A novel syndrome of silent rhinovirus-associated bronchoalveolitis in children with recurrent wheeze.

BACKGROUND: Rhinovirus (RV) infections trigger wheeze episodes in children. Thus, understanding of the lung inflammatory response to RV in children with wheeze is important. OBJECTIVES: This study sought to examine the associations of RV on bronchoalveolar lavage (BAL) granulocyte patterns and biomarkers of inflammation with age in children with treatment-refractory, recurrent wheeze (n = 616). METHODS: Children underwent BAL to examine viral nucleic acid sequences, bacterial cultures, granulocyte counts, and phlebotomy for both general and type-2 inflammatory markers. RESULTS: Despite the absence of cold symptoms, RV was the most common pathogen detected (30%), and when present, was accompanied by BAL granulocytosis in 75% of children. Compared to children with no BAL pathogens (n = 341), those with RV alone (n = 127) had greater (P < .05) isolated neutrophilia (43% vs 16%), mixed eosinophils and neutrophils (26% vs 11%), and less pauci-granulocytic (27% vs 61%) BAL. Children with RV alone furthermore had biomarkers of active infection with higher total blood neutrophils and serum C-reactive protein, but no differences in blood eosinophils or total IgE. With advancing age, the log odds of BAL RV alone were lower, 0.82 (5th-95th percentile CI: 0.76-0.88; P < .001), but higher, 1.58 (5th-95th percentile CI: 1.01-2.51; P = .04), with high-dose daily corticosteroid treatment. CONCLUSIONS: Children with severe recurrent wheeze often (22%) have a silent syndrome of lung RV infection with granulocytic bronchoalveolitis and elevated systemic markers of inflammation. The syndrome is less prevalent by school age and is not informed by markers of type-2 inflammation. The investigators speculate that dysregulated mucosal innate antiviral immunity is a responsible mechanism.

Hereditary C1q Deficiency is Associated with Type 1 Interferon-Pathway Activation and a High Risk of Central Nervous System Inflammation.

Hereditary C1q deficiency (C1QDef) is a rare monogenic disorder leading to defective complement pathway activation and systemic lupus erythematosus (SLE)-like manifestations. The link between impairment of the complement cascade and autoimmunity remains incompletely understood. Here, we assessed type 1 interferon pathway activation in patients with C1QDef. Twelve patients with genetically confirmed C1QDef were recruited through an international collaboration. Clinical, biological and radiological data were collected retrospectively. The expression of a standardized panel of interferon stimulated genes (ISGs) in peripheral blood was measured, and the level of interferon alpha (IFNα) protein in cerebrospinal fluid (CSF) determined using SIMOA technology. Central nervous system (encompassing basal ganglia calcification, encephalitis, vasculitis, chronic pachymeningitis), mucocutaneous and renal involvement were present, respectively, in 10, 11 and 2 of 12 patients, and severe infections recorded in 2/12 patients. Elevated ISG expression was observed in all patients tested (n = 10/10), and serum and CSF IFNα elevated in 2/2 patients. Three patients were treated with Janus-kinase inhibitors (JAKi), with variable outcome; one displaying an apparently favourable response in respect of cutaneous and neurological features, and two others experiencing persistent disease despite JAKi therapy. To our knowledge, we report the largest original series of genetically confirmed C1QDef yet described. Additionally, we present a review of all previously described genetically confirmed cases of C1QDef. Overall, individuals with C1QDef demonstrate many characteristics of recognized monogenic interferonopathies: particularly, cutaneous involvement (malar rash, acral vasculitic/papular rash, chilblains), SLE-like disease, basal ganglia calcification, increased expression of ISGs in peripheral blood, and elevated levels of CSF IFNα.

Post COVID-19 conditions in an Australian pediatric cohort, 3 months following a Delta outbreak.

BACKGROUND: Pediatric long COVID remains incompletely understood with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents. METHODS: The parents/carers of 11,864 patients with PCR-confirmed SARS-CoV-2 were invited, via email or text message, to complete an online survey assessing symptoms and functional impairment. FINDINGS: 1731 (17.6%) responded to the survey. 203 (11.7%) reported continued symptoms and/or functional impairment which were flagged for clinical review, all others reported recovery. Of the 169 subsequently clinically reviewed, 63 had already recovered (37.3%) and 17 had exacerbation of pre-existing condition(s) (10.1%); 63 (37.3%) were diagnosed with a Post COVID Condition (PCC). Of these, 21 (12.4%) were considered to have features compatible with the United Kingdom consensus cases definition for Long COVID. INTERPRETATION: During an outbreak of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recovery, and is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention. IMPACT: Our study provides the only comprehensive estimate of the frequency and spectrum of post-COVID conditions in children from Australia. The high frequency of self-reported recovery, and low frequency of Long COVID compatible illness adds to the literature from other settings. Risk factors for post-COVID conditions in children are identified and include: age >11 year, and previous medical co-morbidity.

New consensus definition on defining and measuring care for children with paediatric feeding disorder.

AIM: This study addresses the absence of a definition of care for children with feeding disorders, limited agreement on key performance indicators (KPIs), and the lack of data linked to those KPIs. METHODS: Clinicians, consumers and researchers involved in outpatient feeding care in New South Wales (NSW), Australia were invited to participate in a two-Phase study. In Phase 1, a modified Delphi method was used. Two rounds of voting resulted in a new consensus definition of a multidisciplinary paediatric feeding clinic. Three further rounds voting determined relevant KPIs. In Phase 2, the KPIs were piloted prospectively in 10 clinics. RESULTS: Twenty-six clinicians, consumers and researchers participated in Phase 1. Participation across five voting rounds declined from 92% to 60% and a valid definition and KPI set were created. In Phase 2, the definition and KPIs were piloted in 10 clinics over 6 weeks. Data for 110 patients were collected. The final KPI set of 28 measures proposed covers clinical features, patient demographics and medical issues, parent-child interaction and outcome measures. CONCLUSIONS: A new definition of a multidisciplinary paediatric feeding clinic is now available, linked to a standardised KPI set covering relevant performance measures. These proved viable in baseline data collection for 10 clinics across NSW. This sets a foundation for further data collection, systematic measurement of care provision and outcomes, and research needed to deliver care improvement for children with paediatric feeding disorder.

Duration of monitoring after cessation of oxygen therapy in infants with bronchiolitis.

AIM: There is no evidence for how long bronchiolitis patients should be observed after coming off oxygen therapy and wide practice variation exists. We aimed to investigate whether it is safe to discharge bronchiolitis patients 4 h after cessation of oxygen therapy. METHODS: A retrospective single-centre cohort study of 884 infants (n = 462 in 2018 vs. n = 422 in 2019) aged 0-24 months admitted with bronchiolitis in 2018 and 2019 was conducted after implementation of a bronchiolitis protocol recommending discharge home 4 h post-cessation of oxygen therapy in 2019. We compared the rate of readmissions and Clinical Reviews/Rapid Responses in the pre- and post-exposure cohorts. RESULTS: There was a significant reduction in median (interquartile range (IQR)) time to discharge post oxygen cessation by 87 min (510 (370-1033) min versus 423 (273-904) min; P < 0.001) and in median (IQR) length of stay by 6.7 h (2.11 (1.54-2.97) days vs. 1.83 (1.17-2.71) days; P < 0.001). There was no significant difference between readmissions in 2018 compared to 2019 (0.6% vs. 1.4%; P = 0.317). In 2018, there were two Clinical Reviews and in 2019 there were two Rapid Responses post-cessation of oxygen. There were 89 patients discharged within 4 h of cessation of oxygen therapy (n = 18 in 2018 vs. n = 71 in 2019; P < 0.001) with no readmissions, Clinical Reviews or Rapid Responses in the 2019 cohort. CONCLUSIONS: This study demonstrates that patients can be discharged 4 h after cessation of supplemental oxygen without increased risk of adverse events.

Feeding difficulties in children with autism spectrum disorder: Aetiology, health impacts and psychotherapeutic interventions.

Feeding difficulties are common and significant issues for children with autism spectrum disorder and their families. Key features of autism are intrinsically linked with factors contributing to these children's feeding difficulties. Following a multidisciplinary assessment to exclude non-behavioural reasons for the feeding difficulty, there are two mainstay modalities of treatment: operant conditioning and systematic desensitisation. Currently, evidence points towards operant conditioning as the most efficacious psychotherapy. However, recent research into cognitive behavioural therapy for older children with feeding difficulties has shown promising results and will be an area to monitor in the coming years. This review outlines the causes and health impacts and evaluates current evidence supporting the available psychotherapeutic interventions for children with autism spectrum disorder experiencing feeding difficulties.

Feeding difficulties in neonates following cardiac surgery: determinants of prolonged feeding-tube use.

Aim The aims of this study were to examine the prevalence and potential correlates of feeding difficulties in infants who underwent cardiac surgery in the neonatal period and to investigate resource utilisation by infants with feeding difficulties. METHODS: All neonates who underwent their first cardiac surgery at the Heart Centre for Children, The Children's Hospital at Westmead, between January and December, 2009 were included. Demographic, preoperative, intraoperative, and postoperative data were collected via electronic medical records. For the purpose of this study, feeding difficulty was defined as the requirement for ongoing tube feeding at the time of discharge home or transfer to another hospital. RESULTS: Out of a total of 79 neonates, 24 (30%) were discharged home or transferred to another hospital with a feeding tube. Feeding difficulties were associated with the presence of a genetic syndrome (p<0.0001), assisted feeding preoperatively (odds ratio (OR)=4.4, p=0.03), and having a palliative procedure before biventricular repair (OR=5.1, p=0.02). Infants with feeding difficulties had significantly more reviews by speech pathologists (M=5.9, SD=7.9), dieticians (M=5.9, SD=5.4), and cardiac clinical nurse consultants (M=1.2, SD=1.4) compared with those without feeding difficulties. CONCLUSIONS: This study identified factors that can be used in the early recognition of infant feeding difficulties, to help guide the direction of limited health resources, as well as being focal points for future research and clinical practice improvement.

Polarization of specific tropomyosin isoforms in gastrointestinal epithelial cells and their impact on CFTR at the apical surface.

Microfilaments have been reported to be polarized in a number of cell types based both on function and isoform composition. There is evidence that microfilaments are involved in the movement of vesicles and the polarized delivery of proteins to specialized membrane domains. We have investigated the composition of actin microfilaments in gastrointestinal epithelial cells and their role in the delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) into the apical membrane using cultured T84 cells as a model. We identified a specific population of microfilaments containing the tropomyosin (Tm) isoforms Tm5a and/or Tm5b, which are polarized in T84 cell monolayers. Polarization of this microfilament population occurs very rapidly in response to cell-cell and cell-substratum contact and is not inhibited by jasplakinolide, suggesting this involves the movement of intact filaments. Colocalization of Tm5a and/or Tm5b and CFTR was observed in long-term cultures. A reduction in Tm5a and Tm5b expression, induced using antisense oligonucleotides, resulted in an increase in both CFTR surface expression and chloride efflux in response to cAMP stimulation. We conclude that Tm isoforms Tm5a and/or Tm5b mark an apical population of microfilaments that can regulate the insertion and/or retention of CFTR into the plasma membrane.

Gastroenteritis in children.

INTRODUCTION: Acute gastroenteritis results from infection of the gastrointestinal tract, most commonly with a virus. It is characterised by rapid onset of diarrhoea with or without vomiting, nausea, fever, and abdominal pain. Diarrhoea is defined as the frequent passage of unformed, liquid stools. Regardless of the cause, the mainstay of management of acute gastroenteritis is provision of adequate fluids to prevent and treat dehydration. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent acute gastroenteritis in children? What are the effects of treatments for acute gastroenteritis in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 42 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of: rotavirus vaccines for the prevention of gastroenteritis; enteral rehydration solutions (oral or gastric), lactose-free feeds, loperamide, probiotics, and zinc for the treatment of gastroenteritis; and ondansetron for the treatment of vomiting.

Gastroenteritis in children.

INTRODUCTION: Acute gastroenteritis results from infection of the gastrointestinal tract, most commonly with a virus. It is characterised by rapid onset of diarrhoea with or without vomiting, nausea, fever, and abdominal pain. Diarrhoea is defined as the frequent passage of unformed, liquid stools. Regardless of the cause, the mainstay of management of acute gastroenteritis is provision of adequate fluids to prevent and treat dehydration. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent acute gastroenteritis in children? What are the effects of treatments for acute gastroenteritis in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of: rotavirus vaccines for the prevention of gastroenteritis; enteral rehydration solutions (oral or gastric), lactose-free feeds, and loperamide for the treatment of gastroenteritis; and ondansetron for the treatment of vomiting.

Gastroenteritis in children.

INTRODUCTION: Diarrhoea is defined as the frequent passage of unformed, liquid stools. Regardless of the cause, the mainstay of management of acute gastroenteritis is provision of adequate fluids to prevent and treat dehydration. METHODS AND OBJECTIVES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute gastroenteritis? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: clear fluids, enteral rehydration solutions (oral or gastric), lactose-free feeds, loperamide.

2. Acute infectious diarrhoea and dehydration in children.

Gastroenteritis in children is still a common reason for consulting a general practitioner and for hospital admission. Rotavirus is the most common cause of gastroenteritis in children and accounts for half of all hospital admissions for severe acute infectious diarrhoea. Most children with gastroenteritis do not develop dehydration and can be treated at home. Children with mild to moderate dehydration should be treated with low osmolarity oral rehydration solutions, and those with severe dehydration or shock need to be admitted for administration of intravenous fluids. Lactose-free feeds should not be routinely used after acute gastroenteritis, but there is some evidence that a lactose-free diet may reduce the duration of diarrhoea. Antimotility drugs are rarely indicated in children with gastroenteritis, as the potential risks outweigh the benefits. The development of a rotavirus vaccine would provide huge public health benefits and cost savings. Other preventive strategies include educating people about personal and food hygiene and encouraging breastfeeding.

Meta-analysis of randomized controlled trials on the benefits and risks of using cisapride for the treatment of gastroesophageal reflux in children.

BACKGROUND AND AIM: Gastroesophageal reflux is a common problem in infancy. Cisapride is a commonly used therapy for gastroesophageal reflux in children. In view of recent concern regarding adverse effects this study aims to evaluate the benefits and risks of cisapride for the treatment of gastroesophageal reflux in children. METHODS: A meta-analysis of randomized controlled trials of cisapride using a random-effects model. RESULTS: Ten trials involving 415 children were identified. There was no evidence of a significant reduction in vomiting severity with cisapride as measured by a clinical score (five trials, standardized weighted mean difference -0.18; 95% confidence interval (CI) -0.51 to 0.15). Twenty-four-hour esophageal pH monitoring data showed the mean reflux index was significantly lower in the children treated with cisapride compared with controls (five trials, weighted mean difference -6.24; 95% CI -8.81 to -3.67). With cisapride treatment, there was no reduction in the mean number of reflux episodes lasting greater than 5 min (three trials, weighted mean difference -0.72; 95% CI -1.92 to 0.47) or in the number of children with esophagitis at final follow up compared with baseline (two trials, relative risk 0.80; 95% CI 0.40 to 1.61). There was no significant difference in reported side-effects or adverse events (six trials, relative risk 1.16; 95% CI 0.95 to 1.41). CONCLUSIONS: No clinically important benefits of cisapride in children with gastroesophageal reflux have been demonstrated. Nor was there any evidence of adverse or harmful events.