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Rapid Responses: Rapid Responses published:
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H.pylori-induced disorders can be evaluated at bed-side by means of Biophysical Semeiotics
- Sergio Stagnaro (18 April 2001)
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Endoscopy in dyspeptic patients under the age of fitty-five
- Luis Bujanda, I Uriarte, C Munoz, A Sanchez (20 April 2001)
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Diagnosis is the key in dyspepsia
- Val Heatley (27 April 2001)
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Author's reply
- Brendan C Delaney (2 May 2001)
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Test and treat not test and scope
- M J Lancaster Smith (2 May 2001)
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There is no scope for H.pylori testing!
- Abhinav Kant (11 May 2001)
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New strategies of the management of dyspepsia should be based on local data
- Helgi Kolk, Heidi-Ingrid Maaroos (27 May 2001)
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Threats to validity
- Johannes C van der Wouden (2 June 2001)
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Sergio Stagnaro, Specialist in Blood, Metabolic and Gastrointestinal Disease
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Sirs, I agree completely with Delaney's conclusions. My belief is, indeed, the result of 45 years of clinical experience with the aid of a new physical semeiotics, cited often also in BMJ.com. See: http://digilander.iol.it/semeioticabiofisica. As a matter of fact, H pylori is notoriously a Gram-neg. bacterium, which can induce antritis, for instance, without stimulating antibody synthesis in the spleen, but activating exclusively the Reticulo-Endothelial System of bone marrows as well as MALT and BALT function. Biophysical Semeitics allows doctor to recognize promptly and easily this particular immunological defence activation, I named Reticulo Endothelial System Hyperfunction Syndrome, "intermediate" type.See: my site,e.g. Appendicitis. In conclusion, a long well established experience allows me to state that H pylori is more often - I say usually - an "innocent bystander", which can sometimes become dangerous, bringing about the above-mentioned biophysical semeiotic syndrome. I hope that the current "fashion" about the role played by this "almighty" Gram-neg. agent in the aetiopathogenesis of human disorders(gastritis B, tumour, arteriosclerosis a.s.o.) will be at its end as soon as possible, in the interest of the NHS and human reason. Yours. Stagnaro Sergio MD. Riva Trigoso (Genoa) Italy. Member NYAS and AAAS |
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Luis Bujanda Department of Gastroenterology. San Eloy Hospital. Baracaldo. Spain, I Uriarte, C Munoz, A Sanchez
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EDITOR- Delaney et al suggest that the “test and endoscopy” strategy increases endoscopy rates over usual practice in primary care in patients with dyspeptic syndrome (DS) under 50 years old. The additional cost is not offset by benefits in symptom relief or quuality of life.1 We are of the opinion that the approach will also depend on the financial cost of endoscopy, the presence or absence of warning signs and on whether the dyspepsia is seen by the gastroenterologist or by the primary care physician. We studied 289 patients referred for specialized digestive evaluation from the primary care with dyspeptic syndrome under the age of 55 years. The mean patient age was 33 years. A proportion of these patients returns for consultation (57%) and in many such cases (45%) endoscopy is requested in view of the persistence of symptoms. Gastroduodenal pathology was identified in half of the cases where endoscopy was performed. The presence of pathology bore no relation to the type of dyspeptic syndrome involved. In our series, gastric cancer was detected in one patient (aged 48 years), while one other (aged 54) had a gastric ulcer with cell atypia. Four percent of the patients with DS between the ages of 46 and 55 years developed malignant or potentially malignant lesions at some time in the course of the disease. In our opinion, this observation alone suffices to advise an initial endoscopy study in patients in this particular age range and who have been referred to the gastroenterologist from the primary care setting for assessment of DS. Similar observations to ours have been made by Bytzer et al.9 in patients with DS who sought medical help in the non-specialized primary care setting (i.e., general practitioners).2 Many patients (66%) empirically treated with H2 blockers were subsequently subjected to endoscopy at one year of follow-up, and gastroduodenal pathology was detected in many of them (32%).2 Despite the inconveniences posed by specialized physician requests for endoscopy in all patients with DS, the approach nevertheless does afford some advantages. In effect, endoscopy makes it possible to detect and treat lesions that otherwise would be difficult to diagnose (e.g., esophagitis in a patient with mixed-type DS); in addition, it avoids inappropriate treatments and reduces patient and physician anxiety.3 No cost analysis was made of the different patient strategies. However, earlier studies involving pathology rates and endoscopy costs similar to our own have reported improved cost-benefit results with the initial diagnosis approach versus empirical treatment.3,4 The impact of HP in our series was not evaluated. However the incidence of HP infection in patients with DS is similar to that observed in healthy subjects of the same age (well below 32 years); furthermore, no specific symptom is associated to HP infection, no cause-effect relationship has been established between the presence of HP and dyspeptic symptoms, and eradicating treatment in these patients affords variable and apparently limited duration results.5 On the other hand, based on the results of serology or breath testing for HP, we cannot predict the presence of a certain type of gastroduodenal pathology such as esophagitis or Barrett's esophagus, and it cannot be defined whether an indiscriminate eradicating approach would increase the risk of gastroesophageal reflux disease, gastric cancer, adenocarcinoma of the cardioesophageal junction, or HP resistance. 1. Delaney BC, Wilson S, Roalfe A, Roberts L, Redman V, Wearn A, Hobbs FDR. Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primare care. BMJ 2001; 322:898-901. 2. Bytzer P, Hansen J. Empirical H2-blocker therapy or prompt endoscopy in the management of dyspepsia. Lancet 1994; 343:811-6. 3. Fendrick AM, Chernow ME, Bloom BS. Alternative management strategies for patients with suspected peptic ulcer disease. Ann Intern Med 1995; 123:260-268 4.Barenys de Lacha M. Coste-efectividad de la erradicación de Helicobacter pylori en la dispepsia. Gastroenterol Hepatol 1999; 22:364-75. 5. Talley NJ, Vakil N, Ballard ED, Fennerty MB. Absence of benefit of eradicating Helicobacter pylori in patients with nonulcer dyspepsia. N Engl J Med 1999; 341:1106-11. |
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Val Heatley, Consultant Gastroenterologist St.James's Univ. Hospital, Leeds UK
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Sir, re: H.pylori "testing and endoscopy" for dyspepsia in primary care The recent publication by Delaney et al. (1) on the above surely misses the point of medical consultations for dyspepsia. Most of us would view the purpose of a consultation as primarily to make a diagnosis before initiating treatment. If, as these authors appear to advocate, the purpose is to initiate "empirical prescribing" since they concluded that this "is therefore the best treatment", then these patients might as well take themselves to a pharmacist and self-medicate. This study is seriously flawed. Firstly, it uses a screening test for H.pylori (Helisal) which has been reported to have sensitivities of only 67 - 88%, with specificity of 78 - 91% (2,3). It is therefore not a very accurate means of detecting H.pylori and presumably explains why so many ulcers appeared in the control H.pylori-negative group (4 out of 48 endoscopies carried out). Secondly, conclusions have been drawn on symptomatic follow-up and quality of life data that was only recorded on just over half of the patients studied. Costs were greater in the study group, who all had endoscopy (we are not told whether these are significantly higher) but certainly some of this was caused by the cost of H.pylori testing which, for some reason, was significantly higher (p<0.0001) in the study group. As the authors themselves acknowledge, endoscopic investigation revealed a significantly greater number of peptic ulcers. Presumably the patients themselves would be interested in knowing this diagnosis, since subsequent successful H.pylori eradication treatment should produce cure of their ulcers rather than having to continue needlessly with "empirical" acid suppressant treatment long-term. The National Institute for Clinical Excellence (NICE) in their recent "Guidance on the use of proton pump inhibitors in the treatment of dyspepsia" (4) concluded that patients diagnosed with non-ulcer dyspepsia (NUD), which Delaney et al. accept are the majority of their patients, "may have symptoms caused by different aetiologies and should not be routinely treated with PPI's". Time has marched on and rather left these authors behind. We have shown that adding serum recognition of the CagA protein and serum pepsinogen I levels to simple but reliable H.pylori serology, further refines diagnostic accuracy and could potentially reduce endoscopy workload for dyspeptic patients by about one half (5). Improved diagnostic accuracy, with specifically tailored treatment, is what dyspeptic patients need, not further encouragement to take "empirical treatment" lifelong without any clear idea of why, apart from amelioration of symptoms. Val Heatley
References 1) BC Delaney, S Wilson, A Roalfe, L Roberts, V Redman, A Wearn, FDR Hobbs Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care. BMJ 2001, 322, 898-901 2) A Duggan, R Logan, A Knifton, R Logan Accuracy of near-patient blood tests for Helicobacter pylori. Lancet 1996, 348, 617 (letter) 3) P Moayyedi, AM Carter, A Catto, RM Heppell, PF Grant, ATR Axon Validation of a rapid whole blood test for diagnosing Helicobacter pylori infection. BMJ 1997, 314, 119 4) National Institute for Clinical Excellence (NICE) Guidance on the Use of Proton Pump Inhibitors in the Treatment of Dyspepsia. NHS, July 2000 5) K Bodger, JI Wyatt, RV Heatley Serologic screening before endosocpy : the value of Helicobacter pylori serology, serum recognition of the CagA and VacA proteins, and serum pepsinogen I. Scandinavian Journal of Gastroenterology 1999, 34(9), 856-863 |
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Brendan C Delaney, Senior Lecturer in Primary Care The University of Birmingham
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Editor, Heatley criticises our recent paper reporting the results of a primary care-based RCT of H.pylori 'test and endoscopy' v. usual management, [1] on the basis that it is 'seriously flawed' and 'misses the point'. Whilst acknowledging that comparators, test performance and patient response rates may all affect study results, we seek to differ from Heatley's conclusions. Whilst medical students are taught to diagnose before initiating treatment, diagnosis is not an end in itself, but a means of selecting appropriate therapy for an individual patient. In primary care many patients consult with milder and less advanced disease than those seen in hospital practice. The question about 'appropriateness' of investigation is a component of many primary care consultations. The comparator chosen in this study was not 'empirical prescribing' ad infinitum as Heatley suggests, but GP's 'usual care' consisting of empirical prescribing, referral, and follow up as judged appropriate by the patients GP. In fact 25% of the control group were endoscoped during the year of follow up. Heatley seems to suggest that all patients presenting to their GP, at all ages, with dyspepsia should be endoscoped at whatever opportunity cost to the NHS? Given that symptom patterns and H.pylori tests do not predict diagnosis, [2] initial empirical prescribing is appropriate for many patients. [3] The Helisal test was locally validated, with a sensitivity of 89% and a specificity of 84%. More accurate tests would reduce the false positive rate, but even if the H.pylori status were known with 100% accuracy, more than half of the additional endoscopy referrals would still have been made. The point is that referral threshold changed by implementing the 'test and endoscope' strategy, and only a primary care trial could have detected this. Although only 61% of patients returned symptom and QoL questionnaires, we had resource use data on 99%, and the result was stable to adjustment for differences in baseline characteristics of non- responders. Costs were significantly higher P=0.0044, due mainly to the cost of the additional 20% of patients endoscoped, as the cost of endoscopy is £246 compared with £12 for an H.pylori test. In any health care system, the balance of expenditure is to a large part determined by the decisions over treatment and investigation made by individual clinicians. Some treatments produce more health gain, and some approaches to management employ more parsimonious use of resources than others. Although we did detect more peptic ulcers, it is not this, but symptom resolution that matters. If more upper GI endoscopies were to be performed in young patients, waiting lists would rise and older patients with serious disease would wait longer for diagnosis. As non-ulcer dyspepsia responds to H.pylori eradication with symptom resolution in one in 15 patients treated, [4] H.pylori 'test and eradicate' has been proposed as a cost-effective management strategy. We have recently received funding from the Medical Research Council to conduct the CUBE trial, an RCT of 'test and eradicate' using a breath test v. 4 weeks PPI for the initial management of dyspepsia. Time does indeed move on, and RCTs do take time, six years from inception to publication in this case. That does not detract from the simple fact that the formulation of guidelines for primary care by extrapolating limited data from selective, non-generalisable secondary care populations produce policies that do not stand up to scrutiny in an RCT. Initial empirical therapy for symptomatic presentations where the risk of serious disease, at presentation at least, is low, remains an essential component of 'gate-keeping' primary care. Without such pragmatic problem solving, the proportion of the NHS expenditure that is consumed by primary care delivering on the over 90% of all the NHS patient contacts would quickly rise considerably above the current 6.5% level. Reliable data fortunately supports common sense in suggesting we do not need to explore yet the consequences of such diagnostic reductionism. 1. Delaney BC, Wilson S, Roalfe A, Roberts L, Redman V, Wearn AM, and Hobbs FDR. Cost-Effectiveness of Helicobacter Pylori Point of Care Testing and Endoscopy if Positive for Initial Management of Dyspepsia in Patients Under 50 Years of Age: Results of a Primary Care-Based Randomised Controlled Trial. BMJ 322, 898-901. 2001. 2. Hansen JM, Bytzer P, deMuckadell OBS. Management of dyspeptic patients in primary care - Value of the unaided clinical diagnosis and of dyspepsia subgrouping. Scand J Gastroenterol 1998;33:799-805 3. National Institute for Clinical Excellence. Guidance on the use of Proton Pump Inhibitors in the treatment of dyspepsia from NICE. July 2000. http://www.nice.org.uk/nice-web/pdf/proton.pdf (accessed 19 March 2001). 4. Moayyedi P, Soo S, Deeks J, Innes MA, Forman D, and Delaney BC. A Systematic Review and Economic Analysis of the Cost-Effectiveness of H Pylori Eradication Therapy in Non-Ulcer Dyspepsia (NUD). BMJ 2000;321:659 -664. Brendan C Delaney MD FRCP MRCGP, Senior Lecturer Sue Wilson PhD MFPHM, Senior Research Fellow Andrea Roalfe MSc, Medical statistician Lesley Roberts BSc, Research Fellow Andrew Wearn MMedSci MRCGP, Lecturer FD Richard Hobbs FRCP FRCGP, Professor of Primary Care and General Practice Department of Primary Care and General Practice The University of Birmingham Medical School Edgbaston Birmingham B15 2TT UK |
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M J Lancaster Smith, Consultant Gastroenterologist Queen Mary's Sidcup NHS Trust
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EDITOR – Delaney at al have shown that near patient testing for H. pylori followed by open access endoscopy for patients with positive results increases endoscopy demand and is not cost-effective1. By contrast trials of “test and treat” strategies without endoscopy in young patients2-4 indicate that this policy has the potential to be cost- effective in the clinical setting. A recent survey of practice in my own department tends to support this proposition. In 1997 as part of locally based dyspepsia management guidelines a “test and treat” policy for dyspeptics under 45 years of age without alarm symptoms was introduced in the community referring patients to the open access endoscopy service at Queen Mary’s Hospital, Sidcup. Only those young patients who remained dyspeptic following treatment appropriate to their H. pylori status and predominant symptoms, were accepted for endoscopy. A comparison of open access referrals from the community before and after the introduction of the guidelines showed that in the 3 years post “test and treat” there was a 4.3% decrease in the referral of young patients but a 21% increase in those over 45. Had the young patient referral rate kept pace with that of older patients it would have increased the open access waiting list by a further 9 weeks over this 3 year period. The policy seems not to have devalued the procedure in this group of young patients, because prior to “test and treat” 54% of young dyspeptics had a normal endoscopy compared to 42% after its implementation; the reduction being almost entirely due to an increase in the diagnosis of oesophagitis. This survey therefore suggests that in contrast to “test and endoscope”, “test and treat” when applied in routine primary care, can reduce endoscopy demand and may therefore be more cost-effective than early endoscopy based strategies. M. J. Lancaster Smith 1. Delaney B.C., Wilson S., Roalfe A., Roberts L., Redman V., Wearn et al. Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care. BMJ 2001; 322: 898-901 (14th April). 2. Heaney A., Collins J.S.A., Watson P.R.G., McFarland J.R., Bamford K.B., Tham T.C.K. A prospective randomised trial of a “test and treat” policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcer-like dyspepsia referred to a hospital clinic. Gut 1999; 45: 186-90. 3. Jones R., Tait C., Sladen G., Weston-Baker J. A trial of a test and treat clarity strategy for Helicobacter pylori positive dyspeptic patients in general practice. Ins. J. Clin. Pract. 1999; 53: 413-16. 4. Lassen A.T., Pedersen F.M., Bytzer P., Schaffalitzky de Muckadell O.B. Helicobacter pylori test-and-eradicate versus prompt endoscopy for management of dyspeptic patients: a randomised trial. Lancet 2000; 356: 455-60. |
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Abhinav Kant, medical student University of Newcastle upon Tyne
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Editor, Delaney et al discovered that H.pylori testing and endoscopy was not a cost-effective strategy in the management of dyspepsia in primary care in 18-49 year olds. Neither did it improve dyspeptic symptoms nor quality of life compared with usual management.(1) We would like to raise three additional points, which may be of interest to the authors and are appropriate for consideration in future studies. Firstly, the study does not appear to have recognised the possible use of supplementary "over the counter" medications. This will undoubtedly affect the severity of the symptoms experienced and will increase the total cost of treatment. We feel that the poor response rate (57%), coupled with the subjective nature of the questionnaire, makes it difficult to assess the impact on the quality of life for all the subjects in the study. We suggest the use of a more subjective measure in the future, although this may be a more expensive approach and difficult to avoid observer bias. The study produced valuable information to guide management of dyspepsia in patients under 50. Perhaps studies in the future should include the over 50s. However, we agree that further studies into the cost-effectiveness of an H.pylori test and eradication strategy compared to empirical prescribing is indicated. Abhinav Kant
3rd year medical students,
All correspondence to abhinav.kant@ncl.ac.uk 1. Delaney BC, Wilson S, Roalfe A, Roberts L, Redman V, Wearn A, Hobbs FDR. Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care. BMJ 2001; 322:898-901. |
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Helgi Kolk Dept. of Family Medicine, University of Tartu, Estonia, Heidi-Ingrid Maaroos
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Dear Sirs, The authors concluded that the test and endoscopy strategy increased endoscopy rates above those seen in usual practice, as well as the costs per patient among subjects under the age of 50 years. At the same time symptoms and quality of life were similar in both groups: traditional management group and test and endoscopy group. Therefore, the latter strategy can not be recommended for primary care. We agree that not all patients with dyspeptic symptoms, especially young females, do need investigation at their first presentation of dyspepsia. Recognising that Helicobacter pylori infection is widespread and represents an important cause of gastrointestinal morbidity, our study shows that other criteria rather than H. pylori seropositivity should be taken into consideration for referral. Our study was carried out in Estonia, where previous seroepidemiological studies have shown 85% prevalence of H. pylori infection among general population (1). The situation is similar in other Eastern European countries (2). We investigated unselected dyspeptic outpatients referred for upper gastrointestinal endoscopies by their family physicians. Persons who had used antibiotics, non-steroidal anti-inflammatory drugs, bismuth compounds or proton pump inhibitors four weeks prior to endoscopy were excluded. H. pylori status was determined by histological and bacteriological methods. Our results show that among 140 investigated patients in age group of younger than 45 years more than 30% of patients (predominantly males) had duodenal ulcer. In one patient gastric cancer was diagnosed. Similar results were obtained in a joint Estonian-Finnish study on the epidemiology of acute upper gastrointestinal haemorrhage (UGIH) (3). The overall incidence of UGIH as well as the incidence rate in younger age groups were considerably lower in Finland compared with Estonia. Furthermore, the incidence of gastric cancer is higher in Estonia than in the Western countries (4). Despite the 36% decrease in the incidence and 42% decrease in the mortality of gastric cancer from 1968 to 1992, Estonia ranked sixth among 67 European populations with respect to incidence of gastric cancer (incidence rates 42.3 for males and 20.6 for females). The incidence of gastric cancer higher than 10.0 for either gender was observed already in the age group 35-40 years and it increased with age. When selecting patients for upper endoscopy, non-invasive tests should be performed with care, especially when commercial serological kits are used, as high infection prevalence renders negative tests unreliable. New serological tests like detection of CagA can improve test accuracy (See also the electronic response of Dr. Val Heatley). Whether the costs of new tests are attractive or not, is yet unknown. At present, carbon urea breath test, which provides the highest sensitivity (96-100%) and specificity (86-100%), is more expensive than endoscopy in Eastern Europe. At the same time, it is not widespread even in the Western countries (5). We conclude that the guidelines for the management of dyspepsia and H. pylori infection meet the needs of family physicians in case they are based on local data. 1. Maaroos HI. Helicobacter pylori infection in Estonian population: is it a health problem? Ann Med 1995;27:613-616. 2. Matysiak-Budnik T, Megraud F. Helicobacter pylori in eastern European countries: what is the current status? Gut 1994; 35:1683-1686. 3. Soplepmann J, Udd M, Peetsalu A, Palmu A. Acute upper gastrointestinal haemorrhage in central Finland province, and in Tartu county, Estonia. Ann Chir Gynaecol 1997;86:222-228 4. Thomson H, Rahu M, Aareleid T, Gornoi K. Cancer Incidence in Estonia 1968-1992, Tallinn, Institute of Experimental and Clinical Medicine, 1996. 5. de Wit NJ, Mendive J, Seifert B, Cardin F, Rubin G. Guidelines on the management of H. pylori in primary care: development of an implementation strategy. Fam Pract 2000;17: S27-S32. |
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Johannes C van der Wouden, senior lecturer Dept of General Practice, Erasmus University, Rotterdam, NL
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Editor, The study by Delaney and coauthors (1) is a fine example of research in general practice. However, there are a number of threats to internal and external validity that need attention.
First, it is not clear whether the general practitioners ‘usual management’ may have changed during the trial because of contamination by the protocol for the group that received intervention treatment. There is a chance that the difference in outcome between both groups would have been larger if the two treatments had been delivered by different groups of general practitioners. Second, though the study was inevitably not blinded, patients may have preferred one of the study arms. Informed as they were, their attitude may have differed from the situation when the general practitioner would have mentioned only one treatment option. Third, in their excellent paper on patient recruitment for this study (2), the authors show that during the first months of recruitment they probably recruited predominantly prevalent cases of dyspepsia, whereas later on the focus changed to incident cases. It would be interesting to test this hypothesis, by looking at the duration of complaints before inclusion, and if this is confirmed, to analyse whether this shows a relation with study outcome. 1. Delaney BC, Wilson S, Roalfe A, Roberts L, Redman V, Wearn A, Hobbs FDR. Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care. BMJ 2001; 322: 898-901. 2. Wilson S, Delaney BC, Roalfe A, Roberts L, Redman V, Wearn AM, Hobbs FDR. Randomised controlled trials in primary care. BMJ 2000; 321: 24-7. |
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