The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

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.     

Stereological evaluation of liver volume in living donor liver transplantation using MDCT via the Cavalieri method.

In living donor liver transplantation (LDLT), obtaining the precise volume of the graft is very important to decrease volume-related postoperative complications, especially in cases with suspected small-for size grafts. We used stereology based on the Cavalieri method (CM), a new method to measure liver graft volume, and compared the results with those obtained through intraoperative measurement (IOM) and through multidetector computed tomography (MDCT) measurement. Liver volumes estimated using the 3 methods were well-correlated with each other (r(2) = 0.94 and P < 0.001 for IOM and CM; r(2) = 0.91 and P < 0.001 for IOM and MDCT, and r(2) = 0.95 and P < 0.001 for CM and MDCT); however, they were different from each other (in descending order, 908 +/- 124 cm(2), 861 +/- 121 cm(2), and 777 +/- 168 cm(2) for MDCT, CM, and IOM, respectively). Although MDCT and CM overestimated the volumes, the results of CM were almost similar to those obtained via IOM. In conclusion, our results suggest that CM measured the liver graft volume more reliably. Thus, its use, particularly in cases with suspected small-for-size graft, may prove useful.     

The effect of metoclopramide on gastric emptying in traumatic brain injury.

OBJECTIVE: Gastric paresis in traumatic brain injury (TBI) hinders the effectiveness of enteral support in this patient group. In this study we have investigated the effect of metoclopramide on gastric emptying in TBI patients. METHOD: In this prospective, randomized, controlled, double-blind study, 19 TBI patients with Glasgow Coma Scale scores of 3-11 were included. In all patients, enteral nutrition was commenced with a nasogastric feeding tube within 48 hours of trauma. Patients were randomized into two groups. In the metoclopramide (M) group, 10 mg metoclopramide was delivered intravenously three times daily for 5 days. In the control (C) group, an equal volume of saline was administered. Besides demographics, gastric emptying according to a paracetamol absorption test at days 0 and 5, time to reach target nutritional requirements, gastric residues, intolerance to feeding, nutritional complications, and clinical outcomes were recorded for each patient. RESULTS: The gastric residue rates were 2.7+/-7.4 mL and 8.1+/-17.7 mL per 100 patient days for groups C and M respectively (p=0.408). Similarly, feeding intolerance and complication rates did not significantly differ between groups C and M, (respectively p=0.543 and 0.930). Gastric emptying parameters also were similar between the study groups. CONCLUSION: We were unable to document any advantage to using metoclopramide in TBI patients. Simple intragastric enteral feeding with close monitoring of the possible complications seems to be sufficient with acceptable morbidity rates.     

Reconstruction of the wrist pseudoarthrosis due to radioulnar fractures with vascularized fibular graft in a child with neurofibromatosis

Nonunion in the forearm following a radioulnar fracture is one of the nightmares of the orthopedic surgeon. Fortunately, it is rare. We treated a large bone defect of the forearm, using a vascularized fibular graft after excision of the unhealed bone segment in a 10-year-old boy with neurofibromatosis. This situation followed a double fracture that had been operated on several times using conventional methods. Following the debridement of the unhealthy tissues in the pseudoarthrotic region, the vascularized fibula was placed on the dorsal surface of the proximal radius fragment. The distal fragment of the radius was inserted into the fibular cavity and fixation was established with a Kirschner wire distally and with a plate proximally. Only two screws were used to fix the plate. The peroneal artery was anastomosed with the radial artery; one of its venae comitantes was anastomosed with the cephalic vein in an end-to-end fashion. After surgery, the elbow was immobilized at 90 degrees of flexion with a splint for 6 weeks. One year after surgery, forearm stabilization and elbow and hand functions were very satisfactory. However, because the distal epiphyses of the bones were destroyed following the repeated surgery and the original trauma itself, a very prominent difference between the two forearms occurred, suggesting the need for bone lengthening in the future. By presenting this case we would like to conclude that one can expect good bone healing with a vascularized bone transfer in these cases when there is not enough space to place screws, but support can be provided by an external splint and K wire.     

Prophylactic effect of UFT on the recurrence of bladder cancer

To evaluate the effect of UFT, a mixture of ftorafur and uracil in a ratio of 1:4, in preventing postoperative recurrence of bladder cancer, we performed a randomized controlled study with a non-medication group as control. UFT was given orally 400 mg a day for 6 months. Of 111 patients, 56 were given UFT and 55 were followed up without any medication. The non-recurrence rate in the group treated with UFT was 62.8% after 1 year and 36.3% after 2 years of follow up, and that of the control group was 45.7% and 39.5%, respectively. The rate of non-recurrence in the UFT group was significantly higher (p less than 0.05) than that of the control group during the period of follow up for 2 years. The incidence of side effects was 6.8% in UFT patients. These results indicate the clinical usefulness of prophylactic administration of UFT for bladder cancer patients.