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Biomedical subjects

B J O'Brien

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

At least 55 records · Page 3Linked to original sources
PubMed1997

Distribution of neurons projecting to the superior colliculus correlates with thick cytochrome oxidase stripes in macaque visual area V2.

In visual area V2 of macaque monkeys, cytochrome oxidase (CO) histochemistry reveals a pattern of alternating densely labeled thick and thin stripe compartments and lightly labeled interstripe compartments. This modular organization has been associated with functionally separate pathways in the visual system. We examined this idea further by comparing the pattern of CO stripes with the distribution of neurons in V2 that project to the superior colliculus. Visually evoked activity in the superior colliculus is known to be greatly reduced by blocking magnocellular but not parvocellular layers of the lateral geniculate nucleus (LGN). From previous evidence that V2 thick stripes are closely associated with the magnocellular LGN pathway, we predicted that a significant proportion of V2 neurons projecting to the superior colliculus would reside in the thick stripes. To test this prediction, the tangential distribution of retrogradely labeled corticotectal cells in V2 was compared with the pattern of CO stripes. We found that neurons projecting to the superior colliculus accumulated preferentially into band-like clusters that were in alignment with alternate CO dense stripes. These stripes were identified as thick stripes on the basis of their physical appearance and/or by their affinity to the monoclonal antibody Cat-301. A significantly smaller proportion of labeled cells was observed in thin and interstripe compartments. These data provide further evidence that the spatial distribution of subcortically projecting neurons can correlate with the internal modular organization of visual areas. Moreover, they support the notion that CO compartments in V2 are associated with functionally different pathways.

Animals↗
PubMed1997

A morphological anomaly of the dorsal lateral geniculate nucleus in Macaca fascicularis.

In the present report we describe a morphological anomaly of the thalamus. In three macaque monkeys (Macaca fascicularis), we observed up to five finger-like protrusions that emanated from the posterior pole of the dorsal lateral geniculate nucleus (LGN) and extended posteriorly between the lateral pulvinar and reticular nucleus of the thalamus. These anomalous fingers measured up to 1.7 mm in length and contained dense accumulations of neurons and glia. The fingers received a direct retinal input from the contralateral eye indicating that they were part of the LGN rather than of other adjacent thalamic nuclei. In order to determine with which subcompartment(s) of the LGN the fingers were associated (parvocellular, magnocellular, or intercalated layers), we examined the immunochemical properties and size of neurons in the fingers and LGN subcompartments. We concluded that the fingers were not associated with the intercalated layers, since neurons in the fingers did not stain with an antibody to calbindin-D28k, whereas intercalated neurons stained intensely with this antibody. In addition, neurons located in the fingers were significantly smaller than those found in the magnocellular layers but were not significantly different in size from neurons in the parvocellular layers. We therefore consider that the fingers are an anomaly of the parvocellular subcompartment of the LGN. Interestingly, in two of the three cases with anomalous fingers, we also observed subsidiary parvocellular laminae, suggesting that these two anomalies were related. In five additional animals, however, we observed subsidiary parvocellular laminae without anomalous fingers. Thus, if there are common mechanisms underlying the development of both anomalous fingers and subsidiary layers, our data indicate that they do not always result in the concomitant expression of both anomalies.

Animals↗
PubMed1997

Benefit-risk ratios in the assessment of the clinical evidence of a new therapy.

All therapeutic decisions involve some trade-off between therapeutic benefits and risks; a new therapy may be associated with greater efficacy but also a greater risk of adverse effects. In making treatment decisions clinicians must examine the clinical evidence regarding the magnitudes of benefit and risk and the precision with which they have been estimated. Ideally this requires a systemic assessment of the quality of the research and the strength of the evidence. We examine how the concept of number needed to treat can be used to improve the current presentation of clinical trials data of efficacy and side-effects to give clinicians a more clinically meaningful and quantitative measure of benefit-risk trade-offs. We propose a benefit-risk ratio that quantifies for a new therapy how many therapeutic (efficacy) events will be achieved for each adverse event incurred. We show how data from a clinical trial with a single binary measure of efficacy and a single adverse event of concern can be used to provide point estimates and confidence intervals for the benefit-risk ratio. The approach is illustrated using data from the GUSTO trial comparing tissue plasminogen activator and streptokinase in the management of patients with acute myocardial infarction.

Confidence Intervals↗
PubMed1997

Cost-benefit analyses in the health-care literature: don't judge a study by its label.

OBJECTIVES: To assess whether health-care related economic evaluations labeled as "cost benefit analyses" (CBA) meet a contemporary definition of CBA methodology and to assess the prevalence of methods used for assigning monetary units to health outcomes. DATA SOURCES: Medline, Current Contents, and HSTAR databases and reference lists of review articles, 1991-1995. STUDY SELECTION: Economic analyses labeled as CBAs were included. Agreement on study selection was assessed. STUDY EVALUATION: CBA studies were classified according to standard definitions of economic analytical techniques. For those valuing health outcomes in monetary units (bona fide CBAs), the method of valuation was classified. RESULTS: 53% of 95 studies were reclassified as cost comparisons because health outcomes were not appraised. Among the 32% considered bona fide CBAs, the human capital approach was employed to value health states in monetary units in 70%. Contingent valuation methods were employed infrequently (13%). CONCLUSIONS: Studies labeled as CBAs in the health-care literature often offer only partial program evaluation. Decisions based only on resource costs are unlikely to improve efficiency in resource allocation. Among bona fide CBAs, the human capital approach was most commonly used to valuing health, despite its limitations. The results of health-care related CBAs should be interpreted with extreme caution.

Cost-Benefit Analysis↗
PubMed1997

On becoming 65 in Ontario. Effects of drug plan eligibility on use of prescription medicines.

OBJECTIVES: The authors assess (1) the effects of first-dollar prescription drug insurance coverage provided by the Ontario Drug Benefit plan at age 65 on prescription drug use by seniors, and (2) the differential effects of this coverage on prescription drug use by seniors with varying levels of health status. METHODS: The authors modeled self-reported prescription drug use contained in the 1990 Ontario Health Survey as a function of eligibility for coverage, controlling for health status and other factors. The two-part model was used and was estimated by maximum likelihood. RESULTS: The provision of first-dollar prescription drug insurance coverage at age 65 is associated with an increase in drug use. Increases in drug use are, however, concentrated primarily among individuals with lower levels of health status. Most of the increased use occurs among individuals already under physician supervision, ie, an increase in the level of use among drug users rather than an increase in the probability of use. CONCLUSIONS: As Ontarians turn age 65 and become eligible for publicly subsidized prescription drugs, their use increases but the effect appears to be restricted mainly to persons with lower levels of health status. Given a growing trend toward reduction of public subsidy and increased reliance on patient cost sharing, more research is needed to quantify the use and health effects of such initiatives.

Age Factors↗
PubMed1997

Cost effectiveness of the prevention and treatment of deep vein thrombosis and pulmonary embolism.

The purpose of this article is to review and critically appraise the cost-effectiveness analyses that have compared various modalities for the prevention and treatment of deep vein thrombosis (DVT) and pulmonary embolism. Studies were identified by MEDLINE search and review of bibliographies of retrieved articles. Original economic analyses for the prevention or treatment of venous thromboembolism published in the English language literature were included in the analysis. In addition to collecting clinical and economic data, the methodological quality of the studies was evaluated using predefined criteria. Separate analyses were performed for studies of the prevention, and of the treatment, of venous thromboembolism following general surgery and following total hip arthroplasty. Fourteen cost-effectiveness analyses involving thromboembolic prophylaxis following total hip arthroplasty and 7 following general surgery met the eligibility criteria for this analysis. Each of the total hip arthroplasty studies containing a 'no intervention arm' determined that effective forms of prophylaxis not only reduced the rates of venous thromboembolic complications, but were less costly than a strategy of not providing venous thromboembolic prophylaxis. Six of 7 studies found low-molecular-weight (LMW) heparin to be more effective, and 4 of 7 found it to be less costly, than either unfractionated heparin or warfarin for the prevention of venous thrombosis following total hip arthroplasty. Following general surgical procedures, 6 of 7 studies found prophylaxis to be both more effective and less costly than no prophylaxis. Two studies also concluded that LMW heparin was more effective and less costly than unfractionated heparin for the prevention of DVT after general surgery. In general, the studies included in this overview were of high methodological quality with 11 of 15 studies fulfilling 4 or more of the 6 criteria for sound cost-effectiveness analyses. Effective venous thromboembolic prophylaxis results in fewer complications and is less costly than no prophylaxis following general surgery and total hip arthroplasty. LMW heparin was reported to be more efficacious and cost effective than unfractionated heparin following general surgery, and unfractionated heparin and warfarin following total hip arthroplasty. However, these findings must be regarded with caution in view of recent clinical trials and a meta-analysis reporting that the efficacy of LMW heparin and unfractionated heparin are similar following general surgery, and the efficacy of LMW heparin and warfarin are similar following total hip arthroplasty. Conclusions about the most cost-effective treatment for DVT await the publication of cost analyses from clinical trials comparing outpatient subcutaneous LMW heparin with inpatient therapy with intravenous unfractionated heparin.

Arthroplasty↗
PubMed1997

A tale of two (or more) cities: geographic transferability of pharmacoeconomic data.

The economic evaluation of a new medicine often must be based on data gathered in multiple countries. Because replication of trials is an expensive and inefficient undertaking, analysts need to determine the validity of transferring cost-effectiveness data from one country to another. Threats to transferring data involve differences among countries with regard to demography and epidemiology of disease, clinical practice and conventions, incentives to and regulation of healthcare providers, relative price levels, consumer preferences, and opportunity cost of resources. Because of these differences, a drug can be cost-effective in one country and not cost-effective in another. Adapting a cost-effectiveness study conducted in one country to another country requires careful scrutiny of the relevance of comparators, practice patterns, and relative price weights.

Canada↗
PubMed1996

Clinical economics review: cost-effectiveness of treatment alternatives for gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is a chronic recurring disorder, which is widespread, especially in Western societies. Faced with increasing health costs and finite resources, an increasingly important part of evaluating new treatments is economic appraisal. In this paper, we review critically the published economic studies of the cost-effectiveness of treatments for gastro-oesophageal reflux disease. Proton pump inhibitors are considered the best choice for the management of grades II-IV oesophagitis and are more cost-effective than H2-receptor antagonists because of their fast healing of oesophagitis, early relief of symptoms, and prevention of recurrent oesophagitis and development of complications.

Cost-Benefit Analysis↗
PubMed1996

Switching the histamine H2 receptor antagonist famotidine to nonprescription status in Canada. An economic evaluation.

The aim of this study was to compare the direct medical costs associated with the treatment of patients with heartburn/nonulcer dyspepsia under 2 scenarios: (i) no nonprescription histamine H2 receptor antagonist (H2RA) is available (the 'status quo scenario'); and (ii) the H2RA famotidine (at a daily dosage of 10mg) is available over-the-counter (OTC) at retail pharmacies (the 'OTC scenario'). We employed a decision analysis model over a 16-week period that considered direct medical costs from 2 alternative perspectives: (i) society, including the cost of self-medication borne by patients; and (ii) a provincial third-party payer for healthcare. Data concerning direct medical costs associated with consumer self-medication and physician prescription of medication (including pharmacist dispensing fees), tests and procedures, and consultations with general practitioners and specialists were drawn from a clinician panel, published unit costs, and special surveys of institutional databases. All costs are reported in 1993 Canadian dollars ($Can; $Can1 = $US0.72, October 1995). From a societal perspective, the expected cost per patient over a 16-week period is not substantially different between the status quo and the OTC scenarios ($Can98 and $Can96, respectively). From a provincial third-party payer perspective, the expected costs per patient for the same scenarios are $Can95 and $Can89, a saving of $Can6 per patient. These results are sensitive to the proportion of patients who initially choose to see their physician rather than self-medicate, and the percentage of patients achieving successful treatment of symptoms. Changes in the rate or the cost of nonprescription medication, tests/procedures and physician visits do not affect the relative cost rankings. The total number of physician visits remained constant in both scenarios. From the societal cost perspective, the availability of famotidine in nonprescription form yields total costs that are similar to the status quo. However, from the perspective of the provincial payer, the expected costs per patient are likely to be slightly lower than the status quo if famotidine is available in unrestricted OTC scenario use. To generate significant savings to provincial payers, the number of people choosing immediate physician contact would have to be reduced, although not substantially, in the OTC scenario.

Canada↗
PubMed1995

Assessing the economic value of a new antidepressant. A willingness-to-pay approach.

Using the method of willingness to pay (WTP), this study assesses the value of a new antidepressant, moclobemide, relative to that of tricyclic antidepressants (TCAs), which have equivalent efficacy but less favourable adverse effect profiles. From a published meta-analysis of controlled clinical trials, we identified 7 adverse effects, the risk of which differed significantly between moclobemide and TCAs. We obtained risk reduction data and descriptions of adverse effects from interviews with 95 individuals who had mild to moderate depression and who had been taking one or more TCAs in the previous year. Using a visual analogue scale, respondents ranked and rated each adverse effect. Participants were then asked (using the scenario of additional out-of-pocket drug payment) to quantify the maximum amount that they would pay for a new drug that reduced each adverse effect by the specified probability. Blurred vision and tremor were ranked and rated as the most bothersome adverse effects, with dry mouth being the least bothersome. On average, respondents were willing to pay an additional $Can22 per month [95% confidence interval (CI) 16-28] to reduce the risk of blurred vision from 10 to 5%. The lowest WTP value was for reducing the risk of dry mouth from 40 to 15%, at $Can11 per month (95% CI 8-15). Although not measured directly, we derived 2 estimates of WTP for multiple (i.e. all 7) risk reductions. We obtained upper and lower WTP limits of $Can118 and $Can36 per month, respectively, depending upon aggregation assumptions. Compared with the TCAs amitriptyline and imipramine, the net cost of moclobemide is greater, but the overall net benefit (WTP minus cost) is ambiguous given uncertainty about WTP aggregation over adverse effects. However, compared with the TCAs desipramine and clomipramine, the net benefit of moclobemide is unambiguously positive. We conclude that the WTP approach is a potentially valuable tool that requires more development for use in healthcare economic evaluation.

Adult↗
PubMed1995

Anomalous patterns of callosal connections develop in visual cortex of monocularly enucleated hamsters.

In this study we analyzed the effect of neonatal monocular enucleation on the pattern of callosal connections in striate cortex of the golden hamster. Callosal connections were revealed in the hemisphere ipsilateral to the remaining eye following multiple injections of either the enzyme horseradish peroxidase or the fluorescent tracer Fluoro-Gold into the contralateral hemisphere. The most salient anomaly induced by the removal of one eye at birth is the appearance of a dense band of callosal connections that runs anteroposteriorly in medial portions of striate cortex. No obvious changes in the laminar distribution of callosal connections were observed. Comparison of our present results with those obtained by Olavarria et al (1987) in monocularly enucleated rats reveals that neonatal enucleation induces remarkably similar anomalies in the callosal patterns of rats and hamsters. This similarity suggests that the role the eyes play in the development of the visual callosal pathway is similar among rodent species. Moreover, the finding of an anomalous callosal band in striate cortex one-eyed hamsters supports the notion that disruption of visual input does not arrest callosal development, but rather leads to the development of entirely new features in the callosal pattern.

Animals↗
PubMed1994

Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement.

OBJECTIVE: To compare the efficacy and cost-effectiveness of enoxaparin, a low-molecular-weight heparin derivative, with that of low-dose warfarin in the prevention of deep-vein thrombosis (DVT) after total hip replacement. DATA SOURCES: English-language articles on enoxaparin and warfarin prophylaxis is patients undergoing total hip replacement published from January 1982 to December 1992. STUDY SELECTION: Four trials of enoxaparin (involving 567 patients) and six trials of warfarin (involving 630) met the following criteria: randomized controlled trial, prophylaxis started no later than 24 hours after surgery and continued for at least 7 days, warfarin dose monitored and adjusted appropriately, enoxaparin dosage 30 mg twice daily, and DVT confirmed by bilateral venography. DATA EXTRACTION: Rates of DVT, cost of prophylaxis, diagnosis and treatment per patient, rate of pulmonary embolism (PE), number of deaths and incremental cost-effectiveness (cost per life-year gained). DATA SYNTHESIS: The pooled rate of DVT was 13.6% with enoxaparin (95% confidence interval [CI] 10.9% to 16.3%) and 20.6% with warfarin (95% CI 17.4% to 23.8%). At a cost of $19.55 per day for enoxaparin the total cost per patient, including prophylaxis and management of DVT, exceeded that per patient receiving warfarin by about $121. For every 10,000 patients treated the use of enoxaparin will prevent 47 cases of DVT, 3 cases of PE and 4 deaths. Thus, the estimated incremental cost-effectiveness of enoxaparin is $29 120 per life-year gained. CONCLUSION: On the basis of current Canadian cost-effectiveness guidelines the results of this study would be considered moderate to strong evidence to adopt enoxaparin prophylaxis against DVT after total hip replacement. However, because of the limited data the estimates are uncertain. Future trials should compare enoxaparin and warfarin and incorporate a prospective economic appraisal.

Cost-Benefit Analysis↗
PubMed1994

Solubilized HLA class I antigen enzyme-linked immunoassay to identify HLA-typing reagents.

The objective of this study was to evaluate the use of sHLA in a solid-phase EIA as a rapid and sensitive way to identify potential IgG HLA class-I-typing reagents. To evaluate the efficacy of the sHLA EIA, we used the assay to screen 259 HLA-A, -B, and -C antisera that our laboratory had procured using the standard NIH LCA. A positive result obtained by the sHLA EIA, which was defined as an EIA ratio of 3 SD above the mean of 91 anti-HLA-negative sera, revealed that 91% (79 of 87) of the A-locus-typing reagents were positive, 96% (150 of 156) of the B-locus antisera were positive, and only 75% (12 of 16) of the C-locus reagents were positive. The typing reagents that were negative by EIA (n = 18) fell into two categories. First, 38% (7 of 18) were negative by sHLA EIA, as they were IgM-typing reagents (NIH LCA reactivity ameliorated by DTT). The second group of the 11 remaining typing reagents had a mean EIA ratio of 1.0 +/- 0.246 (mean +/- 1 SD), which was significantly (P < 0.001) higher than the mean of the 91 negative controls that were used to establish the negative cutoff. The overall sensitivity of the sHLA EIA to detect HLA class-I-directed IgG was 97.2%.

Female↗
PubMed1994

In search of power and significance: issues in the design and analysis of stochastic cost-effectiveness studies in health care.

Application of techniques such as cost-effectiveness analysis (CEA) is growing rapidly in health care. There are two general approaches to analysis: deterministic models based upon assumptions and secondary analysis of retrospective data, and prospective stochastic analyses in which the design of a clinical experiment such as randomised controlled trial is adapted to collect patient-specific data on costs and effects. An important methodological difference between these two approaches is in the quantification and analysis of uncertainty. Whereas the traditional CEA model utilizes sensitivity analysis, the mean-variance data on costs and effects from a prospective trial presents the opportunity to analyze cost-effectiveness using conventional inferential statistical methods. In this study we explored some of the implications of moving economic appraisal away from deterministic models and toward the experimental paradigm. Our specific focus was on the feasibility and desirability of constructing statistical tests of economic hypotheses and estimation of cost-effectiveness ratios with associated 95% confidence intervals. We show how relevant variances can be estimated for this task and discuss the implications for the design and analysis of prospective economic studies.

Confidence Intervals↗
PubMed1994

Statistical versus quantitative significance in the socioeconomic evaluation of medicines.

This article examines the twin concepts of the statistical significance and quantitative importance of observed differences in studies comparing medicines in terms of economic parameters such as cost-effectiveness and measures of health-related quality of life (HRQOL). Central to the design and interpretation of any comparative study, such as a randomised controlled trial, is some prior judgement about the order of magnitude of a difference that would make one switch from one therapy to another. Starting with current definitions of clinically important differences we argue by analogy that the importance of differences in HRQOL require a shift of focus from the physician to the patient for preferences and judgements concerning what is important to them. Whether an intervention offers sufficient value for money (cost effectiveness or cost utility) to warrant resources being reallocated to it is a collective decision requiring the input of public preferences about the relative importance of alternative therapies and health benefits. Ultimately, the importance of the health benefits offered by a new drug is revealed by societal willingness-to-pay. This may be stated implicitly through committees using cost-effectiveness 'league tables' for decision making, or explicitly by consumer surveys of willingness-to-pay in the context of cost-benefit analysis and stemming from the theoretical foundation of welfare economics.

Cost-Benefit Analysis↗
PubMed1993

Efficacy and cost of low-molecular-weight heparin compared with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty.

PURPOSE: To compare the efficacy, safety, and cost-effectiveness of low-molecular-weight heparin with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty. DATA IDENTIFICATION: Studies were identified by MEDLINE search and review of bibliographies of retrieved articles. Hospital resources used in treating deep vein thrombosis and bleeding complications after total hip arthroplasty were estimated using retrospectively collected data from 447 patients who participated in a recently completed randomized controlled deep vein thrombosis prophylaxis trial at our center. STUDY SELECTION: Randomized controlled trials directly comparing a low-molecular-weight heparin preparation with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty were potentially eligible for the meta-analysis. DATA EXTRACTION: Data from eligible studies were extracted independently by two of the authors. Multiple regression analysis of data from the patient cohort was used to estimate the effect of deep vein thrombosis and bleeding on length of hospital stay. A hypothetical North American price for low-molecular-weight heparin was determined based on the ratio between low-molecular-weight heparin and standard heparin in France. Costs were based on weighted per-diem hospital expenditures and physician fees for procedures and reported in 1992 U.S. dollars. RESULTS OF DATA SYNTHESIS: Meta-analysis of six eligible trials determined that low-molecular-weight heparin was significantly more effective than standard heparin at preventing deep vein thrombosis after total hip arthroplasty (common odds ratio, 0.72; 95% CI, 0.53 to 0.95). However, this benefit was restricted to the prevention of proximal deep vein thrombosis (common odds ratio, 0.40; CI, 0.28 to 0.59). No significant differences were found in the rates of distal deep vein thrombosis or total, major, or minor bleeding between the two groups. Based on a 2.6 to 1 price ratio between low-molecular-weight heparin and standard heparin, use of low-molecular-weight heparin would save the health care system about $50,000 per 1000 patients treated. Sensitivity analysis shows that if the low-molecular-weight heparin/standard heparin price ratio exceeds 3.7 (the threshold value lies between 0.8 and 5.5 based on the extremes of the 95% CI of the common odds ratios for deep vein thrombosis and bleeding complications), use of low-molecular-weight heparin is more expensive. At a price ratio of 10, it would cost more than $250,000 to treat 1000 patients with low-molecular-weight heparin compared with standard heparin or about $5000 for each additional deep vein thrombosis prevented with low-molecular-weight heparin. CONCLUSIONS: Low-molecular-weight heparin is more effective and is at least as safe as standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty. Based on the current French price ratio of low-molecular-weight heparin to standard heparin, the use of low-molecular-weight heparin in North America would result in overall savings in cost; however, the relative cost-effectiveness is critically dependent on the price ratio between the two drugs. Further research is needed to compare the cost-effectiveness of low-molecular-weight heparin with other prophylactic regimens and postoperative deep vein thrombosis management strategies.

Cost-Benefit Analysis↗