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Biomedical subjects

A Gafni

Publications and source records attributed to A Gafni.

At least 145 records · Page 8Linked to original sources
PubMed1993

An economic evaluation of varicella vaccine for pediatric liver and kidney transplant recipients.

To evaluate the potential benefit of varicella vaccine for pediatric liver and kidney transplant patients, we determined the consequences of varicella susceptibility for a cohort of susceptible children (n = 44) who received transplants between July 1986 and June 1990 at the Hospital for Sick Children, Toronto. Costs of these consequences were compared with costs with a hypothetical varicella vaccination program in place. The median follow-up was 11.4 months (range, 2-50 months). Total costs in Canadian dollars to the health service without a program were for varicella-related hospital stay ($135,675) and varicella-zoster immune globulin ($4,322). Costs to parents were for lost time ($13,590) and transport ($414). Assuming a vaccine cost of $30/dose and a 90% vaccine efficacy, a pretransplantation vaccination program would have cost $16,205 and saved $3,132/child ($304 for families and $2,828 for the health service) during the study period. Varicella vaccination prior to solid organ transplantation should reduce morbidity in pediatric recipients and provide considerable savings for families and the health system.

Adolescent↗
PubMed1993

Discounting in the economic evaluation of health care interventions.

Do economic theories that underlie discounting have specific implications for program evaluation in health? In this study, both the contemporary practice and the theoretical foundations of discounting are reviewed. The social discount rate controversy is considered, and the two major concepts (i.e., opportunity cost and time preference) involved in the formulation of a social discount rate are outlined. Also described are the arguments for discounting proposed by thinkers in non-economic disciplines. Finally, the implications of choosing a discount rate for evaluation of individual health care programs are considered. It is argued that the conventional practice of discounting all health care programs at a rate of 5% may not consistently reflect societal or individual preference. Specific recommendations arising from this paper are: 1) given the considerable disagreement at the theoretical level as to the appropriate social discount rate, analysts should be specific about what theoretical approach underlies their choice of rate, especially when the analytic result is sensitive to the discount rate; 2) the discount rate chosen should be appropriate for the perspective of the analysis (social vs. individual vs. institutional, etc.); 3) when appropriate, measures should be taken to avoid double discounting, because some health related outcome measures already incorporate individuals' time preference; and 4) it is suggested that the political process may serve as the appropriate means of reflecting social values in the choice of a discount rate. In addition, the authors argue that a consensus conference approach, with political participation, offers a flexible, pragmatic, and explicit way of synthesizing the empirical, normative, and ethical considerations that underlie choice of a discount rate.

Cost of Illness↗
PubMed1992

Time-resolved circularly polarized protein phosphorescence.

The existence of circular polarization in room-temperature protein phosphorescence is demonstrated, and time-resolved circularly polarized phosphorescence (TR-CPP) is used to characterize unique tryptophan environments in multitryptophan proteins. Circularly polarized luminescence studies provide information regarding the excited state chirality of a lumiphore which can be used to extract sensitive structural information. It is shown by time resolving the circular polarization that it is possible to correlate the excited state chirality with unique decay components in a multiexponential phosphorescence decay profile. The present study presents a concurrent analysis of room-temperature time-resolved phosphorescence and TR-CPP of bacterial glucose-6-phosphate dehydrogenase as well as those of horse liver alcohol dehydrogenase. Only one of the two tryptophan residues per subunit of dimeric alcohol dehydrogenase is believed to phosphorescence, while the dimeric glucose-6-phosphate dehydrogenase has eight tryptophan residues per subunit and shows a corresponding complexity in its phosphorescence decay profile. The anisotropy factor [g(em) = delta I/(Itotal/2); delta I = Ileft circular-Iright circular] for alcohol dehydrogenase is time independent, suggesting a unique excited state chirality. The phosphorescence decay of glucose-6-phosphate dehydrogenase can be well fitted with four exponential terms of 4, 23, 76, and 142 msec, and the TR-CPP of this enzyme shows a strong time dependence that can be resolved into four individual time-independent anisotropy factors of -4.0, -2.1, +6.5, and +6.9 (x10(-3)), each respectively associated with one of the four lifetime components. These results demonstrate how the use of TR-CPP can facilitate the study of proteins with multiple lumiphores.

Alcohol Dehydrogenase↗
PubMed1992

Denaturation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides by guanidine hydrochloride; identification of inactive, partially unfolded, dimeric intermediates.

The denaturation of the dimeric enzyme glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides by guanidine hydrochloride has been studied using enzymatic activity, intrinsic fluorescence, circular dichroism, and light scattering measurements. Equilibrium experiments at 25 degrees C revealed that between 0.9 and 1.2 M denaturant the enzyme underwent a conformational change, exposing tryptophan residues to solvent, with some loss of secondary structure and a complete loss of enzymatic activity but without dimer dissociation to subunits. This inactive, partially unfolded, dimeric intermediate was susceptible to slow aggregation, perhaps due to exposure of 'sticky' hydrophobic stretches of the polypeptide chain. A second equilibrium transition, reflecting extensive unfolding and dimer dissociation, occurred only at denaturant concentrations above 1.4 M. Kinetics experiments demonstrated that in the denaturant concentration range of 1.7-1.9 M the fluorescence change occurred in two distinct steps. The first step involved a large, very rapid drop in fluorescence whose rate was strongly dependent on the denaturant concentration. This was followed by a small, relatively slow rise in the emission intensity, the rate of which was independent of denaturant concentration. Enzymatic activity was lost with a denaturant-concentration-dependent rate, which was approx. 3-times slower than the rate of the first step in fluorescence change. A denaturation mechanism incorporating several unfolding intermediates and which accounts for all the above results is presented and discussed. While the fully unfolded enzyme regained up to 55% of its original activity upon dilution of denaturant to a concentration that would be expected to support native enzyme, denaturation intermediates were able to reactivate only minimally and in fact were found to aggregate and precipitate out of solution.

Chemical Precipitation↗
PubMed1992

A bedside decision instrument to elicit a patient's preference concerning adjuvant chemotherapy for breast cancer.

The objective of this study was to develop an instrument to help clinicians inform patients with breast cancer of risks and benefits of adjuvant chemotherapy as derived from clinical trials and to help the informed patient decide whether she prefers treatment or no treatment. The instrument consists of a visual aid (called the decision board) and written material. It provides detailed information on a patient's choices (chemotherapy or no chemotherapy), outcomes (recurrence or not), probabilities of outcomes and their meaning, and quality of life associated with treatment choice and outcome. The validity and reliability of the instrument were evaluated in 30 healthy female volunteers. It was first administered using standard estimates of recurrence for node-negative breast cancer (15% risk of recurrence without treatment, which is reduced to 10% with chemotherapy). A preference for treatment (or no treatment) was then elicited. The validity was evaluated by changing the information provided on risks and benefits and determining whether the preference changed in a predictable manner. To test for reliability, the instrument was administered 2 weeks later. Seventeen women chose chemotherapy and 13 chose no chemotherapy. In the former group, 14 women (82%) switched preference when the magnitude of benefit was reduced, and 16 (94%) switched when the toxicity of treatment was increased. For those women who chose not to receive chemotherapy, 12 (92%) switched when the benefit was increased and 100% switched when toxicity was eliminated. The reliability was excellent (kappa = 0.86). The instrument has been used to elicit treatment preferences in 37 newly presenting patients with high-risk, node-negative breast cancer and has been found to be acceptable and helpful to the patient.

Adult↗
PubMed1992

Cost effectiveness/utility analyses. Do current decision rules lead us to where we want to be?

Despite the growing literature on economic evaluation of health care programmes, little attention has been paid to the theoretical foundations of cost-effectiveness and cost utility analyses and the validity of the decision rules adopted as methods of achieving the stated goals. We show that although applications of the techniques can be used to pursue some managerial objectives in the context of highly constrained environments, such applications are inconsistent with both welfare economic objectives and the interpretations of the findings of these applications. Alternative strategies are identified as potential and practical methods for pursuing welfare economic objectives.

Canada↗
PubMed1992

Acute low back pain and economics of therapy: the iterative loop approach.

We use the measurement iterative loop as a conceptual framework to examine the economics of common therapies for acute non-specific low back pain. The measurement iterative loop systematically assesses the interlocking facets of an illness from the community health perspective, including quantifying burden of illness, etiology, assessment of therapeutic effectiveness, and economic evaluation of therapies. The iterative loop reveals that: (1) burden of illness, although known to be substantial, is so far inaccurately measured, (2) little is known about such factors as provider and patient compliance; and (3) the economics of therapy can guide us in this time of clinical uncertainty when no therapy appears clearly superior. For therapies with at least some support from randomized controlled trials, bedrest appears to be economically superior. Besides burden of illness, compliance, and current therapies, future research should address such "therapeutic" options as early return to work and patient self-management.

Acute Disease↗
PubMed1992

A profile of users of specialty pain clinic services: predictors of use and cost estimates.

During the past decade, the multidisciplinary pain clinic has become a popular alternative to the traditional treatment of persistent pain. There is, however, little information describing this population of health care users nor the impact this new demand has on utilization of health care services. The objectives of this study were three fold: to develop a profile of the characteristics of patients referred to a specialty pain clinic including their psychosocial adjustment to their condition; to identify predictors of the use of the specialty services; and to estimate the cost of health service utilization. This historical cohort analytic survey of 571 patients referred to the clinic assessed them for exposure to selected referral variables through a chart review and sampled (n = 222) these patients' current adjustment and health service use through mailed questionnaire. There were four types of use of specialty clinic services. These included: non-users (n = 210); consultation only (n = 180); and the remaining 32% of the referrals were divided between "users-non complete" (n = 98) and "users-complete" (n = 83). "User" groups were similar in characteristics to each other at referral and follow-up on all the major variables with the exception of two factors: non-users lived further from the clinic than users and users were rated as psychologically more vulnerable than non-users. The best predictors for attending the clinic were the presence of referral information from the referring physician and the geographic location of the patient's referring physician. The prevalence of poor psychosocial adjustment was 55.7%, high by comparison with other specialty clinics. Seventy percent of the variance in psychosocial adjustment to chronic pain was explained by social and cognitive variables. In addition, users of specialty pain clinic services generated proportionately less costs in the use of other health services when they were compared to non-users. The importance of social support and meaning of illness variables in predicting psychosocial adjustment to chronic pain is corroborated in this study as is the relevance of the pain clinic cognitive behavioural approach for these problems. In addition, compared to other chronic pain sufferers with similar characteristics, it appears that the use of the pain clinic contains the use of other services and thus has an important economic impact.

Adaptation, Psychological↗
PubMed1992

Adenine nucleotide translocase greatly increases the partition of trinitrophenyl-ATP into reduced Triton X-100 micelles.

The presence of adenine nucleotide translocase (ANT) was found to greatly enhance the partitioning of the ATP analog 2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate (TNP-ATP) into reduced Triton X-100 micelles. The protein's effect was studied through the quenching of fluorescence of purified ANT, irreversibly inhibited by carboxyatractyloside (CAT), solubilized in reduced Triton X-100 micelles. The dependence of quenching of the protein's time-resolved tryptophan fluorescence on TNP-ATP concentration was measured and found to follow a Stern-Volmer mechanism. However, the calculated quenching constant was too large to be accounted for by the aqueous TNP-ATP concentration. Experiments were therefore conducted to determine the partitioning of the quencher between the three phases present: aqueous, protein-free micelle, and protein micelle; a system also described by the equation of Omann, G. M., and M. Glaser (1985. Biophys. J. 47:623-627.). By measuring the dependence of the apparent quenching rate constant on the protein concentration and protein/micelle ratios, this equation was used to calculate both the quencher partition coefficient into protein-free micelles (Pm) and into protein-micelles (Ppm), as well as the bimolecular quenching rate constant (kpm) in protein micelles. From the quenching experiments, kpm = 5.0 x 10(8)M-1s-1,Pm = 290 and pyrene quenching experiment to be 325, and by a rapid filtration experiment to be 450. Clearly, the presence of the integral membrane protein ANT-CAT in reduced Triton X-100 micelles greatly increases the partition of TNP-ATP into the micelle. ANT alters the properties and thus, the structure of the detergent micelle, which has direct implications for the use of detergent micelles as a model system for membrane proteins and may indicate that analogous effects occur in the mitochondrial membrane.

Adenosine Triphosphate↗
PubMed1992

Consideration of dipole orientation angles yields accurate rate equations for energy transfer in the rapid diffusion limit.

Dipole-dipole energy transfer between suitable donor and acceptor chromophores is an important luminescence quenching mechanism and has been shown to be useful for distance determination at the molecular level. In the rapid diffusion limit, where the excited-state lifetime of the donor is long enough to allow the donor and acceptor to diffuse many times their average separation before deexcitation, it is usually assumed that the relative dipolar orientation is completely averaged due to rotational Brownian motion. Under this simplifying assumption, analytical expressions have been derived earlier for the energy transfer rate between donor and acceptor characterized by different geometries. Most such expressions, however, are only approximate because complete angular averaging is permitted only in a geometry that possesses spherical symmetry surrounding each chromophore. In this paper analytical expressions that correctly account for incomplete angle averaging due to steric hindrance are presented for several geometries. Each of the equations reveals a dependence of the energy transfer rate on chromophore orientation. It is shown that correctly accounting for this effect can lead to improvements in estimates of the distance of closest approach from measured quenching rates based on energy transfer experiments.

Diffusion↗
PubMed1992

Zidovudine for chemoprophylaxis after occupational exposure to HIV-infected blood: an economic evaluation.

Three approaches to the management of health care workers (HCWs) following percutaneous exposure to blood of previously unknown serological status were compared using cost-effectiveness analysis. In strategy A, all HCWs are offered zidovudine as soon as possible after exposure. The decision is made within 72 hours to (1) continue therapy with the drug for 4 weeks if the patient's blood is positive for human immunodeficiency virus (HIV) on testing or (2) discontinue therapy and follow-up if the patient's blood is HIV-negative. Strategy B is similar to A except that zidovudine is not offered. In strategy C the patient's blood is not tested and zidovudine is not offered. The results indicate that for every 100 HCWs managed with strategies A, B, and C, the total costs in Canadian dollars (Can $1.00 = U.S. $0.85) are $47,910, $38,849, and $110,834, respectively. The incremental cost per case of AIDS prevented by A relative to B is $300,140, and that prevented by A relative to C is -$6,244,000 (i.e., A results in savings relative to C).

Cost-Benefit Analysis↗
PubMed1992

Preference based outcome measures for economic evaluation of drug interventions: quality adjusted life years (QALYs) versus healthy years equivalents (HYEs).

Decisions about medical treatment and health programmes involve both technical and value judgements. For the purpose of performing an economic appraisal of different health interventions (including drug interventions), a single global score is essential as the measure of outcome. This measure should enable us to compare different interventions that affect both duration and quality of life at different levels of effect. This article provides a short but critical overview of the most commonly used measure of outcome in such cases--the quality adjusted life years (QALY). We describe the measure and discuss its limitations. More specifically we discuss problems stemming from the fact that QALYs do not fully reflect individual preferences and the fact that different (not necessarily comparable) methods of measurement can be used to generate the weights. We also discuss the issue of the equity implications of the methods used to aggregate the QALY values of individuals to arrive at a community health outcome measure. Our conclusion is that the use of QALY does not coincide with achieving the stated goal of economic evaluations (i.e. efficient allocation of resources to enable maximisation of the health of the community for any given level of resources). An alternative measure of outcome--the healthy years equivalent (HYE), which does not suffer from many of the major limitations associated with the QALY measure--is described and discussed.

Cost-Benefit Analysis↗
PubMed1992

Effectiveness and efficiency of selective vs universal screening for chlamydial infection in sexually active young women.

BACKGROUND: Since chlamydial cervicitis is not associated with specific complaints, screening asymptomatic women is an important initiative to prevent pelvic inflammatory disease and its sequelae. Compared with universal screening, selective screening is less costly but less effective so the cost savings vs the consequences of missing infected women need to be weighed carefully. METHODS: In two family planning clinics, 1002 women were surveyed for chlamydial infection (prevalence, 7%) and its predictors to determine whether universal or selective screening is the most efficient strategy. Two rules for the selection of patients were determined by logistic regression modeling and their relative efficiencies were compared by incremental cost-effectiveness and sensitivity analysis. The validity of the screening rules was tested in 191 students attending a university health clinic. RESULTS: If those with cervical friability, suspicious discharge, urinary frequency, or intermenstrual bleeding had been tested, 55.3% of all women would have been screened and 83.3% of all cases would have been detected. If those reporting a new sex partner in the preceding year had also been tested, 75.4% would have been screened, identifying 93.3% of all cases. The predictive power and practicality of the selection rules were validated in the university health clinic sample. Sensitivity analyses showed selective screening using cervical enzyme immunoassay with blocking confirmation was efficient if the prevalence of chlamydial infection was 16% or less, 11% or less, or 5% or less depending on whether base analyses, overestimated costs, or worst performance scenarios, respectively, were used. CONCLUSIONS: Selective screening based on four or five predictors and confirmed cervical enzyme immunoassay is an effective and efficient strategy in low prevalence settings.

Adult↗
PubMed1991

A comparative study of succinate-supported respiration and ATP/ADP translocation in liver mitochondria from adult and old rats.

This study was undertaken to compare the rates of succinate-supported hepatic mitochondrial respiration between 12 months (adult) and 29 months (old) male Fischer 344 rats. Experiments were also performed to determine the activity of adenine nucleotide translocase and the effect of its inhibition on mitochondrial respiration. Succinate-supported state 3 mitochondrial respiration was found to decline 20% between 12 and 29 months of age in rat liver, along with a similar 25% decrease in the respiratory control ratio with age. Adenine nucleotide translocase activity is shown to decrease 39% from adult to old rat liver mitochondria. This decrease does not, however, account for the decline in state 3 respiration, since translocase activity is approximately 50% greater than state 3 respiration in both adult and old rats. Therefore, adenine nucleotide translocase is not rate-limiting for state 3 mitochondrial respiration. Neither the rate of succinate permeation into the mitochondrial nor the rate of electron transport is rate-limiting for state 3 respiration, indicated by the greatly increased oxygen consumption with addition of the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (m-CCCP). These processes, therefore, are not responsible for the observed decline in state 3 respiration. The implications and possible cause of the age-related decrease in the maximal rate of ATP-synthesis are discussed.

Adenosine Diphosphate↗
PubMed1991

Quenching of tryptophan phosphorescence in Escherichia coli alkaline phosphatase by long-range transfer mechanisms to external agents in the rapid-diffusion limit.

Quenching of the room-temperature phosphorescence of Escherichia coli alkaline phosphatase by several freely diffusing molecules was studied, each of whose absorption spectrum overlaps the long-lived emission of this protein and which therefore can quench the excited triplet state by diffusion-enhanced Förster energy transfer. The presence of additional nonresonance transfer mechanisms was also detected, from a lack of linear dependence of quenching rate on spectral overlap. The quenching agents used were the dye molecules methyl red, methyl orange, and 2-[(4-hydroxyphenyl)azo]benzoic acid, as well as the embedded heme groups of myoglobin, metmyoglobin, and the reduced and oxidized forms of cytochrome c. Quenching was found to be greatly diminished upon reduction of each acceptor, indicating that electron transfer occurs efficiently from the excited tryptophan to the oxidized form of the acceptors. The elimination of this electron transfer in the reduced form affords the opportunity to separately measure the Förster transfer rates for the heme proteins. When the transfer rate constant thus measured for myoglobin is applied to a model where both donor and acceptor proteins are taken to be spherical with both tryptophan and the heme group placed off center (a model whose quenching rate equation is newly presented here), the depth of the phosphorescent tryptophan beneath the surface of alkaline phosphatase is found to be 16 A. This value is close to the depth of tryptophan 109 (which is known to be the phosphorescent residue in alkaline phosphatase), showing that with properly chosen probes this technique is indeed valuable for distance determinations in protein structure studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1991

Endurance-training induced changes in skeletal muscle phosphoglycerate kinase of old Wistar rats.

Sufficiently intense, long-term, endurance training has been shown in several studies to induce a variety of adaptations in skeletal muscle, including a substantial restoration of the activities of several muscle enzymes which are known to be modified during biological aging. This activity-restoration may reflect either an increase in the amounts of enzyme proteins or an enhancement of the specific activities of these molecules. The present study examined the effect of long-term endurance training on the status of phosphoglycerate kinase in skeletal muscle of old rats, as compared with the enzyme isolated either from non-trained old or young animals. The kinetics of heat inactivation, which differ markedly between young and old forms of phosphoglycerate kinase, were used as a sensitive probe for the status of the enzyme. The results reveal a remarkable similarity between the heat inactivation patterns of phosphoglycerate kinase from the muscle of old, exercise-trained rats and enzyme purified from young animals, while enzyme samples isolated from sedentary old animals are significantly more heat-stable. Adaptation to endurance-training is thus evident at the molecular level, and maintains phosphoglycerate kinase in its young form. The aging of this enzyme has been previously shown to involve only conformational changes, which develop following a reversible partial oxidation of reactive cysteine residues. Whether the adaptation of the enzyme to endurance-training results from enhancement in its turnover rate (i.e., dwell time in the cell becoming too short for modifications to develop) or is due to increased protection against oxidation (being the first step in the enzyme's aging) remains to be studied.

Aging↗