Prokinetics prescribing in paediatrics: evidence on cisapride, domperidone, and metoclopramide.

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Prokinetics prescribing in paediatrics: evidence on cisapride, domperidone, and metoclopramide.

J Pediatr Gastroenterol Nutr. 2015 Apr;60(4):508-14

Authors: Mt-Isa S, Tomlin S, Sutcliffe A, Underwood M, Williamson P, Croft NM, Ashby D

Abstract
OBJECTIVES: Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children.
METHODS: We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case-control studies.
RESULTS: The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10-fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified.
CONCLUSIONS: These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good-quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies.

PMID: 25825854 [PubMed - indexed for MEDLINE]

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Dangerous liaisons? Gastroesophageal reflux disease and organizing pneumonia.

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Dangerous liaisons? Gastroesophageal reflux disease and organizing pneumonia.

Respiration. 2015;89(3):192-4

Authors: Drakopanagiotakis F

PMID: 25720852 [PubMed - indexed for MEDLINE]

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Gastroesophageal reflux disease is a risk factor for severity of organizing pneumonia.

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Gastroesophageal reflux disease is a risk factor for severity of organizing pneumonia.

Respiration. 2015;89(2):119-26

Authors: Gaillet G, Favelle O, Guilleminault L, de Muret A, Lemarie E, Lecomte T, Marchand-Adam S, Diot P

Abstract
BACKGROUND: The link between organizing pneumonia (OP) and gastroesophageal reflux disease (GERD) is not well known. There is little evidence in the literature to establish a causal link between GERD and OP.
OBJECTIVES: The aim of the study was to assess the hypothesis that OP is more severe when it is associated with GERD and that it leads to more frequent relapses.
METHODS: In a retrospective study on 44 patients suffering from OP, we compared the clinical, radiological and histological characteristics of 2 groups, 1 composed of patients with GERD (n = 20) and the other of patients without GERD (n = 24).
RESULTS: The GERD group was distinguished by a higher number of patients with migratory alveolar opacities on chest radiography and thoracic computerized tomography (14/20 vs. 9/24; p = 0.03 and 18/20 vs. 13/24; p = 0.01), greater hypoxemia [60 (42-80) vs. 70 (51-112) mm Hg; p = 0.03], greater bronchoalveolar lavage cellularity [0.255 (0.1-1.8) vs. 0.150 (0.05-0.4) g/l; p = 0.035] and more frequent relapses (14/20 vs. 9/24; p = 0.03).
CONCLUSIONS: OP associated with GERD is more severe and results in more frequent relapses. Microinhalation of gastric secretions might induce lung inflammation leading to OP and relapse. We suggest that typical symptoms of GERD such as pyrosis should be investigated in OP.

PMID: 25633753 [PubMed - indexed for MEDLINE]

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Treatment of aneurysmal aberrant right subclavian artery with triple-barrel stent graft.

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Treatment of aneurysmal aberrant right subclavian artery with triple-barrel stent graft.

Ann Vasc Surg. 2015 Apr;29(3):595.e1-3

Authors: Schwein A, Georg Y, Ohana M, Delay C, Lejay A, Thaveau F, Chakfe N

Abstract
Aneurysmal evolution of an aberrant right subclavian artery (ARSA) is an operative indication. Endovascular treatment is a minimally invasive procedure, which offers good short-term and midterm results. We describe a case of a 9-cm diameter ARSA aneurysm in a symptomatic man, treated with the triple-barrel technique using a thoracic aortic stent graft combined with surgical and endovascular revascularization of the supra-aortic trunks. Postoperatively, the patient developed a type III endoleak which was covered. The triple-barrel technique has been a proposed treatment approach for complex aortic arch pathologies and remains a less invasive option when compared with open surgery.

PMID: 25596407 [PubMed - indexed for MEDLINE]

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Hyperplasia of the submucosal glands of the columnar-lined oesophagus.

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Hyperplasia of the submucosal glands of the columnar-lined oesophagus.

Histopathology. 2015 Apr;66(5):726-31

Authors: Lörinc E, Öberg S

Abstract
AIM: To evaluate the presence of multi-layered epithelium (ME) and to compare the distribution, size and morphology of the oesophageal submucosal glands (SMG) beneath reflux exposed metaplastic columnar mucosa with those of normal squamous epithelium in patients with columnar-lined oesophagus (CLO).
METHODS AND RESULTS: In eight oesophageal resection specimens, the SMG of the metaplastic segments were significantly larger than those in the squamous segments of patients with CLO (0.81 versus 0.56 mm(2) , P = <0.001). There was an accumulation of SMG close to the neosquamocolumnar junction (NSCJ), as indicated by a higher median frequency of SMG (0.080 SMG/mm) compared with that of the squamous (0.013 SMG/mm) and metaplastic segments (0.031 SMG/mm) (P = 0.022). The frequency of ME was significantly higher in the metaplastic compared with the normal squamous segments (1/158 mm and 1/341 mm, respectively, P = 0.028) and ME was found almost exclusively (96%) in direct connection with the excretory ducts of SMG.
CONCLUSIONS: Hyperplasia of SMG in the metaplastic segment, accumulation of SMG near the NSCJ, the presence of ME in connection with the excretory ducts of SMG and metaplasia are all reflux-induced morphological changes, possibly induced by stimulation of progenitors in the excretory ducts of the SMG.

PMID: 25382111 [PubMed - indexed for MEDLINE]

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Cytoprotective effects of hydrogen sulfide in novel rat models of non-erosive esophagitis.

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Cytoprotective effects of hydrogen sulfide in novel rat models of non-erosive esophagitis.

PLoS One. 2014;9(10):e110688

Authors: Zayachkivska O, Havryluk O, Hrycevych N, Bula N, Grushka O, Wallace JL

Abstract
Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barrett's esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively). Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury.

PMID: 25333941 [PubMed - indexed for MEDLINE]

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Outcomes at one-year post anastomosis from a national cohort of infants with oesophageal atresia.

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Outcomes at one-year post anastomosis from a national cohort of infants with oesophageal atresia.

PLoS One. 2014;9(8):e106149

Authors: Allin B, Knight M, Johnson P, Burge D, BAPS-CASS

Abstract
BACKGROUND AND AIMS: We aimed to provide a contemporaneous assessment of outcomes at one-year post oesophageal atresia/tracheoesophageal fistula (OA-TOF) repair, focussing particularly on post-operative complications. It is generally accepted that oesophageal stricture is the most common complication and causes significant morbidity. We also aimed to assess the efficacy of prophylactic anti-reflux medication (PARM) in reducing stricture formation.
METHOD: A prospective, multi-centre cohort study of all infants live-born with oesophageal atresia in the United Kingdom and Ireland in 2008/9 was performed, recording clinical management and outcomes at one year. The effect of PARM on stricture formation in infants with the type-c anomaly was assessed using logistic regression analysis.
RESULTS: 151 infants were live-born with oesophageal atresia in the defined reporting period, 126 of whom had the type-c anomaly. One-year follow-up information was returned for 105 infants (70%); the mortality rate was 8.6% (95% CI 4.7-14.3%). Post-operative complications included anastomotic leak (5.4%), recurrent fistula (3.3%) and oesophageal stricture (39%). Seventy-six (60%) of those with type-c anomaly were alive at one-year with returned follow-up, 57(75%) of whom had received PARM. Of these, 24 (42%) developed a stricture, compared to 4 (21%) of those who had not received PARM (adjusted odds ratio 2.60, 95% CI 0.71-9.46, p = 0.147).
CONCLUSIONS: This study provides a benchmark for current outcomes and complication rates following OA-TOF repair, with oesophageal stricture causing significant morbidity. The use of PARM appeared ineffective in preventing strictures. This study creates enough doubt about the efficacy of PARM in preventing stricture formation to warrant further investigation of its use with a randomised controlled trial.

PMID: 25153838 [PubMed - indexed for MEDLINE]

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