Biomedical subjects

G Oster

Publications and source records attributed to G Oster.

At least 73 records · Page 4Linked to original sources

PubMed1995

Coordinated hydrolysis explains the mechanical behavior of kinesin.

The two-headed motor protein kinesin hydrolyzes nucleotide to move unidirectionally along its microtubule track at speeds up to 1000 nm/s (Saxton et al., 1988) and develops forces in excess of 5 pN (Hunt et al., 1994; Svoboda et al., 1994a). Individual kinesin molecules have been studied recently in vitro, and their behavior has been characterized in terms of force-velocity curves and variance measurements (Svoboda and Block, 1994a; Svoboda et al., 1994b). We present a model for force generation in kinesin in which the ATP hydrolysis reactions are coordinated with the relative positions of the two heads. The model explains the experimental data and permits us to study the relative roles of Brownian motion and elastic deformation in the motor mechanism of kinesin.

Animals↗

PubMed1994

The effects of rG-CSF on health-related quality of life in children with congenital agranulocytosis.

A multicentre Phase II clinical trial was recently undertaken to document the value of treatment with recombinant human granulocyte colony-stimulating factor (rG-CSF) in children with congenital agranulocytosis. To assess the impact of such therapy on health-related quality of life (HRQOL), we developed a questionnaire that was administered to the parents of study patients, twice prior to the initiation of treatment, and then monthly thereafter for six months. The questionnaire focused on several aspects of HRQOL that we thought were important in this patient population, including functional status, general health perceptions, activity limitation, disease symptoms, and discomfort associated with therapy. In this paper, we describe the questionnaire that we developed and the process by which it was translated into several languages. We also report on the impact of rG-CSF therapy on HRQOL. A total of 130 questionnaires were administered to the parents of 19 study patients between the ages of four and one-half months and 18 years in 11 study centres in four countries. Although our sample size is small, our findings suggest that treatment with rG-CSF may result in significant improvements in general health perceptions, limitations of daily activities, and symptoms of the disease.

Activities of Daily Living↗

PubMed1994

Childhood vaccination against chickenpox: an analysis of benefits and costs.

OBJECTIVE: To estimate the economic costs and benefits of routine childhood vaccination against varicella infection. DESIGN: Decision-analytic model of the incidence and costs of chickenpox in children assumed to receive varicella vaccine at age 15 months in conjunction with the measles-mumps-rubella vaccine, or not to be vaccinated against varicella. PATIENTS: Hypothetical cohort of 100,000 children. MAIN OUTCOME MEASURES: Costs of vaccination, cumulative incidence of chickenpox to age 25 years, and related disease costs, including medical treatment and work loss. RESULTS: Vaccination of 100,000 children against varicella at age 15 months would cost $4,812,000. The expected number of cases of chickenpox to age 25 years would be reduced from 95,400 to 4800; costs of medical treatment and work loss would correspondingly decline by $1,678,000 and $9,781,000, respectively. On balance, vaccination is estimated to yield net economic benefits of $6,647,000, or $66.47 per vaccinee. CONCLUSION: Vaccination against varicella infection is cost-effective and should be part of the routine immunization schedule for U.S. children.

Adolescent↗

PubMed1994

Cost-effectiveness of ticlopidine in preventing stroke in high-risk patients.

BACKGROUND: Ticlopidine, an antiplatelet agent, when compared with aspirin has been found to reduce the risk of stroke in high-risk patients, ie, those with recent transient ischemic attack, reversible ischemic neurological deficit, amaurosis fugax, or minor stroke. Its cost-effectiveness in such use, however, is unknown. METHODS: We developed a model of primary stroke prevention in which a hypothetical cohort of 100 high-risk men and women 65 years of age was assumed to receive either ticlopidine (500 mg daily) or aspirin (1300 mg daily). Using published data, we estimated lifetime incidence of stroke, life expectancy (unadjusted and adjusted for changes in quality of life), and lifetime medical care costs associated with each therapy. RESULTS: Patients who receive ticlopidine would experience two fewer initial strokes per hundred than those treated with aspirin. Life expectancy would be extended by approximately one-half month, and lifetime medical care costs (discounted at 5%) would increase by about $2300. The cost-effectiveness of ticlopidine, compared with aspirin, is estimated to range from $31,200 to $55,500 per quality-adjusted life-year gained as the utility of life after nonfatal stroke is assumed to vary from 0.75 to 0.95. CONCLUSIONS: Ticlopidine therapy to prevent stroke in high-risk patients is cost-effective by current standards of medical practice.

Aged↗

PubMed1994

Prevention of deep-vein thrombosis following total hip replacement surgery with enoxaparin versus unfractionated heparin: a pharmacoeconomic evaluation.

OBJECTIVE: To compare the use of healthcare services in patients receiving enoxaparin, a low molecular weight heparin versus those receiving unfractionated heparin as prophylaxis against deep-vein thrombosis (DVT) following total hip replacement surgery. DESIGN: Economic evaluation undertaken in conjunction with a randomized, open-label, parallel group, Phase III clinical trial. SETTING: 32 US acute-care hospitals. PATIENTS: 607 patients undergoing elective total hip replacement. INTERVENTIONS: Enoxaparin 30 mg q12h, enoxaparin 40 mg qd, or unfractionated heparin 5000 units q8h started within 24 hours following surgery and continued for 7 days. MAIN OUTCOME MEASURES: (1) Use of selected tests and treatments for DVT; (2) use of selected tests and treatments related to postoperative bleeding; (3) length of stay in hospital; and (4) readmissions to hospital within 14 days. RESULTS: Although the use of selected tests and treatments related to DVT or postoperative bleeding did not differ significantly between the three treatment groups, mean length of stay in the hospital (following the start of study therapy) was shorter among patients receiving enoxaparin 30 mg (9.5 days; p = 0.01) or 40 mg (9.9 days; p < 0.05) than those receiving unfractionated heparin (11.3 days). There was also a trend toward fewer hospital readmissions in both of the enoxaparin groups. CONCLUSIONS: Compared with unfractionated heparin, use of enoxaparin following total hip replacement may decrease the risk of DVT and length of hospital stay.

Adult↗

PubMed1994

Overview of the lenograstim pharmacoeconomics programme.

Lenograstim is a recombinant colony-stimulating factor that has been shown to be a useful adjunctive agent in cancer chemotherapy. Clinical trials have demonstrated the efficacy of lenograstim in correcting chemotherapy-induced neutropenia and associated complications in inflammatory breast cancer and non-Hodgkin's lymphoma, and in facilitating dose intensification of chemotherapy in small cell lung cancer. To meet increasing demands for economic data on new drug entities, a lenograstim pharmacoeconomics programme was established. This programme involved prospective economic evaluations of lenograstim that were undertaken as part of phase III randomised clinical trials by a combined German/Italian health-economics team (inflammatory breast cancer), a French team (non-Hodgkin's lymphoma), and a team from the UK (small cell lung cancer).

Adjuvants, Immunologic↗

PubMed1994

Methodological issues in economic assessments of new therapies. The case of colony-stimulating factors.

Pharmacoeconomic evaluations estimate the value of medical interventions by comparing their clinical consequences and costs. Economic analyses, based on resource use data collected during 3 clinical trials of lenograstim, were performed as part of a lenograstim economic evaluation programme. Undertaking economic evaluations alongside clinical trials presents a number of methodological challenges, since the trials may be performed in atypical settings, have inappropriate follow-up, or use end-points that are not useful for economic evaluation. This paper reports on how these challenges were met in the lenograstim economic evaluation programme. In particular, it was decided that the evaluations would be based on an intent-to-treat perspective, with the same period of follow-up (for costs) for both lenograstim and vehicle groups.

Adjuvants, Immunologic↗

PubMed1994

Pharmacoeconomic evaluation of lenograstim. Conclusions and future directions.

To evaluate the safety and efficacy of lenograstim, a new recombinant human granulocyte colony-stimulating factor (rHuG-CSF), as an adjunct to cancer chemotherapy, 3 phase III randomised clinical trials were recently conducted in Europe in patients with inflammatory breast cancer, non-Hodgkin's lymphoma, and small cell lung cancer. To explore the economic implications of lenograstim therapy, a multinational pharmacoeconomics programme was undertaken using data collected during these clinical trials. This programme consisted of concurrent prospective economic evaluations undertaken by study teams in France (non-Hodgkin's lymphoma), Germany and Italy (a combined evaluation in inflammatory breast cancer) and the UK (small cell lung cancer). In these studies, attention was focused on the direct costs of medical care-principally the costs of cancer chemotherapy as well as its associated morbidity. In 2 of the pharmacoeconomic evaluations (i.e. the French, German/Italian), lenograstim was found to generate cost savings as a result of reductions in morbidity associated with chemotherapy. However, the cost of lenograstim therapy would be likely to exceed these savings, leading to an overall increase in the costs of cancer treatment. Whether the use of lenograstim is cost-effective will therefore largely depend on its impact on patient survival and quality of life, and current practical use. These issues are the focus of additional clinical studies currently underway. In addition, new research is focusing on the clinical benefits of lenograstim in other areas of oncology and haematology. Further pharmacoeconomic studies in these areas are also warranted.

Adjuvants, Immunologic↗

PubMed1994

A phase II study of recombinant human granulocyte-colony stimulating factor (rHuG-CSF, lenograstim) in the treatment of agranulocytosis in children.

The present study evaluated the clinical efficacity and tolerability of the subcutaneous (SC) administration of lenograstim, a glycosylated form of rHuG-CSF identical to human G-CSF, in the treatment of congenital agranulocytosis. Assessment criteria included neutrophil response and response stability, incidence and severity of infection and gingivostomatitis and quality of life. Lenograstim, at induction dosages of 5 (n = 9), 10 (n = 2) or 20 (n = 1) microgram/kg/day SC, produced neutrophil recovery in all of 12 children with congenital agranulocytosis. There was a median delay of 7 days to recovery after establishment of the effective induction dose. Whereas this dosage maintained a stable neutrophil response in 7 patients, the remaining 5 required dosage increases and dose reduction during maintenance therapy was not possible in these 5 cases. Among 4 patients stabilised at a dosage of 5 micrograms/kg/day, in 2 cases a lower minimum effective dose of 2 micrograms/kg/day was attained over the maintenance phase. Administration of twice the daily dose of lenograstim on alternate days was feasible in 3 of 8 patients. Lenograstim therapy reduced the incidence of infection and hospitalisation for infection relative to the prestudy period, while in 6 of 9 cases there was complete recovery from gingivostomatitis. Only one patient discontinued treatment on account of adverse events. Finally, perceived health and disease related symptoms showed a significant (p < 0.001) amelioration in the course of the study. Thus, lenogastrim produced sustained neurotrophil recovery in patients with congenital agranulocytosis, decreased the incidence and severity of infection and improved the quality of life.

Adolescent↗

PubMed1993

The costs of prostatectomy for benign prostatic hyperplasia.

Using claims data for a 5% random sample of Medicare beneficiaries, we estimated the costs of surgical treatment for benign prostatic hyperplasia (BPH), including those related to the initial prostatectomy, the treatment of postsurgical complications, and reoperation within one year. We identified 14,480 men who underwent prostatectomy for BPH during 1986-1987, including 13,730 transurethral and 750 open procedures. Mean total inpatient costs (including all hospital charges and professional service fees) for these procedures were estimated to be $6,501 and $10,223, respectively. Among patients who underwent transurethral and open prostatectomy, we identified 938 (6.8%) and 39 (5.2%) individuals who had at least one readmission for postsurgical complications or reoperation. Total expected costs of transurethral and open prostatectomy, inclusive of readmissions for complications and reoperations within one year, were estimated to be $6,823 and $10,477, respectively. Our study indicates the economic burden represented by surgical treatment of BPH.

Aged↗

PubMed1992

A model for evaluating the cost-effectiveness of cholesterol-lowering treatment.

We describe and illustrate the use of a generalizable model for evaluating the cost-effectiveness of alternative cholesterol-lowering treatments. We combine standard incidence-based techniques for measuring the cost of illness with logistic risk functions from the Framingham Heart Study to project, for persons with known coronary risk characteristics, the likelihood of developing coronary heart disease (CHD) over a lifetime as well as a number of related outcomes, including the expected loss of years of life due to CHD, the expected lifetime direct and indirect costs of CHD, and the changes in these outcomes that would result from cholesterol-lowering treatment.

Adult↗

PubMed1992

Outcomes of cefazolin versus ceftriaxone therapy in treating lower respiratory tract infections in adults.

OBJECTIVE: To determine whether choice of a first- versus third-generation cephalosporin as initial therapy for lower respiratory tract infections in hospitalized adults affects the course and duration of care, both of which may influence antimicrobial treatment cost. DESIGN: Retrospective analysis of discharge abstracts and hospital pharmacy records. SETTING: Forty-eight US acute-care hospitals. PATIENTS: One thousand ninety-two hospitalized adults (aged > 17 y) with principal diagnoses of lower respiratory tract infections (DRGs 79-80, 89-90). INTERVENTIONS: Cefazolin or ceftriaxone, given as sole antimicrobial therapy for at least one day. MAIN OUTCOME MEASURES: (1) The number of patients who received another parenteral antibiotic anytime prior to hospital discharge; (2) the number of days during which patients received any parenteral antibiotic while in the hospital; and (3) the number of days patients remained hospitalized following the start of antibiotic therapy. RESULTS: Patients treated with cefazolin (n = 763) were more likely to receive another parenteral antibiotic while in the hospital (30.3 vs. 20.7 percent; p < 0.001) and received more total days of therapy (7.2 vs. 6.7 d; p < 0.05) than those treated with ceftriaxone (n = 329). Although the time to hospital discharge did not differ in the full sample (9.2 d for both groups), it was greater among those receiving cefazolin (8.6 vs. 8.0 d; p < 0.05) when patients with lengths of stay exceeding 24 days were excluded from both groups. CONCLUSIONS: In addition to acquisition cost, differences in course and duration of care should be considered when determining the most cost-effective choice for antimicrobial therapy.

Adolescent↗

PubMed1992

Cost-effectiveness of drug therapy for hypercholesterolaemia: a review of the literature.

In this article we review published studies of the cost-effectiveness of drug therapy for hypercholesterolaemia to take stock of the principal findings that have been reported to date. We identified 9 studies that met all criteria for inclusion in our review, including 3 of bile-acid sequestrants (cholestyramine, colestipol), 2 of HMG-CoA reductase inhibitor (lovastatin), and 4 that considered both an HMG-CoA reductase inhibitor (simvastatin) and a bile-acid sequestrant (cholestyramine). While these studies were largely consistent in methodological approach, some differences were noted in the costs attributed to drug therapy. The cost-effectiveness of therapy with bile-acid sequestrants was found to range from $100 000 to $209 000 per year of life saved (1991 $US) for middle-aged men (42 to 55 years of age) with moderately high cholesterol levels (280 to 290 mg/dl) and otherwise average coronary risk characteristics. Corresponding cost-effectiveness ratios that have been reported for lovastatin range from $64 000 to $82 000, while those for simvastatin range from $45 000 to $65 000. Studies to date therefore suggest that therapy with HMG-CoA reductase inhibitors (i.e. lovastatin and simvastatin) is substantially more cost-effective than treatment with bile-acid sequestrants.

Age Factors↗

PubMed1992

Economic evaluation of oral ofloxacin versus standard parenteral therapy in the treatment of pneumonia.

The purpose of this study was to examine how inpatient use of oral ofloxacin, a fluoroquinolone antibiotic, affects utilisation of healthcare resources in the treatment of pneumonia. We collected data via chart review from a recent multicentre trial that randomised hospitalised adult patients with pneumonia to oral ofloxacin or standard parenteral therapy of the investigators' choice. We followed a total of 126 patients from randomisation until rule-out of pneumonia, death, loss to follow-up, or 30 days following cure, whichever occurred first. For each patient, we collected data on all inpatient antibiotic usage, duration of stay in hospital, and the utilisation of selected healthcare services following discharge from hospital. While length of stay did not differ between ofloxacin and standard-therapy patients (9.2 vs 11.1 days, respectively; p = 0.28), the cost of inhospital antibiotic therapy for those who received ofloxacin was one-fifth that of patients who were randomised to parenteral therapy ($US47 vs $US268). Costs of outpatient antibiotic therapy were slightly higher for the group receiving ofloxacin ($US26 vs $US3). No difference was noted in the rate of hospital readmission during follow-up. Our study therefore suggests that the use of oral ofloxacin among inpatients with pneumonia reduces the costs of antibiotic treatment compared to standard parenteral therapy.

Administration, Oral↗

PubMed1991

[Compensation claim forms in cases of occupational disability].

Confronted with the contents and questions of the Application Forms, presently in use for disability claims, it appears necessary to revise these forms in several details. Rulings by the Supreme Court to be considered and the existing great variety of definitions in the field of private and legal disability insurance--under the aspects of Social Law in general--call for a critical review, especially with regard to the details to be filled in by the police holder in support of his claim. The author is presenting 2 drafts of revised forms (Application Form for Disability Claims/Medical Report in the Case of Disability), which, in his opinion, should meet the requirements more effectively. On the other hand the author does not claim, that the presented drafts be the ultimate version.

Disability Evaluation↗

PubMed1991

Health-related quality of life among patients undergoing percutaneous transluminal coronary angioplasty.

A randomized clinical trial was recently conducted to investigate whether a new antiplatelet agent could prevent restenosis in patients who had undergone percutaneous transluminal coronary artery angioplasty (PTCA). Approximately 1,200 patients were enrolled at 13 separate clinical sites. To assess the impact of this intervention on health-related quality of life, a patient questionnaire for telephone administration was developed. This questionnaire focused attention on several specific dimensions likely to be important in this patient population: physical well-being, perceived health, emotional well-being, home management, work, recreation, and social and sexual functioning. This paper describes the instrument that was used in this trial and reports on its psychometric [corrected] properties based on completed interviews with approximately 500 patients at study entry and 1 month after PTCA.

Activities of Daily Living↗

PubMed1991

Notochord morphogenesis in Xenopus laevis: simulation of cell behavior underlying tissue convergence and extension.

Cell intercalation and cell shape changes drive notochord morphogenesis in the African frog, Xenopus laevis. Experimental observations show that cells elongate mediolaterally and intercalate between one another, causing the notochord to lengthen and narrow. Descriptive observations provide few clues as to the mechanisms that coordinate and drive these cell movements. It is possible that a few rules governing cell behavior could orchestrate the shaping of the entire tissue. We test this hypothesis by constructing a computer model of the tissue to investigate how rules governing cell motility and cell-cell interactions can account for the major features of notochord morphogenesis. These rules are drawn from the literature on in vitro cell studies and experimental observations of notochord cell behavior. The following types of motility rules are investigated: (1) refractory tissue boundaries that inhibit cell motility, (2) statistical persistence of motion, (3) contact inhibition of protrusion between cells, and (4) polarized and nonpolarized protrusive activity. We show that only the combination of refractory boundaries, contact inhibition and polarized protrusive activity reproduces normal notochord development. Guided by these rules, cells spontaneously align into a parallel array of elongating cells. Self alignment optimizes the geometric conditions for polarized protrusive activity by progressively minimizing contact inhibition between cells. Cell polarization, initiated at refractory tissue boundaries, spreads along successive cell rows into the tissue interior as cells restrict and constrain their neighbors' directional bias. The model demonstrates that several experimentally observed intrinsic cell behaviors, operating simultaneously, may underlie the generation of coordinated cell movements within the developing notochord.

Animals↗

PubMed1990

The risks and benefits of an Rx-to-OTC switch. The case of over-the-counter H2-blockers.

In recent years, many new over-the-counter (OTC) medications have resulted from the granting of OTC status by the U.S. Food and Drug Administration to drug entities that previously were available only by prescription (Rx). While the benefits to consumers of Rx-to-OTC switches may be substantial, they also involve some degree of risk, as usage typically expands and physician supervision diminishes. This study explores the potential utility of techniques of decision analysis in evaluating the balance of these benefits and risks. Histamine H2 receptor antagonists (H2-blockers), which are currently available only by prescription, are presented as a case study and were examined to determine how OTC availability of these agents would alter the patterns, effectiveness, and risks of self-treatment for acid-peptic disorders. Currently, about 5.7 million persons experience an episode of dyspepsia during any given quarter, of whom 3.5 million self-medicate with antacids. Study results indicate that OTC availability of H2-blockers would: 1) increase the proportion of persons with dyspepsia who self-medicate from 61.8% currently to 64.1%; 2) increase the proportion of persons who experience complete relief of their symptoms while self-medicating from 37.9% currently to 43.2%; 3) result in 14 additional cases of serious hematologic disorders and an additional 22,000 instances of minor side effects per quarter, but cause the overall rate of side effects among persons who self-medicate to decline; 4) cause an additional 300 persons per quarter with gastric cancer to self-medicate before seeking professional care, but cause no change in the median time between onset of symptoms and the decision to seek such care; and 5) decrease by 277,000 the number of persons per quarter who seek professional care for dyspepsia. On balance, results suggest that OTC H2-blockers may be a relatively safe and effective means of self-care for acid-peptic disorders, and may substantially reduce the number of patient encounters with the medical care system for minor gastrointestinal complaints. This study also illustrates the potential utility of the techniques of decision analysis to the formulation of drug regulatory policy.

Aged↗