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The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the imbalanced innate immune response of end-stage coronavirus disease 2019 (COVID-19) has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here, we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues ex vivo, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with a rapid increase in tissue-associated viral subgenomic mRNA and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon-stimulated genes, cytokines, and chemokines, related to interferon signaling and immune-cell activation pathways, was broader than that triggered by influenza virus infection. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tracts that are specific to SARS-CoV-2. The studies shed light on the role of the nasal mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early-SARS-CoV-2-infected lung tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19. IMPORTANCE In order to reduce the late-phase morbidity and mortality of COVID-19, there is a need to better understand and target the earliest stages of SARS-CoV-2 infection in the human respiratory tract. Here, we have studied the initial steps of SARS-CoV-2 infection and the consequent innate immune responses within the natural multicellular complexity of human nasal mucosal and lung tissues. Comparing the global innate response patterns of nasal and lung tissues infected in parallel with SARS-CoV-2 and influenza virus, we found distinct virus-host interactions in the upper and lower respiratory tract, which could determine the outcome and unique pathogenesis of SARS-CoV-2 infection. Studies in the nasal mucosal infection model can be employed to assess the impact of viral evolutionary changes and evaluate new therapeutic and preventive measures against SARS-CoV-2 and other human respiratory pathogens.

While COVID-19 has killed millions of people globally, its lasting effects on the health and well-being of entire populations are just becoming clear. As many as 30% of those diagnosed with COVID-19 report continuing health-related problems, regardless of the severity of the initial infection. Given the infection rate in the world, that translates to between 5.4 and 17.9 million globally; about 700 000 in the US. The syndrome goes by many names; here we call it “long COVID.” Patients experience a wide range of symptoms, including serious organ system effects such as pulmonary fibrosis, myocarditis, new diabetes diagnoses, stroke, and other cerebrovascular events. They also experience ongoing pain, fatigue, and cognitive dysfunction. We suggest here that these patients require an integrative health approach, one that combines traditional medical management, non-pharmacological approaches, and behavior and lifestyle changes. Such an approach has been shown to be beneficial in other chronic illnesses such as fibromyalgia, chronic fatigue syndrome, and post-Lyme disease.

Objective. Integrative oncology is widely used by patients with breast cancer. This study aims to investigate the relationship between the survival outcomes of breast cancer patients and the level of involvement in integrative oncology at the institutions treating them. Methods. Claims-based data were used to find 4,815 newly diagnosed breast cancer patients treated between January 2013 and December 2014 for survival analysis. A scoring system was developed by asking oncologists about their institutions’ efforts to educate, support, and provide funding for 12 complementary and lifestyle approaches. Cohort analysis using two-tailed chi-square and a separate multivariate model using SMOTE and lasso regression were used. Nine variables across patient and institutional profiles were included. The model coefficients were exponentiated and presented as odds ratios. Results. 173 patients mapped to 103 institutions and 103 oncologists. The median patient age was 51, and 8% were metastatic. Institutions were scored for integrative oncology involvement and placed into four cohorts. Low-scoring institutions showed less effort to educate, support, and provide integrative therapies compared to others. The 5-year survival of patients in the low cohort was directionally but not significantly lower than others. In the multivariate model, a composite integrative oncology score was shown to increase 5-year survival odds three times for institutions in the low-mid cohort and 48% in the mid-high, compared to the low. Conclusion. Crossing the threshold beyond ‘low’ involvement in integrative oncology represents a new path to incremental survival benefit for many cancer patients. Entities invested in the survival of breast cancer patients should increase education, access, and funding for a core set of six therapies: nutrition counselling, exercise counselling, patient support groups, spiritual services, meditation, and psycho-oncology support.

e18588 Background: A growing body of evidence has shown that a Whole Person Integrative Oncology approach, adding the use of complementary and lifestyle therapies to cancer treatments, benefits patients by improving patient-reported outcomes and potentially extending overall survival. This study aims to investigate the relationship between the survival outcomes of breast cancer patients and the level of involvement in Integrative Oncology at the institutions treating those patients. Methods: Between January 2013 and December 2014, 4,815 breast cancer patients were available for survival analysis using an established claims-based method. These patients were filtered to include those with clear mapping to treating oncologists and treating institutions. To measure each institution’s level of Integrative involvement, a scoring system was developed with the Samueli Foundation and oncologists from each institution were surveyed on the education, availability, and financing of 12 complementary and lifestyle approaches during the treatment timeframe. Statistical analysis using multivariate modeling with logistic regression and a lasso approach were employed. 19 variables across region, patient demographics, and institutional profile were included. Model coefficients are exponentiated and presented as odds-ratios, with less than one having a negative impact on survival and greater than one improved survival. Results: We identified 173 patients mapping to 103 institutions and 103 oncologists who responded to our survey. Median age of breast cancer patients was 51 (range: 32-76). 14 of the patients (8%) were identified as metastatic. The 5-year overall survival among the Low scoring institutions was 89%, Low-Mid 96%, Mid-High 96%, High 95%. Chi square testing across these cohorts showed no statistically significant difference between them. On multivariate modeling, age, geography, metastatic status, academic setting, and Integrative score were predictors of 5-year survival. The most significant 9 variables are shown in Table. Having metastatic disease, treatment at a non NCCN designated facility, treatment at Midwest or Western Region predicts for lower 5-year survival. Older age, treatment at an academic setting, and having a High or Low-Mid Integrative score are predictors of improved survival. Conclusions: This study suggests that in addition to traditional predictors of survival such as metastatic disease and younger age, patients receiving treatment at an institution that supports Integrative Oncology programs may be associated with improved survival. More work is needed to evaluate the relationship between Integrative Oncology and cancer treatment outcomes.[Table: see text]

e24123 Background: The use of Complementary and Lifestyle (C&L) approaches in conjunction with medical treatments is known as Integrative Oncology. While Integrative Oncology practices have been steadily rising in the past few decades, there are still awareness and education gaps that medical professionals can help address for their patients. Methods: Survey-based data collection and analysis was used to assess awareness, perceptions, and usage of Integrative Oncology. Patients were randomly sampled among breast cancer patients diagnosed within 2 years and included all stages (0-IV) and all US regions (NE, South, Midwest, West). Physicians were sampled from a panel of community and academic practices across the US, with the requirement they treat at least 10 breast cancer patients in a typical 3-month period and have been in practice for at least 6 years since residency or fellowship. Results: Survey invitations were sent to 1,901 patients and 2,758 Oncologists; 164 breast cancer patients and 115 Oncologists completed the surveys. Approximately two-thirds of Oncologists and patients agree that C&L approaches contribute to improved quality of life and well-being for patients (table row 1, 2). However, significantly more patients than Oncologists believe that Integrative Oncology also leads to better treatment outcome and survival (row 3). In addition, Oncologists are significantly more aware of C&L practices than are patients (row 4). When asked what percent of breast cancer patients they discuss C&L methods with, Oncologists report 55% average (CI: 50-60%). However, when asked how they became aware of C&L, only 28% of patients (CI: 21-35%) mention their Oncologist/cancer care team or the institution where they were treated (not in table). Ideally, patients desire information about C&L to come directly from Oncologists, but that is not the predominant model (row 5). Conclusions: Many breast cancer patients believe an Integrative approach will improve their treatment outcomes and prefer their providers to discuss this with them.[Table: see text]

Introduction The CERP project aims to create a systems-based model for describing and evaluating resilience, with the expert input of a diverse group of scientists who help to identify metrics and create a testable model of resilience such that it can be applied to the evaluation of resilience, health and fitness in military populations. The specific aims of CERP are to: 1) Review and identify key domains for systems based assessment of health and fitness with particular relevance to military populations; 2) Convene a network of experts (termed the HARNESS group) to review the state of the science and identify metrics to be used in a systems based model of resilience; 3) Use the HARNESS group to identify or create standard analytical processes (criteria and procedures) for implementing resilience and fitness program tracking (i.e., the Health and Fitness Space Map), in part by identifying avenues for testing the created analytical model; and 4) Publish, communicate and disseminate information about this systems framework, its evaluation standards and translational processes widely so that they become available for use in the Department of Defense (DoD), Veterans Affairs (VA) and other systems.

(2000). Cancer Clinical Trials and Subject Use of Natural Herbal Products. Cancer Investigation: Vol. 18, No. 5, pp. 436-439.

Unfortunately, current conventional medical treatments for low back pain are not managing the problem effectively. Standard approaches to treatment, particularly surgery, may even be exacerbating the problem and causing additional pain and suffering. In this context, it is understandable that LBP patients often go outside of the conventional medical system seeking other treatment options. Conventional medical physicians who treat low- back pain patients, therefore, need to become more aware of the fact that their patients may be using complementary/alternative medical therapies.

In this essay, we posit that modern medicine, in its Asclepian focus, has subordinated the need and importance of Hygieian healing and caring, and in so doing has lost a quality that is essential to medicine, and fundamental to its lasting moral value. We argue that an integrative medicine must be based upon a core philosophical foundation that re-enjoins Asclepian and Hygieian approaches in true conceptual and practical dialectic, such that integration represents a synthesis of these orientations in epistemic, humanitarian and ethical domains.While we assert that a core philosophy is critical to the development and sustainability of an integrative medicine, such claims remain vacant in the absence of some meaningful attempt to put these concepts into action. We believe that to apply such philosophical foundations, an approach is necessary that simultaneously engages education, research, practice and policy.This involves not simply studying and co-opting new (or older, more ancient) modalities in a curative paradigm, but represents a paradigm shift that requires and is based upon understanding of, and skills for the application(s) of the most appropriate types of treatment(s) to affect disease, illness and health in a patient-centered model of care.

A RANDOMIZED controlled trial (RCT) is the most reliable method of assessing the efficacy of health care interventions.1,2Reports of RCTs should provide readers with adequate information about what went on in the design, execution, analysis, and interpretation of the trial. Such reports will help readers judge the validity of the trial. There have been several investigations evaluating how RCTs are reported. In an early study, Mahon and Daniel3reviewed 203 reports of drug trials published between 1956 and 1960 in theCanadian Medical Association Journal. Only 11 reports (5.4%) fulfilled their criteria of a valid report. In a review of 45 trials published during 1985 in three leading general medical journals, Pocock and colleagues4reported that a statement about sample size was only mentioned in five (11.1%) of the reports, that only six (13.3%) made use of confidence intervals, and that the statistical analyses tended to