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Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P =.036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P =.04) and at 90d (P =.01), but not at 14d (P =.06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients. [ABSTRACT FROM AUTHOR]

Chisato Izumi,1 Rei Matsuyama,2 Kaoru Yamabe,2 Kosuke Iwasaki,3 Tomomi Takeshima,3 Shannon ME Murphy,4 Lida Teng,5 Ataru Igarashi5,6 1Division of Heart Failure, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; 2Market Access, Edwards Lifesciences Limited, Tokyo, Japan; 3Milliman Inc., Tokyo, Japan; 4Edwards Lifesciences Corporation, Irvine, CA, USA; 5Department of Health Economic and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 6Unit of Public Health and Preventive Medicine Yokohama City University School of Medicine, Kanagawa, JapanCorrespondence: Ataru Igarashi, Department of Health Economic and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan, Tel +81 3 5841 4828, Email atarui1@mac.com Kaoru Yamabe, Market Access, Edwards Lifesciences Limited, Nittochi Nishi-shinjuku Building, 6-10-1, Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan, Tel +81 80 4442 0883, Fax +81 3 6894 0034, Email kaoru_yamabe@edwards.comPurpose: Heart failure (HF) is a serious public health burden that is rapidly increasing in the aging population. Valvular heart disease (VHD) is a known etiology of heart failure (HF); however, the impact of VHD on outcomes of patients with HF has not been well-studied in Japan. This study aimed to determine the rates of VHD in Japanese patients admitted for HF and explore associations of VHD with in-hospital outcomes through a claim-based analysis.Patients and methods: We analyzed claims data from 86,763 HF hospitalizations (January 2017 through December 2019) from the Medical Data Vision database. Common etiologies of HF were examined, then hospitalizations were categorized into those with VHD and those without. Covariate-adjusted models were used to explore the association of VHD with in-hospital mortality, length of stay, and medical cost.Results: Of 86,763 hospitalizations for HF, 13,183 had VHD and 73,580 did not. VHD was the second most frequent etiology of HF (15.2%). The most frequent type of VHD was mitral regurgitation (36.4% of all hospitalizations with VHD), followed by aortic stenosis (33.7%) and aortic regurgitation (16.4%). There was no significant difference in in-hospital mortality between hospitalizations with VHD vs those without (9.0% vs 8.9%; odds ratio [95% CI]: 1.01 [0.95– 1.08]; p=0.723). Hospitalizations with VHD were associated with significantly longer length of stay (26.1 vs 24.8 days; incident rate ratio [95% CI]: 1.05 [1.03– 1.07]; p< 0.001) and higher medical costs (1536 vs 1195 thousand yen; rate ratio [95% CI]: 1.29 [1.25– 1.32]; p< 0.001).Conclusion: VHD was a frequent etiology of HF that was associated with significant medical resource use. Future studies are needed to investigate whether timely VHD treatment could reduce HF progression and its associated healthcare resource utilization.Graphical Abstract: Keywords: length of stay, medical costs, mortality, etiology, hospital claims, medical data vision

Charles Hunley,1 Shannon ME Murphy,2 Michael Bershad,2 Halit O Yapici3 1Department of Critical Care Medicine, Orlando Regional Medical Center, Orlando, FL, USA; 2Edwards Lifesciences, Irvine, CA, USA; 3Boston Strategic Partners, Inc., Boston, MA, USACorrespondence: Charles HunleyDepartment of Critical Care Medicine, Orlando Regional Medical Center, 86 West Underwood Street, Suite 102, Orlando, FL, 32806, USATel +1 407 927 7955Fax +1 321 843 3569Email charles.hunley@orlandohealth.comPurpose: To evaluate the utilization of hypotension diagnosis codes by shock type and year in known hypotensive patients.Patients and Methods: Retrospective analysis of the Medicare fee-for-service claims database. Patients with a shock diagnosis code between 2011 and 2017 were identified using the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM). Based on specific ICD codes corresponding to each shock type, patients were classified into four mutually exclusive cohorts: cardiogenic shock, hypovolemic shock, septic shock, and other/unspecified shock. Annual proportion and counts of cases with at least one hypotension ICD code for each shock cohort were generated to produce 7-year medical code utilization trends. A Cochran-Armitage test for trend was performed to evaluate the statistical significance.Results: A total of 2,200,275 shock patients were analyzed, 13.3% (n=292,192) of which received a hypotension code. Hypovolemic shock cases were the most likely to receive a hypotension code (18.02%, n=46,544), while septic shock cases had the lowest rate (11.48%, n=158,348). The proportion of patients with hypotension codes for other cohorts were 18.0% (n=46,544) for hypovolemic shock and 16.9% (n=32,024) for other/unspecified shock. The presence of hypotension codes decreased by 0.9% between 2011 and 2014, but significantly increased from 10.6% in 2014 to 17.9% in 2017 (p < 0.0001, Z=− 105.05).Conclusion: Hypotension codes are remarkably underutilized in known hypotensive patients. Patients, providers, and researchers are likely to benefit from improved hypotension coding practices.Keywords: blood pressure, clinical coding, data accuracy, International Classification of Diseases

Background: TRPV4 mutations have been identified in Charcot-Marie-Tooth type 2 (CMT2), scapuloperoneal spinal muscular atrophy and distal hereditary motor neuropathy (dHMN).Objective: We aimed to screen the TRPV4 gene in 422 British patients with inherited neuropathy for potentially pathogenic mutations.Methods: We sequenced TRPV4 coding regions and splice junctions in 271 patients with CMT2 and 151 patients with dHMN. Mutations were clinically and genetically characterised and screened in ≥345 matched controls.Results: 13 missense and nonsense variants were identified, of which five were novel and absent from controls (G20R, E218K, N302Y, Y567X and T701I). N302Y and T701I mutations were present in typical CMT2 cases and are potentially pathogenic based on in silico analyses. G20R was detected in a patient with dHMN and her asymptomatic father and is possibly pathogenic with variable expressivity. The Y567X variant segregated with disease in a family with severe CMT2 but also with a MFN2 mutation reported to cause a mild CMT2 phenotype. Although Y567X caused nonsense mediated mRNA decay, the amount of TRPV4 protein on western blotting of patient lymphoblasts was no different to control. Y567X is therefore unlikely to be pathogenic. E218K is unlikely to be pathogenic based on segregation.Conclusions: In this comprehensive analysis of the TRPV4 gene, we identified mutations in <1% of patients with CMT2/dHMN. We found that TRPV4 likely harbours many missense and nonsense non-pathogenic variants that should be analysed in detail to prove pathogenicity before results are given to patients. [ABSTRACT FROM AUTHOR]

Background: Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.Methods: The genes known to cause CMT were sequenced in 1607 patients with CMT (425 patients attending an inherited neuropathy clinic and 1182 patients whose DNA was sent to the authors for genetic testing) to determine the proportion of different subtypes in a UK population.Results: A molecular diagnosis was achieved in 62.6% of patients with CMT attending the inherited neuropathy clinic; in 80.4% of patients with CMT1 (demyelinating CMT) and in 25.2% of those with CMT2 (axonal CMT). Mutations or rearrangements in PMP22, GJB1, MPZ and MFN2 accounted for over 90% of the molecular diagnoses while mutations in all other genes tested were rare.Conclusion: Four commonly available genes account for over 90% of all CMT molecular diagnoses; a diagnostic algorithm is proposed based on these results for use in clinical practice. Any patient with CMT without a mutation in these four genes or with an unusual phenotype should be considered for referral for an expert opinion to maximise the chance of reaching a molecular diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of an intervention comprising (1) a practice-based care coordination program, (2) augmented by pay for performance (P4P) for meeting quality targets, and (3) complemented by a third-party disease management on quality of care and resource use for older adults with diabetes.Data Sources/study Setting: Claims files of a managed care organization (MCO) for 20,943 adults aged 65 and older with diabetes receiving care in Alabama, Tennessee, or Texas, from January 2004 to March 2007.Study Design: A quasi-experimental, longitudinal study in which pre- and postdata from 1,587 patients in nine intervention primary care practices were evaluated against 19,356 patients in MCO comparison practices (>900). Five incentivized quality measures, two nonincentivized measures, and two resource-use measures were investigated. We examined trends and changes in trends from baseline to follow-up, contrasting intervention and comparison group member results.Principal Findings: Quality of care generally improved for both groups during the study period. Only slight differences were seen between the intervention and comparison group trends and changes in trends over time.Conclusions: This study did not generate evidence supporting a beneficial effect of an on-site care coordination intervention augmented by P4P and complemented by third-party disease management on diabetes quality or resource use. [ABSTRACT FROM AUTHOR]

Ambar Lugo-Merly,1 Leonardo J Molina Thurin,2 Natalio J Izquierdo-Encarnacion,3 Stella M Casillas-Murphy,4 Armando Oliver-Cruz5 1School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico; 2San Juan Bautista School of Medicine, Caguas, Puerto Rico; 3Department of Surgery, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico; 4Ojos Puerto Rico, Arecibo, Puerto Rico; 5Department of Ophthalmology, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto RicoCorrespondence: Ambar Lugo-Merly, School of Medicine, University of Puerto Rico, Medical Sciences Campus, PO BOX 365067, San Juan, 00936-5067, Puerto Rico, Tel +1 787 758 2525, Email ambar.lugo@upr.eduPurpose: To report on a patient with Stargardt disease (STGD1) and with an intronic mutation in the ABCA4 gene.Patients and Methods: A 69-year-old female patient presented to the clinic complaining of progressive vision loss. The ophthalmic evaluation was remarkable for a best corrected visual acuity of counting fingers at 5’ in the right eye and 3’ in the left eye. Imaging revealed deep extensive atrophy of the central macula, epithelial pigment hyperplasia, and other areas of multifocal atrophy in the right eye. Furthermore, fundus autofluorescence imaging of the macula showed central hypoautofluorescence with bilateral expansion to the periphery in both eyes. A full-field electroretinogram showed a normal rod response, with decreased cone response, bilaterally. Genetic testing was positive for a homozygous intronic mutation in the ABCA4 gene of the variant c.5714+5G>A.Conclusions and Importance: Patients with STGD1 due to presumed mild or moderate mutations in the ABCA4 gene may have a more severe presentation and progression of the disease. Based on this, the first report of a genotype–phenotype correlation in a Puerto Rican patient with STGD1 disease, genotyping all Puerto Rican patients is warranted.Keywords: Stargardt disease, intronic mutation, ABCA4 gene, macular dystrophy

Introduction: Evidence suggests that brief, skills-based behavioral interventions are effective at improving clinical outcomes related to substance use and HIV, but little data exists on whether such interventions can incidentally improve employment. We examined preliminary changes in employment over six months following Khanya, a brief peer-delivered behavioral intervention to reduce substance use and improve antiretroviral therapy (ART) adherence compared to enhanced treatment as usual (ETAU)., Methods: Adults living with HIV (N = 61) with at least moderate substance use and ART non-adherence were recruited from a primary care clinic in Khayelitsha, South Africa, a community with high rates of unemployment. Participants were randomized 1:1 to Khanya versus ETAU and assessed at baseline, 3- and 6-months. Employment was categorized as unemployed, casually, or full-time employed. Multilevel modeling was used to predict log odds and probability of categorical employment status over time, by arm., Results: At baseline, 78.7% of the sample were unemployed, 16.4% were casually employed, and 4.9% were employed full-time. There was a significant increase in employment in both treatment arms at 3-months (p = 0.03) but only the Khanya arm demonstrated significant increases at 6-months (p = 0.02). At 6-months, 59% of participants in Khanya had any employment (from 13% at baseline), compared to 38% in ETAU (from 29% at baseline)., Conclusions: Study data suggest a brief behavioral intervention for substance use and ART adherence may support employment among people with HIV living in a resource-constrained community. However, future research with larger sample sizes and longer-term follow ups is needed to replicate these findings., Trial Registration: ClinicalTrials.gov identifier: NCT03529409. Trial registered on May 18, 2018., Competing Interests: Declaration of competing interest Dr. Murphy served on an advisory board panel for Indivior, outside the submitted work. Dr. Safren receives royalties for books on cognitive behavioral therapy from Oxford University Press, Guilford Publications, and Springer/Humana Press. The other authors declare they have no competing interests to report., (Copyright © 2024. Published by Elsevier B.V.)

Study Objective(s): To evaluate the cost-effectiveness of implementation facilitation compared with a standard educational strategy to promote emergency department (ED)-initiated buprenorphine with linkage to ongoing opioid use disorder care in the community, from a health care-sector perspective., Methods: A prospective cost-effectiveness analysis was conducted alongside "Project ED Health" (CTN-0069), a hybrid type 3 implementation-effectiveness study conducted at 4 academic EDs. Resources were gathered and valued according to the health care-sector perspective. Three effectiveness measures were evaluated: quality-adjusted life-years, opioid-free years, and patient engagement in community-based opioid use disorder care on the 30th day following the index ED visit. An incremental cost-effectiveness ratio was calculated for each measure of effectiveness. Likelihood of cost-effectiveness was evaluated across a wide range of "value" thresholds through cost-effectiveness acceptability curves., Results: The mean, per-person, health care-sector cost associated with ED-administered buprenorphine following implementation facilitation did not differ significantly from that of standard education ($3,239 versus $4,904), whereas the mean effectiveness for all 3 measures significantly favored the implementation facilitation strategy. Implementation facilitation has a 74% to 75% probability of being considered cost-effective from a health care-sector perspective at the recommended value range of $100,000 to $200,000 per quality-adjusted life-year. Incremental cost-effectiveness ratios estimated using secondary effectiveness measures had a 75% probability of being considered cost-effective at $25,000 per opioid-free year and $38,000 per engagement., Conclusion: Implementation facilitation, relative to a standard educational strategy, has a moderate-to-high likelihood of being considered cost-effective from a health care-sector perspective, depending on decisionmakers' willingness to pay for units of effectiveness., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Variant transthyretin amyloidosis (ATTRv) is a hereditary multisystem disorder with clinical spectrum ranging from predominant cardiomyopathy to polyneuropathy. In the Irish population, the T60A mutation has been previously recognised as the most common genotype., Objectives: The aim of this study is to describe the diagnostic and phenotypic spectrum of patients with T60A ATTRv attending an Irish Expert Amyloidosis Network., Methods: In this observational study design, the medical, laboratory and radiological records of patients enrolled in our amyloidosis registry with a confirmed genotype diagnosis of T60A ATTRv were reviewed., Results: A cohort of 24 patients (12 female) met criteria for inclusion. The median age at diagnosis was 65 years (IQR 59.5-66.5) and median follow-up 44 months (IQR 31-58). Carpal tunnel syndrome was the initial manifestation in almost half (46%) of patients. Overall, a mixed cardioneuro phenotype was demonstrated including autonomic (75%), small (58%) and large fibre (46%) neuropathy largely predating a cardiac phenotype consisting of heart failure (63%), atrial arrhythmia (42%) and bradycardia (13%)., Conclusion: The contemporary clinical spectrum of T60A ATTRv in Ireland is one of patients typically presenting in the seventh decade with an already manifest neuropathy phenotype, largely predating a cardiac phenotype dominated by heart failure., Competing Interests: Competing interests: Professor Emer Joyce is a Principal Investigator in the multi-centre RCT “ATTRibute-CM: Efficacy and Safety of AG-10 in Subjects with Transthyretin Amyloid Cardiomyopathy”. Professor Emer Joyce and Dr Gerard Giblin have received speaker fees from Pfizer Pharmaceutical company. Professor Sinead Murphy has received support for attending meetings and/or travel from Sobi Pharmaceutical company and support for attending meetings/travel and advisory board fees from Alnylam Pharmaceuticals. Dr Gerard Giblin has received educational support from Alnylam Pharmaceuticals., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mental health conditions and concussion history reported by a collegiate athlete may contribute to prolonged recovery and symptom severity after concussion. This work examined the potential associations among concussion history, preexisting conditions, and sex relative to initial symptom severity and recovery duration following sport-related concussion (SRC) in a cohort of Division 1 National Collegiate Athletic Association athletes. This prospective cohort study analyzed symptom severity, recovery, and return-to-play (RTP) times reported post-SRC using data collected as part of the Pac-12 Concussion Assessment, Research and Education Affiliated Program and Health Analytics Program. Health history questionnaires that included self-reported history of preexisting conditions were completed at baseline. When consented athletes were diagnosed with a concussion, daily postconcussion symptom scores were evaluated until an athlete was clinically determined to be asymptomatic. Generalized linear and Cox proportional hazards models were used to determine associations between preexisting conditions and recovery and RTP times. Ninety-two concussions met inclusion criteria. Notable differences in initial symptom severity existed between females and males who had mood disorders (effect size [ d ] = 0.51) and attention-deficit hyperactivity disorder (ADHD; d = 0.93). The number of previous concussions was a strong predictor of athletes reporting preexisting mood disorders, depression, anxiety, and ADHD ( p = 0.008-0.04). Females with ≥2 previous concussions required more days to RTP than males ( d = 0.31-0.72). Weekly recovery and RTP probabilities substantially differed between athletes who did or did not have learning disorders (LDs; hazard ratio [HR] Recovery = 0.32, HR RTP = 0.22, d = 1.96-2.30) and ADHD (HR Recovery = 3.38, HR RTP = 2.74, d = 1.71-4.14). Although no association existed between concussion history and acute symptom severity, collegiate athletes with a history of concussion had higher probabilities of reporting depression, mood disorders, anxiety, and ADHD. Having ADHD or LDs likely strongly affects time to recovery and RTP for collegiate athletes.

Background: In the United States, most (~ 70%) annual newly diagnosed HIV infections are among substance-using sexual minority men (SMM) and gender minority transgender women (trans women). Trans women and SMM are more likely to report or be diagnosed with a substance use disorder (SUD) than their cisgender or heterosexual counterparts and the presence of an SUD substantially increases the risk of HIV infection in both groups. Although Pre-Exposure Prophylaxis (PrEP) is highly effective, initiation, adherence, and persistence are exclusively behavioral outcomes; thus, the biomedical benefits of PrEP are abrogated by substance use. SUD is also associated with reduced quality-of-life, and increased overdose deaths, utilization of high-cost healthcare services, engagement in a street economy, and cycles of incarceration., Objective: To determine the optimal (considering efficacy and cost-effectiveness) strategy for advancement along the PrEP Care Continuum among trans women and SMM with an SUD., Methods: This study will implement a randomized controlled trial, evaluating two Stepped Care approaches involving A.S.K.-PrEP vs. standard of care (SOC) to determine optimal intervention strategies for trans women and SMM with an SUD (N = 250; n = 83 trans women; n = 167 SMM) for advancement along the PrEP Care Continuum. Participants will be randomized (3:1) to Stepped Care (n = 187) or SOC (n = 63). Participants in the Stepped Care arm will be assessed at 3-months for intervention response; responders will be maintained in A.S.K.-PrEP, while non-responders will receive added attention to their SUD via Contingency Management (CM). Non-responders will be re-randomized (1:1) to either (a) receive A.S.K.-PrEP + CM, or (b) shift the primary focus to their SUD (CM alone)., Results: Recruitment and enrollment began in May 2023. Recruitment will span approximately 36 months. Data collection, including all follow-up assessments, is expected to be completed in April 2027., Discussion: Trans women and SMM with an SUD have the two highest HIV prevalence rates in the United States, which underscores the urgent need for effective measures to develop scalable behavioral interventions that can encourage advancement along the PrEP Care Continuum. To improve public health, researchers must identify scalable and cost-effective behavioral interventions to promote PrEP initiation, adherence, and persistence among trans women and SMM who use substances., Trial Registration: This trial has been registered at ClinicalTrials.gov under the number NCT05934877., (© 2024. The Author(s).)

Background: In emergency care settings, screening for disease or risk factors for poor health outcomes among older adults can identify those in need of specialist and early intervention. The aim of this study was to identify barriers and facilitators to implementing older person-centred screening in emergency care settings in the Mid-West of Ireland., Methods: This study employed a qualitative descriptive design underpinned by the theoretical domains framework (TDF). This design informs implementation strategy by establishing a theoretical foundation for focused objectives. One on one semi-structured interviews were conducted with a purposive sample of healthcare workers (HCWs) to explore their screening experiences with older adults in emergency care settings. Information power guided sample size calculation. In data analysis, verbatim interview transcripts were deductively mapped to TDF constructs forming meta-themes that revealed specific barriers and facilitators to person-centred screening for older individuals. These findings will directly inform implementation strategies., Results: Three themes were identified; Preconditions to Implementing Older Person-Centred Screening; Knowledge and Skills Required to Implement Older Person-centred Screening and Motivation to Deliver Older Person-Centred Screening. Overall, screening in emergency care settings is a complicated process which is ideally undertaken by knowledgeable and skilled practitioners with a keen awareness of team dynamics and environmental challenges in acute care settings. These practitioners serve as champions and sources of specialist knowledge and practice. Less experienced clinicians seek supervision and support to undertake screening competently and confidently. Education on frailty and aged related syndromes facilitates screening uptake. Recognition of the value of screening is a clear motivator and leadership is vital to sustain screening practices., Conclusions: Screening serves as an entry point for specialist intervention, necessitating a specialist multidisciplinary team (MDT) approach for effective implementation in emergency care settings. Strengthening screening practices for older adults who attend emergency care settings involves employing audit, supervision and tailored supports. Skilled and experienced practitioners play a key role in mentoring and supporting the broader MDT in screening engagement. Long-term and sustainable implementation relies on utilising existing managerial, practice development and educational resources to underpin screening practices. Communication between Emergency Department (ED) staff, the specialist team and wider geriatric team is vital to ensure a cohesive approach to delivering older person-centred care in the ED., (© 2024. The Author(s).)

Biallelic variants in phosphatidylinositol glycan anchor biosynthesis, class G (PIGG) cause hypotonia, intellectual disability, seizures, and cerebellar features. We present 8 patients from 6 families with a childhood-onset motor neuropathy and neurophysiology demonstrating variable motor conduction block and temporal dispersion. All individuals had a childhood onset tremor, 5 of 8 had cerebellar involvement, and 6 of 8 had childhood febrile seizures. All individuals have biallelic PIGG variants, including the previously reported pathogenic variant Trp505*, plus 6 novel variants. Null enzyme activity is demonstrated via PIGO/PIGG double knockout system for Val339Gly and Gly19Glu, and residual activity for Trp505* due to read-through. Emm negative blood group status was confirmed in 1 family. PIGG should be considered in unsolved motor neuropathy. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

A significant effort in biomedical sciences has been made to examine relationships between sex and the mechanisms underlying various disease states and behaviors, including sleep. Here, we investigated biological sex differences in sleep using male and female C57BL/6J mice (n = 267). Physiological parameters were recorded for 48-h using non-invasive piezoelectric cages to determine total sleep, non-rapid eye movement (NREM) sleep, rapid eye movement (REM)-like sleep, and wakefulness (WAKE). We fit hierarchical generalized linear mixed models with nonlinear time effects and found substantial sex differences in sleep. Female mice slept less overall, with less NREM sleep compared to males. Females also exhibited more REM-like sleep and WAKE and had shorter NREM sleep bout lengths. We also conducted a simulation exercise where we simulated a hypothetical treatment that altered the sleep of female mice, but not male mice. In models that included an appropriate sex by treatment interaction, a female-specific treatment response was accurately estimated when sample sizes were equal but was not detected when sample sizes were unequal, and females were underrepresented. Failure to include both sexes in experimental designs or appropriately account for sex during analysis could lead to inaccurate translational recommendations in pre-clinical sleep studies., (© 2024. The Author(s).)

Music therapy can be a form of preventive or early intervention. It strengthens and utilizes women's own resources to build resilience, aids relaxation, reduces symptoms of anxiety and depression, promotes parent-infant attachment, and adapts to physical and psychological challenges during the perinatal period. The inclusion of music therapy in Irish maternity services has the potential to improve the quality of healthcare delivery provided to parents and infants. Recent studies demonstrate that the prospect of music therapy is welcomed by parents and perinatal healthcare professionals in Ireland, but such services are yet to be formally embedded in maternity care. Building on a cross-sectional survey, this qualitative study employed 6 semi-structured interviews with women and perinatal healthcare professionals in Ireland to understand their perspectives on developing music therapy in Irish maternity care services. Four themes were identified from the thematic analysis of these interviews: (1) music has multiple functions during the perinatal period; (2) music programs contribute to holistic perspectives and approachability in perinatal care; (3) music therapy provides specialist support; and (4) further development of music therapy services is challenging. The findings offer important insights and practical considerations on the key components of the music therapy programs and strategies in developing music therapy in Irish maternity settings. This information can directly inform music therapy researchers and practitioners in designing music therapy programs and developing relevant services in collaboration with maternity care professionals and policymakers., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Music Therapy Association.)

Background: Healthcare professionals have a role to play in reducing perinatal mental health related stigma., Aim: To assess the effectiveness of a video-based educational intervention developed to provide guidance to healthcare professionals on perinatal mental health related stigma reduction strategies., Design: A single group pre-test-post-test pilot study with no control group., Setting(s): A university affiliated maternity hospital in Ireland PARTICIPANTS: A convenience sample of registered midwives, nurses and doctors (n = 60) recruited from October 2020-January 2021., Intervention: A twenty-minute video-based educational intervention., Methods: Respondents (n = 60) completed a pre-test (time point one) and post-test (time point-two) questionnaire, and a three-month follow-up post-test questionnaire (time point-three) (n = 39). The questionnaire included the Mental Illness Clinicians' Attitudes Scale, Reported and Intended Behaviour Scale, Reynolds Empathy Scale and open-ended questions. Wilcoxon Signed Rank Test was selected to evaluate the pre-test post-test scores., Results: The difference in mean Mental Illness: Clinicians' Attitudes-4 scores were statistically significant between time points one and three (z = 3.27, df=36, P = 0.0007) suggesting more positive attitudes towards people with mental health conditions after the intervention. The mean total score for the Reported and Intended Behaviour Scale increased from 18.7 (SD 1.87) at time point one to 19.2 (SD 1.60) at time point two (z= -3.368, df=59, P = 0.0004) suggesting an increase in positive intended behaviours towards those with mental health issues immediately following the intervention. These findings were also corroborated by responses to open-ended survey questions., Conclusions: Further research with a larger sample of healthcare professionals evaluated over a longer period would provide further evidence for the sustainability of the intervention., Tweetableabstract: A video-based intervention can increase healthcare professionals' knowledge of perinatal #mentalhealth related stigma reduction strategies @Journal. Link to article., 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 © 2024. Published by Elsevier Ltd.)

Objective: To describe unicondylar humeral fracture (UHF) repair using cannulated transcondylar screws, report postoperative fracture reduction, healing, and complication rates., Study Design: Retrospective., Animals: A total of 49 client owned dogs with UHF., Methods: Surgical technique and approach (i.e., open, limited open, or minimally invasive) were recorded. Articular step defect (ASD) and gap (Gap) at the humeral condylar articular surface were measured on pre- and postoperative images and reported as percentages. Fracture healing was graded on follow-up radiographs. Functional outcome was based on client questionnaire over the phone. General linear models were used to assess the impact of surgical approach on %ASD, %Gap, whereas Cox regression was used to assess prognostic factors of full fracture healing., Results: A total of 49 fractures repaired with a transcondylar screw with or without an antirotational pin(s) were included. Surgical approach did not have an impact on postoperative %ASD, %Gap or development of complications. The overall complication rate was 26% (11/42), with no revision surgery necessary. Of the dogs that encountered complications, 50% required pin and/or screw removal after fracture healing. For 29 dogs with a minimum of four-month owner telephone questionnaire follow-up, 90% reported no lameness and only three reported intermittent lameness. Achieving complete fracture healing was affected by increased postoperative %ASD (p = .033)., Conclusion: The UHFs repaired by transcondylar cannulated screws had acceptable outcomes and fracture reduction with complication rates being similar regardless of the surgical approach., Clinical Significance: Cannulated screws can be implanted with varying surgical approaches to successfully repair UHFs with comparable clinical outcome to previous reports., (© 2024 The Author(s). Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays). VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R 2  = 0.254; P = 0.04). Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial., Methods: This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts., Results: Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53 % female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95 % CI 4.7, 59.7) more days of OUD treatment relative to usual care., Conclusions: Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment., Competing Interests: Declaration of Competing Interest All authors reviewed and approved the final article. Jennifer F. Bobb has no disclosures. Andrea Altschuler has no disclosures. Hongxiang Qiu has no disclosures. Abigail G. Matthews has no disclosures. Jennifer McCormack has no disclosures. Dr. Campbell has received support managed through her institution from the Industry PMR Consortium, a consortium of companies conducting post marketing studies required by the Food and Drug Administration that assess risks related to opioid analgesic use. Outside of this study, Paige Wartko received funding in the past year from a contract awarded to the Harvard Department of Population Medicine from GlaxoSmithKline to assess medication use in pregnancy and funding from a research contract awarded to Kaiser Permanente Washington Health Research Institute from Syneos Health to conduct Food and Drug Administration-mandated post-marketing research on the risks of opioid analgesic use. Dr. Saxon has received an honorarium from Indivior, Inc., travel support from Alkermes, Inc., and royalties from UpToDate. Onchee Yu received research grant funded by Bayer. Jeffrey Samet has no disclosures. Dr. Boudreau previously received funding from a research contract awarded to Kaiser Permanente Washington Health Research Institute (KPWHRI) from Syneos Health to conduct Food and Drug Administration-mandated post-marketing research on the risks of opioid analgesic use. Dr. Boudreau was an employee of KPWHRI at the time the study was conducted but is now an employee of Genentech, Inc. Amy K. Lee has no disclosures Dr. Glass reports that Pear Therapeutics Inc provided digital therapeutic prescriptions at no cost to Kaiser Permanente Washington during a quality improvement pilot study that he led. Kathrine A. Bradley has no disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Offering medications for opioid use disorder (MOUD) in carceral settings significantly reduces overdose. However, it is unknown to what extent individuals in jails continue MOUD once they leave incarceration. We aimed to assess the relationship between in-jail MOUD and MOUD continuity in the month following release., Methods: We conducted a retrospective cohort study of linked NYC jail-based electronic health records and community Medicaid OUD treatment claims for individuals with OUD discharged from jail between 2011 and 2017. We compared receipt of MOUD within 30 days of release, among those with and without MOUD at release from jail. We tested for effect modification based on MOUD receipt prior to incarceration and assessed factors associated with treatment discontinuation., Results: Of 28,298 eligible incarcerations, 52.8 % received MOUD at release. 30 % of incarcerations with MOUD at release received community-based MOUD within 30 days, compared to 7 % of incarcerations without MOUD (Risk Ratio: 2.62 (2.44-2.82)). Most (69 %) with MOUD claims prior to incarceration who received in-jail MOUD continued treatment in the community, compared to 9 % of those without prior MOUD. Those who received methadone (vs. buprenorphine), were younger, Non-Hispanic Black and with no history of MOUD were less likely to continue MOUD following release., Conclusions: MOUD maintenance in jail is strongly associated with MOUD continuity upon release. Still, findings highlight a gap in treatment continuity upon-reentry, especially among those who initiate MOUD in jail. In the wake of worsening overdose deaths and troubling disparities, improving MOUD continuity among this population remains an urgent priority., Competing Interests: Declaration of Competing Interest Dr. Murphy served on an advisory board panel for Indivior, outside the submitted work. Dr. Krawczyk receives compensation for expert testimony for ongoing opioid litigation. All other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Inherited cerebellar ataxias (CA) are heterogeneous progressive neurological conditions associated with significant functional limitations. This study aimed to assess the implications of inherited CA on patients' self-reported quality of life (QoL) and impairments in work and activities. 129 individuals with ataxia responded to a survey focused on QoL. Health-related QoL was measured using the RAND 36-Item Short Form Survey. An adaptation of the validated Work Productivity and Activity Impairment questionnaire was used to assess the effect of health on work productivity and ability to perform activities over the past week. Nine percent of respondents were currently employed. Individuals with inherited ataxia experienced significant activity impairment, and 75% required professional or informal care. Health-related quality of life (HRQoL) was significantly worse in all areas for the individuals with inherited ataxia compared with Irish population normative values. Participants with Friedreich's ataxia (n = 56) demonstrated worse physical functioning then those with undetermined ataxia (n = 55). Female gender, younger age at symptom onset, current employment, retirement due to age or ataxia, and living in a long-term care facility were associated with higher sub-scores in different domains of HRQoL, while disease duration correlated with worse physical functioning sub-scores. This study is the first cross-sectional study on HRQoL in patients with inherited ataxia in Ireland. It highlights high rates of unemployment, difficulty with daily activities and physical functioning limitations, which is worse than comparative international studies. Given the limited therapeutic options currently available, optimising HRQoL is an important aspect of managing ataxia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Expanding access to naloxone through pharmacies is an important policy goal. Our objective was to characterize national county-level naloxone dispensing of chain versus independent pharmacies., Methods: The primary exposure in our longitudinal analysis was the proportion of chain pharmacies in a county, identified through the U.S. Department of Homeland Security 2010 Infrastructure Foundation-Level Data. We defined counties as having "higher proportion" of chain pharmacies if at least 50% of pharmacies were large national chains. The primary outcome was quarter-year (2016Q1-2019Q2) rate of pharmacy naloxone claims per 100,000 persons from Symphony Health at the county level. We compared the naloxone dispensing rate between county types using 2-sample t tests. We estimated the association between county-level chain pharmacy proportion and rate of naloxone claims using a linear model with year-quarter fixed effects., Results: Nearly one-third of counties (n = 946) were higher proportion. Higher proportion counties had a significantly higher rate of naloxone claims across the study period, in 4 of 6 urban-rural classifications, and in counties with and without naloxone access laws (NALs). The linear model confirmed that higher proportion counties had a significantly higher rate of naloxone claims, adjusting for urban-rural designation, income, population characteristics, opioid mortality rate, coprescribing laws, and NALs., Conclusion: In this national study, we found an association between naloxone dispensing rates and the county-level proportion of chain (vs. independent) pharmacies. Incentivizing naloxone dispensing through educational, regulatory, or legal efforts may improve naloxone availability and dispensing rates-particularly in counties with proportionately high numbers of independent pharmacies., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD)., Methods: This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups., Results: MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release., Conclusion: MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2024. Published by Elsevier B.V.)

The src homology 2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 are two proteins involved in intracellular signaling pathways and have been linked to the pathogenesis of several diseases. Both protein paralogs are well known for their involvement in the formation of various kinds of cancer. SHIP1, which is expressed predominantly in hematopoietic cells, has been implicated as a tumor suppressor in leukemogenesis especially in myeloid leukemia, whereas SHIP2, which is expressed ubiquitously, has been implicated as an oncogene in a wider variety of cancer types and is suggested to be involved in the process of metastasis of carcinoma cells. However, there are numerous other diseases, such as inflammatory diseases as well as allergic responses, Alzheimer's disease, and stroke, in which SHIP1 can play a role. Moreover, SHIP2 overexpression was shown to correlate with opsismodysplasia and Alzheimer's disease, as well as metabolic diseases. The SHIP1-inhibitor 3-α-aminocholestane (3AC), and SHIP1-activators, such as AQX-435 and AQX-1125, and SHIP2-inhibitors, such as K161 and AS1949490, have been developed and partly tested in clinical trials, which indicates the importance of the SHIP-paralogs as possible targets in the therapy of those diseases. The aim of this article is to provide an overview of the current knowledge about the involvement of SHIP proteins in the pathogenesis of cancer and other human diseases and to create awareness that SHIP1 and SHIP2 are more than just tumor suppressors and oncogenes.

RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset [smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001] and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions [smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009]. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V β = -1.06, P < 0.001; lobules VI-VII β = -0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Evidence shows that music can promote the wellbeing of women and infants in the perinatal period. Ireland's National Maternity Strategy (2016-2026) suggests a holistic approach to woman's healthcare needs and music interventions are ideally placed as a non-pharmacological and cost-effective intervention to improve the quality of care offered to women and infants. This cross-sectional survey aimed to explore the healthcare practitioners' personal and professional experiences of using music therapeutically and its impact and barriers in practice. The survey also investigated practitioners' knowledge and attitudes towards the use of music as a therapeutic tool in perinatal care., Methods: A novel online survey was developed and distributed through healthcare practitioners' electronic mailing lists, social media, Perinatal Mental Health staff App, and posters at the regional maternity hospital during 26th June and 26th October 2020. Survey items included demographics, personal and professional use of music, and perspectives on music intervention in perinatal care., Results: Forty-six healthcare practitioners from across 11 professions were recruited and 42 were included in this study. 98 % of perinatal practitioners used music intentionally to support their wellbeing and 75 % referred to using music in their work. While 90 % found music beneficial in their practice, 15 % reported some negative effect. Around two-thirds of the respondents were familiar with the evidence on music and perinatal wellbeing and 95 % thought there was not enough guidance. 40 % considered music therapy an evidence-based practice and 81 % saw a role for music therapy in standard maternity service in Ireland. The qualitative feedback on how music was used personally and professionally, its' reported benefits, negative effects, and barriers are discussed., Discussion: This study offers insights into how healthcare practitioners viewed and applied music in perinatal practice. The findings indicate high interest and positive experiences in using music as a therapeutic tool in perinatal care which highlights the need for more evidence and guidance., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be provided quickly in the event of an overdose. OPCs are programs that are established in Canada and have recently become legally sanctioned in only a few United States jurisdictions., Methods: We conducted a systematic review that summarizes and identifies gaps of economic evidence on establishing OPCs in North America to guide future expansion of OPCs., Results: We included 16 final studies that were evaluated with the Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists. Eight studies reported cost-effectiveness results (eg, cost per overdose avoided or cost per quality-adjusted life-year), with 6 also including cost-benefit; 5 reported only cost-benefit results, and 3 cost offsets. Health outcomes primarily included overdose mortality outcomes or HIV/hepatitis C virus infections averted. Most studies used mathematical modeling and projected OPC outcomes using the experience of a single facility in Vancouver, BC., Conclusions: OPCs were found to be cost-saving or to have favorable cost-effectiveness or cost-benefit ratios across all studies. Future studies should incorporate the experience of OPCs established in various settings and use a greater diversity of modeling designs., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies or the US government., (Copyright © 2024. Published by Elsevier Inc.)

Background: Communities That HEAL (CTH) is a novel, data-driven community-engaged intervention designed to reduce opioid overdose deaths by increasing community engagement, adoption of an integrated set of evidence-based practices, and delivering a communications campaign across healthcare, behavioral-health, criminal-legal, and other community-based settings. The implementation of such a complex initiative requires up-front investments of time and other expenditures (i.e., start-up costs). Despite the importance of these start-up costs in investment decisions to stakeholders, they are typically excluded from cost-effectiveness analyses. The objective of this study is to report a detailed analysis of CTH start-up costs pre-intervention implementation and to describe the relevance of these data for stakeholders to determine implementation feasibility., Methods: This study is guided by the community perspective, reflecting the investments that a real-world community would need to incur to implement the CTH intervention. We adopted an activity-based costing approach, in which resources related to hiring, training, purchasing, and community dashboard creation were identified through macro- and micro-costing techniques from 34 communities with high rates of fatal opioid overdoses, across four states-Kentucky, Massachusetts, New York, and Ohio. Resources were identified and assigned a unit cost using administrative and semi-structured-interview data. All cost estimates were reported in 2019 dollars., Results: State-level average and median start-up cost (representing 8-10 communities per state) were $268,657 and $175,683, respectively. Hiring and training represented 40%, equipment and infrastructure costs represented 24%, and dashboard creation represented 36% of the total average start-up cost. Comparatively, hiring and training represented 49%, purchasing costs represented 18%, and dashboard creation represented 34% of the total median start-up cost., Conclusion: We identified three distinct CTH hiring models that affected start-up costs: hospital-academic (Massachusetts), university-academic (Kentucky and Ohio), and community-leveraged (New York). Hiring, training, and purchasing start-up costs were lowest in New York due to existing local infrastructure. Community-based implementation similar to the New York model may have lower start-up costs due to leveraging of existing infrastructure, relationships, and support from local health departments., (© 2024. The Author(s).)

Background: Sport-related concussion (SRC) is a heterogenous injury that often presents with varied symptoms and impairment. Recently, research has focused on identifying subtypes, or clinical profiles of concussion to be used in assessing and treating athletes with SRC. The purpose of this study was to investigate sex differences in clinical profiles, recovery duration, and initial symptom severity after SRC in a cohort of collegiate athletes in the Pacific-12 Conference (Pac-12)., Methods: This prospective cohort study examined post-SRC symptoms, recovery, and return-to-play times using data from the Pac-12 CARE Affiliated Program and Pac-12 Health Analytics Program. Clinical profiles reported by student-athletes were defined by the number (> 50%) of specific symptoms frequently reported for each profile. Generalized linear mixed models were used to examine associations among sex, clinical profiles, time-to-recovery, and return-to-play times., Results: 479 concussion incidents met inclusion criteria. The probabilities of initial presentation of each clinical profile, initial injury severity scores, and recovery times within a profile did not differ between sexes (p = 0.33-0.98). However, both males and females had > 0.75 probabilities of exhibiting cognitive and ocular profiles. Initial injury severity score was a strong nonlinear predictor of initial number of clinical profiles (p < 0.0001), which did not differ between sexes. The number of clinical profiles was also a nonlinear predictor of time-to-recovery (p = 0.03) and return-to-play times (p < 0.0001)., Conclusions: Initial symptom severity was strongly predictive of the number of acute clinical profiles experienced post-SRC. As the number of clinical profiles increased, time-to-recovery and time to return-to-play also increased. Factors other than sex may be better associated with acute symptom presentation post-concussion as no sex differences were found in reported clinical profiles or recovery. Understanding the number and type of clinical profiles experienced post-SRC may help inform concussion diagnostics and management., (© 2024. The Author(s).)

The Addiction Health Services Research (AHSR) Conference has been held since 2002. This Conference brings together researchers, graduate students, policymakers, and treatment providers to focus improving the organization, distribution, and financing of healthcare resources for prevention/care of SUD. The AHSR 2023 Conference took place in New York City, October 18-20 th , and was hosted by the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV (CHERISH; cherishresearch.org). Attended by more than 300 participants, the Conference comprised several themes relating to the latest research on addiction health services delivery, financing, and impact. The agenda also included pre-conference workshops, distinguished plenary speakers, a multitude of networking opportunities, and career support for early-stage and minority investigators. AHSR 2023 featured 3 plenary sessions, 120 oral presentations, and 143 poster presentations from academics throughout the world. Overall, AHSR 2023 provided numerous opportunities to advance the field of addiction health services research. The state-of-the-art techniques and insights gained by attending scholars will position them to be change-agents in the addiction field going forward., 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: AJG receives an honorarium for an online chapter on alcohol management in the perioperative period from the UpToDate online reference. In the last three years, author AJG has been on the board of directors (without remunerations) of the American Society of Addiction Medicine (ASAM), the Association for Multidisciplinary Education and Research in Substance use and Addiction (AMERSA), and the International Society of Addiction Journal Editors (ISAJE), all non-for-profit organizations. These entities had no bearing over the contents of this manuscript. SMM served on an advisory board panel for Indivior, outside the submitted work.