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In 2011, the UK medical research charity Cure Parkinson’s set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson’s disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P< 5 × 10−8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

Squamous dysplasia precedes invasive squamous cell carcinoma of the esophagus, but there is limited evidence on its surgical management. The “field change effect” further complicates matters, causing multifocal or second primary neoplasms in the esophagus and upper aerodigestive tract. While endoscopic procedures are the primary treatment, surgical resection, either alone or in combination with endoscopy, must be considered given the extent of the disease and organ involvement. This chapter summarizes multifocal squamous dysplasia scenarios and highlights the role of esophagectomy or surgical resection.

In 2011, the UK medical research charity Cure Parkinson’s set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson’s disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.

ObjectiveCell-cell (CC) and cell-matrix (CM) adhesions are essential for epithelial cell survival, yet dissociation-induced apoptosis is frequently circumvented in malignant cells.DesignWe explored CC and CM dependence in 58 gastric cancer (GC) organoids by withdrawing either ROCK inhibitor, matrix or both to evaluate their tumorigenic potential in terms of apoptosis resistance, correlation with oncogenic driver mutations and clinical behaviour. We performed mechanistic studies to determine the role of diffuse-type GC drivers: ARHGAPfusions, RHOAand CDH1,in modulating CC (CCi) or CM (CMi) adhesion independence.Results97% of the tumour organoids were CMi, 66% were CCi and 52% were resistant to double withdrawal (CCi/CMi), while normal organoids were neither CMi nor CCi. Clinically, the CCi/CMi phenotype was associated with an infiltrative tumour edge and advanced tumour stage. Moreover, the CCi/CMi transcriptome signature was associated with poor patient survival when applied to three public GC datasets. CCi/CMi and CCi phenotypes were enriched in diffuse-type GC organoids, especially in those with oncogenic driver perturbation of RHO signalling via RHOAmutation or ARHGAPfusions. Inducible knockout of ARHGAPfusions in CCi/CMi tumour organoids led to resensitisation to CC/CM dissociation-induced apoptosis, upregulation of focal adhesion and tight junction genes, partial reversion to a more normal cystic phenotype and inhibited xenograft formation. Normal gastric organoids engineered with CDH1or RHOAmutations became CMi or CCi, respectively.ConclusionsThe CCi/CMi phenotype has a critical role in malignant transformation and tumour progression, offering new mechanistic information on RHO-ROCK pathway inhibition that contributes to GC pathogenicity.

In the face of global pressures of change and biodiversity loss, crop wild relatives (CWR) and wild‐utilized species (WUS) urgently require conservation attention. To advance conservation, we assembled a national inventory of CWR and WUS in Canada. To assess current ex situ conservation of these plant species, we gathered a virtual metacollection of accession data from botanical gardens and national genebanks. The inventory includes 779 CWR and WUS taxa (658 distinct species), with 263 (222 distinct species) that are related to food crops of national and global importance such as blueberry (Vaccinium corymbosumL.), apple (Malus domestica(Suckow) Borkh.), sunflower (Helianthus annuusL.), and saskatoon (Amelanchierspp.). Sixty‐one food crop relatives are prioritized for breeding potential, and sixteen due to conservation threats. Although most food crop CWR are represented in ex situ collections (91% of species), representation of within‐species diversity is low (median = 5% of Canadian ecogeographic types represented per species). Poor representation of within‐species diversity demands an integrative conservation strategy that emphasizes in situ protection, especially focusing on wild populations in Canada's southern ecoregions where diversity is concentrated. While genebank collections represent higher accession counts per species, botanical gardens include living collections of fruit crop relatives and other woody perennials that are well situated to raise broader awareness of CWR and WUS. To promote further conservation action, we present a web application that enables conservation planners and practitioners to identify local CWR and WUS and to identify within‐species ecogeographic types that are underrepresented in ex situ conservation systems. Canada contains a rich diversity of crop wild relatives and wild‐utilized species, including many relatives of fruit crops.The 61 Canadian food crop wild relatives have high potential utility in crop breeding, and 17 are nationally imperiled.Living collections of woody‐perennial crop wild relatives and wild‐utilized species in botanical gardens complement ex situ conservation in genebanks.Conservation requires integrative strategy, with coordinated in situ action prioritizing Canada's southern regions.Display collections in gardens and new, online tools are situated to advance conservation by raising engagement.

Using National Immunization Survey Child and Teen (2008-2017), we associated state vaccination requirements with hepatitis A (Hep A) vaccination rates in children and adolescents. States with school entry or both childcare and school entry requirements were associated with 35%-40% higher Hep A vaccination rates, compared with states without such requirements.Children and adolescents residing in states with school entry or both childcare and school entry requirements had 35%-40% higher hepatitis A vaccination coverage rates, compared with those residing in states without such requirements.

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Recently identified post-fire carbon fluxes indicate that, to understand whether global fires represent a net carbon source or sink, one must consider both terrestrial carbon retention through pyrogenic carbon production and carbon losses via multiple pathways. Here these legacy source and sink pathways are quantified using a CMIP6 land surface model to estimate Earth’s fire carbon budget. Over the period 1901–2010, global pyrogenic carbon has driven an annual soil carbon accumulation of 337 TgC yr−1, offset by legacy carbon losses totalling −248 TgC yr−1. The residual of these values constrains the maximum annual pyrogenic carbon mineralization to 89 TgC yr−1and the pyrogenic carbon mean residence time to 5,387 years, assuming a steady state. The residual is negative over forests and positive over grassland-savannahs (implying a potential sink), suggesting contrasting roles of vegetation in the fire carbon cycle. The paucity of observational constraints for representing pyrogenic carbon mineralization means that, without assuming a steady state, we are unable to determine the sign of the overall fire carbon balance. Constraining pyrogenic carbon mineralization rates, particularly over grassland-savannahs, is a critical research frontier that would enable a fuller understanding of fire’s role in the Earth system and inform attendant land use and conservation policy.

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AimsBreast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.MethodsOn histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).ResultsBreast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CAmutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CAmutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.ConclusionsBreast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.

IMPORTANCE: Differences in lifetime earning potential between pediatric subspecialties may contribute to shortages in the subspecialty workforce. OBJECTIVES: To evaluate the association between lifetime earning potential and workforce distribution and to investigate the potential role of a pediatric subspecialist–specific loan repayment program (LRP) in workforce expansion. DESIGN, SETTING, AND PARTICIPANTS: This study was performed on publicly available mean debt and compensation data from national physician surveys from 2018 to 2019 of pediatric subspecialists in academic practice. Linear regression analysis was used to evaluate the association between lifetime earning potential and measures of workforce distribution in 2019, including distance to subspecialists, percentage of hospital referral regions with a subspecialist, and ratio of subspecialists to the regional child population as well as between lifetime earning potential in 2018 to 2019 and mean subspecialty fellowship fill rates between 2014 and 2018. The association between the change in lifetime earning potential from 2007 to 2018 and the change in workforce distribution metrics from 2003 to 2019 was also examined. The potential role of a pediatric subspecialist–specific LRP was modeled. EXPOSURES: Lifetime earning potential by subspecialty. MAIN OUTCOMES AND MEASURES: Measures of workforce distribution and fellowship fill rates. RESULTS: This study included mean compensation data representing 7539 pediatric subspecialists, workforce distribution data representing 24 375 pediatric subspecialists, and fellowship fill rates representing a mean of 1344 pediatric subspecialty fellows per year. Higher lifetime earning potential was associated with shorter distance to subspecialists (−0.59 miles/$100 000 increase in lifetime earning potential; 95% CI, –1.10 to –0.09), higher percentage of hospital referral regions with a subspecialist (+1.17%/$100 000 increase in lifetime earning potential; 95% CI, 0.34-2.00), and higher ratio of subspecialists to regional child population (+0.11 subspecialists/100 000 children/$100 000 increase in lifetime earning potential; 95% CI, 0.04-0.19). The subspecialties for which lifetime earning potential increased the least between 2007 and 2018 experienced the least growth in the ratio of subspecialists to regional child population from 2003 to 2019 (+0.11 subspecialists/100 000 children/$100 000 increase in lifetime earning potential; 95% CI, 0.07-0.16). Higher lifetime earning potential was associated with higher mean fellowship fill rates (+0.96% spots filled/$100 000 increase in lifetime earning potential; 95% CI, 0.15-1.77). Implementing a pediatric subspecialist–specific LRP could increase fellowship fill rates and improve workforce distribution. CONCLUSIONS AND RELEVANCE: Lifetime earning potential based on subspecialty may contribute to imbalances in both the current and future pediatric subspecialty workforce. Pediatric subspecialist–specific LRPs, especially for underfilled subspecialties, are potential tools for policy makers to target workforce shortages.

With the increasing use of medications that alter the risk of gastrointestinal bleeding (GIB), comprising aspirin, proton pump inhibitors (PPIs), and Helicobacter pylorieradication therapies, the trends of GIB are evolving. The aim of this study is to determine and predict the trends of GIB and to evaluate the effects of population prescriptions of these medications on GIB incidences. We retrieved patients hospitalized for GIB in all public hospitals in Hong Kong between 2009 and 2019. Monthly age‐ and sex‐standardized GIB data were fitted and predicted, based on population prescriptions of aspirin, nonsteroidal anti‐inflammatory drugs (NSAIDs), anticoagulants, other antiplatelet drugs, PPIs, and H. pyloritherapies, using autoregressive integrated moving average model for time series analysis. The incidence of upper GIB (UGIB) showed a clear declining trend while lower GIB (LGIB) decreased slightly. Older population (>80 years) had the greatest decline in UGIB but was associated with an increase in LGIB. Prescriptions of PPIs and aspirin increased significantly with time. PPIs prescriptions were negatively associated with UGIB incidence (coefficient log(PPIs) −4.58; 95% confidence interval [CI]: −5.69, −3.47). H. pylorieradication in the previous month showed a nonsignificant trend on UGIB (coefficient −0.14; 95% CI: −0.30, 0.02). In contrast, aspirin increased the incidences of UGIB (coefficient 0.06; 95% CI: 0.04, 0.07) and LGIB (coefficient 0.04; 95% CI: 0.03, 0.05). NSAIDs, anticoagulants, and other antiplatelet drugs were not significantly associated with the trend of either UGIB or LGIB. UGIB is predicted to decline continuously but LGIB is projected to rise, particularly with increasing use of aspirin. UGIB incidences were decreasing and had been surpassed by LGIB. Based on population prescriptions of aspirin and PPIs, divergent trends of upper and lower GIB are expected, especially in elderly. Summarize the established knowledge on this subject With increasing use of proton pump inhibitors (PPIs) and Helicobacter pylorieradication therapy, the incidences of upper gastrointestinal bleeding (UGIB) are declining.The increasing use of antiplatelets and anticoagulants, however, increases the risk of both UGIB and lower gastrointestinal bleeding (LGIB).The dynamic contribution of these factors on the incidences of UGIB and LGIB at population level remains uncertain. With increasing use of proton pump inhibitors (PPIs) and Helicobacter pylorieradication therapy, the incidences of upper gastrointestinal bleeding (UGIB) are declining. The increasing use of antiplatelets and anticoagulants, however, increases the risk of both UGIB and lower gastrointestinal bleeding (LGIB). The dynamic contribution of these factors on the incidences of UGIB and LGIB at population level remains uncertain. What are the significant and/or new findings of this study? The incidences of UGIB showed a clear declining trend while LGIB decreased slightly over the past decade in Hong Kong.LGIB had actually surpassed UGIB as the leading source of GIB, especially among older population.The increasing PPIs prescription was associated with the falling incidences of UGIB, whereas the rising use of aspirin was associated with both an increase in UGIB and LGIB.With the increasing use of aspirin and the lack of effective prevention preventive strategies, LGIB would become a major health challenge. The incidences of UGIB showed a clear declining trend while LGIB decreased slightly over the past decade in Hong Kong. LGIB had actually surpassed UGIB as the leading source of GIB, especially among older population. The increasing PPIs prescription was associated with the falling incidences of UGIB, whereas the rising use of aspirin was associated with both an increase in UGIB and LGIB. With the increasing use of aspirin and the lack of effective prevention preventive strategies, LGIB would become a major health challenge.

IMPORTANCE: There is a critical need for careful and independent validation of reported symptomatic efficacy and dopaminergic biomarker changes induced by nilotinib in Parkinson disease (PD). OBJECTIVES: To assess safety and tolerability of nilotinib in participants with moderately advanced PD. Secondary and exploratory objectives were to assess its affect on PD disability, pharmacokinetics, cerebrospinal fluid (CSF) penetration, and biomarkers. DESIGN, SETTING, AND PARTICIPANTS: This was a 6-month, multicenter, randomized parallel-group, double-blind, placebo-controlled trial. Recruitment was from November 20, 2017, to December 28, 2018, and follow-up ended on September 9, 2019. The study was conducted at 25 US sites. The study approached 173 patients, of whom 48 declined, 125 were screened, and 76 who received a stable regimen of PD medications were enrolled (39% screen failure). INTERVENTIONS: Participants were randomized 1:1:1 to placebo, 150-mg nilotinib, or 300-mg nilotinib once daily orally for 6 months, followed by 2-month off-drug evaluation. MAIN OUTCOMES AND MEASURES: The primary outcomes were safety and tolerability. The tolerability end point was defined as the ability to complete the study while receiving the assigned dose. An active arm was considered tolerable if the percentage of participants meeting the tolerability end point for that group was not significantly lower than the percentage observed in the placebo group. Secondary outcomes included change in PD disability (Movement Disorder Society Unified Parkinson’s Disease Rating Scale [MDS-UPDRS], Part II OFF/ON). Exploratory outcomes included serum and CSF pharmacokinetic profile, and CSF dopaminergic biomarkers. RESULTS: At baseline, mean (SD) participants’ age was 64.6 (7.5) years, 52 were male (68%), mean (SD) disease duration was 9.9 years (4.7), MDS-UPDRS Part 1-3 OFF score was 66.4 (19.3), ON score was 48.4 (16.2), and Montreal Cognitive Assessment score was 27.1 (2.2). The number of participants who completed the study receiving the assigned dose were 21 (84%), 19 (76%), and 20 (77%) in the placebo, 150-mg, and 300-mg arms, respectively. Both active doses had acceptable safety profile. The most common reasons for drug suspension were asymptomatic, dose-dependent elevations of amylase, and/or lipase. Nilotinib, 150 mg and 300 mg, exhibited worse MDS-UPDRS-3 ON scores compared with placebo, achieving significance for nilotinib, 300 mg, at month 1 (P &lt; .01). There was no difference in the change of MDS-UPDRS-3 OFF from baseline to 6 months between groups (P = .17). Cerebrospinal fluid/serum ratio of nilotinib concentration was 0.2% to 0.3%. There was no evidence of treatment-related alteration of dopamine metabolites in the CSF. CONCLUSIONS AND RELEVANCE: While we demonstrated acceptable safety and tolerability of nilotinib in our cohort, the low CSF exposure and lack of biomarkers effect combined with the efficacy data trending in the negative direction indicate that nilotinib should not be further tested in PD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03205488

This study aims to describe and analyze KB or family planning practices and their impact on Papuan women. A case study was conducted in Waena Village, one of the Kampung KB in Jayapura City, Papua.

Acute chest syndrome is a leading cause of mortality in patients with sickle cell disease (SCD). Because early detection of acute chest syndrome is directly tied to prognosis, young patients with SCD undergo countless chest radiography screenings throughout their lifetime for commonly occurring acute chest syndrome risk factors such as fever, chest pain, or cough. Chest radiography is not an ideal screening method because it is associated with radiation exposure, which accumulates with repeated imaging. Point-of-care lung ultrasonography is a nonradiating imaging modality that has been used to identify other lung pathology and may have a role in SCD. The goal of this study was to determine the accuracy of point-of-care lung ultrasound to identify an infiltrate suggestive of acute chest syndrome in patients with SCD compared to chest radiography as the gold standard.

Parkinson disease is a complex, age-related, neurodegenerative disease associated with dopamine deficiency and both motor and nonmotor deficits. Many environmental and genetic factors influence Parkinson disease risk, with different factors predominating in different patients. These factors converge on specific pathways, including mitochondrial dysfunction, oxidative stress, protein aggregation, impaired autophagy, and neuroinflammation. Ultimately, treatment of Parkinson disease may focus on targeted therapies for pathophysiologically defined subtypes of Parkinson disease patients.

Novel mesoporous carbon cathode material for Lithium–Sulfur battery were successfully synthesized from the shells of the avocado fruit. The crystalline structure of the formed carbon was characterized via X-Ray diffraction whilst Scanning Electron Microscopy was used to observe the morphology. The electronic conductivity was determined as a function of pressure and the COOH functional group were quantified via a titration. The mesoporous structure of the formed carbon network allows for good sulfur penetration which is translated by decent electrochemical performance both in terms of cycle life and rate capability. Carbons prepared from waste avocado shells and functionalized with HNO3offer a good performance in terms of capacity retention (500 mAh/g of sulfur after 100 cycles). This favorable performance may be attributed to the role of functional COOH groups on the surface of the activated carbon.

ABSTRACTIn this article, we introduce Delta Boosting (DB) as a new member of the boosting family. Similar to the popular Gradient Boosting (GB), this new member is presented as a forward stagewise additive model that attempts to reduce the loss at each iteration by sequentially fitting a simple base learner to complement the running predictions. Instead of relying on the negative gradient, as is the case for GB, DB adopts a new measure called delta as the basis. Delta is defined as the loss minimizer at an observation level. We also show that DB is the optimal boosting member for a wide range of loss functions. The optimality is a consequence of DB solving for the split and adjustment simultaneously to maximize loss reduction at each iteration. In addition, we introduce an asymptotic version of DB that works well for all twice-differentiable strictly convex loss functions. This asymptotic behavior does not depend on the number of observations, but rather on a high number of iterations that can be augmented through common regularization techniques. We show that the basis in the asymptotic extension differs from the basis in GB only by a multiple of the second derivative of the log-likelihood. The multiple is considered to be a correction factor, one that corrects the bias toward the observations with high second derivatives in GB. When negative log-likelihood is used as the loss function, this correction can be interpreted as a credibility adjustment for the process variance. Simulation studies and real data application we conducted suggest that DB is a significant improvement over GB. The performance of the asymptotic version is less dramatic, but the improvement is still compelling. Like GB, DB provides a high transparency to users, and we can review the marginal influence of variables through relative importance charts and the partial dependence plots. We can also assess the overall model performance through evaluating the losses, lifts, and double lifts on the holdout sample.

Interventions to reduce frequent emergency department (ED) use in children are often limited by the inability to predict future risk. We sought to develop a population-based model for predicting Medicaid-insured children at risk for high frequency (HF) of low-resource-intensity (LRI) ED visits.

IMPORTANCE: Cancer care is expensive. Cancer care provided by practice organizations varies in total spending incurred by patients and payers during treatment episodes and in quality of care, and this unnecessary variation contributes to the high cost. OBJECTIVE: To use the variation in total spending and quality of care to assess oncology practice attributes distinguishing “high value” that may be tested and adopted by others to produce similar results. DESIGN, SETTING, AND PARTICIPANTS: “Positive deviance” was used in this exploratory mixed-methods (quantitative and qualitative) analysis of interview results. To quantify value, oncology practices located near the US Pacific Northwest and Midwest with low mean insurer-allowed spending were identified. Among those, practices with high quality were selected. A team then conducted site visits to interview practice personnel from June 2, 2015, through October 3, 2015, and to probe for attributes of high-value care. A qualitative analysis of their interview results was performed, and a panel of experienced oncologists was convened to review attributes occurring uniquely or frequently in low-spending practices for their contribution to value improvement and ease of implementation. Four positive deviant (ie, low-spending) oncology practices and 3 oncology practices that ranked near the middle of the spending distribution were studied. MAIN OUTCOMES AND MEASURES: Thematic saturation in a qualitative analysis of high-value care attributes. RESULTS: From the 7 oncology practices studied, 13 attributes within the following 5 themes emerged: treatment planning and goal setting, services supporting the patient journey, technical support and physical layout, care team organization and function, and external context. Five attributes (ie, conservative use of imaging, early discussion of treatment limitations and consequences, single point of contact, maximal use of registered nurses for interventions, and a multicomponent health care system) most sharply distinguished the high-value practice sites. The expert oncologist panel judged 3 attributes (ie, early and normalized palliative care, ambulatory rapid response, and early discussion of treatment limitations and consequences) to carry the highest immediate potential for lowering spending without compromising the quality of care. CONCLUSIONS AND RELEVANCE: Oncology practice attributes warranting further testing were identified that may lower total spending for high-quality oncology care.