Emergency Medicine Publications

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https://hdl.handle.net/20.500.14038/216

ABOUT THIS COLLECTION

The mission of the Department of Emergency Medicine is to be the preeminent Department of Emergency Medicine in the country by delivering excellent healthcare, with respect and dignity to all patients needing emergent or urgent care services; conducting ground-breaking research that enhances public health; and developing innovative educational programs for all levels of health care providers. This collection showcases journal articles and other publications written by faculty and researchers of the Department of Emergency Medicine.

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Leveraging Trauma Informed Care for Digital Health Intervention Development in Opioid Use Disorder
(2024-10-24) Venkatasubramanian, Krishna; Appleton, Johanna; Ranalli, Tina-Marie; Mankodiya, Kunal; Solanki, Dhaval; Carreiro, Stephanie; Emergency Medicine
Digital health refers to the use of information and communication technologies in medicine (including smartphone apps, wearables, other non-invasive sensors, informatics and telehealth platforms) to prevent illness, deliver treatment, and promote wellness. This rapidly proliferating group of technologies has the potential to reduce harm for people with opioid use disorder (OUD) and facilitate the recovery process; however, development in this space for OUD has been slower compared to that for other medical conditions. Unique issues with OUD management surrounding patient provider relationships, interaction with the healthcare system, autonomy and trust sometimes hinder care approaches, including those in digital health. The trauma informed care framework (TIC), developed for use by organizations to support individuals who have experienced trauma, has particular applicability for digital health interventions in OUD care. This manuscript will serve as a review of TIC principles and how they can be applied to digital health interventions to increase access, equity, and empowerment for people with OUD. We will highlight representative current and pipeline digital technologies for OUD, challenges with these technologies, TIC models for OUD, and the integration of TIC principles into digital technology development to better serve people with OUD. Finally, we will posit strategies to incorporate the aforementioned principles into future research efforts. We ultimately aim to use TIC as a lens through which to develop digital technologies to help individuals with OUD while minimizing harm.
Longitudinal cognitive outcomes are strongly correlated with the Alzheimer’s Disease microbiome
(Wiley, 2025-1-3) Zeamer, Abigail L; Sanborn, Victoria; Drake, Jonathan D; Haran, John P; Bucci, Vanni; Emergency Medicine
Background: It has been shown that dysbiosis, or dysfunction of the gastrointestinal (gut) microbiome is associated with Alzheimer’s disease (AD). Here, we aimed to expand on beyond our previously reported findings of the gut microbiome associating with AD and explore if the gut microbiome is predictive of cognitive performance in individuals with AD. We sought to identity what cognitive domains are associated with the microbiome in our cohort of AD patients and healthy controls without dementia. Method: Older individuals residing in the general community of central Massachusetts were enrolled in our study. At each visit, fecal samples and clinical variables were collected in addition to cognitive testing using the ADAS-Cog-13 tool, such as delayed memory, word recall, recognition etc. Metagenomic profiling was performed on longitudinal fecal samples. Z-scores for different cognitive domains, including memory, executive function and language were generated for the study population. Mixed-effect random forest regression (MERFR) models were created to identify metagenomic features informative of cognitive performance across these different cognitive tests and domains. Result: Replicating our previous work, among AD diagnosed individuals, MERFR models predicted performance on ADAS-Cog 13 from microbial abundance and pathways with a strong accuracy. The ADAS-Cog 13 was not well predicted by the microbiome in the healthy controls. Additionally, in our new analysis across different cognitive domains, Z-Scores were well predicted by MERFR models using microbial abundance and encoded pathways. Conclusion: Not only is the gut microbiome composition highly predictive of AD diagnosis, but there is also a strong correlation of the gut microbiome and cognitive functioning. This is true across the multiple domains of cognition including memory, executive function and language, however different bacterial species were significant in associating with each domain. This work highlights the complexity of the microbiome-gut-brain axis and how the microbiome community makeup might play a role in cognitive decline.
Gut microbiome phytoestrogen production and its protective role in Alzheimer’s disease
(Wiley, 2025-1-3) Loew, Ethan B; McCormick, Beth; Haran, John P; Emergency Medicine
Background: In Alzheimer’s disease (AD), changes in intestinal microbiota and systemic inflammation are concomitant with neuroinflammation and cognitive decline. This has led to the theory of microbial communities or infections as being causative in the development of neuroinflammation and immunosenescence seen in AD. Our research has demonstrated a decreased taxonomic diversity and an increased abundance of pathobionts in the gut of AD patients (Haran, mBio 2019), which is sufficient to promote amyloid and tau deposition in a mouse model (Chen, Gut 2023). It is unclear, however, if effects from the AD microbiome on the central nervous system can be mitigated. Here, we propose a protective mechanism where bacterial metabolites influence cognition via estrogen signaling. Method: We have performed gut microbiome profiling on a cohort of 178 nursing home residents and used in vitro models to quantify the effects of AD-associated bacteria and bacterial products on inflammation. Result: We have identified a commensal bacterium, Adlercreutzia equolifaciens, to be depleted in our cohort of older adults with AD and further depleted in adults with progressive versus stable AD. A. equolifaciens metabolizes dietary isoflavones to produce (s)-equol, a bacterial metabolite which binds to estrogen receptors. We treated cells expressing estrogen receptor beta, which is predominately expressed along the intestinal epithelium, with (s)-equol and demonstrated (s)-equol induces transcription of host genomic estrogen response genes (Vehicle normalized luciferase = 0.007, estradiol = 1.04, (s)-equol = 1.23, p<0.0001). We have further demonstrated that treatment of intestinal epithelial cells with 17β-estradiol induced the transcription of regulators of the innate immune response in an ERβ dependent manner (Vehicle RQ = 0.88, estradiol = 1.84, p<0.05). Finally, we have discovered that colonization with A. equolifaciens in the gut of older adults is associated with lower rates of colonization by the intestinal pathobiont Escherichia (Estimation of regression β-coefficient = -1.422, p<0.05). Conclusion: Adlercreutzia equolifaciens and similar phytoestrogen-metabolizing bacteria may protect the intestinal epithelium against bacterial invasion and subsequent systemic inflammation, thereby preventing cognitive decline. Our continuing work aims to further establish the connection between AD related neurocognitive decline, the microbiome, and immune system. A. equolifaciens is therefore a strong candidate as a microbiome-based therapeutic acting along the gut-brain axis in AD.
Utilizing Latent Dirichlet Allocation and Differential Abundance to Identify Microbial Communities in both the Oral and Fecal Microbiome Associated with Alzheimer’s Disease
(Wiley, 2025-1-3) Huang, Ziyuan; Zeamer, Abigail L; Ward, Doyle; Jo, Cynthia; Bucci, Vanni; Haran, John P; Emergency Medicine
Background: Several studies have found that oral and gut microbiome and their byproducts can impact Alzheimer’s Disease (AD). The objective of our study is to analyze metagenomic sequencing data from paired oral and fecal microbiomes, along with clinical variables, to identify communities of bacteria associated with AD. This research aims to improve our understanding of the microbiome community matrix, and how these communities interact and correlate with AD status compared to healthy controls (HC) through an oral-gut microbial axis. Method: The study includes 223 HC and 43 individuals with AD. During each visit, paired oral and fecal samples were collected, along with clinical variables. Metagenomic profiling was done on all samples. Latent Dirichlet Allocation (LDA) was applied to identify differences in microbial species groups between these two body sites in realtion to AD status. LDA is used as a topic modeling method to uncover the complex structure and function of microbial communities. Subsequently, differential abundance (DA) analysis was performed to identify species with differential abundance at each body site. Result: We identified microbiotal communities sharing similar characteristics and pinpointed representative bacteria within these communities that are highly relevant to AD. Within the oral microbiome, we have identified 27 topics, including several bacteria that are highly relevant to AD. These included Alistipes (beta = 3.919232e-01), Paraprevotella xylaniphila (beta = 1.227791e-01), Desulfovibrio (beta = 6.013213e- 02), and Lachnospiraceae (beta = 2.304369e-02). In the gut, we have identified 50 topics, reflecting the gut is more complex the oral microbiome. Notable bacteria in the gut microbiome include Actinomyces oricola (beta = 6.959554e-01), Roseburia (beta = 8.861444e-02), Bacteroidetes (beta = 5.010610e-01), and Actinomyces gerencseriae (beta = 3.048668e-02). Conclusion: Our study has identified a variety of bacteria that exhibit novel community patterns that associate with AD. In the gut, A. gerencseriae and other oral microbiomes were observed in AD patients. Also, the microbial communities differ between AD and HC. Thereforth, we conclude that translocation of oral and gut microbiota may contribute to AD through an oral-gut-microbiome axis.
Characterization bacterial metabolites and peripheral immune cell populations in stable and progressive Alzheimer’s disease
(Wiley, 2025-1-3) Loew, Ethan B; Tracy, Matthew; Jo, Cynthia; McCormick, Beth; Haran, John P; Emergency Medicine
Background: Alzheimer’s disease (AD) is the most common type of dementia which results in debilitating memory loss as the disease advances. However, among older adults with AD, some may experience rapid cognitive decline while others may maintain a stable cognitive status for years. In addition to the amyloid plaques, tau tangles, and neuronal inflammation characteristic of AD, there is strong evidence of dysregulation in the peripheral immune system, including decreased naïve T cells and increased memory T cells among older adults with AD. It is currently unknown what underlies dysfunction in the peripheral immune system or whether changes in peripheral immune cells are associated with cognitive decline. Method: We have performed unbiased metabolomics and characterized stool metabolites present in 35 AD versus 35 propensity matched healthy controls. In our ongoing work, we are longitudinally characterizing resting peripheral immune cell populations by flow cytometry and gut microbiome composition by metagenomic sequencing. Result: We have identified an increase in the metabolites methionine sulfone (1.46 fold, p<0.05), homocysteine (1.67 fold, p<0.05), and cysteine (1.33 fold, p<0.05) in the stool of older adults with AD compared to controls. Among the population of AD patients experiencing cognitive decline, determined by increasing ADAS-Cog score >6 points over one year (n = 7 declining vs n = 8 stable cognition), we have identified increases in the bacterial genes responsible for methionine production at the point of cognitive decline compared to previous timepoints and between patients with decline versus stable cognition. In accordance with the role of methionine in promoting immune cell proliferation and differentiation, we have compared the composition of peripheral immune cells among adults with declining versus stable cognition and identified a decrease in CD4+/CD62L+ naïve T cells (percent of CD4+ lymphocytes stable 0.3055 vs declining 0.0955, p = 0.0042) and increased effector memory CD4+ T cells (percent of CD4+ lymphocytes, stable = 0.2375 vs declining = 0.4164, p = 0.0225). Conclusion: This longitudinal clinical study identifies changes in stool metabolites and resting peripheral T cell populations in AD patients and among AD patients with cognitive decline. We propose that gut bacterial produced methionine acts to promote peripheral immune differentiation and dysfunction, leading to cognitive decline in AD.
Peritraumatic C-reactive protein levels predict pain outcomes following traumatic stress exposure in a sex-dependent manner [preprint]
(2024-12-07) McKibben, Lauren A; Layne, Miranda N; Albertorio-Sáez, Liz Marie; Zhao, Ying; Branham, Erica M; House, Stacey L; Beaudoin, Francesca L; An, Xinming; Stevens, Jennifer S; Neylan, Thomas C; Clifford, Gari D; Germine, Laura T; Bollen, Kenneth A; Rauch, Scott L; Haran, John P; Storrow, Alan B; Lewandowski, Christopher; Musey, Paul I; Hendry, Phyllis L; Sheikh, Sophia; Jones, Christopher W; Punches, Brittany E; Swor, Robert A; Hudak, Lauren A; Pascual, Jose L; Seamon, Mark J; Datner, Elizabeth M; Peak, David A; Merchant, Roland C; Domeier, Robert M; Rathlev, Niels K; O'Neil, Brian J; Sanchez, Leon D; Bruce, Steven E; Sheridan, John F; Harte, Steven E; Kessler, Ronald C; Koenen, Karestan C; Ressler, Kerry J; McLean, Samuel A; Linnstaedt, Sarah D; Emergency Medicine
Background: Chronic pain following traumatic stress exposure (TSE) is common. Increasing evidence suggests inflammatory/immune mechanisms are induced by TSE, play a key role in the recovery process versus development of post-TSE chronic pain, and are sex specific. In this study, we tested the hypothesis that the inflammatory marker C-reactive protein (CRP) is associated with chronic pain after TSE in a sex-specific manner. Methods: We utilized blood-plasma samples and pain questionnaire data from men (n=99) and (n=223) women enrolled in AURORA, a multi-site emergency department (ED)-based longitudinal study of TSE survivors. We measured CRP using Ella/ELISA from plasma samples collected in the ED ('peritraumatic CRP', n=322) and six months following TSE (n=322). Repeated measures mixed-effects models were used to assess the relationship between peritraumatic CRP and post-TSE chronic pain. Results: Peritraumatic CRP levels significantly predicted post-TSE chronic pain, such that higher levels of CRP were associated with lower levels of pain over time following TSE, but only in men (men:β=-0.24, p=0.037; women:β=0.05, p=0.470). By six months, circulating CRP levels had decreased by more than half in men, but maintained similar levels in women (t(290)=1.926, p=0.055). More men with a decrease in CRP levels had decreasing pain over time versus women (men:83% women:65%; Z=2.21, p=0.027). Conclusions: In men but not women, we found circulating peritraumatic CRP levels predict chronic pain outcomes following TSE and resolution of CRP levels in men over time might be associated with increased pain recovery. Further studies are needed to validate these results.
Relationship Between Acute Severe Acute Respiratory Syndrome Coronavirus 2 Viral Clearance and Long Coronavirus 2019 (Long COVID) Symptoms: A Cohort Study
(2024-12-18) Herbert, Carly; Antar, Annukka A R; Broach, John; Wright, Colton; Stamegna, Pamela; Luzuriaga, Katherine; Hafer, Nathaniel; McManus, David D; Manabe, Yukari C; Soni, Apurv; Medicine; Center for Clinical and Translational Science; Emergency Medicine; Program in Molecular Medicine; Population and Quantitative Health Sciences
Background: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics during acute infection and the development of long coronavirus disease 2019 (COVID-19), or "long COVID," is largely unknown. Methods: Between October 2021 and February 2022, 7361 people not known to have COVID-19 self-collected nasal swab samples for SARS-CoV-2 reverse-transcription polymerase chain reaction testing every 24-48 hours for 10-14 days. Participants whose first known SARS-CoV-2 infection was detected were surveyed for long COVID in August 2023. Their slopes of viral clearance were modeled using linear mixed effects models with random slopes and intercepts, and the relative risk (RR) of long COVID based on viral slopes was calculated using a log binomial model, adjusted for age, symptoms, and variant. Sex-based interaction terms were also evaluated for significance. Results: A total of 172 participants were eligible for analyses, and 59 (34.3%) reported long COVID. The risk of long COVID with 3-4 symptoms (adjusted RR, 2.44 [95% confidence interval, .88-6.82]) and ≥5 symptoms (4.97 [1.90-13.0]) increased with each unit increase in slope of viral clearance. While the probability of long COVID increased with slowed viral clearance among women, the same relationship was not observed among men (interaction term: P = .02). Acute SARS-CoV-2 symptoms of abdominal pain (adjusted RR, 5.41 [95% confidence interval, 2.44-12.0]), nausea (3.01 [1.31-6.89]), and body aches (2.58 [1.26-5.30]) were most strongly associated with long COVID. Conclusions: We observed that slower viral clearance rates during acute COVID-19 were associated with increased risk and more symptoms of long COVID . Early viral-host dynamics appear to be mechanistically linked to the development of long COVID.
Healthy at Home for COPD: An Integrated Digital Monitoring, Treatment, and Pulmonary Rehabilitation Intervention [preprint]
(2024-11-15) O'Connor, Laurel; Behar, Stephanie; Tarrant, Seanan; Stamegna, Pamela; Pretz, Caitlin; Shirshac, Jeanne; Scornavacca, Thomas; Wilkie, Tracey; Fisher, Kimberly; Tigas, Emil; Mullen, Marie; Hyder, Michael; Wong, Steven; Savage, Brendon; Toomey, Shaun; Wang, Biqi; Zai, Adrian; Alper, Eric; Lindenauer, Peter; Dickson, Eric; Broach, John; McManus, David; Kheterpal, Vik; Soni, Apurv; Population and Quantitative Health Sciences; Emergency Medicine
Background: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality in the United States. Frequent exacerbations result in higher use of emergency services and hospitalizations, leading to poor patient outcomes and high costs. Objective: Demonstrate the feasibility of a multimodal, digitally enhanced remote monitoring, treatment, and tele-pulmonary rehabilitation intervention among patients with COPD. Methods: In this pilot clinical trial, community-dwelling adults with moderate-severe COPD were enrolled in a multimodal digital monitoring and treatment program including a Fitbit wearable device, study app that tracked COPD-related symptoms, on-demand mobile integrated health (MIH) services for acute home-based treatment, and tele-pulmonary-rehabilitation. Participants were enrolled in the program for six months. COPD severity and health-related quality of life assessments were performed at baseline, 3 months, and 6 months. Primary feasibility outcomes include recruitment and retention rate, and participant protocol fidelity, which were reported descriptively. Exploratory clinical outcomes included patient-reported quality of life, activation, and intervention satisfaction. Results: Over 18 months, 1,333 patients were approached and 100 (7.5%) were enrolled (mean age 66, 52% female). Ninety-six participants (96%) remained in the study for the full enrollment period. Fifty-five (55%) participated in tele-pulmonary-rehabilitation. Participants wore the Fitbit for a median of 114 days (IQR 183.6) and 16.85 hours/day (4.05), resulting in a median of 1133 minutes (243) per day. Completion rates for scheduled instruments ranged from 78-93%. Nearly all participants (85%) performed COPD ecological momentary assessment at least once with a median of 4.85 recordings. On average, a 2.48-point improvement (p=0.03) in COPD Assessment Test Score was observed from baseline to study completion. The adherence and symptom improvement metrics were not associated with baseline patient activation measures. Conclusions: A multimodal intervention combining preventative care, symptom and biometric monitoring, and home treatment was feasible in adults living with COPD. Participants demonstrated high protocol fidelity and engagement and reported improved quality of life.
Heart rate variability wrist-wearable biomarkers identify adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure
(2024-11-07) Guichard, Lauriane; An, Xinming; Neylan, Thomas C; Clifford, Gari D; Li, Qiao; Ji, Yinyao; Macchio, Lindsay; Baker, Justin; Beaudoin, Francesca L; Jovanovic, Tanja; Linnstaedt, Sarah D; Germine, Laura T; Bollen, Kenneth A; Rauch, Scott L; Haran, John P; Storrow, Alan B; Lewandowski, Christopher; Musey, Paul I; Hendry, Phyllis L; Sheikh, Sophia; Jones, Christopher W; Punches, Brittany E; Swor, Robert A; Gentile, Nina T; Pascual, Jose L; Seamon, Mark J; Datner, Elizabeth M; Pearson, Claire; Peak, David A; Merchant, Roland C; Domeier, Robert M; Rathlev, Niels K; O'Neil, Brian J; Sergot, Paulina; Sanchez, Leon D; Bruce, Steven E; Sheridan, John F; Harte, Steven E; Ressler, Kerry J; Koenen, Karestan C; Kessler, Ronald C; McLean, Samuel A; Emergency Medicine
Adverse posttraumatic neuropsychiatric sequelae (APNS) are common after traumatic events. We examined whether wrist-wearable devices could provide heart rate variability (HRV) biomarkers for recovery after traumatic stress exposure in a large socioeconomically disadvantaged cohort. Participants were enrolled in the emergency department within 72 hours after a traumatic event as part of the AURORA (Advancing Understanding of RecOvery afteR traumA) multicenter prospective observational cohort study and followed over 6 months. HRV biomarkers were derived and validated for associations with specific APNS symptoms at a point in time and changes in symptom severity over time. Sixty-four HRV characteristics were derived and validated as cross-sectional biomarkers of APNS symptoms, including pain (26), re-experiencing (8), somatic (7), avoidance (7), concentration difficulty (6), hyperarousal (5), nightmares (1), anxiety (1), and sleep disturbance (3). Changes in 22 HRV characteristics were derived and validated as biomarkers identifying changes in APNS symptoms, including reexperiencing (11), somatic (3), avoidance (2), concentration difficulty (1), hyperarousal (1), and sleep disturbance (4). Changes in HRV variables over time predicted symptom improvement (PPV 0.68-0.87) and symptom worsening (NPV 0.71-0.90). HRV biomarkers collected from wrist-wearable devices may have utility as screening tools for APNS symptoms that occur after traumatic stress exposure in high-risk populations.
Rationale and design of healthy at home for COPD: an integrated remote patient monitoring and virtual pulmonary rehabilitation pilot study
(2024-10-28) O'Connor, Laurel; Behar, Stephanie; Tarrant, Seanan; Stamegna, Pamela; Pretz, Caitlin; Wang, Biqi; Savage, Brandon; Scornavacca, Thomas Thomas; Shirshac, Jeanne; Wilkie, Tracey; Hyder, Michael; Zai, Adrian; Toomey, Shaun; Mullen, Marie; Fisher, Kimberly; Tigas, Emil; Wong, Steven; McManus, David D; Alper, Eric; Lindenauer, Peter K; Dickson, Eric; Broach, John; Kheterpal, Vik; Soni, Apurv; Population and Quantitative Health Sciences; Emergency Medicine; Family Medicine and Community Health; Medicine
Chronic obstructive pulmonary disease (COPD) is a common, costly, and morbid condition. Pulmonary rehabilitation, close monitoring, and early intervention during acute exacerbations of symptoms represent a comprehensive approach to improve outcomes, but the optimal means of delivering these services is uncertain. Logistical, financial, and social barriers to providing healthcare through face-to-face encounters, paired with recent developments in technology, have stimulated interest in exploring alternative models of care. The Healthy at Home study seeks to determine the feasibility of a multimodal, digitally enhanced intervention provided to participants with COPD longitudinally over 6 months. This paper details the recruitment, methods, and analysis plan for the study, which is recruiting 100 participants in its pilot phase. Participants were provided with several integrated services including a smartwatch to track physiological data, a study app to track symptoms and study instruments, access to a mobile integrated health program for acute clinical needs, and a virtual comprehensive pulmonary support service. Participants shared physiologic, demographic, and symptom reports, electronic health records, and claims data with the study team, facilitating a better understanding of their symptoms and potential care needs longitudinally. The Healthy at Home study seeks to develop a comprehensive digital phenotype of COPD by tracking and responding to multiple indices of disease behavior and facilitating early and nuanced responses to changes in participants' health status. This study is registered at Clinicaltrials.gov (NCT06000696).
Development and Validation of the Decisions to use Opioids Measure
(2024-11-08) Punches, Brittany E; Brown, Jennifer L; Lyons, Michael S; Gillespie, Gordon L; Boyer, Edward W; Anderson, Alison R; Carreiro, Stephanie; Bischof, Jason J; Kauffman, Emily; Young, Henry; Spatholt, David; Tan, Alai; Donneyong, Macarius; Ni, Andy; Bakas, Tamilyn; Emergency Medicine
Background: Millions experience inadequately managed acute pain each year. Opioids are an important tool for managing pain; however, recent reductions in opioid prescriptions have exacerbated preexisting challenges in pain management. Moreover, patient expectations and desires for pain management may drive additional opioid use. There is an important need to characterize patient motivations for using opioids in order to develop promising interventions. The aim of this study was to develop the Decisions To use Opioids (DTO) measure. Methods: We used an exploratory sequential mixed methods design to create items for the DTO measure. Qualitative data from patient interviews and focus groups informed the development of items for the DTO. We evaluated the content validity of candidate items with nine experts using the content validity index (CVI) and conceptual significance. Face validity was assessed via cognitive interviews with five emergency department (ED) participants who experienced acute pain. Results: We generated an initial pool of 52 items. Expert ratings provided evidence of content validity on 40 items, as indicated by an item CVI score of 0.83 or higher. Nine items with CVI scores of <0.83 were retained and revised due to the conceptual significance. The remaining three items were discarded. Conclusions: This study provided evidence of content and face validity of the DTO measure for ED patients. Further psychometric evaluation is needed to gather data regarding the DTO's internal consistency, construct validity, and criterion validity.
Disentangling sex differences in PTSD risk factors
(2024-04-19) Haering, Stephanie; Seligowski, Antonia V; Linnstaedt, Sarah D; Michopoulos, Vasiliki; House, Stacey L; Beaudoin, Francesca L; An, Xinming; Neylan, Thomas C; Clifford, Gari D; Germine, Laura T; Rauch, Scott L; Haran, John P; Storrow, Alan B; Lewandowski, Christopher; Musey, Paul I; Hendry, Phyllis L; Sheikh, Sophia; Jones, Christopher W; Punches, Brittany E; Swor, Robert A; Gentile, Nina T; Hudak, Lauren A; Pascual, Jose L; Seamon, Mark J; Pearson, Claire; Peak, David A; Merchant, Roland C; Domeier, Robert M; Rathlev, Niels K; O'Neil, Brian J; Sanchez, Leon D; Bruce, Steven E; Harte, Steven E; McLean, Samuel A; Kessler, Ronald C; Koenen, Karestan C; Powers, Abigail; Stevens, Jennifer S; Emergency Medicine
Despite extensive research on sex/gender differences in posttraumatic stress disorder (PTSD), underlying mechanisms are still not fully understood. Here we present a systematic overview of three sex/gender-related risk pathways. We assessed 16 risk factors as well as 3-month PTSD severity in a prospective cohort study (n=2924) of acutely traumatized individuals and investigated potential mediators in the pathway between sex assigned at birth and PTSD severity using multiple mediation analysis with regularization. Six risk factors were more prevalent/severe in women, and none were more pronounced in men. Analyses showed that acute stress disorder, neuroticism, lifetime sexual assault exposure, anxiety sensitivity, and pre-trauma anxiety symptoms fully mediated and uniquely contributed to the relationship between sex assigned at birth and PTSD severity. Our results demonstrate different risk mechanisms for women and men. Such knowledge can inform targeted interventions. Our systematic approach to differential risk pathways can be transferred to other mental disorders to guide sex- and gender-sensitive mental health research.
Executive Functioning and Processing Speed as Predictors of Global Cognitive Decline in Alzheimer Disease [preprint]
(2024-11-02) Haran, John P; Barrett, A M; Lai, YuShuan; Odjidja, Samuel N; Dutta, Protiva; McGrath, Patrick M; Samari, Imane; Romeiro, Lethycia; Lopes, Abigail; Bucci, Vanni; McCormick, Beth A; Emergency Medicine; Microbiology; Neurology
Introduction: There is a lack of cognitive tools to predict disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: We assessed patients with MCI, AD, and cognitively healthy controls (cHC) using NIH toolbox assessments for attention/concentration and executive functioning and overall cognitive decline by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Results: Among 183 participants over a median follow-up of 540 days, both between- and within-subjects variance in NIH toolbox and ADAS-Cog assessments increased from cHC to MCI to AD patients. Among patients with AD, pattern comparison processing speed (PCPS) and dimensional change card sort tests (DCCS) declined at 3 and 6 months prior to global cognitive decline (p=0.008 & 0.0012). A 5-point decrease in either PCPS or DCCS increased risk of global cognitive decline (HR 1.32 (1.08-1.60) and 1.62 (1.16-2.26)). Discussion: Testing for cognitive domains of attention/concentration and executive functioning may predict subsequent global cognitive, and functional decline.
Developing personas to inform the design of digital interventions for perinatal mental health
(2024-11-01) Zimmermann, Martha; Yonkers, Kimberly A; Tabb, Karen M; Schaefer, Ana; Peacock-Chambers, Elizabeth; Clare, Camille A; Boudreaux, Edwin D; Lemon, Stephenie C; Byatt, Nancy; Tulu, Bengisu; Psychiatry; Prevention Research Center; Population and Quantitative Health Sciences; Emergency Medicine
Objectives: Digital interventions are increasingly in demand to address mental health concerns, with significant potential to reach populations that disproportionately face barriers to accessing mental health care. Challenges with user engagement, however, persist. The goal of this study was to develop user personas to inform the development of a digital mental health intervention (DMHI) for a perinatal population. Materials and methods: We used participatory User-Centered Design (UCD) methods to generate and validate personas (ie, representative profiles of potential users). We applied this methodology to a case example of an Anxiety Sensitivity Intervention. Phases included (1) Characteristic identification, (2) Persona generation, (3) Persona consolidation, (4) Persona validation, and (5) Persona refinement. Advisory Council members with lived expertise of perinatal mental health conditions generated 6 personas. We used cluster analysis and qualitative analysis to consolidate personas. We used participant interviews with perinatal individuals experiencing depression or anxiety and economic marginalization (n = 12) to qualitatively validate and refine these personas. Results: We identified 4 user personas with potentially unique design needs that we characterized as being "Resilient," "Lonely," "Overwhelmed," and "Aware." Discussion: Personas generated through this process had distinct characteristics and design implications including the need to prioritize (1) content personalization, (2) additional content describing support options and resources (eg, doulas, midwives), (3) careful consideration of the type of information provided by users, and (4) transparent options for information and data sharing. Conclusion: DMHIs will need to be adapted for relevance for a perinatal population. The personas we developed are suggestive of the need for design considerations specific to distinct potential user groups within this population.
Social Buffering of PTSD: Longitudinal Effects and Neural Mediators
(2024-11-25) Santos, Justin L C; Harnett, Nathaniel G; van Rooij, Sanne J H; Ely, Timothy D; Jovanovic, Tanja; Lebois, Lauren A M; Beaudoin, Francesca L; An, Xinming; Neylan, Thomas C; Linnstaedt, Sarah D; Germine, Laura T; Bollen, Kenneth A; Rauch, Scott L; Haran, John P; Storrow, Alan B; Lewandowski, Christopher; Musey, Paul I; Hendry, Phyllis L; Sheikh, Sophia; Jones, Christopher W; Punches, Brittany E; Pascual, Jose L; Seamon, Mark J; Harris, Erica; Pearson, Claire; Peak, David A; Merchant, Roland C; Domeier, Robert M; Rathlev, Niels K; O'Neil, Brian J; Sergot, Paulina; Sanchez, Leon D; Bruce, Steven E; Pizzagalli, Diego A; Harte, Steven E; Ressler, Kerry J; Koenen, Karestan C; McLean, Samuel A; Stevens, Jennifer S; Emergency Medicine
Background: Post-traumatic stress disorder (PTSD) is a well characterized psychiatric disorder featuring changes in mood and arousal following traumatic events. Prior animal and human studies on social support in the peri-traumatic window demonstrate a buffering effect with regards to acute biological and psychological stress symptoms. Fewer studies have explored the magnitude and mechanism on how early, post-trauma social support can reduce longitudinal PTSD severity. Methods: In this study we investigated the beneficial impact of social support on longitudinal PTSD symptoms, and probed brain regions sensitive to this buffering phenomenon, such as the amygdala and ventromedial prefrontal cortex. In the multi-site AURORA study, n=315 participants reported PTSD symptoms (PCL-5) and perceived emotional support (PROMIS) at 2-weeks, 8-weeks, 3-months, and 6-months post-ED visit. Additionally, neuroimaging data was collected at 2 weeks post trauma. Results: We hypothesized that early, post-trauma social support would be linked with greater fractional anisotropic (FA) values in white matter tracts that have known connectivity between the amygdala and prefrontal cortex and would predict reduced neural reactivity to social threat cues in the amygdala. Interestingly, while we observed greater FA in the bilateral cingulum and bilateral uncinate fasciculus as a function of early post-trauma emotional support, we also identified greater threat reactivity in the precuneus/posterior cingulate, a component of the default mode network. Conclusion: Our findings suggest that the neurocircuitry underlying the response to social threat cues are facilitated through broader pathways that involve the posterior hub of the default mode network.
Design, creation, and use of the Test Us Bank (TUB) COVID-19 sample biorepository
(2024-11-12) Broach, John; Achenbach, Chad; Behar, Stephanie; O'Connor, Laurel; Tarrant, Seanan; Ferranto, Julia; Wright, Colton; Hartin, Paul; Orwig, Taylor; Nanavati, Janvi; Kalibala, Benedict; Woods, Kelsey; Shaw, Bernadette; Flahive, Julie; Barton, Bruce; Hafer, Nathaniel; Herbert, Carly; Fahey, Nisha; Gibson, Laura; Simin, Karl; Kowalik, Timothy; Ward, Doyle V; Mirza, Agha W; Murphy, Robert L; Caputo, Matthew; Buchholz, Bryan; Fantasia, Heidi; Koren, Ainat; Marchand, Lisa; Oludare, Simisola; Sogade, Felix; Ritland, Dana; Davis, Cedrice; Grenier, Allen; Baron, Christi; Brent, Ellie; McKenney, Jennifer Bacani; Elder, Nancy; Michaels, LeAnn; Ferrara, Laura; Theron, Grant; Palmer, Zaida; Levy, Barcey; Daly, Jeanette; Parang, Kim; Schmidt, Megan; Buxton, Denis; Heetderks, William; Manabe, Yukari C; Soni, Apurv; McManus, David; Emergency Medicine; Medicine; Center for Clinical and Translational Science; Population and Quantitative Health Sciences; Pediatrics; Biostatistics and Health Services Research; Molecular, Cell, and Cancer Biology; Microbiology
Shortly after the first case of SARS-CoV-2 was diagnosed a public health emergency (PHE) was declared and a multi-agency response was initiated within the US federal government to create and propagate testing capacity. As part of this response, an unprecedented program designated Rapid Acceleration of Diagnostics (RADx) Tech was established by the National Institutes of Health (NIH) to facilitate the development of point-of-care tests for the COVID-19. The RADx Tech Clinical Studies Core (CSC), located at the University of Massachusetts Chan Medical School (UMass Chan), with partnering academic, private, and non-governmental organizations around the country, was tasked with developing clinical studies to support this work. This manuscript details development of a biorepository specifically focused on the collection and storage of samples designed for diagnostic platform development. It highlights the unified collection and annotation process that enabled gathering a diverse set of samples. This diversity encompasses the geography and backgrounds of the participants as well as sample characteristics such as variant type and RT-PCR cycle threshold (CT) value of the corresponding reference sample on a uniform clinical reference platform.
Maladaptive behaviors in disasters: case study evaluation of Hurricane Hugo, Hurricane Katrina and the Haiti Earthquake
(2024-08-27) Milsten, Andrew M; Kang, Christopher S; Nemeth, Ira; Emergency Medicine
Maladaptive behaviors during a disaster refer to actions that do not benefit the individual or society. Quarantelli highlights several maladaptive behaviors myths associated with disasters: widespread antisocial behavior, passivity, role conflict or abandonment, and sudden widespread mental health breakdowns (1). Despite early work reporting these myths, the common perception is that maladaptive behaviors such as rioting, looting, panic, and criminal conduct are prevalent in the wake of disasters. This is despite research by de Ville de Goyet and Arnold which has called on public officials and the media to stop propagating false disaster myths (2, 3). The classic academic response has been that this is a misconception and that, in fact, such behaviors are a very small part of the overall disaster and are mostly non-existent. Misconceptions about the prevalence of maladaptive behaviors can lead to inappropriate resource allocation, such as allocating extra police officers to prevent looting when the overall crime rate for the most part, decreases during disasters (4). Furthermore, while there are several persistent maladaptive behaviors myths, this is confounded by the presence of actual negative behaviors post disaster: false damage claims, insurance fraud, illegally obtaining relief supplies, failure to provide contracted repair services, hoarding of essential items, psychological trauma (which can lead to intergenerational transmission of the disaster memory) and medications and price gouging (5).When reading lay-press articles about recent disasters, it appears that these behaviors are on the rise. This raises the question: Has there been a change in the basic human reaction to disasters and are maladaptive behaviors on the rise? This review article focuses on case studies from three natural disasters: Hurricanes Hugo and Katrina, and the Haiti Earthquake. The goal of this review article is to evaluate these three natural disasters for evidence of maladaptive behaviors.
Harnessing Innovative Technologies to Train Nurses in Suicide Safety Planning With Hospital Patients: Formative Acceptability Evaluation of an eLearning Continuing Education Training
(2024-09-06) Darnell, Doyanne; Pierson, Andria; Tanana, Michael J; Dorsey, Shannon; Boudreaux, Edwin D; Areán, Patricia A; Comtois, Katherine Anne; Center for Accelerating Practices to End Suicide (CAPES); Emergency Medicine
Background: Suicide is the 12th leading cause of death in the United States. Health care provider training is a top research priority identified by the National Action Alliance for Suicide Prevention; however, evidence-based approaches that target skill building are resource intensive and difficult to implement. Novel computer technologies harnessing artificial intelligence are now available, which hold promise for increasing the feasibility of providing trainees opportunities across a range of continuing education contexts to engage in skills practice with constructive feedback on performance. Objective: This pilot study aims to evaluate the feasibility and acceptability of an eLearning training in suicide safety planning among nurses serving patients admitted to a US level 1 trauma center for acute or intensive care. The training included a didactic portion with demonstration, practice of microcounseling skills with a web-based virtual patient (Client Bot Emily), role-play with a patient actor, and automated coding and feedback on general counseling skills based on the role-play via a web-based platform (Lyssn Advisor). Secondarily, we examined learning outcomes of knowledge, confidence, and skills in suicide safety planning descriptively. Methods: Acute and intensive care nurses were recruited between November 1, 2021, and May 31, 2022, to participate in a formative evaluation using pretraining, posttraining, and 6-month follow-up surveys, as well as observation of the nurses' performance in delivering suicide safety planning via standardized patient role-plays over 6 months and rated using the Safety Plan Intervention Rating Scale. Nurses completed the System Usability Scale after interacting with Client Bot Emily and reviewing general counseling scores based on their role-play via Lyssn Advisor. Results: A total of 18 nurses participated in the study; the majority identified as female (n=17, 94%) and White (n=13, 72%). Of the 17 nurses who started the training, 82% (n=14) completed it. On average, the System Usability Scale score for Client Bot Emily was 70.3 (SD 19.7) and for Lyssn Advisor was 65.4 (SD 16.3). On average, nurses endorsed a good bit of knowledge (mean 3.1, SD 0.5) and confidence (mean 2.9, SD 0.5) after the training. After completing the training, none of the nurses scored above the expert-derived cutoff for proficiency on the Safety Plan Intervention Rating Scale (≥14); however, on average, nurses were above the cutoffs for general counseling skills per Lyssn Advisor (empathy: mean 4.1, SD 0.6; collaboration: mean 3.6, SD 0.7). Conclusions: Findings suggest the completion of the training activities and use of novel technologies within this context are feasible. Technologic modifications may enhance the training acceptability and utility, such as increasing the virtual patient conversational abilities and adding automated coding capability for specific suicide safety planning skills. International registered report identifier (irrid): RR2-10.2196/33695.
Elderly male with nausea and vomiting
(2023-04-26) Galletta, Gayle M; Emergency Medicine
A 75-year-old male with a history of atrial fibrillation, type 2 diabetes, congestive heart failure, and cardiomyopathy presented with 1 day history of nausea and vomiting. On physical examination, the patient was afebrile with a blood pressure of 103/59 mm Hg, heart rate of 107, respiration 12, and oxygen saturation 98% on room air. He was frail appearing and awake but confused with pupils at 4 mm. His heart was tachycardic, lungs clear to auscultation, and abdomen soft and non-tender. Neurological examination revealed generalized weakness but was non-focal.
Body Sensor Networks for Personalized Medicine
(2024-01-03) Goldfine, Charlotte E.; Lee, Jasper S.; Davis-Martin, Rachel; Center for Accelerating Practices to End Suicide (CAPES); Emergency Medicine
The past several decades have ushered unprecedented advancements in body sensor networks, which include wearable, implantable and ingestible technologies to measure various aspects of health and wellness related to health and healthcare. The ubiquity of smartphones, smart watches and fitness tracking tools have provided vast amounts of digital physiologic and behavioral data that enable providers to provide personalized medicine based on each individual’s data. These new digital biomarkers of health—prosody of smartphone use, biometric data surrounding health events, geolocation and ambient environment conditions—provide an opportunity for social scientists, engineers and clinicians to advance health interventions antecedent to exacerbations of disease.

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