"Discovery consists of seeing what everybody has seen and
thinking what nobody thought"
-Albert Szent Gyorrgyi, 1937 Nobel Laureate in Physiology and Medicine
Goals:
1.To make a literature review of peptic ulcer as a public health problem in order to summarise the knowledge and have a global aspect of the problem.
2. To elaborate a recommended strategy for treatment and prevention of peptic ulcer in Moldova.
Objectives:
_ To summarise scientific achievement in the peptic ulcer management area.
_To find out the latest published work and to compare with other previous works.
_To elaborate recommendations for the Ministry of Health in Moldova.
_ To show a concrete way of improving of situation in the problem of peptic ulcer management in Moldova.
Introduction
Peptic ulcer disease (PUD) is a disease with characteristic of discrete mucosal defect in the gastric and duodenal parts of gastrointestinal tract, parts most exposed to acid and pepsin secretion. Gastritis also is very often presented as an indistinguishable from ulcer in addressing the problem in the emergency department.
Magnitude of the peptic ulcer in the world:
Peptic ulcer is one of the most common diseases of gastrointestinal tract in the world.
Frequency of PUD (Peptic Ulcer Disease) is decreasing in the developed world but increasing in developing countries. Only in US approximately 10% of Americans eventually develop PUD, and about 10% of patients presenting to the ED with abdominal pain are diagnosed with PUD. Prevalence has decreased in the US over the last 30 years. But 100 000 new cases yearly occurs only in US. Although mortality is low (6 500 deaths yearly), complication as extensive bleeding, perforations, penetration, acute dolor syndrome, malignisation etc. are making patients to suffer a lot. Indirect costs exceed 5.65 billion dollars only for US.1
.
Male to female ratio of gastritis is approximately one to one, but of PUD is approximately 2:1. It is estimated that about 60% of Americans older than 60 years have H. pylori, and about 40% of all population contains this bacteria, but concentration of it is not established. Duodenal ulcers usually occur in those aged 25-75 years, and gastric ulcer incidence peaks in those aged 55-65 years old.
Background information:
ASSESSMENT OF THE HEALTH CARE SYSTEM IN THE REPUBLIC OF MOLDOVA Country and Population
On Jan. 1st, 2001, the population in the Republic of Moldova was 3,634.5 thousand people, i.e. 9,000 less than recorded previous year. The share of population under 15 is considerably higher than the European average and it accounts for 24.2%. These indicators characterize our population as being a relatively young population, but with aging trends. The proportion of population above 65 is quite stable throughout the last 3 years and constitutes 9.3%.
Moldova registers a stable, nevertheless highest, mortality rate due to digestive system disorders, in Europe and NIS over the last years. Since 1999 the mortality due to GIT diseases took its third place in the structure of death by cause.
EMERGENCY SURGERY
Between all causes of postoperative lethality in emergency surgery gastrointestinal hemorrhage are on the second high level after acute pancreatitis, and Perforating gastric and duodenal ulcerative disease are on the fifth place after acute volvulus.
Frequency:
Epidemiology and Importance in Moldova:
PU remains one of the most prevalent and costly diseases in the Republic of Moldova. The prevalence of PU in patients seen by physicians is about 40 000 per year with another estimated 40 000 patients indulging in self-medication. The total patient visits to physicians is about 100 000 per year, and the total costs (adding hospitalizations, tests, medications, etc.) amount to more than 7 milion U.S. dollars! But that is only the financial burden caused by this disease . How about the human suffering, the complications (bleeding, perforation, obstruction) and even the loss of lives (mostly from bleeding)?
Pathophysiology: The mechanisms of mucosal injury in gastritis and PUD are thought to be an imbalance of aggressive factors, such as acid production or pepsin, and defensive factors, such as mucus production, bicarbonate, and blood flow.
Erosive gastritis usually is associated with serious illness or with various drugs. Stress, ethanol, bile, and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt the gastric mucosal barrier, making it vulnerable to normal gastric secretions.
Infection with Helicobacter pylori, a short, spiral-shaped, microaerophilic gram-negative bacillus, is the leading cause of PUD and is associated with virtually all ulcers not induced by NSAIDs . H pylori colonize the deep layers of the mucosal gel that coats the gastric mucosa and presumably disrupts its protective properties. It was isolated in 1982 by J.Robin Warren and Barry Marshall , Western Australia, Royal Perth Hospital, and showed that it caused gastritis and stomach ulcers . H pylori is thought to infect virtually all patients with chronic active gastritis.
PUD appeared from erosion of the GI tract under the influence of H.Pylori. The flagellum presumably helps H.Pylori burrow through the healthy strata that protects the GI tract mucosa.
H.pylori secretes urease, which generates ammonia from urea and this ammonia cloud protects it from the acid ambiance of the GI tract.
H.Pylory infection is a chronic condition that affects about 40% of the world’s population. It is more likely to be spread in the developing countries and between older persons . Its colonization of the GI tract mucosa leads to numerous negative effects, including initiation of a cytotoxin-induced inflammatory response implicated in ulcerogenity and carcinogenity (or gastric metaplasia), increased acid production (through increasing permeability of the GI mucosal strata for hydrogen ions and pepsin) and subsequent damage to the GI tract, tissue damage and weekened host immune defences. A strong association was found between the presence of this microorganism and PUD occurrence. Over 90% patients with duodenal and 70% with gastric ulcers are infected with H.pylory. Transmission occurs via the oral-oral or oral-fecal route7. It is suggested that suboptimal sanitary conditions and habits are important factor of risk.
NSAIDs (NeSteroidAntiInflamator Drugs) and aspirin also interfere with the protective mucus layer by inhibiting mucosal cyclooxygenase activity, reducing levels of mucosal prostaglandins. Many people with known H pylori colonization or who are taking NSAIDs do not suffer from gastritis or PUD, which indicates other important causative factors must be involved. As a risk factors for NSAID induced PUD are: old age, female sex, previous gastric or duodenal irritations from drugs, high dose or multiple NSAIDs, concomitant corticosteroid therapy, treatment with NSAID more than 3 months and H.Pylori presence.
Zollinger-Ellison syndrome is a rare disorder that causes tumors in the pancreas and duodenum and ulcers in the stomach and duodenum. These tumors secrete a substance called gastrin that causes the stomach to produce too much acid, which in turn causes the stomach and duodenal ulcers (peptic ulcers). The ulcers caused by Zollinger-Ellison syndrome are more painful and less responsive to treatment than ordinary peptic ulcers. What causes people with Zollinger-Ellison syndrome to develop tumors is unknown, but the cause may be an abnormal tumor suppressor gene.
Additionally to the factors examined above it is very important to emphasize on contributory risk factors of contribution to the PUD such as: cigarette smoking, genetic factors, psychological factors, beverages/ foods known to cause dyspepsia, ethanol and other chemicals.
CLINICAL PRESENTATION/ SINGS AND SYMPTOMS
Presentation. Dyspepsia is the classic symptoms of PUD. It may manifest either as Epigastric to left upper quadrant pain, frequently described as burning, which may radiate to the back, usually occurs 1-5 hours after meals and may be relieved by food, antacids (duodenal), or vomiting (gastric). Typically follows a daily pattern specific to patient. Some additional characteristics could be distinguished: NSAID-induced gastritis or ulcers are usually silent, sudden onset of symptoms may indicate perforation, gastritis may present as bleeding, which is more likely in elderly patients. Symptoms consistent with anemia (eg, fatigue, dyspnea) may manifest.
Physical exam.
Generally reveals epigastric tenderness. Epigastric tenderness is present and usually mild. Bowel sounds are normal. Signs of peritonitis or GI bleeding may manifest. Perform a rectal examination and Hemoccult testing.
Differencial diagnosis: It is necessary to diferenciate from some diseases which could have the same clinical sings or symptoms. (e.g., acute coronary syndrome
aneurysms, abdominal cholangitis ,cholecystitis and biliary colic, cholelithiasis,
diverticular disease, esophagitis, gastroenteritis, hepatitis, inflammatory bowel, mesenteric ischemia, myocardial infarction, pancreatitis, pulmonary embolism, renal calculi, atrophic gastritis, nonulcer dyspepsia, functional gastrointestinal disorder, atypical appendicitis in the pregnant patient.)
Lab Studies: Usually is not helpful in uncomplicated PUD, but as routine is considered necessary: Complete blood count test is used to evaluate acute or chronic blood loss, electrolytes, BUN, and creatinine are useful tests for critical-appearing patients who require fluid resuscitation, type, cross match and screen are indicated if transfusion in unstable or potentially critical patients is needed, while a blood test for H.PYLORI exists, it is of limited value in the acute setting.
Imaging Studies: A chest x-ray may be useful to detect free abdominal air when perforation is a possibility. Upper GI Series (double contrast). Good for IDing extrinsic lesions and gastric dysmotility, Incorrect Dx in 20 – 30 % of patients, Limited usefulness if trying to R/O malignant GU
Endoscopy: (gold standard) is considered to be more accurate, but unfortunately it cannot be applied in all patients as not everyone could support this procedure. It is recommended to confirm GU healing and to assure that ulcer is not malignant, but in the poor country it is also very expensive procedure and many people will be unable to support required expences.
Procedures: Placement of a nasogastric (NG) tube is helpful to evaluate for upper GI bleeding. Pursue aggressive fluid resuscitation in patients with evidence of massive upper GI bleeding. H. Pylori can be detected by Urea Breath test, Blood antibody test, Stomach biopsy, Stool antigen test.
Breath testing: Non-invasive H pylori testing is as reassuring to the patient as endoscopy and is less uncomfortable and distressing . Breath test is based on checking of ------13C control. Before this test a patient a small high-calorie meal and drink a solution of water to which 13C urea has been added. Further breath specimens will be taken at intervals of 20 , 40, and 60 minutes respectively and these will be sent to a test laboratory. If in patient’s stomach are this bacterias, it will break down the 13C urea and make it possible to detect CO2 labelled with 13C in his breath specimen . It is important to emphasise on low cost of this investigation especially for such country in transition like Moldova.
PUD Management: The main target of ulcer treatment is to decrease pain and other ulcer related symptoms and to recover the ulcer lesion sooner in order to prevent possibly complications which can be fatal for the patient. Of the basic importance should be considered for treatment: Antacids, Sucralfate, Histamine II Receptor Antagonists, Proton Pump Inhibitors, Combination Acid-Suppressive Therapy, Surgery, NSAID Prophylaxis, H.Pylori Eradication
Major attention in ulcer management should emphasize on secondary prevention, prevention of complications. If patient is not investigated at the time of early dyspepsia sings, and in case of H.Pylori presence an adequate antibioticoterapy is administered, this patient is under high risk of ulcer development. PUD will recur in 75% of patients , if no additional treatment is administered after initial nonantibiotic therapy successfully relieves symptoms and heals lesions, while long-term acid suppression may prevent ulcer recurrence, H. pylori eradication is only method that can achieve a complete curative effect! , Symptomatic patients should be tested for H.Pylori breath test.
Treatment goals are the relief of discomfort and protection of the gastric mucosal barrier to promote healing. Eradication of H.Pylori infection is a prolonged and complicated process requiring confirmation of the presence of the organism, which is beyond the scope of practice in the ED. Antacids can’t be sufficient outpatient therapy in mild cases. This is only for symptomatic , temporary relief.
Antacids -- Aluminum-containing and magnesium-containing antacids can be helpful in relieving symptoms of gastritis by neutralizing gastric acids. These agents are inexpensive and safe.
H2-receptor antagonists -- Inhibit the action of histamine on the parietal cell, which inhibits acid secretion. The 4 drugs in this class are all equally effective and are available over the counter in half prescription strength for heartburn treatment. Although the IV administration of H2 blockers may be used to treat acute complications (eg, GI bleeding), the benefits are yet to be proven.
Proton pump inhibitors -- Bind to the proton pump of parietal cell, inhibiting secretion of hydrogen ions into gastric lumen. Proton pump inhibitors relieve pain and heal peptic ulcers more rapidly than H2 antagonists. Drugs in this class are equally effective. They all decrease serum concentrations of drugs that require gastric acidity for absorption, such as ketoconazole or itraconazole.
Gastrointestinal agents -- Are effective in the treatment of peptic ulcers and in preventing relapse. Their mechanism of action is not clear. Multiple doses are required, and they are not as effective as the other options.
Prostaglandins -- Can prevent peptic ulcers in patients taking NSAIDs and may be used with NSAIDs in patients at a high risk of complications.
There are three ways to prevent gastric lesions: to improve the defensive factors, to reduce the aggressive factors and to improve the defensive factors decreasing the aggressive factors at the same time.
1. Improving the Defensive Factors:
The NSAIDs cause a reduction in the production of the “protective Gel”, it is necessary to provide more of this protection. And that is the reason why could be used the synthetic protective gel misoprostol 200 mcg q.i.d. along with the prescribed NSAID. Lots of clinical trials have proven the effectiveness of this approach, but there are some problems: the therapeutic dosage of misoprostol can cause diarrhea and abdominal cramps in lots of patients, and it can induce premature labor or provoke abortion in pregnant women. This last side effect would not seem so important: after all, misoprostol would be just one more of the millions of drugs that we avoid using in pregnant women. Since the thalidomide tragedy all drugs are considered “guilty until proved otherwise”, it is “better be safe than sorry”.
2. Reducing the aggressive factors:
Another logical way to try to prevent PUs while using NSAIDs is compensating the decrease in protective factors that they cause with a corresponding diminution of the aggressive factors, thus tipping the scales in our favor. In the past it was thought that a good way of doing this would be by the frequent ingestion of huge amounts of milk, because of its anti-acid properties. Unfortunately, this elevation of the gastric pH is short-lived and followed by an even greater production of acid, due to a ”rebound” effect stimulated by milk proteins and the very own transitory reduction in the stomach’s acid content. So, in the end, we had even more gastric acid than before. But nowadays we have better ways of doing that, using Antagonists of Type 2 Histamine-Receptors (H2RA) or, even better, Proton Pump Inhibitors (PPI) , but PPIs effect a practically complete interruption of the acid production, making them a lot safer in the prevention of NSAID-related PU.
H2RA:Cimetidine The first of its class to be launched, some decades ago, it promoted a real breakthrough in the prevention and treatment of PUs. The dosage recommended nowadays is 400 mg per day.
Ranitidine The second H2RA launched, it proved to be very well tolerated but still with some clinically significant interactions. Recommended dosage varies from 150 mg q.d. up to 300 mg.
3. Improving the defensive and decreasing the aggressive factors at the same time: eradicating the Helicobacter pylori
The Hp deserves a special classification in the physiopathology of PUs, because it can act in a double manner:
Destroying the host s defensive mechanisms:
The interleukins (specially IL-8) and ensuing inflammatory reactions that are related to the Hp infection cause the formation of “holes” in the stomach’s defensive layer. It is the “leaking roof” theory: if your house has a lot of holes in the roof, it is not hard to figure that you will be in a lot of trouble when the “acid-rain” starts. This theory also explains very nicely why during decades we could treat PUs without even knowing that Hp existed: If you stop the acid secretion the ulcers will heal very nicely and remain so, as long as there is no acid. But, of course, it is the equivalent of leaving the roof of your house full of holes and praying for the rain not to come.
Increasing the host’s aggressive factors:
It is the “no brakes” theory: The Hp and its inflammation-related damages cause a malfunctioning of the gastric D-cells, which in normal conditions are responsible for the production of somatostatin (an inhibitor of G-cells secretion). As a result of the Hp infection, the G-cells end up having “no brakes”, that is, there is no more somatostatin to prevent the G-cells from “over-producing” gastrin and the resulting surplus of gastrin promotes a huge production of acid by the parietal cells. Another variation of this model is the one that states that the Hp, with its “surrounding ammonia cloud”, creates an artificial and confusing alkaline environment, inducing the gastric receptors for acid to erroneously “believe” that we have little or no acid in the stomach. Such “misconception” results in an over-production of gastrin and consequently an increased acid output, but even so the gastric receptors, ”blanketed“ by the Hp-produced alkaline ammonia don’t detect that, therefore we loose the negative feed-back (the “brakes”) and the situation perpetuates itself in an acid-producing escalation.
So, with the Hp playing so many roles at the same time, it is no wonder that we always find a very strong correlation between it and PUs: 85 percent of the gastric ulcers (GU) and almost 100 per cent of the duodenal ulcers (DU) are Hp-related. But how come that the Hp causes DU if he has affinity only for the gastric mucosa? The Hp establishes itself in the stomach and then causes all the things described above, with the resulting acid overproduction provoking the metaplasia of the duodenal epithelium into a gastric-like epithelium, in a vain attempt to better resist the acid excess, which is then deemed appropriate for colonization by the Hp. There are also other causes for PU, specially for GU, where the decisive factor is the loss of defensive factors such as different irrigative drugs, or medication.
About PU in NSAID-taking Hp-positive patients Here I found some conflicting data: some authors believe that there is a synergistic effect between the two of them. Others think that the real problem is that if you want to prevent NSAID-related ulcers you have to use long term PPIs and this acid suppression could lead to migration of the Hp from the gastric antrum to the gastric corpus and cause atrophic gastritis which is a precancerous lesion. Anyway, both of these currents are pro -eradicate the bacterium; the real doubts arise when some clinical trials seem to suggest a “protective” role for the HP.
So it is surely enough to confirm that complete eradication of these bacteria will help considerably in ulcer healing. In order to prevent recurrence of this infection, the patient should be under special sanitary conditions and with long-term HP control supervision. Some recent studies published in English professional literature indicate that the entire gastroenterological and clinical consensuses are in agreement about that: always eradicate Hp in all PU patients , , .
And about the Mucosa-Associated Lymphoid Tissue: normally there are no lymphoid follicles in the stomach, unless there is an Hp infection, and in some cases it can induce a B-lymphocytes lymphoma called MALToma, a malignant tumor that, even in large sizes, can regress and disappear completely just with the Hp eradication, in some cases avoiding the need for surgery or other aggressive therapies!
Lots of things about the Hp are incredible this way, lots of times you do not even find the Hp anymore when you diagnose the cancer because the “gastric atrophy with intestinal metaplasia” that follows the Hp attack is a kind of “defense” of the stomach, that changes its own epithelium into another kind of tissue that is not susceptible to the Hp infection and make precancerouse lesions.
Further Inpatient Care: Patients with significant or potentially significant hemorrhage require admission, usually to the intensive care unit. While in the ED, their care should focus on restoration of intravascular volume by infusion of saline or blood through large bore IV lines as clinically indicated. A central venous catheter to monitor such resuscitation may be considered.
High-risk patients include those with the following characteristics: Bleeding with hemodynamic instability, Repeated hematemesis or any hematochezia, Failure to clear with gastric lavage, Coagulopathy, Comorbid disease (especially cardiac, pulmonary, or renal), Advanced age, Patients with evidence of gastric perforation require operative repair, Hospitalization usually is necessary for gastric outlet obstruction to provide gastric rest and IV fluids. Surgical treatment usually is indicated for persistent or recurrent obstruction. Anticholinergic agents are contraindicated.
Further Outpatient Care: A follow-up visit should be made in 2-6 weeks to evaluate efficacy of treatment. Severe or recurrent symptoms indicate prompt referral for endoscopy and testing for H pylori. Symptomatic relief with therapy does not preclude malignancy.
Complications: Malignancy, Hemorrhage, Perforation, Obstruction
Prognosis: Most cases subside when the cause has been identified and treated appropriately.
Health promotion: Patients should be warned of known or potentially injurious drugs and agents. Some examples are as follows: NSAIDs, Aspirin, Alcohol, Caffeine (eg, coffee, tea, colas).
Activities included in health promotion concerning peptic ulcer will consist of two parts: Patient education and medical professional education. In health promotion of peptic ulcer should be done a special program of health promotion.
Educational programs:
Are oriented mainly on 2 sides: a. Population based & b. Professional (medical) based educational program. The first mentioned program is oriented on school educational classes, institutionalized medical seminars, public medical lectures etc. including personal discussion of medical personal with patients during interaction. It is necessary to explain main necessary points of ulcer prevention from the school age.
Professional program is oriented especially for continuing medical education for doctors and medical assistants, emphasizing of the health promotion techniques among medical personnel and role of health personnel in decreasing of risk factors for peptic ulcer and gastric cancer among population using health educational tools.
Media campaigns will include action of using of all media sources from Moldova including radio, TV-set, local newspaper as well as elaboration of special booklets and pamphlets on the theme of risk factors of peptic ulcer and necessary investigation like breath test (noninvasive, chip, informative) as well as epidemiological measures necessary to prevent future Helicobacter pylori contamination.
A special module will be dedicated to increase sensitiveness of local administration in order to restrict by rules unhealthy behavior and risky behavior which can induce peptic ulcer, such as smoking in a public places etc. Provides the general public and policy leaders with information on health risk, health status, and health needs in Moldova as well as information on policies and programs that can improve community health (such as water supply, residual water treat, public waterclosed etc).
With a help of ecological structures in Moldova and health professionals it will be identified and elaborated measures concerning decreasing of risk factors from the environment including water, air pollution which also could badly induce gastrointestinal diseases, especially peptic ulcer .
Vaccination Of course the most rational way to eradicate an infectious disease is through widespread immunization, like it was done with the smallpox. So the future of the Hp-related ulcers promises to be really nice because there are several vaccines being currently evaluated with very encouraging results in animal testing. Even better results than it could anticipate, because we can expect a vaccine to be, at best, capable of preventing a certain disease, but never to be capable of curing it! The Hp is an entirely different matter even in this aspect: some of the vaccines currently tested are not only preventive but curative as well, eradicating the Hp in the subjects already infected! The only problem is, some of the adjuvants used to improve the vaccines’ immunogenicity are very toxic for humans . So, much more studies will be needed until we can have a safe vaccine commercially available. Then, when discussing about eradication of the Hp, we will be talking only about destroying or not the last samples kept in laboratories for study, as happened to the smallpox virus!
However, the fact is that we have basically 3 causes for chronic PU, being the Hp only one of them. Actually, the prevalence of the Hp nowadays is already declining in the developed countries, thanks mostly to improvements in sanitation, better education and living standards as a whole. But for Moldova this problem is actual. At the same time, we have had a big increase in the incidence of NSAID-related PU.
Prevention of recurrence: Treatment with acid suppression for a long time is done mainly with acid-suppressing medications for at least two years after the initial lesion has healed while the long-term suppression approach is preferable to no additional treatment, it does not facilitate a cure. It should be considered for patients who are not H.Pylori positive or those on chronic NSAID consuming treatment with other risk factors for PUD.
Confirmation of eradication: In some specific cases such like elderly, patients with complicated PUD is necessary confirmation of eradication. It is important that evaluations conducted fewer than four to six weeks within completing PUD therapy may give in wrong results, as the organism may be cleared but not eradicated and return to cause a recurrence. Serologic tests may remain positive for at least one year after H. Pylori eradication, so confirmation of eradication should be determined by urea breath test (best preferred) , or by the stool antigen test or by culture. The last method is most preferred in the symptoms persistence after one or two courses of treatment.
Antibiotic resistance
Consideration of antibiotic resistance is important when decisions regarding combination regimens are being made. Antibiotic resistance to H. pyloris is an important cause of treatment failures in patients who are compliant with therapy of the antibiotics used to eradicate H.pylori resistance rates are currently highest with metronidazole, those of other antibiotics are increasing. Interestingly, metronidazole-containing regimens have been shown to maintain higher efficacy rates in the face of resistance than clarithromycin-containing regimens. Resistance to bismuth subsalicylate or citrate products has not been reported. Health care professionals are encouraged to counsel patients on the importance of therapy compliance and carefully monitor for the possible presence of antibiotic resistance (e.g., therapy failures after 14 days of compliant treatment). Failed combination regimens (especially those containing metronidazole or clarithromycin) should generally not be repeated.
NSAID Prophylaxis
As previously mentioned, patients taking NSAIDs who are at risk for NSAID-induced ulcers should, if at all possible, be switched to an alternative drug. For patients with inflammatory conditions, a switch to the COXIBs can be attempted, the lowest effective NSAID dose should be used and use of multiple NSAIDs should be avoided. Misoprostol (Cytotec), a prostaglandin E analogue, is FDA approved for the prevention of NSAID-induced gastric ulcers.
Studies with acid suppressive therapy have been conflicting. A trial with standard doses of an H2RA reported an increase in the incidence of GI bleeding in patients taking NSAIDs. This facts indicate that substantial acid suppression is required to prevent NSAIDinduced PUD.
Cost-Effectiveness
PUD treatment is associated with numerous direct and indirect costs, including ulcer diagnosis (e.g., endoscopy, physician visits, hospitalizations), symptom relief and ulcer healing, maintenance therapy and H. pylori detection and eradication. Treatment decisions must take into account these numerous factors. Because of their faster rates of symptom relief and ulcer healing and ability to raise intragastric pH high enough to facilitate entry of antibiotics to the site of H. pylori, PPIs have been shown to be more cost-effective than other antisecretory therapies.
While maintenance therapy for PUD is more cost-effective after. healing than no maintenance therapy in patients in whom H. pylori was not eradicated, detecting and eradicating H. pylori and thus, obviating the need for maintenance therapy, is the most cost-effective approach.
PUBLIC HEALTH’S ROLE
Making an overview on this problem from the public health level is important in order to improve significantly present situation in this part of medicine. Public health will have aim to work with doctors and patients make informed decisions by teaching them to differentiate the signs and symptoms of PUD from those of other GI disorders and determining when self-care is appropriate; educating them about the importance of H. pylori eradication; and counseling them on potential therapy-associated side effects and/or drug interactions, as well as the importance of compliance. Patients must clearly understand the signs and symptoms suggestive of bleeding and be aware of the fact that serious PUD associated complications (e.g., hemorrhage) may not necessarily be preceded by less severe warning signs, such as dyspepsia. Patient profile data can be used to proactively screen for patients who should be considered for H. pylori testing and eradication therapy (i.e., those on long-term acid suppressive therapy, those with NSAID-induced ulcers), as well as patients with NSAID induced dyspepsia or PUD who may be candidates for an alternative analgesic (e.g., a COXIB) or prophylactic therapy (e.g., misoprostol or PPI) .
MANAGING PEPTIC ULCER
In the light of this reliable evidence from systematic reviews, broadly speaking, there are four options:
(1). Eradication therapy for patients with symptoms suggestive of peptic ulcer. Investigations reserved for people whose symptoms fail to improve;
(2). Non-invasive tests for H.pylori on symptomatic patients. Eradication therapy offered to those who are positive without further investigation for a definitive diagnosis of peptic ulcer
(3). Non-invasive test for H.pylori on symptomatic patients. Endoscopy for those who are positive, to establish a definitive diagnosis of peptic ulcer before eradication therapy is offered;
(4). Endoscopy to establish a definitive diagnosis for all patients with suspected peptic ulcer alongside a test for H.pylori. Eradication therapy offered to those with proven peptic ulcer and H.pylori infection.
It remains uncertain from present research which of these options, or combinations of options is best, and the choice will also depend upon patient factors , access to diagnostic services and costs.
Both options (1) and (2) will result in a significant proportion of people with no ulcer being treated which is costly (only about 20-25 per cent of dyspepsia patients who are H.pylori positive will have a peptic ulcer), has no current evidence of benefit and may in rare cases be hazardous.
Whilst options (3) and (4) would ensure that treatment is targeted on only those patients with an ulcer infected with H.pylori, they are more invasive and expensive and have potentially large consequences for endoscopy services. However even option (4), in which everyone has endoscopy, has been shown to be more cost-effective than the more usual long-term use of H2-antagonists or proton pump inhibitors .
Large randomised controlled trials are currently underway in primary care settings which will provide information on the effectiveness of different strategies.
ASSESSMENT OF ERADICATION
H.pylori is defined as being eradicated when it is shown to be absent at least four weeks after completion of treatment 11. Eradication can be assessed by the breath test, CLO test, histology or culture, but not by serology. In many cases there may be no benefit from verifying eradication in patients whose symptoms have resolved. Assessment may be important however in monitoring eradication rates and antibiotic resistance within an area.
RECOMMENDATIONS FOR MOLDOVA
1.Clinicians and managers should ensure that a clear policy and treatment protocols are developed in primary and secondary care for the investigation, diagnosis and treatment of patients with suspected peptic ulcer and H.pylori.
2. All patients with proven non-NSAID related peptic ulcer presently on maintenance therapy should be considered for a course of eradication therapy.
3. All patients with newly diagnosed peptic ulcer should be considered for a course of eradication therapy.
4. Health authorities should ensure that there is adequate provision of diagnostic facilities for H.pylori for primary care.
5. Clinicians should only use eradication treatments for which good evidence of cost-effectiveness exists. Unevaluated regimens should only be used within the context of randomised controlled trials.
6. As the evidence in this field is accumulating rapidly, clinicians in Moldova should maintain an awareness of the research in this area, particularly with respect to optimal eradication therapies and diagnostic strategies. There is at present no evidence that a policy of screening asymptomatic patients would be beneficial, so a pilot screening test in one of districts from Moldova will be plausible.
7. Districts should monitor eradication rates and antibiotic resistance as these vary across the Republic of Moldova.
Action: Helicobacter Pylori screening program with breath testing, control and prevention of NSAID side effect (only under medical prescription and with stomach protection ), H.Pylori eradication, Health promotion action (educational programs for doctors and patient).
Conclusion
PUD affects a substantial number of Moldavians and is associated with significant morbidity, mortality and costs to the health care system. Although long considered a recurring disease, the eradication of H. pylori may facilitate a cure. Public health can play an important role in working with patients and health care professionals to optimize treatment, achieve a cure and decrease the likelihood of treatment- associated complications.
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