Knowledge gaps in the management of refractory reflux-like symptoms: Healthcare provider survey.

BACKGROUND: Refractory reflux-like symptoms have a substantial impact on patients and healthcare providers. The aim of the survey was to qualitatively assess the needs and attitudes of practicing clinicians around the management of refractory reflux symptoms and refractory gastroesophageal reflux disease (rGERD). METHODS: An International Working Group for the Classification of Oesophagitis (IWGCO) steering committee invited clinicians to complete an online survey including 17 questions. KEY RESULTS: Of the 113 clinicians who completed the survey, 70% were GIs, 20% were primary care physicians, and 10% were other specialties. Functional heartburn was considered the most common reason for an incomplete response to proton pump inhibitor (PPI) therapy (82%), followed by stress/anxiety (69%). More GIs identified esophageal hypersensitivity as a cause, while more non-GIs identified esophageal dysmotility and non-reflux-related esophageal conditions. As the first step, most clinicians would order investigations (70-88%). Overall, 72% would add supplemental therapy for patients with partial response, but only 58% for those with non-response. Antacid/alginate was the most common choice overall, while non-GIs were more likely to add a prokinetic than were GIs (47.8 vs. 24.1%). Approximately 40% of clinicians would switch PPIs in patients with partial response, but only 29% would do so in non-responders. Preferences for long-term therapy were highly variable. The most common initial investigation was upper endoscopy. Choice of esophageal manometry and pH monitoring was more variable, with no clear preference for whether pH monitoring should be conducted on, or off, PPI therapy. CONCLUSIONS AND INFERENCES: The survey identified a number of challenges for clinicians, especially non-GI physicians, treating patients with refractory reflux-like symptoms or rGERD on a daily basis.

Efficacy of Rikkunshito for Functional Heartburn: A Prospective Pilot Study.

BACKGROUND: Although rikkunshito was reported to be effective for treatment-resistant nonerosive gastroesophageal reflux disease (NERD), it is unclear which Rome IV subgroups of NERD patients benefit fromrikkunshito. This study investigated the efficacy of rikkunshito in patients with functional heartburn. METHODS: Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled and received rikkunshito for 8 weeks. The Frequency Scale for Symptoms of GERD (FSSG), the Japanese translation of the Quality of Life in Reflux and Dyspepsia (QOLRAD-J) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) before, and 4 and 8 weeks after, administration were evaluated. Overall treatment efficacy (OTE) was evaluated at 8 weeks after administration. RESULTS: One patient voluntarily withdrew from treatment at 4 weeks. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score was higher 8 weeks after treatment or at discontinuation than before treatment, the difference was not significant different. HADS score was not significantly lower 8 weeks after treatment or at discontinuation, as compared with before treatment. However, total FSSG and HADS anxiety scores were positively correlated (correlation coefficient: 0.684, P = 0.027). CONCLUSIONS: The findings from this first study of the efficacy of rikkunshito for functional heartburn suggest that it might be effective in such patients.

Untangling Nonerosive Reflux Disease From Functional Heartburn.

Heartburn is a common symptom in clinical practice, but as many as 70% of patients have normal findings from upper endoscopy. Most of these patients have nonerosive reflux disease (NERD) or functional esophageal disorders. NERD is the most common phenotype of gastroesophageal reflux disease, and functional heartburn is the most common cause for refractory heartburn. In patients with NERD, symptoms arise from gastroesophageal reflux and esophageal hypersensitivity, whereas in patients with functional heartburn, symptoms result from esophageal hypersensitivity. A diagnosis of NERD requires endoscopy and reflux testing, whereas a diagnosis of functional heartburn also requires esophageal manometry. NERD is treated most commonly with medical, endoscopic, and surgical antireflux approaches, whereas functional heartburn as well as NERD can be treated with neuromodulators, psychological intervention, and complementary medicine options.

AGA Clinical Practice Update on Functional Heartburn: Expert Review.

BEST PRACTICE ADVICE 1: A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. BEST PRACTICE ADVICE 2: A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 3: Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 4: PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. BEST PRACTICE ADVICE 5: Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. BEST PRACTICE ADVICE 6: Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. BEST PRACTICE ADVICE 7: Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended.

Diagnosis and Management of Functional Heartburn.

Heartburn is among the most common gastrointestinal symptoms presenting to both generalist physicians and gastroenterologists. Heartburn that does not respond to traditional acid suppression is a diagnostic and therapeutic dilemma. In the era of high utilization of proton pump inhibitors, a substantial proportion of patients presenting to the gastroenterologist with chronic symptoms of heartburn do not have a reflux-mediated disease. Subjects without objective evidence of reflux as a cause of their symptoms have "functional heartburn". The diagnostic role of endoscopy, reflux and motility testing in functional heartburn (FH) patients is discussed. Lifestyle modifications, pharmacological interventions, and alternative therapies for FH are also presented. Recognition of patients with FH allows earlier assignment of these patients to different treatment algorithms, which may allow greater likelihood of success of treatment, diminished resource utilization and improved quality of life. Further data on this large and understudied group of patients is necessary to allow improvement in treatment algorithms and a more evidence-based approach to care of these patients.

Identification and management of tardive dyskinesia: A case series and literature review.

Tardive dyskinesia (TD) is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking dopamine receptor-blocking agents. The pathophysiology of TD is complex, multifactorial and still not fully understood. Although there is no identified effective and standard treatment for TD, several agents have been tried for the management of this motor disturbance. The aim of this case series is to review the literature in regard to the identification, diagnosis and the treatment of TD with anticholinergics, anticholinergic medication withdrawal, cholinergic agents, botulinum toxin intramuscular injections, tetrabenazine, levetiracetam, propranolol and zolpidem, and to describe one case of TD that responded favorably to clonazepam and two cases of TD that responded favorably to Ginkgo biloba.

Influence of inhomogeneous static magnetic field-exposure on patients with erosive gastritis: a randomized, self- and placebo-controlled, double-blind, single centre, pilot study.

This pilot study was devoted to the effect of static magnetic field (SMF)-exposure on erosive gastritis. The randomized, self- and placebo-controlled, double-blind, pilot study included 16 patients of the 2nd Department of Internal Medicine, Semmelweis University diagnosed with erosive gastritis. The instrumental analysis followed a qualitative (pre-intervention) assessment of the symptoms by the patient: lower heartburn (in the ventricle), upper heartburn (in the oesophagus), epigastric pain, regurgitation, bloating and dry cough. Medical diagnosis included a double-line upper panendoscopy followed by 30 min local inhomogeneous SMF-exposure intervention at the lower sternal region over the stomach with peak-to-peak magnetic induction of 3 mT and 30 mT m(-1) gradient at the target site. A qualitative (post-intervention) assessment of the same symptoms closed the examination. Sham- or SMF-exposure was used in a double-blind manner. The authors succeeded in justifying the clinically and statistically significant beneficial effect of the SMF- over sham-exposure on the symptoms of erosive gastritis, the average effect of inhibition was 56% by p = 0.001, n = 42 + 96. This pilot study was aimed to encourage gastroenterologists to test local, inhomogeneous SMF-exposure on erosive gastritis patients, so this intervention may become an evidence-based alternative or complementary method in the clinical use especially in cases when conventional therapy options are contraindicated.

A rapid, simple questionnaire to assess gastrointestinal symptoms after oral ferrous sulphate supplementation.

BACKGROUND: Oral iron supplementation is often associated with rapid onset of gastrointestinal side-effects. The aim of this study was to develop and trial a short, simple questionnaire to capture these early side-effects and to determine which symptoms are more discriminating. METHODS: The study was a double-blind placebo-controlled randomized parallel trial with one week treatment followed by one week wash-out. Subjects were randomized into two treatment groups (n = 10/group) to receive either ferrous sulphate (200 mg capsules containing 65 mg of iron) or placebo, both to be taken at mealtimes twice daily during the treatment period. Subjects completed the questionnaires daily for 14 days. The questionnaire included gastrointestinal symptoms commonly reported to be associated with the oral intake of ferrous iron salts (i.e. nausea, vomiting, heartburn, abdominal pain, diarrhoea, and constipation). RESULTS: Seventy five per cent of participants reporting the presence of one or more symptoms in the first week of the study were in the ferrous sulphate group. In the second week of the study (i.e. wash-out), 67% of the participants reporting one or more symptom(s) were in the ferrous sulphate group. In the first week of the study (treatment) the number of symptoms reported by participants in the ferrous sulphate group (mean ± SEM = 6.7 ± 1.7) was significantly higher than that for participants in the placebo group (1.2 ± 0.5) (p = 0.01). In the second week of the study (wash-out) the number of symptoms reported by participants in the ferrous sulphate group (4.6 ± 2.0) appeared higher than for participants in the placebo group (1.0 ± 0.7) although this did not reach significance (p = 0.12). Events for which the gastrointestinal symptom questionnaire was most discriminatory between ferrous sulphate and placebo groups were: heartburn, abdominal pain and the presence of black stools (all p ≤ 0.03). CONCLUSIONS: A tool for the detection of commonly-occurring side effects should not require large study numbers to be effective. With just 10 subjects per group (iron or placebo), this simple questionnaire measures gastrointestinal side-effects associated with oral iron (ferrous sulphate) supplementation, and would be appropriate for use in intervention studies or clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02146053 (21/05/2014).

Multimodality evaluation of patients with gastroesophageal reflux disease symptoms who have failed empiric proton pump inhibitor therapy.

Patients with symptoms suggestive of gastroesophageal reflux disease (GERD), such as chest pain, heartburn, regurgitation, and dysphagia, are typically treated initially with a course of proton pump inhibitors (PPIs). The evaluation of patients who have either not responded at all or partially and inadequately responded to such therapy requires a more detailed history and may involve an endoscopy and esophageal biopsies, followed by esophageal manometry, ambulatory esophageal pH monitoring, and gastric emptying scanning. To assess the merits of a multimodality 'structural' and 'functional' assessment of the esophagus in patients who have inadequately controlled GERD symptoms despite using empiric PPI, a retrospective cohort study of patients without any response or with poor symptomatic control to empiric PPI (>2 months duration) who were referred to an Esophageal Studies Unit was conducted. Patients were studied using symptom questionnaires, endoscopy (+ or - for erosive disease, or Barrett's metaplasia) and multilevel esophageal biopsies (eosinophilia, metaplasia), esophageal motility (aperistalsis, dysmotility), 24-hour ambulatory esophageal pH monitoring (+ if % total time pH < 4 > 5%), and gastric emptying scanning (+ if >10% retention at 4 hours and >70% at 2 hours). Over 3 years, 275 patients (147 men and 128 women) aged 16-89 years underwent complete multimodality testing. Forty percent (n= 109) had nonerosive reflux disease (esophagogastroduodenoscopy [EGD]-, biopsy-, pH+); 19.3% (n= 53) had erosive esophagitis (EGD+); 5.5% (n= 15) Barrett's esophagus (EGD+, metaplasia+); 5.5% (n= 15) eosinophilic esophagitis (biopsy+); 2.5% (n= 7) had achalasia and 5.8% (n= 16) other dysmotility (motility+, pH-); 16% (n= 44) had functional heartburn (EGD-, pH-), and 5.8% (n= 16) had gastroparesis (gastric scan+). Cumulative symptom scores for chest pain, heartburn, regurgitation, and dysphagia were similar among the groups (mean range 1.1-1.35 on a 0-3 scale). Multimodality evaluation changed the diagnosis of GERD in 34.5% of cases and led to or guided alternative therapies in 42%. Overlap diagnoses were frequent: 10/15 (67%) of patients with eosinophilic esophagitis, 12/16 (75%) of patients with gastroparesis, and 11/23 (48%) of patients with achalasia or dysmotility had concomitant pathologic acid reflux by pH studies. Patients with persistent GERD symptoms despite empiric PPI therapy benefit from multimodality evaluation that may change the diagnosis and guide therapy in more than one third of such cases. Because symptoms are not specific and overlap diagnoses are frequent and multifaceted, objective evidence-driven therapies should be considered in such patients.

Effect of acid swallowing on esophageal contraction in patients with heartburn related to hypersensitivity.

BACKGROUND AND AIM: There are heterogeneous subgroups among those with heartburn, and data on these individuals are relatively scant. We aimed to evaluate the effect of acid challenge on the segmental contractions of esophageal smooth muscle in endoscopy-negative patients with normal esophageal acid exposure. METHODS: High-resolution esophageal manometry (HRM) was performed on 30 endoscopy-negative patients with heartburn accompanied by normal esophageal acid exposure using 10 water swallows followed by 10 acidic pomegranate juice swallows. Patients were classified into functional heartburn (FH) and hypersensitive esophagus (HE) groups based on the results of 24-hr impedance pH testing. HRM topographic plots were analyzed and maximal wave amplitude and pressure volumes were measured for proximal and distal smooth muscle segments. RESULTS: The pressure volume of the distal smooth muscle segment in the HE group measured during acidic swallows was higher than during water swallows (2224.1 ± 68.2 mmHg/cm per s versus 2105.6 ± 66.4 mmHg/cm per s, P = 0.027). A prominent shift in the pressure volume to the distal smooth muscle segment was observed in the HE group compared with the FH group (segmental ratio: 2.72 ± 0.08 versus 2.39 ± 0.07, P = 0.005). Manometric measurements during acidic swallows revealed that this shift was augmented in the HE group. The optimal ratio of pomegranate juice swallowing for discrimination of FH from HE was 2.82, with a sensitivity of 88.9% and a specificity of 100%. CONCLUSIONS: Hypercontractile response of distal smooth muscle segment to acid swallowing was more prominent in the HE group than the FH group.

Esofagitis eosinofílica en el diagnóstico de pirosis / Eosinophilic oesophagitis in the diagnosis of heartburn

La esofagitis eosinofílica es una entidad poco frecuente, más común en niños, caracterizada por la infiltración de la mucosa esofágica por múltiples leucocitos eosinófilos. Su clínica más frecuente es disfagia, impactación y pirosis. La apariencia endoscópica varía de una mucosa casi normal a la aparición de anillos o incluso estenosis esofágica. El diagnóstico definitivo es anatomopatológico y el tratamiento actual se basa en el uso de corticoides tópicos. Se presenta, a continuación, el caso de un joven de 17 años con clínica de disfagia y pirosis, diagnosticado de dicha enfermedad tras la realización de endoscopia, con buena evolución clínica tras el tratamiento corticoideo (AU)

Eosinophilic oesophagitis is a rare entity, more common in children, and characterised by the infiltration of the oesophageal mucosa by multiple eosinophilic leukocytes. Its most common clinical symptoms are dysphagia, food impaction and heartburn. The endoscopic appearance varies from an almost normal mucosa to the appearance of rings or oesophageal stricture. The final diagnosis is by histopathology and the current treatment is based on the use of topical corticosteroids. The case is presented of a 17 year-old with symptoms of dysphagia and heartburn. The disease was diagnosed after endoscopy, with a good clinical outcome after corticosteroid treatment (AU)

Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn.

BACKGROUND: The current standard of care in proton pump inhibitor failure is to double the proton pump inhibitor dose, despite limited therapeutic gain. Aims To determine the efficacy of adding acupuncture vs. doubling the proton pump inhibitor dose in gastro-oesophageal reflux disease patients who failed symptomatically on proton pump inhibitors once daily. METHODS: Thirty patients with classic heartburn symptoms who continued to be symptomatic on standard-dose proton pump inhibitors were enrolled into the study. All participants underwent upper endoscopy while on proton pump inhibitors once daily. Subsequently, patients were randomized to either adding acupuncture to their proton pump inhibitor or doubling the proton pump inhibitor dose over a period of 4 weeks. Acupuncture was delivered twice a week by an expert. RESULTS: The two groups did not differ in demographic parameters. The acupuncture + proton pump inhibitor group demonstrated a significant decrease in the mean daytime heartburn, night-time heartburn and acid regurgitation scores at the end of treatment when compared with baseline, while the double-dose proton pump inhibitor group did not demonstrate a significant change in their clinical endpoints. Mean general health score was only significantly improved in the acupuncture + proton pump inhibitor group. CONCLUSION: Adding acupuncture is more effective than doubling the proton pump inhibitor dose in controlling gastro-oesophageal reflux disease-related symptoms in patients who failed standard-dose proton pump inhibitors.

Symptom association probability and symptom sensitivity index: preferable but still suboptimal predictors of response to high dose omeprazole.

BACKGROUND: Twenty four hour oesophageal pH monitoring is frequently used to quantify the association between a patient's symptom and gastro-oesophageal reflux. Three indices (symptom association probability (SAP), symptom index (SI), and symptom sensitivity index (SSI)) are used to quantify and establish this relation. AIMS: The aim of the present study was to compare these indices against the omeprazole test (OT) as an objective indicator of reflux induced symptoms. METHODS: Fifty two patients with a predominant symptom of heartburn were enrolled from gastroenterology and primary care clinics. Baseline symptom score was calculated at the fist visit. All patients underwent 24 hour oesophageal pH monitoring, and symptom-reflux association indices were calculated. All patients were placed on high dose omeprazole (40 mg in the morning, 20 mg at night) after completion of pH monitoring and symptom score was recorded again after one week. RESULTS: Thirty eight patients completed the study. All three indices were significantly related to each other (p<0.001). SAP and SSI (with a new cut off of 1.3, but not with the commonly used 5%) had statistically significant relations with OT (p<0.05 for both). SSI had the highest positive and negative predictive values and sensitivity. The specificity of SSI and SAP was equal and lower than SI. Areas under the receiver operating characteristic (ROC) curve for the three indices were not significantly different from each other or from a hypothetical non-discriminating test. Per cent time pH <4, sex, and age had no relation to OT and no effect on its correlation with association indices. No cut off point could be found at which the results of SI could be related significantly to the OT results. CONCLUSION: SAP and SSI are significantly related to symptomatic response to high dose omeprazole; however, they are far from perfect, with a significant number of discordant cases as well as relatively small areas under the ROC curves. We suggest that the new cut off of 1.3 be used for SSI in the future. Further research is needed to identify possible methods to improve the discrimination power of these indices or to identify possible patient characteristics that may affect this relation.