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INTRODUCTION: Functional constipation (FC) is a common childhood condition, diagnosed via the Rome IV criteria. Standard therapy includes lifestyle and dietary modification followed by initiation of osmotic laxative therapy. About 30% of children continue to experience symptoms related to FC despite appropriate management. New pharmacologic, surgical, and neuromodulatory therapies for FC are now available for use in adult and pediatric populations. In 2023, the first pharmacologic agent, linaclotide, obtained FDA approval for treatment of FC in children 6-17 years old. AREAS COVERED: This article reviews current and emerging pharmacologic, surgical, and neuromodulation therapies for the management of FC in pediatric patients. Efficacy and safety data regarding each of these modalities was reviewed and discussed. EXPERT OPINION: Advancements in therapeutics available for the management of FC necessitate further investigation on safety and efficacy in pediatric populations. Careful consideration should be taken in choosing an available treatment with limited pediatric evidence as adult and pediatric FC have different underlying pathophysiology and require a different therapeutic approach. Standardization of methodology and pediatric endpoints are needed to optimize ability to compare efficacy of different treatments. We predict the future of pediatric FC management will include a personalized approach to care, resulting in improved outcomes.
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OBJECTIVES: Ineffective esophageal motility (IEM) on high-resolution manometry (HRM) is not consistently associated with specific clinical syndromes or outcomes. We evaluated the prevalence, clinical features, management, and outcomes of pediatric IEM patients across the United States. METHODS: Clinical and manometric characteristics of children undergoing esophageal HRM during 2021-2022 were collected from 12 pediatric motility centers. Clinical presentation, test results, management strategies, and outcomes were compared between children with IEM and normal HRM. RESULTS: Of 236 children (median age 15 years, 63.6% female, 79.2% Caucasian), 62 (23.6%) patients had IEM, and 174 (73.7%) patients had normal HRM, with similar demographics, medical history, clinical presentation, and median symptom duration. Reflux monitoring was performed more often for IEM patients (25.8% vs. 8.6%, p = 0.002), but other adjunctive testing was similar. Among 101 patients with follow-up, symptomatic cohorts declined in both groups in relation to the initial presentation (p > 0.107 for each comparison) with management targeting symptoms, particularly acid suppression. Though prokinetics were used more often and behavioral therapy less often in IEM (p ≤ 0.015 for each comparison), symptom outcomes were similar between IEM and normal HRM. Despite a higher proportion with residual dysphagia on follow-up in IEM (64.0% vs. 39.1%, p = 0.043), an alternate mechanism for dysphagia was identified more often in IEM (68.8%) compared to normal HRM (27.8%, p = 0.017). CONCLUSIONS: IEM is a descriptive manometric pattern rather than a clinical diagnosis requiring specific intervention in children. Management based on clinical presentation provides consistent symptom outcomes.
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OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years of age with functional constipation (FC). This study evaluated the dose-response, safety, and efficacy of 4 weeks of linaclotide compared with placebo in children 2-5 years of age with FC. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, multidose study, 35 children with FC (based on Rome III criteria) were randomized 3:1 to receive linaclotide (18, 36, or 72 µg, for groups 1, 2, and 3, respectively) and 5:1 to receive linaclotide 9, 18, 36, or 72 µg (group 4), or matching placebo. Key endpoints were the changes from baseline in overall spontaneous bowel movement (SBM) frequency (SBMs/week), stool consistency, and straining, as well as the proportion of days with fecal incontinence during the study intervention period. Adverse events (AEs) were recorded. RESULTS: Of the randomized patients, 34 (97.1%) completed the treatment period and 33 (94.3%) completed the posttreatment period. Mean change from baseline over the treatment period for three of the four key efficacy endpoints showed greater improvement in the linaclotide 72 µg group versus placebo. A dose-response trend was seen for stool consistency in patients receiving linaclotide. Four patients randomized to linaclotide experienced treatment-emergent AEs, one of which was treatment-related (mild diarrhea). All AEs were mild or moderate and none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population and an efficacy trend was seen with linaclotide 72 µg versus placebo.
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Bothersome gastrointestinal (GI) signs/symptoms, including abdominal pain, distension, nausea, and flatulence, are common in children. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is frequently recommended for children with GI symptoms. Currently, there are no studies on the effect of FODMAPs in healthy schoolchildren. In this cross-sectional study, schoolchildren reported an association between FODMAPs and GI symptoms through a standardized questionnaire and images of 20 common staples known to be rich in FODMAPs. A total of 208 schoolchildren aged 8-18 years old participated. A proportion of 38.0% of children reported GI symptoms, with abdominal pain (33%) being the most common complaint followed by abdominal distension (24%) and nausea (23%). The majority of children who reported intolerances to FODMAP-containing foods were intolerant to less than two food groups (76%). While vegetables and legumes (26%), particularly black beans (11%) and onions (7%), emerged as the most common group of triggers, milk (12%) stood out as the single food most frequently associated with GI symptoms. In conclusion, there was a high prevalence of FODMAPs intolerance among schoolchildren. Larger studies are recommended to confirm these findings and to inform possible dietary interventions to reduce the effect of FODMAPs on schoolchildren.
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BACKGROUND: Therapy-resistant constipation often is a frustrating clinical entity recognised by the persistence of infrequent and painful bowel movements faecal incontinence and abdominal pain despite intensive treatment. It is important to clearly define therapy-resistant constipation before children are subjected to invasive diagnostic and therapeutic procedures. AIM: To conduct a systematic review determining how paediatric interventional studies define therapy-resistant constipation. METHOD: We searched CENTRAL, MEDLINE, Embase, WHO ICTR and ClinicalTrials.gov. Studies that included patients with therapy-resistant constipation were identified. Data were extracted on criteria used for defining therapy-resistant constipation and reported using a meta-narrative approach highlighting areas of convergence and divergence in the findings. RESULTS: A total of 1553 abstracts were screened in duplicate, and 47 studies were included in the review. There were at least seven definitions used in the paediatric literature to define medically resistant constipation. The term intractable was used in 24 articles and 21 used the term refractory to describe therapy-resistant constipation. Out of them, only 14 articles have attempted to provide an explicit definition including a predefined time and prior therapy. There were 10 studies without a clear definition for therapy-resistant constipation. The duration before being diagnosed as therapy-resistant constipation varied from 1 months to 2 years among studies. Seven studies employed the Rome criteria (Rome III or Rome IV) to characterising constipation while five adopted the Rome III and European and North American paediatric societies definition of paediatric gastroenterology, hepatology and nutrition guideline of management of constipation in children. CONCLUSION: The current literature has no explicit definition for therapy-resistant constipation in children. There is a need for a detailed consensus definition to ensure consistency of future research and to avoid unnecessary and maybe even harmful, invasive diagnostic and therapeutic interventions.
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Constipação Intestinal , Humanos , Constipação Intestinal/terapia , Constipação Intestinal/diagnóstico , Constipação Intestinal/tratamento farmacológico , Criança , Adolescente , Pré-EscolarRESUMO
BACKGROUND: The diagnosis of disorders of gut-brain interaction (DGBI) in children is exclusively based on clinical criteria called the Rome criteria. The inter-rater reliability (IRR) measures how well two raters agree with a diagnosis using the same diagnostic tool. Previous versions of the Rome criteria showed only fair to moderate IRR. There have been no studies assessing the IRR of the current edition of the pediatric Rome criteria (Rome IV). This study sought to investigate the IRR of the pediatric Rome IV criteria and compare its reliability with the previous versions of the Rome criteria. We hypothesized that changes made to Rome IV would result in higher IRR than previous versions. METHODS: This study used the same methodology as the previous studies on Rome II and III, including identical clinical vignettes, number of raters, and levels of expertise. Participants included 10 pediatric gastroenterology fellows and 10 pediatric gastroenterology specialists. IRR was assessed using the percentage of agreement and Cohen's kappa coefficient to account for possible agreement by chance. RESULTS: The average IRR percentage of agreement using the Rome IV criteria was 55% for pediatric gastroenterologists and 48.5% for fellows, indicating moderate agreement (k = 0.54 for specialists, k = 0.47 for fellows). The results demonstrated higher percentages of agreement and kappa coefficients compared to the Rome II and III criteria. CONCLUSIONS: The findings demonstrate improved reliability in Rome IV compared to Rome II and III, suggesting that the changes incorporated into the Rome IV criteria have enhanced diagnostic consistency. Despite the advancements, the reliability is still moderate, indicating the need for further refinement of future versions of the Rome criteria.
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Gastroenteropatias , Humanos , Reprodutibilidade dos Testes , Criança , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Eixo Encéfalo-Intestino/fisiologia , Pediatria/métodos , Feminino , Masculino , Variações Dependentes do ObservadorRESUMO
OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 µg, B: 18 or 36 µg, or C: 36 or 72 µg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 µg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 µg] and 2.86 in 12- to 17-year-olds [72 µg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.
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Constipação Intestinal , Agonistas da Guanilil Ciclase C , Peptídeos , Humanos , Constipação Intestinal/tratamento farmacológico , Criança , Adolescente , Método Duplo-Cego , Feminino , Masculino , Peptídeos/uso terapêutico , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Resultado do Tratamento , Agonistas da Guanilil Ciclase C/uso terapêutico , Agonistas da Guanilil Ciclase C/administração & dosagem , Defecação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/administração & dosagemRESUMO
OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7-17 years old with irritable bowel syndrome with constipation (IBS-C). METHODS: In this 4-week, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study, children with IBS-C were randomized to once-daily placebo or linaclotide (Dose A: 18 or 36 µg, B: 36 or 72 µg, and C: 72 µg or 145 µg, or 290 µg); those aged 7-11 years in a 1:1:1:1 allocation based on weight (18 to <35 kg:18 µg, 36 µg, or 72 µg; or ≥35 kg: 36 µg, 72 µg, or 145 µg), and those aged 12-17 years in a 1:1:1:1:1 allocation (the higher option of Doses A-C or 290 µg). The primary efficacy endpoint was a change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed. RESULTS: Efficacy, safety, and tolerability were assessed in 101 patients. In the intent-to-treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290 µg: 3.26) compared with placebo. The most reported treatment-emergent adverse events were diarrhea and pain, with most cases being mild and none being severe. CONCLUSIONS: Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.
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Síndrome do Intestino Irritável , Peptídeos , Criança , Humanos , Adolescente , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Resultado do Tratamento , Constipação Intestinal/tratamento farmacológico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Método Duplo-CegoRESUMO
BACKGROUND: Linaclotide, a guanylate cyclase C agonist, has been approved in the USA for the treatment of chronic idiopathic constipation and irritable bowel syndrome with predominant constipation in adults. We aimed to assess the efficacy and safety of linaclotide in paediatric patients aged 6-17 years with functional constipation. METHODS: This randomised, double-blind, placebo-controlled, multicentre, phase 3 study was done at 64 clinic or hospital sites in seven countries (USA, Canada, Israel, Italy, the Netherlands, Ukraine, and Estonia). Patients aged 6-17 years who met modified Rome III criteria for functional constipation were randomly assigned (1:1), with a block size of four and stratified by age (6-11 years and 12-17 years), to receive either oral linaclotide 72 µg or placebo once daily for 12 weeks. Participants, investigators, and data assessors were masked to assignment. The primary efficacy endpoint was change from baseline (CFB) in the 12-week frequency rate of spontaneous bowel movements (SBMs; occurring in the absence of rescue medication on the calendar day of or before the bowel movement) per week and the secondary efficacy endpoint was CFB in stool consistency over the 12-week treatment period; efficacy and safety were analysed in all patients in the randomised population who received at least one dose of study intervention (modified intention-to-treat population and safety population, respectively). The study is registered with ClinicalTrials.gov, NCT04026113, and the functional constipation part of the study is complete. FINDINGS: Between Oct 1, 2019, and March 21, 2022, 330 patients were enrolled and randomly assigned to linaclotide (n=166) or placebo (n=164). Two patients in the linaclotide group did not receive any treatment; thus, efficacy and safety endpoints were assessed in 328 patients (164 patients in each group). 293 (89%) patients completed the 12-week treatment period (148 in the linaclotide group and 145 in the placebo group). 181 (55%) of 328 patients were female and 147 (45%) were male. At baseline, the mean frequency rate for SBMs was 1·28 SBMs per week (SD 0·87) for placebo and 1·16 SBMs per week (0·83) for linaclotide, increasing to 2·29 SBMs per week (1·99) for placebo and 3·41 SBMs per week (2·76) for linaclotide during intervention. Compared with placebo (least-squares mean [LSM] CFB 1·05 SBMs per week [SE 0·19]), patients treated with linaclotide showed significant improvement in SBM frequency (LSM CFB 2·22 SBMs per week [0·19]; LSM CFB difference 1·17 SBMs per week [95% CI 0·65-1·69]; p<0·0001). Linaclotide also significantly improved stool consistency over placebo (LSM CFB 1·11 [SE 0·08] vs 0·69 [0·08]; LSM CFB difference 0·42 [95% CI 0·21-0·64]; p=0·0001). The most reported treatment-emergent adverse event (TEAE) by patients treated with linaclotide was diarrhoea (seven [4%] of 164 vs three [2%] of 164 patients in the placebo group) and by patients treated with placebo was COVID-19 (five [3%] vs four [2%] in the linaclotide group). The most frequent treatment-related TEAE was diarrhoea (linaclotide: six [4%] patients; placebo: two [1%] patients). One serious adverse event of special interest (treatment-related severe diarrhoea resulting in dehydration and hospitalisation) occurred in a female patient aged 17 years in the linaclotide group; this case resolved without sequelae after administration of intravenous fluids. No deaths occurred during the study. INTERPRETATION: Linaclotide is an efficacious and well tolerated treatment for functional constipation in paediatric patients and has subsequently been approved by the US Food and Drug Administration for this indication. FUNDING: AbbVie and Ironwood Pharmaceuticals.
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Constipação Intestinal , Peptídeos , Adulto , Humanos , Masculino , Feminino , Criança , Resultado do Tratamento , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/induzido quimicamente , Peptídeos/efeitos adversos , Diarreia/induzido quimicamente , Método Duplo-CegoRESUMO
BACKGROUND: Multiple psychological factors influence disorders of gut-brain interaction (DGBIs). We aimed to evaluate psychological distress in Colombian schoolchildren with and without DGBIs. METHODS: We included children ages 8-18 years without organic medical conditions from largest regional public schools in Colombia. Children completed Spanish versions of Rome III diagnostic questionnaire for DGBIs, State Trait Anxiety Inventory for Children (STAIC), Children's Somatization Inventory (CSI), and a measure of coping efficacy. These data, demographic and socioeconomic characteristics, were compared between children with DGBIs and healthy peers. Exploratory analyses investigated differences between youth with symptoms of functional abdominal pain disorders (FAPDs) compared with healthy peers. KEY RESULTS: Of 1496 children, 281 (mean age 12.9 ± 2.2 years, 49.8% females) self-reported criteria for DGBIs and 125 reported (44.5%) FAPDs. Children with DGBIs had higher trait anxiety, emotional sensitivity, somatization including GI, non-GI, pain-related, and non-pain-related subscales (p < 0.001 each) and lower coping efficacy (p = 0.02) compared to healthy peers. Females had higher trait anxiety and somatization (p = 0.04 and p = 0.005, respectively). State and trait anxiety and coping efficacy differed based on location in children with DGBIs (p = 0.02, p = 0.03, and p < 0.001, respectively). Children with FAPDs had higher trait anxiety (p = 0.02) and somatization (p < 0.001) compared to healthy youth. CONCLUSIONS & INFERENCES: Children with DGBIs had higher anxiety, emotional sensitivity, and somatization, and lower coping efficacy compared with healthy youth. This highlights the importance of appraising psychological distress characteristics as well as incorporating conflict resolution, assertiveness training, and resilience building during the treatment of DGBIs.
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Dor Abdominal , Ansiedade , Criança , Feminino , Adolescente , Humanos , Masculino , Dor Abdominal/psicologia , Ansiedade/diagnóstico , Inquéritos e Questionários , Adaptação Psicológica , EncéfaloRESUMO
INTRODUCTION: To date, no international guidelines have been published for the treatment of paediatric functional abdominal pain disorders (FAPDs), subcategorised into functional abdominal pain-not otherwise specified (FAP-NOS), irritable bowel syndrome (IBS), functional dyspepsia and abdominal migraine (AM). We aim for a treatment guideline, focusing on FAP-NOS, IBS and AM, that appreciates the extensive array of available therapies in this field. We present the prospective operating procedure and technical summary protocol in this manuscript. METHODS: Grading of Recommendations, Assessment, Development and Evaluation (GRADE) will be followed in the development of the guideline, following the approach as laid out in the GRADE handbook, supported by the WHO. The Guideline Development Group (GDG) is formed by paediatric gastroenterologists from both the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, as well as the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Also, one clinical psychologist with expertise in FAPDs is a voting member in the GDG. A final consensus list of treatment options is translated into 'patient, intervention, comparison, outcome' format options. Prospective agreement on the magnitude of health benefits or harms categories was reached through a Delphi process among the GDG to support grading of the literature.There will be a detailed technical evidence review with randomised controlled trial data that will be judged for risk of bias with the Cochrane tool. Recommendations are preferably based on GRADE but could also be best practice statements following the available evidence. A full Delphi process will be used to make recommendations using online response systems. This set of procedures has been approved by all members of the GDG.
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Dispepsia , Gastroenterologia , Síndrome do Intestino Irritável , Transtornos de Enxaqueca , Criança , Humanos , Dor Abdominal , Dispepsia/tratamento farmacológico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Guias de Prática Clínica como AssuntoRESUMO
Down syndrome (DS) is associated with multiple medical comorbidities. Perhaps related to such, caregivers of individuals with DS report lower quality of life (QoL) compared to individuals without DS. It has been shown that disorders of gut-brain interaction (DGBI) such as functional constipation (FC) and irritable bowel syndrome (IBS) are common in individuals with DS. We measured caregiver-reported QoL in individuals with DS with a DGBI and compared them to individuals with DS without a DGBI via a cross-sectional national survey. All measures of QoL were lower in those with DS who meet criteria for a DGBI compared to those with DS without a DGBI. Males and females with DS and at least one DGBI had similar QoL scores. While FC was the most common DGBI seen in individuals with DS, there was no difference in any aspect of QoL in subjects with FC when compared to individuals with other DGBIs. However, all measures of QoL were lower in those with IBS compared to individuals with other DGBIs. These findings suggest that management of gastrointestinal symptoms from DGBIs, particularly IBS, may serve as a target for increasing QoL in a notable subset of individuals with DS.
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Encefalopatias , Síndrome de Down , Síndrome do Intestino Irritável , Masculino , Feminino , Criança , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/diagnóstico , Qualidade de Vida , Síndrome de Down/complicações , Estudos Transversais , Constipação Intestinal/complicações , Constipação Intestinal/diagnóstico , Encéfalo , Inquéritos e QuestionáriosRESUMO
BACKGROUND: There are no validated measures to assess chronic abdominal pain (AP) in clinical trials of children with disorders of gut-brain interaction (DGBIs). Currently used AP measures are extrapolated from studies on adults or children with acute AP. The primary aim of the study was to assess the commonly used pain scales in children with DGBIs. The secondary aim of the study was to compare specific pain measures with the overall subjective assessment of AP well-being in children. METHODS: A sub-study from multicenter crossover randomized controlled trial (RCT) was conducted. Children with AP-DGBIs completed daily diaries for 7 weeks. It included three widely used AP scales: the numeric rating scale (NRS), the visual analog scale (VAS), the Faces Pain Scale Revised (FPS-R), and a global improvement question. Strength of correlations among scales and questions was assessed with the Pearson correlation coefficient (r). KEY RESULTS: Thirty subjects completed the study. Children completed 4975 of 5880 (84.6%) pain and global responses. The VAS and NRS had strongest correlation among them, r = 0.893 (p < 0.001). The FPS-R also demonstrated strong correlations with the VAS r = 0.773 (p < 0.001), NRS = 0.783 (p < 0.001). The three scales exhibited weaker but significant correlations with the global question. Strong correlations were consistent when stratified by age groups. CONCLUSION: This is the first study to assess the most used AP scales in children with DGBIs. It supports the Rome IV recommendations on using the VAS and NRS scales. It also suggests that FPS-R, that was not part of Rome IV, can also be used in RCTs. Congruent with the biopsychosocial model, there was a weaker correlation between AP measures and the global question. This suggests that the global question measures more domains than AP alone and that it should also be incorporated in DGBIs RCTs in children.
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Dor Abdominal , Encéfalo , Adulto , Humanos , Criança , Dor Abdominal/diagnóstico , Medição da Dor , Reprodutibilidade dos TestesRESUMO
Cannabinoid hyperemesis syndrome (CHS) is associated with tetrahydrocannabinol, and rarely has been reported with cannabidiol. Cannabidiol is used in treatment-refractory epilepsy. This is a case of a pediatric patient with Lennox-Gastaut syndrome on cannabidiol, who was started on the ketogenic diet with significant seizure reduction. However, within 6 months he developed monthly bouts of severe emesis unresponsive to conventional anti-emetic therapy. Based on the stereotypical nature of his vomiting episodes, CHS was suspected. Cannabidiol was discontinued and within 2 months his emesis resolved. He has had no increase in seizure frequency or hospitalizations for emesis since cannabidiol was discontinued nearly 1 year ago. This is the first case of CHS secondary to cannabidiol for refractory epilepsy reported in the literature. We review the mechanism by which cannabidiol is believed to reduce seizures and be both anti- and pro-emetic, mainly through interactions with cannabinoid receptors and transient receptor channels.
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Background/Aims: Disorders of brain-gut interaction (DGBIs) are present in adults and children around the world. Down syndrome (DS) is the most common chromosomal condition in humans. While DS has associations with many organic medical conditions, the frequency of DGBIs in children and adolescents with DS has not previously been studied. We assess the rate of DGBIs in children and adolescents 4-18 years of age with DS in the United States using the Rome IV criteria by caregiver report. Methods: This is a cross-sectional national survey study in which caregivers (n = 114) of children with DS completed an online survey about their child's gastrointestinal symptoms and quality of life (QoL). Results: Using the Rome IV parent-report diagnostic questionnaire, 51.8% of children met symptom-based criteria for at least 1 DGBI. Functional constipation (36.0%) and irritable bowel syndrome (14.9%) were the most common disorders identified. QoL was lower in children with at least 1 disorder as compared to children who did not meet criteria for any disorders (mean QoL = 62.3 vs mean QoL = 72.9, P < 0.001). Almost all children with DS and concomitant autism (87.5%) had at least 1 DGBI. Conclusions: DGBIs are common in children with DS and are associated with diminished QoL.
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Most children with functional constipation (FC) improve with conventional treatments. However, a proportion of children have poor treatment outcomes. Management of intractable FC may include botulinum toxin injections, transanal irrigation, antegrade enemas, colonic resections, and in some cases sacral nerve stimulation (SNS). SNS is surgically placed, not readily available and expensive. Posterior tibial nerve stimulation (PTNS) allows transmission of electronic impulses and retrograde stimulation to the sacral nerve plexus in a portable, simple and non-invasive fashion. To assess the efficacy and safety of transcutaneous PTNS for the treatment of FC in children. Single-center, prospective interventional study. Children 4-14 years with Rome IV diagnosis of FC received ten daily PTNS (30 min/day) sessions. Electrodes placed over skin of ankle. Strength of stimulus was below pain threshold. Outcomes were assessed during treatment and 7 days after. Twenty-three subjects enrolled. Two children excluded (acute gastroenteritis, COVID-19 contact). Twenty completed the study (4-14 years), (8.4 ± 3.2 years, 71.4% female). We found significant improvement in the consistency of bowel movements (BM) (p = 0.005), fecal incontinence (FI) (p = 0.005), abdominal pain presence (p = < 0.001) and intensity (p = 0.005), and a significant for improvement in blood in stools (p = 0.037). There was 86.3% improvement in abdominal pain. 96.7% reported treatment satisfaction. Only one child required rescue therapy. CONCLUSION: We found significant improvement in stool consistency, FI, abdominal pain, and hematochezia. This suggests that transcutaneous PTNS could be a promising noninvasive treatment for FC in children. Large studies are needed. WHAT IS KNOWN: ⢠Functional constipation is one of the most common disorders in children. ⢠Current management of functional constipation consists of an integrative approach that includes medications, diet and behavioral strategies. WHAT IS NEW: ⢠Posterior tibial nerve stimulation is a novel noninvasive and easy to use therapy that can improve stool consistency, fecal incontinence and blood in stools.
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COVID-19 , Incontinência Fecal , Estimulação Elétrica Nervosa Transcutânea , Criança , Humanos , Feminino , Masculino , Incontinência Fecal/terapia , Estudos Prospectivos , Nervo Tibial/fisiologia , Resultado do Tratamento , Constipação Intestinal/terapia , Dor Abdominal , Qualidade de VidaRESUMO
Background: Functional Abdominal Pain disorders (FAPDs) are a group of heterogeneous gastrointestinal disorders with unclear pathophysiology. In children, FAPDs are more common in the winter months than summer months. The possible influence of school stressors has been proposed. Previously, our group showed differences in bacterial relative abundances and alpha diversity in the gut microbiome and its relationship with stressors in a cross-sectional evaluation of children suffering from FAPDs compared to a healthy control group. We present longitudinal data to assess whether the gut microbiome changes over school terms in the control and FAPDs groups. Methods: The longitudinal study included children with FAPDs (n = 28) and healthy controls (n = 54). Gastrointestinal symptoms, as well as stool microbiome, were assessed in both groups. Stool samples were serially collected from all participants during both the school term and summer vacation. The stool samples were subjected to total genomic extraction, 16S rRNA amplicon sequencing, and bioinformatics analysis. The gut microbiome was compared at school and during vacation. Other metrics, alpha diversity, and beta diversity, were also compared between the two school terms in every group. Results: In the healthy group, there were differences in microbiome composition between school terms and summer vacation. Conversely, we found no differences in the FAPDs group between the two terms. The healthy control group revealed differences (p-value < 0.05) in 55 bacterial species between the school term and vacation. Several of the differentially abundant identified bacteria were involved in short-chain fatty acids production (SCFAs), inflammation reduction, and gut homeostasis. Alpha diversity metrics, such as the Shannon index, were different in the control group and remained unchanged in the FAPDs group. Conclusion: Although preliminary, our findings suggest that the gut microbiome is static in FAPDs. This compares with a more dynamic healthy gut microbiome. Further studies are warranted to corroborate this and understand the interplay between stress, symptoms, and a less diverse and static microbiome. Future studies will also account for different variables such as diet and other patient demographic criteria that were missing in the current study.
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BACKGROUND & AIMS: Many studies have assessed risk factors of irritable bowel syndrome (IBS) and other abdominal pain-related disorders of gut-brain interaction (AP-DGBI); however, the role of these factors is unclear due to heterogeneous study designs. The aim of this systematic review was to extensively evaluate the literature and determine clinical risk and protective factors for the presence and persistence of AP-DGBI in children and adults. METHODS: A PubMed search identified studies investigating potential risk and protective factors for AP-DGBI in adults and children. Inclusion criteria included fully published studies with a control group; exclusion criteria included poor-quality studies (using a validated scale). For each factor, the proportion of studies that found the factor to be a risk factor, protective factor, or neither was summarized. The number of studies, diagnostic criteria, number of subjects, and average study quality rating provided further context. Whenever possible, a meta-analysis generated pooled odds ratios or mean difference. RESULTS: The systematic review included 348 studies. Female sex, gastroenteritis, abuse, stress, psychological disorders, somatic symptoms, and poor sleep were consistent risk factors for developing AP-DGBI in adults and children. In adults, additional risk factors included obesity, smoking, and increased use of medical resources. Protective AP-DGBI factors in adults included social support and optimism; no studies for protective factors were found for children. CONCLUSIONS: There are multiple risk factors for AP-DGBI in adults and children. These include female sex, gastroenteritis, abuse, stress, poor sleep, obesity, psychological disorders, and somatic symptoms. Additional studies are needed in children, on protective factors, and on factors associated with persistence of AP-DGBI.
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Gastroenterite , Gastroenteropatias , Síndrome do Intestino Irritável , Sintomas Inexplicáveis , Dor Abdominal/epidemiologia , Dor Abdominal/etiologia , Adulto , Encéfalo , Criança , Feminino , Gastroenterite/complicações , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Humanos , Síndrome do Intestino Irritável/complicações , Obesidade/complicações , Fatores de RiscoRESUMO
INTRODUCTION: Children with joint hypermobility, postural orthostatic tachycardia syndrome, and orthostatic hypotension report autonomic symptoms such as dizziness, nausea, headaches, and palpitations. It is unclear if there is a pathophysiological link between connective tissue disorders and autonomic symptoms. There is no published data on the prevalence of disorder at the community level. PRIMARY OBJECTIVE: To assess the prevalence of joint hypermobility, orthostatic hypotension, and postural or thostatic tachycardia syndrome in children. SECONDARY OBJECTIVE: To determine the relationship bet ween joint hypermobility, orthostatic hypotension, and postural orthostatic tachycardia syndrome. PATIENTS AND METHOD: Participants aged 10 to 18 years were selected from public schools in three Colombian cities. The surveys included historical questions on the incidence of dizziness, nausea, headache, tremor, blurred vision, vertigo, anxiety, near syncope and syncope, sweating, palpitations triggered by standing in the two months prior to the investigation. Each of these signs and symptoms was also assessed during the recumbency (10 minutes) and standing (2, 5 and 10 minutes) phases of the investigation. HR and BP measurements were obtained at the same intervals. Joint mobility was measured with a mechanical goniometer and assessed with the Beighton score. RESULTS: Prevalence of joint hyperlaxity: 87 of 306 (28.4%). Prevalence of orthostatic hypotension: 5 of 306 (1.6%). Prevalen ce of postural orthostatic tachycardia syndrome: 6 of 306 (2.0%). Of 87 children with joint hyperlaxi ty, only 1 child had joint hyperlaxity at the same time as postural hypotension (1.2%) (p = 0.6735), and 1 child had joint hyperlaxity and postural orthostatic tachycardia syndrome simultaneously (1.2%) (p = 0.5188). CONCLUSION: Children with joint hyperlaxity did not have a higher prevalence of postural orthostatic tachycardia syndrome and orthostatic hypotension. It seems unlikely that con nective tissue disorders are responsible for most cases of postural orthostatic tachycardia syndrome and orthostatic hypotension in the community. Of note, the pathophysiology of postural orthostatic tachycardia syndrome and orthostatic hypotension requires further investigation.