Cost-effectiveness analysis of inhaled zanamivir in the treatment of influenza A and B in high-risk patients.

OBJECTIVE: To evaluate the cost effectiveness of zanamivir 10 mg twice daily for 5 days in the treatment of influenza in high-risk patients. DESIGN: Bootstrap cost-effectiveness analysis incorporating within-trial analysis of pooled patient-level cost and effect data. SETTING: UK unit costs and utilities applied to high-risk patients drawn from 6 multinational clinical trials. PATIENTS: A total of 154 zanamivir and 167 placebo high-risk patients were included in the analysis. MAIN OUTCOME MEASURES: Cost per day of normal activities; cost per symptom-free day; cost per complication averted; cost per quality-adjusted life-year (QALY). RESULTS: The mean benefit was estimated to be 2.5 days [95% confidence interval (CI): 0.68 to 4.27] of normal activities gained; 2.0 (95% CI: 0.56 to 3.51) symptom-free days; and a 9% reduction in complications (95% CI: 0 to 18%). Excluding the effect of rare hospitalisation costs, the cost (1999 values) of gaining a day of normal activities was 9.50 Pounds (95% CI: 5 Pounds to 39 Pounds); cost per symptom-free day was 11.56 Pounds (95% CI: 6 Pounds to 43 Pounds); cost per complication averted was 262 Pounds (95% CI: 90 Pounds to 1574 Pounds). Influenza was estimated to reduce utility by 0.883 per day, demonstrating the debilitating effect of the disease. Extrapolating a day of normal activities to a standard utility measure resulted in a cost per QALY of 3900 Pounds excluding inpatient costs (7490 Pounds including inpatient costs). Cost-effectiveness acceptability curves demonstrated 90% certainty that zanamivir would be cost effective at 8000 Pounds per QALY. CONCLUSIONS: Significant health benefits can be obtained with zanamivir treatment in high-risk patients. The cost per QALY for zanamivir in these patients compares well with that of other commonly used pharmacological interventions.

Cost effectiveness of zanamivir for the treatment of influenza in a high risk population in Australia.

OBJECTIVE: To use data from a clinical trial of zanamivir, a new antiviral drug, to estimate the costs and effectiveness of alternative treatment strategies for a high-risk population in Australia visiting a physician for treatment of influenza or influenza-like illness within 36 hours of symptom onset. DESIGN AND SETTING: This was a modelling study using data from a randomised, double-blind, placebo-controlled trial with centres in Australia, New Zealand and South Africa. Cost data were taken from standard Australian sources. METHODS: Efficacy data from the clinical trial were used to populate a computer model designed to estimate the costs and health outcomes associated with alternative treatments for influenza and influenza-like illness. Only patients who consulted the physician within 36 hours of symptom onset were included in this trial. Cost data were used to translate the clinical data into treatment cost estimates. RESULTS: Treatment with zanamivir for this high risk population results in an incremental cost of $A14.20 per day of symptoms avoided in the base case. The cost per quality-adjusted life-year (QALY) gained is $A11,715. The results are sensitive to several parameter values, including the influenza-positive rate and the impact of zanamivir on days to alleviate symptoms and hospitalisation. CONCLUSIONS: Influenza is costly for the high risk population who seek physician treatment. Treatment with zanamivir for this population is cost effective based on an $A78,000 per QALY benchmark. Zanamivir could be cost saving if it reduces the hospitalisation rate.

Impact of zanamivir treatment on productivity, health status and healthcare resource use in patients with influenza. Zanamivir Study Group.

OBJECTIVE: This study examined the impact of zanamivir treatment on patient morbidity in patients with influenza. DESIGN AND SETTING: This was a multicentre, randomised, double-blind, parallel-group study conducted in 14 countries in Europe and North America during the winter of 1995/1996. PATIENTS AND PARTICIPANTS: The study included 722 individuals with virologically confirmed influenza. INTERVENTIONS: Two different zanamivir treatment regimens [twice daily (bid) or 4 times daily (qid) for 5 days] were compared with placebo. MAIN OUTCOME MEASURES AND RESULTS: Efficacy was measured using a number of patient-assessment questionnaires. Results showed that significantly fewer patients with influenza who were treated with zanamivir had additional contacts with healthcare professionals compared with those who received placebo (8 vs 14%; p < or = 0.049, bid and qid vs placebo). Individuals treated with zanamivir also spent fewer days absent from work (placebo: mean = 3.28 days; qid: mean = 2.52 days; p = 0.031) or college/school (placebo: mean = 2.90 days; bid: mean = 2.24 days; p = 0.032), and showed significant improvements in productivity compared with placebo. The health status questionnaire revealed significant improvements in patient well-being over the first 5 days of the study in those treated with zanamivir compared with those who received placebo. CONCLUSIONS: Zanamivir treatment reduced absenteeism, improved patient productivity and well-being, and reduced the additional use of healthcare resources in patients with influenza.

Novel surveillance and cure of a donor-transmitted lymphoma in a renal allograft recipient.

BACKGROUND: In this report we describe a malignant lymphoma of donor origin inadvertently transplanted into two renal allograft recipients, despite standard comprehensive donor screening. The successful clearance of the tumor from both patients and a novel method of surveillance are detailed. METHODS: Initial management consisted of withdrawal of immunosuppression to promote rejection of the allograft and the transplanted tumor in both patients, followed by graft removal. Peripheral blood microchimerism was assessed in both recipients using nested polymerase chain reaction to detect the DYZ3 gene on the Y chromosome (donor male, recipients female). RESULTS: Although microchimerism was detected on day 6 after transplantation and day 1 after explantation, repeat peripheral blood examination at 1, 3, and 6 months after explantation demonstrated no microchimerism. Both patients remain well at 12 months and have been relisted for transplantation. CONCLUSION: Despite inadvertent transplantation of a previously undiagnosed malignancy of donor origin, the recipients' immune response was able to eliminate donor tumor cells after the withdrawal of immunosuppression. Repeated surveillance of peripheral blood from both recipients, using a novel application of the technique of nested polymerase chain reaction to amplify donor DNA, demonstrated no persistence of donor cells, supporting effective eradication of the donor malignancy.

Role of donor leukocyte chimerism in establishing the etiology of neutropenia after liver transplantation.

BACKGROUND: The quantitation of donor leukocyte chimerism may aid in establishing the etiology of neutropenia after liver transplantation. METHODS: The incidence and clinical and laboratory characteristics of severe neutropenia were studied in adults who have undergone liver transplantation at our institution over the last 4 years. RESULTS: Severe neutropenia developed in 5 of 156 patients (3%). The clinical and pathological features were nonspecific. In two patients with a delayed diagnosis of graft-versus-host disease (GVHD), donor leukocytes comprised > or = 50% of the circulating peripheral blood mononuclear cells. In a third patient, an earlier diagnosis of GVHD was suspected on the basis of a donor leukocyte count of 3-10% in the peripheral blood. In contrast, donor leukocyte chimerism was < or = 0.01% in two patients with probable drug-induced neutropenia CONCLUSIONS: The determination of donor leukocyte chimerism has an important role in the investigation of neutropenia after liver transplantation, allowing early diagnosis and treatment of GVHD.

A pharmacoeconomic model for the treatment of influenza.

OBJECTIVE: The aim of this study was to develop a generic treatment algorithm for influenza and influenza-like illness (ILI) that could be used to estimate the costs and outcomes of current and new treatments for influenza in different countries for different patient subgroups. METHODS: A series of possible treatment pathways was identified and the probabilities of different patient subgroups following each pathway were estimated by using the published literature. The health outcomes and health service use and unit costs for each pathway were estimated from trial data and standard data sources. An interactive computer model was created, the base-case input parameter values were assigned, and estimates of the current costs of influenza and ILI in different population subgroups estimated. Sensitivity analyses were performed by changing input parameter values. RESULTS: The average healthcare cost of influenza and ILI per person in the US was $US72 for the general population and $US330 for a high risk population (1997 values). The average total cost per patient (healthcare cost plus productivity losses) was $US320 for the general population and $US546 for a high risk population. These costs are sensitive to changes in the proportion of patients visiting a physician and to the proportion of patients hospitalised with complications of the disease. Days to alleviate major symptoms and other health outcome measures are sensitive to the percentage of patients who receive antiviral therapy as well as to the efficacy of this therapy. CONCLUSIONS: The costs and health outcomes of influenza and ILI depend on the extent to which patients visit a physician, the use of antiviral drugs, and the incidence of complications requiring hospital care. The computer model will allow decision-makers to assess the cost effectiveness and the potential budget impact of new antivirals for treating influenza.

The effect of venous drainage on glucose homeostasis after experimental pancreas transplantation.

In this canine study, glucose homeostasis after clinical pancreas transplantation is complex, with the relative effect of systemic versus portal delivery of insulin remaining unresolved. Thirty-two pancreatectomized dogs received either systemic venous drainage (SVD) with bladder exocrine drainage (n = 16), or portal venous drainage (PVD) with gastric exocrine drainage (n = 16). Cyclosporine (CsA) based immunosuppression was commenced on day -7. The effect of immunosuppression was a significant increase in fasting blood glucose (FBGL) (P = 0.002), fasting insulin (P = 0.024), AUC for insulin (P = 0.009), and K values decreased (P = 0.009). FBGL and K values remained abnormal after transplantation with no significant difference seen between SVD and PVD. However, fasting insulin became significantly lower after PVD and AUC insulin fell in both groups. CsA levels fell in both groups after transplantation, mirroring the fall in AUC insulin, and implicating CsA as a major cause of peripheral resistance to insulin. In conclusion, PVD did not demonstrate a significant advantage over SVD in handling an intravenous glucose challenge. The need for pancreatectomy in large animals may make them an unsatisfactory experimental model to evaluate the glucoregulatory effects of pancreas allotransplantation.

Experimental hyperacute rejection in pancreas allotransplants.

A model of sensitization by intraperitoneal lymph node inoculation was developed to test the hypothesis that hyperacute rejection (HAR) could occur in sensitized recipients of vascularized pancreas allografts. Ten pairs of outbred mongrel dogs that were lymphocytotoxic cross-match assay negative were inoculated with homogenized lymph nodes on either three or four occasions at fortnightly intervals before renal transplantation. A renal allograft from the same donor was used to test the HAR response and to further enhance sensitization by rejection of a vascularized organ. Pancreas transplants were performed 2 weeks later, with biopsies of the graft and blood samples taken at 0, 10, 20, and 30 min and then at 30-min intervals until the grafts were no longer viable. All renal and pancreas grafts were rejected in a classical hyperacute pattern. Within 4 min of revascularization of the pancreas, central lobular hemorrhage and vascular congestion appeared, followed by general edema. Histology demonstrated parallel changes of edema, vascular congestion, necrosis, hemorrhage, and leukocytic infiltrate, which all preceded graft infarction. A sharp decline in both arterial and venous white blood cell count and platelets occurred within 10 min of revascularization with initial sequestration and subsequent release of platelets from the graft (P=0.02). In summary, HAR of the allografted pancreas can be observed by the surgeon within minutes of revascularization, with predictable macroscopic and microscopic changes. This study supports the use of routine lymphocytotoxic cross-match tests for all recipients of pancreas transplants and implies that particular care is warranted in regraft pancreas allograft recipients.

Recovery of gastrointestinal function after renal transplantation in a patient with sclerosing peritonitis secondary to continuous ambulatory peritoneal dialysis.

We describe the rapid and dramatic improvement in gastrointestinal function that occurred after successful renal transplantation in a women with severe sclerosing peritonitis secondary to continuous ambulatory peritoneal dialysis (CAPD). We postulate that the antiinflammatory effect of the immunosuppressive agents was the most important factor leading to the patient's recovery.