Development of a validated patient-reported symptom metric for pediatric Eosinophilic Esophagitis: qualitative methods

<p>Abstract</p> <p>Background</p> <p>Previous attempts to measure symptoms in pediatric Eosinophilic Esophagitis (EoE) have not fully included patients and parents in the item development process. We sought to identify and validate key patient self-reported and parent proxy-reported outcomes (PROs) specific to EoE.</p> <p>Methods</p> <p>We developed methodology for focus and cognitive interviews based on the Food and Drug Administration (FDA) guidelines for PROs, the validated generic PedsQL™ guidelines, and the consolidated criteria for reporting qualitative research (COREQ). Both child (ages 8-12 and 13-18) and parent-proxy (ages 2-4, 5-7, 8-12, and 13-18) interviews were conducted.</p> <p>Results</p> <p>We conducted 75 interviews to construct the new instrument. Items were identified and developed from individual focus interviews, followed by cognitive interviews for face and content validation. Initial domains of symptom frequency and severity were developed, and open-ended questions were used to generate specific items during the focus interviews. Once developed, the instrument construct, instructions, timeframe, scoring, and specific items were systematically reviewed with a separate group of patients and their parents during the cognitive interviews.</p> <p>Conclusions</p> <p>To capture the full impact of pediatric EoE, both histologic findings and PROs need to be included as equally important outcome measures. We have developed the face and content validated Pediatric Eosinophilic Esophagitis Symptom Score (PEESS™ v2.0). The PEESS™ v2.0 metric is now undergoing multisite national field testing as the next iterative instrument development phase.</p

Georgios I

Απεικόνιση: φωτογραφί

Multiple endocrine neoplasia 2B: Differential increase in enteric nerve subgroups in muscle and mucosa.

Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome caused by an activating mutation of the RET gene, leading to enteric gangliomatosis. This child presented with constipation at 1-mo old, was diagnosed with MEN2B by rectal biopsy at 4 mo, had thyroidectomy at 9 mo and a colectomy at 4 years. We studied the extent of neuronal and nerve fibre proliferation and which classes of enteric nerves are affected by examining the colon with multiple neuronal antibodies. Resected transverse colon was fixed, frozen, sectioned and processed for fluorescence immunohistochemistry labelling with antibodies against TUJ1, Hu, ChAT, NOS, VIP, SP and CGRP and cKit. Control transverse colon was from the normal margin of Hirschsprung (HSCR) colon (4-year-old) and a child with familial adenomatous polyposis (FAP, 12 year). Myenteric ganglia were increased in size to as wide as the circular muscle. There was a large increase in nerve cells and nerve fibres. ChAT-, NOS-, VIP- and SP-immunoreactive nerve fibres all increased in the myenteric ganglia. NOS-IR nerves preferentially increased in the muscle, while VIP and SP increased in submucosal ganglia and mucosal nerve fibres. The density of ICC was normal. RET overactivation in MEN2B lead to a large increase in intrinsic nerve fibres in the myenteric and submucosal ganglia, with a relative increase in NOS-IR nerve fibres in the circular muscle and VIP and SP in the submucosal ganglia and mucosa. The changes were associated with severe constipation resulting in colectomy at 4 years

Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?

To permit normal postnatal germ cell development, the mammalian testis undergoes a complex, multi-staged process of descent to the scrotum. Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing for orchidopexy

Dietary exclusion of fructose and lactose after positive breath tests improved rapid-transit constipation in children

Aims: Exclusion of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) from the diet is effective in alleviating symptoms of irritable bowel syndrome (IBS) in adults. Rapid-transit constipation (RTC) is a recently discovered subset of chronic constipation and has been linked to food intolerance. The aim of this study was to audit the effect of specific FODMAP elimination diets in children with RTC. Methods: This was an audit of children presenting to a tertiary children's hospital surgeon with refractory chronic constipation who had rapid transit in the proximal colon on nuclear imaging; had hydrogen/methane breath tests for fructose, lactose, and/or sorbitol intolerance; and were advised to exclude positive sugar under clinical supervision. Patients filled in a questionnaire rating severity of constipation, abdominal pain, and pain on defecation with a visual analogue scale (VAS, 0 = none, 10 = high) and stool consistency for 6 months before and after dietary exclusion. Results: In responses from 29 children (5-15 years, 21 males), 70% eliminated fructose, and 40% eliminated lactose. There was a significant reduction in the severity of constipation (VAS mean ± SEM, pre 5.8 ± 0.5 vs post 3.3 ± 0.6, P < 0.0001), abdominal pain (5.1 ± 0.6 vs 2.8 ± 0.5, P = 0.0004), pain on defecation (5.8 ± 0.6 vs 2.6 ± 0.5, P < 0.0001), and increase in stool wetness (Bristol Stool Scale pre 3.3 ± 0.3 vs post 3.9 ± 0.2, P = 0.004). Conclusion: Children with RTC showed significant improvements in constipation and pain after excluding the sugar indicated by positive breath tests, suggesting that specific sugar-exclusion diets may have a role in the management of RTC in children