Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response.

The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases ( http://www.pboselab.ca/spatial_OSCC/ ; http://www.pboselab.ca/dynamo_OSCC/ ) that can be foundational for developing novel targeted therapies.

Limited options to manage specialty drug spending.

Spending on specialty drugs--typically high-cost biologic medications to treat complex medical conditions--is growing at a high rate and represents an increasing share of U.S. pharmaceutical spending and overall health spending. Absence of generic substitutes, or even brand-name therapeutic equivalents in many cases, gives drug manufacturers near-monopoly pricing power and makes conventional tools of benefit design and utilization management less effective, according to a new qualitative study from the Center for Studying Health System Change (HSC). Despite the dearth of substitutes, cost pressures have prompted some employers to increase patient cost sharing for specialty drugs. Some believe this is counter-productive, since it can expose patients to large financial obligations and may reduce patient adherence, which in turn may lead to higher costs. Utilization management has focused on prior authorization and quantity limits, rather than step-therapy approaches--where lower-cost options must first be tried--that are prevalent with conventional drugs. Unlike conventional drugs, a substantial share of specialty drugs--typically clinician-administered drugs--are covered under the medical benefit rather than the pharmacy benefit. The challenges of such coverage--high drug mark-ups by physicians, less utilization data, less control for health plans and employers--have led to attempts to integrate medical and pharmacy benefits, but such efforts are still in early development. Health plans are experimenting with a range of innovations to control spending, but the most meaningful, wide-ranging innovations may not be feasible until substitutes, such as biosimilars, become widely available, which for many specialty drugs will not occur for many years.

Emergency preparedness and community coalitions: opportunities and challenges.

Being prepared for a natural disaster, infectious disease outbreak or other emergency where many injured or ill people need medical care while maintaining ongoing operations is a significant challenge for local health systems. Emergency preparedness requires coordination of diverse entities at the local, regional and national levels. Given the diversity of stakeholders, fragmentation of local health care systems and limited resources, developing and sustaining broad community coalitions focused on emergency preparedness is difficult. While some stakeholders, such as hospitals and local emergency medical services, consistently work together, other important groups--for example, primary care clinicians and nursing homes--typically do not participate in emergency-preparedness coalitions, according to a new qualitative study of 10 U.S. communities by the Center for Studying Health System Change (HSC). Challenges to developing and sustaining community coalitions may reflect the structure of preparedness activities, which are typically administered by designated staff in hospitals or large medical practices. There are two general approaches policy makers could consider to broaden participation in emergency-preparedness coalitions: providing incentives for more stakeholders to join existing coalitions or building preparedness into activities providers already are pursuing. Moreover, rather than defining and measuring processes associated with collaboration--such as coalition membership or development of certain planning documents--policy makers might consider defining the outcomes expected of a successful collaboration in the event of a disaster, without regard to the specific form that collaboration takes.

After-hours care and its coordination with primary care in the U.S.

BACKGROUND: Despite expectations that medical homes provide "24 × 7 coverage" there is little to guide primary care practices in developing sustainable models for accessible and coordinated after-hours care. OBJECTIVE: To identify and describe models of after-hours care in the U.S. that are delivered in primary care sites or coordinated with a patient's usual primary care provider. DESIGN: Qualitative analysis of data from in-depth telephone interviews. SETTING: Primary care practices in 16 states and the organizations they partner with to provide after-hours coverage. PARTICIPANTS: Forty-four primary care physicians, practice managers, nurses and health plan representatives from 28 organizations. APPROACH: Analyses examined after-hours care models, facilitators, barriers and lessons learned. RESULTS: Based on 28 organizations interviewed, five broad models of after-hours care were identified, ranging in the extent to which they provide continuity and patient access. Key themes included: 1) The feasibility of a model varies for many reasons, including patient preferences and needs, the local health care market supply, and financial compensation; 2) A shared electronic health record and systematic notification procedures were extremely helpful in maintaining information continuity between providers; and 3) after-hours care is best implemented as part of a larger practice approach to access and continuity. CONCLUSION: After-hours care coordinated with a patient's usual primary care provider is facilitated by consideration of patient demand, provider capacity, a shared electronic health record, systematic notification procedures and a broader practice approach to improving primary care access and continuity. Payer support is important to increasing patients' access to after-hours care.

Employer-sponsored health insurance: down but not out.

Rising costs and the lingering fallout from the great recession are altering the calculus of employer approaches to offering health benefits, according to findings from the Center for Studying Health System Change's (HSC) 2010 site visits to 12 nationally representative metropolitan communities. Employers responded to the economic downturn by continuing to shift health care costs to employees, with the trend more pronounced in small, mid-sized and low-wage firms. At the same time, employers and health plans are dissatisfied and frustrated with their inability to influence medical cost trends by controlling utilization or negotiating more-favorable provider contracts. In an alternative attempt to control costs, employers increasingly are turning to wellness programs, although the payoff remains unclear. Employer uncertainty about how national reform will affect their health benefits programs suggests they are likely to continue their current course in the near term. Looking toward 2014 when many reform provisions take effect, employer responses likely will vary across communities, reflecting differences in state approaches to reform implementation, such as insurance exchange design, and local labor market conditions.