Episodic versus prophylactic infusions for hemophilia A: a cost-effectiveness analysis

OBJECTIVE: To assess the incremental cost-effectiveness of prophylactic compared with episodic care in boys with severe hemophilia A. SETTING: Eleven U.S. hemophilia treatment centers. METHODS: Charge data from a randomly selected cohort of 70 boys receiving episodic infusions for bleeding events and from all 27 boys receiving infusions prophylactically were collected from documents obtained from the hemophilia treatment centers during a period of approximately 2 years. Published and public sources were used for conversion to cost, lifetime earnings, and earnings losses from disability. A model was constructed for a hypothetical patient from ages 3 to 50 years by means of three infusion scenarios. RESULTS: The cohort receiving prophylactic treatment had fewer bleeding events each year (median, 3 vs 31) but used more concentrate (3323 vs 1015 units/kg per year). Factor VIII concentrate accounted for more than 93% of the cost of both episodic and prophylactic care. Compared with episodic infusion, prophylaxis from ages 3 to 20 years costs $1100 per bleeding event prevented, in comparison with $1380 for prophylaxis from ages 3 to 50 years. The total cost of prophylactic care from ages 3 to 50 years would equal the current total cost of episodic care if the price of the concentrate were decreased by 50%. CONCLUSION: Prophylactic care markedly reduces the number of bleeding events and should prevent joint function impairment, but at substantial cost.     

Prophylactic treatment for hemophilia A patients: a pilot study

Prophylactic treatment with factor VIII concentrate was given to six hemophilia A boys whose factor VIII:C ranged from 1% to 3.5% at Ramathibodi Hospital. The age ranged from 11 to 16 years with the median age of 12 years old. Each patient received factor VIII concentrate twice a week in the dosage of 8-10 unit per kg for one year. During the prophylactic period, bleeding episodes seldom occurred. They did not need hospitalization. The absence from school was reduced. They became muscular from regular daily exercise. They could join the activity at school and lived a near normal life. The patients and family were very happy since they did not have to worry about bleeding. No adverse effect was found. The only constraint was the cost. It cost 180,000 baht (US$ 7,200) per year or 15,000 baht (US$ 600) per month for a 25 kg hemophiliac boy.     

Stereotaxy reduces cost of brain tumor resection

BACKGROUND: Health care professionals are under increasing pressure to contain the cost of health care. Simultaneously, medical technology continues to advance. Medical institutions must therefore consider the costs and benefits before using a new technology. Using a direct costing system, we determined the cost efficacy of stereotaxy applied to the resection of brain mass lesions. METHODS: Twenty-nine patients underwent a stereotactically guided craniotomy and brain tumor resection. Fifteen of them underwent general and fourteen received local anesthesia. Twelve other patients, comprising a historical reference group, underwent a standard craniotomy and brain tumor resection under general anesthesia. costs were determined for every hospital charge item in all patients. Cost efficiency was then compared between the two groups. RESULTS: Patients treated stereotactically incurred additional costs in frame placement and neuroimaging. These costs were offset by savings in operating room time, patient acuity, length of stay, respiratory care, and medications. Savings were greatest for patients who had local anesthesia. Overall, patients treated by stereotactic craniotomy had a total hospitalization cost of $8,495.19, whereas those treated with standard craniotomy incurred a cost of $11,365.23 (p < 0.001). CONCLUSION: Stereotaxy is cost effective for the surgical treatment of brain tumors. Accurate estimates of cost can justify the use of medical technology. Directly measured cost data is a useful index for any cost containment program.     

Recombinant human factor IX: replacement therapy, prophylaxis, and pharmacokinetics in canine hemophilia B

Recombinant human factor IX (rFIX) has been expressed in transduced cultured cell systems since 1985. Because there has been limited in vivo testing of rFIX in hemophilia B subjects, this study was undertaken using the severe hemophilia B canines of the Chapel Hill strain. Three groups of hemophilic dogs received either 50, 100, or 200 IU/kg of rFIX. As a control, a fourth group of hemophilic dogs received 50 IU/kg of a high purity, plasma-derived human FIX (pdFIX). The coagulant and hemostatic effects of rFIX and pdFIX were similar with all comparative dosing regimens. Based on activity data, the elimination half-life of rFIX was 18.9 +/- 2.3 hours and pdFIX was 17.9 +/- 2.1 hours. A prophylactic regimen administering rFIX daily resulted in a continuous therapeutic level of plasma FIX and was accompanied by a two-fold increase in recovery levels by day 5, compared to that observed with administration of a single bolus. The mechanisms of the high to complete recovery of FIX with the prophylactic regimen could depend not only on the degree of saturation of the vascular endothelial binding sites but also on the altered dynamics of the balance of FIX distribution between the intravascular and extravascular compartments. The pharmacokinetic (PK) parameters for rFIX and pdFIX were similar. However, the relative PK values for V1 and V5s of both products on day 5 differed greatly from day 1 and may reflect the changing equilibrium of FIX between compartments with elevated levels of plasma FIX. Neutralizing antihuman FIX antibodies resulting from human FIX antigen being administered to FIX deficient dogs were observed beginning at 14 days. The antigenicity of rFIX and pdFIX appeared to be comparable. Despite the very different procedures used for production of rFIX and pdFIX products, in vivo testing in hemophilia B dogs showed the functional behavior of these products is similar; they are highly effective for replacement therapy and for prophylaxis.     

Cost-analysis of prophylactic antibiotics in spontaneous bacterial peritonitis

BACKGROUND & AIMS: Antibiotic prophylaxis has been shown to decrease the incidence of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. The aim of this study was to test whether antibiotic prophylaxis for SBP is cost-effective and to compare the costs associated with different patient groups and treatment strategies. METHODS: A cost-effectiveness analysis was performed using a Markov chain model. The costs incurred during 1-year treatment with prophylactic antibiotics vs. no prophylaxis in patients with cirrhosis and ascites were calculated. The incidence rates of primary and recurrent SBP and the mortality rate of SBP were obtained from the literature. Total direct costs of SBP treatment were determined from the wholesale price of drugs and from disbursements by the Health Care Financing Administration. RESULTS: Norfloxacin prophylaxis resulted in savings between $2216 and $8545 per patient per year, depending on the patient group studied. Trimethoprim-sulfamethoxazole prophylaxis resulted in savings between $2934 and $9251 per patient per year. The groups that benefited most from prophylaxis were patients with an ascitic fluid total protein concentration of < or = 1 g/dL and those with a previous history of SBP. CONCLUSIONS: The use of prophylactic antibiotics to decrease the incidence of SBP is a cost-saving strategy in patients with cirrhosis and ascites.     

Carcinoma of the head of the pancreas arising from the uncinate process

The objectives of our study was to answer the following questions: (1) What are the socioeconomic costs and benefits of different haemophilia treatment strategies? (2) Which savings can be achieved through a comprehensive care program? (3) How are haemophiliacs integrated into their social life? (4) What are the annual costs of treating haemophilia from a third party payer perspective? In this cross-sectional study, 840 consecutive haemophiliacs attending 16 haemophiliac treatment centres in 10 European countries at were entered in the study. The following six parameters were analysed: sociodemographic patient data, the type of substitution (on demand or prophylaxis), transfusion-transmitted diseases, the functional joint status, quality of life as well as the total costs of therapy. Three kinds of substitution modalities were distinguished: on demand therapy, pure and modified prophylaxis. The average number of medical visits, the average length of hospital stay, regular drug therapy and the average number of days off work per bleeding joint were recorded from the medical charts as a basis for the subsequent assessment of the costs of therapy. The total study sample comprised of 566 patients. Interestingly, statistically more significant (P = 0.0005) patients were unemployed in the on-demand group (14%) than in the prophylaxis group (3.4%). There was a higher ratio of white collar workers in the on-demand group as compared to the prophylaxis group and vice versa for blue collar workers. The distribution of blue collar workers, clerk, self-employed persons, students and housemen were quite comparable between the patients of the on-demand and prophylactic therapeutic regimen. The labor force participation rate was 55.2% in the patients in the on demand and 59.3% in the patients in the modified prophylactic group. The labor force participation rate across all patients was 56%. Patients on demand therapy used on average 38.3 (median: 12.5) units/kg/week as compared to 68.6 (median: 6) units/kg/week in the prophylaxis group. The mean usage across all patients was 46.1 (median 19.7) units/kg/week. There were an average of 7.4 (median: 3) joint bleeds per patient across all patients during the 6-month observation period. In the on-demand group 8.8 (median: 5) joint bleeds were recorded versus 3.1 joint bleeds (median: 0) in the prophylactic group. This difference was statistically different (95% CI of difference: 4.33-7.07). Our data suggest that patients receiving prophylactic clotting factor therapy require less additional health care resources, mainly due to the reduction in the number of joint bleeds.     

Malaria at Christmas: risks of prophylaxis versus risks of malaria

A large increase in the number of falciparum malaria cases imported into the UK was reported to the malaria reference laboratory in the first quarter of 1998. Contributory factors were unusually heavy rains in east Africa and a reduction in the use of the most effective antimalarial drug, mefloquine. There was also an increase in the number of cases of severe malaria in the UK. During December 1997 and January 1998, the Hospital for Tropical Diseases, London, treated 5 patients for severe malaria and gave advice on 20 more patients with malaria who had been admitted to intensive care units throughout England. 4 of the severe cases treated at the hospital are reported. In 3 of those 4 cases, incorrect, misleading, or inadequate advice was given by health care professionals. Media coverage of the adverse effects of antimalarial drugs has contributed to confusion about prophylactic regimens among both health care professionals and the public. The incidence of falciparum malaria among travellers who do not take prophylactic drugs is about 0.6% in east Africa and 3.5% in west Africa over a 2-week travel period. Travellers need to take measures to avoid being bitten by mosquitoes and should be taught to promptly seek medical help if they develop a fever while abroad or after they return. Moreover, using any one of the recommended prophylactic regimens is better than not using a potent regimen or no prophylaxis at all. Mefloquine is 90% protective against malaria in sub-Saharan Africa. While the efficacy of proguanil and chloroquine in 1987 was about 70% in west Africa and 50% in east Africa, those levels are now probably lower. The side effects of antimalarial drugs are discussed.     

Prophylactic replacement therapy in hemophilia. A case report (author's transl)

In a six year old boy with severe hemophilia prophylactic substitution of factor VIII was started in 1973 in order to prevent early invalidity due to series of bleeding in the right anklejoint. A substitution of factor VIII over 8 months with 21 resp. 30 U/kg body-weight did not lead to a significant improvement. But since the factor VIII in a dosage of 18 U/kg body-weight is given three times a week no bleeding occurred during the treatment time of 14 months and also the ability to walk improved to an excellent degree.--So far no signs of hepatitis or an factor-VIII-antibody could be detected.--Some results from the prophylactic treatment of severe hemophilia and Christmas disease are cited from the literature.     

The impact of payor/provider type on health care use and expenditures among the frail elderly

OBJECTIVES: This study examined whether health care expenditures and usage by the frail elderly differ under three payor/provider types: Medicare fee for service, Medicare health maintenance organization (HMO), and dual Medicare-Medicaid enrollment. METHODS: In-home interviews were conducted among 450 frail elderly patients of a San Diego, Calif, health care system. Cost and use data were collected from providers. RESULTS: Analyses revealed no difference in total expenditures between fee-for-service and HMO enrollees, but Medicare-Medicaid beneficiaries' expenditures were 46.8% higher than those for HMO enrollees and 52.2% higher than those for the fee-for-service group. Fee-for-service participants were less than half as likely as HMO enrollees to have two or more hospital admissions, but hospital usage rates between those two payor/provider groups did not differ. Not were there payor/provider differences in access to home health care, but HMO home health care users received significantly fewer services than the others. CONCLUSIONS: The care provided to these HMO beneficiaries resulted in a combination of restricted home health use and higher multiple hospitalizations. This raises compelling questions for future research. For the dually enrolled, stronger cost containment may be required.     

The pathophysiology of stress urinary incontinence in women and its implications for surgical treatment

OBJECTIVES: To estimate the total costs of multiple sclerosis (MS) for all Canadians in 1994. METHODS: Prevalence-based study estimating disease-related societal costs for Canadians with MS in 1994. The human capital approach was used to estimate the value of lost productivity due to illness. Two components were revealed: first, direct costs, in terms of expenditures on hospital care, other institutions, physician services, other health professionals, drugs, and other expenditures; and second, indirect costs, in terms of lost productivity due to premature mortality and disability. RESULTS: The total costs of MS for Canadians were $502.3 million in 1994, with direct and indirect cost components at $188.6 million and $313.7 million, respectively. CONCLUSIONS: This study highlights the scope and magnitude of the economic consequences of MS for Canadians. The costs calculated may be used to provide guidance in the setting of national priorities for research and prevention activities.     

Long-term patterns of service use and cost among patients with both psychiatric and substance abuse disorders

OBJECTIVES: This is a longitudinal study designed to determine: (1) if patients dually diagnosed with psychiatric and substance abuse disorders incur higher health care costs than other psychiatric patients and (2) if higher costs can be attributed to particular subgroups of the dually diagnosed or types of care. METHODS: Two cohorts of veterans treated in Veterans Affairs mental health programs at the start of fiscal year 1991 were followed for 6 years: one cohort of inpatients (n = 9,813) and the other of outpatients (n = 58,001). Data were analyzed on utilization of all types of Veterans Affairs health care. Repeated measures analysis of variance was used to examine cost differentials between dually diagnosed patients and other patients. RESULTS: Dually diagnosed outpatients incurred consistently higher health care costs than other psychiatric outpatients, attributable to higher rates of inpatient psychiatric and substance abuse care; however, this difference decreased with time. Costs were substantially higher in the inpatient cohort overall, but there were no differences in cost between dually diagnosed and other patients. CONCLUSIONS: In an atmosphere of cost cutting and moves toward outpatient care, the dually diagnosed may lose access to needed mental health services. Possibilities of developing more intensive outpatient services for these patients should be explored.     

Cost-effectiveness of chemoprophylaxis after occupational exposure to HIV

OBJECTIVES: To assess the economic efficiency of recent US Public Health Service recommendations for chemoprophylaxis with a combination of antiretroviral drugs following high-risk occupational exposure to human immunodeficiency virus (HIV). To provide a framework for evaluating the relative effectiveness and costs associated with candidate postexposure prophylaxis (PEP) regimens. METHODS: Standard techniques of cost-effectiveness and cost-utility analysis were used. The analysis compares the costs and consequences of a hypothetical, voluntary combination-drug PEP program consisting of counseling for all HIV-exposed health care workers, followed by chemoprophylaxis for those who elect it vs an alternative in which PEP is not offered. A societal perspective was adopted and a 5% discount rate was used. Hospital costs of recommended treatment regimens (zidovudine alone or in combination with lamivudine and indinavir) were used, following the dosing schedules recommended by the US Public Health Service. Estimates of lifetime treatment costs for HIV and acquired immunodeficiency syndrome were obtained from the literature. Because the effectiveness of combination PEP has not been established, the effectiveness of zidovudine PEP was used in the base-case analyses. MAIN OUTCOME MEASURES: Net PEP program costs, number of HIV infections averted, cost per HIV infection averted, and cost-utility ratio (net cost per discounted quality-adjusted life-year saved) for zidovudine, lamivudine, and indinavir combination PEP. Lower bounds on the effectiveness required for combination regimens to be considered incrementally cost saving, relative to zidovudine PEP alone, were calculated. Multiple sensitivity and threshold analyses were performed to assess the impact of uncertainty in key parameters. RESULTS: Under base-case assumptions, the net cost of a combination PEP program for a hypothetical cohort of 10,000 HIV-exposed health care workers is about $4.8 million. Nearly 18 HIV infections are prevented. The net cost per averted infection is just less than $400,000, which exceeds estimated lifetime HIV and acquired immunodeficiency syndrome treatment costs. Although combination PEP is not cost saving, the cost-utility ratio (about $37,000 per quality-adjusted life-year in the base case) is within the range conventionally considered cost-effective, provided that chemoprophylaxis is delivered in accordance with Public Health Service guidelines. Small incremental improvements in the effectiveness of PEP are associated with large overall societal savings. CONCLUSIONS: Under most reasonable assumptions, chemoprophylaxis with zidovudine, lamivudine, and indinavir following moderate- to high-risk occupational exposures is cost-effective for society. If combination PEP is minimally more effective than zidovudine PEP, then the added expense of including lamivudine and indinavir in the drug regimen is clearly justified.     

Transmission of paratuberculosis

Antenatally, as more women are being treated in the home setting rather than the hospital setting, diagnostic modalities such as ultrasonographic imaging need to be available for use by the home care provider. In the home setting, the care provider and treatment modalities are brought to the patient, whereas patients managed in the hospital setting must attend the provider site to receive the same services. Without the availability of diagnostic ultrasonography in the home setting, pregnant women who are treated in the home rather than the hospital are required to incur an added financial and physical burden associated with attendance at care. Financially, nonreimbursed out-of-pocket costs incurred by the patient may include costs of transportation, costs of child care, and loss of wages. Physically, patients are prevented from maintaining recommended bed rest and dietary treatment regimens. Ultrasonographic evaluations can be performed safely in the home setting by nurses who have received added educational preparation and ultrasonographic imaging experience, thereby providing the essential care often necessary for women who experience pregnancies complicated by high-risk conditions.     

Pharmaceutical services in the treatment of hemophiliac patients

Pharmaceutical services in the treatment of hemophiliac patients in Sweden are described. To prevent arthropathy and improve quality of life, patients with severe hemophilia receive prophylactic treatment. Hemophiliac patients are referred for diagnosis, treatment, and follow-up to one of three hemophilia treatment centers. Patients are seen once or twice yearly for routine checkups. A new system for the distribution of antihemophilic factor and factor IX has been implemented to improve availability and reduce risks and costs. Patients registered at a center receive antihemophilic factor or factor IX from the corresponding hospital pharmacy. The number of different manufactured batches to which a patient can be exposed is restricted, and complete distribution data are recorded for each patient, enabling follow-up studies and facilitating withdrawals of faulty batches. Distribution of emergency kits to patients who do not receive supervised home therapy ensures the availability of treatment for bleeding episodes. Two studies performed to explore ways to reduce drug waste led to improvements in patient information, product guidelines, and equipment and a better understanding of the problems associated with product changes. Specialized pharmaceutical services in Sweden contributed to successful hemophilia treatment and reduced its cost.     

Immunosuppressive treatment of a spontaneous inhibitor hemophilia A using cyclophosphamide, vincristine and prednisone following prior Factor VIII stimulation

A 59-year-old patient who presented with hematuria and recurrent soft tissue bleeding was found to have a factor VIII inhibitor level of 52 Bethesda units (BU)/ml and acquired hemophilia was diagnosed. After treatment with immunoglobulins (0.4 g IgG/kg per day for one week) the factor VIII inhibitor titer decreased to 12 BU/ml. Because of another episode of retroperitoneal hemorrhage, the patient was put on an immunosuppressive combination therapy which was first described by Lian et al. (1988). Our patient was infused with a factor VIII concentrate followed by cyclophosphamide, vincristine and prednisone. This regimen was repeated every 3-4 weeks. After 6 courses a further decline in the factor VIII inhibitor concentration, but no complete eradication of the autoantibody, was achieved. The factor VIII inhibitor level has remained at 2.5 BU/ml for more than 7 weeks without further bleeding episodes. The pathophysiology and treatment of acquired hemophilia are discussed.     

The effect of cost sharing on the use of chiropractic services

OBJECTIVES: Chiropractic care is increasing in the United States, and there are few data about the effect of cost sharing on the use of chiropractic services. This study calculates the effect of cost sharing on chiropractic use. METHODS: The authors analyzed data from the RAND Health Insurance Experiment, a randomized controlled trial of the effect of cost sharing on the use of health services. Families in six US sites were randomized to receive fee-for-service care that was free or required one of several levels of cost sharing, or to receive care from a health maintenance organization (HMO). Enrollees were followed for 3 or 5 years. All fee-for-service plans covered chiropractic services. Persons assigned to the HMO experimental group received free fee-for-service chiropractic care; persons in the HMO control group had 95% cost sharing for chiropractic services. The authors calculated the mean annual chiropractic expense per person in each of the fee-for-service plans, and also predicted their chiropractic expenditures using a two-equation model. Chiropractic use among persons receiving HMO and fee-for-service care were compared. RESULTS: Chiropractic care is very sensitive to price, with any level of coinsurance of 25% or greater decreasing chiropractic expenditures by approximately half. Access to free chiropractic care among HMO enrollees increased chiropractic use ninefold, whereas access to free medical care decreased fee-for-service chiropractic care by 80%. CONCLUSIONS: Chiropractic care is more sensitive to price than general medical care, outpatient medical care, or dental care, or and nearly as sensitive as outpatient mental health care. A substantial cross-price effect with medical care may exist.     

Factor VIII inhibitors in patients with hemophilia A: epidemiology of inhibitor development and induction of immune tolerance for factor VIII

Factor (F) VIII inhibitor development remains one of the most serious complications in the treatment of hemophilia A. Former and recent studies on inhibitor development revealed that patients with severe hemophilia A and positive inhibitor family history are at highest risk of developing an inhibitor. Comparison of recent inhibitor incidence studies on previously untreated patients indicate that the risk of inhibitor development under treatment with recombinant FVIII concentrates is comparable to the inhibitor incidence under FVIII substitution by plasma-derived concentrates. However, longer observation periods are necessary to draw final conclusions. Since inhibitor development may result in inefficacy of FVIII concentrates in the treatment of severe bleedings, the induction of immune tolerance (IT) is still of main concern. Various regimens to induce IT by application of FVIII concentrates have been conducted up to now. Success rate appears to be influenced by low to high responder status, number of exposure days before onset of treatment, and dosage of therapeutic regimen. Especially, discontinuation of IT therapy seems to be associated with failure of therapy. Taking into account available data on IT therapy, we recommend early onset of a high dosage regimen in high responder patients as soon as possible after inhibitor detection, as this is associated with higher success rate and shorter elimination time.     

Implantable venous access devices in children with hemophilia: a report of low infection rates

OBJECTIVE: The objective of this study was to define the efficacy and complications of implantable venous access devices (IVADs) in children with hemophilia. STUDY DESIGN: Records were reviewed on all patients with congenital blood coagulation disorders monitored at two children's hospitals in whom one or more central venous catheters had been placed. RESULTS: Since 1989 external and implantable central venous catheters have been inserted to enhance venous access for regular factor concentrate infusion in 45 patients with hemophilia ranging in age from 8 months to 19.5 years (median 7.4 years); 37 patients had factor VIII deficiency and 8 factor IX deficiency. Hemorrhagic complications of catheter placement were infrequent and minor. In the 41 patients having one or more IVADs in place for a median of 31 months, only six episodes of bacteremia occurred in 5 patients during 44,070 days of follow-up. The overall rate of bacteremia complicating IVADs in these patients was 0.14 episodes per 1000 catheter days. Other catheter-related complications were uncommon. Catheters are still in place in 33 patients for a median of 32 months. CONCLUSION: The low risk of infection and other complications associated with the use of IVADs makes the use of these devices attractive in the treatment of patients with hemophilia who require frequent venous access for factor concentrate infusions.