The nature and characteristics of problem gaming, with a focus on ICD-11 diagnoses.

PURPOSE OF REVIEW: This review describes the diagnoses related to problem gaming that are included in ICD-11, published by the WHO in 2022. It summarizes the recent literature on the prevalence of Gaming Disorder, its structure, antecedents and comorbidities, and explores whether the range of diagnoses currently available adequately covers the range of experiences seen with problem gaming. RECENT FINDINGS: Overall, between 3 and 6% of the population worldwide are reported to have a gaming disorder as defined by ICD-11 or DSM-5. However, most studies are constrained by methodological issues such as nonrepresentative samples and the use of brief questionnaires to determine prevalence. ICD-11 Gaming Disorder is a psychometrically sound diagnosis. There is no diagnosis that currently captures the experience of harm from gaming, where the requirements for the diagnosis of Gaming Disorder are not reached. SUMMARY: There is evidence in support of the proposed new entity of 'Harmful Gaming', which encompasses mental and physical harm/impairment due to a repeated pattern of gaming, but where requirements for the diagnosis of Gaming Disorder are not met. Such a diagnosis would complete the spectrum of diagnoses available for problem or unhealthy gaming, similar to those for unhealthy substance use, and would provide a framework for a public health approach to reducing the overall harm from unhealthy gaming.

Alcohol use and alcohol use disorders in sub-Saharan Africa: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Population-level alcohol use data are available from high-income countries, but limited research has been conducted in sub-Saharan Africa. This systematic review and meta-analysis aimed to summarize population-level alcohol use in sub-Saharan Africa. METHOD: Databases searched included PubMed, EMBASE, PsycINFO and AJOL, without language restrictions. Searches were also conducted in the Global Health Data Exchange (GHDx) and Google Scholar. Search terms encompassed 'substance' or 'substance-related disorders' and 'prevalence' and 'sub-Saharan Africa'. We included general population studies on alcohol use (including any use, high-risk alcohol use and alcohol use disorders) from 2018 onwards. Prevalence data for alcohol use among sub-Saharan African adolescents (10-17) and adults (18+) were extracted. Analyses included life-time and past 12- and 6-month alcohol use. RESULTS: We included 141 papers. Among adolescents, the life-time prevalence of alcohol use was 23.3% [95% confidence interval (CI) = 11.3-37.1%], 36.2% (CI = 18.4-56.1%) in the past year and 11.3% (CI = 4.5-20.4%) in the past 6 months. Among adolescents, 12-month prevalence of alcohol use disorder and alcohol dependence were 7.7% (CI = 0.0-27.8%) and 4.1% (CI = 1.4-7.9%), respectively. Among adults, the life-time prevalence of alcohol use was 34.9% (CI = 17.7-54.1%), 27.1% (CI = 5.0-56.4%) in the past year and 32.2% (CI = 19.8-46.0%) in the past 6 months. Among adults, the 12-month prevalence of alcohol use disorder and alcohol dependence were 9.5% (CI = 0.0-30.4%) and 4.3% (CI = 0.8-9.8%), respectively. The highest weighted life-time prevalence of alcohol use, 86.4%, was reported in Tanzania among adults. The highest weighted past 6-month prevalence of alcohol use, 80.6%, was found in Zambia among adolescents. CONCLUSION: Alcohol use patterns vary across countries and subregions within sub-Saharan Africa, and comprehensive population-level data on alcohol use remain scarce in numerous sub-Saharan African countries. The prevalence of alcohol use disorder is common among adolescents in sub-Saharan Africa.

Regional and Country Prevalence Estimates of Unsafe Sex Among Adolescents in 68 Low-Income and Middle-Income Countries.

Prioritizing adolescent health is a public health priority to achieve the sustainable development goals, including reducing the risk of unsafe sex. Data on unsafe sex have remained scarce among adolescents in low-and middle-income countries (LMICs). To estimate the prevalence of unsafe sex in LMICs, we conducted secondary data analysis on the Global School-based Student Health Surveys among 244,863 students aged 13-17 years from 68 countries across five World Health Organization regions. The overall prevalence of ever had sex was 16.2%. The highest to lowest regional prevalence estimation of ever had sex was 30.5% (28.9-32.1) in the Americas, 28.6% (26.8-30.4) in Africa, 10.9% (9.2-12.6) in the Eastern Mediterranean, 9.6% (8.8-10.5) in South-East Asia, and 8.0% (6.8-9.1) in the Western Pacific. The highest prevalence of sexual intercourse before age 14 and practicing sexual intercourse without condom use were 36.5% (34.5-38.5) and 32.2% (30.1-34.3) in Africa, respectively. Findings suggest that current interventions are inadequate in promoting the uptake of safe sexual behaviors and an urgent intervention is needed.

Assessment of the Effects of Abrocitinib on the Pharmacokinetics of Probe Substrates of Cytochrome P450 1A2, 2B6 and 2C19 Enzymes and Hormonal Oral Contraceptives in Healthy Individuals.

BACKGROUND AND OBJECTIVE: Abrocitinib is an oral small-molecule Janus kinase (JAK)-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis. In vitro studies indicated that abrocitinib is a weak time-dependent inhibitor of cytochrome P450 (CYP) 2C19/3A and a weak inducer of CYP1A2/2B6/2C19/3A. To assess the potential effect of abrocitinib on concomitant medications, drug-drug interaction (DDI) studies were conducted for abrocitinib with sensitive probe substrates of these CYP enzymes. The impact of abrocitinib on hormonal oral contraceptives (ethinyl estradiol and levonorgestrel), as substrates of CYP3A and important concomitant medications for female patients, was also evaluated. METHODS: Three Phase 1 DDI studies were performed to assess the impact of abrocitinib 200 mg once daily (QD) on the probe substrates of: (1) 1A2 (caffeine), 2B6 (efavirenz) and 2C19 (omeprazole) in a cocktail study; (2) 3A (midazolam); and (3) 3A (oral contraceptives). RESULTS: After multiple doses of abrocitinib 200 mg QD, there is a lack of effect on the pharmacokinetics of midazolam, efavirenz and contraceptives. Abrocitinib increased the area under the concentration time curve from 0 to infinity (AUCinf) and the maximum concentration (Cmax) of omeprazole by approximately 189 and 134%, respectively. Abrocitinib increased the AUCinf of caffeine by 40% with lack of effect on Cmax. CONCLUSIONS: Based on the study results, abrocitinib is a moderate inhibitor of CYP2C19. Caution should be exercised when using abrocitinib concomitantly with narrow therapeutic index medicines that are primarily metabolized by CYP2C19 enzyme. Abrocitinib is a mild inhibitor of CYP1A2; however, the impact is not clinically relevant, and no general dose adjustment is recommended for CYP1A2 substrates. Abrocitinib does not inhibit CYP3A or induce CYP1A2/2B6/2C19/3A and does not affect the pharmacokinetics of contraceptives. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov registration IDs: NCT03647670, NCT05067439, NCT03662516.

A systematic review of second-hand smoking mass media campaigns (2002-2022).

BACKGROUND: Second-hand smoking (SHS) increases the risk of chronic disease in adults and poses a serious health threat to children. Mass media campaigns are instrumental in raising awareness and reducing SHS exposure. There is a need to identify recent SHS mass media campaigns and assess their sustainability in terms of knowledge, attitudes, and behavioural changes. This systematic review summarises the characteristics and outcomes of mass media campaigns on SHS prevention. METHODS: PubMed, Embase, Web of Science, and grey literature were searched in November 2022 for SHS campaigns implemented between 2016 and 2022. The eligibility criteria included campaigns on the dangers or effects of SHS with any target group, dissemination medium, study design, or language. The database search identified 1,413 peer-reviewed titles, of which 82 full-texts were screened, with 14 meeting the eligibility criteria. The grey literature search identified 9,807 sources, of which 61 were included. We extracted data on the campaign characteristics, metrics, and smoking-related outcomes. The JBI critical appraisal tool was used to assess the risk of bias of the included studies. RESULTS: We found 73 SHS campaigns conducted between 2002 and 2022, across 50 countries. The campaigns reached 378 million people. The reported recall rates range from 8 to 76%. Of the 11 studies that reported smoking-related outcomes, 10 reported increased knowledge in understanding SHS risks (73-85%), five reported an increased prevalence of smoke-free homes, and two reported an increase in number of participants persuading others to quit smoking. Two studies reported a decrease in overall smoking, whereas three studies observed a reduction in smoking in the presence of children. CONCLUSION: The available data provide some support for the effectiveness of SHS campaigns in reducing smoking behaviours in homes and around children. However, the certainty of evidence was low due to the lack of a control group and the substantial heterogeneity in the outcomes assessed. Future campaigns need comprehensive evaluation and reporting to reduce publication bias.

Systematic review and meta-analysis of text messaging interventions to support tobacco cessation.

OBJECTIVE: To review randomised controlled trials (RCTs) investigating the effectiveness of text message-based interventions for smoking cessation, including the effects of dose (number of text messages) and concomitant use of behavioural or pharmacological interventions. DATA SOURCES: We searched seven databases (PubMed, CINAHL, PsycINFO, Scopus, EMBASE, Cochrane Library and Web of Science), Google Scholar and the reference lists of relevant publications for RCTs. Eligible studies included participants aged ≥15 years who smoked tobacco at enrolment. STUDY SELECTION: One reviewer screened titles and abstracts and two reviewers independently screened full texts of articles. DATA EXTRACTION: One of three reviewers independently extracted data on study and intervention characteristics and smoking abstinence rates using Qualtrics software. DATA SYNTHESIS: 30 of the 40 included studies reported higher rates of smoking cessation among those receiving text messaging interventions compared with comparators, but only 10 were statistically significant. A meta-analysis of seven RCTs found that participants receiving text messages were significantly more likely to quit smoking compared with participants in no/minimal intervention or 'usual care' conditions (risk ratio 1.87, 95% CI 1.52 to 2.29, p <0.001). Three trials found no benefit from a higher dose of text messages on smoking cessation. Two trials that tested the added benefit of text messaging to pharmacotherapy reported outcomes in favour of adding text messaging. CONCLUSIONS: Findings suggest that text messaging-based interventions are effective at promoting smoking cessation. Further research is required to establish if any additional benefit is gained from an increased number of text messages or concurrent pharmacotherapy or behavioural counselling.

Transitions to polysubstance use: Prospective cohort study of adolescents in Australia.

BACKGROUND AND AIMS: Adolescent polysubstance use has been associated with adverse social and health outcomes. Our aim was to measure rates and transitions to polysubstance use during adolescence and identify factors associated with initiation and discontinuation of polysubstance use. DESIGN: Prospective cohort study. Multistate Markov modelling was used to estimate rates and identify correlates of transitions between substance use states. SETTING AND PARTICIPANTS: Adolescent-parent dyads (n = 1927; adolescents in grade 7, age ≈13 years) were recruited from Australian schools during 2010/11 (Wave 1). Adolescents were surveyed annually until 2016/17 (n = 1503; age ≈19 years; Wave 7) and parents were surveyed annually until 2014/15 (Wave 5). MEASUREMENTS: Alcohol, tobacco, cannabis and 3,4-methylenedioxymethamphetamine (MDMA) use outcomes were collected at Waves 3-7. Potential confounders were collected at Waves 1-6 and consisted of sex, anxiety and depression symptoms and externalizing problems, parental monitoring, family conflict and cohesion, parental substance use and peer substance use. Covariates were age and family socioeconomic status. FINDINGS: Few adolescents engaged in polysubstance use at earlier waves (Wave 3: 5%; Wave 4: 8%), but proportions increased sharply across adolescence (Waves 5-7: 17%, 24%, 36%). Rates of transitioning to polysubstance use increased with age, with few (<9%) adolescents transitioning out. More externalizing problems (odds ratio [OR] = 1.10; 99.6% confidence interval [CI] = 1.07-1.14), parental heavy episodic drinking (OR = 1.22; 99.6% CI = 1.07-1.40), parental illicit substance use (OR = 3.56; 99.6% CI = 1.43-8.86), peer alcohol use (OR = 5.68; 99.6% CI = 1.59-20.50) and peer smoking (OR = 4.18; 99.6% CI = 1.95-8.81) were associated with transitioning to polysubstance use. CONCLUSIONS: Polysubstance use in Australia appears to be rare during early adolescence but more common in later adolescence with low rates of transitioning out. Externalizing problems and greater parental and peer substance use are risk factors for adolescent polysubstance use that may be suitable intervention targets.

Designing observational studies for credible causal inference in addiction research-Directed acyclic graphs, modified disjunctive cause criterion and target trial emulation.

Randomized controlled trials (RCTs) are considered the gold standard for causal inference. With a sufficient sample size, randomization removes confounding up to the time of randomization and allows the treatment effect to be isolated. However, RCTs may have limited generalizability and transportability and are often not feasible in addiction research due to ethical or logistical constraints. The importance of observational studies from real-world settings has been increasingly recognized in research on health. This paper provides an overview of modern approaches to designing observational studies that enable causal inference. It illustrates three key techniques, Directed Acyclic Graphs (DAGs), modified Disjunctive Cause Criterion and Target Trial Emulation, and discusses the strengths and limitations of their applications.

Utility of a guiding catheter for conduction system pacing: An early multicenter experience.

Background: Conduction system pacing (CSP), either as His bundle pacing (HBP) or as left bundle branch area pacing (LBBAP), may be superior to right ventricular apical or septal pacing. Objective: The study sought to present acute results for a new guiding catheter (Biotronik Selectra 3D) designed for CSP implantations of a retractable screw-in lead (Biotronik Solia S). Methods: The primary endpoint of the prospective, international nonrandomized BIO|MASTER.Selectra 3D study was freedom from catheter-related serious adverse device effects (SADEs) within 1 week of lead implantation. Results: Of 157 enrolled patients, CSP was achieved in 147 (93.6%) patients. No SADEs occurred within 7 days. LBBAP was achieved in 82 patients (45 as crossover from an HBP attempt) and HBP in 65 (44.2%) patients. In centers considering both HBP and LBBAP, the CSP implantation success approached 99%. Successful CSP implantations lasted on average ∼50 minutes (fluoroscopy ∼6 minutes). Most procedures (87.9%) needed only 1 catheter, even after switch from HBP to LBBAP. The catheter's handling was rated largely positive. In patients without bundle branch block, mean QRS duration increased from 106 ms (intrinsic) to 122 ms (CSP) (P = .001). In patients with bundle branch block, mean QRS duration decreased from 151 ms (intrinsic) to 137 ms (CSP) (P = .004). Conclusion: The Selectra 3D catheter is a valuable tool for HBP and LBBAP implantations of the stylet-supported pacemaker leads. When implanters considered both HBP and LBBAP, the success rate was ∼99%. Flexibility to change between different approaches may be advisable in heterogeneous and challenging areas, such as CSP implantations.

Virology-the path forward.

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.

Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes.

Human cytomegalovirus (HCMV) utilizes peripheral blood monocytes as a means to systemically disseminate throughout the host. Following viral entry, HCMV stimulates non-canonical Akt signaling leading to the activation of mTORC1 and the subsequent translation of select antiapoptotic proteins within infected monocytes. However, the full extent to which the HCMV-initiated Akt/mTORC1 signaling axis reshapes the monocyte translatome is unclear. We found HCMV entry alone was able to stimulate widescale changes to mRNA translation levels and that inhibition of mTOR, a component of mTORC1, dramatically attenuated HCMV-induced protein synthesis. Although monocytes treated with normal myeloid growth factors also exhibited increased levels of translation, mTOR inhibition had no effect, suggesting HCMV activation of mTOR stimulates the acquisition of a unique translatome within infected monocytes. Indeed, polyribosomal profiling of HCMV-infected monocytes identified distinct prosurvival transcripts that were preferentially loaded with ribosomes when compared to growth factor-treated cells. Sirtuin 1 (SIRT1), a deacetylase that exerts prosurvival effects through regulation of the PI3K/Akt pathway, was found to be highly enriched following HCMV infection in an mTOR-dependent manner. Importantly, SIRT1 inhibition led to the death of HCMV-infected monocytes while having minimal effect on uninfected cells. SIRT1 also supported a positive feedback loop to sustain Akt/mTORC1 signaling following viral entry. Taken together, HCMV profoundly reshapes mRNA translation in an mTOR-dependent manner to enhance the synthesis of select factors necessary for the survival of infected monocytes.IMPORTANCEHuman cytomegalovirus (HCMV) infection is a significant cause of morbidity and mortality among the immunonaïve and immunocompromised. Peripheral blood monocytes are a major cell type responsible for disseminating the virus from the initial site of infection. In order for monocytes to mediate viral spread within the host, HCMV must subvert the naturally short lifespan of these cells. In this study, we performed polysomal profiling analysis, which demonstrated HCMV to globally redirect mRNA translation toward the synthesis of cellular prosurvival factors within infected monocytes. Specifically, HCMV entry into monocytes induced the translation of cellular SIRT1 to generate an antiapoptotic state. Defining the precise mechanisms through which HCMV stimulates survival will provide insight into novel anti-HCMV drugs able to target infected monocytes.

Participation in Australian drug treatment programs for individuals engaging in high-risk substance use: Data from a nationally representative sample.

INTRODUCTION: Substance use, including drugs, alcohol and smoking have a significant health, social and economic impact. We aim to assess the rate and factors associated with treatment access among individuals with high-risk substance use. METHOD: This study is a cross-sectional analysis of the 2019 Australian National Drug Strategy Household Survey (N = 22,015). Participants were persons with high-risk substance use based on the Alcohol, Smoking and Substance Involvement Screening Test-Lite (ASSIST-Lite) and current smokers. We measured self-reports of past 12-month engagement in a tobacco, alcohol or other drugs treatment program. RESULTS: Overall, 0.4% had high-risk drug use (0.3% cannabis, 0.1% meth/amphetamine or 0.1% opioids), 7.4% had high-risk alcohol use, and 14.0% currently smoked. Among high-risk users, past 12-month treatment access rates were 50.6% [22.3-78.9%] for opioids, 27.1% [8.1-46.1%] for meth/amphetamine, 14.5% [4.3-24.7%] for cannabis, 9.6% [8.1-11.0%] for alcohol and 11.7% [10.6-12.9%] for current smoking. The primary source of treatment support was information and education (12.7% drugs, 4.6% alcohol, 4.0% smoking), followed by counselling (6.7% drugs, 4.5% alcohol, 3.0% smoking). Online or internet support was accessed by 5.9% (drug) and 1.6% (alcohol) people with high-risk use. Psychological distress was associated with treatment access (drugs: odds ratio 3.03 [0.77-11.95], p = 0.111; alcohol: odds ratio 3.16 [2.20-4.56], p ≤ 0.001; smoking: odds ratio 1.95 [1.52-2.49], p ≤ 0.001). DISCUSSION AND CONCLUSIONS: The proportion of people engaging in risky substance use who had used treatment programs remains low, especially for alcohol. Public health strategies to scale up treatment access are warranted.

Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated with Improved Quality of Life Outcomes in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. OBJECTIVES: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. METHODS: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. RESULTS: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. CONCLUSION: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies.

Abrocitinib efficacy and safety in moderate-to-severe atopic dermatitis by race, ethnicity, and Fitzpatrick skin type.

BACKGROUND: Response to abrocitinib treatment for moderate-to-severe atopic dermatitis (AD) has not been evaluated across racial and ethnic subpopulations. OBJECTIVE: To assess the efficacy and safety of abrocitinib on the basis of patient race, ethnicity, and Fitzpatrick skin type (FST). METHODS: Data were pooled post hoc from patients treated with abrocitinib 200 mg, 100 mg, or placebo in 3 monotherapy trials (NCT02780167, NCT03349060, and NCT03575871). Race and ethnicity were self-reported; FST was determined by study investigators. Evaluations through Week 12 include the following: (1) Investigator's Global Assessment of clear or almost-clear skin; (2) greater than or equal to 75% improvement in Eczema Area and Severity Index or SCORing AD; (3) a greater-than-or-equal-to 4-point improvement in Peak Pruritus Numerical Rating Scale score; (4) least squares mean changes in Dermatology Life Quality Index and Patient-Oriented Eczema Measure scores; and (5) treatment-emergent adverse events. RESULTS: The sample comprised 628 White, 204 Asian, and 83 Black patients; 37 were Hispanic or Latino; 624 had FST I to III and 320 had FST IV to VI. Treatment with either abrocitinib dose was associated with greater proportions of patients achieving Investigator's Global Assessment of clear or almost-clear skin, ≥ 75% improvement in Eczema Area and Severity Index, ≥ 75% improvement in SCORing AD, and a ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale, or greater score changes from baseline in Dermatology Life Quality Index and Patient-Oriented Eczema Measure vs placebo regardless of race, ethnicity, or FST. Dose-response was most prominent in White patients. In Black patients, the effects of the 2 doses were similar. Treatment-emergent adverse events were more common in White and Black than in Asian patients. CONCLUSION: Abrocitinib was more efficacious than placebo across the racial and ethnic groups and ranges of phototypes analyzed. Studies with increased representation of populations of color are warranted to elucidate potential variations in response across diverse populations. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02780167 (phase 2b), NCT03349060 (phase 3 MONO-1), and NCT03575871 (phase 3 MONO-2).

What is the hype on #MedicinalCannabis in the United States? A content analysis of medicinal cannabis tweets.

INTRODUCTION: Medicinal cannabis is now legal in 44 US jurisdictions. Between 2020 and 2021 alone, four US jurisdictions legalised medicinal cannabis. The aim of this study is to identify themes in medicinal cannabis tweets from US jurisdictions with different legal statuses of cannabis from January to June 2021. METHODS: A total of 25,099 historical tweets from 51 US jurisdictions were collected using Python. Content analysis was performed on a random sample of tweets accounting for the population size of each US jurisdictions (n = 750). Results were presented separately by tweets posted from jurisdictions where all cannabis use (non-medicinal and medicinal) is 'fully legalised', 'illegal' and legal for 'medical-only' use. RESULTS: Four themes were identified: 'Policy', 'Therapeutic value', 'Sales and industry opportunities' and 'Adverse effects'. Most of the tweets were posted by the public. The most common theme was related to 'Policy' (32.5%-61.5% of the tweets). Tweets on 'Therapeutic value' were prevalent in all jurisdictions and accounted for 23.8%-32.1% of the tweets. Sales and promotional activities were prominent even in illegal jurisdictions (12.1%-26.5% of the tweets). Fewer than 10% of tweets were about intoxication and withdrawal symptoms. DISCUSSION AND CONCLUSION: This study has explored if content themes of medicinal cannabis tweets differed by cannabis legal status. Most tweets were pro-cannabis and they were related to policy, therapeutic value, and sales and industry opportunities. Tweets on unsubstantiated health claims, adverse effects and crime warrants continued surveillance as these conversations could allow us to estimate cannabis-related harms to inform health surveillance.

Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2.

BACKGROUND: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. METHODS: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. RESULTS: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4-6, and 10 were associated with 0 days, 3-4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0-1, 4-5, and 10 were associated with 0-10%, 20-30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. CONCLUSION: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. CLINICAL TRIAL REGISTRATION: NCT03575871.

Atopic dermatitis (AD), also called atopic eczema, is a common skin disease that is associated with itch and reduced quality of life. Abrocitinib, a recently approved medicine for AD, was shown in clinical trials to improve itch, which is considered the most bothersome symptom to people with AD. Abrocitinib also improved sleep outcomes and work productivity in people with moderate or severe AD. It is unknown if improvement in itch can lead to improvement in sleep and work productivity. We analyzed data from the JADE MONO-2 study, which included 391 people who received treatment with abrocitinib or placebo for 12 weeks. We used mathematical modelling to study relationships between itch and sleep or work productivity. We also wanted to study if the improvements in itch and sleep with abrocitinib treatment had an impact on work productivity. We found that a relationship existed between itch, sleep disturbance, and work impairment; as itch improved, so too did sleep disturbance and work impairment. When people were treated with abrocitinib, they experienced relief from itch, which improved sleep, which in turn reduced work productivity loss. Larger and longer studies are needed to confirm these results. This analysis further informs the expectations of patients with moderate or severe AD as it relates to progression of symptom relief after treatment with abrocitinib.

A systematic review and meta-analysis of the relationship between youth drinking, self-posting of alcohol use and other social media engagement (2012-21).

BACKGROUND AND AIM: Social networking sites (SNS) are interactive internet-based social platforms that facilitate information sharing. A growing body of literature on exposure to, and self-posting of, alcohol-related content on SNS has examined the relationship between SNS use and alcohol consumption in young people. This study aims to synthesise the literature exploring the relationship between exposure (i.e. viewing or listening of alcohol-related media) and self-posting (i.e. uploading images or text of alcohol content) of alcohol-related media on SNS on alcohol consumption. METHODS: A pre-registered systematic review was conducted in June 2022 within PubMed, Scopus, PsycINFO and Web of Science. Original prospective and cross-sectional studies assessing youth and young adults (≤ 24 years of age) that measured exposure to alcohol-related media or posting of alcohol-related content on SNS and self-reported alcohol consumption outcomes were included. Meta-analyses were conducted on comparable methodologies. RESULTS: Thirty studies were included (n = 19,386). Meta-analyses of cross-sectional studies showed both greater exposure (five studies; pooled ß = 0.34, 95% confidence interval [CI] = 0.23, 0.44, i2 = 27.7%) and self-posting of alcohol-related content (six studies; pooled ß = 0.57, 95%CI = 0.25,0.88, i2 = 97.8%) was associated with greater alcohol consumption. Meta-analyses of three prospective studies also identified that greater exposure predicted greater future alcohol consumption (three studies; pooled ß = 0.13, 95%CI = 0.11,0.15, i2 = 0.0%). Narrative analyses of studies that could not be meta-analysed due to incompatible methodologies were also conducted. Most studies (all four prospective, one of two cross-sectional) identified positive associations between exposure to alcohol-related content and greater average consumption. Most studies (three of four prospective, four of six cross-sectional) reported a positive association between of alcohol-related self-posting and greater average alcohol consumption. CONCLUSIONS: Both exposure to, and self-posting of, alcohol-related content on social networking sites are positively associated with current average consumption, problem drinking, and drinking frequency.

Prevalence and correlates of positive parental attitudes towards cannabis use and use intention in Australia during 2016 and 2019.

INTRODUCTION: With recent policy changes around medicinal cannabis in Australia, there is concern about the influence of changing norms of cannabis use on adults who are actively parenting. METHODS: This repeated cross-sectional population study used National and Drug Strategy and Household Surveys to estimate the changes and correlates of cannabis-related attitudes (support of legalisation, approve of regular use, would try or use if legal) among Australian parents from 2016 to 2019. RESULTS: The estimated proportion of parents who supported legalisation and approved regular cannabis use increased significantly. Parents who would try cannabis if it was legal grew from 5.9% (95 %CI: 5.2, 6.7) to 8.1% (95 %CI: 7.2, 9.0). Parents who said they would use cannabis more often increased from 1.6 (95 % CI: 1.2, 1.9) to 2.9 (95 %CI: 2.4, 3.4), an 81% jump in the three years. The strongest associations were observed between a very high level of psychological distress and regular smoking and drinking. For example, people with a very high level of psychological distress were 2.16 times (95 %CI: 1.42, 3.28) and 2.48 times (95 %CI: 1.61, 3.83) more likely to approve legalisation and regular cannabis use, respectively. Daily drinking was associated with higher odds of trying cannabis (OR = 1.66; CI: 1.25-2.20). DISCUSSION AND CONCLUSION: The proportion of parents who would try or use cannabis more often represents a sizeable pool of potential new and frequent users. This highlights the need for education and intervention strategies for parents who use cannabis and care for young children. The associations between mental health and substance use suggest that more research is needed to understand the impact of legalisation on vulnerable groups.

Effect of abrocitinib on skin biomarkers in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: This is the first report on the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the expression of skin biomarkers in patients with moderate-to-severe atopic dermatitis (AD). METHODS: JADE MOA (NCT03915496) was a double-blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. The primary endpoint was change from baseline in markers of inflammation (matrix metalloproteinase [MMP]-12), epidermal hyperplasia (keratin-16 [KRT16]), T-helper 2 (Th2) immune response (C-C motif chemokine ligand [CCL]17, CCL18, and CCL26), and Th22 immune response (S100 calcium binding protein A8, A9, and A12 [S100A8, S100A9, and S100A12]) in skin through 12 weeks. RESULTS: A total of 46 patients received abrocitinib 200 mg (n = 14), abrocitinib 100 mg (n = 16), or placebo (n = 16). Abrocitinib improved AD clinical signs and reduced itch. Gene expression of MMP-12, KRT16, S100A8, S100A9, and S100A12 was significantly decreased from baseline with abrocitinib 200 mg (at Weeks 2, 4, and 12) and abrocitinib 100 mg (at Weeks 4 and 12) in a dose-dependent manner. Abrocitinib 200 mg resulted in significant decreases from baseline in CCL17 expression at Week 12 and CCL18 expression at Weeks 2, 4, and 12; no significant decreases were observed for CCL26. CONCLUSIONS: Alongside improvements in clinical signs and symptoms of AD, 12 weeks of abrocitinib treatment resulted in downregulation of genes associated with inflammation, epidermal hyperplasia, and Th2 and Th22 immune responses in the skin of patients with moderate-to-severe AD.