Primary immunodeficiency associated with a SAMD9L mutation

Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.

Health-related quality of life, mental health and caregiver burden in children with autosomal recessive polycystic kidney disease (ARPKD)

Objective: To examine whether established patient-reported outcome measures are suitable for capturing the impact of ARPKD in children and their families. Method(s): We assessed 44 children with ARPKD (40 families) with respect to patients' health-related quality of life ((hr- QOL) using PedsQLTM ESRD module) and mental health (strength and difficulties questionnaire (SDQ)) as well as family and caregiver burden (Impact on family score (IFS) und Ulm inventory of parental caregiver QOL (ULQIE)) and compared them to published data and 36 healthy control children matched for age and time. Result(s): Patients were aged 9.5 +/- 5.9 years (vs. controls 8.8 +/- 5.0, p = ns) and 21 (48%) were female (vs. 19 controls (53%), p = ns). Mean eGFR was 81 ml/min*1.73m2 (range 4 - 165);7 received dialysis and 11 had functioning kidney transplants (KTX, 2 combined with liver transplants). Eight patients had developmental delay secondary to medical complications, while chronic illness was an exclusion criterion for healthy controls. 61 caregivers of affected children had same gender-distribution (61% vs. 60% mothers) and age (both 42 +/- 7 years) and number of dependent children (1.8 +/- 0.9 vs. 2.0 +/- 0.8) as 57 caregivers of healthy children. The mean proxy reported PedsQL Total score was 77.5 +/- 10.6 (range 59 - 96). It correlated significantly to eGFR (r = 0.5, p < 0.01, (also within the subpopulations pre- and post-KTX)). Parents reported greater mental health problems in affected than in control children with a higher SDQ total score mainly due to higher scores in the hyperactivity and peerinteraction subscales. ULQIE revealed that parents of affected children had significantly lower levels of physical functioning, self-fulfillment and general QOL, but despite higher emotional burden scores they indicated similar satisfaction with family life. Impact on family scores were in a similar range to those of children with moderate to severe disabilities. Conclusion(s): The good spread of PedsQLTM ESRD-scores and their correlation to renal function indicates that it captures significant aspects of ARPKD, however, it may need further adjustment to include liver complications. All four chosen instruments revealed significant impact of ARPKD on hrQOL and mental health of affected children as well as family life and parental wellbeing in comparison to healthy controls. More problems with peer-interactions may also be due to more stringent shielding of chronically ill children from social contacts during the COVID pandemic compared to healthy children.

Heart Rate Variability and Pregnancy Complications: Systematic Review.

BACKGROUND: The autonomic nervous system (ANS) is known as a critical regulatory system for pregnancy-induced adaptations. If it fails to function, life-threatening pregnancy complications could occur. Hence, understanding and monitoring the underlying mechanism of action for these complications are necessary. OBJECTIVE: We aimed to systematically review the literature concerned with the associations between heart rate variability (HRV), as an ANS biomarker, and pregnancy complications. METHODS: We performed a comprehensive search in the PubMed, Medline Completion, CINAHL Completion, Web of Science Core Collection Classic, Cochrane Library, and SCOPUS databases in February 2022 with no time span limitation. We included studies concerned with the association between any pregnancy complications and HRV, with or without a control group. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was used for the review of the studies, and Covidence software was used for the study selection process. For data synthesis, we used the guideline by Popay et al. RESULTS: Finally, 12 studies with 6656 participants were included. Despite the methodological divergency that hindered a comprehensive comparison, our findings suggest that ANS is linked with some common pregnancy complications including fetal growth. However, existing studies do not support an association between ANS and gestational diabetes mellitus. Studies that linked pulmonary and central nervous system disorders with ANS function did not provide enough evidence to draw conclusions. CONCLUSIONS: This review highlights the importance of understanding and monitoring the underlying mechanism of ANS in pregnancy-induced adaptations and the need for further research with robust methodology in this area.

Reliability and acceptability of web-based administration of spanish ages and stages questionnaires third edition

to analyse the reliability of 6 age intervals of Spanish web-based Ages and Stages Questionnaires Third Edition (WB-ASQ-3) and parents' acceptability, in a clinical practice context, during COVID-19 pandemic and lockdown in Chile. Cross-sectional study with a longitudinal component. Internal consistency was analysed by Cronbach's alpha and Pearson product-moment correlation, Pearson's correlations between intervals questionnaires were analysed. Acceptability was determined using a parental satisfaction survey. 1061 children completed 2318 validated questionnaires. Scores were compared with normative sample, except for Gross motor at 8 and 12 months, and Communication at 12, 18 and 24 months, without differences to the previous Chileans sample. In domain analysis, Cronbach's alpha ranged from 0.36 to 0.80 and reached 0.74 to 0.81 for the overall test. Strong positive correlation between the domain and overall score was obtained. Correlation between most questionnaires at different ages was positive and significant. Parental surveys show high satisfaction;parents were thankful for being able to monitor children's development. WB-ASQ-3 is a reliable and feasible screening system, particularly when the test is taken as a whole, rather than by domains. It is remarkably high acceptability among parents, especially in complex times such as the lockdown and the COVID-19 pandemic. (PsycInfo Database Record (c) 2023 APA, all rights reserved) AD -, Paula Schonhaut, Luisa: lschonhaut@alemana.cl Schonhaut, Luisa: Clinica Alemana, Faculty of Medicine, Universidad del Desarrollo, Santiago, Chile Armijo, Ivan: Faculty of Psychology, Universidad del Desarrollo, Santiago, Chile Rojas B., Paula: Clinica Alemana, Faculty of Medicine, Universidad del Desarrollo, Santiago, Chile Cabrera, Leonardo: Clinica Alemana, Faculty of Medicine, Universidad del Desarrollo, Santiago, Chile Boisier, Roberto: Clinica Alemana, Faculty of Medicine, Universidad del Desarrollo, Santiago, Chile

First in-neonate use of non-invasive transcutaneous auricular vagus nerve stimulation: 18-month neurodevelopmental and sensory follow-up

Objective: Non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) paired with oral feeding is a novel intervention for infants with feeding delays that may improve feeding and help avoid a gastrostomy tube (Gtube). However, the long-term impact of this neurostimulation on infant's development remains unknown. We investigated the neurodevelopmental and sensory outcomes of infants who received taVNS paired with bottle feeding. Method(s): Twenty-one of 35 toddlers who participated in the open label trial of taVNS paired with one or two feeds a day for 2-3 weeks, underwent comprehensive developmental assessments at 18 months of age using Cognitive Adaptive Test, Clinical Linguistics and Auditory Milestone, and Peabody gross motor scores. Twelve of those assessed achieved full oral feeds ('responders') and 9 had G-tube placed for feeds ('non-responders'). Before COVID, 12 toddlers (5 responders, 7 non-responders) were also assessed in the home using the Bayley-III and Sensory Profile (SP-2) assessments. Area deprivation index (ADI) was used to measure resource poor environments and relate to test scores. We used Fishers exact test and Pearson correlation coefficients to compare neurodevelopmental and sensory performance in responders versus non-responders. Result(s): taVNS responders showed significantly better general sensory processing in SP-2 than did non-responders (p =0.04). There were no significant differences in Bayley-III or CAT/CLAMS/ASQ scores in areas of cognition, receptive language, fine motor, and gross motor skills in this small sample size, but are similar to published scores for preterm infants who received G-tubes. ADI was not significantly associated with neurodevelopmental scores. Conclusion(s): These results suggest that taVNS paired with feeding may have a potential long-term positive neurodevelopmental effect on sensory processing in neonates with poor feeding. The current open-label results need testing in randomized controlled trials of taVNS paired with oral feeding in developmentally delayed infants failing oral feeds. Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Neurodevelopment, taVNS, feeding, developmental delaysCopyright © 2023

Severe Prps1 Deficiency and Response to S-Adenosylmethionine and Nicotinamide Riboside Supplementation

Background: PRPS1 deficiency spectrum is an X-linked condition caused by pathogenic variants in PRPS1, which encodes for the PRPP enzyme involved in the purine synthesis pathway, among other metabolic pathways. Severely affected individuals, also known as Arts syndrome, have congenital sensorineural hearing loss, optic atrophy, developmental delays, ataxia, hypotonia, and recurrent infections. Infections often precipitate worsening of symptoms and many individuals pass away in childhood. Mildly to moderately affected individuals can have isolated hearing loss, also known as DFNX1, or hearing loss with later onset ataxia and optic neuropathy concerns, also known as CMTX5. Given the importance of PRPP in the role of purine synthesis as well as other cellular processes, including formation of NAD(P), supplementation of these pathways is a logical approach for these patients. 2 Arts syndrome patients were previously supplemented with S-adenosylmethionine, starting in mid-childhood, with improvement in infection severity and frequency, as well as stabilization of other symptoms. Recently another Arts syndrome patient was supplemented with S-adenosylmethionine and nicotinamide riboside, starting in early childhood, with improvement in infection frequency and developmental gains. Here we present a now 23 month old male patient with severe PRPS1 deficiency spectrum symptoms, who was started on S-adenosylmethionine and nicotinamide riboside supplementation. Result(s): This is a 23 month old male with developmental delay, retinal dystrophy, congenital bilateral sensorineural hearing loss, and hypotonia with a PRPS1 c.383A > T / p.Asp128Val likely pathogenic variant. He does not have a history of recurrent infections, however family reports relative isolation due to the Covid-19 pandemic. He sat unsupported at 10 months, crawled at 14 months, pulled to stand at 18 months, and is nonverbal. His uric acid testing was in the low range of normal. He had normal purine testing with low normal xanthine and hypoxanthine levels. At 19 months the patient started 20 mg/kg/d S-adenosylmethionine supplementation. At 20 months this was increased to 40 mg/kg/d S-adenosylmethionine and he started on 30 mg/kg/d nicotinamide riboside supplementation. Parents reported subjective improvement in strength and endurance with supplementation. He made significant developmental gains including walking with a walker. He had done well with occasional upper respiratory infections without regression in skills, worsening hypotonia, or increased respiratory needs. Unfortunately, very recently he had a cardiac arrest secondary to respiratory failure from rhinovirus/enterovirus and H. influzenzae pneumonia, for which he remains hospitalized at this time. Conclusion(s): This is the 4th reported patient with severe PRPS1 deficiency treated with S-adenosylmethionine supplementation and the 2nd reported patient treated with nicotinamide riboside supplementation. Both supplements have a limited side effect profile and have a biochemical basis for consideration in PRPS1 deficiency. He initially did well on supplementation with improvements in strength and endurance, as well as developmental gains, however his current trajectory remains to be seen. Unfortunately, NAD/NADP, ADP/ATP, and similar markers were unavailable to us and we plan to continue clinical monitoring on supplementation. Further studies are needed to evaluate the effectiveness of S-adenosylmethionine and nicotinamide riboside supplementation in these patients.Copyright © 2023

Intrauterine device practices amongst adolescent patients

Background: Adolescent pregnancy is a worldwide public health issue, and the intrauterine device (IUD) has been shown to be a safe and highly effective method of long-acting reversible contraception (LARC) in this group. Patient concerns regarding IUDs are common, which should be addressed during routine office visits. Recently, both Pediatric and Gynecologic societies have recommended the IUD as a first line contraceptive for adolescents given their safety and efficacy. We are hoping to understand current IUD practices amongst providers, elucidate barriers to IUD insertion, and explore whether there have been any changes in IUD insertion patterns since the advent of the COVID-19 pandemic, which has increased telehealth and reduced operating room (OR) availability. Method(s): Survey was disseminated to NASPAG (North American Society for Pediatric and Adolescent Gynecologists) members via the listserv on two separate occasions. Consent was obtained upon completion of the survey. Results from the survey are anonymous. Results were tabulated with descriptive statistics. Ethics approval was obtained (REB22-0269). Result(s): There were 55 respondents, with the majority being Pediatric and Adolescent Gynecologists (71%) from North America (93%). As per providers, adolescents most frequently seek out the IUD for contraception (45%) and menstrual management (42%). Providers felt that the most common barrier to the IUD was misconceptions/myths (67%), as well as pain with insertion (64%). Most practitioners had no change in their IUD prescribing patterns since the start of the pandemic (62%), while some performed more office insertions (11%) and some reduced their IUD practice because of less operative time (15%) and less in-person appointments. Although many physicians perform office insertions, many found that a Procedural Sedation Center facilitated wait times (38%) or felt that such a center would be helpful (33%). Cases being done in the OR were often patients with disabilities/developmental delay (95%) or anxiety (75%). Conclusion(s): Our survey demonstrated that there are still some misconceptions surrounding the IUD. Education on contraception, specifically LARCs, is pivotal in decreasing adolescent pregnancy rates, reducing barriers to IUD use, and improving the attitude of adolescents toward the IUD. Pain with insertion is another limiting factor and a Procedural Sedation Center may be helpful in managing pain expectations and increasing acceptance of the IUD. Although there was no significant change in IUD practices during COVID, a decrease in operating room availability and increase in telehealth may impede IUD prescribing, especially in patients with developmental delay or disabilities who may require insertion in the OR.Copyright © 2023

Low Treatment Fidelity as an Indication to Switch Interventions: Pivoting From Child-Parent Psychotherapy to Parent-Child Interaction Therapy for Early Childhood Trauma

Young children who experience trauma and adverse experiences are at an increased risk of developing an insecure attachment style as well as negative physical and mental health problems. These can include internalizing and externalizing behavioral problems, developmental delay, emotional dysregulation, and aggression. Several evidence-based interventions exist to treat young children with symptoms related to trauma, each with different foundational theories. This article presents the case of a 4-year-old boy with posttraumatic stress disorder who was in the middle of a legal fight between caregivers and transitioning between caregivers' homes. Initially, therapy began with Child-Parent Psychotherapy to address caregivers' first concerns. Later, the therapeutical approach was switched to Parent-Child Interaction Therapy due to difficulty with treatment fidelity related to caregivers' symptoms and conflict. This case demonstrates great improvement in treatment fidelity and subsequently problem behaviors after switching to an intervention that allowed to address behavior management shortcomings in a family with ongoing conflict.Copyright © The Author(s) 2022.

Feasibility and acceptability of parenting interventions delivered in Spanish to caregivers of children with autism and other developmental delays: A mixed-methods design

Parents of children with autism spectrum disorder (ASD) or developmental delay (DD) experience increased stress due to raising a child with a disability, particularly if the child also presents with challenging behaviors. As such, there is benefit to developing evidence-based interventions that: 1) help parents cope with stress, and 2) manage the challenging behaviors of their children. This is particularly true for underserved groups, including Spanish-speaking Hispanic/Latinx populations, who are often underrepresented in intervention research. Two promising interventions in reducing caregiver stress are psychoeducation/support groups and mindfulness-based stress reduction (MBSR);an intervention effective in reducing child challenging behaviors is Behavioral Parent Training (BPT). This study piloted these three interventions for 60 Spanish-speaking Hispanic caregivers of children with ASD or DD as part of a larger, randomized-controlled trial. We sought to examine the feasibility and acceptability of these interventions both within this Spanish-speaking cohort, and compared to previously run English-speaking cohorts. Additionally, due to unforeseen circumstances of COVID-19, the BPT intervention was modified for telehealth delivery, allowing for initial exploration of the modality for this population. Results from attendance and satisfaction data, as well as participant focus groups, showed that Spanish-speaking participants attended sessions at similar rates and demonstrated preference for psychoeducation/support groups over MBSR compared to English-speaking participants, while finding BPT strategies generally acceptable. Participants reported appreciating the knowledge gained and sense of community established in the psychoeducation/support groups. Implications and future directions, including potential cultural adaptation of materials to maximize participant engagement and buy-in, are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The headache of diagnosing cerebellitis

Case Report:We describe a case of a non-verbal 5-yearold patient with autism and global developmental delay who presented with headache, nausea, vomiting, and decreased oral intake and found to have acute cerebellar syndrome/cerebellitis secondary to COVID-19 infection. Method(s): Chart Review. Summary of Results: A 5-year-old male with autism spectrum disorder and global developmental delay presented with one week history of headache, nausea, and non-bilious, non-bloody emesis. Despite intravenous fluid resuscitation and anti-emetic treatment, the patient continued to have persistent emesis with decreased oral intake and urine output. Physical exam findings were notable for aniscoria with right pupil larger than left, fixed upward gaze deviation, horizontal nystagmus, and nuchal rigidity. Patient was able to move all extremities spontaneously with normal tone and without rigidity or hyperreflexia. A complete blood cell count was consistent with the following: WBC 17.29 K/uL, hemoglobin level 12.8 g/dL, hematocrit 38.9%, and platelet count 482 K/ uL. C-reactive protein <4.0 mg/L and procalcitonin 0.12 ng/mL. CT Head on hospital day one showed no acute intracranial abnormality. Due to the patient's acute neurological changes, MRI brain was obtained and revealed patchy areas of hyperintensity in both the cerebellar hemispheres with moderate swelling of the cerebellum causing narrowing of the posterior fossa extra-axial cerebrospinal fluid (CSF) spaces. In addition, there was obstruction of the cerebral aqueduct due to extrinsic mass effect by the swollen cerebellum. CSF studies were notable for the following: 148 total nucleated cells with 75% lymphocytes and 17% monocytes and 2 red blood cells, protein was elevated at 113 mg/dL, and glucose was normal at 52 mg/dL. Meningitis and encephalitis panel was without any acute findings. Other laboratory testing was negative for tuberculosis, syphilis, chlamydia, HIV, and EBV. The patient tested positive for COVID-19 virus about one month prior to the onset of symptoms. Imaging and laboratory results in the setting of obstructive hydrocephalus with associated symptoms of nausea, emesis, headache, and upward gaze deviation are consistent with acute cerebellar syndrome, or cerebellitis. Due to obstructive hydrocephalus and inflammation of the cerebellum, patient was started on high-dose steroids, and neurosurgery placed external ventricular drain (EVD). The patient worked closely with physical medicine and rehabilitation as well as speech therapy, physical therapy, and occupational therapy to make a full recovery following this illness. Conclusion(s): Headache, nausea, and vomiting are often seen as benign findings;however, it is important to obtain specific details regarding the timing of symptoms, especially in the setting of a non-verbal patient. Because inflammation of the cerebellum can lead to hydrocephalus and potential herniation, prompt diagnosis is crucial to prevent long term effects of cerebellitis. Copyright © 2023 Southern Society for Clinical Investigation.

Planning and executing a health fair to bridge accessibility gaps and language barriers for the Hispanic community in Mobile County, Alabama

Purpose of Study: Community health fairs have been developed to address the unmet needs for disease prevention and health education among underserved communities. Hispanic communities experience significant non-financial barriers (e.g., cultural and linguistic) that also contribute to lower rates of access and utilization of health care services, including important preventive screening services. Around 3% of Mobile County's population is Hispanic. The aim of this event was: (1) To perform basic health screening, provide health education, and administer COVID-19 and Influenza vaccines to children under the age of 18 years. (2) To act as a bridge between the Hispanic families in the community and the available resources to help them overcome barriers to accessing quality care. Methods Used: We started by identifying and finalizing the location and the date for the health fair with help from the Guadalupe Center (a faith-based organization). We planned to divide the health fair into three specialized zones: Health Screening, Health Education, and Vaccination. The Health Screening zone would include anthropometry, developmental screening, and vision screening. The Health Education zone would educate the families on asthma care, breastfeeding, drowning prevention, road safety, safe sleep practices, oral hygiene, adverse childhood experiences, and healthy lifestyle. The Vaccination Zone would administer COVID-19 and Influenza vaccines. We designed and printed brochures for all health education topics in English and in Spanish. Age and gender appropriate 'Health Passports' with growth charts and other key parameters to record the child's health status were also created. Resident and medical student volunteers were trained regarding documentation, health screening, health education, and referrals to early intervention or specialist services that accepted uninsured or Medicaid patients. Summary of Results: A total of 49 children underwent health screening and health education. Each child's health status was documented in age and gender appropriate 'Health Passport'. In addition to this, these children and their parents were educated at the various health education stations and provided with brochures. Around 40% of the children that were screened had an abnormal vision screen, the parents of these children were given a list of available resources for further follow-up. Six children with developmental delay were identified and early intervention forms were filled out for two and more information regarding the Individualized Education Program (IEP) was given to the other four families. Eight children were vaccinated for COVID-19 and five were vaccinated for Influenza. Conclusion(s): The Hispanic community has persistently faced barriers to access healthcare due to literacy and socioeconomic status. Academic institutions and community- based organizations must work to develop and sustain culturally relevant health education and outreach events to reduce these disparities. Copyright © 2023 Southern Society for Clinical Investigation.

'In the circumstances I think we've all managed really well' an exploration of the impact of the COVID-19 restrictions on a Child Development Advisor (Portage) Service.

Background: The Child Development Advisor (CDA)  (Portage) service provides developmental support to children with significant developmental delays and emotional support for their families through fortnightly home visits. However, the onset of the COVID-19 pandemic and subsequent restrictions imposed to control its spread prevented services from providing face-to-face sessions with families and caregivers, thus removing the CDA (Portage) service's primary means of supporting children and their families. This article aims to explore the impact of those changes on a team of CDAs. Methods: Semi-structured interviews were conducted with six CDAs representing the CDA (Portage) service within one NHS Health Board. Findings: The CDAs expressed feeling an initial negative impact of the COVID-19 restrictions on the service, but in the longer term they noticed a number of positive impacts, including caregiver empowerment and improved working with other professionals. Conclusion: Despite having their primary means of providing support removed as part of the COVID-19 restrictions, the service has been able to adapt to continuously support families and promote child development throughout the pandemic and inadvertently developed a service offer that may be more beneficial for both families and professionals in the future.

The Rule of Low Molecular Weight Heparin in Children with Misc Case Series in Tertiary Hospital in Indonesia

BACKGROUND AND AIM: The number of children and adults infected with SARS-CoV-2 are disproportionate, due to relatively different clinical manifestations and lack of SARS-CoV-2 detection in children. Recently, there was an emergence of clustered cases of children infected with SARS-CoV-2 presenting with severe clinical manifestation that comprised gastrointestinal symptoms, features of myocarditis, hemodynamic instability, coagulopathy and mucocutaneous inflammation reaction. This entire severe spectrum of SARS-CoV-2 infection is referred to as Multisystem Inflammatory Syndrome in Children (MIS-C). This study aims to review 3 cases of MIS-C in our centre, Sanglah Hospital. METHOD(S): This study reported 3 cases of MIS-C in patients aged 1-8 years old. Out of 3 cases, 2 cases were complicated with other underlying disease, case 1 was complicated with pleural tuberculosis while case 3 was complicated with malnutrition, down syndrome and global developmental delay (GDD). RESULT(S): All patients presented with high fever ranging from 38,6oC to 40oC, multi-organ involvement, evidence of increased inflammatory markers (ESR, CRP, procalcitonin) and increased D-dimer. All patients were treated with low molecular weight heparin using enoxaparin, multivitamin and other symptomatic treatments according to their clinical manifestations and underlying condition. CONCLUSION(S): Number of MIS-C cases has been increasing from over the world suggesting that this hyperinflammatory disease should be widely recognized and necessitate prompt treatment. MIS-C is a potentially serious and life-threatening illness, with reported mortality rate of approximately 2%. Main treatment of MIS-C comprised of immunomodulators, antiplatelet, anticoagulant, systemic glucocorticoids and other supporting therapy.

Accessible and Specialized Covid-19 Testing for Children and Youth with Medical Complexity

BACKGROUND: COVID-19 testing for symptomatic individuals is a key public health measure for infection prevention and control. However, COVID-19 testing can be uncomfortable without appropriate supports and can lead to testing hesitancy amongst certain populations such as children with medical complexity (CMC) and those with underlying neurological and respiratory conditions. To support COVID-19 testing, a specialized initiative was developed for CMC and their families onsite at The Hospital for Sick Children to enhance testing uptake, reduce barriers to access, and support a safe and accommodated testing environment for families. Multiple modalities of testing were involved and could be completed in their personal vehicle, with specialized support from nurses and child life if needed. OBJECTIVE(S): The objectives of our study were to investigate the characteristics of CMC and their families who underwent COVID-19 testing through our program, evaluate indications for testing, and collect case positivity rates. DESIGN/METHODS: Prospective data, including testing and population characteristics, were collected from December 2020-August 2021 through a centralized system, and was analyzed using descriptive methods. RESULT(S): 335 children (Table 1) with medical complexity came to the COVID-19 Assessment Center for testing. Of those who were tested 88% (294) had neurodevelopmental conditions with highly challenging behaviours (e.g. autism, developmental delay), and 12% (28) were classified as CMC (i.e. those with active use of medical technology e.g. tracheostomy, G-tube etc.). Of those tested, 6% (21) tested positive for COVID-19. Sixty percent (199) were tested due to having symptoms consistent with COVID-19, 27% (90) had a COVID-19 exposure, 8% (26) were exposed and tested as part of outbreak management and 5% were of an unknown criteria. The majority of completed tests (74%) were nasopharyngeal (NP) swabs, 18% completed saliva tests and 6% completed anterior nares/throat swab tests. Thirteen percent (43) of families requested additional supports such as extra nurses, child life specialists or other accommodations. All patients had a dedicated paediatric nurse and received testing in their personal vehicle. CONCLUSION(S): CMC and their families face unique barriers to COVID-19 testing. A specialized testing centre for CMC was able to support families by providing unique opportunities for testing, revealing a 6% COVID-19 positivity rate. NP swabs that can be painful were supported through in-vehicle testing with dedicated pediatric nurses. Robust health and safety measures, including a coordinated testing approach, are necessary to ensure accessible testing opportunities for CMC and their families. Further research is needed to be able to support this unique population.

Trisomy 18p detected in DNA from saliva but absent in DNA from blood

Molecular diagnostic testing using DNA from saliva specimens markedly increased recently due to the ease of sample collection, compared to peripheral blood, during the COVID-19 pandemic. Published literature suggests that DNA from saliva is primarily composed of epithelial cells (70-90%), with the remainder being primarily leukocytes (10-30%). Here, we describe a case followed by our clinicians since 2007 characterized by developmental delay, autism, a somewhat coarse face with full cheeks, up-slanting palpebral fissures, thin corpus callosum, and a full-scale IQ of 60. This patient had an extensive work-up including high-resolution blood chromosome analysis, FISH for 22q microdeletion, three separate microarrays (various platforms), FMR1 molecular analysis, urine oligosaccharides analysis, an autism gene panel by NGS, and whole-exome sequencing, none of which identified a satisfactory diagnosis. These tests were performed on two peripheral blood samples collected at different times. Recently, a new microarray was ordered on a saliva sample from this patient, and an apparently non-mosaic gain of 18p was detected. The possibility of a sample swap was eliminated by comparing the SNP genotype of the saliva sample to the previously tested blood sample. The limit of detection for mosaicism in genomic microarrays is around 20%, so it is possible that the 18p duplication was present at a level undetectable by microarray in the peripheral blood samples. This case suggests that the differences between DNA obtained from saliva and peripheral blood may be, in some cases, more drastic than previously recognized. By testing primarily with DNA from peripheral blood, significant mosaic abnormalities may go undetected. Copyright © 2022

A systematic review of GAS implementation practices by caregivers in randomized controlled trials

Aims: Goal attainment scaling (GAS) is an established individualized, patient-centered outcome measure widely used to capture the patient's voice. Although it was first introduced ~ 60 years ago, there are few published guidelines for implementing GAS. This is especially true for its use with caregivers. We conducted a systematic review of randomized controlled trials where GAS was implemented with caregiver input. Method(s): The search protocol was registered in PROSPERO (Oct 2021). We searched Medline, Embase, Cochrane, PsycInfo and CINAHL databases. Variations of these keywords were searched: randomized controlled trials, family caregiver and proxy, goal setting/planning/ attainment/achievement. Three researchers screened and reviewed articles, with one reviewer screening all s and full texts, and the second reviewer screening 25% of s. Covidence software was used to perform screening and data extraction. Result(s): Of 2205 studies imported for screening, 20 studies were included for the final data extraction. Most studies (55%) had GAS as a primary outcome, with over 75% of studies having children as study participants. The most common disorders represented in the review were cerebral palsy (40%), developmental delay disorders (25%) and dementia/Alzheimer's disease (20%). Essential details including the number of goals set, number of attainment levels, baseline level, and training given to GAS facilitators were missing from most studies. Disease-specific semi-standardized goal inventories were not provided. The traditional five-point GAS scale from -2 to + 2 was most commonly implemented, with -1 level being the baseline. Both caregivers and patients were involved in the goalsetting process, with clinicians assessing goal attainment post-intervention. T-tests were often used to analyze most between-group treatment effects, and mean change score was the most common effect size measure reported (median of the mean change score = 5.4, ranging from 0.8 to 45.2). Conclusion(s): GAS with caregivers was feasible in randomized controlled trials across a range of disorders, in diverse patient populations and across disciplines. Many crucial details related to the specifics of GAS implementation were not reported, this limits the potential for reproducibility. A standardized checklist for consistent reporting of GAS details seems useful. In addition, the inclusion of semi-standardized goal inventories may enhance the application of this patient-centered outcome measure.

Feasibility and acceptability of parenting interventions delivered in Spanish to caregivers of children with autism and other developmental delays: A mixed-methods design

Parents of children with autism spectrum disorder (ASD) or developmental delay (DD) experience increased stress due to raising a child with a disability, particularly if the child also presents with challenging behaviors. As such, there is benefit to developing evidence-based interventions that: 1) help parents cope with stress, and 2) manage the challenging behaviors of their children. This is particularly true for underserved groups, including Spanish-speaking Hispanic/Latinx populations, who are often underrepresented in intervention research. Two promising interventions in reducing caregiver stress are psychoeducation/support groups and mindfulness-based stress reduction (MBSR);an intervention effective in reducing child challenging behaviors is Behavioral Parent Training (BPT). This study piloted these three interventions for 60 Spanish-speaking Hispanic caregivers of children with ASD or DD as part of a larger, randomized-controlled trial. We sought to examine the feasibility and acceptability of these interventions both within this Spanish-speaking cohort, and compared to previously run English-speaking cohorts. Additionally, due to unforeseen circumstances of COVID-19, the BPT intervention was modified for telehealth delivery, allowing for initial exploration of the modality for this population. Results from attendance and satisfaction data, as well as participant focus groups, showed that Spanish-speaking participants attended sessions at similar rates and demonstrated preference for psychoeducation/support groups over MBSR compared to English-speaking participants, while finding BPT strategies generally acceptable. Participants reported appreciating the knowledge gained and sense of community established in the psychoeducation/support groups. Implications and future directions, including potential cultural adaptation of materials to maximize participant engagement and buy-in, are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Early screening tool for developmental delay in infancy: Quantified assessment of movement asymmetry using IR-UWB radar.

In the untact COVID-19 era, the feasibility of a noncontact, impulse-radio ultrawideband (IR-UWB) radar sensor has important medical implications. Premature birth is a major risk factor for brain injury and developmental delay; therefore, early intervention is crucial for potentially achieving better developmental outcomes. Early detection and screening tests in infancy are limited to the quantification of differences between normal and spastic movements. This study investigated the quantified asymmetry in the general movements of an infant with hydrocephalus and proposes IR-UWB radar as a novel, early screening tool for developmental delay. To support this state-of-the-art technology, data from actigraphy and video camcorder recordings were adopted simultaneously to compare relevant time series as the infant grew. The data from the three different methods were highly concordant; specifically, the ρz values comparing radar and actigraphy, which served as the reference for measuring movements, showed excellent agreement, with values of 0.66 on the left and 0.56 on the right. The total amount of movement measured by radar over time increased overall; movements were almost dominant on the left at first (75.2% of total movements), but following shunt surgery, the frequency of movement on both sides was similar (54.8% of total movements). As the hydrocephalus improved, the lateralization of movement on radar began to coincide with the clinical features. These results support the important complementary role of this radar system in predicting motor disorders very early in life.