Association of ACO Shared Savings Success and Serious Illness Spending.

EXECUTIVE SUMMARY: Accountable care organizations (ACOs) need confidence in their return on investment to implement changes in care delivery that prioritize seriously ill and high-cost Medicare beneficiaries. The objective of this study was to characterize spending on seriously ill beneficiaries in ACOs with Medicare Shared Savings Program (MSSP) contracts and the association of spending with ACO shared savings. The population included Medicare fee-for-service beneficiaries identified with serious illness (N = 2,109,573) using the Medicare Master Beneficiary Summary File for 100% of ACO-attributed beneficiaries linked to MSSP beneficiary files (2014-2016). Lower spending for seriously ill Medicare beneficiaries and risk-bearing contracts in ACOs were associated with achieving ACO shared savings in the MSSP. For most ACOs, the seriously ill contribute approximately half of the spending and constitute 8%-13% of the attributed population. Patient and geographic (county) factors explained $2,329 of the observed difference in per beneficiary per year spending on seriously ill beneficiaries between high- and low-spending ACOs. The remaining $12,536 may indicate variation as a result of potentially modifiable factors. Consequently, if 10% of attributed beneficiaries were seriously ill, an ACO that moved from the worst to the best quartile of per capita serious illness spending could realize a reduction of $1,200 per beneficiary per year for the ACO population overall. Though the prevalence and case mix of seriously ill populations vary across ACOs, this association suggests that care provided for seriously ill patients is an important consideration for ACOs to achieve MSSP shared savings.

Variation in Specialty Outpatient Care Patterns in the Medicare Population.

BACKGROUND: Multiple payment reform efforts are under way to improve the value of care delivered to Medicare beneficiaries, yet few directly address the interface between primary and specialty care. OBJECTIVE: To describe regional variation in outpatient visits for individual specialties and the association between specialty physician-specific payments and patient-reported satisfaction with care and health status. DESIGN: Retrospective cross-sectional study. PATIENTS: A 20 % random sample of Medicare fee-for-service beneficiaries in 2012. MAIN MEASURES: Regions were grouped into quartiles of specialist index, defined as the observed/expected regional likelihood of having an outpatient visit to a specialist, for ten common specialties, adjusting for age, sex, and race. Outcomes were per capita specialty-specific physician payments and Medicare Current Beneficiary Survey responses. KEY RESULTS: The proportion of beneficiaries seeing a specialist varied the most for endocrinology and gastroenterology (3.7- and 3.9-fold difference between the highest and lowest quartiles, respectively) and least for orthopedics and urology (1.5- and 1.7-fold difference, respectively). Multiple analyses suggested that this variation was not explained by prevalence of disease. Average specialty-specific payments were strongly associated with the likelihood of visiting a specialist. Differences in per capita payments from lowest (Q1) to highest quartiles (Q4) were greatest for cardiology ($89, $135, $172, $251) and dermatology ($46, $64, $82, $124). Satisfaction with overall care (median [interquartile range] across specialties: Q1, 93.3 % [92.6-93.7 %]; Q4, 93.1 % [92.9-93.2 %]) and self-reported health status (Q1, 37.1 % [36.9-37.7 %]; Q4, 38.2 % [37.2-38.4 %]) was similar across quartiles. Satisfaction with access to specialty care was consistently lower in the lowest quartile of specialty index (Q1, 89.7 % [89.2-91.1 %]; Q4, 94.5 % [94.4-94.8 %]). CONCLUSIONS: Substantial regional variability in outpatient specialist visits is associated with greater payments with limited benefits in terms of patient-reported satisfaction with care or reported health status. Reducing outpatient physician visits may represent an important opportunity to improve the efficiency of care.

Comparison of breast cancer risk in women with and without systemic lupus erythematosus in a Medicare population.

Studies have suggested a decreased breast cancer risk in women with systemic lupus erythematosus. However, these studies enrolled younger patients identified primarily from lupus clinics. We compared the 5-year incidence of breast cancer among women with and without a diagnosis of SLE in a large population-based study of Medicare beneficiaries. We used a 20 % sample to create a cohort of 3,670,138 women from 2006 Medicare claims data with and without SLE at baseline. The study had 80 % power to detect whether the 5-year breast cancer incidence in the SLE cohort was 13 % higher or lower than the non-SLE cohort. Of the 18,423 women with SLE, 21 % were African American and 53 % were ≥65 years. The absolute age-adjusted risk for breast cancer in women with SLE was 2.23 (95 % CI 1.94-2.55) and 2.14 (95 % CI 1.96-2.34) in controls per 100 women. The overall absolute age and race adjusted incidence rate was 1.04 (95 % CI 0.90-1.21). Among women with SLE from "Others" (Hispanic, Native American, and/or Asian), the age-adjusted risk for breast cancer was 2.44 per 100 women (95 % CI 1.07-2.18), and age-adjusted incidence rate was 1.52 (95 % CI 1.07-2.18). In contrast to prior clinic-based studies, this population-based cohort study showed that the risk of breast cancer in women with SLE was not lower than in women without SLE. Women with SLE should follow routine breast cancer screening recommendations for their age group to avoid delay in diagnosis, because the presence of SLE may affect selection of early breast cancer therapies.

Design, synthesis of diaminopyrimidine inhibitors targeting IgE- and IgG-mediated activation of Fc receptor signaling.

Using cultured human mast cells (CHMC) the optimization of 2,4-diaminopyrimidine compounds leading to 22, R406 is described. Compound 22 is a potent upstream inhibitor of mast cell degranulation and its mechanism of action is via inhibition of Syk kinase. Compound 22 has significant activity in inhibiting both IgE- and IgG-mediated activation of Fc receptor (FcR) in mast cells and basophils, and in addition inhibits Syk kinase-dependent activity of FcR-mediated activation of monocytes, macrophages, neutrophils, and B cell receptor (BCR)-mediated activation of B lymphocytes. Overall, the biological activity of 22 suggests that it has potential for application as a novel therapeutic for the treatment of an array of autoimmune maladies and hematological malignancies.

Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.

Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined.

R723, a selective JAK2 inhibitor, effectively treats JAK2V617F-induced murine myeloproliferative neoplasm.

The activating mutations in JAK2 (including JAK2V617F) that have been described in patients with myeloproliferative neoplasms (MPNs) are linked directly to MPN pathogenesis. We developed R723, an orally bioavailable small molecule that inhibits JAK2 activity in vitro by 50% at a concentration of 2nM, while having minimal effects on JAK3, TYK2, and JAK1 activity. R723 inhibited cytokine-independent CFU-E growth and constitutive activation of STAT5 in primary hematopoietic cells expressing JAK2V617F. In an anemia mouse model induced by phenylhydrazine, R723 inhibited erythropoiesis. In a leukemia mouse model using Ba/F3 cells expressing JAK2V617F, R723 treatment prolonged survival and decreased tumor burden. In V617F-transgenic mice that closely mimic human primary myelofibrosis, R723 treatment improved survival, hepatosplenomegaly, leukocytosis, and thrombocytosis. R723 preferentially targeted the JAK2-dependent pathway rather than the JAK1- and JAK3-dependent pathways in vivo, and its effects on T and B lymphocytes were mild compared with its effects on myeloid cells. Our preclinical data indicate that R723 has a favorable safety profile and the potential to become an efficacious treatment for patients with JAK2V617F-positive MPNs.

Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation.

The metabolism of the spleen tyrosine kinase inhibitor N4-(2,2-dimethyl-3-oxo-4-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethyoxyphenyl)-2,4-pyrimidinediamine (R406) and its oral prodrug N4-(2,2-dimethyl-4-[(dihydrogenphosphonoxy)methyl]-3-oxo-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethyoxyphenyl)-2,4-pyrimidinediamine disodium hexahydrate (R788, fostamatinib) was determined in vitro and in humans. R788 was rapidly converted to R406 by human intestinal microsomes, and only low levels of R788 were observed in plasma of human subjects after oral administration of (14)C-R788. R406 was the major drug-related compound in plasma from human subjects, and only low levels of metabolites were observed in plasma. The plasma metabolites of R406 were identified as a sulfate conjugate and glucuronide conjugate of the para-O-demethylated metabolite of R406 (R529) and a direct N-glucuronide conjugate of R406. Elimination of drug-related material into the urine accounted for 19% of the administered dose, and the major metabolite in urine from all the human subjects was the lactam N-glucuronide of R406. On average, 80% of the total drug was recovered in feces. Two drug-related peaks were observed; one peak was identified as R406, and the other peak was identified as a unique 3,5-benzene diol metabolite of R406. The 3,5-benzene diol metabolite appeared to result from the subsequent O-demethylations and dehydroxylation of R529 by anaerobic gut bacteria because only R529 was converted to this metabolite after the in vitro incubation with human fecal samples. These data indicate that the major fecal metabolite of R406 observed in humans is a product of a hepatic cytochrome P450-mediated O-demethylation and subsequent O-demethylations and dehydroxylation by gut bacteria.

Prospective or retrospective ACO attribution matters for seriously ill patients.

OBJECTIVES: Since 2019, the Medicare Shared Savings Program (MSSP) has allowed accountable care organizations (ACOs) to choose either retrospectively or prospectively attributed ACO populations. To understand how ACOs' choice of attribution method affects incentives for care among seriously ill Medicare beneficiaries, this study compares beneficiary characteristics and Medicare per capita expenditures between prospective and retrospective ACO populations. STUDY DESIGN: This retrospective, cross-sectional analysis describes survival, patient characteristics, and Medicare spending for Medicare fee-for-service beneficiaries identified with serious illness (n = 1,600,629) using 100% Medicare Master Beneficiary Summary and MSSP beneficiary files (2014-2016). METHODS: We used generalized linear models with ACO and year fixed effects to estimate the average within-ACO difference between potential retrospective and prospective ACO populations. RESULTS: Dying in the first 90 days of the performance year was associated with reduced odds of retrospective ACO attribution (odds ratio [OR], 0.24; 95% CI, 0.24-0.25) relative to beneficiaries surviving 270 days or longer. Similarly, hospice use was associated with reduced odds of retrospective assignment (OR, 0.80; 95% CI, 0.79-0.80). Among ACOs that did not achieve shared savings, average per capita Medicare expenditures (after truncation) were $2459 (95% CI, $2192-$2725) higher for prospective vs retrospective ACO populations. The difference was $834 (95% CI, $402-$1266) greater per capita among ACOs that achieved shared savings. CONCLUSIONS: The difference in survival and spending for ACO populations captured by prospective vs retrospective attribution methods means that ACOs may need to employ different care management strategies to improve performance depending on their attribution method.

Sodium Oxybate: A Cause of Extreme Involuntary Weight Loss in a Young Lady.

We present a case of a young lady with extreme involuntary weight loss and alarming constitutional symptoms found ultimately to be all due to a single medication's side effects. The objective of this case report is to alert physicians, especially in a primary care setting, that the side effects of a medication used mostly in a highly specialized field of neurology, sodium oxybate (SXB), can cause extreme involuntary weight loss in addition to chronic night sweats and symptoms of clinical depression.

Association of Primary Care Providers' Beliefs of Statins for Primary Prevention and Statin Prescription.

Background The 2013 American College of Cardiology/American Heart Association Cholesterol Treatment Guideline increased the number of primary prevention patients eligible for statin therapy, yet uptake of these guidelines has been modest. Little is known of how primary care provider ( PCP ) beliefs influence statin prescription. Methods and Results We surveyed 164 PCP s from a community-based North Carolina network in 2017 about statin therapy. We evaluated statin initiation among the PCP s' statin-eligible patients between 2014 and 2015 without a previous prescription. Seventy-two PCP s (43.9%) completed the survey. The median estimate of the relative risk reduction for high-intensity statins was 45% (interquartile range, 25%-50%). A minority of providers (27.8%) believed statins caused diabetes mellitus, and only 16.7% reported always/very often discussing this with patients. Most PCPs (97.2%) believed that statins cause myopathy, and 72.3% reported always/very often discussing this with patients. Most (77.7%) reported always/very often using the 10-year atherosclerotic cardiovascular disease risk calculator, although many reported that in most cases other risk factors or patient preferences influenced prescribing (59.8% and 43.1%, respectively). Of 6172 statin-eligible patients, 22.3% received a prescription for a moderate- or high-intensity statin at follow-up. Providers reporting greater reliance on risk factors beyond atherosclerotic cardiovascular disease risk were less likely to prescribe statins. Conclusions Although beliefs and approaches to statin discussions vary among community PCP s, new prescription rates are low and minimally associated with those beliefs. These results highlight the complexity of increasing statin prescriptions for primary prevention and suggest that strategies to facilitate standardized discussions and to address external influences on patient beliefs warrant future study.

Trends in hospital-physician integration in medical oncology.

OBJECTIVES: Hospitals have rapidly acquired medical oncology practices in recent years. Experts disagree as to whether these trends are related to oncology-specific market factors or reflect a general trend of hospital-physician integration. The objective of this study was to compare the prevalence, geographic variation, and trends in physicians billing from hospital outpatient departments in medical oncology with other specialties. STUDY DESIGN: Retrospective analysis of Medicare claims data for 2012 and 2013. METHODS: We calculated the proportion of physicians and practitioners in the 15 highest-volume specialties who billed the majority of evaluation and management visits from hospital outpatient departments in each year, nationally and by state. RESULTS: We included 338,998 and 352,321 providers in 2012 and 2013, respectively, of whom 9715 and 9969 were medical oncologists. Among the 15 specialties examined, medical oncology had the highest proportion of hospital outpatient department billing in 2012 and 2013 (35.0% and 38.3%, respectively). Medical oncology also experienced the greatest absolute change (3.3%) between the years, followed by thoracic surgery (2.4%) and cardiology (2.0%). There was marked state-level variation, with the proportion of medical oncologists based in hospital outpatient departments ranging from 0% in Nevada to 100% in Idaho. CONCLUSIONS: Hospital-physician integration has been more pronounced in medical oncology than in other high-volume specialties and is increasing at a faster rate. Policy makers should take these findings into consideration, particularly with respect to recent proposals that may continue to fuel these trends.

Association of Practice-Level Hospital Use With End-of-Life Outcomes, Readmission, and Weekend Hospitalization Among Medicare Beneficiaries With Cancer.

PURPOSE: To determine the relationships between hospital use of treating oncology practices and patient outcomes. PATIENTS AND METHODS: Retrospective analysis of 397,646 Medicare beneficiaries who received anticancer therapy in 2012. Each beneficiary was associated with a practice; practices were ranked on the basis of risk-adjusted hospital use, that is, inpatient intensity. Outcomes included 30-day readmission, weekend admissions, intensive care unit stays in the last month of life, and hospice stay of ≥ 7 days. Outcomes were measured for each quartile of practice-level inpatient intensity. We fit multivariable logistic regression models to calculate adjusted odds ratios (ORs) for each outcome for each quartile of inpatient intensity. RESULTS: Total 30-day readmissions were 22.8% and 31.9% (OR, 1.45; 95% CI, 1.39 to 1.50) for patients in practices with the lowest versus highest quartiles of inpatient intensity, respectively; unplanned readmissions were 19.8% and 27.1% (OR, 1.36; 95% CI, 1.31 to 1.41), respectively. The proportion of admissions that occurred on weekends was similar across quartiles. Patients of practices in the highest quartiles of inpatient intensity had higher rates of death in an ICU stay in the last month of life (25.5% versus 18.0%; OR, 1.33; 95% CI, 1.19 to 1.49) and a lower rate of hospice stay of at least 7 days (50.9% to 42.5%; OR, 0.79; 95% CI, 0.74 to 0.86). CONCLUSION: Medical oncology practices that seek to reduce hospitalizations should consider focusing initially on processes related to end-of-life care and care transitions.

Practice-Level Variation in Outpatient Cardiac Care and Association With Outcomes.

BACKGROUND: Utilization of cardiac services varies across regions and hospitals, yet little is known regarding variation in the intensity of outpatient cardiac care across cardiology physician practices or the association with clinical endpoints, an area of potential importance to promote efficient care. METHODS AND RESULTS: We included 7 160 732 Medicare beneficiaries who received services from 5635 cardiology practices in 2012. Beneficiaries were assigned to practices providing the plurality of office visits, and practices were ranked and assigned to quartiles using the ratio of observed to predicted annual payments per beneficiary for common cardiac services (outpatient intensity index). The median (interquartile range) outpatient intensity index was 1.00 (0.81-1.24). Mean payments for beneficiaries attributed to practices in the highest (Q4) and lowest (Q1) quartile of outpatient intensity were: all cardiac payments (Q4 $1272 vs Q1 $581; ratio, 2.2); cardiac catheterization (Q4 $215 vs Q1 $64; ratio, 3.4); myocardial perfusion imaging (Q4 $253 vs Q1 $83; ratio, 3.0); and electrophysiology device procedures (Q4 $353 vs Q1 $142; ratio, 2.5). The adjusted odds ratios (95% CI) for 1 incremental quartile of outpatient intensity for each outcome was: cardiac surgical/procedural hospitalization (1.09 [1.09, 1.10]); cardiac medical hospitalization (1.00 [0.99, 1.00]); noncardiac hospitalization (0.99 [0.99, 0.99]); and death at 1 year (1.00 [0.99, 1.00]). CONCLUSION: Substantial variation in the intensity of outpatient care exists at the cardiology practice level, and higher intensity is not associated with reduced mortality or hospitalizations. Outpatient cardiac care is a potentially important target for efforts to improve efficiency in the Medicare population.

Patterns of care for clinically distinct segments of high cost Medicare beneficiaries.

BACKGROUND: Efforts to improve the efficiency of care for the Medicare population commonly target high cost beneficiaries. We describe and evaluate a novel management approach, population segmentation, for identifying and managing high cost beneficiaries. METHODS: A retrospective cross-sectional analysis of 6,919,439 Medicare fee-for-service beneficiaries in 2012. We defined and characterized eight distinct clinical population segments, and assessed heterogeneity in managing practitioners. RESULTS: The eight segments comprised 9.8% of the population and 47.6% of annual Medicare payments. The eight segments included 61% and 69% of the population in the top decile and top 5% of annual Medicare payments. The positive-predictive values within each segment for meeting thresholds of Medicare payments ranged from 72% to 100%, 30% to 83%, and 14% to 56% for the upper quartile, upper decile, and upper 5% of Medicare payments respectively. Sensitivity and positive-predictive values were substantially improved over predictive algorithms based on historical utilization patterns and comorbidities. The mean [95% confidence interval] number of unique practitioners and practices delivering E&M services ranged from 1.82 [1.79-1.84] to 6.94 [6.91-6.98] and 1.48 [1.46-1.50] to 4.98 [4.95-5.00] respectively. The percentage of cognitive services delivered by primary care practitioners ranged from 23.8% to 67.9% across segments, with significant variability among specialty types. CONCLUSIONS: Most high cost Medicare beneficiaries can be identified based on a single clinical reason and are managed by different practitioners. IMPLICATIONS: Population segmentation holds potential to improve efficiency in the Medicare population by identifying opportunities to improve care for specific populations and managing clinicians, and forecasting and evaluating the impact of specific interventions.

Wide variation in payments for Medicare beneficiary oncology services suggests room for practice-level improvement.

In recent years many policy makers have recommended alternative payment models in medical oncology in order to reduce costs and improve patient outcomes. Yet information on how oncology practices differ in their use of key service categories is limited. We measured annual payments for key service categories delivered to fee-for-service Medicare beneficiaries receiving care from 1,534 medical oncology practices in 2011-12. In 2012, differences in payments per beneficiary at the seventy-fifth-percentile practice compared to the twenty-fifth-percentile practice were $3,866 for chemotherapy (including administration and supportive care drugs), $1,872 for acute medical hospitalizations, and $439 for advanced imaging. Supportive care drugs, bevacizumab, and positron-emission tomography accounted for the greatest percentage of variation. Average practice payments for service categories were highly correlated across years but not correlated with each other, which suggests that service categories may be affected by different physician practice characteristics. These differences, even when clinical guidelines exist, demonstrate the potential for quality improvement that could be accelerated through alternative payment models.

Utilization of darbepoetin alfa in relation to cancer patients' hemoglobin levels.

OBJECTIVE: Previous labeling and guidelines recommended initiating erythropoiesis agents (ESAs) for chemotherapy-induced anemia (CIA) at hemoglobin (Hb) levels < 11 g/dL, maintaining near 12 g/dL, and withholding at > or = 13 g/dL. This study analyzed adherence with recommendations in administration of darbepoetin (DA) to cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of Hb levels at which DA was administered using Varian electronic medical records (EMRs). The dataset comprises 141 694 cancer patients from 82 sites across 13 states. The study evaluated DA administrations with respect to recorded Hb for 8988 patients from 1/1/05 to 5/31/07. MAIN OUTCOME MEASURES: Proportion of DA administrations at Hb > or = 12 and Hb > or = 13 g/dL. Hb level was analyzed for all administrations, stratified by year and anemia type (CIA, anemia-of-cancer, and myelodysplastic syndrome). RESULTS: There were 51 111 DA administrations with Hb results. The proportion of administrations at Hb > or = 12 g/dL was 7.2% and at Hb > or = 13 g/dL was 0.6%, and for CIA 6.9%/0.6%, anemia of cancer (AOC) 8.8%/0.8%, and myelodysplastic syndrome (MDS) 6.5%/0.6%. The proportion of all DA administrations at Hb > or = 12 g/dL and > or = 13 g/dL declined from 8.6% to 5.3% (p < 0.0001) and from 0.7% to 0.4% (p < 0.0007), respectively during 1/1/05-5/31/07. CONCLUSIONS: In this population, DA administration at Hb > or = 12 g/dL and Hb > or = 13 g/dL occurred in 7.2% and 0.6% of administrations, respectively, a approximately 93% adherence rate with recommendations. Further research is required to understand dose titrations at Hb 12-13 g/dL, and whether similar patterns are observed for other ESAs, and in other practice settings. This study provides context for the debate regarding the utilization, benefits and risks of ESAs in cancer patients.