Capsule endoscopy in suspected small bowel Crohn's disease: economic impact of disease diagnosis and treatment.

AIM: To model clinical and economic benefits of capsule endoscopy (CE) compared to ileo-colonoscopy and small bowel follow-through (SBFT) for evaluation of suspected Crohn's disease (CD). METHODS: Using decision analytic modeling, total and yearly costs of diagnostic work-up for suspected CD were calculated, including procedure-related adverse events, hospitalizations, office visits, and medications. The model compared CE to SBFT following ileo-colonoscopy and secondarily compared CE to SBFT for initial evaluation. RESULTS: Aggregate charges for newly diagnosed, medically managed patients are approximately $8295. Patients requiring aggressive medical management costs are $29,508; requiring hospitalization, $49,074. At sensitivity > 98.7% and specificity of > 86.4%, CE is less costly than SBFT. CONCLUSION: Costs of CE for diagnostic evaluation of suspected CD is comparable to SBFT and may be used immediately following ileo-colonoscopy.

Bone marrow recovery following use of systemic (153)Sm-lexidronam and (89)Sr-chloride for bone pain palliation after myelosuppressive therapy.

PURPOSE: Using plasma flt3 ((FMS (Friend murine strain))-like tyrosine kinase 3)-ligand cytokine (FL) as a biomarker, the purpose of this study was to determine whether patients receiving palliative radionuclide treatment following chemotherapy experienced enhanced myelosuppression. MATERIALS AND METHODS: A total of 48 patients with solid tumors who failed multi-agent chemotherapy were investigated; they previously received 1-3 cycles of combination chemotherapy over 4-10 months. Patients were divided into four cohorts including 10 patients with early stage solid tumors prior to chemotherapy induction (naive group), 10 patients with (non-metastatic) malignancy actively undergoing chemotherapy without radionuclide follow-up (chemotherapy-alone group), 13 patients who underwent standard (1.0 mCi/kg) dose (153)Sm ((153)samarium)-lexidronam therapy following chemotherapy ((153)Sm group), and 15 patients who underwent standard (4 mCi) dose (89)Sr ((89)strontium)-chloride therapy following chemotherapy ((89)Sr group). Plasma FL was measured using a quantitative sandwich enzyme immunoassay and CBC (complete blood count), measuring WBC (white blood cell) and PLT (platelet), was performed. RESULTS: Plasma FL concentration demonstrated a gradual decrease after chemotherapy. In patients who received (153)Sm within two weeks of completing chemotherapy, there is a distinguishable spike in FL concentration at approximately three weeks after dose administration, which precedes a decrease in WBC and PLT counts. On the other hand, a spike in FL levels in patients who received (89)Sr therapy is noted at approximately 10 weeks (p < 0.034). CONCLUSIONS: Increases in FL concentration associated with (153)Sm-lexidronam therapy following combination chemotherapy occurred earlier and returned to control levels more rapidly than did those in patients similarly treated with (89)Sr. These differences might be associated with the shorter decay half-life and lower particle emission energies of (153)Sm.

Improvement in sensory pain rating after palliative systemic radionuclide therapy in patients with advanced prostate cancer.

This study assessed whether baseline and short-term patient-reported quality of life (QOL) differs in patients with symptomatic metastatic prostate cancer undergoing palliative management using opioids, nonsteroidal anti-inflammatory agents (NSAIDs), (89)strontium chloride ((89)Sr), and samarium-lexidronam ((153)Sm). Males were grouped according to primary palliative intervention: opioids (n = 40), NSAIDs (n = 40), (89)Sr chloride (n = 25), and (153)Sm (n = 25). The short form of the self-administered McGill Pain Questionnaire was used to measure QOL at baseline, 4 and 8 weeks after initiation of treatment. Clinical data were collected from patients' medical records. Statistical analyses were conducted using descriptive methods and the Student t test. A significant increase in the sensory pain rating was observed in the patients treated by NSAIDs ([upward arrow]21%) and (89)Sr ([upward arrow]46%), whereas those treated by opioids ([downward arrow]27%) and (153)Sm ([downward arrow]27%) demonstrated a significant (P < 0.05) decrease in this subscore. There was a longitudinal decrease in QOL over time in patients treated by NSAIDs and (89)Sr as measured by the total pain rating score, whereas those treated with the other agents experienced improved QOL. This study demonstrates improvement in QOL achieved using (153)Sm, which is comparable to that achieved with the use of opioids during this observation interval.

Cost-utility analysis of the cyberknife system for metastatic spinal tumors.

OBJECTIVE: Using decision analysis, a cost-utility study evaluated the cost-effectiveness of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) in comparison to external beam radiation therapy in the treatment of metastatic spinal malignancies. METHODS: The published literature provided evidence on the effectiveness of the comparator interventions in the absence of primary outcomes data. Costs of care were derived from Centers for Medicare and Medicaid Services fee schedules. A Markov model was constructed from the payer perspective to simulate the outcomes of patients undergoing nonchemotherapeutic interventions for metastatic spinal tumors. Because cancer therapies bear significant health and economic consequences, the impact of treatment-related toxicities was integrated into the model. Given the terminal nature of these conditions and the limited life expectancy of the patient population, the time horizon for the analysis was limited to 12 months. RESULTS: Patients treated with CyberKnife SRS gained an additional net health benefit of 0.08 quality-adjusted life year; the calculated cost of CyberKnife SRS was $1933 less than external beam radiation therapy for comparable effectiveness. The incremental cost per benefit for this strategy ($41 500 per quality-adjusted life year) met payers' willingness-to-pay criteria. CONCLUSION: Cost-utility analysis demonstrated that CyberKnife SRS was a superior, cost-effective primary intervention for patients with metastatic spinal tumors compared with conventional external beam radiation therapy.

Comparative costs of treatment with epoetin alfa and darbepoetin alfa for anemia in the oncology and nephrology settings.

The presence of anemia adversely affects clinical- and patient-centered outcomes in patients whose health status is already compromised, such as those with cancer or chronic kidney disease. Treatment of anemia is an important component in the management of these diseases and has been shown to improve outcomes. The use of the erythropoietin-stimulating therapies epoetin alfa and darbepoetin alfa as alternatives to blood transfusion has demonstrated value in clinical trials, but both drugs are associated with high costs. Observational studies represent the next level of evaluation that can be used to evaluate and compare the costs and outcomes associated with each of these agents in actual clinical practice. Such studies, complemented by clinical trials and modeling, can help identify the least costly option and may characterize differences in effectiveness, so that payers can make informed decisions with regard to treatment and the appropriate use of these agents.

Dosing patterns, hematologic outcomes, and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia.

OBJECTIVE: Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting. METHODS: This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for > or = 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24-week study period. RESULTS: A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (> or = Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (> or = 11 g/dL) (p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24-week cumulative doses were EPO 279 336 +/- 68 302 units and DARB 1084 +/- 246 microg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = 3400 US dollars, DARB = 4726 US dollars; FSS: EPO = 1528 US dollars, DARB = 2379 US dollars). CONCLUSIONS: Extended dosing (Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39-56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.

Strategies for Reporting Evidence-Based Clinical Studies Involving Positron Imaging.

The objective of this investigation was to determine whether publications on positron imaging for lung cancer adhered to basic principles of data reporting and analysis according to the requirements established by payer organizations. The study sample consisted of 26 articles retrieved from the published literature for the interval 1980 to 1998. These articles were reviewed to assess the use and reporting of eight fundamental principles covering evidence-based data analysis that were formulated from payer-sponsored technology assessment program evaluations. These principles were derived from reviewing payer-sponsored assessments and reimbursement recommendations concerning diagnostic imaging technologies. The overall adherence to these basic principles was poor. The median number of principles to which articles adhered was two. In particular, the literature did not adequately include information about the role of imaging results in overall patient care, and, therefore, made any recommendations concerning the role of positron imaging in lung cancer patient management problematic. Strategies for publishing the results of positron imaging studies in the medical literature should include appropriate information that is required by payers for establishing reimbursement and clinical policies.

Design of Prospective Clinical Trials for Assessment of PET.

This article will briefly review measures of accuracy for diagnostic tests. We will present valid, methodologically rigorous prospective clinical trial design features that avoid bias and that can generate high-quality evidence on the diagnostic accuracy of PET and its impact on diagnostic decision-making and therapeutic efficacy. Knowledge of the principles of Evidence-based Medicine, and an understanding of the key elements of designing a methodologically rigorous, prospective clinical trial will permit avoidance of the previous study design limitations and weaknesses of the existing literature on diagnostic imaging modalities. Published results of studies that are valid, obtained rapidly, and generalizable, will provide important support for the paradigm shift away from informal, opinion-driven decision-making in health care, toward a process that is evidence-based, rationale and considerate of our available resources and their most effective use in patient care.

Reimbursement and Technology Assessment for Positron Imaging.

The lack of consistent reimbursement for positron imaging has hampered the growth of this modality, thereby denying patients access to this important technology. Reimbursement has improved dramatically over the past three to five years with the most significant step occurring in January, 1998, which is when Medicare reimbursement was approved for staging lung cancer and characterizing indeterminate pulmonary nodules. The decision to reimburse for positron imaging for oncologic applications would not have occurred if clinical data were not available, and if the clinical effectiveness of positron imaging were not validated through technology assessments conducted by qualified research organizations. Even with the reality of reimbursement, the process by which positron imaging studies are reimbursed needs to be explored and standardized. On the Medicare front, each Medicare carrier will need help from the positron imaging community in implementing the Medicare National Coverage Instructions. The rate of reimbursement for positron imaging is a constant concern, especially with the variation of positron imaging devices and their associated capital and operational costs. This article summarizes the process involved in reimbursement for positron imaging, i.e., contracting with third-party payers and obtaining the support of referring physicians for positron imaging. The process of technology assessment for new procedures is integral to the growth, development and acceptance of positron imaging procedures by government and private-payer entities. We have made a significant step forward in reimbursement, but there is tremendous work to be done in establishing the process of reimbursement for positron imaging.

Misoprostol Inhibits Polymethylmethacrylate-Stimulated Lysosomal Degranulation and IL-1 Release from Neutrophils.

Endoprosthetic orthopedic implants may loosen over time. The mechanism of this loosening process remains poorly understood. Wear debris sloughed from bone cement (polymethylmethacrylate, PMMA) and orthopedic implant materials (metal, ultrahigh-molecular-weight polyethylene) may stimulate inflammatory responses in phagocytic cells which populate the bone-implant interface (synovial-like membrane). This investigation aimed to determine whether the prostaglandin-E(1) (PGE(1)) analog misoprostol might modulate PMMA-stimulated phagocytic cell degranulation and the release of interleukins such as IL-1. Lysozyme and IL-1 release from PMMA-stimulated neutrophils in vitro were measured as approximately 0.07 &mgr;g per 10(6) cells per min and 4 pg per 10(6) cells per min, respectively. These rates decreased to 0.03 &mgr;g per 10(6) cells per min and 1.7 pg per 10(6) cells per min, respectively, after the addition of 50 nM misoprostol to the incubation medium. Misoprostol inhibited degranulation and cytokine release in a dose-dependent manner. Consequently, misoprostol modulates PMMA-stimulated inflammatory responses. These responses appear to be mediated by prostanoids, and the regulation of prostanoids at the bone-implant interface may modulate the release of inflammatory osteolytic mediators (PGE(2)) which contribute to implant loosening.