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Holocord syringomyelia (HSM) is characterized by a continuous spinal cord cavitation along its entire length and is currently poorly documented in dogs. This retrospective multicentric case series investigates the clinical and MRI findings in 18 dogs with HSM. The median age at presentation was 82 months (range 9-108 months) and French Bulldogs were overrepresented (50%). Signs of myelopathy attributed to HSM were detected in 12 dogs (67%), spinal pain/paresthesia/allodynia in eight (44%), and four dogs (22%) had no HSM-associated signs. The most common neuroanatomical localization was C1-C5 spinal cord segments. On MRI, the cranial limit of HSM was at C1 vertebra in seven (39%) and at C2 in 11 dogs (61%). The caudal limit extended to L3 in four dogs (22%), L4 or L5 in six dogs (33%) each, and L6 in two dogs (11%). The conus medullaris terminated at L5 in one dog (6%), L6 in 11 (61%), and L7 in six dogs (33%). Seventeen dogs (94%) exhibited MRI features of Chiari-like and/or other intracranial/cranio-cervical junction malformations. One dog (6%) was treated surgically, 11 (61%) medically, and six (33%) received no treatment. Over a median follow-up of 12 months (range 2-65 months) in 16 dogs, one dog (6%) improved, nine (56%) deteriorated, four (25%) were static, and two (13%) remained free of HSM-associated signs. This is the first study to describe canine HSM, highlighting a possible breed predisposition in French Bulldogs. The frequent occurrence of myelopathy and disease progression underscores the need for further research into the underlying etiopathogenesis, natural disease evolution, and response to therapeutic interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Douralidou, Mari, Wyatt, Minguez, Fernandez, Anselmi and Posporis.)

Background: Hospitals use triage systems to prioritize the needs of patients within available resources. Misclassification of a patient can lead to either adverse outcomes in a patient who did not receive appropriate care in the case of undertriage or a waste of hospital resources in the case of overtriage. Recent advances in machine learning algorithms allow for the quantification of variables important to under- and overtriage., Objective: This study aimed to identify clinical features most strongly associated with triage misclassification using a machine learning classification model to capture nonlinear relationships., Methods: Multicenter retrospective cohort data from 2 big regional hospitals in Norway were extracted. The South African Triage System is used at Bergen University Hospital, and the Rapid Emergency Triage and Treatment System is used at Trondheim University Hospital. Variables included triage score, age, sex, arrival time, subject area affiliation, reason for emergency department contact, discharge location, level of care, and time of death were retrieved. Random forest classification models were used to identify features with the strongest association with overtriage and undertriage in clinical practice in Bergen and Trondheim. We reported variable importance as SHAP (SHapley Additive exPlanations)-values., Results: We collected data on 205,488 patient records from Bergen University Hospital and 304,997 patient records from Trondheim University Hospital. Overall, overtriage was very uncommon at both hospitals (all <0.1%), with undertriage differing between both locations, with 0.8% at Bergen and 0.2% at Trondheim University Hospital. Demographics were similar for both hospitals. However, the percentage given a high-priority triage score (red or orange) was higher in Bergen (24%) compared with 9% in Trondheim. The clinical referral department was found to be the variable with the strongest association with undertriage (mean SHAP +0.62 and +0.37 for Bergen and Trondheim, respectively)., Conclusions: We identified subgroups of patients consistently undertriaged using 2 common triage systems. While the importance of clinical patient characteristics to triage misclassification varies by triage system and location, we found consistent evidence between the two locations that the clinical referral department is the most important variable associated with triage misclassification. Replication of this approach at other centers could help to further improve triage scoring systems and improve patient care worldwide., (©Sage Wyatt, Dagfinn Lunde Markussen, Mounir Haizoune, Anders Strand Vestbø, Yeneabeba Tilahun Sima, Maria Ilene Sandboe, Marcus Landschulze, Hauke Bartsch, Christopher Martin Sauer. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.12.2024.)

Background: Prevalence of depression is increasing in young people. Behaviour change interventions providing benefits equal to or greater than talking therapies or pharmacological alternatives are needed. Exercise could be beneficial for young people with depression, but we lack robust trials of its effectiveness., Objective: To test whether an exercise intervention targeting young people with depression is feasible, including recruitment and retention of young people, recruitment and training of exercise professionals and intervention delivery., Design: Three-arm cluster feasibility randomised controlled trial with embedded process evaluation and health economic data collection., Setting: Local community venues in Hertfordshire, Bedfordshire and Norfolk., Participants: Young people aged 13-17 years experiencing mild to moderate low mood or depression (indicated by scoring 17-36 on the Child Depression Inventory version 2) identified by mental health services, schools or self-referral., Interventions: Participants were randomised to one of three groups: high-intensity exercise, low-intensity exercise or a social activity control. Group sessions ran twice-weekly for 12 weeks delivered by registered exercise professionals, supported by mental health support workers., Main Outcome Measures: Referral, recruitment and retention rates; attendance at group sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data, and adverse events measured at baseline and at 3 and 6 months; resource use; and reach and representativeness., Results: Of 321 referrals to the study, 173 were assessed for eligibility, and of the target sample size of 81, 15 were recruited and 14 were randomised (one withdrew). The retention rate was 71.4% and attendance at intervention sessions was > 67%; data completeness was > 80% for baseline assessments. Follow-up completion rate at 14 weeks was > 80% for most outcomes, with 50% for accelerometer data in the low-intensity group. Trial processes and the intervention were acceptable to young people. Barriers to and facilitators of intervention delivery were identified., Limitations: Findings highlighted challenges around recruitment, delivery of exercise interventions and informed ways of addressing barriers to recruitment for future studies. The study was conducted between October 2020 and August 2022 and consequently the COVID-19 pandemic had a disruptive impact on implementation., Conclusions: A large randomised trial of the effectiveness of the intervention is not feasible using the current study design, but issues relating to recruitment could be addressed with further work., Future Work: Developing appropriate recruitment strategies via triage services, general practitioner practices, schools and social media and early engagement with the local Clinical Research Network to support recruitment to the study would address the significant shortfalls identified. Young people who are deemed unsuitable for mental health services should be followed up to be offered participation in such interventions. Collaborations between the NHS services and sports delivery partners should consider in-person contact with young people rather than remote consultations. Recruiting through general practitioner practices is effective and relatively inexpensive. The role of community engagement (socialmedia, public health agencies, community groups) needs to be further explored. Strong public and patient involvement and engagement via young people advisory groups is important to ensure that research is relevant to young people., Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/78/10.

Objectives: Although primary care is central to healthcare provision, inconsistent methods and data sources mean that relatively little is known about long-term trends in general practice consultation rates. We aimed to explore long-term trends in English general practice consultation rates using two electronic health records databases, Clinical Practice Research Datalink Gold and Aurum, from 1995 to 2021., Methods: Consultations were identified and classified using a set of rules and code lists. Consultation rates were calculated as the ratio of the count of consultations and the registration duration. We used negative binomial regression to model the relationship between the number of consultations and the patient's age, sex and year from each database. These models are then used to estimate annual crude consultation rates for England., Results: The number of general practices in the Gold database decreased from 346 (1995) to 41 (2021), while in Aurum, it increased from 555 (1995) to 1347 (2021). In Gold, the average number of consultations per person-year increased from 2.91 in 1995 to 5.12 in 2012, then fell to 4.59 in 2019 and to 4.12 in 2021. In Aurum, average consultations per person-year rose from 2.17 (1995) to 4.89 (2012), then fell to 4.76 (2019) and rose again to 5.40 (2021). Half of the total increase in consultations from Aurum was due to a new consultation code, for 'AccurX consultations', an electronic messaging system for communication with patients., Conclusion: Trends in general practice consultation showed three distinct epochs: rising from 1995 to 2012, falling from 2012 to 2019 and rising in Aurum but falling in Gold from 2019 to 2021. Consultation rates in Gold were higher than Aurum until the inclusion of a new consultation code in Aurum in 2019, which underscores the need for operational definitions of a consultation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore variation in rates of acute care utilization for mental health conditions, including hospitalizations and emergency department (ED) visits, across high-income countries before and during the COVID-19 pandemic., Data Sources and Study Setting: Administrative patient-level data between 2017 and 2020 of eight high-income countries: Canada, England, Finland, France, New Zealand, Spain, Switzerland, and the United States (US)., Study Design: Multi-country retrospective observational study using a federated data approach that evaluated age-sex standardized rates of hospitalizations and ED visits for mental health conditions., Principal Findings: There was significant variation in rates of acute mental health care utilization across countries. Among the subset of four countries with both hospitalization and ED data, the US had the highest pre-COVID-19 combined average annual acute care rate of 1613 episodes/100,000 people (95% CI: 1428, 1797). Finland had the lowest rate of 776 (686, 866). When examining hospitalization rates only, France had the highest rate of inpatient hospitalizations of 988/100,000 (95% CI 858, 1118) while Spain had the lowest at 87/100,000 (95% CI 76, 99). For ED rates for mental health conditions, the US had the highest rate of 958/100,000 (95% CI 861, 1055) while France had the lowest rate with 241/100,000 (95% CI 216, 265). Notable shifts coinciding with the onset of the COVID-19 pandemic were observed including a substitution of care setting in the US from ED to inpatient care, and overall declines in acute care utilization in Canada and France., Conclusion: The study underscores the importance of understanding and addressing variation in acute care utilization for mental health conditions, including the differential effect of COVID-19, across different health care systems. Further research is needed to elucidate the extent to which factors such as workforce capacity, access barriers, financial incentives, COVID-19 preparedness, and community-based care may contribute to these variations., What Is Known on This Topic: Approximately one billion people globally live with a mental health condition, with significant consequences for individuals and societies. Rates of mental health diagnoses vary across high-income countries, with substantial differences in access to effective care. The COVID-19 pandemic has exacerbated mental health challenges globally, with varying impacts across countries., What This Study Adds: This study provides a comprehensive international comparison of hospitalization and emergency department visit rates for mental health conditions across eight high-income countries. It highlights significant variations in acute care utilization patterns, particularly in countries that are more likely to care for people with mental health conditions in emergency departments rather than inpatient facilities The study identifies temporal and cross-country differences in acute care management of mental health conditions coinciding with the onset of the COVID-19 pandemic., (© 2024 The Author(s). Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Objective: To describe the approach for placement of a transcerebellar fourth ventriculoperitoneal shunt for management of presumed fourth ventricle arachnoid diverticulum and secondary obstructive hydrocephalus of a dog. To describe the outcome of this procedure., Study Design: Case report., Animals: Male entire English springer spaniel, 3 years 9 months of age., Methods: The dog was initially presented for management of acute, progressive, and multifocal brainstem and forebrain dysfunction. Magnetic resonance imaging revealed internal obstructive hypertensive hydrocephalus. The dog was managed via ventriculoperitoneal shunting from the left lateral ventricle and made an excellent recovery. The dog acutely deteriorated 18 months after initial discharge and follow-up magnetic resonance imaging confirmed the ventricular shunt remained in situ with normal-sized lateral ventricles but revealed a cystlike lesion within the fourth ventricle, presumed to be a fourth ventricle arachnoid diverticulum. The diverticulum was causing mass effect and resultant compression of adjacent neuroparenchyma. A second ventriculoperitoneal shunt was subsequently placed into the fourth ventricle via the caudal cranial fossa and cerebellum. This was attached to a three-way connector, to which the existing shunt (within the left lateral ventricle) was also attached, and then secured to the existing medium-pressure valve., Results: Postoperatively, the dog immediately developed mild vestibular-cerebellar ataxia, with a marked improvement after 3 months. There were no shunt-associated complications. Long-term follow up at 40 months after the second surgical procedure revealed a normal neurological examination., Conclusion: Transcerebellar ventriculoperitoneal shunt placement for treatment of a presumed fourth ventricle arachnoid diverticulum was performed and was associated with a favorable long-term outcome., (© 2024 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Objectives: The planning process for a new hospital relies on assumptions about future levels of demand. Typically, such assumptions are characterised by point estimates, the flaw-of-averages, base-rate neglect and overoptimism from an inside view. To counteract these limitations, we elicited an outside view of probabilistic forecasts based on judgements of experts about the extent to which various types of hospital activity might be mitigated over 20 years, in support of the New Hospital Programme (NHP) in the English National Health Service., Design: A prospective online elicitation exercise, over two rounds, to forecast the reduction (0% no reduction to 100% total reduction) in 77 types of hospital activity across England via five types of activity mitigation: outpatient attendance avoidance (n=8); inpatient admission avoidance (n=31); A&E attendance avoidance (n=12); outpatient delivery mode (n=4); inpatient length of stay reduction (n=22) and eight types of activity groups.Primary outcomes are the aggregated forecasts representing the percentage reduction (0%-100%) in hospital activity across England based on 'surprisingly low' (10th percentile-P10) to 'surprisingly high' (90th percentile-P90) forecasts from 17 experts., Results: We had 657 forecasts from 17 experts. The most pessimistic forecast was for inpatient avoidance of frail elderly admissions (mean 5.71%, P10=0.43%, P90=16.40%). The most optimistic forecast was for inpatient admission avoidance for vascular surgery (mean 48.27%, P10=19.82%, P90=78.57%). The overall (n=77) aggregate means ranged from a low of 5.71% to a high of 48.27% with an average width of 50.08%. Experts highlighted mainly four types of mitigation mechanisms-prevention, displacement, quality improvement and de-adoption., Conclusion: A national elicitation exercise has provided long-term aggregate forecasts across England that make explicit the wide variation and uncertainty associated with future mitigation activities from an outside perspective. These aggregate forecasts may now be incorporated into the NHP, providing a more robust foundation for planning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Investigative genetic genealogy (IGG) has emerged as a highly effective tool for tying a forensic DNA sample to an identity. While much of the attention paid to IGG has focused on cases where the DNA is from an unknown suspect, IGG has also been used to help close hundreds of unidentified human remains (UHR) cases. Genome-wide single-nucleotide polymorphism (SNP) genotype data can be obtained from forensic samples using microarray genotyping or whole-genome sequencing (WGS) with protocols optimized for degraded DNA. After bioinformatic processing, the SNP data can be uploaded to public GG databases that allow law enforcement usage, where it can be compared with other users' data to find distant relatives. A genetic genealogist can then build the family trees of the relatives to narrow down the identity of the source of the forensic DNA sample. To date, 367 UHR identifications using IGG have been publicly announced. The same IGG techniques developed and refined for UHR cases have significant potential for disaster victim identification, where DNA is often extremely compromised, and close family references may not be available. This paper reviews the laboratory, bioinformatic, and genealogical techniques used in IGG for UHR cases and presents three case studies that demonstrate how IGG is assisting with remains identification., (© 2024 American Academy of Forensic Sciences.)

Background: Prior studies on maternal cardiovascular disease (CVD) mortality and hypertensive disorders of pregnancy (HDP) have focused only on a woman's first birth and have not accounted for successive affected pregnancies., Objectives: The objective of this study is to identify mothers' risk of CVD mortality considering lifetime reproductive history., Methods: We used data from the Medical Birth Registry of Norway, the Norwegian Cause of Death Registry, and the Norwegian National Population Register to identify all mothers who gave birth from 1967 to 2020. Our outcome was mothers' CVD death before age 70. The primary exposure was the lifetime history of HDP. The secondary exposure was the order of HDP and gestational age at delivery of pregnancies with HDP. We used Cox regression models to estimate hazard ratio (HR) and 95% confidence interval (CI), adjusting for education, mother's age, and year of last birth. These models were stratified by the lifetime number of births., Results: Among 987,378 mothers, 86,294 had HDP in at least one birth. The highest CVD mortality, relative to mothers without HDP, was among those with a pre-term HDP in their first two births, although this represented 1.0% of mothers with HDP (HR 5.12, 95% CI 2.66, 9.86). Multiparous mothers with term HDP in their first birth only had no increased risk of CVD relative to mothers without HDP (36.9% of all mothers with HDP; HR 1.12, 95% CI 0.95, 1.32). All other mothers with HDP had a 1.5- to 4-fold increased risk of CVD mortality., Conclusions: This study identified heterogeneity in the risk of CVD mortality among mothers with a history of HDP. A third of these mothers are not at higher risk compared to women without HDP, while some less common patterns of HDP history are associated with severe risk of CVD mortality., (© 2024 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

This Chapter describes methods for the biosynthetic substitution of the mononuclear, non-heme iron in plant and animal lipoxygenases (LOXs). Substitution of this iron center for a manganese ion results in an inactive, yet faithful structural surrogate of the LOX enzymes. This metal ion substitution permits structural and dynamical studies of enzyme-substrate complexes in solution and immobilized on lipid membrane surfaces. Representative procedures for two LOXs, soybean lipoxygenase (SLO) from plants and human epithelial 15-lipoxygenase-2 (15-LOX-2) from mammals, are described as examples., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To summarize findings from a case of adrenocortical hemorrhage following tetracosactide injection during ACTH stimulation testing for monitoring of trilostane therapy in a dog., Animal: A 12-year old neutered male dog with adrenal-dependent hypercortisolism., Clinical Presentation, Progression, and Procedures: 4 hours after ACTH stimulation testing, the patient developed vomiting, lethargy, and abdominal pain. Abdominal ultrasound was performed before and after an ACTH stimulation test. Following ACTH stimulation testing, there was progressive bilateral adrenal enlargement and free abdominal fluid had developed. This was considered to be caused by adrenocortical inflammation and hemorrhage secondary to the synthetic ACTH analog, tetracosactide, used during stimulation testing. A resting cortisol performed 5 hours after tetracosactide injection was not consistent with iatrogenic hypoadrenocorticism., Treatment and Outcome: The patient was managed with analgesia, IV fluids, and corticosteroids and made a full recovery., Clinical Relevance: To the authors' knowledge, this was the first reported case of adrenocortical hemorrhage following administration of a synthetic ACTH analog in a dog. This should be considered as a rare potential complication of ACTH stimulation testing.

Objectives: To assess the relative productivity of primary medical services in England and the impact of the COVID-19 pandemic on productivity levels., Setting: Primary medical services for 59 million patients (98% of the population in England), in 101 clinical commissioning groups (CCGs), across two time periods: period 1, pre-pandemic, April to December 2019 and period 2, pandemic, April to December 2020., Methods: We use data envelopment analysis (DEA) to assess relative productivity with four input measures (the number of full-time equivalent general practitioners, nurses, other direct patient contact staff and administrators), and five output measures (face-to-face appointments, remote consultations, home visits, referrals to secondary care and prescriptions). Our units of analysis were CCGs. DEA assigns an efficiency score to a CCG, taking a value between 0 and 100%, by benchmarking it against the most productive CCGs. We use Tobit regression to examine the association between productivity and other factors., Results: The mean bias-corrected efficiency score of primary medical services in CCGs was 92.9% (interquartile range 92.0% to 95.7%) in period 1, falling to 90.6% (interquartile range 86.8% to 95.2%) in period 2. In period 1, CCGs with a higher proportion of registered patients aged over 65 years, higher levels of deprivation, lower levels of disease prevalence, higher nurse to GP ratios and higher GP to other direct patient contact staff ratios, achieved statistically significantly higher general practice efficiency scores (p < 0.05). In period 2, only the ratio of GP to other direct patient contact staff was associated with efficiency scores (p > 0.05)., Conclusions: Our analysis indicates only modest geographic variation in productivity of primary medical services when measured at the level of clinical commissioning groups and a small reduction in productivity during the pandemic. Further work to establish relative productivity of individual GP practices is warranted once sufficient data on appointment rates by GP practice is available., (© 2023. Crown.)

Objective: The objective is to quantify the rate of opioid and benzodiazepine prescribing for the diagnosis of shoulder osteoarthritis across a large healthcare system and to describe the impact of a clinical decision support intervention on prescribing patterns., Design: A prospective observational study., Setting: One large healthcare system., Patients and Participants: Adult patients presenting with shoulder osteoarthritis., Interventions: A clinical decision support intervention that presents an alert to prescribers when patients meet criteria for increased risk of opioid use disorder., Main Outcome Measure: The percentage of patients receiving an opioid or benzodiazepine, the percentage who had at least one risk factor for misuse, and the percent of encounters in which the prescribing decision was influenced by the alert were the main outcome measures., Results: A total of 5,380 outpatient encounters with a diagnosis of shoulder osteoarthritis were included. Twenty-nine percent (n = 1,548) of these encounters resulted in an opioid or benzodiazepine prescription. One-third of those who received a prescription had at least one risk factor for prescription misuse. Patients were more likely to receive opioids from the emergency department or urgent care facilities (40 percent of encounters) compared to outpatient facilities (28 percent) (p < .0001). Forty-four percent of the opioid prescriptions were for "potent opioids" (morphine milliequivalent conversion factor > 1). Of the 612 encounters triggering an alert, the prescribing decision was influenced (modified or not prescribed) in 53 encounters (8.7 percent). All but four (0.65 percent) of these encounters resulted in an opioid prescription., Conclusion: Despite evidence against routine opioid use for osteoarthritis, one-third of patients with a primary diagnosis of glenohumeral osteoarthritis received an opioid prescription. Of those who received a prescription, over one-third had a risk factor for opioid misuse. An electronic clinic decision support tool influenced the prescription in less than 10 percent of encounters.

γ-herpesviruses (γHVs) encode BCL2 homologues (vBCL2) that bind the Bcl-2 homology 3 domains (BH3Ds) of diverse proteins, inhibiting apoptosis and promoting host cell and virus survival. vBCLs encoded by Kaposi sarcoma-associated HV (KSHV) and γHV68 downregulate autophagy, a degradative cellular process crucial for homeostasis and innate immune responses to pathogens, by binding to a BH3D in BECN1, a key autophagy protein. Epstein-Barr virus (EBV) encodes a vBCL2 called BHRF1. Here we show that unlike the KSHV and γHV68 vBCL2s, BHRF1 does not bind the isolated BECN1 BH3D. We use yeast two-hybrid assays to identify the minimal region of BECN1 required and sufficient for binding BHRF1. We confirm that this is a direct, albeit weak, interaction via affinity pull-down assays and isothermal titration calorimetry. To understand the structural bases of BHRF1 specificity, we determined the 2.6 Å crystal structure of BHRF1 bound to the BID BH3D, which binds ∼400-times tighter to BHRF1 than does BECN1, and performed a detailed structural comparison with complexes of diverse BH3Ds bound to BHRF1 and to other antiapoptotic BCL2s. Lastly, we used mammalian cell autophagy assays to demonstrate that BHRF1 downregulates autophagy and that a cell-permeable peptide derived from the BID BH3D inhibits BHRF1-mediated downregulation of autophagy. In summary, our results suggest that BHRF1 downregulates autophagy by noncanonical binding of a flexible region of BECN1 that includes but is not limited to the BH3D and that BH3D-derived peptides that bind better to BHRF1 can block downregulation of autophagy by BHRF1.

Background: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect., Methods: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages., Results: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation., Conclusions: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step., Trial Registration: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049., Competing Interests: Declaration of Competing Interest Prof. Naomi Fineberg reports in the past 3 years she has held research or networking grants from the UK NIHR, COST Action, Orchard; accepted travel and/or hospitality expenses from the BAP, ECNP, RCPsych, CINP, International Forum of Mood and Anxiety Disorders, World Psychiatric Association; received payment from Elsevier for editorial duties and the Mental Health Academy for lecturing. Previously, she has accepted paid speaking engagements in various industry supported symposia and recruited patients for various industry-sponsored studies in the field of OCD treatment. She leads an NHS treatment service for OCD. She holds Board membership for various registered charities linked to OCD. She gives expert advice on psychopharmacology to the UK MHRA. She has participated in a WHO working group focussing on diagnosis and classification of obsessive compulsive or related disorders for the ICD-11. Eduardo Cinosi, Megan Smith, Amanda Busby, Ibrahim Aslan, Arun Enara, Kabir Garg, Matthew Garner, Robert Gordon, Natalie Hall, Nathan Huneke, Daniel Meron, David Wellsted, Solange Wyatt and Luca Pellegrini have no competing interests to declare. Prof. Trevor W Robbins provides consultancy for Cambridge Cognition and receives royalties for CANTAB. He offers consultancy for Arcadia, Takeda, Cassava, Greenfield Bioventures. He has received research grants from Shionogi and GlaxoSmithKline. He has received Editorial Honoraria from Springer, Nature and Elsevier. Prof. David S. Baldwin is a Medical Patron of Anxiety UK and was Clinical Advisor to the National Clinical Audit of Anxiety and Depression (2017–20). He receives an editorial fee from Wiley for his work with Human Psychopharmacology., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Early detection of firearm discharge has become increasingly critical for situational awareness in both civilian and military domains. The ability to determine the location and model of a discharged firearm is vital, as this can inform effective response plans. To this end, several gunshot audio datasets have been released that aim to facilitate gunshot detection and classification of a discharged firearm based on acoustic signatures. However, these datasets often suffer from a lack of variety in the orientations of recording devices around the source of the gunshot. Additionally, these datasets often suffer from the absence of proper time synchronization, which prevents the usage of these datasets for determining the Direction of Arrival (DoA) of the sound. In this paper, we present a multi-firearm, multi-orientation time-synchronized audio dataset collected in a semi-controlled real-world setting - providing us a degree of supervision - using several edge devices positioned in and around an outdoor firing range., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Spaceflight presents a multifaceted environment for plants, combining the effects on growth of many stressors and factors including altered gravity, the influence of experiment hardware, and increased radiation exposure. To help understand the plant response to this complex suite of factors this study compared transcriptomic analysis of 15 Arabidopsis thaliana spaceflight experiments deposited in the National Aeronautics and Space Administration's GeneLab data repository. These data were reanalyzed for genes showing significant differential expression in spaceflight versus ground controls using a single common computational pipeline for either the microarray or the RNA-seq datasets. Such a standardized approach to analysis should greatly increase the robustness of comparisons made between datasets. This analysis was coupled with extensive cross-referencing to a curated matrix of metadata associated with these experiments. Our study reveals that factors such as analysis type (i.e., microarray versus RNA-seq) or environmental and hardware conditions have important confounding effects on comparisons seeking to define plant reactions to spaceflight. The metadata matrix allows selection of studies with high similarity scores, i.e., that share multiple elements of experimental design, such as plant age or flight hardware. Comparisons between these studies then helps reduce the complexity in drawing conclusions arising from comparisons made between experiments with very different designs., (© 2023. The Author(s).)

Background: Telehealth usage has been promoted in all settings but has been identified as a panacea to issues of access and equity in the rural context. However, uptake and widespread integration of telehealth across all parts of the health system has been slow, with a myriad of barriers documented, including in rural settings. The crisis of the COVID-19 pandemic, saw barriers rapidly overturned with the unprecedented and exponential rise in telehealth usage. The uniqueness of the crisis forced telehealth adoption, but as the urgency stabilises, pandemic learnings must be captured, utilised, and built upon in a post-pandemic world. The aim of this study was to document staff experiences and perceptions of delivering rural psychological therapies via telehealth during the pandemic and to capture learnings for future rural telehealth delivery., Methods: An online cross-sectional survey that explored mental health professional's experiences, use, and perceptions of telehealth before and after pandemic-enforced changes to service delivery., Results: Sixty-two respondents completed the questionnaire (response rate 68%). Both the delivery of telehealth via telephone and online video conferencing significantly increased during the pandemic (66% vs 98%, p < .001 for telephone and 10% vs 89%, p < 0.001 for online video). Respondents indicated that client's access to services and attendance had improved with telehealth use but their attention and focus during sessions and non-verbal communication had been negatively affected. The challenges for older adults, people with learning and sensory disabilities, and residents in remote areas with poorer mobile/internet connectivity were identified. Despite these challenges, none of the respondents indicated a preference to return to fully face-to-face service delivery with most (86%) preferring to deliver psychological therapies fully or mostly via telehealth., Conclusions: This study addresses three major gaps in knowledge: the experience of delivering local telehealth solutions to address rural mental health needs, the provision of strong rural-specific telehealth recommendations, and the dearth of rural research emanating from the United Kingdom. As the world settles into a living with COVID-19 era, the uniqueness of the rural telehealth context may be forgotten as urban myopia continues to dominate telehealth policy and uptake. It is critical that rural resourcing and digital connectivity are addressed., (© 2023. The Author(s).)

Objective: To investigate the time to treatment initiation (TTI) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients after diagnosis in Indonesia and biological, psychological and social factors associated with the time interval., Methods: This study was conducted in Persahabatan Hospital, Jakarta using a mixed-methods approach. Registry data and medical records of MDR/RR-TB patients were collected and matched (hospital dataset), and linked with psychosocial assessment results (linked dataset). Descriptive analysis was conducted to understand patient characteristics and the distribution of TTI after RR-TB diagnosis by GeneXpert. Generalised linear regression was used to analyse factors associated with delay duration, and logistic regression to explore factors associated with the delay longer than the median duration for both datasets (basic vs. extended model). In-depth interviews were conducted with patients and healthcare workers to understand the procedure of treatment initiation and how different factors led to delay., Results: The hospital dataset included 275 patient-matched cases, and 188 were further linked with psychosocial assessment results. The median time interval was 24 days [interquartile range (IQR) 23.5] and 26 days (IQR 21.25), respectively. Regression analysis showed that in the extended model, comorbidities (exp [coefficient]= 1.93), unemployment (exp [coefficient] = 1.80) and poor knowledge of MDR/RR-TB (exp (coefficient) = 1.67) seemed to have the strongest effects on prolonging the time interval (p < 0.05). Unsuccessful TB treatment history was the only factor that significantly increased the risk of delay longer than the median duration (p < 0.05) in the basic model, while none of the factors were significant in the extended model. The qualitative study identified provider-side factors (centralised service provision and insufficient human resources) and patient-side factors (physical weakness, psychological stress and financial concern) associated with treatment delay., Conclusion: MDR/RR-TB patients in Persahabatan Hospital, Jakarta, Indonesia waited around 25 days for treatment initiation after RR-TB diagnosis. Health system solutions are needed to address challenges facing both MDR/RR-TB patients and healthcare providers to reduce delay in treatment initiation., (© 2022 John Wiley & Sons Ltd.)

This paper presents learnings from trauma recovery mechanisms and social movements from around the world relating to a survivor's role and as such- their agency. It unpacks various conceptual frameworks as possible alternative, effective and strategic pathways in torture rehabilitation. Ongoing and new challenges such as resourcing, cultural adaptability limitations, lack of access to services and inhumane foreign policies pose barriers to established systems that render some practices inadequate in terms of meaningful service delivery or social impact for torture survivors (Wheildon et al., 2022, p. 1689). It is well documented that "Torture aims to dehumanise survivors through calculated acts of cruelty to remove the survivors' dignity and make them powerless." (Luci and Di Rado, 2020, p. 3). As such this paper deliberately straddles multiple thematic fields, all grappling with relatable notions of restoring power or agency to survivors. At the risk of discursiveness into fields beyond torture rehabilitation then, this paper aims to showcase and learn from other successful movements. It also invites you as the reader into this discourse of inquiry and self-reflection, in order to counter the ten- dency of assuming a prescriptive, blanket (or blank) meaning of survivor engagement activities. Its findings suggest the manifestation of bespoke programming according to context and survivors' needs. It does not suggest a systematic overhaul, but rather a shift of incremental and cumulative changes that are recognised as advantageous. This paper deep dives into theories on agency, looking firstly at the broader archetypes that provide commonality and structure before then exploring particularities from different contexts. Implications for practice are then discussed, with nuances drawn out from the findings.

Introduction: While the literature encourages engaging torture survivors in the direction and provision of services, little is known about how best to do this., Method: We surveyed 82 member centres of the International Rehabilitation Council for TortureVictims (IRCT), a worldwide network of anti-torture organisations, and interviewed fourteen staff members and executive directors about current practices, best practices, and the advantages and disadvantages of engaging survivors., Results: While few agencies involve survivors extensively, those that did found survivor engagement helped agencies engage in better planning, service provision, and advocacy, while at the same time being healing and empowering for survivors. Agency staff described strategies to minimize retraumatization, particularly in not encouraging survivors to share the story of their trauma, but to engage in other ways. Agency staff suggested a number of ways to engage survivors in program direction, service provision, and advocacy, which included having survivors serve on the board of directors, hiring survivors as staff, involving survivors in advocacy, advising staff and volunteers on how better to provide services, and working as community outreach workers and mediators., Conclusion: IRCT member centres can engage survivors in programming without retraumatizing them, and there are many advantages to doing so.

Objectives: The Veterans Administration (VA) Mobility Screening and Solutions Tool (VA MSST) was developed to screen a patient's safe mobility level 'in the moment' and provide clinical decision support related to the use of safe patient handling and mobility (SPHM) equipment. This evidence-based flowchart tool is a common language tool that enables any healthcare worker at any time to accurately measure and communicate patient mobility and transfer equipment needs across disciplines and settings., Methods: The VA MSST has four levels and differentiates between the need for powered and non-powered equipment depending on the patient's independence. Subject matter experts wrote scenarios for interrater reliability and validity testing. The initial VA MSST draft iteration was reviewed by 163 VA staff (mostly physical therapists and occupational therapists) amongst simulation scenarios and provided content validity, and additional insight and suggestions. Revisions were made to create the final VA MSST which was evaluated by over 200 healthcare workers from varied disciplines (including medical doctors, advanced practice registered nurses, registered nurses, licensed practical nurses, certified nursing assistants, occupational therapists, physical therapists, speech therapists, radiology and ultrasound technicians, etc.). An instruction video and eighteen scenario videos were embedded in an online survey. The survey intended to demonstrate the interrater reliability and validity (concurrent and construct) of the VA MSST. Over 500 VA staff (raters) received a survey invitation via email., Results: Raters (N = 230) from multiple disciplines and healthcare settings independently screened patient mobility status for each of 18 scenarios using the VA MSST. The raters were diverse in their age and years of experience. The estimated interrater reliability (IRR) for VA MSST was excellent and statistically significant with an estimated Krippendorff's alpha (ICC (C, k)) of 0.998 [95% CI: 0.996-0.999]. Eighty-two percent of raters reported that overall VA MSST instructions were clear or very clear and understandable. VA MSST ratings made by technicians and nursing assistants group correlated strongly (r = 0.99, p < 0.001) with the 'gold standard' (experienced physical therapists), suggesting a high concurrent validity of the tool. The VA MSST significantly discriminated between the different levels of patient mobility required for safe mobilization as intended (each difference, p < 0.0001); this suggests a good construct validity., Conclusions: The VA MSST is an evidence-based flowchart screening and decision support tool that demonstrates excellent interrater reliability across disciplines and settings. VA MSST has strong face and content validity, as well as good concurrent and construct validity., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: This study reports on the impact of a clinical decision support tool embedded in the electronic medical record and characterizes the demographics, prescribing patterns, and risk factors associated with opioid and benzodiazepine misuse in the older adult population., Significance: This study reports on prescribing patterns for patients ≥65 years-old who presented to Emergency Departments (ED) or Urgent Care (UC) facilities across a large healthcare system following a fall (n = 34,334 encounters; n = 25,469 patients). This system implemented a clinical decision support intervention which provides an alert when the patient has an evidence-based risk factor for prescription drug misuse; prescribers can continue, amend or cancel the prescription., Results: Of older adults presenting with a fall, 31.4% (N = 7986) received an opioid or benzodiazepine prescription. Women and younger patients (65-74) had a higher likelihood of receiving a prescription ( P < .0001). 11% had ≥1 risk factor. Women were more likely to receive an early refill ( P = .0002) and younger (65-74) men were more likely to have a past positive toxicology ( P < .0001). A prescription was initiated in 8,591 encounters, and 946 (9.0%) triggered an alert. In 58 cases, the alert resulted in a prescription modification, and in 80 the prescription was canceled., Conclusions: Documented risk for opioid misuse in the elderly was 10% among patients presenting to the ED/UC after a fall. The dangers associated with opioid/benzodiazepine use increase with age as does fall risk. Awareness of risk factors is an important first step; more work is needed to address potentially hazardous prescriptions in this population., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Madhav Karunakar, MD: Consultancy for Osteocentric Technologies, Speakers Bureau for Johnson and Johnson (AO). Joseph R. Hsu, MD: Consultancy for Globus Medical and personal fees from Smith and Nephew speakers’ bureau. Michael Bosse, MD: Stock ownership in an orthopaedic implant company and a grant from the Department of Defense. Christopher Griggs, MD: Board membership for American College of Emergency Physicians; payment from Boston University for preparation of pain management and opioid prescribing educational materials. Daniel Leas, MD: Consultancy for Restor3d and ownership in Pressio. Michael Runyon, MD: Research fundign from Abbot Laboratories and Bristol-Myers Squibb., (© The Author(s) 2022.)

Objectives: To examine the frequency and distribution of infant feeding-related presentations at emergency departments (EDs) before and during the SARS-CoV-2 pandemic., Setting: Attendances at 48 major EDs in England in two 50-week periods before and during the COVID-19 pandemic: period 1, April 2, 2019 to March 10, 2020 and period 2, April 1, 2020 to March 10, 2021., Methods: We estimated the change in frequency of ED presentations by age group and diagnosis before and after the start of the SARS-CoV-2 pandemic in England. We compared changes in the frequency of attendances of infant-feeding related presentations by infant age, sex, ethnicity, deprivation, rurality, arrival mode, arrival time, acuity, mother's age, gravidity and mental health, birth length of stay, attendance duration, and disposal (i.e., admission or discharge)., Results: While total ED attendances fell by 16.7% (95% CI -16.8% to -16.6%), infant attendances increased for feeding problems (+7.5% 95% CI 2.3% to 13.0%), neonatal jaundice (+12.8%, 95% CI 3.3% to 23.3%) and gastro-esophageal reflux (+9.7%, 95% CI 4.4% to 15.2%). These increases were more pronounced amongst first babies (+22.4%, 95% CI 13.1% to 32.5%), and where the stay in hospital after birth was brief (0-1 days, +20.1%, 95% CI 14.8% to 25.7%). Our analysis suggests that many of these attendances were of low acuity., Conclusions: While ED attendances reduced dramatically and systematically with the COVID-19 pandemic, presentations for infant feeding issues increased, implying growth in the unmet needs of new mothers and infants., Competing Interests: SR has been a member of the NICE Maternal and Child Nutrition Guideline Specialist Committee since 2022., (Copyright © 2022, Wyatt et al.)

Background: Elective hip replacement is a cost-effective means of improving hip function. Previous research has suggested that the supply of hip replacements in the NHS is governed by the inverse care law. We examine whether inequities in supply improved in England and Wales between 2006 and 2016., Methods: We compare levels of need and supply of NHS funded hip replacements to adults aged 50+ years, across quintiles of deprivation in England and Wales between 2006 and 2016. We use data from routine health records and a large longitudinal study and adjust for age and sex using general additive negative-binomial regression., Findings: The number of NHS-funded hip replacements per 100,000 population rose substantially from 272.6 and 266.7 in 2002, to 539.7 and 466.3 in 2018 in England and Wales respectively. Having adjusted for age and sex, people living in the most deprived quintile were 2.36 (95% CI, 1.69 to 3.29) times more likely to need a hip replacement in 2006 than those living in quintile 3, whereas those living in the least deprived quintile were 0.45 (95% CI, 0.39 to 0.69) as likely. Despite this, people living in the most deprived quintile were 0.81 (95% CI, 0.78 to 0.83) times as likely in England and 0.93 (95% CI, 0.84 to 1.04) as likely in Wales to receive an NHS-funded hip replacement in 2006 than those living in quintile 3. We found no evidence that these substantial inequities had reduced between 2006 and 2016., Interpretation: With respect to hip-replacement surgery in England and Wales, policy ambitions to reduce healthcare inequities have not been realised., Funding: This work was supported by Health Data Research UK., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 Published by Elsevier Ltd.)

In the central nervous system, most neurons co-express TrkB and TrkC, the tyrosine kinase receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3). As NT3 can also activate TrkB, it has been difficult to understand how NT3 and TrkC can exert unique roles in the assembly of neuronal circuits. Using neurons differentiated from human embryonic stem cells expressing both TrkB and TrkC, we compared Trk activation by BDNF and NT3. To avoid the complications resulting from TrkB activation by NT3, we also generated neurons from stem cells engineered to lack TrkB. We found that NT3 activates TrkC at concentrations lower than those of BDNF needed to activate TrkB. Downstream of Trk activation, the changes in gene expression caused by TrkC activation were found to be similar to those resulting from TrkB activation by BDNF, including a number of genes involved in synaptic plasticity. At high NT3 concentrations, receptor selectivity was lost as a result of TrkB activation. In addition, TrkC was down-regulated, as was also the case with TrkB at high BDNF concentrations. By contrast, receptor selectivity as well as reactivation were preserved when neurons were exposed to low neurotrophin concentrations. These results indicate that the selectivity of NT3/TrkC signalling can be explained by the ability of NT3 to activate TrkC at concentrations lower than those needed to activate TrkB. They also suggest that in a therapeutic perspective, the dosage of Trk receptor agonists will need to be taken into account if prolonged receptor activation is to be achieved., (© 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Opioids are frequently used for acute pain management of musculoskeletal injuries, which can lead to misuse and abuse. This study aimed to identify the opioid prescribing rate for ankle fractures treated nonoperatively in the ambulatory and emergency department setting across a single healthcare system and to identify patients considered at high risk for abuse, misuse, or diversion of prescription opioids that received an opioid. A retrospective cohort study was performed at a large healthcare system. The case list included nonoperatively treated emergency department, urgent care and outpatient clinic visits for ankle fracture and was merged with the Prescription Reporting With Immediate Medication Mapping (PRIMUM) database to identify encounters with prescription for opioids. Descriptive statistics characterize patient demographics, treatment location and prescriber type. Rates of prescribing among subgroups were calculated. There were 1,324 patient encounters identified, of which, 630 (47.6%) received a prescription opioid. The majority of patients were 18-64 years old (60.3%). Patients within this age range were more likely to receive an opioid prescription compared to other age groups (p < .0001). Patients treated in the emergency department were significantly more likely to receive an opioid medication (68.3%) compared to patients treated at urgent care (33.7%) or in the ambulatory setting (16.4%) (p < .0001). Utilizing the PRIMUM tool, 14.2% of prescriptions were provided to patients with at least one risk factor. Despite the recent emphasis on opioid stewardship, 14.2% of patients with risk factors for misuse, abuse, or diversion received opioid analgesics in this study, identifying an area of improvement for prescribers., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: This study investigates the distribution of the workforce of one large National Health Service (NHS) employer in relation to socioeconomic deprivation and how sickness absence rates varied across these levels of deprivation., Design: Share of the working age population that was employed at the NHS organisation mapped by area deprivation. The study used negative binomial regression models to investigate the extent to which wage level, occupational group and area deprivation were associated with sickness absence among employees., Setting: The study used electronic staff records (2018-2019) of a large NHS organisation in the North West of England., Results: In the most deprived areas, an additional person per 1000 working age population were employed at this NHS organisation compared with the most affluent areas. Employees from the most deprived quintile had 1.41 (95% CI 1.16 to 1.70) times the higher sickness rates than the employees from the least deprived quintile, when adjusting for age and sex. These differences were largely explained by differences in wage levels and occupation groups, with the lowest wage employees having 2.5 (95% CI 1.87 to 3.42) times the sickness absence rate as the highest wage group and the nursing and midwifery employees having 1.8 (95% CI 1.50 to 2.24) times the sickness absence rate as the administrative and clerical group., Conclusion: This large NHS organisation employed people disproportionately from deprived areas. They were considerably more likely to experience sickness absence compared with people from affluent areas. This appears to be because they were more likely to be in lower wage employment and employed in nursing and nursing assistant. Workplace health policies need to target these workers, adapting to their needs while enabling improvements in their working conditions, pay and career progression., Competing Interests: Competing interests: BB and KD are supported by the NIHR Applied Research Collaboration North West Coast; BB is supported by the NIHR School for Public Health Research; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Posttraumatic stress disorder (PTSD) is associated with higher rates of chronic pain and increased risk of developing Opioid use disorder. This paper evaluates the impact of PRIMUM, an electronic health record-embedded (EHR) clinical decision support intervention on opioid prescribing patterns for patients with diagnosis of PTSD., Methods: Inpatient, emergency department (ED), urgent care, and outpatient encounters with ICD-10 codes F43.1 (PTSD), F43.10 (PTSD, unspecified), F43.11 (PTSD, acute), and F43.12 (PTSD, chronic) at Atrium Health between 1/1/2016 and 12/29/2018 were included in the study., Results: A total of 3121 patients with a diagnosis of PTSD were seen in 37,443 encounters during the study period. Ten percent (n = 3761) of the encounters resulted in prescriptions for opioids and PRIMUM alerts were triggered in 1488 of these encounters. These alerts resulted in "decision influenced" for 17% of patients (n = 255) or no prescriptions for opioids or benzodiazepines for 5.8% (n = 86). The majority of the prescriptions were below 50 Morphine milligram equivalents (MME)/day, but there were 570 (15.5%) prescriptions for doses of 50-90 MME and 721 (19.6%) prescriptions for >90 MME/day., Discussion and Conclusion: The PRIMUM alert system helps improve patient safety. PRIMUM affected clinician decisions 17% of the time, and the effect was greater in patients with opioid overdose history and those presenting for early refills., Scientific Significance: The effectiveness of clinical support interventions for opioid prescribing for patients with PTSD has not been documented previously. Our findings provide novel evidence that the EHR can be used to improve patient safety among patients with PTSD in the context of substance use., (© 2022 American Academy of Addiction Psychiatry.)

Background: We investigate whether admission from a consultant-led ED is associated with ED occupancy or crowding and inpatient (bed) occupancy., Methods: We used general additive logistic regression to explore the relationship between the probability of an ED patient being admitted, ED crowding and inpatient occupancy levels. We adjust for patient, temporal and attendance characteristics using data from 13 English NHS Hospital Trusts in 2019. We define quintiles of occupancy in ED and for four types of inpatients: emergency, overnight elective, day case and maternity., Results: Compared with periods of average occupancy in ED, a patient attending during a period of very high (upper quintile) occupancy was 3.3% less likely (relative risk (RR) 0.967, 95% CI 0.958 to 0.977) to be admitted, whereas a patient arriving at a time of low ED occupancy was 3.9% more likely (RR 1.039 95% CI 1.028 to 1.050) to be admitted. When the number of overnight elective, day-case and maternity inpatients reaches the upper quintile then the probability of admission from ED rises by 1.1% (RR 1.011 95% CI 1.001 to 1.021), 3.8% (RR 1.038 95% CI 1.025 to 1.051) and 1.0% (RR 1.010 95% CI 1.001 to 1.020), respectively. Compared with periods of average emergency inpatient occupancy, a patient attending during a period of very high emergency inpatient occupancy was 1.0% less likely (RR 0.990 95% CI 0.980 to 0.999) to be admitted and a patient arriving at a time of very low emergency inpatient occupancy was 0.8% less likely (RR 0.992 95% CI 0.958 to 0.977) to be admitted., Conclusions: Admission thresholds are modestly associated with ED and inpatient occupancy when these reach extreme levels. Admission thresholds are higher when the number of emergency inpatients is particularly high. This may indicate that riskier discharge decisions are taken when beds are full. Admission thresholds are also high when pressures within the hospital are particularly low, suggesting the potential to safely reduce avoidable admissions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Almost all pregnant people in Sri Lanka receive antenatal care by public health midwives. While there is strong infrastructure in Sri Lanka for postpartum mental health care, the current practices within antenatal mental health care have not been externally evaluated. The purpose of this study is to investigate the current clinical guidelines and experiences of how public health midwives diagnose and treat antenatal depression., Methods: We conducted in-depth interviews with 12 public health midwives from four antenatal clinics in the Bope Poddala division in Galle, Sri Lanka and reviewed and extracted information on antenatal depression from clinical guidelines. Data was collected in Sinhala and translated into English. We used applied thematic analysis and worked closely with our local team to ensure data trustworthiness., Results: Midwives (n = 12) reported varying degrees of knowledge on antenatal depression and did not have standardized diagnosis patterns. However, they were very consistent in their clinical practices, following guidelines for referral and follow-up of case management, building strong rapport. In their practice, midwives continue to face challenges of lack of human resources and high stigma around mental illness. They suggested that that care could be improved with use of a standardized diagnostic tool, and easier access to specialist care. We found the clinical guideline on the diagnosis and treatment of antenatal depression is lacking key details on symptoms for appropriate diagnosis, but it clearly guides on how to navigate treatment., Conclusions: Public health midwives are following the clinical guideline to refer pregnant women who need intervention for antenatal depression and follow-up for case management. However, there is a need for more specific and context-relevant guidelines, especially for diagnosis of antenatal depression. Formative research is needed to explore intervention strategies to improve antenatal depression management in Sri Lanka., (© 2022. The Author(s).)

Background: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder which often proves refractory to current treatment approaches. Transcranial direct current stimulation (tDCS), a noninvasive form of neurostimulation, with potential for development as a self-administered intervention, has shown potential as a safe and efficacious treatment for OCD in a small number of trials. The two most promising stimulation sites are located above the orbitofrontal cortex (OFC) and the supplementary motor area (SMA)., Methods: The aim of this feasibility study is to inform the development of a definitive trial, focussing on the acceptability, safety of the intervention, feasibility of recruitment, adherence and tolerability to tDCS and study assessments and the size of the treatment effect. To this end, we will deliver a double-blind, sham-controlled, crossover randomised multicentre study in 25 adults with OCD. Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated and given in counterbalanced order. Each course comprises four 20-min stimulations, delivered over two consecutive days, separated by at least 4 weeks' washout period. We will collect information about recruitment, study conduct and tDCS delivery. Blinded raters will assess clinical outcomes before, during and up to 4 weeks after stimulation using validated scales. We will include relevant objective neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning., Discussion: We will analyse the magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure, to estimate effect size and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Additionally, qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, as well as the impact on their overall quality of life. These clinical outcomes will enable the project team to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the treatment in a full-scale trial., Trial Registration: ISRCTN17937049 . (date applied 08/07/2019). Recruitment (ongoing) began 23rd July 2019 and is anticipated to complete 30th April 2021., (© 2021. The Author(s).)

Background: The needs of children in care are a government priority, yet the evidence base for effective interventions to support the emotional wellbeing of children in care is lacking. Research suggests that supporting the carer-child relationship, by promoting the carer's reflective parenting, may be an effective approach to improving the wellbeing of these children., Methods: The study comprises a definitive, superiority, two-armed, parallel, pragmatic, randomised controlled trial, with embedded process evaluation and economic evaluation, and an internal pilot, to evaluate the effectiveness, and cost-effectiveness, of the Reflective Fostering Programme. Randomisation is at the individual level using a 1:1 allocation ratio. The study is being conducted in local authority sites across England, and is targeted at foster carers (including kinship carers) looking after children aged 4 to 13. Consenting participants are randomly allocated to the Reflective Fostering Programme (intervention arm) in addition to usual support or usual support alone (control arm). The primary outcome is behavioural and emotional wellbeing of the child 12 months post-baseline, and secondary outcomes include the following: foster carer's level of stress, quality of life, reflective capacity, compassion fatigue and burnout, placement stability, the quality of the child-carer relationship, child's capacity for emotional regulation, and achievement of personalised goals set by the carer., Discussion: A feasibility study has indicated effectiveness of the Programme in improving the child-carer relationship and emotional and behavioural wellbeing of children in care. This study will test the effectiveness and cost-effectiveness of implementing the Reflective Fostering Programme as an additional aid to the support already available to local authority foster carers., Trial Registration: ISRCTN 70832140 ., (© 2021. The Author(s).)

Nontarget data acquisition for target analysis (nDATA) workflows using liquid chromatography-high-resolution accurate mass (LC-HRAM) spectrometry, spectral screening software, and a compound database have generated interest because of their potential for screening of pesticides in foods. However, these procedures and particularly the instrument processing software need to be thoroughly evaluated before implementation in routine analysis. In this work, 25 laboratories participated in a collaborative study to evaluate an nDATA workflow on high moisture produce (apple, banana, broccoli, carrot, grape, lettuce, orange, potato, strawberry, and tomato). Samples were extracted in each laboratory by quick, easy, cheap, effective, rugged, and safe (QuEChERS), and data were acquired by ultrahigh-performance liquid chromatography (UHPLC) coupled to a high-resolution quadrupole Orbitrap (QOrbitrap) or quadrupole time-of-flight (QTOF) mass spectrometer operating in full-scan mass spectrometry (MS) data-independent tandem mass spectrometry (LC-FS MS/DIA MS/MS) acquisition mode. The nDATA workflow was evaluated using a restricted compound database with 51 pesticides and vendor processing software. Pesticide identifications were determined by retention time ( t R , ±0.5 min relative to the reference retention times used in the compound database) and mass errors (δ M ) of the precursor (RTP, δ M ≤ ±5 ppm) and product ions (RTPI, δ M ≤ ±10 ppm). The elution profiles of all 51 pesticides were within ±0.5 min among 24 of the participating laboratories. Successful screening was determined by false positive and false negative rates of <5% in unfortified (pesticide-free) and fortified (10 and 100 μg/kg) produce matrices. Pesticide responses were dependent on the pesticide, matrix, and instrument. The false negative rates were 0.7 and 0.1% at 10 and 100 μg/kg, respectively, and the false positive rate was 1.1% from results of the participating LC-HRAM platforms. Further evaluation was achieved by providing produce samples spiked with pesticides at concentrations blinded to the laboratories. Twenty-two of the 25 laboratories were successful in identifying all fortified pesticides (0-7 pesticides ranging from 5 to 50 μg/kg) for each produce sample (99.7% detection rate). These studies provide convincing evidence that the nDATA comprehensive approach broadens the screening capabilities of pesticide analyses and provide a platform with the potential to be easily extended to a larger number of other chemical residues and contaminants in foods.

Background: There is a high prevalence of antenatal depression in low-or-middle-income countries, but information about risk factors in these settings is still lacking. The purpose of this study is to measure the prevalence of and explore risk factors associated with antenatal depressive symptoms in Galle, Sri Lanka., Methods: This study used a mixed-method approach. The quantitative portion included 505 pregnant women from Galle, Sri Lanka, with health record data, responses to psychometric questionnaires (MSPSS and PRAQ-R2), and antenatal depression screening (EPDS). The qualitative portion included interviews with public health midwives about their experiences and routine clinical practices with women with antenatal depressive symptoms., Results: Prevalence of antenatal depressive symptoms was 7.5%, highest in women over the age of 30 (13.0%, OR = 3.88, 95%CI = 1.71 - 9.97), with diabetes (21.9%, OR = 3.99, 95%CI = 1.50 - 9.56), or pre-eclampsia in a previous pregnancy (19.4%, OR = 3.32, 95%CI = 1.17 - 8.21). Lower prevalence was observed in the primiparous (3.3%, OR = 0.29, 95%CI = 0.12 - 0.64) employed outside the home (3.6%, OR = 0.33, 95%CI = 0.13 - 0.72), or upper-middle class (2.3%, OR = 0.17, 95%CI = 0.04 - 0.56). Anxiety levels were elevated in depressed women (OR = 1.13, 95%CI = 1.07 - 1.20), while perceived social support was lower (OR = 0.91, 95%CI = 0.89 - 0.93). After multivariable adjustment, only parity (OR = 0.20, 95%CI 0.05 - 0.74) and social support from a "special person" (OR = 0.94, 95%CI = 0.77 - 0.95) remained significantly associated with depressive symptoms. Qualitative findings also identified antenatal health problems and poor social support as risk factors for depressive symptoms. They also identified different contributing factors to poor mental health based on ethnicity, higher stress levels among women working outside the home, and misinformation about health conditions as a cause of poor mental health., Conclusions: Prevalence of antenatal depressive symptoms in Galle is lower than the recorded prevalence in other regions of Sri Lanka. Risk factors for antenatal depressive symptoms were identified on biological, psychological, and social axes. These variables should be considered when developing future guidelines for mental health and obstetric treatment in this context., (© 2021. The Author(s).)

Resistance to algae contamination is an important characteristic of insulators used in overhead power distribution in coastal environments. It is therefore important to understand the parameters governing algae adhesion onto polymer insulator materials such as silicone. Flow cell-based shear experiments were conducted in order to characterize the adhesion strength of algae onto polydimethylsiloxane surfaces, comparing fresh polymer substrates with those that have been soaked in water and saline solutions for 1 month. Both freshwater algae and seawater species could withstand considerably less drag force and were therefore more easily removed when the polymer was soaked in salt water. The polymer surface was found to be unaltered in terms of its roughness, contact angle, and lack of water uptake; no macroscopic surface characterization was therefore able to account for the differences in cell adhesion strength resulting from the soaking treatment. Surface-specific nonlinear vibrational spectroscopy, however, revealed subtle differences in the orientation of surface methyl groups that resulted from the water and saline exposure.

Introduction: Caesarean section (C-section) has been a public health concern globally. This study investigated the change in C-section rate in 1998-2017 in Indonesia and explored the socioeconomic, geographic and health system factors associated with the use of C-section., Methods: We analysed data from demographic health surveys in 2002-2003, 2007, 2012 and 2017 in Indonesia. We included women who reported giving birth within 5 years of each round of the survey (n=56 462) into the analysis. Cross-tabulation was used to examine change of C-section rate by year. We conducted bivariate and multivariate logistic regressions to study the determinants of C-section use., Results: In Indonesia, the C-section rate increased from 4.0% in 1998 to 18.5% in 2017. In 2017, the C-section rate in urban areas (22.9%) was almost two times that in rural areas (11.8%). It was almost three times among the richest wealth quintile (36.5%), compared with the poorest wealth quintile (12.9%). Between 2008 and 2017, the difference in the C-section rate by public services enlarged between the poorest and the richest groups. The absolute increase of the C-sections by private services was more than public services over time. In 2013-2017, the C-section rates by public and private services were 22.5% and 23.1%, respectively. After adjusting for all variables, higher education, higher household wealth, primiparity and use of public childbirth services were positively associated with C-section., Conclusions: The C-section rate increased steadily in the past two decades in Indonesia. Women's socioeconomic status and health system factors were associated with the increased use of C-section., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Details of the design and implementation of an open-source platform for studying the adhesion of cells attached to solid substrata are provided. The hardware is based on a laser-cut flow channel connected to a programmable syringe pump. The software automates all aspects of the flow rate profile, data acquisition and image analysis. An example of the pelagic diatom Thalassiosira rotula adhered to poly(dimethyl siloxane) surfaces is provided. The procedure described enables the shear rate to be converted to drag force for arbitrary-shaped objects, of utility to the study of many cell species, especially ones that are obviously non-spherical. It was determined that 90% of cells are removed with the application of drag forces < 3 × 10 - 12 N, and that this value is relatively independent of the incubation time on the surface. This result is important to understand how marine species interact with polymer surfaces that are used in electrical insulator applications.

Traumatic brain injury is associated with a high risk of mortality in veterinary patients, however publications describing valid prognostic indicators are currently lacking. The objective of this retrospective observational study was to determine whether early CT findings are associated with short-term prognosis following traumatic brain injury (TBI) in dogs. An electronic database was searched for dogs with TBI that underwent CT within 72 h of injury; 40 dogs met the inclusion criteria. CT findings were graded based on a Modified Advanced Imaging System (MAIS) from grade I (normal brain parenchyma) to VI (bilateral lesions affecting the brainstem with or without any foregoing lesions of lesser grades). Other imaging features recorded included presence of midline shift, intracranial hemorrhage, brain herniation, skull fractures, and percentage of total brain parenchyma affected. Outcome measures included survival to discharge and occurrence of immediate onset posttraumatic seizures. Thirty dogs (75%) survived to discharge. Seven dogs (17.5%) suffered posttraumatic seizures. There was no association between survival to discharge and posttraumatic seizures. No imaging features evaluated were associated with the study outcome measures. Therefore, the current study failed to identify any early CT imaging features with prognostic significance in canine TBI patients. Limitations associated with CT may preclude its use for prognostication; however, modifications to the current MAIS and evaluation in a larger study population may yield more useful results. Despite this, CT is a valuable tool in the detection of structural abnormalities following TBI in dogs that warrants further investigation., (© 2020 American College of Veterinary Radiology.)

Recent work has shown that neuregulin-4 (NRG4) is a physiological regulator of the growth of sympathetic axons and CNS dendrites in the developing nervous system. Here, we have investigated whether NRG4 plays a role in sensory axon growth and the establishment of cutaneous sensory innervation. Imaging early nerve fibers in the well-characterized cutaneous trigeminal territory, the brachial plexus, and thorax revealed very marked and highly significant decreases in nerve fiber length and branching density in Nrg4 -/- embryos compared with Nrg4 +/+ littermates. NRG4 promoted neurotrophin-independent sensory axon growth from correspondingly early trigeminal ganglion and DRG neurons in culture but not from enteroceptive nodose ganglion neurons. High levels of Nrg4 mRNA were detected in cutaneous tissues but not in sensory ganglia. Our findings suggest that NRG4 is an important target-derived factor that participates in the establishment of early cutaneous sensory innervation., (© 2021 The Authors. Developmental Neurobiology published by Wiley Periodicals LLC.)

Background: The SARS-CoV-2 outbreak and associated lockdown measures have challenged healthcare. We examine how attendances to ED in England were impacted., Methods: Interrupted time series regression (January 2019 to June 2020) of data from EDs in 41 English NHS Trusts was used to estimate the initial decrease in attendances and the rate of increase following an interruption from 11 March - 7 April 2020, which included the 23 March lockdown in England., Findings: The SARS-CoV-2 interruption led to an initial 51.1% reduction (95% CI 46.3-55.9%) in ED attendances followed by a linear increase in attendances of 3.0% per week (95% CI 2.5-3.5%).  Significantly larger initial reductions were seen in those aged 0-19 years (69.1%), Indian (64.9%), Pakistani (71.8%), Bangladeshi (75.3%), African (63.5%) and Chinese people (74.5%), self-conveying attendees (60.3%) and those presenting with contusions or abrasions (66.9%), muscle and tendon injuries (65.6%), and those with a diagnosis that was not classifiable (72.7%).  Significantly smaller initial reductions were seen in those aged 65-74 years (42.6%), 75+ years (40.1%), those conveyed by ambulance (31.9%), and those presenting with the following conditions: central nervous system (44.9%), haematological (44.0%), cardiac (43.7%), gastrointestinal (43.4%), gynaecological (43.2%), psychiatric (40.4%), poisoning (39.7%), cerebro-vascular (39.0%), endocrinological (36.1%), other vascular (34.6%), and maxillo-facial (19.7%). No significant differences in the initial reduction of activity were seen in subgroups defined by sex, deprivation, urbanicity or acuity., Interpretation: The SARS-CoV-2 outbreak and lockdown substantially reduced ED activity. The reduction varied by age groups, ethnicity, arrival mode and diagnostic group but not by sex, deprivation, urbanicity or acuity., Funding: No funding to declare., Competing Interests: No conflicts of interest to declare, (© 2021 The Author(s).)

Purpose: To quantify the prevalence of opioid and benzodiazepine prescriptions for patients with rotator cuff disease across a large health care system and to describe evidence-based risk factors for opioid use within this population., Methods: We conducted a retrospective cohort study at a major health care system of all patients with qualifying diagnostic codes. Emergency department, urgent care, and outpatient encounters between January and December 2016 for an acute rotator cuff tear, listed as the primary diagnosis, were included. Encounters with prescriptions for opioids or benzodiazepines were identified using the Prescription Reporting With Immediate Medication Utilization Mapping (PRIMUM) system. Descriptive statistics and the rate of controlled-substance prescribing were calculated for the population as a whole and among subgroups., Results: We identified 9,376 encounters meeting the inclusion criteria. Of these encounters, 1,559 (16.6%) resulted in 1 or more prescriptions for an opioid or benzodiazepine that were issued during the visit. A total of 2,007 opioid and/or benzodiazepine prescriptions were issued for the 1,559 encounters (rate of 1.29 prescriptions per prescribing encounter). This represented 5,310 patients, of whom 1,096 (20.6%) received a prescription for an opioid or benzodiazepine during at least 1 of their encounters. Of patients who received a prescription, 20.9% had at least 1 risk factor for prescription misuse; 3.6% of patients had more than 1 risk factor. There were no demographic differences between patients with risk factors and patients without them., Conclusions: The prescribing of opioids for the treatment of pain in patients with rotator cuff disease remains high across multiple locations and specialties within a large health care system. Using alternative pain management pathways as primary prevention for opioid misuse and abuse in high opioid-prescribing locations-and especially for patients identified as having a high risk of opioid misuse-is an important practice to continue in our shift away from opioid use as a health care system., Level of Evidence: Level IV, case series., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Background: Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery., Methods: The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13-17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a 'healthy living' behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness., Discussion: UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression., Trial Registration: ISRCTN, ISRCTN66452702 . Registered 9 April 2020.

Background: New healthcare models are being explored to enhance care coordination, efficiency, and outcomes. Evidence is scarce regarding the impact of vertical integration of primary and secondary care on emergency department (ED) attendances, unplanned hospital admissions, and readmissions., Aim: To examine the impact of vertical integration of an NHS provider hospital and 10 general practices on unplanned hospital care DESIGN AND SETTING: A retrospective database study using synthetic controls of an NHS hospital in Wolverhampton integrated with 10 general practices, providing primary medical services for 67 402 registered patients., Method: For each vertical integration GP practice, a synthetic counterpart was constructed. The difference in rate of ED attendances, unplanned hospital admissions, and unplanned hospital readmissions was compared, and pooled across vertical integration practices versus synthetic control practices pre-intervention versus post-intervention., Results: Across the 10 practices, pooled rates of ED attendances did not change significantly after vertical integration. However, there were statistically significant reductions in the rates of unplanned hospital admissions (-0.11, 95% CI = -0.18 to -0.045, P = 0.0012) and unplanned hospital readmissions (-0.021, 95% CI = -0.037 to -0.0049, P = 0.012), per 100 patients per month. These effect sizes represent 888 avoided unplanned hospital admissions and 168 readmissions for a population of 67 402 patients per annum. Utilising NHS reference costs, the estimated savings from the reductions in unplanned care are ∼£1.7 million., Conclusion: Vertical integration was associated with a reduction in the rate of unplanned hospital admissions and readmissions in this study. Further work is required to understand the mechanisms involved in this complex intervention, to assess the generalisability of these findings, and to determine the impact on patient satisfaction, health outcomes, and GP workload., (©The Authors.)

CD40-activated CD40L reverse signaling is a major physiological regulator of neural process growth from many kinds of developing neurons. Here we have investigated whether CD40L-reverse signaling also influences dendrite spine number and morphology in striatal medium spiny neurons (MSNs). Golgi preparations revealed no differences in the spine density, but because the dendrite arbors of MSNs were larger and branched in Cd40 -/- mice, the total number of spines was greater in Cd40 -/- mice. We also detected more mature spines compared with wild-type littermates. Western blot revealed that MSN cultures from Cd40 -/- mice had significantly less PSD-95 and there were changes in RhoA/B/C and Cdc42. Immunocytochemistry revealed that PSD-95 was clustered in spines in Cd40 -/- neurons compared with more diffuse labeling in Cd40 +/+ neurons. Activation of CD40L-reverse signaling with CD40-Fc prevented the changes observed in Cd40 -/- cultures. Our findings suggest that CD40L-reverse signaling influences dendrite spine morphology and related protein expression and distribution., (Copyright © 2020 Carriba, Wyatt and Davies.)

Background: Safe Patient Handling and Mobility (SPHM) programs reduce staff injuries from lifting and repositioning patients. Early Mobility programs improve many patient-centered outcomes. Reframing SPHM equipment as mobilization tools can help safely mobilize hospitalized patients to their highest abilities., Problem: Combining SPHM and Early Mobility programs is logical, but to date, no one has articulated the process of integration., Intervention: A quality improvement process was developed at the Phoenix Veterans Affairs Health Care System to integrate an Early Exercise and Progressive Mobility initiative in the intensive care unit into an ongoing SPHM program using the Iowa Model for Evidence-Based Implementation., Results: Integration of these programs was possible through extensive collaboration between stakeholders throughout planning, implementation, and refinement phases. Interdisciplinary Early Exercise and Progressive Mobility simulation training, standardized assessment, communication of patient status, and appropriate equipment use facilitated staff confidence to safely mobilize patients., Conclusions: Successful integration of Early Exercise and Progressive Mobility and SPHM was achieved at the Phoenix Veterans Affairs Health Care System.

US physicians prescribe opioids at a high rate relative to other countries. Of the US physicians surveyed, almost half report having prescribed an inappropriate opioid due to concerns about patient satisfaction scores. We investigated patterns in controlled substance prescribing practices, patient risk factors, and associated Press Ganey patient satisfaction scores at a sample of orthopaedic surgery and primary care clinics over a 6month time period. Primary care practices had higher proportions of prescriptions, and patient risk profiles varied across sites. However, overall satisfaction was high, with little variation between sites (78.3 81.3%). Satisfaction with pain control was lower and more varied (67.1 78.0%). A total of 4,229 Press Ganey survey responses were received, including 7,232 comments, of which only 10 (0.1%) expressed frustration for not receiving opioids. Opioid prescriptions had minimal association with Press Ganey scores among varied practices and patient populations. Prescribers should prescribe opioids appropriately without fear that this will negatively impact their satisfaction scores. (Journal of Surgical Orthopaedic Advances 29(1):59, 2020).