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.

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.

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.

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.

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.

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.

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.

Combinatorial modification of natural products: synthesis and in vitro analysis of derivatives of thiazole peptide antibiotic GE2270 A: A-ring modifications.

Thiazole peptide GE2270 A (1) possesses potent antimicrobial activity against many gram-positive pathogens, including methicillin resistant Staphylococcus aureus (S. aureus, MRSA; MIC(90)=0.06 microg/mL) and vancomycin resistant Enterococcus spp. (VRE; MIC(90)=0.03 microg/mL); however its poor aqueous solubility has prohibited its development for the clinical treatment of infections. An integrated combinatorial and medicinal chemistry program was employed to identify derivatives of 1 that retain activity but possess greatly enhanced aqueous solubility.