Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.

High-throughput DNA sequencing is increasingly employed to diagnose single gene neurological and neuromuscular disorders. Large volumes of data present new challenges in data interpretation and its useful translation into clinical and genetic counselling for families. Even when a plausible gene is identified with confidence, interpretation of the clinical significance and inheritance pattern of variants can be challenging. We report our approach to evaluating variants in the skeletal muscle chloride channel ClC-1 identified in 223 probands with myotonia congenita as an example of these challenges. Sequencing of CLCN1, the gene that encodes CLC-1, is central to the diagnosis of myotonia congenita. However, interpreting the pathogenicity and inheritance pattern of novel variants is notoriously difficult as both dominant and recessive mutations are reported throughout the channel sequence, ClC-1 structure-function is poorly understood and significant intra- and interfamilial variability in phenotype is reported. Heterologous expression systems to study functional consequences of CIC-1 variants are widely reported to aid the assessment of pathogenicity and inheritance pattern. However, heterogeneity of reported analyses does not allow for the systematic correlation of available functional and genetic data. We report the systematic evaluation of 95 CIC-1 variants in 223 probands, the largest reported patient cohort, in which we apply standardized functional analyses and correlate this with clinical assessment and inheritance pattern. Such correlation is important to determine whether functional data improves the accuracy of variant interpretation and likely mode of inheritance. Our data provide an evidence-based approach that functional characterization of ClC-1 variants improves clinical interpretation of their pathogenicity and inheritance pattern, and serve as reference for 34 previously unreported and 28 previously uncharacterized CLCN1 variants. In addition, we identify novel pathogenic mechanisms and find that variants that alter voltage dependence of activation cluster in the first half of the transmembrane domains and variants that yield no currents cluster in the second half of the transmembrane domain. None of the variants in the intracellular domains were associated with dominant functional features or dominant inheritance pattern of myotonia congenita. Our data help provide an initial estimate of the anticipated inheritance pattern based on the location of a novel variant and shows that systematic functional characterization can significantly refine the assessment of risk of an associated inheritance pattern and consequently the clinical and genetic counselling.

Exploring the psychological impact of contact tracing work on staff during the COVID-19 pandemic.

BACKGROUND: Contact tracing is a key control measure in the response to the COVID-19 pandemic. While quantitative research has been conducted on the psychological impact of the pandemic on other frontline healthcare workers, none has explored the impact on contact tracing staff. METHODS: A longitudinal study was conducted using two repeated measures with contact tracing staff employed in Ireland during the COVID-19 pandemic using two-tailed independent samples t tests and exploratory linear mixed models. RESULTS: The study sample included 137 contact tracers in March 2021 (T1) and 218 in September 2021 (T3). There was an increase from T1 to T3 in burnout related exhaustion (p < 0·001), post-traumatic stress disorder (PTSD) symptom scores (p < 0·001), mental distress (p < 0·01), perceived stress (p < 0·001) and tension and pressure (p < 0·001). In those aged 18-30, there was an increase in exhaustion related burnout (p < 0·01), PTSD symptoms (p < 0·05), and tension and pressure scores (p < 0·05). Additionally, participants with a background in healthcare showed an increase in PTSD symptom scores by T3 (p < 0·001), reaching mean scores equivalent to those of participants who did not have a background in healthcare. CONCLUSIONS: Contact tracing staff working during the COVID-19 pandemic experienced an increase in adverse psychological outcomes. These findings highlight a need for further research on psychological supports required by contact tracing staff with differing demographic profiles.

Buprenorphine treatment retention and comorbidities among patients with opioid use disorder in a primary care setting.

BACKGROUND AND OBJECTIVES: More information is needed about comorbidities among patients receiving buprenorphine maintenance treatment and their relationship with retention. METHODS: Retrospective electronic health record data over a 5-year period from primary care patients receiving buprenorphine for the treatment of opioid use disorder were examined (N = 899). The present analysis determined the prevalence of comorbidities and examined associations with treatment retention as defined by cumulative duration of buprenorphine prescription. RESULTS: Tobacco use and comorbidities including hypertension were prevalent but did not predict retention according to survival analyses controlling for demographic characteristics. Retention was poorer among patients testing positive for cocaine (HR = 1.38, 95% CI: 1.09-1.74, p = .007) and patients with hepatitis C virus (HR = 1.17, 95% CI: 1.01-1.37, p = .04). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This study provides new knowledge of previously unexamined associations between comorbidities (e.g., hypertension) and buprenorphine treatment retention. The robust association between cocaine use and poorer buprenorphine retention serves to resolve prior conflicting data in the literature.

An exploration of food industry led reformulation on fortified food staples in Ireland.

BACKGROUND: Food industry led reformulation efforts have attempted to address the prevalence of obesity by modifying nutrient compositions in food products. This study explored progress in nutrient composition alterations in products in Irish supermarkets by comparing the nutrient labels of products sold in 2014 and 2017. METHODS: We conducted two supermarket audits in 2014 and 2017 to examine the changes in the nutrient profile of cereals, breads, spreads, unflavoured milks, yogurts and juices. Information on the nutrients of interest to the study (energy, protein, fat, carbohydrate, saturated fat, salt, sugar and some micronutrients) were extracted and stored in Microsoft Excel. The nutrient profile of each product was compared across the two timepoints. Our study shows that the mean level of sugars in cereals remains high and that the mean level of salt remains high in cereals, breads, and spreads. RESULTS: In total, 143 products were directly compared (86 cereals, 26 breads, 17 spreads and 14 milks). Our study shows that the composition of salt and sugar in cereal, bread, spreads and milk has declined by 12 and 7%, respectively. Saturated fat has declined in cereals (7%), but has increased in breads (12%), spreads (1%), and milks (5%). Manufacturers increased the serving sizes in nine cereals and one milk. CONCLUSIONS: From a population health perspective, the results are encouraging but care should be exercised by the food industry not to allow total fat and saturated fat levels to creep upwards. Further research and engagement of public health specialists and the food industry are needed.

Co-design of a school-based physical activity intervention for adolescent females in a disadvantaged community: insights from the Girls Active Project (GAP).

BACKGROUND: Globally, adolescents' physical activity (PA) participation rates are low, particularly among lower socioeconomic groups, with females consistently the least active. The aim of this study was to co-design, with adolescent females, a school-based PA intervention in a single-sex, females-only designated disadvantaged post-primary school in Ireland. This involved using the Behaviour Change Wheel (BCW) and Public and Patient Involvement (PPI). This paper outlines the novel methodological approach taken. METHODS: The three stages 1) understand the behaviour, 2) identify intervention options, and 3) identify content and implementation options of the BCW guide is described. A student PPI Youth Advisory Group (YAG) (n = 8, aged 15-17) was established. Mixed-methods were used with students (n = 287, aged 12-18) and teachers (n = 7) to capture current self-reported PA levels and to identify factors influencing adolescent females' PA behaviour in their school setting. The intervention options, content and implementation options were identified through discussion groups with the YAG. The Template for Intervention Description and Replication (TIDieR) checklist was used to specify details of the intervention. RESULTS: Just 1.4% of the students in this sample reported meeting the recommended PA guidelines. Students identified having more 'time' as the strongest predictor to becoming more active in school (Mean = 4.01, 95% CI 3.91 to 4.12). Social influences, environmental context and resources, behavioural regulation, beliefs about capabilities, goals, and reinforcement emerged from the qualitative data as factors influencing PA behaviour at school. The BCW co-design process resulted in the identification of seven intervention functions, four policy categories and 21 Behaviour Change Techniques. The Girls Active Project (GAP) intervention, a peer-led, after-school PA programme was proposed. CONCLUSIONS: This paper describes how the BCW, a comprehensive, evidence-based, theory-driven framework was used in combination with PPI to co-design a school-based intervention aimed to increase adolescent females' PA levels. This approach could be replicated in other settings to develop targeted behavioural interventions in populations with specific demographic characteristics.

An exploration of the levels of clinical autonomy of advanced nurse practitioners: A narrative literature review.

AIMS AND OBJECTIVES: The aims of the review are to synthesise current evidence about advanced nurse practitioner clinical autonomy and consider how this may inform clinical practice and research. BACKGROUND: Clinical autonomy is one of the cornerstones of advanced nursing practice globally, yet there is limited synthesis of clinical autonomy in the literature. DESIGN: This is a narrative literature review. DATA SOURCES: The databases Cumulative Index to Nursing and Allied Health Literature, EBSCO host, Cochrane Library, CINAHL and MEDLINE were searched for publications between 2005 and 2020 inclusive. REVIEW METHODS: A systematic approach was used to analyse the literature reviewed. Two reviewers undertook quality appraisal. RESULTS: Nineteen articles were selected. Four major themes emerged: (1) 'ANP Stepping Up'-moving into and accepting advanced nursing practice roles and clinical responsibilities; (2) 'ANP Living It'-ANPs' ability to act independently including an understanding of task mastery and self-determination; (3) 'ANP Bounce-back ability'-depicted in challenges that threaten their ability to practice clinically autonomously; (4) 'ANP Setting in Motion'-indirect care activities and service-level improvements. CONCLUSION: A clearer understanding of advanced nurse practitioner clinical autonomy could help develop more in-depth knowledge. Research of advanced nurse practitioners' clinical autonomy would improve full utilisation in clinical practice.

Experiences of residents, family members and staff in residential care settings for older people during COVID-19: A mixed methods study.

AIM: The aim of this study was to explore the COVID-19 pandemic as it was experienced by people on the front line in residential care settings for older people in the Republic of Ireland (ROI). BACKGROUND: The COVID-19 pandemic had a disproportionate effect in residential care settings for older people in Ireland. METHODS: A two-phased mixed methods study was conducted, consisting of an online survey administered shortly after the first wave of the virus to staff, residents and family members and one-to-one interviews with family members shortly after wave 2 of the virus. RESULTS: Isolation, loss of connectedness as well as a reduction in the level/quality of care provision led to significant adverse impacts for both residents and their families. Staff reported high levels of stress, trauma and burnout. Family input to care was suspended, with adverse consequences. CONCLUSION: The pandemic had an extremely adverse impact on residents, family members and staff in care settings for older people. IMPLICATIONS FOR NURSING MANAGEMENT: Strategies to ensure that residents' physical, emotional and social needs and staffs' professional and personal needs are appropriately supported during future waves of the pandemic should now be implemented.

Attention-Deficit/Hyperactivity Disorder Symptoms Are Associated with Greater Delay Discounting of Condom-Protected Sex and Money.

Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risk of detrimental life outcomes. Recent research also indicates that ADHD is associated with sexual risk behavior, such as unprotected sex. Some risky sexual behaviors may be driven, in part, by preference for immediate rewards, referred to as delay discounting, which is prominent in etiological models of ADHD. Therefore, the present study examined the effect of delay on preference for both monetary and sexual outcomes in adults with many ADHD symptoms (both on and off medication) and with fewer ADHD symptoms. Online participants (N = 275; n = 161 males, n = 114 females) completed a monetary delay discounting task, assessing preference for smaller sooner versus larger delayed hypothetical money, and the Sexual Delay Discounting Task, assessing preference for condom use in hypothetical casual sex scenarios based on delay until condom availability. Those with greater ADHD symptoms discounted delayed monetary outcomes as well as delayed condom-protected sex (i.e., preferred sooner money rewards and immediate unprotected sex) significantly more than those with fewer symptoms; however, no effect of current medication use was found across monetary or sexual delay discounting among those with greater ADHD symptoms. This study is the first to demonstrate the relation between ADHD symptoms and reduced condom-use likelihood. Increased discounting of delayed condom-protected sex might constitute one mechanism of risky sexual behavior among individuals with ADHD symptoms. Interventions geared toward increasing condom use in situations in which condoms may otherwise be unavailable, may mitigate risky sexual behaviors and their associated harms in this population.

Voluntary folic acid fortification levels of food staples in Ireland continue to decline: further implications for passive folic acid intakes?

BACKGROUND: Ireland previously had widespread voluntary fortification but research at Dublin City University carried out in 2014 by our research group demonstrated a major decline in the number of food staples fortified with folic acid in Irish supermarkets over the previous 10 years. The aim of the study was to repeat the audit conducted 3 years ago to compare the levels of folic acid fortification of foodstuffs over this time-frame. METHODS: Over a period of 8-weeks between June and August 2017, the nutrition labels of all foodstuffs that might typically be fortified with micronutrients for sale in the supermarkets with the majority of market share in Ireland were examined. The amount of added folic acid detailed on the label was compared with those captured in 2014. RESULTS: In total, 1081 products with added micronutrients were examined. In percentage terms, there has been a decline of Folic Acid (FA) fortified products within the food groups-spreads, breads, cereals, cereal snacks, milks, fruit juices, yogurts/yogurt drinks and energy drinks since 2014. DISCUSSION: The number of food staples fortified with FA continues to decline demonstrating that voluntary fortification in Ireland is no longer an effective measure for passively augmenting the folic acid levels of consumers.

Algorithm-Driven Substance Use Disorder Treatment for Inner-City Clients With Serious Mental Illness and Multiple Impairments.

ABSTRACT: Mental health clients with serious mental illness in urban settings experience multiple chronic stresses related to poverty, unemployment, discrimination, homelessness, incarceration, hospitalization, posttraumatic stress disorder, pain syndromes, traumatic brain injury, and other problems. Substance use disorder exacerbates these difficulties. This study examined the efficacy of algorithm-driven substance use disorder treatments for 305 inner-city mental health clients with multiple challenges. Researchers assessed substance use quarterly using a combination of standardized self-reports and case manager ratings. Of the 305 multiply impaired clients who began treatment, 200 (66%) completed 2 years of treatment. One fourth (n = 53) of the completers were responders who developed abstinence and improved community function; one half (n = 97) were partial responders, who reduced substance use but did not become abstinent; and one fourth (n = 50) were nonresponders. Evidence-based interventions for substance use disorder can be effective for multiply impaired, inner-city clients, but numerous complications may hinder recovery.

'We know what we should eat but we don't ': a qualitative study in Irish secondary schools.

Healthy eating opportunities for young people need to be provided in the school setting. Links between formal education and local policies and practices, and active involvement of students are emphasized in whole school approaches to health promotion. In many jurisdictions, schools struggle to provide nutritious food that is acceptable to students. The aim of this study was to conduct an in-depth exploration of school food and students' food choice with students, teachers and principals in six Irish secondary schools. Students conducted their own focus groups with peers, and a researcher conducted focus groups with teachers and one-to-one interviews with principals. Students, teachers and principals expressed dissatisfaction with food provision within their respective schools and reported unhealthy dietary behaviours among the student body as the norm. Divergent views, however, emerged regarding education, knowledge and the primary drivers of food choice. Teachers and principals saw a role for more education modules and students believed environmental infrastructures, practices and policies needed to be addressed to improve behaviours. This consultation with students, teachers and principals highlight that, in addition to education, the social and environmental aspects of food choice and eating at school deserve attention in future research and policy.

Developing a national undergraduate standardized curriculum for future healthcare professionals on "Making Every Contact Count" for chronic disease prevention in the Republic of Ireland.

This report describes the development of the first national undergraduate interprofessional standardized curriculum in chronic disease prevention for healthcare professionals in the Republic of Ireland. This project brought together for the first time all higher education institutions nationwide in a novel collaboration with the national health service i.e. the Health Service Executive (HSE), to develop a standardized national curriculum for undergraduate health care professions. The curriculum sits within the framework of Making Every Contact Count, the goal of which is to re-orientate health services to embed the ethos of prevention through lifestyle behavior change as part of the routine care of health professionals. The core focus of Making Every Contact Count is chronic disease prevention, targeting four main lifestyle risk factors for chronic disease; tobacco use, alcohol consumption, physical inactivity and unhealthy eating. Making Every Contact Count is a key component of Healthy Ireland, the Irish national framework for health and wellbeing. The aim of the curriculum is to prepare newly qualified health professionals with the skills needed to support patients to achieve lifestyle behavior change delivered as part of routine clinical care.

Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.

Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of PDHA1 (NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency.

Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy.

Abnormal protein aggregation is observed in an expanding number of neurodegenerative diseases. Here, we describe a mechanism for intracellular toxic protein aggregation induced by an unusual mutation event in families affected by axonal neuropathy. These families carry distinct frameshift variants in NEFH (neurofilament heavy), leading to a loss of the terminating codon and translation of the 3' UTR into an extra 40 amino acids. In silico aggregation prediction suggested the terminal 20 residues of the altered NEFH to be amyloidogenic, which we confirmed experimentally by serial deletion analysis. The presence of this amyloidogenic motif fused to NEFH caused prominent and toxic protein aggregates in transfected cells and disrupted motor neurons in zebrafish. We identified a similar aggregation-inducing mechanism in NEFL (neurofilament light) and FUS (fused in sarcoma), in which mutations are known to cause aggregation in Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis, respectively. In summary, we present a protein-aggregation-triggering mechanism that should be taken into consideration during the evaluation of stop-loss variants.

Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.

BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. Variants in NaV1.4 that directly alter skeletal muscle excitability can cause myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome. SCN4A variants have also been found in infants with life-threatening apnoea and laryngospasm. We therefore hypothesised that rare, functionally disruptive SCN4A variants might be over-represented in infants who died from SIDS. METHODS: We did a case-control study, including two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched controls without a history of cardiovascular, respiratory, or neurological disease. We compared the frequency of rare variants in SCN4A between groups (minor allele frequency <0·00005 in the Exome Aggregation Consortium). We assessed biophysical characterisation of the variant channels using a heterologous expression system. FINDINGS: Four (1·4%) of the 278 infants in the SIDS cohort had a rare functionally disruptive SCN4A variant compared with none (0%) of 729 ethnically matched controls (p=0·0057). INTERPRETATION: Rare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. These findings indicate that dysfunction of muscle sodium channels is a potentially modifiable risk factor in a subset of infant sudden deaths. FUNDING: UK Medical Research Council, the Wellcome Trust, National Institute for Health Research, the British Heart Foundation, Biotronik, Cardiac Risk in the Young, Higher Education Funding Council for England, Dravet Syndrome UK, the Epilepsy Society, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.

What Attracts Medical Students to Primary Care? A Nominal Group Evaluation.

OBJECTIVE: To examine the perceptions of first-year medical students on their experiences in primary care. METHODS: Nominal group technique sessions were conducted with first-year medical students for 5 years. Questions were designed to evaluate primary care experiences and the role of primary care physicians. The questions explored what would make them consider primary care, what would detract from it, and what primary care has to offer that no other specialty can. Responses were weighted and ranked. The main outcome was the top five responses to three questions that were obtained at each session. RESULTS: Thirty-four students generated 280 responses to 3 questions. The top 5 responses for each year resulted in 29 experiences that strengthen enthusiasm: patient interactions (weighted sum, 43%), physician interactions/role modeling (22%), community interactions (20%), healthcare system/finances (8%), and other (6%). The top 5 responses resulted in 26 experiences that weaken enthusiasm, including hidden curriculum (45%), poor role models (29%), uncertainties about the healthcare system such as finances and documentation (20%), and patient interactions (6%). The top 5 responses regarding the uniqueness of primary care resulted in 37 experiences, including patient interactions (38%), continuity of care (20%), knowledge base (13%), community impact (10%), lifestyle benefits (10%), and education/prevention (9%). CONCLUSIONS: Medical students highlighted unique relationships with patients and continuity of care as experiences that increase their enthusiasm for primary care. Negative experiences that weakened enthusiasm for primary care included hidden curriculum and poor role models. Programs that provide experiences in primary care can increase student interest in primary care careers.

Researchers' experiences and lessons learned from doing mixed-methods research with a population with intellectual disabilities: Insights from the SOPHIE study.

Researchers are challenged to provide opportunities for people with intellectual disabilities (IDs) and their families to become participants in research. This article explores the processes and procedures involved in conducting a mixed-methods study. The preparation for the study is described and explained. Recruitment is examined by describing the process and analysing phone calls made to potential participants. Reflections of research team members help to develop the analysis and contribute to a discussion of the fieldwork. Lessons learned show that research projects involving people with IDs and their families need careful planning and have additional costs. The research team requires a mix of expertise. Traditional recruitment methods may not be suitable, and researchers need to build good relationships with gatekeepers so that participants can be contacted directly. Good quality research with people with IDs and their families is possible once suitable strategies are employed throughout the research process.

Optimization of folic acid supplementation in the prevention of neural tube defects.

Background: We examined the relationship between timing and duration of folic acid (FA) supplementation in achieving red blood cell (RBC) folate levels in early pregnancy which are optimal (>906 nmol/l) for the prevention of neural tube defects (NTDs). Methods: Clinical, FA supplementation and dietary folate details were computerized at the first antenatal visit. Maternal blood samples were analysed for RBC and serum folate. Results: Of the 502 women, 98.2% (n = 493) reported taking FA. There was a positive correlation between duration of supplementation and both RBC folate (r = 0.43, P < 0.001) and serum folate (rho = 0.29, P < 0.001). The optimal RBC folate level was achieved in 80.4% (n = 46) of women who started FA 400 µg 4-8 weeks before their LMP compared with only 53.6% (n = 153) in women who started 4-8 weeks after their LMP (P < 0.001). Conclusions: This study provides, for the first time, information on both the timing and duration of FA that will achieve the optimum RBC folate levels associated with the prevention of NTDs. Women who are taking FA (400 µg) need to start before they conceive.

Double jeopardy: a review of weight gain and weight management strategies for psychotropic medication prescribing during methadone maintenance treatment.

Methadone maintenance treatment (MMT) is an important treatment tool for the opioid epidemic. One challenge is that many persons who present for MMT also have co-occurring psychiatric disorders. Individually, both methadone and psychiatric medications carry risk of weight gain. Therefore, concurrent prescribing of methadone and psychiatric medications places dual diagnosis patients at even greater risk. As a parallel obesity epidemic grows, results from clinical trials assessing weight gain and weight management strategies among MMT and psychiatric patients can both inform and guide clinical practice. This study reviews findings from a literature search for recent clinical trials that focused on weight gain and weight management strategies during MMT with concurrent psychotropic medication use. While several studies have documented weight gain during MMT and psychotropic medication treatment, this study failed to identify recent work that explored concurrent prescribing. Most weight management strategies involved the use of additional medications and available data suggests that MMT and concurrent use of psychotropic medications increases the risk for obesity. More robust research is needed on weight gain and potential mitigation strategies when these treatment modalities are jointly utilized. Clarification of underlying biological mechanisms and development of non-pharmacological interventions merit further consideration.

Working Memory Training for Adolescents With Cannabis Use Disorders: A Randomized Controlled Trial.

Adolescent cannabis use is associated with working memory impairment. The present randomized controlled trial assigned adolescents ages 14 to 21 enrolled in cannabis use treatment to receive either working memory training (experimental group) or a control training (control group) as an adjunctive treatment. Cognitive function, drug use, and other outcomes were assessed before and after training. We observed few differences in cognitive, functional, or self-reported drug use outcomes as a function of training group, although tetrahydrocannabinol (THC) urinalysis results favored the experimental group. These findings are similar to previous studies in substance users, which have shown limited transfer effects for working memory training.