Open fractures: evidence-based best practices.

Open fracture management is a common challenge to orthopaedic trauma surgeons and a burdensome condition to the patient, health care, and entire society. Fracture-related infection (FRI) is the leading morbid complication to avoid during open fracture management because it leads to sepsis, nonunion, limb loss, and overall very poor region-specific and general functional outcomes. This review, based on a symposium presented at the 2022 OTA International Trauma Care Forum, provides a practical and evidence-based summary on key strategies to prevent FRI in open fractures, which can be grouped as optimizing host factors, antimicrobial prophylaxis, surgical site management (skin preparation, debridement, and wound irrigation), provision of skeletal stability, and soft-tissue coverage. When it is applicable, strategies are differentiated between optimal resource and resource-limited settings.

From progression to progress: The future of multiple sclerosis.

Significant advances have been made in the diagnosis and treatment of multiple sclerosis in recent years yet challenges remain. The current classification of MS phenotypes according to disease activity and progression, for example, does not adequately reflect the underlying pathophysiological mechanisms that may be acting in an individual with MS at different time points. Thus, there is a need for clinicians to transition to a management approach based on the underlying pathophysiological mechanisms that drive disability in MS. A Canadian expert panel convened in January 2023 to discuss priorities for clinical discovery and scientific exploration that would help advance the field. Five key areas of focus included: identifying a mechanism-based disease classification system; developing biomarkers (imaging, fluid, digital) to identify pathologic processes; implementing a data-driven approach to integrate genetic/environmental risk factors, clinical findings, imaging and biomarker data, and patient-reported outcomes to better characterize the many factors associated with disability progression; utilizing precision-based treatment strategies to target different disease processes; and potentially preventing disease through Epstein-Barr virus (EBV) vaccination, counselling about environmental risk factors (e.g. obesity, exercise, vitamin D/sun exposure, smoking) and other measures. Many of the tools needed to meet these needs are currently available. Further work is required to validate emerging biomarkers and tailor treatment strategies to the needs of individual patients. The hope is that a more complete view of the individual's pathobiology will enable clinicians to usher in an era of truly personalized medicine, in which more informed treatment decisions throughout the disease course achieve better long-term outcomes.

Development and Validation of the Combined Action Observation and Motor Imagery Ability Questionnaire.

Combined use of action observation and motor imagery (AOMI) is an increasingly popular motor-simulation intervention, which involves observing movements on video while simultaneously imagining the feeling of movement execution. Measuring and reporting participant imagery-ability characteristics are essential in motor-simulation research, but no measure of AOMI ability currently exists. Accordingly, the AOMI Ability Questionnaire (AOMI-AQ) was developed to address this gap in the literature. In Study 1, two hundred eleven participants completed the AOMI-AQ and the kinesthetic imagery subscales of the Movement Imagery Questionnaire-3 and Vividness of Motor Imagery Questionnaire-2. Following exploratory factor analysis, an 8-item AOMI-AQ was found to correlate positively with existing motor-imagery measures. In Study 2, one hundred seventy-four participants completed the AOMI-AQ for a second time after a period of 7-10 days. Results indicate a good test-retest reliability for the AOMI-AQ. The new AOMI-AQ measure provides a valid and reliable tool for researchers and practitioners wishing to assess AOMI ability.

Prophylactic Regenerative Peripheral Nerve Interface (RPNI) Surgery in Pediatric Lower Limb Amputation Patients.

OBJECTIVE: To evaluate the prophylactic effect of Regenerative Peripheral Nerve Interface (RPNI) surgery on pediatric post-amputation pain. SUMMARY OF BACKGROUND DATA: Chronic post-amputation pain is a debilitating and refractory sequela of limb amputation affecting up to 83% of pediatric patients with limb loss, resulting in disability and decreased quality of life. We postulate that prophylactic RPNI surgery performed during amputation may decrease the incidence of symptomatic neuroma and development of phantom limb pain, as well as limit analgesic use among pediatric patients with limb loss. METHODS: Retrospective chart review was performed on pediatric patients between the ages of 8 and 21 years who underwent major lower limb amputation with and without RPNI surgery. Documented neuroma and phantom limb pain scores as well as analgesic use was recorded. Narcotic use was converted to milligrams morphine equivalents per day (MME/day) while overall analgesic use was converted to Medication Quantification Scale version III (MQSIII) scores. Analysis was performed using Stata. RESULTS: Forty-four pediatric patients were identified; 25 RPNI patients and 19 controls. Seventy-nine percent of control patients developed chronic post-amputation pain versus 21% of RPNI patients (P<0.001). Among the patients who developed post-amputation pain, 20% of controls developed clinical neuroma pain, compared to 0% of RPNI patients (P<0.001). Additionally, RPNI patients demonstrated a significant decrease in pain score (P=0.007) and narcotic usage (P<0.01), compared to controls. Overall analgesic use did not vary significantly between groups. CONCLUSIONS: Prophylactic RPNI surgery shows promise for pediatric patients undergoing major lower limb amputation by preventing both symptomatic neuromas and possibly the development of phantom limb pain.

Characterizing Ertapenem Neurotoxicity: A Systematic Review and Experience at a Tertiary Medical Center.

Ertapenem-induced neurotoxicity has not been well characterized and is potentially underreported. We conducted a systematic review of the literature and included 11 additional cases from the University of Washington Medicine health system. A total of 125 individual patient cases were included in the data analysis. The mean age was 72 years, and 62% and 42% of patients had renal dysfunction and preexisting central nervous system (CNS) conditions, respectively. Only 15% of patients received inappropriately high ertapenem dosing based on kidney function. Patients developed neurological signs and symptoms after a median of 4 days (interquartile range, 3-9 days). The most common clinical features were seizures (70%), altered level of consciousness or delirium (27%), and hallucinations (17%). An estimated incidence in our health system was 1 in 102 courses of ertapenem. Ertapenem neurotoxicity should be suspected when a patient with renal dysfunction or predisposing CNS conditions develops neurological signs and symptoms, especially within several days after initiating the antibiotic. This study underscores the need for a large prospective study to assess the true incidence and outcomes of ertapenem neurotoxicity.

Automated synthesis of [89Zr]ZrCl4, [89Zr]ZrDFOSquaramide-bisPh(PSMA) and [89Zr]ZrDFOSquaramide-TATE.

BACKGROUND: Automated [89Zr]Zr-radiolabeling processes have the potential to streamline the production of [89Zr]Zr-labelled PET imaging agents. Most radiolabeling protocols use [89Zr][Zr(ox)4]4- as the starting material and oxalate is removed after radiolabeling. In some instances, radiolabeling with [89Zr]ZrCl4 as starting material gives better radiochemical yields at lower reaction temperatures. In this work, a fully-automated process for production of [89Zr]ZrCl4 is reported and its use for the synthesis of [89Zr]ZrDFOSq-bisPhPSMA and [89Zr]ZrDFOSq-TATE. RESULTS: A simple automated process for the isolation of [89Zr]ZrCl4 by trapping [89Zr][Zr(ox)4]4- on a bicarbonate-activated strong anion exchange cartridge followed by elution with 0.1 M HCl in 1 M NaCl was developed. [89Zr]ZrCl4 was routinely recovered from [89Zr][Zr(ox)4]4- in > 95% yield in mildly acidic solution of 0.1 M HCl in 1 M NaCl using a fully-automated process. The [89Zr]ZrCl4 was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [89Zr]ZrCl4 was used for direct automated radiolabeling reactions to produce [89Zr]Zr-DFOSquaramide-bisPhPSMA and [89Zr]ZrDFOSquaramide-TATE in 80-90% over all RCY in > 95% RCP. CONCLUSIONS: This method for the production of [89Zr]ZrCl4 does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [89Zr]ZrCl4 and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.

An Ionic Liquid-Based Biorefinery Approach for Duckweed Utilization.

This study establishes a foundation for the ionic liquid (IL) pretreatment of duckweed biomass. An optimized IL-based process was designed to exploit the unique properties of duckweed including efficient metal removal, potential starch accumulation, and protein accumulation. Two ILs, namely, dimethylethanolammonium formate ([DMEtA][HCOO]) and N,N-dimethylbutylammonium hydrogen sulfate ([DMBA][HSO4]), were investigated for the pretreatment of two duckweed species (Spirodela polyrhiza and Lemna minor). The evaluation focused on starch recovery, sugar release, protein recovery, and metal extraction capabilities. [DMEtA][HCOO] demonstrated near-quantitative starch recoveries at 120 °C, while [DMBA][HSO4] showed similar performance at 90 °C within a reaction time of 2 h. Saccharification yields for most pulps exceeded 90% after 8 h of hydrolysis, outperforming "traditional" lignocellulosic biomasses such as miscanthus or sugarcane bagasse. Approximately 50 and 80 wt % of the protein were solubilized in [DMEtA][HCOO] and [DMBA][HSO4], respectively, while the remaining protein distributed between the pulp and lignin. However, the solubilized protein in the IL could not be recovered due to its low molecular weight. Regarding metal extraction, [DMEtA][HCOO] demonstrated higher efficiency, achieving 81% removal of Ni from Lemna minor's pulps, whereas [DMBA][HSO4] extracted only 28% of Ni with slightly higher pulp concentrations. These findings indicate the need for further optimization in concurrent metal extraction using ILs.

IL-4-STAT6 axis amplifies histamine-induced vascular endothelial dysfunction and hypovolemic shock.

BACKGROUND: Mast cell (MC)-derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We have previously revealed a synergistic interaction between the cytokine IL-4 and the MC-derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis are unknown. OBJECTIVE: To identify the IL-4-induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylaxic reactions. METHODS: RNAseq, Western blot, Ca2+ imaging and barrier functional analyses on the vascular endothelial cell line (EA.hy926). Pharmacologic degraders (selective PROTAC (proteolysis-targeting chimera) and genetic (lentiviral shRNA) inhibitors were used to determine the roles of STAT3 and STAT6 in conjunction with in vivo model systems of histamine-induced hypovolemic shock. RESULTS: IL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-Cadherin degradation, intracellular calcium flux, phospho-Src levels and required transcription and de novo protein synthesis. RNAseq analyses of IL-4 stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth and transcription factor motif analyses revealed a significant enrichment of differential expressed genes (DEGs) with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both STAT3Y705 and STAT3S727 phosphorylation. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function, however IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3-independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6-dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4-mediated amplification of histamine-induced hypovolemia. CONCLUSIONS: These studies unveil a novel role of the IL-4/ STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis.

Major surgical conditions of childhood and their lifelong implications: comprehensive review.

BACKGROUND: In recent decades, the survival of children with congenital anomalies and paediatric cancer has improved dramatically such that there has been a steady shift towards understanding their lifelong health outcomes. Paediatric surgeons will actively manage such conditions in childhood and adolescence, however, adult surgeons must later care for these 'grown-ups' in adulthood. This article aims to highlight some of those rare disorders encountered by paediatric surgeons requiring long-term follow-up, their management in childhood and their survivorship impact, in order that the adult specialist may be better equipped with skills and knowledge to manage these patients into adulthood. METHODS: A comprehensive literature review was performed to identify relevant publications. Research studies, review articles and guidelines were sought, focusing on the paediatric management and long-term outcomes of surgical conditions of childhood. The article has been written for adult surgeon readership. RESULTS: This article describes the aforementioned conditions, their management in childhood and their lifelong implications, including: oesophageal atresia, tracheo-oesophageal fistula, malrotation, short bowel syndrome, duodenal atresia, gastroschisis, exomphalos, choledochal malformations, biliary atresia, Hirschsprung disease, anorectal malformations, congenital diaphragmatic hernia, congenital lung lesions and paediatric cancer. CONCLUSION: The increasing survivorship of children affected by surgical conditions will translate into a growing population of adults with lifelong conditions and specialist healthcare needs. The importance of transition from childhood to adulthood is becoming realized. It is hoped that this timely review will enthuse the readership to offer care for such vulnerable patients, and to collaborate with paediatric surgeons in providing successful and seamless transitional care.

Generalizable Approach to Quantifying Guideline-Directed Medical Therapy.

BACKGROUND: Quantifying guideline-directed medical therapy (GDMT) intensity is foundational for improving heart failure (HF) care. Existing measures discount dose intensity or use inconsistent weighting. METHODS: The Kansas City Medical Optimization (KCMO) score is the average of total daily to target dose percentages for eligible GDMT, reflecting the percentage of optimal GDMT prescribed (range, 0-100). In Change the Management of Patients With HF, we computed KCMO, HF collaboratory (0-7), and modified HF Collaboratory (0-100) scores for each patient at baseline and for 1-year change in established GDMT at the time (mineralocorticoid receptor antagonist, ß-blocker, ACE [angiotensin-converting enzyme] inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor). We compared baseline and 1-year change distributions and the coefficient of variation (SD/mean) across scores. RESULTS: Among 4532 patients at baseline, mean KCMO, HF collaboratory, and modified HF Collaboratory scores were 38.8 (SD, 25.7), 3.4 (1.7), and 42.2 (22.2), respectively. The mean 1-year change (n=4061) for KCMO was -1.94 (17.8); HF collaborator, -0.11 (1.32); and modified HF Collaboratory, -1.35 (19.8). KCMO had the highest coefficient of variation (0.66), indicating greater variability around the mean than the HF collaboratory (0.49) and modified HF Collaboratory (0.53) scores, reflecting higher resolution of the variability in GDMT intensity across patients. CONCLUSIONS: KCMO measures GDMT intensity by incorporating dosing and treatment eligibility, provides more granularity than existing methods, is easily interpretable (percentage of ideal GDMT), and can be adapted as performance measures evolve. Further study of its association with outcomes and its usefulness for quality assessment and improvement is needed.

The Application of Virtual Reality in Shoulder Surgery Rehabilitation.

To achieve a positive functional prognosis in orthopedic surgery, particularly in shoulder surgeries, effective rehabilitation is essential. Recently, there has been growing interest in the use of virtual reality (VR) in the field of orthopedics, particularly for preoperative education and training, as well as clinical and home-based rehabilitation. This report describes the process of developing an application utilizing Meta Quest 2 VR technology (Meta, CA, USA) for rehabilitation after shoulder surgery. This application assists patients in performing postoperative exercises at home by wearing VR equipment tailored to their postoperative weeks. The advantages of VR rehabilitation lie in overcoming the limitations of traditional rehabilitation methods and providing patients with a better rehabilitation experience. Moreover, automating the rehabilitation process and reducing patients' visits to clinics can lead to cost savings. This report raises expectations for the potential and scalability of VR utilization, extending beyond orthopedics to other fields. In addition, it anticipates that with better feedback and motivation, the rehabilitation effects for patients can be further enhanced.

Accommodating detection limits of multiple exposures in environmental mixture analyses: an overview of statistical approaches.

BACKGROUND: Identifying the impact of environmental mixtures on human health is an important topic. However, such studies face challenges when exposure measurements lie below limit of detection (LOD). While various approaches for accommodating a single exposure subject to LOD have been used, their impact on mixture analysis has not been thoroughly investigated. Our study aims to understand the impact of five popular LOD accommodation approaches on mixture analysis results with multiple exposures subject to LOD, including omitting subjects with any exposures below LOD (complete case analysis); single imputations by LOD/ 2 , and by estimates from a censored accelerated failure time (AFT) model; and multiple imputation (MI) with or without truncation based on LOD. METHODS: In extensive simulation studies with high-dimensional and highly correlated exposures and a continuous health outcome, we examined the performance of each LOD approach on three mixture analysis methods: elastic net regression, weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR). We further analyzed data from the National Health and Nutrition Examination Survey (NHANES) on how persistent organic pollutants (POPs) influenced leukocyte telomere length (LTL). RESULTS: Complete case analysis was inefficient and could result in severe bias for some mixture methods. Imputation by LOD/ 2 showed unstable performance across mixture methods. Conventional MI was associated with consistent mild biases, which can be reduced by using a truncated distribution for imputation. Estimating censored values by AFT models had a minimal impact on the results. In the NHANES analysis, imputation by LOD/ 2 , truncated MI and censored AFT models performed similarly, with a positive overall effect of POPs on LTL while PCB126, PCB169 and furan 2,3,4,7,8-pncdf being the most important exposures. CONCLUSIONS: Our study favored using truncated MI and censored AFT models to accommodate values below LOD for the stability of downstream mixture analysis.

Benefits and Limits of Phasing Alleles for Network Inference of Allopolyploid Complexes.

Accurately reconstructing the reticulate histories of polyploids remains a central challenge for understanding plant evolution. Although phylogenetic networks can provide insights into relationships among polyploid lineages, inferring networks may be hindered by the complexities of homology determination in polyploid taxa. We use simulations to show that phasing alleles from allopolyploid individuals can improve phylogenetic network inference under the multispecies coalescent by obtaining the true network with fewer loci compared to haplotype consensus sequences or sequences with heterozygous bases represented as ambiguity codes. Phased allelic data can also improve divergence time estimates for networks, which is helpful for evaluating allopolyploid speciation hypotheses and proposing mechanisms of speciation. To achieve these outcomes in empirical data, we present a novel pipeline that leverages a recently developed phasing algorithm to reliably phase alleles from polyploids. This pipeline is especially appropriate for target enrichment data, where depth of coverage is typically high enough to phase entire loci. We provide an empirical example in the North American Dryopteris fern complex that demonstrates insights from phased data as well as the challenges of network inference. We establish that our pipeline (PATÉ: Phased Alleles from Target Enrichment data) is capable of recovering a high proportion of phased loci from both diploids and polyploids. These data may improve network estimates compared to using haplotype consensus assemblies by accurately inferring the direction of gene flow, but statistical non-identifiability of phylogenetic networks poses a barrier to inferring the evolutionary history of reticulate complexes.

Immunohistochemistry as an adjunct for challenging histological patterns of borderline Brenner tumors: An illustrative study of 4 cases.

Borderline Brenner tumors (BBT) have a range of morphology that shows considerable overlap with that of malignant Brenner tumors (MBT). In particular, two histological patterns of BBT can be particularly challenging: 1) BBT with intraepithelial carcinoma (BBT-IEC) and 2) BBT with a small nested pattern (BBT-SNP). BBT-IEC is characterized by a tumor with the low-power non-infiltrative silhouette of a conventional BBT, but with increased cytological atypia and mitotic activity similar to that of MBT. Conversely, BBT-SNP is characterized by a complex proliferation of small tumor nests that closely resemble the infiltrative growth pattern of MBT, but without the obligate cytologic atypia and mitotic activity of MBT. We suggest that the combination of p16, p53 and Ki-67 may be helpful in distinguishing these 2 patterns of BBT from both conventional BBT and from MBT. While both conventional BBT and BBT-IEC show a null pattern of p16 expression, our case of BBT-IEC showed aberrant p53 overexpression, albeit with a maturation pattern similar to that described for TP53 mutant mucinous ovarian carcinoma and differentiated vulvar intraepithelial neoplasia (dVIN). Similarly, while BBT-SNP shows an infiltrative-like growth pattern similar to that of MBT, our case also showed a wild-type pattern of p53 expression and a Ki-67 proliferative index similar to areas with conventional BBT histology. In conclusion, in our small case series, we show that the use of immunohistochemistry for p53 and Ki-67 may help to distinguish challenging patterns of BBT from MBT. Further studies are needed to validate this finding in a larger case cohort.

Essential oil composition of passiflora foetida L. (passifloraceae) flowers and chemical-biology study of the leaves extracts and isolated compound.

Passiflora foetida is a climbing herb employed in ethno-medicine for the treatment of various ailments. The essential oil from flowers of P. foetida was obtained by hydrodistillation. The ethanol extract of the leaves was dissolved in water, then partitioned with n-hexane and n-butanol to obtain the various fractions; the fractions and isolated compound were subjected to in vitro antioxidant activity. Gas chromatography-mass spectrometry afforded the identification of forty-two constituents in the floral oil, dominated by ß-caryophyllene (17.2%), cedrol (11.5%), and α-humulene (11.5%). The n-butanol fraction was the most active (70% inhibition and absorbance 0.401; 100 µg/mL) in the 2,2-diphenyl-1-picrylhydrazyl radicals and ferric reducing power assays, respectively. Chromatographic analysis facilitated the isolation of 8-C-ß-d-glucosylapigenin (vitexin) from the butanol fraction of P. foetida. Vitexin demonstrated good antioxidant activities (75% inhibition and absorbance 0.424; 100 µg/mL) compared with ascorbic acid. The volatile metabolites of P. foetida flowers are reported for the first time.

Daughter circumcision and maternal life satisfaction: a cultural moderation effect revealed across two multicountry studies.

INTRODUCTION: The present paper assessed the relationship between maternal life satisfaction (MLS) and the intergenerational transmission of female genital cutting (FGC, female circumcision). It was hypothesised that the association would be more strongly positive in countries in which FGC is more prevalent (ie, culturally normative), suggesting a practice that is socially reinforcing within sociocultural contexts in which it is common. METHODS: Across two studies with more than 85 000 participants in 15 African and Asian countries, mothers completed surveys reporting on their own FGC experiences and those of their daughters' and on their educational history and socioeconomic status. RESULTS: The association between MLS and daughter circumcision was weak but positive for the full sample. Contrary to predictions, in countries in which FGC is uncommon, it was more positively associated with MLS, and in countries in which it is common, it was weakly or negatively associated with MLS. CONCLUSION: Results are contrary to the notion that the intergenerational transmission of FGC is a function of happiness deriving from its cultural normativity. They suggest, instead, a diversity of social motives depending on cultural context. Customised messaging to reduce the intergenerational transmission of FGC is discussed.

Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

An open pilot trial of a behavioural intervention to reduce violence by young adults with early psychosis receiving treatment in an early intervention services setting: A protocol.

AIMS: Despite the public health impact of violence among young adults with psychosis, behavioural interventions to reduce the risk of engaging in violence remain rare. For young adults with early psychosis, cognitive behavioural therapy (CBT)-based psychotherapy has efficacy in reducing impairment and improving functioning. However, no CBT-based intervention to reduce violence has been formally adapted for young adults with early psychosis. This protocol outlines the first clinical trial of a behavioural intervention to reduce violence for young adults with early psychosis. This study is set in an early intervention services (EIS) setting and seeks to adapt and pilot Psychological Intervention for Complex PTSD and Schizophrenia-Spectrum Disorder (PICASSO), a CBT-based intervention, through an iterative process utilizing mixed-methods assessments. METHODS: All research will occur at OnTrackNY, the largest EIS program in the United States. This study will consist of an open pilot trial, with four EIS clinicians delivering the intervention to one to two EIS participants per round. In this mixed-methods study, both quantitative measures (acceptability, feasibility and hypothesized mediators of target outcome collected on a weekly basis) and qualitative interviews (with EIS clinicians at weeks 4, 8 and 12) will be conducted. Transcripts will be analyzed using thematic content analysis. Two to three rounds of iterative modifications are anticipated (n = 10-16 EIS participants total). RESULTS: Recruitment began in February 2024 and is expected to continue over a 9-12-month period. CONCLUSIONS: Because violent behaviour causes interpersonal disruptions such as incarceration and increased caregiver burden, an innovative intervention to reduce violence risk could have broader health impact for this vulnerable population. Adapting the PICASSO intervention to the EIS setting will optimize its acceptability and feasibility by the intended target population.

Advances in Drug Treatments for Companion Animal Obesity.

Companion animal obesity has emerged as a significant veterinary health concern globally, with escalating rates posing challenges for preventive and therapeutic interventions. Obesity not only leads to immediate health problems but also contributes to various comorbidities affecting animal well-being and longevity, with consequent emotional and financial burdens on owners. While past treatment strategies have shown limited success, recent breakthroughs in human medicine present new opportunities for addressing this complex issue in companion animals. Here, we discuss the potential of GLP-1 receptor agonists, specifically semaglutide and tirzepatide, already approved for human use, for addressing companion animal obesity. These drugs, originally developed to treat type 2 diabetes in humans and subsequently repurposed to treat obesity, have demonstrated remarkable weight loss effects in rodents, non-human primates and people. Additionally, newer drug combinations have shown even more promising results in clinical trials. Despite current cost and supply challenges, advancements in oral and/or extended-release formulations and increased production may make these drugs more accessible for veterinary use. Thus, these drugs may have utility in companion animal weight management, and future feasibility studies exploring their efficacy and safety in treating companion animal obesity are warranted.