Clinical and healthcare utilization outcomes during the 6 months following COVID infection in children.

BACKGROUND: We aimed to identify the impact of COVID infection in children in the US prior to vaccine availability on clinical and healthcare utilization outcomes within 6 months of infection. METHODS: Using claims data from a large national insurer, we identified 223,842 children with a COVID diagnosis in May 2020-March 2021 and matched them to 223,842 children with a COVID test and no diagnosis. We compared the two cohorts' outcomes during the 6 months after infection/test. RESULTS: Uncommon acute adverse events occurring in <0.5% of cases, including MIS-C (relative risk (RR) = 45.2), myocarditis (RR = 10.3), acute heart failure (RR = 2.14), sepsis (RR = 2.02), and viral pneumonia (RR = 2.43) were more frequent in the COVID cohort (all p < 0.001). Development of arrhythmias (RR = 1.24, p < 0.001) and atherosclerotic cardiovascular disease (RR = 1.41, p = 0.007) were more common in the COVID group, while behavioral health disorders were less common (RR = 0.94, p < 0.001). Lab testing and imaging were slightly higher in the COVID group (RR ranging 1.05-1.11 depending on the service and timeframe), though medical costs did not increase. CONCLUSION: Severe disease and diagnoses of new conditions are rare in children following COVID infection. We observed an increase in cardiac complications, though they may not last long term. IMPACT: Few studies have analyzed the association between COVID infection and medium-term outcomes in children. Our study of >447,000 geographically and socioeconomically diverse children in the US found that uncommon acute adverse events, including myocarditis, MIS-C, and acute heart failure, were more frequent in children with COVID than matched controls, and development of arrhythmias and cardiovascular disease were 1.2 and 1.4 times more common, respectively. Six-month healthcare utilization was similar between cohorts. We provide data on the risks of COVID in children, particularly with respect to cardiac complications, that decision makers may find useful when weighing the benefits and harms of preventive measures.

A promising new tool for literacy instruction: The morphological matrix.

There is growing interest in the role that morphological knowledge plays in literacy acquisition, but there is no research directly comparing the efficacy of different forms of morphological instruction. Here we compare two methods of teaching English morphology in the context of a memory experiment when words were organized by affix during study (e.g., a list of words was presented that all share an affix, such as , , , , etc.) or by base during study (e.g., a list of words was presented that all share a base, such as , , , ). We show that memory for morphologically complex words is better in both conditions compared to a control condition that does not highlight the morphological composition of words, and most importantly, show that studying words in a base-centric format improves memory further still. We argue that the morphological matrix that organizes words around a common base may provide an important new tool for literacy instruction.

The importance of correctly characterising the English spelling system when devising and evaluating methods of reading instruction: Comment on Taylor, Davis, and Rastle (2017).

Taylor, Davis, and Rastle employed an artificial language learning paradigm to compare phonics and meaning-based approaches to reading instruction. Adults were taught consonant, vowel, and consonant (CVC) words composed of novel letters when the mappings between letters and sounds were completely systematic and the mappings between letters and meaning were completely arbitrary. At test, performance on naming tasks was better following training that emphasised the phonological rather than the semantic mappings, whereas performance on semantic tasks was similar in the two conditions. The authors concluded that these findings support phonics for early reading instruction in English. However, in our view, these conclusions are not justified given that the artificial language mischaracterised both the phonological and semantic mappings in English. Furthermore, the way participants studied the arbitrary letter-meaning correspondences bears little relation to meaning-based strategies used in schools. To compare phonics with meaning-based instruction it must be determined whether phonics is better than alternative forms of instruction that fully exploit the regularities within the semantic route. This is rarely assessed because of a widespread and mistaken assumption that underpins so much basic and applied research, namely, that the main function of spellings is to represent sounds.

A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.

Thousands die each year from sudden infant death syndrome (SIDS). Neither the cause nor basis for varied prevalence in different populations is understood. While 2 cases have been associated with mutations in type Valpha, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental influences in disease pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were carriers of the heterozygous genotype, which was previously associated with increased risk for arrhythmia in adults. This suggests that infants with 2 copies of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were found to operate normally under baseline conditions in vitro. As risk factors for SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were subjected to lowered intracellular pH. Only Y1103 channels gained abnormal function, demonstrating late reopenings suppressible by the drug mexiletine. The variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene-environment interaction. Overall, homozygous and rare heterozygous SCN5A missense variants were found in approximately 5% of cases. If our findings are replicated, prospective genetic testing of SIDS cases and screening with counseling for at-risk families warrant consideration.

Epigenetic abnormalities associated with a chromosome 18(q21-q22) inversion and a Gilles de la Tourette syndrome phenotype.

Gilles de la Tourette syndrome (GTS) is a potentially debilitating neuropsychiatric disorder defined by the presence of both vocal and motor tics. Despite evidence that this and a related phenotypic spectrum, including chronic tics (CT) and Obsessive Compulsive Disorder (OCD), are genetically mediated, no gene involved in disease etiology has been identified. Chromosomal abnormalities have long been proposed to play a causative role in isolated cases of GTS spectrum phenomena, but confirmation of this hypothesis has yet to be forthcoming. We describe an i(18q21.1-q22.2) inversion in a patient with CT and OCD. We have fine mapped the telomeric aspect of the rearrangement to within 1 Mb of a previously reported 18q22 breakpoint that cosegregated in a family with GTS and related phenotypes. A comprehensive characterization of this genomic interval led to the identification of two transcripts, neither of which was found to be structurally disrupted. Analysis of the epigenetic characteristics of the region demonstrated a significant increase in replication asynchrony in the patient compared to controls, with the inverted chromosome showing delayed replication timing across at least a 500-kb interval. These findings are consistent with long-range functional dysregulation of one or more genes in the region. Our data support a link between chromosomal aberrations and epigenetic mechanisms in GTS and suggest that the study of the functional consequences of balanced chromosomal rearrangements is warranted in patients with phenotypes of interest, irrespective of the findings regarding structurally disrupted transcripts.