-ketoglutarate solution. An analysis of each solution, in reference to clinical trials with specific organs, is presented and assessed to find the efficacy of each in a clinical environment. Also to view each solution from an economical standpoint, and in the end develop an overall understanding of the key similarities and differences between each solution in order to assess appropriate use of each in a clinical setting. DATA SOURCES: A literature search was conducted by using PubMed, MEDLINE, BIOSIS, Embase, and other online data bases to find the most recent studies of University of Wisconsin and histidine-tryptophan-ketoglutarate solutions. Search terms included University of Wisconsin solution, histidine-tryptophan-ketoglutarate, preservation solution, cost analysis, biliary complication, and other related subjects. STUDY SELECTION: Previous research was selected from the literature search to provide basic information on the 2 solutions and also to provide clinical examples of each solution and the efficacy of each with specific organs. DATA SYNTHESIS: Information and published articles on the 2 solutions were gathered for descriptive and comparative purposes. CONCLUSIONS: The 2 solutions appear equally effective in organ preservation. Each solution has its own organ-specific qualities, and each has different complications. The studies reviewed here indicate that the differences are minor and thus suggest that the 2 solutions are equally acceptable for clinical use. Of the 2 solutions, histidine-tryptophan-ketoglutarate costs less than University of Wisconsin solution.

Increased pancreatitis in allografts flushed with histidine-tryptophan-ketoglutarate solution: a cautionary tale.

We reviewed pancreas transplantation outcomes after Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solution use between 2001 and 2007 at two transplant centers. While equivalence has been claimed for kidney and liver transplant outcomes after the use of HTK or UW preservation solution, consensus has not been reached on equivalence when flushing pancreata. Others have reported comparable patient and graft survival rates, but found an association between the use of HTK and an increase in the incidence of acute rejection and pancreatitis. In reviewing our experiences, we found in pancreata flushed with HTK a higher incidence of postoperative complications including graft pancreatitis, use of octreotide and a decreased rate of insulin-independence at hospital discharge. These findings prompted us to critically review our centers' experience to determine if there is a basis for suspecting a causal relationship.

Predictors of outcome in severely head-injured children.

OBJECTIVE: Determine variables in the acute care period associated with survival and pediatric intensive care unit (PICU) length of stay (LOS) for children with severe traumatic brain injury. DESIGN: Retrospective cohort. SETTING: Level 1 pediatric trauma center. PATIENTS: Children (0-17 yrs) admitted 1991 to 1995 with nonpenetrating traumatic brain injury and admission Glasgow Coma Scale score of or=14. Predictors of outcome were abstracted, including Pediatric Trauma Score, Glasgow Coma Scale score, Pediatric Risk of Mortality, physiologic variables, computed tomography evidence of brain injury, and neuroresuscitative medications. The fatality rate was 24%. Age and gender were similar between groups (p >or= .1). Survival was independently predicted by 6-hr Glasgow Coma Scale score (odds ratio [OR] 4.6; 95% confidence interval [CI] 2.06-11.9; p < .001) and maximum systolic blood pressure (OR 1.05; 95% CI 1.01-1.09; p < .02). Odds of survival increased 19-fold when maximum systolic blood pressure was >or=135 mm Hg (OR 18.8; 95% CI 2.0-178.0; p < .01). By discharge, 67% of patients had an age-appropriate Glasgow Coma Scale score. Median hospital costs were 8,798 dollars for survivors: only mannitol use independently predicted high cost (odds ratio 4.9; 95% CI 1.2-19.1; p < .01). For survivors, median PICU LOS was 2 days, although 25% had LOS >6 days. Six-hour Glasgow Coma Scale score (OR 0.62; 95% CI 0.48-0.80; p < .001) and mannitol (OR 7.9; 95% CI 2.3-27.3; p < .001) were each independently associated with a prolonged LOS among survivors. CONCLUSIONS: Patients with higher 6-hr Glasgow Coma Scale scores were more likely to survive. Adjusting for severity of injury, survival was associated with maximum systolic blood pressure >or=135 mm Hg, suggesting that supranormal blood pressures are associated with improved outcome. Mannitol administration was associated with prolonged LOS, yet conferred no survival advantage. We suggest reevaluation of blood pressure targets and mannitol use in children with severe traumatic brain injury.