RESUMEN
PURPOSE: Childhood stricturing Crohn's disease (CD) has significant morbidity. Interventions including resection, stricturoplasty and endoscopic balloon dilatation (EBD) are often required. Optimal intervention modality and timing, and use of adjuvant medical therapies, remains unclear. We aim to review the therapies used in paediatric stricturing CD. METHODS: A systematic review in accordance with PRISMA was performed (PROSPERO: CRD42020164464). Demographics, stricture features, interventions and outcomes were extracted. RESULTS: Fourteen studies were selected, including 177 patients (183 strictures). Strictures presented at 40.6 months (range 14-108) following CD diagnosis. Medical therapy was used in 142 patients for an average of 20.4 months (2-36), with a complete response in 11 (8%). Interventions were undertaken in 138 patients: 53 (38%) resections, 39 (28%) stricturoplasties, and 17 (12%) EBD. Complications occurred in 11% of resections, versus 15% stricturoplasties, versus 6% EBD (p = 0.223). At a median follow-up of 1.9 years (interquartile range 1.2-2.4) pooled stricture recurrence was 22%. Resection had 9% recurrence, versus 38% stricturoplasty, versus 47% EBD (p < 0.001). CONCLUSIONS: Resection is associated with a low incidence of recurrence and complications. There remains a paucity of evidence regarding adjuvant medical therapy and the role of EBD. We propose a minimum reported dataset for interventions in paediatric stricturing CD.
Asunto(s)
Enfermedad de Crohn/terapia , Endoscopía Gastrointestinal , Adolescente , Cateterismo , Niño , Preescolar , Constricción Patológica/complicaciones , Constricción Patológica/cirugía , Enfermedad de Crohn/complicaciones , Dilatación , Endoscopía Gastrointestinal/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Recurrencia , Resultado del TratamientoRESUMEN
PURPOSE: To generate 3-dimensional (3D) printed ultrasound (US)-compatible vascular models (3DPVAM) and test them for noninferiority in training medical students in femoral artery access. MATERIALS AND METHODS: A 3DPVAM of normal femoral artery (FA) anatomy was developed from an anonymized computerized tomography (CT) examination. Students were randomized to a 3DPVAM or a commercial model (CM) simulation experience (SE) for US-guided FA access. Students completed a pre-SE questionnaire ranking their self-confidence in accessing the artery on a 5-point Likert scale. A standardized SE was administered by interventional radiology faculty or trainees. Students completed a post-SE questionnaire ranking comfort with FA access on a Likert scale. Student questionnaire results from the 3DPVAM group were compared with those from the CM group by using chi-square, Wilcoxon signed-rank, and noninferiority analyses. RESULTS: Twenty-six and twenty-three students were randomized to 3DPVAM and commercial model training, respectively. A total of 76.9% of 3DPVAM trainees and 82.6% of CM trainees did not feel confident performing FA access prior to the SE. In both groups, training increased student confidence by 2 Likert points (3DPVAM: P < 0.001; CM P < 0.001). The confidence increase in 3DPVAM trainees was noninferior to that in CM trainees (P < 0.001). CONCLUSIONS: Generation of a custom-made 3DPVAM is feasible, producing comparable subjective training outcomes to those of CM. Custom-made 3D-printed training models, including incorporation of more complex anatomical configurations, could be used to instruct medical students in procedural skills.
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Cateterismo Periférico/métodos , Educación de Pregrado en Medicina/métodos , Arteria Femoral/diagnóstico por imagen , Modelos Anatómicos , Modelos Cardiovasculares , Impresión Tridimensional , Radiografía Intervencional/métodos , Radiología Intervencionista/educación , Estudiantes de Medicina , Competencia Clínica , Angiografía por Tomografía Computarizada , Curriculum , Humanos , PuncionesRESUMEN
BACKGROUND AND AIMS: Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase the risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab (IFX) with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). METHODS: We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from May 31, 2007 through June 30, 2016. Patients were 17 years old or younger and had Crohn's disease, ulcerative colitis, or IBD-unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% confidence intervals (CIs), using the Surveillance, Epidemiology, and End Results Program (SEER) database. RESULTS: Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with malignancy had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX as the only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to IFX (SIR, 1.69; 95% CI, 0.46-4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59-5.56), even when patients were stratified by thiopurine exposure. CONCLUSIONS: In determination of age-, sex-, and race-adjusted SIRs using data from a large clinical study and the SEER database, we found that IFX exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD.
Asunto(s)
Antiinflamatorios/uso terapéutico , Productos Biológicos/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Infliximab/efectos adversos , Linfohistiocitosis Hemofagocítica/epidemiología , Neoplasias/epidemiología , Adolescente , Distribución por Edad , Antiinflamatorios/efectos adversos , Niño , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Europa (Continente)/epidemiología , Femenino , Fármacos Gastrointestinales/efectos adversos , Humanos , Huésped Inmunocomprometido , Incidencia , Linfohistiocitosis Hemofagocítica/inducido químicamente , Linfohistiocitosis Hemofagocítica/diagnóstico , Masculino , Neoplasias/inducido químicamente , Neoplasias/diagnóstico , América del Norte/epidemiología , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Programa de VERF , Distribución por Sexo , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: Iron deficiency anaemia frequently complicates inflammatory bowel disease (IBD) in children and adults. Oral iron may exacerbate gastrointestinal symptoms and absorption may be insufficient in intestinal inflammation. Even where oral iron is successful, repletion of iron stores can be unacceptably slow. Intravenous iron compounds were in the past associated with serious adverse reactions and historically were considered a last resort in children. New generation preparations have a safer profile in adults, although reluctance to use them in children may persist, where safety data are lacking. We investigate the safety and efficacy of ferric carboxymaltose and iron sucrose in children. METHODS: We retrospectively identified all children with IBD who received parenteral iron over a 38-month period in a single regional referral centre. Safety, tolerability and adverse events were established by case note review. Efficacy was assessed by change in haematinic indices pre- and post-treatment. RESULTS: Forty-one children (18 male; median age 14 years, range 3-17) received a total of 104 iron infusions. Of these, 44% (18) had Crohn's disease; 56% (23) ulcerative colitis. Thirty-five received ferric carboxymaltose, seven iron sucrose and one both. Three children developed mild rash post infusion which resolved quickly with chlorphenamine. Mean increase in haemoglobin was 2.5 g dl-1 (0.3-5.8). Iron levels increased by a mean of 8.4 g dl-1 (1-25), transferrin saturation by 16.2% (2-47). Transferrin decreased by 0.84 g dl-1 (0.3-3.4). CONCLUSIONS: New generation parenteral iron preparations are safe, well tolerated and efficacious in children with iron deficiency anaemia and IBD.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Enfermedad de Crohn/complicaciones , Compuestos Férricos/administración & dosificación , Sacarato de Óxido Férrico/administración & dosificación , Maltosa/análogos & derivados , Adolescente , Anemia Ferropénica/etiología , Niño , Preescolar , Femenino , Compuestos Férricos/efectos adversos , Sacarato de Óxido Férrico/efectos adversos , Hemoglobinas/metabolismo , Humanos , Infusiones Intravenosas , Masculino , Maltosa/administración & dosificación , Maltosa/efectos adversos , Estudios Retrospectivos , Transferrina/metabolismoRESUMEN
OBJECTIVES: The aim of the study was to summarize short-term effectiveness, safety, and cost of using infliximab biosimilar (IFX-B) drugs, (Inflectra [Hospira] and Remsima [NAAP]) compared to originator infliximab (IFX-O) (Remicade [MSD]) in biologic naive pediatric inflammatory bowel disease in the United Kingdom. METHODS: Prospective audit of patients starting anti-tumour necrosis factor (TNF) therapy. Disease severity, response to treatment, and remission rate was measured by Pediatric Crohn's Disease Activity Index (PCDAI) and/or Physician Global Assessment. RESULTS: Between March 2015 and February 2016, 278 patients (175 IFX-O, 82 IFX-B, and 21 Adalimumab) were started on anti-TNF therapy. This was compared with collected data on 398 patients started on IFX-O from 2011 to 2015. At initiation, median PCDAI was 36 (20,48) (nâ=â42) in the IFX-O group and 28 (20,40) (nâ=â29) in the IFX-B group, (Pâ=â0.08). Immunosuppression rates were similar: 150/175 (86%) for IFX-O and 65/82 (79%) for IFX-B (Pâ>â0.05). Post induction, median PCDAI score was 5 (0,11) (nâ=â19) and 0 (0,8) (nâ=â15) in the IFX-O and IFX-B groups, respectively (Pâ=â0.35). There was no difference in response to treatment using Physician Global Assessment 85% (nâ=â28) in IFX-O group and 86% (nâ=â19) in IFX-B group (Pâ>â0.05). Adverse events at initiation and post induction were not different between both groups (Pâ>â0.05). Using conservative calculations, £875,000 would have been saved for a 1-year period with universal adoption of biosimilars in patients who were instead treated with IFX-O. CONCLUSIONS: IFX-B is likely as effective as IFX-O in treating IBD in comparable pediatric populations. Sites should adopt infliximab biosimilar for new starts due to cost reduction with no difference in other parameters.
Asunto(s)
Biosimilares Farmacéuticos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Adolescente , Niño , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Auditoría Médica , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Reino UnidoRESUMEN
OBJECTIVE: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index. RESULTS: A total of 37 centers participated (23/25 specialist pediatric inflammatory bowel disease sites). A total of 524 patients were included: 429 with Crohn disease (CD), 76 with ulcerative colitis (UC), and 19 with IBD unclassified (IBDU). Eighty-seven percent (488/562) of anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (interquartile range 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by Physician Global Assessment compared to 41% (88/217) by Paediatric Crohn Disease Activity Index (Kappa (κ) 0.28â=âonly "fair agreement"; Pâ<â0.001.Where documented, 77% (53/69) of patients with CD responded to induction; and 65% (46/71) entered remission. A total of 2287 infusions and 301.96 years of patient' follow-up (nâ=â385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Peri-anal abscess drainage was less common after anti-TNF initiation (CD), that is 26% (27/102) before, 7% (3/42) after (Pâ=â0.01); however, pre and post anti-TNF data collection was not over equal time periods. CONCLUSIONS: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools, which need to be addressed to improve ongoing patient care.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Terapia de Inmunosupresión/métodos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Anticuerpos Monoclonales Humanizados/efectos adversos , Niño , Preescolar , Auditoría Clínica , Femenino , Fármacos Gastrointestinales/efectos adversos , Humanos , Terapia de Inmunosupresión/efectos adversos , Lactante , Masculino , Estudios Prospectivos , Inducción de Remisión , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Reino UnidoRESUMEN
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.
Asunto(s)
Colectomía , Enfermedad de Crohn/cirugía , Intestino Delgado/cirugía , Atención Perioperativa/métodos , Anastomosis Quirúrgica , Antiinflamatorios/uso terapéutico , Terapia Biológica , Quimioterapia Adyuvante , Niño , Colectomía/métodos , Enfermedad de Crohn/tratamiento farmacológico , Procedimientos Quirúrgicos Electivos , Humanos , Inmunosupresores/uso terapéutico , Selección de Paciente , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Recurrencia , Prevención Secundaria/métodosRESUMEN
BACKGROUND: We have previously reported evidence of in vitro sensitisation to cow's milk protein in peripheral blood mononuclear cells (PBMCs) in preterm infants with necrotising enterocolitis (NEC). In the present study, we document the changes in the PBMC responses to stimulation with mitogen (phytohaemagglutinin) and cow's milk proteins ß-lactoglobulin (ß-lg) and casein over time: from the acute presentation of NEC, to initial recovery (reinitiation of enteral feeds), to full recovery (full feeding). METHODS: Of the 14 preterm infants recruited with acute NEC, 12 were followed until fully enterally fed (2 died during the acute phase). Cytokine secretion (interferon-γ [IFN-γ], interleukin 4, [IL-4], IL-10, and transforming growth factor-ß1 [TGF-ß1]) by PBMCs in response to stimulation by phytohaemagglutinin, ß-lg, and casein was measured by enzyme-linked immunospot in the acute phase and subsequently at recovery and full recovery. RESULTS: The high levels of cytokine secretion (IFN-γ, IL-4, IL-10, and TGF-ß1) observed in response to ß-lg and casein in the acute phase increased by a further 50% to 100% at recovery (P < 0.005). At full recovery (full feeding), however, IFN-γ, IL-4, and IL-10 secretion response had returned to, or below, acute-phase levels, whereas the augmented TGF-ß1 response was maintained (P = 0.005 vs acute level). This response pattern was similar for casein, and did not appear to be influenced by the nature of the feed used following NEC (breast milk/formula/hydrolysed formula). CONCLUSIONS: The evolution of the cytokine response profile in parallel with the clinical recovery from NEC is consistent with a putative role for TGF-ß1 in regulation of inflammation, and possibly also oral tolerance.
Asunto(s)
Citocinas/metabolismo , Enterocolitis Necrotizante/inmunología , Enfermedades del Recién Nacido/inmunología , Recien Nacido Prematuro/inmunología , Inflamación/inmunología , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/inmunología , Animales , Caseínas/inmunología , Caseínas/farmacología , Bovinos , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/terapia , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/metabolismo , Enfermedades del Recién Nacido/terapia , Recien Nacido Prematuro/metabolismo , Inflamación/metabolismo , Mediadores de Inflamación/sangre , Lactoglobulinas/inmunología , Lactoglobulinas/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Estudios Longitudinales , Masculino , Leche , Hipersensibilidad a la Leche/metabolismo , Proteínas de la Leche/farmacología , Apoyo Nutricional , Fitohemaglutininas/inmunología , Fitohemaglutininas/farmacología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Combined immunosuppression by immunomodulators and biological therapy has become standard in the medical management of moderate-to-severe inflammatory bowel disease (IBD) because of clearly demonstrated efficacy. Clinical studies, registries, and case reports warn of the increased risk of infections, particularly opportunistic infections; however, already in the steroid monotherapy era, patients are at risk because it is accepted that a patient should be considered immunosuppressed when receiving a daily dose of 20 mg of prednisone for 2 weeks. Prescriptions increasingly involve azathioprine, methotrexate, and various biological agents. The TREAT registry evaluated safety in >6000 adult patients, half of them treated with infliximab (IFX) for about 1.9 years. IFX-treated patients had an increased risk of infections and this was associated with disease severity and concomitant prednisone use. The REACH study, evaluating the efficacy of IFX in children with moderate-to-severe Crohn disease, refractory to immunomodulatory treatment, reports serious infections as the major adverse events and their frequency is higher with shorter treatment intervals. The combination of immunosuppressive medications is a risk factor for opportunistic infections. Exhaustive guidelines on prophylaxis, diagnosis, and management of opportunistic infections in adult patients with IBD have been published by a European Crohn's and Colitis Organization working group, including clear evidence-based statements. We have reviewed the literature on infections in pediatric IBD as well as the European Crohn's and Colitis Organization guidelines to present a commentary on infection prophylaxis for the pediatric age group.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/complicaciones , Infecciones Oportunistas/etiología , Prednisona/efectos adversos , Quimioterapia Combinada/efectos adversos , Europa (Continente) , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab , Infecciones Oportunistas/prevención & control , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sociedades MédicasRESUMEN
Enteral feeding with cow's milk formula is associated with neonatal necrotizing enterocolitis (NEC) and sepsis. Dietary antigen sensitization may play a role in promoting and/or sustaining inflammation in both conditions. Aiming at investigating cow's milk protein (CMP)-specific cytokine responses in preterm infants with NEC and sepsis, 14 babies with NEC, 14 matched healthy controls, and 10 septic controls were recruited. Unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) secreting IFN-γ, IL-4, IL-10, and TGF-ß1 were counted by the single-cell enzyme-linked immunospot (ELISPOT) assay. During the acute phase of NEC, patients showed a general pattern of a high level of cytokine secretion both when unstimulated and stimulated by mitogen [phytohaemagglutinin (PHA)] and CMPs: beta-lactoglobulin (ß-lg) and casein. These responses were more marked to ß-lg for IFN-γ, IL-4, and IL-10 than TGF-ß1. Cytokine responses in sepsis were lower than in NEC (lowest in healthy controls, with a minimal TGF-ß1 response). At term, lower frequencies of cytokine-secreting cells were elicited than during the acute phase, except for TGF-ß1 secreting cells, which increased at term (in response to PHA and CMPs) particularly following not only NEC but also sepsis.
Asunto(s)
Citocinas/metabolismo , Enterocolitis Necrotizante/inmunología , Mediadores de Inflamación/metabolismo , Leucocitos Mononucleares/inmunología , Proteínas de la Leche/inmunología , Sepsis/inmunología , Estudios de Casos y Controles , Caseínas/inmunología , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Lactoglobulinas/inmunología , Masculino , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the results of surgery in children with Crohn disease (CD) not responding to medical therapy and establish whether surgery improves growth and nutrition. PATIENTS AND METHODS: Children with CD diagnosed between 1998 and 2008 were reviewed. Relapse was defined by Harvey-Bradshaw index >5. Data, reported as median (range), were compared by Fisher exact test and repeated-measures ANOVA. RESULTS: One hundred forty-one children, ages 12.7 years (3.5-16.8), were identified; 27 (19%) required surgery 14.5 months (1.1-61.8) after diagnosis. Twenty-one had elective surgery (19 isolated ileocaecal disease and stricture, 2 diffuse disease of ileum); 6 had emergency surgery (3 peritonitis, 2 haemorrhage, 1 perforation). Surgery included 18 ileocaecal resection and end-to-end anastomosis, 5 stoma formation, 2 left hemicolectomy and end-to-end anastomosis, and 2 stricturoplasty. Follow-up was 2.5 years (1-9.4). Growth and nutrition improved by 6 and 12 months after surgery, with a significant increase in weight z score (P < 0.0001), height z score (P < 0.0001), albumin (30 [13-36] vs 39 [30-46] vs 40 [33-45], P < 0.0001), and haemoglobin [10 (6.8-13.2) vs 11.7 (8.2-13.7) vs 12.0 (9.3-14.7), P < 0.0001]. All patients of the received azathioprine (2-2.5 mg · kg⻹ · day⻹) after surgery. Fifteen patients (55%) relapsed with a modified Harvey-Bradshaw index of 8 (6-11) within 11.5 months (4.2-33.4). Of these, 5 patients (18%) relapsed within 1 year. Five patients (18%) had further surgery (2 anastomotic strictures, 2 diseased stoma, and 1 enterocutaneous fistula). CONCLUSIONS: Growth and nutrition following surgery for CD improve, but there is a high relapse rate. Despite this, the improved growth and nutrition before relapse may be beneficial during puberty and justify surgery in children not responding to medications.
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Enfermedad de Crohn/cirugía , Trastornos del Crecimiento/etiología , Crecimiento , Adolescente , Estatura , Niño , Preescolar , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/metabolismo , Trastornos del Crecimiento/metabolismo , Hemoglobinas/metabolismo , Humanos , Recurrencia , Estudios Retrospectivos , Albúmina Sérica/metabolismo , Resultado del Tratamiento , Aumento de PesoRESUMEN
AIMS: To assess self-reported QoL in children with achalasia aged 5-18 and compare this with both disease and healthy control children in a prospective study. METHODS: All children diagnosed with achalasia at one hospital were asked to participate in this study by completing the self-report module of the validated PedsQL™ generic QoL assessment. All children attending a tertiary paediatric gastroenterology clinic from February 2009 to May 2009 with chronic constipation or inflammatory bowel disease were asked to participate in this study as disease controls. The PedsQL™ considers physical, emotional, social and school domains and is scored from 0-100. Healthy children were also recruited from the same site. Groups were compared using Analysis of Variance with Tukey's post-hoc test. RESULTS: One hundred and sixty one children completed the assessment (90 (56%) male, mean age 11.3 yrs ± 3.4 years) including 17 children with achalasia, 44 with chronic constipation, 59 with inflammatory bowel disease and 41 healthy children. QoL was significantly lower in the achalasia group compared to both children with IBD (73 vs. 82, p = 0.035) and healthy children (73 vs. 84, p = 0.005), and was comparable to that of children with chronic constipation (73 vs. 74, p = 0.99). CONCLUSION: Children with achalasia report a significantly lower QoL compared to children with inflammatory bowel disease and healthy children.
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Acalasia del Esófago/fisiopatología , Acalasia del Esófago/psicología , Adolescente , Estudios de Casos y Controles , Niño , Estreñimiento/fisiopatología , Estreñimiento/psicología , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/fisiopatología , Enfermedades Inflamatorias del Intestino/psicología , Londres , Masculino , Estudios Prospectivos , Calidad de Vida , Perfil de Impacto de EnfermedadRESUMEN
Breast milk prebiotic oligosaccharides are believed to promote enteral tolerance. Many mothers delivering preterm are unable to provide sufficient milk. We conducted a multicenter, randomized, controlled trial comparing preterm formula containing 0.8 g/100 mL short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides in a 9:1 ratio and an otherwise identical formula, using formula only to augment insufficient maternal milk volume. Infants were randomized within 24 h of birth. The primary outcome (PO) was time to establish a total milk intake of 150 mL/kg/d PO and the principal secondary outcome (PSO) was proportion of time between birth and 28 d/discharge that a total milk intake of ≥ 150 mL/kg/d was tolerated. Other secondary outcomes included growth, fecal characteristics, gastrointestinal signs, necrotizing enterocolitis, and bloodstream infection. Outcomes were compared adjusted for prespecified covariates. We recruited 160 infants appropriately grown for GA <33 wk. There were no significant differences in PO or PSOs. After covariate adjustment, we showed significant benefit from trial formula in PSO with increasing infant immaturity (2.9% improved tolerance for a baby born at 28-wk gestation and 9.9% at 26-wk gestation; p < 0.001) but decreased or no benefit in babies >31-wk gestation. Prebiotic supplementation appears safe and may benefit enteral tolerance in the most immature infants.
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Suplementos Dietéticos , Nutrición Enteral , Alimentos Infantiles , Recien Nacido Prematuro/fisiología , Oligosacáridos/administración & dosificación , Prebióticos , Método Doble Ciego , Femenino , Humanos , Recién Nacido , Masculino , Leche Humana/química , Resultado del TratamientoRESUMEN
BACKGROUND: Oesophageal achalasia is a rare disorder in childhood. Common treatments in adults include oesophageal cardiomyotomy (laparoscopic or open) with fundoplication. We aimed to assess the results of laparoscopic oesophageal cardiomyotomy without fundoplication for treatment of achalasia in children. METHODS: We reviewed the results of laparoscopic oesophageal cardiomyotomy between January 1998 and June 2008. Patients below the age of 18 years, who had undergone laparoscopic oesophageal cardiomyotomy without an anti-reflux procedure by a single surgeon, were identified. Data were collected from patient notes. Results are reported as median (range). RESULTS: There were 20 patients (13 males and 7 females). Median age at surgery was 12 years (5-15 years) and weight was 38 kg (15-53 kg). Median duration of symptoms before surgery was 2.4 years (1.5-5 years). Duration of surgery was 96 min (60-160 min). Four patients (20%) required conversion to the open technique. In the remaining 16 children, fluids were started at a median of 7 h (6-8 h) post-operatively, and solid feeds were commenced at 22 h (20-24 h). Median length of hospital stay was 3 days (1-5 days). Median length of follow-up was 60 months (8-114 months). None of the patients had evidence of gastro-oesophageal reflux post-operatively. Five patients (25%) continued to experience dysphagia, with one of them also experiencing vomiting. Two patients were found to have oesophageal stricture and three patients were found to have oesophageal dysmotility. The remaining patients are asymptomatic. CONCLUSIONS: These results suggest that laparoscopic oesophageal cardiomyotomy is a valid treatment in children with achalasia. In our experience, an adjunctive anti-reflux procedure is not required, as there was no evidence of post-operative gastro-oesophageal reflux in all patients. Oesophageal stricture and dysmotility account for residual post-operative symptoms.
Asunto(s)
Acalasia del Esófago/cirugía , Esófago/cirugía , Adolescente , Niño , Preescolar , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Fundoplicación , Humanos , Laparoscopía , MasculinoRESUMEN
Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.
Asunto(s)
Alginatos/administración & dosificación , Sistemas de Liberación de Medicamentos , Mucosa Gástrica/metabolismo , Alginatos/química , Ácido Glucurónico/administración & dosificación , Ácido Glucurónico/química , Ácidos Hexurónicos/administración & dosificación , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Matemática , Microscopía Confocal , Microscopía Electrónica de Rastreo , Fotograbar , Riboflavina/administración & dosificación , Riboflavina/química , SolubilidadRESUMEN
Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.
Asunto(s)
Colectomía/estadística & datos numéricos , Colitis Ulcerosa/terapia , Inmunosupresores/uso terapéutico , Esteroides/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Niño , Preescolar , Colectomía/efectos adversos , Colitis Ulcerosa/epidemiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Reino Unido/epidemiologíaAsunto(s)
Síndromes de Malabsorción , Mucolipidosis , Índice de Severidad de la Enfermedad , Ultrasonografía Prenatal , Femenino , Humanos , Recién Nacido , Síndromes de Malabsorción/diagnóstico por imagen , Microvellosidades/diagnóstico por imagen , Microvellosidades/patología , Mucolipidosis/diagnóstico por imagen , FenotipoRESUMEN
BACKGROUND: Because of previous concerns about the efficacy and safety of oral iron for treating iron deficiency anaemia in inflammatory bowel disease [IBD], particularly in young people, we compared the effects of ferrous sulphate on haemoglobin response, disease activity and psychometric scores in adolescents and adults with IBD. We also assessed the relation of baseline serum hepcidin to haemoglobin response. METHODS: We undertook a prospective, open-label, 6-week non-inferiority trial of the effects of ferrous sulphate 200 mg twice daily on haemoglobin, iron status, hepcidin, disease activity (Harvey-Bradshaw Index, Simple Colitis Clinical Activity Index, C-reactive protein [CRP]), faecal calprotectin and psychometric scores in 45 adolescents [age 13-18 years] and 43 adults [>18 years]. RESULTS: On intention-to-treat analysis, ferrous sulphate produced similar rises in haemoglobin in adolescents {before treatment 10.3 g/dl [0.18] (mean [SEM]), after 11.7 [0.23]: p < 0.0001} and adults (10.9 g/dl [0.14], 11.9 [0.19]: p < 0.0001); transferrin saturation, ferritin [in adolescents] and hepcidin [in adults] also increased significantly. On per-protocol univariate analysis, the haemoglobin response was inversely related to baseline haemoglobin, CRP and hepcidin. Oral iron did not alter disease activity; it improved Short IBDQ and Perceived Stress Questionnaire scores in adults. CONCLUSION: Oral ferrous sulphate was no less effective or well-tolerated in adolescents than adults, and did not increase disease activity in this short-term study. The inverse relation between baseline CRP and hepcidin levels and the haemoglobin response suggests that CRP or hepcidin measurements could influence decisions on whether iron should be given orally or intravenously. [ClinTrials.gov registration number NCT01991314].
Asunto(s)
Anemia Ferropénica/sangre , Anemia Ferropénica/tratamiento farmacológico , Compuestos Ferrosos/uso terapéutico , Hemoglobinas/metabolismo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Anemia Ferropénica/etiología , Anemia Ferropénica/psicología , Heces/química , Femenino , Ferritinas/sangre , Compuestos Ferrosos/administración & dosificación , Compuestos Ferrosos/efectos adversos , Hepcidinas/sangre , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/psicología , Análisis de Intención de Tratar , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Transferrina/metabolismoRESUMEN
Gastro-retentive dosage forms have the potential to improve local therapy and decrease the variation in bioavailability that is observed with a number of commercially available immediate and modified release preparations. In this study, a dosage form has been developed, utilising freeze-dried calcium alginate beads, designed to float on the surface of the stomach contents thus prolonging the retention time. The aim of the study was to also assess the in vivo behaviour of the radio-labelled calcium alginate beads when they were administered under fasting conditions with either water or an aqueous solution of citric acid, a potential gut transit delaying substance. The study was performed in healthy male volunteers who swallowed the radio-labelled calcium alginate beads after a 10h overnight fast. Gamma scintigraphy was selected as the method to monitor the movement of the calcium alginate beads. The volunteers consumed no further food or drink until gastric emptying of the calcium alginate beads was complete. The results indicated that prolonged gastric retention was achieved when the dosage form was administered with the citric acid solution when compared to retention in the absence of citric acid. Citric acid, therefore, has the potential to delay the gastric emptying of the calcium alginate beads when administered to fasted volunteers.