Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

Managing heartburn and reflux in primary care.

ABSTRACT: This article describes an algorithmic approach to caring for patients presenting with heartburn and reflux, including empiric treatment with acid-suppression therapy and a data-driven approach to diagnostic testing. This article also reviews the efficacy and safety profile of the widely available and commonly used proton pump inhibitors. Refining our approach to diagnostic testing can reduce time to diagnosis, better control patients' symptoms, and limit complications of longstanding disease.

Review of recent evidence on the management of heartburn in pregnant and breastfeeding women.

Gastroesophageal reflux disease (GERD) is one the most common medical complaints in pregnant women. Some women continue to experience GERD symptoms after delivery. Effective management of GERD symptoms is important to improve productivity and quality of life. Management of heartburn in pregnant and breastfeeding women involves lifestyle modifications, dietary modifications, non-pharmaceutical remedies and pharmaceutical drugs. For most patients, lifestyle/dietary modifications are helpful in reducing GERD symptoms. For patients who require a more intense intervention, various types of pharmaceutical drugs are available. However, the suitability of each treatment for use during pregnancy and lactation must be taken into consideration. This article explores the reported efficacy and safety of these treatment options in pregnant and breastfeeding women. Recommended treatment algorithm in pregnant and breastfeeding women have been developed.

Functional Chest Pain and Esophageal Hypersensitivity: A Clinical Approach.

Functional chest pain, functional heartburn, and reflux hypersensitivity are 3 functional esophageal disorders defined by the Rome IV criteria. Specific criteria, combining symptoms and the results of objective testing, allow for an accurate diagnosis of these conditions. Management may include medications targeted at optimizing acid suppression or neuromodulation, as well as a host of complementary or alternative treatment options. Psychological and behavioral interventions, such as cognitive behavioral therapy and hypnotherapy, have displayed substantial benefits in the treatment of functional chest pain and functional heartburn. Acid suppression and focused neuromodulation are key evidence-based treatment options for reflux hypersensitivity.

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.

Treatment of Dyspepsia, Heartburn, and Related Symptoms with Gastricumeel Compared to Proton Pump Inhibitors: A Prospective Reference-Controlled Observational Study.

BACKGROUND: Dyspepsia and heartburn are extremely common conditions, thus a search for safe and effective treatment alternatives is justified. OBJECTIVES: To demonstrate the noninferiority of Gastricumeel (Ga6) in terms of effectiveness and safety to proton pump inhibitors (PPIs) in the treatment of patients with dyspepsia and/or heartburn. METHODS: Prospective, comparative, observational cohort study. Patients with dyspepsia or heartburn were treated either with Ga6 or with PPIs as monotherapy during approximately 6 weeks. The intensity of eight symptoms was assessed as well as overall condition, treatment compliance and tolerability, and any adverse drug reactions. Adjustment for covariates was done via the calculation of propensity scores in logistic regression. RESULTS: A total of 640 patients (447 Ga6, 193 PPIs) from 48 German general practices participated. More than half the patients had suspected acute gastritis and around 40% of patients had heartburn. Adjusted between-treatment difference scores of changes in the intensity of the eight assessed symptoms were within the bounds for noninferiority of Ga6 compared to PPIs. Effectiveness ratings were comparable; compliance and tolerability were rated better in the Ga6 group. CONCLUSION: It is worth considering Ga6 as a safe and effective treatment option in the management of dyspepsia and heartburn.

Randomised clinical trial: oesophageal radiofrequency energy delivery versus sham for PPI-refractory heartburn.

BACKGROUND: Oesophageal radiofrequency reduces use of proton pump inhibitors (PPIs) in patients with gastro-oesophageal reflux disease responding to PPIs. AIM: To determine the efficacy of oesophageal radiofrequency in patients with PPI-refractory heartburn. METHODS: A randomised, double-blind, sham-controlled multicentre study was designed to assess the efficacy of oesophageal radiofrequency in PPI non-responding patients with heartburn. Patients had moderate-to-severe heartburn defined by at least 3 occurrences a week, and not improved by continuous PPI treatment. The primary endpoint was clinical success at week 24, defined by intake of less than 7 PPI doses over the 2 preceding weeks and adequate symptom control determined by the patient. RESULTS: Sixty two patients were randomised, 29 to the oesophageal radiofrequency group and 33 to the sham group. Intention-to-treat analysis showed that 1/29 (3.4%) and 5/33 (15.1%) achieved the primary endpoint in the oesophageal radiofrequency and sham groups, respectively (NS). There was no significant difference between oesophageal radiofrequency and sham regarding the number of days without heartburn, days with PPI consumption in the last 2 weeks, and patients not taking PPIs. No pH-impedance parameter was associated with clinical response. The occurrence of adverse events was similar in both groups. CONCLUSION: This sham-controlled, randomised study did not demonstrate any efficacy of oesophageal radiofrequency for the treatment of PPI-refractory heartburn regarding symptom relief or consumption of PPIs. ClinicalTrials.gov NCT01682265.

Refractory Gastroesophageal Reflux Disease and Functional Heartburn.

This report discusses the potential mechanisms that might underlie refractory GERD and functional heartburn, and how to distinguish among those mechanisms using a systematic evaluation that includes careful medical history, endoscopy with esophageal biopsy, esophageal manometry, and esophageal multichannel intraluminal impedance-pH monitoring. The report provides an approach to patient management that depends on the underlying mechanism identified by this systematic evaluation.

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.

Review article: the management of heartburn during pregnancy and lactation.

BACKGROUND: Gestational reflux is common, affecting up to 80% of pregnant women. Most symptoms will abate during lactation. During both of these periods, interventions used to relieve symptoms focus on a "step-up" methodology with progressive intensification of treatment. This begins with lifestyle modifications. AIM: To provide guidance in the treatment of reflux in pregnancy and lactation, as well as briefly summarising the pathogenesis, clinical presentation and diagnostic workup. METHODS: A comprehensive search, using online databases PubMed and MEDLINE, along with relevant manuscripts published in English between 1966 and 2019 was used. All abstracts were screened, potentially relevant articles were researched, and bibliographies were reviewed. RESULTS: Only a small percentage of relevant drugs are contraindicated for use in pregnancy or while breastfeeding. However, not all drug agents have been extensively evaluated in pregnant women or during the breastfeeding period. Antacids, alginates, and sucralfate are the first-line therapeutic agents. If symptoms persist, any of the H2 RAs can be used except for nizatidine (due to foetal teratogenicity or harm in animal studies). PPIs are reserved for women with intractable symptoms or complicated GERD; all are FDA category B drugs, except for omeprazole, which is a category C drug. CONCLUSIONS: The management of heartburn during pregnancy and lactation begins with lifestyle modifications. In situations where disease severity increases, medical providers must discuss risks and benefits of these medicines with the patient in detail.

Effectiveness of Manual Treatment on Pregnancy Symptoms: Usefulness of Manual Treatment in Treating Pregnancy Symptoms.

OBJECTIVES: To determine the usefulness of manual treatment in reducing or eliminating pregnancy symptoms during first and second trimester. METHODS: Manual treatment of the cervical and thoracic spine was performed in a group of 115 pregnant women who developed pregnancy symptoms during normal pregnancy. A rotational traction of the cervical spine was applied. Patients in whom the treatment was unsuccessful underwent second round of treatment after a pause of a minimum 3 days. Patients for whom the treatment was initially successful but later relapsed also repeated whole procedure. Pregnancy symptoms analyzed in this study were heartburn, nausea, vomiting, dizziness, headache, insomnia, neck pain, hyperosmia and hypersalivating. RESULTS: Manual treatment successfully treated pregnancy symptoms in 91 (79.1%) patients, it was partially successful for 22 (19.1%), and unsuccessful for 2 patients (1.7%) after the first treatment. After the second treatment, out of a total 56 patients, the treatment was completely successful in 40 (71.4%), partially successful in 14 (25%), and unsuccessful in 2 (3.6%) patients. The highest success rate was in eliminating headache (97.3%), vomiting (95.9%), dizziness (94.5%), nausea (92.9%), neck pain (92.9%), insomnia (91.9%), heartburn (88.8%), hyperosmia (78.5%) and hyper salivating (78%). CONCLUSION: Manual therapy in pregnancy is a drugless, etiological, usually highly effective therapy. It is a low cost, rapid, safe, and well tolerated treatment for pregnancy symptoms which frequently has an immediate effect, thus making it an optimal treatment for pregnancy symptoms.

Functional Gastrointestinal Disorders: Functional Upper Gastrointestinal Disorders in Adults.

Functional upper gastrointestinal disorders are common and cause significant patient distress and health care cost. These disorders typically are classified as either esophageal or gastroduodenal. Functional esophageal disorders include functional heartburn, reflux hypersensitivity, and functional dysphagia. Functional gastroduodenal disorders include functional dyspepsia and cyclic vomiting syndrome. Cyclic vomiting syndrome should be suspected in any patient with multiple episodes of vomiting with no apparent cause that completely resolve between episodes. Evaluation often is dependent on clinical findings. Therefore, a thorough history and physical examination are required to rule out any structural organic etiologies of red flag signs and symptoms. Diagnosis is ultimately based on Rome IV criteria. Education about the condition and lifestyle modifications is an ideal initial management for all functional upper gastrointestinal disorders. When this strategy alone is ineffective, behavioral therapy and pharmacotherapy can be useful. For patients with functional dyspepsia, acid suppression therapy and Helicobacter pylori eradication may be effective for improving long-term symptomatology. For patients who do not benefit from initial medical treatment, antidepressants and bismuth may be useful.

Refractory Heartburn: A Challenging Problem in Clinical Practice.

Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Heartburn and regurgitation are the typical symptoms of GERD. The treatment of GERD encompasses lifestyle modifications, pharmacological, endoscopic, and surgical therapy. The majority of the patients respond to 4-8 weeks of proton-pump inhibitors therapy, but 20-42% will demonstrate partial or complete lack of response to treatment. While these patients have been considered as having refractory heartburn, a subset of them does not have GERD or have not been adequately treated. The main causes of refractory heartburn include: poor compliance; inadequate proton-pump inhibitors dosage; incorrect diagnosis; comorbidities; genotypic differences; residual gastroesophageal reflux; eosinophilic esophagitis and others. Treatment is commonly directed toward the underlying cause of patients' refractory heartburn.

Assessing Old and New Diagnostic Tests for Gastroesophageal Reflux Disease.

A detailed critique of objective measurements of gastroesophageal reflux disease (GERD) would improve management of patients suspecting of having reflux, leading to rational selection of treatment and better outcomes. Many diagnostic tests for GERD have been developed over the past decades. We analyze their development, positive- and negative-predictive values, and ability to predict response to treatment. These features are important for development of medical, surgical, and endoscopic therapies for GERD. We discuss the value of available diagnostic tests and review their role in management of patients with persistent reflux symptoms despite adequate medical or surgical treatment. This is becoming a significant health economic problem, due to the widespread use of proton pump inhibitors. GERD is believed to cause nonesophageal symptoms, such as those provoked by ear, nose, throat, or respiratory disorders. We analyze the value of GERD diagnostic tests in evaluation of these troublesome, nonesophageal symptoms.

The Role of Esophageal Hypersensitivity in Functional Heartburn.

Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.

The course of achalasia one to four decades after initial treatment.

BACKGROUND: Most follow-up studies of achalasia are limited to <5 years. AIM: To study the long-term efficacy of pneumatic dilation (PD) and myotomy in achalasia at least 10 years after treatment. METHODS: We performed a retrospective cohort study of achalasia patients with >10 years follow-up after initial myotomy or pneumatic dilation. Symptom recurrence which required repeat dilation or surgery was compared between pneumatic dilation and myotomy. RESULTS: One hundred and fifty patients (112 myotomy, 38 pneumatic dilation) of similar characteristics were studied. The mean duration of follow-up after initial treatment was 17.5 ± 7.2 years (10-40 years). Symptoms recurrence rate was 60.7% (100% pneumatic dilation patients vs. 47.3% myotomy), hazard ratio 0.24 demonstrating a lower need for repeat dilation or surgery with myotomy than pneumatic dilation (P = 0.008). All pneumatic dilation patients underwent myotomy in 4 ± 4 (0-16 years). Forty of 53 myotomy patients had symptom recurrence prompting further treatment: 16 pneumatic dilation, 11 myotomy and 13 both. The mean time to repeat procedure was 6.9 years (0-40). The myotomy group required fewer dilations and/or surgeries than the pneumatic dilation group (1.6 vs. 3.6, P < 0.001). 13 patients (10.1%) progressed to end-stage achalasia (five myotomy, eight pneumatic dilation) over 40 years. At last follow-up, 57/62 (92%) patients had absent or mild dysphagia, 53/62 (85%) patients had regurgitation less than once per week and 37 (60.7%) had heartburn episodes <1/week similar for pneumatic dilation and myotomy (P = 0.27). CONCLUSION: Although the majority of patients treated for achalasia do well after decades of treatment, most patients may need a series of endoscopic and/or surgical procedures to maintain effective symptom control.

Between GERD and NERD: the relevance of weakly acidic reflux.

Nonerosive reflux disease (NERD) is a common condition and the most frequent phenotype of gastroesophageal reflux disease (GERD). NERD is extremely heterogeneous and includes patients with negative endoscopy but abnormal esophageal acid exposure and/or positive reflux-symptom association analysis (hypersensitive esophagus). This segregation is only possible owing to the use of impedance-pH monitoring. Indeed, weakly acidic reflux represents one of the most common causes of refractory symptoms in patients evaluated off antisecretory therapy and, more importantly, during antisecretory drug treatment. Patients with heartburn who do not have any type of reflux underlying their symptoms (functional heartburn) must be excluded from the category of GERD. The drawbacks of impedance-pH are mainly due to the day-to-day variability of the test and the fact that the accuracy of the symptom-reflux correlation scores is often far from perfect. Some histopathological characteristics, such as dilated intercellular spaces, can be helpful in distinguishing patients with NERD through esophageal biopsies. Patients with NERD in whom acid is the main pathogenetic factor respond successfully to proton pump inhibitor therapy, while those with hypersensitive esophagus to weakly acidic reflux could be treated with reflux inhibitors or surgery, although further controlled studies are required.

Interventions for Treating Heartburn in Pregnancy.

Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library.