Paracetamol overdose in Danish children and adolescents during the Covid-19 restrictions.

INTRODUCTION: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health. METHODS: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes. RESULTS: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value. CONCLUSIONS: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health. FUNDING: None. TRIAL REGISTRATION: Not relevant.

A Novel Synonymous Variant in the AVP Gene Associated with Autosomal Dominant Familial Neurohypophyseal Diabetes Insipidus Causes Partial RNA Missplicing.

OBJECTIVE: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is characterized by severe polyuria and polydipsia and is caused by variations in the gene encoding the AVP prohormone. This study aimed to ascertain a correct diagnosis, to identify the underlying genetic cause of adFNDI in a Swedish family, and to test the hypothesis that the identified synonymous exonic variant in the AVP gene (c.324G>A) causes missplicing and endoplasmic reticulum (ER) retention of the prohormone. DESIGN/PATIENTS: Three affected family members were admitted for fluid deprivation test and dDAVP (1-deamino-8-d-arginine-vasopressin) challenge test. Direct sequencing of the AVP gene was performed in the affected subjects, and genotyping of the identified variant was performed in family members. The variant was examined by expression of AVP minigenes containing the entire coding regions as well as intron 2 of AVP. METHODS/RESULTS: Clinical tests revealed significant phenotypical variation with both complete and partial adFNDI phenotype. DNA analysis revealed a synonymous c.324G>A substitution in one allele of the AVP gene in affected family members only. Cellular studies revealed both normally spliced and misspliced pre-mRNA in cells transfected with the AVP c.324G>A minigene. Confocal laser scanning microscopy showed collective localization of the variant prohormone to ER and vesicular structures at the tip of cellular processes. CONCLUSION: We identified a synonymous variant affecting the second nucleotide of exon 3 in the AVP gene (c.324G>A) in a family in which adFNDI segregates. Notably, we showed that this variant causes partial missplicing of pre-mRNA, resulting in accumulation of the variant prohormone in ER. Our study suggests that even a small amount of aberrant mRNA might be sufficient to disturb cellular function, resulting in adFNDI.

Transanal irrigation is effective in functional fecal incontinence.

Functional fecal incontinence (FFI) is divided into cases related to functional constipation (FC) and cases without concomitant constipation termed functional non-retentive fecal incontinence (FNRFI). Transanal irrigation (TAI) is widely used in children with neurogenic fecal incontinence but is less studied in children with functional defecation disorders. The aim was to evaluate the feasibility and efficacy of TAI in the treatment of FFI. A retrospective study in 72 children (mean age 9.2 ± 2.2 years, 47 males) with treatment-resistant FFI was performed. All children accepted treatment and 35% (n = 25) were titrated to daily sessions. Of the 63 children who fulfilled the Rome III criteria of constipation, 46 (73%) showed full response with complete remission of incontinence episodes. Eleven (17%) showed partial response (≥50% reduction). Of nine children with FNRFI, four (44%) showed full response whereas two (22%) showed partial response. We found no significant difference in the reduction of incontinence episodes between the children with FC (87%) and children with FNRFI (68%) (p = 0.11). CONCLUSION: TAI is an effective, well-tolerated, and safe choice in children with FC. No clinical parameters seemed to predict response to treatment. The number of children with FNRFI was low, but TAI seemed effective in this group of children. What is Known: • Functional fecal incontinence (FFI) is a frequent, chronic condition with significant impact on children's quality of life. • Transanal irrigation (TAI) is used in children with neurogenic bowel dysfunction but less studied in children with functional defecation disorders. What is New: • TAI seems an effective, well-tolerated, and safe choice in children with FFI due to functional constipation. • Albeit the number of children with functional non-retentive fecal incontinence was low in our study, TAI seems effective also in this group of children.

A novel variant in the SLC12A1 gene in two families with antenatal Bartter syndrome.

AIM: Bartter syndrome is an autosomal-recessive inherited disease in which patients present with hypokalaemia and metabolic alkalosis. We present two apparently nonrelated cases with antenatal Bartter syndrome type I, due to a novel variant in the SLC12A1 gene encoding the bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2 in the thick ascending limb of the loop of Henle. METHODS: Blood samples were received from the two cases and 19 of their relatives, and deoxyribonucleic acid was extracted. The coding regions of the SLC12A1 gene were amplified using polymerase chain reaction, followed by bidirectional direct deoxyribonucleic acid sequencing. RESULTS: Each affected child in the two families was homozygous for a novel inherited variant in the SLC12A1gene, c.1614T>A. The variant predicts a change from a tyrosine codon to a stop codon (p.Tyr538Ter). The two cases presented antenatally and at six months of age, respectively. CONCLUSION: The two cases were homozygous for the same variant in the SLC12A1 gene, but presented clinically at different ages. This could eventually be explained by the presence of other gene variants or environmental factors modifying the phenotypes. The phenotypes of the patients were similar to other patients with antenatal Bartter syndrome.

Follow-up in Childhood Functional Constipation: A Randomized, Controlled Clinical Trial.

OBJECTIVES: Guidelines recommend close follow-up during the treatment of childhood functional constipation. Only sparse evidence exists on how follow-up is best implemented. Our aim was to evaluate whether follow-up by phone or self-management through Web-based information improved treatment outcomes. METHODS: In this randomized controlled trial, conducted in secondary care, 235 children, ages 2 to 16 years, who fulfilled the Rome III criteria of childhood constipation, were assigned to 1 of the 3 follow-up regimens: control group (no scheduled contact), phone group (2 scheduled phone contacts), and Web group (access to Web-based information). PRIMARY OUTCOME: number of successfully treated children after 3, 6, and 12 months. SECONDARY OUTCOMES: phone contacts, relapse, fecal incontinence, and laxative use. RESULTS: After 3 and 6 months, significantly more children in the Web group (79.7%/75.9%) were successfully treated compared with the control and phone groups (59.7%/63.6% and 63.3%/64.6%) (P = 0.007/P = 0.03). No difference was found after 12 months (control, 72.7%; phone, 68.4%; Web group, 78.5%; P = 0.40). Extra phone consultations were significantly more frequent in the Web group (44.3%) compared with the control group (28.6%) (P = 0.04). Before 3 months, 45.5% of phone consultations were completed in the Web group versus 28.8% and 25.8% in the control and phone groups (P = 0.05/P = 0.02). Relapses, fecal incontinence, and laxative use were not different between interventions. CONCLUSIONS: Improved self-management behavior caused by access to self-motivated Web-based information induced faster short-term recovery during the treatment of functional constipation. Patient empowerment rather than health care-promoted follow-up may be a step toward more effective treatment for childhood constipation.

Bladder and bowel dysfunction and the resolution of urinary incontinence with successful management of bowel symptoms in children.

AIM: To investigate the effect of treating defecation problems on urinary incontinence in children suffering from combined urinary bladder and bowel dysfunction (BBD). METHODS: We established a clinical database from medical records of all children referred to the urinary incontinence and gastroenterology outpatient clinics with BBD. The following variables were extracted: symptoms of constipation, faecal incontinence, urinary incontinence, age at onset of symptoms, treatment, including duration and response. All children went through the same treatment protocol. Faecal disorders were treated primarily and once relieved, the daytime incontinence was managed and followed by intervention for nocturnal enuresis. RESULTS: In total, 73 children were included in the study. The treatment regimen resulted in resolution of the defecation disorder in 96% of the patients. Of the children with daytime urinary incontinence, 68% had at least a 50% reduction in number of daytime incontinence episodes by successful relief of bowel dysfunction and 27% became completely continent during daytime. Only 17% of the children suffering from enuresis had a significant reduction in number of wet nights after relief of their faecal problem. CONCLUSION: The empirical treatment approach of managing bowel symptoms before intervening for bladder dysfunction in children with BBD is found to be appropriate.

Management of functional constipation in children with lower urinary tract symptoms: report from the Standardization Committee of the International Children's Continence Society.

PURPOSE: We present a consensus view of members of the International Children's Continence Society (ICCS) together with pediatric gastroenterologists, experts in the field of functional gastrointestinal disorders, on the management of functional constipation in children with lower urinary tract symptoms. MATERIALS AND METHODS: Discussions were held by the board of the ICCS and a multidisciplinary core group of authors was appointed. The draft document review process was open to all ICCS members via the website. Feedback was considered by the core authors and, by agreement, amendments were made as necessary. RESULTS: Guidelines on the assessment, and pharmacological and nonpharmacological management of functional constipation in children with lower urinary tract symptoms are outlined. CONCLUSIONS: The final document is not a systematic literature review. It includes relevant research when available, as well as expert opinion on the current understanding of functional constipation in children with lower urinary tract symptoms. The document is intended to be clinically useful in primary, secondary and tertiary care settings.