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IntroductionThe high failure rate of clinical trials in traumatic brain injury (TBI) may be attributable, in part, to the use of untested or insensitive measurement instruments. Of more than 1,000 clinical outcome assessment measures (COAs) for TBI, few have been systematically vetted to determine their performance within specific "contexts of use (COU)." As described in guidance issued by the U.S. Food and Drug Administration (FDA), the COU specifies the population of interest and the purpose for which the COA will be employed. COAs are commonly used for screening, diagnostic categorization, outcome prediction, and establishing treatment effectiveness. COA selection typically relies on expert consensus; there is no established methodology to match the appropriateness of a particular COA to a specific COU. We developed and pilot-tested the Evidence-Based Clinical Outcome assessment Platform (EB-COP) to systematically and transparently evaluate the suitability of TBI COAs for specific purposes.Methods and findingsFollowing a review of existing literature and published guidelines on psychometric standards for COAs, we developed a 6-step, semi-automated, evidence-based assessment platform to grade COA performance for six specific purposes: diagnosis, symptom detection, prognosis, natural history, subgroup stratification and treatment effectiveness. Mandatory quality indicators (QIs) were identified for each purpose using a modified Delphi consensus-building process. The EB-COP framework was incorporated into a Qualtrics software platform and pilot-tested on the Glasgow Outcome Scale-Extended (GOSE), the most widely-used COA in TBI clinical studies.ConclusionThe EB-COP provides a systematic methodology for conducting more precise, evidence-based assessment of COAs by evaluating performance within specific COUs. The EB-COP platform was shown to be feasible when applied to a TBI COA frequently used to detect treatment effects and can be modified to address other populations and COUs. Additional testing and validation of the EB-COP are warranted.

ObjectiveTo update the 1997 American Academy of Neurology (AAN) practice parameter regarding sports concussion, focusing on 4 questions: 1) What factors increase/decrease concussion risk? 2) What diagnostic tools identify those with concussion and those at increased risk for severe/prolonged early impairments, neurologic catastrophe, or chronic neurobehavioral impairment? 3) What clinical factors identify those at increased risk for severe/prolonged early postconcussion impairments, neurologic catastrophe, recurrent concussions, or chronic neurobehavioral impairment? 4) What interventions enhance recovery, reduce recurrent concussion risk, or diminish long-term sequelae? The complete guideline on which this summary is based is available as an online data supplement to this article.MethodsWe systematically reviewed the literature from 1955 to June 2012 for pertinent evidence. We assessed evidence for quality and synthesized into conclusions using a modified Grading of Recommendations Assessment, Development and Evaluation process. We used a modified Delphi process to develop recommendations.ResultsSpecific risk factors can increase or decrease concussion risk. Diagnostic tools to help identify individuals with concussion include graded symptom checklists, the Standardized Assessment of Concussion, neuropsychological assessments, and the Balance Error Scoring System. Ongoing clinical symptoms, concussion history, and younger age identify those at risk for postconcussion impairments. Risk factors for recurrent concussion include history of multiple concussions, particularly within 10 days after initial concussion. Risk factors for chronic neurobehavioral impairment include concussion exposure and APOE ε4 genotype. Data are insufficient to show that any intervention enhances recovery or diminishes long-term sequelae postconcussion. Practice recommendations are presented for preparticipation counseling, management of suspected concussion, and management of diagnosed concussion.

The aim of the study was to investigate job satisfaction and job commitment of coaches of the three major racket sports in Greek tennis, table-tennis and badminton. One hundred and ten (N = 110) tennis (NT= 61), table-tennis (NTT = 31) and badminton (NB = 18) coaches responded to the Coach Satisfaction Questionnaire (CSQ), an eleven-factor instrument which assesses coaches’ job satisfaction and to the Occupational-Organizational Commitment Scale, a six factor questionnaire which evaluates the different forms of occupational and organizational commitment. Forty six of the coaches were full-time (NFT = 46) whereas of the rest, sixty four were part-time (NPT = 64). The results of a series of t-tests, ANOVAs and correlation analyses revealed various significant differences and relationships. Some of the most important are that: a) tennis coaches and full-time coaches were more satisfied in most of the job satisfaction dimensions, b) significant correlations were noticed between “job satisfaction” and “organizational commitment” variables, c) “autonomy”, was a predictor of “organizational affective commitment”, d) “satisfaction with coaching job” was the unique predictor of occupational affective and “occupational normative commitment” and e) “team performance” was the only predictor of “occupational continuance commitment”. Most of the results are in accordance with the existing job satisfaction literature however, further research is needed on human relation practices of National Federations and/or sport clubs associated with them, in order to have a better understanding of how certain practices and policies lead to higher levels of job satisfaction, organizational and occupational commitment among racket sport coaches.

Adolescent sexual offending represents an ongoing social, judicial, clinical, and policy issue for services. The current study investigated the characteristics, criminal versatility, and rates of recidivism of a cohort of 156 male adolescent sexual offenders who were referred for psychological assessments by the courts between 1996 and 2007 in Singapore. Analyses revealed that specialists (sex-only offenders; n = 71, M(follow-up) = 56.99 months, SD(follow-up) = 31.33) and generalists (criminally versatile offenders; n = 77, M (follow-up) = 67.83 months, SD(follow-up) = 36.55) differed with respect to offense characteristics (e.g., sexually assaulting familial victims) and recidivistic outcomes. Although both groups sexually reoffended at roughly the same rate (14.3% vs. 9.9%), consistent with their typology, significantly more of the generalists reoffended violently (18.2% vs. 1.4%), sexually and/or violently (27.3% vs. 11.3%), nonviolently (37.7% vs. 16.9%), and engaged in any further criminal behaviors (45.5% vs. 23.9%) during follow-up. Adjusting for total number of offenses and age at first sexual offense, Cox regression analyses showed that generalists were significantly more likely than specialists to reoffend violently (hazard ratio = 9.31; 95% confidence interval = 1.15-76.39). The differences between generalists and specialists suggest a valid typological distinction with a higher risk trajectory for the generalists. These findings therefore have important clinical implications for assessment, management, and intervention planning for adolescent sexual offenders. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to explore the mental health and offending histories for all cases that resulted in fatal use of force by Victoria Police between November 1982 and February 2007. Methods: Forty-eight fatalities were extracted from the Use of Force (UoF) Register, and then linked with the mental health and police contacts databases. These data were supplemented, where necessary, with relevant information from Coronial Reports and an Office of Police Integrity Report. Results: All but six cases had involved recorded histories with mental health and criminal justice systems before the fatal incident occurred. Rates of all Axis I disorders were significantly overrepresented, with estimated rates of psychosis and schizophrenia 11.3- and 17.3-fold higher than estimated rates in the general population (95% confidence intervals = 6.3-20.2 and 9.2-32.4, respectively). Although the number of fatalities has halved since inception of Project Beacon (32 before vs 16 after 1995), there has been no reduction in representation of mental illness among those fatally shot. Conclusions: The significant over-representation of Axis I disorders, including severe mental disorders of psychosis and schizophrenia, is of considerable concern for both the police and the mental health providers. Functional interagency partnerships and police training on how to interact with people in distress are recommended to address the overrepresentation of mentally ill persons in these encounters. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) in children is effectively treated by racemic oral methylphenidate (dl-MPH). The d-isomer (d-MPH) has been developed as an improved treatment for ADHD since only half the racemic dose is used. This study, performed in healthy subjects, assessed the effect of food on the pharmacokinetics of dexmethylphenidate hydrochloride (d-MPH HCl) in a single dose (2 x 10-mg tablets), two-way crossover with d-MPH administered to subjects in both a fasting state or after a high-fat breakfast. There were no serious or unexpected adverse events during the course of this study, with most events reported in comparable numbers of fed and fasted subjects. The bioequivalence of d-MPH was similar with or without food, with 90% confidence intervals of 88.2% to 104.6% and 105.9% to 118.2% for ln(C(max)) and ln[(AUC(0-infinity))], respectively. There was a marginal but statistically significant 1-hour increase in t(max) in the fed versus fasted state, reflecting an absorption delay. The rate of formation of the major metabolite, d-ritalinic acid (d-RA), was marginally decreased ( approximately 14%) after food. The extent of exposure to d-RA was similar (within 1.2%) between both treatments. There was a marginal but statistically significant difference in mean t(max) for d-RA between fed and fasted conditions, with peak concentration occurring 1.5 hours later after d-MPH administration with food. There was no measurable in vivo chiral inversion of d-MPH to l-MPH in plasma. In addition, the metabolism of d-MPH was stereospecific as d-MPH only produced d-RA. In summary, food had no substantial effect on the bioavailability of d-MPH, with an equivalent rate and extent of exposure obtained. Therefore, d-MPH can be administered without regard to food intake. [ABSTRACT FROM AUTHOR]

Thalidomide is approved in the United States for treating erythema nodosum leprosum, a complication of leprosy. The present study determined the single-dose oral pharmacokinetics and dose proportionality from 50 to 400 mg of Celgene's commercial Thalomid thalidomide formulation in an open-label, single-dose, three-way crossover study. Fifteen healthy subjects were given 50, 200, and 400 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using noncompartmental methods, and dose proportionality was assessed by linear regression of dose-normalized Cmax and AUC0-infinity. No serious or unexpected adverse events occurred. The most common adverse events were dizziness, somnolence, headache, and nausea. One patient was discontinued because of pharyngitis. There was a significant deviation from proportionality for Cmax with increases being less than proportional than changes in dose. AUC0-infinity increased proportionally with dose, suggesting that the overall amount of thalidomide absorbed, as well as its clearance, is independent of dose over the range used. V/F was found to increase with dose. This was most likely due to the terminal rate constant, which is used to calculate V/F, actually representing the absorption process rather than elimination (i.e., flip-flop phenomenon). The terminal rate constant (absorption rate constant) for the highest dose was 50% less than for the other two lower doses. The less than proportional increases in Cmax were most likely due to thalidomide's low aqueous solubility. Thalidomide shows reasonable dose proportionality with respect to AUC from 50 to 400 mg. [ABSTRACT FROM AUTHOR]

Iain G McKinnon,1,2 Stuart DM Thomas,3–5 Heather L Noga,6 Jane Senior7 1Institute of Health and Society, Newcastle University, Academic Psychiatry, Campus for Ageing and Vitality, 2Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK; 3School of Global, Urban and Social Studies, RMIT University, Melbourne, VIC, 4Legal Intersections Research Centre, University of Wollongong, Wollongong, NSW, 5Southern Clinical School, Monash University, Clayton, VIC, Australia; 6School of Criminology, Simon Fraser University, Burnaby, BC, Canada; 7Offender Health Research Network, University of Manchester, Manchester, UK Abstract: This paper is a scoping review of the available evidence regarding health care issues in police custody. It describes the types and prevalence of health disorders encountered in custody and provides an overview of current practice and recent innovations in police custody health care. In contrast to the health of prisoners, the health of police custody detainees has, until recently, received little academic or clinical attention. Studies on health care in police custody identified for this review are limited to a few geographical jurisdictions, including the UK, continental Europe, North America, and Australia. There are significant health concerns among police detainees including acute injury, chronic physical health problems, mental and cognitive disorders, and the risks associated with drug and alcohol intoxication or withdrawal. There is some evidence that deaths in police custody have reduced where attention has been paid to the latter issue. Police personnel continue to experience difficulties identifying detainees with health issues relevant to their safe detention, but research shows that the use of evidence-based screening tools improves detection of such morbidities. Innovations in police custody health care mainly relate to detainees with mental disorders, including improved identification of illness, timely access to mental health services, the protection of the rights of mentally disordered detainees, and the diversion of mentally disordered persons from the criminal justice system into appropriate health and social care interventions. There is a lack of rigorous research relating to interventions for physical health problems, protecting those at risk of substance withdrawal, and detainees with preexisting or peri-arrest injures. Research to improve the health of police custody detainees requires greater priority, focusing on case identification and service redesign to address high levels of morbidity and to facilitate health promotion and prevention activities. Keywords: police, vulnerable detainees, criminal justice system, deaths in custody, mentally disordered offenders, police health care innovations

The widespread collection of unofficial fees at health facilities is a common form of rent-seeking behaviour in Bangladesh. Typically, unofficial fees come in the form of cash payments for the performance of required services, for direct purchase of drugs and medical-surgical requisites, and for service access. Using observational and interview methods, this study explores linkages between official and unofficial fees at three Bangladesh health facility levels: primary care Thana Health Complexes, secondary or district hospitals, and medical college hospitals. The study estimates payment levels for different income classes and different payor types at these facilities, thereby highlighting potential equity, price and institutional questions associated with unofficial fees. Not only does the practice have clear income and equity effects, there also appear to be direct effects upon patient satisfaction, perception of quality, and the ability to pay for health services. The article concludes with a discussion of 'rent capture' processes in Bangladesh facilities and the effect of unofficial fees in six areas of health sector reform: displaced official policies, reduced merit goods production, upward income redistribution, distorted human resource development, growth of facility inefficiency, and obstruction of market reforms. [ABSTRACT FROM PUBLISHER]

Six studies were undertaken to develop a unidimensional, example-anchored rating scale measuring general health motivation (GHM), an important key to understanding health promotion behaviors. GHM differs conceptually from motivation pertaining to disease prevention, which is expressed as avoiding specific precursors to disease and death. Health promotion is not disease-specific (Pender, 1984) but is connected with positive social consequences (Becker, Maiman, Kirscht, Haefner, & Drachman, 1977). For our purposes, GHM is an individual's expressed intent to perform those behaviors that positively contribute to health. [ABSTRACT FROM AUTHOR]

Background: Hypoxic microenvironments in tumors contribute to transformation, which may alter metabolism, growth, and therapeutic responsiveness. The alpha-enolase gene encodes both a glycolytic enzyme (alpha-enolase) and a DNA-binding tumor suppressor protein, c-myc binding protein (MBP-1). These divergent alpha-enolase gene products play central roles in glucose metabolism and growth regulation and their differential regulation may be critical for tumor adaptation to hypoxia. We have previously shown that MBP-1 and its binding to the c-myc P2 promoter regulates the metabolic and cellular growth changes that occur in response to altered exogenous glucose concentrations.Results: To examine the regulation of alpha-enolase and MBP-1 by a hypoxic microenvironment in breast cancer, MCF-7 cells were grown in low, physiologic, or high glucose under 1% oxygen. Our results demonstrate that adaptation to hypoxia involves attenuation of MBP-1 translation and loss of MBP-1-mediated regulation of c-myc transcription, evidenced by decreased MBP-1 binding to the c-myc P2 promoter. This allows for a robust increase in c-myc expression, "early c-myc response", which stimulates aerobic glycolysis resulting in tumor acclimation to oxidative stress. Increased alpha-enolase mRNA and preferential translation/post-translational modification may also allow for acclimatization to low oxygen, particularly under low glucose concentrations.Conclusions: These results demonstrate that malignant cells adapt to hypoxia by modulating alpha-enolase/MBP-1 levels and suggest a mechanism for tumor cell induction of the hyperglycolytic state. This important "feedback" mechanism may help transformed cells to escape the apoptotic cascade, allowing for survival during limited glucose and oxygen availability. [ABSTRACT FROM AUTHOR]

Background: The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies., Objectives: This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies., Design: This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018)., Methods: TMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records., Results: In 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range, 0-46.83). Forty-eight patients (12%) had TMB ⩾10 mutations/Mb, 90% of which were B-cell or T-cell NHL. In 85 samples with available PD-L1 scores, 11 were high; 26, low; and 48, no tumor cell expression. PD-L1 TPS positive (⩾1%) was most common in T-cell NHL (7/9 (77%) cases) followed by B-cell NHL (21/51 (41%) cases). TMB ⩾4 mutations/Mb and PD-L1 score ⩾1% were significantly associated with shorter overall survival (OS) from diagnosis, with hazard ratio (HR) = 1.46 ( p  = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 ( p  = 0.04, 95% CI 1.04-4.30), respectively; the relationship was more pronounced when PD-L1 ⩾50% versus <50% was used (HR = 2.80, p  = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient R 2  = 0.04, p  = 0.04)., Conclusion: TMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies., Trial Registration: ClinicalTrials.gov NCT02478931., Competing Interests: E.S.S. is an employee of Foundation Medicine and is a stock owner in Roche. A.M.G. receives consulting fees from Seattle Genetics. R.K. is funded in part by 5U01CA180888-08 and 5UG1CA233198-05. R.K. has received research funding from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, and TopAlliance and from the NCI; as well as consultant and/or speaker fees and/or advisory board/consultant for Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Inc., Biological Dynamics, Caris, Datar Cancer Genetics, Daiichi, EISAI, EOM Pharmaceuticals, Iylon, LabCorp, Merck, NeoGenomics, Neomed, Pfizer, Prosperdtx, Regeneron, Roche, TD2/Volastra, Turning Point Therapeutics, X-Biotech; has an equity interest in CureMatch Inc. and IDbyDNA; serves on the Board of CureMatch and CureMetrix, and is a co-founder of CureMatch. A.-R.J., A.H.T., S.D.T., P.R., and P.J.S. declare no competing financial interests., (© The Author(s), 2024.)

Objective: People detained in short-term police custody often have complex health conditions that may necessitate emergency care, yet little is known about their management in EDs. The present study aimed to understand ED doctors' experiences and perceptions regarding the appropriateness and management of detainee transfers from police watch-houses to the EDs., Methods: A qualitative descriptive study, using semi-structured interviews undertaken with ED doctors working in five purposively sampled EDs across Queensland, Australia. Data were analysed using inductive content analysis., Results: Fifteen ED specialists and trainees participated. Participants reported that their overarching approach was to provide equitable care for watch-house detainees, as they would for any patient. This equitable approach needed to be responsive to complicating factors common to this population, including presence of police guards; restraints; complexity (physical/mental/social) of presentation; reliance on police to transport; ED doctors' often limited understanding of the watch-house environment; justice processes and uncertain legal disposition; communication with the watch-house; and detainees misreporting symptoms. Thresholds for assessment and treatment of detainees were contextualised to the needs of the patient, ED environment, and imperatives of other relevant agencies (e.g. police). Participants often relied on existing strategies to deliver quality care despite challenges, but also identified a need for additional strategies, including education for ED staff; improved communication with watch-houses; standardised paperwork; extended models of watch-house healthcare; and integrated medical records., Conclusions: Providing equitable healthcare to patients transported from watch-houses to the EDs is challenging but essential. Numerous opportunities exist to enhance the delivery of optimal care for this underserved population., (© 2024 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

This discussion provides commentary on the paper by Ethan M. Alt, Xiuya Chang, Xun Jiang, Qing Liu, May Mo, H. Amy Xia, and Joseph G. Ibrahim entitled "LEAP: the latent exchangeability prior for borrowing information from historical data". The authors propose a novel method to bridge the incorporation of supplemental information into a study while also identifying potentially exchangeable subgroups to better facilitate information sharing. In this discussion, we highlight the potential relationship with other Bayesian model averaging approaches, such as multisource exchangeability modeling, and provide a brief numeric case study to illustrate how the concepts behind latent exchangeability prior may also improve the performance of existing methods. The results provided by Alt et al. are exciting, and we believe that the method represents a meaningful approach to more efficient information sharing., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Biometric Society.)

The current wave of the opioid epidemic has contributed to a record number of drug-related overdoses and a significant proportion of people who experience opioid use disorder are admitted to local jails. These correctional facilities serve as the principal entry point to the criminal justice system as nearly every person who is taken into custody is admitted to a local detention center. Although jails are recognized as primary intervention points for people who may require treatment for opioid use disorder, services in these facilities remain deficient. The absence of jail-based treatment has become a pressing concern as the number of drug-related deaths in custody continues to rise and the risk of post-release overdose also remains high. The present study draws on the opioid-related module of the 2019 Bureau of Justice Statistics' Census of Jails to assess the relationships between the characteristics of 2588 local detention centers and the availability of treatment services. These specific approaches included screening for opioid use disorder, providing medication to manage withdrawal symptoms, administering medication for opioid use disorder (MOUD), providing overdose reversal medication at the time of release, and linking people with community-based care following release from the detention center. The results demonstrate facilities located in the Northeast, larger jails, those in urban areas, and detention centers with higher turnover rates are significantly more likely to provide a wider variety of opioid treatment services. These findings have important implications for the prioritization of policies and the allocation of resources to support the adoption of opioid treatment services in local jails., (© 2024. National Council for Mental Wellbeing.)

Selective outcome reporting can result in overestimation of treatment effects, research waste, and reduced openness and transparency. This review aimed to examine selective outcome reporting in trials of behavioural health interventions and determine potential outcome reporting bias. A review of nine health psychology and behavioural medicine journals was conducted to identify randomised controlled trials of behavioural health interventions published since 2019. Discrepancies in outcome reporting were observed in 90% of the 29 trials with corresponding registrations/protocols. Discrepancies included 72% of trials omitting prespecified outcomes; 55% of trials introduced new outcomes. Thirty-eight percent of trials omitted prespecified and introduced new outcomes. Three trials (10%) downgraded primary outcomes in registrations/protocols to secondary outcomes in final reports; downgraded outcomes were not statistically significant in two trials. Five trials (17%) upgraded secondary outcomes to primary outcomes; upgraded outcomes were statistically significant in all trials. In final reports, three trials (7%) omitted outcomes from the methods section; three trials (7%) introduced new outcomes in results that were not in the methods. These findings indicate that selective outcome reporting is a problem in behavioural health intervention trials. Journal- and trialist-level approaches are needed to minimise selective outcome reporting in health psychology and behavioural medicine.

Histamine performs dual roles as an immune regulator and a neurotransmitter in the mammalian brain. The histaminergic system plays a vital role in the regulation of wakefulness, cognition, neuroinflammation, and neurogenesis that are substantially disrupted in various neurodegenerative and neurodevelopmental disorders. Histamine H3 receptor (H3R) antagonists and inverse agonists potentiate the endogenous release of brain histamine and have been shown to enhance cognitive abilities in animal models of several brain disorders. Microglial activation and subsequent neuroinflammation are implicated in impacting embryonic and adult neurogenesis, contributing to the development of Alzheimer's disease (AD), Parkinson's disease (PD), and autism spectrum disorder (ASD). Acknowledging the importance of microglia in both neuroinflammation and neurodevelopment, as well as their regulation by histamine, offers an intriguing therapeutic target for these disorders. The inhibition of brain H3Rs has been found to facilitate a shift from a proinflammatory M1 state to an anti-inflammatory M2 state, leading to a reduction in the activity of microglial cells. Also, pharmacological studies have demonstrated that H3R antagonists showed positive effects by reducing the proinflammatory biomarkers, suggesting their potential role in simultaneously modulating crucial brain neurotransmissions and signaling cascades such as the PI3K/AKT/GSK-3β pathway. In this review, we highlight the potential therapeutic role of the H3R antagonists in addressing the pathology and cognitive decline in brain disorders, e.g., AD, PD, and ASD, with an inflammatory component.

Thousand and one amino acid kinase 1 (TAOK1) is a sterile 20 family Serine/Threonine kinase linked to microtubule dynamics, checkpoint signaling, DNA damage response, and neurological functions. Molecular-level alterations of TAOK1 have been associated with neurodevelopment disorders and cancers. Despite their known involvement in physiological and pathophysiological processes, and as a core member of the hippo signaling pathway, the phosphoregulatory network of TAOK1 has not been visualized. Aimed to explore this network, we first analyzed the predominantly detected and differentially regulated TAOK1 phosphosites in global phosphoproteome datasets across diverse experimental conditions. Based on 709 qualitative and 210 quantitative differential cellular phosphoproteome datasets that were systematically assembled, we identified that phosphorylation at Ser421, Ser9, Ser965, and Ser445 predominantly represented TAOK1 in almost 75% of these datasets. Surprisingly, the functional role of all these phosphosites in TAOK1 remains unexplored. Hence, we employed a robust strategy to extract the phosphosites in proteins that significantly correlated in expression with predominant TAOK1 phosphosites. This led to the first categorization of the phosphosites including those in the currently known and predicted interactors, kinases, and substrates, that positively/negatively correlated with the expression status of each predominant TAOK1 phosphosites. Subsequently, we also analyzed the phosphosites in core proteins of the hippo signaling pathway. Based on the TAOK1 phosphoregulatory network analysis, we inferred the potential role of the predominant TAOK1 phosphosites. Especially, we propose pSer9 as an autophosphorylation and TAOK1 kinase activity-associated phosphosite and pS421, the most frequently detected phosphosite in TAOK1, as a significant regulatory phosphosite involved in the maintenance of genome integrity. Considering that the impact of all phosphosites that predominantly represent each kinase is essential for the efficient interpretation of global phosphoproteome datasets, we believe that the approach undertaken in this study is suitable to be extended to other kinases for accelerated research., Competing Interests: Declaration of Competing Interest none, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The most recent wave of the opioid epidemic has contributed to record number of drug overdoses. Most fatal outcomes are associated with opioids and methamphetamine; two substances that tend to be used at high rates among criminal justice populations. Despite the steady rise in the number of overdoses in local detention centers, many correctional facilities do not conduct routine screens for opioid and methamphetamine use disorders. This study examines the utility of the UNCOPE, a 6-item brief screen, to detect probable Diagnostic and Statistical Manual for Mental Disorders , fifth edition (DSM-5) diagnoses for these 2 specific substance use disorders (SUDs). The study also examines key indicators of these specific SUDs., Methods: Data were collected from comprehensive substance use assessments conducted with 717 adults who were recently admitted to 4 county jails., Results: Findings indicate that 3 positive UNCOPE responses accurately detected 99.8% of opioid use disorder diagnoses and 98.7% of methamphetamine use disorder diagnoses. Receiver operating characteristic curve results generate an area under the curve at 0.99 for severe opioid use cases and 0.98 for severe methamphetamine use cases. Subsequent analyses indicate 2 of the 6 items on the UNCOPE function to accurately identify 100% of cases classified with opioid use disorder and 99.6% of cases classified with methamphetamine use disorder., Conclusions: Evidence suggests that UNCOPE is a practical and efficient approach to identifying opioid and methamphetamine use disorders. In addition, 2 items can serve as an ultra-brief method to detecting these conditions at the time of admission to detention centers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To compare procedural and long-term costs associated with the use of Balloon-Expandable Covered Stents (BECS) in the management of Aortoiliac Occlusive Disease (AIOD)., Materials and Methods: A cost-consequence model was developed to simulate the intra- and post-operative management of patients with AIOD from the perspective of private health-payers. The study assessed the costs of the LifeStream (BD, Franklin Lakes, New Jersey), iCAST/Advanta V12 (Getinge, Goteborg, Sweden), BeGraft Peripheral (Bentley, Hechingen, Germany), and Viabahn Balloon Expandable (VBX) (W.L. Gore, Flagstaff, Arizona) BECS devices. Device costs were identified from the Australian Prosthesis List, whereas clinical outcomes of BECS were estimated from a systematic review of the literature. Costs were calculated over 24 and 36 month time horizons and reported in US dollars., Results: Long-term, per-patient cost of each device at 24 and 36 months was $6253/$6634 for the LifeStream; $6359/$6869 for the iCAST/Advanta V12; $4806 (data available to 24 months) for the BeGraft Peripheral; and $4839/$5046 for the Viabahn VBX, respectively. Most of the cost difference was attributed to the number of stents required per treated limb and frequency of clinically-driven target lesion revascularization events., Conclusions: Best-available clinical evidence and economic modeling demonstrates that the BeGraft Peripheral and Viabahn VBX were of similar cost and the least costly options at 24 months, whereas at 36 months, the lowest cost BECS option for the treatment of AIOD was the Viabahn VBX., Clinical Impact: This analysis supports economically informed decision-making for health-payers managing systems that care for patients with AIOD. Stent length and avoiding reintervention were identified as key areas of cost-saving for future BECS development., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.L.V. is a consultant with modest honorarium to Medtronic, BD, W.L. Gore, Philips, Abbott Vascular, Boston Scientific, Nectero, Surmodics, Intervene, Vesteck, R3 Medical, and Cook Medical and holds equity in Provisio Inc, EBR Systems, and Vesteck Inc. A.H. is a medical advisory board member for Medtronic, Boston Scientific, Philips, W.L. Gore, Nectero, and Vesteck. S.D.T. is a consultant for BD, Abbott Vascular, and Medtronic. All other authors have nothing to declare.

Background: Arteriovenous fistulae (AVF) and Arteriovenous Grafts (AVG) may present a problematic vascular access for renal replacement therapy (RRT), reliant on recurrent specialist nurse and medical evaluation. Dysfunctional accesses are frequently referred 'out of the dialysis clinic' for specialist sonographic examination, with associated delays potentiating loss of vascular access viability and/or need for emergency intervention. Definitive anatomical and functional diagnostics based in the dialysis unit may help to solve these delays and associated complications., Objectives: This publication reports a novel vascular access monitoring concept, Robotic Tomographic Ultrasound (RTU)., Research Design: Robotic Tomographic Ultrasound incorporates a semi-autonomous, robotic vascular ultrasound system and purpose designed analysis software that can be deployed at the point of care. Three-dimensional scan data, as well as conventional B-Mode and Doppler data are obtained by the system and transferred to a cloud based reporting and analysis software. Scans are remotely annotated and interpreted by a sonographer, with diagnostic data presented securely to clinicians on their preferred web based application/web connected device., Results: Software developed specifically for pre AVF mapping, maturation and monitoring protocols, analyse the data and then present interpreted results to all caring clinicians to assist with decision making. Vascular access planning can be determined with high confidence with data from the Map module. Maturation data can be presented in line with institutional requirements to the dialysis nurse, facilitating precocious needle access., Conclusion: Robotic Tomographic Ultrasound is a novel approach to vascular access management that may reduce the risk of loss of functional access by regular monitoring with the system; automated alerts guiding clinicians to the need for pre-emptive intervention, and the potential to increase longevity of the vascular access., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All Authors are employees and shareholders for Vexev Pty Ltd.

Purpose: Healthcare avoidance and delay (HAD) in the transgender population has been well documented, and research has explored a range of associated factors that help to identify those most at risk of HAD. This review addresses a gap in the research by synthesizing research exploring associations between HAD and demographic factors., Methods: A systematic search of literature published at any time up to December 2021 was conducted, using five databases (EBSCO, EMBASE, PubMed, Scopus, and Web of Science) and manually searching reference lists of included studies. After exclusion of duplicates, 608 unique records were subjected to double screening. Papers reporting statistical analyses of HAD in association with any sociodemographic variables were included in this review. Papers consisted of nineteen cross-sectional studies. Narrative synthesis was used to address findings., Results: Nineteen studies met inclusion criteria, exploring HAD in association with a wide range of demographic factors, including sex and gender, social transition factors, age, race and ethnicity, socioeconomic factors, veteran status, education, sexuality, relationship status, citizenship, place of residence, and state demographics. Findings identified intra-community demographic risk factors, with consistent evidence for increased HAD among transmasculine, and younger, participants. Lower income and higher educational attainment were also associated with increased HAD, while remaining areas had weak or little evidence for association with HAD., Conclusion: This review expands knowledge in this area by highlighting demographic factors associated with increased HAD in research literature, and exploring how these may be further investigated to address substantial gaps in the body of research., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Siobhan D. Thomas reports financial support was provided by Irish Research Council., (© 2023 The Authors. Published by Elsevier Inc. CC BY 4.0.)

Treatment programs for people with histories of sexual violence form a critical part of criminal justice service rehabilitation. Completion of these programs is often a precondition of release. Meta-analytic reviews suggest moderate benefit is associated with treatment completion, although effect sizes vary. This study examined whether commencement of open versus closed group programs was associated with treatment completion and recidivism. Participants were 426 adult men who commenced treatment between April 1, 2014, and December 31, 2017. Participants were followed-up until June 30, 2018. Programs varied by type (open versus closed), location (in-custody versus in-community) and intensity (moderate versus high). No significant differences were observed between open and closed programs for treatment completion but men who were treated in-custody were more likely to complete treatment when compared to those men who commenced treatment in the community. No significant differences were observed between open and closed programs for sexual or for any recidivism.

The coordination chemistry of scorpionate ligands based on borates containing the 7-azaindole heterocycle is relatively unexplored. Thus, there is a requirement to further understand their coordination chemistry. This article outlines the synthesis and characterization of a family of complexes containing anionic flexible scorpionate ligands of the type [(R)(bis-7-azaindolyl)borohydride] - ([ R Bai ] - ), where R = Me, Ph or naphthyl. The three ligands were coordinated to a series of copper(I) complexes containing a phosphine co-ligand to form the complexes, [Cu( Me Bai )(PPh 3 )] ( 1 ), [Cu( Ph Bai )(PPh 3 )] ( 2 ), [Cu( Naphth Bai )(PPh 3 )] ( 3 ), [Cu( Me Bai )(PCy 3 )] ( 4 ), [Cu( Ph Bai )(PCy 3 )] ( 5 ) and [Cu( Naphth Bai )(PCy 3 )] ( 6 ). Additional copper(II) complexes, namely, [Cu( Me Bai ) 2 ] ( 7 ) and [Cu( Ph Bai ) 2 ] ( 8 ), were obtained during attempts to obtain single crystals from complexes 4 and 2 , respectively. Complexes 7 and 8 were also prepared independently from CuCl 2 and two equivalents of the corresponding Li[ R Bai ] salt alongside an additional complex, namely, [Cu( Naphth Bai ) 2 ] ( 9 ). The copper(I) and copper(II) complexes were characterized using spectroscopic and analytical methods. Furthermore, a crystal structure was obtained for eight of the nine complexes. In all cases, the boron-based ligand was found to bind to the metal centers via a κ 3 - N , N , H coordination mode.

Introduction: Juxta-anastomotic stenosis (JXAS) is a common problem afflicting the arteriovenous fistula (AVF). This study aimed to evaluate the safety and long-term efficacy of an interwoven nitinol stent (Supera, Abbott Vascular, Santa Clara, CA, USA) in the treatment of radiocephalic AVF JXAS., Methods: A single-center, retrospective, observational study was conducted of patients with failing AVF due to JXAS treated with an interwoven nitinol stent. End points included JXAS target lesion primary patency, access circuit primary patency, assisted access circuit primary patency, and endovascular intervention rate (EIR)., Results: Sixty patients were treated with a Supera stent in the JXAS between February 2014 and March 2020. One patient was excluded (AVF used for illicit drug use), leaving 59 patients (67.8% male, mean age 66.9 ± 11.4 years [range: 40-84]) with typical medical comorbidities. Overall, 45.8% of patients had previous AVF intervention. The stent was inserted with a 100% technical success rate with a mean follow-up of 729.6 ± 456.0 days (range: 5-2182 days). Juxta-anastomotic stenosis target lesion primary patency was 68.2 ± 6.6%, 53.3 ± 7.5%, and 46.2 ± 8.1% at 12, 24, and 36 months, respectively. The EIR was .64 (0-3.29) procedures/patient/year, after which the assisted access circuit primary patency rate was 94.3 ± 3.2% at 12, 24, and 36 month time points. Three thrombosed circuits occurred which were all successfully salvaged with no difference in patency by indication for procedure and no AVFs lost/abandoned out to 3 years. Avoidance of stent post-dilatation and the presence of stent mal-apposition were associated with improved primary patency, and reduced EIR, which may suggest an importance in vessel preparation prior to stent implantation., Conclusion: Interwoven nitinol stent treatment of the failing AVF with JXAS results in promising 3 year JXAS patency, with a low rate of endovascular re-intervention for those circuits developing restenosis. All AVFs were maintained over 3 years, demonstrating this treatment allows for long-term radiocephalic AVF vascular access.

Little is known about the acute changes in cutaneous microvascular function that occur in response to exercise, the accumulation of which may provide the basis for beneficial chronic cutaneous vascular adaptations. Therefore, we examined the effects of acute exercise on cutaneous thermal hyperaemia. Twelve healthy, recreationally active participants (11 male, 1 female) performed 30-minute cycling at 50 % (low-intensity exercise, LOW) or 75 % (high-intensity exercise, HIGH) maximum heart rate. Laser Doppler flowmetry (LDF) and rapid local skin heating were used to quantify cutaneous thermal hyperaemia before (PRE), immediately following (IMM) and 1-h (1HR) after exercise. Baseline, axon reflex peak, axon reflex nadir, plateau, maximum skin blood flow responses to rapid local heating (42 °C for 30-min followed by 44 °C for 15-min) at each stage were assessed and indexed as cutaneous vascular conductance [CVC = flux / mean arterial blood pressure (MAP), PU·mm Hg -1 ], and expressed as a percentage of maximum (%CVC max ). Exercise increased heart rate (HR), MAP and skin blood flow (all P < 0.001), and to a greater extent during HIGH (all P < 0.001). The axon reflex peak and nadir were increased immediately and 1-h after exercise (all comparisons P < 0.01 vs. PRE), which did not differ between intensities (peak: P = 0.34, axon reflex nadir: P = 0.91). The endothelium-dependent plateau response was slightly elevated after exercise (P = 0.06), with no effect of intensity (P = 0.58) nor any interaction effect (P = 0.55). CONCLUSION: Exercise increases cutaneous microvascular axonal responses to local heating for up to 1-h, suggesting an augmented sensory afferent function post-exercise. Acute exercise may only modestly affect endothelial function in cutaneous microcirculation., Competing Interests: Declaration of competing interest 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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication along with repetitive stereotypic behaviors. Currently, there are no specific biomarkers for diagnostic screening or treatments available for autistic patients. Numerous genetic disorders are associated with high prevalence of ASD, including tuberous sclerosis complex, phosphatase and tensin homolog, and fragile X syndrome. Preclinical investigations in animal models of these diseases have revealed irregularities in the PI3K/Akt/mTOR signaling pathway as well as ASD-related behavioral defects. Reversal of the downstream molecular irregularities, associated with mTOR hyperactivation, improved the behavioral deficits observed in the preclinical investigations. Plant bioactive molecules have shown beneficial pre-clinical evidence in ASD treatment by modulating the PI3K/Akt/mTOR pathway. In this review, we summarize the involvement of the PI3K/Akt/mTOR pathway as well as the genetic alterations of the pathway components and its critical impact on the development of the autism spectrum disorder. Mutations in negative regulators of mTORC1, such as TSC1, TSC2, and PTEN, result in ASD-like phenotypes through the disruption of the mTORC1-mediated signaling. We further discuss the various naturally occurring phytoconstituents that have been identified to be bioactive and modulate the pathway to prevent its disruption and contribute to beneficial therapeutic effects in ASD.

Apigenin is a naturally occurring dietary flavonoid found abundantly in fruits and vegetables. It possesses a wide range of biological properties that exert antioxidant, anti-inflammatory, anticancer, and antibacterial effects. These effects have been reported to be beneficial in the treatment of atherosclerosis, stroke, hypertension, ischemia/reperfusion-induced myocardial injury, and diabetic cardiomyopathy, and provide protection against drug-induced cardiotoxicity. These potential therapeutic effects advocate the exploration of the cardioprotective actions of apigenin. This review focuses on apigenin, and the possible pharmacological mechanisms involved in the protection against cardiovascular diseases. We further discuss its therapeutic uses and highlight its potential applications in the treatment of various cardiovascular disorders. Apigenin displays encouraging results, which may have implications in the development of novel strategies for the treatment of cardiovascular diseases. With the commercial availability of apigenin as a dietary supplement, the outcomes of preclinical studies may provide the investigational basis for future translational strategies evaluating the potential of apigenin in the treatment of cardiovascular disorders. Further preclinical and clinical investigations are required to characterize the safety and efficacy of apigenin and establish it as a nutraceutical as well as a therapeutic agent to be used alone or as an adjuvant with current drugs.

Dysregulation in brain neurotransmitters underlies several neuropsychiatric disorders, e.g., autism spectrum disorder (ASD). Also, abnormalities in the extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway pave the way for neuroinflammation, neurodegeneration, and altered learning phenotype in ASD. Therefore, the effects of chronic systemic administration of the multiple-targeting antagonist ST-713 at the histamine H3 receptor (H3R) and dopamine D2/D3 receptors (D2/D3R) on repetitive self-grooming, aggressive behaviors, and abnormalities in the MAPK pathway in BTBR T + Itpr3tf/J (BTBR) mice were assessed. The results showed that ST-713 (2.5, 5, and 10 mg/kg, i.p.) mitigated repetitive self-grooming and aggression in BTBR mice (all p < 0.05), and the ameliorative effects of the most promising dose of ST-713 (5 mg/kg, i.p.) on behaviors were completely abrogated by co-administration of the H3R agonist (R)-α-methylhistamine or the anticholinergic drug scopolamine. Moreover, the elevated levels of several MAPK pathway proteins and induced proinflammatory markers such as tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and IL-6 were significantly suppressed following chronic administration of ST-713 (5 mg/kg, i.p.) (all p < 0.01). Furthermore, ST-713 significantly increased the levels of histamine and dopamine in hippocampal tissue of treated BTBR mice (all p < 0.01). The current observations signify the potential role of such multiple-targeting compounds, e.g., ST-713, in multifactorial neurodevelopmental disorders such as ASD.

Dimethyl fumarate (DMF) is a small molecule that has been shown to assert potent in vivo immunoregulatory and anti-inflammatory therapeutic actions. The drug has been approved and is currently in use for treating multiple sclerosis and psoriasis in the USA and Europe. Since inflammatory reactions have been significantly implicated in the etiology and progression of diverse disease states, the pharmacological actions of DMF are presently being explored and generalized to other diseases where inflammation needs to be suppressed and immunoregulation is desirable, either as a monotherapeutic agent or as an adjuvant. In this review, we focus on DMF, and present an overview of its mechanism of action while briefly discussing its pharmacokinetic profile. We further discuss in detail its pharmacological uses and highlight its potential applications in the treatment of cardiovascular diseases. DMF, with its unique combination of anti-inflammatory and vasculoprotective effects, has the potential to be repurposed as a therapeutic agent in patients with atherosclerotic cardiovascular disease. The clinical studies mentioned in this review with respect to the beneficial effects of DMF in atherosclerosis involve observations in patients with multiple sclerosis and psoriasis in small cohorts and for short durations. The findings of these studies need to be assessed in larger prospective clinical trials, ideally with a double-blind randomized study design, investigating the effects on cardiovascular endpoints as well as morbidity and mortality. The long-term impact of DMF therapy on cardiovascular diseases also needs to be confirmed.

Background: The clinical utility of the native arteriovenous fistula (AVF) has been limited by the prolonged time required for maturation, the low overall maturation rate, and subsequent abandonment. Endovascular intervention has been increasingly accepted as the first-line therapy for AVF stenosis. The objective of the present study was to evaluate the AVF formation outcomes when early endovascular intervention was selectively performed to bring about timely AVF maturation., Methods: We performed a retrospective study (February 2014 to February 2020) of 82 AVF consecutive patients (mean age, 62.5 ± 13.5 years; range, 17-83; 58 men [70.7%]) with end-stage renal failure who had undergone vascular access construction at a single institution. The 4-year AVF patency, vascular diameters, hemodialysis parameters, reintervention rate, and mortality were analyzed., Results: Radiocephalic AVF was the most common fistula constructed (71 patients; 88.6%). The evaluation at a mean of 46.2 ± 56.0 days (range, 5-343 days) after AVF formation revealed 33 immature AVFs (40.2%). Subsequently, 19 patients had undergone endovascular procedures, including angioplasty and/or stenting of the juxta-anastomosis, cannulation zones, and/or outflow segments to bring about timely maturation of the AVF. Hence, 93.9% of the AVFs had reached functional patency (maturation) by 6 months after formation, with a mean time to maturation of 67.8 ± 65.9 days (range, 5-320 days). After reaching maturation, the primary access functional patency was 82% ± 4.3% at 6 months, 58% ± 5.5% at 12 months, and 34% ± 6.8% at 48 months. The primary assisted access functional patency was 95% ± 2.4% at 6 months, 90% ± 3.3% at 12 months, and 83% ± 4.7% at 48 months. A total of 121 endovascular interventions were performed to maintain patency, equating to an endovascular reintervention rate of 0.37 procedure/patient year. The mean arterial, venous, and brachial flow rates did not change significantly after maturation with a mean AVF (primary assisted functional patency) survival time of 5.9 ± 0.26 years (range, 5.33-6.36 years) from maturation. Only 12 thromboses had occurred after the first follow-up review after AVF formation. These were all salvaged using endovascular techniques, leading to 100% total secondary functional patency at 4 years. The 5-year estimated all-cause mortality was 45.6% ± 12.7%., Conclusions: The AVF maturation rate and interval to maturation were improved when early endovascular intervention was selectively performed after AVF formation. This allowed for near universal maturation. In addition, once matured, the use of ongoing endovascular reinterventions allowed for a low reintervention rate and long-term patency, providing reliable long-term renal vascular access., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

At Michigan State University (MSU), the AGEP learning community features the participation of over 70% of the African-American, Latinx, and Native-American under-represented minorities (URM), also referred to as Black, Indigenous, and People of Color (BIPOC) doctoral students in fields sponsored by the National Science Foundation (NSF). Monthly learning community (LC) meetings allow AGEP participants to create dialogues across disciplines through informal oral presentations about current research. The learning communities also offer opportunities to share key information regarding graduate school success and experience; thus providing a social network that extends beyond the academic setting. At MSU, AGEP also provides an interdisciplinary and multigenerational environment that includes graduate students, faculty members, post-docs and prospective graduate students. Using monthly surveys over a 4-year period, we evaluated the impact of this AGEP initiative focusing on the utility of the program, perceptions of departmental climate, career plans and institutional support. Findings indicate that AGEP participants consider their experiences in the program as vital elements in the development of their professional identity, psychological safety, and career readiness. Experiences that were identified included networking across departments, focus on career placement, involvement in minority recruitment and professional development opportunities. Additionally, AGEP community participants resonated with the "sense of community" that is at the core of the MSU AGEP program legacy. In this article, we proposed a variation of Tomlinson's Graduate Student Capital model to describe the AGEP participants' perceptions and experiences in MSU AGEP. Within this 4-year period, we report over 70% graduation rate (completing with advanced degrees). More than half of Ph.D. students and almost 30% of master's degree students decided to pursue academia as their careers. In addition, we found a high satisfaction rate of AGEP among the participants. Our analysis on graduate student capital helped us identify motivating capital development by years spent at MSU and as an AGEP member. These findings may provide some insight into which capitals may be deemed important for students relative to their experiences at MSU and in AGEP and how their priorities change as they transition toward graduation., 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 © 2021 Thomas, Ali, Alcover, Augustin and Wilson.)

Objectives: The aim of this study was to seek expert consensus regarding the features that predict adverse outcomes in order to develop a dedicated angiographic classification system for femoropopliteal artery dissection., Background: Dissection of the femoral and popliteal arteries is common after percutaneous angioplasty. Its classification is important. However, all current classification systems have significant limitations., Methods: Delphi consensus methodology was performed over 3 rounds, using an expert panel of 17 interventionalists. Each was asked to rank dissection features with the potential to lead to acute technical failure and/or early restenosis and then which combination of features would require the placement of a metallic scaffold to avoid those outcomes. Results were used to develop a novel grading system and dissection treatment algorithm., Results: Four main characteristics were identified from a comprehensive preliminary list. There was a good level of agreement between panelists from 773 responses (48 combinations). All panelists recommended scaffolding if a dissection produced a ≥50% diameter reduction (100%). Most recommended scaffolding if the dissection had a spiral shape (73%-100%), was severely flow limiting (93%-100%), or had complex morphology defined by long and multiple dissections (65%-100%). Multiple combinations of those features were more likely to receive a recommendation to scaffold., Conclusions: Scaffolding of a postangioplasty dissection is recommended in the presence of significant diameter reduction, spiral shape, flow impairment, or adverse morphology (DISFORM). The DISFORM classification system has been developed as a tool to provide uniform language to standardize reporting and for discussion of dissection treatment and prognosis., Competing Interests: Funding Support and Author Disclosures Dr Schneider is a medical advisory board member for Medtronic, Boston Scientific, and Philips; and consultant for Surmodics, Silk Road Medical, Medtronic, Cardiovascular Systems Inc, Cagent, CTI Vascular Ag, Illuminate, Intervene, Limflow, and Devoro. Dr Thomas is a consultant for Abbott Vascular, Medtronic, and Philips Healthcare. Dr Brodmann is a consultant for BD Bard, Philips, Medtronic, Boston Scientific, Biotronik, Cook Medical, Cagent, Shockwave, MedAlliance, Soundbite, Reflow Medical, and Bayer Healthcare. Dr Armstrong is a consultant for Abbott Vascular, Boston Scientific, Cardiovascular Systems, Medtronic, Philips Healthcare, PA Bypass, and Shockwave. Dr Holden is a medical advisory board member for Gore, Boston Scientific, Philips Healthcare, and Medtronic; and is a clinical investigator for Cook, BD Bard, Shockwave, Intact Medical, Surmodics, Cagent, and Trireme Medical. Dr Varcoe is a consultant for Abbott Vascular, Intact Medical, Shockwave, Medtronic, BD Bard, Philips Healthcare, Surmodics, and Intervene. All paid honoraria were modest. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: A late increased mortality risk has been reported in a summary level meta-analysis of patients with femoropopliteal artery occlusive disease treated with paclitaxel-coated angioplasty balloons and stents. However, at the longer follow up timepoints that analysis was limited by small trial numbers and few participants. The aim of this study was to report an updated summary level risk of all-cause mortality after treatment with paclitaxel-coated devices in that same patient group., Materials and Methods: We performed a systematic review and meta-analysis of randomized controlled trials to investigate the mortality outcomes associated with paclitaxel-coated devices used to treat patients with occlusive disease of femoropopliteal arteries (last search date December 10, 2020). The single primary endpoint was all-cause mortality., Results: We identified 34 randomized controlled trials (7654 patients; 84% intermittent claudication). There were 622 deaths among 4147 (15.0%) subjects in the paclitaxel device group and 475 deaths among 3507 (13.5%) subjects in the noncoated control group [relative risk ratio (RR) 1.07, 95% confidence interval (CI) 0.96 to 1.20, p=0.20, I 2 =0%). All-cause mortality was similar between groups at 12 months (34 studies, 7654 patients; RR 0.99, 95% CI 0.81 to 1.22, p=0.94, I 2 =0%), 24 months (20 studies, 3799 patients; RR 1.16, 95% CI 0.87 to 1.55, p=0.31, I 2 =0%), and 60 months (9 studies, 2288 patients; RR 1.19, 95% CI 0.98 to 1.45, p=0.08, I 2 =0%)., Conclusion: This updated meta-analysis with included additional trials and larger patient numbers shows no evidence of increased risk of all-cause mortality in patients treated with paclitaxel-coated devices, compared with uncoated devices for femoropopliteal disease at all time points to 60 months. There is therefore no justification to limit their use, or alter regulatory body follow-up recommendations in this patient population., Systematic Review Registration: CRD42020216140.

Objective: Definitive treatment techniques for symptomatic deep venous reflux have been relegated to complex and invasive open surgery which is rarely performed today. The BlueLeaf System provides an endovenous method for the formation of deep venous valves without an implant, avoiding the complications associated with permanent foreign materials. The system has the adaptability to form valves within the femoral and popliteal veins at multiple levels in a single procedure. The aim was to determine the midterm safety and efficacy of this novel device in an early feasibility study., Methods: Feasibility of endovenous deep venous valve formation was assessed in patients with chronic venous insufficiency (Clinical, Etiologic, Anatomic, Pathophysiologic [CEAP] 4-6). Follow-up was completed through 1 year, assessing vein patency and reflux time (RT) with duplex ultrasound examination. Venous clinical improvement was evaluated using the revised Venous Clinical Severity Scale., Results: Of the 14 patients, 13 (93%) had successful formation of at least one monocuspid valve, with a mean number of 1.4 valves (range, 0-3 valves) per patient. There were no device-related serious adverse events during the index procedure. There were no deep venous thromboses reported at any time point, including 10 patients through the 1-year follow-up. In patients with at least one valve formed, site reported duplex ultrasound examination measured the average RT in the popliteal vein below valve formations, was 3.0 ± 1.0 seconds at baseline, 3.9 ± 3.1 seconds at 30 days, and 3.6 ± 2.1 seconds at 360 days. The revised Venous Clinical Severity Scale improved in all 13 successfully treated patients, decreasing from 15.0 ± 6.0 at baseline to 11.6 ± 5.5 at 30 days, 10.7 ± 5.3 at 210 days, and 9.4 ± 5.0 at 360 days (P = .0002; baseline to 360 days). Among the five patients with an ulcer who reached the 360-day follow-up visit, all (100%) healed at least one ulcer. Two patients (40%) healed all ulcers and three patients (60%) had a decrease in ulcers number but remained at C6 at 360 days. The five patients with a total of nine active ulcers at baseline had four active ulcers at 360 days., Conclusions: The BlueLeaf System holds promise as a minimally invasive means to safely form fully autogenous deep venous valves. Reconstructed deep veins remained patent, without deep venous thrombosis and symptomatic improvement was consistently observed; however, a decrease in the RT was not. Incremental device design improvements have been undertaken to improve valve function. The results of these iterations await further clinical evaluation., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)