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Biomedical subjects

B J O'Brien

Publications and source records attributed to B J O'Brien.

At least 73 records · Page 4Linked to original sources
PubMed1993

Impact of chemotherapy-associated nausea and vomiting on patients' functional status and on costs: survey of five Canadian centres.

OBJECTIVE: To estimate the effect of chemotherapy-associated nausea and emesis on patients' functional status and on costs to the health care system, the patients and society before antagonists to the serotonin (5-hydroxytryptamine) receptor subtype 5-HT3 became available. DESIGN: A 5-day prospective survey between February and May 1991 of patients receiving chemotherapy for cancer. Data were obtained from questionnaires completed by nurses and patients. SETTING: Five Canadian cancer treatment centres in Ontario (three) and Quebec (two). PATIENTS: Outpatients and inpatients 18 years of age and older who were scheduled to receive chemotherapy with a moderate to high potential for emesis as defined by standardized criteria. Patients were excluded if they were scheduled to receive an investigational antiemetic or had received chemotherapy within the previous 7 days. Of the 128 who were eligible, 112 agreed to participate; 107 returned the completed questionnaire, but the data for 15 were excluded because the patients received multiple-day chemotherapy. MAIN OUTCOME MEASURES: The degree of nausea (on a seven-point scale) and the frequency of emesis (vomiting or retching) were recorded for each day of the survey. Functional status was assessed before and after chemotherapy by means of the Functional Living Index-Emesis (FLIE). The direct health care costs and the indirect costs (e.g., of time off work) associated with nausea and emesis were estimated from the survey responses and secondary data sources. RESULTS: On the day of chemotherapy 38 of the 92 patients (41%) experienced emesis with or without nausea, and over the 5 days of the survey 72 patients (78%) reported at least one episode of nausea or emesis. The absolute risk of either problem decreased over time, but the risk of nausea relative to emesis increased over time. The FLIE scores indicated significant worsening of functional status after chemotherapy. On the day after treatment the main impact was from emesis, particularly with regard to leisure activities, household tasks and hardship to the family. Nausea had a significantly greater impact than emesis on overall functioning. The additional direct health care cost for managing emesis was estimated to be $63 and the indirect cost $121. CONCLUSIONS: Despite prophylaxis with antiemetic drugs, nausea and emesis were significant problems in this population receiving chemotherapy. The management of emesis consumed relatively small amounts of health care resources, but there were costs outside the hospital for patients and others.

Activities of Daily Living↗
PubMed1993

Relationship between functional status and health-related quality-of-life after myocardial infarction.

Despite increasing use in clinical and economic studies, no gold standard exists for the measurement of health-related quality of life (HRQL). One approach to assessing the validity of an HRQL instrument for a particular disease population is to examine the empirical relationship between HRQL patient scores and other accepted measures of health or functional status. In 185 patients (mean age 60 years, 79% male) at six months after myocardial infarction, we examined the relationship between patient responses to the Nottingham Health Profile (NHP), a generic HRQL instrument, and physician classification of patients by two widely used functional status indicators: the New York Heart Association (NYHA) classification and the Karnofsky Performance Status Scale. Analysis of NHP scores by NYHA strata confirms that lower HRQL is associated with poorer cardiac functional status (P < 0.0001) and this gradient is observed over all six NHP domains. Statistically significant (P < 0.001) associations were observed between patients' NYHA class and NHP domain scores for energy (Spearman r = 0.52), physical mobility (r = 0.45) and pain (r = 0.43). NHP scores for patients in NYHA Class I were similar to male population controls. A similarly consistent relationship was found between NHP and Karnofsky. We conclude that the NHP is able to discriminate between patients with differing levels of cardiac functioning as classified by NYHA and patient functioning as classified by Karnofsky. Demonstration of such discriminative properties is one important component in assessing the construct validity of HRQL measures.

Activities of Daily Living↗
PubMed1992

Cost effectiveness of the implantable cardioverter defibrillator: a preliminary analysis.

BACKGROUND: An implantable cardioverter defibrillator (ICD) may be effective in reducing the risk of sudden cardiac death. The high cost of ICD treatment, however, compared with alternatives raises the question of whether this new technology is an efficient use of scarce health care resources. OBJECTIVE: To estimate the incremental cost effectiveness of the implantable cardioverter defibrillator compared with drug treatment with amiodarone in the management of patients at high risk of sudden cardiac death. DESIGN: A cost effectiveness model was constructed from data already published and other secondary sources. Differences in patient survival were calculated from life tables for comparable ICD and amiodarone patient series. Costs were based on typical patient management protocols derived from current United Kingdom practice and interviews with physicians. MAIN OUTCOME MEASURES: Cost effectiveness of ICD treatment was computed over 20 years; all future costs and effects were discounted at 6% per year. RESULTS: Estimated life expectancy was 11.1 and 6.7 years with ICD and amiodarone respectively; the discounted 20 year difference lies in the range 1.7 to 3.7 years. Discounted 20 year treatment costs were 28,400 pounds for the ICD and 2300 pounds for amiodarone. Cost effectiveness of ICD treatment lies in the range of 15,400 pounds to 8200 pounds per life-year gained. CONCLUSIONS: Cost effectiveness of ICD treatment is similar to some existing cardiac programmes funded under the NHS but uncertainty exists due to limitations of the data. Costs of ICD treatment may fall in the future as the life of the device increases and less invasive implantation methods are needed. The effectivess of ICD compared with amiodarone is currently being studied by a randomised controlled trial.

Amiodarone↗
PubMed1992

Economic evaluation of ondansetron: preliminary analysis using clinical trial data prior to price setting.

This study combines secondary analysis of efficacy and side-effect data from a randomised controlled trial with estimates of resource use to evaluate the likely economic effects of the new antiemetic agent ondansetron. Costs, effects and cost-effectiveness of ondansetron in the prophylaxis of acute nausea and vomiting induced by chemotherapy are assessed relative to antiemetic therapy with metoclopramide. Superior efficacy of ondansetron is quantified both in terms of significant emesis avoided and emesis management costs avoided. A simple cost analysis, with the metoclopramide dosage priced at 10 pounds, indicates that therapy with ondansetron would give equivalent net treatment costs, at a price ratio (ondansetron/metoclopramide) of 2.3 to 1. If therapeutic success is defined as the avoidance of emesis and antiemetic side-effects, then the two therapies would be equally cost-effective at a drug price ratio of 5 to 1. We conclude that, (i) economic evaluation prior to price setting is feasible and informative; (ii) such models can indicate prospective data collection priorities.

Adult↗
PubMed1990

An economic evaluation of transdermal glyceryl trinitrate in the prevention of intravenous infusion failure.

A common cause of peripheral intravenous infusion failure is due to the patient developing phlebitis or extravasation. Recent clinical trials indicate that the use of transdermal glyceryl trinitrate (GTN patches) can reduce the incidence of infusion failure and hence the costs of re-infusion. In this study we conduct an economic evaluation of this new pharmaceutical application to determine whether the use of such patches results in hospital resource cost savings. Time-to-first infusion failure probabilities from a placebo-controlled trial are used to model the sequential failure problem as a Markov process. Using estimated staff and materials costs for first and subsequent infusions, we calculate the expected cost per infused patient to time t for treatment and control groups. Using this simple comparative cost method, results indicate that the net impact on hospital resources from patch usage is dependent upon the total required length of infusion time. Analysis of infusion time thresholds indicates that for patients requiring long-term (t greater than 50 hours) periods of infusion the use of patches is likely to generate resource savings. We conclude that to realize such resource savings clinical decisions to infuse with GTN patches should incorporate the prior probability that the total required length of infusion time exceeds 50 hours.

Administration, Cutaneous↗
PubMed1990

Willingness to accept risk in the treatment of rheumatic disease.

STUDY OBJECTIVE: The aim was to assess patients willingness to accept mortal risk in the drug treatment of chronic rheumatic disease. DESIGN: A non-random sample of consecutive patients were interviewed with a standardised survey instrument. SETTING: The study took place in the Royal National Hospital for Rheumatic Diseases, Bath, UK. PATIENTS: 100 consecutive in- and out-patients aged 65 or less were interviewed, 50 with rheumatoid arthritis and 50 with ankylosing spondylitis. Mean age was 48 years with mean disease duration of 14 years. The rheumatoid arthritis group was mainly female (84%), v 26% in the ankylosing spondylitis group. MEASUREMENTS AND MAIN RESULTS: Risk preferences were elicited using the method of standard gamble in the context of a hypothetical new drug. Patients indicated the maximum percentage probability of mortality they regarded as acceptable to achieve four different levels of benefit: total cure (20.7%), relief of pain (16.9%), relief of stiffness (13.1%), return to normal functioning (14.5%). Rheumatoid arthritis patients displayed a higher (p less than 0.05) willingness to accept risk than ankylosing spondylitis patients for all gambles except relief of stiffness. Analysis of variance indicated that willingness to accept risk decreases with the duration of disease and increases with reductions in self assessed health status. CONCLUSIONS: Evaluative methods such as standard gamble can elicit useful risk-benefit preference data from patients to assist those who manage clinical risks.

Adult↗
PubMed1990

An evaluation of right and left ventricular function after anatomical correction and intra-atrial repair operations for complete transposition of the great arteries.

Anatomical correction of complete transposition of the great arteries has the potential advantage over intra-atrial repair in that the left ventricle becomes the systemic pump. To investigate the importance of this, we evaluated right and left ventricular function in 21 patients after anatomical correction and in 21 patients after Mustard or Senning operations. First-pass and equilibrium-gated radionuclide angiography were used to measure right and left ventricular ejection fractions between 17 and 78 (mean, 47) months after anatomical correction and between 3 and 187 (mean, 67) months after intra-atrial repair. The mean age of the patient groups at the time of study was 52 and 84 months, respectively. The right ventricular ejection fraction ranged from 35% to 78% (mean, 58%) in patients after anatomical correction and from 27% to 68% (mean, 51%) after intra-atrial repair (p = 0.066). The left ventricular ejection fraction ranged from 39% to 74% (mean, 58%) after anatomical correction and from 35% to 74% (mean, 58%) after intra-atrial repair (p = 0.86). The mean right and left ventricular ejection fractions of both groups were significantly lower than those of normal children. Individuals with systemic ventricular dysfunction were identified after both types of operations; however, symptomatic dysfunction occurred only after intra-atrial repair (p = 0.24).

Cardiac Surgical Procedures↗
PubMed1990

Perception of prescription drug risks: a survey of patients with ankylosing spondylitis.

The ways in which patients perceive the risks of prescription drugs are likely to influence treatment preferences and compliance decisions. But very little is known about the perceived frequency of adverse drug reactions (ADR), their perceived causation and attitudes towards the safety regulation of prescription drugs. A sample of 1,034 patients with ankylosing spondylitis (AS) completed a postal questionnaire on the risks of medicines in general and nonsteroidal antiinflammatory drugs (NSAID) in particular. Serious ADR were perceived to be more frequent with NSAID than prescription drugs generally, and those who had experienced a previous ADR (47%) judged ADR to be more frequent (p less than 0.001). When asked to rate the likelihood that each of 7 reasons were causative of ADR, the most likely reason was perceived to be inadequate information to the patient about the drug, and secondly inadequate patient followup by the prescribing doctor. Responses to a hypothetical AS drug risk scenario indicated high safety expectations for antirheumatic agents; 61% thought that the government should take a drug off the market if there is any evidence of fatal ADR. The results of this survey suggest the need for greater patient information and education on the risks and benefits of medicines to modify perceptions and false expectations.

Adult↗
PubMed1989

Words or numbers? The evaluation of probability expressions in general practice.

A sample of 56 general practitioners were asked to rate, on a percentage scale, 23 words or phrases which denote frequency or likelihood. The hypothetical context of the exercise was that of communicating to patients the probability of a side-effect (headache) arising from an unspecified prescription medicine. Median phrase ratings ranged from 'never' at 0% to 'certain' at 95% with a 50% rating given to the phrase 'reasonable chance'. Despite relatively large variance in ratings between respondents, the median ratings of a number of phrases were similar, and some identical, to other studies from different medical professionals. Although the clinical context in which a given expression of probability is used may affect its meaning, the results are encouraging and suggest that phrases denoting likelihood might be systematically codified to enhance communication between doctor and patient. To move towards this objective more research is needed to evaluate how patients interpret expressions of probability, and the relative effectiveness of different modes of communicating likelihood.

Communication↗
PubMed1988

A game-theoretic approach to donor kidney sharing.

Graft survival in renal transplantation is a function, amongst other things, of the degree of histocompatibility lymphocyte-A (HLA) tissue matching achieved between donor and recipient. Yet a donor procured at centre A might match a transplant candidate at centre B and vice versa. This raises the question of whether, and under what circumstances, surgeons will offer and exchange donor kidneys and gain from such trade in terms of graft survival. We analyse the problem in a game-theoretic framework where the choice of strategy 'to offer or not?' is evaluated in the context of the uncertainty of reciprocation by the other player(s) in the game. The equilibrium solution to a number of variations of the game is predicted to be non-cooperation resulting in collectively sub-optimal graft survival rates. Some policy options for improving cooperation are considered including exchange incentives and coercive measures.

Cooperative Behavior↗
PubMed1988

The Nottingham Health Profile as a measure of quality of life following combined heart and lung transplantation.

This paper reports on the use of the Nottingham Health Profile as a measure of patient quality of life before and after combined heart and lung transplantation at Harefield Hospital. A total of 125 profiles from 48 patients were analysed. In both section 1 and section 2 of the profile, large and statistically significant (p less than 0.05) improvements in quality of life were associated with transplantation. The profile proved easy to use either as part of an interview during assessment for transplantation or as a postal follow-up postoperatively.

Adult↗
PubMed1987

Measuring the effectiveness of heart transplant programmes: quality of life data and their relationship to survival analysis.

This paper explores the problems of benefit measurement in the economic evaluation of heart transplant programmes. We present data from our evaluation of the U.K. heart transplant programmes on both survival and quality of life and we examine the relationship between the two. The quality of life measure used, the Nottingham Health Profile (NHP), is described and results presented. We attempt to aggregate this profile measure into a single index score and combine these data with life expectancy gains to produce estimates of Quality Adjusted Life Years (QALYs) gained for heart transplantation. In addition we examine the extent to which pre-transplant NHP scores can be used as predictors of post-transplant survival.

Adult↗
PubMed1985

Physicochemical characterization of the alpha-peptide of the sodium channel from rat brain.

The alpha-peptide of the rat brain sodium channel of apparent molecular weight 260K has been purified to homogeneity in order to determine its structural and chemical properties. By negative-stain electron microscopy, the molecule morphology of the solubilized channel protein appears as a stack of disks or rouleaux whose dimensions are 40 A X 200 A. Measurement of the secondary structure by circular dichroism shows that the alpha-peptide is a conformationally flexible polypeptide that contains mostly beta-sheet and random-coil in mixed detergent-phospholipid micelles and folds into a conformation that has approximately 65% alpha-helix after reconstitution into phosphatidylcholine vesicles. Preparative polyacrylamide gel electrophoresis was used to obtain a chemically homogeneous peptide to analyze the amino acid and carbohydrate composition. The amino acid composition shows a reasonably high content of acidic amino acids with no striking excess of hydrophobic amino acids, while carbohydrate analyses show that carbohydrate is 31% by weight of the protein with sialic acid representing over 50% of the total carbohydrates. The high alpha-helical content, the amino acid composition, and the large carbohydrate mass are similar to those of the eel electroplax sodium channel and appear to be general features of the sodium channels which have been analyzed structurally and chemically to date.

Animals↗
PubMed1985

Characterization of mammalian neurofilament triplet proteins. Subunit stoichiometry and morphology of native and reconstituted filaments.

The three major proteins of mammalian neurofilaments of molecular weights 179,000 (NF1), 129,000 (NF2), and 66,500 (NF3) have been purified to homogeneity by multiple anion-exchange and hydroxylapatite absorption chromatography in 8 M urea. Silver staining of polyacrylamide gels of the purified proteins show single bands. In order to gain further insight into the molecular organization of the neurofilament triplet proteins, the molar stoichiometries and morphologies of native and reconstituted filaments and those isolated from developing brain were studied. Denaturing polyacrylamide gel electrophoresis followed by quantitative dye-binding analysis shows that the molar ratio of the three components in neurofilaments isolated from bovine spinal cord myelinated nerve is 4:2:1 (NF3:NF2:NF1). Comparison of the molar ratios of each component in neurofilaments isolated from rat, bovine, and human brain shows a variation in the ratio of each of these polypeptides and raises questions about the physiological uniqueness of the molar composition of the neurofilament triplet. Reconstitution of the three bovine polypeptides into 10-nm filaments was accomplished under conditions in which the NF3 protein was limiting. Reassembly of 10-nm filaments with varying amounts of NF2 and NF1 indicate that the NF3 homopolymer has a limiting capacity to bind NF2 and NF1 and is saturated at a molar ratio of 2:2:1 (NF3:NF2:NF1). Isolation of the neurofilament complex at various stages of rat brain maturation indicates that NF3 and NF2 are integrated into the neurofilament complex as early as embryonic day 17, while NF1 copurifies with these proteins at postnatal day 16, eventually reaching a molar stoichiometry of 2:2:1 in the adult rat. The molecular stoichiometry of the neurofilament proteins, the differential integration of these proteins during brain development, and the variation of the molar composition between mammalian species suggest accessory roles for the NF2 and NF1 proteins in the neurofilament complex.

Amino Acids↗
PubMedDate not supplied

Confidence intervals for cost-effectiveness ratios: an application of Fieller's theorem.

Application of cost-effectiveness analysis (CEA) is growing rapidly in health care. Two general approaches to analysis are differentiated by the type of data available: (i) deterministic models based upon secondary analysis of retrospective data from one or more trials and other sources; and (ii) stochastic analyses in which the design of a randomized controlled trial is adapted to collect prospectively patient-specific data on costs and effectiveness. An important methodological difference between these two approaches is in how uncertainty is handled. Deterministic CEA models typically rely upon sensitivity analysis to determine the robustness of findings to alternative assumptions, whereas stochastic (CEA) analysis, as part of prospective studies, permits the use of conventional statistical methods on the cost and effectiveness data for both inference (hypothesis testing) and estimation. This paper presents a procedure for the statistical analysis of cost-effectiveness data, with specific application to those studies for which effectiveness is measured as a binary outcome. Specifically, Fieller's Theorem was used to calculate confidence intervals for ratios of the two random variables of between-treatment differences in observed costs and effectiveness, i.e. the incremental cost-effectiveness ratio.

Computer Simulation↗