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Rapid Responses: Rapid Responses published:
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Misuse of proton pump inhibitors
- Mario Guslandi (4 January 2008)
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BNF says PPIs are not that expensive.
- John Leigh (4 January 2008)
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PPIs in general practice
- Lewis Miller (4 January 2008)
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Have the eauthors read the NICE guidelines?
- Graham Wheatley (5 January 2008)
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Alternative Therapy - Is Milk Intolerance to Blame
- Hugh Barnard MBA BSc(Hons) FCIOB (5 January 2008)
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PPI Problem recognised 5+ years ago!
- A. Breck McKay, Prof Daryl Wall (5 January 2008)
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Re: PPIs in general practice
- Raymond C Seidler (5 January 2008)
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Old news.
- Steven Ford (5 January 2008)
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Local Auditing and Guidelines Needed for the Appropriate Management of Dyspepsia
- Saurabh Upadhyay (5 January 2008)
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Prophylactic PPIs for Dual Antiplatelet Therapy
- Daniel A Jones (6 January 2008)
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A hospital "antacid policy" to combat clostridium difficile infection is timely
- Jecko Thachil (6 January 2008)
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Needs Looked at..
- GRAEME MACKENZIE (7 January 2008)
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Inappropriate proton pump inhibitor usage- a timely reminder
- shaji sebastian, HU3 2JZ (7 January 2008)
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Appropiate use of PPIs
- John Leigh (7 January 2008)
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Overprescribing PPI's-they are a cheaper option
- Ian R Sykes (7 January 2008)
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Small Price to pay
- Jessy Saini (8 January 2008)
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PPIs
- Milind M Deshpande, Poornima Deshpande (8 January 2008)
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Missing the point still?!!
- Dr A. Breck McKay (9 January 2008)
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Overprescribing proton pump inhibitors
- Alun L Cooper (10 January 2008)
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£100 million pounds is not the only cost of PPI overuse
- Richard Cunningham (11 January 2008)
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Indigestion?
- John C Welch (14 January 2008)
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Use of PPI in patients on aspirin therapy
- H. Mei-Ling Ball (17 January 2008)
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misoprostol could be safer for prophylaxis against aspirin-related ulcers
- oscar,m jolobe (19 January 2008)
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Incredibly wrong, biased, and why?
- Andrew C Barnes (20 January 2008)
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Proton pump inhibitors – prescribe with caution
- Asha Srikanth, Viswanath V Kaushik, Consultant Rheumatologist (31 January 2008)
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PPI on PPI
- John G Gooderham (7 February 2008)
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Mario Guslandi, Head, Clinical Hepato-Gastroenterology Unit Division of Gastroenterology, S.Raffaele University Hospital. 20100 Milan, Italy
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Your Editorial on overprescribing proton pump inhibitors (PPIs) effectively describes a situation which appears to be similar in every country. In Italy the misuse of PPIs is equally common, leading the local Health Authorities to exert pressure on GPs in order to limit excessive and/or inappropriate prescribing of those drugs. This is a matter of debate because such measures seem to interfere with the physicians' prerogative of prescribing according to their conscience and experience, but economy is tight and resources are limited. In addition to the exhaustive review by Forgacs & Loganayagam about the misuse of PPIs in treating dyspepsia, I would like to point out another inappropriate, widespread employ, namely their presciption as "gastroprotective" agents for the occasional intake of a non-steroidal anti-inflammatory agent (NSAID) for a day or two - prescribing in patients at risk and on long-term NSAID intake is another matter entirely- and for patients on corticosteroids. The adverse effects of steroids on the gastroduodenal mucosa have been overemphasized in the past (1) and there is no evidence whatsoever that PPIs can effectly prevent the risk (if any) of developing an ulcer during steroid therapy. 1. Guslandi M, Tittobello A.Steroid ulcers: a myth revisited. BMJ 1992; 304: 655-6 Competing interests: None declared |
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John Leigh, GP Washington
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Alginates and antacids are frequently more expensive than PPIs. These prices are taken from the latest BNF, with ranitidine for comparison: Lansoprazole 15 mg x30 = £2.59
So in many cases it is therefore CHEAPER for the doctor to prescribe a generic PPI than it is to prescribe an antacid. Furthermore, patients find PPIs easier to take and carry around, and they often are more effective. Looked at in this light, the decision by many primary care physicians to prescribe PPIs for what can be debilitating symptoms seems to make sense. Competing interests: None declared |
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Lewis Miller, GP Principal Woodstock Medical Centre
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I plead guilty to over prescribing PPI drugs. Why do I do this? Because patients want me to, stupid! These drugs are very safe and effective and many of the adverse effects described are common to all effective acid supressant medication. The main reason why Bodies such as NICE advise other treatments for dyspepsia is because of cost. Patients get used to the effect of PPIs on their symptoms and dont want to change. I agree with them. Who would want a black & white TV if they could get colour? Patients collectively pay for the NHS and I dont see why they shouldnt get what they want, within reason of course. The NHS should negotiate a better deal with the drug firms instead of slagging off doctors who prescribe these drugs. There are currently 4 pharmaceutical firms selling PPI drugs in the UK so this should be very possible. Go to it. Competing interests: None declared |
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Graham Wheatley, GP principal Munro Medical Centre, West Elloe Avenue, Spalding PE11 2BY
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I was interested in the authors' statement that the NICE quidelines in 2000 recommended "relatively selective use" of PPIs. The most recent NICE guidelines are from 2005 and, perhaps not surprisingly in view of their effectiveness, inexpensiveness and relative freedom from side effects, recommends PPIs extensively as the first-line drug threatment when lifestyle changes are ineffective. Nowhere are H2RA's recommended to be used first on the grounds of reduced cost, possibily as the cost saving (about £2 per mont of treatment) is small compared to the PPI's advantages. In other words NICE appear to have taken the view are literally "cost-effective". Instead of asking "How can we get doctors to follow guidelines?", perhaps we should be asking "How can we get commentators to read the guidelines they erroniously criticise others for not following?" The authors article has already been picked up by The Independent newspaper, whose interpretation is: "doctors hand out powerful indigestion medicines to anyone who wants them". I'm sure the authors would agree is far from demonstrated by their article, but is the consequence of publishing overheated and ill-informed criticism. Competing interests: None declared |
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Hugh Barnard MBA BSc(Hons) FCIOB, Builder & Developer Goodall Barnard Ltd, Sherborne St John, Basingstoke, RG24 9HJ
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Perhaps some NHS costs could be saved by considering this as a cause. For fifty years I suffered very painful acidosis and gastric reflux and was twice treated a few years ago for heliobacter pylori, which seemed to make no significant difference. Later, on my brother's advice I ceased taking liquid milk to reduce excess nasal mucosal production and associated nasal blockage only to find that within a few months my stomach acid problems had disappeared. Substitutes of Bio Yoghurt and some cheeses seem not to cause any acid producing reaction. Competing interests: None declared |
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A. Breck McKay, Family Physician/Researcher Victoria Point Brisbane Australia 4152, Prof Daryl Wall
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Dear Editor, Back in June 2002, based on clinical cases we wrote the following letter to many journals, only to be 'ignored'. Now PPIs are recommended on a similar basis to prednisones: start high and reduce rapidly and exercise great caution over long periods. It seems that nothing has changed and the problem still exists! As we stated in June 2002: "We have become increasingly concerned about the long term side effects being identified in General Practice/Surgery patients, with the current extensive, long term use of the proton pump inhibitors (PPIs). We now share an increasing number of patients with dependence on the PPIs, who experience acute, severe gastritis and gastro-oesophageal reflux, if they suddenly stop or miss their PPIs and some are now displaying refractory gastroparesis and severely delayed jejuno-ileal and colonic peristalsis on trying to reduce or stop their PPI medication , when the PPI has been in use for extended periods (>3 to 60 months). Three example patients, all under 46 and very fit, developed reflux and gastritis, and following long term use of PPIs (36-60 months), have all developed refractory-to-cisapride, gastroparesis and delayed total gut dysmotility and bloating, (repeatedly shown by all investigative modalities), and they suffer acute, explosive, exacerbation of their gastritis and reflux, on attempted cessation of the PPIs. All have been offered "corrective surgery" for their conditions, which are now identified as physiologically explainable, side effects of long term PPI use. Since the PPIs block the normal homeostasis of the gastro-jejuno- ileal-colonic function, (due to their very specific, acid production blocking only, cellular-molecular actions*); this allows the multiple secondary interdependent hormonal levels to increase/decrease out of control and thus the parietal cells massively increase their cell surface membrane folds (x7-14), until they appear fan-like on the gastric surface, and thus increases their ability to produce sudden large quantities of acid, when the PPI stops. This results in a Zollinger- Ellison like syndrome and the patients restart their PPIs or even increase the dose, compounding the situation! (Personal communication with two separate Brisbane Gastroenterologists/Researchers has confirmed the visible changes to the stomach lining and the need to slowly reduce the PPI dosage). We have been unable to identify any similar reports in the current medical literature and we were concerned when we found that independent gastroenterologists were aware of the indicated effects, but had not considered them to be a problem. This raises the question of doctors and drug companies failing to remember, understand and appreciate the basic anatomy, physiology and biochemistry of the whole body function and the importance of the homeostatic balance and interdependence of the physical, chemical, hormonal, autonomic (central, midbrain, spinal chord, local ganglia and gut wall levels), and hypothalamic-pituitary-adrenal axis, in the total management of gut syndromes, and raises the question of the need to appreciate the dysautonomias as a new area of medical disease and dysfunction. As medical practitioners we must return to review and apply our basic medical sciences knowledge, to realise the harm that is occurring to our patients from our treatments and we must consider reducing PPI medications by very gradual steps, (as we have to do with the steroids); and question the drive by pharmaceutical companies pursuit of ever better dollar producing drugs, (via funding of research) that do more harm, parallel to their good; to the total human, when such basic homeostatic systems are forgotten or ignored. * ( The PPIs only block the cellular/molecular acid production and allow secondary build up or excessive reduction of the hormones gastrin, cholecystokinin, secretin, glucagon, motilin, VIP, substance P, somatostatin and other biologically active polypetides, which changes all the homeostasis processes of the whole gastro-intestinal system). Dr A Breck McKay, Family Physician P.O. Box 144, Carina, Qld 4152 Ph 61 417 592 332 Professor Daryl Wall Director of Surgery Princess Alexandra Hospital Ipswich Road BRISBANE Competing interests: None declared |
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Raymond C Seidler, general practitioner in Kings Cross New South Wales Australia
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Perhaps it would be salutary to consider how rare it is now to see patients with perforated ulcers or even serious gastric or duodenal ulceration. These were commonplace in my early days of general practice 25 years ago. The proton pump inhibitors as a class are effective and whenever I instigated a withdrawal regime for long-term patients, they returned complaining of a recurrence of their old symptoms, demanding another prescription. Dyspeptics of the world are obviously a large population and have voted to stay on the medication that works. It might be more helpful to find non-pharmaceutical ways of dealing with hyper acidity in such a large proportion of our patient load. Competing interests: None declared |
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Steven Ford, GP Haydon & Allen valleys Medical Practice
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Editor The authors are more than a decade and a half late with this piece and too timid in their scope. BMJ. 1991 February 2; 302(6771): 288. bears a letter from me recommending that not only indigestion remedies but a host of other pharmaceuticals should be available on the NHS only when there is objective evidence of significant disease. Non-life threatening symptoms and disease should always be handled by the NHS by way of assessment and advice but few, especially when definitely, probably or plausibly the consequence of lifestyle choice, should be treated at the tax payers expense. If only I were Emperor all problems would evaporate as the dew in the dawn sun. Steven Ford Competing interests: Untrammelled delusions of grandeur in conjunction with raving narcissism. |
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Saurabh Upadhyay, Foundation doctor Ninewells Hospital and Medical School, Dundee DD1 9SY
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As Forgacs I & Loganayagam A have indicated in their editorial, the overprescribing of PPIs is common practice both in primary as well as secondary care. The extent may be debatable. I believe that the main reasons for this are, a lack of awareness of the NICE guidelines or an awareness but an overprotective attitude of physicians who hence do not follow the guidelines. I believe the reason for this is that most of the PPI prescribing is done by junior doctors in hospitals, albeit, occasionally under the prompting of their seniors. At the time of patient discharge, even if the symptoms have resolved, this medication gets transfered on to the TTO. This may well be due to an oversite of the doctor or the belief that continuation of the PPI will be a good and effective prophylactic measure. GPs continue prescribing the PPI on repeat prescriptions under the assumption that if started in hospital then there must be a good reason for it and that deprivation may be harmful to the patient. I feel that local auditing and providing guidlines on when to prescribe and for what duration, may be the most practical solution. Where symptoms appear to be due to hyperacidity, an antacid or a low dose acid suppresor should be prescribed. Use of the least expensive PPI should help reduce costs. Mild symptoms should initially be managed by lifestyle modifications including weightloss, reduction in alcohol consumption and cessation of smoking. Trainees should then be provided with written information and guidlines on management of dyspepsia at the time of their initial induction on to the ward. In the long run such measures should be cost effective as well. Competing interests: None declared |
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Daniel A Jones, SHO Cardiology Basildon and Thurrock NHS Trust
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The editorial by Forgacs & Loganayagam have indicated the overprescribing of PPIs is common practice both in primary and secondary care, based on NICE quidelines published in 2000. The relatively selective indications stated in these guidelines do not include the use of PPIs as a strategy for GI bleeding prevention. A review in the BMJ by Professor Sung in October 2006, states that the recommended strategy to prevent upper gastrointestinal bleeding in patients on one or two antiplatelet agents is the use of Proton Pump Inhibitors1 This is an important consideration with the use of aspirin and other antiplatelet agents dramatically increasing in the past decade predominantly for primary and secondary prevention of myocardial and cerebrovascular ischaemia. The combination of aspirin and clopidogrel has become a class I recommendation after percutaneous coronary interventions in the US and Europe.2. Older people, those with a history of gastrointestinal bleeding or peptic ulcer, and those who use non-steroidal anti- inflammatory drugs or cyclo-oxygenase-2 inhibitors are more likely to develop aspirin induced bleeding 3 so the use of PPIs in these patients as a preventive measure is an increasing practice in the UK4. Studies have demonstrated decreased bleeding risk with the use of PPIs 4,5. The cost, morbidity and mortality of GI bleeding is far superior to the rare side effects and low cost of a Proton pump inhibitor. The general overuse of PPIs is accepted however the authors of the review do not appear to have taken into account the use of PPIs as a prophylatic measure in suitable patients, and doing so would account for a significant proportion of this supposed inappropriate use. References 1. Sung J Combining aspirin with antithrombotic agents BMJ 2006; 333: 712-713 2) Smith SC, Feldman TE, Hirshfeld JW, Jacobs AK, Kern MJ, King SB III, et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention—summary article: a report of the American College of Cardiology/American Heart Association task force on practice guideline. Circulation 2006;113: 156-75. 3).Lanas A, Bajador E, Serrano P, Fuentes J, Carreno S, Guardia J, et al. Nitrovasodilators, low-dose aspirin, other non-steroidal antiinflammatory drugs and the risk of upper gastrointestinal bleeding. N Engl J Med 2000;343: 834. 4). Schreiner G et al. Evaluation of Proton Pump Inhibitor Use in Patients With Acute Coronary Syndromes Based on Risk Factors for Gastrointestinal Bleed. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine. 6(4):169-172, December 2007. 5).Bulsara M et al. Factors Associated With Upper Gastrointestinal Bleeding After Percutaneous Coronary Intervention: A Case-Control Study. The American Journal of Gastroenterology 2007 102 (11)2411-2417. Competing interests: None declared |
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Jecko Thachil, SpR Liverpool University
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The editorial by Forgacs and Loganayagam on the overuse of proton pump inhibitors is timely and apt [1]. This is more so with the increasing risk of clostridium difficile infection in hospitals for which it has been shown to be a risk factor [2]. The ability of the vegetative form of C. difficile to survive in gastric contents with an elevated pH caused by excess use of PPI has been suggested as a potential mechanism [3]. Though the inappropriate and excess use of antibiotics is well established in the causation of C.difficile infection, the possible role of PPI is often overlooked. It is therefore important that PPIs are as intelligently used as the antimicrobials in every hospital. The editorial mentions several papers which report the misuse of PPIs. In addition to these, Grubb et al showed as many as 71% of patients in general medicine wards receiving some sort of acid suppression without an appropriate indication [4]. In another study of 357 patients who received stress ulcer prophylaxis during their intensive care unit (ICU) stay, 80% continued on gastric acid suppressants on transfer from the ICU, with 60% of the therapy being inappropriate [5]. Out of these 25% of the patients were discharged from the hospital with inappropriate prescription of gastric acid suppressants. The problem is not unique to hospital practice and the family physicians have also shown to contribute [6]. It is helpful in these circumstances to have a hospital “antacid policy” where the judicious use of gastric acid suppressant therapy (not limited to PPIs) is advised to accompany the antimicrobial protocol and thus limit C.difficile infection. There is also the need for the increased awareness among general practitioners about the appropriate use of these “apparently safe” drugs. Consideration could also be made to withholding them while the patients receive broad spectrum antibiotics. It is also timely to perform audits and research to identify the length of time the PPIs should be prescribed for an adequate effect. Lifestyle measures should be advised to patients, which have been well established to help in many situations of excessive acid production. References 1. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008; 336: 2-3. 2. Dial S, Delaney JAC, Barkun AN, et al. Use of gastric acid- suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005; 294:2989-95. 3. Jump RL, Pultz MJ, Donskey CJ. Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C. difficile-associated diarrhoea? Antimicrob Agents Chemother. 2007; 51: 2883-7. 4. Grube RR, May DB. Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm. 2007; 64: 1396-400. 5. Wohlt PD, Hansen LA, Fish JT. Inappropriate continuation of stress ulcer prophylactic therapy after discharge. Ann Pharmacother. 2007; 41: 1611-6. 6. Scagliarini R, Magnani E, Pratico A, Bocchini R, Sambo P, Pazzi P. Inadequate use of acid-suppressive therapy in hospitalized patients and its implications for general practice. Dig Dis Sci. 2005; 50: 2307-11. Competing interests: None declared |
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GRAEME MACKENZIE, GP OUT OF HOURS NORTH CUMBRIA
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As an out of hours GP, virtually everyone over 65 seems to be on a PPI these days. Must phone my stockbroker. Competing interests: None declared |
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shaji sebastian, consultant gastroenterologist Hull Royal Infirmary, HU3 2JZ
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Forgacs et al (1) should be congratulated in bringing to the forefront the widespread problem of inappropriate use of proton pump inhibitors (PPIs). Apart from the cost considerations, the worrying increase in the prescription rate of these drugs and the suggested link to opportunistic infections such as Clostridium Difficle deserve more attention. There is also a concern of the association of PPI induced hypergastrinemia with certain neoplasm’s (2). Unfortunately the problem is reported across the world as alluded by the authors. Our own study showed that at a given time 32% of all hospitalised patients in an acute hospital were on PPIs with only 37% of these for valid indications (3). The factors contributing to inappropriate prescription has not been well elucidated although surprisingly increasing patients’ age appears to be a factor in some studies (3,4). One area not covered by Forgacs et al is the emerging data suggesting inappropriate use of rather expensive intravenous PPIs in hospital setting and the cost implications for this is considerable (4). Also the prescriptions initiated within hospital are often carried over in general practice. As the national dyspepsia guidelines have not reduced the over prescription of PPIs, it is time for individual institutions and organisations to find their on PPI prescribing policies to address this problem. References: 1. Forgacs I, Loganayagam A. Over prescribing proton pump inhibitors. BMJ 2008; 336(7634):2-3 2.Georgopoulos SD, Polymeros D,Triantafyllou K et al. Hypergastrinemia is associated with increased risk of distal colon adenomas. Digestion 2006; 71(1)42-6. 3. Sebastian S, Kernan N, Qasim A, et al. Appropriateness of gastric antisecretory therapy in hospital practice. Ir J Med Sci 2003; 172(3):115- 7. 4. Afif W, Alsulaiman R, Martel M, Barkun AN. Predictors of inappropriate utilization of intravenous proton pump inhibitors. Aliment Pharmacol Ther 2007; 25(5):609-17. Competing interests: None declared |
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John Leigh, GP Washington
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Dear Sir, Thach states "There is also the need for the increased awareness among general practitioners about the appropriate use of these “apparently safe” drugs." As mentioned by several respondents, including myself, PPIs are cheap, overall very safe, and effective. I do not need a hospital physician to tell me what is appropriate use of a particular drug in the community, much as I would not dream of telling hospital physicians what is appropriate use of specific medications in a hospital setting. Competing interests: I'm a General Practitioner |
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Ian R Sykes, General Practitioner Oakham Surgery B69 1RZ
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Dear Editor, In line with other comments, I would like to point out the inaccuracy of the opening title in your editorial on proton pump inhibitors (1), that they are expensive:they are not, and for many patients, generic lansoprazole is the cheapest option, as well as the easiest to take. Taken from the most recent British National Formulary (BNF) (2), are the following prices with the number of days of treatment for which the price is applicable: Lansoprazole 15mg daily (28) £2.59
Proton pump inhibitors are also very effective, and if the patient was not taking this drug, then they would almost certainly either be buying or requesting a script for other treatment. I personally have yet to see a serious reaction in patients taking this drug. 1.Forgacs I, Loganayagam A Overprescribing proton pump inhibitors BMJ 2008;336:2 2.BNF 2007;54:40-50 Yours sincerely,
Competing interests: None declared |
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Jessy Saini, GP Trainee Black Country VTS
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Having read your recent article I feel that whether we think the cost of PPI’s is too high or too low the fact remains that they are a revolutionary treatment and given the alternative total cost of a patient needing hospital stay from perforated peptic ulcer or indeed the psychological distress associated with major surgery, it is a small price to pay. As a training General Practitioner I do not feel that my practice will change in any way and I will continue to prescribe Proton Pump Inhibitors if the patients clinical condition warrants them. Competing interests: None declared |
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Milind M Deshpande, Consulting Orthosurgeon Vivekanand hospital,Hubli,India,580029, Poornima Deshpande
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Sir Anything in excess and a cheap quick fix solution to a common symptom has demerits. Have professionals forgotten the role of diet, counselling and exercise? The juice is often required even for drug absorption. So the PPI may affect the co-prescribed drug absorption too and later still to come will be the drug interactions! What about the excess of the molecule that coexists with PPI? For e.g. omeprazole sodium, omeprazole magnesium, omeprazole sodium bicarbonate. The hypertensives On omeprazole sodium stand to loose while migraineurs may gain from the magnesium and the renal tubular acidotics from the bicarbs! Irrationale the combination may be! The modern era additives, preservatives in tasty diet, the pesticides in artificial drinks, insecticide sprayed vegetables, trans fatty acids in the repeatedly heated oils, the aginamotu fast foods, colours in foods, the addicts, the hungry poor and the sedentary affluent overeating stressed officer are the closest friends of the PPI S. Cyclic courses rather than a routine is a better alternative when one wants to use them for patients on long term drugs like aspirin, NSAIDS, steroids, Bisphosphonates. People smoke despite statutory warnings but its their lookout. If so then why can’t PPIS carry a statutory? That it may invite gastric malignancy on long-term use! The acidity symptom may be a MI and so beware the PPI overprescriber! Regards Milind, Poornima. Competing interests: None declared |
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Dr A. Breck McKay, Family/Musculoskeletal Physicain Victoira Point, Brisbane, Australia
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The rapid responses have been very interesting.... BUT they seem to be missing the real problem: When prednisone/steroids became available they were expensive, but had magnificent benefits then they got cheaper and massively overused and the horrific side effects were noticed! Then a rational restricted use protocol was developed.. When barbiturates were first available they were expensive and when they became cheaper and abused they were related to nasty side effects,(addiction, overdose etc) and a rational restricted use protocol was developed and now:- The NSAIDs followed the same pattern and now have a rational and restricted use protocol. PPI's have become cheap and massively prescribed... BUT... everyone is missing the major and most important point... just as excess use and abuse of steroids/ barbiturates & NSAIDS caused massive long term side effects:- SO DO PPIs to whole body function! Bearing in mind the gasto-intestinal specialists' 'apparant ignorance' of the long term side effects to all gut areas & whole body, it is time to develop a rational restricted use protocol (high initial dose BD, to once daily to alternate daily at weekly intervals),and using simpler and cheaper but less harmful antacids and the histamine H2 receotor agonists in the interim periods, at the Family Physician/GP level. What are the massive costs of the indicated side effects of these drugs causing already...yet alone over longer terms? No one knows!!! There are only three listed long term review studies on PPIs, two based on cost (1,2) and one on age (3).. none on dysautonomic or other side effects to the whole gut system as indicated in my 2002 letter. So why has there been no research on those oesophagus, stomach and whole of gut problems, so often encountered in Family Medicine/General Practice? The most frequent specialist advice to my patients have received has been to increase the dose!!! "First do no harm"? Forgotten or just ignored? I am becoming older, wiser and more cynical of specialist limited advice as my experience grows...(now >47 years!!) References: 1: O'Connor JB, Provenzale D, Brazer S. Economic considerations in the treatment of gastroesophageal reflux disease: a review. Am J Gastroenterol. 2000 Dec;95(12):3356-64. Review. PMID: 11151862 [PubMed - indexed for MEDLINE] 2: Goeree R, O'Brien B, Hunt R, Blackhouse G, Willan A, Watson J. Economic evaluation of long-term management strategies for erosive oesophagitis. Pharmacoeconomics. 1999 Dec;16(6):679-97. PMID: 10724795 [PubMed - indexed for MEDLINE] 3: Lazzaroni M, Bianchi Porro G. Treatment of peptic ulcer in the elderly. Proton pump inhibitors and histamine H2 receptor antagonists. Drugs Aging. 1996 Oct;9(4):251-61. Review. PMID: 8894523 [PubMed - indexed for MEDLINE] Competing interests: None declared |
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Alun L Cooper, GP Bridge Medical Centre
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Dear Editor, Forgacs & Loganayagam discuss the over prescribing of proton pump inhibitors (PPI) in clinical practice (1). However, we would like to point out that PPIs are not a recognised cause of osteoporosis, as stated in this editorial. The cited article by Yang et al.(2) found that chronic use of proton pump inhibitors (PPI) was associated with increased risk of hip fracture, consistent with other studies linking their use to increased fracture risk (3,4,5). This association is particularly relevant to the management of osteoporosis as bisphosphonates, the most common group of medications prescribed for patients with osteoporosis, are associated with upper gastro-intestinal effects, such as dyspepsia (6,7), which may lead to additional prescribing of PPIs (8). Therefore, minimising the use of PPIs should also be an important consideration in the management of osteoporotic patients. Yours faithfully, Dr Alun Cooper REFERENCES 1.Forgacs I, Loganayagam A. Overprescribing of proton pump inhibitors. BMJ 2008; 336:2-3. (5 January). 2.Yang Y-X, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006; 296 (24), 2947-2953. 3.Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medication and the risk of fracture. Calcif Tissue Int. 2006; 79, 76-83. 4.Yu E W, Shinoff C, Blackwell T, Ensrud K, Hillier T, Bauer D C. Use of acid-suppressive medications and risk of bone loss and fracture in postmenopausal women. J Bone Min Res 2006; 21 (Suppl. 1), S281. 5.De Vries F, Cooper AL, Logan RF, Cockle SM, van Staa TP, Cooper C. Fracture risk in patients receiving concomitant bisphosphonate and acid- suppressive medication or bisphosphonates alone. Osteoporosis Int. 2007; 18(Suppl 3):S261. 6.Barrera BA, Wilton LV, Harris S, Shakir SAW. Prescription-event monitoring study on 13,164 patients prescribed risedronate in primary care in England. Osteoporos Int. 2005; 16, 1989-1998. 7.Biswas PN, Wilton LV, Shakir SAW. Pharmacovigilance study of alendronate in England. Osteoporos Int. 2003; 14, 507-514. 8.Roughead EE, McGeechan K, Sayer GP. Bisphosphonate use and subsequent prescription of acid suppressants. Br J Clin Pharm. 2004; 57(6), 813-816. Competing interests: None declared |
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Richard Cunningham, Consultant Microbiologist Derriford Hospital Plymouth, PL6 8DH
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Forgacs and Loganayagam (1) have written a thorough and measured summary of the economic costs of unnecessary PPI use. However, the wasted NHS resource they describe pales into insignificance beside the hundreds of extra deaths from C.difficile this may cause each year. First described in 2003 (2), the positive association between PPI use and C.difficile has now been confirmed in numerous studies worldwide, a systematic review (3), and recently an animal model (4). In 1999, there were about 10 million community PPI prescriptions in England & Wales, and less than 20,000 reported cases of C.difficile. By 2006 there were about 25 million PPI prescriptions, and 55,000 cases of C.difficile. Antibiotic prescriptions actually fell over this period, and contrary to the popular press, hospitals are cleaner now than they have been for many years. There is no longer any doubt that PPIs and Cdifficile are associated. If this is a causal association, overuse of these drugs may be causing many thousands of additional cases, and hundreds of deaths in the UK each year. PPIs are highly effective when used appropriately, but this does not excuse ignoring NICE guidance and a potentially lethal adverse effect. 1) Forgacs I, Loganayagam A. Over prescribing proton pump inhibitors. BMJ 2008; 336(7634):2-3 2) Cunningham R, Dale B, Undy B, Gaunt PNG. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. Journal of Hospital Infection 2003;54:243-245. 3) Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol 2007;102:1-10. 4) Kaur S, Vaishnavi C, Prasad K, Ray P, Kochhar R. Comparative role of antibiotic and proton pump inhibitor in experimental Clostridium difficle infection in mice. Microbiol. Immunol. 2007;51(12):1209-1214 Competing interests: None declared |
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John C Welch, GP Wairau Hospital Blenheim New Zealand
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The excessive use of PPI drugs is not limited to the UK. In New Zealand I have noted an association between polypharmacy and the use of PPI. In such cases I have been known to jokingly suggest to patients that their PPI is for treating the indigestion caused by their "drug salad." Dr J Welch
Competing interests: None declared |
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H. Mei-Ling Ball, Foundation Doctor Kingston NHS Trust
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Editor, I read with interest the article on overprescribing of PPIs. It is common practice for juniors to co-prescribe PPIs for patients who are being commenced on aspirin therapy as primary or secondary prevention for cardiovascular disease. Especially amongst juniors this is fuelled by a desire to prevent upper GI bleeds but is often not evidence based. A web based search brought me to the NHS Primary Care Answering Scheme web site www.clinicalanswers.nhs.uk where the question of appropriate prescribing of PPIs in conjunction with aspirin therapy is discussed. They suggest using PPI's in conjunction with aspirin for "people at high risk of GI adverse effects or who continue to have dyspepsia", or alternatively using clopidogrel. They go on to quote from a study on NSAIDs that patients with one or more risk factors of; age over 65 years, previous history, comorbidity, prolonged use, high doses, and other drugs, like aspirin or anticoagulants: gastroprotection, principally a PPI is indicated. (Bandolier. Gastroprotection with NSAID: do we follow guidelines? 2007) In an effort to reduce some of the excessive prescription of PPIs it might be helpful to include this in local hospital guidelines especially for junior staff and pharmacists. Competing interests: None declared |
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oscar,m jolobe, retired geriatrician manchester medical society, c/o john rylands university library, oxford road, manchestre M13 9PP
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Awareness of potentially lethal side effects of omeprazole, such as increased predisposition to clostridium difficile infection, would justify a resurgence of interest in the use of misoprostol for prophylaxis against aspirin-related peptic ulceration. Misoprostol 200 mcg qds is just as effective as lansaprazole 15-30 mg/d in preventing gastric ulceration in long-term users of non steriodal anti inflammators drugs(NSAID's)(1), of which aspirin is an example. The incidence of misoprostol-related gastrointestinal side effects, such as abdominal cramps and diahrroea, can be reduced by halving the dose to 200 mcg bd. At that dose prophylactic efficacy is not as good as with the 200 mcg qds dose. Nevertheless, the incidence of NSAID-related gastric ulceration is significantly(p=0.02) lower in patients receiving misoprostol 200 mcg bd than in the placebo group. Likewise the incidence of duodenal ulceration is significantly(p=0.04) lower in patients receiveing misoprostol 200 mcg bd than in the placebo group(2). More recent anxieties relate to the possibility of attenuation of the antiplatelet action of clopidogrel during combined therapy with aspirin when omeprazole is co-prescribed to prevent peptic ulceration. What has been found is that omeprazole significantly(p < 0.0001) decreased clopidogrel inhibitory effect on P2Y12(3), the ADP activated receptor which plays a central role in platelet activation(4), and is the target of P2Y12 receptor antagonists such as clopidogrel(5) References (1) Graham D., Agrawal NM., Campbell DR et al Ulcer prevention in long-term users of non-steriodal anti-inflammatory drugs Archives of Internal Medicine 2002:162:169075 (2) Raskin JB., White RH., Jackson JE et al Misoprostol dosage in the prevention of non-steriodal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens Annals of Internal Medicine 1995:123:344-50 (3) Gilard M., Arnaud B., Cornily J-C et al Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin Journal of the American College of Cardiology 2008:51:256-60 (4) Dorsam RT., Kunapuli SP Central role of the P2Y12 receptor in platelete function Journal of Clinical Investigation 2004:113:340-5 (5) Malinin A., Pokov A., Sperling M et al Monitoring platelet inhibition after clopidogrel with the VerifyNow- P2Y12(r) rapid analyser: The VERIfy Thrombosis risk ASsessment(VERITAS) study Thrombosis Research 2007:119:277-84 Competing interests: None declared |
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Andrew C Barnes, Civilian Medical Practitioner British Forces Germany
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Is this article inspired by one of Mr Brown’s spin “doctors”? It contains some incredible errors: 1. “The first generic proton pump inhibitor (omeprazole) was
introduced in 2002.” Wrong! Omeprazole has been in widespread use since
the 1980s. The fact that a serious side-effect profile has not emerged is
very reassuring.
Watch for bias: 1. The repeated use of “over-prescribing” and “over-use” descriptions
are like they are proven. The lay media pick up on this. I disagree.
Instead of political campaigns against doctors, why not take action? If money is the real underlying issue, make patients pay for it by central regulation. Failing that political decision, I am happy to continue to prescribe this wonder drug liberally for my patients… Competing interests: None declared |
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Asha Srikanth, Specialist Registrar Rheumatology Lincoln County Hospital, Lincoln, Viswanath V Kaushik, Consultant Rheumatologist
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Dear Sir, We read with interest your article on the over prescribing of proton pump inhibitors(PPIs) (1). The authors explain the economic implications associated with over prescription of PPIs and possible adverse events which stem from this. One such possible side effect associated with PPIs, which has come to light in the recent years, is increased fracture risk secondary to accelerated osteoporosis (2). Osteoporosis is defined as a reduction in bone mass and disruption of bone architecture, resulting in reduced bone strength and increased fracture risk. Hip fracture is one of the significant presentations of osteoporosis. The mortality rate during the first year after a hip fracture is estimated to be around 20% (3). Hip fractures have big socioeconomic implications incurring huge health care costs due to inevitable hospitalisation, surgery and rehabilitation. One year following a hip fracture, it has been found that 40% of patients are unable to walk independently, 60% cannot carry out at least one activity of daily living, and 80% or more are unable to carry out at least one independent activity of daily living, such as shopping, or driving (4). An acidic environment in the gastrointestinal tract facilitates the release of ionised calcium from insoluble calcium salts, such as, calcium carbonate (5). Proton pump inhibitors by reducing gastric acidity interferes with calcium absorption . In a case control study by Yang et al in 2006, they found that long-term PPI therapy, particularly at high doses, is associated with increased risk of hip fracture. The adjusted odds ratio for hip fracture associated with more that 1 year of PPI therapy was 1.44 (95% confidence interval) (2). Dyspepsia and regurgitation are common side effects encountered with bisphosphonates which is the first line treatment for osteoporosis. de Vries et al, in 2007, conducted a retrospective cohort study using the General Practice Research Database and found that there was an increased risk of hip fractures in patients taking concomitant bisphosphonates and PPIs (6). They suggest that acid-suppressant medications may attenuate the protective effects of bisphosphonates on fracture risk. We agree that a judicious evidence based use of proton pump inhibitors is warranted and prescriptions should be reviewed on a regularly. Over prescribing PPIs is not only associated with economic implications but also significant mortality. References 1.Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. Bmj 2008;336(7634):2-3. 2.Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. Jama 2006;296(24):2947-53. 3. Rowe R. Comment: preventive strategies: is current clinical practice effective for bones? Br J Clin Pract 1996;50(1):47-9. 4.Cooper C. The crippling consequences of fractures and their impact on quality of life. Am J Med 1997;103(2A):12S-17S; discussion 17S-19S. 5. Sheikh MS, Santa Ana CA, Nicar MJ, Schiller LR, Fordtran JS. Gastrointestinal absorption of calcium from milk and calcium salts. N Engl J Med 1987;317(9):532-6. 6. de Vries F, Cooper AL, Logan RF, Cockle SM, van Staa TP, Cooper C. Fracture risk in patients receiving concomitant bisphosphonate and acid- suppressive medication or bisphosphonates alone. Osteoporosis Int 2007;18(Suppl 3):S261. Competing interests: None declared |
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John G Gooderham, Member of PPI Forum 38 Broomfield Drive, Billinghurst, RH14 9TJ
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From the perspective of Patient & Public Involvement (PPI)might Proton Pump Inhibitor (PPI)prescribing be a case of "waste not, want not"? Competing interests: Member of West Sussex PPI Forum |
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