Pandemic Highlights Urgency for New Methodologies for Evidence Generation

Randomized controlled trials, which many consider to be the gold standard of clinical research, were developed in the 1940s. [...]individual patients in the real world react often very differently to a specific drug than what has been predicted by the "mean" of a clinical trial. Many biopharmaceutical companies and AI startups are betting that with enough data, these methods will work so well that they will help to accelerate the discovery of new therapies for the novel corona virus, 2019-nCoV (see go.nature.com/3aLd0ll). * Causal AI methods might be uniquely positioned to discover underlying causes of disease and clinical response to treatment on an individual level, making personalized medicine real.

Accelerating Clinical Trial Design and Operations

Fully-integrated, component-based CDMS offers flexibility, customization, and efficiency Effective and efficient clinical data collection and management is one of the key factors affecting clinical trial success and is of heightened importance during the COVID-19 pandemic.1 Not only have the scope and complexity of clinical trials continued to increase over the past decade, but the volume and diversity of clinical study data grows ever larger. Researchers have accelerated the development of vaccines and therapeutics for COVID-19 as evidenced by the 4,846 trials found on clinicaltrials. gov.2 The COVID-19 pandemic presents a unique opportunity for understanding technologies that can enable trial data management and their effects on streamlining;and expediting clinical trial design and implementation. Specific measurements evaluated in this study were: database build efficiency, velocity of data collection, frequency of protocol amendments on the database, and the time impact of mid-study updates to the database. [...]the ability to execute mid-study updates or post-go live changes with minimal to no downtime (< one hour) allowed the users and sponsors to work in parallel rather than in serial fashion, speeding up trial start dates and implementation of protocol amendments, and accommodating adaptive COVID-19 trial design.

A Hospital System's Journey Toward Zero Harm: Reducing Postoperative Respiratory Failure

Postoperative respiratory failure is a significant cause of morbidity and mortality. Early identification of patients at moderate to high risk of postoperative respiratory failure is critical to effective prevention strategies. A multi-disciplinary team developed a robust process for the early identification of at-risk patients and the prevention of respiratory failure in the perioperative setting.

The Impact of COVID-19 Pandemic on Palliative Care Services as Perceived by Healthcare Professionals: A Systematic Review

Background: The Covid-19 pandemic stretched healthcare systems' capacity, imposed the reorganization and reprioritization of services under the burden of scarce resources, and altered the traditional way that care was provided. Palliative care, though designed to address complex needs such as relief from severe suffering, difficult decision making and complicated grief was not an exception;its holistic approach of care was seriously challenged due to infection spread restrictions. Objective: To review the impact on palliative care services from healthcare professionals' perspective. Methodology: A systematic review according to the Preferred Reporting Items for Systematic Review and MetaAnalysis (PRISMA) was conducted via PubMed in October 2022. Eligibility criteria included original studies that had used a qualitative, quantitative, or mixed design approach to evaluate the impact on services, delivery of care, and emotional status of palliative healthcare professionals. Results: Out of 2040 initial records, 32 studies were included in the review coming from various countries and settings with representative participation of multidisciplinary palliative care teams' members. Reported impacts concerned organizational aspects and provision of services, altered delivery of care, and implications for the mental health of involved staff. Increased workload, visiting restrictions, use of Personal Protective Equipment, and remote contact were perceived as factors compromising the quality of care provided and impeding palliative healthcare professionals from fulfilling their holistic care role. Moral distress was the most exacerbated emotional impact. Conclusions: Despite the important role that palliative care can play during a health crisis, this was not always adequately reflected on pandemic plans. In the era of the Covid-19, Palliative care entered a phase of change;whether this fact may compromise or accelerate its evolvement depends on how lessons learned will be used in future planning.

Considerations for the Management of Oncology Patients During the COVID-19 Pandemic

[...]we highlight ongoing investigational treatment approaches that are so relevant to the care of oncology patients during this extraordinary pandemic. While many therapeutic strategies are currently being evaluated as possible COVID-19 treatments, there are currently no highly effective antiviral therapies or vaccines available to combat this virus, and mortality in severe disease remains high.6 Risk factors for severe illness resulting from COVID-19 are age greater than 65 years, diabetes, chronic lung disease, and obesity,7 and cancer patients who contract COVID-19, in particular, have been shown to have worse outcomes.8 In the initial experience reported from Wuhan, China, 1% of cancer patients were noted to contract COVID-19, compared with just 0.29% incidence in the general population.8 This may be attributed to greater detection rates in more closely surveilled cancer patients, but it could also be associated with nosocomial exposures and diminished im mune defenses.8 Cancer patients were also observed to be at higher risk for the development of severe COVID-19, which may be due to generally advanced age, increased prevalence of tobacco use, and higher incidence of comorbid pulmonary disease.9 Liang et al also demonstrated that cancer patients were more likely to require intensive care or experience mortality as compared with other COVID-19 patients (39% vs 8%).9 Cancer treatment may also increase COVID-19 susceptibility. Lin et al recommend LMWH at 100 U/kg every 12 hours for at least 3 to 5 days.8 In addition, a study performed in Tongji Hospital in Wuhan reviewed 449 patients with severe COVID-19, with 94 patients receiving LMWH (40-60 mg/day) and 5 receiving unfractionated heparin (1000-15,000 U/day) for 7 days or longer;the results showed that the 28-day mortality for LMWH or unfractionated heparin users with a sepsis-induced coagulopathy score of ≥4 and D-dimers >6 times the upper limit of normal was lower than that of non-LMWH or unfractionated heparin users.14 This has led several institutions, including our own, to institute anticoagulation protocols based on various parameters such as D-dimer levels.17 Pathophysiology of COVID-19 Coronaviruses are large, single-stranded, positive-sense RNA strand that encapsulate within a membrane envelope surrounded by glycoprotein spikes, forming a crown-like appearance.18 Less-pathogenic endemic human coronaviruses such as OC43, HKU1, NL63, and 229E exist, causing seasonally, self-limited upper respiratory symptoms.19 In contrast, more severe respiratory symptoms are caused by zoonotic human coronaviruses, including severe acute respiratory distress syndrome coronavirus (SARSCoV) discovered in November 2002 in Guangdong, China;Middle Eastern respiratory syndrome-related coronavirus (MERS-CoV) identified in 2012 in Saudi Arabia;and COVID-19.18 The subfamily, Coronavirinae, is divided into 4 classes of coronaviruses: α, β, δ, and γ. ACE2 has been shown to promote anti-inflammatory and antifibrotic effects, and it protects these cells from ARDS.19 In SARS-CoV-2, ACE2 ectodomain can shed as a result of spikes from the viral glycoprotein, reducing the catalytic function of ACE2 and promoting ARDS.19 In addition, SARS-CoV-2 has been shown to reduce synthesis of interferon-α and interferon-β and to increase inflammatory cytokines and chemokines.20 In lung adenocarcinomas, ACE2 gene expression

Predictors of COVID-19 Vaccination Uptake and Reasons for Decline of Vaccination: A Systematic Review

Background: Various COVID-19 vaccines with proven safety and effectiveness are available now but vaccine hesitancy remains a public threat. COVID-19 vaccines uptake appears to have an essential role in the successful control of the COVID-19 pandemic. Objective: To examine predictors of COVID-19 vaccination uptake and reasons for decline of vaccination. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for this systematic review. We searched Medline, PubMed, Web of Science, Scopus, ProQuest, CINAHL, and a preprint service (medRxiv). We used the following key-words: vaccin·, COVID-19, and uptake. We included all types of studies (quantitative, qualitative, and mixed methods) reporting COVID-19 vaccination uptake. The review protocol was registered with PROSPERO (CRD42021267460). Results: Twelve studies met the inclusion and exclusion criteria. COVID-19 vaccination uptake ranged from 28.6% to 98% in the general population, while among healthcare workers ranged from 33.3% to 94.5%, and among patients ranged from 36% to 80%. The main predictors of COVID-19 vaccination uptake were male gender, white race, older age, higher socioeconomic status, higher self-perceived COVID-19 vulnerability, increased information about COVID-19 vaccines, and chronic illness. The most important reasons for decline of vaccination were concerns about the safety and effectiveness of vaccines, illness, medication, pregnancy, fertility, breastfeeding, religious reasons, ethical reasons, previous COVID-19 diagnosis, self-estimation that COVID-19 is not a severe disease, and limited knowledge about the vaccines. Conclusions: Several factors affect COVID-19 vaccination uptake, while various reasons affect people's decision to refuse to take a COVID-19 vaccine. These findings are essential to further enhance our understanding of COVID-19 vaccination uptake and design specific interventions. Given the high prevalence of COVID-19 vaccine hesitancy, our findings have major implications for the delivery of COVID-19 vaccination programmes in the public with special attention to people who are undecided or unlikely to take a COVID-19 vaccine.

MeTA-Edu: uma nova metodologia para validação de tecnologias educacionais aplicada à prevenção da COVID-19 em adultos com câncer

Introdução: O uso de tecnologias educacionais validadas favorece o acesso às informações confiáveis e adequadas e representa uma importante ferramenta de comunicação de risco para portadores de câncer durante emergências em saúde pública. Objetivo: Avaliar a validade e confiabilidade de uma cartilha eletrônica sobre a COVID-19 para adultos portadores de câncer. Métodos: Estudo metodológico de validação por 22 juízes especialistas residentes vinculados à plataforma nacional de curriculum vitae do Brasil. A amostragem foi realizada por conveniência e bola-de-neve, e a seleção, conforme os critérios de Jasper. A validade da cartilha foi avaliada por questionário eletrônico através do índice de validade de conteúdo (CVI), coeficiente de correlação intraclasse (ICC), o instrumento de avaliação da adequabilidade de materiais (SAM) e a análise temática metalinguística para tecnologias educacionais (MeTA-Edu) de proposições dissertativas. Resultados: A banca avaliadora foi composta por 22 doutores com características sociodemográficas homogêneas e elevado especialização na área de educação (86,4%) e experiência docente (média = 17,8 anos). De modo geral, a tecnologia educacional foi validada pelos juízes especialistas quanto ao conteúdo (CVI global = 0,953) com alto grau de concordância (ICC= 0,958) e adequação de conteúdo, literacia necessária para a compreensão, desenho gráfico, layout e tipografia, estimulação e motivação de aprendizagem e adequação cultural (SAM= 90,6%). Após análise temática, foram identificadas 94 proposições dissertativas, principalmente no tipo de linguagem visual (47,9%), e função referencial/informativa (68,1%). Assim, 83,0% das sugestões foram acatadas e 17,0%, rejeitadas mediante justificativa. Conclusão: A validade e confiabilidade da cartilha "Descomplicando a COVID-19 para pessoas com câncer” foi ratificada pelos juízes especialistas. Estes achados podem contribuir para a otimização metodológica da validação de tecnologias educacionais e inovação de estratégias de educação em saúde, subsidiando a assistência oncológica em tempos de crise.Alternate abstract: Introduction: validated educational technologies favor access to reliable and adequate information, representing a critical risk communication tool for cancer patients during public health emergencies. Objective: to assess the validity and reliability of an electronic booklet on COVID-19 for adults with cancer. Methods: methodological validation by a panel of 22 experts linked to Brazil's national curriculum vitae database. Sampling was performed by convenience, snowball, and selection techniques according to Jasper's criteria. The validity of the booklet was evaluated by an electronic questionnaire using the content validity index (CVI), intraclass correlation coefficient (ICC), the suitability assessment of materials (SAM) instrument, and the metalinguistic thematic analysis for educational technologies (MeTA-Edu) of dissertation proposals. Results: the expert panel consisted of 22 doctors with homogeneous sociodemographic characteristics, high specialization in education (86.4%), and teaching experience (average = 17.8 years). In general, the educational technology was validated by experts for content (overall CVI = 0.953) with a high degree of agreement (ICC = 0.958) and suitability of the content, literacy demand, graphics, layout, and typography, learning stimulation and motivation, and cultural appropriateness (SAM = 90.6%). After thematic analysis, 94 dissertation proposals were identified, mainly of the visual language type (47.9%) and referential/informative function (68.1%). Most expert suggestions were accepted (83.0%), and only 17.0% were rejected. Conclusion: the validity and reliability of the booklet "Uncomplicating COVID-19 for people with cancer” were ratified by experts. These findings can contribute to the methodological optimization of the validation of educational technologies and innovation of health education strategies, subsidizing cancer care in times of crisis.

Use of multidisciplinary positive deviance seminars to improve efficiency in a high-volume arthroplasty practice: a pilot study

Delivery of health care is coming to an inflection point in regard to supply and demand, with joint replacement demand in Canada increasing from 2014 to 2019 by 20.1% for hip replacement and 22.5% for knee replacement.1 Increasing demand, combined with delays related to the COVID-19 pandemic, has created a large backlog of surgical procedures, especially in countries with universal health care like Canada and the United Kingdom, where efficient delivery of health care is even more critical.2-4 Prolonged surgical wait-lists are further compounded by systemic inefficiencies: in North America, health care functions at a productivity level of about 43%;in the surgical care setting, inefficient use of time and space accounts for 30% of costs.5 To address this, various initiatives to increase throughput, such as high-efficiency operating rooms (ORs) and parallel processing with anesthesia block rooms, have been suggested.6 At our institution, to address wait times and increasing demands, 4-joint rooms were instituted in 2004, but successful completion of 4 joint replacement procedures within the assigned OR time (i.e., 4 joints between 0730 and 1530) has been inconsistent.7 This lack of efficiency, with overtime and lack of improvement, can lead to staff disengagement, fatigue and a sense of impossibility of the task at hand.8 To foster self-improvement and staff engagement to work as a team, various models of team efficiency have been developed using the Lean method, Six Sigma and process mapping, which can be quite effective but very resource intensive.9,10 An alternative approach that has shown excellent results in improving the quality of individual surgeon practices is positive deviance (PD) seminars,11,12 which use individual performance feedback to identify team members who outperform their peers. Positive deviance has been effectively used in health care, public health, education and the private sector.13 Positive deviance seminars focus on individual strengths and resources already present, instead of negatives that require improvement. Measures The time interval data were recorded by the circulating nurse using the Surgical Information Systems. The time intervals used to determine OR efficiency were a modified version of those defined by the Association of Anesthesia Clinical Directors:14 anesthesia preparation time;patient in room to anesthesia ready, surgical preparation time;anesthesia ready to procedure start, procedure duration;(procedure start time to procedure finish), anesthesia finish time;procedure finish to patient out of room, and turnover time;start of room cleanup to patient in room.

Self-Reported Migraine and Health-Related Quality of Life of Greek Nursing Students: A Cross-Sectional Study

Background. Migraine is unquestionably a serious cause of dysfunction. Objective. To investigate the prevalence and impact of migraine on the health-related quality of life in Greek nursing students. Methods. Cross-sectional study with 140 nursing students in their 3rd or 4th year of studies. The research tools used were the ID Migraine™ questionnaire, the Migraine Assessment Disability questionnaire, the Medical Outcomes Study questionnaire (SF-36) and a demographics and history of headache form. Results. Self-reported migraine was found to be at 43.6%, self-reported migraine with physician-confirmed diagnosis was at 16.4%, and migraine detected by ID Migraine™ was at 48%. The main trigger factors of migraine were not sleeping at night, fasting for many hours and stress. Males showed a lower degree of migraine-related disability and better mental health. Students with a negative ID Migraine™ had a better health-related quality of life. The self-reported social health score of nursing students was much worse compared to standardized reference scores for the general population in Greece. Conclusions. Preventing migraine and improving students' health-related quality of life should involve a variety of interventions such as psychosocial support and health promotion, stress management, as well as healthy sleeping and eating habits.

Risky Business: Violence in Healthcare

Though Dr. Phillips' story got more attention in the press and physician murders are more sensationalized, his story is unfortunately not unique;less than two weeks after the Tulsa shooting, a nurse, and a paramedic were stabbed and critically injured by a patient in a St. Louis hospital.2 Overall, there is not a lot of data on the murders of healthcare workers, but the Bureau of Labor statistics reported 64 on-the-job fatalities for healthcare workers in 2020.3 Non-fatal assaults, on the other hand, are far more prevalent, with close to half a million in 2020,4 and with healthcare accounting for nearly as many serious violent injuries as all other industries combined.5,6 The data are limited by the sheer lack of reporting on workplace violence. The cumulative burden of violence faced by psychiatric and nursing home nurses has contributed to a staggering shortfall of nurses in these areas.1617 In Missouri, the Department of Mental Health reports that "35% of registered nurse positions are vacant, 57% of licensed practical nurses are vacant, [and] 32% of entry-level psychiatric tech positions are vacant" and are unable to be filled.17 Despite the overall elevated rates of violence in United States (U.S.),18 American healthcare workers experience comparable rates of violence as workers in other countries.19 Studies show that healthcare workers who were born and educated in another country, but currently practice in the U.S. are more susceptible to workplace violence.20 This is likely due to both xenophobic attitudes towards foreign physicians,21 as well as potential language barriers.20,21 ThelmpactofCOVID-19 In the context of the ongoing Covid-19 pandemic, violence against healthcare workers has worsened;the baseline environment is tenser, 'fuses' are substantially shorter, and it is far easier for violence to materialize. Data suggests that the benefits gained from de-escalation training extinguishes at about six months, underlining the need for continuous education.38 Studies of risk assessment in psychiatric wards found a significant reduction in patient aggression after implementing a risk assessment on violent patients.39,40 Several patient risk assessments tools exist, ranging in length from three to sixteen metrics.41

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes

PURPOSE OF THE STUDY: Given the similarities between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki's disease, most patients with MIS-C have been treated with intravenous immune globulin (IVIG), the standard of care for Kawasaki's disease. However, other immunomodulatory therapies, including corticosteroids and biologics, have been used to counter the cytokine-related inflammatory changes in MIS-C. The purpose of this study was to describe the pattern of immunomodulatory therapies used in patients with MIS-C in the United States and to assess the relative effectiveness of IVIG plus corticosteroids (CSTs), compared with IVIG alone, in the initial treatment of MIS-C. STUDY POPULATION: The Overcoming COVID-19 surveillance registry identified 596 patients as having MIS-C at each of the 58 participating hospitals between March 15 and October 31, 2020. Of these, 518 (87%) were flagged as receiving at least 1 immunomodulatory treatment. The researchers then analyzed longitudinal data collected in this cohort, including demographic characteristics, underlying medical conditions, signs and symptoms at presentation, clinical course, laboratory test results, diagnostic studies, treatments, complications, and outcomes. METHODS: Statistical comparisons between IVIG+CSTs and IVIG treatment groups were done by population sampling using propensity score matching;among the patients treated with IVIG plus glucocorticoids or IVIG alone on day 0, a total of 206 could be matched at a 1:1 ratio and based on propensity scores. To compare the potential effectiveness of initial immunomodulatory treatment, the authors prespecified a primary composite outcome of cardiovascular dysfunction (left ventricular ejection fraction < 55% and/or shock needing vasopressor support) on day 2 or beyond, up until discharge. Secondary outcome measures included the primary outcome components, escalation of immunomodulation treatment after day 1, and recurrent or persistent fever on day 2 and beyond. The potential effectiveness of treatment in primary and secondary outcomes was also assessed using an inverse-probability weighted analysis. RESULTS: Of the patients treated, 241 (47%) received IVIG and CSTs;107 (21%) received IVIG, CSTs, and a biologic (anakinra, etanercept, infliximab, or tocilizumab);89 (17%) received IVIG only;and 81 (16%) received other treatments, including CSTs only, a biologic only, CSTs and a biologic, or IVIG and a biologic. Highest illness severity was seen in the 107 patients who received IVIG, CSTs, and a biologic combined. Treatment patterns changed over time, with an observed decrease in the fraction of cases treated with IVIG alone, offset primarily by an increase in the use of IVIG with CSTs together. In the propensity-score-matched analysis, initial treatment with IVIG + CSTs was associated with a lower risk of cardiovascular dysfunction and less escalation of immunomodulatory treatments later in hospitalization, but the risks of persistent or recurrent fever and length of stay in the ICU were not clearly lower. The inverse-probability-weighted analysis confirmed the findings of the propensity-score-matched analysis. CONCLUSIONS: The authors found that initial treatment with IVIG plus glucocorticoids for MIS-C was associated with a lower risk of cardiovascular dysfunction than initial treatment with IVIG alone.

Profound Dysregulation of T cell Homeostasis and Function in Patients With Severe COVID-19

PURPOSE OF THE STUDY: T cell lymphopenia is prevalent in severe coronavirus disease 2019 (COVID-19). This study evaluated associations with homeostatic and functional T cell responses in COVID-19 with the goal of identifying immunologic features of severe disease. STUDY POPULATION: Patients aged 18 years and older with symptomatic, real time-quantitative polymerase chain reaction confirmed SARS-CoV-2 (mild, n = 54;severe, n = 49) were recruited at 4 hospitals in the Canton of Zurich, Switzerland from April 2 to August 19, 2020, and a group of healthy controls recruited for comparison (n = 27). A subset (mild, n = 28;severe, n = 38, healthy, n = 22) had comprehensive T cell characterization. METHODS: In this prospective, observational, cross-sectional study, symptomatic participants with mild and severe COVID-19 and healthy controls were sampled at a single time point. Phenotypic and functional characteristics of T cells were evaluated using 40-parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. RESULTS: Compared with mild disease, severe COVID-19 was associated with T cell lymphopenia and redistribution of T cell populations, including loss of naïve and memory CD4+ and CD8+ T cells, skewing toward CD4+ T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Individuals with severe disease and T cell lymphopenia had signs of tissue migration, extensive T cell apoptosis, and impaired T cell responses to common viral antigens. Patients with severe disease also showed elevated interleukin-7 and increased T cell proliferation. Those sampled longest after symptom onset had higher T cell counts and improved antiviral T cell responses. CONCLUSIONS: Severe COVID-19 is characterized by extensive T cell dysfunction. Reduced naïve T cells and virus-specific memory T cell numbers are associated with severe disease and impaired T cell responses to viral antigens, particularly early in the disease. Increased T follicular helper cells may contribute to a robust antibody response often observed in COVID-19. T cell apoptosis is associated with lymphopenia and homeostatic T cell proliferation and T cell recovery in the later stages of disease.

Effect of Nutrition Education on Weight and School Meal Intake among Korean Children During COVID-19

Background: Prevalence of childhood obesity is accelerating worldwide due to COVID-19. Nutrition education at a younger age is important for children to maintain a normal weight and form balanced eating habits. We examined whether nutrition education in school can help children control their weight and properly eat school meals during the COVID-19 pandemic in Korea. Methods: We conducted nutrition education for 2nd and 3rd-grade elementary school students (n=450, girls 47%) for 6 months. Noncontact nutrition education materials were provided every month, and taste education was conducted through face-to-face classes. Body composition, nutrients by school meal intake were investigated at baseline and 6 months. Results: Underweight students decreased (9.8% to 6.0%), while students with normal weight (5th<BMI<85th percentile) increased (73.6% to 76.4%) after education (p=0.001). Change rates of % body fat were higher in the underweight group (UG) (14.8±20.2%) and normal weight group (NG) (9.9±25.4%) than in the overweight and obese group (OG) (1.5±8.9%) (p=0.004). School meal intake rates were increased in UG (63.7±10.0% to 75.6±5.1%), NG (68.8±11.7% to 76.8±6.0%), and OG (75.2±10.9% to 78.5±6.2%) (p<0.05). Energy intake was increased in UG (333.2±64.4kcal to 424.8±38.1kcal), NG (352.9±65.1kcal to 438.0±49.5kcal), and OG (403.0±59.2kcal to 464.6±51.2kcal) (p<0.001). Fat intake was increased in UG and NG, but there was no significant difference in the OG. Protein and calcium intake were also increased in UG and NG (p<0.05). Conclusions: Through school-based face-to-face and non-contact nutrition education, their weight was changed to a normal level, and it contributed to increasing the intake of balanced school meals. ·Funding source: This research was supported by a fund (No. 2020ER640102) by Research of Korea Disease Control and Prevention Agency.

COVID-19 Outcomes: The Impact of Obesity Within Racial Groups

Background: The COVID-19 pandemic has thrust the obesity epidemic into the spotlight, revealing that obesity is no longer a disease that harms in the long run, but one that can have acutely devastating effects. Studies have suggested that obesity not only increases your risk of hospitalization, mechanical ventilation and death but increases your risk of becoming infected. Rapid data collection started in late 2019 as the COVID-19 spread from its site of origination, Wuhan, China. Initial observational studies noted that Hypertension, Type 2 Diabetes and Coronary Artery Disease were the most common comorbid conditions in patients with more severe complications. Although data was collected in China regarding BMI, it was not until April 2020 when the editors of the American published Obesity medical journal stated that obesity would likely prove to be independent risk factor for more severe disease. This observation was likely yet to be realized in the Chinese data given the significantly lower rates of obesity than the United States. In 2019, the overall rate of obesity among Chinese adults was 13.58%. The rate of obesity in the United States in 2017-2018, the last reported data from National Health and Nutrition Examination Survey, was 42.4%. COVID-19 also revealed conspicuous health care disparities that have been documented for decades with little national spotlight until July 2021. Federal data reported that the Black American life expectancy decreased almost 3 years from 2019 to 2020 compared to 1.2 years for White Americans. In our study we examine the association of four clinical complications from COVID-19 infection among Black/African American and White/Caucasian patients with overweight and obesity while controlling for co-morbid conditions. Our aim is to identify if different risk exists between ethnicity groups in overweight and obese patients, controlling for additional comorbidities. We hypothesize that racial disparities in COVID outcomes persist. Methods: A random sample of 3,000 records was extracted from the COVID19 DataMart through the University of Virginia Health System EMR. This included patients who tested positive by RT-PCR for SARS-CoV-2 using swab specimens between March 2020 and July 2021. We limited this study to Black/African American or White/ Caucasian patients age > 18 with a BMI >25, for a total of 1,904 patients. Measurements Four clinical outcomes from COVID-19 were examined;hospitalization, length of hospital stay (LOS), ventilator dependence and mortality. LOS was measured by an indicator constructed within the EMR calculating the difference between admission and discharge dates. Ventilator dependence and mortality were binary indicators related to COVID-19. Race was dichotomized as Black/ African American or White/Caucasian. We controlled for comorbidies with the Charlson Comorbidity Index (CCI), which accounts for 17 conditions. Patients were divided into four groups based on the CCI score. CCI score and corresponding weighted category were computed using the "comorbidity" package in R. Based on patients' BMI, we computed a variable indicating BMI category: 25< and <30;>30 and <35;>35. Sex and age were controlled. Sample Size Calculation We used the "pwr" package in R to compute the minimum required sample size that would offer 80% power and significance level of 0.05 to detect a small effect size. This was attainable in our analysis. Statistical Analysis Means and standard deviations were applied to continuous variables. We ran bivariate comparisons between the four outcomes of interest and race. Unadjusted odds ratios with corresponding 95% Confidence intervals (CI) are presented for hospitalized, ventilation required and mortality. A t-test is presented for mean comparisons of LOS by race. Four regression models were constructed for each respective outcome of interest while controlling for race, CCI category, BMI category, age and sex. Logistic regression models estimated the odds of hospitalization, ventilation dependence and mortality, and a linear model to estimate effe ts of covariate on LOS. All hypothesis tests were 2-sided with a significance level of 5%. R version 4.1.1 was used for all analyses. As a sensitivity analysis, we replicated these models in a sub-sample of patients who were infected between March 2020 and February 2021 (n = 756). Results: 1,904 patients were included in the main cohort and 756 in the sensitivity cohort. The mean age was 45.7 and 46.3 in the sensitivity cohort. Females comprised 58.5% and 81% of the sensitivity cohort. Average LOS was significantly greater for Black patients than WHITE patients. Hospitalization rates for White patients were significantly lower than those for Black patients. Ventilation did not differ significantly between White and Black patients. Mortality rates were lower for White patients compared to Black patients. In the regression model White patients had significantly shorter LOS compared to Black patients. Patients with low and mild CCI risk had significantly shorter LOS compared to patients in the severe risk category. Patients with a BMI category or >35 had shorter LOS compared to those with BMI <30;males had significantly longer LOS compared to females. Race did not have a significant effect on hospitalization after controlling for CCI category, sex, BMI category and age. Patients with low and mild CCI had significantly lower odds of being hospitalized. Males had significantly greater odds of being hospitalized compared to females. Race did not have a significant effect on ventilation. Male patients had significantly higher odds of needing ventilation. Patients with low CCI risk had significantly lower odds of needing ventilation. Increase in age was associated with increased odds of needing ventilation. Race was significantly associated with mortality. White patients had significantly lower odds of death compared to Black patients. Patients in the low and mild CCI risk had lower odds of death. White patients had significantly shorter LOS compared to Black patients. Patients with low and mild CCI risk had significantly shorter LOS compared to patients in the severe risk category. Race did not have a significant effect on hospitalization. Patients with low and mild CCI risk had significantly lower odds of being hospitalized. Race did not have a significant effect on ventilation. Patients with low and moderate CCI risk had significantly lower odds of needing ventilation. Increase in age was associated with increased odds of needing ventilation. Race was associated with mortality after controlling for CCI category, sex, BMI category and age at a p value = 0.05. White patients had lower odds of death compared to Black patients. Conclusions: Our findings emphasize that racial differences persist when we look at only patients that have overweight and obesity. The racial disparities are not due to just obesity and its common co-morbidities. There are other factors contributing to these outcomes. These factors are likely multifactorial. It could be due to a combination of social and environmental factors that prevent or delay these patients from receiving care. Furthermore there may be differences in the care these patients receive once in the health care system. Further examination of these socioeconomic factors are just as important as mechanistic causes in order to decrease healthcare disparities.

Effects of Colchicine on Serum Alpha-Defensins in Adults With Obesity

Background: Human neutrophil peptides (HNPs), also known as a-defensins, are innate immune system components that regulate blood coagulation pathways and are associated with increased production of proinflammatory cytokines in people with obesity. Colchicine is well-known to impede neutrophil function and reduce inflammation through multiple pathways. In a recent study of patients who were hospitalized with COVID-19 infection, two 0.5mg doses of colchicine acutely reduced participants' elevated plasma a-defensin concentrations. However, colchicine's long-term effects on circulating a-defensins remain unclear. Methods: We examined colchicine's effects on serum a-defensin concentrations in patients with obesity who participated in a randomized, double-blind, placebo-controlled trial of 40 nondiabetic individuals with elevated high-sensitivity c-reactive protein (hsCRP), obesity and metabolic syndrome (MetS). Participants were randomized to colchicine 0.6mg or placebo twice daily for 3 months. Total HNP1-3 concentrations were determined by enzyme-linked immunosorbent assay (sensitivity 150 pg/mL) at baseline and after 3 months' treatment. Differences between groups in log-transformed HNP 1-3 were analyzed using ANOVA with repeated measures. Results: This study included data from 18 people randomized to colchicine (Mean±SD: age 48.4±13.5y;BMI 39.3±6.3kg/m2;72% female) and 17 randomized to placebo (age 46.3±10.0y;BMI 42.5±8.4kg/m2;79% female). In both groups, HNP1-3 decreased at follow-up (time p=0.002). When comparing the group x time interaction for the colchicine and placebo groups, there was no significant difference in HNP1-3 (p = 0.20). Conclusions: In this small pilot study of people with obesity, metabolic syndrome, and high baseline hsCRP, colchicine did not significantly affect circulating a-defensins. Larger studies may be required to definitively determine colchicine's long-term effects on a-defensins.

Efficacy and Safety Analysis of Setmelanotide as a Novel Treatment for Hypothalamic Obesity

Background: Hypothalamic injury and impaired melanocortin-4 receptor (MC4R) pathway signaling, often a result of surgery or radiation for a benign tumor, may lead to hypothalamic obesity (HO). After injury, sudden weight gain and appetite changes unresponsive to existing therapies develop. Setmelanotide, an MC4R agonist, is approved for chronic weight management in patients with certain MC4R pathway-associated diseases. We report interim results of a Phase 2 study of setmelanotide in HO (NCT04725240). Methods: Patients aged 6-40 years with body mass index (BMI) >95th percentile (children 6 to <18 years) or >35 kg/m2 (adults >18 years) and HO caused by structural hypothalamic damage secondary to craniopharyngioma or other benign brain tumor, surgical resection, and/or chemotherapy were enrolled. The setmelanotide dose was initiated by age, with 2-4 weeks of titration to 3.0 mg once daily, followed by 12-14 weeks at the target dose. The primary endpoint was the proportion of patients achieving >5% BMI reduction at Week 16. A key secondary endpoint was the composite proportion of children with >0.2-point reduction in BMI Z score and adults with >5% weight loss. Hunger was assessed daily using a numerical rating scale, where 0 = not hungry at all and 10 = hungriest possible. Results: Eleven patients were included (baseline mean [SD;range] age, 14.6 [4.8;6-23] years and mean [SD] BMI, 38.7 [5.7] kg/m2). All patients (90% CI, 76.2%-100%) had >5% reduction in BMI (p<0.0001);81.8% (90% CI, 53.0%-96.7%) had >10% reduction (p<0.0001). Mean (range) change in BMI was -17.2% (-37.2%, -6.7%). Mean (SD) change in hunger score was -2.7 (2.6). Frequent adverse events included nausea (63.6%), vomiting (45.5%), diarrhea (36.4%), and COVID-19 (36.4%). Two patients discontinued because of adverse events. Conclusions: These early results warrant continued evaluation of setmelanotide in this population with a high unmet medical need and no approved therapies.

Obesity And Covid-19: A Descriptive Review

Background: According to data provided by the World Health Organization (WHO), 5,941,223 confirmed cases and 366,601 deaths had already been reported by May 31, 2020. Higher rates of infection, hospitalization, submission to the Intensive Care Units, and fatalities were attributed to obese patients. Objective: To gather the available data on obesity and SARS-CoV-2 infection. The study specifically covers combined pathophysiology and prognosis and will be updated until September 2020. Methods: This is a literature review study with a narrative-descriptive approach. The search was carried out in September 2020, with the totality of articles from that same year, when the pandemic of the new coronavirus was declared by the World Health Organization. Results: The search on the data platform resulted in 121 articles, of which 86 were classified as reviews and 35, systematic reviews, totaling 18 reviews and 7 systematic reviews at the end, with a total value of 16 articles with sufficient quality. Obesity is associated with increased severity of COVID-19 in the infected individual with this disease, due to the chronic inflammatory process, with high levels of pro-inflammatory leptin and a lower concentration of antiinflammatory adiponectin, which causes a response delayed and inferior immune system. Conclusions: Individuals with this association have an easier time in the formation of possible clots, due to chronic inflammation and impaired fibrinolysis, which qualifies them as individuals of significant thrombogenic risk. Thus, individuals with obesity are an important risk group when considering its association with the disease of the new coronavirus.

An Innovative Curriculum Increases Internal Medicine Residents' Obesity-Care Self-Efficacy

Background: Residency offers opportunities to address obesity-care knowledge gaps, but few curricula exist. We aimed to develop and rigorously test an obesity medicine curriculum for internal medicine (IM) residents. Methods: We conducted a prospective study comparing IM residents' obesity-care self-efficacy between a residency program receiving the curriculum (n=20) and a control program (n=19). From Feb-April 2020, we delivered a curriculum that combined online modules with live case-based discussions on guidelineconcordant obesity care (lifestyle, medications, surgery);enhanced with tools for documentation and patient communication. We determined residents' change in counseling self-efficacy on nutrition, behavior change, anti-obesity medications (AOM), and bariatric surgery on 4-point Likert scales at baseline and 5 months. We also assessed change in self-reported clinical practice habits. We used t-tests to compare mean change in outcomes both within and between groups. Results: Overall, 64% of residents were women and evenly distributed across post-graduate years. Curriculum residents had statistically significant within-group increases in all self-efficacy domains (nutrition 0.8;behavior 1.2;AOM 1.2;surgery 0.9 (p<0.01)) and statistically significant within-group increases in three practice habits (behavior 0.8, AOM 0.8, surgery 0.6 (p<0.02)). Relative to controls, curriculum residents had statistically significant improvements in all self-efficacy domains (between-group differences: nutrition 0.6 (p=0.02);behavior 0.8 (p<0.01);AOM 0.7 (p=0.03);surgery 0.5 (p=0.03)). We found no between-group differences in practice habits. Conclusions: A curriculum increased residents' obesity-care selfefficacy and produced improvements beyond those achieved with usual IM training. While curriculum residents reported increases in practice habits, the between-group changes were not statistically significant - possibly related to COVID19 disruptions. Future studies should determine effect on clinical practice.

mRNA technology

What can we expect from mRNA vaccines going forward? A brief history of mRNA vaccines Experiments showing that mRNA could be introduced into cells to generate an immune response against the encoded protein date to the 1990s, although technical challenges including the biological instability of mRNA and the induction of undesirable inflammatory responses by unmodified nucleic acid hampered development of this technology into clinical application.3,4 Advances including chemical modifications to the nucleo-side constituents of the mRNA polymer and the use of a lipid outer coating for delivery of the mRNA formed the basis for this technology to enter human studies.5,6 These changes led to increased production of the target protein after inoculation with fewer inflammatory adverse effects (AEs), while retaining induction of an immune response.7-9 These technologic advances were the basis for the COVID-19 mRNA vaccines in widespread use today. The sequence of events that leads to induction of effective immunity includes the following: O Creation of a nucleic acid sequence that results in production of the protein or a part of the protein against which a specific immune response is desired (immunogen) O Delivery of that sequence into the cell to engage the cellular machinery for producing the immunogen O Induction of inflammatory pathways to stimulate adaptive immunity leading to antibodies and T cells that respond to the immunogen Immune protein sensors that initiate inflammation are present in all cell types. A killed virus vaccine platform is the basis for Sinopharm and Coro-naVac vaccines developed in China and the BBV152 vaccine made in In-dia.15 Vaccines based on this plat form have been given to billions of individuals worldwide.16 Manufacture of these vaccines early in the pandemic required the ability to grow infectious viruses in a controlled setting, which unlike manufacture of mRNA vaccines carries nonzero transmission risk. Because these vaccines do not produce proteins in the immunized individual, they tend to be better at inducing antibody-based protection than cellular responses.

Changes in Use of Low-Value Services During the COVID-19 Pandemic

The COVID-19 pandemic led to a significant disruption, then recovery, of health care services use. Prior research has not examined the relative rates of resumption of high-value and low-value care. We examined the use of 6 common low-value services that received a D grade from the US Preventive Services Task Force compared with clinically comparable high-value services in a large commercially insured population nationwide from before the pandemic to April 1, 2021. We found that, overall, low-value services and high-value services were disrupted similarly. In aggregate, low-value care declined to 56.2% and high-value care to 53.2% in the initial month of the pandemic (April 2020) relative to baseline (number of visits in 2019 normalized by relevant enrolled population), then rebounded to 83.1% of baseline for low-value services and 95.0% of baseline for high-value services by January 2021. Substantial heterogeneity appeared across clinical contexts, such as prostate cancer screening for men 70 years and older rebounding to 111.8% of baseline and asymptomatic chronic obstructive pulmonary disease screening remaining at 38.5% of baseline in January 2021. This suggests that although, on average, resuming lower-value services may have been perceived to be a lesser priority by providers and patients, the pandemic may have had heterogeneous effects on consumer and provider decision-making along the dimension of clinical value. This enhances our understanding of how disruptions affect the relationship between clinical value and usage of different services and suggests the need for more targeted interventions to reduce low-value care.