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Pharmacokinetics-Informed Neural Network for Predicting Opioid Administration Moments with Wearable Sensors
No full textLong-term and high-dose prescription opioid use places individuals at risk for opioid misuse, opioid use disorder (OUD), and overdose. Existing methods for monitoring opioid use and detecting misuse rely on self-reports, which are prone to reporting bias, and toxicology testing, which may be infeasible in outpatient settings. Although wearable technologies for monitoring day-to-day health metrics have gained significant traction in recent years due to their ease of use, flexibility, and advancements in sensor technology, their application within the opioid use space remains underexplored. In the current work, we demonstrate that oral opioid administrations can be detected using physiological signals collected from a wrist sensor. More importantly, we show that models informed by opioid pharmacokinetics increase reliability in predicting the timing of opioid administrations. Forty-two individuals who were prescribed opioids as a part of their medical treatment in-hospital and after discharge were enrolled. Participants wore a wrist sensor throughout the study, while opioid administrations were tracked using electronic medical records and self-reports. We collected 1,983 hours of sensor data containing 187 opioid administrations from the inpatient setting and 927 hours of sensor data containing 40 opioid administrations from the outpatient setting. We demonstrate that a self-supervised pre-trained model, capable of learning the canonical time series of plasma concentration of the drug derived from opioid pharmacokinetics, can reliably detect opioid administration in both settings. Our work suggests the potential of pharmacokinetic-informed, data-driven models to objectively detect opioid use in daily life
Community Radiology Beyond the Relative Value Unit
No full textAcademic institutions receive direct and indirect financial benefits based on the communities they serve, including research funding, which is essential for advancing medicine. To strive for social equity and to minimize disparities in outcomes between populations, diversity in research participation that is representative of the global population is necessary. Diversity in members of the clinical research team is also important because it fosters scientific innovation, increases the likelihood of participation in under-resourced populations, and enhances public trust
A Pilot Randomized Controlled Trial of Augmented Reality Just-in-Time Guidance for the Performance of Rugged Field Procedures
No full textMedical resuscitations in rugged prehospital settings require emergency personnel to perform high-risk procedures in low-resource conditions. Just-in-Time Guidance (JITG) utilizing augmented reality (AR) guidance may be a solution. There is little literature on the utility of AR-mediated JITG tools for facilitating the performance of emergent field care.
The objective of this study was to investigate the feasibility and efficacy of a novel AR-mediated JITG tool for emergency field procedures. Emergency medical technician-basic (EMT-B) and paramedic cohorts were randomized to either video training (control) or JITG-AR guidance (intervention) groups for performing bag-valve-mask (BVM) ventilation, intraosseous (IO) line placement, and needle-decompression (Needle-d) in a medium-fidelity simulation environment. For the interventional condition, subjects used an AR technology platform to perform the tasks. The primary outcome was participant task performance; the secondary outcomes were participant-reported acceptability. Participant task score, task time, and acceptability ratings were reported descriptively and compared between the control and intervention groups using chi-square analysis for binary variables and unpaired t-testing for continuous variables.
Sixty participants were enrolled (mean age 34.8 years; 72% male). In the EMT-B cohort, there was no difference in average task performance score between the control and JITG groups for the BVM and IO tasks; however, the control group had higher performance scores for the Needle-d task (mean score difference 22%; P = .01). In the paramedic cohort, there was no difference in performance scores between the control and JITG group for the BVM and Needle-d tasks, but the control group had higher task scores for the IO task (mean score difference 23%; P = .01). For all task and participant types, the control group performed tasks more quickly than in the JITG group. There was no difference in participant usability or usefulness ratings between the JITG or control conditions for any of the tasks, although paramedics reported they were less likely to use the JITG equipment again (mean difference 1.96 rating points; P = .02).
This study demonstrated preliminary evidence that AR-mediated guidance for emergency medical procedures is feasible and acceptable. These observations, coupled with AR's promise for real-time interaction and on-going technological advancements, suggest the potential for this modality in training and practice that justifies future investigation.This material is based upon work supported by the United States Army Medical Research and Development Command (USAMRDC)/Telemedicine & Advanced Technology Research Center (TATRC) under Contract No. W81XWH20C0034.No embarg
Diet and Physical Activity Behaviors of Breast Cancer Survivors: A Scoping Review
No full textObjectives: This scoping review explored insight into the current evidence on adherence to health behavior guidelines, specifically diet and physical activity among breast cancer survivors.
Methods: A scoping review was conducted through databases including PubMed, CINAHL, Scopus, Web of Science, and SPORTDiscus with Full Text in November 2022, following the JBI methodology. The search strategy combined the keywords i) diet OR nutrition OR eating OR exercise OR physical activity OR fitness and ii) breast cancer survivors OR patients with breast cancer.
Results: Twelve original research studies were included; most were conducted in the United States (50%), followed by the European countries (33.34%). Most studies exclusively focused on physical activity (83.33%) and assessed adherence to the physical activity guidelines for Americans (30%), along with the American Cancer Society (20%) and American College of Sports Medicine (20%) guidelines. Overweight or obesity, comorbidity, race, and quality of life were reported as factors associated with physical activity. Independence of disease status was significantly associated with fruit and vegetable intake.
Conclusion: Studies reported a wide range of prevalence of adherence to dietary and physical activity recommendations among breast cancer survivors. Further studies are needed to explore diet and physical activity in the context of factors affecting these behaviors among cancer survivors to support the development of healthy behavior, improve health outcomes, and reduce the disease burden among this population.
Implication for nursing practice: Nurses have a key role in educating and coordinating multidiscipline teams to initiate and provide cancer survivorship care. These findings indicate that nurses should consider developing targeted strategies and education to promote dietary patterns and physical activity adherence among breast cancer survivors.No embarg
Dominant myosin storage myopathy mutations disrupt striated muscles in Drosophila and the myosin tail-tail interactome of human cardiac thick filaments
Get PDFMyosin storage myopathy (MSM) is a rare skeletal muscle disorder caused by mutations in the slow muscle/β-cardiac myosin heavy chain (MHC) gene. MSM missense mutations frequently disrupt the tail's stabilizing heptad repeat motif. Disease hallmarks include subsarcolemmal hyaline-like β-MHC aggregates, muscle weakness and, occasionally, cardiomyopathy. We generated transgenic, heterozygous Drosophila to examine the dominant physiological and structural effects of the L1793P, R1845W, and E1883K MHC MSM mutations on diverse muscles. The MHC variants reduced lifespan and flight and jump abilities. Moreover, confocal and electron microscopy revealed that they provoked indirect flight muscle breaks and myofibrillar disarray/degeneration with filamentous inclusions. Incorporation of GFP-myosin enabled in situ determination of thick filament lengths, which were significantly reduced in all mutants. Semi-automated heartbeat analysis uncovered aberrant cardiac function, which worsened with age. Thus, our fly models phenocopied traits observed among MSM patients. We additionally mapped the mutations onto a recently-determined, 6Å resolution, cryo-EM structure of the human cardiac thick filament. The R1845W mutation replaces a basic arginine with a polar-neutral, bulkier tryptophan, while E1883K reverses charge at critical filament loci. Both would be expected to disrupt the core and the outer shell of the backbone structure. Replacing L1793 with a proline, a potent breaker of alpha-helices, could disturb the coiled-coil of the myosin rod and alter the tail-tail interactome. Hence, all mutations likely destabilize and weaken the filament backbone. This may trigger disease in humans, while potentially analogous perturbations are likely to yield the observed thick filament and muscle disruption in our fly models.No embarg
Social Buffering of Posttraumatic Stress Disorder: Longitudinal Effects and Neural Mediators
Get PDFBackground: 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.No embarg
An orbitocortical-thalamic circuit suppresses binge alcohol-drinking [preprint]
Get PDFThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Alcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.Neuroscienc
EXCELLENT Registry: A Prospective, Multicenter, Global Registry of Endovascular Stroke Treatment With the EMBOTRAP Device
No full textBackground: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots.
Methods: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee.
Results: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P<0.001), pointing to a potential preprocedure indicator of challenging clot.
Conclusions: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03685578.No embarg
Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling [preprint]
No full textThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity. Yet, the degree to which these cells communicate to coordinate this process remains an open question. Here, we use whisker removal in postnatal mice to induce activity-dependent synapse removal in the barrel cortex. We show that astrocytes do not engulf synapses in this paradigm. Instead, astrocytes reduce their contact with synapses prior to microglia-mediated synapse engulfment. We further show that reduced astrocyte-contact with synapses is dependent on microglial CX3CL1-CX3CR1 signaling and release of Wnts from microglia following whisker removal. These results demonstrate an activity-dependent mechanism by which microglia instruct astrocyte-synapse interactions, which then provides a permissive environment for microglia to remove synapses. We further show that this mechanism is critical to remodel synapses in a changing sensory environment and this signaling is upregulated in several disease contexts.Neuroscienc
Evaluating Criteria for Symptoms Suggestive of Early Osteoarthritis Over Two Years Post-Anterior Cruciate Ligament Reconstruction: Data From the New Zealand Anterior Cruciate Ligament Registry
Get PDFObjective: The objectives were to determine the prevalence of meeting criteria for symptoms suggestive of early osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) and to characterize the longitudinal changes in these symptoms during the first two years post-ACLR.
Methods: We analyzed data from 10,231 patients aged 14 to 40 years in the New Zealand ACL Registry who completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6, 12, and 24 months post-ACLR. Symptoms suggestive of early OA were defined as scoring ≤85% on at least two of four KOOS subscales. Longitudinal patterns of change were categorized as persistent, resolution, new, inconsistent, or no symptoms across the three visits. Prevalence and odds ratios (ORs) of symptoms were compared across visits, sex, and age groups using generalized estimating equations, and longitudinal patterns of symptom change were analyzed using multinomial logistic regression.
Results: Prevalence of meeting criteria of symptoms suggestive of early OA was 68% at 6 months, 54% at 12 months, and 46% at 24 months post-ACLR. Longitudinally, 33% had persistent symptoms, 23% had no symptoms, 29% showed symptom resolution, 6% developed new symptoms, and 9% had inconsistent symptoms. Women consistently showed higher odds of symptoms (OR range 1.17-1.52). Older age groups demonstrated higher odds of symptoms, particularly at 6 months (OR range 1.64-2.45).
Conclusion: Symptoms suggestive of early OA are highly prevalent within two years post-ACLR, with one third of patients experiencing persistent symptoms. These findings indicate that symptoms are more likely to persist rather than newly develop, emphasizing the importance of early identification and targeted interventions.No embarg