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Biomedical subjects

M E Singer

Publications and source records attributed to M E Singer.

At least 19 recordsLinked to original sources

Cost effectiveness of screening for hepatitis C virus in asymptomatic, average-risk adults.

PURPOSE: To estimate the cost effectiveness of screening for hepatitis C in asymptomatic, average-risk adults. METHODS: We used a Markov decision analysis model to estimate the lifetime cost effectiveness of three screening strategies: (1) initial screening for hepatitis C antibody by third-generation enzyme-linked immunosorbent assay (ELISA), followed by confirmatory testing for hepatitis C virus ribonucleic acid (RNA) using polymerase chain reaction (PCR); (2) initial screening for hepatitis C virus RNA by PCR only; and (3) the current practice of not screening. The patient population comprised a hypothetical cohort of average-risk adults presenting to their regular primary health care provider for routine physical examination. The main outcome measure was cost per additional quality-adjusted life-year (QALY) gained. RESULTS: The no screening strategy was the dominant strategy in the baseline analysis. The model was most sensitive to the reduction in quality of life related to patient awareness of hepatitis C infection. Screening with ELISA and PCR was preferred when this value was <0.01 and was cost effective if more than half of the patients who tested positive for hepatitis C actually initiated treatment, or if the annual rate of progression to cirrhosis was greater than 2.5%. Screening with PCR only was never cost effective. CONCLUSIONS: This analysis does not support the widespread screening for hepatitis C among asymptomatic, average-risk adults.

Adult↗

Cost-effectiveness analysis in radiology.

In the past 20 years, there has been increasing recognition of the need to consider cost in medical decision making. This period has seen an explosion in the number of economic evaluations appearing in the medical literature. Cost-effectiveness analysis is an objective systematic technique for comparing alternative health care strategies on both cost and effectiveness simultaneously. Cost-effectiveness analysis can be used to inform medical decision makers in the establishment of clinical practice guidelines and in the setting of health policy. Cost-effectiveness analysis is a state-of-the-art research tool with its own terminology and methods. It is critical that radiologists become familiar with the concepts and procedures of cost-effectiveness analysis so they can properly evaluate cost-effectiveness analysis studies and be more knowledgeable participants in the health care decision-making process. This article explains the rationale, terminology, and methods of cost-effectiveness analysis as applied to radiology.

Cost-Benefit Analysis↗

Managed care for the Medicaid disabled: effect on utilization and costs.

The objective of this study was to describe the effect on health care utilization and costs of a program of managed care for the Medicaid disabled. The study was designed as a pre/post enrollment cohort comparison and was carried out in three Ohio counties. The subjects were disabled Medicaid-insured patients who voluntarily enrolled in a managed care program for at least 6 months between July 1, 1995 and December 31, 1997, and who had (1) at least one Medicaid claim in the 24-months pre-enrollment period and (2) overall satisfactory postenrollment encounter-level data. Ohio Medicaid provided claims and reimbursements (costs) for the pre-enrollment period and encounter-level data for the postenrollment period. Postenrollment costs were estimated by applying category-specific average pre-enrollment costs to postenrollment utilization data. We measured the following per patient-month: (1) trends in category-specific utilization and costs for up to 24 months before and after enrollment, (2) differences in overall and category-specific costs 1 year before and after enrollment, and (3) changes in the distribution of services 1 year before and after enrollment. Utilization categories included inpatient care, outpatient hospital (including emergency department) care, physician services, prescription medications, durable medical equipment and supplies, and home health care. We found that satisfactory encounter data were available in two of three counties. Of 1,179 enrollees, 592 met all inclusion criteria. Before enrollment, utilization and costs were increasing significantly in four of six categories and were unchanging in two. Postenrollment, decreasing utilization was observed for three categories, one remained unchanged, and two were increasing, but from a lower "baseline." Except for physician services and home health care, there were lower utilization and estimated costs in all categories in the year after enrollment. Estimated inpatient and total costs declined by $155/patient-month (44.9%) and $210/patient-month (37.1%), respectively. Findings were similar across sites. Inpatient care, outpatient hospital care, and prescription medications accounted for 97% of the reductions in estimated costs in the postenrollment period. Among patients voluntarily enrolled for at least 6 months, managed care for the Medicaid disabled was associated with striking decreases in health care utilization and estimated costs. The effect of managed care on these patients' satisfaction, access to specialized services, quality of care, and health outcomes are understood incompletely.

Case Management↗

Comparison of risk-adjustment systems for the medicaid-eligible disabled population.

OBJECTIVE: The objective of this study was to compare 2 approaches for subjecting capitation rates for disabled Medicaid-eligible patients in managed care plans to risk adjustment, the Disability Payment System (DPS) and the Ohio Prior Expenditure System (OPES). DESIGN: This was a retrospective cohort. SETTING AND SUBJECTS: The subjects were 157,142 nonelderly disabled individuals eligible for > or =1 month during state fiscal year 1995 (SFY95) for a 3-county Ohio Medicaid managed care demonstration project. DATA SOURCE: Data were from the Ohio Medicaid eligibility and fee-for-service claims files. ANALYSIS: As per OPES policy, individuals were classified by the duration of their eligibility in SFY93 as "old" eligibles (> or =6 months) or "new" eligibles (<6 months). Published relative payment weights for each system were adjusted and used to predict SFY95 expenditures in a budget-neutral comparison. Measures were variance in SFY95 expenditures explained by predicted payments (R2) and predictive ratios (predicted payment/actual SFY95 expenditure). Individuals with HIV/AIDS and hematological conditions, who enrolled disproportionately across the demonstration counties, were analyzed separately. RESULTS: Of the 157,142 individuals, 56.4% were new eligibles; 40.1% of the old eligibles had no claims-documented chronic disease diagnosis in the baseline year. The overall R2 was 0.091 with OPES and 0.057 with DPS. Neither system predicted >1% of individual-level expenditures for new eligibles. OPES severely underpaid for eligibles in the top percentile of predicted expenditures; DPS had mixed results. DPS predicted SFY95 expenditures substantially better than OPES for the enrollment bias categories. CONCLUSIONS: Before Medicaid programs move to full-risk capitation for disabled populations, better risk-adjustment methods are needed, especially for eligible patients with little claims experience, high predicted expenditures, or enrollment-bias conditions.

Adolescent↗

Cost-effectiveness analysis of hepatitis A vaccination strategies for adults.

Our objective in this study was to determine the cost-effectiveness of hepatitis A vaccination strategies in healthy adults in the United States. We constructed a decision model simulating costs and health consequences for otherwise healthy adults with respect to hepatitis A prevention. Three strategies were compared: (1) no intervention, (2) vaccination against hepatitis A, and (3) testing for antibodies to hepatitis A and vaccinating those without antibodies. Costs and probabilities were obtained from the published literature. One- and two- way sensitivity analyses were performed. Under baseline conditions, the "test" strategy cost $230,100 per life-year saved compared with the "no intervention" strategy. The incremental cost-effectiveness of the "vaccination" strategy compared with the "test" strategy was $20.1 million per life-year saved. The "test" strategy was cost-effective when the hepatitis A case fatality rate exceeded 17% (baseline 2.7%). The "vaccination" strategy was cost-effective when 1 dose of vaccine cost $7 or less (baseline $57). Under baseline conditions, neither the "test" nor the "vaccination" strategies are considered cost-effective according to current standards. Large changes in hepatitis A incidence, mortality rates, or vaccine cost are required for either of the intervention strategies to approach potentially cost-effectiveness. Such conditions may occur in areas in which hepatitis A is endemic, and/or under mass-vaccination scenarios.

Cost-Benefit Analysis↗

Cost effectiveness of interferon alpha2b combined with ribavirin for the treatment of chronic hepatitis C.

Treatment of chronic hepatitis C with Interferon (IFN) alpha2b monotherapy results in 10% to 15% sustained virological response (SVR). Combining IFN with ribavirin increases this response. In this analysis, using the Markov model, 6 treatment strategies for chronic hepatitis C (previously untreated) were compared on the basis of incremental cost per additional quality-adjusted life years ($/QALY). Our results showed that the no treatment strategy was associated with a cost of $38,747 and 13.10 QALYs. The strategy using IFN alone for 48 weeks was associated with a cost of $35,642 and 14.05 QALYs. The strategy using IFN monotherapy followed by combination therapy for nonresponders and relapsers was associated with a cost of $34, 561 and 15.53 QALYs. A similar strategy, but limiting combination to relapsers only, was associated with a cost of $34,758 and 14.40 QALYs. The strategy using IFN with ribavirin as the initial therapy for all patients was associated with a cost of $34,792 and 15.31 QALYs. Finally, the strategy using viral genotyping first and then adjusting the duration of combination therapy based on genotype was associated with a cost of $37,263 and 15.89 QALYs. The strategy using genotyping to guide duration of combination therapy was the most cost-effective approach with an incremental cost-effectiveness ratio of $7,500 per QALY. Sensitivity analyses confirmed the robustness of these results. We conclude that combination of IFN and ribavirin with duration of therapy based on the viral genotype, is a cost-effective approach in treating patients with chronic hepatitis C.

Antiviral Agents↗

Rapid growth of rehabilitation services in traditional community-based nursing homes.

OBJECTIVE: To describe the changes in rehabilitation therapy services in nursing homes based in the community during a period of rapid escalation of Medicare payments to nursing homes. SETTING: All Medicaid-certified nursing homes in Ohio. SUBJECTS: The 52,705 residents newly admitted to nursing homes in 1994 and 1995. DESIGN: Retrospective trend analysis of administrative data. MAIN OUTCOME MEASURES: For newly admitted residents receiving 90 or more minutes of rehabilitation therapy per week, the trends in percentage and in the amount and type of therapy received were determined for eight quarters. RESULTS: Of all newly admitted residents, 50.5% received 90 or more minutes of therapy. When they received such therapy it averaged 412 minutes per week (SD = 259). Those residents who received rehabilitation services increased by 2.2% each quarter (p<.001), and the amount of therapy they received increased by 6.4 minutes each quarter (p<.0001). All three types of rehabilitation therapy-physical, occupational, and speech-increased (p<.015) over the study period. CONCLUSIONS: The traditional nursing home is an important site for the provision of rehabilitation therapy services. Rehabilitation specialists should be aware of these trends as they plan for the future of rehabilitation. The effectiveness of this increased provision of therapy service in terms of measurable outcomes needs to be evaluated.

Aged↗

The cost-effectiveness of strategies to assess gastroesophageal reflux as an exacerbating factor in asthma.

OBJECTIVES: We sought to evaluate the cost-effectiveness of diagnostic strategies to determine whether or not acid reflux exacerbates asthma, and to identify which asthma response probabilities are most important in a cost-effective workup of this problem. METHODS: We performed a cost-effectiveness analysis, comparing 11 diagnostic strategies to assess the role that acid reflux plays in asthma. Probabilities and costs were derived from the published literature. Average and incremental costs, effectiveness, and cost-effectiveness were calculated for each strategy. Sensitivity analyses were performed. RESULTS: The most cost-effective diagnostic approach is to begin with omeprazole 20 mg/day for 3 months, followed by 24-h pH testing on drug in nonresponders. If 24-h pH testing is positive, increase the omeprazole dose every 3 months until the patient responds or a maximum of 60 mg/day is given. This strategy costs $730 per case correctly diagnosed. When the cost of pH testing exceeds $586 or the cost of omeprazole 20 mg/day is <$53 per month, omeprazole 20 mg/day for 3 months followed by 60 mg/day for the same duration in nonresponders becomes more cost-effective. CONCLUSIONS: Empiric acid reflux suppression, followed by pH testing in nonresponders, is the most cost-effective means of determining whether GERD is aggravating a patient's asthma.

Asthma↗

Barriers to adequate delivery of hemodialysis.

Mortality rates among American hemodialysis patients are the highest in the industrialized world. Measures of delivered dialysis (Kt/V) correspond strongly with survival and are estimated to be inadequate in one third of patients. We sought to determine the importance of potential barriers to adequate dialysis, including patient-related and technical factors. Using a cross-sectional study design, we abstracted the charts of 721 randomly selected patients from all 22 chronic hemodialysis units in northeast Ohio. For each of 1,836 treatments provided to these patients, we assessed delivered dialysis (Kt/V) and patient-related factors (ie, hypotension, intradialytic symptoms, and treatment time missed due to noncompliance or transportation problems) and technical factors (ie, dialysis prescription, type of vascular access, clotting, and dialyzer reuse). We used hierarchical regression analysis to determine which potential barriers were independently related to delivered dialysis after adjustment for patient demographic and medical characteristics. Barriers independently related to dialysis delivery (all P values < 0.001) included patient noncompliance, present in 3% of treatments; low dialysis prescription, 14%; use of a catheter for vascular access, 11%; and clotting, 1%. The prevalence of identified barriers varied dramatically across facilities (eg, the prevalence of low dialysis prescription ranged from 0% to 37%, while the prevalence of catheter use ranged from 3% to 28%). In conclusion, patient noncompliance, low dialysis prescription, catheter use, and clotting are the most important barriers to dialysis delivery. Further work is needed to develop interventions to overcome these barriers and to determine the effect of such interventions on dialysis adequacy and patient survival.

Adult↗

Construction of an Escherichia coli-Rhodococcus shuttle vector and plasmid transformation in Rhodococcus spp.

A plasmid transformation system for Rhodococcus sp. strain H13-A was developed by using an Escherichia coli-Rhodococcus shuttle plasmid constructed in this study. Rhodococcus sp. strain H13-A contains three cryptic indigenous plasmids, designated pMVS100, pMVS200, and pMVS300, of 75, 19.5, and 13.4 kilobases (kb), respectively. A 3.8-kb restriction fragment of pMVS300 was cloned into pIJ30, a 6.3-kb pBR322 derivative, containing the E. coli origin of replication (ori) and ampicillin resistance determinant (bla), as well as a Streptomyces gene for thiostrepton resistance, tsr. The resulting 10.1-kb recombinant plasmid, designated pMVS301, was isolated from E. coli DH1(pMVS301) and transformed into Rhodococcus sp. strain AS-50, a derivative of strain H13-A, by polyethylene glycol-assisted transformation of Rhodococcus protoplasts and selection for thiostrepton-resistant transformants. Thiostrepton-resistant transformants were also ampicillin resistant and were shown to contain pMVS301, which was subsequently isolated and transformed back into E. coli. The cloned 3.8-kb fragment of Rhodococcus DNA in pMVS301 contains a Rhodococcus origin of replication, since the hybrid plasmid was capable of replication in both genera. The plasmid was identical in E. coli and Rhodococcus transformants as determined by restriction analysis and was maintained as a stable, independent replicon in both organisms. Optimization of the transformation procedure resulted in transformation frequencies in the range of 10(5) transformants per micrograms of pMVS301 DNA in Rhodococcus sp. strain H13-A and derivative strains. The plasmid host range extends to strains of Rhodococcus erythropolis, R. globulerus, and R. equi, whereas stable transformants were not obtained with R. rhodochrous or with several coryneform bacteria tested as recipients. A restriction map demonstrated 14 unique restriction sites in pMVS301, some of which are potentially useful for molecular cloning in Rhodococcus spp. and other actinomycetes. This is the first report of plasmid transformation and of heterologous gene expression in a Rhodococcus sp.

Ampicillin↗

Growth of Acinetobacter sp. strain HO1-N on n-hexadecanol: physiological and ultrastructural characteristics.

The growth of Acinetobacter sp. strain HO1-N on hexadecanol results in the formation of intracytoplasmic membranes and intracellular rectangular inclusions containing one of the end products of hexadecanol metabolism, hexadecyl palmitate. The intracellular inclusions were purified and characterized as "wax ester inclusions" consisting of 85.6% hexadecyl palmitate, 4.8% hexadecanol, and 9.6% phospholipid, with a phospholipid-to-protein ratio of 0.42 mumol of lipid phosphate per mg of inclusion protein. The cellular lipids consisted of 69.8% hexadecyl palmitate, 22.8% phospholipid, 1.9% triglyceride, 4.7% mono- and diglyceride, 0.1% free fatty acid, and 0.8% hexadecanol, as compared with 98% hexadecyl palmitate and 1.9% triglyceride, which comprised the extracellular lipids. Cell-associated hexadecanol represented 0.05% of the exogenously supplied hexadecanol, with hexadecyl palmitate accounting for 14.7% of the total cellular dry weight. Acinetobacter sp. strain HO1-N possesses a mechanism for the intracellular packaging of hexadecyl palmitate in wax ester inclusions, which differ in structure and chemical composition from "hydrocarbon inclusions" isolated from hexadecane-grown cells.

Acinetobacter↗

Fatty aldehyde dehydrogenases in Acinetobacter sp. strain HO1-N: role in hexadecanol metabolism.

The role of fatty aldehyde dehydrogenases (FALDHs) in hexadecane and hexadecanol metabolism was studied in Acinetobacter sp. strain HO1-N. Two distinct FALDHs were demonstrated in Acinetobacter sp. strain HO1-N: a membrane-bound, NADP-dependent FALDH activity induced 5-, 15-, and 9-fold by growth on hexadecanol, dodecyl aldehyde, and hexadecane, respectively, and a constitutive, NAD-dependent, membrane-localized FALDH. The NADP-dependent FALDH exhibited apparent Km and Vmax values for decyl aldehyde of 5.0, 13.0, 18.0, and 18.3 microM and 537.0, 500.0, 25.0, and 38.0 nmol/min in hexadecane-, hexadecanol-, ethanol-, palmitate-grown cells, respectively. FALDH isozymes ald-a, ald-b, and ald-c were demonstrated by gel electrophoresis in extracts of hexadecane- and hexadecanol-grown cells. ald-a, ald-b, and ald-d were present in dodecyl aldehyde-grown cells, while palmitate-grown control cells contained ald-b and ald-d. Dodecyl aldehyde-negative mutants were isolated and grouped into two phenotypic classes based on growth: class 1 mutants were hexadecane and hexadecanol negative and class 2 mutants were hexadecane and hexadecanol positive. Specific activity of NADP-dependent FALDH in Ald21 (class 1 mutant) was 85% lower than that of wild-type FALDH, while the specific activity of Ald24 (class 2 mutant) was 55% greater than that of wild-type FALDH. Ald21R, a dodecyl aldehyde-positive revertant able to grow on hexadecane, hexadecanol, and dodecyl aldehyde, exhibited a 100% increase in the specific activity of the NADP-dependent FALDH. The oxidation of [3H]hexadecane byAld21 yielded the accumulation of 61% more fatty aldehyde than the wild type, while Ald24 accumulated 27% more fatty aldehyde, 95% more fatty alcohol, and 65% more wax ester than the wild type. This study provides genetic and physiological evidence for the role of fatty aldehyde as an essential metabolic intermediate and NADP-dependent FALDH as a key enzyme in the dissimilation of hexadecane, hexadecanol, and dodecyl aldehyde in Acinetobactor sp. strain HO1-N.

Acinetobacter↗

Alcohol dehydrogenases in Acinetobacter sp. strain HO1-N: role in hexadecane and hexadecanol metabolism.

Multiple alcohol dehydrogenases (ADH) were demonstrated in Acinetobacter sp. strain HO1-N. ADH-A and ADH-B were distinguished on the basis of electrophoretic mobility, pyridine nucleotide cofactor requirement, and substrate specificity. ADH-A is a soluble, NAD-linked, inducible ethanol dehydrogenase (EDH) exhibiting an apparent Km for ethanol of 512 microM and a Vmax of 138 nmol/min. An ethanol-negative mutant (Eth1) was isolated which contained 6.5% of wild-type EDH activity and was deficient in ADH-A. Eth1 exhibited normal growth on hexadecane and hexadecanol. A second ethanol-negative mutant (Eth3) was acetaldehyde dehydrogenase (ALDH) deficient, having 12.5% of wild-type ALDH activity. Eth3 had threefold-higher EDH activity than the wild-type strain. ALDH is a soluble, NAD-linked, ethanol-inducible enzyme which exhibited an apparent Km for acetaldehyde of 50 microM and a Vmax of 183 nmol/min. Eth3 exhibited normal growth on hexadecane, hexadecanol, and fatty aldehyde. ADH-B is a soluble, constitutive, NADP-linked ADH which was active with medium-chain-length alcohols. Hexadecanol dehydrogenase (HDH), a soluble and membrane-bound, NAD-linked ADH, was induced 5- to 11-fold by growth on hexadecane or hexadecanol. HDH exhibited apparent Kms for hexadecanol of 1.6 and 2.8 microM in crude extracts derived from hexadecane- and hexadecanol-grown cells, respectively. HDH was distinct from ADH-A and ADH-B, since HDH and ADH-A were not coinduced; Eth1 had wild-type levels of HDH; and HDH requires NAD, while ADH-B requires NADP. NAD- and NADP-independent HDH activity was not detected in the soluble or membrane fraction of extracts derived from hexadecane- or hexadecanol-grown cells. NAD-linked HDH appears to possess a functional role in hexadecane and hexadecanol dissimilation.

Acinetobacter↗