Modeling the enigma of complex disease etiology.

BACKGROUND: Complex diseases often present as a diagnosis riddle, further complicated by the combination of multiple phenotypes and diseases as features of other diseases. With the aim of enhancing the determination of key etiological factors, we developed and tested a complex disease model that encompasses diverse factors that in combination result in complex diseases. This model was developed to address the challenges of classifying complex diseases given the evolving nature of understanding of disease and interaction and contributions of genetic, environmental, and social factors. METHODS: Here we present a new approach for modeling complex diseases that integrates the multiple contributing genetic, epigenetic, environmental, host and social pathogenic effects causing disease. The model was developed to provide a guide for capturing diverse mechanisms of complex diseases. Assessment of disease drivers for asthma, diabetes and fetal alcohol syndrome tested the model. RESULTS: We provide a detailed rationale for a model representing the classification of complex disease using three test conditions of asthma, diabetes and fetal alcohol syndrome. Model assessment resulted in the reassessment of the three complex disease classifications and identified driving factors, thus improving the model. The model is robust and flexible to capture new information as the understanding of complex disease improves. CONCLUSIONS: The Human Disease Ontology's Complex Disease model offers a mechanism for defining more accurate disease classification as a tool for more precise clinical diagnosis. This broader representation of complex disease, therefore, has implications for clinicians and researchers who are tasked with creating evidence-based and consensus-based recommendations and for public health tracking of complex disease. The new model facilitates the comparison of etiological factors between complex, common and rare diseases and is available at the Human Disease Ontology website.

Dose Response of Bulky Tumors in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This study sought to assess whether there is a radiotherapy (RT) dose response for bulky tumors in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Patients with r/r DLBCL (age ≥18 years) treated with salvage- or palliative-intent RT (2008-2020) at a single institution were included. Course-level data were examined to assess in-field responses of index lesions. Courses used for either post-therapy consolidation, CNS or skin disease, and TBI conditioning were excluded. Index lesion size ≥7.5 cm was considered bulky. EQD2s (α/β = 10) were calculated to accurately compare biologic effective doses between conventional and hypofractionated (≥2.5 Gy/fraction) schemes. Post-treatment responses of index lesions were classified using Lugano Criteria. Objective response rates (ORR), defined as achieving either CR or PR, were compared between non-bulky and bulky tumors using Fisher's exact test. Freedom from local progression (FFLP) and overall survival (OS, patient-level data) from RT start date were recorded. Bulky disease impacts on FFLP and OS were assessed using Kaplan-Meier and multivariable-adjusted Cox proportional hazard regression analyzes. 151 r/r DLBCL patients underwent 183 RT courses (median follow-up time: 6 months, IQR: 2-17 months). Median age at RT was 67 years (IQR: 56-72 years) with a male/female ratio of 55%/45%. Non-bulky and bulky tumors were treated in 109 (60%) and 74 (40%) cases, respectively. Intent was classified as salvage or palliative in 68 (37%) and 115 (63%) cases, respectively. Median EQD2 was 33 Gy (IQR: 23-39 Gy) with hypofractionation used in 84 (46%) cases. Of those with post-RT imaging (n = 146, 80%), there was a trend towards lower ORR for bulky vs. non-bulky tumors (50% vs. 65%, p = 0.087;CR: 21% vs. 42%, PR: 29% vs. 23%, SD: 28% vs. 14%, PD: 22% vs. 22%). For bulky tumors, RT regimens with EQD2s >30 Gy were associated with better ORR (≤30 Gy vs. >30 Gy: 27% vs. 64%, p = 0.014), whereas a lower EQD2 cut-off was sufficient for non-bulky tumors (<20 Gy vs. ≥20 Gy: 38% vs. 73%, p = 0.0076). In all courses, bulky tumors were significantly associated with shorter FFLP (median: 5.6 months vs. not reached, HR = 2.30, 95% CI: 1.24-4.26, p = 0.0079) and OS (median: 3.7 vs. 10.1 months, HR = 1.66, 95% CI: 1.06-2.58, p = 0.025). Amongst bulky tumors, there was a trend towards improved FFLP with RT regimens with higher EQD2s (20-30 Gy vs. <20 Gy - median: 4.2 vs. 2.3 months, HR = 0.38, 95% CI: 0.09-1.62, p = 0.19;>30 Gy vs. <20 Gy - median: not reached vs. 2.3 months, HR = 0.34, 95% CI: 0.11-1.01, p = 0.053). In this study, bulky r/r DLBCL tumors were associated with less favorable outcomes in salvage and palliative settings. If durable local control of bulky tumors is needed, RT regimens using higher EQD2s (>30 Gy) should be considered, including cases where shortened, hypofractionated courses are opted for such as during the SARS-CoV-2 pandemic, bridging to CAR-T cell infusion, or prior to allogeneic stem cell transplantation. [ FROM AUTHOR] Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Reflections from Faculty/Scholars

Numerous commentators have observed that higher education in the United States is at a crossroads. As educational institutions contemplate furloughs, transformations of their core technologies, and other deep-seated changes, employee and union involvement are essential in determining new strategies and tactics for implementation. Faculty and staff have immense local knowledge which administrators often lack. Collective bargaining in higher education has the potential to serve two functions, one of which is common and one that is all too rare. The common function is setting wages, hours, and working conditions, which is specified in relevant federal and state laws. The less common, but crucial function is to codify past innovations in employment relations and to set the stage for future innovations. The need to transform collective bargaining in higher education is a product of fundamental challenges to higher education, many of which have been accelerated by the COVID-19 pandemic. © 2022 Taylor & Francis.

Establishing a SARS-CoV-2 Monoclonal Antibody Infusion Clinic: Early Trends in Outcomes and Disparities

Background. SARS-CoV-2 monoclonal antibodies (SMA) have demonstrated efficacy in treatment of early, mild to moderate COVID-19 in patients at high risk for progression to severe COVID-19. We created an SMA infusion clinic at a large, urban academic medical center using both internal and community-based referral mechanisms to promote the equitable distribution of treatment. Methods. Data were analyzed from clinic referrals from December 13, 2020 through April 20, 2021. Patient demographics, census-based area deprivation index (ADI) scores (scale of 1-10, with 1 representing least socioeconomic deprivation and 10 representing most), and relevant comorbidities were collected. Outcomes included days of symptoms until referral, patient receipt of SMA therapy after referral, adverse events, and ER visits and hospitalizations within 14 days of SMA administration. Association between demographic factors and relevant outcomes were determined using chi-square or Wilcoxon rank-sum tests as appropriate. Results. 47/433 (11%) referred patients were ineligible based on inclusion and exclusion criteria. Of eligible patients, 310/386 (80%) received treatment;patients who did not receive treatment either declined (93%), could not be contacted (5%), no-showed (1%), or were admitted for hypoxia (1%). Of treated patients, only 3 (1%) had adverse reactions. Within 14 days of SMA administration, 28 (9%) patients visited the ER or were admitted for COVID-19. Black patients had a longer median duration of symptoms prior to referral compared to White patients (5 vs. 3 days, p < 0.01) (Figure 1). White patients were more likely to receive SMA after referral compared to Black patients (88% vs. 64%, p < 0.01), as were patients with ADI score 1-5 compared to those with ADI score 6-10 (88% vs. 70%, p < 0.01) (Figures 2 and 3). Black patients who received SMA had a higher rate of ER visits or admissions than White patients, although the difference was not statistically significant (14% vs. 7%, p = 0.10). Conclusion. Rate of adverse reactions and COVID-related ER visits or admissions were low in patients who received SMA. Despite efforts to promote the equitable distribution of treatment through multiple referral mechanisms, racial and socioeconomic disparities still exist.

Introduction: Theorizing media ventriloquism

The introduction defines “media ventriloquism” and explains its value in an era wherein interactions are increasingly mediated. The political stakes of the project are high, particularly when the world is witnessing technological manipulation on a grand scale, yet the theoretical lens used in this volume allows the authors to approach ventriloquism from a number of disciplines and apply it to texts from nineteenth-century spiritualism to early Hollywood talkies to Korean video games. The introduction explains how the chapters are organized into sections and coins two new terms that unify their focus: the “technovocalic body, " which builds on Steven Connor’s idea of the vocalic body, and the “screen voice, " which is rooted in Sigmund Freud’s discussion of the screen memory. To explain these terms, the chapter turns to recent films by Spike Lee and Boots Riley and also references classics such as Singin’ in the Rain and Julie Dash’s Illusions. © Oxford University Press 2021.

Cohort of patients of the eps (Entity providing health services) sanitas with rheumatic diseases and covid19

Objectives: It is unclear whether autoimmune diseases increased the risk, worsened the prognosis, or the outcome of patients with SARS-CoV-2 infection. Methods: Observational, cross-sectional study, data collected from a historical cohort of patients with rheumatic diseases between the period of March 2020 and August 2020. Results: 192 patients were included, the majority were women (Women: 68.8%) the most common rheumatic disease was rheumatoid arthritis, followed by Sjögren's syndrome (Table 1). The most frequent associated comorbidity was arterial hypertension (27%), followed by renal disease (8.1%) and diabetes mellitus (8%). The most frequent symptom was headache (92.2%), followed by cough (58.5%), anosmia (44.9%), odynophagia (44.7%) and fever (44.5%). There was some alteration in the measurement of D-dimer, Ferritin, LDH, fibrinogen, troponin, leukocyte count, lymphocytes, platelets, acute phase reactants, transaminases, and creatinine. 36 (18.8%) patients required hospitalization, 10 in the ICU with mechanical ventilatory support. Most of the patients were undergoing treatment with conventional disease-modifying drugs (DMARDcs) (68.8%), 15(8.8%) were undergoing treatment with biological therapy. The main form of contagion suspected was contact with a family member or coworker. Of the total number of patients, 15 (7.8%) died associated with some complication from COVID19 Conclusion: We obtained similar results to international cohorts(1), highlighting important data such as the predominance of rheumatoid arthritis vs other rheumatic disease, the greater use of DMARDcs compared to other therapies and mortality. Likewise, studies should continue to evaluate the behavior of the SARS-COV-2 infection in patients with rheumatic diseases, to understand this infection better.

Nursing care plan for the prevention of pressure ulcers secondary to prone positioning in COVID-19 patients

Introduction: Prone position (PP) is a therapeutic alternative widely used and recommended in patients with COVID-19. Although PP is a non-invasive procedure, it is complex and could be associated with complications such as the development of pressure ulcers (PU). We aimed to propose a standardized nursing care plan in terms of NANDA-International, NIC (Nursing Interventions Classification) and NOC (Nursing Outcomes Classification) to prevent PU secondary to the PP in people with COVID-19. Content synthesis: In patients with COVID-19, in addition to risk factors such as advanced age and the presence of comorbidities, PP contributes to the presence of pressure ulcer risk nursing diagnoses [00249], of deterioration of skin [00047] and tissue [00248] integrity. On the other hand, the nursing intervention for the prevention of pressure ulcers [3540], due to the specificity and scientific basis of its activities, is key to minimize the development of this complication, improve the quality of care and the prognosis in this type of patients. Finally, to evaluate the effectiveness of nursing care, we propose the nursing results (NOC): consequences of immobility: physiological [0204] and tissue integrity: skin and mucous membranes [1101]. Conclusion: PP is a recommended adjunctive therapy for the management of critically ill COVID-19 patients due to its benefits to improve lung function. However, it is associated with adverse effects such as PU. This article presents recommendations based on a narrative review for a better implementation of preventive nursing care that reduces the frequency of PU in this population. © 2021 River Publishers. All rights reserved.