Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Objective: Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP's feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

The development and internal validation of a multivariable model predicting 6-month mortality for people with opioid use disorder presenting to community drug services in England: a protocol.

BACKGROUND: People with opioid use disorder have substantially higher standardised mortality rates compared to the general population; however, lack of clear individual prognostic information presents challenges to prioritise or target interventions within drug treatment services. Previous prognostic models have been developed to estimate the risk of developing opioid use disorder and opioid-related overdose in people routinely prescribed opioids but, to our knowledge, none have been developed to estimate mortality risk in people accessing drug services with opioid use disorder. Initial presentation to drug services is a pragmatic time to evaluate mortality risk given the contemporaneous routine collection of prognostic indicators and as a decision point for appropriate service prioritisation and targeted intervention delivery. This study aims to develop and internally validate a model to estimate 6-month mortality risk for people with opioid use disorder from prognostic indicators recorded at initial assessment in drug services in England. METHODS: An English national dataset containing records from individuals presenting to drug services between 1 April 2013 and 1 April 2023 (n > 800,000) (the National Drug Treatment Monitoring System (NDTMS)) linked to their lifetime hospitalisation and death records (Hospital Episode Statistics-Office of National Statistics (HES-ONS)). Twelve candidate prognostic indicator variables were identified based on literature review of demographic and clinical features associated with increased mortality for people in treatment for opioid use disorder. Variables will be extracted at initial presentation to drug services with mortality measured at 6 months. Two multivariable Cox regression models will be developed one for 6-month all-cause mortality and one for 6-month drug-related mortality using backward elimination with a fractional polynomial approach for continuous variables. Internal validation will be undertaken using bootstrapping methods. Discrimination of both models will be reported using Harrel's c and d-statistics. Calibration curves and slopes will be presented comparing expected and observed event rates. DISCUSSION: The models developed and internally validated in this study aim to improve clinical assessment of mortality risk for people with opioid use disorder presenting to drug services in England. External validation in different populations will be required to develop the model into a tool to assist future clinical decision-making.

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism.

LAY ABSTRACT: Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

Autistic and non-autistic transgender youth are similar in gender development and sexuality phenotypes.

Increasing rhetoric regarding the common intersection of autism and gender diversity has resulted in legislation banning autistic transgender youth from accessing standard of care supports, as well as legislative efforts banning all youth gender care in part justified by the proportional over-occurrence of autism. Yet, no study has investigated whether autistic and non-autistic transgender youth present fundamentally different gender-related phenotypes. To address this gap, we extensively characterized autism, gender diversity, and sexuality among autistic and non-autistic transgender binary youth (N = 66, Mage = 17.17, SDage = 2.12) in order to investigate similarities and/or differences in gender and sexuality phenotypes. Neither autism diagnostic status nor continuous autistic traits were significantly related to any gender or sexuality phenotypes. These findings suggest that the developmental and experiential features of gender diversity are very similar between autistic and non-autistic transgender adolescents. Future research is needed to determine whether the similarity in profiles is maintained over time into adulthood.

Polygenic Scores Clarify the Relationship Between Mental Health and Gender Diversity.

Background: Gender-diverse individuals are at increased risk for mental health problems, but it is unclear whether this is due to shared environmental or genetic factors. Methods: In two SPARK samples, we tested for associations of 16 polygenic scores (PGSs) with quantitative measures of gender diversity and mental health. In study 1, 639 independent adults (59% autistic) reported their mental health with the Adult Self-Report and their gender diversity with the Gender Self-Report (GSR). The GSR has 2 dimensions: binary (degree of identification with the gender opposite that implied by sex designated at birth) and nonbinary (degree of identification with a gender that is neither male nor female). In study 2 (N = 5165), we used a categorical measure of gender identity. Results: In study 1, neuropsychiatric PGSs were positively associated with Adult Self-Report scores: externalizing was positively associated with the attention-deficit/hyperactivity disorder PGS (ß = 0.10 [0.03-0.17]), and internalizing was positively associated with the PGSs for depression (ß = 0.07 [0-0.14]) and neuroticism (ß = 0.10 [0.03-0.17]). Interestingly, GSR scores were not significantly associated with any neuropsychiatric PGS. However, GSR nonbinary was positively associated with the cognitive performance PGS (ß = 0.11 [0.05-0.18]), with the effect size comparable in magnitude to the associations of the neuropsychiatric PGSs with the Adult Self-Report. Additionally, GSR binary was positively associated with the nonheterosexual sexual behavior PGS (ß = 0.07 [0-0.14]). In study 2, the cognitive performance PGS effect replicated; transgender and nonbinary individuals had higher PGSs (t316 = 4.16). Conclusions: We showed that while gender diversity is phenotypically positively associated with mental health problems, the strongest PGS associations with gender diversity were with the cognitive performance PGS, not the neuropsychiatric PGSs.

This research explores the connection between gender diversity, mental health, and genetic factors. It reveals that gender-diverse individuals often experience more mental health issues. Interestingly, rather than finding evidence linking these mental health challenges to genetic risk factors, the study discovered a replicable positive correlation between gender diversity and genetic markers for higher cognitive performance. This suggests that gender-diverse individuals typically have more of these cognitive performance gene variants. Finally, the study presents some early evidence suggesting that interactions between the environment (e.g., stigma) and genetic risk explain some of the elevated risk to mental health in gender-diverse individuals.

Clinical Pharmacokinetics and Pharmacodynamics of Naloxone.

Naloxone is a World Health Organization (WHO)-listed essential medicine and is the first choice for treating the respiratory depression of opioids, also by lay-people witnessing an opioid overdose. Naloxone acts by competitive displacement of opioid agonists at the µ-opioid receptor (MOR). Its effect depends on pharmacological characteristics of the opioid agonist, such as dissociation rate from the MOR receptor and constitution of the victim. Aim of treatment is a balancing act between restoration of respiration (not consciousness) and avoidance of withdrawal, achieved by titration to response after initial doses of 0.4-2 mg. Naloxone is rapidly eliminated [half-life (t1/2) 60-120 min] due to high clearance. Metabolites are inactive. Major routes for administration are intravenous, intramuscular, and intranasal, the latter primarily for take-home naloxone. Nasal bioavailability is about 50%. Nasal uptake [mean time to maximum concentration (Tmax) 15-30 min] is likely slower than intramuscular, as reversal of respiration lag behind intramuscular naloxone in overdose victims. The intraindividual, interindividual and between-study variability in pharmacokinetics in volunteers are large. Variability in the target population is unknown. The duration of action of 1 mg intravenous (IV) is 2 h, possibly longer by intramuscular and intranasal administration. Initial parenteral doses of 0.4-0.8 mg are usually sufficient to restore breathing after heroin overdose. Fentanyl overdoses likely require higher doses of naloxone. Controlled clinical trials are feasible in opioid overdose but are absent in cohorts with synthetic opioids. Modeling studies provide valuable insight in pharmacotherapy but cannot replace clinical trials. Laypeople should always have access to at least two dose kits for their interim intervention.

Reaching "The Other Half": Teacher Referral Increases Inclusivity in Intervention Research for Neurodivergent School-Age Children.

OBJECTIVE: Researchers employed two recruitment strategies in a school-based comparative effectiveness trial for students with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism. This study assessed the: 1) effectiveness of school-based referrals for identifying students meeting diagnostic criteria and 2) impact of eliminating requirements for existing diagnoses on recruitment, sample characteristics, and intervention response. METHOD: Autistic students and students with ADHD in schools serving underresourced communities were recruited for an executive functioning (EF) intervention trial over 2 years. In Year 1, school staff nominated students with previous diagnoses. In Year 2, school staff nominated students demonstrating EF challenges associated with ADHD or autism; previous diagnosis was not required. Study staff then confirmed diagnoses. RESULTS: More students were included in Year 2 (N = 106) than Year 1 (N = 37). In Year 2, 96% of students referred by school staff met diagnostic criteria for ADHD or autism, 53% of whom were not previously diagnosed. Newly identified students were less likely than previously diagnosed students to be receiving services and, for those with ADHD, were more likely to speak primarily Spanish at home. Previously diagnosed and newly identified students did not differ on other demographic variables or intervention response. Caregivers of previously diagnosed students reported more symptoms than caregivers of newly identified students for both diagnostic groups. Previously diagnosed students with ADHD had more researcher-rated symptoms than newly identified students. CONCLUSIONS: Recruitment for an intervention study using behavior-based referrals from school staff enhanced enrollment without compromising the sample's diagnostic integrity and engaged children who otherwise would have been excluded.

Short report: Recommendations for education, clinical practice, research, and policy on promoting well-being in autistic youth and adults through a positive focus on sexuality and gender diversity.

LAY ABSTRACT: In this article, we propose recommendations on what we can do to promote that autistic people can enjoy their sexuality and gender identity, because that contributes to overall well-being.First, we briefly summarize the existing research on sexuality and gender diversity in autistic individuals.Next, we propose recommendations for how to promote sexual and gender diversity-related health and well-being. Based on what is known about sexuality, gender diversity, and relationships in autistic adolescents and adults, we convened an international group of autistic and non-autistic researchers, advocates, parents, and professionals to develop recommendations to promote sexual and gender health in autistic people.The resulting recommendations were checked through an online survey distributed to autistic people across the world. The online participants endorsed the importance of eight final recommendations related to:1. Providing education and information on sexuality, relationships, and gender diversity to autistic individuals and their families;2. Improving expertise in and accessibility to healthcare for sexuality, relationships, and gender-related questions, with specific attention to prevention of and support after sexual victimization; and3. Meaningfully including the autism community in future research that addresses well-being relating to sexuality, relationships, and gender diversity.These community-driven recommendations aim to promote sexual health and well-being in autistic individuals internationally.

What impacts the acceptability of wearable devices that detect opioid overdose in people who use opioids? A qualitative study.

INTRODUCTION: Drug-related deaths involving an opioid are at all-time highs across the United Kingdom. Current overdose antidotes (naloxone) require events to be witnessed and recognised for reversal. Wearable technologies have potential for remote overdose detection or response but their acceptability among people who use opioids (PWUO) is not well understood. This study explored facilitators and barriers to wearable technology acceptability to PWUO. METHODS: Twenty-four participants (79% male, average age 46 years) with current (n = 15) and past (n = 9) illicit heroin use and 54% (n = 13) who were engaged in opioid substitution therapy participated in semi-structured interviews (n = 7) and three focus groups (n = 17) in London and Nottingham from March to June 2022. Participants evaluated real devices, discussing characteristics, engagement factors, target populations, implementation strategies and preferences. Conversations were recorded, transcribed and thematically analysed. RESULTS: Three themes emerged: device-, person- and environment-specific factors impacting acceptability. Facilitators included inconspicuousness under the device theme and targeting subpopulations of PWUO at the individual theme. Barriers included affordability of devices and limited technology access within the environment theme. Trust in device accuracy for high and overdose differentiation was a crucial facilitator, while trust between technology and PWUO was a significant environmental barrier. DISCUSSION AND CONCLUSIONS: Determinants of acceptability can be categorised into device, person and environmental factors. PWUO, on the whole, require devices that are inconspicuous, comfortable, accessible, easy to use, controlled by trustworthy organisations and highly accurate. Device developers must consider how the type of end-user and their environment moderate acceptability of the device.

Cannabidiol does not attenuate acute delta-9-tetrahydrocannabinol-induced attentional bias in healthy volunteers: A randomised, double-blind, cross-over study.

AIMS: To test how attentional bias and explicit liking are influenced by delta-9-tetrahydrocannabinol (THC) and whether these effects are moderated by cannabidiol (CBD). DESIGN: Double-blind, randomised, within-subjects cross-over study. SETTING: NIHR Wellcome Trust Clinical Research Facility at King's College Hospital, London, United Kingdom. PARTICIPANTS/CASES: Forty-six infrequent cannabis users (cannabis use <1 per week). INTERVENTION(S): Across four sessions, participants inhaled vaporised cannabis containing 10 mg of THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1) or 30 mg (3:1) of CBD, administered in a randomised order and counter-balanced across participants (a total of 24 order groups). MEASUREMENTS: Participants completed two tasks: (1) Attentional Bias (AB), comparing reaction times toward visual probes presented behind 28 target stimuli (cannabis/food) compared with probes behind corresponding non-target (neutral) stimuli. Participants responding more quickly to probes behind target than non-target stimuli would indicate greater attentional bias to cannabis/food; (2) Picture Rating (PR), where all AB stimuli were rated on a 7-point pleasantness scale, measuring explicit liking. FINDINGS: During the AB task, participants were more biased toward cannabis stimuli in the 0:1 condition compared with baseline (mean difference = 12.2, 95% confidence intervals [CIs] = 1.20-23.3, d = 0.41, P = 0.03). No other significant AB or PR differences were found between cannabis and food stimuli between baseline and 0:1 condition (P > 0.05). No significant CBD effect was found on AB or PR task performance at any dose (P > 0.05). There was additionally no cumulative effect of THC exposure on AB or PR outcomes (P > 0.05). CONCLUSIONS: A double-blind, randomised, cross-over study among infrequent cannabis users found that inhaled delta-9-tetrahydrocannabinol increased attentional bias toward cannabis in the absence of explicit liking, a marker of liability toward cannabis use disorder. At the concentrations normally found in legal and illegal cannabis, cannabidiol had no influence on this effect.

Cognitive and Developmental Profiles Associated with Self-Reported Sexual and Gender Minority Stigmatization Among Binary Transgender Adolescents.

OBJECTIVE: Sexual and gender minority (SGM) stigmatization is a key factor related to transgender adolescent mental health. While previous research has focused on direct associations between stigmatization and mental health, the present study of transgender youth, equitably recruited across the autism spectrum, examines cognitive and developmental factors in relation to the self-report of experienced and perceived SGM stigmatization. METHOD: 65 binary transgender adolescents (43% transfeminine; ages 13-21 years) were intentionally recruited across the spectrum of autism traits from no traits to full criteria autism. Participants completed measures of autism-related social differences, cognitive abilities, and self-reported directly experienced and perceived SGM stigma. Autism-related social differences, cognitive abilities, and age were studied in relation to both SGM stigma factors. RESULTS: Autism-related social differences were negatively associated with level of directly experienced SGM stigma but unassociated with perceived stigma. Greater cognitive ability was positively associated with level of perceived SGM stigma, but unassociated with report of directly experienced stigma. Older age was positively associated with level of perceived SGM stigma. There was a statistical trend toward older age positively associated with level of directly experienced stigma. CONCLUSIONS: The present study identifies candidate cognitive and developmental influences on self-reported SGM stigmatization among transgender adolescents, evenly recruited across the autism spectrum. The factors which may impact the perception and experience of stigmatization have been notably under-explored in the mental health field. The examination of these individual characteristics may allow for more precise predictive models for research with transgender youth, and ultimately, in clinical care.

Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT.

Background: Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed. Objectives: To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption. Design: Multicentre, three-arm, parallel-group, randomised controlled clinical trial. Setting: Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands). Participants: Adults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate. Interventions: (1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation. Main outcome measures: Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule. Results: Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to -6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to -2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported. Limitations: The trial's primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted. Conclusions: Medication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate. Future work: Given our findings in relation to Contingency Management enhancing Medication Management adherence, future trials should be developed to explore its effectiveness and cost-effectiveness with other alcohol interventions where there is evidence of poor adherence. Trial registration: This trial is registered as ISRCTN17083622 https://doi.org/10.1186/ISRCTN17083622. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 22. See the NIHR Journals Library website for further project information.

Many people who are trying to stop drinking alcohol can find it difficult to remain alcohol free. There is a medication called acamprosate (Campral) that can reduce cravings thereby increasing the likelihood of abstinence. However, some people have trouble taking the right amount of acamprosate tablets needed every day at the right time, preferably at mealtimes. This means the medication is not as effective. We have tested some new ways to help support people taking acamprosate. We tested three different strategies to find the best way to support people taking acamprosate. We recruited 739 people aged 18 and over who were receiving alcohol treatment to stop drinking and were taking acamprosate. We randomly allocated these people to three groups. The first was Standard Support, the usual support people receive when taking acamprosate. The second group received Standard Support plus Medication Management. This consisted of 12 telephone calls over 6 months with a trained pharmacist to discuss the importance of taking the right amount of the medication, how the medication works and strategies to help people take the medication correctly. The third group received Standard Support, Medication Management and Contingency Management. This involved giving people shopping vouchers for participating with Medication Management calls. The maximum value of vouchers per person was £120. People who were in the group receiving Medication Management and Contingency Management took a greater number of acamprosate tablets. We also found that Medication Management plus Contingency Management was more cost-effective; there were greater gains in health with a smaller cost per person compared to Standard Support alone. This shows that there is likely to be a benefit to patients of Medication Management plus Contingency Management for supporting people taking acamprosate.

Conceptualising retention in treatment with long-acting injectable buprenorphine (for opioid use disorder) as a journey: Findings from a longitudinal qualitative study.

BACKGROUND: Conceptualisations of the 'patient journey' are popular within health service research. Patient journeys provide a person-centred approach to health care that typically prioritise subjective patient experience with the aim of improving relevant forms of intervention. This article explores the conceptualisation of retention in treatment for opioid use disorder (OUD) using long-acting injectable buprenorphine (LAIB) as a journey. METHODS: Data derive from a longitudinal qualitative study, involving semi-structured interviews (held at six time-points), with participants who each initiated LAIB for the first time. Data analysis for this article focuses exclusively upon the experiences of those who had continued with LAIB treatment throughout one year (11 participants). Framework and thematic narrative analyses of 64 interviews with 11 participants sought to identify 'retention-narratives' that would indicate a 'retention journey' associated with LAIB treatment. FINDINGS: Shared treatment experiences consisted of three distinct phases (Withdrawal and Separation, Transformation, and Engagement) that progressed in a linear and intersecting manner through time. Each phase had features that defined treatment experiences at a given time but changed as treatment progressed. All 11 participants experienced multiple features within each of the three treatment phases and all participants reported separation from their respective service provider throughout the first 12 months of treatment. Although some valued the latter separation, most were dissatisfied by reduced levels of contact. CONCLUSION: Retention in treatment for OUD with LAIB, for at least 12-months, can be conceptualised as a journey. This conceptualisation emphasises the benefits (and challenges) clinicians and patients may expect to encounter during the first year of a LAIB treatment programme. An added implication of conceptualising LAIB treatment in this manner is that optimal benefits of the medication (as observed by participants) began to emerge during 'months 7-12' of the retention journey.

Common Intersection of Autism and Gender Diversity in Youth: Clinical Perspectives and Practices.

Autism and gender diversity often intersect. Many transgender youth seeking gender-related medical interventions are autistic. Clinicians serving these youth lack an autism-specific evidence base to guide gender care decisions. At present, care decisions are based on extrapolation of care models from transgender youth samples, generally. At this point, there is no evidence to suggest that autistic youth are likely to experience shifts in gender or gender-related medical requests, although this has been insufficiently studied. In this article, cowritten by expert clinicians and autistic gender-diverse collaborators, an overview of clinical care considerations and the current evidence base is provided.

Measuring flexibility in autistic adults: Exploring the factor structure of the flexibility scale self report.

Cognitive flexibility differences are common for autistic individuals and have an impact on a range of clinical outcomes. However, there is currently a lack of well validated measurement tools to assess flexibility in adulthood. The Flexibility Scale was originally designed as a parent-report measure of real-world flexibility challenges in youth. The original Flexibility Scale provides a total score and five subscales: Routines and Rituals, Transitions and Change, Special Interests, Social Flexibility, and Generativity. In this study, we evaluate the factorial validity of the Flexibility Scale as a self-report (Flexibility Scale Self Report) measure of cognitive flexibility, adapted from the original Flexibility Scale, for use by autistic adults. This study includes both a primary sample (n = 813; mean age = 40.3; 59% female) and an independently recruited replication sample (n = 120; mean age = 32.8; 74% female) of individuals who completed the Flexibility Scale Self Report. The analysis consisted of an initial confirmatory factor analysis (CFA) of the original Flexibility Scale structure, followed by exploratory factor analysis (EFA) and factor optimization within a structural equation modeling framework to identify the optimal structure for the questionnaire in adults. The identified structure was then replicated through CFA in the replication sample. Our results indicate an alternative optimal scale structure from the original Flexibility Scale, which includes fewer items, and only three (Routines/Rituals, Transitions and Change, Special Interests) of the five subscales contributing to the flexibility total score. Comparisons revealed no structural differences within the scale based on sex assigned at birth. Here the Generativity and Social Flexibility scales are treated as independent but related scales. The implications for measurement of cognitive flexibility in clinical and research settings, as well as theoretical underpinnings are discussed.

A study protocol for a European, mixed methods, prospective, cohort study of the effectiveness of naloxone administration by community members, in reversing opioid overdose: NalPORS.

BACKGROUND: Worldwide, opioid use causes more than 100,000 overdose deaths annually. Naloxone has proven efficacy in reversing opioid overdoses and is approved as an emergency antidote to opioid overdose. Take home naloxone (THN) programmes have been introduced to provide 'community members', who are likely to observe opioid overdoses, with naloxone kits and train them to recognise an overdose and administer naloxone. The acceptability and feasibility of THN programmes has been demonstrated, but the real-life effectiveness of naloxone administration by community members is not known. In recent years, the approval of several concentrated naloxone nasal-spray formulations (in addition to injectable formulations, eg.prenoxad) potentially increases acceptability and scope for wider provision. This study aims to determine the effectiveness of THN (all formulations) in real-world conditions. METHODS: A European, multi-country, prospective cohort study, to assess the use of THN by community members to reverse opioid overdoses in a six-month, follow-up period. Participants provided with THN from participating harm reduction and drug treatment sites will be recruited to the study and followed-up for six months. We are particularly interested in the experiences of community members who have been provided with THN and have witnessed an opioid overdose. All participants who witness an opioid overdose during the six-month period (target approx. 600) will be asked to take part in a structured interview about this event. Of these, 60 will be invited to participate in a qualitative interview. A Post Authorisation Efficacy Study (PAES) for the concentrated nasal naloxone, Nyxoid, has been integrated into the study design. DISCUSSION: There are many challenges involved in evaluating the real-life effectiveness of THN. It is not possible to use a randomised trial design, recruitment of community members provided with THN will depend upon recruitment sites distributing THN kits, and the type of THN received by participants will depend on regulations and on local clinical and policy decision-makers. Following up this population, some of whom may be itinerant, over the 6-month study period will be challenging, but we plan to maintain contact with participants through regular text message reminders and staff contact. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05072249. Date of Registration: 8.10.2021.

Non-Prescribed Substance Use during the First Month of Treatment by People Receiving Depot Buprenorphine for Opioid Use Disorder.

Background: Non-prescribed substance use (NPSU) during the treatment of opioid use disorder (OUD) is a recognized phenomenon. The use of non-prescribed substances is associated with discontinuing treatment and drop-out can occur within the early weeks of treatment, before benefit from treatment occurs. Recent developments in treatment include long-acting, slow-release depot buprenorphine injections. This article focuses on NPSU during the first month of treatment with depot buprenorphine, addressing the frequency with which it occurs, the substances used, and reasons for use. Methods: 70 semi-structured interviews (held at three time-points) were conducted with 26 patients initiating depot buprenorphine as part of a longitudinal qualitative study. Analysis prioritized content and framework analyses. Findings: 17/26 participants self-reported NPSU at various times during the first month of treatment. NPSU typically involved heroin, crack-cocaine and some use of benzodiazepines and/or cannabis. Participants' reasons for heroin use were connected to their subjective accounts of opioid withdrawal symptoms, the management of pain, and experimentation (to test the blockade effect of buprenorphine). Frequency of heroin use was typically episodic rather than sustained. Participants associated crack-cocaine use with stimulant-craving and social connections, and considered their use of this substance to be difficult to manage. Conclusions: Patients' initial engagement with treatment for OUD is rarely examined in qualitative research. This study highlights how NPSU amongst patients receiving new forms of such treatment continues to be a challenge. As such, shared decision-making (between providers and patients) regarding treatment goals and NPSU should be central to the delivery of depot buprenorphine treatment programmes.

Expanding upon the relationship between gender-affirming hormone therapy, neural connectivity, mental health, and body image dissatisfaction.

OBJECTIVE: Transgender/non-binary (TNB) youth are at increased risk for anxiety, depression, and suicidality compared to cisgender youth. Gender affirming hormone therapy (GAHT, i.e., testosterone or estrogen) is a standard of care option for TNB youth, and we have recently shown that GAHT (testosterone) in transgender youth assigned a female sex at birth is associated with reductions in internalizing symptomatology. The current analysis explores: 1) whether these benefits are observed in both TNB youth assigned female at birth (TNBAFAB) and TNB youth assigned male at birth (TNBAMAB) and 2) the extent to which body image dissatisfaction and alteration in neural circuitry relate to internalizing symptoms. METHOD: The current study is an expansion of a previous publication from our lab that explored the association between gender-affirming testosterone and internalizing symptomatology. While participants in our previous study consisted of 42 TNBAFAB youth, participants in the current study included adolescent TNBAFAB receiving GAHT (n = 21; GAHT+) and not receiving GAHT (n = 29; GAHT-) as well as adolescent GAHT+ TNBAMAB (n = 15) and GAHT- TNBAMAB (n = 17). Participants reported symptoms of trait and social anxiety, depression, suicidality in the past year, and body image dissatisfaction. Brain activation was measured during a face processing task designed to elicit amygdala activation during functional MRI. RESULTS: GAHT+ TNBAFAB had significantly lower rates of social anxiety, depression, and suicidality compared to GAHT- TNBAFAB. While there were no significant relationships between estrogen and depression and anxiety symptoms, longer duration of estrogen was related to less suicidality. Both testosterone and estrogen administration were related to significantly lower rates of body image dissatisfaction compared to GAHT- youth. No significant differences emerged for BOLD response in the left or right amygdala during the face processing task, however, there was a significant main effect of GAHT on functional connectivity between the right amygdala and the ventromedial prefrontal cortex, such that GAHT+ youth had stronger co-activation between the two regions during the task. Body image dissatisfaction, greater functional connectivity, their interaction effect, and age predicted depression symptomatology and body image dissatisfaction additionally predicted suicidality in the past year. CONCLUSION: The current study suggests that GAHT is associated with fewer short-term internalizing symptoms in TNBAFAB than in TNBAMAB, although internalizing symptoms among TNBAMAB may diminish with longer durations of estrogen treatment. Controlling for age and sex assigned at birth, our findings indicate that less body image dissatisfaction and greater functional connectivity between the amygdala and ventromedial prefrontal cortex were both predictors of fewer levels of internalizing symptoms following GAHT.

The Intersection of Autism and Transgender and Nonbinary Identities: Community and Academic Dialogue on Research and Advocacy.

Many transgender people are autistic. Community expressions of the autism transgender intersection abound. Some commentators have questioned the proportional overrepresentation of autism among gender-diverse people, suggesting these individuals may not be truly autistic or truly transgender. However, increasing evidence challenges assertions that deny the authenticity of co-occurring autistic and transgender identities. Specifically, research by authors of this article indicates autistic transgender people show neurophenotypes generally consistent with cisgender autistic people and implicit gender phenotypes consistent with nonautistic transgender people. This article features a dialogue between eight leading experts in the field of intersectional autism and gender diversity, including clinicians, researchers, community advocates, and experts who are themselves autistic transgender. Key topics of discussion included: how research findings on autism and gender diversity inform respectful and supportive responses to autistic transgender people; the benefits and harms of increased societal attention toward the autism transgender intersection; and research and advocacy priorities. The expert panel concluded the following: (1) it is important to respect transgender autistic people's wellness and resilience, while also acknowledging the pathologization and stigmatization they face; (2) autistic gender-diverse people are experts of their own identity and should be involved in all aspects of research and clinical care; (3) research is needed to understand the disparities autistic transgender people face; (4) attempts to restrict autistic transgender people's access to gender care are unsupported by existing research; (5) adult gender care may benefit from incorporating universal design principles and neurodiversity-affirming strategies to reduce barriers to care and improve clinician-client communication in treatment delivery and the informed consent process; (6) cross-cultural and cross-societal research will improve best care practices in diverse contexts; (7) research and advocacy must be inclusive across ethnoracial identities, including in leadership and perspectives represented; and (8) a life span developmental framework is needed for adult research in this field.