IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l-1 at baseline were randomized to receive clazakizumab (2.5 mg, 5 mg or 10 mg, n = 32 per dose group) or placebo (n = 31) every 4 weeks. The primary endpoint was the change from baseline in hs-CRP to week 12, expressed as the geometric mean ratio. Clazakizumab treatment signficantly reduced serum hs-CRP concentrations at week 12 by 86%, 90% and 92% relative to placebo in patients randomized to 2.5 mg, 5 mg or 10 mg clazakizumab, respectively (all P < 0.0001), meeting the primary outcome. With regard to secondary endpoints, clazakizumab treatment reduced serum fibrinogen, amyloid A, secretory phospholipase A2, and lipoprotein(a) concentrations, as well as increased mean serum albumin concentrations at 12 weeks, relative to placebo. The proportion of patients who achieved hs-CRP < 2.0 mg l-1 was 79%, 82% and 79% in the 2.5 mg, 5 mg and 10 mg clazakizumab groups, respectively, compared with 0% of placebo-treated patients. With regard to safety, no cases of sustained grade 3 or 4 thrombocytopenia or neutropenia were observed. Serious infections were seen with similar frequency in the placebo, clazakizumab 2.5 mg and clazakizumab 5 mg groups, but were numerically more frequent in the clazakizumab 10 mg group. The results of this trial indicate that in patients receiving maintenance dialysis, clazakizumab reduced inflammatory biomarkers associated with cardiovascular events. ClinicalTrials.gov registration: NCT05485961 .

Tactile processing in mouse cortex depends on action context.

The brain receives constant tactile input, but only a subset guides ongoing behavior. Actions associated with tactile stimuli thus endow them with behavioral relevance. It remains unclear how the relevance of tactile stimuli affects processing in the somatosensory (S1) cortex. We developed a cross-modal selection task in which head-fixed mice switched between responding to tactile stimuli in the presence of visual distractors or to visual stimuli in the presence of tactile distractors using licking movements to the left or right side in different blocks of trials. S1 spiking encoded tactile stimuli, licking actions, and direction of licking in response to tactile but not visual stimuli. Bidirectional optogenetic manipulations showed that sensory-motor activity in S1 guided behavior when touch but not vision was relevant. Our results show that S1 activity and its impact on behavior depend on the actions associated with a tactile stimulus.

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

This study examines the association between brain dynamic functional network connectivity (dFNC) and current/future posttraumatic stress (PTS) symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.179, pcorrected= 0.021) and future (r=-0.166, pcorrected= 0.029) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.192, pcorrected = 0.021). We additionally observed that the association between the network dynamics of the inter-network brain state with symptom severity is more pronounced in females (r=-0.244, pcorrected = 0.014). Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger protective effect of inter-network brain states against symptom severity in females, underscoring the importance of sex differences.

Relationship between on-demand telehealth visits and emergency department and hospital surge during the COVID-19 pandemic.

Objectives: The relationship between COVID-19-related telehealth calls could be used to predict emergency department visits and hospital surges 3 days later potentially facilitating staffing adjustments in advance of patient arrivals. The purpose of this research was to study the temporal association between frequencies of on demand telehealth calls and emergency department surges during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods: This cohort study examined patients who self-initiated synchronous audio-video on-demand telehealth calls between January 1, 2020 and June 30, 2022, and compared these to emergency department arrivals. The exposure in question was a synchronous audio-video on-demand telehealth visit. Our main outcome measured was frequency of emergency department visits. After autocorrelation, a multivariate linear regression model was utilized to determine temporal relationships between the two variables. Results: This cohort study examined 42,429 synchronous audio-video on-demand telehealth calls, of which 43.6% were COVID-19 related, and 540,686 emergency department visits, of which 3.9% were diagnosed with COVID-19. COVID-19-related telehealth calls 3 days prior were predictive of emergency department encounters (r 2 = 0.85, p < 0.001). Emergency department encounters were strongly correlated with hospital admissions (r 2 = 0.71, p < 0.001). Conclusions: Our results demonstrate that telehealth calls related to COVID-19 were an accurate predictor of emergency department encounters 3 days later, and emergency department encounters are highly correlated with hospital admissions. Limitations include that we only assessed a single health system in the region covered by the telemedicine healthcare professionals. We did not examine direct links between these two encounter types nor severity of illness at the patient level. Understanding that telehealth calls related to COVID-19 are highly predictive of emergency department encounters within 3 days may provide a brief but important window to upstaff hospitals at the beginning of future COVID-19 surges.

"Once I take that one bite": the consideration of harm reduction as a strategy to support dietary change for patients with diabetes.

BACKGROUND: Despite well-established guidelines to treat diabetes, many people with diabetes struggle to manage their disease. For many, this struggle is related to challenges achieving nutrition-related lifestyle changes. We examined how people with diabetes describe barriers to maintaining a healthy diet and considered the benefits of using a harm reduction approach to assist patients to achieve nutrition-related goals. METHODS: This is a secondary analysis of 89 interviews conducted with adults who had type 1 or type 2 diabetes. Interviews were analyzed using a content analysis approach. Themes regarding food or diet were initially captured in a "food" node. Data in the food node were then sub-coded for this analysis, again using a content analysis approach. RESULTS: Participants frequently used addiction language to talk about their relationship with food, at times referring to themselves as "an addict" and describing food as "their drug." Participants perceived their unhealthy food choices either as a sign of weakness or as "cheating." They also identified food's ability to comfort them and an unwillingness to change as particular challenges to sustaining a healthier diet. CONCLUSION: Participants often described their relationship with food through an addiction lens. A harm reduction approach has been associated with positive outcomes among those with substance abuse disorder. Patient-centered communication incorporating the harm reduction model may improve the patient-clinician relationship and thus improve patient outcomes and quality-of-life while reducing health-related stigma in diabetes care. Future work should explore the effectiveness of this approach in patients with diabetes. TRIAL REGISTRATION: Registered on ClinicalTrials.gov, NCT02792777. Registration information submitted 02/06/2016, with the registration first posted on the ClinicalTrials.gov website 08/06/2016. Data collection began on 29/04/2016.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

A clock-dependent brake for rhythmic arousal in the dorsomedial hypothalamus.

Circadian clocks generate rhythms of arousal, but the underlying molecular and cellular mechanisms remain unclear. In Drosophila, the clock output molecule WIDE AWAKE (WAKE) labels rhythmic neural networks and cyclically regulates sleep and arousal. Here, we show, in a male mouse model, that mWAKE/ANKFN1 labels a subpopulation of dorsomedial hypothalamus (DMH) neurons involved in rhythmic arousal and acts in the DMH to reduce arousal at night. In vivo Ca2+ imaging reveals elevated DMHmWAKE activity during wakefulness and rapid eye movement (REM) sleep, while patch-clamp recordings show that DMHmWAKE neurons fire more frequently at night. Chemogenetic manipulations demonstrate that DMHmWAKE neurons are necessary and sufficient for arousal. Single-cell profiling coupled with optogenetic activation experiments suggest that GABAergic DMHmWAKE neurons promote arousal. Surprisingly, our data suggest that mWAKE acts as a clock-dependent brake on arousal during the night, when mice are normally active. mWAKE levels peak at night under clock control, and loss of mWAKE leads to hyperarousal and greater DMHmWAKE neuronal excitability specifically at night. These results suggest that the clock does not solely promote arousal during an animal's active period, but instead uses opposing processes to produce appropriate levels of arousal in a time-dependent manner.

Osteoimmune-modulating and BMP-2-eluting anodised 3D printed titanium for accelerated bone regeneration.

3D printing of titanium (Ti) metal has potential to transform the field of personalised orthopaedics and dental implants. However, the impacts of controlled surface topographical features of 3D printed Ti implants on their interactions with the cellular microenvironment and incorporation of biological growth factors, which are critical in guiding the integration of implants with bone, are not well studied. In the present study, we explore the role of surface topological features of 3D printed Ti implants using an anodised titania nanotube (TiNT) surface layer in guiding their immune cell interaction and ability to deliver bioactive form of growth factors. TiNT layers with precisely controlled pore diameter (between 21and 130 nm) were anodically grown on 3D printed Ti surfaces to impart a nano-micro rough topology. Immune biomarker profiles at gene and protein levels show that anodised 3D Ti surfaces with smaller pores resulted in classical activation of macrophages (M1-like), while larger pores (i.e., >100 nm) promoted alternate activation of macrophages (M2-like). The in vitro bone mineralisation studies using the conditioned media from the immunomodulatory studies elucidate a clear impact of pore diameter on bone mineralisation. The tubular structure of TiNTs was utilised as a container to incorporate recombinant human bone morphogenetic protein-2 (BMP-2) in the presence of various sugar and polymeric cryoprotectants. Sucrose offered the most sustainable release of preserved BMP-2 from TiNTs. Downstream effects of released BMP-2 on macrophages as well as bone mineralisation were assessed showing bioactivity retention of the released rhBMP-2. Overall, the TiNT surface topography in combination with controlled, sustained, and local release of bioactive growth factors can potentially enhance the osseointegration outcomes of custom 3D printed Ti implants in the clinic.

Triple therapy for Helicobacter pylori eradication and the risk of hypoglycemia in patients with diabetes: a population-based cohort study.

The incidence of type 2 diabetes mellitus has risen globally, from 108 million cases in 1980 to 422 million cases in 2014. Although controlling glycemic levels in patients with diabetes is crucial, insulin and sulfonylureas can cause hypoglycemic episodes and even potentially fatal events such as comas, seizures, life-threatening arrhythmias, and myocardial infarctions. Several antibiotics have been documented to cause hypoglycemic episodes; the use of antibiotics along with insulin or sulfonylureas might further increase the risk of hypoglycemia. Therefore, researchers must determine which antibiotics carry a risk of inducing severe hypoglycemic events. The prevalence of H. pylori infection remains high in most countries, and the infection is often treated with triple therapy involving amoxicillin, clarithromycin, and a proton pump inhibitor (PPI). Several case reports have reported that hypoglycemia can occur when used with patients who also take diabetes medication. Therefore, we hypothesized that patients with diabetes have an increased risk of hypoglycemic episodes when being treated with triple therapy for H. pylori infection. By analyzing medical records from Taiwan's National Health Insurance Research Database, we found a significant association between hypoglycemia and triple therapy treatment for diabetic patients with peptic ulcer disease. Prescribing triple therapy to patients with diabetes and peptic ulcers significantly increased the risk of a hypoglycemic episode (adjusted odds ratio [aOR] = 1.75, 95% confidence interval [CI]: 1.64 to 1.88, P < 0.001). Similarly, the highest aOR (5.77, 95% CI 4.82 to 6.92) was found in patients with diabetes and peptic ulcers who had hypoglycemic episodes within 30 days after triple therapy treatment. Many patients with diabetes require H.pylori eradication for peptic ulcer treatment, and vigilance toward the risk of hypoglycemia in this population is thus necessary.

Association Between SARS-CoV-2 Variants and Frequency of Acute Symptoms: Analysis of a Multi-institutional Prospective Cohort Study-December 20, 2020-June 20, 2022.

Background: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Methods: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. Results: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). Conclusions: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. Trial registration: NCT04610515.

Patient-Important Needs and Goals Related to Nutrition Interventions during Cancer Treatment.

Patients with cancer often experience nutrition-related challenges for which they are subsequently connected with nutritional support. Yet to date there are no validated tools to assess whether nutrition interventions sufficiently address patients' needs. A vital step toward developing a tool is to identify primary patient-important goals related to receiving nutrition support during cancer care. To that end, we interviewed patients and clinicians to identify nutrition-related needs and goals of patients undergoing cancer treatment. We interviewed 31 patients undergoing cancer treatment and 17 clinicians at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, PA. Two coders analyzed transcripts using a conventional qualitative content analysis approach. Patients and clinicians both identified weight maintenance, improved food satisfaction and intake, and improved quality of life metrics - such as reduced emotional and financial stress - as top nutrition-related goals. Participants also highlighted the importance of patients receiving food they like and having control over what they eat when designing optimal nutrition interventions. These findings will be used in future work to create a patient-centered assessment tool designed to capture a range of patient goals related to nutrition interventions.

White Paper: Best Practices in the Communication and Management of Actionable Incidental Findings in Emergency Department Imaging.

PURPOSE: Actionable incidental findings (AIFs) are common in radiologic imaging. Imaging is commonly performed in emergency department (ED) visits, and AIFs are frequently encountered, but the ED presents unique challenges for communication and follow-up of these findings. The authors formed a multidisciplinary panel to seek consensus regarding best practices in the reporting, communication, and follow-up of AIFs on ED imaging tests. METHODS: A 15-member panel was formed, nominated by the ACR and American College of Emergency Physicians, to represent radiologists, emergency physicians, patients, and those involved in health care systems and quality. A modified Delphi process was used to identify areas of best practice and seek consensus. The panel identified four areas: (1) report elements and structure, (2) communication of findings with patients, (3) communication of findings with clinicians, and (4) follow-up and tracking systems. A survey was constructed to seek consensus and was anonymously administered in two rounds, with a priori agreement requiring at least 80% consensus. Discussion occurred after the first round, with readministration of questions where consensus was not initially achieved. RESULTS: Consensus was reached in the four areas identified. There was particularly strong consensus that AIFs represent a system-level issue, with need for approaches that do not depend on individual clinicians or patients to ensure communication and completion of recommended follow-up. CONCLUSIONS: This multidisciplinary collaboration represents consensus results on best practices regarding the reporting and communication of AIFs in the ED setting.

Interprofessional Intervention to Reduce Emergency Department Visits in Black Individuals with Diabetes.

Black individuals with diabetes have high rates of emergency department (ED) use. This randomized controlled trial compared the efficacy of Diabetes Interprofessional Team to Enhance Adherence to Medical Care (DM I-TEAM) versus Usual Medical Care (UMC) to reduce number of return ED visits/hospitalizations over 12 months in 200 Black individuals with diabetes after an ED visit. DM I-TEAM consisted of community health worker-delivered diabetes education and behavior activation, telehealth visits with a diabetes nurse educator and primary care physicians, and clinical pharmacist recommendations to reduce potentially inappropriate medications (PIMs). Secondary outcomes included glycemic control, PIMs use, diabetes self-management, diabetes self-efficacy, depression, and medical trust. Participants had a mean age of 64.9 years and 73.0% were women. The 2 treatment groups were similar in baseline characteristics. Sixty-eight (69.4%) DM I-TEAM participants and 69 (67.6%) UMC participants had at least 1 incident ED visit/hospitalization over 12 months. The adjusted incidence rate ratio for DM I-TEAM versus UMC was 1.11 (95% confidence interval 0.79-1.56; P = 0.54). DM I-TEAM participants attained significantly better diabetes self-management, diabetes self-efficacy, and institutional trust than UMC participants. There were no treatment group differences in hemoglobin A1c level nor PIMs use. Among Black individuals with diabetes, a novel culturally relevant intervention was no better than usual care at preventing return ED visits/hospitalizations over 1 year. Before reasonable clinical interventions such as DM I-TEAM can be effective, reducing system-level barriers to health, building community health care capacity, and designing interventions that better align with the everyday realities of patients' lives are necessary. clinicaltrials.gov NCT03393338.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Identifying Value Factors in Institutional Leaders' Perspectives on Investing in Health Professions Educators.

Importance: Investing in educators, educational innovation, and scholarship is essential for excellence in health professions education and health care. Funds for education innovations and educator development remain at significant risk because they virtually never generate offsetting revenue. A broader shared framework is needed to determine the value of such investments. Objective: To explore the value factors using the value measurement methodology domains (individual, financial, operational, social or societal, strategic or political) that health professions leaders placed on educator investment programs, including intramural grants and endowed chairs. Design, Setting, and Participants: This qualitative study used semi-structured interviews with participants from an urban academic health professions institution and its affiliated systems that were conducted between June and September 2019 and were audio recorded and transcribed. Thematic analysis was used to identify themes with a constructivist orientation. Participants included 31 leaders at multiple levels of the organization (eg, deans, department chairs, and health system leaders) and with a range of experience. Individuals who did not respond initially were followed up with until a sufficient representation of leader roles was achieved. Main Outcomes and Measures: Outcomes include value factors defined by the leaders for educator investment programs across the 5 value measurement methodology domains: individual, financial, operational, social or societal, and strategic or political. Results: This study included 29 leaders (5 [17%] campus or university leaders; 3 [10%] health systems leaders; 6 [21%] health professions school leaders; 15 [52%] department leaders). They identified value factors across the 5 value measurement methods domains. Individual factors emphasized the impact on faculty career, stature, and personal and professional development. Financial factors included tangible support, the ability to attract additional resources, and the importance of these investments as a monetary input rather than output. Operational factors identified educational programs and faculty recruitment or retention. Social and societal factors showcased scholarship and dissemination benefits to the external community beyond the organization and to the internal community of faculty, learners, and patients. Strategic and political factors highlighted impact on culture and symbolism, innovation, and organizational success. Conclusions and Relevance: These findings suggest that health sciences and health system leaders find value in funding educator investment programs in multiple domains beyond direct financial return on investment. These value factors can inform program design and evaluation, effective feedback to leaders, and advocacy for future investments. This approach can be used by other institutions to identify context-specific value factors.

Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.

BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.

Utility of Wrist-Wearable Data for Assessing Pain, Sleep, and Anxiety Outcomes After Traumatic Stress Exposure.

Importance: Adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure are common and have higher incidence among socioeconomically disadvantaged populations. Pain, depression, avoidance of trauma reminders, reexperiencing trauma, anxiety, hyperarousal, sleep disruption, and nightmares have been reported. Wrist-wearable devices with accelerometers capable of assessing 24-hour rest-activity characteristics are prevalent and may have utility in measuring these outcomes. Objective: To evaluate whether wrist-wearable devices can provide useful biomarkers for recovery after traumatic stress exposure. Design, Setting, and Participants: Data were analyzed from a diverse cohort of individuals seen in the emergency department after experiencing a traumatic stress exposure, as part of the Advancing Understanding of Recovery After Trauma (AURORA) study. Participants recruited from 27 emergency departments wore wrist-wearable devices for 8 weeks, beginning in the emergency department, and completed serial assessments of neuropsychiatric symptoms. A total of 19 019 patients were screened. Of these, 3040 patients met study criteria, provided informed consent, and completed baseline assessments. A total of 2021 provided data from wrist-wearable devices, completed the 8-week assessment, and were included in this analysis. The data were randomly divided into 2 equal parts (n = 1010) for biomarker identification and validation. Data were collected from September 2017 to January 2020, and data were analyzed from May 2020 to November 2022. Exposures: Participants were recruited for the study after experiencing a traumatic stress exposure (most commonly motor vehicle collision). Main Outcomes and Measures: Rest-activity characteristics were derived and validated from wrist-wearable devices associated with specific self-reported symptom domains at a point in time and changes in symptom severity over time. Results: Of 2021 included patients, 1257 (62.2%) were female, and the mean (SD) age was 35.8 (13.0) years. Eight wrist-wearable device biomarkers for symptoms of adverse posttraumatic neuropsychiatric sequelae exceeded significance thresholds in the derivation cohort. One of these, reduced 24-hour activity variance, was associated with greater pain severity (r = -0.14; 95% CI, -0.20 to -0.07). Changes in 6 rest-activity measures were associated with changes in pain over time, and changes in the number of transitions between sleep and wake over time were associated with changes in pain, sleep, and anxiety. Simple cutoffs for these biomarkers identified individuals with good recovery for pain (positive predictive value [PPV], 0.85; 95% CI, 0.82-0.88), sleep (PPV, 0.63; 95% CI, 0.59-0.67, and anxiety (PPV, 0.76; 95% CI, 0.72-0.80) with high predictive value. Conclusions and Relevance: These findings suggest that wrist-wearable device biomarkers may have utility as screening tools for pain, sleep, and anxiety symptom outcomes after trauma exposure in high-risk populations.

Use of serial smartphone-based assessments to characterize diverse neuropsychiatric symptom trajectories in a large trauma survivor cohort.

The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.

Urgent and non-emergent telehealth care for seniors: Findings from a multi-site impact study.

INTRODUCTION: The global pandemic has raised awareness of the need for alternative ways to deliver care, notably telehealth. Prior to this study, research has been mixed on its effectiveness and impact on downstream utilization, especially for seniors. Our multi-institution study of more than 300,000 telehealth visits for seniors evaluates the clinical outcomes and healthcare utilization for urgent and non-emergent symptoms. METHODS: We conducted a retrospective cohort study from November 2015 to March 2019, leveraging different models of telehealth from three health systems, comparing them to in-person visits for urgent and non-emergent needs of seniors based on International Classification of Diseases, 10th edition diagnoses. The study population was adults aged 60 years or older who had access to telehealth and were affiliated with and resided in the geographic region of the healthcare organization providing telehealth. The primary outcomes of interest were visit resolution and episodes of care for those that required follow-up. RESULTS: In total, 313,516 telehealth visits were analysed across three healthcare organizations. Telehealth encounters were successful in resolving urgent and non-emergent needs in 84.0-86.7% of cases. When visits required follow-up, over 95% were resolved in less than three visits for both telehealth and in-person cohorts. DISCUSSION: While in-person visits have traditionally been the gold standard, our results suggest that when deployed within the confines of a patient's existing primary care and health system provider, telehealth can be an effective alternative to in-person care for urgent and non-emergent needs of seniors without increasing downstream utilization.