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Despite the significant burden of chronic pain in sickle cell disease (SCD), non-pharmacological approaches to manage pain in SCD are lacking. Behavioral interventions incorporating digital cognitive-behavioral therapy CBT) for pain should be compared to available education efforts. To compare a CBT intervention tailored for adults with SCD to a digital pain/SCD education intervention (Education) on improving pain and associated symptoms. Multisite randomized comparative effectiveness trial. Seven comprehensive SCD centers and virtual recruitment through community organizations in the United States. Adults (age 18+) with SCD-related chronic pain and/or daily opioid use randomized to CBT or Education. Over 12 weeks, the CBT arm received an app-based intervention for pain management; the Education arm received digital pain/SCD education. Both groups received interactive chatbot lessons plus personalized health coach support. Changes in pain interference scale (primary); and other patient-reported outcomes (secondary), including pain intensity, depression, anxiety, quality of life, and self-efficacy over 6 months. 453 participants completed screening, 359 (79%) were randomized to CBT (n=181) or Education (n=178), 332 (92%) were Black African American, 238 (66.3%) female. At 6 months, 250 (70%) participants (n=125 per arm) completed follow-up assessments, 93 (26%) missed their follow-up window, 16 (4%) withdrew. Engagement with the chatbot content was variable (76% connected, 48% completed ≥1 lesson). However, 80% of participants completed ≥1 session with a health coach via phone, video, or text. The 6 month change in pain interference for CBT (-2.13; 95% CI, -3.42 to -0.84) and Education (-2.66; 95%CI, -3.97 to -1.36) was not significantly different (mean difference: 0.54; 95%CI, -1.30 to 2.37; *P=*0.57). Daily pain intensity ratings did not change for either group. There were no between-arm differences in depression, anxiety, and quality of life. CBT and Education did not differ in their effect on pain and mental health in SCD when combined with health coaching. Variable engagement with digital components and high engagement with health coaching may explain the lack of between-group differences, but these findings also provide insights into delivering digital interventions in racial minority and hard-to-reach populations. Trial Registration: ClinicalTrials.gov NCT04419168., (Copyright © 2024 American Society of Hematology.)

Background and Aim: Eosinophilic esophagitis (EoE) is a chronic disease which may progress to a fibro-stenotic phenotype due to esophageal sub-epithelial fibrosis. Esophageal wall thickening in patients with EoE has been demonstrated in a few studies using endoscopic ultrasound (EUS). The aim of this study was to longitudinally assess the endoscopic appearance, wall thickness, histology, and dysphagia score of EoE patients., Methods: Patients with EoE were recruited and studied between February 2012 and April 2021. Patients were evaluated on two separate occasions at least 12 months apart with endoscopy, EUS, and esophageal mucosal biopsies. The dysphagia score and epidemiology data were also assessed., Results: A total of 16 EoE patients were included with a mean follow-up duration of 2.2 ± 1.2 years. In 14/16 (88%) patients, the total wall thickness of the distal esophagus significantly increased ( P  = 0.0012) as a result of thickening of the muscularis propria ( P  = 0.0218). However, only 1/14 (7%) patient had an increase in the dysphagia score, while 8/14 (57%) and 5/14 (36%) had a stable and reduced dysphagia score, respectively. No differences were found in the total thickness of other esophageal regions, dysphagia score, endoscopic appearance, and eosinophil count over time., Conclusion: Distal esophageal wall thickness increases with time in EoE patients, independent of the dysphagia score and eosinophil count., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Thickening of the esophageal wall in patients with eosinophilic esophagitis (EoE) and gastro-esophageal reflux disease (GERD) has been shown in studies using endoscopic ultrasound (EUS). We hypothesise that transmural inflammation in EoE results in prominent esophageal wall thickening compared with the mucosal inflammation in GERD. The aim of this study was to compare the relationship among dysphagia, endoscopic appearance, wall thickness, histology, and motility in EoE and GORD., Methods: EoE and GERD patients were prospectively studied between February 2012 and April 2021. Patients were studied on 2 separate occasions with endoscopy, EUS and mucosal biopsies, followed by high-resolution manometry. Epidemiology and dysphagia data were obtained., Results: A total of 45 patients (31 EoE, 14 GERD) were included. There were no significant differences in age, sex, duration of disease and presence of esophageal motility disorders. EoE patients had a higher dysphagia score (P < 0.001), EREFS score (P < 0.001) and peak eosinophil count (P < 0.001) compared with GERD patients. Thickness of the submucosa in the distal esophagus in EoE was significantly higher than GERD (P = 0.003) and positively correlated with duration of disease (P = 0.01, R = 0.67). Positive correlation was also found between dysphagia score and distal total esophageal wall thickness (P = 0.03, R = 0.39) in EoE patients. No correlation was found between these variables in GERD patients., Conclusion: Distal esophageal wall thickness positively correlates with dysphagia score in EoE but not GERD. This appears to be related to the composition of the submucosa which can be identified using EUS., (© 2022. Crown.)

Background and Aim: The prevalence and incidence of eosinophilic esophagitis (EoE) has been increasing over recent years. However, the natural history remains incompletely understood particularly the differences in disease characteristics and progression of childhood-onset and adult-onset EoE. The aim of this study was to evaluate the disease characteristics and progression of childhood-onset and adult-onset EoE., Methods: A cross-sectional, questionnaire-based study, on 87 adults and 67 children from 2 major tertiary hospitals in South Australia was conducted. Data of those who were diagnosed with EoE between 1999 and 2018 were collected and correlated with medical records., Results: Of the 87 adults with EoE, 34 (39%) were diagnosed at the age of < 18 years (childhood-onset EoE). Reflux symptoms were more common in childhood-onset EoE, whereas asthma was more common in adult-onset EoE. The median duration of symptoms prior to diagnosis of EoE was > 1-4 years in childhood-onset disease (44%) and ≥ 10 years in adult-onset disease (34%). Food impaction was significantly more common on initial presentation in those with adult-onset EoE, whereas weight loss was more common in childhood-onset EoE. At the time of questionnaire, regurgitation, abdominal pain, and bloating were more common in childhood-onset EoE. Those with childhood-onset EoE were more likely to have multiple symptoms at questionnaire when compared with their adult-onset counterparts. In both groups, 15% (5/34 childhood-onset EoE and 8/53 adult-onset EoE) were asymptomatic at the time of questionnaire., Conclusion: Childhood-onset EoE appears to be a progressive disease from childhood to adulthood, however with more inflammatory-type symptoms post transition compared to those with adult-onset EoE., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) are the most common causes of chronic oesophagitis and dysphagia associated with oesophageal mucosal eosinophilia. Distinguishing between the two is imperative but challenging due to overlapping clinical and histological features. A diagnosis of EoE requires clinical, histological and endoscopic correlation whereas a diagnosis of GORD is mainly clinical without the need for other investigations. Both entities may exhibit oesophageal eosinophilia at a similar level making a histological distinction between them difficult. Although the term proton-pump inhibitor responsive oesophageal eosinophilia has recently been retracted from the guidelines, a relationship between EoE and GORD still exists. This relationship is complex as they may coexist, either interacting bidirectionally or are unrelated. This review aims to outline the differences and potential relationship between the two conditions, with specific focus on histology, immunology, pathogenesis and treatment., Competing Interests: Conflict-of-interest statement: There is no conflict of interest to disclose from all authors.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Background & Aims: Achalasia is a disorder of esophageal motility with a reported incidence of 0.5 to 1.6 per 100,000 persons per year in Europe, Asia, Canada, and America. However, estimates of incidence values have been derived predominantly from retrospective searches of databases of hospital discharge codes and personal communications with gastroenterologists, and are likely to be incorrect. We performed a cohort study based on esophageal manometry findings to determine the incidence of achalasia in South Australia., Methods: We collected data from the Australian Bureau of Statistics on the South Australian population. Cases of achalasia diagnosed by esophageal manometry were identified from the 3 adult manometry laboratory databases in South Australia. Endoscopy reports and case notes were reviewed for correlations with diagnoses. The annual incidence of achalasia in the South Australian population was calculated for the decade 2004 to 2013. Findings were standardized to those of the European Standard Population based on age., Results: The annual incidence of achalasia in South Australia ranged from 2.3 to 2.8 per 100,000 persons. The mean age at diagnosis was 62.1 ± 18.1 years. The incidence of achalasia increased with age (Spearman rho, 0.95; P < .01). The age-standardized incidence ranged from 2.1 (95% CI, 1.8-2.3) to 2.5 (95% CI, 2.2-2.7)., Conclusions: Based on a cohort study of esophageal manometry, we determined the incidence of achalasia in South Australia to be 2.3 to 2.8 per 100,000 persons and to increase with age. South Australia's relative geographic isolation and the population's access to manometry allowed for more accurate identification of cases than hospital code analyses, with a low probability of missed cases., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Achalasia can be subdivided into manometric subtypes according to the Chicago classification. These subtypes are proposed to predict outcome after treatment. This hypothesis was tested using a database of patients who underwent laparoscopic Heller's cardiomyotomy with anterior fundoplication., Methods: All patients who underwent Heller's cardiomyotomy for achalasia between June 1993 and March 2015 were identified from an institutional database. Manometry tracings were retrieved and re-reported according the Chicago classification. Outcome was assessed by a postal questionnaire, and designated a success if the modified Eckardt score was 3 or less, and the patient had not undergone subsequent surgery or pneumatic dilatation. Difference in outcome after cardiomyotomy was analysed with a mixed-effects logistic regression model., Results: Sixty, 111 and 24 patients had type I, II and II achalasia respectively. Patients with type III achalasia were more likely to be older than those with type I or II (mean age 63 versus 50 and 49 years respectively; P = 0·001). Some 176 of 195 patients returned questionnaires after surgery. Type III achalasia was less likely to have a successful outcome than type II (odds ratio (OR) 0·38, 95 per cent c.i. 0·15 to 0·94; P = 0·035). There was no significant difference in outcome between types I and II achalasia (II versus I: OR 0·87, 0·47 to 1·60; P 0·663). The success rate at 3-year follow-up was 69 per cent (22 of 32) for type I, 66 per cent (33 of 50) for type II and 31 per cent (4 of 13) for type III., Conclusion: Type III achalasia is a predictor of poor outcome after cardiomyotomy. There was no difference in outcome between types I and II achalasia., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Trans-sphincteric pressure gradient (TSPG) seems to play a relevant role in eliciting refluxes during transient lower esophageal sphincter relaxations (TLESRs). Intra-bolus pressure (IBP) is considered to be correlated to esophageal wall tone. We aimed to evaluate the relationship between IBP, TSPG during TLESRs and the dynamic properties of refluxate in gastroesophageal reflux disease. Sixteen non-erosive reflux disease (NERD), 10 erosive disease (ERD) patients and 12 healthy volunteers (HVs), underwent 24-hour impedance-pH monitoring and combined high-resolution manometry-impedance before and 60 minutes. After a meal, ERD patients presented a significantly lower mean IBP (4.7 ± 1.6 mmHg) respect to NERD patients (8.9 ± 2.8 mmHg) and HVs (9.2 ± 3.2 mmHg). NERD patients with physiological abnormal acid exposure time showed a mean IBP (10.4 ± 3.1 mmHg) significantly higher than that in NERD with pathological abnormal acid exposure time (5.1 ± 1.5 mmHg). The TSPG value was significantly higher during TLESRs accompanied by reflux than during TLESRs not associated with reflux, both in patients and in HVs. A significant direct correlation was found between IBP, TSPG and proximal spread of refluxes in patients and in HVs. Gastroesophageal reflux disease patients display different degrees of esophageal distension. An increased compliance of the distal esophagus may accommodate larger volumes of refluxate and likely facilitates the injuries development. Higher TSPG values appear to facilitate the occurrence of refluxes during TLESRs. In patients with NERD, higher TSPG and IBP values favor proximal spread of refluxate and hence may play a relevant role in symptom generation., (© 2015 International Society for Diseases of the Esophagus.)

Achalasia is a motility disorder encountered by surgeons during the investigation and treatment of dysphagia. Recent advances in manometry technology, a widely accepted new classification system and a new treatment rapidly gaining international acceptance, have changed the working knowledge required to successfully manage patients with achalasia. We review the Chicago classification subtypes of achalasia with type II achalasia being a predictor of success and type III achalasia a predictor of treatment failure. We review per-oral endoscopic myotomy as an emerging treatment option and its potential for improving the treatment of type III achalasia., (© 2016 Royal Australasian College of Surgeons.)

Background: With proton pump inhibitors and current sophisticated endoscopic techniques, the number of patients requiring surgical intervention for upper gastrointestinal bleeding has decreased considerably while trans-arterial embolization is being used more often. There are few direct comparisons between the effectiveness of surgery and embolization., Methods: A retrospective study of patients from two Australian teaching hospitals who had surgery or trans-arterial embolization (n = 103) for severe upper gastrointestinal haemorrhage between 2004 and 2012 was carried out. Patient demographics, co-morbidities, disease pathology, length of stay, complications, and overall clinical outcome and mortality were compared., Results: There were 65 men and 38 women. The median age was 70 (range 36-95) years. Patients requiring emergency surgical intervention (n = 79) or trans-arterial embolization (n = 24) were compared. The rate of re-bleeding after embolization (42%) was significantly higher compared with the surgery group (19%) (P = 0.02). The requirement for further intervention (either surgery or embolization) was also higher in the embolization group (33%) compared with the surgery group (13%) (P = 0.03). There was no statistical difference in mortality between the embolization group (5/24, 20.8%) and the surgical group (13/79, 16.5%) (P = 0.75)., Conclusion: Emergency surgery and embolization are required in 2.6% of patients with upper gastrointestinal bleeding. Both techniques have high mortalities reflecting the age, co-morbidities and severity of bleeding in this patient group., (© 2014 Royal Australasian College of Surgeons.)

Aim: To evaluate the practice of nutritional assessment and management of hospitalised patients with cirrhosis and the impact of malnutrition on their clinical outcome., Methods: This was a retrospective cohort study on patients with liver cirrhosis consecutively admitted to the Department of Gastroenterology and Hepatology at the Royal Adelaide Hospital over 24 mo. Details were gathered related to the patients' demographics, disease severity, nutritional status and assessment, biochemistry and clinical outcomes. Nutritional status was assessed by a dietician and determined by subjective global assessment. Estimated energy and protein requirements were calculated by Simple Ratio Method. Intake was estimated from dietary history and/or food charts, and represented as a percentage of estimated daily requirements. Median duration of follow up was 14.9 (0-41.4) mo., Results: Of the 231 cirrhotic patients (167 male, age: 56.3 ± 0.9 years, 9% Child-Pugh A, 42% Child-Pugh B and 49% Child-Pugh C), 131 (57%) had formal nutritional assessment during their admission and 74 (56%) were judged to have malnutrition. In-hospital caloric (15.6 ± 1.2 kcal/kg vs 23.7 ± 2.3 kcal/kg, P = 0.0003) and protein intake (0.65 ± 0.06 g/kg vs 1.01 ± 0.07 g/kg, P = 0.0003) was significantly reduced in patients with malnutrition. Of the malnourished cohort, 12 (16%) received enteral nutrition during hospitalisation and only 6 (8%) received ongoing dietetic review and assessment following discharge from hospital. The overall mortality was 51%, and was higher in patients with malnutrition compared to those without (HR = 5.29, 95%CI: 2.31-12.1; P < 0.001)., Conclusion: Malnutrition is common in hospitalised patients with cirrhosis and is associated with higher mortality. Formal nutritional assessment, however, is inadequate. This highlights the need for meticulous nutritional evaluation and management in these patients.

Background and Study Aims: Colonoscopy with inhaled methoxyflurane (Penthrox) is well tolerated in unselected subjects and is not associated with respiratory depression. The aim of this prospective study was to compare the feasibility, safety, and post-procedural outcomes of portable methoxyflurane used as an analgesic agent during colonoscopy with those of anesthesia-assisted deep sedation (AADS) in subjects with morbid obesity and/or obstructive sleep apnea (OSA)., Patients and Methods: The outcomes of 140 patients with morbid obesity/OSA who underwent colonoscopy with either Penthrox inhalation (n = 85; 46 men, 39 women; mean age 57.2 ± 1.1 years) or AADS (n = 55; 27 men, 28 women; mean age, 54.9 ± 1.1 years) were prospectively assessed., Results: All Penthrox-assisted colonoscopies were successful, without any requirement for additional intravenous sedation. Compared with AADS, Penthrox was associated with a shorter total procedural time (24 ± 1 vs. 52 ± 1 minutes, P < 0.001), a lower incidence of hypotension (3 /85 vs. 23 /55, P < 0.001), and a lower incidence of respiratory desaturation (0 /85 vs. 14 /55, P < 0.001). The patients in the Penthrox group recovered more rapidly and were discharged much earlier than those in the AADS group (27 ± 2 vs. 97 ± 5 minutes, P < 0.0001). Of those who underwent colonoscopy with Penthrox, 90 % were willing to receive Penthrox again for colonoscopy. More importantly, of the patients who underwent colonoscopy with Penthrox and had had AADS for previous colonoscopy, 82 % (28 /34) preferred to receive Penthrox for future colonoscopies. Penthrox-assisted colonoscopy cost significantly less than colonoscopy with AADS ($ 332 vs. $ 725, P < 0.001), with a cost saving of approximately $ 400 for each additional complication avoided., Conclusions: Compared with AADS, Penthrox is highly feasible and safe in patients with morbid obesity/OSA undergoing colonoscopy and is associated with fewer cardiorespiratory complications. Because of the advantages of this approach in regard to procedural time, recovery time, and cost benefit in comparison with AADS, further evaluation in a randomized trial is warranted.

Purpose of Review: Combined impedance-manometry was introduced just over 20 years ago for the assessment of esophageal motor function. Since then, technical developments have led to the introduction of high-resolution impedance-manometry (HRIM). However, analysis of the impedance and manometry recordings has remained separate and relatively unchanged since the introduction of HRIM, and it is unclear whether the addition of impedance has had a significant impact on the management of esophageal motor disorders., Recent Findings: The major technical advance over the past 12 months or so has been the development of automated impedance-manometry (AIM) analysis, in which the impedance and manometric data are analyzed together to assess the interactions between pressure and flow. This analysis has revealed subtle abnormalities in esophageal function in patients with nonobstructive dysphagia who have normal manometry and conventional impedance analyses. AIM analysis has also revealed preoperative characteristics in patients that may predict the occurrence of postfundoplication dysphagia., Summary: Through ongoing technical development, impedance-manometry is becoming increasingly useful clinically to assess esophageal motility disorders as well as to provide further insights into esophageal physiology.

Background & Aims: Transient lower esophageal sphincter relaxations (TLESRs) contribute to episodes of reflux. Few studies have assessed the frequencies or compositions of TLESRs and reflux episodes in patients with reflux disease. We used combined high-resolution manometry and impedance monitoring to analyze reflux episodes and esophageal motility in these patients, compared with those of healthy individuals., Methods: We evaluated the frequency of TLESRs and the relationship between the reflux pattern and esophageal pressures during TLESRs in 14 patients with nonerosive reflux disease (NERD) and 11 controls. Study participants underwent combined high-resolution manometry and impedance monitoring before and 60 minutes after a solid and liquid meal. The diagnosis of NERD was confirmed by a 24-hour pH impedance test., Results: The frequency of TLESRs did not differ between patients with NERD and controls. In patients with NERD, TLESRs were associated more often with reflux episodes than in controls (93% ± 6% vs 66% ± 19%; P < .05). Patients with NERD had a higher percentage of pure liquid reflux episodes (33% ± 15% vs 10% ± 2%; P < .05), whereas controls had a higher percentage of mixed reflux episodes (45% ± 16% vs 67% ± 17% in patients with NERD; P < .05). Patients with NERD also had a higher percentage of reflux (liquid and mixed) associated with common cavities (74% ± 18% vs 50% ± 20% in controls; P < .05)., Conclusions: In contrast to previous studies, we found that TLESRs are associated more often with reflux in patients with NERD than control subjects; this association increases when only liquid and mixed refluxes are considered. These findings indicate that factors involved in the occurrence of reflux in patients with NERD during TLESRs are different from those in healthy subjects., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Bleeding peptic ulcer (BPU) frequently occurs in the absence of preceding dyspeptic symptoms. We have observed that patients with BPU had a diminished symptom response to nutrient challenge test compared to uncomplicated peptic ulcer disease (uPUD). We postulated that more symptoms are manifest in patients with uPUD than BPU because there are greater derangements in gastric motor function., Aim: To assess gastric emptying in patients with BPU, uPUD and healthy controls (HC)., Methods: We studied 17 patients with BPU, 10 with uPUD, and 15 HC. After an 8-hour fast, subjects ingested 200 ml of an enteral feeding solution, containing 5 MBq (99m)Tc-rhenium sulphide colloid, every 5 min up to a cumulative volume of 800 ml. Gastric emptying was measured by scintigraphy for the total, proximal and distal stomach., Results: Patients with uPUD had significantly higher gastric retention in the proximal and total stomach at 100 min than HC and BPU, while BPU had similar percent retention to HC. Patients with uPUD had significantly higher cumulative symptom response to the nutrient challenge than did HC and BPU, while BPU had similar symptom responses to HC., Conclusions: Patients with uPUD have significantly delayed gastric emptying compared to HC and BPU. Data suggest that in addition to alterations of visceral sensory function, altered gastric motor function occurs during a nutrient challenge in uPUD but not BPU. Gastric motor function may contribute to the manifestation of dyspeptic symptoms in PUD.

Objective: Inhaled methoxyflurane (Penthrox, Medical Device International, Melbourne, Australia) has been used extensively in Australasia (Australia and New Zealand) to manage trauma-related pain. The aim is to evaluate the efficacy, safety, and outcome of Penthrox for colonoscopy., Design: Prospective randomized study., Setting: Three tertiary endoscopic centers., Patients: Two hundred fifty-one patients were randomized to receive either Penthrox (n = 125, 70 men, 51.4 ± 1.1 years old) or intravenous midazolam and fentanyl (M&F; n = 126, 72 men, 54.9 ± 1.1 years old) during colonoscopy., Main Outcome Measurement: Discomfort (visual analogue scale [VAS] pain score), anxiety (State-Trait Anxiety Inventory Form Y [STAI-Y] anxiety score), colonoscopy performance, adverse events, and recovery time., Results: Precolonoscopy VAS pain and STAI-Y scores were comparable between the 2 groups. There were no differences between groups in (1) pain VAS or STAI Y-1 anxiety scores during or immediately after colonoscopy, (2) procedural success rate (Penthrox: 121/125 vs M&F: 124/126), (3) hypotension during colonoscopy (7/125 vs 8/126), (4) tachycardia (5/125 vs 3/126), (5) cecal arrival time (8 ± 1 vs 8 ± 1 minutes), or (6) polyp detection rate (30/125 vs 43/126). Additional intravenous sedation was required in 10 patients (8%) who received Penthrox. Patients receiving Penthrox alone had no desaturation (oxygen saturation [SaO(2)] < 90%) events (0/115 vs 5/126; P = .03), awoke quicker (3 ± 0 vs 19 ± 1 minutes; P < .001) and were ready for discharge earlier (37 ± 1 vs 66 ± 2 minutes; P < .001) than those receiving intravenous M&F., Limitations: Inhaled Penthrox is not yet available in the United States and Europe., Conclusions: Patient-controlled analgesia with inhaled Penthrox is feasible and as effective as conventional sedation for colonoscopy with shorter recovery time, is not associated with respiratory depression, and does not influence the procedural success and polyp detection., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Data regarding the utility of the Glasgow-Blatchford bleeding score (GBS) in hospitalized patients with upper GI hemorrhage are limited., Objective: To evaluate the performance of the GBS in predicting clinical outcomes and the need for interventions in patients with upper GI hemorrhage., Design: Prospective observational study., Setting: Single, tertiary-care endoscopic center., Patients: Between July 2010 and July 2012, 888 consecutive hospitalized patients managed for upper GI hemorrhage were entered into the study., Intervention: GBS and Rockall scores., Main Outcome Measurements: GBS and Rockall scores were prospectively calculated. The performance of these scores to predict the need for interventions and outcomes was assessed by using a receiver operating characteristic curve., Results: Endoscopy was performed in 708 patients (80%). A total of 286 patients (40.3%) required endoscopic therapy, and 29 patients (3.8%) underwent surgery. GBS and post-endoscopy Rockall scores (post-E RS) were superior to pre-endoscopy Rockall scores in predicting the need for endoscopic therapy (area under the curve [AUC] 0.76 vs 0.76 vs 0.66, respectively) and rebleeding (AUC 0.71 vs 0.64 vs 0.57). The GBS was superior to Rockall scores in predicting the need for blood transfusion (AUC 0.81 vs 0.70 vs 0.68) and surgery (AUC 0.71 vs 0.64 vs 0.51). Patients with GBS scores ≤ 3 did not require intervention., Limitations: Subjective decision making as to need for endoscopic therapy and blood transfusion., Conclusion: Compared with post-E RS, the GBS was superior in predicting the need for blood transfusion and surgery in hospitalized patients with upper GI hemorrhage and was equivalent in predicting the need for endoscopic therapy, rebleeding, and death. There are potential cutoff GBS scores that allow risk stratification for upper GI hemorrhage, which warrant further evaluation., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep, but the mechanism remains unclear., Aim: To review the literature concerning gastro-oesophageal reflux during the sleep period, with particular reference to the sleep/awake state at reflux onset., Methods: Studies identified by systematic literature searches were assessed., Results: Overall patterns of reflux during the sleep period show consistently that oesophageal acid clearance is slower, and reflux frequency and oesophageal acid exposure are higher in patients with GERD than in healthy individuals. Of the 17 mechanistic studies identified by the searches, 15 reported that a minority of reflux episodes occurred during stable sleep, but the prevailing sleep state at the onset of reflux in these studies remains unclear owing to insufficient temporal resolution of recording or analysis methods. Two studies, in healthy individuals and patients with GERD, analysed sleep and pH with adequate resolution for temporal alignment of sleep state and the onset of reflux: all 232 sleep period reflux episodes evaluated occurred during arousals from sleep lasting less than 15 s or during longer duration awakenings. Six mechanistic studies found that transient lower oesophageal sphincter relaxations were the most common mechanism of sleep period reflux., Conclusions: Contrary to the prevailing view, subjective impairment of sleep in GERD is unlikely to be due to the occurrence of reflux during stable sleep, but could result from slow clearance of acid reflux that occurs during arousals or awakenings from sleep. Definitive studies are needed on the sleep/awake state at reflux onset across the full GERD spectrum., (© 2013 John Wiley & Sons Ltd.)

Objective: To investigate late objective outcomes 14 years after laparoscopic anterior 180-degree partial versus Nissen fundoplication., Background: Clinical outcomes from randomized clinical trials suggest good outcomes for anterior 180-degree partial fundoplication, with similar control of reflux symptoms and less side effects, compared with Nissen fundoplication. However, objective outcomes at late follow-up have not been reported., Methods: A subset of participants from a randomized trial of anterior 180-degree versus Nissen fundoplication underwent stationary esophageal high-resolution manometry and ambulatory 24-hour impedance-pH monitoring at 14 years' follow-up. The subset and other patients in the trial also completed a standardized clinical questionnaire to ensure that they were representative of the overall trial., Results: Eighteen patients (8 anterior, 10 Nissen) underwent objective testing and had a symptom profile similar to those who did not (n = 59) have testing. Total esophageal acid exposure time and the total number of acid and weakly acidic reflux episodes per 24 hours were higher after anterior fundoplication than after Nissen fundoplication. Proximal, midesophageal and distal reflux were proportionately increased after anterior 180-degree fundoplication. The number of liquid and mixed reflux episodes was also higher after anterior fundoplication, which was accompanied by higher clinical heartburn scores. There were no differences in gas reflux, gastric belches, and supragastric belches, which is in line with the observation that gas-related symptoms were similar for both groups. Mean LES resting and relaxation nadir pressure were lower after anterior fundoplication, which was reflected by lower dysphagia scores. Patient satisfaction was similar after both procedures., Conclusions: At 14 years after randomization, this study demonstrated that acid, weakly acidic, liquid and mixed reflux episodes are more common after anterior 180-degree fundoplication than after Nissen fundoplication. On the contrary, gas reflux and gastric belching and patient satisfaction are similar for both procedures. Mean LES resting and relaxation nadir pressure are lower after anterior fundoplication. Overall, these findings suggest less effective reflux control after anterior 180-degree partial fundoplication, offset by less dysphagia, leading to a clinical outcome that is equivalent to Nissen fundoplication at late follow-up.

Purpose: Scintigraphy is considered the most accurate technique for the measurement of gastric emptying (GE) but, for patients in the intensive care unit, it is technically demanding, involves radiation and can interfere with care. The (13)C-octanoate breath test ((13)C-OBT) is a simple, non-invasive technique that does not involve radiation exposure., Aim: To evaluate the performance of the (13)C-OBT in the assessment of GE in critically ill patients., Methods: The GE was assessed in 33 mechanically ventilated patients (23 M; 54.3 ± 3.0 yrs; APACHE II: 22.0 ± 1.1). Following test meal administration (100 ml Ensure(®)), concurrent scintigraphic measurement and breath samples ((13)C-OBT) were collected over 4 h. Scintigraphic meal retention was determined and the gastric emptying coefficient (GEC) and half emptying time [t50(BT)] were calculated for the (13)C-OBT. Delayed GE was defined as meal retention >13 % at 180 min., Results: Delayed GE was identified in 27/33 patients. Meal retention correlated modestly with t50(BT) (r = 0.55-0.66; P < 0.001) and well with GEC (r = -0.63 to -0.74; P < 0.0001). The strength of agreement between the two techniques was highest between GEC and retention at 120 min. The best cut-off GEC for defining delayed GE was 3.25 (AUC = 0.75; 95 % CI = 0.52-0.99; P = 0.05), with 89 % sensitivity and 67 % specificity to detect delayed GE. The GE was delayed in all (23/23) patients with feed intolerance (GRV > 250 ml) on scintigraphy and 91 % (21/23) patients on (13)C-OBT., Conclusion: In critical illness, there was a correlation between (13)C-OBT and gastric scintigraphy, with GEC performing as a better and more sensitive marker of detecting delayed GE than t50. However the relatively wide 95 % confidence intervals suggest that (13)C-OBT is more suitable as a technique to assess GE in a group setting for research studies rather than for individual patients in clinical practice.

Background and Aim: Data on the relationship between epidemiological changes in food bolus impaction (FBI) and its relationship to eosinophilic esophagitis (EoE) are limited. The aim of this study was to evaluate changes in the prevalence and etiology of FBI at the Royal Adelaide Hospital over 15 years., Methods: Details of all patients who presented with FBI to Royal Adelaide Hospital (1996-2010) were reviewed from a prospective database. Detailed endoscopic and histological findings were examined for patients admitted under the Gastroenterology team., Results: From 1996-2010, 539 patients were admitted. Prevalence of FBI increased overtime, with a male preponderance. The age at presentation was significantly lower in 2006-2010 (56.2 ± 1.6 years) compared with 2001-2005 (61.6 ± 1.9 years, P=0.03). There was a reduction in the proportion of patients with peptic-related stricture (from 75% [1996-2000] to 41% [2006-2010] [P<0.001]) and an increase in the prevalence of EoE (from 0% [1996-2000] to 35% [2006-2010], P<0.001). The proportion of patients who had esophageal biopsies taken at the index endoscopy also increased (8% [1996-2000] vs 28% [2001-2005] and 61% [2006-2010], P<0.01). There were no significant changes in rate of malignancy or post-surgical strictures. Endoscopic removal of food bolus was required in 86% of cases and, of these, 98% were successful with no complication or death., Conclusions: The prevalence of FBI has increased over the last 15 years. This was associated with an increased prevalence of EoE and a reduction in age of presentation and peptic-related strictures. These findings suggest that EoE is an important cause of FBI and that esophageal mucosal biopsy should be performed in all cases of FBI., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Objective: Inadequate nutrition is common in critical illness due in part to gastric stasis. However, recent data suggest that altered small intestinal mucosal function may be a contributing factor. The aim of this study was to examine the effects of critical illness on sucrose absorption, permeability, and mucosal morphology., Design: Prospective, observational study., Setting: Tertiary critical care unit., Subjects: Twenty mechanically ventilated patients (19 men; 52.2 ± 20.5 yr; 9 feed intolerant; Acute Physiology and Chronic Health Evaluation II score 16.2 ± 6.0) and 20 healthy subjects (14 men; 51.6 ± 21.5 yr)., Interventions: Following a 4-hr fast, a "meal" (100 kcal Ensure, 20-g enriched C-sucrose, 1.1 g rhamnose, 7.5 mL lactulose) was administered into the small intestine. Sucrose absorption was evaluated by analyzing 13CO2 concentration (cumulative percent of administered 13C dose recovered) in expiratory breath samples taken at timed intervals. At 90 minutes, a plasma lactulose/rhamnose concentration was also measured, with lactulose/rhamnose ratio, a marker of small intestinal mucosal permeability. When possible duodenal biopsies were taken in critically ill patients on insertion of the small intestinal feeding catheter and examined for disaccharidase levels and histology. Data are mean ± SD., Results: When compared with healthy subjects, critically ill patients had significantly reduced cumulative CO2 recovery (90 min: 1.78% ± 1.98% vs. 8.04% ± 2.55%; p < 0.001) and increased lactulose/rhamnose ratio (2.77 ± 4.24 vs.1.10 ± 0.98; p = 0.03). The lactulose/rhamnose ratio was greater in feed-intolerant patients (4.06 ± 5.38; p = 0.003). In five patients, duodenal mucosal biopsy showed mild to moderate epithelial injury. Sucrase levels were normal in all patients., Conclusions: Sucrose absorption is reduced and intestinal permeability increased in critically ill patients, possibly indicating an impairment of small intestinal mucosal function. These results, however, are discordant with duodenal mucosal histology and sucrase levels. This may reflect an inactivation of sucrase in vivo or inadequate nutrient exposure to the brush border due to small intestinal dysmotility.

Aim: To investigate the outcome of patients with symptoms of gastroesophageal reflux disease (GERD) referred for endoscopy at 2 and 6 mo post endoscopy., Methods: Consecutive patients referred for upper endoscopy for assessment of GERD symptoms at two large metropolitan hospitals were invited to participate in a 6-mo non-interventional (observational) study. The two institutions are situated in geographically and socially disparate areas. Data collection was by self-completion of questionnaires including the patient assessment of upper gastrointestinal disorders symptoms severity and from hospital records. Endoscopic finding using the Los-Angeles classification, symptom severity and it's clinically relevant improvement as change of at least 25%, therapy and socio-demographic factors were assessed., Results: Baseline data were available for 266 patients and 2-mo and 6-mo follow-up data for 128 and 108 patients respectively. At baseline, 128 patients had erosive and 138 non-erosive reflux disease. Allmost all patient had proton pump inhibitor (PPI) therapy in the past. Overall, patients with non-erosive GERD at the index endoscopy had significantly more severe symptoms as compared to patients with erosive or even complicated GERD while there was no difference with regard to medication. After 2 and 6 mo there was a small, but statistically significant improvement in symptom severity (7.02 ± 5.5 vs 5.9 ± 5.4 and 5.5 ± 5.4 respectively); however, the majority of patients continued to have symptoms (i.e., after 6 mo 81% with GERD symptoms). Advantaged socioeconomic status as well as being unemployed was associated with greater improvement., Conclusion: The majority of GORD patients receive PPI therapy before being referred for endoscopy even though many have symptoms that do not sufficiently respond to PPI therapy.

Background: Automated integrated analysis of impedance and pressure signals has been reported to identify patients at risk of developing dysphagia post fundoplication. This study aimed to investigate this analysis in the evaluation of patients with non-obstructive dysphagia (NOD) and normal manometry (NOD/NM)., Methods: Combined impedance-manometry was performed in 42 patients (27F : 15M; 56.2 ± 5.1 years) and compared with that of 24 healthy subjects (8F : 16M; 48.2 ± 2.9 years). Both liquid and viscous boluses were tested. MATLAB-based algorithms defined the median intrabolus pressure (IBP), IBP slope, peak pressure (PP), and timing of bolus flow relative to peak pressure (TNadImp-PP). An index of pressure and flow (PFI) in the distal esophagus was derived from these variables., Key Results: Diagnoses based on conventional manometric assessment: diffuse spasm (n = 5), non-specific motor disorders (n = 19), and normal (n = 11). Patients with achalasia (n = 7) were excluded from automated impedance-manometry (AIM) analysis. Only 2/11 (18%) patients with NOD/NM had evidence of flow abnormality on conventional impedance analysis. Several variables derived by integrated impedance-pressure analysis were significantly different in patients as compared with healthy: higher PNadImp (P < 0.01), IBP (P < 0.01) and IBP slope (P < 0.05), and shorter TNadImp&#95;PP (P = 0.01). The PFI of NOD/NM patients was significantly higher than that in healthy (liquid: 6.7 vs 1.2, P = 0.02; viscous: 27.1 vs 5.7, P < 0.001) and 9/11 NOD/NM patients had abnormal PFI. Overall, the addition of AIM analysis provided diagnoses and/or a plausible explanation in 95% (40/42) of patients who presented with NOD., Conclusions & Inferences: Compared with conventional pressure-impedance assessment, integrated analysis is more sensitive in detecting subtle abnormalities in esophageal function in patients with NOD and normal manometry., (© 2012 Blackwell Publishing Ltd.)

Purpose: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate., Methods and Materials: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion., Results: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques., Conclusions: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Background: Conventional measures of esophageal pressures or bolus transport fail to identify patients at risk of dysphagia after laparoscopic fundoplication., Methods: Liquid and viscous swallows were evaluated with impedance/manometry in 19 patients with reflux disease before and after surgery. A new method of automated impedance manometry (AIM) analysis correlated esophageal pressure with impedance data and automatically calculated a range of pressure and bolus movement variables. An iterative analysis determined whether any variables were altered in relation to dysphagia. Standard measures of esophago-gastric junction pressure, bolus presence time, and total bolus transit time were also evaluated., Key Results: At 5 months postop, 15 patients reported some dysphagia, including 7 with new-onset dysphagia. For viscous boluses, three AIM-derived pressure-flow variables recorded preoperatively varied significantly in relation to postoperative dysphagia. These were: time from nadir esophageal impedance to peak esophageal pressure (TNadImp-PeakP), median intra-bolus pressure (IBP, mmHg), and the rate of bolus pressure rise (IBP slope, mmHgs(-1) ). These variables were combined to form a dysphagia risk index (DRI=IBP×IBP&#95;slope/TNadImp-PeakP). DRI values derived from preoperative measurements were significantly elevated in those with postoperative dysphagia (DRI=58, IQR=21-408 vs no dysphagia DRI=9, IQR=2-19, P<0.02). A DRI >14 was optimally predictive of dysphagia (sensitivity 75% and specificity 93%)., Conclusions & Inferences: Before surgery, a greater and faster compression of a swallowed viscous bolus with less bolus flow time relates to postoperative dysphagia. Thus, susceptibility to postfundoplication dysphagia is related to a pre-existing sub-clinical variation of esophageal function., (© 2012 Blackwell Publishing Ltd.)

Background: Inflammatory bowel disease (IBD) is a chronic disease requiring long-term management. General practitioners (GPs) are often the first point of contact for initial symptoms and flares. Thus we assessed GPs' attitudes to and knowledge of IBD., Methods: A state-wide postal survey of GPs was performed collecting demographic details, practice and attitudes in IBD-specific management and knowledge., Results: Of 1800 GPs surveyed in South Australia, 409 responded; 58% were male, 80% Australian trained and 73% practised in metropolitan areas. Most GPs (92%) reported seeing zero to five IBD patients per month. Overall, 37% of the GPs reported being generally 'uncomfortable' with IBD management. Specifically, they were only somewhat comfortable in providing/using maintenance therapy, steroid therapy or unspecified therapy for an acute flare. They were uncomfortable with the use of immunomodulators and biologicals (71 and 91% respectively). No GP reported never referring, referring sometimes (12%), often (34%) or always (55%). Most (87%) GPs rated their communication with private specialists positively; while only 32% were satisfied with support from public hospitals. Of concern, most (70%) monitored patients on immunosuppression on a case-by-case basis rather than by protocol. In multivariable analyses, GPs' IBD-specific knowledge did not influence comfort with overall management, nor did knowledge influence GP comfort with any particular therapy., Conclusion: Individual GPs care for few IBD patients and have variable attitudes in their practice. Whether improvement can realistically be achieved given individual GP's paucity of patients is questionable. These data support the provision of better support and specific action plans for IBD patients., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Dysphagia is common in the general population, and is generally due to either mechanical obstruction or dysmotility. Patient demographics and symptom evaluation are often useful in determining the likely cause, and guide subsequent investigation and management. Oropharyngeal dysphagia is usually caused by neurological conditions where treatment options are limited. Conversely, many of the esophageal causes of dysphagia are amenable to therapy. Gastroscopy is often the first test of choice, given its diagnostic and therapeutic potential, especially when mechanical causes are concerned. Esophageal motor function can be assessed by a variety of techniques, ranging from radiology such as barium swallow, to dedicated motility tests such as manometry and impedance monitoring. The choice of test relies on the clinical indication and the results should be interpreted in conjunction with the patients' symptoms. High-resolution manometry with topography is now the new benchmark for motility studies. Several new techniques for motility testing have also become available, such as esophageal ultrasound and functional lumen imaging probe, but are currently limited to the research setting., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: The advent of drugs that inhibit transient lower esophageal sphincter relaxation (TLESR) necessitates accurate identification and scoring. We assessed the intra- and inter-assessor variability of the existing objective criteria for TLESR, improving them where necessary., Methods: Two 3-h postprandial esophageal manometric and pH recordings were performed in 20 healthy volunteers. Each recording was duplicated. The recordings were analyzed by five experienced observers for TLESRs based on their expert opinion. TLESRs were also analyzed for the presence of the original four criteria as well as inhibition of the crural diaphragm (ID), a prominent after-contraction (AC), acid reflux and an esophageal common cavity., Key Results: The overall inter- and intra-observer agreements for TLESRs scored, according to observer's expert opinion, were 59% (range 56-67%) and 74% (60-89%), respectively. When TLESRs were restricted to those fulfilling the original criteria, these agreements fell to 46% (40-53%) and 60% (44-67%), respectively. Cleaning the recordings by removal of technically flawed sections improved agreements by 5%. Inclusion of additional criteria (ID and AC) resulted in inter- and intra-observer agreements of 62% (52-70%) and 69% (53-79%), respectively. A consensus analysis performed collectively by three observers and based on the new criteria (original ± ID and AC) resulted in 84% agreement between the paired recordings., Conclusions & Inferences: The original criteria for the definition of TLESRs allows for substantial inter- and intra-observer variability, which can be reduced by incorporation of additional objective criteria. However, the highest level of intra-observer agreement can be achieved by consensus analysis., (© 2011 Blackwell Publishing Ltd.)