Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei.

AIMS: Papillary renal neoplasm with reverse polarity (PRNRP) is a newly documented rare tumour type. Its molecular pathological features have thus far been very little studied. METHODS AND RESULTS: There were 13 PRNRP cases including 3 The Cancer Genome Atlas (TCGA) cases and our 10 cases in this study. The 3 TCGA cases were found by a combined analysis of GATA3 mRNA expression levels and digital slides from the TCGA papillary renal cell carcinoma project. KRAS codon 12 mutations were identified in the three PRNRPs from TCGA. Of our 10 PRNRP cases, the mutations were also discovered using Sanger sequencing in seven (77.8%) of nine cases with available DNA, where KRAS p.G12V (n = 3), p.G12D (n = 2), p.G12R (n = 1) and p.G12C (n = 1) alterations were found. PRNRP shared similar gene expression profiles with renal distal tubules via an interprofile correlation analysis. Gene set enrichment analysis revealed that genes involved in 'KEGG aldosterone regulated sodium reabsorption' or 'hallmark apical surface' were enriched in PRNRP. Moreover, polarised immunostaining patterns for L1CAM and EMA in the distal tubule were maintained in PRNRP. CONCLUSIONS: These results imply that the tumour potentially originates from the distal tubule, especially from the cortical collecting duct, and probably retains its cell polarity, except for nuclear inversion. We therefore propose that oncocytic papillary renal neoplasm with inverted nuclei (OPRNIN) is a better name for this tumour type. OPRNIN is a kidney site-specific KRAS mutation neoplasm different from conventional papillary renal cell carcinoma.

Sleep apnea testing and outcomes in a large cohort of Medicare beneficiaries with newly diagnosed heart failure.

RATIONALE: Previous studies have demonstrated a high prevalence of sleep apnea (SA) in patients with chronic heart failure (HF), which is associated with higher rates of morbidity, mortality, and health care use. OBJECTIVES: To investigate the reported incidence, treatment, outcomes, and economic cost of SA in new-onset HF in a large U.S. database. METHODS: This retrospective cohort study used the 2003 to 2005 Medicare Standard Analytical Files and included subjects with newly diagnosed HF from the first quarter of 2004, without prior diagnosis of SA, stratified by testing, diagnosis, and treatment status. MEASUREMENTS AND MAIN RESULTS: Among a study population of 30,719 incident subjects with HF, only 1,263 (4%) were clinically suspected to have SA. Of these, 553 (2% of the total cohort) received SA testing, and 545 received treatment. After adjustment for age, sex, and comorbidities, subjects with HF who were tested, diagnosed, and treated for SA had a better 2-year survival rate compared with subjects with HF who were not tested (hazard ratio, 0.33 [95% confidence interval, 0.21-0.51], P < 0.0001). Similarly, among subjects who were tested and diagnosed, those who were treated had a better 2-year survival rate than those who were not treated (hazard ratio, 0.49 [95% confidence interval, 0.29-0.84], P = 0.009). CONCLUSIONS: In Medicare beneficiaries with HF, comorbid SA is most often not tested and consequently subjects are underdiagnosed and not treated. Meanwhile, in the few subjects in whom a diagnosis of SA is established and treatment is executed, survival improves significantly. These results support the importance of SA testing and treatment for patients newly diagnosed with HF.

NKX6-1 Is a Less Sensitive But Specific Biomarker of Chromophobe Renal Cell Carcinoma.

NKX6-1 is a transcription factor that plays a key role in the development, differentiation, and identity maintenance of beta cells of pancreatic islets. Although NKX6-1 expression has also been discovered in pancreatic well-differentiated neuroendocrine tumors (WDNETs) and duodenal WDNETs, its expression in chromophobe renal cell carcinoma (chRCC) is unexplored. Analysis of mRNA expression and immunohistochemistry of NKX6-1 was performed using the kidney cancer cohort from The Cancer Genome Atlas (TCGA) and paraffin-embedded whole-tissue slides from our 196 collected cases, including 48 chRCCs (43 classic and 5 eosinophilic subtypes), 24 renal oncocytomas (ROs), 46 clear cell renal cell carcinomas, 41 papillary renal cell carcinomas, 14 renal urothelial carcinomas, 7 low-grade oncocytic renal tumors (LOTs), 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. NKX6-1 expression was almost exclusively upregulated in chRCC at both the mRNA and protein levels compared with other renal tumors. NKX6-1 was immunohistochemically positive in 39 of 48 (81.3%) chRCCs, but negative in 46 clear cell renal cell carcinomas, 24 ROs, 7 low-grade oncocytic renal tumors, 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. Diffuse, moderate, and focal NKX6-1 staining were seen in 21, 4, and 14 of the 39 chRCCs, respectively. In contrast, NKX6-1 was focally positive in only 1 of 41 (2.4%) papillary renal cell carcinomas and 2 of 14 (14.3%) renal urothelial carcinomas. Therefore, the sensitivity and specificity of NKX6-1 staining were 81.3% and 98% for chRCC, respectively. In conclusion, NKX6-1 may be a novel potential marker for differentiating chRCC from other renal neoplasms, especially from RO.

Development of an activity-based costing model to evaluate physician office practice profitability.

OBJECTIVE: Newer treatment regimens for age-related macular degeneration have significantly affected traditional and non-traditional retinal services across all types of practice settings around the country as they seek to find a balance among delivering best patient care, keeping operating costs under control, and maintaining profitability. DESIGN: A systematic retrospective review of a multi-city, multi-physician retinal practice's accounting system to obtain data on revenues, expenses, and profit. Data reviewed were from practice management systems to obtain claims level data on clinical procedures across 7 primary activity centers: non-laser surgery, laser surgery, office visits, optical coherence tomography (OCT), non-OCT diagnostics, drugs and drug injections, and research. PARTICIPANTS: All treated patients from a retina practice from January 1, 2005, to December 31, 2007. METHODS: Retrospective claims data review from a multi-physician retina practice detailing Current Procedural Terminology and Healthcare Common Procedure Coding System procedures performed and billed, submitted charges, allowed charges, and net collections. Analyses were performed by an outside firm and verified by a risk advisory firm. MAIN OUTCOME MEASURES: Identifying practice efficiencies/inefficiencies as they relate to patient care. RESULTS: An elaborate analysis using activity-based costing (ABC) showed that increased office visits and OCT and non-OCT diagnostics had a significant negative impact on the practice's profit margins, whereas surgical procedures contributed to the majority of the practice's profit margins because of the lower operating costs associated with surgery. CONCLUSIONS: The practice was able to accommodate the demand in patient volume, medical retina services, and medical imaging with the advent of anti-vascular endothelial growth factor therapy and realized a seismic shift in operating costs. The practice attempted to deliver state-of-the-art patient care in a cost-effective manner, yet underwent a significant decline in its financial health.

Temporal changes in hospital costs for left ventricular assist device implantation.

BACKGROUND: A recent prospective, randomized controlled trial demonstrated that a continuous-flow (CF) left ventricular assist device (LVAD) resulted in improved survival at 12 and 24 months compared to a pulsatile-flow (PF) device. The current study examines the hospitalization costs associated with treatment of New York Heart Failure Class IV patients when implanted with a CF LVAD and compares them to previously reported costs of a PF LVAD in the same population. METHODS: Hospital billing data were analyzed for CF LVAD patients in the HeartMate II Destination Therapy trial to determine costs associated with the implantation admission. Hospital charges were converted to costs using hospital specific cost-to-charge ratios. Hospital costs were evaluated based on patient outcomes and compared to previously reported results from patients who received a pulsatile flow LVAD in Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Multivariate models were created to determine the primary determinates of cost. RESULTS: Hospital bills were available for 83 CF and 52 PF LVAD patients. Hospital length of stay and in-hospital mortality were lower in the CF cohort. Inflation-adjusted hospital costs were significantly lower for CF patients compared to PF patients (mean: $193,812 vs. $384,260, p < 0.001). Clinical factors that strongly influenced hospitalization costs included bleeding, respiratory failure, and infection. CONCLUSIONS: There has been a 50% reduction in the hospitalization cost associated with LVAD implantation since 2001. Improvements in operative technique and postoperative management appear to play critical roles in the observed cost reduction.

FOXI1 expression in chromophobe renal cell carcinoma and renal oncocytoma: a study of The Cancer Genome Atlas transcriptome-based outlier mining and immunohistochemistry.

FOXI1 is a forkhead family transcription factor that plays a key role in differentiation and functional maintenance for the renal intercalated cell (IC). The diagnostic utility of FOXI1 is rarely studied thus far. Comparative analyses of FOXI1 mRNA expression in normal kidney tissue and different renal neoplasms including chromophobe renal cell carcinoma (chRCC), renal oncocytoma (RO), and other renal cell carcinomas were conducted using transcriptomic data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and single-cell RNA-seq datasets, in combination with integrative analyses using mutant data, karyotype data, and digital slides for cases with anomalous FOXI1 expression in TCGA. Formalin-fixed, paraffin-embedded whole-tissue slides of varied primary renal neoplasms (n = 367) were subjected to FOXI1 staining for validating FOXI1 transcription levels. We confirmed that FOXI1 was significantly upregulated at mRNA levels in ICs, chRCCs, and ROs compared with other renal tubule cell and renal cell carcinoma subtypes. Furthermore, most of the cases with FOXI1 expression outliers were misclassified in the TCGA kidney cancer project. An underlying novel entity with frequent mutations involved in the mTOR pathway was also found. FOXI1 immunoreactivity was consistently noted in ICs of the distal nephron. FOXI1 staining was positive in 85 of 93 chRCCs and 13 of 18 ROs, respectively. FOXI1 staining was not seen in renal neoplasms (n = 254) derived from non-ICs. In conclusion, FOXI1 expression in normal kidney tissue is restricted to ICs. This cell type-specific expression is retained during neoplastic transformation from ICs to chRCCs or ROs. FOXI1 is thereby a potential biomarker of IC-related tumors.

Costs and rehabilitation use of stroke survivors: a retrospective study of Medicare beneficiaries.

OBJECTIVE: To examine mortality, costs, and rehabilitation use in patients with stroke and stroke-related hemiparesis during a 4-year period following stroke onset. METHOD: This study was a retrospective, longitudinal claims analysis. Patients newly diagnosed with stroke and discharged from the hospital were identified from a 5% random sample of Medicare beneficiaries. Mortality, total Medicare costs, use of rehabilitation, and associated costs in stroke survivors with or without hemiparesis were the main outcome measures. RESULTS: Out of 4,604 newly diagnosed stroke patients, 1,166 developed hemiparesis. The 4-year mortality rate was significantly higher in the hemiparesis cohort than the nonhemiparesis cohort (55.2% vs. 47.5%; p < .01). The average Medicare cost per patient over the 4-year period was $77,143 for the hemiparesis cohort and $53,319 for the nonhemiparesis cohort (p < .01). A significantly higher proportion of patients in the hemiparesis cohort received rehabilitation than in the nonhemiparesis cohort (84% vs. 36% in Year 1, 30% vs. 10% in Year 2, 21% vs. 9% in Year 3, 16% vs. 7% in Year 4). Among patients who received rehabilitation, costs were significantly higher for the hemiparesis cohort ($17,680) than for the nonhemiparesis cohort ($7,841) in the fi rst year. While most rehabilitation costs for the hemiparesis cohort were incurred in the hospital inpatient setting in the fi rst year, the cost burden shifted to skilled nursing facilities and home health agencies in the following 3 years. CONCLUSIONS: Hemiparesis following stroke onset contributes to a higher mortality rate and higher Medicare costs in both the short and long term.

Cost-effectiveness analysis of antifungal prophylaxis in patients undergoing hematopoietic stem cell transplantation.

BACKGROUND: Micafungin sodium is indicated for the prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation (HSCT). One Phase III, multi-institutional, randomized, doubleblind comparative trial involving 882 adult and pediatric patients found that micafungin was more effective, in terms of significantly lower rates of systemic fungal infections and empiric antifungal therapy (AFT), than fluconazole as antifungal prophylaxis during the neutropenic phase following HSCT. Thus, despite the higher cost of micafungin versus fluconazole, micafungin prophylaxis may be associated with reduced costs. OBJECTIVE: The aim of this analysis was to determine the cost-effectiveness of micafungin prophylaxis compared with fluconazole prophylaxis in patients undergoing HSCT. METHODS: Efficacy data were taken from the clinical study. The economic analysis was conducted from the hospital perspective, using costs incurred from admission through discharge. Each of the patients was assigned costs and effectiveness based on outcomes data from the clinical study. Published literature was used to estimate hospital costs associated with HSCT and prophylaxis, empiric AFT, and treatment of a probable or proven Candida or Aspergillus infection. Mean costs and effectiveness were calculated in each treatment group. To test the variability of the results using repeated sampling, a bootstrapping analysis was also conducted, with 1,000 simulations of random samples of 100 patients from each treatment group. If appropriate to describe the results, incremental cost effectiveness ratios were calculated, and sensitivity analyses were conducted by varying components of cost. RESULTS: This analysis included data from 882 patients (527 males, 355 females; micafungin, 425 patients, mean age, 43.2 years [range, 0.6-73.0 years]; fluconazole, 457 patients, mean age, 41.9 years [range, 0.6-71.0 years]). Total hospital costs per patient were USD121,098 and USD124,957 in micafungin and fluconazole recipients, respectively-a difference of USD3,859. The bootstrapping analysis found that micafungin prophylaxis was cost-saving in 72.4% of the samples compared with 9.2% with fluconazole prophylaxis. Sensitivity analyses on estimated hospital costs found that micafungin was a cost-effective therapy. CONCLUSION: In this analysis of data from a clinical study in adults and children undergoing HSCT, micafungin prophylaxis was associated with reduced hospital costs, and resultant total patient costs, compared with fluconazole prophylaxis.

A multiple-domain framework of clinical, economic, and patient-reported outcomes for evaluating benefits of intervention in atopic dermatitis.

Atopic dermatitis (AD) increases health care utilization, affects patient quality of life, places a burden on caregivers, decreases patient/parent productivity, and adds to health care costs. Few studies have examined the effect of specific treatment modalities across a variety of AD-related outcomes. This prospective, multicenter, open-label longitudinal study of adult and pediatric patients with moderate to severe AD was conducted to evaluate the effect of a specific therapeutic intervention on AD-related outcomes over a period of 6 months. Surveys collected physician clinical assessments and patient- and caregiver-reported data across the following domains: clinical outcome, health care utilization/costs, quality of life, physical appearance, productivity/absenteeism, and medication compliance. This study is intended to help guide future research efforts on the net costs and benefits of different interventions across a diverse set of domains and in larger populations.

Efficacy and economics of topical calcineurin inhibitors for the treatment of atopic dermatitis.

Atopic dermatitis is a chronic, relapsing inflammatory skin disease that frequently affects infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5-20% of the pediatric population. Studies have shown that atopic dermatitis is associated with considerable economic costs and decreased quality of life. There is no proven curative therapy at present for atopic dermatitis; first-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of histamine H1 receptor antagonists (antihistamines) and oral antibacterials as appropriate. Topical corticosteroids, while effective in many patients, carry the concern of local and systemic adverse effects. As a result, physicians and patients are reluctant to utilize stronger topical corticosteroids in certain areas of the body and for prolonged periods of time. The purpose of this article is to review the efficacy and economics of topical calcineurin inhibitors in the treatment of atopic dermatitis. This new class of agents (specifically tacrolimus ointment and pimecrolimus cream) represents an exciting advance in the treatment of atopic dermatitis. Clinical data show that topical calcineurin inhibitors are effective and do not cause the adverse effects associated with topical corticosteroids. Several studies have provided evidence that topical calcineurin inhibitors positively affect the quality of life of patients and their caregivers. Compared with branded topical corticosteroids and previous standards of care, topical calcineurin inhibitors appear to be a cost-effective treatment option. Drawing comparisons between tacrolimus and pimecrolimus is difficult because definitive head-to-head comparative studies involving these drugs have not been conducted.

Prolonged length of stay associated with air leak following pulmonary resection has a negative impact on hospital margin.

BACKGROUND: Protracted hospitalizations due to air leaks following lung resections are a significant source of morbidity and prolonged hospital length of stay (LOS), with potentially significant impact on hospital margins. This study aimed to evaluate the relationship between air leaks, LOS, and financial outcomes among discharges following lung resections. MATERIALS AND METHODS: The Medicare Provider Analysis and Review file for fiscal year 2012 was utilized to identify inpatient hospital discharges that recorded International Classification of Diseases (ICD-9) procedure codes for lobectomy, segmentectomy, and lung volume reduction surgery (n=21,717). Discharges coded with postoperative air leaks (ICD-9-CM codes 512.2 and 512.84) were defined as the air leak diagnosis group (n=2,947), then subcategorized by LOS: 1) <7 days; 2) 7-10 days; and 3) ≥11 days. Median hospital charges, costs, payments, and payment-to-cost ratios were compared between non-air leak and air leak groups, and across LOS subcategories. RESULTS: For identified patients, hospital charges, costs, and payments were significantly greater among patients with air leak diagnoses compared to patients without (P<0.001). Hospital charges and costs increased substantially with prolonged LOS, but were not matched by a proportionate increase in hospital payments. Patients with LOS <7, 7-10, and ≥11 days had median hospital charges of US $57,129, $73,572, and $115,623, and costs of $17,594, $21,711, and $33,786, respectively. Hospital payment increases were substantially lower at $16,494, $16,307, and $19,337, respectively. The payment-to-cost ratio significantly lowered with each LOS increase (P<0.001). Higher inpatient hospital mortality was observed among the LOS ≥11 days subgroup compared with the LOS <11 days subgroup (P<0.001). CONCLUSION: Patients who develop prolonged air leaks after lobectomy, segmentectomy, or lung volume reduction surgery have the best clinical and financial outcomes. Hospitals experience markedly lower payment-to-cost ratios as LOS increases. Interventions minimizing air leak or allowing outpatient management will improve financial performance and hospital margins for lung surgery.

The economics of topical immunomodulators for the treatment of atopic dermatitis.

Atopic dermatitis is a common, chronic, relapsing inflammatory skin disease frequently affecting infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5--20% of the paediatric population. First-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of antihistamines and oral antibacterials. Topical corticosteroids improve the lesions of atopic dermatitis; however, concern on the part of physicians and patients regarding adverse effects has led to reluctance to utilise topical corticosteroids early and especially for prolonged periods. Topical immunomodulators (TIMs), including tacrolimus ointment and pimecrolimus cream, were recently introduced for the treatment of atopic dermatitis. Clinical data show that TIMs are effective in atopic dermatitis, yet do not cause the significant adverse effects associated with topical corticosteroids. Questions remain regarding the place of TIMs as a treatment for atopic dermatitis and how to use them most effectively, from both therapeutic and pharmacoeconomic standpoints. Specifically, two major issues remain unresolved: (i) how TIMs measure up to other therapies, especially topical corticosteroids; and (ii) how members of the TIM drug class compare against each other. Previous research has established that atopic dermatitis has a significant impact on quality of life (QOL) and carries a substantial economic burden. Some studies have also measured the utility of various atopic dermatitis disease states. While there is a need for further research, early economic studies provide evidence that TIMs positively affect the QOL of patients and families. In certain patients, TIMs may be cost effective and have an acceptable incremental cost utility compared with topical corticosteroids.Making cost-effectiveness comparisons between tacrolimus and pimecrolimus is challenging because there are limited head-to-head comparative data. Given currently available efficacy data, the results of one study suggest that tacrolimus may be more cost effective than pimecrolimus in paediatric patients with moderate atopic dermatitis. The full economic and QOL benefits of both agents are yet to be completely understood. The studies reviewed herein are the first to delineate the pharmacoeconomic benefits of TIMs in atopic dermatitis, and lay the foundation for future analyses. TIMs represent an exciting advance in the treatment of atopic dermatitis. Additional research will help determine the proper place of TIMs among the current array of therapeutic options for atopic dermatitis.

Look beyond financial conflicts of interest in evaluating industry-academia collaborations in burden-of-illness and outcomes research studies in dermatology.

Financial relationships exist among industry, scientific investigators, and academic medical centers. These relationships can foster research in the basic sciences, clinical trials, health economics evaluations, and other outcomes assessment studies. To govern the conduct of burden-of-illness and outcomes research studies involving collaborations between industry and academia, we propose voluntary standards related to: 1) the development of and adherence to standards for research conduct and reporting; 2) disclosure, discussion, and management of potential impacts of financial conflicts of interest; and 3) transparency in research methods and open access to study results.

Validation of expert opinion in identifying comorbidities associated with atopic dermatitis/eczema.

BACKGROUND: The use of expert opinion is widespread in economic studies of healthcare utilisation; however, few studies have attempted to assess the validity of assumptions derived from such sources. OBJECTIVE: To examine the use of such expert opinion in determining comorbidities associated with atopic dermatitis/eczema (AD/E), which were assessed as part of a recent third-party payer cost-of-illness study. DESIGN: To identify the disease-related comorbidities that would represent costs associated with AD/E, physicians on an expert panel were asked individually and then collectively to group all International Classification of Diseases, 9(th) Edition-Clinical Modification (ICD-9-CM) diagnosis codes as 'most likely', 'possibly' or 'definitely not' related to the costs of identifying and treating patients with AD/E. Claims representing $US464 million in payer reimbursements from nearly 125 000 patients with AD/E were identified within two separate claims databases (1997 values). Over 850 ICD-9-CM diagnosis codes were identified in the first-listed position from these claims. For each group of 'most likely', 'possibly' and 'definitely not' related diagnosis codes, prevalence rates were compared within AD/E and non-AD/E populations from the two historical payer claims databases. Adjusted and non-adjusted odds ratios were calculated by comparing prevalence rates between AD/E and non-AD/E patients in the same payer population. RESULTS: The mean prevalence rate of any diagnosis code in the AD/E population was 0.65 +/- 1.82% (SD) with a mean odds ratio of 1.81 +/- 0.96. Comorbidities considered by the expert panel 'most likely' to be associated with AD/E had higher prevalence rates (3.28 +/- 3.63%) and odds ratios (2.14 +/- 1.14). Comorbidities considered to be 'possibly' related to AD/E had prevalence rates and odds ratios of 3.01 +/- 5.06% and 1.84 +/- 0.82, respectively. Comorbidities considered to be 'definitely not' related to AD/E had the lowest prevalence rates (0.45 +/- 1.09%) and odds ratios (1.80 +/- 0.97). CONCLUSIONS: Comparing the result of consensus panels with actual claims histories validated the use of expert opinion in determining comorbidities associated with AD/E. Expert opinion yielded valid results in terms of identifying comorbidities that manifested frequently and disproportionately in the AD/E population. Limited statistical measurements of comorbidities would have been less specific than expert opinion. Future cost-of-illness studies should consider alternative data sources and methodologies to enhance the validity and importance of expert opinion and to corroborate their findings.

Cost-effectiveness analysis of Mammostrat® compared with Oncotype DX® to inform the treatment of breast cancer.

PURPOSE: To compare the cost-effectiveness of the tumor subtyping assays Mammostrat® and Oncotype DX® for assessing risk of recurrence in early-stage breast cancer and the potential benefit of adjuvant chemotherapy. METHODS: Cost-effectiveness analysis from a US third-party payer perspective. A 10 year Markov model was developed to estimate costs and effects of using each method of risk assessment. The percentages of patients assessed as high, moderate, or low risk were obtained from multicenter, prospective, randomized controlled trials. The analysis simulated the experience of women progressing through various model states representing clinical treatments and subsequent disease. Published recurrence data for Mammostrat® were adjusted appropriately to account for differences between definitions and samples of Oncotype DX® and Mammostrat® in the original clinical trials. Cost and utility data were obtained from previously published studies. Sensitivity analyses examined how base-case results might differ when input values and assumptions varied. RESULTS: Base-case costs for women assessed using Mammostrat® were $15,782, compared with $18,051 for women assessed with Oncotype DX®. Thus, cost savings of $2,268 resulted from using Mammostrat®. Both Mammostrat® and Oncotype DX® resulted in similar life years (9.880 and 9.882) and quality-adjusted life years (7.935 and 7.940), respectively. Sensitivity analyses demonstrated that the assumptions made about recurrence are the key drivers of model results. DISCUSSION: Cost savings associated with the use of Mammostrat® instead of Oncotype DX® are largely due to the difference in cost between the two tests. Since survival and quality-adjusted life years were similar using either assay, Mammostrat® has economic advantages for women with early-stage breast cancer.

Cost of placement and complications associated with osseointegrated bone-conducting hearing prostheses: a retrospective analysis of medicare billing data.

OBJECTIVE: To report the cost of placement and complications related to osseointegrated bone-conducting hearing prostheses (OBHPs) in a Medicare population. MATERIALS AND METHODS: We performed a retrospective analysis of nationwide Medicare claims data for operative and nonoperative complications associated with the placement of percutaneous OBHPs between the first quarter of 2007 and the second quarter of 2009 for which there were 6 subsequent quarters of follow-up. We used Medicare Standard Analytical Files (SAF), which contain a 5% random sample of Medicare fee-for-service beneficiaries, excluding those that also were enrolled in a managed-care organization. RESULTS: We identified 118 patients who had OBHPs placed in the requisite period. Their complication billing data were analyzed for the six-quarters after initial placement. Seventy patients (59%) had no billing codes for complications or repeat procedures after receiving the implant, whereas 48 patients (41%) had such codes. The total adjusted mean cost with repeat/revision operations or complications was $7,812 per patient compared with $6,733 for those without these issues, an increase of $1,079 or 16%. DISCUSSION: We estimate that complications associated with the implantation of percutaneous OBHPs led to $417,616 in additional costs in the entire Medicare fee-for-service population during the study period and that the total cost of placement of these devices together with the cost of their complications totaled $6,789,248. In conclusion, the Medicare SAF database suggests that complications associated with OBHP increased the overall cost of placement by 16%. Like all surgical procedures, these complications and their associated costs should be taken into account when considering treatment options for patients who experience hearing loss.

New thinking on clinical utility: hard lessons for molecular diagnostics.

OBJECTIVES: To describe 5 basic requirements for planning, implementing, and proving clinical utility for diagnostic tests, drawing on recent reimbursement decisions. STUDY DESIGN: Review of recent reimbursement decisions by Palmetto GBA's MolDx program, and summary of lessons learned. METHODS: Qualitative review of publicly available coverage and reimbursement decisions, plus our industry experience. RESULTS: Lack of clinical utility data is the most commonly cited reason for why companies fail to receive favorable coverage and reimbursement decisions in this rapidly growing industry. We summarize 5 strategies to establish clinical utility and secure coverage with reimbursement: 1) understanding that outcomes are hard to capture, but that clinical behavior change is always proximate to outcomes change, 2) starting clinical utility studies early, 3) learning from successes and failures, 4) determining clinical utility with rigorous science, and 5) understanding that clinical utility studies may need to involve private payers and providers from the start. CONCLUSIONS: Coverage and reimbursement are shifting from relatively low entry barriers to higher, evidence-based barriers that will require test developers to generate evidence of the net clinical benefits before widespread clinical use will occur. Concerted, early investment in rigorously designed clinical utility studies is necessary.

Cost effectiveness analysis of a next generation risk assessment score for cardiovascular disease.

OBJECTIVES: The goal of this study is to determine the cost-effectiveness of MIRISK VP, a next generation coronary heart disease risk assessment score, in correctly reclassifying and appropriately treating asymptomatic, intermediate risk patients. STUDY DESIGN: A Markov model was employed with simulated subjects based on the Multi-Ethnic Study of Atherosclerosis (MESA). This study evaluated three treatment strategies: (i) practice at MESA enrollment, (ii) current guidelines, and (iii) MIRISK VP in MESA. METHODS: The model assessed patient healthcare costs and outcomes, expressed in terms of life years and quality-adjusted life years (QALYs), over the lifetime of the cohort from the provider and payer perspective. A total of 50,000 hypothetical individuals were used in the model. A sensitivity analysis was conducted (based on the various input parameters) for the entire cohort and also for individuals aged 65 and older. RESULTS: Guiding treatment with MIRISK VP leads to the highest net monetary benefits when compared to the 'Practice at MESA Enrollment' or to the 'Current Guidelines' strategies. MIRISK VP resulted in a lower mortality rate from any CHD event and a modest increase in QALY of 0.12-0.17 years compared to the other two approaches. LIMITATIONS: This study has limitations of not comparing performance against strategies other than the FRS, the results are simulated as with all models, the model does not incorporate indirect healthcare costs, and the impact of patient or physician behaviors on outcomes were not taken into account. CONCLUSIONS: MIRISK VP has the potential to improve patient outcomes compared to the alternative strategies. It is marginally more costly than both the 'Practice at MESA Enrollment' and the 'Current Guidelines' strategies, but it provides increased effectiveness, which leads to positive net monetary benefits over either strategy.

Transition to a novel advanced integrated vitrectomy platform: comparison of the surgical impact of moving from the Accurus vitrectomy platform to the Constellation Vision System for microincisional vitrectomy surgery.

BACKGROUND: Microincisional vitrectomy surgery (MIVS) is the current standard surgical approach for pars plana vitrectomy. Historically, the most common surgical platform for vitrectomy surgery, since its introduction in 1997, has been the Accurus vitrectomy system. Recent introduction of the next generation of vitrectomy platforms has generated concerns associated with transitioning to new technology in the operating room environment. This study compared, in a matched fashion, surgical use of the Accurus vitrectomy system and the next generation Constellation Vision System to evaluate surgical efficiencies, complications, and user perceptions of this transition. METHODS: Electronic health records were abstracted as a hospital quality assurance activity and included all vitreoretinal surgical procedures at the Bascom Palmer Eye Institute, Anne Bates Leach Eye Hospital, during two discrete 12-month time periods. These two periods reflected dedicated usage of the Accurus (June 2008-May 2009) and Constellation Vision (July 2009-June 2010) systems. Data were limited to a single surgeon and evaluated for operating room (OR) total time usage/day, OR case time/case, and OR surgical time/case. Further analysis evaluated all patients undergoing combined MIVS and clear cornea phacoemulsification/intraocular lens (IOL) implantation during each individual time period to determine the impact of the instrumentation on these parameters. All records were evaluated for intraoperative complications. RESULTS: Five hundred and fourteen eligible patients underwent MIVS during the 2-year study windows, with 281 patients undergoing surgery with the Accurus system and 233 patients undergoing surgery with the Constellation system. Combined MIVS and phacoemulsification with IOL implantation was performed 141 times during this period with the Accurus and 158 times during the second study period with the Constellation. Total number of patients operated per day increased from 7.55 with Accurus to 8.53 with Constellation. Surgical room time decreased from 56 minutes with Accurus to 52 minutes with Constellation, and procedure time decreased from 35 minutes with Accurus to 31 minutes with Constellation (P < 0.004). Combined MIVS/phacoemulsification surgery saw similar declines in surgical room time and procedure time (P < 0.001). Subset analysis of procedures limited by case number per day (eg, four cases/day, five cases/day, six cases/day, and seven or more cases/day) showed similar outcomes with a decrease in surgical room time and procedure time. No increases in surgery-related complications were noted by quality assurance review during these time periods. DISCUSSION: Transitioning to advanced surgical technology is a complex issue for the surgeon, the hospital team, and the hospital administration. This study documents improvement in three significant measures of surgical efficiency: operative number of patients per day, operative room time, and surgical procedure time that reflect the positive impact of the novel, combined, integrated, posterior and anterior, ophthalmologic surgical platform of the Constellation Vision System. These data are imperative to evaluate the impact of transition from one surgical platform to another. During this transition, hospital quality assurance review and surgeon evaluation of operative complications showed no increased concerns for the shift from the Accurus to the Constellation Vision System surgical platform. Further, both operative staff and surgeons felt that the transition to the Constellation was not associated with increases in difficulty with setup, turnover, or use and that the Constellation decreased safety concerns for surgical usage. Ultimately, in this case, new technology benefited the surgeon, the patient, and the hospital.

Cost-effectiveness analysis of continuous-flow left ventricular assist devices as destination therapy.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) have become the dominant devices for mechanical circulatory support, but their cost-effectiveness is undetermined. This study assessed the cost-effectiveness of continuous-flow devices for destination therapy versus optimal medical management in advanced heart failure and compared the results with previous estimates for pulsatile devices. METHODS AND RESULTS: A Markov model was developed to assess cost-effectiveness. Survival, hospitalization rates, quality of life, and cost data were obtained for advanced heart failure patients treated medically or with a continuous-flow LVAD. Rates of clinical outcomes for all patients were obtained from clinical trial databases. Medicare prospective payments were used to estimate the cost of heart failure admissions. The cost of LVAD implantation was obtained prospectively from hospital claims within a clinical trial. Compared with medically managed patients, continuous-flow LVAD patients had higher 5-year costs ($360 407 versus $62 856), quality-adjusted life years (1.87 versus 0.37), and life years (2.42 versus 0.64). The incremental cost-effectiveness ratio of the continuous-flow device was $198 184 per quality-adjusted life year and $167 208 per life year. This equates to a 75% reduction in incremental cost-effectiveness ratio compared with the $802 700 per quality-adjusted life year for the pulsatile-flow device. The results were most sensitive to the cost of device implantation, long-term survival, cost per rehospitalization, and utility associated with patients' functional status. CONCLUSIONS: The cost-effectiveness associated with continuous-flow LVADs for destination therapy has improved significantly relative to the pulsatile flow devices. This change is explained by significant improvements in survival and functional status and reduction in implantation costs.