How Academic Medical Centers Can Navigate the Pandemic and Its Aftermath: Solutions for 3 Major Issues.

The COVID-19 crisis has seriously affected academic medical centers (AMCs) on multiple levels. Combined with many trends that were already under way pre pandemic, the current situation has generated significant disruption and underscored the need for change within and across AMCs. In this article, the authors explore some of the major issues and propose actionable solutions in 3 areas of concentration. First, the impact on medical students is considered, particularly the trade-offs associated with online learning and the need to place greater pedagogical emphasis on virtual care delivery and other skills that will be increasingly in demand. Solutions described include greater utilization of technology, building more public health knowledge into the curriculum, and partnering with a wide range of academic disciplines. Second, leadership recruiting, vital to long-term success for AMCs, has been complicated by the crisis. Pressures discussed include adapting to the dynamics of competitive physician labor markets as well as attracting candidates with the skill sets to meet the requirements of a shifting AMC leadership landscape. Solutions proposed in this domain include making search processes more focused and streamlined, prioritizing creativity and flexibility as core management capabilities to be sought, and enhancing efforts with assistance from outside advisors. Finally, attention is devoted to the severe financial impact wrought by the pandemic, creating challenges whose resolution is central to planning future AMC directions. Specific challenges include recovery of lost clinical revenue and cash flow, determining how to deal with research funding, and the precarious economic balancing act engendered by the need to continue distance education. A full embrace of telehealth, collaborative policy-making among the many AMC constituencies, and committing fully to being in the vanguard of the transition to value-based care form the solution set offered.

ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder.

Geographically dispersed patients, inconsistent treatment tracking, and limited infrastructure slow research for many orphan diseases. We assess the feasibility of a patient-powered study design to overcome these challenges for Castleman disease, a rare hematologic disorder. Here, we report initial results from the ACCELERATE natural history registry. ACCELERATE includes a traditional physician-reported arm and a patient-powered arm, which enables patients to directly contribute medical data and biospecimens. This study design enables successful enrollment, with the 5-year minimum enrollment goal being met in 2 years. A median of 683 clinical, laboratory, and imaging data elements are captured per patient in the patient-powered arm compared with 37 in the physician-reported arm. These data reveal subgrouping characteristics, identify off-label treatments, support treatment guidelines, and are used in 17 clinical and translational studies. This feasibility study demonstrates that the direct-to-patient design is effective for collecting natural history data and biospecimens, tracking therapies, and providing critical research infrastructure.

Identifying and targeting pathogenic PI3K/AKT/mTOR signaling in IL-6-blockade-refractory idiopathic multicentric Castleman disease.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is a hematologic illness involving cytokine-induced lymphoproliferation, systemic inflammation, cytopenias, and life-threatening multi-organ dysfunction. The molecular underpinnings of interleukin-6(IL-6)-blockade refractory patients remain unknown; no targeted therapies exist. In this study, we searched for therapeutic targets in IL-6-blockade refractory iMCD patients with the thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin myelofibrosis, renal dysfunction, organomegaly (TAFRO) clinical subtype. METHODS: We analyzed tissues and blood samples from three IL-6-blockade refractory iMCD-TAFRO patients. Cytokine panels, quantitative serum proteomics, flow cytometry of PBMCs, and pathway analyses were employed to identify novel therapeutic targets. To confirm elevated mTOR signaling, a candidate therapeutic target from the above assays, immunohistochemistry was performed for phosphorylated S6, a read-out of mTOR activation, in three iMCD lymph node tissue samples and controls. Proteomic, immunophenotypic, and clinical response assessments were performed to quantify the effects of administration of the mTOR inhibitor, sirolimus. RESULTS: Studies of three IL-6-blockade refractory iMCD cases revealed increased CD8+ T cell activation, VEGF-A, and PI3K/Akt/mTOR pathway activity. Administration of sirolimus significantly attenuated CD8+ T cell activation and decreased VEGF-A levels. Sirolimus induced clinical benefit responses in all three patients with durable and ongoing remissions of 66, 19, and 19 months. CONCLUSION: This precision medicine approach identifies PI3K/Akt/mTOR signaling as the first pharmacologically-targetable pathogenic process in IL-6-blockade refractory iMCD. Prospective evaluation of sirolimus in treatment-refractory iMCD is planned (NCT03933904). FUNDING: Castleman's Awareness & Research Effort/Castleman Disease Collaborative Network, Penn Center for Precision Medicine, University Research Foundation, Intramural NIH funding, and National Heart Lung and Blood Institute.

A Randomized Controlled Trial to Improve the Success of Women Assistant Professors.

BACKGROUND: Given the persistent disparity in the advancement of women compared with men faculty in academic medicine, it is critical to develop effective interventions to enhance women's careers. We carried out a cluster-randomized, multifaceted intervention to improve the success of women assistant professors at a research-intensive medical school. MATERIALS AND METHODS: Twenty-seven departments/divisions were randomly assigned to intervention or control groups. The three-tiered intervention included components that were aimed at (1) the professional development of women assistant professors, (2) changes at the department/division level through faculty-led task forces, and (3) engagement of institutional leaders. Generalized linear models were used to test associations between assignment and outcomes, adjusting for correlations induced by the clustered design. RESULTS: Academic productivity and work self-efficacy improved significantly over the 3-year trial in both intervention and control groups, but the improvements did not differ between the groups. Average hours worked per week declined significantly more for faculty in the intervention group as compared with the control group (-3.82 vs. -1.39 hours, respectively, p = 0.006). The PhD faculty in the intervention group published significantly more than PhD controls; however, no differences were observed between MDs in the intervention group and MDs in the control group. CONCLUSIONS: Significant improvements in academic productivity and work self-efficacy occurred in both intervention and control groups, potentially due to school-wide intervention effects. A greater decline in work hours in the intervention group despite similar increases in academic productivity may reflect learning to "work smarter" or reveal efficiencies brought about as a result of the multifaceted intervention. The intervention appeared to benefit the academic productivity of faculty with PhDs, but not MDs, suggesting that interventions should be more intense or tailored to specific faculty groups.

Idiopathic multicentric Castleman's disease: a systematic literature review.

BACKGROUND: Multicentric Castleman's disease describes a group of poorly understood lymphoproliferative disorders driven by proinflammatory hypercytokinaemia. Patients have heterogeneous clinical features, characteristic lymph node histopathology, and often deadly multiple organ dysfunction. Human herpesvirus 8 (HHV8) causes multicentric Castleman's disease in immunosuppressed patients. The cause of HHV8-negative multicentric Castleman's disease is idiopathic; such cases are called idiopathic multicentric Castleman's disease. An absence of centralised information about idiopathic multicentric Castleman's disease represents a major challenge for clinicians and researchers. We aimed to characterise clinical features of, treatments for, and outcomes of idiopathic multicentric Castleman's disease. METHODS: We did a systematic literature review and searched PubMed, the Cochrane database, and ClinicalTrials.gov from January, 1995, with keywords including "Castleman's disease" and "giant lymph node hyperplasia". Inclusion criteria were pathology-confirmed Castleman's disease in multiple nodes and minimum clinical and treatment information on individual patients. Patients with HHV8 or HIV infection or diseases known to cause Castleman-like histopathology were excluded. FINDINGS: Our search identified 626 (33%) patients with HHV8-negative multicentric Castleman's disease from 1923 cases of multicentric Castleman's disease. 128 patients with idiopathic multicentric Castleman's disease met all inclusion criteria for the systematic review. Furthermore, aggregated data for 127 patients with idiopathic multicentric Castleman's disease were presented from clinical trials, which were excluded from primary analyses because patient-level data were not available. Clinical features of idiopathic multicentric Castleman's disease included multicentric lymphadenopathy (128/128), anaemia (79/91), elevated C-reactive protein (65/79), hypergammaglobulinaemia (63/82), hypoalbuminaemia (57/63), elevated interleukin 6 (57/63), hepatomegaly or splenomegaly (52/67), fever (33/64), oedema, ascites, anasarca, or a combination (29/37), elevated soluble interleukin 2 receptor (20/21), and elevated VEGF (16/20). First-line treatments for idiopathic multicentric Castleman's disease included corticosteroids (47/128 [37%]), cytotoxic chemotherapy (47/128 [37%]), and anti-interleukin 6 therapy (11/128 [9%]). 49 (42%) of 116 patients failed first-line therapy, 2-year survival was 88% (95% CI 81-95; 114 total patients, 12 events, 36 censored), and 27 (22%) of 121 patients died by the end of their observed follow-up (median 29 months [IQR 12-50]). 24 (19%) of 128 patients with idiopathic multicentric Castleman's disease had a diagnosis of a separate malignant disease, significantly higher than the frequency expected in age-matched controls (6%). INTERPRETATION: Our systematic review provides comprehensive information about clinical features, treatment, and outcomes of idiopathic multicentric Castleman's disease, which accounts for at least 33% of all cases of multicentric Castleman's disease. Our findings will assist with prompt recognition, diagnostic criteria development, and effective management of the disease. FUNDING: None.

Clinical decision support improves physician guideline adherence for laboratory monitoring of chronic kidney disease: a matched cohort study.

BACKGROUND: Guidelines exist for chronic kidney disease (CKD) but are not well implemented in clinical practice. We evaluated the impact of a guideline-based clinical decision support system (CDSS) on laboratory monitoring and achievement of laboratory targets in stage 3-4 CKD patients. METHODS: We performed a matched cohort study of 12,353 stage 3-4 CKD patients whose physicians opted to receive an automated guideline-based CDSS with CKD-related lab results, and 42,996 matched controls whose physicians did not receive the CDSS. Physicians were from US community-based physician practices utilizing a large, commercial laboratory (LabCorp®). We compared the percentage of laboratory tests obtained within guideline-recommended intervals and the percentage of results within guideline target ranges between CDSS and non-CDSS patients. Laboratory tests analyzed included estimated glomerular filtration rate, plasma parathyroid hormone, serum calcium, phosphorus, 25-hydroxy vitamin D (25-D), total carbon dioxide, transferrin saturation (TSAT), LDL cholesterol (LDL-C), blood hemoglobin, and urine protein measurements. RESULTS: Physicians who used the CDSS ordered all CKD-relevant testing more in accord with guidelines than those who did not use the system. Odds ratios favoring CDSS ranged from 1.29 (TSAT) to 1.88 (serum phosphorus) [CI, 1.20 to 2.01], p < 0.001 for all tests. The CDSS impact was greater for primary care physicians versus nephrologists. CDSS physicians met guideline targets for LDL-C and 25-D more often, but hemoglobin targets less often, than non-CDSS physicians. Use of CDSS did not impact guideline target achievement for the remaining tests. CONCLUSIONS: Use of an automated laboratory-based CDSS may improve physician adherence to guidelines with respect to timely monitoring of CKD.

American medical education at a crossroads.

New medical-education models in which research plays a modest role could engender a two-tiered educational system, cause a reduction in the physician-scientist pipeline, and diminish the translation of biomedical advances.

A review of the mental health issues of diabetes conference.

Individuals with type 1 diabetes are at increased risk for depression, anxiety disorder, and eating disorder diagnoses. People with type 1 diabetes are also at risk for subclinical levels of diabetes distress and anxiety. These mental/behavioral health comorbidities of diabetes are associated with poor adherence to treatment and poor glycemic control, thus increasing the risk for serious short- and long-term physical complications, which can result in blindness, amputations, stroke, cognitive decline, decreased quality of life, as well as premature death. When mental health comorbidities of diabetes are not diagnosed and treated, the financial cost to society and health care systems is catastrophic, and the human suffering that results is profound. This review summarizes state-of-the-art presentations and working group scholarly reports from the Mental Health Issues of Diabetes Conference (7-8 October 2013, Philadelphia, PA), which included stakeholders from the National Institutes of Health, people living with type 1 diabetes and their families, diabetes consumer advocacy groups, the insurance industry, as well as psychologists, psychiatrists, endocrinologists, and nurse practitioners who are all nationally and internationally recognized experts in type 1 diabetes research and care. At this landmark conference current evidence for the incidence and the consequences of mental health problems in type 1 diabetes was presented, supporting the integration of mental health screening and mental health care into routine diabetes medical care. Future research directions were recommended to establish the efficacy and cost-effectiveness of paradigms of diabetes care in which physical and mental health care are both priorities.

'One Medicine - One Health' at the School of Veterinary Medicine of the University of Pennsylvania - the first 125 years.

The University of Pennsylvania's School of Veterinary Medicine (Penn Vet), in partnership with other veterinary schools and health professions, is positioned well to advance an international 'One Medicine - One Health' initiative. Founded in 1884 by the University's Medical Faculty, the School has been a leader in moulding the education and practice of veterinary medicine in the nation and the world. Successfully integrating biomedical research into all aspects of veterinary medical education, the School has made significant contributions to basic and clinical research by exemplifying 'One Medicine'. In looking to the future, Penn Vet will embrace the broader 'One Health' mission as well.

The changing relationships between academic health centers and their universities: a look at the University of Pennsylvania.

After a period of financial losses in the University of Pennsylvania Health System stemming from a combination of internal decision making and negative external market forces, the university set out to make substantial changes in the governance and administrative organization overseeing its health system and medical school. The changes were designed to assure the university and its trustees that financial controls were strengthened and that the missions of research, education, and patient care were balanced. The governance changes included creating a structure whereby a single administrative leader was responsible for all three missions--education, research, and clinical care--and reported directly to the president of the university. Further, existing governing boards responsible for various entities within the school of medicine and health system were disbanded, and a new single board was created to oversee PENN Medicine, the overarching organization established in 2001 and now responsible for oversight of the University of Pennsylvania School of Medicine and the University of Pennsylvania Health System. The realignment initiated by these major changes spawned additional refinements in leadership responsibilities and process controls that, together with the new governance model, are credited with financial recovery and stronger performance in all aspects of the enterprise. These structural changes led to greater emphasis on integrating and coordinating programs to take advantage of PENN Medicine's home in a leading university.

Institutional leadership and faculty response: fostering professionalism at the University of Pennsylvania School of Medicine.

Fostering professionalism requires institutional leadership and faculty buy-in. At the University of Pennsylvania School of Medicine, policies and educational programs were developed to enhance professionalism in three areas: conduct of clinical trials, relations with pharmaceutical manufacturers, and the clinical and teaching environment. Responsible conduct of clinical trials has been addressed with mandatory online education and certification for clinical investigators, but some still fail to recognize conflicts of interest. Activity of pharmaceutical representatives has been strictly regulated, meals and gifts from pharmaceutical companies prohibited, and the role of the pharmaceutical industry in the formulary process and in continuing medical education curtailed. Some faculty members have resented such restrictions, particularly in regard to their opportunity to give paid lectures. Professionalism in the clinical and teaching environment has been addressed with interdisciplinary rounding, experiential learning for medical students and residents in small groups, increased recognition of role models of professionalism, and active management of disruptive physicians. Leadership has been exerted through policy development, open communications, and moral suasion and example. Faculty members have expressed both their support and their reservations. Development of communication strategies continues, including town hall meetings, small groups and critical incident narratives, and individual feedback. The understanding and endorsement of faculty, staff, and trainees are an essential element of the professionalism effort.

The Clinical Research Forum and Association of American Physicians disagree with criticism of the NIH Roadmap.

As representatives of 50 leading academic medical centers focusing on clinical research and many of academic medicine's scientific leaders, the Clinical Research Forum and Association of American Physicians disagree with the JCI's recent editorials on the NIH Roadmap, Elias Zerhouni's leadership, and the future directions of biomedical research.

Rekindling student interest in generalist careers.

Despite changes in the structure of the U.S. health care system, patients continue to need and seek out generalist physicians. However, the proportion of U.S. graduates of medical schools who choose to enter generalist residency training decreased from 50% in 1998 to less than 40% in the 2004 match. Unless we act now to reverse this trend, we may face a shortage of primary care physicians to care for the complex medical needs of an aging population. This article reviews the history of and trends in career choice and proposes 4 evidence-based recommendations to rekindle student interest in generalist careers: 1) We must improve satisfaction and enthusiasm among generalist physician role models. 2) Schools of medicine should redouble their efforts to produce primary care physicians. 3) We must facilitate the pathway from medical school to generalist residency. 4) The U.S. government should increase funding for primary care research and research training. In the absence of a major overhaul of economic incentives in favor of generalist careers, we will need to work at these multiple levels to restore balance to the generalist physician workforce and align with the desires and expectations of patients for continuing healing relationships with generalist physicians.