An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms.

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.

Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity.

Stroke is a multiphasic process in which initial cerebral ischemia is followed by secondary injury from immune responses to ischemic brain components. Here we demonstrate that peripheral CD11b+CD45+ myeloid cells magnify stroke injury via activation of triggering receptor expressed on myeloid cells 1 (TREM1), an amplifier of proinflammatory innate immune responses. TREM1 was induced within hours after stroke peripherally in CD11b+CD45+ cells trafficking to ischemic brain. TREM1 inhibition genetically or pharmacologically improved outcome via protective antioxidant and anti-inflammatory mechanisms. Positron electron tomography imaging using radiolabeled antibody recognizing TREM1 revealed elevated TREM1 expression in spleen and, unexpectedly, in intestine. In the lamina propria, noradrenergic-dependent increases in gut permeability induced TREM1 on inflammatory Ly6C+MHCII+ macrophages, further increasing epithelial permeability and facilitating bacterial translocation across the gut barrier. Thus, following stroke, peripheral TREM1 induction amplifies proinflammatory responses to both brain-derived and intestinal-derived immunogenic components. Critically, targeting this specific innate immune pathway reduces cerebral injury.

Dairying, diseases and the evolution of lactase persistence in Europe.

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

Human Ageing Genomic Resources: updates on key databases in ageing research.

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).

Contribution of the histone variant H2A.Z to expression of responsive genes in plants.

The histone variant H2A.Z plays a critical role in chromatin-based processes such as transcription, replication, and repair in eukaryotes. Although many H2A.Z-associated processes and features are conserved in plants and animals, a distinguishing feature of plant chromatin is the enrichment of H2A.Z in the bodies of genes that exhibit dynamic expression, particularly in response to differentiation and the environment. Recent work sheds new light on the plant machinery that enables dynamic changes in H2A.Z enrichment and identifies additional chromatin-based pathways that contribute to transcriptional properties of H2A.Z-enriched chromatin. In particular, analysis of a variety of responsive loci reveals a repressive role for H2A.Z in expression of responsive genes and identifies roles for SWR1 and INO80 chromatin remodelers in enabling dynamic regulation of H2A.Z levels and transcription. These studies lay the groundwork for understanding how this ancient histone variant is harnessed by plants to enable responsive and dynamic gene expression (Graphical Abstract).

Successful Treatment of Carbapenem-Resistant Acinetobacter baumannii Meningitis with Sulbactam-Durlobactam.

BACKGROUND: The treatment of carbapenem-resistant Acinetobacter baumannii/calcoaceticus complex (CRAB) presents significant treatment challenges. METHODS: We report the case of a 42-year-old woman with CRAB meningitis who experienced persistently positive cerebrospinal fluid (CSF) cultures for 13 days despite treatment with high-dose ampicillin-sulbactam and cefiderocol. On day 13, she was transitioned to sulbactam-durlobactam and meropenem; four subsequent CSF cultures remained negative. After 14 days of sulbactam-durlobactam, she was cured of infection. Whole genome sequencing investigations identified putative mechanisms that contributed to reduced cefiderocol susceptibility observed during cefiderocol therapy. Blood and CSF samples were collected pre-dose and 3-hours post initiation of a sulbactam-durlobactam infusion. RESULTS: The CRAB isolate belonged to sequence type 2. An acquired blaOXA-23 and an intrinsic blaOXA-51-like (i.e., blaOXA-66) carbapenemase gene were identified. The paradoxical effect (i.e., no growth at lower cefiderocol dilutions but growth at higher dilutions) was observed by broth microdilution after 8 days of cefiderocol exposure but not by disk diffusion. Potential markers of resistance to cefiderocol included mutations in the start codon of piuA and piuC iron transport genes and a A515V substitution in PBP3, the primary target of cefiderocol. Sulbactam and durlobactam were detected in CSF at both timepoints, indicating CSF penetration. CONCLUSIONS: This case describes successful treatment of refractory CRAB meningitis with the administration of sulbactam-durlobactam and meropenem and highlights the need to be cognizant of the paradoxical effect that can be observed with broth microdilution testing of CRAB isolates with cefiderocol.

Optogenetic stimulation reveals a latent tipping point in cortical networks during ictogenesis.

Brain-state transitions are readily apparent from changes in brain rhythms,1 but are difficult to predict, suggestive that the underlying cause is latent to passive recording methods. Among the most important transitions, clinically, are the starts of seizures. We here show that an 'active probing' approach may have several important benefits for epileptic management, including by helping predict these transitions. We used mice expressing the optogenetic actuator, channelrhodopsin, in pyramidal cells, allowing this population to be stimulated in isolation. Intermittent stimulation at frequencies as low as 0.033 Hz (period = 30 s) delayed the onset of seizure-like events in an acute brain slice model of ictogenesis, but the effect was lost if stimulation was delivered at even lower frequencies (1/min). Notably, active probing additionally provides advance indication of when seizure-like activity is imminent, revealed by monitoring the postsynaptic response to stimulation. The postsynaptic response, recorded extracellularly, showed an all-or-nothing change in both amplitude and duration, a few hundred seconds before seizure-like activity began-a sufficient length of time to provide a helpful warning of an impending seizure. The change in the postsynaptic response then persisted for the remainder of the recording, indicative of a state change from a pre-epileptic to a pro-epileptic network. This occurred in parallel with a large increase in the stimulation-triggered Ca2+ entry into pyramidal dendrites, and a step increase in the number of evoked postsynaptic action potentials, both consistent with a reduction in the threshold for dendritic action potentials. In 0 Mg2+ bathing media, the reduced threshold was not associated with changes in glutamatergic synaptic function, nor of GABAergic release from either parvalbumin or somatostatin interneurons, but simulations indicate that the step change in the optogenetic response can instead arise from incremental increases in intracellular [Cl-]. The change in the response to stimulation was replicated by artificially raising intracellular [Cl-], using the optogenetic chloride pump, halorhodopsin. By contrast, increases in extracellular [K+] cannot account for the firing patterns in the response to stimulation, although this, and other cellular changes, may contribute to ictal initiation in other circumstances. We describe how these various cellular changes form a synergistic network of positive feedback mechanisms, which may explain the precipitous nature of seizure onset. This model of seizure initiation draws together several major lines of epilepsy research as well as providing an important proof-of-principle regarding the utility of open-loop brain stimulation for clinical management of the condition.

Development and Evaluation of a Patient Cirrhosis Knowledge Assessment.

BACKGROUND AND AIMS: Self-management skills improve outcomes for patients with cirrhosis. While education programs exist to teach these skills, there are limited patient assessments to evaluate their efficacy. We aimed to develop and evaluate cirrhosis knowledge assessments for patients with compensated and decompensated cirrhosis. METHODS: Across two institutions, a 4-stage process was undertaken: first, we developed a comprehensive set of questions regarding cirrhosis self-management. Second, the questions underwent critical review by patients and hepatology providers. Third, patients with cirrhosis answered these questions before and after a written educational tool. Questions were updated based on results. Fourth, patients answered the updated questions before and after a video educational tool. Binomial test or paired sample t-test was used to compare pre- and post-tests depending on question type. RESULTS: In phase 3, 134 patients completed pre- and post-tests. 44% were decompensated, 81% were diagnosed with cirrhosis at least 3 years, and 52% were 60-75 years. 95% of single-answer questions were answered correctly by at least 70% of patients in the pre-test. None of the answers improved significantly with education. After phase 3, 6 questions were removed and 6 questions were edited to increase challenge. In phase 4, 96 patients (42 compensated, 54 decompensated) completed pre- and post-tests. In the compensated assessment, 3 questions improved after education and the summative score increased (7.9 to 9.0, P < 0.001). In the decompensated assessment, 4 questions improved after education and the summative score increased (7.0 to 7.7, P = 0.004). CONCLUSION: Through a rigorous process, we created and evaluated cirrhosis knowledge assessments for patients with compensated and decompensated cirrhosis. Further validation is required and then these assessments can be used to improve patient education.

Comparison of two testing strategies for Mycoplasma genitalium in emergency department patients across a statewide health system.

PURPOSE: Mycoplasma genitalium (Mgen) is a sexually transmitted infection (STI) that has an estimated prevalence in the general population of 2.3% in women and 1.1% in men aged 21-23 years. (Hilbert and Reno, 2018) A cross-sectional study conducted in a community emergency department (ED) determined that the prevalence of Mgen was 14.8% in asymptomatic female patients. (Centers for Disease Control and Prevention (CDC). Sexually Transmitted Infections Treatment Guidelines, 2021) The Centers for Disease Control and Prevention (CDC) 2021 STI Treatment Guidelines recommend testing for Mgen in select circumstances. This study aims to determine what testing strategy in ED patients results in the most appropriate treatment of Mgen based on CDC recommendations. METHODS: This multicenter, retrospective, pre- and post-intervention cohort study assessed adherence to CDC recommendations for appropriate management of Mgen in ED patients. Inclusion criteria were patients at least 18 years of age discharged from one of the 15 ED sites within the health system studied who were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis (T. vaginalis), and Mgen. Subjects were excluded if they were pregnant, sexually assaulted, or had indeterminate STI results. For cohort 1, which included patients evaluated from May 2022 through July 2022, Mgen was incorporated into the standard STI testing panel. Cohort 2 consisted of patients evaluated from September 2022 through November 2022; testing for Mgen in cohort 2 was optional, and a testing algorithm based on CDC recommendations was disseminated to ED sites. The primary endpoint was the number of subjects treated appropriately for Mgen in accordance with CDC recommendations. Cohort 1 secondary endpoints included overall prevalence of Mgen in patients who presented to ED sites for STI testing and prevalence in ICD-10 code diagnosed PID. Secondary endpoints for both cohorts included baseline characteristics of patients who tested positive for Mgen. RESULTS: Percent appropriate treatment did not differ significantly between cohort 1 (21%) and cohort 2 (20%), (p > 0.9). However, greater than three times as many subjects were inappropriately treated for Mgen in cohort 1 when the health system studied did not adhere to current CDC Mgen testing recommendations. The overall prevalence of Mgen in ED patients who were tested for STIs was 13.1%. The prevalence of PID ICD-10 diagnosis code in patients positive for Mgen was 2.9%. Based on results of a risk factor analysis to determine if certain baseline characteristics are indicators for a positive infection with Mgen, a positive Mgen result was significantly associated with a positive result for T. vaginalis (p = 0.042). CONCLUSIONS: Evidence regarding the preferred testing strategy for Mgen is currently limited. This study demonstrates that testing all STI presenting patients for Mgen results in antibiotic overuse, so adhering to CDC testing recommendations is important. Prevalence of positive Mgen result in ED patients tested for STIs was similar to results of previously published literature. Risk factor analysis results could be used as a screening method to determine what patients should be considered for Mgen testing. Based on the results of this study, we recommend against including Mgen on the standard ED STI testing panel at this time.

Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate-Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.

BACKGROUND: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). METHODS: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. CONCLUSIONS: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

Continuous Neuromuscular Blockade for Bronchopulmonary Dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common late morbidity for premature infants. Continuous neuromuscular blockade (CNMB) is suggested for the most unstable phase of BPD, despite no outcome data. We explored the association between duration of CNMB for severe BPD and mortality. DESIGN: Medical record review of children <5 years old admitted from 2016 to 2022 with BPD and one or more course of CNMB for ≥14 days. RESULTS: Twelve children received a total of 20 episodes of CNMB for ≥14 days (range 14-173 d) during their hospitalization. Most (10/12) were born at <28 weeks' gestation and most (11/12) with birth weight <1,000 g; 7/12 were of Black race/ethnicity. All were hospitalized since birth. Most (10/12) were initially transferred from an outside neonatal intensive care unit (ICU), typically after a >60-day hospitalization (9/12). Half (6/12) of them had a ≥60-day stay in our neonatal ICU before transferring to our pediatric ICU for, generally, ≥90 days (8/12). The primary study outcome was survival to discharge: 2/12 survived. Both had shorter courses of CNMB (19 and 25 d); only one child who died had a course ≤25 days. Just two infants had increasing length Z-scores during hospitalization; only one infant had a final length Z-score > - 2. CONCLUSION: In this case series of infants with severe BPD, there were no survivors among those receiving ≥25 days of CNMB. Linear growth, an essential growth parameter for infants with BPD, decreased in most patients. These data do not support the use of ≥25 days of CNMB to prevent mortality in infants with severe BPD. KEY POINTS: · This is a case series of neuromuscular blockade for severe BPD.. · Neuromuscular blockade did not improve linear growth.. · Ten out of 12 infants who were on prolonged neuromuscular blockade died..

Helmet Therapy for the Management of Deformational Plagiocephaly in Pediatric Patients with Shunted Hydrocephalus.

OBJECTIVE: To evaluate the safety and efficacy of helmet therapy for deformational plagiocephaly in patients with shunted hydrocephalus. DESIGN: Retrospective chart review. SETTING: Institutional, tertiary-care hospital. PATIENTS: All patients at St. Louis Children's Hospital between 2014 and 2021 with shunted hydrocephalus who underwent helmet therapy for deformational plagiocephaly. INTERVENTIONS: Helmet therapy. MAIN OUTCOME MEASURES: Cranial vault asymmetry (CVA), cranial vault asymmetry index (CVAI), and cephalic index (CI) were measured before and after completion of helmet therapy. RESULTS: There were 37 patients with shunted hydrocephalus and documented deformational plagiocephaly. Twelve were managed with helmet therapy. Average age at helmeting initiation and time between shunt placement and helmeting initiation was 5.8 and 4.6 months, respectively. Average CVA, CVAI, and CI at helmeting initiation and termination was 11.6, 7.98, and 85.2, and 6.95, 4.49, and 83.7, respectively. Average duration of helmeting was 3.7 months. CVA and CVAI were significantly lower after helmeting (P = .0028 and .0021) and 11/12 patients had overall improvement in plagiocephaly. CONCLUSIONS: Helmet therapy appears to be a safe and efficacious management strategy for deformational plagiocephaly in patients with shunted hydrocephalus. Despite the occasional need for additional fittings and surveillance beyond the normal schedule, in all cases appropriately fitting helmets were achieved and no major adverse events occurred. This cohort represents a proof of principle for the safety and efficacy of helmet therapy in patients with shunted hydrocephalus. Further work in larger prospective cohorts is needed to confirm these initial findings.

Linking Immigrants with Nutrition Knowledge (Project LINK): An Innovative Approach to Improve Cultural Competence in Dietetic Education.

Linking Immigrants with Nutrition Knowledge (Project LINK) was a service-learning cultural competence training programme completed by undergraduate dietetic students enrolled in the University of Saskatchewan's (USASK) nutrition and dietetic programme.This paper evaluates the impact of participation in the programme on students' cultural competence. We conducted a cross-sectional survey and qualitative analysis of reflective essays of 107 participants of Project LINK from 2011 to 2014. Cumulative logistic regression models assessed the impact of the intervention on students' cultural competencies. The Akaike information criterion compared models and Spearman correlation coefficient identified possible correlation among pre- and post-intervention data points. Student reflective essays were analyzed by inductive thematic analysis.All cultural competencies improved comparing pre- and post-participation in Project LINK. Odds of increasing one level of student knowledge were 110 times of that prior to Project LINK. Comparing student competencies before and after Project LINK, the odds of increasing one level of students' skills were six times greater, five times greater for increasing one level of students' ability to interact or encounter, and 2.8 times greater for increasing one level of students' attitude.The results of this study indicate Project LINK has successfully increased cultural competence and underscores the importance of combining opportunities for practical experience in addition to classroom-based training on cultural competence.

"I Prefer to Stay Away": A Qualitative Study of Patients in an Opioid-Sparing Pain Management Protocol.

OBJECTIVE: The aim of this study was to explore beliefs and behaviors of opioid pain medications among patients undergoing elective surgery. BACKGROUND: Opioid dependence after surgery is a major contributor to the ongoing opioid epidemic. Recent efforts by surgeons and health systems have sought to improve the education patients receive regarding safe opioid use after surgery; however, little is known about patients' pre-existing beliefs surrounding opioids. METHODS: Semistructured interviews were conducted with patients who underwent 1 of 4 common elective surgical procedures at 1 institution. Patients were specifically asked about their knowledge and beliefs about opioids before surgery and their opinions of opioid-sparing recovery after surgery. Coding was conducted through iterative steps, beginning with an initial cycle of rapid analysis, followed by focused coding, and thematic analysis. RESULTS: Twenty-one patients were interviewed. Three major themes emerged regarding patient opinions about using opioids after surgery. First, there was widespread awareness among patients about opioid medications, and preoperatively, patients had specific intentions about using opioids, often informed by this awareness. Second, patients described a spectrum of opioid related behavior which both aligned and conflicted with preoperative intentions. Third, there was tension among patients about opioid-free postoperative recovery, with patients expressing support, opposition, and emphasis on tailoring recovery to patient needs. CONCLUSIONS: Patients undergoing common surgical procedures often arrive at their surgical encounter with strong, pre-formed opinions about opioids. Eliciting these preexisting opinions may help surgeons better counsel patients about safe opioid use after surgery.

Cost-effectiveness of Staple Line Reinforcement in Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: To perform a cost-effectiveness analysis of staple-line reinforcement in laparoscopic sleeve gastrectomy. SUMMARY OF BACKGROUND DATA: Exponential increases in surgical costs have underscored the critical need for evidence-based methods to determine the relative value of surgical devices. One such device is staple-line reinforcement, thought to decrease bleeding rates in laparoscopic sleeve gastrectomy. METHODS: Two intervention arms were modeled, staple-line reinforcement and standard nonreinforced stapling. Bleed and leak rates and 30-day treatment costs were obtained from national and state registries. Quality-adjusted life-year (QALY) values were drawn from previous literature. Device prices were drawn from institutional data. A final incremental cost-effectiveness ratio was calculated, and one-way and probabilistic sensitivity analyses were performed. RESULTS: A total of 346,530 patient records from 2012 to 2018 were included. Complication rates for the reinforced and standard cohorts were 0.05% for major bleed in both cohorts ( P = 0.8841); 0.45% compared with 0.59% for minor bleed ( P < 0.0001); and 0.24% compared with 0.26% for leak ( P = 0.4812). Median cost for a major bleed was $5552 ($3287, $16,817) and $2406 ($1861, $3484) for a minor bleed. Median leak cost was $9897 ($4589, $21,619) and median cost for patients who did not experience a bleed, leak, or other serious complication was $1908 ($1712, $2739). Mean incremental cost of reinforced stapling compared with standard was $819.60/surgery. Net QALY gain with reinforced stapling compared with standard was 0.00002. The resultant incremental cost-effectiveness ratio was $40,553,000/QALY. One-way and probabilistic sensitivity analyses failed to produce a value below $150,000/QALY. CONCLUSIONS: Compared with standard stapling, reinforced stapling reduces minor postoperative bleeding but not major bleeding or leaks and is not cost-effective if routinely used in laparoscopic sleeve gastrectomy.

A Randomized Clinical Trial of Clinician-Supported PTSD Coach in VA Primary Care Patients.

BACKGROUND: Posttraumatic stress disorder (PTSD) is common in primary care patients; however, evidence-based treatments are typically only available in specialty mental healthcare settings and often not accessed. OBJECTIVE: To test the effectiveness of a brief primary care-based treatment, Clinician-Supported PTSD Coach (CS PTSD Coach) was compared with Primary Care Mental Health Integration-Treatment as Usual (PCMHI-TAU) in (1) reducing PTSD severity, (2) engaging veterans in specialty mental health care, and (3) patient satisfaction with care. DESIGN: Multi-site randomized pragmatic clinical trial. PARTICIPANTS: A total of 234 veterans with PTSD symptoms who were not currently accessing PTSD treatment. INTERVENTION: CS PTSD Coach was designed to be implemented in Veterans Affairs PCMHI and combines mental health clinician support with the "PTSD Coach" mobile app. Four 30-min sessions encourage daily use of symptom management strategies. MAIN MEASURES: PTSD severity was measured by clinician-rated interviews pre- and post-treatment (8 weeks). Self-report measures assessed PTSD, depression, and quality of life at pretreatment, posttreatment, and 16- and 24-week follow-ups, and patient satisfaction at post-treatment. Mental healthcare utilization was extracted from medical records. KEY RESULTS: Clinician-rated PTSD severity did not differ by condition at post-treatment. CS PTSD Coach participants improved more on patient-reported PTSD severity at post-treatment than TAU participants (D = .28, p = .021). Coach participants who continued to have problematic PTSD symptoms at post-treatment were not more likely to engage in 2 sessions of specialty mental health treatment than TAU participants. Coach participants engaged in 74% more sessions in the intervention and reported higher treatment satisfaction than TAU participants (p < .001). CONCLUSIONS: A structured 4-session intervention designed to align with patient preferences for care resulted in more patient-reported PTSD symptom relief, greater utilization of mental health treatment, and overall treatment satisfaction than TAU, but not more clinician-rated PTSD symptom relief or engagement in specialty mental health.

Consensus on level descriptors for a functional children's eating and drinking activity scale.

AIM: To agree wording of level descriptors for a measure of functional outcome of children's eating and drinking. METHOD: An online, modified Delphi method was used to gather feedback on current level descriptor wording and generate rewording suggestions. Thirty speech and language therapists, working in a variety of settings and geographical locations, were invited to be part of the Delphi expert panel. Content analysis was used to evaluate participants' comments and develop consensus level descriptors. Consensus for acceptable wording was set at 80% agreement. Face validity was assessed using 5-point Likert scales. RESULTS: Nineteen expert speech and language therapists (median experience 18 years) completed round one; 15 out of 19 completed round two. Level descriptor rating reached 80% agreement in two rounds. Additionally, 93% of participants agreed the scale would accurately capture change in their setting, with 87% likely to use the scale in practice. INTERPRETATION: This study has produced agreed wording for a functional measure of eating and drinking activity suitable for use with paediatrics feeding disorders, regardless of disease aetiology, presentation, age, or setting. Potential for widespread use is supported. Further evaluation of the tool's reliability and validity is required.

Back to the future: Progressing memory research in eating disorders.

OBJECTIVE: Human behaviors, thoughts, and emotions are guided by memories of the past. Thus, there can be little doubt that memory plays a fundamental role in the behaviors (e.g., binging), thoughts (e.g., body-image concerns), and emotions (e.g., guilt) that characterize eating disorders (EDs). Although a growing body of research has begun to investigate the role of memory in EDs, this literature is limited in numerous ways and has yet to be integrated into an overarching framework. METHODS: In the present article, we provide an operational framework for characterizing different domains of memory, briefly review existing ED memory research within this framework, and highlight crucial gaps in the literature. RESULTS: We distinguish between three domains of memory-episodic, procedural, and working-which differ based on functional attributes and underlying neural systems. Most recent ED memory research has focused on procedural memory broadly defined (e.g., reinforcement learning), and findings within all three memory domains are highly mixed. Further, few studies have attempted to assess these different domains simultaneously, though most behavior is achieved through coordination and competition between memory systems. We, therefore, offer recommendations for how to move ED research forward within each domain of memory and how to study the interactions between memory systems, using illustrative examples from other areas of basic and clinical research. DISCUSSION: A stronger and more integrated understanding of the mechanisms that connect memory of past experiences to present ED behavior may yield more comprehensive theoretical models of EDs that guide novel treatment approaches. PUBLIC SIGNIFICANCE: Memories of previous eating-related experiences may contribute to the onset and maintenance of eating disorders (EDs). However, research on the role of memory in EDs is limited, and distinct domains of ED memory research are rarely connected. We, therefore, offer a framework for organizing, progressing, and integrating ED memory research, to provide a better foundation for improving ED treatment and intervention going forward.

Implementation of a women's reproductive behavioral health telemedicine program: a qualitative study of barriers and facilitators in obstetric and pediatric clinics.

BACKGROUND: Perinatal Mood and Anxiety Disorders and Substance Use Disorders are common and result in significant morbidities and mortality. Despite evidence-based treatment availability, multiple barriers exist to care delivery. Because telemedicine offers opportunities to overcome these barriers, the objective of this study was to characterize barriers and facilitators to implementing a mental health and substance use disorder telemedicine program in community obstetric and pediatric clinics. METHODS: Interviews and site surveys were completed with practices engaged in a Women's Reproductive Behavioral Health Telemedicine program (N = 6 sites; 18 participants) at the Medical University of South Carolina and telemedicine providers involved in care delivery (N = 4). Using a structured interview guide based on implementation science principles, we assessed program implementation experiences and perceived barriers and facilitators to implementation. A template analysis approach was used to analyze qualitative data within and across groups. RESULTS: The primary program facilitator was service demand driven by the lack of available maternal mental health and substance use disorder services. Strong commitment to the importance of addressing these health concerns provided a foundation for successful program implementation yet practical challenges such as staffing, space, and technology support were notable barriers. Services were supported by establishing good teamwork within the clinic and with the telemedicine team. CONCLUSION: Capitalizing on clinics' commitment to care for women's needs and a high demand for mental health and substance use disorder services while also addressing resource and technology needs will facilitate telemedicine program success. Study results may have implications for potential marketing, onboarding and monitoring implementation strategies to support clinics engaging in telemedicine programs.