Search PubMed⌕ Search

Biomedical subjects

A Gafni

Publications and source records attributed to A Gafni.

At least 127 records · Page 7Linked to original sources
PubMed1994

Cost-effectiveness ratios: in a league of their own.

There is an increasing tendency for papers appearing in the medical literature to propose or use league tables of cost-effectiveness ratios as a means of comparing health-care interventions. In this paper we identify what the information in cost-effectiveness league tables tells us and how this is inadequate and inappropriate for addressing questions about improving efficiency in the use of resources at either the broad system level or at the individual care-group level. We present an alternative approach which provides decision makers with a practical way of deciding whether the adoption of a particular programme represents an unambiguous improvement in economic efficiency.

Canada↗
PubMed1994

Time-resolved room temperature protein phosphorescence: nonexponential decay from single emitting tryptophans.

The single room temperature phosphorescent (RTP) residue of horse liver alcohol dehydrogenase (LADH). Trp-314, and of alkaline phosphatase (AP), Trp-109, show nonexponential phosphorescence decays when the data are collected to a high degree of precision. Using the maximum entropy method (MEM) for the analysis of these decays, it is shown that AP phosphorescence decay is dominated by a single Gaussian distribution, whereas for LADH the data reveal two amplitude packets. The lifetime-normalized width of the MEM distribution for both proteins is larger than that obtained for model monoexponential chromophores (e.g., terbium in water and pyrene in cyclohexane). Experiments show that the nonexponential decay is fundamental; i.e., an intrinsic property of the pure protein. Because phosphorescence reports on the state of the emitting chromophore, such nonexponential behavior could be caused by the presence of excited state reactions. However, it is also well known that the phosphorescence lifetime of a tryptophan residue is strongly dependent on the local flexibility around the indole moiety. Hence, the nonexponential phosphorescence decay may also be caused by the presence of at least two states of different local rigidity (in the vicinity of the phosphorescing tryptophan) corresponding to different ground state conformers. The observation that in the chemically homogeneous LADH sample the phosphorescence decay kinetics depends on the excitation wavelength further supports this latter interpretation. This dependence is caused by the wavelength-selective excitation of Trp-314 in a subensemble of LADH molecules with differing hydrophobic and rigid environments. With this interpretation, the data show that interconversion of these states occurs on a time scale long compared with the phosphorescence decay (0.1-1.0 s). Further experiments reveal that with increasing temperature the distributed phosphorescence decay rates for both AP and LADH broaden, thus indicating that either 1) the number of conformational states populated at higher temperature increases or 2) the temperature differentially affects individual conformer states. The nature of the observed heterogeneous triplet state kinetics and their relationship to aspects of protein dynamics are discussed.

Alcohol Dehydrogenase↗
PubMed1994

Chemotherapy waste reduction through shelf-life extension.

Minimization of total drug expenditures within the health care system, without affecting patient outcome has become a rational goal in today's economic, environment. The objective of this study was to observe the effect of extending the shelf-life for three chemotherapy medications, [doxorubicin, epirubicin and mitoxantrone] on wastage of these medications. Prior to and following the introduction of new, longer, shelf-lives for these three medications, prospective, non-randomized, unblinded four-month chemotherapy wastage audits for all chemotherapy medications were completed at 18 institutional sites within Ontario (six Ontario Cancer Treatment and Research Foundation clinics, ten Ontario hospitals and two preparation sites in a large cancer treatment centre). Data were provided by 18 sites in 1989 but from only 12 sites in 1990. Ten of the 12 sites extended their shelf-lives for each of doxorubicin, epirubicin and mitoxantrone, and on average, waste at these sites was reduced to less than 1% of the 1989 total for epirubicin, less than 15% for doxorubicin and 35% for mitoxantrone. Many sites eliminated waste entirely for these drugs. For sites which did not extend their shelf-lives, the waste remained unchanged. We conclude that appropriate extension of the shelf-life for chemotherapy medications can reduce waste, and is a relatively simple method of reducing expenditures without affecting health outcomes or adding additional complications to IV chemotherapy.

Analysis of Variance↗
PubMed1994

The standard gamble method: what is being measured and how it is interpreted.

OBJECTIVE: The Standard Gamble (SG) technique is recommended for measurement of individuals' preferences under uncertainty and to express the outcome of different therapeutic choices in utility values to be used in clinical decision analysis and health program evaluation. The article alerts users of this technique to problems stemming from inappropriate interpretation of results of measurements using the SG method. STUDY DESIGN: We review different situations where the SG method is used to measure individuals' or group preferences. PRINCIPAL FINDINGS: We demonstrate inappropriate interpretation of the time dimension at the individual level; issues stemming from the aggregation of individual utility values measured using different time horizons; the potential for double counting of the time preference effect when discounting future quality-adjusted life years (QALYs); and problems associated with using the SG technique to measure temporary health states. CONCLUSIONS: The inappropriate interpretations stem mainly either from ignoring the time dimension, which is inextricably bound to the health of the individual, or form adding assumptions, in addition to those required by von Neumann-Morgenstern (vNM) utility theory, that are not supported by empirical evidence. An alternative approach to QALYs, the healthy years equivalent (HYE), which incorporates the SG but avoids many of these problems, is described.

Decision Support Techniques↗
PubMed1994

An innovative model of system-linked community care: home-based traction as an alternative to institutional treatment.

Home-based traction is an alternative treatment to conventional hospital-based traction for children with orthopedic conditions such as congenital dislocated hip and Legg-Perthes disease. The application of a proposed theoretical model is used to describe the process of the home-based traction innovation. Creativity and innovation occasions a reconceptualization of stresses. The reconceptualization of stress, plus the operational support of coordinated in-home services, can help families and nurses in the community and in the hospital develop, implement, and evaluate this kind of innovative care. In applying the home-based traction professionals empower and legitimize parents as resourceful co-providers of care. The legitimizing of the alternative in-home service affords parents a more optimistic appraisal of their situation as manageable. Parents are free to develop a coordinated response to their overall circumstance, including the treatment of their one child's illness. The evaluation of this home-based traction example found the alternative to be acceptable, safe, effective in accomplishing treatment goals, and less expensive than conventional hospital-based traction.

Adult↗
PubMed1993

Thermal switching between enhanced and arrested reactivation of bacterial glucose-6-phosphate dehydrogenase assisted by GroEL in the absence of ATP.

Facilitation of protein folding by GroEL usually requires involvement of GroES and ATP. In their absence nascent proteins tend to be arrested on GroEL or, if released, fail to show enhancement of reactivation yield relative to that observed without the chaperonin. In contrast, the yield of reactivation of glucose-6-phosphate dehydrogenase (Glu-6-PDH) from Leuconostoc mesenteroides at 20 degrees C is increased 2-3-fold (to over 80%) by GroEL alone. ATP greatly enhances the rate of GroEL-assisted reactivation and slightly increases its yield to 90%. The efficiency of the GroEL-assisted reactivation of Glu-6-PDH is strongly dependent on temperature. A switch from enhanced to fully arrested reactivation occurs over a narrow temperature range from 25 to 30 degrees C in the presence of GroEL when ATP is absent. At physiological temperature therefore, reactivation is fully arrested by GroEL if ATP is absent and in its presence the protein is released in a form not committed to correct folding. The data shows that the committing step in Glu-6-PDH refolding occurs while the nascent protein is bound to GroEL, a step which is temperature-sensitive. The extreme temperature sensitivity of this step indicates a sharp structural transition in GroEL.

Adenosine Triphosphate↗
PubMed1993

Renaturation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides after denaturation in 4 M guanidine hydrochloride: kinetics of aggregation and reactivation.

In 4 M guanidine hydrochloride (GdnHCl), the dimeric enzyme glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides (G6PD) dissociated to subunits and was extensively unfolded. Rapid dilution of this high GdnHCl concentration allowed G6PD to partially renature, as measured by enzyme reactivation, to a level which depended on the conditions employed. The fraction of the enzyme which did not renature aggregated and precipitated out of solution, a process which could not be substantially prevented by stabilizing additives. Based on the enzyme concentration dependence of the reactivation yield and on a comparison of the aggregation and reactivation rates, it was determined that aggregation and reactivation compete kinetically for a partially-folded intermediate only very early in the process, during the rapid GdnHCl-dilution step. The kinetics of G6PD reactivation were sigmoidal, indicating that this process involves more than one rate-limiting reaction. The kinetics depended on enzyme concentration in a higher than first-order manner, indicating that association of subunits is one of the rate-limiting reactions. A renaturation mechanism compatible with these observations is described, which involves a bi-unimolecular (subunit association-folding) reaction sequence, with rate constants equal to 2.19 microM-1 min-1 and 0.140 min-1, respectively. This mechanism involves an inactive, dimeric, G6PD-folding intermediate, a species whose existence has recently been established by equilibrium denaturation experiments (Plomer, J.J. and Gafni, A. (1992) Biochim. Biophys. Acta 1122, 234-242).

Buffers↗
PubMed1993

Guidelines for the adoption of new technologies: a prescription for uncontrolled growth in expenditures and how to avoid the problem.

The guidelines proposed by Laupacis and associates do not stem from economic theory and are a prescription for uncontrolled growth in health care expenditure. In particular, cost-effectiveness ratios provide information relevant to allocation decisions only in very special circumstances that do not usually apply in practice. When two interventions are compared a positive cost-effectiveness ratio (the common case) can tell us, at best, what additional costs will be incurred to generate the additional outcomes. From an economic perspective the information required to determine the attractiveness of a new technology is different: the source of the additional resource requirements must be identified and the opportunity cost of their redeployment estimated. Because the cost-effectiveness ratio (cost/-QALY) is sensitive to the method chosen to calculate QALYs, guidelines that do not specify (or justify) the appropriate method for calculating outcomes are unlikely to produce comparable results (or common yardsticks). In a health care system such as Canada's in which there is always pressure to introduce more effective technology, even if it is more costly, there is a risk of using such noncomparable data to justify adoption of particular technologies. The method of technology evaluation proposed by us is consistent with the stated goal of maximizing the community's health-related well-being for a given level of resources allocated to health care and ensures that new technologies are adopted only if this adoption represents an improvement in resource allocation.

Canada↗
PubMed1993

Economics, health and health economics: HYEs (healthy-years equivalent) versus QALYs (quality-adjusted live-year)

This paper responds to Culyer and Wagstaff's (CW) and Buckingham's (B) arguments. We refute their claim about the equivalence of HYEs and QALYs; they fail to distinguish between choice under uncertainty and under certainty. CW assume that all individuals have a specific form of utility function, which yields their conclusion of equivalence. B's arguments confuse the measurement technique and the utility theory from which it stems; his argument about the normative superiority of the QALY construct is inconsistent with economic thinking. The HYE, by being compatible with the principles of economics, is superior to the QALY for economic evaluations of health care interventions.

Canada↗
PubMed1993

Searching for a common currency: critical appraisal of the scientific basis underlying European harmonization of the measurement of health related quality of life (EuroQol)

The EuroQol has recently been proposed as a measure of health-related quality of life based on individuals' valuations of health states. The derived values would be used in assessing cost-effectiveness and establishing priorities across a wide range of health-care activities. In this paper we identify some of the limitations of the EuroQol in its role as a particular method for deriving the more generic QALYs. More specifically we explore the implications of using the EuroQol as a measure of individuals' and communities' valuation of health outcomes. We show that the EuroQol suffers from several major limitations and thus cannot be relied upon to provide a valid measure to be used in economic appraisals or studies concerned with establishing priorities as proposed by its proponents. An alternative approach is identified and discussed.

Europe↗
PubMed1993

Detection of intermediate protein conformations by room temperature tryptophan phosphorescence spectroscopy during denaturation of Escherichia coli alkaline phosphatase.

The reversible denaturation of Escherichia coli alkaline phosphatase (AP) was followed by monitoring changes in enzymatic activity as well as by measurements of the time-resolved room temperature phosphorescence from Trp 109. It is well known that the denaturants, ethylene diamine tetraacetic acid (EDTA), acid and guanidine hydrochloride (GdnHCl) inactive AP by different mechanisms as reflected by differences in the time dependence of inactivation. However, further information about structural changes that result during inactivation is obtained by measurement of the phosphorescence intensity and radiative decay rate. Time-resolved tryptophan phosphorescence is exquisitely sensitive to changes in the local environment of the emitting residue, unlike the steady state phosphorescence intensity which is a composite of both the lifetime and concentration of the emitting protein species. The results show that while inactivation in EDTA proceeds by loss of the zinc ion as expected, denaturation in acid or GdnHCl produces a heterogeneous population of AP molecules, detected by a distribution analysis of the phosphorescence lifetime, which may reflect multiple pathways to the final unfolded state. Time-resolved phosphorescence also demonstrates the existence of an enzymatically active but structurally less rigid intermediate state during unfolding. As the rigidity decreases, the susceptibility to further denaturation decreases at lower pH but increases with GdnHCl concentration. The experiments provide new insight into the mechanism of denaturation of AP and demonstrate the sensitivity of time-resolved room temperature phosphorescence to the structural details of intermediate states produced during unfolding of proteins.

Alkaline Phosphatase↗
PubMed1993

Preoperative HIV testing: is it less expensive than universal precautions?

Universal precautions are officially recommended to prevent HIV transmission in health care settings but for elective surgery some advocate routine preoperative HIV testing. These strategies have not been tested in clinical trials but universal precautions are very expensive and not cost-effective. Thus, for elective surgery, routine testing might save resources by permitting selective use of additional barrier precautions. We performed an economic evaluation to compare both strategies, using a simple approach to determine if routine testing (RT) is less expensive than universal precautions (UP). Conservatively assuming equal effectiveness in preventing HIV transmission, we compared a minimized estimate for the average cost of RT with a maximized estimate for the average cost of UP per elective operation. The minimized estimate for RT (US$57) was greater than the maximized estimate for UP (US$36) per procedure. Results were stable or strengthened by sensitivity analysis. Routine HIV testing is not a valid economic alternative to UP for elective surgery. The simple methodology used in this study can be a preliminary strategy to review other strategies for preventing HIV transmission. This method is particularly useful when data are inadequate for a formal economic evaluation to determine the utility of collecting the detailed information necessary for a full comparison.

Blotting, Western↗
PubMed1993

Determination of the aggregation number of detergent micelles using steady-state fluorescence quenching.

The development of a simple, reliable method for determination of detergent micelle aggregation number that relies solely on measurement of steady-state fluorescence quenching is presented. The degree of steady-state fluorescence quenching of a micelle-solubilized fluorophore (pyrene) by a quencher that partitions greatly into the micelles (coumarin 153) is dependent on the micelle concentration, which can therefore be determined. The aggregation number is calculated as the micelle concentration/detergent monomer concentration (the total detergent concentration above the critical micelle concentration). For the determination to be accurate, the partition coefficient of the quencher into the micelle phase is determined and used to calculate the micellar concentration of quencher. Also, the quenching of pyrene by a coumarin 153 molecule within the same micelle must be complete, and this was confirmed by time-resolved fluorescence measurements. Aggregation numbers were determined for one cationic and several nonionic detergents and were found to be consistent with literature values. The approach presented is an improvement on a previous luminescence quenching technique (Turro, N.J., and A. Yekta. 1978. J. Am. Chem. Soc. 100:5951-5952) and can be used on cationic, anionic, and nonionic detergents with micelles ranging greatly in size and under varying conditions, such as detergent concentration, ionic strength, or temperature.

Biophysical Phenomena↗
PubMed1993

Economic evaluation of intravenous immune globulin therapy for Kawasaki syndrome.

OBJECTIVE: To determine the costs and clinical outcomes of three alternative treatments of the acute phase of Kawasaki syndrome: aspirin alone; low doses of intravenously administered immune globulin (IVIG-LD), 400 mg/kg per dose for 4 days; and high doses of intravenously administered immune globulin (IVIG-HD), 2.0 gm/kg for one dose. DESIGN: A model was developed that assumed the inclusion of 100 patients with acute Kawasaki syndrome in each treatment option. Costs were valued by using the Chedoke-McMaster Corporate Cost Model in 1992 Canadian dollars. Clinical outcome, based on the published literature, was measured by the prevalence of coronary artery dilation at 7 weeks from the diagnosis of Kawasaki syndrome. RESULTS: For every 100 patients with Kawasaki syndrome, the cost was reduced by $323,400 when aspirin therapy alone was changed to IVIG-HD therapy and 14 cases of coronary artery dilation were thereby prevented. When IVIG-HD therapy was compared with IVIG-LD therapy, the cost was reduced by $118,200 because two cases of coronary artery aneurysm were prevented. This latter result was sensitive to the duration of hospitalization, with IVIG-HD costing $8500 more for every 100 patients than IVIG-LD when it was assumed that both groups were hospitalized for 5 days, an unlikely occurrence. CONCLUSIONS: Treatment with IVIG-HD for Kawasaki syndrome is preferred because it results in both lower costs and lower rates of coronary artery dilation.

Aspirin↗