The impact of federal warnings on publically funded desmopressin utilization among children in Ontario.

OBJECTIVE: To determine whether safety warnings issued by health regulatory agencies regarding desmopressin treatment influenced treatment rates among children. PATIENT POPULATION AND METHODS: We conducted a time-series analysis using health administrative data from Ontario, Canada, between January 1, 2003 and March 31, 2010. We examined desmopressin prescribing rates among children (<13 years) and investigated the impact of a United States Food and Drug Administration warning (December 2007) and a subsequent Health Canada warning (July 2008) on these rates. A secondary analysis stratified rates according to route of administration. RESULTS: On average, quarterly desmopressin treatment rates were 29.8% lower following the two warnings (4.7 per 1000 population) compared with the period prior to warnings being issued (6.7 per 1000 population). Structural break analyses identified a significant decrease in overall desmopressin prescribing rates in Q3 2008, with the 95% confidence interval (CI) spanning both safety warnings (Q4 2007 to Q1 2009). A secondary analysis of prescribing rates for oral formulations found consistent results (structural break Q4 2008, 95% CI Q2 2007 to Q2 2009). The average quarterly prescribing rate of intranasal formulations declined by 73.1% following the warnings compared with the period preceding the warnings. CONCLUSION: Safety warnings issued by regulatory agencies dramatically influenced desmopressin use among Ontario's children.

Cost reduction of perioperative coagulation management in cardiac surgery: value of "bedside" thrombelastography (ROTEM).

OBJECTIVE: Demographic changes and aggressive platelet inhibition have resulted in a marked increase in blood- and coagulation product expenditure and costs in cardiac surgery. We analyzed "bedside" coagulation test (ROTEM) in order to verify clot forming quality for the purpose of finding a cost-effective treatment path. METHODS: Annual treatment costs of all cardiosurgical patients were analyzed before (729 patients) and after (693 patients) implementation of "bedside" ROTEM. Cumulative numbers and costs of platelet concentrates (PltC), fresh frozen plasma (FFP), red blood cell units (RBC), and coagulation factors: pooled coagulation concentrates (PCC), recombinant factor VIIa (rFVIIa), factor XIII (FXIII), and fibrinogen were assessed. Average monthly numbers and costs were compared. Number of resternotomies and early mortality was assessed and compared in both periods. RESULTS: After ROTEM implementation cumulative RBC expenditure showed 25% decrease while PltC exhibited 50% decrease. FFP expenditure remained unchanged. PCC, FXIII were markedly reduced (-80%) while rFVIIa were entirely omitted. Fibrinogen, however, increased two-fold. Cumulative average monthly costs of all blood products decreased from 66,000 euro to 45,000 euro (-32%). Coagulation factor average monthly costs decreased from 60,000 euro to 30,000 euro (-50%) yielding combined savings of 44%. In contrast, average monthly costs for ROTEM were 1.580 euro. Total number of resternotomies decreased from 6.6% to 5.5% while early mortality (5.9%; 6.0%) remained stable. CONCLUSION: Cumulative costs for treatment of perioperative coagulation disorders can be reduced by "bedside" ROTEM analysis to achieve a selective substitution management. Saved costs for blood- and coagulation products clearly outweighed the expenses of ROTEM. Adequate differential coagulation management can therefore be cost-effective.

Cost/benefit analysis of pharmacologic hemostasis.

BACKGROUND: Surgical bleeding with possible associated coagulopathies is a major source of morbidity and mortality. More than 27% of patients receive unnecessary blood or blood-product transfusions during cardiac operations. Analysis of the cost-benefit of pharmacologic hemostasis can be accomplished by relating all the components of cost, which include both direct and indirect costs to both direct and indirect benefits to the patient. METHODS: A significant reduction in transfusion requirements can be achieved by the systematic application of a clinical algorithm. An alternative is to use drugs that enhance hemostasis. Four such drugs commonly used are desmopressin acetate, tranexamic acid, epsilon-aminocaproic acid, and aprotinin. All these agents have been shown to successfully reduce bleeding and the need for transfusion. It appears that the order of efficacy (greatest to least) is aprotinin, tranexamic acid, epsilon-aminocaproic acid, and desmopressin acetate. RESULTS: Cost/benefit analysis associated with the use of these agents is complex. The direct costs of these drug treatments can be balanced against the costs related to blood and blood-product administration. Using epsilon-aminocaproic acid, blood used is valued at $30, whereas the drug treatment cost is less than $2. Aprotinin use results in costs of more than $500, with the drug costing $900. CONCLUSIONS: Improved hemostasis should also result in indirect cost savings from reduced operating room time, reduced intensive care unit and hospital stay, and the avoidance of reoperation for bleeding.

Hemophilia and von Willebrand's disease: 2. Management. Association of Hemophilia Clinic Directors of Canada.

OBJECTIVE: To present current strategies for the treatment of hemophilia and von Willebrand's disease. OPTIONS: Prophylactic and corrective therapy with hemostatic and adjunctive agents: DDAVP (1-desamino-8-D-arginine vasopressin [desmopressin acetate]), recombinant coagulation products (human Factor VIII and human Factor VIIa) or virally inactivated plasma-derived products (high- or ultra-high-purity human Factor VIII or human Factor VIII concentrate containing von Willebrand factor activity, porcine Factor VIII, high-purity human Factor IX, human prothrombin-complex concentrate, human activated prothrombin-complex concentrate), adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant. The induction of immune tolerance in patients in whom inhibitors develop should also be considered. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of our reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and pertinent to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: Proper prophylactic or early treatment with appropriate hemostatic agents minimizes morbidity and functional disability and improves quality of life. Economic gains are realized through the reduction of mortality and morbidity and their associated costs. The patient has a better opportunity to contribute to society through gainful employment and the fulfillment of social roles. Potential harms include HIV infection, hepatitis B, hepatitis C and the development of inhibitor antibodies to clotting-factor concentrates. The risk of viral transmission has been minimized through the development of procedures for the viral inactivation of plasma-derived clotting-factor concentrates and through the use of recombinant coagulation-factor concentrates and other non-plasma-derived hemostatic agents. RECOMMENDATIONS: DDAVP is the drug of choice for patients with mild hemophilia or type 1 or 2 (except 2B) von Willebrand's disease whose response to DDAVP in previous testing has been found to be adequate. Therapeutic blood components of choice include recombinant products and virally inactivated plasma-derived products. In Canada the recommended products are recombinant Factor VIII for hemophilia A, high-purity plasma-derived Factor IX for hemophilia B and plasma-derived Factor VIII concentrates containing adequate von Willebrand factor (e.g., Haemate P) for von Willebrand's disease. Dosages vary according to specific indications. Adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant are useful for the treatment of oral or dental bleeds and localized bleeds in accessible sites. In patients with inhibitor antibodies, high-dose human or porcine Factor VIII is usually effective when the inhibitor titre is less than 5 Bethesda units/mL. In nonresponsive patients, or in those whose inhibitor titre is higher, "bypassing" agents (e.g., activated prothrombin-complex concentrate and recombinant Factor VIIa) are useful. Long-term management may include immune-tolerance induction. VALIDATION: These recommendations were reviewed and approved by the Association of Hemophilia Clinic Directors of Canada (AHCDC) and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. No similar consensus statements or practice guidelines are available for comparison. SPONSORS: These recommendations were developed at the request of the Canadian Blood Agency, which funds the provision of all coagulation-factor concentrates for people with congenital bleeding disorders, and were developed and endorsed by the AHCDC and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society.

[Costs of the treatment of enuresis nocturna. Health economic consequences of alternative methods in the treatment of enuresis nocturna]. / Omkostningerne ved behandling af enuresis nocturna. Samfundsøkonomiske konsekvenser af alternative metoder til behandling af enuresis nocturna.

The health economic consequences of treating nocturnal enuresis with a buzzer alarm is compared to treatment with Desmopressin. Based on age specific prevalence estimates and reported effects of the two treatments a cost-effectiveness analysis (CEA) was performed. The analysis showed a considerable difference between the costs of the two alternative treatments. A treatment based upon the buzzer alarm could result in a net saving to society of 19.2 million DKK, while a treatment based upon Desmopressin could result in expenses for society of 44.8 million DKK. A treatment based on a combination of the two will be economically neutral to the society. Treatment with a buzzer alarm or a combined treatment is therefore from a health economic point of view preferable. The health economic consequences of the introduction of new treatments are discussed, and it is recommended that health economic analyses are performed before the introduction of new treatments.

Response of patients with bleeding disorder to DDAVP administration.

DDAVP has been shown to provide hemostasis in patients with bleeding disorder. Thirty-one episodes of intravenous DDAVP administration (0.3-0.4 microgram/kg) in 22 patients with bleeding disorder were studied. There were 13 patients with hemophilia A, 1 with type I vWD and 8 with inherited and acquired platelet dysfunction. The age ranged from 2.3-26 yrs (mean +/- SD = 10 +/- 4.8). None of the 3 severe hemophilia A patients responded to the treatment. Two out of five episodes in 4 moderate hemophilia A patients responded clinically and had minute increments of F VIII:C. Ten out of eleven episodes (91%) in 6 mild hemophilia A patients had good responses. The dental procedures for these patients were successfully performed without blood component transfusion. The increments of F VIII:C ranged from 1.5-6.8 folds over the baseline levels (mean +/- SD = 2.5 +/- 1.4). In addition, two episodes of epistaxis in a vWD patient responded excellently and one dental procedure was successfully performed by giving DDAVP. The increments of F VIII:C and vWF:Ag ranged from 2.8-12.5 and 2.9-8 fold over the baseline levels respectively. The prolonged bleeding times were shorten to 6.5-7 minutes. Only three out of eight episodes in 8 inherited and acquired platelet dysfunction patients showed temporary responses. The bleeding time responses did not correlate with in vitro platelet aggregation.