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Intermediate H. pylori (Hp) seroprevalence rates in Canadian inuit, despite detection of Hp DNA from local water
April 1998
• G0912 INTERMEDIATE H. PYLORI (Hp) SEROPREVALENCE RATES IN CANADIAN INUIT, DESPITE DETECTION OF Hp DNA FROM LOCAL WATER. I Mckeown, P Orr, A Kabani, J Embil, M Dawood, G Coghlan, G Smart, S Macdonald, M Sargent, and CN Bernstein. Depts. of Medicine, Medical Microbiology, and Community Medicine, University of Manitoba, Cadham Provincial Laboratory & Rh Research Lab, Winnipeg, Manitoba, Canada Last year we reported very high seroprevalence rates among Canada's Native Indians living in a northern community with living conditions similar to developing nations (GE !997 A216). Aims: a) determine the seroprevaience of Hp among Inuit of the Canadian central Arctic, b) determine whether Hp could be detected by PCR from local water supplies. Methods: Subjects from Chesterfield Inlet (CI) (pop=314), and Repulse Bay (RB) (pop=514), 2 traditional Inuit communities underwent health and demographic interviews and l0 cc venipuncture. RBCs were analyzed for ABO and Lewis blood groups and serum was batch analyzed for Hp IgG by ELISA. 4 L batches of water were collected from various water source sites and frozen until ready for PCR DNA amplification. Nested PCR was performed using Hp-specific primers and the amplicons probed with an internal Dig-labeled probe. The labeled probe sequence used was CTAGAGACTATGATGTGCTG. Results: 261/818 (32%) subjects from 82% of potential households were enrolled with a mean age of 31.7 yrs. The communities were similar in all demographic respects except for higher rates of heartburn (23.7%) and dyspepsia (35.1%) in CI compared with 10.9% and 19.7% in RB and lower rates of having > 7 inhabitants/dwelling in CI (10.5%) vs RB (47.6%). Household chlorinated water (1980 in CI, 1969 in RB) and flush toilets (1985 in CI~ 1980 in RB) were the norm. 50.9% of subjects in CI and 51% in RB were seropositive for Hp. Of Hp seropositive cases, 56.7% were seropositive for Cag A. 53.3% and 45% were blood type O, and A, respectively and 92.6% were Lewis (a-b+). Although significantly more males than females in RB were Hp positive there were no other significant predictors of Hp positivity. There was no difference in Hp positivity based on cohort analysis of subjects born before or after water treatment and flush toilets were introduced. Hp DNA was recovered from the water delivery truck but not the lakes in CI and from the lakes but not the delivery truck in RB. Conclusions: The seroprevalence rate of HP in the Inuit of Canada is intermediate between that of developing and developed communities. Hp DNA is found in the water of these Inuit communities. Although all subjects have chlorinated water delivered to their homes and flush toilets, these have relatively recently been introduced. Any effects of improved water and toileting sanitation may be overridden by overcrowding of living conditions. Furthermore, their traditional lifestyles involve much time away from home and the use of potable water sources. It is possible that seroprevalence rates are lower than expected because of host susceptibility factors yet to be defined. • G0913 ENDOSCOPIC DILATATION IS SAFE AND EFFECTIVE IN TREATING THE ESOPHAGEAL STRICTURES OF EPIDERMOLYSIS BULLOSA. J Meenan; RPH Thompson. Dept. Gastroenterology, St. Thomas' Hospital, London, United Kingdom. Epidermal blister formation and subsequent scarfing are the hallmarks of dystrophic epidermolysis bullosa (EB). Esophageal stricturing occurs commonly and compromises markedly the nutritional status of these patients. The safety and value of endoscopic oesophageal dilatation in EB is uncertain as the necessary radial force applied may lead to further stricture formation and perforation is thought to be common. METHODS: Forty-seven patients with EB (male:14, femaie:33) of median age 17 yrs. (3-61yrs.) at index endoscopy, were evaluated by barium swallow/video fluoroscopy. Patients were given a general anaesthetic using a laryngeal mask, obviating the need for tracheal intubation. Endoscopy was performed using a paediatric endoscope (Olympus PQ20). Stricture dilatation was performed using "through the scope" (TTS) balloon catheters (Microvasive). A balloon (45Fr or 48Fr), length 8crn, was inflated to 45psi for 2 minutes. Therapeutic benefit was evaluated by a gastroenterology/dietetic team. The procedure was repeated until dysphagia was relieved, or, if symptoms recurred at a later date. RESULTS: A median of 2 barium studies (0-16) were performed per patient, identifying strictures at a median 20cm from the incisors (15-29cm). Each patient underwent a median of 1 dilatation (1-14) with a median follow-up period of 3.5yrs. (0.3-7.5yrs.). Two procedures failed, but, subsequent attempts were successful. One anaesthetic-related death occurred. DISCUSSION: These results suggest that endoscopic dilatation for EB-related esophageal strictures is not associated with a large risk of perforation. Additionally, this procedure is of long-lasting benefit in the relief of dysphagia.
Esophageal, Gastric, and Duodenal Disorders A223 G0914 CAN A COMPUTERIZED NEURAL NETWORK IDENTIFY RESPONDERS TO OMEPRAZOLE IN PATIENTS WITH DYSPEPSIA? ANALYSIS OF A DANISH MULTICENTER TRIAL IN GENERAL PRACTICE. _V., Meineche-Schmidt., E. Christensen. Dept. of General Practice, The Panum Institute, Dept. of Internal Medicine 1, Bispebjerg Hospital, University of Copenhagen, Denmark.
The effect of omeprazole in dyspepsia is difficult to predict. It is of interest to investigate if certain combinations of data characterizing the patients can identify responders and non-responders to omeprazole therapy. Computerized neural network analysis is a new powerful method that allows simultaneous appreciation of numerous inputs to predict a given output. Aim: To investigate if a neural network could be developed to identify responders to omeprazole among patients with dyspepsia. Method: Our recent randomized clinical trial including 471 patients with ulcer-like or reflux-like dyspepsia (defined according to the proposal of an International Working Party (1)) demonstrated complete relief of symptoms in 50% after omeprazole (N=243) 20 mg daily for 2 weeks and in 35% after placebo (N=228). The 471 patients were randomly divided in a model sample (N=236) and a test sample (N=235). The model sample was used to develop a feed forward neural network with 16 inputs (15 variables showing some (p < 0.2) association with the treatment effect, and the treatment variable), 11 hidden units and one output (the response) using sigmoidai transfer functions and back propagation training. Using the trained network, the predicted outcome was obtained for each patient in the test sample, both for the given treatment and for the other treatment to give the predicted therapeutic gain of omeprazole. Results: The neural network predicted 89 as poor, 102 as medium, and 44 as good omeprazole responders. However, in these groups the observed therapeutic gain of omeprazole was 20%, 17% and 24%, respectively (p:NS). Neural networks with a larger and a smaller number of input variables and hidden units did not improve the results. Conclusion.: The ability of the neural network to identify responders to omeprazole in dyspepsia was poor and markedly less than that of a previously presented therapeutic index developed from the same data using logistic regression analysis. [1] Colin Jones DG. Lancet 1988; i: 576-9. This study was supported in part by Astra, Denmark. G0915 HEALTHCARE CONSUMPTION AND QUALITY OF LIFE IN PATIENTS WITH FUNCTIONAL DYSPEPSIA AFTER OMEPRAZOLE TREATMENT. V. Meineche-Schmidt*, N.J. Talley, A. Pap, H. Kordecki, V. Schmid, L. Ohlsson, P. Wahlqvist, I. Wiklund, E. Bolling-Steruevald, B. Hermenius, (on behalf of an international Multicentre Study Group). *General Practice, Kokkedal, Denmark. Background & Aim: Patients with functional dyspepsia have symptoms that fluctuate over time. The impact of the disease on health care consumption is largely unknown and in particular the long term economic and clinical value of providing symptom control has not been documented. We aimed to follow patients for 3 months after a four week treatment period to evaluate the impact of initial therapy on health care consumption, absence from work and quality of life. Methods: Patients from six European countries (Denmark, France, Germany, Holland, Hungary and Poland) (n=567, 215 males, 18-80 years) diagnosed with functional dyspepsia and previously treated in a four week study with omeprazole 20 mg, 10 mg or identical placebo, were eligible for inclusion in a 3 month follow-up study off therapy. Healthcare consumption after the initial 4 week treatment period was measured in terms of number of clinic visits and days on medication due to dyspeptic symptoms. Direct medical costs (clinic visits and medication) and total costs (adding costs due to absence from work) were calculated for each participating country. Quality of life was measured at study entry (baseline) and after 3 months, using validated measures (Psycological General Wellbeing Index and Gastrointestinal Symptom Rating Scale). Results: On an Intention-To-Treat (IT]') analysis (n=559), patients with complete relief of symptoms at the end of the initial 4 week treatment had fewer clinic visits (1.5 versus 2.0 mean visits), fewer days on medication (9 versus 22.7 mean days) and fewer hours of absence from work (1.5 versus 3.4 mean hours) over the three month period. The mean direct medical costs were significantly lower for patients with complete relief of symptoms at study entry than for patients with symptoms in four out of the six countries (France, Germany, Hungary and Poland) and the mean total costs were significantly lower in three of the countries (France, Hungary and Poland). Quality of life (PGWB) was better still after three months for patients who had achieved complete relief of symptoms compared with those who had persistent symptoms at entry. Conclusions: The results suggest that symptom resolution in patients with functional dyspepsia reduces subsequent healthcare costs as well as total costs, including absence from work and has a positive impact on quality of life in a period of at least 3 months after cessation of initial treatment. This study was supported by Astra H~issle AB, Sweden
• G0912 INTERMEDIATE H. PYLORI (Hp) SEROPREVALENCE RATES IN CANADIAN INUIT, DESPITE DETECTION OF Hp DNA FROM LOCAL WATER. I Mckeown, P Orr, A Kabani, J Embil, M Dawood, G Coghlan, G Smart, S Macdonald, M Sargent, and CN Bernstein. Depts. of Medicine, Medical Microbiology, and Community Medicine, University of Manitoba, Cadham Provincial Laboratory & Rh Research Lab, Winnipeg, Manitoba, Canada Last year we reported very high seroprevalence rates among Canada's Native Indians living in a northern community with living conditions similar to developing nations (GE !997 A216). Aims: a) determine the seroprevaience of Hp among Inuit of the Canadian central Arctic, b) determine whether Hp could be detected by PCR from local water supplies. Methods: Subjects from Chesterfield Inlet (CI) (pop=314), and Repulse Bay (RB) (pop=514), 2 traditional Inuit communities underwent health and demographic interviews and l0 cc venipuncture. RBCs were analyzed for ABO and Lewis blood groups and serum was batch analyzed for Hp IgG by ELISA. 4 L batches of water were collected from various water source sites and frozen until ready for PCR DNA amplification. Nested PCR was performed using Hp-specific primers and the amplicons probed with an internal Dig-labeled probe. The labeled probe sequence used was CTAGAGACTATGATGTGCTG. Results: 261/818 (32%) subjects from 82% of potential households were enrolled with a mean age of 31.7 yrs. The communities were similar in all demographic respects except for higher rates of heartburn (23.7%) and dyspepsia (35.1%) in CI compared with 10.9% and 19.7% in RB and lower rates of having > 7 inhabitants/dwelling in CI (10.5%) vs RB (47.6%). Household chlorinated water (1980 in CI, 1969 in RB) and flush toilets (1985 in CI~ 1980 in RB) were the norm. 50.9% of subjects in CI and 51% in RB were seropositive for Hp. Of Hp seropositive cases, 56.7% were seropositive for Cag A. 53.3% and 45% were blood type O, and A, respectively and 92.6% were Lewis (a-b+). Although significantly more males than females in RB were Hp positive there were no other significant predictors of Hp positivity. There was no difference in Hp positivity based on cohort analysis of subjects born before or after water treatment and flush toilets were introduced. Hp DNA was recovered from the water delivery truck but not the lakes in CI and from the lakes but not the delivery truck in RB. Conclusions: The seroprevalence rate of HP in the Inuit of Canada is intermediate between that of developing and developed communities. Hp DNA is found in the water of these Inuit communities. Although all subjects have chlorinated water delivered to their homes and flush toilets, these have relatively recently been introduced. Any effects of improved water and toileting sanitation may be overridden by overcrowding of living conditions. Furthermore, their traditional lifestyles involve much time away from home and the use of potable water sources. It is possible that seroprevalence rates are lower than expected because of host susceptibility factors yet to be defined. • G0913 ENDOSCOPIC DILATATION IS SAFE AND EFFECTIVE IN TREATING THE ESOPHAGEAL STRICTURES OF EPIDERMOLYSIS BULLOSA. J Meenan; RPH Thompson. Dept. Gastroenterology, St. Thomas' Hospital, London, United Kingdom. Epidermal blister formation and subsequent scarfing are the hallmarks of dystrophic epidermolysis bullosa (EB). Esophageal stricturing occurs commonly and compromises markedly the nutritional status of these patients. The safety and value of endoscopic oesophageal dilatation in EB is uncertain as the necessary radial force applied may lead to further stricture formation and perforation is thought to be common. METHODS: Forty-seven patients with EB (male:14, femaie:33) of median age 17 yrs. (3-61yrs.) at index endoscopy, were evaluated by barium swallow/video fluoroscopy. Patients were given a general anaesthetic using a laryngeal mask, obviating the need for tracheal intubation. Endoscopy was performed using a paediatric endoscope (Olympus PQ20). Stricture dilatation was performed using "through the scope" (TTS) balloon catheters (Microvasive). A balloon (45Fr or 48Fr), length 8crn, was inflated to 45psi for 2 minutes. Therapeutic benefit was evaluated by a gastroenterology/dietetic team. The procedure was repeated until dysphagia was relieved, or, if symptoms recurred at a later date. RESULTS: A median of 2 barium studies (0-16) were performed per patient, identifying strictures at a median 20cm from the incisors (15-29cm). Each patient underwent a median of 1 dilatation (1-14) with a median follow-up period of 3.5yrs. (0.3-7.5yrs.). Two procedures failed, but, subsequent attempts were successful. One anaesthetic-related death occurred. DISCUSSION: These results suggest that endoscopic dilatation for EB-related esophageal strictures is not associated with a large risk of perforation. Additionally, this procedure is of long-lasting benefit in the relief of dysphagia.
Esophageal, Gastric, and Duodenal Disorders A223 G0914 CAN A COMPUTERIZED NEURAL NETWORK IDENTIFY RESPONDERS TO OMEPRAZOLE IN PATIENTS WITH DYSPEPSIA? ANALYSIS OF A DANISH MULTICENTER TRIAL IN GENERAL PRACTICE. _V., Meineche-Schmidt., E. Christensen. Dept. of General Practice, The Panum Institute, Dept. of Internal Medicine 1, Bispebjerg Hospital, University of Copenhagen, Denmark.
The effect of omeprazole in dyspepsia is difficult to predict. It is of interest to investigate if certain combinations of data characterizing the patients can identify responders and non-responders to omeprazole therapy. Computerized neural network analysis is a new powerful method that allows simultaneous appreciation of numerous inputs to predict a given output. Aim: To investigate if a neural network could be developed to identify responders to omeprazole among patients with dyspepsia. Method: Our recent randomized clinical trial including 471 patients with ulcer-like or reflux-like dyspepsia (defined according to the proposal of an International Working Party (1)) demonstrated complete relief of symptoms in 50% after omeprazole (N=243) 20 mg daily for 2 weeks and in 35% after placebo (N=228). The 471 patients were randomly divided in a model sample (N=236) and a test sample (N=235). The model sample was used to develop a feed forward neural network with 16 inputs (15 variables showing some (p < 0.2) association with the treatment effect, and the treatment variable), 11 hidden units and one output (the response) using sigmoidai transfer functions and back propagation training. Using the trained network, the predicted outcome was obtained for each patient in the test sample, both for the given treatment and for the other treatment to give the predicted therapeutic gain of omeprazole. Results: The neural network predicted 89 as poor, 102 as medium, and 44 as good omeprazole responders. However, in these groups the observed therapeutic gain of omeprazole was 20%, 17% and 24%, respectively (p:NS). Neural networks with a larger and a smaller number of input variables and hidden units did not improve the results. Conclusion.: The ability of the neural network to identify responders to omeprazole in dyspepsia was poor and markedly less than that of a previously presented therapeutic index developed from the same data using logistic regression analysis. [1] Colin Jones DG. Lancet 1988; i: 576-9. This study was supported in part by Astra, Denmark. G0915 HEALTHCARE CONSUMPTION AND QUALITY OF LIFE IN PATIENTS WITH FUNCTIONAL DYSPEPSIA AFTER OMEPRAZOLE TREATMENT. V. Meineche-Schmidt*, N.J. Talley, A. Pap, H. Kordecki, V. Schmid, L. Ohlsson, P. Wahlqvist, I. Wiklund, E. Bolling-Steruevald, B. Hermenius, (on behalf of an international Multicentre Study Group). *General Practice, Kokkedal, Denmark. Background & Aim: Patients with functional dyspepsia have symptoms that fluctuate over time. The impact of the disease on health care consumption is largely unknown and in particular the long term economic and clinical value of providing symptom control has not been documented. We aimed to follow patients for 3 months after a four week treatment period to evaluate the impact of initial therapy on health care consumption, absence from work and quality of life. Methods: Patients from six European countries (Denmark, France, Germany, Holland, Hungary and Poland) (n=567, 215 males, 18-80 years) diagnosed with functional dyspepsia and previously treated in a four week study with omeprazole 20 mg, 10 mg or identical placebo, were eligible for inclusion in a 3 month follow-up study off therapy. Healthcare consumption after the initial 4 week treatment period was measured in terms of number of clinic visits and days on medication due to dyspeptic symptoms. Direct medical costs (clinic visits and medication) and total costs (adding costs due to absence from work) were calculated for each participating country. Quality of life was measured at study entry (baseline) and after 3 months, using validated measures (Psycological General Wellbeing Index and Gastrointestinal Symptom Rating Scale). Results: On an Intention-To-Treat (IT]') analysis (n=559), patients with complete relief of symptoms at the end of the initial 4 week treatment had fewer clinic visits (1.5 versus 2.0 mean visits), fewer days on medication (9 versus 22.7 mean days) and fewer hours of absence from work (1.5 versus 3.4 mean hours) over the three month period. The mean direct medical costs were significantly lower for patients with complete relief of symptoms at study entry than for patients with symptoms in four out of the six countries (France, Germany, Hungary and Poland) and the mean total costs were significantly lower in three of the countries (France, Hungary and Poland). Quality of life (PGWB) was better still after three months for patients who had achieved complete relief of symptoms compared with those who had persistent symptoms at entry. Conclusions: The results suggest that symptom resolution in patients with functional dyspepsia reduces subsequent healthcare costs as well as total costs, including absence from work and has a positive impact on quality of life in a period of at least 3 months after cessation of initial treatment. This study was supported by Astra H~issle AB, Sweden