The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.     

The Effect of Health Plan Characteristics on Medicare+Choice Enrollment

Objective. To provide national estimates of the effect of out-of-pocket premiums and benefits on Medicare beneficiaries' choice among managed care health plans.
Data Sources/Study Setting. The data represent the population of all Medicare+Choice (M+C) plans offered to Medicare beneficiaries in the United States in 1999.
Study Design. The dependent variable is the log of the ratio of the market share of the j th health plan to the lowest cost plan in the beneficiary's county of residence. The explanatory variables are measures of premiums and benefits in the j th health plan relative to the premiums and benefits in the lowest cost plan.
Data Collection Methods. The data are from the 1999 Medicare Compare database, and M+C enrollment data from the Centers for Medicare and Medicaid Services (CMS).
Principal Findings. A $10 increase in an M+C plan's out-of-pocket premium, relative to its competitors, is associated with a decrease of four percentage points in the j th plan's market share (i.e., from 25 to 21 percent), holding the premiums of competing plans constant.
Conclusions. Although our price elasticity estimates are low, the market share losses associated with small changes in a health plan's premium, relative to its competitors, may be sufficient to discipline premiums in a competitive market. Bidding behavior by plans in the Medicare Competitive Pricing Demonstration supports this conclusion.     

Transbronchial needle aspiration in the diagnosis of bronchogenic carcinoma

Transbronchial needle aspiration (TBNA) was performed as a diagnostic procedure in 91 consecutive patients ultimately proven to have bronchogenic carcinoma. Results of TBNA were compared, in the same patients, to the diagnostic yield of cytologic examination of sputum, endobronchial brushings and washings, and endobronchial/transbronchial biopsy. The diagnostic yield for sputum was 13 percent (10 of 75); brushings, 40 percent (34 of 84); washings, 29 percent (26 of 89); biopsy, 56 percent (42 of 75); and TBNA, 45 percent (41 of 91). Aspirates were positive in 35 percent of patients with adenocarcinoma, 41 percent with squamous cell carcinoma, 52 percent with large cell undifferentiated carcinoma, and 55 percent of patients with small cell carcinoma. Carinal aspirates were positive in 54 percent (6 of 11); paratracheal aspirates, 57 percent (13 of 23); parabronchial aspirates, 39 percent (11 of 28); endobronchial, 78 percent (7 of 9), and peripheral mass or solitary pulmonary nodule, 40 percent (17 of 42). The overall diagnostic yield for brushings, washings, and biopsy was 64 percent. The addition of TBNA increased the yield to 71 percent. Bronchogenic carcinoma was diagnosed solely by TBNA in six patients, all with extrabronchial or extratracheal lesions. We conclude that TBNA increases the diagnostic yield of bronchoscopy, particularly in patients with extratracheal and extrabronchial lesions. An equally important observation is that TBNA fails to contribute significantly to the diagnosis of cancer in patients with lesions readily accessible by conventional bronchoscopic techniques. Exceptions to this observation include occasional patients with necrotic endobronchial tumors, submucosal lesions, and rarely patients with peripheral lung nodules or masses.     

Human microsporidial infections.

Microsporidia are obligate intracellular spore-forming protozoal parasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes of vertebrates. More than 100 microsporidial genera and almost 1,000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Among persons not infected with human immunodeficiency virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic-antiprotozoal drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured with albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing antimicrosporidial drugs. Furthermore, molecular techniques are being developed for diagnostic purposes, taxonomic classification, and analysis of phylogenetic relationships of microsporidia.     

Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans

The effects of caffeine ingestion and exposure to bright light, both separately and in combination, on salivary melatonin and tympanic temperature were assessed in humans. Four treatments during a 45.5 h sleep deprivation period were compared: Dim Light-Placebo, Dim Light-Caffeine, Bright Light-Placebo and Bright-Light Caffeine. The Dim Light-Caffeine condition (200 mg twice each night) relative to the Dim Light-Placebo condition suppressed nighttime melatonin levels and attenuated the normal decrease in temperature. Combining caffeine ingestion with bright light exposure (≥2000 lux) suppressed melatonin and attenuated the normal nighttime drop in temperature to a larger degree than either condition alone; i.e. effects were additive. Circadian effects were also observed in that the amplitude and phase of the temperature rhythm were altered during treatment. These findings establish that the human melatonin system is responsive to caffeine. Other evidence suggests that caffeine may influence melatonin and temperature levels through antagonism of the neuromodulator adenosine.     

Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen