The University of Massachusetts Center for Clinical and Translational Science (UMCCTS) was founded in 2006 to enhance clinical and translational research across the five University of Massachusetts campuses and our clinical partners, UMass Memorial Health Care and Baystate Medical Center. The UMCCTS is part of the Clinical and Translational Science Award (CTSA) program, funded by the National Center for Advancing Translational Sciences (Grant # UL1-TR001453) at the National Institutes of Health (NIH). This collection showcases publications that are the result of UMCCTS supported research.


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Recently Published

  • Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes [preprint]

    Chan, Lauren E; Casiraghi, Elena; Laraway, Bryan; Coleman, Ben; Blau, Hannah; Zaman, Adnin; Harris, Nomi; Wilkins, Kenneth; Gargano, Michael; Valentini, Giorgio; et al. (2022-08-30)
    Background: With the continuing COVID-19 pandemic, identifying medications that improve COVID-19 outcomes is crucial. Studies suggest that use of metformin, an oral antihyperglycemic, is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemic medications. Some patients without diabetes, including those with polycystic ovary syndrome (PCOS) and prediabetes, are prescribed metformin for off-label use, which provides an opportunity to further investigate the effect of metformin on COVID-19. Participants: In this observational, retrospective analysis, we leveraged the harmonized electronic health record data from 53 hospitals to construct cohorts of COVID-19 positive, metformin users without diabetes and propensity-weighted control users of levothyroxine (a medication for hypothyroidism that is not known to affect COVID-19 outcome) who had either PCOS (n = 282) or prediabetes (n = 3136). The primary outcome of interest was COVID-19 severity, which was classified as: mild, mild ED (emergency department), moderate, severe, or mortality/hospice. Results: In the prediabetes cohort, metformin use was associated with a lower rate of COVID-19 with severity of mild ED or worse (OR: 0.630, 95% CI 0.450 - 0.882, p < 0.05) and a lower rate of COVID-19 with severity of moderate or worse (OR: 0.490, 95% CI 0.336 - 0.715, p < 0.001). In patients with PCOS, we found no significant association between metformin use and COVID-19 severity, although the number of patients was relatively small. Conclusions: Metformin was associated with less severe COVID-19 in patients with prediabetes, as seen in previous studies of patients with diabetes. This is an important finding, since prediabetes affects between 19 and 38% of the US population, and COVID-19 is an ongoing public health emergency. Further observational and prospective studies will clarify the relationship between metformin and COVID-19 severity in patients with prediabetes, and whether metformin usage may reduce COVID-19 severity.
  • Lay Beliefs About Doctors' Knowledge of and Reasons for Recommending COVID-19 Vaccines

    Fisher, Kimberly A; Nguyen, Ngoc; Mazor, Kathleen M (2022-08-29)
    Commonly cited as the most trusted source of information about COVID-19 vaccines, healthcare providers have an important role in promoting COVID-19 vaccination While a healthcare provider recommendation is associated with greater likelihood of being vaccinated against COVID-193, there is limited understanding of lay beliefs about providers’ knowledge of COVID-19 vaccines and reasons for promoting vaccination.
  • Trends in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seroprevalence in Massachusetts Estimated from Newborn Screening Specimens

    Ma, Kevin C; Hale, Jaime E; Grad, Yonatan H; Alter, Galit; Luzuriaga, Katherine; Eaton, Roger B; Fischinger, Stephanie; Kaur, Devinder; Brody, Robin; Siddiqui, Sameed M; et al. (2022-08-24)
    Background: Estimating the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for setting public health policies. We leveraged deidentified Massachusetts newborn screening specimens as an accessible, retrospective source of maternal antibodies for estimating statewide seroprevalence in a nontest-seeking population. Methods: We analyzed 72 117 newborn specimens collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification. Results: Statewide seroprevalence was estimated to be 0.03% (90% credible interval [CI], 0.00-0.11) in November 2019 and rose to 1.47% (90% CI: 1.00-2.13) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onward, reaching 2.15% (90% CI: 1.56-2.98) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black (β = .024; 90% CI: 0.004-0.044); i.e., a 10% increase in community percent non-Hispanic Black was associated with 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter. Conclusions: Cumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable.
  • Impact of individual and treatment characteristics on wearable sensor-based digital biomarkers of opioid use

    Chapman, Brittany P.; Gullapalli, Bhanu Teja; Rahman, Tauhidur; Smelson, David; Boyer, Edward W; Carreiro, Stephanie P. (2022-08-22)
    Opioid use disorder is one of the most pressing public health problems of our time. Mobile health tools, including wearable sensors, have great potential in this space, but have been underutilized. Of specific interest are digital biomarkers, or end-user generated physiologic or behavioral measurements that correlate with health or pathology. The current manuscript describes a longitudinal, observational study of adult patients receiving opioid analgesics for acute painful conditions. Participants in the study are monitored with a wrist-worn E4 sensor, during which time physiologic parameters (heart rate/variability, electrodermal activity, skin temperature, and accelerometry) are collected continuously. Opioid use events are recorded via electronic medical record and self-report. Three-hundred thirty-nine discreet dose opioid events from 36 participant are analyzed among 2070 h of sensor data. Fifty-one features are extracted from the data and initially compared pre- and post-opioid administration, and subsequently are used to generate machine learning models. Model performance is compared based on individual and treatment characteristics. The best performing machine learning model to detect opioid administration is a Channel-Temporal Attention-Temporal Convolutional Network (CTA-TCN) model using raw data from the wearable sensor. History of intravenous drug use is associated with better model performance, while middle age, and co-administration of non-narcotic analgesia or sedative drugs are associated with worse model performance. These characteristics may be candidate input features for future opioid detection model iterations. Once mature, this technology could provide clinicians with actionable data on opioid use patterns in real-world settings, and predictive analytics for early identification of opioid use disorder risk.
  • Risk Factors Associated with Post-Acute Sequelae of SARS-CoV-2 in an EHR Cohort: A National COVID Cohort Collaborative (N3C) Analysis as part of the NIH RECOVER program [preprint]

    Hill, Elaine; Mehta, Hemal; Sharma, Suchetha; Mane, Klint; Xie, Catherine; Cathey, Emily; Loomba, Johanna; Russell, Seth; Spratt, Heidi; DeWitt, Peter E; et al. (2022-08-17)
    Background: More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID). Objective: To identify risk factors associated with PASC/long-COVID. Design: Retrospective case-control study. Setting: 31 health systems in the United States from the National COVID Cohort Collaborative (N3C). Patients: 8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system. Measurements: Risk factors included demographics, comorbidities, and treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC. Results: Among 8,325 individuals with PASC, the majority were >50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30+ days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls. Conclusions: This national study identified important risk factors for PASC such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course.
  • Association Between Patient Portal Use and Perceived Patient-Centered Communication Among Adults With Cancer: Cross-sectional Survey Study

    Zaidi, Maryum; Amante, Daniel J; Anderson, Ekaterina; Ito Fukunaga, Mayuko; Faro, Jamie M; Frisard, Christine; Sadasivam, Rajani S; Lemon, Stephenie C. (2022-08-09)
    Background: Patient-centered communication (PCC) plays a vital role in effective cancer management and care. Patient portals are increasingly available to patients and hold potential as a valuable tool to facilitate PCC. However, whether more frequent use of patient portals is associated with increased perceived PCC and which mechanisms might mediate this relationship have not been fully studied. Objective: The goal of this study was to investigate the association between the frequency of access of patient portals and perceived PCC in patients diagnosed with cancer. We further sought to examine whether this association was mediated by patients' self-efficacy in health information-seeking. Methods: We used data from the Health Information National Trend Survey 5 (HINTS 5) cycle 3 (2019) and cycle 4 (2020). This analysis includes 1222 individuals who self-reported having a current or past diagnosis of cancer. Perceived PCC was measured with a 7-item HINTS 5-derived scale and classified as low, medium, or high. Patient portal use was measured by a single item assessing the frequency of use. Self-efficacy about health information-seeking was assessed with a 1-item measure assessing confidence in obtaining health information. We used adjusted multinomial logistic regression models to estimate relative risk ratios (RRRs)/effect sizes of the association between patient portal use and perceived PCC. Mediation by health information self-efficacy was investigated using the Baron and Kenny and Karlson-Holm-Breen methods. Results: A total of 54.5% of the sample reported that they had not accessed their patient portals in the past 12 months, 12.6% accessed it 1 to 2 times, 24.8% accessed it 3 to 9 times, and 8.2% accessed it 10 or more times. Overall, the frequency of accessing the patient portal was marginally associated (P=.06) with perceived PCC in an adjusted multinominal logistic regression model. Patients who accessed their patient portal 10 or more times in the previous 12 months were almost 4 times more likely (RRR 3.8, 95% CI 1.6-9.0) to report high perceived PCC. In mediation analysis, the association between patient portal use and perceived PCC was attenuated adjusting for health information-seeking self-efficacy, but those with the most frequent patient portal use (10 or more times in the previous 12 months) were still almost 2.5 times more likely to report high perceived PCC (RRR 2.4, 95% CI 1.1-5.6) compared to those with no portal use. Conclusions: Increased frequency of patient portal use was associated with higher PCC, and an individual's health information-seeking self-efficacy partially mediated this association. These findings emphasize the importance of encouraging patients and providers to use patient portals to assist in patient-centeredness of cancer care. Interventions to promote the adoption and use of patient portals could incorporate strategies to improve health information self-efficacy.
  • Who is pregnant? defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C) [preprint]

    Jones, Sara; Bradwell, Katie R; Chan, Lauren E; Olson-Chen, Courtney; Tarleton, Jessica; Wilkins, Kenneth J; Qin, Qiuyuan; Faherty, Emily Groene; Lau, Yan Kwan; Xie, Catherine; et al. (2022-08-06)
    Objective: To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and methods: We developed a comprehensive approach, named H ierarchy and rule-based pregnancy episode I nference integrated with P regnancy P rogression S ignatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results: We identified 628,165 pregnant persons with 816,471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, spontaneous abortions), and 23.3% had unknown outcomes. We were able to estimate start dates within one week of precision for 431,173 (52.8%) episodes. 66,019 (8.1%) episodes had incident COVID-19 during pregnancy. Across varying COVID-19 cohorts, patient characteristics were generally similar though pregnancy outcomes differed. Discussion: HIPPS provides support for pregnancy-related variables based on EHR data for researchers to define pregnancy cohorts. Our approach performed well based on clinician validation. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational aging that addresses data inconsistency and missingness in EHR data.
  • Healthcare use in commercially insured youth with mental health disorders

    Hugunin, Julie; Davis, Maryann; Larkin, Celine; Baek, Jonggyu; Skehan, Brian; Lapane, Kate L (2022-07-26)
    Background: The objective of this study is to describe age-related patterns of outpatient healthcare utilization in youth and young adults with mental health disorders. Method: We used the IBM® MarketScan® Commercial Database to identify 359,413 youth and young adults (12-27 years) with a mental health disorder continuously enrolled in private health insurance in 2018. Exploratory analysis was used to describe patterns of outpatient healthcare use (e.g., primary, reproductive, mental health care) and therapeutic management (e.g., medication prescriptions, psychotherapy) by age. Period prevalence and median number of visits are reported. Additional analysis explored utilization patterns by mental health disorder. Results: The prevalence of outpatient mental health care and primary care decreased with age, with a larger drop in primary care utilization. While 74.0-78.4% of those aged 12-17 years used both outpatient mental health care and primary care, 53.1-59.7% of those aged 18-27 years did. Most 18-19-year-olds had a visit with an internal medicine or family medicine specialist, a minority had a pediatrician visit. The prevalence of medication management increased with age, while the prevalence of psychotherapy decreased. Conclusions: Taken together, this descriptive study illustrates age-related differences in outpatient healthcare utilization among those with mental health disorders. Additionally, those with the most severe mental health disorders seem to be least connected to outpatient care. This knowledge can inform efforts to improve utilization of healthcare across the transition to adulthood.
  • Development and test-retest reliability of a screening tool for axial spondyloarthritis

    Shridharmurthy, Divya; Lapane, Kate L.; Khan, Sara; Yi, Esther; Baek, Jonggyu; Kay, Jonathan; Liu, Shao-Hsien (2022-07-08)
    Background: People with axial Spondyloarthritis (axSpA) suffer from lengthy diagnostic delays of ~7 years. The usage of screening tools to identify axSpA patients in primary care can reduce diagnostic delays by facilitating early referral to rheumatologic care. The purpose of this study was to examine the psychometric properties of a potential screening tool for patients with axSpA. Method: Content validity was evaluated by soliciting feedback from 7 rheumatologists regarding the relevance and content representativeness of the proposed screening questions. For the test-retest study, participants ≥18 years of age with chronic back pain (≥3 months) without a diagnosis of mechanical or inflammatory back pain (n = 91) were e-recruited through ResearchMatch. Participation included completing identical baseline and follow-up questionnaires ~14 days apart. Weighted quadratic kappa was used to measure test-retest reliability between the two ratings of the ordinal scales. Construct validity was examined using exploratory factor analysis (EFA) and items with factor loadings ≥0.6 were extracted. Scale dimensionality and simplified factorial solutions were measured using Kaiser's criteria (Eigenvalue >1). Cronbach's alpha was used to measure internal consistency. Results: Most participants were women, non-Hispanic white, and had at least some college education, with a mean age of 45 years. On average, the age at onset of back pain was 31 years. Eleven questions yielded test-retest reliabilities ranging from 0.6 to 0.76. Results from EFA extracted two factors relating to: 1) how pain affects daily life functioning and 2) whether pain improves with movement. Internal consistency was high for questions evaluating how pain affects life, with a Cronbach's alpha of 0.81. Following assessment for validity and reliability, the questionnaire was revised to create the 6-item screening tool. Conclusions: The 6-item SpA-SED screening tool designed to identify potential cases of axSpA was found to have good test-retest reliability and high internal consistency.
  • Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study [preprint]

    Ge, Jin; Digitale, Jean C; Pletcher, Mark J; Lai, Jennifer C (2022-07-08)
    Background and aims: The incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients. Methods: We identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients. Results: We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively.Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days. Conclusions: In this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.
  • COVID-19: a gray swan's impact on the adoption of novel medical technologies

    Dunlap, Denise; Santos, Roberto S.; Lilly, Craig M.; Teebagy, Sean; Hafer, Nathaniel S.; Buchholz, Bryan O.; McManus, David D. (2022-07-08)
    The COVID-19 pandemic offers a unique context and opportunity to investigate changes in healthcare professional perceptions towards the adoption of novel medical technologies, such as point-of-care technologies (POCTs). POCTs are a nascent technology that has experienced rapid growth as a result of COVID-19 due to their ability to increase healthcare accessibility via near-patient delivery, including at-home. We surveyed healthcare professionals before and during COVID-19 to explore whether the pandemic altered their perceptions about the usefulness of POCTs. Our network analysis method provided a structure for understanding this changing phenomenon. We uncovered that POCTs are not only useful for diagnosing COVID-19, but healthcare professionals also perceive them as increasingly important for diagnosing other diseases, such as cardiovascular, endocrine, respiratory, and metabolic diseases. Healthcare professionals also viewed POCTs as facilitating the humanization of epidemiology by improving disease management/monitoring and strengthening the clinician-patient relationship. As the accuracy and integration of these technologies into mainstream healthcare delivery improves, hurdles to their adoption dissipate, thereby encouraging healthcare professionals to rely upon them more frequently to diagnose, manage, and monitor diseases. The technological advances made in POCTs during COVID-19, combined with shifting positive perceptions of their utility by healthcare professionals, may better prepare us for the next pandemic.
  • Racial differences in the association of accelerated aging with future cardiovascular events and all-cause mortality: the coronary artery risk development in young adults study, 2007-2018

    Forrester, Sarah N; Zmora, Rachel; Schreiner, Pamela J; Jacobs, David R; Roger, Veronique L; Thorpe, Roland J; Kiefe, Catarina I (2022-07-01)
    Objective: Variability of Cardiovascular disease (CVD) risk, including racial difference, is not fully accounted for by the variability of traditional CVD risk factors. We used a multiple biomarker model as a framework to explore known racial differences in CVD burden. Design: We measured associations between accelerated aging (AccA) measured by a combination of biomarkers, and cardiovascular morbidity and all-cause mortality using data from the Coronary Artery Risk Development in Young Adults study (CARDIA). AccA was defined as the difference between biological age, calculated using biomarkers with the Klemera and Doubal method, and chronological age. Using logistic regression, we assessed overall and race-specific associations between AccA, CVD, and all-cause mortality. Results: Among our cohort of 2959 Black or White middle-aged adults, after adjustment, a one-year increase in AccA was associated with increased odds of CVD (Odds Ratio (OR) = 1.04; 95% CI: 1.02, 1.06), stroke (OR = 1.12; 95% CI: 1.07, 1.17), and all-cause mortality (OR = 1.05; 95% CI: 1.02, 1.08). We did not find significant overall racial differences, but we did find race by sex differences where Black men differed markedly from White men in the strength of association with CVD (OR = 1.06, 95% CI: 1.01, 1.12). Conclusions: We provide evidence that AccA is associated with future CVD.
  • Th2 to Th1 Transition Is Required for Induction of Skin Lesions in an Inducible and Recurrent Murine Model of Cutaneous Lupus-Like Inflammation

    Haddadi, Nazgol-Sadat; Mande, Purvi; Brodeur, Tia Y; Hao, Kaiyuan; Ryan, Grace E.; Moses, Stephanie; Subramanian, Sharon; Picari, Xhuliana; Afshari, Khashayar; Marshak-Rothstein, Ann; et al. (2022-06-27)
    Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by a strong IFN signature, normally associated with type I IFNs. However, increasing evidence points to an additional role for IFNγ, or at least a pathogenic T effector subset dependent on IFNγ, for disease progression. Nevertheless, Th2 effector subsets have also been implicated in CLE. We have now assessed the role of specific T cell subsets in the initiation and persistence of skin disease using a T cell-inducible murine model of CLE, dependent on KJ1-26 T cell recognition of an ovalbumin fusion protein. We found that only Th2-skewed cells, and not Th1-skewed cells, induced the development of skin lesions. However, we provide strong evidence that the Th2 disease-initiating cells convert to a more Th1-like functional phenotype in vivo by the time the skin lesions are apparent. This phenotype is maintained and potentiates over time, as T cells isolated from the skin, following a second induction of self-antigen, expressed more IFN-γ than T cells isolated at the time of the initial response. Transcriptional analysis identified additional changes in the KJ1-26 T cells at four weeks post injection, with higher expression levels of interferon stimulated genes (ISGs) including CXCL9, IRF5, IFIH1, and MX1. Further, injection of IFN-γ-/- T cells faied to induce skin disease in mice. We concluded that Th2 cells trigger skin lesion formation in CLE, and these cells switch to a Th1-like phenotype in the context of a TLR7-driven immune environment that is stable within the T cell memory compartment.
  • Design and Preliminary Findings of Adherence to the Self-Testing for Our Protection From COVID-19 (STOP COVID-19) Risk-Based Testing Protocol: Prospective Digital Study

    Herbert, Carly; Broach, John P.; Gerber, Ben S.; Fahey, Nisha; Orvek, Elizabeth Aaker; Lazar, Peter; Ferranto, Julia M.; Noorishirazi, Kamran; Valpady, Shivakumar; Shi, Qiming; et al. (2022-06-16)
    BACKGROUND: Serial testing for SARS-CoV-2 is recommended to reduce spread of the virus; however, little is known about adherence to recommended testing schedules and reporting practices to health departments. OBJECTIVE: The Self-Testing for Our Protection from COVID-19 (STOP COVID-19) study aims to examine adherence to a risk-based COVID-19 testing strategy using rapid antigen tests and reporting of test results to health departments. METHODS: STOP COVID-19 is a 12-week digital study, facilitated using a smartphone app for testing assistance and reporting. We are recruiting 20,000 participants throughout the United States. Participants are stratified into high- and low-risk groups based on history of COVID-19 infection and vaccination status. High-risk participants are instructed to perform twice-weekly testing for COVID-19 using rapid antigen tests, while low-risk participants test only in the case of symptoms or exposure to COVID-19. All participants complete COVID-19 surveillance surveys, and rapid antigen results are recorded within the smartphone app. Primary outcomes include participant adherence to a risk-based serial testing protocol and percentage of rapid tests reported to health departments. RESULTS: As of February 2022, 3496 participants have enrolled, including 1083 high-risk participants. Out of 13,730 tests completed, participants have reported 13,480 (98.18%, 95% CI 97.9%-98.4%) results to state public health departments with full personal identifying information or anonymously. Among 622 high-risk participants who finished the study period, 35.9% showed high adherence to the study testing protocol. Participants with high adherence reported a higher percentage of test results to the state health department with full identifying information than those in the moderate- or low-adherence groups (high: 71.7%, 95% CI 70.3%-73.1%; moderate: 68.3%, 95% CI 66.0%-70.5%; low: 63.1%, 59.5%-66.6%). CONCLUSIONS: Preliminary results from the STOP COVID-19 study provide important insights into rapid antigen test reporting and usage, and can thus inform the use of rapid testing interventions for COVID-19 surveillance.
  • Perspectives on addressing bipolar disorder in the obstetric setting

    Masters, Grace A; Xu, Lulu; Cooper, Katherine M; Moore Simas, Tiffany A; Brenckle, Linda; Mackie, Thomas I; Schaefer, Ana J; Straus, John; Byatt, Nancy (2022-05-25)
    Objective: Perinatal Psychiatry Access Programs have emerged to help obstetric professionals meet the needs of perinatal individuals with mental health conditions, including bipolar disorder (BD). We elucidate obstetric professionals' perspectives on barriers and facilitators to managing BD in perinatal patients, and how Access Programs may affect these processes. Methods: We conducted three focus groups with obstetric professionals, two with- and one without-exposure to an Access Program, the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms. Focus groups discussed experiences, barriers, facilitators, and solutions to caring for perinatal individuals with BD. Qualitative data were coded and analyzed by two independent coders; emergent themes were examined across exposure groups. Results: Thirty-one obstetric professionals (7 without-exposure, 24 with-exposure) participated. Identified themes included: (1) gaps in perinatal BD education; (2) challenges in patient assessment; (3) MCPAP for Moms as a facilitator for addressing BD; and (4) importance of continued outreach and destigmaization to increase care collaboration. Conclusions: Barriers to obstetric professionals accessing adequate mental healthcare for their patients with BD abound. With psychiatric supports in place, it is possible to build obstetric professionals' capacity to address BD. Perinatal Psychiatry Access Programs can facilitate obstetric professionals bridging these gaps in mental health care.
  • NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study

    Reese, Justin T; Coleman, Ben; Chan, Lauren; Blau, Hannah; Callahan, Tiffany J; Cappelletti, Luca; Fontana, Tommaso; Bradwell, Katie R; Harris, Nomi L; Casiraghi, Elena; et al. (2022-05-15)
    Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use. Methods: A 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis. Results: Logistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53-0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47-0.56), invasive ventilation (OR: 0.59 95% CI: 0.55-0.64), AKI (OR: 0.67 95% CI: 0.63-0.72), or ECMO (OR: 0.51 95% CI: 0.36-0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations. Conclusions: Study interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database.
  • Predictive algorithm to stratify newborns at-risk for child undernutrition in India: Secondary analysis of the National Family Health Survey-4

    Soni, Apurv; Fahey, Nisha; Ash, Arlene; Bhutta, Zulfiqar; Li, Wenjun; Moore Simas, Tiffany A.; Nimbalkar, Somashekhar; Allison, Jeroan (2022-05-14)
    Background: India is at the epicentre of global child undernutrition. Strategies to identify at-risk populations are needed in the context of limited resources. Methods: Data from children under the age of five surveyed in the 2015-2016 National Family Health Survey were used. Child undernutrition was assessed using anthropometric measurements. Predictor variables were identified from the extant literature and included if they could be measured at the time of delivery. Survey-weighted logistic regression was applied to model the outcome. Internal validation of the model was performed using 200 bootstrapped samples representing half of the total data sets. Results: In 2016, 54.4% (95% CI = 54.0%-54.8%) of Indian children were undernourished, according to a composite index of anthropometric failure. The predictive model for overall undernutrition included maternal (height, education, reproductive history, number of antenatal visits), child (sex, birthweight), and household characteristics (district of residence, caste, rural residence, toilet availability, presence of a separate kitchen). The model demonstrated reasonable discrimination ability (optimism-adjusted c = 0.67). The group of children classified in the lowest decile for risk of undernutrition had a prevalence of 25.9%, while the group classified in the highest decile had a prevalence of 77.4%. Conclusions: It is possible to stratify newborns at the time of delivery based on their risk for undernutrition in the first five years of life. The model developed by this study represents a first step in adopting a risk-score based approach for the most vulnerable population to receive services in a timely manner.
  • Novel Framework for Measuring Whole Knee Osteoarthritis Progression Using Magnetic Resonance Imaging

    Driban, Jeffrey B.; Price, Lori Lyn; LaValley, Michael P.; Lo, Grace H.; Zhang, Ming; Harkey, Matthew S.; Canavatchel, Amanda; McAlindon, Timothy E. (2022-05-01)
    OBJECTIVE: We developed and validated a set of composite scores that combine quantitative magnetic resonance imaging (MRI)-based measurements of hyaline cartilage damage, bone marrow lesions (BMLs), and effusion-synovitis into composite scores. METHODS: We selected 300 participants (n = 100 for development cohort; n = 200 for validation cohort) from the Osteoarthritis Initiative with complete clinical, radiographic, and MRI data at baseline and 24 months. We used semiautomated programs to quantify tibiofemoral and patellar cartilage damage, BML volume, and whole-knee effusion-synovitis volume. The candidate composite scores were formed by summing changes from baseline to 24 months based on prespecified methods. We evaluated the candidate composite scores for 1) the ability to differentiate groups with and without knee osteoarthritis progression (17 radiographic and patient-reported definitions), 2) sensitivity to change (standardized response means), and 3) relative performance relating to legacy outcome measures of knee osteoarthritis progression. RESULTS: Three of 13 developed composite scores qualified for testing in the validation cohort (ranked by sensitivity to change): whole-knee cumulative cartilage damage, unweighted total knee score, and BML plus effusion-synovitis volume. Change in cumulative cartilage damage associated with radiographic progression (Kellgren/Lawrence grade: odds ratio [OR] 1.84; joint space width progression: OR 2.11). Changes in the unweighted total knee score (OR 1.97) and BML plus effusion-synovitis score (OR 1.92) associated with Western Ontario and McMaster Universities Osteoarthritis Index knee pain progression. CONCLUSION: Two composite scores emerged, reflecting discrete domains of knee osteoarthritis progression. First, cumulative damage, which is measured by a whole-knee cartilage damage score, reflects the damage accrued over time. Second, dynamic disease activity, which is measured by a BML plus effusion-synovitis score, relates to changes in a patient's state of disease and symptoms.
  • Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution

    Ke, Ruian; Martinez, Pamela P; Smith, Rebecca L; Gibson, Laura L; Achenbach, Chad J; McFall, Sally; Qi, Chao; Jacob, Joshua; Dembele, Etienne; Bundy, Camille; et al. (2022-04-13)
    Background: The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus. Methods: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. Results: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. Conclusions: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.
  • Association of trends in child undernutrition and implementation of the National Rural Health Mission in India: A nationally representative serial cross-sectional study on data from 1992 to 2015

    Soni, Apurv; Fahey, Nisha; Bhutta, Zulfiqar; Li, Wenjun; Moore Simas, Tiffany A.; Nimbalkar, Somashekhar; Allison, Jeroan J. (2022-04-08)
    BACKGROUND: India launched the National Rural Health Mission (NRHM) in 2005 to strengthen its primary healthcare system in high-focus and northeast-focus states. One of the NRHM objectives was to reduce child undernutrition in India. METHODS AND FINDINGS: We used data from 1992, 1998, 2005, and 2015 National Family Health Survey (NFHS) of India to evaluate trends in child undernutrition prevalence before and after NRHM and across different categories of focus states. Stunting, Wasting, and Comprehensive Index of Anthropometric Failure (CIAF) were assessed using the World Health Organization (WHO) growth curves to assess chronic, acute, and overall undernutrition. The study included 187,452 children aged 3 years or under. Survey-weighted and confounder-adjusted average annualized reduction rates (AARRs) and predicted probability ratios were used to assess trends and socioeconomic disparities for child undernutrition, respectively. Nationwide, the prevalence of all types of undernutrition decreased from 1992 to 2015. However, the trends varied before and after NRHM implementation and differentially by focus states. After NRHM, acute undernutrition declined more rapidly among high-focus states (AARR 1.0%) but increased in normal-focus states (AARR -1.9% per year; p-value for the difference < 0.001). In contrast, the prevalence of chronic undernutrition declined more rapidly (AARR 1.6%) in the normal-focus states in comparison to high-focus states (0.3%; p-value for the difference = 0.01). Income and caste-based disparities in acute undernutrition decreased but did not disappear after the implementation of the NRHM. However, similar disparities in prevalence of chronic undernutrition appear to be exacerbated after the implementation of the NRHM. Major limitations of this study include the observational and cross-sectional design, which preclude our ability to draw causal inferences. CONCLUSIONS: Our results suggests that NRHM implementation might be associated with improvement in wasting (acute) rather than stunting (chronic) forms of undernutrition. Strategies to combat undernutrition equitably, especially in high-focus states, are needed.

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