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Clinical Pharmacology and Therapeutics Jun 2021Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric...
Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.
Topics: Cytochrome P-450 CYP2C19; Gastroesophageal Reflux; Genotype; Humans; Pharmacogenetics; Proton Pump Inhibitors
PubMed: 32770672
DOI: 10.1002/cpt.2015 -
The Cochrane Database of Systematic... Aug 2023Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary... (Review)
Review
BACKGROUND
Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary and secondary care, affecting approximately 50% of infants under three months old. The natural history of GOR in infancy is generally of a self-limiting condition that improves with age, but older children and children with co-existing medical conditions can have more protracted symptoms. The distinction between gastro-oesophageal reflux disease (GORD) and GOR is debated. Current National Institute of Health and Care Excellence (NICE) guidelines define GORD as GOR causing symptoms severe enough to merit treatment. This is an update of a review first published in 2014.
OBJECTIVES
To assess the effects of pharmacological treatments for GOR in infants and children.
SEARCH METHODS
For this update, we searched CENTRAL, MEDLINE, Embase, and Web of Science up to 17 September 2022. We also searched for ongoing trials in clinical trials registries, contacted experts in the field, and searched the reference lists of trials and reviews for any additional trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any currently-available pharmacological treatment for GOR in children with placebo or another medication. We excluded studies assessing dietary management of GORD and studies of thickened feeds. We included studies in infants and children up to 16 years old.
DATA COLLECTION AND ANALYSIS
We used standard methodology expected by Cochrane.
MAIN RESULTS
We included 36 RCTs involving 2251 children and infants. We were able to extract summary data from 14 RCTs; the remaining trials had insufficient data for extraction. We were unable to pool results in a meta-analysis due to methodological differences in the included studies (including heterogeneous outcomes, study populations, and study design). We present the results in two groups by age: infants up to 12 months old, and children aged 12 months to 16 years old. Infants Omeprazole versus placebo: there is no clear effect on symptoms from omeprazole. One study (30 infants; very low-certainty evidence) showed cry/fuss time in infants aged three to 12 months had altered from 246 ± 105 minutes/day at baseline (mean +/- standard deviation (SD)) to 191 ± 120 minutes/day in the omeprazole group and from 287 ± 132 minutes/day to 201 ± 100 minutes/day in the placebo group (mean difference (MD) 10 minutes/day lower (95% confidence interval (CI) -89.1 to 69.1)). The reflux index changed in the omeprazole group from 9.9 ± 5.8% in 24 hours to 1.0 ± 1.3% and in the placebo group from 7.2 ± 6.0% to 5.3 ± 4.9% in 24 hours (MD 7% lower, 95% CI -4.7 to -9.3). Omeprazole versus ranitidine: one study (76 infants; very low-certainty evidence) showed omeprazole may or may not provide symptomatic benefit equivalent to ranitidine. Symptom scores in the omeprazole group changed from 51.9 ± 5.4 to 2.4 ± 1.2, and in the ranitidine group from 47 ± 5.6 to 2.5 ± 0.6 after two weeks: MD -4.97 (95% CI -7.33 to -2.61). Esomeprazole versus placebo: esomeprazole appeared to show no additional reduction in the number of GORD symptoms compared to placebo (1 study, 52 neonates; very low-certainty evidence): both the esomeprazole group (184.7 ± 78.5 to 156.7 ± 75.1) and placebo group (183.1 ± 77.5 to 158.3 ± 75.9) improved: MD -3.2 (95% CI -4.6 to -1.8). Children Proton pump inhibitors (PPIs) at different doses may provide little to no symptomatic and endoscopic benefit. Rabeprazole given at different doses (0.5 mg/kg and 1 mg/kg) may provide similar symptom improvement (127 children in total; very low-certainty evidence). In the lower-dose group (0.5 mg/kg), symptom scores improved in both a low-weight group of children (< 15 kg) (mean -10.6 ± SD 11.13) and a high-weight group of children (> 15 kg) (mean -13.6 ± 13.1). In the higher-dose groups (1 mg/kg), scores improved in the low-weight (-9 ± 11.2) and higher-weight groups (-8.3 ± 9.2). For the higher-weight group, symptom score mean difference between the two different dosing regimens was 2.3 (95% CI -2 to 6.6), and for the lower-weight group, symptom score MD was 4.6 (95% CI -2.9 to 12). Pantoprazole: pantoprazole may or may not improve symptom scores at 0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg pantoprazole in children aged one to five years by week eight, with no difference between 0.3 mg/kg and 1.2 mg/kg dosing (0.3 mg/kg mean -2.4 ± 1.7; 1.2 mg/kg -1.7 ± 1.2: MD 0.7 (95% CI -0.4 to 1.8)) (one study, 60 children; very low-certainty evidence). There were insufficient summary data to assess other medications.
AUTHORS' CONCLUSIONS
There is very low-certainty evidence about symptom improvements and changes in pH indices for infants. There are no summary data for endoscopic changes. Medications may or may not provide a benefit (based on very low-certainty evidence) for infants whose symptoms remain bothersome, despite nonmedical interventions or parental reassurance. If a medication is required, there is no clear evidence based on summary data for omeprazole, esomeprazole (in neonates), H₂antagonists, and alginates for symptom improvements (very low-certainty evidence). Further studies with longer follow-up are needed. In older children with GORD, in studies with summary data extracted, there is very low-certainty evidence that PPIs (rabeprazole and pantoprazole) may or may not improve GORD outcomes. No robust data exist for other medications. Further RCT evidence is required in all areas, including subgroups (preterm babies and children with neurodisabilities).
Topics: Adolescent; Child; Humans; Infant; Infant, Newborn; Esomeprazole; Gastroesophageal Reflux; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Ranitidine
PubMed: 37635269
DOI: 10.1002/14651858.CD008550.pub3 -
The Cochrane Database of Systematic... 2003Fasting before general anaesthesia aims to reduce the volume and acidity of stomach contents during surgery, thus reducing the risk of regurgitation/aspiration. Recent... (Review)
Review
BACKGROUND
Fasting before general anaesthesia aims to reduce the volume and acidity of stomach contents during surgery, thus reducing the risk of regurgitation/aspiration. Recent guidelines have recommended a shift in fasting policy from the standard 'nil by mouth from midnight' approach to more relaxed policies which permit a period of restricted fluid intake up to a few hours before surgery. The evidence underpinning these guidelines however, was scattered across a range of journals, in a variety of languages, used a variety of outcome measures and methodologies to evaluate fasting regimens that differed in duration and the type and volume of intake permitted during a restricted fasting period. Practice has been slow to change.
OBJECTIVES
To systematically review the effect of different preoperative fasting regimens (duration, type and volume of permitted intake) on perioperative complications and patient wellbeing (including aspiration, regurgitation and related morbidity, thirst, hunger, pain, nausea, vomiting, anxiety) in different adult populations.
SEARCH STRATEGY
Electronic databases, conference proceedings and reference lists from relevant articles were searched for studies of preoperative fasting in August 2003 and experts in the area were consulted.
SELECTION CRITERIA
Randomised controlled trials which compared the effect on postoperative complications of different preoperative fasting regimens on adults were included.
DATA COLLECTION AND ANALYSIS
Details of the eligible studies were independently extracted by two reviewers and where relevant information was unavailable from the text attempts were made to contact the authors.
MAIN RESULTS
Thirty eight randomised controlled comparisons (made within 22 trials) were identified. Most were based on 'healthy' adult participants who were not considered to be at increased risk of regurgitation or aspiration during anaesthesia. Few trials reported the incidence of aspiration/regurgitation or related morbidity but relied on indirect measures of patient safety i.e. intra-operative gastric volume and pH. There was no evidence that the volume or pH of participants' gastric contents differed significantly depending on whether the groups were permitted a shortened preoperative fluid fast or continued a standard fast. Fluids evaluated included water, coffee, fruit juice, clear fluids and other drinks (e.g. isotonic drink, carbohydrate drink). Participants given a drink of water preoperatively were found to have a significantly lower volume of gastric contents than the groups that followed a standard fasting regimen. This difference was modest and clinically insignificant. There was no indication that the volume of fluid permitted during the preoperative period (i.e. low or high) resulted in a difference in outcomes from those participants that followed a standard fast. Few trials specifically investigated the preoperative fasting regimen for patient populations considered to be at increased risk during anaesthesia of regurgitation/aspiration and related morbidity.
REVIEWER'S CONCLUSIONS
There was no evidence to suggest a shortened fluid fast results in an increased risk of aspiration, regurgitation or related morbidity compared with the standard 'nil by mouth from midnight' fasting policy. Permitting patients to drink water preoperatively resulted in significantly lower gastric volumes. Clinicians should be encouraged to appraise this evidence for themselves and when necessary adjust any remaining standard fasting policies (nil-by-mouth from midnight) for patients that are not considered 'at-risk' during anaesthesia.
Topics: Adult; Anesthesia, General; Drinking; Fasting; Gastroesophageal Reflux; Humans; Intraoperative Complications; Pneumonia, Aspiration; Randomized Controlled Trials as Topic
PubMed: 14584013
DOI: 10.1002/14651858.CD004423 -
Obesity Surgery Dec 2023This systematic review and meta-analysis aimed to investigate the incidence of new-onset gastroesophageal reflux, reflux change, esophagitis, Barrett's esophagus, and... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to investigate the incidence of new-onset gastroesophageal reflux, reflux change, esophagitis, Barrett's esophagus, and revision due to reflux, gastritis, and marginal ulcer after one-anastomosis gastric bypass (OAGB). We performed subgroup analyses based on primary and revisional OAGB and time of follow-up. Meta-analysis of 87 studies with 27,775 patients showed a 6% rate of new-onset reflux after OAGB. Preoperative reflux status did not change significantly after OAGB. The rate of esophagitis and Barrett's esophagus was 15% and 1%, respectively. The new-onset reflux rate after OAGB was significantly higher than gastric bypass but not different with sleeve gastrectomy. The current study showed a relatively low rate of reflux and its complications after OAGB, but it was significantly higher than Roux-en-Y gastric bypass.
Topics: Humans; Gastric Bypass; Obesity, Morbid; Barrett Esophagus; Gastroesophageal Reflux; Esophagitis; Gastrectomy; Retrospective Studies
PubMed: 37880462
DOI: 10.1007/s11695-023-06866-y -
Journal of Gastroenterology and... Aug 2019Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD.
METHODS
We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption.
RESULTS
Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs.
CONCLUSIONS
This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.
Topics: Bayes Theorem; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Network Meta-Analysis; Patient Selection; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Sulfonamides; Time Factors; Treatment Outcome; Wound Healing
PubMed: 30883868
DOI: 10.1111/jgh.14664 -
The Laryngoscope Jan 2021The mechanism by which recurrent croup occurs is unknown. Gastroesophageal reflux is commonly implicated, although this relationship is only loosely documented. We... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The mechanism by which recurrent croup occurs is unknown. Gastroesophageal reflux is commonly implicated, although this relationship is only loosely documented. We conducted a systematic review with a meta-analysis component to evaluate the relationship between recurrent croup and gastroesophageal reflux disease (GERD), and to assess for evidence of improvement in croup symptoms when treated.
STYLE DESIGN
Systematic Review and Meta Analysis.
METHODS
We searched five separate databases. Studies were included if they discussed the relationship between croup and GERD in children, >5 subjects, and available in English. Literature retrieved was assessed according to pre-specified criteria. Retrieved articles were reviewed by two independent authors and decisions mediated by a third author. If there was a difference of opinion after first review, a second review was performed to obtain consensus. Heterogeneity was calculated and summarized in forest plots.
RESULTS
Of 346 initial records, 15 met inclusion criteria. These were two retrospective cohort and 13 cross-sectional studies. Thirteen of 15 articles support an association between recurrent croup and GERD. Although heterogeneity is high among studies that reported prevalence of GERD, there is less uncertainty in results for improvement to recurrent croup after GERD treatment. Most studies lacked a control group and all carry a moderate-to-high risk of bias.
CONCLUSION
There is limited evidence linking GERD to recurrent croup; Further research is needed to assess for causality as most studies are retrospective, lack a control group, and have a study design exposing them to bias. Patients treated with reflux medication appear to demonstrate a reduced incidence of croup symptoms.
LEVEL OF EVIDENCE
1 Laryngoscope, 131:209-217, 2021.
Topics: Child, Preschool; Croup; Gastroesophageal Reflux; Humans; Infant; Recurrence
PubMed: 32040207
DOI: 10.1002/lary.28544 -
Otology & Neurotology : Official... Aug 2021To investigate the relationship between laryngopharyngeal reflux (LPR) and recurrent (ROM) or chronic otitis media with effusion (COME).
OBJECTIVES
To investigate the relationship between laryngopharyngeal reflux (LPR) and recurrent (ROM) or chronic otitis media with effusion (COME).
DATABASES
PubMed, Scopus, and Cochrane Library.
METHODS
Three authors searched articles published between January 1980 and September 2020 about the association between LPR and the development of recurrent or chronic otitis media. Inclusion, exclusion, diagnostic criteria, and clinical outcome evaluation of included studies were analyzed using PRISMA criteria. The bias analysis of included studies was evaluated with the Tool to assess Risk of Bias of the CLARITY group.
RESULTS
Twenty-six clinical and three experimental articles met our inclusion criteria, accounting for 1,624 children and 144 adults with COME or ROM. According to the pH study type, the prevalence of LPR and gastroesophageal reflux disease (GERD) in OM patients were 28.7% (range, 8-100%) and 40.7 (range, 18-64%), respectively. The majority of studies identified pepsin or pepsinogen in middle ear effusion, with a range of mean concentrations depending on the technique used to measure pepsin. There was an important heterogeneity between studies regarding definition of COME, ROM, and LPR, exclusion criteria, methods used to measure pepsin/pepsinogen in middle ear secretions and outcome assessments.
CONCLUSION
The association between LPR and OM is still unclear. Future clinical and experimental studies are needed to investigate the association between LPR and OM in both children and adults through extensive gastric content analysis in middle ear suppurations and impedance-pH monitoring considering acid, weakly acid, and alkaline reflux events.
Topics: Child; Humans; Laryngopharyngeal Reflux; Otitis Media; Otitis Media with Effusion; Pepsin A; Pepsinogen A
PubMed: 33710157
DOI: 10.1097/MAO.0000000000003123 -
PloS One 2020To investigate the role of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in the development of dental disorders.
OBJECTIVES
To investigate the role of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in the development of dental disorders.
METHODS
The first outcome was review of the role of reflux in the development of dental disorders in adults. The second outcome was review of the potential pathophysiological mechanisms underlying the association between reflux and dental disorders. Three investigators screened publications for eligibility and exclusion based on predetermined criteria through a literature search conducted on PubMed, Cochrane Library, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
RESULTS
From 386 publications, 24 studies were kept for analysis. Objective approaches were used in 16 studies to confirm GERD diagnosis. Pharyngeal reflux episodes (LPR) were considered in 2 studies. No study considered nonacid reflux. The study results supported a higher prevalence of dental erosion and caries in reflux patients compared with healthy individuals. Patients with dental erosion have a higher prevalence of reflux than controls. The pathophysiological mechanisms would involve changes in the saliva physiology. No study investigated the microbiota modifications related to reflux although the findings are supporting the critical role of microbiota change in the development of dental disorders. There is an important heterogeneity between studies about diagnostic methods and clinical outcome evaluation.
CONCLUSION
The involvement of reflux in the development of dental disorders is not formally demonstrated and requires future investigations considering pharyngeal acid and nonacid reflux episodes and in particular their potential impact on oral microbiota.
Topics: Dental Caries; Esophagitis, Peptic; Humans; Laryngopharyngeal Reflux; Prevalence; Risk Factors; Saliva
PubMed: 32797062
DOI: 10.1371/journal.pone.0237581 -
Gastro Hep Advances 2023Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder that may complicate conditions such as obstructive airway disease. Our group has...
BACKGROUND AND AIMS
Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder that may complicate conditions such as obstructive airway disease. Our group has identified predictive biomarkers of GERD in particulate exposed first responders with obstructive airway disease. In addition, GERD diagnosis and treatment is costly and invasive. In light of these clinical concerns, we aimed to systematically review studies identifying noninvasive, multiOmic, and multicompartmental biomarkers of GERD.
METHODS
A systematic review of PubMed and Embase was performed using keywords focusing on reflux disease and biomarkers and registered with PROSPERO. We included original human studies in English, articles focusing on noninvasive biomarkers of GERD published after December 31, 2009. GERD subtypes (non-erosive reflux disease and erosive esophagitis) and related conditions (Barrett's Esophagus [BE] and Esophageal Adenocarcinoma). Predictive measures were synthesized and risk of bias assessed (Newcastle-Ottawa Scale).
RESULTS
Initial search identified n = 238 studies andn 13 articles remained after applying inclusion/exclusion criteria. Salivary pepsin was the most studied biomarker with significant sensitivity and specificity for GERD. Serum assessment showed elevated levels of Tumor Necrosis Factor-alpha in both GERD and Barrett's. Exhaled breath volatile sulfur compounds and acetic acid were associated with GERD. Oral Microbiome: Models with , , and showed the greatest discrimination between BE and controls vs ; ROC 0.94 (95% confidence interval; 0.85-1.00).
CONCLUSION
Prior studies identified significant multiOmic, multicompartmental noninvasive biomarker risks for GERD and BE. However, studies have a high risk of bias and the reliability and accuracy of the biomarkers identified are greatly limited, which further highlights the need to discover and validate clinically relevant noninvasive biomarkers of GERD.
PubMed: 38009162
DOI: 10.1016/j.gastha.2023.01.014 -
Alimentary Pharmacology & Therapeutics Oct 2013Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep, but the mechanism remains unclear. (Review)
Review
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.
Topics: Gastroesophageal Reflux; Humans; Sleep
PubMed: 23957437
DOI: 10.1111/apt.12445