Primary care research and clinical practice: gastroenterology

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1 Primary are researh Correspondene to: Professor R Jones, King s College London, Department of General Pratie & Primary Care, 5 Lambeth Walk, London SE11 6SP, UK; roger.jones@kl.a.uk Reeived 8 February 2008 Aepted 29 June 2008 Primary are researh and linial pratie: gastroenterology R Jones ABSTRACT Gastrointestinal problems aount for a signifiant proportion of general pratitioners workload, and gastrointestinal aners, taken together, make up the largest group of malignanies. Approximately 10% of onsultations in general pratie in the UK are for gastrointestinal symptoms or problems, split roughly equally between the upper and lower gastrointestinal trat. Gastroenterology represents about 10% of the work of hospital speialists and the presribing osts involved in the management of gastrointestinal disorders in general pratie are around 14% of the drug budget. These disorders range from relatively minor and self limiting onditions suh as aute gastritis and aute gastroenteritis, through the more signifiant, hroni digestive disorders suh as gastro-oesophageal reflux disease (GORD), irritable bowel syndrome (IBS) and oelia disease, to muh more serious problems inluding inflammatory bowel disease (IBD) and upper gastrointestinal and oloretal aner. Gastrointestinal problems aount for a signifiant proportion of the workload of general pratitioners (GPs), and gastrointestinal aners, taken together, make up the largest group of malignanies. GPs have important roles in early diagnosti deision making, separating the minority of patients with potential alarm symptoms, suggestive of serious disease and mandating early investigation, from the majority whose symptoms are less signifiant and whose onditions may well resolve spontaneously or with minimal intervention. GPs and their teams have the responsibility for the long term are of many of the hroni gastrointestinal disorders, inluding gastro-oesophageal reflux disease (GORD), irritable bowel syndrome (IBS), oelia disease and inflammatory bowel disease (IBD), and general pratie has a potentially important role in sreening for oloretal aner, although this has not yet been fully realised. However, there is evidene from surveys undertaken in the UK 1 and Europe 2 that the management of the ommon gastrointestinal disorders by GPs is inonsistent and often does not onform to existing evidene or evidene based guidelines. Organisations suh as the British Soiety of Gastroenterology (BSG) and the Primary Care Soiety for Gastroenterology (PCSG) produe suh guidane, whih is also available through Cohrane reviews and soures suh as Clinial Evidene. Until perhaps 20 years ago, most primary are management of digestive disorders relied heavily on evidene olleted in hospital based studies, or on no evidene at all. Over the last two deades, however, primary are researh in gastroenterology has generated a great deal of important information about the epidemiology, natural history, diagnosis and management of many of the ommon gastrointestinal disorders. This paper sets out to desribe some of the researh that has been undertaken in primary are, its ontribution to linial pratie, and important areas for future researh. THE GENERAL PRACTICE CONTEXT The results of linial researh undertaken in general pratie need to be interpreted against a bakground of a hanging National Health Servie (NHS), with new and emerging roles for GPs, as hroni disease management and other aspets of patient are ontinue to shift from the seondary to the primary are setor. For many years GPs have been involved in hospital endosopy, and there are now at least 400 GP endosopists working around the ountry. The General Pratitioners with Speial Interests Sheme, established by the Department of Health and the Royal College of General Pratitioners, 3 provides a framework for the development of speialist interests in gastroenterology, and this trend is likely to ontinue. The ways in whih primary are servies are delivered are beginning to hange fundamentally. Private provision of primary are, in diret ompetition with traditional NHS providers, is now enouraged, and there is a strong poliy move towards inreasing entralisation of GP and other ommunity servies in larger groupings in newly equipped entres known as polylinis. 4 A further important onsideration is the introdution of a pay-for-performane omponent into the ontratual arrangements for GPs, through the introdution of the Quality and Outomes Framework (QOF). 5 The QOF provides finanial inentives for the attainment of speified targets in the management of a number of hroni disorders, inluding diabetes, asthma, stroke and hypertension, but not, at present, for any gastrointestinal disorders. The QOF has, in a sense, partially solved the problem of implementation of linial pratie guidelines by providing diret finanial rewards for their inorporation into routine general pratie are. RESEARCH METHODS IN PRIMARY CARE GASTROENTEROLOGY Researh publiations over the last 20 years exemplify a range of methodologies used in the study of gastrointestinal problems in general pratie. Epidemiologial survey methods have been used effetively beause of the aurate denominator provided by GPs registered lists of patients, Postgrad Med J: first published as /pgmj on 21 Otober Downloaded from on 8 Otober 2018 by guest. Proteted by opyright. 454 Postgrad Med J 2008;84: doi: /pgmj

2 Primary are researh aompanied by the general publi s willingness to respond to postal questionnaires measuring the prevalene and harateristis of gastrointestinal symptoms or disorders. Follow ups to these ross setional surveys, less frequently performed, an provide lues to the natural history of ommon gastrointestinal symptoms. The behaviour of patients (suh as fators affeting their likelihood to onsult with gastrointestinal disorders) and physiians (suh as their patterns and rates of usage of investigations and hoie of drug treatments) have been studied by a ombination of quantitative and qualitative (interview and narrative) methods, while linial trials of therapeuti interventions have been onduted in a number of disease areas. The potential of large databases, suh as the General Pratie Researh Database (GPRD) whih is the world s largest primary are database, ontaining information on approximately 13 million patient years, has been reognised for some time, and a number of important studies have been published on the natural history of gastrointestinal disorders, patterns of treatment, outomes of treatment, and the signifiane of alarm symptoms in early aner diagnosis, as desribed later. Finally, GPs have frequently been involved in systemati reviews and meta-analyses of published studies whih have attempted to identify aggregate findings of partiular interest in the management of gastrointestinal disorders in general pratie. 6 7 KEY RESEARCH FINDINGS Epidemiology The earliest epidemiologial studies in primary are gastroenterology were published in the mid 1980s and desribed the pattern and prevalene of dyspepsia, 8 9 IBS 10 and retal bleeding 11 in the general population, using general pratie lists as the data soure for the denominator and postal questionnaires sent to a stratified sample of subjets (patients) as the numerator. As well as providing important information about the ubiquity and the demographi and other fators assoiated with ommon gastrointestinal disorders, these studies began to raise the awareness of the importane of understanding patients deisions to onsult liniians about ommon symptoms. In the ase of dyspepsia, for example, while around 20% of the population experiene dyspepti symptoms, only about a quarter to one third of these patients ever seek medial advie for them. Similar findings emerged in studies on IBS and retal bleeding and these results have influened the way in whih seondary are olleagues view the onsulting patient population. Epidemiologial work in oelia disease emphasised the extent to whih this important ondition is under-reognised and under-diagnosed in general pratie, 12 and these early papers have undoubtedly had a signifiant impat on raising awareness of the ondition itself and of the symptomati and linial fators whih plae patients at inreased risk. Epidemiologial work on IBD showed the ondition to be onsiderably more ommon than previously estimated from hospital based studies, with areful general pratie based studies defining preise prevalene rates for ulerative olitis and Crohn s disease 13 and their impat on patients. 14 Natural history The great pioneer of natural history studies in general pratie was John Fry, whose painstaking manual reording of his patients onsultations over a period of many years provided early and aurate data on the inidene and prevalene of many important onditions, partiularly pepti uler disease, and of their progression over time. 15 Population based studies of the natural history of ommon gastrointestinal disorders are less frequent, although useful work on dyspepsia and IBS has been undertaken in the UK, Sweden and the Netherlands using repeated ross-setional population surveys Findings from these studies inlude the observation that the majority of patients presenting in general pratie with abdominal pain improve, with symptom resolution in 68% at 12 months, and that funtional diagnoses suh as IBS and non-uler dyspepsia frequently overlap and are unstable, with patients moving from one funtional diagnosti group to another over a 12 month observation period. Reently the use of the GPRD has allowed, through long term (retrospetive) data analysis, a learer understanding and, in some ways, a more preise quantitative appreiation of the prevalene and progression of onditions suh as dyspepsia and IBS The GPRD has also been used to examine the assoiations between various disorders, suh as that between psyhologial fators and IBS, 20 and GORD and asthma. 21 Anxiety and depression ontinue to be prevalent omorbidities in IBS. Before diagnosis prevalene of depression is 13%, ompared with 5% in ontrols, rising to 20% vs 10% after diagnosis. Corresponding figures for anxiety are 11% before diagnosis and 13% after diagnosis, ompared to 6% and 7%, respetively, in non-ibs ontrols. There are lear assoiations between asthma and GORD, so that patients with a diagnosis of asthma have an inreased risk (odds ratio 1.5, p,0.01) of developing reflux in a 3 year follow-up period, with a non-signifiant trend towards an inreased rate of asthma diagnoses in patients with an established diagnosis of GORD. Patient and professional behaviour Some of the most influential researh in primary are gastroenterology has been onerned with individuals deisions to onsult primary are physiians with digestive symptoms. Most digestive symptoms and disorders are ommon in the general population, with some 20% of subjets reporting dyspepsia, 15% IBS and 20% GORD in any 12 month period, but only a minority of these patients seek medial advie. The finding that psyhologial and emotional onerns, inluding fears of aner and heart disease and beliefs that their symptoms might represent serious disease, are more important than symptom severity in dyspepti patients deisions to onsult were striking findings, 22 whih have been repliated in onditions suh as IBS 23 and retal bleeding. 11 The influene of more formal psyhologial and psyhiatri disorders anxiety and depression are somewhat ontroversial. Early reports suggested that patients with dyspepsia and IBS who reported more psyhosoial morbidity were more likely to onsult than those without, but more reent studies, partiularly in Australia and North Ameria, have found a lesser effet of psyhologial problems in the onsultation deision. The behaviour of liniians has also been a subjet of researh interest, partiularly in relation to their variability in the use of Heliobater pylori testing and eradiation in dyspepsia, or in their rates of presription of proton pump inhibitors. 26 Qualitative methods have been used to improve our understanding of the fators affeting behaviour hange among GPs and the ways in whih new management or presribing habits are sustained and embedded These studies have emphasised the role of therapeuti experienes with individual patients in determining presribing behaviour and the relative importane of influenes suh as publiations, ontinuing medial eduation and aademi detailing on liniians uptake of new treatments. Postgrad Med J: first published as /pgmj on 21 Otober Downloaded from on 8 Otober 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

3 Primary are researh Diagnosis Effetive management of gastrointestinal disorders in general pratie depends on GPs appreiation of key diagnosti riteria, and there is growing evidene that aurate diagnosis and better linial management an be ahieved by the use of strutured questionnaires and other instruments, suh as the Reflux Disease Questionnaire (RDQ), 29 the Gastro-oesophageal Reflux Disease Impat Sale (GIS), 30 and the Rome Criteria for the diagnosis of IBS. 31 While only a minority of GPs ondut upper and lower gastrointestinal endosopy in their surgeries or other ommunity settings, the majority of GPs in the UK now have diret aess to upper endosopy and, to a slightly lesser extent, to flexible sigmoidosopy and olonosopy in hospitals. H pylori serology and arbon urea breath testing are both readily available, although aess to oesophageal manometry, ph-metry and more sophistiated investigations requires onsultant referral. A good deal of researh has been arried out on the ways in whih GPs use various diagnosti approahes in gastroenterology, partiularly endosopy, but also H pylori testing and empirial antiseretory therapy. Early studies of open aess endosopy for GPs emphasised that GPs used the servies as effetively and responsibly as their hospital olleagues, as well as providing new information on the pattern and prevalene of endosopially diagnosed gastrointestinal disorders in general pratie populations. 32 The reognition of the value of open aess endosopy in the mid 1980s led to a national move towards the provision of widespread open aess for all GPs. In the pre-h pylori era there was lively debate about the benefits and disbenefits of early endosopy versus empirial antiseretory therapy, and valuable work in Denmark initially suggested that a prompt endosopy strategy was likely to be more ost effetive than the use of empirial H 2 blokade. 33 More reently the debate has entred around the relative values of H pylori testing and endosopy in the investigation and management of dyspepsia in general pratie, and further trials from the Copenhagen group have onfirmed the appropriateness of a test and treat strategy ompared with early endosopy or empirial therapy. 34 However, as H pylori infetion beomes less of a problem in western European ountries and non-heliobater ulers (that is, those aused by non-steroidal antiinflammatory drugs) beome more important, these questions have somewhat less urreny. Work on the GPRD has also been valuable in relation to early diagnosis in primary are. A large study of several thousand patients presenting in general pratie with alarm symptoms, inluding dysphagia and retal bleeding, provided, for the first time, risk information about aner diagnosis (and timing) in men and women in different age strata. 35 Although the overall positive preditive values (PPVs) for a aner diagnosis following presentation with alarm symptoms are relatively low (for example, haematuria has a PPV of only 3.4% for urinary trat aner, and dysphagia a PPV of only 2.4% for oesophageal aner in women) in partiular groups, notably elderly men, preditive values for a aner diagnosis within the first 90 days of presentation rise steeply (for example, haemoptysis has a PPV of 17% for lung aner in men over 75 years of age, and dysphagia a PPV of 9% for oesophageal aner in men over 65). These results indiate that urgent investigation in at-risk groups is justified, while sounding a word of aution about overinvestigation in lower risk patients. Treatment Most of the major trials of the drug treatment of pepti uleration, GORD and IBD have been onduted in multientre settings oordinated by hospital speialists, although a number of innovative studies of drug treatment have been undertaken in primary are. In the 1980s the Trondheim group pioneered the use of n of 1 trials to examine the effet of antiseretory therapy in dyspepsia and to predit patients for whom antiseretory therapy is likely to be important. 36 A number of non-endosopi randomised ontrolled trials, using proton pump inhibitors, have emphasised the value of these agents in the empirial management of patients with upper gastrointestinal symptoms, while other work in primary are has doumented the pattern of usage of PPIs and some of the fators assoiated with GPs deisions to presribe PPIs empirially or following upper gastrointestinal investigations. 39 Although a number of randomised ontrolled trials (RCTs) of new agents developed for the treatment of IBS have been onduted in general pratie, 40 problems with side effets and effiay have meant that most of these drugs are not available in the UK, and has led to a reorientation of the treatment of IBS towards non-drug treatments. Following on from enouraging work in hospital settings, a large RCT of ognitive behavioural therapy (CBT) for IBS in general pratie showed a signifiant benefit of CBT when it was added to standard treatment with mebeverine, with benefiial symptomati effets and a positive impat on work and soial funtioning persisting for between 3 6 months after a nurse delivered ourse of six CBT sessions. 41 Cost effetive analysis onfirmed a modest inrease in osts in the CBT group, 42 and the reently published BSG guidelines on IBS inlude a reommendation that patients who respond unsatisfatorily to simple, initial treatment should be onsidered for CBT as part of their management. 43 RESEARCH AGENDA Early and aurate diagnosis of gastrointestinal disorders the aners and the non-malignant onditions remains the most important goal. Delays in diagnosis of IBS, for example, are often assoiated with unneessary referral to inappropriate speialists, leading to inappropriate surgial proedures suh as hysteretomy 44 and holeystetomy. 45 Delayed diagnosis or failure of diagnosis of oelia disease and IBD are ommonly reported and are likely to have signifiant adverse effets for patients, while the onsequenes of failing to detet aner in patients presenting with alarm symptoms are self evident. The researh agenda in these irumstanes probably has less to do with an evidene gap than an implementation gap most of the symptoms and risk fators assoiated with these onditions are fairly well doumented, but it seems that aurate diagnosis is Current important researh questions How an GPs improve the timeliness and auray of diagnosis of gastrointestinal (GI) aner and other serious GI disorders (suh as oelia disease and inflammatory bowel disease)? How an information tehnology best be used in the onsultation to support high quality management of GI disorders? How an the views and experienes of patients and servie users best be inorporated into the development of meaningful outomes for therapeuti trials and health servies researh? How an primary are best ontribute to sreening for oloretal aner and to the are of survivors of oloretal aner and other GI malignanies? Postgrad Med J: first published as /pgmj on 21 Otober Downloaded from on 8 Otober 2018 by guest. Proteted by opyright. 456 Postgrad Med J 2008;84: doi: /pgmj

4 Primary are researh diffiult for many GPs, and it is worth thinking about the reasons for this. One is simply that gastrointestinal problems, although they aount for 1 in 10 patients seen in our surgeries, do not arry the same weight or threat as the more traditional killer onditions suh as stroke, oronary heart disease, diabetes and respiratory disease. As desribed above, the QOF offers a potentially powerful mehanism for utting the implementation orner, by providing natural inentives for the ahievement of targets speified in finanial pratie guidelines, but does not yet inlude targets for gastrointestinal disorders. A national projet urrently underway, funded by the Health Foundation ( gpp/image/) is now attempting to develop quality riteria for the management of GORD, IBS, oelia disease and IBD, based on a synthesis of patients views and urrent best evidene and guidelines, and has the potential to inform future iterations of the QOF. General pratie in the UK does, however, have two very important advantages whih should, potentially, support improved management of GI disorders, and these are the registered patient list and the sophistiation of GP omputer systems. Sreening, surveillane, ase finding, audit and review an all readily be undertaken using omputerised reords and databases, and most omputer systems an readily be adapted to inlude pop up or drop down prompts and templates to enourage appropriate ations and appropriate surveillane of patients with aute and hroni presentations of GI problems. Modern primary are omputer systems are also apable of produing high quality, personalised information for patients about gastrointestinal disorders. CORE, the digestive diseases harity, already produes an exellent range of well produed patient information leaflets whih are available in paper and eletroni format, and these have proven to be of great interest to patients taking part in reent fous group researh on GI topis, at whih they have also expressed a desire to have learer explanation and ideas about prognosis, partiularly in the hroni, funtional GI disorders. In terms of primary researh, evaluation of the role of nondrug interventions in onditions inluding IBS, GORD, nonuler dyspepsia and other funtional bowel disorders is at an early stage in general pratie; more trials are needed to define the plae of the talk therapies, inluding CBT, hypnotherapy and psyhotherapy, either alone or as adjunts to drug therapies, in the management of these onditions, whih an sometimes prove refratory. The opportunity to deliver personalised gut orientated CBT via the internet is an exiting Key learning points General pratie requires a strong evidene base of researh onduted in primary are to delivery high quality are for gastrointestinal (GI) disorders. Over the last 20 years numerous researh studies in primary are have ontributed to the evidene base. These inlude epidemiologial (ross setional and longitudinal) studies, linial trials, evaluations of omplex interventions, seondary analyses of large databases, and qualitative researh. Understanding of natural history and management of many ommon GI disorders suh as dyspepsia, gastro-oesophageal reflux disease, irritable bowel syndrome, Heliobater pylori infetion, inflammatory bowel disease, and GI aners has inreased onsiderably as a result of this researh. Contat information British Soiety of Gastroenterology: Primary Care Soiety for Gastroenterology: org.uk/ European Soiety for Primary Care Gastroenterology: CORE, the Digestive Diseases Charity: oreharity.org.uk/ innovation worthy of areful study. The emerging strutures within the UK Clinial Researh Networks, inluding the loal Primary Care Researh Networks and the supporting Comprehensive Researh Networks, provide a new impetus and infrastruture for the ondut of trials in general pratie, and it will be important to make full use of these new opportunities. Competing interests: The author is founding president of the PCSG and was founding hair of ESPCG. REFERENCES 1. Jones R, Stevens R. Management of ommon gastrointestinal disorders in general pratie: PCSG National Survey Seifert B, Rubin G, de Wit N, et al. The management of ommon gastrointestinal disorders in general pratie: a survey by the European Soiety for Primary Care Gastroenterology (ESPCG) in six European ountries. Dig Liv Dis 2008;40: Rosen R, Stevens R, Jones R. General pratitioners with speial linial interests. BMJ 2003;327: Finh R. When is a polylini not a polylini? BMJ 2008;336: Majeed A, Lester H, Bindman A. Improving the quality of are with performane indiators. BMJ 2007;335: Moayyedi P, Soo S, Deeks J, et al. Systemati review and eonomi evaluation of Heliobater pylori eradiation treatment for non-uler dyspepsia. Dyspepsia Review Group. BMJ 2000;321: Moayyedi P, Soo S, Deeks J, et al. Pharmaologial interventions for non-uler dyspepsia. Cohrane Database of Systemati Reviews (4): CD001960, Jones RH, Lydeard S. Prevalene of symptoms of dyspepsia in the ommunity. BMJ 1989;298: Jones RH, Lydeard S, Hobbs FDR, et al. Dyspepsia in England and Sotland. Gut 1990;31: Jones RH, Lydeard S. Irritable bowel syndrome in the general population. BMJ 1992;304: Crosland A, Jones R. Retal bleeding: prevalene and onsultation behaviour. BMJ 1995;311: Hin H, Bird G, Fisher P, et al. Coelia disease in primary are: ase finding study. BMJ 1999;318: Rubin GP, Hungin AP, Kelly PJ, et al. Inflammatory bowel disease: epidemiology and management in an English general pratie population. Aliment Pharmaol Ther 2000;14: Rubin GP, Hungin APS, Chinn DJ, et al. Quality of life in patients with established inflammatory bowel disease: a UK general pratie survey. Aliment Pharmaol Ther 2004;19: Fry J. Common diseases. Lanaster: MTP Press, Jones RH, Lydeard S. Dyspepsia in the ommunity: a follow-up study. Br J Clin Prat 1992;46: Agreus L, Svardsudd K, Nyren O, et al. Irritable bowel syndrome and dyspepsia in the general population: overlap and lak of stability over time. Gastroenterology 1995;109: Muris JW, Starmans R, Fijten GH, et al. One-year prognosis of abdominal omplaints in general pratie: a prospetive study of patients in whom no organi ause is found. Br J Gen Prat 1996;46: Wallander MA, Johansson S, Ruigomez A, et al. Dyspepsia in general pratie: inidene, risk fators, omorbidity and mortality. Fam Prat 2007b;24: Jones R, Latinovi R, Charlton J, et al. Physial and psyhologial o-morbidity in irritable bowel syndrome: a mathed ohort study using the General Pratie Researh Database. Aliment Pharmaol Ther 2006;24: Ruigomez A, Garia Rodriguez LA, Wallander MA, et al. Gastroesophageal reflux disease and asthma: a longitudinal study in UK general pratie. Chest 2005;128: Lydeard S, Jones RH. Fators affeting the deision to onsult with dyspepsia: omparison of onsulters and non-onsulters. J R Coll Gen Prat 1989;39: Kettell J, Jones RH, Lydeard S. Reasons for onsultation in irritable bowel syndrome: symptoms and patient harateristis. Br J Gen Prat 1992;42: Postgrad Med J: first published as /pgmj on 21 Otober Downloaded from on 8 Otober 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

5 Primary are researh 24. Koloski NA, Boye PM, Talley NJ. Is health are seeking for irritable bowel syndrome and funtional dyspepsia a soially learned response to illness? Dig Dis Si 2005;50: Koloski NA, Boye PM, Talley NJ. Somatization an independent psyhosoial risk fator for irritable bowel syndrome but not dyspepsia: a population-based study. Eur J Gastroenterol Hepatol 2006;18: Hungin AP, Rubin GP, O Flanagan H. Long-term presribing of proton pump inhibitors in general pratie. Br J Gen Prat 1999;49: Raghunath AS, Hungin APS, Cornford CS, et al. Use of proton pump inhibitors: an exploration of the attitudes, knowledge and pereptions of general pratitioners. Digestion 2005;72: Armstrong D, Reyburn H, Jones R. A study of general pratitioners reasons for hanging their presribing behaviour. BMJ 1996;312: Shaw MJ, Talley NJ, Beebe TJ, et al. Initial validation of a diagnosti questionnaire for gastroesophageal reflux disease. Am J Gastroenterol 2001;96: Jones R, Coyne K, Wiklund I. The gastro-oesophageal reflux disease impat sale a patient management tool for primary are. Aliment Pharmaol Ther 2007;25: Longstreth GF, Thompson WG, Chey WD, et al. Funtional bowel disorders. Gastroenterology 2006;130: Jones RH. Upper gastrointestinal endosopy a view from general pratie. J R Coll Gen Prat 1986;36: Bytzer P, Hansen JM, Shaffalitzky de Mukadell OB. Empirial H2-bloker therapy or prompt endosopy in management of dyspepsia. Lanet 1994;343: Lassen AT, Pedersen FM, Bytzer P, et al. Heliobater pylori test-and-eradiate versus prompt endosopy for management. Lanet 2000;356: Jones R, Latinovi R, Charlton J, et al. Alarm symptoms in the early diagnosis of aner in primary are. BMJ 2007;334: Johansson T, Petersen H, Kristensen P, et al. Cimetidine on-demand in dyspepsia. Experiene with randomized ontrolled single-subjet trials. San J Gastroenterol 1992;27: Jones RH, Baxter G. Lansoprazole 30 mg daily versus ranitidine 150 mg bd in the treatment of aid-related dyspepsia in general pratie. Aliment Pharmaol Ther 1997;11: Jones R, Crouh SL. Low-dose lansoprazole provides greater relief of heartburn and epigastri pain than low-dose omeprazole in patients with aid-related dyspepsia. Aliment Pharmaol Ther 1999;13: Hungin AP, Rubin G, O Flanagan H. Fators influening ompliane in long-term proton pump inhibitor therapy in general pratie. Br J Gen Prat 1999;49: Jones RH, Holtmann G, Rodrigo L, et al. Alosetron relieves pain and improves bowel funtion ompared with mebeverine in female nononstipated irritable bowel syndrome patients. Aliment Pharmaol Ther 1999;13: Kennedy T, Jones R, Darnley S, et al. Cognitive behaviour therapy in addition to antispasmodi treatment for irritable bowel syndrome in primary are: randomized ontrolled trial. BMJ 2005;331: MCrone P, Knapp M, Kennedy T, et al. Cost-effetiveness of ognitive behaviour therapy in addition to mebeverine for irritable bowel syndrome. Eur J Gastroenterol Hepatol 2008;20: British Soiety of Gastroenterology. Guidelines on the irritable bowel syndrome: mehanisms and pratial management. May Kennedy TM, Jones RH. The epidemiology of hysteretomy and irritable bowel syndrome in a UK population. Int J Clin Prat 2000;54: Kennedy TM, Jones RH. Epidemiology of holeystetomy and irritable bowel syndrome in a UK population. Br J Surgery 2000;12: Take advantage of BMJ Journals remarkable atalogue of titles with Related Colletions No busy professional has time to browse through all pertinent journals to find relevant artiles, but with Related Colletions you no longer have to. Follow the Related Colletions link from any artile and use the Show Colletions from other Journals to expand your searh aross all BMJ Journals. Or simply follow the Browse by topi link on the home page. By setting up your own olletions and reeiving alerts every time an artile is added to your hosen area, you an build up your own signifiant body of knowledge. Postgrad Med J: first published as /pgmj on 21 Otober Downloaded from on 8 Otober 2018 by guest. Proteted by opyright. 458 Postgrad Med J 2008;84: doi: /pgmj

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