Trends in sepsis and pneumonia during COVID-19: lessons from BPCIA.

OBJECTIVES: The COVID-19 pandemic affected care delivery nationwide for all patients, influencing cost and utilization for patients both with and without COVID-19. Our first analysis assessed changes in utilization for patients with sepsis without COVID-19 prior to vs during the pandemic. Our second analysis assessed cost and utilization changes during the pandemic for patients with sepsis or pneumonia both with and without COVID-19. STUDY DESIGN: A retrospective case-control study was utilized to determine differences in cost and utilization for patients with sepsis or pneumonia, relative to a COVID-19 diagnosis. METHODS: Claims data from 8 teaching hospitals participating in sepsis and pneumonia episodes in the Bundled Payments for Care Improvement Advanced (BPCIA) model were utilized. BPCIA is a Medicare value-based care bundled payment program that aims to decrease costs and increase quality of care through a 90-day total cost of care model. RESULTS: The first analysis (N = 1092) found that non-COVID-19 patients with sepsis had 26% higher hospice utilization (P < .05) and 38% higher mortality (P < .0001) during the pandemic vs the prepandemic period. The second analysis (N = 640) found that during the pandemic, patients with sepsis or pneumonia with COVID-19 had 70% more skilled nursing facility (SNF) use (P < .0001), 132% higher SNF costs (P < .0001), and 21% higher total episode costs (P < .0001) compared with patients without COVID-19. CONCLUSIONS: COVID-19 has affected care patterns for all patients. Patients without COVID-19 postponed care and used lower-acuity care settings, whereas patients with COVID-19 were more costly and utilized postacute care at a higher rate. These analyses inform future care coordination initiatives, given the ongoing pandemic.

Succeeding in Medicare's newest bundled payment program: Results from teaching hospitals.

BACKGROUND: In 2018, Medicare implemented a successor to its Bundled Payments for Care Improvement (BPCI) program, BPCI Advanced, with stricter participation rules and new financial incentives to reduce spending. METHODS: Using claims-based episode data from thirteen participants, we compared spending and utilization in the first fifteen months of the new program (October 2018 to December 2019) to hospital- and episode-specific target prices, with a deep dive into clinical correlates for the most commonly-selected clinical episodes, sepsis and congestive heart failure. RESULTS: Twelve out of thirteen participants in a collaborative of teaching hospitals achieved shared savings for both Medicare and their own institution. Aggregate hospital shared savings were 5.8% of benchmark prices across 6,131 patients in 16 clinical episodes (p<0.001), appreciably higher than the reference savings rates reported after the first period of Medicare's predecessor BPCI program. Differences in shared savings across hospitals for sepsis and congestive heart failure correlated with reductions in patients' use of post-acute care, including reductions in skilled nursing facility, readmission, and home health rates. Evidence is presented showing reductions in patient utilization for cost-intensive post-acute settings accompanied increases in the proportion of patients exclusively utilizing non-institutional care after discharge from an anchor stay or procedure. CONCLUSIONS: These findings provide an example of the fulfillment of a core promise of bundled payments to uncover new opportunities for reduced spending. LEVEL OF EVIDENCE: Non-random cohort of hospitals.

Evaluating the Addition of Clinical and Staging Data to Improve the Pricing Methodology of the Oncology Care Model.

PURPOSE: The Oncology Care Model (OCM) is the largest value-based care model focusing on oncology, but the current pricing methodology excludes relevant data on the cancer stage and current clinical status, limiting the precision of the risk adjustment. METHODS: This analysis evaluated 15,580 episodes of breast cancer, lung cancer, and multiple myeloma, starting between July 1, 2016, and January 1, 2020, with data from a cohort of OCM practices affiliated with academic medical centers. The authors merged clinical data with claims for OCM episodes defined by the Center for Medicare and Medicaid Innovation to identify potential quality improvement opportunities. The regression model evaluated the association of the cancer stage at initial diagnosis and current clinical status with variance to the OCM target price. RESULTS: Cancer stage at the time of initial diagnosis was significant for breast and lung cancers, with stage IV episodes having the highest losses of -$6,700 (USD) for breast cancer (P < .001) and -$18,470 (USD) for lung cancer (P < .001). Current clinical status had a significant impact for all three cancers in the analysis, with losses correlated with clinical complexity. Breast cancer and multiple myeloma episodes categorized as recurrent or progressive disease had significantly higher losses than stable episodes, at -$6,755 (USD) for breast (P < .001) and -$19,448 (USD) for multiple myeloma (P < .001). Lung cancer episodes categorized as initial diagnosis had significantly fewer losses than stable episodes, at -$3,751 (USD) (P = .001). CONCLUSION: As the Center for Medicare and Medicaid Innovation designs and launches new oncology-related models, the agency should adopt methodologies that more accurately set target prices, by incorporating relevant clinical data within cancer types to minimize penalizing practices that provide guideline-concordant cancer care.

The Endangered State of Medicare Reimbursement for Cardiothoracic Surgery: A Call to Action.

Reimbursement for cardiothoracic surgery continues to be threatened with enormous financial cuts ranging from 5% to 10% in recent years. In this policy perspective, we describe the history of reimbursement for cardiothoracic surgery, highlight areas in need of urgent reform, propose possible solutions that Congress and the Executive Branch may enact, and call cardiothoracic surgeons to action on this critical issue. Meaningful engagement of members of The Society of Thoracic Surgeons with their elected representatives is the only way to prevent these cuts.

Cardiac Xenotransplantation: Progress in Preclinical Models and Prospects for Clinical Translation.

Survival of pig cardiac xenografts in a non-human primate (NHP) model has improved significantly over the last 4 years with the introduction of costimulation blockade based immunosuppression (IS) and genetically engineered (GE) pig donors. The longest survival of a cardiac xenograft in the heterotopic (HHTx) position was almost 3 years and only rejected when IS was stopped. Recent reports of cardiac xenograft survival in a life-sustaining orthotopic (OHTx) position for 6 months is a significant step forward. Despite these achievements, there are still several barriers to the clinical success of xenotransplantation (XTx). This includes the possible transmission of porcine pathogens with pig donors and continued xenograft growth after XTx. Both these concerns, and issues with additional incompatibilities, have been addressed recently with the genetic modification of pigs. This review discusses the spectrum of issues related to cardiac xenotransplantation, recent progress in preclinical models, and its feasibility for clinical translation.

Expert Consensus: Telehealth Skills for Health Care Professionals.

Background: The COVID-19 pandemic has driven most clinicians, from those practicing in small independent practices to those in large system, to adopt virtual care. However, individuals and organizations may lack the experience and skills that would be considered fundamental prerequisites to adopting telehealth in less urgent times. What are those skills? Before the pandemic, the Association of American Medical Colleges (AAMC) convened national experts to identify and articulate a consensus set of critical telehealth skills for clinicians. Methods: Through a structured review of the literature, followed by several rounds of review and refinement by committee and community members via a modified Delphi process, the committee came to consensus on a set of skills required by clinicians to provide quality care via telehealth. Conclusion: The consensus set of telehealth skills presented in this paper, developed by the AAMC and national experts, can serve providers and health systems seeking to ensure that clinicians are prepared to meet the demand for care delivered via telehealth now and in the future.

Comprehensive review of evaluation and management of cardiac paragangliomas.

Cardiac paraganglioma (PGL) is a rare neuroendocrine tumour causing significant morbidity primarily due to norepinephrine secretion potentially causing severe hypertension, palpitations, lethal tachyarrhythmias, stroke and syncope. Cardiologists are faced with two clinical scenarios. The first is the elevated norepinephrine, whose actions must be properly counteracted by adrenoceptor blockade to avoid catastrophic consequences. The second is to evaluate the precise location of a cardiac PGL and its spread since compression of cardiovascular structures may result in ischaemia, angina, non-noradrenergic-induced arrhythmia, cardiac dysfunction or failure. Thus, appropriate assessment of elevated norepinephrine by its metabolite normetanephrine is a gold biochemical standard at present. Furthermore, dedicated cardiac CT, MRI and transthoracic echocardiogram are necessary for the precise anatomic information of cardiac PGL. Moreover, a cardiologist needs to be aware of advanced functional imaging using 68Ga-DOTA(0)-Tyr(3)-octreotide positron emission tomography/CT, which offers the best cardiac PGL-specific diagnostic accuracy and helps to stage and rule out metastasis, determining the next therapeutic strategies. Patients should also undergo genetic testing, especially for mutations in genes encoding succinate dehydrogenase enzyme subunits that are most commonly present as a genetic cause of these tumours. Curative surgical resection after appropriate α-adrenoceptor and ß-adrenoceptor blockade in norepinephrine-secreting tumours is the primary therapeutic strategy. Therefore, appropriate and up-to-date knowledge about early diagnosis and management of cardiac PGLs is paramount for optimal outcomes in patients where a cardiologist is an essential team member of a multidisciplinary team in its management.

Intramyocardial Bone Marrow Stem Cells in Patients Undergoing Cardiac Surgical Revascularization.

BACKGROUND: Bone marrow stromal or stem cells (BMSCs) remain a promising potential therapy for ischemic cardiomyopathy. The primary objective of this study was to evaluate the safety and feasibility of direct intramyocardial injection of autologous BMSCs in patients undergoing transmyocardial revascularization (TMR) or coronary artery bypass graft surgery (CABG). METHODS: A phase I trial was conducted on adult patients who had ischemic heart disease with depressed left ventricular ejection fraction and who were scheduled to undergo TMR or CABG. Autologous BMSCs were expanded for 3 weeks before the scheduled surgery. After completion of surgical revascularization, BMSCs were directly injected into ischemic myocardium. Safety and feasibility of therapy were assessed. Cardiac functional status and changes in quality of life were evaluated at 1 year. RESULTS: A total of 14 patients underwent simultaneous BMSC and surgical revascularization therapy (TMR+BMSCs = 10; CABG+BMSCs = 4). BMSCs were successfully expanded, and no significant complications occurred as a result of the procedure. Regional contractility in the cell-treated areas demonstrated improvement at 12 months compared with baseline (TMR+BMSCs Δ strain: -4.6% ± 2.1%; P = .02; CABG+MSCs Δ strain: -4.2% ± 6.0%; P = .30). Quality of life was enhanced, with substantial reduction in angina scores at 1 year after treatment (TMR+BMSCs: 1.3 ± 1.2; CABG+MSCs: 1.0 ± 1.4). CONCLUSIONS: In this phase I trial, direct intramyocardial injection of autologous BMSCs in conjunction with TMR or CABG was technically feasible and could be performed safely. Preliminary results demonstrate improved cardiac function and quality of life in patients at 1 year after treatment.

Financial and Clinical Impact of Transfer Patients at Major Teaching Hospitals.

PURPOSE: The authors examined the "hub-and-spoke" health care system in the United States for patients transferred from one hospital ("spoke") to a major teaching hospital ("hub") and assessed the financial and clinical impact of this system on major teaching hospitals. METHOD: The authors surveyed Council of Teaching Hospitals and Health Systems members to collect detailed financial and clinical data from fiscal year 2015 for transfer cases and nontransfer cases (cases directly admitted to the teaching hospital). Data included computed margins (the difference between revenue received and direct and indirect facility costs as estimated by the hospitals) as well as case severity, average length of stay (ALOS), time of admission, surgical or medical status, and other situational variables for All Patient Refined Diagnosis Related Groups (APR-DRGs). The authors used an ordinary least-squares regression model with fixed effects to analyze the data. RESULTS: Twenty-six hospitals provided data. The average difference between transfer and nontransfer cases was a 2.18 day longer ALOS and a $1,716 lower computed margin, for a case in the same APR-DRG and hospital (P < .001 for both outcomes). Transfer cases had a 19% higher case severity of illness rating and were disproportionately represented among complex APR-DRGs. Transfer patients were 14% more likely to be Medicaid beneficiaries. CONCLUSIONS: Compared with nontransfer cases, transfer cases at major teaching hospitals were more complex and resulted in greater resource utilization, affecting the financial margins on which teaching hospitals rely to support their multipart mission.

Intra-Abdominal Heterotopic Cardiac Xenotransplantation: Pearls and Pitfalls.

Heterotopic cardiac xenotransplantation in the intra-abdominal position has been studied extensively in a pig-to-baboon model to define the optimal donor genetics and immunosuppressive regimen to prevent xenograft rejection. Extensive investigation using this model is a necessary stepping stone toward the development of a life-supporting animal model, with the ultimate goal of demonstrating suitability for clinical cardiac xenotransplantation trials. Aspects of surgical technique, pre- and post-operative care, graft monitoring, and minimization of infectious risk have all required refinement and optimization of heterotopic cardiac xenotransplantation over time. This review details non-immunologic obstacles relevant to this model described by our group and in the literature, as well as strategies that have been developed to address these specific challenges.

Cardiac xenografts show reduced survival in the absence of transgenic human thrombomodulin expression in donor pigs.

A combination of genetic manipulations of donor organs and target-specific immunosuppression is instrumental in achieving long-term cardiac xenograft survival. Recently, results from our preclinical pig-to-baboon heterotopic cardiac xenotransplantation model suggest that a three-pronged approach is successful in extending xenograft survival: (a) α-1,3-galactosyl transferase (Gal) gene knockout in donor pigs (GTKO) to prevent Gal-specific antibody-mediated rejection; (b) transgenic expression of human complement regulatory proteins (hCRP; hCD46) and human thromboregulatory protein thrombomodulin (hTBM) to avoid complement activation and coagulation dysregulation; and (c) effective induction and maintenance of immunomodulation, particularly through co-stimulation blockade of CD40-CD40L pathways with anti-CD40 (2C10R4) monoclonal antibody (mAb). Using this combination of manipulations, we reported significant improvement in cardiac xenograft survival. In this study, we are reporting the survival of cardiac xenotransplantation recipients (n = 3) receiving xenografts from pigs without the expression of hTBM (GTKO.CD46). We observed that all grafts underwent rejection at an early time point (median 70 days) despite utilization of our previously reported successful immunosuppression regimen and effective control of non-Gal antibody response. These results support our hypothesis that transgenic expression of human thrombomodulin in donor pigs confers an independent protective effect for xenograft survival in the setting of a co-stimulation blockade-based immunomodulatory regimen.

Consideration of appropriate clinical applications for cardiac xenotransplantation.

The field of cardiac xenotransplantation has entered an exciting era due to recent advances in the field. Although several hurdles remain, the use of rapidly evolving transgenic technology has the potential to address current allogeneic donor pool constraints and mechanical circulatory system device limitations. The success of xenotransplantation will undoubtedly be dependent on specific patient selection criteria. Defining these particular indications for xenotransplantation is important as we approach the possibility of clinical applications.

Circulating cell-free DNA as a biomarker of tissue injury: Assessment in a cardiac xenotransplantation model.

BACKGROUND: Observational studies suggest that cell-free DNA (cfDNA) is a biomarker of tissue injury in a range of conditions including organ transplantation. However, the lack of model systems to study cfDNA and its relevance to tissue injury has limited the advancements in this field. We hypothesized that the predictable course of acute humoral xenograft rejection (AHXR) in organ transplants from genetically engineered donors provides an ideal system for assessing circulating cfDNA as a marker of tissue injury. METHODS: Genetically modified pig donor hearts were heterotopically transplanted into baboons (n = 7). Cell-free DNA was extracted from pre-transplant and post-transplant baboon plasma samples for shotgun sequencing. After alignment of sequence reads to pig and baboon reference sequences, we computed the percentage of xenograft-derived cfDNA (xdcfDNA) relative to recipient by counting uniquely aligned pig and baboon sequence reads. RESULTS: The xdcfDNA percentage was high early post-transplantation and decayed exponentially to low stable levels (baseline); the decay half-life was 3.0 days. Post-transplantation baseline xdcfDNA levels were higher for transplant recipients that subsequently developed graft loss than in the 1 animal that did not reject the graft (3.2% vs 0.5%). Elevations in xdcfDNA percentage coincided with increased troponin and clinical evidence of rejection. Importantly, elevations in xdcfDNA percentage preceded clinical signs of rejection or increases in troponin levels. CONCLUSION: Cross-species xdcfDNA kinetics in relation to acute rejection are similar to the patterns in human allografts. These observations in a xenotransplantation model support the body of evidence suggesting that circulating cfDNA is a marker of tissue injury.

A Multidisciplinary Protocol-Driven Approach to Improve Extubation Times After Cardiac Surgery.

BACKGROUND: Prolonged intubation after cardiac surgery is associated with significant morbidity. A fast-track extubation protocol primarily driven by bedside providers was instituted for all postoperative cardiac surgery patients to facilitate safe and expeditious extubation. METHODS: A retrospective review of 1,581 cardiac surgery patients over an 8-year period was performed. Before 2011, nonprotocolized standard perioperative management was utilized (n = 807). From 2011 onward, a fast-track extubation (FTE) protocol directed by bedside providers was instituted (n = 774). Postoperatively, patients were placed on pressure-regulated volume control and titrated down to minimal support to maintain peripheral capillary oxygen saturation greater than 94%. For patients deemed ready for weaning (no evidence of hypoxia, hemodynamic instability, and so forth), a 30-minute continuous positive airway pressure trial was performed. Patients meeting all neurologic, respiratory, and cardiovascular criteria were extubated. The impact of the FTE algorithm on timely extubation, clinical outcomes, and safety was assessed. RESULTS: Baseline preoperative and intraoperative characteristics were similar between pre-FTE and FTE groups. Before instituting the FTE protocol, the rate of early extubation (less than 6 hours) was 43.7%, and increased to 64.1% during the FTE era (p < 0.001). Median time to extubation was also found to be significantly decreased: 295 minutes (interquartile range: 288) versus 385 minutes (interquartile range: 362, p = 0.041). There was no statistically significant difference in reintubation rates or 30-day mortality. CONCLUSIONS: The institution of a bedside provider-directed FTE pathway reduced overall intubation times and increased the rate of early extubation, without an increase in reintubation or mortality. This program-wide multidisciplinary approach appears to promote safe and expeditious extubation of cardiac surgery patients.