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Biomedical subjects

G C Brown

Publications and source records attributed to G C Brown.

At least 37 records · Page 2Linked to original sources
PubMed2001

The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: Photodynamic therapy (PDT) has recently been demonstrated to be beneficial for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Herein, we determine the cost-effectiveness of PDT for the treatment of subfoveal choroidal neovascularization (CNV) in patients with disciform degeneration in one eye and whose second and better-seeing eye develops visual loss secondary to predominantly classic subfoveal CNV. The analysis was performed from the perspective of a for-profit third-party insurer. DESIGN: Cost-utility Markov models were created to determine the cost-effectiveness of PDT under two different scenarios, by using efficacy data derived from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study and patient-based utilities. METHODS: Decision analyses were performed by incorporating data from the TAP Study, expected longevity data, and patient-based utilities. Cost-effective models were then created by incorporating incremental medical costs. Various sensitivity analyses were carried out to determine the robustness of our models. A Monte Carlo simulation was also used to determine whether there was a significant difference in quality-of-life adjusted years (QALYs) gained between PDT therapy and the placebo. RESULTS: For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/40 vision at baseline in this affected eye (base case 1), PDT was associated with a 10.7% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.1342 QALYs over a 2-year period). For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/200 vision at baseline in this affected eye (base case 2), PDT was associated with a 7.8% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.0669 QALYs over a 2-year period). Sensitivity analysis showed our models were robust and that PDT was usually the dominant treatment choice. Our cost-effective model demonstrated that the cost for a QALY was $86,721 (US dollars discounted at 3%) for base case 1, assuming 5.5 treatments; and $173,984 (USD discounted at 3%) for base case 2. CONCLUSIONS: PDT will cost a third-party insurer $86,721 for an AMD patient with 20/40 vision in the better-seeing eye to obtain one QALY and $173,984 for an AMD patient with 20/200 vision in the better-seeing eye to obtain one QALY. PDT can be considered to be a treatment that is of only minimal cost-effectiveness for AMD patients who have subfoveal CNV in their second and better-seeing eyes and who have good presenting visual acuity at baseline. It is a cost-ineffective treatment for AMD patients who have poor visual acuities in their affected better-seeing eyes.

Aged↗
PubMed2001

A utility analysis correlation with visual acuity: methodologies and vision in the better and poorer eyes.

OBJECTIVE: To ascertain the correlation between visual acuity levels and ophthalmic utility values obtained using time tradeoff and standard gamble utility analysis methodologies. METHODS: Three hundred twenty-five consecutive patients with visual loss to 20/40 or less in at least one eye with predominantly vitreoretinal pathology were evaluated in a cross-sectional fashion using a standardized testing methodology to obtain ophthalmic time tradeoff and standard gamble utility values. Spearman correlation coefficients were employed to correlate the utility values with visual acuity in better seeing and poorer seeing eyes. RESULTS: The Spearman correlation coefficient for time tradeoff utility values and vision in the better seeing eye was 0.455 (p < 0.001), while that for time tradeoff utility values and visual acuity in the poorer seeing eye was 0.268 (p < 0.001). The coefficient for standard gamble utility values and the better seeing eye was 0.371 (p < 0.001), while that for standard gamble utility values and vision in the poorer seeing eye was 0.250 (p < 0.001). CONCLUSIONS: There is a greater correlation between ophthalmic utility values and vision in the better seeing eye, as versus vision in the poorer seeing eye. Time tradeoff ophthalmic utility values demonstrate a greater correlation with vision in the better seeing eye than do standard gamble utility values.

Aged↗
PubMed2001

Patient-initiated second medical opinions: their necessity and economic cost.

PURPOSE: To assess the value of patient-initiated second medical opinions (SMO). METHODS: The authors prospectively collected demographic data from 100 consecutive patients. The authors recorded major changes in the patients' care, such as inappropriate surgery recommended, inadequate treatment performed, and appropriate treatment not recommended. The authors also recorded costs incurred or saved by the patients and the third-party payers. RESULTS: In nearly 15 of the cases, the authors had major disagreements with the initial diagnosis or management. Surgery had been recommended in 28 cases. They advised against it in nine. In 72 cases, no surgery had been recommended. They advised and performed it in five. The management of five other patients was not in accordance with that recommended by large clinical trials or was inadequately done. Including the consultation fees, surgery performed or advised against, retinal angiography, and ultrasonography, the 100 SMO cost third-party payers $12,426. If the authors subtract the cost of noncontroversial surgery they recommended and if the patients had paid the consultation fee and had brought along their fluorescein angiograms, third-party payers would have saved $4,079. CONCLUSION: The savings SMO generated by eliminating unnecessary surgery resulted in improved patient care at minimal cost to third-party payers.

Adolescent↗
PubMed2001

The cost-effectiveness of early vitrectomy for the treatment of vitreous hemorrhage in diabetic retinopathy.

Diabetic vitrectomy has been found to be efficacious for the treatment of vitreous hemorrhage secondary to diabetic retinopathy. The purpose of this study is to determine the cost-effectiveness of early vitrectomy for the management of vitreous hemorrhage secondary to diabetic retinopathy. The analysis was performed from the perspective of a third-party insurer. A cost-utility Markov model was used to determine the cost per quality-adjusted life year (QALY) gained from early versus deferral of vitrectomy. The model used 2-, 3-, and 4-year results from the Diabetic Retinopathy Vitrectomy Study, patient-based utilities, life expectancy data, and incremental medical costs. Early vitrectomy was the dominant strategy and was associated with a gain of 0.41 QALYs over the 57-year expected life span for a hypothetical patient. The cost per additional QALY gained from early vitrectomy treatment was $1910 (US$ discounted at 3%). When sensitivity analyses were performed by varying efficacy probabilities and utilities across their 95% confidence intervals, early treatment was always the dominant strategy. Additionally, even at the extreme sensitivity values, the cost per QALY of early vitrectomy treatment remained under $10,000. Overall, early vitrectomy for the treatment of vitreous hemorrhage secondary to diabetic retinopathy is highly cost-effective.

Adult↗
PubMed2001

Utility values associated with blindness in an adult population.

AIM: To ascertain utility values associated with varying degrees of legal blindness. METHODS: A cross sectional study on three group of patients. There were: (1) 15 patients with complete absence of vision (no light perception) in at least one eye who were asked to assume a scenario of no light perception in the second eye as well, (2) 17 patients with light perception to counting fingers in the better seeing eye, and (3) 33 patients with 20/200-20/400 vision in the better seeing eye. Utility values were measured using the time trade-off and standard gamble methods in each of the three groups. RESULTS: The mean time trade-off utility value for the no light perception group with the theoretical scenario of bilateral absence of light perception was 0.26 (95% CI, 0.19-0.33). The mean utility value for the light perception to counting fingers group was 0.47 (95% CI, 0.33-0.61), and the mean utility value for the 20/200-20/400 group was 0.65 (95% CI, 0.58-0.72). Thus, patients with no light perception in one eye, who were presented with the same scenario in the second eye as well, were willing to trade almost 3 out of every 4 years of remaining life in return for perfect vision in each eye. Those with light perception to counting fingers would trade approximately 1 of 2 remaining years and those with 20/200-20/400 would trade approximately 1 of 3 remaining years. CONCLUSIONS: There is a wide range of utility values associated with legal blindness. The utility value decreases dramatically with perceived total loss of vision (absence of light perception in each eye), compared with counting fingers to light perception vision, indicating that the preservation of even small amounts of vision in patients with legal blindness is critically important to their wellbeing and functioning in life.

Adult↗
PubMed2001

Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation.

Incubation of rat aortas with endotoxin and interferon-gamma for 24 h resulted in an aortic oxygen consumption that was substantially inhibited and strongly oxygen dependent (37% inhibition at 160 microM O(2) and 62% inhibition at 80 microM O(2) relative to untreated aortas). This respiratory inhibition was reversed by a nitric oxide (NO) scavenger (oxyhemoglobin) or by an inhibitor of inducible NO synthase [N-(3-(aminomethyl)benzyl)acetamide x 2HCl, 1400W], but not by an inhibitor of soluble guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one). Addition of 1 microM NO to untreated aortas caused rapid and reversible inhibition of oxygen consumption that was greater at lower oxygen concentrations. Incubation of endothelial cells isolated from rat aortas with endotoxin and interferon-gamma for 24 h resulted in a steady-state NO concentration of approximately 0.5 microM and 90% inhibition of cellular oxygen consumption that was immediately reversed by an NO scavenger (oxyhemoglobin). These results suggest that during inflammation and sepsis, tissue respiration may be substantially reduced due to inhibition by NO of cytochrome oxidase.

Amidines↗
PubMed2001

Physician manpower and health care expenditures in the United States: a thirty-year perspective.

Data gathered on the number of physicians and health care costs in the United States over a 30-year period from 1970 through 1999 were correlated and analyzed using bivariate linear regression. The rise in the number of practicing physicians theoretically predicts 96 percent of the variability in rise of total U.S. health expenditures, 96 percent of the variability in rise of physician service expenditures, 98 percent of the variability in rise of hospital service expenditures, and 86 percent of the variability in rise of prescription pharmaceutical expenditures. If the rate of growth in the number of physicians continues unchanged in the current fee-for-service climate, the model herein predicts that the growth in health care costs will likely continue to rise substantially faster than the rate of growth of the U.S. population and the rate of inflation. The addition of nonphysician providers with the same clinical privileges will likely exacerbate the situation of rapidly escalating medical costs. It is also possible that the excess number of physicians and other health care providers with the same clinical privileges as physicians may decrease the overall quality of health care. Reducing the rise in the number of physicians and nonphysician practitioners may help to decrease overall health care expenditures and improve overall quality of health care in the United States.

Allied Health Personnel↗
PubMed2001

The reproducibility of ophthalmic utility values.

PURPOSE: Utility values have been used in the ophthalmic literature to measure the quality of life associated with a health state. By convention, a utility value of 1.0 is associated with perfect health, and a value of 0.0 is associated with death. Construct validity of utility values has been demonstrated, particularly in regard to decreasing utility values as the vision decreases in the better seeing eye, but long-term test-retest reliability has not been demonstrated. The purpose of this study was to demonstrate the test-retest reliability of ophthalmic utility values. METHODS: One hundred fifteen patients with ophthalmic diseases and stable visual acuity underwent time trade-off utility analysis with retesting at various intervals ranging from 1 month to 2 years. The results were analyzed using the Wilcoxon signed rank test. The study was designed to have an 50% power, using a two-sided alpha of 5%, to be able to detect a 10% difference between the test and retest groups. RESULTS: The mean time from testing to retesting was 0.87 years, with a median time of 1.0 year and range of 1 month to 2 years. The mean utility value in the test group was 0.766 (SD = .21; 95% CI, 0.730-0.802), while the mean utility value in the retest group was 0.763 (SD = .22; 95% CI, 0.724-0.802). The difference between the means of the test-retest groups was not significant (P = .99). The intraclass correlation between the initial and follow-up utility scores was .5246 (P < .00005). CONCLUSIONS: Ophthalmic utility values appear to have good test-retest reliability over prolonged periods of time. This information is important because it gives researchers increased confidence in the validity of basic tools for ophthalmic cost-effective (cost-utility) analyses.

Adult↗
PubMed2000

Diffusion control of protein phosphorylation in signal transduction pathways.

Multiple signalling proteins are phosphorylated and dephosphorylated at separate cellular locations, which potentially causes spatial gradients of phospho-proteins within the cell. We have derived relationships that enable us to estimate the extent to which a protein kinase, a phosphatase and the diffusion of signalling proteins control the protein phosphorylation flux and the phospho-protein gradient. Two different cellular geometries were analysed: (1) the kinase is located on one planar membrane and the phosphatase on a second parallel planar membrane, and (2) the kinase is located on the plasma membrane of a spherical cell and the phosphatase is distributed homogeneously in the cytoplasm. We demonstrate that the control contribution of protein diffusion is potentially significant, given the measured rates for protein kinases, phosphatases and diffusion. If the distance between the membranes is 1 microm or greater, the control by diffusion can reach 33% or more, with the rest of the control (67%) shared by the kinase and the phosphatase. At distances of less than 0.1 microm, diffusion does not limit protein phosphorylation. For a spherical cell of radius 10 microm, a protein diffusion coefficient of 10(-8) cm(2). s(-1) and rate constants for the kinase and the phosphatase of approx. 1 s(-1), control over the phosphorylation flux resides mainly with the phosphatase and protein diffusion, with approximately equal contributions of each of these. The ratio of phospho-protein concentrations at the cell membrane and the cell centre (the dynamic compartmentation of the phospho-protein) is shown to be controlled by the rates of the protein phosphatase and of diffusion. The kinase can contribute significantly to the control of the absolute value of the phospho-protein gradient.

Cell Membrane↗
PubMed2000

Reversal of nitric oxide-, peroxynitrite- and S-nitrosothiol-induced inhibition of mitochondrial respiration or complex I activity by light and thiols.

Nitric oxide (NO) and its derivatives peroxynitrite and S-nitrosothiols inhibit mitochondrial respiration by various means, but the mechanisms and/or the reversibility of such inhibitions are not clear. We find that the NO-induced inhibition of respiration in isolated mitochondria due to inhibition of cytochrome oxidase is acutely reversible by light. Light also acutely reversed the inhibition of respiration within iNOS-expressing macrophages, and this reversal was partly due to light-induced breakdown of NO, and partly due to reversal of the NO-induced inhibition of cytochrome oxidase. NO did not cause inhibition of complex I activity within isolated mitochondria, but 0.34 mM peroxynitrite, 1 mM S-nitroso-N-acetylpenicillamine or 1 mM S-nitrosoglutathione did cause substantial inhibition of complex I activity. Inhibition by these reagents was reversed by light, dithiothreitol or glutathione-ethyl ester, either partially or completely, depending on the reagent used. The rapid inhibition of complex I activity by S-nitroso-N-acetylpenicillamine also occurred in conditions where there was little or no release of free NO, suggesting that the inhibition was due to transnitrosylation of the complex. These findings have implications for the physiological and pathological regulation of respiration by NO and its derivatives.

Animals↗
PubMed2000

Nitric oxide donors, nitrosothiols and mitochondrial respiration inhibitors induce caspase activation by different mechanisms.

We investigated to what extent different types of NO donors induce caspase activation by opening of the mitochondrial permeability transition pore (PTP) or inhibition of mitochondrial respiration. We found that nitrosothiols can directly open the PTP in isolated mitochondria and cause cytochrome c release, whereas NONOate donors can not. In macrophages nitrosothiols cause caspase activation that is blocked by cyclosporin A or calcium chelation, both of which prevent PTP opening, whereas caspase activation caused by NONOates is much less sensitive to these agents. Inhibitors of mitochondrial respiration did not promote PTP opening in isolated mitochondria, and although they cause caspase activation in macrophages, this activation was slower than that caused by NO donors, and was relatively insensitive to cyclosporin and calcium chelators suggesting that PTP opening was not involved.

Animals↗
PubMed2000

Utility values and age-related macular degeneration.

OBJECTIVE: To ascertain the utility values associated with age-related macular degeneration and varying degrees of visual loss. DESIGN: A cross-sectional study. PARTICIPANTS: Eighty white patients with unilateral or bilateral age-related macular degeneration in 1 or both eyes, and visual loss to a minimum of the 20/40 level in at least 1 eye. MAIN OUTCOME MEASURES: Utility values were measured in 5 groups according to the visual acuity in the better-seeing eye, 1 (20/20 to 20/25), 2 (20/30 to 20/ 50), 3 (20/60 to 20/100), 4 (20/200 to 20/400), and 5 (counting fingers to light perception), using the time trade-off and the standard gamble methods. Conventionally assigned anchor utility values were 1.0 for perfect health and 0.0 for death. RESULTS: The mean utility value for the total group with age-related macular degeneration was 0.72 (95% confidence interval [CI], 0.66-0.78) using the time trade-off method and 0.81 (95% CI, 0.76-0.86) using the standard gamble method. Using the time trade-off method correlated with the visual acuity in the better-seeing eye, the results were as follow: group 1, 0.89 (95% CI, 0.82-0.96), group 2, 0.81 (95% CI, 0.73-0.89), group 3, 0.57 (95% CI, 0.47-0.67), group 4, 0.52 (95% CI, 0.38-0.66), and group 5, 0.40 (95% CI, 0.29-0.50). Thus, those patients in group 1 were willing to trade 11% of their remaining lifetime in return for perfect vision in each eye, whereas those in group 5 were willing to trade 60% of their remaining lifetime in return for perfect vision in each eye. CONCLUSION: Age-related macular degeneration causes a substantial decrease in patient utility values and is highly dependent on the degree of visual loss in the better-seeing eye.

Aged↗
PubMed2000

Arteriovenous adventitial sheathotomy for the treatment of macular edema associated with branch retinal vein occlusion.

PURPOSE: To report arteriovenous adventitial sheathotomy for treatment of macular edema associated with branch retinal vein occlusion. METHODS: Case reports with review. Five eyes of five patients with best-corrected visual acuity of less than 20/200 secondary to branch retinal vein occlusion had pars plana vitrectomy and arteriovenous adventitial sheathotomy and were followed postoperatively for a mean of 6.5 years (range, 5 to 7 years). RESULTS: In four of five eyes, the best-corrected visual acuity improved to 20/30 to 20/70. In the remaining eye, visual acuity remained at finger counting secondary to macular ischemia. CONCLUSION: Arteriovenous adventitial sheathotomy may be beneficial for select patients with poor vision secondary to branch retinal vein occlusion.

Aged↗
PubMed2000

Difference between ophthalmologists' and patients' perceptions of quality of life associated with age-related macular degeneration.

BACKGROUND: There may be a wide disparity between the perceptions of patients and those of their treating physicians concerning the quality of life associated with a given state of health. Because of this potential for difference of opinion, we performed a study to evaluate patients' and ophthalmologists' perceptions of quality of life, as measured by utility analysis, associated with visual loss secondary to age-related macular degeneration (AMD). METHODS: Cross-sectional study. Utilities were assessed, by means of both the time trade-off method and the standard gamble method, for various degrees of theoretical visual loss secondary to AMD for ophthalmologists-in-training and graduate ophthalmologists. These were compared to utilities for a known population of patients with actual visual loss due to AMD. A utility of 1.0 is associated with perfect health, whereas a utility of 0.0 is associated with death. RESULTS: With both the time trade-off and standard gamble methods, the patients had lower mean utilities than did the ophthalmologists for the same degrees of visual loss secondary to AMD. The ophthalmologists were significantly less willing than the patients to trade years of remaining life for perfect vision with the time tradeoff method (p < or = 0.01), and with the standard gamble method they were less willing than the patients to take the risk of dying in return for perfect vision. Given the scenario of counting fingers or worse vision in both eyes, the ophthalmologists were willing to trade 3.3 of every 10 years of remaining life for perfect vision in both eyes, whereas the patients with actual vision of counting fingers or worse in both eyes were willing to trade 6.0 of every 10 years of remaining life for this result. INTERPRETATION: When presented with the scenario of visual loss secondary to AMD, ophthalmologists substantially underestimated its effect on patients' quality of life.

Adult↗