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An evidence-based, Latin-American consensus ongastro-oesophageal reflux diseaseHenry Cohena, Joaquim Prado P. Moraes-Filhob, Maria Luisa Cafferatac,Giselle Tomassoc, Graciela Salisd, Oscar Gonza´leze, Jorge Valenzuelaf,Prateek Sharmag, Peter Malfertheinerh, David Armstrongi, Lars Lundellj,Rodolfo Cortik, Paulo Sakaib, Ivan Ceconellob and the Latin-AmericanGORD Consensus Group* In recognition of the high prevalence of gastro-oesophageal Department of Gastroenterology, Uruguayan Medical School, Montevideo, Uruguay, bDepartment of Gastroenterology, University of Sao Paulo School of reflux disease (GORD) and its importance in Latin America, Medicine, Sao Paolo, Brazil, cPerinatal Research Unit, Hospital de Clinicas, the InterAmerican Association of Gastroenterology and the Montevideo, Uruguay, dDepartment of Gastroenterology, Posadas Hospital,Buenos Aires, Argentina, eDepartment of Gastroenterology, St Joseph Hospital, InterAmerican Society of Digestive Endoscopy organized a Bogota, Colombia, fDepartment of Gastroenterology, Las Condes Clinic, Latin-American Consensus on GORD in Cancun, Mexico in Santiago, Chile, gSchool of Medicine, University of Kansas, Kansas City, USA, hDepartment of Medicine, Otto Von Guericke University, Magdeburg, Germany, September 2004. The main objectives of the consensus iDepartment of Medicine, McMaster University, HSC-4W8, MUMC. 1200 Main meeting were to provide evidence-based guidance with Street, West Hamilton, Ontario, L8N 325, Canada, jDepartment of Surgery,Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden and respect to the diagnosis and treatment of GORD, relevant to kDepartment of Gastroenterology, Carlos Bonorino Udaondo Hospital, Capital, all countries in the region. The methodology, results and recommendations of the consensus are described in Correspondence to Henry Cohen, Department of Gastroenterology, detail. Eur J Gastroenterol Hepatol 18:349–368 Uruguayan Medical School, Avenida Italia 2370, 11600 Montevideo, Uruguay Lippincott Williams & Wilkins.
Received 11 July 2005 Accepted 13 October 2005 European Journal of Gastroenterology & Hepatology 2006, 18:349–368 Keywords: consensus, diagnosis, gastro-oesophageal reflux, oesophagitis,therapy (tobacco, alcohol and coffee intake) and body mass index Gastro-oesophageal reflux disease (GORD) is one of the populational study a probabilistic most common disorders in medical practice. Data from model was used. The results showed the global north America [1] indicate that heartburn, the most prevalence of heartburn was 11.9% (1651 individuals).
predominant symptom of the disease, occurs at least once a week in 19.8% of the studied population. Similar data (637 individuals) and GORD in 7.3% (1014 individuals).
have been reported in other developed nations [2], but The average ages of both groups were similar (men information on the prevalence of GORD in Latin- 36.9 ± 15.0; women 39.6 ± 15.1 years). Women were American countries is scarce. However, a population- more affected in both groups. The occurrence of GORD based national study from Brazil, enrolling 13 959 adults increased with age, and was more prevalent after the age was conducted in 22 Brazilian cities. The inclusion of 55 years. The BMI was in the normal range and was criteria were the presence of heartburn at least once a week (‘heartburn group') and age greater than 16 years.
25.3 ± 5.2 kg/m2). In both groups the individuals related Individuals with heartburn with a frequency of more than their symptoms to food intake, fatty and spicy foods once a week were considered as having gastro-oesopha- (heartburn group 64.7%, 28.5%, 17.7%; GORD group geal reflux disease (‘GORD group'). Factors related to the 55.0%, 25.9%, 11.7%, respectively). In the GORD group, complaint were asked, such as predisposing factors, habits stress (24.2%) and health problems (22.3%) were morerelated to the symptoms than in the heartburn group *Latin-American GORD Consensus Group (20.0 and 15.0%, respectively).
President of AIGE: Carlos Zapata.
President of SIED: Daniel Taullard.
Delegates of the countries: Jorge Chang Mayorga, Guatemala; Esteban Trakal, They concluded that the global prevalence of heartburn Argentina; Carlos Contardo Zambrano, Peru; Carlos Rodrı´guez Ulloa, Peru;Fernando Contreras, Dominican Republic; Carmelo Blasco, Paraguay; Miguel (11.9%) is relatively high in the Brazilian urban popula- Angel Valdovinos, Mexico; Miguel Abdo Francis, Mexico; Rafael Ortun˜o tion, although lower than the reported figures in other Escalante, Bolivia; Luiz Leite Luna, Brazil; Maria Vergara Albarracin, Chile; countries. Heartburn and GORD have a higher preva- Manuel Paniagua Este´vez, Cuba; Gonzalo Estape Carriquirry, Uruguay; MariaElena Ruiz, Venezuela; Marianella Madrigal Borloz, Costa Rica.
lence in women and both are related to food intake, fatty c 2006 Lippincott Williams & Wilkins Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 and spicy foods. GORD is more prevalent in individuals opinion that any group of people may display when older than 35 years [3].
considering a topic, appropriate methods are needed fororganizing and synthesizing subjective judgements when An interesting paper published recently by Argentinean uncertainties or differences of opinion exist.
authors studied self-reported questionnaires validated atthe Mayo Clinic, USA, submitted to 1000 individuals A Latin-American consensus on the diagnosis and aged 18–80 years from 17 different areas in the country treatment of GORD was organized to review the best [4]. The overall prevalence of any typical GORD evidence available from the literature and the possible symptom experienced in the previous year was 61.2%.
influences of different demographic, socioeconomic and The prevalence of frequent GORD symptoms was 23%, disease factors on the management of this disease in this and the prevalence of GORD was 11.9%. The authors concluded that, in Argentina, the typical symptoms ofGORD are highly prevalent at the national level.
Specialists from Latin-American gastroenterology socie-ties, representing 16 countries, were invited by the Inter- No other reliable data could be found in the search American Association of Gastroenterology (AIGE) and performed on the epidemiology of GORD in Latin the InterAmerican Society of Digestive Endoscopy America. Because of the high prevalence of GORD, its (SIED), to take part in a meeting held in Cancun, significant impact on quality of life [5,6], the severity of Mexico, in September 2004. The aim of the consensus its complications, the number of related hospitalizations meeting was to discuss, in depth, and to vote on the main and its economic consequences [7], several national and issues relevant to the diagnosis and treatment of GORD, international consensus conferences have been developed in accordance with evidence-based medicine recommen- dations. This article represents the conclusions andrecommendations of this consensus meeting.
The need for consensus meetings reflects not only anincreasing interest in this important disorder, but also a lack of unanimity with respect to diagnostic and In December 2003, the Boards of Directors of the AIGE therapeutic approaches, uncertainty about the value of and the SIED decided to hold a Latin-American different management options and variations in practice consensus meeting on the management of GORD. Two between physicians and between countries.
gastroenterologists (H.C. and J.P.P.M.F.) were invited tocoordinate the consensus.
Ideally, clinical practice should be guided by thestandards of evidence-based medicine, derived from The main objectives of the consensus were that it should: rigorously conducted studies. However, there are few (i) be representative of and relevant to all countries healthcare areas for which sufficient evidence-based affiliated to AIGE and SIED; (ii) be evidence based; research exists to guide all decisions, and in some (iii) deal with the major management issues relevant to instances appropriate studies may never be available. It GORD: diagnosis and treatment; (iv) include invited is not unusual that diagnostic and therapeutic procedures experts from Latin America, north America and Europe; are introduced and incorporated into practice without a and (v) follow the methodology of the National Institutes rigorous evaluation of their quality. In some cases, the of Health (NIH) for the organization of a consensus procedures may prove to be beneficial, but on occasion the evaluation of these procedures may demonstrate thatthey do not produce the expected benefits, or even that Member countries of AIGE and SIED were invited to they are ineffective or harmful. Unfortunately, it may be send one or two delegates to participate in the consensus difficult to discontinue the use of such procedures once meeting. Nineteen delegates representing 16 countries they have been implemented, and it is therefore attended the meeting. Each country had a vote.
imperative to demonstrate the effectiveness of any Delegates were asked to vote if the evidence was not diagnostic method or treatment before it is adopted grade A. It was agreed that 70% of the votes were required for the approval of a recommendation. FourLatin-American and four international experts were also When rigorously conducted studies are not available, it is invited but were not entitled to vote.
inevitable that the development of guidelines is basedalso, to a greater or less extent, on the opinion and Two experts (G.T. and M.L.C.) in evidence-based experience of clinicians and experts. The development of medicine were invited to produce a systematic review a consensus must, therefore, incorporate both judgement- (systematic search, critical appraisal and summary of the based statements, endorsed by the group, in addition to evidence) of the diagnosis and treatment of GORD, evidence-based statements. Given the diversity of based on an extensive, systematic review of the literature.
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An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
A literature search was conducted, using Medline, the Grade of recommendation and levels of evidence [17] Cochrane Library and LILACS for the period up until March 2004. The search strategies were directed to adult patients with GORD; Barrett's oesophagus and paediatric Systematic review of RCT of good GORD were excluded. Therapeutic studies were in- methodological quality and with cluded if they assessed any of the following outcomes: Individual RCT with narrow confidence heartburn relief, healing of oesophagitis, heartburn remission, oesophagitis relapse, heartburn relapse, quality Non-controlled studies (dramatic findings) of life, satisfaction and hospital stay in surgical therapies.
Systematic review of cohort studies (with The language of the articles should be English, French or Individual cohort study (including low Spanish. The main search included gastro-oesophageal quality RCT, e.g. < 80% follow-up) Non-controlled cohort studies/ecological reflux (MeSH term), heartburn (MeSH term), oesopha- gitis (MeSH term). To obtain articles on diagnosis, the Systematic review of case–control search was limited to specificity and to obtain articles on studies (with homogeneity) Individual case–control study treatment, the search was limited to randomized Case series/poor quality cohort or case– controlled trials (pt). The search also included clinical Expert opinion without explicit critical practice guidelines, other consensus from Latin-American appraisal or based on physiology, and other countries and references of the studies. Three bench research or ‘first principles' investigators conducted the literature searches, indepen- RCT, Randomized controlled trial.
dently. In addition, Latin-American experts were asked tosearch the local literature and to submit the papers to theevidence-based experts; these region-specific studieswere included only if they fulfilled the eligibility criteria Barrett's oesophagus. Only two therapeutic studies fulfilled the elegibility criteria from the local literatureselected by the Latin-American experts.
The methodological quality was assessed using the usersguide for the medical literature for diagnostic [14] and Levels of evidence and grades of recommendation were treatment studies [15].
established according to the classification of the OxfordCentre for Evidence-Based Medicine for levels of Diagnostic results were expressed in terms of likelihood evidence [17] (Table 1). Grade A is highly recommended ratio (LR), which summarizes the ability of a test to and corresponds to evidence level 1 studies (systematic revise the previous probability of disease.
review of randomized controlled trials or a largerandomized controlled trial with low probability of bias Intervention study results were synthesized in a meta- or without bias).
analysis using the Review Manager 4.2 software [16].
Results were expressed as relative risks (RR) with 95% A grade A recommendation resulted in unanimous confidence intervals (CI) and as RR reduction with 95% acceptance by the consensus delegates and was not CI. A cost evaluation was not considered.
submitted to a formal voting process.
Grades B, C or D recommendations were accepted by The literature search identified 211 diagnostic studies; consensus upon voting.
after quality assessment, 92 studies were considered tofulfil the inclusion criteria. The remaining 119 studies Diagnosis of gastro-oesophageal reflux disease: avail- were excluded because they did not report measures of accuracy or were primary or secondary diagnostic studies.
The following issues were assessed: (i) definition of There were no Latin-American diagnostic studies to be GORD; (ii) 24 h pH monitoring; (iii) symptom-based decisions; (iv) upper endoscopy; (v) histology; (vi)oesophageal manometry; (vii) contrast radiology; (viii) For the treatment of GORD, 140 studies and a systematic impedance; (ix) bile monitoring (Bilitec); and (x) review were identified; of these, 93 studies fulfilled the therapeutic trial [e.g. the proton pump inhibitor (PPI) inclusion criteria for the consensus process. The remain- ing 47 studies were excluded because they were ofinadequate methodological quality, trials that had not Definition of gastro-oesophageal reflux disease assessed the results included in the consensus, they had GORD is a recurrent condition related to the retrograde included healthy volunteers as participants, they were flux of gastric contents (with or without duodenal paediatric trials, or they had included patients with contents) into the oesophagus or adjacent organs. It Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 Operative characteristics of ambulatory oesophageal pH for both non-erosive reflux disease and erosive oesopha- gitis. Patients reporting frequent symptoms would also appear to have more severe symptomatic episodes. Thosereporting severe heartburn are more likely to report daily Phase II studiesDe Meester [18] episodes than those presenting with mild symptoms.
Schindlbeck et al.a [19] Both the severity and frequency of symptoms improve Fuchs et al. [20] Phase III studies with medical treatment.
Vitale et al. [21] The threshold at which symptom intensity (severity or Jorgensen et al. [23] Bollschweiler et al. [24] frequency) leads to a change in the quality of life doesnot appear to be absolute, but is determined, at least LR + , Positive likelihood ratio.
aReceiver operator bidimensional curve.
partly, by how the quality of life is evaluated. From theGenval Workshop, it was determined that GORD ispresent when symptoms occur at least two or more times presents a varied spectrum of symptoms impairing the a week, based upon the negative impact that symptom patient's quality of life and it may present with or without frequency has on the patient's quality of life [7].
tissue damage.
Although there are very few data to indicate thatsymptom frequency is the sole determinant of quality 24-Hour pH monitoring of life in GORD, it is generally accepted, based on the For the purpose of the consensus, ambulatory oesopha- responses to various questionnaires [26] that reflux geal 24 h pH monitoring was considered to provide the symptoms occurring on two or more days a week is the most objective measurement of abnormal gastro-oesopha- threshold at which GORD has an impact on an geal reflux. This test is considered the best available, individual's quality of life.
but with some reservations, because of the inter andintraindividual variability of its findings, its inability to The adequate definition of heartburn and regurgitation assess oesophageal mucosal resistance, and controversy could improve diagnostic capability, because the inter- regarding an accepted threshold for differentiating pretation of these symptoms can vary between patients between normal and abnormal oesophageal acid exposure and doctors, and also between different physicians. Several (Table 2) [18–24].
questionnaires are being developed [27–29] to improvethe diagnostic utility of these symptoms, but they have not Although still considered by some to be the gold standard yet been fully validated. Currently, neither the presence of for the diagnosis of GORD, ambulatory 24-h oesophageal typical reflux symptoms (heartburn or regurgitation) nor pH monitoring using a standard pH electrode is not a the use of scores or questionnaires is sufficient to make an procedure without problems. However, it does provide a accurate diagnosis of GORD. If GORD were diagnosed on standardized measure of oesophageal acid exposure the basis of typical symptoms, 30% of individuals with against which to compare other diagnostic tests. In the GORD would not be diagnosed and 47% of healthy following sections, the sensitivity, specificity and positive individuals would be diagnosed incorrectly as having LR of these other diagnostic tests are calculated in GORD (evidence type 2; Table 3) [25,30–33].
comparison with oesophageal pH monitoring for thediagnosis of GORD. Assuming a prevalence or pretest In conclusion, the presence of typical symptoms probability of GORD of 25%, the analysis indicates the does not ensure the diagnosis of GORD.
extent to which a positive test changes the probabilitythat the individual has GORD.
Clinical symptoms Four studies have compared endoscopy with 24 h pH The symptoms considered typical of GORD are heart- monitoring for the diagnosis of GORD (Table 4) burn and regurgitation. Although these symptoms have relatively high sensitivity (B70%) for the diagnosis ofGORD, they have a low specificity (53%) [25]. There are If GORD were to be diagnosed using endoscopy, 40% of as yet no gold standard tests available for comparison.
individuals with GORD would not be diagnosed and 24% Until an ‘ideal' diagnostic method becomes available, the of healthy individuals would be diagnosed incorrectly as importance of the data obtained from history for making having GORD. Evidence type 2c.
the diagnosis of such a prevalent condition must beevaluated. Data from clinical studies indicate that boththe severity and the frequency of the symptoms are In conclusion, conventional endoscopy is a important, and also that there is a relationship between valuable investigation for the diagnosis of the severity of symptoms and quality of life impairment GORD but suffers from a lack of specificity.
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An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
Ability of the test to diagnose gastro-oesophageal reflux disease on the basis of clinical symptoms Author phase III studies Clinical symptoms Probability of GORD (%)a Klauser et al. [25] Klauser et al. [30] Carlsson et al. [31] Johnson et al. [33] Johnson et al. [33] GORD, Gastro-oesophageal reflux disease; LR + , positive likelihood ratio; RDQ, reflux disease questionnaire.
aAssuming that prevalence or pretest probability for GORD is 25%, a patient with clinical symptoms will have a 30–40% probability of suffering from GORD (post-testprobability).
Ability of endoscopy to diagnose gastro-oesophageal reflux disease compared with pH monitoring GORD probability (%)a Endoscopy versus pH monitoringRichter [34] Fuchs et al. [20] Bollschweiler et al. [24] Ottignon et al. [35] GORD, Gastro-oesophageal reflux disease; LR, likelihood ratio.
aCompared with pH monitoring, if endoscopy is positive, the probability of having GORD would increase from 25 to 40% based on some studies, or 85% based on otherstudies.
Ability of the histology test to diagnose gastro-oesophageal reflux disease compared with pH monitoring plus clinical symptoms, pH monitoring plus the proton pump inhibitor test and versus clinical symptoms Versus pH monitoring plus clinical symptomsSchindlbeck et al. [36] Ottignon et al. [35] Kasapidis et al. [37] Versus pH monitoring plus PPI testNarayani et al. [38] Versus clinical symptomsNandurkar et al. [39] Funch-Jensen et al. [40] GORD, Gastro-oesophageal reflux disease; LR, likelihood ratio; PPI, proton pump inhibitor.
aAssuming a GORD prevalence of 25%, if the histology test is positive, the probability of having GORD would rise to 35–59%.
Oesophageal manometry Six studies with acceptable methodological quality were Four studies were included (Table 6) [20,24,42,43].
included (Table 5) [35–40].
There was a great heterogeneity between studies. Data The positive LR for oesophageal biopsy are low, so a from Richter [42] suggest that, if manometry was used as a positive test does not significantly modify the probability diagnostic test for GORD, 42% of diseased individuals of having GORD.
would remain without the diagnosis and 16% of healthyindividuals would be diagnosed as having GORD. Evi- If oesophageal biopsies were used to diagnose non-erosive dence type 2c.
GORD (using the criteria of Ismail-Beigi et al. [41]), 24%of individuals with GORD would not be diagnosed, Oesophageal manometry has limited indications in whereas 61% of healthy individuals would be diagnosed GORD: (i) To investigate oesophageal motility in incorrectly as having GORD. Evidence type 2c.
selected patients being considered for antireflux surgery,with the aim of helping the surgeon to define the optimal In conclusion, investigating the histology of plan of therapy. Oesophageal manometry may be needed the distal oesophageal squamous epithelium to identify achalasia or scleroderma; in the presence of is not considered valuable in the diagnosis of either, surgery may be inappropriate or an alternative procedure may be indicated. (ii) To determine the Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 Ability of oesophageal manometry to diagnose gastro-oesophageal reflux disease GORD probability (%) LOS < 10 mmHgJohansson et al. [43] Fuchs et al. [20] LOS < 6 mmHg + abnormal lengthBollschweiler et al. [24] GORD, Gastro-oesophageal reflux disease; LOS, lower oesophageal sphincter; LR, likelihood ratio.
Ability of contrast radiology to diagnose gastro-oesophageal reflux disease GORD probability (%) Oesophagitis +Richter [42] Thompson et al. [44] GORD, Gastro-oesophageal reflux disease; LR, likelihood ratio.
Ability of the proton pump inhibitor test to diagnose gastro-oesophageal reflux disease compared with pH monitoring Patients with positive Phase III studyBate et al. [45] Fass et al. [46]b Juul-Hansen et al. [48]c Schenk et al. [49]b GORD, Gastro-oesophageal reflux disease; LR, likelihood ratio.
aUsing pH monitoring as the gold standard and assuming a 25% GORD prevalence and an LR + of 1.69, the probability of having GORD after a positive therapeutic testonly increases to 38%.
bOmeprazole 40 mg.
cLansoprazole 60 mg.
precise location of the lower oesophageal sphincter to Bile reflux monitoring permit the accurate placement of a pH electrode.
No studies were included. This is considered to be acostly method, with limited availability and manytechnical difficulties. It has not been validated for the In conclusion, manometry is not considered to diagnosis of GORD.
be a valuable diagnostic test for GORD.
Contrast radiology In conclusion, there is no evidence warranting Two studies were included (Table 7) [42,44].
its use in routine clinical practice.
In all studies included to evaluate radiology, the positive Therapeutic trials LR were less than 10, indicating that it has a limited effect Proton pump inhibitor test versus 24-h pH monitoring on the post-test probability of GORD. Evidence type 2c.
See Table 8 [45–49].
In conclusion, radiology is not considered to Proton pump inhibitor test versus endoscopy be a valuable diagnostic test for GORD.
See Table 9 [49–54]. The PPI therapeutic test wasassessed as a diagnostic test in 11 studies (five using pH monitoring and six using endoscopy as a comparator).
No studies were included. This is considered an Studies showed heterogeneity with respect to the different drugs used, doses, time and the evaluationmethod of the therapeutic response.
In conclusion, there is currently no evidencewarranting its use in the routine care of On the basis of these studies, a positive response to empirical treatment with PPI, 22–29% of individuals with Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
Ability of the proton pump inhibitor test to diagnose gastro-oesophageal reflux disease compared with endoscopy GORD prevalence (%) Patients with positive Phase III studyCarlsson et al. [50] Galmiche et al. [51] Hatlebakk et al. [52] Schenk et al. [49] Johnsson et al. [53] Venables et al. [54] GORD, Gastro-oesophageal reflux disease; LR, likelihood ratio.
aUsing endoscopy as the gold standard and assuming a 25% GORD prevalence and a positive combined LR + of 1.20, the probability of having GORD after a positivetest would be only 30%.
GORD would not be diagnosed (possibly because they could not conclude from the evidence that either lifestyle would have needed a higher dose or longer duration of changes or diet had any benefit in the treatment of treatment), whereas 46–59% of healthy individuals would GORD [55–68].
be diagnosed incorrectly with GORD; thus, a positiveresponse to a PPI test is not sufficient to establish a Antacids, alginates and sucralfate diagnosis of GORD with confidence. Furthermore, a The best evidence is that the alginate–antacids combina- positive PPI test may also indicate the presence of tion was superior to placebo in patients with GORD.
another acid-related condition, an enhanced oesophageal We identified four randomized controlled trials [69–72] sensitivity to acid exposure or a placebo effect.
evaluating 186 patients. Fifty-three per cent of theantacids–alginate patients reported symptom improve- In conclusion, successful short-term treatment ment compared with 20% of the placebo group (RR 0.60; with a PPI in patients suspected of having 95% CI 0.39–0.91). The absolute difference in symptom GORD adds only confirmatory information to cure rates was 31% (95% CI 16–47%) giving a number the diagnosis of GORD as established by needed to treat of three (95% CI 2–6).
currently accepted reference standards. Evi-dence type 2a.
Two trials evaluated antacids versus placebo for symptomrelief, and reported no statistical differences betweenthe groups [69,73]. Two trials evaluating 74 patients Therapeutic management: available evidence [73,74], which compared antacids and placebo for the The primary treatment objectives are the alleviation of healing of oesophagitis found no statistical differences symptoms, the healing of mucosal lesions and the between the two groups.
prevention of recurrence and complications. From thepractical point of view the delegates were asked todiscuss and make recommendations, on the basis of the There was only a small amount of data comparing available evidence and their personal experience, for the antacids alone with an antacids–alginate combination.
following issues: (i) the behavioural approach (diet andlifestyle changes); (ii) the role of antacids, alginates and Two evaluable studies involving 81 patients [69,75] sucralfate; (iii) pharmacological therapy [prokinetics, suggested that the antacids–alginate combination had a similar efficacy to antacids alone in improving symptoms, 2 receptor antagonists (H2 RA), PPI]; (iv) maintenance therapy (prokinetics, histamine H but these results were not statistically significant. One trial PPI); (v) pharmacological versus surgical therapy; (vi) was excluded because it did not assess the outcomes surgical therapy: indications; (vii) surgical treatment: specified for the consensus meeting (retrosternal pain) [76].
open or laparoscopic; (viii) the treatment of Helicobacterpylori infection; and (ix) endoscopic treatment.
Two trials compared H2 RA plus alginate with regularantacids–alginate in heartburn relief of 249 GORD Behavioural approach: diet and lifestyle changes patients [77,78]. Forty per cent of the H2 RA group We found 14 randomized controlled trials on this topic.
reported symptom improvement compared with 21% in None of them fulfilled the eligibility criteria. The reasons the antacid group. Both trials showed a trend in favour of for exclusion were: assessment of healthy volunteers, H2 RA therapy, and revealed a statistically significant assessment of outcomes that were not selected for the difference in favour of H2 RA therapy with an absolute consensus (oesophageal sphincter motor activity and difference in cure rates of 18% (95% CI 7–29%), number oesophageal pH), and one study was in German. We needed to treat equalled six (95% CI 3–14).
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European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 One trial compared H2 RA with antacid therapy for doubtful whether additional data will ever be heartburn relief and the healing of oesophagitis, and reported. Regarding sucralfate therapy, the data showed that H2 RA treatment was superior to antacid are not sufficient to allow a conclusion over its therapy [79].
efficacy. Evidence type 2.
One trial that compared H2 RA plus alginate with H2 RA Pharmacological therapy therapy alone found no difference in the relief of Gastro-oesophageal reflux disease-like symptoms and endoscopy- symptoms in GORD patients at 6 weeks, although a negative reflux disease statistically significant effect in favour of the combination Short-term treatment (1–12 weeks) should be given for therapy was reported at 12 weeks [80].
GORD-like symptoms and endoscopy-negative refluxdisease (ENRD) [83]: empirical and ENRD treatment.
One trial including 141 patients evaluated sucralfate gelversus placebo in patients with non-erosive GORD, and Prokinetics (cisapride, domperidone and metoclopramide) versus reported that sucralfate gel was significantly better than placebo in the treatment of patients with GORD [81].
Prokinetics are effective for heartburn relief (day andnight time) when compared with placebo [52,84–86].
One trial that assessed self-directed treatment forepisodic heartburn compared famotidine with antacids, Cisapride is the prokinetic drug that was studied most both at different doses, with placebo in patients with extensively for GORD treatment; however, it has recently intermittent heartburn. It showed that famotidine and been withdrawn from many markets.
antacids provided more rapid and more frequent heart-burn relief than placebo [82].
H2 Receptor antagonists versus placeboH2 RA are effective for heartburn relief (day and night In conclusion, there is a paucity of evidence time) and for an overall improvement when compared addressing antacids and antacids–alginate com- with placebo [84,87–93].
binations. There is some evidence that anta-cids–alginate combinations are effective for the Meta-analysis showed that H2 RA improved heartburn short-term control of symptoms in patients with relief at night time compared with placebo in 23% on GORD, but therapeutic gain is small. It is empirical treatment and 20% of ENRD patients. In Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy-negative reflux disease.
Comparison: 02 H2RA versus placeboOutcome: 01 Pain free at night Relative risk (random) Relative risk (random) 01 Empirical treatment 0.56 [0.38, 0.84] 0.89 [0.68, 1.17] 0.79 [0.66, 0.94] Subtotal (95% CI) 0.77 [0.63, 0.94] Test for heterogeneity chi-square = 3.51 df = 2 P = 0.1732Test for overall effect = −2.54 P = 0.0102 Treatment of ENRD 0.80 [0.59, 1.08] Subtotal (95% CI) 0.80 [0.59, 1.08] Test for heterogeneity chi-square = 0.00 df = 0Test for overall effect = −1.45 P = 0.15 Short-term empirical treatment in patients with gastro-oesophageal reflux disease-like symptoms. Histamine H2 receptor antagonist versus placebo.
Outcome: pain free at night. CI, Confidence interval; ENRD, endoscopy-negative reflux disease; H2RA, histamine H2 receptor antagonist.
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An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy negative reflux disease.
Comparison: 02 H2RA versus placebo 02 Pain free at day Relative risk (random) Relative risk (random) 01 Empirical treatment 0.77 [0.60, 0.99] 0.50 [0.19, 1.33] 0.93 [0.72, 1.19] 0.77 [0.66, 0.90] Subtotal (95% CI) 0.80 [0.71, 0.89] Test for heterogeneity chi-square = 2.67 df = 3 P = 0.4455Test for overall effect = −3.92 P = 0.0001 02 Treatment of ENRD 0.75 [0.61, 0.93] Subtotal (95% CI) 0.75 [0.61, 0.93] Test for heterogeneity chi-square = 0.00 df = 0Test for overall effect = −2.66 P = 0.008 Short-term empirical treatment in patients with gastro-oesophageal reflux disease-like symptoms. Histamine H2 receptor antagonist versus placebo.
Outcome: painfree in day. CI, Confidence interval; ENRD, endoscopy-negative reflux disease; H2 RA, histamine H2 receptor antagonist; PPI, protonpump inhibitor.
addition, in relation to heartburn relief in the day time, ment). In ENRD patients, PPI improved heartburn relief the improvement was 20 and 25%, respectively.
in 28% compared with prokinetics, therefore whenthey are compared with H2 RA the differences are of statistically borderline significance [52,99,102–110] 2 RA improved overall symptom relief compared with placebo in 28% on empirical treatment, but in ENRD (Figs 6–8).
patients there were no significant differences betweenthe treatment groups (Fig. 1, Fig. 2 and Fig. 3).
No significant difference in efficacy between H2 RAand prokinetics was demonstrated in the trial reviewed Proton pump inhibitors versus placebo PPI are effective for heartburn relief (day and night time)and for achieving an overall improvement when compared Proton pump inhibitors versus proton pump inhibitors with placebo [49,50,52,94–100,102].
Omeprazole 20 mg was better than 10 mg in heartburnrelief [54,99,111]. There were no differences between PPI improve overall symptom relief in 37% compared esomeprazole 40 mg and esomeprazole 20 mg or between with placebo in ENRD patients (Fig. 4). PPI improve esomeprazole 40 mg versus omeprazole 20 mg in heart- heartburn relief in 63 and 32% compared with placebo burn relief [112].
both on empirical treatment and ENRD patients (Fig. 5).
In conclusion, the evidence indicates that PPI PPI are effective at achieving wellbeing and satisfaction are superior to H2 RA in achieving an overall to a level similar to that observed in a healthy population improvement in empirical treatment and in when compared with placebo [101].
ENRD patients. In relation to heartburn relief,PPI are more effective than H2 RA and Proton pump inhibitors versus H2 receptor antagonists and versus prokinetics in empirical treatment, and PPI seem to be superior to H2 RA in ENRD PPI are significantly more effective than H2 RA and patients. There were no differences between prokinetics for heartburn relief and overall symptom PPI. Omeprazole 20 mg was better than ome- improvement in studied patients (as empirical treat- prazole 10 mg. Evidence type 1.
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European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy negative reflux disease.
Comparison: 02 H2RA versus placeboOutcome: 03 Overall improvement Relative risk (random) Relative risk (random) 01 Empirical treatment 0.78 [0.63, 0.97] 0.68 [0.61, 0.76] 0.58 [0.42, 0.75] 0.79 [0.70, 0.89] Subtotal (95% CI) 0.72 [0.63, 0.81] Test for heterogeneity chi-square = 6.67 df = 3 P = 0.0831 Test for overall effect = −5.30 P < 0.00001 02 Treatment of ENRD 0.20 [0.06, 0.66] 0.65 [0.46, 0.92] Subtotal (95% CI) 0.41 [0.13, 1.33] Test for heterogeneity chi-square = 3.78 df = 1 P = 0.052 Test for overall effect = −1.48 P = 0.14 Short-term empirical treatment in patients with gastro-oesophageal reflux disease-like symptoms. Histamine H2 receptor antagonist versusplacebo. Outcome: overall improvement. CI, Confidence interval; ENRD, endoscopy-negative reflux disease; H2 RA, histamine H2 receptorantagonist.
Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy negative reflux disease.
Comparison: 01 PPI versus placeboOutcome: 01 Overall improvement Relative risk (random) Relative risk (random) 01 Endoscopy negative reflux disease 0.75 [0.58, 0.96] 0.56 [0.47, 0.67] 0.64 [0.50, 0.83] 0.58 [0.39, 0.88] Subtotal (95% CI) 0.63 [0.55, 0.72] Test for heterogeneity chi-square = 3.55 df = 3 P = 0.3149 Test for overall effect = −6.83 P < 0.00001 Short-term empirical treatment in patients with gastro-oesophageal reflux disease-like symptoms. Proton pump inhibitor versus placebo. Outcome:overall improvement. CI, Confidence interval; PPI, proton pump inhibitor.
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An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy-negative reflux disease.
Comparison: 01 PPI versus placeboOutcome: 02 Heartburn relief Relative risk (random) Relative risk (random) 01 Empirical treatment 0.35 [0.26, 0.46] 0.38 [0.32, 0.46] Subtotal (95% CI) 0.37 [0.32, 0.44] Test for heterogeneity chi-square = 0.42 df = 1 P = 0.5189 Test for overall effect = −12.73 P < 0.0000102 Endoscopy negative reflux disease 0.58 [0.47, 0.73] 0.94 [0.79, 1.11] 0.59 [0.51, 0.68] 0.73 [0.65, 0.82] 0.65 [0.59, 0.73] 0.56 [0.36, 0.86] Subtotal (95% CI) 0.68 [0.59, 0.78] Test for heterogeneity chi-square = 22.09 df = 5 P = 0.0005Test for overall effect = −5.36 P < 0.00001 Short-term treatment endoscopy-negative reflux disease. Proton pump inhibitor versus placebo. Outcome: heartburn relief. CI, Confidence interval;PPI, proton pump inhibitor.
Short-term treatment in patients with oesophagitis omeprazole 20 mg, rabeprazole 20 mg and omeprazole Prokinetics versus placebo 40 mg, pantoprazole 40 mg and omeprazole 40 mg, or Only one trial [113] was found, which did not show any pantoprazole 20 mg and omeprazole 20 mg for oesophagitis statistically significant differences in the healing of healing, symptom relief and heartburn relief. Omeprazole 40 mg was better than omeprazole 20 mg, and pantoprazole30 mg was better than pantoprazole 15 mg for oesophagitis healing at 4 weeks [119–129]. Omeprazole 20 mg was more 2 Receptor antagonists versus placebo effective than omeprazole 10 mg in healing oesophagitis 2 RA were effective for the healing of oesophagitis and the relief of heartburn compared with placebo [114].
[50]. Two trials reported that esomeprazole 40 mg producedgreater healing rates at 8 weeks and greater heartburn resolution rates than omeprazole 20 mg (typical RR for 2 Receptor antagonists versus H2 receptor antagonists There were no differences between famotidine 40 mg and healing oesophagitis 1.10, 95% CI 1.08–1.13). One trial famotidine 20 mg a day, between ranitidine and cimeti- reported that esomeprazole 40 mg produced a greater dine, or between ranitidine 150 mg twice a day versus healing rate than lansoprazole 30 mg (RR 1.04, 95% CI ranitidine 150 mg four times a day [114,115].
1.02–1.06). Esomeprazole 40 mg has been shown to be moreeffective than omeprazole 20 mg or lansoprazole 30 mg in Proton pump inhibitors versus H 2 receptor antagonists PPI were more effective than H2 RA for the healing ofoesophagitis [116–118].
Although statistically significant, it has been debatedwhether these differences are clinically relevant. (No doubt PPI improved the healing of oesophagitis in 46% substantial differences in efficacy prevail in LA grade C and D cases in favour of esomeprazole) [130–132].
2 RA (95% CI 55–39%; Fig. 9).
Proton pump inhibitors versus proton pump inhibitors In conclusion, evidence shows that in patients There were no significant differences between omeprazole with oesophagitis a course of PPI or H2 RA is 20 mg and lansoprazole 30 mg, rabeprazole 20 mg and effective in healing oesophagitis. PPI are sig- Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy-negative reflux disease.
04 PPI versus H2RA 01 Heartburn remission Relative risk (random) Relative risk (random) 01 Empirical treatment 0.60 [0.46, 0.78] 0.71 [0.63, 0.80] 0.49 [0.37, 0.66] 0.74 [0.63, 0.86] 0.75 [0.67, 0.85] Subtotal (95% CI) 0.69 [0.61, 0.77] Test for heterogeneity chi-square = 8.95 df = 4 P = 0.0623Test for overall effect = −6.60 P < 0.00001 02 Endoscopy negative reflux disease 0.83 [0.54, 1.27] 0.49 [0.32, 0.77] 0.88 [0.75, 1.02] Subtotal (95% CI) 0.74 [0.53, 1.03] Test for heterogeneity chi-square = 5.66 df = 2 P = 0.059 Test for overall effect = −1.78 P = 0.08 Short-term treatment endoscopy-negative reflux disease. Proton pump inhibitor versus histamine H2 receptor antagonist. Outcome: Heartburnremission. CI, Confidence interval; H2 RA, histamine H2 receptor antagonist; PPI, proton pump inhibitor.
nificantly better than H2 RA in healing oeso- effective than placebo in controlling disease phagitis and in achieving heartburn relief.
manifestations. Evidence type 1.
Among different PPI, esomeprazole has beenshown to be statistically more effective thanomeprazole or lansoprazole in healing oeso- Patients with oesophagitis phagitis, an effect that is most predominant in Proton pump inhibitors versus placebo LA grade C and D cases. Evidence type 1.
PPI (omeprazole, esomeprazole) are more effectivethan placebo at maintaining the healing of oesophagitis Maintenance therapy and the patient free of heartburn at one month Patients without oesophagitis (endoscopy-negative reflux disease) Proton pump inhibitors versus placebo (on demand)PPI as ‘on demand' therapy are more effective than Proton pump inhibitors versus proton pump inhibitors placebo in maintaining heartburn remission [133,134].
Evidence has shown no differences between rabeprazole10 mg Proton pump inhibitors at different doses or rabeprazole 20 mg and omeprazole 20 mg [140], Omeprazole 20 mg is better than omeprazole 10 mg as ‘on lansoprazole 30 mg and pantoprazole 40 mg [141], demand' therapy at maintaining heartburn remission lansoprazole 30 mg and omeprazole 20 mg [141], panto- prazole 40 mg and omeprazole 20 mg [141], pantoprazole20 mg and pantoprazole 40 mg [142] in maintain- Two trials [135,136], which compared esomeprazole and omeprazole were excluded because they assessed only remission. One trial showed that both esomeprazole direct medical costs.
40 mg and esomeprazole 20 mg were effective in main-taining the healing of oesophagitis [137,138] and In conclusion, evidence shows that in patients that omeprazole 20 mg was better than omeprazole with ENRD, ‘on demand' PPI therapy is more 10 mg [121].
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An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy negative reflux disease.
Comparison: 04 PPI versus H2RAOutcome: 02 Overall improvement Relative risk (random) Relative risk (random) 01 Empirical treatment 0.29 [0.17, 0.51] Subtotal (95% CI) 0.29 [0.17, 0.51] Test for heterogeneity chi-square = 0.00 df = 0 Test for overall effect = −4.34 P = 0.0000 02 Endoscopy negative reflux disease 0.83 [0.76, 0.91] Subtotal (95% CI) 0.83 [0.76, 0.91] Test for heterogeneity chi-square = 0.00 df = 0 Test for overall effect = −4.03 P=0.0001 Short-term treatment endoscopy-negative reflux disease. Proton pump inhibitor versus histamine H2 receptor antagonist. Outcome: overallimprovement. CI, Confidence interval; H2 RA, histamine H2 receptor antagonist; PPI, proton pump inhibitor.
Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refluxdisease-like symptoms and endoscopy negative reflux disease.
Comparison: 05 PPI versus prokineticOutcome: 01 Heartburn remission Relative risk (random) Relative risk (random) 01 Empirical treatment 0.67 [0.55, 0.82] 0.40 [0.30, 0.54] Subtotal (95% CI) 0.53 [0.32, 0.87] Test for heterogeneity chi-square = 7.94 df = 1 P = 0.0048Test for overall effect = −2.48 P = 0.01 02 Endoscopy-negative reflux disease 0.72 [0.56, 0.92] Subtotal (95% CI) 0.72 [0.56, 0.92] Test for heterogeneity chi-square = 0.00 df = 0Test for overall effect = −2.59 P = 0.009 Favours prokinetic Short-term treatment endoscopy-negative reflux disease. Proton pump inhibitor versus prokinetics. Outcome: Heartburn remission. CI, Confidenceinterval; PPI, proton pump inhibitor.
One study showed that esomeprazole 20 mg was more One study showed that esomeprazole 20 mg maintained a 12% higher proportion of patients in remission than did remission in patients with healed reflux oesophagitis lansoprazole 15 mg, over the 6-month course of treatment (RR 1.12, 95% CI 1.06–1.19) [143]. In a recent Cochrane Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 Short-term treatment in patients with oesophagitis Comparison: 01 PPIs versus H2RAsOutcome: 01 Healing of the oesophagitis 0.64 [0.52, 0.79] 0.37 [0.19, 0.72] 0.35 [0.21, 0.60] 0.54 [0.45, 0.66] Total events: 90 (treatment), 167 (control)Test for heterogeneity: Chi2 = 6.06, df = 2 (P = 0.05), I2 = 67.0%Test for overall effect: Z = 6.25 (P < 0.00001) Favours treatment Short-term treatment in patients with oesophagitis. Proton pump inhibitor versus histamine H2 receptor antagonist. Outcome: Healing of theoesophagitis. H2 RA, histamine H2 receptor antagonist; PPI, proton pump inhibitor.
systematic review, Donnellan et al. [144] stated that One study [149], which compared surgical therapy with esomeprazole 20 mg should be at least as effective as omeprazole 20 mg a day, showed that clinical remission at omeprazole 20 mg.
3 years was higher in the surgical group. However, whenthe dose of omeprazole was adjusted (40–60 mg a day) as Proton pump inhibitors versus H needed, the relapse rates were more similar between the 2 receptor antagonists PPI are better than H 2 RA for heartburn remission at 12 months, keeping the patient free of heartburn at 12 weeksand for preventing a relapse of oesophagitis at 24 weeks Another study compared continuous therapy (included antacids and ranitidine), symptomatic medical therapy(antacids and ranitidine if symptoms could not be H2 Receptor antagonists versus placebo controlled) and surgical therapy [150]. The study was H2 RA are better than placebo for maintaining heartburn conducted to assess pulmonary function at one year, and remission and preventing relapse of oesophagitis at 6 concluded that there were no differences between the months [147].
three groups for this outcome.
In conclusion, evidence shows that continuous Spechler et al. [151] assessed long-term outcomes in the PPI therapy is superior to placebo. PPI were follow-up study of a randomized controlled trial [152].
The authors reported that GORD symptoms were 2 RA for maintenance treatment of patients with oesophagitis. There were no significantly less severe in the surgical treatment group significant differences between omeprazole and when drug therapy was discontinued, but not when rabeprazole, or between pantoprazole and patients were permitted to take antireflux medications.
lansoprazole. However, 20 mg a day of esome- During a follow-up period of 10–13 years, the authors prazole was better than 15 mg a day of found that patients with complicated GORD who were lansoprazole at maintaining endoscopic remis- treated with antireflux surgery were significantly less sion. At the end of the inclusion period of likely to take antireflux medications regularly, and when studies for this consensus there were no those medications were discontinued, their GORD other papers comparing esomeprazole with symptoms were significantly less severe than those of other PPI for maintenance therapy. Evidence medically treated patients. There was no significant difference between the groups in the rates of neoplasticand peptic complications of GORD, physical and mentalwellbeing scores, and satisfaction with antireflux therapy.
Pharmacological versus surgical therapyOne study showed that surgical therapy produced higher Surgical treatment: open surgery versus laparoscopy healing rates at 2 years compared with medical treatment There is good evidence (type 1) that both laparoscopic (ranitidine) in asthmatic patients [148].
and open surgery are effective methods in the operative Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
treatment of GORD in the short term, and that they produce a significant improvement in patients' gastro- The following were considered criteria justifying the intestinal symptoms and quality of life. The laparoscopic indication of endoscopy: (i) in all patients over 45 years of approach is better than open surgery when considering age with typical symptoms; (ii) in patients less than 45 postoperative pain, the use of analgesia, time of hospitaliza- years of age with typical symptoms that fail to respond to tion, and ventilatory function [153,154]. Evidence showed a trial of PPI therapy (therapeutic diagnostic test); (iii) in that persistent severe dysphagia was more common after patients with alarm symptoms (dysphagia, odynophagia, laparoscopic antireflux surgery than after open surgery. The anaemia, weight loss, haemorrhage); (iv) in patients with results of a systematic review of the literature showed that long-standing symptoms ( > 5 years). Voting: 94.4% there were no significant differences between laparoscopicand open fundoplication regarding the recurrence of GORD, dysphagia, bloating and reoperation rates [155].
Biopsy of the oesophagus is not indicated if noendoscopic lesions are found. Voting: 94.4% Treatment of Helicobacter pylori infectionThere is good evidence (type 1) showing that H. pylori infection has no effect on GORD, and that its eradication The indications below were suggested for ambulatory, 24- does not worsen GORD symptoms [156,157].
h oesophageal pHmetry: (i) patients with no response toPPI (to be performed without discontinuing antireflux Endoscopic treatment medication). Voting: 100%; (ii) non-erosive disease with There is no evidence from randomized controlled trials to no response to therapy (to be performed with patient assess the effectiveness of endoscopic treatment in comparison with medical or surgical therapy.
(iii) atypical GORD manifestations (respiratory, ear noseand throat, chest pain). Voting: 100%; (iv) recurrence of symptoms after antireflux surgery and in the absence of lesions in the oesophageal mucosa. Voting: 100% The methodological analysis of the evidence available onthe various diagnostic tests for GORD shows that none of them could be considered highly effective. There is no The following are considered indications for manometry gold standard test for the diagnosis of GORD.
in GORD: (i) preoperative study to rule out any primarymotor disorder. Voting: 94.4%; (ii) Before placement of a As a consequence, the decisions taken by the consensus pH electrode. Voting: 100% on diagnosis of GORD had to be voted, as expert opinion.
The diagnostic group suggested the following indications for GORD is a recurrent condition related to the retrograde contrast radiology in GORD: (i) patients with alarm flow of gastric contents with or without duodenal symptoms, especially dysphagia. Voting: 94.4%; (ii) patients contents towards the oesophagus or adjacent organs. It with GORD before antireflux surgery. Voting 94.4%; presents a varied spectrum of symptoms that can impair (iii) after antireflux surgery in patients with symptomatic the patient's quality of life and it may present with or relapse. Voting: 78.5% without tissue damage. Voting: 100% acceptance This is considered an investigational method. There is The group that worked on diagnosis defined the typical currently no evidence warranting its use in the routine symptoms in order to speak in similar terms and to clinical management of GORD. Voting: 100% compare outcomes in the future. The following issueswere agreed upon: Bile reflux monitoringThis was considered to be a costly method, with many technical difficulties. There is no evidence warranting its Ascending retrosternal burning sensation. For the diag- use in clinical practice. Voting: 94.4% nosis of GORD, it should be present two or more times aweek, for more than 3 months during the past year, not Diagnostic: therapeutic test with a proton pump inhibitor necessarily continuous. Voting: 71.4% As stated by Numans et al. [158], ‘although there may bediagnostic uncertainty, a PPI trial might be reasonable in patients without alarm symptoms or other suspected Effortless return of the gastric contents into the complications of GORD [132,159]. On the other hand, oesophagus and at times, into the mouth. Voting: 100% the decision to begin with a PPI has long-term economic Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
European Journal of Gastroenterology & Hepatology 2006, Vol 18 No 4 and clinical implications because responding patients will Available proton pump inhibitors probably continue treatment even though a diagnosis has Proton pump inhibitor Full daily dose (mg) not been clearly established. Until better methods are available to establish a confident diagnosis, the empirical treatment approach (and selection of the dose and type of acid-suppressing agents) should be individualized on the basis of the clinical setting, the response to therapy, andjudicious diagnostic testing' [132].
Antacids, alginates and sucralfate Considering the previous statement, the consensus Delegates unanimously agreed (100%) that the use of suggested the following indications: (i) to perform PPI these medications could be considered in special situa- test on patients under 45 years of age with typical tions (such as the occurrence of adverse events with H2 symptoms; (ii) as there was no agreement on the optimal RA or PPI) to provide transient symptomatic relief (grade dose or duration of PPI therapy, professionals are free to D recommendation).
choose the dosage, the duration of the therapeutic trialand the criteria applied to interpret the patient's Pharmacological therapy response. Voting: 84.4% Short course treatmentThere is good evidence (type 1) supporting the use of Diagnostic management PPI instead of H2 RA or prokinetics for the initial The following measures are recommended: management of patients with erosive and non-erosiveGORD. Doses and drugs are described in Table 11 (gradeA recommendation).
Patients under 45 years with typical symptoms(i) Diagnostic therapeutic testing with PPI and sympto-matic re-evaluation. Voting: 100% (there was no agree- PPI should be the initial therapy of choice (4–8 weeks).
ment on dosages and test duration); (ii) if there is a good Esomeprazole can be recommended as the first choice response, discontinue treatment and evaluate at follow- compared with lansoprazole and omeprazole, but more up. Voting: 100%; (iii) if there is no response: ensure evidence that compares this drug with other PPI was not compliance with treatment and if a lack of response is available at the date of this consensus (grade A recom- confirmed, the patient should undergo endoscopy. Voting: H2 RA and prokinetics are considered to be second-linetherapy (grade A recommendation).
Patients over 45 years with typical symptomsInitial endoscopy. Voting: 100% Maintenance therapyThere is good evidence (type 1) supporting the use of Therapeutic managementThe following measures are recommended: PPI instead of H2 RA or prokinetics in the maintenancetreatment of patients with GORD (with or withouterosive oesophagitis). Consequently, patients needing Behavioural approach: diet and lifestyle changes ongoing treatment should be offered any PPI as a first Diet and lifestyle changes were defined according to choice treatment for maintenance. Esomeprazole has Moraes-Filho et al. [12] (Table 10); on the basis of this, been shown to be better than lansoprazole at main- the delegates agreed unanimously (100%) that dietary tenance dosage in one trial, but evidence that compares esomeprazole with other PPI was not yet available at the decided by each physician in the light of his/her clinical time of this consensus, so the PPI of choice could be experience on a case-by-case basis (grade D recommen- esomeprazole or it could also be prescribed in accordance with the physician's personal preference (grade Arecommendation).
Behavioural modifications in the treatment of gastro- oesophageal reflux disease [12] Pharmacological versus surgical therapy Elevation of the headboard of the bed (15 cm) Surgical intervention is an alternative approach compar- Ingestion of the following foods in moderation and based on symptom correlation: able to pharmacological therapy in terms of efficacy fatty foods, citrus, coffee, chocolate, alcoholic and carbonated beverage, mint,tomato-based products (grade A recommendation).
Special care with ‘at risk' medications: anticholinergics, theophylline, tricyclic antidepressants, calcium antagonists, b-adrenergic agonists, alendronate Avoidance of large meals Surgical treatment: indications Drastic reduction in, or cessation of, smoking The evidence reviewed showed that the individuals who Reduction of body weight, of overweight respond to medical therapy but who are unable or Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
An evidence-based, Latin-American consensus on gastro-oesophageal reflux disease Cohen et al.
unwilling to continue on it are good candidates for surgery consensus on gastroesophageal reflux disease: proposals for assessment, (grade A recommendation). It was agreed by the classification, and management. Am J Gastroenterol 2002; 97:241–248.
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Bowel cancer From diagnosis to recovery making cancer less frightening by enlightening 1 Some of the information in this booklet is taken with permission from the patient information website of Cancer Research UK. www.cancerresearchuk.org/about-cancer Bowel cancer From diagnosis to recovery About this booklet We have developed this booklet because we recognise that bowel cancer is one of the most common cancers in Ireland. About 2,500 men and women are diagnosed here each year.

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ISSN: 1536·8378 (print), 1536-8386 (electronic) Electromagn Bioi Med, Early Online: 1-12 AND MEDICINE © 2013 lnforma Healthcare USA, Inc. DOl: 10.3109/15368378.2013.817334· ORIGINAL ARTICLE Extra-low-frequency magnetic fields alter cancer cells through metabolic restriction Ying Li1 2 and PauI Heroux 2 'lnVitroPJus Laboratol'f, Department of Surgel'f, Royal Victoria Hospital,Montreal, QC,Canada and 2Department of Epidemiology, Biostatistics and