Health care economic analyses.
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Biomedical subjects
Publications and source records attributed to Sanjay Sharma.
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PURPOSE OF REVIEW: The purpose of the review is to examine the role of value-based medicine and its impact, or potential impact, on vitreoretinal interventions. RECENT FINDINGS: Value-based medicine integrates evidence-based data from clinical trials with the patient-perceived improvement in quality of life conferred by an intervention. Cost-utility analysis, the healthcare economic instrument used to create a value-based medicine database, is being increasingly used to study the cost-effectiveness of vitreoretinal interventions. SUMMARY: Vitreoretinal interventions are generally cost-effective because of the great value they impart to patients. Laser surgical procedures, such as for diabetic retinopathy, threshold retinopathy of prematurity, and exudative macular degeneration appear to be especially cost-effective as a group.
PURPOSE OF REVIEW: To review how to critically appraise a research article pertaining to changes in health-related quality of life (HRQoL) related to interventions for age-related macular degeneration (AMD). RECENT FINDINGS: We searched PubMed using a strategy that combined the text-words, "macular degeneration" and "quality of life" (n = 73; January 17, 2004), while limiting the search to "clinical trials" (n = 6; of which 3 were published within the past year). A randomized clinical trial evaluating the efficacy of self-management as an intervention for AMD has been selected to introduce the reader to the concept of how to critically review a research paper pertaining to HRQoL in AMD. Other pertinent articles used in this review include recent results published from the Age-Related Eye Disease Study and the Submacular Surgery Trial. SUMMARY: The NEI-VFQ is a reliable, valid, and responsive tool when applied to patients with AMD. Self-management of patients with AMD has been demonstrated to improve their HRQoL by way of an internally valid randomized clinical trial. In this issue of Current Opinion in Ophthalmology, we confront the issue of how to assess the validity and importance of a research paper pertaining to the issue of quality of life. To introduce this topic, we will present a real world clinical example to better understand how quality of life may aid in medical decision making.
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Multifocal sclerosing hemangioma of the lung is a rare entity. While solitary pulmonary lesions by themselves are uncommon and few reports have been described, multifocal bilateral lesions are rare and limited instances have been cited in indexed medical literature. We herewith describe a case of multiple sclerosing hemangiomas of the lung, in a patient who also had a vascular malformation over the calf.
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XR5944 (MLN944) is a novel DNA targeting agent with potent antitumor activity, both in vitro and in vivo, against several murine and human tumor models. We have used an ATP-tumor chemosensitivity assay to assess the ex vivo sensitivity of a variety of solid tumors (n = 90) and a CCRF-CEM leukemia cell line selected with XR5944. Differences in gene expression between the parental CCRF-CEM and the resistant subline were investigated by quantitative reverse transcription-PCR. Immunohistochemistry for topoisomerases I and IIalpha and multidrug resistance (MDR1) protein was done on those tumors for which tissue was available (n = 32). The CCRF-CEM XR5944 line showed increased mRNA levels of MDR1, major vault protein, and MDR-associated protein 1 compared with the parental line, whereas the expression of topoisomerases I, IIalpha, and IIbeta was essentially unchanged, suggesting that XR5944 is susceptible to MDR mechanisms. The median IC90 and IC50 values for XR5944 in tumor-derived cells were 68 and 26 nmol/L, respectively, 6-fold greater than in resistant cell lines. XR5944 was 40- to 300-fold more potent than the other cytotoxics tested, such as doxorubicin, topotecan, and paclitaxel. Breast and gynecologic malignancies were most sensitive to XR5944, whereas gastrointestinal tumors showed greater resistance. A positive correlation (r = 0.68; P < 0.0001) was found between the IC50 values of XR5944 and P-glycoprotein/MDR1 staining but not with either topoisomerase I or IIalpha immunohistochemistry index. These data support the rapid introduction of XR5944 to clinical trials and suggest that it may be effective against a broad spectrum of tumor types, especially ovarian and breast cancer.
PURPOSE: To ascertain the extent to which ophthalmologic interventions have been evaluated in value-based medicine format. METHODS: Retrospective literature review. Papers in the healthcare literature utilizing cost-utility analysis were reviewed by researchers at the Center for Value-Based Medicine, Flourtown, Pennsylvania. A literature review of papers addressing the cost-utility analysis of ophthalmologic procedures in the United States over a 12-year period from 1992 to 2003 was undertaken using the National Library of Medicine and EMBASE databases. The cost-utility of ophthalmologic interventions in inflation-adjusted (real) year 2003 US dollars expended per quality-adjusted life-year (dollars/QALY) was ascertained in all instances. RESULTS: A total of 19 papers were found, including a total of 25 interventions. The median cost-utility of ophthalmologic interventions was 5,219 dollars/QALY, with a range from 746 dollars/QALY to 6.5 million dollars/QALY. CONCLUSIONS: The majority of ophthalmologic interventions are especially cost-effective by conventional standards. This is because of the substantial value that ophthalmologic interventions confer to patients with eye diseases for the resources expended.
OBJECTIVES: The aim of this study was to examine the characteristics of non-sustained ventricular tachycardia (NSVT) episodes during Holter monitoring and to determine their relationship to age and prognosis. BACKGROUND: It has been suggested that NSVT is only of prognostic importance in patients with hypertrophic cardiomyopathy (HCM) when repetitive, prolonged, or associated with symptoms. METHODS: We studied 531 patients with HCM (323 male, 39 +/- 15 years). All underwent ambulatory electrocardiogram monitoring (41 +/- 11 h). RESULTS: A total of 104 patients (19.6%) had NSVT. The proportion of patients with NSVT increased with age (p = 0.008). Maximum left ventricular wall thickness and left atrial size were greater in patients with NSVT. Mean follow-up was 70 +/- 40 months. Sixty-eight patients died, 32 from sudden cardiac death (SCD). Twenty-one patients received an implantable cardioverter defibrillator (ICD). There were four appropriate ICD discharges. In patients < or =30 years (but not >30), five-year freedom from sudden death was lower in those with NSVT (77.6% [95% confidence interval (CI): 59.8 to 95.4] vs. 94.1% [95% CI: 90.2 to 98.0]; p = 0.003). There was no relation between the duration, frequency, or rate of NSVT runs and prognosis at any age. The odds ratio of sudden death in patients < or =30 years of age with NSVT was 4.35 (95% CI: 1.54 to 12.28; p = 0.006) compared with 2.16 (95% CI: 0.82 to 5.69; p = 0.1) in patients >30 years of age. CONCLUSIONS: Non-sustained ventricular tachycardia is associated with a substantial increase in sudden death risk in young patients with HCM. A relation between the frequency, duration, and rate of NSVT episodes could not be demonstrated.
BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centres.
OBJECTIVES: We sought to assess the efficacy of biventricular pacing with respect to both peak and submaximal measures of exercise in patients with New York Heart Association class III heart failure (HF) and intraventricular conduction delay in a randomized, blinded study. BACKGROUND: Submaximal and maximal changes in exercise capacity need evaluating in this patient population with this novel therapy. METHODS: Graded exercise and 6-min walk tests were performed in patients randomized to three months each of active (atrio-biventricular) and inactive pacing. Minute ventilation (VE), oxygen uptake (VO(2)), ventilated carbon dioxide (VCO(2)) and heart rate were measured in patients achieving a respiratory quotient >1 (n = 30). Oxygen pulse, anaerobic threshold (AT) and ventilatory efficiency (VE/VCO(2)) were calculated. RESULTS: Active biventricular pacing increased peak VO(2) (15.8 +/- 4.3 vs. 14.4 +/- 4.6 ml/kg/min, p = 0.02), exercise time (501 +/- 223 s vs. 437 +/- 233 s, p < 0.001) and oxygen pulse (9.3 +/- 2.8 vs. 8.1 +/- 3.1 ml/beat, p < 0.01) compared with inactive pacing. The submaximal measures of exercise capacity significantly increased with active pacing: AT (11.2 +/- 4.1 ml/kg/min vs. 9.5 +/- 2.3 ml/kg/min, p = 0.02) and 6-min walk (414 +/- 94 m vs. 359 +/- 94 m, p = 0.001). Minute ventilation/ventilated carbon dioxide improved (32 +/- 9 vs. 36 +/- 11, p = 0.03) with normalization of the VE/VCO(2) slope in 59% of patients (chi-square test, p = 0.002) with active pacing. CONCLUSIONS: Biventricular pacing may improve maximal and submaximal exercise capacity in patients with advanced HF and intraventricular conduction delay.
PURPOSE: To assess the visual utility values of patients with ocular disease and to compare these values with those of patients with systemic health states DESIGN: Cross-sectional utility value assessment. METHODS: Consecutive patients with ophthalmic diseases were interviewed in a one-on-one fashion using a standardized time tradeoff utility value assessment form. These values were compared with utility values for systemic health states present in the literature. INTERVENTION: None. MAIN OUTCOME MEASURE: Time tradeoff utility value on a scale ranging from 1.0 (perfect visual health) to 0.0 (death). The ophthalmic patient groups were stratified into 4 visual groups dependent on the visual acuity in the better-seeing eye. The groups were as follows: group 1, 20/20 to 20/25; group 2, 20/30 to 20/50; group 3, 20/60 to 20/100; group 4, 20/200 to no light perception. RESULTS: A total of 500 subjects were enrolled in the study. The mean utility values for the visually stratified groups were: group 1, 0.88; group 2, 0.81; group 3, 0.72; group 4, 0.61. Comparable respective systemic health state utility values for each of the ophthalmic groups were: diabetes mellitus, status after kidney transplantation, moderate stroke, and moderately severe stroke. CONCLUSIONS: Visual loss is associated with a substantial and measurable diminution in quality of life. This diminution in quality of life can be directly compared with that induced by systemic health states.
PURPOSE: To evaluate the anatomic closure rate and visual outcome in patients undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling with and without indocyanine green (ICG) enhancement. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS: One hundred ninety-three consecutive patients (204 eyes) seen at the Barnes Retina Institute with the clinical diagnosis of macular hole who underwent PPV between January 1998 and December 2000. INTERVENTION: A consecutive series of 97 patients undergoing PPV with or without unilateral epiretinal membrane removal without ILM peeling (group 1), 44 patients with PPV and ILM peeling without ICG (group 2), and 35 patients with ICG-assisted ILM peeling (group 3). RESULTS: Overall, 86.4% of the holes closed with one operation, with 75 of 97 (77.3%) eyes in group 1, 43 of 44 (97.7%) eyes in group 2, and 34 of 35 (97.1%) eyes in group 3 (chi(2)= 10.51, P = 0.007). Of the eyes that did not close, 18 patients in group 1 underwent repeat surgery, with 90 of 97 (92.8%) eyes ultimately achieving closure. Visual acuity after surgery was 20/50 or better in 55 of 97 (56.7%) patients, 31 of 44 (70.4%) patients, and 18 of 35 (51.4%) patients in groups 1, 2, and 3, respectively (chi(2) = 3.43, P = 0.18) and increased by 2 or more lines from their preoperative status in 63 of 97 (64.9%) patients, 34 of 44 (77.3%) patients, and 25 of 35 (71.4%) patients, respectively (chi(2)= 2.25, P = 0.32). Multivariate logistic regression demonstrated that use of ILM peeling during vitrectomy increases the chances of developing 20/50 vision or better (odds ratio [OR], 2.4; 95% confidence interval, 1.06-5.45; P = 0.04). No eyes received concurrent cataract extraction with macular hole surgery, but 75 of 166 (45.2%) required cataract extraction postoperatively. Complications included 20 retinal tears, 4 retinal detachments, and 34 patients with postoperative elevations in intraocular pressure (IOP; defined as IOP greater than 30 mmHg). CONCLUSIONS: Although this study is limited by the shorter follow-up in patients undergoing ILM peeling with or without ICG relative to the control group, our experience indicates that the use of ILM peeling is associated with a statistically significant improvement in the rate of primary macular hole closure with a single operation.
OBJECTIVE: To perform a reference case cost-utility analysis of second-eye cataract surgery by using the current literature on cataract outcomes and complications. DESIGN: Computer-based econometric modeling. METHODS: Visual acuity data of patients treated and observed over a 4-month postoperative period were obtained from the U.S. National Cataract Patient Outcomes Research Team report. The results from this prospective study were combined with those of other studies that investigated the complication rates of cataract surgery to complete the cohort of patients and outcomes. These synthesized data were incorporated with time trade-off utility values, which accounted for prior successful cataract surgery in the fellow eye. Cost-utility determinations were made with decision analysis, and present value modeling was used to account for the time value of money and health state consequences. MAIN OUTCOME MEASURES: The number of quality-adjusted life-years (QALYs) gained was calculated for the study group undergoing second-eye cataract surgery, assuming that the postoperative vision in the second eye was equivalent to the vision in the first eye after surgery (20/27). This was divided into the cost of the procedure to find the number of year 2001 nominal U.S. dollars spent per QALY gained. RESULTS: Second-eye cataract surgery, as compared with unilateral pseudophakia, resulted in a mean gain of 1.31 undiscounted QALYs per patient treated. A 3% annual discount rate, dependent on the duration of benefit, was used, yielding 0.92 discounted QALYs gained over a 12-year life expectancy. The mean discounted cost of treatment for each patient totaled 2509 US dollars. The cost divided by the QALYs gained (benefit) resulted in 2727 US dollars per QALY gained for this procedure. Sensitivity analysis varying costs and utility values revealed a range from 2045 US dollars to 3649 US dollars per QALY gained. CONCLUSIONS: Second-eye cataract surgery is an extremely cost-effective procedure when compared with other interventions across medical specialties. The cost-effectiveness of second-eye surgery diminishes only slightly from the 2023 US dollars per QALY gained from first-eye cataract surgery. This suggests that patients with good vision in one eye and visual loss from cataract in the fellow eye derive substantial benefit from cataract extraction.
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Direct tumor injections of CpG (ODN #1826) into murine tumors markedly suppressed the tumor growth and increased the survival of the mice. Tumor growth was reduced by 60-67% in Colon Tumor 26 (CT-26) and B-16 melanoma tumors treated with CpG as compared to untreated one. In CT-26 and B-16 tumors treated with CpG, the average survival of the animals were prolonged to 26 and 28 d as compared to 16 and 18 d in control respectively. Long-term surviving animals in CT-26 tumor groups were also protected from a subsequent injection of a lethal dose of tumor cells. In the present study, effect of CpG was mediated through CD8+ T cells, as their depletion resulted in the abrogation of the therapeutic effects of the CpG. It suggests that direct tumor injection might be a simple means of achieving a clinical response in cancer patients.