Nat Neurosci. 2024 Apr 22. doi: 10.1038/s41593-024-01624-4. Online ahead of print.

ABSTRACT

Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1-C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, differential expression and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional program for adolescent brain development, which can lead to atypical supragranular cortical connectivity in people at high genetic risk for schizophrenia.

PMID:38649755 | DOI:10.1038/s41593-024-01624-4

Sci Rep. 2024 Apr 22;14(1):9230. doi: 10.1038/s41598-024-57942-x.

ABSTRACT

With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.

PMID:38649688 | DOI:10.1038/s41598-024-57942-x

Commun Biol. 2024 Apr 22;7(1):485. doi: 10.1038/s42003-024-06016-9.

ABSTRACT

Converging evidence implicates disrupted brain connectivity in autism spectrum disorder (ASD); however, the mechanisms linking altered connectivity early in development to the emergence of ASD symptomatology remain poorly understood. Here we examined whether atypicalities in the Salience Network - an early-emerging neural network involved in orienting attention to the most salient aspects of one's internal and external environment - may predict the development of ASD symptoms such as reduced social attention and atypical sensory processing. Six-week-old infants at high likelihood of developing ASD based on family history exhibited stronger Salience Network connectivity with sensorimotor regions; infants at typical likelihood of developing ASD demonstrated stronger Salience Network connectivity with prefrontal regions involved in social attention. Infants with higher connectivity with sensorimotor regions had lower connectivity with prefrontal regions, suggesting a direct tradeoff between attention to basic sensory versus socially-relevant information. Early alterations in Salience Network connectivity predicted subsequent ASD symptomatology, providing a plausible mechanistic account for the unfolding of atypical developmental trajectories associated with vulnerability to ASD.

PMID:38649483 | DOI:10.1038/s42003-024-06016-9

PLoS One. 2024 Apr 22;19(4):e0302238. doi: 10.1371/journal.pone.0302238. eCollection 2024.

ABSTRACT

In recent years, research has been demonstrating that movement analysis, utilizing machine learning methods, can be a promising aid for clinicians in supporting autism diagnostic process. Within this field of research, we aim to explore new models and delve into the detailed observation of certain features that previous literature has identified as prominent in the classification process. Our study employs a game-based tablet application to collect motor data. We use artificial neural networks to analyze raw trajectories in a "drag and drop" task. We compare a two-features model (utilizing only raw coordinates) with a four-features model (including velocities and accelerations). The aim is to assess the effectiveness of raw data analysis and determine the impact of acceleration on autism classification. Our results revealed that both models demonstrate promising accuracy in classifying motor trajectories. The four-features model consistently outperforms the two-features model, as evidenced by accuracy values (0.90 vs. 0.76). However, our findings support the potential of raw data analysis in objectively assessing motor behaviors related to autism. While the four-features model excels, the two-features model still achieves reasonable accuracy. Addressing limitations related to sample size and noise is essential for future research. Our study emphasizes the importance of integrating intelligent solutions to enhance and assist autism traditional diagnostic process and intervention, paving the way for more effective tools in assessing motor skills.

PMID:38648209 | DOI:10.1371/journal.pone.0302238

Lancet Reg Health Am. 2024 Apr 18;33:100736. doi: 10.1016/j.lana.2024.100736. eCollection 2024 May.

ABSTRACT

BACKGROUND: Patients with autism spectrum disorders (ASD) experience higher rates of perioperative anxiety and are likely to receive premedication. Little is known about nonpharmaceutical interventions which may decrease anxiety. This study aims to evaluate the use of an adaptive sensory environment (ASE) to reduce ASD patient anxiety during the perioperative process.

METHODS: Our feasibility study (ClinicalTrials.govNCT04994613) enrolled 60 patients in two parallel groups randomized to a control (no ASE) or intervention group (ASE). We included all surgical patients aged three to twelve years, with a formal diagnosis of ASD, Asperger's Syndrome, or pervasive developmental disorder not otherwise specified. Preoperative behaviors were recorded by an unblinded nurse utilizing the validated Modified Yale Preoperative Anxiety Scale (mYPAS). The difference in score on the mYPAS was the primary outcome, and an intention-to-treat analysis was employed. A generalized estimating equations model was used to compare mYPAS scores controlling for significant independent variables.

FINDINGS: 58 patients were analyzed after 1:1 randomization of 30 patients to each group. Groups were balanced except the median number of intraoperative pain medications was significantly lower in the ASE group (1 vs. 3, p = 0.012). Mean (SD) age for all patients was 7.2 (2.9) years, range 2.6-12.7. 72.4% (42/58) were White and all were Non-Hispanic or Latino. 74% were Male (21/30 ASE and 22/28 Control) and 26% were Female (9/30 ASE and 6/28 Control). No differences were found in mYPAS scores between groups at three time periods (43.5 vs. 42, p = 0.88, 47.8 vs. 48.4, p = 0.76, and 36.4 vs. 43.8, p = 0.15, ASE vs. control group, respectively). The ASE group had a significant within-group decrease in mYPAS scores from nursing intake to transition (p = 0.030).

INTERPRETATION: An ASE did not significantly reduce perioperative anxiety. However, the promising results deserve further investigation.

FUNDING: Dayton Children's Hospital Foundation Robert C. Cohn Memorial Research Grant.

PMID:38645550 | PMC:PMC11031801 | DOI:10.1016/j.lana.2024.100736

Front Psychiatry. 2024 Apr 5;15:1253199. doi: 10.3389/fpsyt.2024.1253199. eCollection 2024.

ABSTRACT

Motor dysfunction is increasingly being viewed as a core characteristic of autism spectrum disorder (ASD) in children. In particular, children with ASD have difficulty in learning new motor skills and there is a need to develop effective methods to improve this. Previous research has found that children with ASD may retain the ability to implicitly learn motor skills in comparison to their explicit learning of motor skills, which is typically impaired. This literature mini review focuses on summarizing the study of implicit learning in the acquisition of motor skills in children with ASD. First, we briefly introduce several common implicit learning methods in children's motor skill learning. Second, we focus on the role of two important implicit learning approaches in motor skill learning, namely, an external focus of attention and analogy learning. Finally, based on our review of the existing studies, we present an outlook for future research and the areas that need to be improved in the practical teaching of implicit learning in the acquisition of motor skills in children with ASD.

PMID:38645416 | PMC:PMC11026583 | DOI:10.3389/fpsyt.2024.1253199

medRxiv [Preprint]. 2024 Apr 13:2024.04.10.24305539. doi: 10.1101/2024.04.10.24305539.

ABSTRACT

Genetic variants linked to autism are thought to change cognition and behaviour by altering the structure and function of the brain. Although a substantial body of literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic variants are linked to changes in cortical macro- and micro-structure. We investigated this using neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4,928). Using polygenic scores and genetic correlations we observe a robust negative association between common variants for autism and a magnetic resonance imaging derived phenotype for neurite density (intracellular volume fraction) in the general population. This result is consistent across both children and adults, in both the cortex and in white matter tracts, and confirmed using polygenic scores and genetic correlations. There were no sex differences in this association. Mendelian randomisation analyses provide no evidence for a causal relationship between autism and intracellular volume fraction, although this should be revisited using better powered instruments. Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density.

PMID:38645251 | PMC:PMC11030520 | DOI:10.1101/2024.04.10.24305539

Disabil Rehabil. 2024 Apr 21:1-11. doi: 10.1080/09638288.2024.2340704. Online ahead of print.

ABSTRACT

PURPOSE: There is a need for valid and reliable clinical assessment tools to assess cardiorespiratory fitness (CRF) levels in adolescents with autism. Therefore, this study aimed to examine the concurrent validity and test-retest reliability of the Astrand-Rhyming Test (ART) in this population.

MATERIALS AND METHODS: 45 adolescents with autism aged 12-18 years (n = 32 males, 14.47 ± 1.79 years) performed the ART twice (test-retest reliability) and completed a maximal cardiopulmonary exercise test (CPET) (concurrent validity). Reliability parameters included Pearson correlations, intraclass correlation coefficients (ICCs), standard error of measurements (SEM), minimal detectable changes (MDC), coefficients of variation, paired sample t-tests, linear regressions and Bland-Altman plots. The concurrent validity was evaluated with Pearson correlations, ICCs, paired sample t-tests, linear regressions and Bland-Altman plots.

RESULTS: Strong test-retest reliability (r = 0.84-0.85, ICC = 0.84-0.85) was found for the ART, but the wide limits of agreement intervals suggest the presence of substantial variability. The large SEM (4.73-5.08 mL/kg/min) and MDC (13.20-14.07 mL/kg/min) values suggest lower absolute reliability. Moderate to strong levels of association (r = 0.74-0.75) and agreement (ICC = 0.59-0.66) were found between estimated (ART1) and measured (CPET) VO2 max levels, but significant systematic differences (5.71-8.82 mL/kg/min) were observed.

CONCLUSION: The ART is an accessible and promising method to monitor submaximal CRF levels over time but is less appropriate to estimate maximal CRF levels in this population.

PMID:38644598 | DOI:10.1080/09638288.2024.2340704

AJOB Empir Bioeth. 2024 Apr 21:1-18. doi: 10.1080/23294515.2024.2336903. Online ahead of print.

ABSTRACT

BACKGROUND: Autism self-advocates' views regarding genetic tests for autism are important, but critical questions about their perspectives arise.

METHODS: We interviewed 11 autism self-advocates, recruited through autism self-advocacy websites, for 1 h each.

RESULTS: Interviewees viewed genetic testing and its potential pros and cons through the lens of their own indiviudal perceived challenges, needs and struggles, especially concerning stigma and discrimination, lack of accommodations and misunderstandings from society about autism, their particular needs for services, and being blamed by others and by themselves for autistic traits. Their views of genetic testing tended not to be binary, but rather depended on how the genetic test results would be used. Interviewees perceived pros of genetic testing both in general and with regard to themselves (e.g., by providing "scientific proof" of autism as a diagnosis and possibly increasing availability of services). But they also perceived disadvantages and limitations of testing (e.g., possible eugenic applications). Participants distinguished between what they felt would be best for themselves and for the autistic community as a whole. When asked if they would undergo testing for themselves, if offered, interviewees added several considerations (e.g., undergoing testing because they support science in general). Interviewees were divided whether a genetic diagnosis would or should reduce self-blame, and several were wary of testing unless treatment, prevention or societal attitudes changed. Weighing these competing pros and cons could be difficult.

CONCLUSIONS: This study, the first to use in-depth qualitative interviews to assess views of autism self-advocates regarding genetic testing, highlights key complexities. Respondents felt that such testing is neither wholly good or bad in itself, but rather may be acceptable depending on how it is used, and should be employed in beneficial, not harmful ways. These findings have important implications for practice, education of multiple stakeholders, research, and policy.

PMID:38643392 | DOI:10.1080/23294515.2024.2336903

Sci Rep. 2024 Apr 20;14(1):9065. doi: 10.1038/s41598-024-59532-3.

ABSTRACT

Autistic people frequently experience negative judgements from non-autistic people, often fuelled by misconceptions that autistic people lack empathy. Understanding responses to negative social judgement among autistic people is crucial because of the potential negative impact on wellbeing and future interactions. We investigated the role of autistic traits, social anxiety, and depression on behavioural indices of social rejection in 20 autistic (AUT; 11 males) and 40 non-autistic (N-AUT; 21 males) university students. Participants completed the Social Judgement Task (SJT) where they predicted whether they were liked by another person, then received feedback on whether those evaluations were correct. Participants also completed an Age Judgement Task (AJT) where they estimated the age of the pictured person. The AUT group had lower positive expectation scores, meaning less tendency to predict being liked. Across the whole sample, higher social anxiety predicted greater tendency to anticipate rejection from others, not autistic traits. These findings suggest early experiences of rejection might lead to a negative self-bias in autistic people and emphasise the importance of using a transdiagnostic approach by showing that social anxiety rather than autistic traits is associated with expectation of social rejection.

PMID:38643251 | PMC:PMC11032319 | DOI:10.1038/s41598-024-59532-3

Lipids Health Dis. 2024 Apr 20;23(1):114. doi: 10.1186/s12944-024-02075-3.

ABSTRACT

Disturbances in cholesterol homeostasis have been associated with ASD. Lipid rafts are central in many transmembrane signaling pathways (including mTOR) and changes in raft cholesterol content affect their order function. Cholesterol levels are controlled by several mechanisms, including endoplasmic reticulum associated degradation (ERAD) of the rate limiting HMGCoA reductase. A new approach to increase cholesterol via temporary ERAD blockade using a benign bacterial toxin-derived competitor for the ERAD translocon is suggested.A new lock and key model for cholesterol/lipid raft dependent signaling is proposed in which the rafts provide both the afferent and efferent 'tumblers' across the membrane to allow 'lock and key' receptor transmembrane signals.

PMID:38643132 | PMC:PMC11032007 | DOI:10.1186/s12944-024-02075-3

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Apr 18:S2451-9022(24)00108-3. doi: 10.1016/j.bpsc.2024.04.006. Online ahead of print.

ABSTRACT

BACKGROUND: Atypical anticipation of social reward has been indicated to lie at the core of the social challenges faced by individuals with autism spectrum disorder (ASD). However, past research has yielded inconsistent results, often overlooking crucial characteristics of stimuli. Here, we investigated ASD reward processing using social and non-social tangible stimuli, carefully matched on several key dimensions.

METHODS: We examined the anticipation and consumption of social (interpersonal touch) and non-social (flavored milk) rewards in 25 high-functioning ASD and 25 neurotypical adult individuals. Besides subjective ratings of wanting and liking, we measured physical energetic expenditure to get the rewards, brain activity with neuroimaging, and facial reactions through electromyography, on a trial-by-trial basis.

RESULTS: ASD participants did not exhibit reduced motivation for social or non-social rewards; their subjective ratings, motivated efforts, and facial reactions were comparable to those of neurotypical participants. However, anticipation of higher-value rewards increased neural activation in lateral parietal cortices, sensorimotor regions and the orbitofrontal cortex. Moreover, ASD participants exhibited hyperconnectivity between frontal medial regions and occipital regions and the thalamus.

CONCLUSIONS: Individuals with ASD experiencing rewards with tangible characteristics, whether social or non-social, displayed typical subjective and objective motivational and hedonic responses. Notably, the observed hyperactivations in sensory and attentional nodes during anticipation suggest atypical sensory over-processing of forthcoming rewards rather than decreased reward value. While these atypicalities may not manifest in observable behavior here, they could impact real-life social interactions that require nuanced predictions, potentially leading to the misperception of ASD reduced interest in rewarding social stimuli.

PMID:38642898 | DOI:10.1016/j.bpsc.2024.04.006

J Autism Dev Disord. 2024 Apr 20. doi: 10.1007/s10803-024-06333-2. Online ahead of print.

ABSTRACT

PURPOSE: Professional supports play an important role in aiding autistic children's learning, participation, and overall wellbeing. Yet, limited research exists on stakeholders' perspectives and preferences regarding targeted outcomes for children undergoing support facilitated by professionals. This study investigated stakeholder views on the priority and appropriateness of outcomes intentionally targeted during the provision of supports to autistic children.

METHOD: A survey of 181 participants (including 72 autistic adults, 85 parents, and 69 professionals) from Australia and New Zealand was conducted. Participants rated the appropriateness and priority of 47 potential child and parent outcomes within the context of support.

RESULTS: The highest priority outcome was improving child mental wellbeing, with the lowest being reducing sensory seeking or avoidant behaviours. Priority ratings for certain outcomes differed based on the child's age. Over half of the participants rated reducing sensory seeking/avoidant behaviours and reducing focused interests as inappropriate outcomes of supports. Further, variations in the appropriateness of outcomes differed among participant groups.

CONCLUSION: Reflecting the growing acceptance of neurodiversity-affirming practices, these results underscore support for targeting outcomes that are meaningful to the autistic and autism communities, with less emphasis on those which reflect neurotypical behavioural standards.

PMID:38642180 | DOI:10.1007/s10803-024-06333-2

J Autism Dev Disord. 2024 Apr 20. doi: 10.1007/s10803-024-06262-0. Online ahead of print.

ABSTRACT

Past research has highlighted the importance of early identification of developmental differences to improve targeted access to early interventions or supports. As such, it is of particular importance in the context of children at elevated likelihood of autism (such as where an older sibling has a diagnosis of autism), to better understand when and which early concerns are important as predictors of which children will benefit from pre-diagnostic supports. This study explored the number and frequency of retrospective parent reported concerns within the first year of life for children diagnosed with autism, both those who had an older sibling diagnosed with autism and those who did not, as well as for undiagnosed siblings. We found that at both 0-6 and 7-12 months, the only factor related to the presence or absence of early parent reported concerns was child diagnostic status, with the presence of reported early concerns more likely for children with a diagnosis of autism. These findings suggest that for children at elevated likelihood of autism, parents' concerns are driven primarily by developmental differences, with child's birth order and sibling diagnostic status not impacting on parent early concerns.

PMID:38642179 | DOI:10.1007/s10803-024-06262-0

Autism. 2024 Apr 20:13623613241246091. doi: 10.1177/13623613241246091. Online ahead of print.

ABSTRACT

Many autistic people struggle with mental health problems like anxiety, depression, inattention, and aggression, which can be challenging to treat. Executive function challenges, which impact many autistic individuals, may serve as a risk factor for mental health problems or make treating mental health conditions more difficult. While some people respond well to medication or therapy, others do not. This study tried to understand if there are different subgroups of autistic young people who may have similar patterns of executive function strengths and challenges-like flexibility, planning, self-monitoring, and emotion regulation. Then, we investigated whether executive function subgroups were related to mental health problems in autistic youth. We found three different types of executive function subgroups in autistic youth, each with different patterns of mental health problems. This helps us identify specific profiles of executive function strengths and challenges that may be helpful with identifying personalized supports, services, and treatment strategies for mental health conditions.

PMID:38642028 | DOI:10.1177/13623613241246091

Autism Res. 2024 Apr 20. doi: 10.1002/aur.3136. Online ahead of print.

ABSTRACT

To date, information on associations between motor skills and executive functions (EF) in autistic children is limited. The purpose of this study was to compare motor skills and EF performance between autistic children and typically developing (TD) children and to examine the relationships between motor skills and EF in these two groups. Forty-eight autistic children and 48 TD children aged 6 to 12 years were recruited for this study. Motor skills were measured with the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). EF was assessed with the Stroop Color and Word Test, the Wisconsin Card Sorting Task (WCST), and the Test of Attentional Performance: Go/No-go test. Independent sample t-tests were used to compare the BOT-2 scores and EF measures between autistic children and TD children. Pearson product-moment correlation and regressions were conducted to assess the relationships between the BOT-2 scores and the EF measures for each group. Results showed that autistic children scored significantly lower than TD children on all four BOT-2 composite scores and a total motor composite. Autistic children also demonstrated significantly lower levels of performance on all EF measures than TD children. Further, autistic children showed more significant associations between motor skills and EF than TD children, particularly pronounced in the domains of fine manual control and manual coordination to cognitive flexibility, as well as manual coordination and inhibitory control. Continued development of motor skills and EF in autistic children is important. The relationships between motor skills and EF were significant among autistic children, suggesting future research on promoting EF through motor skill interventions in autistic children is required.

PMID:38641916 | DOI:10.1002/aur.3136

Autism Res. 2024 Apr 19. doi: 10.1002/aur.3138. Online ahead of print.

ABSTRACT

An early detection of Neurodevelopmental Disorders (NDDs) is crucial for their prognosis; however, the clinical heterogeneity of some disorders, such as autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD) is an obstacle to accurate diagnoses in children. In order to facilitate the screening process, the current study aimed to identify symptom-based clusters among a community-based sample of preschool and school-aged children, using behavioral characteristics reported by teachers. A total of 6894 children were assessed on four key variables: social communication differences, restricted behavior patterns, restless-impulsiveness, and emotional lability (pre-schoolers) or inattention and hyperactivity-impulsivity (school-aged). From these behavioral profiles, four clusters were identified for each age group. A cluster of ASD + ADHD and others including children with no pathology was clearly identified, whereas two other clusters were characterized by subthreshold ASD and/or ADHD symptoms. In the school-age children, the presence of ADHD was consistently observed with ASD patterns. In pre-schoolers, teachers were more proficient at identifying children who received a diagnosis for either ASD and/or ADHD from an early stage. Considering the significance of early detection and intervention of NDDs, teachers' insights are important. Therefore, promptly identifying subthreshold symptoms in children can help to minimize consequences in social and academic functioning.

PMID:38641914 | DOI:10.1002/aur.3138

Ann Intern Med. 2024 Apr 19. doi: 10.7326/M23-2788. Online ahead of print.

ABSTRACT

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs.

METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE.

AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes.

RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence).

• Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

• Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

PMID:38639546 | DOI:10.7326/M23-2788

J Psychiatr Res. 2024 Apr 16;174:172-180. doi: 10.1016/j.jpsychires.2024.04.027. Online ahead of print.

ABSTRACT

Growing evidence suggested that individuals with autism spectrum disorder (ASD) associated with stroke and cardiovascular disease (CVD). However, the causal association between ASD and the risk of stroke and CVD remains unclear. To validate this, we performed two-sample Mendelian randomization (MR) and two-step mediation MR analyses, using relevant genetic variants sourced from the largest genome-wide association studies (GWASs). Two-sample MR evidence indicated causal relationships between ASD and any stroke (OR = 1.1184, 95% CI: 1.0302-1.2142, P < 0.01), ischemic stroke (IS) (OR = 1.1157, 95% CI: 1.0237-1.2160, P = 0.01), large-artery atherosclerotic stroke (LAS) (OR = 1.2902, 95% CI: 1.0395-1.6013, P = 0.02), atrial fibrillation (AF) (OR = 1.0820, 95% CI: 1.0019-1.1684, P = 0.04), and heart failure (HF) (OR = 1.1018, 95% CI: 1.0007-1.2132, P = 0.05). Additionally, two-step mediation MR suggested that type 2 diabetes mellitus (T2DM) partially mediated this effect (OR = 1.14, 95%CI: 1.02-1.28, P = 0.03). The mediated proportion were 10.96% (95% CI: 0.58%-12.10%) for any stroke, 11.77% (95% CI: 10.58%-12.97%) for IS, 10.62% (95% CI: 8.04%-13.20%) for LAS, and 7.57% (95% CI: 6.79%-8.36%) for HF. However, no mediated effect was observed between ASD and AF risk. These findings have implications for the development of prevention strategies and interventions for stroke and CVD in patients with ASD.

PMID:38640796 | DOI:10.1016/j.jpsychires.2024.04.027

Am J Occup Ther. 2024 May 1;78(3):7803205040. doi: 10.5014/ajot.2024.050444.

ABSTRACT

IMPORTANCE: Caregivers are essential partners in caregiver-mediated interventions that build on family routines and practices. Research identifying how participation as an intervention partner influences caregivers' outcomes, including stress and self-efficacy, is scarce.

OBJECTIVE: To evaluate caregiver outcomes (stress, self-efficacy, and positive feeding responses and confidence) after participation in the Engaged Eaters Program.

DESIGN: Quasi-experimental pretest-posttest design.

SETTING: In-home via telehealth.

PARTICIPANTS: Fourteen primary caregivers of an autistic child (ages 2-7 yr) with feeding challenges.

INTERVENTION: The Engaged Eaters Program-Telehealth, a caregiver-mediated 6-mo in-home telehealth feeding intervention for autistic children ages 2 to 7 yr that included 24 intervention visits, eight caregiver training modules, and consultation with a dietician.

OUTCOMES AND MEASURES: Relationships between child feeding challenge severity and caregiver outcomes and individual differences in caregivers' intervention responses were evaluated. We assessed caregivers' stress (Parenting Stress Index, Fourth Edition Short Form), self-efficacy (Parent Sense of Competence Scale), Positive Feeding Responses and Confidence (PFRC; composite score of items from other assessments), and individual intervention response using pre- to postintervention change in scores.

RESULTS: Exploration of individual differences revealed that only caregivers with intake PFRC scores below the mean made significant improvements by the end of the intervention. No significant group-level changes were identified for stress, self-efficacy, or PFRC. Feeding challenge severity was not significantly related to caregiver outcomes.

CONCLUSIONS AND RELEVANCE: The results emphasize the importance of considering baseline practices, efficacy, and caregiver confidence when engaging caregivers in intervention. Future research should explore the nuanced relationship between caregiver outcomes and child characteristics. Plain-Language Summary: Caregivers are essential partners with feeding interventions that build on family routines and practices. When working with caregivers, occupational therapists should consider caregivers' readiness for and responses to an intervention because intervention practices may differentially affect caregivers' parenting practices, confidence, and self-efficacy. Caregivers' responses may also affect the overall effectiveness of a caregiver-mediated intervention. Positionality Statement: The term caregiver-mediated in used throughout this article in place of parent-mediated to be inclusive of all types of caregivers.

PMID:38640088 | DOI:10.5014/ajot.2024.050444