The genetic and epigenetic basis of ependymoma

Introduction  

Although ependymoma is the third most common pediatric brain tumor, we know little about the genetic/epigenetic basis of its initiation, maintenance, or progression. This is due in part to the heterogeneity of the disease, as well as the small sample size of the cohorts analyzed in most studies.     

Abnormal fluorine-18-fluorodeoxyglucose uptake in benign esophageal leiomyoma

A benign esophageal leiomyoma with abnormally increased fluorine-18-fluorodeoxyglucose uptake on positron emission tomography (PET) was resected thoracoscopically. The tumor, of which the maximum standardized uptake value of the lesion was 4.7, was well defined and 38 mm in diameter. Neither mitotic activity nor degeneration was found histologically; and immunoreactivity for CD34, CD117, MIB-1, and glucose transporter-1 was negative immunohistochemically. A diagnosis of gastrointestinal stromal tumor was ruled out by an oncogenic kinase gene mutation study. This case cautions against PET-dependent evaluation for malignant potential of esophageal submucosal tumors.     

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.     

Incisor trauma in an adolescent Arab population: prevalence, severity, and occlusal risk factors.

INTRODUCTION: Incisor trauma is a significant clinical problem in children and adolescents. The purposes of this study were to report on the prevalence and severity of incisor trauma in a large population-based sample of adolescent Kuwaiti residents in the early permanent dentition, to determine the ages of and reasons for the injuries, and to test for any effects of sex, incisor occlusion, and lip coverage on the prevalence of incisor trauma. METHODS: Presence and type of traumatic injury were scored according to the National Institute of Dental Research index in a population-based sample of 795 girls and 788 boys with a mean age of 13.24 years (SD 0.42). RESULTS: Trauma prevalence was higher (P < .001) in boys (19.3%) than in girls (9.7%), and in the maxilla (13.6%) than in the mandible (1.5%). Most (77.3 %) of the affected subjects had only 1 injured tooth, and most (83.7%) of the traumatized teeth were maxillary central incisors. A total of 90.3% of the injuries were unrepaired enamel or enamel/dentin fractures. The major reasons for the injuries were falls and blows indoors (48.4%) or outdoors (41.6%). Nearly two-thirds (63.0%) of the traumas occurred at age 10 years or later. Mean overjet (OJ) was larger (3.9 v 3.0 mm, P < .01), and lip incompetence more frequent (12.7% v 7.3%, P < .01) among the subjects with injured maxillary incisors than among those without. Logistic regression showed that the odds of maxillary incisor trauma were 2.8 times higher in subjects with OJ between 6.5 and 9.0 mm, and 3.7 times higher in subjects with OJ > or = 9.5 mm than in subjects with OJ < or = 3.5 mm. CONCLUSIONS: Multiple logistic regression showed that the risk of maxillary incisor trauma was about 2 times higher in boys than in girls, and that the risk increased by 13% for every millimeter of increase in OJ. Lip competence was not included in the model. No associations were found between occlusion and mandibular incisor trauma.