Four dimensions of naturalistic language production in aphasia after stroke.

There is a rich tradition of research on the neuroanatomical correlates of spoken language production in aphasia using constrained tasks (e.g., picture naming), which offer controlled insights into the distinct processes that govern speech and language (i.e., lexical-semantic access, morphosyntactic construction, phonological encoding, speech motor programming/execution). Yet these tasks do not necessarily reflect everyday language use. In contrast, naturalistic language production (also referred to as connected speech or discourse) more closely approximates typical processing demands, requiring the dynamic integration of all aspects of speech and language. The brain bases of naturalistic language production remain relatively unknown, however, in part because of the difficulty in deriving features that are salient, quantifiable, and interpretable relative to both speech-language processes and the extant literature. The present cross-sectional observational study seeks to address these challenges by leveraging a validated and comprehensive auditory-perceptual measurement system that yields four explanatory dimensions of performance-Paraphasia (misselection of words and sounds), Logopenia (paucity of words), Agrammatism (grammatical omissions), and Motor speech (impaired speech motor programming/execution). We used this system to characterize naturalistic language production in a large and representative sample of individuals with acute post-stroke aphasia (n = 118). Scores on each of the four dimensions were correlated with lesion metrics, and multivariate associations among the dimensions and brain regions were then explored. Our findings revealed distinct yet overlapping neuroanatomical correlates throughout the left-hemisphere language network. Paraphasia and Logopenia were associated primarily with posterior regions, spanning both dorsal and ventral streams, which are critical for lexical-semantic access and phonological encoding. In contrast, Agrammatism and Motor speech were associated primarily with anterior regions of the dorsal stream that are involved in morphosyntactic construction and speech motor planning/execution respectively. Collectively, we view these results as constituting a brain-behavior model of naturalistic language production in aphasia, aligning with both historical and contemporary accounts of the neurobiology of spoken language production.

Evaluation of depressive and anxiety symptoms in childhood-onset systemic lupus erythematosus: Frequency, course, and associated risk factors.

BACKGROUND: Depressive and anxiety symptoms are common in childhood-onset systemic lupus erythematosus (cSLE), yet their etiology and course remain unclear. We investigated the frequency of depressive and anxiety symptoms longitudinally in youth with cSLE, and associated socio-demographic and disease factors. METHODS: Participants 8-18 years with cSLE completed baseline measures [demographic questionnaire, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Screen for Childhood Anxiety Related Disorders (SCARED), and psychiatric interview] and follow-up measures (CES-DC and SCARED) > 6 months later. Prevalence of clinically significant depressive (score >15 on CES-DC) or anxiety symptoms (score ≥25 on SCARED) was calculated at baseline and follow-up. Baseline psychiatric interview diagnoses were tabulated. Relationships between socio-demographics (neighborhood-level material deprivation, ethnic concentration, adverse childhood event history, psychiatric condition in a first-degree relative), disease-related factors (disease duration, major organ disease, disease activity, glucocorticoid use, comorbid medical condition) and baseline depressive and anxiety scores, were examined in linear regression models. Factors with univariate associations with p < 0.2 were included in multivariable adjusted models. RESULTS: At baseline, of 51 participants with a mean disease duration of 4.3 years (SD 2.7), 35% (n = 18) and 35% (n = 18) had clinically significant depressive and anxiety symptoms, respectively. Anxiety disorder was diagnosed by psychiatric interview in 14% (n = 7), depressive disorders in 6% (n = 3), and post-traumatic stress disorder in 4% (n = 2). Adverse childhood events and first-degree relative with psychiatric condition were present in 40% (n = 20) and 37% (n = 18), respectively. In multivariable regression analysis, baseline depressive symptoms were positively correlated with neighbourhood-level material deprivation (ß = 4.2, 95% CI [1.0, 7.3], p = 0.01) and psychiatric condition in a first-degree relative (ß = 7.3, 95% CI [2.2, 12.4], p = 0.006). No associations were found between baseline anxiety scores and patient factors. At a median follow-up of 13.5 months (IQR 10.5, 18) for CES-DC (n = 34) and SCARED (n = 44), depressive and anxiety symptoms were persistent (18%, n = 6; 16%, n = 7), and newly present (24%, n = 8; 16% n = 7) at follow-up. CONCLUSION: In this sample, depressive and anxiety symptoms were prevalent and persistent. Depressive symptoms correlated with neighborhood-level material deprivation, and family psychiatric history. These findings support routine psychosocial assessment in cSLE, and provision of appropriate resources.

Recovery from aphasia in the first year after stroke.

Most individuals who experience aphasia after a stroke recover to some extent, with the majority of gains taking place in the first year. The nature and time course of this recovery process is only partially understood, especially its dependence on lesion location and extent, which are the most important determinants of outcome. The aim of this study was to provide a comprehensive description of patterns of recovery from aphasia in the first year after stroke. We recruited 334 patients with acute left hemisphere supratentorial ischaemic or haemorrhagic stroke and evaluated their speech and language function within 5 days using the Quick Aphasia Battery (QAB). At this initial time point, 218 patients presented with aphasia. Individuals with aphasia were followed longitudinally, with follow-up evaluations of speech and language at 1 month, 3 months, and 1 year post-stroke, wherever possible. Lesions were manually delineated based on acute clinical MRI or CT imaging. Patients with and without aphasia were divided into 13 groups of individuals with similar, commonly occurring patterns of brain damage. Trajectories of recovery were then investigated as a function of group (i.e. lesion location and extent) and speech/language domain (overall language function, word comprehension, sentence comprehension, word finding, grammatical construction, phonological encoding, speech motor programming, speech motor execution, and reading). We found that aphasia is dynamic, multidimensional, and gradated, with little explanatory role for aphasia subtypes or binary concepts such as fluency. Patients with circumscribed frontal lesions recovered well, consistent with some previous observations. More surprisingly, most patients with larger frontal lesions extending into the parietal or temporal lobes also recovered well, as did patients with relatively circumscribed temporal, temporoparietal, or parietal lesions. Persistent moderate or severe deficits were common only in patients with extensive damage throughout the middle cerebral artery distribution or extensive temporoparietal damage. There were striking differences between speech/language domains in their rates of recovery and relationships to overall language function, suggesting that specific domains differ in the extent to which they are redundantly represented throughout the language network, as opposed to depending on specialized cortical substrates. Our findings have an immediate clinical application in that they will enable clinicians to estimate the likely course of recovery for individual patients, as well as the uncertainty of these predictions, based on acutely observable neurological factors.

Global State of the Art and Science of Childhood Dysphagia: Similarities and Disparities in Burden.

Feeding/swallowing and airway protection are complex functions, essential for survival, and continue to evolve throughout the lifetime. Medical and surgical advances across the globe have improved the long-term survival of medically complex children at the cost of increasing comorbidities, including dysfunctional swallowing (dysphagia). Dysphagia is prominent in children with histories of preterm birth, neurologic and neuromuscular diagnoses, developmental delays, and aerodigestive disorders; and is associated with medical, health, and neurodevelopmental problems; and long-term socioeconomic, caregiver, health system, and social burdens. Despite these survival and population trends, data on global prevalence of childhood dysphagia and associated burdens are limited, and practice variations are common. This article reviews current global population and resource-dependent influences on current trends for children with dysphagia, disparities in the availability and access to specialized multidisciplinary care, and potential impacts on burdens. A patient example will illustrate some questions to be considered and decision-making options in relation to age and development, availability and accessibility to resources, as well as diverse cultures and family values. Precise recognition of feeding/swallowing disorders and follow-up intervention are enhanced by awareness and knowledge of global disparities in resources. Initiatives are needed, which address geographic and economic barriers to providing optimal care to children with dysphagia.

A Neurosurgical Functional Dissection of the Middle Precentral Gyrus during Speech Production.

Classical models have traditionally focused on the left posterior inferior frontal gyrus (Broca's area) as a key region for motor planning of speech production. However, converging evidence suggests that it is not critical for either speech motor planning or execution. Alternative cortical areas supporting high-level speech motor planning have yet to be defined. In this review, we focus on the precentral gyrus, whose role in speech production is often thought to be limited to lower-level articulatory muscle control. In particular, we highlight neurosurgical investigations that have shed light on a cortical region anatomically located near the midpoint of the precentral gyrus, hence called the middle precentral gyrus (midPrCG). The midPrCG is functionally located between dorsal hand and ventral orofacial cortical representations and exhibits unique sensorimotor and multisensory functions relevant for speech processing. This includes motor control of the larynx, auditory processing, as well as a role in reading and writing. Furthermore, direct electrical stimulation of midPrCG can evoke complex movements, such as vocalization, and selective injury can cause deficits in verbal fluency, such as pure apraxia of speech. Based on these findings, we propose that midPrCG is essential to phonological-motoric aspects of speech production, especially syllabic-level speech sequencing, a role traditionally ascribed to Broca's area. The midPrCG is a cortical brain area that should be included in contemporary models of speech production with a unique role in speech motor planning and execution.

Towards development of treat to target (T2T) in childhood-onset systemic lupus erythematosus: PReS-endorsed overarching principles and points-to-consider from an international task force.

OBJECTIVES: Application of 'treat-to-target' (T2T) in childhood-onset systemic lupus erythematosus (cSLE) may improve care and health outcomes. This initiative aimed to harmonise existing evidence and expert opinion regarding T2T for cSLE. METHODS: An international T2T Task Force was formed of specialists in paediatric rheumatology, paediatric nephrology, adult rheumatology, patient and parent representatives. A steering committee formulated a set of draft overarching principles and points-to-consider, based on evidence from systematic literature review. Two on-line preconsensus meeting Delphi surveys explored healthcare professionals' views on these provisional overarching principles and points-to-consider. A virtual consensus meeting employed a modified nominal group technique to discuss, modify and vote on each overarching principle/point-to-consider. Agreement of >80% of Task Force members was considered consensus. RESULTS: The Task Force agreed on four overarching principles and fourteen points-to-consider. It was agreed that both treatment targets and therapeutic strategies should be subject to shared decision making with the patient/caregivers, with full remission the preferred target, and low disease activity acceptable where remission cannot be achieved. Important elements of the points-to-consider included: aiming for prevention of flare and organ damage; glucocorticoid sparing; proactively addressing factors that impact health-related quality of life (fatigue, pain, mental health, educational challenges, medication side effects); and aiming for maintenance of the target over the long-term. An extensive research agenda was also formulated. CONCLUSIONS: These international, consensus agreed overarching principles and points-to-consider for T2T in cSLE lay the foundation for future T2T approaches in cSLE, endorsed by the Paediatric Rheumatology European Society.

Genetics of osteonecrosis in children and adults with systemic lupus erythematosus.

OBJECTIVES: Genetics plays an important role in SLE risk, as well as osteonecrosis (ON), a significant and often debilitating complication of SLE. We aimed to identify genetic risk loci for ON in people with childhood-onset (cSLE) and adult-onset (aSLE) SLE. METHODS: We enrolled participants from two tertiary care centres who met classification criteria for SLE. Participants had prospectively collected clinical data and were genotyped on a multiethnic array. Un-genotyped single nucleotide polymorphisms (SNPs) were imputed, and ancestry was inferred using principal components (PCs). Our outcome was symptomatic ON confirmed by imaging. We completed time-to-ON and logistic regression of ON genome-wide association studies (GWASs) with covariates for sex, age of SLE diagnosis, five PCs for ancestry, corticosteroid use and selected SLE manifestations. We conducted separate analyses for cSLE and aSLE and meta-analysed results using inverse-variance weighting. Genome-wide significance was P < 5 × 10-8. RESULTS: The study included 940 participants with SLE, 87% female and 56% with cSLE. ON was present in 7.6% (n = 71). Median age of SLE diagnosis was 16.9 years (interquartile range [IQR]: 13.5, 29.3), with median follow-up of 8.0 years (IQR: 4.2, 15.7). Meta-GWAS of cSLE and aSLE time-to-ON of 4 431 911 SNPs identified a significant Chr.2 SNP, rs34118383 (minor allele frequency = 0.18), intronic to WIPF1 (hazard ratio = 3.2 [95% CI: 2.2, 4.8]; P = 1.0 × 10-8). CONCLUSION: We identified an intronic WIPF1 variant associated with a 3.2 times increased hazard for ON (95% CI: 2.2, 4.8; P = 1.0 × 10-8) during SLE follow-up, independent of corticosteroid exposure. The effect of the SNP on time-to-ON was similar in cSLE and aSLE. This novel discovery represents a potential ON risk locus. Our results warrant replication.

Genetics of longitudinal kidney function in children and adults with systemic lupus erythematosus.

OBJECTIVES: Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE. METHODS: Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags. RESULTS: We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR: 3.9-15.3). LN was associated with lower within-person mean eGFR [LN: 93.8 (s.d. 26.4) vs non-LN: 101.6 (s.d. 17.7) mL/min per 1.73 m2; P < 0.0001] and higher variance [LN median: 157.0 (IQR: 89.5, 268.9) vs non-LN median: 84.9 (IQR: 46.9, 138.2) (mL/min per 1.73 m2)2; P < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance. CONCLUSION: We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci.

A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

OBJECTIVE: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. METHODS: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. RESULTS: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. CONCLUSION: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.

Assessing Electronic Health Record (EHR) Use during a Major EHR Transition: An Innovative Mixed Methods Approach.

BACKGROUND: Electronic health record (EHR) transitions are inherently disruptive to healthcare workers who must rapidly learn a new EHR and adapt to altered clinical workflows. Healthcare workers' perceptions of EHR usability and their EHR use patterns following transitions are poorly understood. The Department of Veterans Affairs (VA) is currently replacing its homegrown EHR with a commercial Cerner EHR, presenting a unique opportunity to examine EHR use trends and usability perceptions. OBJECTIVE: To assess EHR usability and uptake up to 1-year post-transition at the first VA EHR transition site using a novel longitudinal, mixed methods approach. DESIGN: A concurrent mixed methods strategy using EHR use metrics and qualitative interview data. PARTICIPANTS: 141 clinicians with data from select EHR use metrics in Cerner Lights On Network®. Interviews with 25 healthcare workers in various clinical and administrative roles. APPROACH: We assessed changes in total EHR time, documentation time, and order time per patient post-transition. Interview transcripts (n = 90) were coded and analyzed for content specific to EHR usability. KEY RESULTS: Total EHR time, documentation time, and order time all decreased precipitously within the first four months after go-live and demonstrated gradual improvements over 12 months. Interview participants expressed ongoing concerns with the EHR's usability and functionality up to a year after go-live such as tasks taking longer than the old system and inefficiencies related to inadequate training and inherent features of the new system. These sentiments did not seem to reflect the observed improvements in EHR use metrics. CONCLUSIONS: The integration of quantitative and qualitative data yielded a complex picture of EHR usability. Participants described persistent challenges with EHR usability 1 year after go-live contrasting with observed improvements in EHR use metrics. Combining findings across methods can provide a clearer, contextualized understanding of EHR adoption and use patterns during EHR transitions.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. METHODS: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. RESULTS: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. CONCLUSIONS: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

Eliciting Insights From Chat Logs of the 25X5 Symposium to Reduce Documentation Burden: Novel Application of Topic Modeling.

BACKGROUND: Addressing clinician documentation burden through "targeted solutions" is a growing priority for many organizations ranging from government and academia to industry. Between January and February 2021, the 25 by 5: Symposium to Reduce Documentation Burden on US Clinicians by 75% (25X5 Symposium) convened across 2 weekly 2-hour sessions among experts and stakeholders to generate actionable goals for reducing clinician documentation over the next 5 years. Throughout this web-based symposium, we passively collected attendees' contributions to a chat functionality-with their knowledge that the content would be deidentified and made publicly available. This presented a novel opportunity to synthesize and understand participants' perceptions and interests from chat messages. We performed a content analysis of 25X5 Symposium chat logs to identify themes about reducing clinician documentation burden. OBJECTIVE: The objective of this study was to explore unstructured chat log content from the web-based 25X5 Symposium to elicit latent insights on clinician documentation burden among clinicians, health care leaders, and other stakeholders using topic modeling. METHODS: Across the 6 sessions, we captured 1787 messages among 167 unique chat participants cumulatively; 14 were private messages not included in the analysis. We implemented a latent Dirichlet allocation (LDA) topic model on the aggregated dataset to identify clinician documentation burden topics mentioned in the chat logs. Coherence scores and manual examination informed optimal model selection. Next, 5 domain experts independently and qualitatively assigned descriptive labels to model-identified topics and classified them into higher-level categories, which were finalized through a panel consensus. RESULTS: We uncovered ten topics using the LDA model: (1) determining data and documentation needs (422/1773, 23.8%); (2) collectively reassessing documentation requirements in electronic health records (EHRs) (252/1773, 14.2%); (3) focusing documentation on patient narrative (162/1773, 9.1%); (4) documentation that adds value (147/1773, 8.3%); (5) regulatory impact on clinician burden (142/1773, 8%); (6) improved EHR user interface and design (128/1773, 7.2%); (7) addressing poor usability (122/1773, 6.9%); (8) sharing 25X5 Symposium resources (122/1773, 6.9%); (9) capturing data related to clinician practice (113/1773, 6.4%); and (10) the role of quality measures and technology in burnout (110/1773, 6.2%). Among these 10 topics, 5 high-level categories emerged: consensus building (821/1773, 46.3%), burden sources (365/1773, 20.6%), EHR design (250/1773, 14.1%), patient-centered care (162/1773, 9.1%), and symposium comments (122/1773, 6.9%). CONCLUSIONS: We conducted a topic modeling analysis on 25X5 Symposium multiparticipant chat logs to explore the feasibility of this novel application and elicit additional insights on clinician documentation burden among attendees. Based on the results of our LDA analysis, consensus building, burden sources, EHR design, and patient-centered care may be important themes to consider when addressing clinician documentation burden. Our findings demonstrate the value of topic modeling in discovering topics associated with clinician documentation burden using unstructured textual content. Topic modeling may be a suitable approach to examine latent themes presented in web-based symposium chat logs.

Aspiration in the First Year of Life and Later Tube Feeding: A Retrospective Cohort from a Low-Income Country.

The objective of this study is to investigate in infants submitted to videofluoroscopic swallowing study (VFSS) during the first year of life, the association between aspiration and later tube feeding, and to identify potential risk factors related to feeding route outcome. Retrospective cohort study with data from electronic health records was performed. Data were collected from infants < 12 months of age who underwent VFSS during inpatient hospital stay in the period between 2013 and 2018. Patient charts after 24 months of age were reviewed to ascertain the outcome and study factors, including VFSS findings, neonatal data, clinical comorbidities, nutritional status, ICU admissions, and hospital readmissions. Relative risk (RR) for tube feeding was calculated, and a Poisson regression with robust variance was used to identify potential risk factors. VFSS data from 164 patients < 1 year old were retrieved, of whom 112 (68%) contributed with data about feeding route after 2 years of age. Most infants were preterm < 37 weeks (66%), with a median age of 9.28 weeks at the time of the exam. Aspiration occurred in 33% of the patients, with no statistically significant difference between full-term or premature infants (p = 0.173). The relative risk of tube feeding after the age of 2 among infants who aspirated in VFSS was 0.74 (CI 0.25-2.16, p = 0.573). Poisson regression analysis showed that number of hospital readmissions (RR 1.04, 95%CI 1.01-1.07, p = 0.005) and gestational age < 34 weeks (RR 0.26, 95%CI 0.07-0.089, p = 0.032) were associated with later tube feeding. Early VFSS findings have low predictive value regarding later feeding route. Aspiration events should be considered as complementary information for clinical decision.

Therapeutic Management with Airway Clearance in Children with Robin Sequence and Association with Swallowing Outcomes: A Systematic Review and Meta-analysis.

Dysphagia in Robin Sequence can be present in varying degrees, requiring multidisciplinary management and specific swallowing assessment by a specialist. Most studies published to date have evaluated only respiratory outcomes, and the available evidence on the improvement of swallowing is questionable. To conduct a systematic review and meta-analysis of studies evaluating swallowing in children with Robin Sequence before and after airway clearance procedures. The research question was developed based on the PICO strategy. The literature search was performed in electronic databases and gray literature. Studies were selected by 3 independent reviewers. The risk of bias and level of evidence of the studies were assessed. A proportion meta-analysis was performed to calculate the prevalence of dysphagia after airway clearance procedures. The search identified 4938 studies, 5 of which were included. All studies had limitations in terms of design and sample size. The prevalence of dysphagia after airway clearance was obtained by analyzing treatment subgroups: mandibular distraction osteogenesis, mandibular distraction osteogenesis + tracheostomy tube, and nasopharyngeal tube. Clinical and/or instrumental assessment was assessed by a swallowing specialist. The meta-analysis was precluded by the limitations of the studies, especially regarding sample size, which affected the accuracy of the findings. Dysphagia remained unresolved in 55% of children (95% CI 1-99%). The methodological quality of the studies indicated a high risk of bias and very low level of evidence. It was not possible to confirm that airway clearance techniques used in Robin Sequence improve dysphagia.

TNF inhibition in vasculitis management in adenosine deaminase 2 deficiency (DADA2).

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited autoinflammatory disorder caused by a loss of functional ADA2 protein. TNF inhibition (TNFi) has proven to be highly effective in treating inflammatory manifestations. OBJECTIVE: We sought to explore the pathophysiology and the underlying mechanisms of TNF-inhibitor response in these patients. METHODS: We performed Sanger sequencing of the ADA2 gene. We used flow cytometry, intracellular cytokine staining, transcriptome analysis, immunohistochemistry, and cell differentiation experiments to define an inflammatory signature in patients with DADA2 and studied their response to TNF-inhibitor treatment. RESULTS: We demonstrated increased inflammatory signals and overproduction of cytokines mediated by IFN and nuclear factor kappa B pathways in patients' primary cells. Treatment with TNFi led to reduction in inflammation, rescued the skewed differentiation toward the proinflammatory M1 macrophage subset, and restored integrity of endothelial cells in blood vessels. We also report 8 novel disease-associated variants in 7 patients with DADA2. CONCLUSIONS: Our data explore the cellular mechanism underlying effective treatment with TNFi therapies in DADA2. DADA2 vasculitis is strongly related to the presence of activated myeloid cells, and the endothelial cell damage is rescued with anti-TNF treatment.

Defining Telehealth for Research, Implementation, and Equity.

When the COVID-19 pandemic spurred a disruption in health care delivery, the role of telehealth shifted from an option to a near necessity to maintain access when in-person care was deemed too risky. Each state and many organizations developed temporary telehealth policies for the COVID-19 emergency, each policy with its own definitions, coverage, government cases, and regulations. As pandemic-era policies are now being replaced with more permanent guidelines, we are presented with an opportunity to reevaluate how telehealth is integrated into routine health care delivery. We believe that the timing and nature of the sequential steps for redefining telehealth are critical and that it is important to develop a clear and agreed-on definition of telehealth and its components at this time. We further suggest a necessary preliminary step is to support clear communication and interoperability throughout the development of this definition. Precise and standardized definitions could create an unambiguous environment for clinical care for both patients and providers while enabling researchers to have more precise control over their investigations of telehealth. A consensus when defining telehealth and its derivatives at this critical stage could create a consistent expectation of care for all patients and those who set the standards of care, as it has for other clinical scenarios with clear guidelines.

Instrumental Swallowing Assessments in the Neonatal and Pediatric Populations: A Systematic Review.

The scientific scope of swallowing disorders in the neonatal and pediatric populations is growing exponentially; however, the preponderance of evidence for evaluation protocols has been concentrated in non-instrumental evaluations creating a lack of research about protocols for instrumental swallowing assessment. Thus, the purpose of this study was to systematically review the literature to identify and to report protocols used in instrumental assessments through videofluoroscopic swallow study (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES) in the neonatal and pediatric populations to support clinical decision making. The search strategy was applied in five online databases, no filters were applied to restrict languages or publication dates and the gray literature was reviewed. PRISMA statement was used to guide the construction of this review. The studies included validated and unvalidated protocols, the validated protocols had their risk of bias estimated using the QUADAS-2. In total, 13 studies were included in the final review, of these eleven assessed through QUADAS-2, and two classified with low risk of bias. One study is in the process of standardization and validation of an instrumental assessment protocol for swallowing in bottle-fed infants through VFSS. Information about validity and reliability of published protocols for instrumental evaluation in the neonatal and pediatric populations is limited. Therefore, further research is needs to development studies aiming to standardize and validate protocols for instrumental assessments in these populations.

Translation, Cultural Adaptation, Reliability, and Validity Evidence of the Feeding/Swallowing Impact Survey (FS-IS) to Brazilian Portuguese.

The purpose of this study was to translate and adapt the Feeding/Swallowing Impact Survey (FS-IS) into Brazilian Portuguese and provide a validated instrument for caregivers of children with feeding/swallowing disorders. This cross-cultural study involved initial translation, synthesis of translations, back-translation, Committee of Experts, and pre-test. The sample consisted of 95 primary caregivers of children with feeding/swallowing disorders classified by Pediatric Dysphagia Evaluation Protocol (PDEP) in mild (n = 9), moderate-severe (n = 40), or profound (n = 46) dysphagia. Reliability and evidence of validity based on test content, response processes, internal structure and the relations to other variables were investigated. Internal consistency, test-retest, exploratory and confirmatory factor analysis were performed, in addition to the correlation with PedsQL™ Family Impact Module (PedsQLTMFIM). The pre-test participants did not report any difficulties in understanding the translated version. The Brazilian Portuguese version of FS-IS (Pt-Br-FS-IS) presented Cronbach's Alpha of 0.83, Exploratory Factor Analysis verified that the instrument would not be unifactorial (KMO = 0.74 and Bartlett's sphericity test p < 0.001) and Confirmatory Factor Analysis confirmed the original model in three subscales with χ2/df = 1.23, CFI = 0.92, TLI = 0.90, RMSEA (90% CI) 0.049 (0.011-0.073) adjustment indexes and the ICC was excellent in all subscales and total score. The correlation with PedsQL™FIM was significant in the total score and subscales. This study successfully translated and cross-culturally adapted the FS-IS instrument to the Brazilian Portuguese language and the investigation of its reliability and validity evidence suggests that the Pt-Br-FS-IS is a reliable and valid tool to measure the impact of feeding/swallowing disorders on the quality of life of caregivers of affected children.

Causal pathways to health-related quality of life in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

OBJECTIVE: Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to decreased health-related quality of life (HRQoL) in children with JIA. METHODS: Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL [measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ)] at five disease stages: (i) diagnosis, (ii) 3-9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility. RESULTS: We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data. CONCLUSION: Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.

Evaluation of self-report screening measures in the detection of depressive and anxiety disorders among children and adolescents with systemic lupus erythematosus.

BACKGROUND: There are no validated screening measures for depressive or anxiety disorders in childhood Systemic Lupus Erythematosus (cSLE). We investigated cross-sectionally (1) the prevalence of depressive and anxiety disorder in cSLE. (2) the validity of the Centre for Epidemiologic Studies Depression Scale for Children (CES-DC) and the Screen for Childhood Anxiety and Related Disorders (SCARED) measures in identifyingthese disorders. METHODS: Participants 8-18 years with cSLE/incipient cSLE completed CES-DC, SCARED, and Quality OfMy Life (QOML) measures. Parents completed the SCARED-Parent measure. Diagnosis was by gold-standard psychiatric interview and determined prevalence of psychiatric disorder. Receiver Operating Characteristics Area under the Curve (ROCAUC) evaluated screening measure diagnostic performance. RESULTS: Ofseventy-two parent-child dyads, 56 interviews were completed. Mean screen scores were: CES-DC = 15 (range 1-49, SD 12), SCARED-C = 22 (range 2-61, SD 14), SCARED-P = 13 (range 0-36, SD 8). Depressive disorder screen positivity (CES-DC ≥ 15) was 35% (vs. prevalence 5%). Anxiety disorder screen positivity (SCARED ≥ 25) was 39% (vs. prevalence 16%). CES-DC ROCAUC = 0.98 and SCARED-C ROCAUC = 0.7 (cut-points 38 and 32 respectively). CONCLUSIONS: Diagnostic thresholds for depressive and anxiety disorderscreening measures are high for both CES-DC and SCARED-C in cSLE. Brief focused interview should follow to determine whether psychiatric evaluation is warranted.