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1.
Subst Use Addctn J ; : 29767342241241399, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591813

RESUMO

BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is a public health framework for addressing adolescent substance use. Implementation of SBIRT in schools carries the potential to improve substance use treatment access and service acceptance for students, but faces barriers related to knowledge deficits, low comfort, and lack of training in screening and brief interventions among school-based mental health (SBMH) providers. This report describes the development and acceptability evaluation of a school-based SBIRT program designed to overcome common implementation barriers of SBIRT related to provider confidence, knowledge, and training deficits by supplementing the traditional model with telehealth-delivered addiction consultation and education (ACE). METHODS: Program components include core SBIRT trainings, telehealth-delivered ACE sessions, and outreach support for SBMH providers. Each ACE session included a didactic expert presentation on a clinical topic and a provider-presented patient case with discussion. Sessions were delivered using a Project ECHO-based hub-and-spoke format with monthly 1-hour virtual meetings. Interviews and surveys with SBMH providers on substance use screening and intervention practices and perceived barriers were used to inform program design choices and tailor the curriculum. Acceptability data were collected at 9 months. RESULTS: SBMH provider participants reported increased confidence, knowledge, and evidence-based screening and early intervention practices, and high acceptability, satisfaction, and benefit from the program. Ongoing barriers to referral to treatment were reported. CONCLUSION: This pilot study suggests that supplementing traditional SBIRT with telehealth-delivered ACE sessions can address common implementation barriers and serve as a scalable model to improve SBIRT adoption in schools.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38552901

RESUMO

OBJECTIVE: Dramatic changes in state-level cannabis laws (CL) over the past 25 years have shifted societal beliefs throughout the United States, with unknown implications for youth. In the present study, we conducted an updated systematic review and meta-analysis examining estimated effects of medical cannabis legalization (MCL) and recreational cannabis legalization (RCL) on past-month cannabis use among US youth. METHOD: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, followed by a subsequent meta-analysis investigating the associations between state-level cannabis laws (ie, MCL vs non-MCL, and RCL vs non-RCL) and past-month cannabis use prevalence among US adolescents and young adults. Supplemental analyses examined age-group effects and design-related factors. RESULTS: Our search identified 4,604 citations, 34 and 30 of which were included in qualitative and quantitative analyses, respectively. Meta-analysis of MCL studies identified no significant association between MCL and change in past-month youth cannabis use (odds ratio [OR] = 0.981, 95% CI = 0.960, 1.003). Meta-analysis of RCL studies showed significantly increased odds of past-month cannabis use (OR = 1.134, 95% CI = 1.116-1.153). Meta-analysis of more recent studies, however, showed a significantly increased odds of past-month cannabis use among both adolescents and young adults (OR = 1.089, 95% CI = 1.015,1.169, and OR = 1.221, 95% CI = 1.188,1.255, respectively). CONCLUSION: Cannabis legalization has complex and heterogenous effects on youth use that may differ across law types. Our meta-analytic results showed modest positive effects of RCL on past-month cannabis use (more so in young adults than in adolescents) and minimal effects of MCL on these outcomes in US youth. Given the shift toward recreational legalization, additional focus on RCL effects is warranted.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38461894

RESUMO

Deaths due to unintentional opioid overdose among youth living in the United States have risen at an extraordinary rate over the past 4 years.1 After remaining stable over the preceding decade, the rate of drug overdose deaths increased more than 2.3-fold from 2019 to 2021 to a record high of 5.49 deaths per 100,000 youth.1 This rise in fatal overdoses is largely due to increased prevalence of illicitly manufactured fentanyl in the drug supply. In 2021, fentanyl was identified in 77.1% of overdose deaths among US adolescents, a 23.5-fold increase from 2010, compared to 13.3% for benzodiazepines, 5.8% for prescription opioids, and 2.3% for heroin.1 Compared to other phases of the opioid crisis, fentanyl-related overdoses are characterized by extraordinarily broad geographic and sociodemographic reach.

4.
Invest Ophthalmol Vis Sci ; 65(2): 26, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38349786

RESUMO

Purpose: Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability. Methods: More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans. Automated segmentation yielded thicknesses for the combined ganglion cell and inner plexiform layer (GCIPL) in Early Treatment of Diabetic Retinopathy Study subfields. Participants with diseases likely to affect these layers or segmentation accuracy were excluded. Inner and outer ratios were defined as the ratio of temporal-to-nasal GCIPL thickness for inner and outer subfields respectively. Corresponding ratios were obtained from a smaller cohort undergoing OCTs with a different device (three-dimensional (3D)-OCT, Topcon, Japan). Results: Scans from 2300 twins (1150 pairs) were included (mean [SD] age, 53.9 (16.5) years). Mean (SD) inner and outer ratios were 0.89 (0.09) and 0.84 (0.11), correlating negatively with age (coefficients, -0.17 and -0.21, respectively). In males (150 pairs) ratios were higher and did not correlate significantly with age. Intrapair correlation coefficients were higher in monozygotic than dizygotic pairs; age-adjusted heritability estimates were 0.20 and 0.23 for inner and outer ratios, respectively. For the second cohort (n = 166), mean (SD) ratios were 0.93 (0.08) and 0.91 (0.09), significantly greater than for the larger cohort. Conclusions: Our study gives reference values for temporal-to-nasal macular GCIPL subfield ratios. Weak negative correlations with age emerged. Genetic factors may contribute to ∼20% to 23% of the variance in healthy individuals. The ratios differ according to the OCT platform used.


Assuntos
Retinopatia Diabética , Retina , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Neurônios , Fibras Nervosas , Tomografia de Coerência Óptica/métodos
5.
6.
J Am Acad Child Adolesc Psychiatry ; 63(3): 345-354, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37385585

RESUMO

OBJECTIVE: Cannabis use is associated with suicide-related outcomes in both adolescents and adults, and may be increasing amid shifting cannabis policies. However, little is known about the impact of medical marijuana legalization (MML) and recreational marijuana legalization (RML) policies on youth suicide. Using 20 years of national data, we examined associations between MML, RML, and suicide-related mortality among US individuals aged 12 to 25 years, and assessed whether they varied based on age and sex. METHOD: Suicide deaths (N = 113,512) from the 2000-2019 National Vital Statistics System Multiple Cause of Death files for age groups 12 to 13, 14 to 16, 17 to 19, 20 to 22, and 23 to 25 years were examined in relation to time-varying cannabis law status using a staggered adoption difference-in-difference (DiD) approach with a negative binomial regression to determine associations between MML, RML, and suicide rates, controlling for individual- and state-level covariates and accounting for the varying effective dates of MML and RML by state. RESULTS: The overall unadjusted annual suicide rate was 10.93/100,000, varying from 9.76 (states without marijuana laws (ML)) to 12.78 (MML states) to 16.68 (RML states). In multivariable analysis, both MML (incidence rate ratio [IRR] = 1.10, 95% CI: 1.05-1.15) and RML (IRR = 1.16, 95% CI: 1.06-1.27) were associated with higher suicide rates among female youth compared to those in states without ML. Youth aged 14 to 16 years had higher rates of suicide in states with RML compared to states with MML (IRR = 1.14, 95% CI: 1.00-1.30) and states without ML (IRR = 1.09, 95% CI: 1.00-1.20). Findings were consistent across sensitivity analyses. CONCLUSION: MML and RML were associated with increased suicide-related mortality in female youth and 14- to- 16-year-old individuals of both sexes. Mechanisms through which cannabis policies are related to increased youth suicide warrant further study and should inform legislative reform.


Assuntos
Cannabis , Maconha Medicinal , Adulto , Masculino , Adolescente , Humanos , Feminino , Estados Unidos/epidemiologia , Legislação de Medicamentos , Incidência
7.
Eye (Lond) ; 38(3): 434-441, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37717107

RESUMO

The prevalence of myopia is increasing across the world. Controlling myopia progression would be beneficial to reduce adverse outcomes such as retinal detachment and myopic maculopathy which are associated with increased axial length. Pharmacological control of myopia progression with atropine has been investigated since the 19th century and the benefits of slowing myopia progression are considered against the side-effects of near blur and photophobia. More recently, randomised trials have focused on determining the optimum concentration of atropine leading to low-concentration atropine being used to manage myopia progression by practitioners across the world. Currently, in the United Kingdom, there is no licensed pharmacological intervention for myopia management. The aim of this review is to interpret the available data to inform clinical practice. We conducted a narrative review of the literature and identified peer-reviewed randomised controlled trials using the search terms 'myopia' and 'atropine', limited to the English language. We identified two key studies, which were the Atropine in the Treatment Of Myopia (ATOM) and Low-concentration Atropine for Myopia Progression (LAMP). Further studies were identified using the above search terms and the references from the identified literature. Atropine 0.01% has a modest effect on controlling axial length progression. Atropine 0.05% appears to be superior to atropine 0.01% in managing myopia progression. There is a dose-dependent rebound effect when treatment is stopped. Atropine is a well-tolerated, safe, and effective intervention. Treatment would be needed for several years and into adolescence, until axial length progression is stable.


Assuntos
Atropina , Miopia , Humanos , Atropina/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Miopia/tratamento farmacológico , Prevalência , Reino Unido , Progressão da Doença , Refração Ocular , Midriáticos/uso terapêutico
8.
Doc Ophthalmol ; 148(1): 25-36, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37924416

RESUMO

PURPOSE: Both rod and cone-driven signals contribute to the electroretinogram (ERG) elicited by a standard strong flash in the dark. Negative ERGs usually reflect inner retinal dysfunction. However, in diseases where rod photoreceptor function is selectively lost, a negative waveform might represent the response of the dark-adapted cone system. To investigate the dark-adapted cone-driven waveform in healthy individuals, we delivered flashes on a dim blue background, designed to saturate the rods, but minimally adapt the cones. METHODS: ERGs were recorded, using conductive fibre electrodes, in adults from the TwinsUK cohort. Responses to 13 cd m-2 s white xenon flashes (similar to the standard DA 10 flash), delivered on a blue background, were analysed. Photopic and scotopic strengths of the background were 1.3 and 30 cd m-2, respectively; through a dilated pupil, this is expected to largely saturate the rods, but adapt the cones much less than the standard ISCEV background. RESULTS: Mean (SD) participant age was 62.5 (11.3) years (93% female). ERGs from 203 right and 204 left eyes were included, with mean (SD) b/a ratios of 1.22 (0.28) and 1.18 (0.28), respectively (medians, 1.19 and 1.17). Proportions with negative waveforms were 23 and 26%, respectively. Right and left eye b/a ratios were strongly correlated (correlation coefficient 0.74, p < 0.0001). We found no significant correlation of b/a ratio with age. CONCLUSIONS: Over 20% of eyes showed b/a ratios less than 1, consistent with the notion that dark-adapted cone-driven responses to standard bright flashes can have negative waveforms. The majority had ratios greater than 1. Thus, whilst selective loss of rod function can yield a negative waveform (with reduced a-wave) in some, our findings also suggest that loss of rod function can occur without necessarily yielding a negative ERG. One potential limitation is possible mild cone system adaptation by the background.


Assuntos
Eletrorretinografia , Células Fotorreceptoras Retinianas Cones , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Prevalência , Adaptação à Escuridão , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/fisiologia
9.
Invest Ophthalmol Vis Sci ; 64(14): 28, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37982764

RESUMO

Purpose: Changes in refractive error during young adulthood is common yet risk factors at this age are largely unexplored. This study explored risk factors for these changes, including gene-environmental interactions. Methods: Spherical equivalent refraction (SER) and axial length (AL) for 624 community-based adults were measured at 20 (baseline) and 28 years old. Participants were genotyped and their polygenic scores (PGS) for refractive error calculated. Self-reported screen time (computer, television, and mobile devices) from 20 to 28 years old were collected prospectively and longitudinal trajectories were generated. Past sun exposure was quantified using conjunctival ultraviolet autofluorescence (CUVAF) area. Results: Median change in SER and AL were -0.023 diopters (D)/year (interquartile range [IQR] = -0.062 to -0.008) and +0.01 mm/year (IQR = 0.000 to 0.026), respectively. Sex, baseline myopia, parental myopia, screen time, CUVAF, and PGS were significantly associated with myopic shift. Collectively, these factors accounted for approximately 20% of the variance in refractive error change, with screen time, CUVAF, and PGS each explaining approximately 1% of the variance. Four trajectories for total screen time were found: "consistently low" (n = 148), "consistently high" (n = 250), "consistently very high" (n = 76), and "increasing" (n = 150). Myopic shift was faster in those with "consistently high" or "consistently very high" screen time compared to "consistently-low" (P ≤ 0.031). For each z-score increase in PGS, changes in SER and AL increased by -0.005 D/year and 0.002 mm/year (P ≤ 0.045). Of the three types of screen time, only computer time was associated with myopic shift (P ≤ 0.040). There was no two- or three-way interaction effect between PGS, CUVAF, or screen time (P ≥ 0.26). Conclusions: Higher total or computer screen time, less sun exposure, and genetic predisposition are each independently associated with greater myopic shifts during young adulthood. Given that these factors explained only a small amount of the variance, there are likely other factors driving refractive error change during young adulthood.


Assuntos
Miopia , Erros de Refração , Adulto , Humanos , Adulto Jovem , Predisposição Genética para Doença , Tempo de Tela , Luz Solar/efeitos adversos , Erros de Refração/genética , Miopia/genética , Túnica Conjuntiva
10.
Ocul Surf ; 30: 196-203, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37783428

RESUMO

PURPOSE: To investigate the hypothesis that a Mediterranean diet is associated with a lower risk of having dry eye disease (DED) in the general population. METHODS: DED was assessed using the Women's Health Study (WHS) dry eye questionnaire in 58,993 participants from the Dutch Lifelines Cohort with complete available dietary data (20-94 years, 60% female). Level of adherence to a traditional Mediterranean diet was assessed using the modified Mediterranean Diet Score (mMDS). High-sensitivity C-reactive Protein (hsCRP) was included as a marker of whole-body inflammation. Logistic regressions were used to examine the relationship between WHS-defined DED and mMDS, corrected for age, sex, BMI, education, income, and 48 potentially confounding comorbidities. The association between mMDS and hsCRP, and hsCRP and DED, was further explored in separate regressions. RESULTS: Of all participants, 9.1% had DED. In contrast to the hypothesis, higher mMDS levels were associated with greater odds of DED, corrected for demographics, smoking status, BMI, and comorbidities (OR 1.034, 95%CI: 1.015 to 1.055, P = 0.001). Moreover, there was a highly significant relationship between increasing mMDS and lower circulating hsCRP levels; however, there was no significant relationship between hsCRP and DED. CONCLUSIONS: Stronger adherence to a Mediterranean diet does not appear to be associated with lower odds of having DED in the general population. Furthermore, there was no association between hsCRP and DED in this study. However, the previously described link between a Mediterranean diet and lower hsCRP was confirmed in this large population-based study.


Assuntos
Dieta Mediterrânea , Síndromes do Olho Seco , Humanos , Feminino , Masculino , Proteína C-Reativa/metabolismo , Inflamação , Inquéritos e Questionários , Síndromes do Olho Seco/epidemiologia , Fatores de Risco
11.
Subst Use Misuse ; 58(13): 1771-1779, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37584421

RESUMO

Introduction: Adolescent-onset cannabis use (CU) (before age 18) is associated with multiple adverse psychosocial outcomes, but rates of CU peak between the ages of 18 and 22, coinciding with college matriculation. Whether CU among college-enrolled young adults is associated with similar psychosocial outcomes is poorly understood. In the present study, we examined relationships between CU and multiple psychosocial outcomes in North American college students. Methods: Data for this report come from N = 40,250 North American college students ages 18-to-25 years (mean age = 20.7 years, 69% female, 66% Caucasian) who participated in the Healthy Minds Study (HMS) 2016-17. HMS is a web-based annual survey querying multiple mental health, substance use, and psychosocial variables in representative student populations from 53 universities across North America. Student respondents were stratified in two groups based upon their self-report of past 30-day CU and compared on psychosocial variables. Results: Approximately 20% (n = 8,327) of student respondents reported past 30-day CU. After adjusting for socio-demographics, knowledge of campus services, and use of other drugs, the odds of depression (aOR = 1.3), suicidal thoughts and behaviors (aORs ∼1.4-1.7), anxiety (aOR = 1.2), eating disorders (aOR = 1.2), and violence victimization (aOR = 1.4) were all higher for CU students. Additionally, CU students had higher rates of other drug use and lower rates of perceived supportive relationships. Conclusion: Our results indicated that CU is common among North American college students and associated with adverse psychosocial consequences across multiple domains. Based upon these findings, colleges should consider expanding educational, prevention, and early-intervention programs for students who use cannabis.


Assuntos
Cannabis , Alucinógenos , Transtornos Relacionados ao Uso de Substâncias , Adulto Jovem , Adolescente , Humanos , Feminino , Adulto , Masculino , Funcionamento Psicossocial , Saúde Mental , Inquéritos e Questionários , Estudantes/psicologia , Universidades
12.
J Psychopharmacol ; 37(9): 849-865, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37650489

RESUMO

Hallucinogenic mushrooms have been used in religious and cultural ceremonies for centuries. Of late, psilocybin, the psychoactive compound in hallucinogenic mushrooms, has received increased public interest as a novel drug for treating mood and substance use disorders (SUDs). In addition, in recent years, some states in the United States have legalized psilocybin for medical and recreational use. Given this, clinicians need to understand the potential benefits and risks related to using psilocybin for therapeutic purposes so that they can accurately advise patients. This expert narrative review summarizes the scientific basis and clinical evidence on the safety and efficacy of psilocybin-assisted therapy for treating psychiatric disorders and SUDs. The results of this review are structured as a more extensive discussion about psilocybin's history, putative mechanisms of action, and recent legislative changes to its legal status. There is modest evidence of psilocybin-assisted therapy for treating depression and anxiety disorders. In addition, early data suggest that psilocybin-assisted therapy may effectively reduce harmful drinking in patients with alcohol use disorders. The evidence further suggests psilocybin, when administered under supervision (psilocybin-assisted therapy), the side effects experienced are mild and transient. The occurrence of severe adverse events following psilocybin administration is uncommon. Still, a recent clinical trial found that individuals in the psilocybin arm had increased suicidal ideations and non-suicidal self-injurious behaviors. Given this, further investigation into the safety and efficacy of psilocybin-assisted therapy is warranted to determine which patient subgroups are most likely to benefit and which are most likely to experience adverse outcomes related to its use.


Assuntos
Alcoolismo , Alucinógenos , Humanos , Psilocibina/efeitos adversos , Alucinógenos/efeitos adversos , Afeto , Transtornos de Ansiedade
13.
Cells ; 12(15)2023 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-37566048

RESUMO

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential.


Assuntos
Glaucoma , Mitofagia , Humanos , Glaucoma/patologia , Pressão Intraocular , Células Ganglionares da Retina/metabolismo , Mitocôndrias/metabolismo
14.
Invest Ophthalmol Vis Sci ; 64(10): 9, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37428499

RESUMO

Purpose: The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs). Methods: This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling. Results: In this population (mean age = 62.0 years [SD = 10.4 years], range = 40-89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4-16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0-22.7), and VMA was diagnosed in 11.8% (10.8-13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6-52.8) for ERM, 53.2% (95% CI = 41.8-63.2) for PVD, and 48.1% (95% CI = 33.6-58) for VMA. Conclusions: Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis.


Assuntos
Membrana Epirretiniana , Doenças Orbitárias , Doenças Retinianas , Perfurações Retinianas , Descolamento do Vítreo , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Descolamento do Vítreo/diagnóstico , Descolamento do Vítreo/epidemiologia , Descolamento do Vítreo/genética , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/epidemiologia , Perfurações Retinianas/genética , Corpo Vítreo/patologia , Prevalência , Estudos Transversais , Doenças Retinianas/diagnóstico , Doenças Retinianas/epidemiologia , Doenças Retinianas/genética , Membrana Epirretiniana/epidemiologia , Membrana Epirretiniana/genética , Membrana Epirretiniana/diagnóstico , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos
15.
Invest Ophthalmol Vis Sci ; 64(7): 31, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37342033

RESUMO

Purpose: To determine whether the ABCA4 retinopathy-associated variant p.Asn1868Ile (c.5603A>T) is associated with retinal structure or subclinical disease among the general population. Methods: UK Biobank participants of European ancestry with available spectral-domain optical coherence tomography (OCT) passing quality control metrics and exome sequencing data were included. Regression analyses using both linear and recessive models tested for the association between the p.Asn1868Ile variant and total retinal thickness, clinically relevant segmented layer thicknesses, and visual acuity. Further regression analyses were performed with automated quality control metrics to determine if the p.Asn1868Ile variant is associated with poor quality or abnormal scans. Results: Retinal layer segmentation and sequencing data for the p.Asn1868Ile variant were available for 26,558 participants, following exclusions. We identified no significant association between the p.Asn1868Ile variant and retinal thickness, any of the segmented layers, or visual acuity. There was also no significant difference for homozygous p.Asn1868Ile when tested under the assumption of a recessive model. No association was identified for any of the quality control metrics, and a χ2 test showed that participants with the p.Asn1868Ile variant were not more likely to be excluded during quality control due to poor quality scans (P = 0.56). Conclusions: The p.Asn1868Ile variant does not appear to affect the retinal structure or have pathogenic or subclinical effects on its own within the general population. The variant is likely to require other specific cis- or trans-acting modifying factors to cause ABCA4 retinopathy.


Assuntos
Bancos de Espécimes Biológicos , Doenças Retinianas , Humanos , Retina/patologia , Doenças Retinianas/genética , Doenças Retinianas/patologia , Tomografia de Coerência Óptica/métodos , Genótipo , Reino Unido , Transportadores de Cassetes de Ligação de ATP/genética
16.
EBioMedicine ; 92: 104615, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37201334

RESUMO

BACKGROUND: Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by progressive degeneration of the optic nerve that leads to irreversible visual impairment. Multiple epidemiological studies suggest an association between POAG and major neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Parkinson's disease). However, the nature of the overlap between neurodegenerative disorders, brain morphology and glaucoma remains inconclusive. METHOD: In this study, we performed a comprehensive assessment of the genetic and causal relationship between POAG and neurodegenerative disorders, leveraging genome-wide association data from studies of magnetic resonance imaging of the brain, POAG, and four major neurodegenerative disorders. FINDINGS: This study found a genetic overlap and causal relationship between POAG and its related phenotypes (i.e., intraocular pressure and optic nerve morphology traits) and brain morphology in 19 regions. We also identified 11 loci with a significant local genetic correlation and a high probability of sharing the same causal variant between neurodegenerative disorders and POAG or its related phenotypes. Of interest, a region on chromosome 17 corresponding to MAPT, a well-known risk locus for Alzheimer's and Parkinson's disease, was shared between POAG, optic nerve degeneration traits, and Alzheimer's and Parkinson's diseases. Despite these local genetic overlaps, we did not identify strong evidence of a causal association between these neurodegenerative disorders and glaucoma. INTERPRETATION: Our findings indicate a distinctive and likely independent neurodegenerative process for POAG involving several brain regions although several POAG or optic nerve degeneration risk loci are shared with neurodegenerative disorders, consistent with a pleiotropic effect rather than a causal relationship between these traits. FUNDING: PG was supported by an NHMRC Investigator Grant (#1173390), SM by an NHMRC Senior Research Fellowship and an NHMRC Program Grant (APP1150144), DM by an NHMRC Fellowship, LP is funded by the NEIEY015473 and EY032559 grants, SS is supported by an NIH-Oxford Cambridge Fellowship and NIH T32 grant (GM136577), APK is supported by a UK Research and Innovation Future Leaders Fellowship, an Alcon Research Institute Young Investigator Award and a Lister Institute for Preventive Medicine Award.


Assuntos
Doença de Alzheimer , Glaucoma de Ângulo Aberto , Glaucoma , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/patologia , Estudo de Associação Genômica Ampla , Doença de Parkinson/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Glaucoma/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Degeneração Neural/genética , Degeneração Neural/patologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-37220016

RESUMO

Introduction: Dramatic shifts in marijuana laws, along with federal deregulation of hemp with the 2018 Farm Bill, have resulted in increased availability and use of cannabidiol (CBD) supplements throughout the United States (US). Given the rapid increase in CBD use in the U.S. general population, in this study, we aim to characterize primary care physician (PCP) attitudes and practice behaviors and to assess whether differences in provider attitudes and behaviors vary as a function of marijuana legalization (ML) status in the state of practice. Materials and Methods: Data are from an online provider survey on CBD supplement-related attitudes, beliefs, and behaviors administered to 508 PCPs as part of a larger mixed methods study. Participating PCPs were recruited from the Mayo Clinic Healthcare Network and provided medical care in primary care settings across four U.S. states (Minnesota, Wisconsin, Florida, and Arizona). Results: The survey response rate was 45.4% (n=236/508). According to providers, CBD was frequently brought up in PCP settings, typically by patients. PCPs were generally hesitant to screen for or discuss CBD with their patients and identified multiple barriers to open patient-provider dialogue about CBD. PCPs practicing in states that had passed ML were more receptive to patients using CBD supplements, whereas PCPs practicing in states that had not passed ML were more concerned about CBD-related side effects. Regardless of state ML status, most PCPs did not feel that they should be recommending CBD supplements to their patients. Most PCPs reported believing that CBD was unhelpful for most conditions for which it is marketed, with chronic non-cancer pain and anxiety/stress being exceptions. PCP respondents generally felt that they had insufficient knowledge/training around CBD. Conclusions: Results from this mixed methods study show that PCPs practicing in the U.S. rarely screen for or discuss CBD use with their patients and report several barriers to engage in proactive CBD-focused practice behaviors. Furthermore, survey results show that some PCP attitudes, practice behaviors, and barriers vary as a function of state ML status. These findings may guide medical education efforts and inform primary care practice modifications aimed at enhancing screening and monitoring of patient CBD use by PCPs.

18.
Clin Med Insights Pediatr ; 17: 11795565231162297, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36993933

RESUMO

Cannabis vaping has emerged as a predominant mode of cannabis use among United States (US) adolescents and young adults (AYA) primarily due to the popularity of modifiable designs of vaping devices coupled with changes in cannabis policies and increased availability of cannabinoid products. New methods for cannabis vaping by e-liquid/oil vaping, dry plant vaping, and cannabis concentrate vaping (ie, dabbing) have had high uptake among American youth with unclear long-term health implications. Issues with contamination, mislabeling, and expansion of the vaped cannabis market to include not only delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD) but also delta-9-THC analogs (eg, delta-8 and delta-10) sold as hemp-derived "legal highs" further complicated this healthcare space. Recent research suggests that cannabis/THC vaping carries distinct and overlapping risks when compared to cannabis smoking and may be associated with greater risk for acute lung injuries, seizures, and acute psychiatric symptoms. Primary care clinicians providing care for AYA are in an ideal position to identify cannabis misuse and intervene early to address cannabis vaping. To improve public health outcomes, a need exists for pediatric clinicians to be educated about different ways/methods that youth are vaping cannabinoid products and associated risks related to cannabinoid vaping. Further, pediatric clinicians need to be trained how to effectively screen for and discuss cannabis vaping with their youth patients. In the current article, we present a clinically focused review of cannabis vaping among young people with 3 main aims to: (1) identify and describe the cannabis vaping products commonly used by American youth; (2) review the health correlates of youth cannabis vaping; and (3) discuss clinical considerations related to identifying and treating youth who vape cannabis.

19.
PLoS Genet ; 19(2): e1010583, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36757925

RESUMO

The eye is the window through which light is transmitted and visual sensory signalling originates. It is also a window through which elements of the cardiovascular and nervous systems can be directly inspected, using ophthalmoscopy or retinal imaging. Measurements of ocular parameters may therefore offer important information on the physiology and homeostasis of these two important systems. Here we report the results of a genetic characterisation of retinal vasculature. Four genome-wide association studies performed on different aspects of retinal vasculometry phenotypes, such as arteriolar and venular tortuosity and width, found significant similarities between retinal vascular characteristics and cardiometabolic health. Our analyses identified 119 different regions of association with traits of retinal vasculature, including 89 loci associated arteriolar tortuosity, the strongest of which was rs35131825 (p = 2.00×10-108), 2 loci with arteriolar width (rs12969347, p = 3.30×10-09 and rs5442, p = 1.9E-15), 17 other loci associated with venular tortuosity and 11 novel associations with venular width. Our causal inference analyses also found that factors linked to arteriolar tortuosity cause elevated diastolic blood pressure and not vice versa.


Assuntos
Estudo de Associação Genômica Ampla , Vasos Retinianos , Fatores de Risco , Retina , Fenótipo
20.
Ocul Surf ; 28: 11-17, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36621639

RESUMO

PURPOSE: Sedentary behavior (SB) has been linked with low-grade systemic inflammation, which could play a role in the development of dry eye disease (DED). This cross-sectional study aims to investigate the association between SB and DED. METHODS: We assessed 48,418 participants from the population-based Lifelines cohort (58% female, 18-96 years). Women's Health Study (WHS)-defined DED was the primary outcome. SB was assessed using the Marshall Sitting Questionnaire. The relationship between DED and SB was analyzed using logistic regressions, corrected for age, sex, BMI, smoking status, demographics, and 48 comorbidities. Any potential modifying effect of physical activity (PA) was also assessed, and the analyses were repeated excluding the most computer-intensive domains, investigating SB independent from screen exposure. RESULTS: WHS-defined DED was present in 9.1% of participants. Greater SB was associated with an increased risk of DED (odds ratio (OR) 1.015 per hour/day, 95%CI 1.005-1.024, P = 0.004). The association between SB and DED was only significant for those with less than WHO-recommended PA (OR 1.022, 95%CI 1.002-1.042, P = 0.027), and not in participants meeting WHO's recommendation (OR 1.011, 95%CI 0.999-1.023, P = 0.076). Lastly, when excluding computer-related sitting, the relationship between SB and DED was attenuated, and no longer significant (OR 1.009, 95%CI 0.996-1.023, P = 0.19). CONCLUSIONS: Greater sedentary time was tied to an increased risk of DED, especially for those with lower PA levels than WHO recommendations. However, as there was no significant association when computer-intensive sitting time was excluded, screen use could explain the observed relationship and should be noted as a possible key confounder.


Assuntos
Síndromes do Olho Seco , Comportamento Sedentário , Humanos , Feminino , Masculino , Estudos Transversais , Fatores de Risco , Inquéritos e Questionários , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/etiologia
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