Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity.

AIMS/HYPOTHESIS: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected 'hub' cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility, which we explore here by focusing on the imprinted gene Nnat (encoding neuronatin [NNAT]), which is required for normal insulin synthesis and secretion. METHODS: Single-cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing enhanced GFP under the control of the Nnat enhancer/promoter regions were generated for FACS of beta cells and downstream analysis of CpG methylation by bisulphite sequencing and RNA-seq, respectively. Animals deleted for the de novo methyltransferase DNA methyltransferase 3 alpha (DNMT3A) from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 AM and Cal-590 AM. Insulin secretion was measured using homogeneous time-resolved fluorescence imaging. RESULTS: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic datasets demonstrated the early establishment of Nnat-positive and -negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a subpopulation specialised for insulin production, and were diminished in db/db mice. 'Hub' cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialisation. CONCLUSIONS/INTERPRETATION: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD048465.

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.

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.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Why creatives don't find the oddball odd: Neural and psychological evidence for atypical salience processing.

Creativity has previously been linked with various attentional phenomena, including unfocused or broad attention. Although this has typically been interpreted through an executive functioning framework, such phenomena may also arise from atypical incentive salience processing. Across two studies, we examine this hypothesis both neurally and psychologically. First we examine the relationship between figural creativity and event-related potentials during an audio-visual oddball task, finding that rater creativity of drawings is associated with a diminished P300 response at midline electrodes, while abstractness and elaborateness of the drawings is associated with an altered distribution of the P300 over posterior electrodes. These findings support the notion that creativity may involve an atypical attribution of salience to prominent information. We further explore the incentive salience hypothesis by examining relationships between creativity and a psychological indicator of incentive salience captured by participants' ratings of enjoyment (liking) and their motivation to pursue (wanting) diverse real world rewards, as well as their positive spontaneous thoughts about those rewards. Here we find enhanced motivation to pursue activities as well as a reduced relationship between the overall tendency to enjoy rewards and the tendency to pursue them. Collectively, these findings indicate that creativity may be associated with atypical allocation of attentional and motivational resources to novel and rewarding information, potentially allowing more types of information access to attentional resources and motivating more diverse behaviors. We discuss the possibility that salience attribution in creatives may be less dependent on task-relevance or hedonic pleasure, and suggest that atypical salience attribution may represent a trait-like feature of creativity.

Boosting inpatient exercise after hip fracture using an alternative workforce: a mixed methods implementation evaluation.

BACKGROUND: Hip fracture has a devastating impact on individuals and is an increasing burden for health systems and society. Compared to usual care, increased physiotherapy provision has demonstrated efficacy in improving patient and health service outcomes in this population. However, physiotherapy workforce challenges prevent sustained implementation. METHODS: Our aim was to evaluate the safety, feasibility, acceptability, effectiveness and implementation cost of thrice daily physiotherapy for patients in the acute care setting after hip fracture at two public hospitals. We added twice-daily exercise implemented by an alternative workforce, to usual care consisting of daily mobility practice by a physiotherapist. Sites identified their preferred alternative workforce, with pre-registration physiotherapy students and allied health assistants chosen. We used a mixed methods approach, using the Consolidated Framework for Implementation Research (CFIR) as a determinant framework to guide implementation planning and data collection. We compared hospital length of stay data to a reference cohort. RESULTS: We recruited 25 patients during the study period. Acute care hospital length of stay decreased from 11 days in the reference cohort to 8 days in the BOOST cohort (mean difference - 3.3 days, 95%CI -5.4 to -1.2 days, p = 0.003). Intervention fidelity was 72% indicating feasibility, no safety concerns were attributed to the intervention, and uptake was 96% of all eligible patients. The intervention was acceptable to patients, carers and healthcare providers. This intervention was cost-effective from the acute orthopaedic service perspective. CONCLUSION: Higher daily frequency of physiotherapy can be safely, feasibly and effectively implemented by an alternative workforce for patients in the acute care setting following hip fracture surgery.

COVID-19 Pivoted Virtual Skills Teaching Model: Project ECHO Ontario Skin and Wound Care Boot Camp.

OBJECTIVE: To describe a virtual, competency-based skin and wound care (SWC) skills training model. The ECHO (Extension for Community Healthcare Outcomes) Ontario SWC pivoted from an in-person boot camp to a virtual format because of the COVID-19 pandemic. METHODS: An outcome-based program evaluation was conducted. Participants first watched guided commentary and videos of experts performing in nine SWC multiskills videos, then practiced and video-recorded themselves performing those skills; these recordings were assessed by facilitators. Data were collected using pre-post surveys and rubric-based assessments. Descriptive statistics and thematic analysis were applied to data analysis. RESULTS: Fifty-five healthcare professionals participated in the virtual boot camp, measured by the submission of at least one video. A total of 216 videos were submitted and 215 assessment rubrics were completed. Twenty-nine participants completed the pre-boot camp survey (53% response rate) and 26 responded to the post-boot camp survey (47% response rate). The strengths of the boot camp included the applicability of virtual learning to clinical settings, boot camp supplies, tool kits, and teaching strategies. The analysis of survey responses indicated that average proficiency scores were greater than 80% for three videos, 50% to 70% for three of the videos, and less than 50% for three of the videos. Participants received lower scores in local wound care and hand washing points of contact. The barriers of the boot camp included technical issues, time, level of knowledge required at times, and lack of equipment and access to interprofessional teams. CONCLUSIONS: This virtual ECHO SWC model expanded access to practical skills acquisition. The professional development model presented here is generalizable to other healthcare domains.

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

Network analysis with either Illumina or MinION reveals that detecting vertebrate species requires metabarcoding of iDNA from a diverse fly community.

DNA obtained from invertebrates (iDNA) can be metabarcoded in order to survey vertebrate communities. However, little attention has been paid to the interaction between the invertebrate and vertebrate species. Here, we tested for specialization by sampling the dung and carrion fly community of a swamp forest remnant along a disturbance gradient (10 sites: 80-310 m from a road). Approximately, 60% of the baited 407 flies yielded 294 vertebrate identifications based on two COI fragments and 16S. A bipartite network analysis found no statistically significant specialization in the interactions between fly and vertebrate species, but uncommon fly species can carry the signal for vertebrate species that are otherwise difficult to detect with iDNA. A spatial analysis revealed that most of the 20 vertebrate species reported in this study could be detected within 150 m of the road (18 spp.) and that the fly community sourced for iDNA was unexpectedly rich (24 species, 3 families). They carried DNA for rare and common species inhabiting different layers of the forest (ground-dwelling: wild boar, Sunda pangolin, skinks, rats; arboreal: long-tailed macaque, Raffles' banded langur; flying: pin-striped tit-babbler, olive-winged bulbul). All our results were obtained with a new, greatly simplified iDNA protocol that eliminates DNA extraction by obtaining template directly through dissolving fly faeces and regurgitates with water. Lastly, we show that MinION- and Illumina-based metabarcoding yield similar results. We conclude by urging more studies that use different baits and involve experiments that are capable of revealing the dispersal capabilities of the flies carrying the iDNA.

Modification of a Transvalvular Microaxial Flow Pump for Instantaneous Determination of Native Cardiac Output and Volume.

BACKGROUND: The current Impella cardiopulmonary (CP) pump, used for mechanical circulatory support in patients with cardiogenic shock (CS), cannot assess native cardiac output (CO) and left ventricular (LV) volumes. These data are valuable in facilitating device management and weaning. Admittance technology allows for accurate assessment of cardiac chamber volumes. OBJECTIVES: This study tested the ability to engineer admittance electrodes onto an existing Impella CP pump to assess total and native CO as well as LV chamber volumes in an instantaneous manner. METHODS: Impella CP pumps were fitted with 4 admittance electrodes and were placed in the LVs of adult swine (n = 9) that were subjected to 3 different hemodynamic conditions, including Impella CP speed adjustments, administration of escalating doses of dobutamine and microsphere injections into the left main artery to result in cardiac injury. CO, according to admittance electrodes, was calculated from LV volumes and heart rate. In addition, CO was calculated in each instance via thermodilution, continuous CO measurement, the Fick principle, and aortic velocity-time integral by means of echocardiography. RESULTS: Modified Impella CP pumps were placed in swine LVs successfully. CO, as determined by admittance electrodes, was similar by trend to other methods of CO assessment. It was corrected for pump speed to calculate native CO, and calculated LV chamber volumes trended as expected in each experimental protocol. CONCLUSIONS: We report, for the first time, that an Impella CP pump can be fitted with admittance electrodes and used to determine total and native CO in various hemodynamic situations. CONDENSED ABSTRACT: Transvalvular mechanical circulatory support devices such as the Impella CP do not have the ability to provide real-time information on native cardiac output (CO) and left ventricular (LV) volumes. This information is critical in device management and in weaning in patients with cardiogenic shock. We demonstrate, for the first time, that Impella CP pumps coupled with admittance electrodes are able to determine native CO and LV chamber volumes in multiple hemodynamic situations such as Impella pump speed adjustments, escalating dobutamine administration and cardiac injury from microsphere injection.

Derivation and Validation of a Brief Emergency Department-Based Prediction Tool for Posttraumatic Stress After Motor Vehicle Collision.

STUDY OBJECTIVE: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department (ED) patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision. METHODS: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration. RESULTS: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort. CONCLUSION: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.

Improved delivery of rate-adaptive pacing using an impedance-derived contractility sensor in high-intensity exercise: A case report.

Effective rate-adaptive pacing may be difficult in the presence of atrial fibrillation (AF), and is important during high-intensity exercise. This case presents a 74-year-old elite cyclist with AF and a biventricular pacemaker after atrioventricular (AV) node ablation. He reported sudden breathlessness due to heart rate drops, caused by breaching the artefact threshold on the minute-ventilation sensor. He was exchanged to a generator with an impedance-derived contractility sensor (closed-loop stimulation), resulting in resolution of symptoms, and no further rate drops. This is the first description of the utility of closed-loop stimulation in high-intensity exercise.

Fatty infiltrate and neck muscle volume in individuals with chronic whiplash associated disorders compared to healthy controls - a cross sectional case-control study.

BACKGROUND: The underlying pathophysiological mechanisms of chronic Whiplash Associated Disorders (WAD) are not fully understood. More knowledge of morphology is needed to better understand the disorder, improve diagnostics and treatments. The aim was to investigate dorsal neck muscle volume (MV) and muscle fat infiltration (MFI) in relation to self-reported neck disability among 30 participants with chronic WAD grade II-III compared to 30 matched healthy controls. METHODS: MV and MFI at spinal segments C4 through C7 in both sexes with mild- to moderate chronic WAD (n = 20), severe chronic WAD (n = 10), and age- and sex matched healthy controls (n = 30) was compared. Muscles: trapezius, splenius, semispinalis capitis and semispinalis cervicis were segmented by a blinded assessor and analyzed. RESULTS: Higher MFI was found in right trapezius (p = 0.007, Cohen's d = 0.9) among participants with severe chronic WAD compared to healthy controls. No other significant difference was found for MFI (p = 0.22-0.95) or MV (p = 0.20-0.76). CONCLUSIONS: There are quantifiable changes in muscle composition of right trapezius on the side of dominant pain and/or symptoms, among participants with severe chronic WAD. No other statistically significant differences were shown for MFI or MV. These findings add knowledge of the association between MFI, muscle size and self-reported neck disability in chronic WAD. TRIAL REGISTRATION: NA. This is a cross-sectional case-control embedded in a cohort study.

A modified full-thickness labial/buccal rotational flap reconstruction technique following bilateral rostral maxillectomy and nasal planectomy for resection of maxillary tumors: Technique and results in two dogs.

OBJECTIVE: To describe a naso-facial reconstruction technique following bilateral rostral maxillectomy and its functional and cosmetic outcomes. ANIMALS: Two dogs. STUDY DESIGN: Clinical case series. METHODS: Two dogs were presented with a right rostral maxillary mass. Preoperative biopsy and staging revealed a biologically high-grade and histologically low-grade fibrosarcoma (Hi-Lo FSA). A combined nasal planectomy and radical bilateral rostral maxillectomy was performed sparing the labial/buccal mucocutaneous flaps bilaterally. Surgery resulted in asymmetry of the width of the flaps; the narrower flap was rotated medially to reconstruct the lip and create an oral vestibule. The wider flap was rotated medially to cover the remaining dorsolateral opening of the nasal conchae. The flaps overlapped in a parallel manner, discretely concealing the nasal passages, and separating them from the oral cavity. Hemorrhage occurred in both dogs, with one dog requiring a blood transfusion postoperatively. RESULTS: Oral Hi-Lo FSA with tumor-free margins was confirmed in both dogs. Both dogs recovered uneventfully within 4 weeks. Owners reported being very satisfied with the functional (return to normal exercise/activities and uncompromised respiration) and cosmetic outcomes. Based on the owners' telephone follow up, no tumor recurrence was noted at 15 (Dog 1) and 6 (Dog 2) months postoperatively. CONCLUSION: The full-thickness bilateral labial/buccal rotational flaps were used successfully to reconstruct the rostral maxilla, external nose and facial defects involving the nasal cavity. The technique resulted in acceptable functional and cosmetic outcomes and can be considered for naso-facial reconstruction in selected cases.

Harmonized Quality Assurance/Quality Control Provisions for Nontargeted Measurement of Urinary Pesticide Biomarkers in the HBM4EU Multisite SPECIMEn Study.

A set of quality assurance/quality control (QA/QC) criteria for nontargeted measurement of pesticide exposure markers in a large-scale study of human urine has been proposed and applied across five laboratories within the HBM4EU project. Quality control material, including reference standards and fortified pooled urine samples (QC urine) were prepared in a centralized way and distributed across participants to monitor analytical performance and consistency of the liquid chromatography coupled to high-resolution mass spectrometry data generated with a harmonized workflow. Signal intensities, mass accuracy, and retention times of selected QA/QC markers covering a broad range of physicochemical properties were monitored across QC solvent standards, QC urine samples, study urine samples, and procedural blanks, setting acceptance thresholds for repeatability and accuracy. Overall, results showed high repeatability of the collected data. The RSDs of the signal intensities were typically below 20-30% in QC and study samples, with good stability of the chromatographic separation (retention time drift within 2-4 s intrabatch and 5 s interbatch) and excellent mass accuracy (average error < 2 ppm). The use of the proposed criteria allowed for the identification of handling errors, instrumental issues, and potential batch effects. This is the first elaboration of harmonized QA/QC criteria applied across multiple laboratories to assess the quality of data generated by nontargeted analysis of human samples.

Socio-demographic and trauma-related predictors of PTSD within 8 weeks of a motor vehicle collision in the AURORA study.

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.

Prior histories of posttraumatic stress disorder and major depression and their onset and course in the three months after a motor vehicle collision in the AURORA study.

BACKGROUND: A better understanding of the extent to which prior occurrences of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) predict psychopathological reactions to subsequent traumas might be useful in targeting posttraumatic preventive interventions. METHODS: Data come from 1306 patients presenting to 29 U.S. emergency departments (EDs) after a motor vehicle collision (MVC) in the advancing understanding of recovery after trauma study. Patients completed self-reports in the ED and 2-weeks, 8-weeks, and 3-months post-MVC. Associations of pre-MVC probable PTSD and probable MDE histories with subsequent 3-months post-MVC probable PTSD and probable MDE were examined along with mediation through intervening peritraumatic, 2-, and 8-week disorders. RESULTS: 27.6% of patients had 3-month post-MVC probable PTSD and/or MDE. Pre-MVC lifetime histories of these disorders were not only significant (relative risk = 2.6-7.4) but were dominant (63.1% population attributable risk proportion [PARP]) predictors of this 3-month outcome, with 46.6% prevalence of the outcome among patients with pre-MVC disorder histories versus 9.9% among those without such histories. The associations of pre-MVC lifetime disorders with the 3-month outcome were mediated largely by 2- and 8-week probable PTSD and MDE (PARP decreasing to 22.8% with controls for these intervening disorders). Decomposition showed that pre-MVC lifetime histories predicted both onset and persistence of these intervening disorders as well as the higher conditional prevalence of the 3-month outcome in the presence of these intervening disorders. CONCLUSIONS: Assessments of pre-MVC PTSD and MDE histories and follow-ups at 2 and 8 weeks could help target early interventions for psychopathological reactions to MVCs.

Iatrogenic cardiac perforation due to pacemaker and defibrillator leads: a contemporary multicentre experience.

AIMS: To determine the incidence, clinical features, management, and outcomes of pacemaker (PM) and implantable cardioverter-defibrillator (ICD) lead cardiac perforation. Cardiac perforations due to PM and ICD leads are rare but serious complications. Clinical features vary widely and may cause diagnostic delay. Management strategies are non-guideline based due to paucity of data. METHODS AND RESULTS: A multicentre retrospective series including 3 UK cardiac tertiary centres from 2016 to 2020. Patient, device, and lead characteristics were obtained including 6-month outcomes. Seventy cases of perforation were identified from 10 631 procedures; perforation rate was 0.50% for local implants. Thirty-nine (56%) patients were female, mean ( ± standard deviation) age 74 ( ± 13.8) years. Left ventricular ejection fraction 51 ( ± 13.2) %. Median time to diagnosis was 9 (range: 0-989) days. Computed tomography (CT) diagnosed perforation with 97% sensitivity. Lead parameter abnormalities were present in 86% (whole cohort) and 98.6% for perforations diagnosed >24 h. Chest pain was the commonest symptom, present in 46%. The management strategy was percutaneous in 98.6% with complete procedural success in 98.6%. Pericardial effusion with tamponade was present in 17% and was associated with significantly increased mortality and major complications. Anticoagulation status was associated with tamponade by multivariate analysis (odds ratio 21.7, 95% confidence interval: 1.7-275.5, P = 0.018). CONCLUSIONS: Perforation was rare (0.50%) and managed successfully by a percutaneous strategy with good outcomes. Tamponade was associated with increased mortality and major complications. Anticoagulation status was an independent predictor of tamponade. Case complexity is highly variable and requires skilled operators with a multi-disciplinary approach to achieve good outcomes.

Lateral Corticospinal Tract and Dorsal Column Damage: Predictive Relationships With Motor and Sensory Scores at Discharge From Acute Rehabilitation After Spinal Cord Injury.

OBJECTIVE: To determine if lateral corticospinal tract (LCST) integrity demonstrates a significant predictive relationship with future ipsilateral lower extremity motor function (LEMS) and if dorsal column (DC) integrity demonstrates a significant predictive relationship with future light touch (LT) sensory function post spinal cord injury (SCI) at time of discharge from inpatient rehabilitation. DESIGN: Retrospective analyses of imaging and clinical outcomes. SETTING: University and academic hospital. PARTICIPANTS: A total of 151 participants (N=151) with SCI. INTERVENTIONS: Inpatient rehabilitation. MAIN OUTCOME MEASURES: LEMS and LT scores at discharge from inpatient rehabilitation. RESULTS: In 151 participants, right LCST spared tissue demonstrated a significant predictive relationship with right LEMS percentage recovered (ß=0.56; 95% confidence interval [CI], 0.37-0.73; R=0.43; P<.001). Left LCST spared tissue demonstrated a significant predictive relationship with left LEMS percentage recovered (ß=0.66; 95% CI, 0.50-0.82; R=0.51; P<.001). DC spared tissue demonstrated a significant predictive relationship with LT percentage recovered (ß=0.69; 95% CI, 0.52-0.87; R=0.55; P<.001). When subgrouping the participants into motor complete vs incomplete SCI, motor relationships were no longer significant, but the sensory relationship remained significant. Those who had no voluntary motor function but recovered some also had significantly greater LCST spared tissue than those who did not recover motor function. CONCLUSIONS: LCST demonstrated significant moderate predictive relationships with lower extremity motor function at the time of discharge from inpatient rehabilitation, in an ipsilesional manner. DC integrity demonstrated a significant moderate predictive relationship with recovered function of LT. With further development, these neuroimaging methods might be used to predict potential deficits after SCI and to provide corresponding targeted interventions.

How Is the Probability of Reporting Various Levels of Pain 12 Months After Noncatastrophic Injuries Associated with the Level of Peritraumatic Distress?

BACKGROUND: Psychological factors have been shown to be consistent predictors of chronic pain in people with musculoskeletal injuries. However, few prognostic studies have considered multiple risk factors including peritraumatic distress. In addition, previous research has not considered that the associations between peritraumatic distress and pain levels can vary across pain outcomes. QUESTION/PURPOSE: To determine whether an easily measurable level of baseline distress is associated with pain levels 1 year after noncatastrophic traumatic injuries when the outcome to be assessed is not normally distributed. METHODS: This was a prospective cohort study. The data were captured from two cohorts in London, Ontario, Canada, and Chicago, IL, USA. Participants were adults with acute noncatastrophic (that is, not treated with surgery or hospitalization) musculoskeletal injuries of any etiology with various injury locations (60% [145 of 241] spinal and 40% [96 of 241] peripheral) that presented to local urgent care centers. Other inclusion criteria included English/French speakers and having no other disorder that would affect their pain levels. In total, between the years 2015 and 2018, 241 participants were recruited based on the inclusion criteria. Ninety-three percent (225 of 241) of participants provided baseline data, and of these, 48% (109 of 225) were lost to follow-up in 1 year. Based on a complete case approach, this study included 116 participants who ranged in age from 18 to 66 years and 69% (80) of whom were women. The Traumatic Injuries Distress Scale (TIDS) was used to evaluate distress at baseline (within 4 weeks of injury). The TIDS is a validated, reliable 12-item risk prognosis screening tool that takes less than 3 minutes to complete with questions regarding uncontrolled pain, negative affect, and intrusion/hyperarousal. The minimum and maximum possible scores are 0 and 24, with higher scores indicating higher levels of distress. The Numeric Pain Rating Scale (NPRS) was used to assess the pain level at baseline and again 12 months postinjury. To complete the NPRS, participants rate the severity of their pain on a scale of 0 to 10, with 0 indicating no pain and 10 indicating the worst pain imaginable. NPRS scores of 1 to 3 indicate mild pain, 4 to 6 indicate moderate pain and 7 or higher indicate severe pain. As a preliminary analysis, to assess whether the participants as a group experienced recovery, a paired samples t-test was used to compare NPRS scores at baseline and 12 months. In all, 52% (60 of 116) of participants reported no pain (NPRS = 0), and mean pain intensity scores improved from 4.8 ± 2.1 at baseline to 1.6 ± 1.6 at 12-month follow-up (p < 0.001). Quantile regression was used to describe the association between baseline distress and pain levels 1 year after the injury. This technique was used because it reveals the relationships at different quantiles of the pain outcome distribution. RESULTS: The results indicate some people (52% [60 of 116]) recovered regardless of their baseline level of distress (30th quantile of the NPRS: ß = 0). However, in those with persisting pain, higher levels of baseline distress are associated with greater levels of pain 12 months after the injury (50th quantile of the NPRS: ß = 0.11; p = 0.01; 70th quantile of the NPRS: ß = 0.27; p < 0.001; 90th quantile of the NPRS: ß = 0.31; p = 0.01). According to this model, with a baseline TIDS score of 5, there is 10% probability that patients will report moderate or greater levels of pain (4 or higher of 10) 12 months later. This probability then increases as the TIDS score increases. For instance, at a score of 13 on the TIDS, the probability of a patient reporting moderate or higher levels of pain increases to 30%, and the probability of reporting severe pain (higher than 6 of 10) is 10%. CONCLUSION: Clinicians and surgeons in orthopaedic settings can screen for the presence of peritraumatic distress using the TIDS, which is an easily administered tool that does not require extensive knowledge of psychology, and by using it they can identify those with higher levels of distress who are more likely to have persistent, long-term pain. A score of 4 or less indicates a low risk of persistent pain, a score between 5 and 12 (endpoints included) indicates moderate risk, and a score of 13 or higher indicates high risk. Future studies should investigate whether certain immediate interventions for peritraumatic distress in the aftermath of trauma can decrease the likelihood that a patient will develop chronic pain after injury. As an analysis technique, quantile regression is useful to assess complex associations in many orthopaedic settings in which a certain outcome is expected to occur in most patients leading to non-normally distributed data. LEVEL OF EVIDENCE: Level II, therapeutic study.