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  Implementing virtual desktops for clinical research at an academic health center: a case report

  Zai, Adrian; Wong, Steven; Guilarte-Walker, Yurima; Langlois, Paul; Coleman, Brian; Soni, Apurv; McManus, David D; Luzuriaga, Katherine (2024-08-28)

  Objectives: To address the challenges of sharing clinical research data through the implementation of cloud-based virtual desktops, enhancing collaboration among researchers while maintaining data security. Materials and methods: This case study details the deployment of virtual desktops at UMass Chan Medical School (UMass Chan). The process involved forming a Research Informatics Steering Executive workgroup, identifying key requirements, implementing Amazon WorkSpaces, and establishing configurable data management for research support. Results: Key lessons include the significance of collaboration, balancing user-friendliness and functionality, flexibility in data management, maximizing virtual desktop efficiency within budget constraints, and continuous user feedback. The implementation of virtual desktops supports secure collaborative research, advancing medical knowledge and improving healthcare outcomes. Discussion: The structured approach to implementing virtual desktops addresses data security, regulatory compliance, and real-time collaboration challenges. Continuous feedback and iterative improvements have enhanced the system's effectiveness. Conclusion: The successful implementation of virtual desktops at UMass Chan demonstrates the potential for such systems to support secure, collaborative research, offering insights for similar initiatives in other academic health centers.
• Nirmatrelvir/Ritonavir (Paxlovid) Use Among Individuals at Risk of Severe COVID-19: An Analysis of the National COVID Cohort Collaborative (N3C)

  Xiao, Xuya; Alexander, G Caleb; Mehta, Hemalkumar B (2024-08-04)

  Purpose: Paxlovid is effective in reducing COVID-19 hospitalization and mortality. This study characterized Paxlovid use and evaluated racial/ethnic disparities over time among community-dwelling adults at high risk of progression to severe COVID-19 disease. Methods: This retrospective cohort study used the National COVID Cohort Collaborative (N3C) data and included individuals aged 18 years or older diagnosed with COVID-19 between January 2022 and December 2023. The study cohort included nonhospitalized individuals who were at high risk of COVID-19 progression, and selected the first COVID-19 episode in each quarter, including reinfection episodes. Paxlovid use was defined as receiving Paxlovid within ±5 days of a COVID-19 diagnosis. We used descriptive statistics to characterize Paxlovid use overall and by calendar quarter and race/ethnicity. We used a generalized estimating equations (GEE) models to quantify the association of race/ethnicity with Paxlovid use controlling for age, gender, and clinical characteristics. Results: Among 1 264 215 individuals at high risk of disease progression (1 404 607 episodes), Paxlovid use increased from 1.2% in January-March 2022 to 35.1% in October-December 2023. Paxlovid use was more common among non-Hispanic White individuals (23.9%) than non-Hispanic Black (16.5%) and Latinx/e (16.7%) patients. After adjusting age, gender, and clinical characteristics, Paxlovid use was less likely among non-Hispanic Black (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.68-0.70) and Latinx/e (OR 0.72, CI 0.71-0.73) patients than non-Hispanic White patients. Conclusions: Among a large, diverse cohort of community-dwelling individuals with COVID-19, nearly two out of three eligible individuals did not receive Paxlovid, and minoritized racial/ethnic groups were less likely to use Paxlovid than their non-Hispanic White individuals.
• Factors associated with non-adherence to dual-energy x-ray absorptiometry screening during the COVID-19 pandemic in an academic medical center

  Shi, Qiming; Cheah, Jonathan T; Zai, Adrian (2024-07-30)

  This study explored why some elderly females do not adhere to their bone density tests. It found that factors like age, race, marital status, insurance type, social vulnerability index, and vaccination status influence completion of these tests. Addressing these differences could improve the management of bone health in older adults. Purpose: This study investigated factors influencing the cancellation of dual-energy x-ray absorptiometry (DXA) scans among females aged 65 and above during the COVID-19 pandemic. Methods: Utilizing a dataset of 19,066 females from 2021 to 2023, the research employed chi-squared tests and logistic regression analyses to examine demographic, socio-economic, and health-related determinants of DXA scan adherence. Results: Key findings revealed that younger seniors, White patients, married individuals, those with commercial/private or Medicare insurance, and vaccinated persons were more likely to complete DXA scans. In contrast, Asian and African American females, along with those from higher Social Vulnerability Index areas, showed lower completion rates. Conclusion: These results highlight the need for tailored strategies to improve osteoporosis screening adherence, focusing on identified demographic groups to enhance overall healthcare outcomes in osteoporosis management.
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  Minding the margins: Evaluating the impact of COVID-19 among Latinx and Black communities with optimal qualitative serological assessment tools

  Binder, Raquel A; Matta, Angela M; Forconi, Catherine S; Oduor, Cliff I; Bedekar, Prajakta; Patrone, Paul N; Kearsley, Anthony J; Odwar, Boaz; Batista, Jennifer; Forrester, Sarah N; et al. (2024-07-25)

  COVID-19 disproportionately affected minorities, while research barriers to engage underserved communities persist. Serological studies reveal infection and vaccination histories within these communities, however lack of consensus on downstream evaluation methods impede meta-analyses and dampen the broader public health impact. To reveal the impact of COVID-19 and vaccine uptake among diverse communities and to develop rigorous serological downstream evaluation methods, we engaged racial and ethnic minorities in Massachusetts in a cross-sectional study (April-July 2022), screened blood and saliva for SARS-CoV-2 and human endemic coronavirus (hCoV) antibodies by bead-based multiplex assay and point-of-care (POC) test and developed across-plate normalization and classification boundary methods for optimal qualitative serological assessments. Among 290 participants, 91.4% reported receiving at least one dose of a COVID-19 vaccine, while 41.7% reported past SARS-CoV-2 infections, which was confirmed by POC- and multiplex-based saliva and blood IgG seroprevalences. We found significant differences in antigen-specific IgA and IgG antibody outcomes and indication of cross-reactivity with hCoV OC43. Finally, 26.5% of participants reported lingering COVID-19 symptoms, mostly middle-aged Latinas. Hence, prolonged COVID-19 symptoms were common among our underserved population and require public health attention, despite high COVID-19 vaccine uptake. Saliva served as a less-invasive sample-type for IgG-based serosurveys and hCoV cross-reactivity needed to be evaluated for reliable SARS-CoV-2 serosurvey results. The use of the developed rigorous downstream qualitative serological assessment methods will help standardize serosurvey outcomes and meta-analyses for future serosurveys beyond SARS-CoV-2.
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  Relationship between acute SARS-CoV-2 viral clearance with Long COVID Symptoms: a cohort study [preprint]

  Herbert, Carly; Antar, Annukka A R; Broach, John; Wright, Colton; Stamegna, Pamela; Luzuriaga, Katherine; Hafer, Nathaniel; McManus, David D; Manabe, Yukari C; Soni, Apurv (2024-07-05)

  Introduction: The relationship between SARS-CoV-2 viral dynamics during acute infection and the development of long COVID is largely unknown. Methods: A total of 7361 asymptomatic community-dwelling people enrolled in the Test Us at Home parent study between October 2021 and February 2022. Participants self-collected anterior nasal swabs for SARS-CoV-2 RT-PCR testing every 24-48 hours for 10-14 days, regardless of symptom or infection status. Participants who had no history of COVID-19 at enrollment and who were subsequently found to have ≥1 positive SARS-CoV-2 RT-PCR test during the parent study were recontacted in August 2023 and asked whether they had experienced long COVID, defined as the development of new symptoms lasting 3 months or longer following SARS-CoV-2 infection. Participant's cycle threshold values were converted into viral loads, and slopes of viral clearance were modeled using post-nadir viral loads. Using a log binomial model with the modeled slopes as the exposure, we calculated the relative risk of subsequently developing long COVID with 1-2 symptoms, 3-4 symptoms, or 5+ symptoms, adjusting for age, number of symptoms, and SARS-CoV-2 variant. Adjusted relative risk (aRR) of individual long COVID symptoms based on viral clearance was also calculated. Results: 172 participants were eligible for analyses, and 59 (34.3%) reported experiencing long COVID. The risk of long COVID with 3-4 symptoms and 5+ symptoms increased by 2.44 times (aRR: 2.44; 95% CI: 0.88-6.82) and 4.97 times (aRR: 4.97; 95% CI: 1.90-13.0) per viral load slope-unit increase, respectively. Participants who developed long COVID had significantly longer times from peak viral load to viral clearance during acute disease than those who never developed long COVID (8.65 [95% CI: 8.28-9.01] vs. 10.0 [95% CI: 9.25-10.8]). The slope of viral clearance was significantly positively associated with long COVID symptoms of fatigue (aRR: 2.86; 95% CI: 1.22-6.69), brain fog (aRR: 4.94; 95% CI: 2.21-11.0), shortness of breath (aRR: 5.05; 95% CI: 1.24-20.6), and gastrointestinal symptoms (aRR: 5.46; 95% CI: 1.54-19.3). Discussion: We observed that longer time from peak viral load to viral RNA clearance during acute COVID-19 was associated with an increased risk of developing long COVID. Further, slower clearance rates were associated with greater number of symptoms of long COVID. These findings suggest that early viral-host dynamics are mechanistically important in the subsequent development of long COVID.
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  IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease

  Friedline, Randall H; Noh, Hye Lim; Suk, Sujin; Albusharif, Mahaa; Dagdeviren, Sezin; Saengnipanthkul, Suchaorn; Kim, Bukyung; Kim, Allison M; Kim, Lauren H; Tauer, Lauren A; et al. (2024-06-29)

  Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2-/-) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2-/- mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.
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  A Bayesian Survival Analysis on Long COVID and non Long COVID patients: A Cohort Study Using National COVID Cohort Collaborative (N3C) Data [preprint]

  Jiang, Sihang; Loomba, Johanna; Zhou, Andrea; Sharma, Suchetha; Sengupta, Saurav; Liu, Jiebei; Brown, Donald (2024-06-25)

  Since the outbreak of COVID-19 pandemic in 2020, numerous researches and studies have focused on the long-term effects of COVID infection. The Centers for Disease Control (CDC) implemented an additional code into the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) for reporting 'Post COVID-19 condition, unspecified (U09.9)' effective on October 1st 2021, representing that Long COVID is a real illness with potential chronic conditions. The National COVID Cohort Collaborative (N3C) provides researchers with abundant electronic health records (EHR) data by aggregating and harmonizing EHR data across different clinical organizations in the United States, making it convenient to build up a survival analysis on Long COVID patients and non Long COVID patients among large amounts of COVID positive patients.
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  Performance of and Severe Acute Respiratory Syndrome Coronavirus 2 Diagnostics Based on Symptom Onset and Close Contact Exposure: An Analysis From the Test Us at Home Prospective Cohort Study

  Herbert, Carly; Wang, Biqi; Lin, Honghuang; Yan, Yi; Hafer, Nathaniel; Pretz, Caitlin; Stamegna, Pamela; Wright, Colton; Suvarna, Thejas; Harman, Emma; et al. (2024-05-31)

  Background: Understanding changes in diagnostic performance after symptom onset and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure within different populations is crucial to guide the use of diagnostics for SARS-CoV-2. Methods: The Test Us at Home study was a longitudinal cohort study that enrolled individuals across the United States between October 2021 and February 2022. Participants performed paired antigen-detection rapid diagnostic tests (Ag-RDTs) and reverse-transcriptase polymerase chain reaction (RT-PCR) tests at home every 48 hours for 15 days and self-reported symptoms and known coronavirus disease 2019 exposures immediately before testing. The percent positivity for Ag-RDTs and RT-PCR tests was calculated each day after symptom onset and exposure and stratified by vaccination status, variant, age category, and sex. Results: The highest percent positivity occurred 2 days after symptom onset (RT-PCR, 91.2%; Ag-RDT, 71.1%) and 6 days after exposure (RT-PCR, 91.8%; Ag-RDT, 86.2%). RT-PCR and Ag-RDT performance did not differ by vaccination status, variant, age category, or sex. The percent positivity for Ag-RDTs was lower among exposed, asymptomatic than among symptomatic individuals (37.5% (95% confidence interval [CI], 13.7%-69.4%) vs 90.3% (75.1%-96.7%). Cumulatively, Ag-RDTs detected 84.9% (95% CI, 78.2%-89.8%) of infections within 4 days of symptom onset. For exposed participants, Ag-RDTs detected 94.0% (95% CI, 86.7%-97.4%) of RT-PCR-confirmed infections within 6 days of exposure. Conclusions: The percent positivity for Ag-RDTs and RT-PCR tests was highest 2 days after symptom onset and 6 days after exposure, and performance increased with serial testing. The percent positivity of Ag-RDTs was lowest among asymptomatic individuals but did not differ by sex, variant, vaccination status, or age category.
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  SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C)

  Rahman, Asif; Russell, Michael; Zheng, Wanhong; Eckrich, Daniel; Ahmed, Imtiaz (2024-05-30)

  Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.
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  Face-off Droop: A Case Report of Pediatric Stroke

  Robertson, Duncan; Peirce, Hayden F; Nicpon, Marek D; Otterson, Eric M; O'Connor, Laurel; Rissmiller, Julia G; Binder, Zachary W (2024-04-24)

  Introduction: Cerebrovascular accidents rarely occur in children; the incidence of ischemic stroke in patients <16 years of age is between 0.6-7.9/100,000. However, they are the fourth most common cause of acute neurological deficits in the pediatric population, and possible cases should be evaluated with a high index of suspicion to ensure timely intervention. Case report: We describe a previously healthy 17-year-old male who presented to the pediatric emergency department with a left facial droop and hemiparesis consistent with a stroke. The patient's age and lack of comorbidities made this an extremely uncommon presentation. Our patient's neurologic symptoms were believed to have been caused by a recent traumatic clavicular injury sustained two weeks prior, which subsequently led to vascular insult. Conclusion: Cerebrovascular accidents are an important cause of morbidity and mortality in pediatric patients. Cerebrovascular accidents in children are most often secondary to congenital causes; however, care should be taken to assess for acquired causes, such as trauma to major blood vessels. While rarely implicated in traumatic injuries, arterial structures posterior to the medial clavicle can result in severe complications.
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  CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators

  Jiang, Hao-Ching; Park, Sung Jin; Wang, I-Hao; Bear, Daniel M; Nowlan, Alexandra; Greer, Paul L (2024-04-18)

  The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.
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  Sampling of healthcare professionals' perspective on point-of-care technologies from 2019-2021: A survey of benefits, concerns, and development

  Orwig, Taylor; Sutaria, Shiv; Wang, Ziyue; Howard-Wilson, Sakeina; Dunlap, Denise; Lilly, Craig M; Buchholz, Bryan; McManus, David D; Hafer, Nathaniel (2024-03-08)

  Point-of-care technology (POCT) plays a vital role in modern healthcare by providing a fast diagnosis, improving patient management, and extending healthcare access to remote and resource-limited areas. The objective of this study was to understand how healthcare professionals in the United States perceived POCTs during 2019-2021 to assess the decision-making process of implementing these newer technologies into everyday practice. A 5-point Likert scale survey was sent to respondents to evaluate their perceptions of benefits, concerns, characteristics, and development of point-of-care technologies. The 2021 survey was distributed November 1st, 2021- February 15th, 2022, with a total of 168 independent survey responses received. Of the respondents, 59% identified as male, 73% were white, and 48% have been in practice for over 20 years. The results showed that most agreed that POCTs improve patient management (94%) and improve clinician confidence in decision making (92%). Healthcare professionals were most concerned with potentially not being reimbursed for the cost of the POCT (37%). When asked to rank the top 3 important characteristics of POCT, respondents chose accuracy, ease of use, and availability. It is important to note this survey was conducted during the COVID-19 pandemic. To achieve an even greater representation of healthcare professionals' point of view on POCTs, further work to obtain responses from a larger, more diverse population of providers is needed.
• Social engagement and cognitive impairment among nursing home residents: The role of sensory impairment

  Xu, Shu; Jesdale, William M; Dubé, Catherine E; Nielsen, Natalia N; McPhillips, Emily A; Lapane, Kate L (2024-03-05)

  Background and objectives: Using US national nursing home data, this cross-sectional study sought to evaluate 1) the association between lack of social engagement and level of cognitive impairment; and 2) the extent to which this association differs by hearing and visual impairment. Research design and methods: Our sample included 793,846 nursing home residents aged ≥ 50 years. The Index of Social Engagement was categorized as none/lower (0, 1, 2) or higher levels (3 through 6). Cognitive Performance Scale was grouped as intact/mild (0, 1, 2), moderate (3, 4), or severe (5, 6). Multinomial models provided adjusted odds ratio (aOR) and 95 % confidence intervals (CI) between none/lower social engagement and cognitive impairment. We estimated relative excess risk due to interaction (RERI) to quantify the joint effects of social engagement and sensory impairment types. Results: Overall, 12.6 % had lower social engagement, 30.3 % had hearing impairment, and 40.3 % had visual impairment. Compared to residents with high social engagement, those with lower social engagement were more likely to have moderate/severe cognitive impairment (aORmoderate = 2.21, 95 % CI 2.17-2.26; aORsevere = 6.49, 95 % CI 6.24-6.74). The impact of low social engagement on cognitive impairment was more profound among residents with hearing impairment and/or visual impairment (RERIhearing = 3.89, 95 % CI 3.62-4.17; RERIvisual = 25.2, 95 % CI 23.9-26.6)). Discussion and implications: Residents with lower social engagement had higher levels of cognitive impairment. Residents with sensory impairments are potentially more susceptible to the negative impact of lower levels of social engagement on level of cognitive impairment.
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  Racial and Ethnic Disparities in Use of Colorectal Cancer Screening Among Adults With Chronic Medical Conditions: BRFSS 2012-2020

  Castañeda-Avila, Maira A; Tisminetzky, Mayra; Oyinbo, Atinuke G; Lapane, Kate L (2024-02-22)

  Introduction: People with chronic conditions and people with colorectal cancer (CRC) may share common risk factors; thus, CRC screening is important for people with chronic conditions. We examined racial and ethnic differences in the use of CRC screening among people with various numbers of chronic conditions. Methods: We included data on adult respondents aged 50 to 75 years from the Behavioral Risk Factor Surveillance System in 2012 through 2020. We categorized counts of 9 conditions as 0, 1, 2, 3, and ≥4. We classified self-reported CRC screening status as up to date or not. We used Poisson models to estimate adjusted prevalence ratios (APRs) among the different counts of chronic conditions in 4 racial and ethnic groups: Hispanic adults with limited English proficiency (LEP), Hispanic adults without LEP, non-Hispanic Black adults, and non-Hispanic White adults. Results: Overall, 66.5% of respondents were up to date with CRC screening. The prevalence of being up to date increased with the number of chronic conditions. We found disparities among racial and ethnic groups. Hispanic respondents with LEP had lower rates than non-Hispanic White adults of being up to date with CRC screening across all counts of chronic conditions (APR for 0 conditions = 0.67; 95% CI, 0.64-0.71; APR for ≥4 conditions = 0.85; 95% CI, 0.79-0.91). Hispanic respondents without LEP with 0, 1, or 2 conditions were less likely than non-Hispanic White respondents to be up to date with CRC screening. We found no significant differences between non-Hispanic Black and non-Hispanic White respondents. Conclusion: We found disparities among Hispanic BRFSS respondents with LEP, who had lower rates than non-Hispanic White respondents of being up to date with CRC screening, regardless of the number of chronic conditions. Tailored interventions are needed to address these disparities and improve screening rates, particularly among Hispanic people.
• Persistent False Positive Covid-19 Rapid Antigen Tests

  Herbert, Carly; McManus, David D; Soni, Apurv (2024-02-22)

  Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially. The percentage of rapid antigen tests with false positive results is reported to be less than 1%. However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders.
• Strengthening Quality Measurement to Predict Success for Total Knee Arthroplasty: Results from a Nationally Representative Total Knee Arthroplasty Cohort

  Zheng, Hua; Ash, Arlene S.; Yang, Wenyun; Liu, Shao-Hsien; Allison, Jeroan J.; Ayers, David C (2024-01-25)

  Background: When performed well on appropriate patients, total knee arthroplasty (TKA) can dramatically improve quality of life. Patient-reported outcome measures (PROMs) are increasingly used to measure outcome following TKA. Accurate prediction of improvement in PROMs after TKA potentially plays an important role in judging the surgical quality of the health-care institutions as well as informing preoperative shared decision-making. Starting in 2027, the U.S. Centers for Medicare & Medicaid Services (CMS) will begin mandating PROM reporting to assess the quality of TKAs. Methods: Using data from a national cohort of patients undergoing primary unilateral TKA, we developed an original model that closely followed a CMS-proposed measure to predict success, defined as achieving substantial clinical benefit, specifically at least a 20-point improvement on the Knee injury and Osteoarthritis Outcome Score, Joint Arthroplasty (KOOS, JR) at 1 year, and an enhanced model with just 1 additional predictor: the baseline KOOS, JR. We evaluated each model's performance using the area under the receiver operator characteristic curve (AUC) and the ratio of observed to expected (model-predicted) outcomes (O:E ratio). Results: We studied 5,958 patients with a mean age of 67 years; 63% were women, 93% were White, and 87% were overweight or obese. Adding the baseline KOOS, JR improved the AUC from 0.58 to 0.73. Ninety-four percent of those in the top decile of predicted probability of success under the enhanced model achieved success, compared with 34% in its bottom decile. Analogous numbers for the original model were less discriminating: 77% compared with 57%. Only the enhanced model predicted success accurately across the spectrum of baseline scores. The findings were virtually identical when we replicated these analyses on only patients ≥65 years of age. Conclusions: Adding a baseline knee-specific PROM score to a quality measurement model in a nationally representative cohort dramatically improved its predictive power, eliminating ceiling and floor effects and mispredictions for readily identifiable patient subgroups. The enhanced model neither favors nor discourages care for those with greater knee dysfunction and requires no new data collection. Level of evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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  Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C [preprint]

  Preiss, Alexander; Bhatia, Abhishek; Zang, Chengxi; Aragon, Leyna V; Baratta, John M; Baskaran, Monika; Blancero, Frank; Brannock, M Daniel; Chew, Robert F; Díaz, Iván; et al. (2024-01-22)

  Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.
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  Practice Site Heterogeneity within and between Medicaid Accountable Care Organizations

  Dyer, Zachary; Alcusky, Matthew J; Himmelstein, Jay; Ash, Arlene S.; Kerrissey, Michaela (2024-01-20)

  The existing literature has considered accountable care organizations (ACOs) as whole entities, neglecting potentially important variations in the characteristics and experiences of the individual practice sites that comprise them. In this observational cross-sectional study, our aim is to characterize the experience, capacity, and process heterogeneity at the practice site level within and between Medicaid ACOs, drawing on the Massachusetts Medicaid and Children's Health Insurance Program (MassHealth), which launched an ACO reform effort in 2018. We used a 2019 survey of a representative sample of administrators from practice sites participating in Medicaid ACOs in Massachusetts (n = 225). We quantified the clustering of responses by practice site within all 17 Medicaid ACOs in Massachusetts for measures of process change, previous experience with alternative payment models, and changes in the practices' ability to deliver high-quality care. Using multilevel logistic models, we calculated median odds ratios (MORs) and intraclass correlation coefficients (ICCs) to quantify the variation within and between ACOs for each measure. We found greater heterogeneity within the ACOs than between them for all measures, regardless of practice site and ACO characteristics (all ICCs ≤ 0.26). Our research indicates diverse experience with, and capacity for, implementing ACO initiatives across practice sites in Medicaid ACOs. Future research and program design should account for characteristics of practice sites within ACOs.
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  Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19

  Sidky, Hythem; Hansen, Kristen A; Girvin, Andrew T; Hotaling, Nathan; Michael, Sam G; Gersing, Ken; Sahner, David K (2024-01-09)

  Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 ×10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.
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  Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

  Mitra, Amit Kumar; Mukherjee, Ujjal Kumar; Mazumder, Suman; Madhira, Vithal; Bergquist, Timothy; Shao, Yu Raymond; LIu, Feifan; Song, Qianqian; Su, Jing; Kumar, Shaji; et al. (2023-12-07)

  Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

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