Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs

CONTEXT: Chronic hepatitis C (CHC) infection affects nearly 4 million people in the United States. Treatment with interferon alfa-2b has been limited by its cost and low likelihood of long-term response. OBJECTIVE: To examine the cost-effectiveness of alternative pretreatment management strategies for patients with CHC. DESIGN: Decision and cost-effectiveness analysis using a Markov model to examine prevalence of genotypes, viral load, and histological characteristics in relation to the sustained response rate with treatment. Data were based on a previously published decision model and a MEDLINE literature search for hepatitis C, biopsy, and liver from 1966 to 1996. PATIENTS: A hypothetical population of patients with CHC infection and elevated serum alanine aminotransferase level. INTERVENTIONS: Combinations of liver biopsy, genotyping, and quantitative viral load determination prior to a single 6-month course of interferon alfa-2b; empirical interferon treatment; and conservative management. MAIN OUTCOME MEASURES: Proportion of sustained responders, lifetime costs, life expectancy, and quality-adjusted life expectancy. RESULTS: Strategies involving hepatitis C virus (HCV) RNA testing had marginal cost-effectiveness ratios up to $4400 per discounted quality-adjusted life-year gained but would miss up to 36% of sustained responders. Empirical interferon treatment had a marginal cost-effectiveness ratio of $12400 per discounted quality-adjusted life-year gained and reached all potential sustained responders. Strategies involving liver biopsy were more expensive and would miss 6% of sustained responders and yield slightly lower life expectancies. CONCLUSIONS: Routine liver biopsy before treatment with interferon increases the cost of managing patients with CHC without improving health outcomes. Using quantitative HCV RNA testing to guide therapy misses some potential sustained responders. Empirical interferon treatment has a marginal cost-effectiveness ratio within the bounds of other commonly accepted therapies and misses none of the sustained responders.     

Translumbar placement of inferior vena caval catheters: a solution for challenging hemodialysis access

Access to the central venous circulation for hemodialysis has traditionally been achieved via the subclavian or jugular venous routes. With ongoing improvements in medical management, many hemodialysis recipients develop exhaustion of these routes and require alternative means of central venous access. Inferior vena caval (IVC) catheters have been placed with a percutaneous translumbar approach to allow central venous access for chemotherapy, harvesting of stem cells, and total parenteral nutrition. Translumbar placement of IVC catheters has become accepted by some as a useful and reliable alternative in patients who require long-term hemodialysis but have exhausted traditional access sites. IVC catheters have been placed in patients with IVC filters, and IVC filters have been placed in patients with IVC catheters. Complications include those associated with central venous catheters, for example, sepsis, fibrin sheaths, and thrombosis. A complication specific to placement of IVC hemodialysis catheters is migration of the catheter into the subcutaneous soft tissues, retroperitoneum, or iliac veins. Translumbar placement of IVC catheters is performed only in patients considered to have few or no other medical options and is not intended as a primary means of central venous access.     

Cost-effectiveness of therapies for patients with nonvalvular atrial fibrillation

BACKGROUND: The most appropriate treatment(s) for patients with atrial fibrillation remains uncertain. OBJECTIVE: To examine the cost-effectiveness of anti-thrombotic and antiarrhythmic treatment strategies for atrial fibrillation. METHODS: We performed decision and cost-effectiveness analyses using a Markov state transition model. We gathered data from the English-language literature using MEDLINE searches and bibliographies from selected articles. We obtained financial data from nationwide physician-fee references, a medical center's cost accounting system, and one of New England's larger managed care organizations. We examined strategies that included combinations of cardioversion, antiarrhythmic therapy with quinidine, sotalol hydrochloride, or amiodarone, and anticoagulant or antiplatelet therapy. RESULTS: For a 65-year-old man with nonvalvular atrial fibrillation, any intervention results in a significant gain in quality-adjusted life years (QALYs) compared with no specific therapy. Use of aspirin results in the largest incremental gain (1.2 QALYs). Cardioversion followed by the use of amiodarone and warfarin together is the most effective strategy, yielding a gain of 2.3 QALYs compared with no specific therapy. The marginal cost-effectiveness ratios of cardioversion followed by aspirin, with or without amiodarone, are $33800 per QALY and $10800 per QALY, respectively. Cardioversion followed by amiodarone and warfarin has a marginal cost-effectiveness ratio of $92400 per QALY compared with amiodarone and aspirin. Strategies that include cardioversion followed by either quinidine or sotalol are both more expensive and less effective than competing strategies. CONCLUSIONS: Cardioversion of patients with nonvalvular atrial fibrillation followed by the use of aspirin alone or with amiodarone has a reasonable marginal cost-effectiveness ratio. While cardioversion followed by the use of amiodarone and warfarin results in the greatest gain in quality-adjusted life expectancy, it is expensive (ie, has a high marginal cost-effectiveness ratio) compared with aspirin and amiodarone. Finally, for patients who are bothered little by symptoms of atrial fibrillation, cardioversion followed by either aspirin or warfarin without subsequent antiarrhythmic therapy is the treatment of choice.     

1H NMR investigation of distal mutant deoxy myoglobins. Interpretation of proximal His contact shifts in terms of a localized distal water molecule

1H NMR spectra of a series of distal point mutants of human and sperm whale deoxy myoglobin have been recorded and their spectral parameters compared with those of wild type. The substitutions investigated include His64(E7)-->Gly, Ala, Val, Leu, Ile, and Gln and Val68(E11)-->Ala, Ile. The three resonances from the proximal His F8 imidazole ring, as well as two heme methyl signals, are identified in each of the proteins. Significant perturbations of the NMR spectra of mutant deoxy myoglobins (Mbs) occurred only upon substitution of His64(E7) by any non-polar residue, with only minor variation in parameters throughout the range of side chains. These spectral changes are attributed to the elimination of a non-coordinated ordered water molecule in the distal pocket found hydrogen bonded to His64(E7) in crystals of wild-type deoxy Mb, but abolished in the His64(E7)-->Leu mutant deoxy Mb crystal (Quillin, M. L., Arduini, R. M., Olson, J. S., and Philips, G. N., Jr. (1993) J. Mol. Biol. 234, 140-155). The observed spectral changes, increased His F8 ring spin delocalization, and decreased heme in-plane asymmetry, can be directly attributed to the weakening of the effective axial field and a decrease in the asymmetry in the rhombic ligand field resulting from removal of the water molecule. The hyperfine shift patterns for the mutants His64(E7)-->Gln and Val68(E11)-->Ile deoxy Mbs are minimally perturbed from that of wild type and are interpreted to reflect a conserved distal water-binding site. In the point mutant Val68(E11)-->Ala, the decreased covalency to the axial His F8 is interpreted as reflecting a conserved distal water molecule that can interact more strongly with the iron due to the reduced steric bulk of the E11 side chain. The differential 1H NMR spectral parameters for the His F8 resonances in the two subunits of T state deoxy Hb A are shown to be similarly consistent with the known occupation of the distal water binding site in the alpha-, but not beta-subunit.     

Method of purification affects some interfacial properties of pulmonary surfactant proteins B and C and their mixtures with dipalmitoylphosphatidylcholine

Two methods were employed for preparation of lipid extracts from porcine lung surfactant. Pulmonary surfactant proteins SP-B and SP-C were isolated from the extracts using gel-exclusion chromatography on LH-60 with chloroform:methanol acidified with hydrochloric acid. Monolayers of pure SP-B or SP-C isolated from butanol lipid extracts spread at the air-water interface showed larger molecular areas than those determined in films of SP-B or SP-C isolated from chloroform surfactant extracts. Aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC) supplemented with 2.5 and 5.0 wt% of SP-B or SP-C obtained from butanol extracts adsorbed faster to the air-water interface than their counterparts reconstituted with proteins isolated from chloroform extracts. Surface pressure-area characteristics of spread monolayers of DPPC plus SP-B or SP-C did not depend on the method of isolation of the proteins. The diagrams of the mean molecular areas vs. composition for the monolayers of DPPC plus SP-B or SP-C showed positive deviations from the additivity rule, independently of the procedure used for preparation of lipid extract surfactant. Matrix-assisted laser desorption/ionization spectrometry of the proteins isolated from different extraction solvents was consistent with some differences in the chemical compositions of SP-Bs. Butylation of SP-B during extraction of surfactant pellet with butanol may account for the differences observed in the molecular masses of SP-Bs isolated by the two different extraction protocols. The study suggests that the method of purification of SP-B and SP-C may modify their ability to enhance the adsorption rates of DPPC/protein mixtures, and this may be relevant to the formulation of protein-supplemented lipids for exogenous treatment of pulmonary surfactant insufficiency.     

Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience

BACKGROUND: The Quebec Neuroblastoma Screening (QNS) Project completed a 5-year program for measuring urinary vanillylmandelic acid (VMA)/homovanillic acid (HVA) levels at age 3 weeks and/or 6 months in 89% of 476,603 Quebec-born infants from 1989-1994; 45 screening positive preclinical cases (S-positive cases) and 20 congenital/neonatal (C/N) cases were identified. As of April 1997, an additional 59 cases in the same birth cohort were diagnosed clinically; these neuroblastomas developed after screening verified normal VMA/HVA levels (S-negative cases). METHODS: Pathology specimens from 45 of 59 S-negative cases were reviewed centrally and classified according to the Shimada system. Results were compared with clinical data and also with S-positive and C/N cases. RESULTS: Of 45 S-negative cases, 27 tumors had favorable histology (FH) and 18 had unfavorable histology (UH). Approximately 52% of FH tumors were diagnosed before age 1 year, whereas UH tumors were nearly exclusively (94%) diagnosed after age 1 year (P < 0.01). Approximately 89% of FH tumors were Stage I, II, or IV-S, whereas 72% UH tumors were Stage III or IV (P < 0.001). All children with FH tumors were alive at last follow-up (range of follow-up period: 9-79 months; median, 35 months), whereas 8 children with UH tumors died of disease even after limited follow-up (range of follow-up period: 0-60 months; median, 20 months). By contrast, S-positive and C/N cases were predominantly (97%) FH tumors, often (76%) Stage I, II, or IV-S, with excellent clinical outcome (survival rate of 98%). CONCLUSIONS: The majority of the UH neuroblastomas that developed in the birth cohort of the QNS Project were included in the group of S-negative cases and could not be detected by the screening at age 3 weeks and/or 6 months.