How Should Functionally Equivalent Drugs be Reimbursed?

Statutory reimbursement agencies as well as private insurers throughout member states of the Organization for Economic Cooperation and Development (OECD) reimburse the cost of medicines on the basis of criteria that include robust clinical evidence, budget impact analysis, and incremental cost effectiveness. The Centers for Medicare and Medicaid Services (CMS) in the US are no exception to this rule and are, in principle, seeking to maximize benefit for their Medicare enrollees, whilst ensuring reasonable drug outlays for the small number of drugs that they reimburse. This paper provides a retrospective analysis of the way two functionally equivalent drugs are treated for reimbursement purposes by the CMS; the period under consideration was 2001–3. The two drugs, epoetin-α and darbepoetin-α, are used for the treatment of anemia in renal failure and in patients receiving chemotherapy. By reviewing the publicly available pharmacological and clinical data of epoetin-α and darbepoetin-α, the paper confirms the two drugs’ functional equivalence, despite their structural differences. The implications of dose conversion ratios and costs to Medicare are subsequently explored. It is argued that the issue of dose equivalence between epoetin-α and darbepoetin-α has significant implications for patients, practitioners, and payors. A payor’s perspective is adopted in this respect, whereby clinical evidence and pricing data are used simultaneously. Based on the clinical evidence, a dose conversion ratio for epoetin-α:darbepoetin-α is established, which achieves a comparable clinical effect for the two drugs and this is set to be <254IU:1μg. The incremental costs to Medicare are calculated subsequently. The Average Wholesale Price and the Outpatient Prospective Payment System rule that Medicare uses to reimburse providers are used and suggest that treatment of cancer patients with chemotherapy-related anemia with epoetin-α would save Medicare an estimated $US600 million each year. Patients would also benefit significantly in terms of lower co-payments for epoetin-α. The evidence is supportive of the decision made by the CMS to reimburse the two drugs at the rate reflecting the achievement of comparable clinical effects and therefore reducing the pass-through payments for darbepoetin-α to zero for the 2002–3 fiscal year.     

The role of neck dissection in the eradication of salivary carcinomas]

From 1955 to 1984, radical neck dissection (RND) had been done in 300 salivary carcinoma patients, 114 of which had regional lymph node metastasis, with a 38% metastatic rate. Respective 3, 5, 10, 15, 20 year survival rates were 76, 64, 47, 35, 35% in a 3 to 20 years follow-up study in 283 patients (94.33%). The following four points are concluded: 1. The metastatic rate is determined not only on tumor staging, but more to its typing (pathologic behaviour). 2. Elective RND gave a better prognosis than therapeutic and negative metastasis has a better survival chance than positive where the low level metastasis is the worst. 3. According to pathologic typing, Elective RND is indicated for undifferentiated adenocarcinoma, high malignant mucoepidermoid carcinoma, squamous cell carcinoma, adenocarcinoma and papillary cystic adenocarcinoma, therapeutic RND for malignant pleomorphic adenoma, acinic cell carcinoma and mucoepidermoid carcinoma. 4. Unilateral RND is indicated for all but sublingual and buccal tumors.     

乳腺良恶性病变的磁共振T2*W首过灌注成像与血管生成相关性研究

Objective： To study the diagnostic value of T2^＊-weighted first-pass perfusion imaging in breast tumors. Methods： We analyzed the magnetic resonance imaging （MRI） information along with the pathological and immunohistochemistry results. Magnetic resonance imaging was performed in 28 patients with breast tumor. The time to signal intensity curves were generated according to the T2^＊-weighted first-pass perfusion imaging. The curve＇s maximal signal intensity drop rate and maximal signal intensity decrease time were analyzed and compared with the pathological diagnoses after surgery. Results： Malignant breast lesions showed higher maximal signal intensity drop rate （44.69% ± 17.07 vs. 17.22% ±7.49, P 〈 0.001） than benign lesions, but there was no significant difference of maximal signal decrease time between those two lesions （23.94 s ± 4.92 vs. 20.02 s ± 6.83, P 〉 0.05）. Conclusion： The T2^＊-weighted first-pass perfusion imaging has enough sensitivity and specificity in breast tumor diagnosis.     

激素性股骨头坏死家兔血浆及软骨中一氧化氮含量的变化

[目的]探讨一氧化氮在激素性股骨头坏死发病中的作用.[方法]制作激素性股骨头坏死家兔模型后,在不同时期测定血浆及软骨中的一氧化氮含量,观察股骨头的组织学变化.[结果]激素性股骨头坏死家兔血浆和软骨中的一氧化氮含量均明显升高,股骨头髓腔中的脂肪细胞明显增多,骨小梁变细、稀疏及断裂,空骨陷窝明显增多.电子显微镜观察见骨细胞核染色质浓缩,体积缩小,胞浆中内质网及线粒体肿胀变性,粗面内质网上的核糖体脱落.[结论]一氧化氮参与激素性股骨头坏死的发病过程.     

Successful balloon pulmonary valvuloplasty for congenital valvular pulmonary stenosis in an octogenarian.

While balloon valvuloplasty has been widely used for the treatment of congenital valvular pulmonary stenosis (PS) in children and adults, its use in elderly patients is less common. An 80-year-old woman with congenital valvular PS received valvuloplasty with double-balloon technique. Right ventricle systolic pressure and pulmonary valve systolic pressure gradient decreased from 95 to 44 mm Hg and from 75 to 35 mm Hg, respectively. Follow-up Doppler echocardiography 2 months later showed further decrease in the transvalvular systolic pressure gradient to 29 mm Hg. The patient had symptomatic relief, and no major complication was noted. Balloon pulmonary valvuloplasty can be an effective treatment for elderly patients with congenital valvular PS.     

Recurrent acalculous cholecystitis and sclerosing cholangitis in a patient with X-linked hyper-immunoglobulin M syndrome.

X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand (CD40L) gene with normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE. Liver disease may occur as a clinical manifestation in XHIGM. This complication appears to increase with age. We report an 18-year-old male patient who had recurrent episodes of acalculous cholecystitis (AC) and sclerosing cholangitis (SC). The diagnosis of XHIGM was confirmed by the finding of CD40L expression < 1% of normal and a tyrosine 169 asparaginase (t526a) mutation in exon 5 (the tumor necrosis factor domain) of the CD40L gene. The patient had direct hyperbilirubinemia (direct bilirubin 5.5 mg/dL, total bilirubin 8.7 mg/dL), cholestasis (alkaline phosphatase 1133 U/L, gamma-glutamyl transferase 1019 U/L) and elevated transaminases (aspartate aminotransferase 70 U/L, alanine aminotransferase 101 U/L). Findings on abdominal ultrasound and abdominal computed tomography were compatible with AC. After the fourth episode of cholecystitis, cholecystectomy and liver biopsy were performed. Operative cholangiography revealed poor opacification of the hepatic duct and proximal common bile duct; the upstream intrahepatic bile ducts were not visualized. The biopsy specimen showed marked fibrosis of the portal areas. Enterococcus species was cultured from the bile. Children or adolescents with recurrent AC and SC should be evaluated for an underlying immunodeficiency syndrome such as XHIGM.     

Matched-unrelated-donor bone marrow transplantation for children with leukemia.

BACKGROUND AND PURPOSE: This report describes the results of matched-unrelated-donor transplant for leukemia or myelodysplasia in the first 23 recipient children at a single medical center in Taiwan. METHODS: Between August 1994 and February 2003, 23 consecutive children with leukemia or myelodysplasia underwent matched-unrelated-donor bone marrow transplantation (BMT). The preparative regimen consisted of fractionated total body irradiation and cyclophosphamide in 6 patients; busulfan in combination with etoposide and cyclophosphamide in 4 patients who received cranial irradiation before transplantation; and busulfan and cyclophosphamide in 13 patients. RESULTS: Engraftment was achieved in 91.3% of cases. Acute graft-versus-host disease (GVHD) occurred in 18 of 21 patients who engrafted (85.7%). Event-free survival for all patients was 24.46 +/- 9.24%. The 12 children with standard-risk disease had better event-free survival than the 11 children with high-risk disease (46.88 +/- 15.03% vs 0%, p < or = 0.001). CONCLUSIONS: The major obstacles to successful matched-unrelated-donor BMT are acute GVHD, relapse and infection. Early transplantation and patient selection, prophylactic and therapeutic maneuvers for GVHD, as well as appropriate donor selection and virus prophylaxis may improve the results.     

Morphology of corticotectal cells in the primary visual cortex of hooded rats

In primary visual cortex of hooded rats, pyramidal cells in layer V may be classified as long, medium, or short, on the basis of the layer in which the apical dendrite terminates. The present study determines which of these types of pyramidal cells project to the superior colliculus. Two different strategies were used to label corticotectal cells with horseradish peroxidase (HRP). In the first set of experiments, a large number of corticotectal cells were labeled by retrograde transport following injection of HRP into the superior colliculus. In the second set of experiments, single unit recording was used to identify corticotectal cells physiologically by antidromic activation from the superior colliculus. These cells were then impaled and labeled by intracellular iontophoresis of HRP. The results from both techniques suggest that only long pyramidal cells send an axon to the superior colliculus. These cells are distinguished by an apical dendrite that extends into layer I. We conclude that in hooded rats corticotectal cells in primary visual cortex are the long pyramids in layer V.