Biomedical subjects

B J O'Brien

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

At least 19 recordsLinked to original sources

PubMed2006

Six minute walk distance is greater when performed in a group than alone.

OBJECTIVE: To investigate whether the distance covered in the six minute walk test was affected by walking with a group of others in comparison with performing the test alone. METHODS: Eight healthy men (mean (SD) age 21.0 (0.9) years) and eight healthy women (mean (SD) age 20.8 (2.0) years) performed in random order two six minute walk tests either alone or in a group of four on two separate occasions one week apart. RESULTS: Distance covered increased significantly from a mean of 653 (61) m in the individual male tests to 735 (79) m in the male group tests (p<0.05), and 616 (75) m in the individual female tests to 701 (54) m in the female group tests (p<0.01). The men increased the distance walked in six minutes by 12.5% and the women by 13.7% when they performed the test as a group. CONCLUSION: Performing the six minute walk test in a group facilitates its execution.

Adult↗

PubMed2003

Effects of noise on the spike timing precision of retinal ganglion cells.

Information in a spike train is limited by variability in the spike timing. This variability is caused by noise from several sources including synapses and membrane channels; but how deleterious each noise source is and how they affect spike train coding is unknown. Combining physiology and a multicompartment model, we studied the effect of synaptic input noise and voltage-gated channel noise on spike train reliability for a mammalian ganglion cell. For tonic stimuli, the SD of the interspike intervals increased supralinearly with increasing interspike interval. When the cell was driven by current injection, voltage-gated channel noise and background synaptic noise caused fluctuations in the interspike interval of comparable amplitude. Spikes initiated on the dendrites could cause additional spike timing fluctuations. For transient stimuli, synaptic noise was dominant and spontaneous background activity strongly increased fluctuations in spike timing but decreased the latency of the first spike.

Adaptation, Physiological↗

PubMed2002

Analysis of uncertainty in health care cost-effectiveness studies: an introduction to statistical issues and methods.

Cost-effectiveness analysis is now an integral part of health technology assessment and addresses the question of whether a new treatment or other health care program offers good value for money. In this paper we introduce the basic framework for decision making with cost-effectiveness data and then review recent developments in statistical methods for analysis of uncertainty when cost-effectiveness estimates are based on observed data from a clinical trial. Although much research has focused on methods for calculating confidence intervals for cost-effectiveness ratios using bootstrapping or Fieller's method, these calculations can be problematic with a ratio-based statistic where numerator and/or denominator can be zero. We advocate plotting the joint density of cost and effect differences, together with cumulative density plots known as cost-effectiveness acceptability curves (CEACs) to summarize the overall value-for-money of interventions. We also outline the net-benefit formulation of the cost-effectiveness problem and show that it has particular advantages over the standard incremental cost-effectiveness ratio formulation.

Clinical Trials as Topic↗

PubMed2001

Cost-effectiveness analysis when the WTA is greater than the WTP.

The incremental cost effectiveness ratio has long been the standard parameter of interest in the assessment of the cost-effectiveness of a new treatment. However, due to concerns with interpretability and statistical inference, authors have suggested using the willingness-to-pay for a unit of health benefit to define the incremental net benefit as an alternative. The incremental net benefit has a more consistent interpretation and is amenable to routine statistical procedures. These procedures rely on the fact that the willingness-to-accept compensation for a loss of a unit of health benefit (at some cost saving) is the same as the willingness-to-pay for it. Theoretical and empirical evidence suggest, however, that in health care the willingness-to-accept is about twice as much as the willingness-to-pay. We use Bayesian methods to provide a statistical procedure for the cost-effectiveness comparison of two arms of a randomized clinical trial that allows the willingness-to-pay and the willingness-to-accept to have different values. An example is provided.

Bayes Theorem↗

PubMed2001

The retinal input to calbindin-D28k-defined subdivisions in macaque inferior pulvinar.

Several studies have provided evidence for direct retinal input to the pulvinar of macaques monkeys, but there is no general agreement regarding the extent of this projection. Moreover, it is not known how retinal input correlates with chemoarchitectonic subdivisions recently recognized within the large, classical divisions of the pulvinar. The potential implications of this correlation have become more evident after reports that chemoarchitectonic subdivisions of the inferior pulvinar (PI) have specific patterns of connections with cortical visual areas. We have therefore re-examined the retino-PI projection using intraocular injections of horseradish peroxides, and correlated it with pulvinar subdivisions revealed using an antibody for calbindin-D28k. Retinal projections were found preferentially within the medial subdivision of the PI, with some involvement of the posterior and central calbindin-D28k defined subdivisions.

Animals↗

PubMed2001

Impact of reference-based pricing of nitrates on the use and costs of anti-anginal drugs.

BACKGROUND: Reference-based pricing limits reimbursement for a group of drugs that are deemed therapeutically equivalent to the cost of the lowest-priced product within that group. We estimated the effect of reference-based pricing of nitrate drugs used for long-term prophylaxis on prescribing of and expenditures on nitrates and other anti-anginal drugs dispensed to senior citizens in British Columbia. METHODS: We assessed trends in the monthly volume of prescriptions of anti-anginal drugs and the associated drug ingredient cost paid by the province's publicly funded drug subsidy program, Pharmacare, and by the patients themselves for the period April 1994 to May 1999. Trends in monthly rates of nitrate expenditures per 100,000 senior citizens before the introduction of reference-based pricing were extrapolated to infer what expenditures would have been without the policy. RESULTS: During the 3 1/2 years after reference-based pricing was introduced, Pharmacare expenditures on nitrates prescribed to senior citizens declined by $14.9 million (95% confidence interval $10.7 to $19.1 million). Most of these savings were due to the lower prices that Pharmacare paid for sustained-release nitroglycerin tablets and the nitroglycerin patch, which were the 2 most frequently prescribed nitrates before the introduction of reference-based pricing; $1.2 million (8%) of the savings represented expenditures by senior citizens who purchased drugs that were only partially reimbursed. There were no compensatory increases in expenditures for other anti-anginal drugs. Use of sublingual nitroglycerin--a marker for deteriorating health in patients with angina--did not increase after the introduction of reference-based pricing. The nitroglycerin patch is now the most frequently prescribed nitrate, owing to the fact that Pharmacare resumed the provision of full subsidies for the drug after its manufacturers voluntarily reduced retail prices. INTERPRETATION: Evidence to date suggests that reference-based pricing of nitrates has achieved its primary goal of reducing drug expenditures. The effects of this policy on patient health, associated health care costs and administrative costs remain to be investigated.

Aged↗

PubMed2001

Effect of clinical risk stratification on cost-effectiveness of the implantable cardioverter-defibrillator: the Canadian implantable defibrillator study.

BACKGROUND: Three randomized clinical trials showed that implantable cardioverter-defibrillators (ICDs) reduce the risk of death in survivors of ventricular tachyarrhythmias, but the cost per year of life gained is high. A substudy of the Canadian Implantable Defibrillator Study (CIDS) showed that 3 clinical factors, age >/=70 years, left ventricular ejection fraction </=35%, and New York Heart Association class III, predicted the risk of death and benefit from the ICD. We estimated the extent to which selecting patients for ICD therapy based on these risk factors makes ICD therapy more economically attractive. METHODS AND RESULTS: Patients in CIDS were grouped according to whether they had >/=2 of 3 risk factors. Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in mean cost to the difference in life expectancy between the 2 groups. Over 6.3 years, the mean cost per patient in the ICD group was Canadian (C) $87 715 versus $38 600 in the amiodarone group (C$1 approximately US$0.67). Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone, for an incremental cost-effectiveness of ICD therapy of C$213 543 per life-year gained. The cost per life-year gained in patients with >/=2 factors was C$65 195, compared with C$916 659 with <2 risk factors. CONCLUSIONS: The cost-effectiveness of ICD therapy varies by patient risk factor status. The use of ICD therapy in patients who have >/=2 risk factors of age >/=70 years, left ventricular ejection fraction </=35%, and NYHA class III is C$65 195 to gain a year of life.

Aged↗

PubMed2001

Cost-effectiveness of the implantable cardioverter-defibrillator: results from the Canadian Implantable Defibrillator Study (CIDS).

BACKGROUND: In the Canadian Implantable Defibrillator Study (CIDS), we assessed the cost-effectiveness of the implantable cardioverter-defibrillator (ICD) in reducing the risk of death in survivors of previous ventricular tachycardia (VT) or fibrillation (VF). METHODS AND RESULTS: Healthcare resource use was collected prospectively on the first 430 patients enrolled in CIDS (n=212 ICD, n=218 amiodarone). Mean cost per patient, adjusted for censoring, was computed for each group based on initial therapy assignment. Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in cost (ICD minus amiodarone) to the difference in life expectancy (both discounted at 3% per year). All costs are in 1999 Canadian dollars (C$1 approximately US$0.65). Over 6.3 years, mean cost per patient in the ICD group was C$87 715 versus C$38 600 in the amiodarone group (difference C$49 115; 95% CI C$25 502 to C$69 508). Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone (difference 0.23, 95% CI -0.09 to 0.55), for incremental cost-effectiveness of ICD therapy of C$213 543 per life-year gained. ICD benefit was greater in patients with low left ventricular ejection fraction (<35%), and cost-effectiveness in this group was more attractive (C$108 484). Alternative extrapolations of survival benefit and costs to 12 years indicated cost-effectiveness in the range of C$100 000 to C$150 000 per life-year gained. CONCLUSIONS: At C$213 543, the value for the money offered by ICD therapy is not attractive by currently accepted standards. Further research is warranted to identify the indications and patient subgroups for whom ICDs are a cost-effective use of resources.

Cost-Benefit Analysis↗

PubMed2001

The death of cost-minimization analysis?

Four different types of evaluation methods, cost-benefit analysis (CBA), cost-utility analysis (CUA), cost-effectiveness analysis (CEA) and cost-minimization analysis (CMA), are usually distinguished. In this note, we pronounce the (near) death of CMA by showing the rare circumstances under which CMA is an appropriate method of analysis. We argue that it is inappropriate for separate and sequential hypothesis tests on differences in effects and costs to determine whether incremental cost-effectiveness (or cost-utility) should be estimated. We further argue that the analytic focus should be on the estimation of the joint density of cost and effect differences, the quantification of uncertainty surrounding the incremental cost-effectiveness ratio and the presentation of such data as cost-effectiveness acceptability curves. Two examples from recently published CEA are employed to illustrate the issues. The first shows a situation where analysts might be tempted (inappropriately) to employ CMA rather than CEA. The second illustrates one of the rare circumstances in which CMA may be justified as a legitimate form of analysis.

Anticoagulants↗

PubMed2001

Cost prediction models for the comparison of two groups.

For trial-based economic evaluation where patient-specific cost data are not routinely available, cost prediction models are commonly used to estimate total cost for each patient. Typically, multiple regression techniques are used on data from diagnosis-matched, non-trial patients (where patient-level cost data are available) to model cost as a function of covariates that are observed on the trial subjects (e.g. length of hospital stay, procedures, etc.). The estimated beta coefficients provide a means of estimating the total cost for each patient in the trial. However, the variability of the beta coefficients due the measurement and sampling error is seldom included in the overall variance expression for mean costs by treatment group. In this paper we provide a method for estimating this variance and provide an example application

Angina, Unstable↗

PubMed2001

Challenges for model-based economic evaluations of postmenopausal osteoporosis interventions.

Assessing the cost-effectiveness of long-term treatment for osteoporosis requires use of mathematical models to estimate health effects and costs for competing interventions. The primary motivations for model-based analyses include the lack of long-term clinical trial outcome data and the lack of data comparing all relevant treatments within randomized clinical trials. We report on specific modeling challenges that arose in the development of a model of the natural history of postmenopausal osteoporosis that is suitable for assessing the cost-effectiveness of osteoporosis interventions among various population subgroups in diverse countries. These include choice of modeling changes in bone mineral density (BMD) or in fracture rate, definition of health states, modeling mortality and costs of long-term care following fracture, incorporation of health utility, and model validation. This report should facilitate future postmenopausal osteoporosis model development and provide insight for decision-makers who must evaluate model-based economic analyses of postmenopausal osteoporosis interventions.

Aged↗

PubMed2001

Cost-Effectiveness of tolterodine for patients with urge incontinence who discontinue initial therapy with oxybutynin: a Canadian perspective.

BACKGROUND: Tolterodine is a novel muscarinic receptor antagonist for the treatment of overactive bladder. OBJECTIVE: The purpose of this study was to examine the cost-effectiveness of tolterodine for patients with urge incontinence (UI) who discontinue initial therapy with oxybutynin in a Canadian setting. METHODS: We compared 2 treatment strategies for the management of adult patients with UI: (1) generic oxybutynin with no further treatment for patients who discontinue and (2) generic oxybutynin with switch to tolterodine (2 mg BID) for patients who discontinue. We developed a 1-year Markov model (4-week cycle length) with transitions between disease states of normal, mild, moderate, and severe. Transition probabilities over 12 weeks were obtained from randomized trial data, and drug discontinuation rates were obtained from Quebec prescription claims data. Outcome measures were time in "normal" health state and quality-adjusted life-years (QALYs) using EuroQol-5D utility scores from a survey of Swedish patients with overactive bladder. Costs to the health care payer and patient out-of-pocket costs (in Canadian dollars) were included. RESULTS: For patients who discontinue oxybutynin, the use of tolterodine is associated with approximately 6 months per year in a normal health or mild disease state, compared with approximately 3 months for those who do not receive further drug therapy after discontinuation. Tolterodine use resulted in an annual additional cost per patient of Can $163. The incremental cost per QALY was Can $9,982 and appeared to be robust to alternative model parameter assumptions. CONCLUSION: Use of tolterodine in patients with UI who discontinue initial therapy with generic oxybutynin lies within currently accepted benchmarks for cost-effectiveness.

Benzhydryl Compounds↗

PubMed2001

Cost-effectiveness of beta-blocker therapy with metoprolol or with carvedilol for treatment of heart failure in Canada.

OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness of beta-blocker therapy with either metoprolol or carvedilol in addition to conventional therapy for patients with heart failure (HF) in Canada. DESIGN: A Markov simulation was used to estimate the costs and life expectancy for treating patients with conventional therapy alone and with the addition of metoprolol or carvedilol. Although carvedilol has been marketed in Canada since 1999, metoprolol succinate has yet to be marketed there, so the price is unknown. Therefore we input a Canadian price based on the price ratio of the 2 drugs in the United States. RESULTS: For subjects aged 60 years at HF onset, the expected years of life are 4.53 years for those treated with conventional therapy alone, 5.70 years for those who receive conventional therapy plus metoprolol, and 6.21 years for those who receive conventional therapy plus carvedilol. The expected costs (in 1999 Canadian dollars) are $8,989, $13,833, and $18,114, respectively. This yields incremental cost-effectiveness ratios (ICERs) for metoprolol relative to conventional therapy alone of $4,140 per life-year gained, and for carvedilol relative to metoprolol, the ICER is $8,394 per life-year gained. CONCLUSIONS: In addition to conventional therapy with furosemide and angiotensin converting enzyme inhibitors, treatment with either metoprolol or carvedilol confers a survival benefit that is attractive from a cost-effectiveness point of view. Until better information becomes available, it is not possible to distinguish between the two beta-blockers on the basis of cost-effectiveness. This means that the choice of beta-blockers for HF should be based largely on clinical considerations because both beta-blockers prolong life at relatively low cost.

Adrenergic beta-Antagonists↗

PubMed2001

Economic evaluation of a new acellular vaccine for pertussis in Canada.

OBJECTIVE: Pertussis is a highly contagious infection affecting mainly children. Acellular pertussis vaccines were recently introduced in Canada based on evidence of improved safety and efficacy over whole cell vaccines, the current standard of care. The following study reports the economic impact of replacing the whole cell vaccine (wP) by a new acellular vaccine (aP) in the Ontario pertussis immunisation programme. DESIGN: For a hypothetical cohort of 100,000 children from birth to the age of 8 years, the costs and consequences of pertussis vaccination with either aP or wP were compared. A decision analytical model was constructed for vaccine delivery, treatment of pertussis cases and vaccine adverse events, with analyses from the viewpoints of the Ontario Ministry of Health and society. MAIN OUTCOME MEASURES AND RESULTS: The main outcomes were expected number of pertussis cases, hospitalisations, and workdays lost by parents. Data on vaccine effectiveness, pertussis incidence, and other parameters used in the model were from published literature. Costs were discounted at 5%, and extensive sensitivity analyses were undertaken. Over 8 years, in a cohort of 100,000 children, the introduction of aP would prevent 10,500 cases of pertussis, avoiding 504 hospital admissions and 73,500 days of work absence. For Ontario, healthcare cost savings over the same period would amount to 275,585 Canadian dollars ($Can), and societal savings to $Can9,752,864

Canada↗

PubMed2001

Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for Helicobacter pylori eradication.

OBJECTIVE: To assess the cost effectiveness of a multidrug prepackaged regimen for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg, amoxicillin 1 g, all twice daily), relative to alternative pharmacological strategies in the management of confirmed duodenal ulcer over a 1-year period from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry of Health) excluding the patient copayment; and (ii) a healthcare payer perspective including the patient copayment. DESIGN: A decision-analytical model was developed to estimate expected per patient costs [1998 Canadian dollars ($ Can)], weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA), PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM) and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT). MAIN OUTCOME MEASURES AND RESULTS: All PPI-based regimens had higher expected costs but better outcomes relative to RAN-BMT. From a strict healthcare payer perspective, PPI-CM ($Can 209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs than Hp-PAC ($Can 211). However, these 3 regimens all shared identical outcomes (51.2 weeks without ulcer). When the current Ontario, Canada, $Can 2 patient copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214) than PPI-CM ($Can 216). CONCLUSION: From a strict healthcare payer perspective, Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness (relative to RAN-BMT) of $Can 5.77 per ulcer week averted. When the patient copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5 per ulcer week averted). Regardless of perspective, Hp-PAC and PPI-CM differed by only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2 weeks for both. More data on the clinical and statistical differences in H. pylori eradication with Hp-PAC and PPI-CM would be useful. This analysis does not in clude the possible advantage of Hp-PAC in terms of compliance and antibacterial resistance.

Anti-Bacterial Agents↗

PubMed2001

Examining the Saskatchewan health drug database for antidepressant use: the case of fluoxetine.

OBJECTIVE: To examine the use of fluoxetine in an adult population in Saskatchewan. METHODS: All adults in the Saskatchewan health care databases who had begun fluoxetine therapy between January 1992 and June 1996 and had not received an antidepressant in the six months before the index fluoxetine prescription were identified. Fluoxetine use for the subsequent six-month period was examined. The rates of completion of six months of fluoxetine, rates of stopping, switching to another serotonin-selective reuptake inhibitor (SSRI) or other class of antidepressant, resumption of fluoxetine, as well as average dosages taken and mean duration of therapy were determined. Rates were summarized as means with standard deviation. RESULTS: Data were obtained for 11,322 subjects, of whom 68.2% were women; 17.4% were 65 years of age or older. The average prescribed daily dose of fluoxetine was 22.5 mg (SD=21.7) and the average duration was 88.1 days (SD=57.2). Only 18.9% of patients filled prescriptions for six months, 7049 (62.3%) stopped fluoxetine at least once for one month or more, and 17.3% were titrated to a higher dose, on average 71 days (SD=44) after the initiation of fluoxetine. The proportion of patients switching to another antidepressant was 13.6% (3.3% to another SSRI, 10.3% to other classes), after a mean of 69 days (SD=51) of fluoxetine treatment. CONCLUSIONS: The authors' data suggest that there is a potential underutilization of fluoxetine in the study population. Further research may be warranted to determine the proportion of depressed patients in this population and to better understand the stop-switch-resume pattern of antidepressant use.

Age Distribution↗

PubMed2000

Organization of callosal linkages in visual area V2 of macaque monkey.

In visual area V2 of the macaque monkey callosal cells accumulate in finger-like bands that extend 7-8 mm from the V1/V2 border, or approximately half the width of area V2. The present study investigated whether or not callosal connections in area V2 link loci that are located at the same distance from the V1/V2 border in both hemispheres. We analyzed the patterns of retrograde labeling in V2 resulting from restricted injections of fluorescent tracers placed at different distances from the V1/V2 border in contralateral area V2. The results show that varying the distance of V2 tracer injections from the V1/V2 border led to a corresponding variation in the location of labeled callosal cells in contralateral V2. Injections into V2 placed on or close to the V1 border produced labeled cells that accumulated on or close to the V1 border in contralateral V2, whereas injections into V2 placed away from the V1 border produced labeled cells that accumulated mainly away from the V1 border. These results provide evidence that callosal fibers in V2 preferentially link loci that are located at similar distances from the V1/V2 border in both hemispheres. Relating this connectivity pattern to the topographic map of V2 suggests that callosal fibers link topographically mirror-symmetrical regions of V2, i.e., callosal fibers near the V1/V2 border interconnect areas representing visual fields on, or close to, the vertical meridian, whereas callosal connections from regions away from the V1/V2 border interconnect visuotopically mismatched visual fields that extend onto opposite hemifields.

Animals↗

PubMed2000

Systematic implementation of an advance directive program in nursing homes: a randomized controlled trial.

CONTEXT: Although advance directives are commonly used in the community, little is known about the effects of their systematic implementation. OBJECTIVES: To examine the effect of systematically implementing an advance directive in nursing homes on patient and family satisfaction with involvement in decision making and on health care costs. DESIGN: Randomized controlled trial conducted June 1, 1994, to August 31, 1998. SETTING AND PARTICIPANTS: A total of 1292 residents in 6 Ontario nursing homes with more than 100 residents each. INTERVENTION: The Let Me Decide advance directive program included educating staff in local hospitals and nursing homes, residents, and families about advance directives and offering competent residents or next-of-kin of mentally incompetent residents an advance directive that provided a range of health care choices for life-threatening illness, cardiac arrest, and nutrition. The 6 nursing homes were pair-matched on key characteristics, and 1 home per pair was randomized to take part in the program. Control nursing homes continued with prior policies concerning advance directives. MAIN OUTCOME MEASURES: Residents' and families' satisfaction with health care and health care services utilization over 18 months, compared between intervention and control nursing homes. RESULTS: Of 527 participating residents in intervention nursing homes, 49% of competent residents and 78% of families of incompetent residents completed advance directives. Satisfaction was not significantly different in intervention and control nursing homes. The mean difference (scale, 1-7) between intervention and control homes was -0.16 (95 % confidence interval [CI], -0.41 to 0.10) for competent residents and 0.07 (95% CI, -0.08 to 0.23) for families of incompetent residents. Intervention nursing homes reported fewer hospitalizations per resident (mean, 0.27 vs 0.48; P = .001) and less resource use (average total cost per patient, Can $3490 vs Can $5239; P = .01) than control nursing homes. Proportion of deaths in intervention (24%) and control (28%) nursing homes were similar (P = .20). CONCLUSION: Our data suggest that systematic implementation of a program to increase use of advance directives reduces health care services utilization without affecting satisfaction or mortality.

Advance Directives↗