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Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population.
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Erros Inatos do Metabolismo dos Carboidratos , Humanos , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/genética , Sacarose Alimentar , Amido , Complexo Sacarase-Isomaltase/genética , Complexo Sacarase-Isomaltase/deficiênciaRESUMO
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
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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OBJECTIVES: Rumination syndrome (RS) beginning in early childhood or infancy is understudied and challenging to treat. Our objective is to compare the characteristics and outcomes of early-onset (EO) and adolescent-onset (AO) patients with RS. METHODS: We conducted an ambidirectional cohort study of children diagnosed with RS at our institution. Patients were included in two groups: EO (RS symptom onset ≤5 years and diagnosis ≤12 years) and AO (onset >12 years). Patient characteristics, severity, and outcomes were compared between the groups. RESULTS: We included 49 EO and 52 AO RS patients. The median ages of symptom onset and diagnosis in EO were 3.5 and 6 years, respectively; AO, 14.5 and 15 years. EO RS had a slight male predominance while AO was predominantly female (p = 0.016). EO patients were more likely to have developmental delay (24% vs. 8%, p = 0.029) and less likely to have depression (0% vs. 23%, p < 0.001) or anxiety (14% vs. 40%, p = 0.004). At baseline, EO RS was less severe than AO RS: EO RS had greater regurgitation frequency (p < 0.001) but lower vomiting frequency (p = 0.001), resulting in less meal skipping (p < 0.001), reliance on tube feeding or parenteral nutrition (p < 0.001), and weight loss (p = 0.035). EO RS symptoms improved over time: at follow-up, patients had lower regurgitation (p < 0.001) and vomiting frequency (p < 0.001) compared to baseline. CONCLUSION: EO RS is clinically distinct from AO RS, with differences in sex distribution, comorbid conditions, and severity of initial presentation. The pathogenesis and natural history of EO RS may be distinct from that of AO RS.
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Síndrome da Ruminação , Criança , Humanos , Masculino , Pré-Escolar , Feminino , Adolescente , Estudos de Coortes , Idade de Início , Redução de Peso , Vômito/etiologiaRESUMO
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
BACKGROUND: For children with constipation and fecal incontinence treated with antegrade continence enemas (ACE), a fluoroscopic study with contrast administered via appendicostomy/cecostomy can define the anatomy of the colon and simulate the flush to investigate associated symptoms or inadequate response. These studies can at times show retrograde flow into the small intestine. Our objective was to investigate the significance of this finding. METHODS: We reviewed studies at our institution with contrast administered via appendicostomy/cecostomy in children treated with ACE, identifying those demonstrating retrograde flow of contrast. We recorded demographics, medical history, interventions, and outcomes. RESULTS: We identified 162 studies (52% male, median age 10.7 years) with contrast via appendicostomy (76%) or cecostomy (24%). Diagnoses included anorectal malformation (38%), spinal cord anomaly (26%), functional constipation (24%), colonic dysmotility (18%), and Hirschsprung disease (12%). Fifty-nine (36%) studies showed retrograde flow: 28/59 children (48%) were not responding adequately and 21/59 (36%) had symptoms with ACE. Children with retrograde flow were more likely to have symptoms with ACE than those without (36% vs. 15%, p < 0.01). Fourteen children underwent interventions for this finding, including administering flushes more distally (4/8 responded), changing positioning of the child during flush administration, (1/2 responded), and slowing administration (1/1 responded). Retrograde flow was associated with younger age (p < 0.01), not sex or underlying diagnosis. CONCLUSION: Identifying retrograde flow during studies with contrast administered via appendicostomy/cecostomy can be useful for children with a poor response or symptoms associated with ACE, as adjustments to the mechanics of the flush can alleviate those symptoms. LEVEL OF EVIDENCE: Prognostic study, Level III.
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OBJECTIVE: We aimed to compare symptom frequency and severity in children with functional abdominal pain disorders (FAPDs) and to evaluate anxiety, quality of life (QoL) and global health during Coronavirus disease 2019 (COVID-19) related quarantine and after 17 months. METHODS: Children diagnosed with FAPDs between October 2019 and February 2020 at 5 different centers were enrolled and prospectively interviewed during the COVID-19 quarantine and 17 months later when schools, hospital services, and routine activities had re-opened to the public. The patients were asked to complete the Rome IV questionnaire, the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core Scale, the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and global health questionnaires. Data about COVID-19 infection and its clinical outcome were also collected. RESULTS: Ninety-nine out of 180 (55%) children completed the follow-up. The number of patients reporting a worsening of their symptoms was significantly higher at follow-up when compared to the quarantine period (24/99 [24.2%] vs. 12/99 [12.1%]; p = 0.04). The PedsQL 4.0 subtotal score at follow-up significantly decreased at 17 months of follow-up (65.57 [0-100]) when compared to the quarantine (71 [0-100], p = 0.03). Emotional functioning was the most significantly reduced (Follow-up: 64.7 [0-100] vs. Quarantine: 75 [0-100]; p = 0.006). We did not identify significant differences in symptoms and QoL between COVID-19 infected children and the remaining cohort at the two time points. CONCLUSIONS: An improvement of symptoms and QoL was observed during the quarantine, followed by a worsening at-follow-up. These findings reinforce the hypothesis that the nest effect overweighted COVID-19 fears during the quarantine and highlight the importance of psychological factors in symptom exacerbation.
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Dor Abdominal , Ansiedade , COVID-19 , Qualidade de Vida , Quarentena , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , COVID-19/complicações , Criança , Feminino , Masculino , Dor Abdominal/etiologia , Adolescente , Quarentena/psicologia , Ansiedade/epidemiologia , Seguimentos , Estudos Prospectivos , SARS-CoV-2 , Inquéritos e Questionários , Índice de Gravidade de Doença , PandemiasRESUMO
OBJECTIVES: For children with intractable functional constipation (FC), there are no evidence-based guidelines for subsequent evaluation and treatment. Our objective was to assess the practice patterns of a large, international cohort of pediatric gastroenterologists. METHODS: We administered a survey to physicians who attended the 2nd World Congress of Pediatric Neurogastroenterology and Motility held in Columbus, Ohio (USA) in September 2023. The survey included 29 questions on diagnostic testing, nonpharmacological and pharmacological treatment, and surgical options for children with intractable FC. RESULTS: Ninety physicians from 18 countries completed the survey. For children with intractable FC, anorectal manometry was the most commonly used diagnostic test. North American responders were more likely than Europeans to use stimulant laxatives (97% vs. 77%, p = 0.032), prosecretory medications (69% vs. 8%, p < 0.001), and antegrade continence enemas (ACE; 83% vs. 46%, p = 0.009) for management. Europeans were more likely than North Americans to require colonic transit testing before surgery (85% vs. 30%, p < 0.001). We found major differences in management practices between Americans and the rest of the world, including use of prosecretory drugs (73% vs. 7%, p < 0.001), anal botulinum toxin injections (81% vs. 58%, p = 0.018), ACE (81% vs. 58% p = 0.018), diverting ileostomies (56% vs. 26%, p = 0.006), and colonic resections (42% vs. 16%, p = 0.012). No differences were found when respondents were compared by years of experience. CONCLUSIONS: Practice patterns in the evaluation and treatment of children with intractable FC differ widely among pediatric gastroenterologists from around the world. A clinical guideline regarding diagnostic testing and surgical decision-making is needed.
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Constipação Intestinal , Padrões de Prática Médica , Humanos , Constipação Intestinal/terapia , Constipação Intestinal/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Criança , Laxantes/uso terapêutico , Inquéritos e Questionários , Manometria/estatística & dados numéricos , Feminino , Masculino , Gastroenterologia/estatística & dados numéricosRESUMO
OBJECTIVES: Rumination syndrome (RS) is challenging to diagnose, which can lead to diagnostic delays. Our objective was to evaluate the length of time from RS symptom onset to diagnosis in patients referred to our institution and to examine whether this duration predicts treatment outcomes. METHODS: We conducted a review of patients with RS evaluated at our institution. Data were collected from chart review and patient/family reported questionnaires. We evaluated the time from symptom onset to diagnosis over time and whether it was associated with symptom resolution. RESULTS: We included 247 patients with RS (60% female, median age of 14 years, interquartile range [IQR]: 9-16 years). The median age at symptom onset was 11 years (IQR: 5-14 years) and median age at diagnosis was 13 years (IQR: 9-15 years) for a median duration of 1 year (IQR: 0-3 years) between symptom onset and diagnosis. Length of time between symptom onset and diagnosis did not change significantly at our institution from 2016 to 2022. Among the 164 children with outcome data, 47 (29%) met criteria for symptom resolution after treatment. A longer time to diagnosis was associated with a lower likelihood of symptom resolution after treatment (p = 0.01). CONCLUSION: In our experience, the time to RS diagnosis after symptom onset is shorter than previously described. A longer delay in diagnosis is associated with lower likelihood of symptom resolution after treatment, emphasizing the importance of a prompt recognition of rumination symptoms and a timely diagnosis.
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OBJECTIVES: We have had success treating children with severe rumination syndrome using a multidisciplinary intensive outpatient program (IOP) involving multiple treatment sessions daily. During the coronavirus disease 2019 (COVID-19) pandemic, we temporarily transitioned care to telemedicine. The objective of this study is to compare outcomes of patients with rumination syndrome who completed IOP treatment in person versus by telemedicine. METHODS: We performed a retrospective review of patients diagnosed with rumination syndrome who participated in IOP treatment from 2018 to 2020. Similar treatment sessions were performed involving medical and behavioral techniques provided by a multidisciplinary team during telemedicine visits. Families/patients were asked to complete a survey outlining their child's current rumination symptom severity and review the IOP. RESULTS: We included 34 patients (79% F, median age 15 years, range 7-19 years) who completed IOP treatment. Twenty-six patients (76%) were treated in person and 8 patients (24%) by telemedicine. For patients treated in person, 76% (19/25) had improvement in symptoms while 16% (4/25) had complete resolution of symptoms. For patients treated by telemedicine, 88% (7/8) had improvement in their symptoms. There were no significant differences between groups in likelihood of improvement. Overall, 78% (18/23) preferred in person therapy while 17% (4/23) did not have a preference. All 18 of the in-person cohort who completed follow-up surveys preferred in-person management. CONCLUSIONS: Multidisciplinary intensive outpatient treatment for children and adolescents with severe rumination syndrome is effective. Although telemedicine may be an alternative to in person therapy, majority of families prefer in person visits.
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COVID-19 , Síndrome da Ruminação , Telemedicina , Adolescente , Criança , Humanos , Adulto Jovem , Adulto , COVID-19/terapia , Pacientes Ambulatoriais , Assistência Ambulatorial , Telemedicina/métodosRESUMO
OBJECTIVES: Rumination syndrome (RS) can be challenging to treat and data on treatment outcomes in children are limited. The objective of this study was to evaluate outcomes of children with RS treated with tailored outpatient and inpatient strategies. METHODS: We performed a retrospective cohort study of children <18 years old with RS evaluated at our institution from 2018 to 2020. At our institution, we use a multidisciplinary, tiered approach to treatment based on presentation severity. Children with RS either undergo outpatient treatment program (OP) or participate in an intensive outpatient program (IOP) or an intensive inpatient program (IP). We reviewed baseline characteristics and assessed severity (including frequency of regurgitation/vomiting, route of nutrition, and weight loss) at baseline, at completion of treatment, and at a follow-up time point. RESULTS: We included 171 children with RS (64% female, median age 13 years, interquartile range (IQR) 10-15), 123 of whom had post-treatment data after completing OP, IOP, or IP. At baseline, 66% of patients were vomiting daily and 40% were losing weight. After treatment, 72% of OP, 95% of IOP, and 96% of IP patients reported that symptoms were better or fully resolved compared to baseline. In all 3 treatment groups, patients were vomiting, losing weight, and skipping meals significantly less after treatment compared to baseline. At follow-up (median 5.3 months), 86% of IOP and 66% of IP patients had symptoms that remained better or resolved. CONCLUSIONS: RS can cause severe symptoms, impacting nutritional status and school participation. However, multidisciplinary care in a tiered approach leads to significant symptomatic improvement.
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Síndrome da Ruminação , Adolescente , Criança , Feminino , Humanos , Masculino , Assistência Ambulatorial , Estudos Retrospectivos , Resultado do Tratamento , Vômito/etiologia , Vômito/terapiaRESUMO
OBJECTIVES: The objective of this study is to investigate long-term outcomes of antegrade continence enema (ACE) treatment in children with constipation or fecal incontinence. METHODS: Prospective cohort study including pediatric patients with organic or functional defecation disorders who started ACE treatment. Data were collected at baseline and at follow-up (FU) from 6 weeks until 60 months. We assessed parent and patient-reported gastrointestinal health-related quality of life (HRQoL) using the Pediatric Quality of Life Inventory Gastrointestinal Symptoms Module (PedsQL-GI), gastrointestinal symptoms, adverse events, and patient satisfaction. RESULTS: Thirty-eight children were included (61% male, median age 7.7 years, interquartile range 5.5-12.2). Twenty-two children (58%) were diagnosed with functional constipation (FC), 10 (26%) with an anorectal malformation, and 6 (16%) with Hirschsprung disease. FU questionnaires were completed by 22 children (58%) at 6 months, 16 children (42%) at 12 months, 20 children (53%) at 24 months, and 10 children (26%) at 36 months. PedsQL-GI scores improved overall with a significant increase at 12- and 24-month FU for children with FC and a significant increase in parent reported PedsQL-GI score at 36-month FU for children with organic causes. Minor adverse events, such as granulation tissue, were reported in one-third of children, and 10% of children needed a surgical revision of their ACE. The majority of all parents and children reported that they would "probably" or "definitely" choose ACE again. CONCLUSION: ACE treatment is perceived positively by patients and parents and can lead to long-term improvement in gastrointestinal HRQoL in children with organic or functional defecation disorders.
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Incontinência Fecal , Humanos , Criança , Masculino , Feminino , Incontinência Fecal/terapia , Qualidade de Vida , Estudos Prospectivos , Resultado do Tratamento , Constipação Intestinal/terapia , Enema/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVES: Our objective was to investigate if there is a difference in the detection of the rectoanal inhibitory reflex (RAIR) when an anorectal manometry (ARM) is performed awake or under general anesthesia. METHODS: A retrospective review of ARM studies was performed to identify children who had undergone ARMs both while awake and under general anesthesia. We compared ARM outcomes including the detection of the RAIR and anal canal resting pressure. RESULTS: Thirty-four children had received ARMs both while awake and under general anesthesia (53% female, median age at first ARM 7.5 years [range 3-18 years]). In 9 of 34 (26%) children the RAIR was solely identified during ARM under general anesthesia and not during ARM while awake. In 6 of 9 (66%) this was unrelated to the balloon volumes used during balloon inflations. In 4 of 34 (12%) children, assessment of the RAIR was inconclusive during ARM under general anesthesia due to too low, or loss of anal canal pressure. In 2 of those children, ARMs while awake showed presence of a RAIR. Anal canal resting pressures were higher during ARM while awake versus ARM under general anesthesia (median 70 [interquartile range, IQR 59-85] vs 46 mmHg [IQR 36-65] respectively, P < 0.001). CONCLUSIONS: General anesthesia may affect the detection of a RAIR in 2 ways. On the one hand, it may facilitate better visualization in children in whom a RAIR could not be visualized while awake. On the other hand, it may cause a loss of anal canal pressure resulting in an inconclusive test result.
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Reto , Vigília , Humanos , Criança , Feminino , Pré-Escolar , Adolescente , Masculino , Manometria/métodos , Canal Anal , Reflexo , Anestesia GeralRESUMO
Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype-phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first 'European Forum on Visceral Myopathy'. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy.
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Pseudo-Obstrução Intestinal , Desnutrição , Animais , Criança , Humanos , Qualidade de Vida , Modelos Animais , Mutação , Doenças RarasRESUMO
BACKGROUND & AIMS: Pediatric functional constipation (PFC) is a common problem in children that causes distress and presents treatment challenges to health care professionals. We conducted a randomized, placebo-controlled trial (study 1) in patients with PFC (6-17 years of age) to evaluate the efficacy and safety of lubiprostone, followed by an open-label extension for those who completed the placebo-controlled phase (study 2). METHODS: Study 1 (NCT02042183) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 12-week study evaluating the efficacy and safety of lubiprostone 12 µg twice daily (BID) and 24 µg BID. Study 2 (NCT02138136) was a phase 3, long-term, open-label extension of study 1. In both studies, lubiprostone doses were based on patients' weight. Efficacy was assessed solely based on study 1, with a primary endpoint of overall spontaneous bowel movement (SBM) response (increase of ≥1 SBM/wk vs baseline and ≥3 SBMs/wk for ≥9 weeks, including 3 of the final 4 weeks). RESULTS: 606 patients were randomized to treatment (placebo: n = 202; lubiprostone: n = 404) in study 1. No statistically significant difference in overall SBM response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P = .2245). Both the 12-µg BID and 24-µg BID doses of lubiprostone were well tolerated in the double-blind and extension phases, with a safety profile consistent with that seen in adult studies. CONCLUSIONS: Lubiprostone did not demonstrate statistically significant effectiveness over placebo in children and adolescents with PFC but did demonstrate a safety profile similar to that in adults. (ClinicalTrials.gov: Number: NCT02042183; Number: NCT02138136).
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Constipação Intestinal , Defecação , Adolescente , Adulto , Criança , Constipação Intestinal/tratamento farmacológico , Método Duplo-Cego , Pessoal de Saúde , Humanos , Lubiprostona/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.
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Enterite , Eosinofilia , Esofagite Eosinofílica , Gastrite , Humanos , Consenso , Enterite/diagnóstico , Enterite/complicações , Gastrite/diagnóstico , Gastrite/complicações , Eosinofilia/diagnóstico , Eosinofilia/complicações , Esofagite Eosinofílica/complicaçõesRESUMO
OBJECTIVES: To evaluate whether providing a constipation action plan (CAP) to families of children with constipation at outpatient gastroenterology (GI) visits affects health care utilization of the GI department. METHODS: We created a CAP to be included in the after visit summary of children seen in our GI Clinic. We compared the number of patient telephone calls, electronic messages, and urgent care (UC) visits, emergency department (ED) visits, and hospitalizations within 3 months after the visit of patients who received the CAP compared to those who did not using inverse probability treatment weighting (IPTW) analysis. For families who received the CAP at a follow-up visit, we compared these variables in the 3 months before and after the CAP was provided using paired t test and McNemar's test as appropriate. RESULTS: We included 336 patients who received the CAP and 2812 who did not. After IPTW adjustment, there were fewer patient telephone calls for patients who received the CAP (P = 0.0006). The difference in patient electronic messages was not statistically significant (P = 0.09). For the 45 patients who received the CAP at a follow-up visit, there were on average 1.8 more patient telephone calls made prior to receiving the CAP than after (95% confidence interval (CI) = 0.8-2.8; P = 0.0007) and 2.3 more patient electronic messages received (95% CI = 0.1-4.5; P = 0.04). There were no differences in UC/emergency department visits or hospitalizations. CONCLUSIONS: We found that providing a CAP to families of children with constipation decreases health care utilization. Further studies are needed to determine whether this impacts patient outcomes.
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Serviço Hospitalar de Emergência , Aceitação pelo Paciente de Cuidados de Saúde , Criança , Humanos , Assistência Ambulatorial , Hospitalização , Constipação Intestinal/terapiaRESUMO
OBJECTIVES: To identify predictors of hospitalization in pediatric patients presenting to an emergency department (ED) for a cyclic vomiting syndrome (CVS) attack. STUDY DESIGN: We retrospectively reviewed patients with CVS seen at our institution between 2015 and 2018 and included those who met the Rome IV criteria for CVS. We identified all CVS-related ED visits and subsequently performed a case-control analysis, utilizing multivariate logistic regression, to identify clinical and demographic factors that may predict hospitalization. RESULTS: In total, 219 patients with CVS (using International Statistical Classification of Diseases and Related Health Problems, 10th Revision) were identified, of which 65% met the inclusion criteria (median age 11 years). We identified 152 CVS-related ED visits, of which 62% resulted in hospitalization. Factors found to predict hospitalization using multivariate analyses included male sex (P = .04), younger age (P = .027), delayed presentation (>24 hours) to the ED (P < .001), and longer wait time prior treatment with antiemetics (P = .029). CONCLUSION: One-quarter of all patients with CVS had presented to the ED and nearly two-thirds of these ED visits resulted in hospitalization. A delayed presentation to the ED following the onset of symptoms was the strongest independent predictor of hospital admission, alongside male sex, younger age, and longer ED wait times before treatment with antiemetics. These findings suggest that early intervention may be key to successfully mitigating the risk of hospitalization for a CVS attack.
Assuntos
Regras de Decisão Clínica , Hospitalização/estatística & dados numéricos , Índice de Gravidade de Doença , Vômito/diagnóstico , Vômito/terapia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Serviço Hospitalar de Emergência/estatística & dados numéricos , Utilização de Instalações e Serviços/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , Estudos Retrospectivos , Tempo para o Tratamento/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: To identify esophageal sensitivity phenotypes relative to acid (SAcid), bolus (SBolus), acid and bolus (SAcid+Bolus), and none (SNone) exposures in infants suspected with gastroesophageal reflux disease (GERD). METHODS: Symptomatic infants (N = 279) were evaluated for GERD at 42 (40-45) weeks postmenstrual age using 24-h pH-impedance. Symptom-associated probability (SAP) for acid and bolus components defined esophageal sensitivity: (1) SAcid as SAP ≥ 95% for acid (pH < 4), (2) SBolus as SAP ≥ 95% for bolus, (3) SAcid+Bolus as SAP ≥ 95% for acid and bolus, or (4) SNone as SAP < 95% for acid and bolus. RESULTS: Esophageal sensitivity prevalence (SAcid, SBolus, SAcid+Bolus, SNone) was 28 (10%), 94 (34%), 65 (23%), and 92 (33%), respectively. Emesis occurred more in SBolus and SAcid+Bolus vs SNone (p < 0.05). Magnitude (#/day) of cough and emesis events increased with SBolus and SAcid+Bolus vs SNone (p < 0.05). SAcid+Bolus had increased acid exposure vs SNone (p < 0.05). Distributions of feeding and breathing methods were distinct in infants with SBolus vs SNone (both, p < 0.05). Multivariate analysis revealed that arching and irritability events/day were lesser at higher PMAs (p < 0.001) and greater for infants on NCPAP (p < 0.01) with SBolus and SAcid+Bolus (p < 0.05). Coughs/day was greater at higher PMAs (p < 0.001) for infants with gavage and transitional feeding methods (p < 0.02) with SBolus and SAcid+Bolus (p < 0.05) but lesser with Trach (p < 0.001). Number of emesis events/day were greater with SBolus and SAcid+Bolus (p < 0.001). Sneezes/day decreased for infants on Trach (p = 0.02). CONCLUSIONS: Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. We differentiated esophageal sensitivity phenotypes in NICU infants referred for GERD symptoms using pH-impedance. Acid sensitivity alone was rare, which may explain poor response to acid suppressives; aerodigestive symptoms were predominantly linked with bolus spread. Magnitude of esophageal acid exposure and esophageal sensitivity to bolus spread may explain the pathophysiological basis for symptoms. IMPACT: Objective GERD diagnosis and reasons for symptoms in NICU infants remains unclear. Differentiation of esophageal sensitivities by acid and bolus components of GER reveal distinct symptom profiles, specifically the bolus component of GER significantly contributes to symptom occurrence. Acid only sensitivity to GER is rare, and acid-suppressive therapy alone may not improve symptoms in a majority of NICU infants. Magnitude of esophageal acid exposure and esophageal sensitivity to any bolus spread may explain the pathophysiological basis for symptoms. Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. GERD treatments should be individualized to the patient's GERD phenotype and likely also target the bolus component of GER.
Assuntos
Esôfago/patologia , Refluxo Gastroesofágico/patologia , Tosse , Cuidados Críticos , Impedância Elétrica , Nutrição Enteral , Esôfago/metabolismo , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lactente , Recém-Nascido Prematuro/fisiologia , Unidades de Terapia Intensiva , Unidades de Terapia Intensiva Neonatal , Masculino , Análise Multivariada , Fenótipo , Probabilidade , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To test the hypothesis that a feeding bundle concurrent with acid suppression is superior to acid suppression alone in improving gastroesophageal reflux disease (GERD) attributed-symptom scores and feeding outcomes in neonatal ICU infants. METHODS: Infants (N = 76) between 34 and 60 weeks' postmenstrual age with acid reflux index > 3% were randomly allocated to study (acid-suppressive therapy + feeding bundle) or conventional (acid-suppressive therapy only) arms for 4 weeks. Feeding bundle included: total fluid volume < 140 mL/kg/day, fed over 30 min in right lateral position, and supine postprandial position. Primary outcome was independent oral feeding and/or ≥6-point decrease in symptom score (I-GERQ-R). Secondary outcomes included growth (weight, length, head circumference), length of hospital stay (LOHS, days), airway (oxygen at discharge), and developmental (Bayley scores) milestones. RESULTS: Of 688 screened: 76 infants were randomized and used for the primary outcome as intent-to-treat, and secondary outcomes analyzed for 72 infants (N = 35 conventional, N = 37 study). For study vs. conventional groups, respectively: (a) 33% (95% CI, 19-49%) vs. 44% (95% CI, 28-62%), P = 0.28 achieved primary outcome success, and (b) secondary outcomes did not significantly differ (P > 0.05). CONCLUSIONS: Feeding strategy modifications concurrent with acid suppression are not superior to PPI alone in improving GERD symptoms or discharge feeding, short-term and long-term outcomes. IMPACT: Conservative feeding therapies are thought to modify GERD symptoms and its consequences. However, in this randomized controlled trial in convalescing neonatal ICU infants with GERD symptoms, when controlling for preterm or full-term birth and severity of esophageal acid reflux index, the effectiveness of acid suppression plus a feeding modification bundle (volume restriction, intra- and postprandial body positions, and prolonged feeding periods) vs. acid suppression alone, administered over a 4-week period was not superior in improving symptom scores or feeding outcomes. Restrictive feeding strategies are of no impact in modifying GERD symptoms or clinically meaningful outcomes. Further studies are needed to define true GERD and to identify effective therapies in modifying pathophysiology and outcomes. The improvement in symptoms and feeding outcomes over time irrespective of feeding modifications may suggest a maturational effect. This study justifies the use of placebo-controlled randomized clinical trial among NICU infants with objectively defined GERD.