Search

OBJECTIVES: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. METHODS: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. RESULTS: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. CONCLUSIONS: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

In the last 40 years, there has been a huge increase in autism genetics research and a rapidly growing number of discoveries. We now know autism is one of the most highly heritable disorders with negligible shared environmental contributions. Recent discoveries also show that rare variants of large effect size as well as small effect common gene variants all contribute to autism risk. These discoveries challenge traditional diagnostic boundaries and highlight huge heterogeneity in autism. In this review, we consider some of the key findings that are shaping current understanding of autism and what these discoveries mean for clinicians.

In the last 40 years, there has been a huge increase in autism genetics research and a rapidly growing number of discoveries. We now know autism is one of the most highly heritable disorders with negligible shared environmental contributions. Recent discoveries also show that rare variants of large effect size as well as small effect common gene variants all contribute to autism risk. These discoveries challenge traditional diagnostic boundaries and highlight huge heterogeneity in autism. In this review, we consider some of the key findings that are shaping current understanding of autism and what these discoveries mean for clinicians., Author(s): Anita Thapar [sup.1] , Michael Rutter [sup.2] Author Affiliations: (1) grid.5600.3, 0000 0001 0807 5670, Division of Psychological Medicine and Clinical Neurosciences and MRC Centre for Neuropsychiatric Genetics and [...]

Beginning in the 1960s, the Isle of Wight studies were among the first to investigate developmental reading problems in representative, population-based samples, using the tools of epidemiology. In this paper, we provide an overview of the contribution of the Isle of Wight studies to research on reading disabilities. We begin with an account of the surveys of primary school children, then move on to describe the programme of epidemiological and longitudinal research that flowed from them. The early studies provided some of the first systematic evidence on the extent and correlates of severe developmental reading problems, and their overlaps with other childhood difficulties. Subsequent studies documented the persistence of early reading problems into adolescence; provided comparative data on rates of reading problems in an inner city area; and most recently explored the long-term persistence of literacy problems up to mid-life.

Objectives: Off‐label use of Ciprodex® (ciprofloxacin‐dexamethasone: CPD), an antibiotic‐steroid combination solution, in the airway has been reported by pediatric otolaryngologists with anecdotal success. We examined national trends regarding off‐label CPD use including prevalence, common indications, prescriber patterns, adverse events, and accessibility. Methods: 15‐item cross‐sectional survey was distributed to American Society of Pediatric Otolaryngology members from January–April 2022. Univariate analyses were performed to compare responses for users of off‐label CPD versus non‐users. Ease of access was compared across geographies and practice types using multivariate logistic regressions. Results: Of the 163 complete responses (26.6% response rate), 156 (95.7%) reported using off‐label CPD. Most common indications for off‐label CPD were tracheal granulation (87.8%, n = 137) and choanal atresia (82.1%, n = 128). Ease of access was significantly increased in the Midwest (OR:18.79, 95%CI:3.63–1.24, p = 0.001) and West (OR:29.92, 95%CI:3.55–682.00, p = 0.006). Ease of access was significantly lower at tertiary referral centers (OR:0.11, 95%CI:0.01–0.64, p = 0.041) and private practices (OR:0.04, 95%CI:0.002–0.33, p = 0.009) compared to academic free‐standing children's hospitals. Two‐thirds of respondents reported feeling "Very Comfortable" with the safety profile of off‐label CPD; 99.4% (n = 156) felt that the benefits outweighed the risks of off‐label use. Seven respondents (4.5%) reported adverse events (e.g., local allergic reaction, cushingoid symptoms) from off‐label use. Conclusions: Our findings (26.6% response rate) suggest that off‐label CPD is commonly used by pediatric otolaryngologists, many of whom reported feeling that the benefits of off‐label CPD outweigh the risks. Our results establish a baseline for future efforts to assess the efficacy and safety of off‐label CPD and to improve its accessibility. Level of Evidence: V Laryngoscope, 134:2922–2930, 2024 [ABSTRACT FROM AUTHOR]

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.

Data on psychiatric problems in adults with autism are inconsistent, with estimated rates ranging from around 25% to over 75%. We assessed difficulties related to mental health in 58 adults with autism (10 females, 48 males; mean age 44?years) whom we have followed over four decades. All were of average non-verbal intelligence quotient when diagnosed as children. Overall ratings of mental health problems were based on data from the Family History Schedule (Bolton et al., 1994). Informant reports indicated that many of the cohort (44%) had experienced no mental health problems in adulthood; 28% had experienced mild to moderate difficulties, 23% had severe and 5% very severe problems. Depression was the most commonly reported problem. Among those adults (n?=?22) able to report on their own mental state, again many (45%) reported no mental health problems, although 27% reported very severe mental health problems related to anxiety, depression and/or obsessive-compulsive symptoms. Informant ratings of poor mental health were not associated with gender, severity of autism in childhood, or child or adult intelligence quotient, but there were small correlations with overall social functioning (rho?=?0.34) and current autism severity (rho?=?0.37). The findings highlight the difficulties of assessing mental health problems in adults with autism and the need for appropriately validated measures.