Development of Tetramethylenedisulfotetramine (TETS) Hapten Library: Synthesis, Electrophysiological Studies, and Immune Response in Rabbits.

There is a need for fast detection methods for the banned rodenticide tetramethylenedisulfotetramine (TETS), a highly potent blocker of the γ-aminobutyric acid (GABAA ) receptors. General synthetic approach toward two groups of analogues was developed. Screening of the resulting library of compounds by FLIPR or whole-cell voltage-clamp revealed that, despite the structural differences, some of the TETS analogues retained GABAA receptor inhibition; however, their potency was an order of magnitude lower. Antibodies raised in rabbits against some of the TETS analogues conjugated to protein recognized free TETS and will be used for the development of an immunoassay for TETS.

Knee cartilage T2 characteristics and evolution in relation to morphologic abnormalities detected at 3-T MR imaging: a longitudinal study of the normal control cohort from the Osteoarthritis Initiative.

PURPOSE: To determine the frequency of degenerative knee morphologic abnormalities in asymptomatic individuals by using 3-T magnetic resonance (MR) imaging and to investigate the characteristics and evolution of cartilage T2 values in relation to morphologic abnormalities with a longitudinal study. MATERIALS AND METHODS: The study was approved by the institutional review board and was compliant with HIPAA. Ninety-five asymptomatic subjects aged 45-78 years who were free of risk factors for osteoarthritis (OA) were selected from the Osteoarthritis Initiative normal control cohort and examined with radiography and 3-T MR imaging. Data obtained at both baseline and 2-year follow-up were analyzed. OA-related knee abnormalities were analyzed by using the whole-organ MR imaging score (WORMS). Cartilage T2 maps were generated by using sagittal two-dimensional multiecho spin-echo images of the right knee. Statistical significance was determined with the Student t test, the paired t test, a mixed random effects model, one-way analysis of variance, and a multiple linear regression model. RESULTS: Knee abnormalities were identified with a high frequency (90% at baseline and 92% at 2-year follow-up). The prevalence of hyaline cartilage lesions was particularly high (86% at baseline and 84% at follow-up). A significant longitudinal increase in T2 was detected in the tibiofemoral cartilage but not the patellofemoral cartilage (P = .0072). The longitudinal change in T2 was significantly associated with worsening of the cartilage WORMS (P = .038). CONCLUSION: Asymptomatic subjects have a high frequency of OA-related morphologic abnormalities. A significant increase in tibiofemoral cartilage T2 was detected over the 2-year period. A greater increase in T2 was associated with increased progression of cartilage morphologic abnormalities.

Treating hepatitis C in the prison population is cost-saving.

UNLABELLED: The prevalence of chronic hepatitis C infection in U.S. prisons is 12% to 31%. Treatment of this substantial portion of the population has been subject to much controversy, both medically and legally. Studies have demonstrated that treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin is a cost-effective measure in the general population; however, no study has addressed whether the same is true of the prison population. The aim of this study was to determine the cost-effectiveness of hepatitis C treatment with PEG IFN and ribavirin in the U.S. prison population. Cost-effectiveness was determined via a decision analysis model employing Markov simulation. The cohort of prisoners had a distribution of genotypes and stages of fibrosis in accordance with prior studies evaluating inmate populations. The probability of transitioning from one health state to another, reinfection rates, in-prison and out-of-prison mortality rates, sustained viral response rates, costs, and quality of life weights were also obtained from the literature. Sensitivity analysis was performed. In a strategy without a pretreatment liver biopsy, treatment was cost-effective for all ages and genotypes. This model was robust to rates of disease progression, mortality rates, reinfection rates, sustained viral response rates, and costs. In a strategy employing a pretreatment liver biopsy, treatment was also cost-saving for prisoners of all ages and genotypes with portal fibrosis, bridging fibrosis, or compensated cirrhosis. Treatment was not cost-effective in patients between the ages of 40 and 49 with no fibrosis and genotype 1. CONCLUSION: Treatment of chronic hepatitis C with PEG IFN and ribavirin in U.S. prisons results in both improved quality of life and savings in cost for almost all segments of the inmate population. If the decision to treat hepatitis C is based on pharmaco-economic measures, this significant proportion of infected individuals should not be denied access to therapy.

Hepatitis B prophylaxis in patients undergoing chemotherapy for lymphoma: a decision analysis model.

UNLABELLED: Hepatitis B reactivation is a major cause of morbidity and mortality in patients undergoing chemotherapy for lymphomas. These patients may experience direct liver-related complications or reduced cancer survival because of interruptions in chemotherapy. Our aim was to compare the costs and outcomes of 2 different chronic hepatitis B management strategies. In hepatitis B carriers undergoing chemotherapy, we pursued a decision analysis model to compare the costs and clinical outcomes of using lamivudine prophylaxis versus initiating lamivudine only when clinically overt hepatitis occurred. Our results indicate that the use of lamivudine prophylaxis is cost-effective. Even though the use of lamivudine prophylaxis was associated with an incremental cost of $1530 per patient ($18,707 versus $17,177), both the number and severity of hepatitis B reactivations were reduced. None of the patients in the prophylaxis group had liver-related deaths versus 20 who died in the no-prophylaxis group. Cancer deaths were also reduced from 47-39 with lamivudine prophylaxis, presumably because of the increased need for cessation or modification of chemotherapy in patients who had severe hepatitis B virus flares. The incremental cost-effectiveness ratio of using lamivudine prophylaxis was $33,514 per life year saved. CONCLUSION: Our results provide pharmacoeconomic support for the use of lamivudine prophylaxis in patients undergoing chemotherapy for lymphoma treatment.