Su1184 A Randomised Study Comparing 10 Days Concomitant and Sequential Treatments for the...

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Su1181 Combination Therapy With Eradication Agents Is Useful for Successful Eradication of Helicobacter pylori in Japan Tomoari Kamada, Kazuhiko Inoue, Noriaki Manabe, Minoru Fujita, Hiroshi Matsumoto, Hiroshi Imamura, Ken-ichi Tarumi, Naohito Yamashita, Hiroaki Kusunoki, Keisuke Honda, Tetsuo Watanabe, Akiko Shiotani, Jiro Hata, Ken Haruma Background: Eradication therapy for Helicobacter pylori-related chronic gastritis was approved for coverage by the Japanese national insurance in February 2013. Therefore, the use of eradication therapy has rapidly increased in Japan. The primary eradication rate of H. pylori using the 7-day triple therapy has gradually decreased in recent years. Drug resistance to clarithromycin (CAM), poor treatment compliance, and smoking are factors associated with eradication failure. A recent study showed that combination of eradication agents is useful for increasing eradication success, because combination treatments are prepared using daily dosages on one sheet. In our study, we prospectively compared the eradication rate in patients receiving conventional therapy with three drugs to that in patients receiving combination therapy. Patients and methods: Between July 2012 and September 2013, we included 276 patients (147 men and 129 women; mean age, 62.2 years) with H. pylori-positive peptic ulcers and gastritis. Combination therapy (Lansap®; lansoprazole 30 mg plus amoxicillin 750 mg plus CAM 200 mg) was administered to 54 patients twice a day for 7 days, and conventional therapy (omeprazole 20 mg or esomeprazole 20 mg or rabeprazole 20 mg plus amoxicillin 750 mg plus CAM 200 mg) was administered to 221 patients as individual drugs twice a day for 7 days. The 13C-urea breath test was used to confirm the eradication of H. pylori at least 6 weeks after the completion of eradication therapy. Patients who had undergone H. pylori eradication therapy in the past and patients who used proton pump inhibitors and antibiotics within 4 weeks were excluded. Results: No significant difference was observed in the background criteria of patients between the combination group and conventional group. The eradication rate (per protocol analysis) in the combination group was 90.3% (47/52), which was significantly different from that in the conventional group (74.9%; 161/215; p< 0.01). In addition, the eradication rate in intention-to-treat (ITT) analysis was significantly higher in the combination group (85.4%, 47/55) than in the conventional group (72.8%, 161/221; p< 0.01). No significant difference was observed in the incidence of adverse drug reactions (such as diarrhea, dysgeusia, and eruption) between the two groups (combination group 4.1%; conventional group 4.7%). Conclusions: Our study suggested that combination therapy with eradication agents is more useful for successful eradication of H. pylori than conventional therapy, although the primary eradication rate has decreased in Japan in the recent years. The underlying reason for the decrease in the primary eradication rate might be greater compliance to combination therapy. Su1182 Usefulness of the Non-Invasive Rapid Urease Test Using Gastric Mucus for the Diagnosis of Helicobacter pylori Infection Tomoari Kamada, Ken Haruma, Tetsuo Watanabe, Machi Tsukamoto, Takahisa Murao, Manabu Ishii, Minoru Fujita, Hiroshi Matsumoto, Hiroshi Imamura, Noriaki Manabe, Ken-ichi Tarumi, Naohito Yamashita, Hiroaki Kusunoki, Keisuke Honda, Kazuhiko Inoue, Jiro Hata, Akiko Shiotani Background and Objectives: Helicobacter pylori is a microaerophilic, gram negative, patho- genic bacterium that produces the enzyme urease. These organisms are usually present in the gastric mucus and lumen of the gastric pit. The rapid urease test (RUT), which is invasive and based on bacterial urease production, is frequently performed to detect H. pylori because it is a rapid and easy endoscopic method. Non-invasive diagnosis of H. pylori infection is very important in patients receiving anticoagulants because of an increased risk of bleeding associated with specimen collection. However, biopsy samples need to be obtained during endoscopy for accurate diagnosis of H. pylori infection by the RUT. Our study aimed to compare the accuracy of the non-invasive RUT using gastric mucus samples with that of conventional RUT using gastric biopsy specimens. Subjects and Methods: The study included 270 patients (126 men, 144 women; mean age, 56.2 years; 39 post-eradicated patients) with dyspepsia who underwent endoscopic examination at two hospitals from April 2013 until October 2013. After routine endoscopic examination, gastric mucus was collected for the non-invasive RUT and a biopsy sample was collected for the conventional RUT using a biopsy forceps through the channel of the endoscope along the greater curvature of the corpus in all subjects. These samples were examined for the presence of H. pylori 2 h after sample collection using the same RUT kit. Exclusion criteria included a 1-month history of proton pump inhibitor use. Results: There were no differences in the baseline characteristics between the non-invasive RUT group and the conventional RUT group. The overall accor- dance rate was 97.8% (264/270) between the groups. In 120 H. pylori-positive patients who underwent conventional RUT, the accordance rate was 95.8% (115/120) for non- invasive RUT, and in 150 H. pylori-negative patients who underwent conventional RUT, the accordance rate was 99.3% (149/150) for non-invasive RUT. In the H. pylori-eradicated group, the accordance rate was 94.8% (37/39) between the groups. Conclusions: The RUT using a gastric mucus sample can accurately detect H. pylori during screening. In addition, this method could be useful to prevent the risk of developing bleeding complications such as cardiovascular or cerebral diseases in patients receiving anticoagulants. Su1183 Rebamipide, Mucosal-Protective and Ulcer-Healing Drug, Improves Chronic Inflammation of the Corpus After H. pylori Eradication: A Multicenter Study in Japan Tomoari Kamada, Motonori Sato, Tadashi Tokutomi, Mutsuhiro Hara, Tetsuo Watanabe, Takahisa Murao, Hiroshi Matsumoto, Noriaki Manabe, Masanori Ito, Kazuhiko Inoue, Akiko Shiotani, Takashi Akiyama, Jiro Hata, Ken Haruma Background and Objectives: H. pylori infection is closely associated with gastric cancer, and preventive effects against gastric cancer by its eradication have been recently demonstrated. However, considering the occasional development of metachronous gastric cancer after H. S-397 AGA Abstracts pylori eradication, it is important to evaluate the need for continuing medication after its eradication. Our previous report indicated that residual inflammation of the corpus after H. pylori eradication is a risk factor for development of metachronous gastric cancer. Rebamipide is a drug used to treat gastritis or gastric ulcer, and it has free radical scavenging activity, antioxidant activity, and anti-inflammatory activity. In this study, we investigated the changes in histological gastritis and subjective symptoms in patients receiving rebamipide treatment after H. pylori eradication. Subjects and Methods: The study included 208 patients who underwent H. pylori eradication after endoscopic treatment for early gastric cancer, gastric ulcers and gastritis. Of these patients, 169 who were confirmed to have achieved successful eradication by the urea breath test, were randomly allocated to 2 groups: the rebamipide group (n= 82) and the untreated group (n= 87). The primary endpoints were the histopatho- logical findings according to the updated Sydney system from the greater curvature of the antrum, greater curvature of the middle corpus, and lesser curvature of the middle corpus at the start of the study and after 1 year. The secondary endpoints were the changes in serum gastrin and pepsinogen levels and changes in subjective symptoms (F scale). Results: Analysis at 1 year after the start of the study was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. No inter-group differences in terms of histological gastritis, serum gastrin levels, serum pepsinogen levels, or F scale score were noted at the start of the study. Mucosal activity and atrophy of the antrum and corpus were improved in the rebamipide group than in the untreated group, but no inter-group difference was significant. However, chronic inflammation affecting the lesser curvature of the corpus was improved to a significantly greater extent in the rebamipide group than in the untreated group (rebamipide group, 1.12 ± 0.56 vs. untreated group, 1.35 ± 0.52; p< 0.05). The serum gastrin and pepsinogen levels and F scale score also decreased significantly after eradication in both groups, but no inter-group difference was evident. Conclusions: Rebami- pide treatment after H. pylori eradication significantly alleviated chronic inflammation of the lesser curvature of the gastric corpus compared to the untreated group. Thus, we believe that long-term rebamipide treatment after H. pylori eradication might be prevent the onset of gastric tumors in the future. Su1184 A Randomised Study Comparing 10 Days Concomitant and Sequential Treatments for the Eradication of Helicobacter pylori, in a High Clarithromycin Resistance Area Sotirios D. Georgopoulos, Elias Xirouchakis, Evanthia Zampeli, Beatriz Martinez- Gonzalez, Elias Grivas, Charis C. Spiliadi, Maria Sotiropoulou, Kalliopi Petraki, Fotini Laoudi, Kostantinos Zografos, Dionyssios N. Sgouras, Panagiotis Kasapidis, Andreas Mentis, Spyridon Michopoulos Aims: Our study compares the effectiveness and safety of quadruple non-bismuth "concomitant" and "sequential" regimens for H. pylori eradication in a high clarithromycin resistance area. Patients and methods: This is a prospective randomised clinical trial in three participating centres from Greece. Up to now we have included 187 H. pylori positive patients, without previous eradication attempt, with functional dyspepsia or peptic ulcer disease. All patients had a positive CLO-test and/or histology and culture. They randomised to receive either sequential (esomeprazole 40 mg and amoxicillin 1 g bid for 5 days, followed by 5 days of esomeprazole 40 mg, clarithromycin 500 mg and metronidazole 500 mg bid), or concomitant treatment (all drugs taken concomitantly bid for 10 days). Eradication was confirmed by 13C-urea breath test or histology 4-6 weeks after treatment. Adverse events and adherence to treatment were evaluated. Results: Ninety two patients (39F/53M, aged 18-83, mean 54years, 38.2% smokers, 28.9% with ulcer disease) allocated to concomitant and 95 (43F/52M, aged 20-94, mean 51.7years, 33.7% smokers, 21.7% with ulcer disease) to sequential treatment. Positive (159/180, 88%) cultures revealed 35.7% resistance to metronidazole, 23.9% to clarithromycin, 8.2% to both and 9.4% to levofloxacin. Eradication rates were, respectively, 89.1% (82/92) versus 80% (76/95) by intention to treat (p=0.1) and 93.1% (82/88) versus 82.6% (76/92) per protocol (p=0.03). Adherence to treatment was overall 98% (95%CI 95,9-99,6) and comparable among regimens. Eradication rates according to resistances were: 37/37, 100% and 40/42, 95.2% for dual sensitive strains (p= 0.4), 18/18, 100% and 19/25, 76% for metronidazole single resistant strains (p=0.032), 9/ 12, 75% and 9/12, 75% for clarithromycin single resistant strains (p=1), and 7/9, 77.7% and 1/4, 25% for dual resistance strains (p=0.2) for concomitant and sequential regimens respectively. Treatment related side effects were reported in 45% of patients, without differ- ences among treatment arms, and no treatment discontinuation. Conclusions: Concomitant treatment has a significant advantage over sequential therapy. Noteworthy, it is overcoming 90% eradication rate in per protocol analysis regardless of the high clarithromycin resistance of the group. This difference is probably due to the lower efficacy of sequential than concomitant regimen on metronidazole resistant strains. Both regimens were well tolerated and safe for the patients. Su1185 Can We Achieve the Same Results From Repetitive Testing of 13CO2 Breath Samples for the Diagnosis of Helicobacter pylori? Tsachi Tsadok Perets, Einav Shporn, Dalal Hamouda, Yaron Niv, Ram Dickman Background: Long-term storage does not affect the stability of breath test samples for the diagnosis of Helicobacter pylori (H.pylori) infection. Unfortunately, results from repetitive testing of 13CO2 of the same breath samples are not available. Aim: To evaluate the repeatability of 13CO2 concentrations in the same breath sample over time. Methods: Consecutive breath samples for the diagnosis of H.pylori were collected in duplicates, before and after administration of 75 mg urea-13C dissolved in 50 ml of orange juice. Results were expressed as delta 13CO2 (d13CO2) and a cut-off value above 3.5 parts per thousand was used to define a positive test. A total of 202 positive breath samples were used for the analysis of repeatability and precision. Each sample was analyzed in a mass spectrometer 7 days after collection, and in intervals of 7 days for an additional 3 weeks, for a total duration of 1 month. Assessment of repeatability and precision was obtained by comparing the d13CO2 of the first run to the results of the three subsequent d13CO2 runs.. All samples were stored at room temperature. Results: In the second run, 200/202 (99%) samples were AGA Abstracts

Transcript of Su1184 A Randomised Study Comparing 10 Days Concomitant and Sequential Treatments for the...

Page 1: Su1184 A Randomised Study Comparing 10 Days Concomitant and Sequential Treatments for the Eradication of Helicobacter pylori, in a High Clarithromycin Resistance Area

Su1181

Combination Therapy With Eradication Agents Is Useful for SuccessfulEradication of Helicobacter pylori in JapanTomoari Kamada, Kazuhiko Inoue, Noriaki Manabe, Minoru Fujita, Hiroshi Matsumoto,Hiroshi Imamura, Ken-ichi Tarumi, Naohito Yamashita, Hiroaki Kusunoki, KeisukeHonda, Tetsuo Watanabe, Akiko Shiotani, Jiro Hata, Ken Haruma

Background: Eradication therapy for Helicobacter pylori-related chronic gastritis wasapproved for coverage by the Japanese national insurance in February 2013. Therefore, theuse of eradication therapy has rapidly increased in Japan. The primary eradication rate ofH. pylori using the 7-day triple therapy has gradually decreased in recent years. Drugresistance to clarithromycin (CAM), poor treatment compliance, and smoking are factorsassociated with eradication failure. A recent study showed that combination of eradicationagents is useful for increasing eradication success, because combination treatments areprepared using daily dosages on one sheet. In our study, we prospectively compared theeradication rate in patients receiving conventional therapy with three drugs to that in patientsreceiving combination therapy. Patients and methods: Between July 2012 and September2013, we included 276 patients (147 men and 129 women; mean age, 62.2 years) with H.pylori-positive peptic ulcers and gastritis. Combination therapy (Lansap®; lansoprazole 30mg plus amoxicillin 750 mg plus CAM 200 mg) was administered to 54 patients twice aday for 7 days, and conventional therapy (omeprazole 20 mg or esomeprazole 20 mg orrabeprazole 20 mg plus amoxicillin 750 mg plus CAM 200 mg) was administered to 221patients as individual drugs twice a day for 7 days. The 13C-urea breath test was used toconfirm the eradication of H. pylori at least 6 weeks after the completion of eradicationtherapy. Patients who had undergone H. pylori eradication therapy in the past and patientswho used proton pump inhibitors and antibiotics within 4 weeks were excluded. Results:No significant difference was observed in the background criteria of patients between thecombination group and conventional group. The eradication rate (per protocol analysis) inthe combination group was 90.3% (47/52), which was significantly different from that inthe conventional group (74.9%; 161/215; p< 0.01). In addition, the eradication rate inintention-to-treat (ITT) analysis was significantly higher in the combination group (85.4%,47/55) than in the conventional group (72.8%, 161/221; p< 0.01). No significant differencewas observed in the incidence of adverse drug reactions (such as diarrhea, dysgeusia, anderuption) between the two groups (combination group 4.1%; conventional group 4.7%).Conclusions: Our study suggested that combination therapy with eradication agents is moreuseful for successful eradication of H. pylori than conventional therapy, although the primaryeradication rate has decreased in Japan in the recent years. The underlying reason for thedecrease in the primary eradication rate might be greater compliance to combination therapy.

Su1182

Usefulness of the Non-Invasive Rapid Urease Test Using Gastric Mucus for theDiagnosis of Helicobacter pylori InfectionTomoari Kamada, Ken Haruma, Tetsuo Watanabe, Machi Tsukamoto, Takahisa Murao,Manabu Ishii, Minoru Fujita, Hiroshi Matsumoto, Hiroshi Imamura, Noriaki Manabe,Ken-ichi Tarumi, Naohito Yamashita, Hiroaki Kusunoki, Keisuke Honda, Kazuhiko Inoue,Jiro Hata, Akiko Shiotani

Background and Objectives: Helicobacter pylori is a microaerophilic, gram negative, patho-genic bacterium that produces the enzyme urease. These organisms are usually present inthe gastric mucus and lumen of the gastric pit. The rapid urease test (RUT), which is invasiveand based on bacterial urease production, is frequently performed to detect H. pylori becauseit is a rapid and easy endoscopic method. Non-invasive diagnosis of H. pylori infection isvery important in patients receiving anticoagulants because of an increased risk of bleedingassociated with specimen collection. However, biopsy samples need to be obtained duringendoscopy for accurate diagnosis of H. pylori infection by the RUT. Our study aimed tocompare the accuracy of the non-invasive RUT using gastric mucus samples with that ofconventional RUT using gastric biopsy specimens. Subjects and Methods: The study included270 patients (126 men, 144 women; mean age, 56.2 years; 39 post-eradicated patients)with dyspepsia who underwent endoscopic examination at two hospitals from April 2013until October 2013. After routine endoscopic examination, gastric mucus was collected forthe non-invasive RUT and a biopsy sample was collected for the conventional RUT usinga biopsy forceps through the channel of the endoscope along the greater curvature of thecorpus in all subjects. These samples were examined for the presence of H. pylori 2 h aftersample collection using the same RUT kit. Exclusion criteria included a 1-month history ofproton pump inhibitor use. Results: There were no differences in the baseline characteristicsbetween the non-invasive RUT group and the conventional RUT group. The overall accor-dance rate was 97.8% (264/270) between the groups. In 120 H. pylori-positive patientswho underwent conventional RUT, the accordance rate was 95.8% (115/120) for non-invasive RUT, and in 150 H. pylori-negative patients who underwent conventional RUT,the accordance rate was 99.3% (149/150) for non-invasive RUT. In the H. pylori-eradicatedgroup, the accordance rate was 94.8% (37/39) between the groups. Conclusions: The RUTusing a gastric mucus sample can accurately detect H. pylori during screening. In addition,this method could be useful to prevent the risk of developing bleeding complications suchas cardiovascular or cerebral diseases in patients receiving anticoagulants.

Su1183

Rebamipide, Mucosal-Protective and Ulcer-Healing Drug, Improves ChronicInflammation of the Corpus After H. pylori Eradication: A Multicenter Studyin JapanTomoari Kamada, Motonori Sato, Tadashi Tokutomi, Mutsuhiro Hara, Tetsuo Watanabe,Takahisa Murao, Hiroshi Matsumoto, Noriaki Manabe, Masanori Ito, Kazuhiko Inoue,Akiko Shiotani, Takashi Akiyama, Jiro Hata, Ken Haruma

Background and Objectives: H. pylori infection is closely associated with gastric cancer, andpreventive effects against gastric cancer by its eradication have been recently demonstrated.However, considering the occasional development of metachronous gastric cancer after H.

S-397 AGA Abstracts

pylori eradication, it is important to evaluate the need for continuing medication after itseradication. Our previous report indicated that residual inflammation of the corpus after H.pylori eradication is a risk factor for development of metachronous gastric cancer. Rebamipideis a drug used to treat gastritis or gastric ulcer, and it has free radical scavenging activity,antioxidant activity, and anti-inflammatory activity. In this study, we investigated the changesin histological gastritis and subjective symptoms in patients receiving rebamipide treatmentafter H. pylori eradication. Subjects and Methods: The study included 208 patients whounderwent H. pylori eradication after endoscopic treatment for early gastric cancer, gastriculcers and gastritis. Of these patients, 169 who were confirmed to have achieved successfuleradication by the urea breath test, were randomly allocated to 2 groups: the rebamipidegroup (n= 82) and the untreated group (n= 87). The primary endpoints were the histopatho-logical findings according to the updated Sydney system from the greater curvature of theantrum, greater curvature of the middle corpus, and lesser curvature of the middle corpusat the start of the study and after 1 year. The secondary endpoints were the changes inserum gastrin and pepsinogen levels and changes in subjective symptoms (F scale). Results:Analysis at 1 year after the start of the study was possible in 50 cases from the rebamipidegroup and 53 cases from the untreated group. No inter-group differences in terms ofhistological gastritis, serum gastrin levels, serum pepsinogen levels, or F scale score werenoted at the start of the study. Mucosal activity and atrophy of the antrum and corpus wereimproved in the rebamipide group than in the untreated group, but no inter-group differencewas significant. However, chronic inflammation affecting the lesser curvature of the corpuswas improved to a significantly greater extent in the rebamipide group than in the untreatedgroup (rebamipide group, 1.12 ± 0.56 vs. untreated group, 1.35 ± 0.52; p< 0.05). Theserum gastrin and pepsinogen levels and F scale score also decreased significantly aftereradication in both groups, but no inter-group difference was evident. Conclusions: Rebami-pide treatment after H. pylori eradication significantly alleviated chronic inflammation ofthe lesser curvature of the gastric corpus compared to the untreated group. Thus, we believethat long-term rebamipide treatment after H. pylori eradication might be prevent the onsetof gastric tumors in the future.

Su1184

A Randomised Study Comparing 10 Days Concomitant and SequentialTreatments for the Eradication of Helicobacter pylori, in a High ClarithromycinResistance AreaSotirios D. Georgopoulos, Elias Xirouchakis, Evanthia Zampeli, Beatriz Martinez-Gonzalez, Elias Grivas, Charis C. Spiliadi, Maria Sotiropoulou, Kalliopi Petraki, FotiniLaoudi, Kostantinos Zografos, Dionyssios N. Sgouras, Panagiotis Kasapidis, AndreasMentis, Spyridon Michopoulos

Aims: Our study compares the effectiveness and safety of quadruple non-bismuth"concomitant" and "sequential" regimens for H. pylori eradication in a high clarithromycinresistance area. Patients and methods: This is a prospective randomised clinical trial in threeparticipating centres from Greece. Up to now we have included 187 H. pylori positivepatients, without previous eradication attempt, with functional dyspepsia or peptic ulcerdisease. All patients had a positive CLO-test and/or histology and culture. They randomisedto receive either sequential (esomeprazole 40 mg and amoxicillin 1 g bid for 5 days, followedby 5 days of esomeprazole 40 mg, clarithromycin 500 mg and metronidazole 500 mg bid),or concomitant treatment (all drugs taken concomitantly bid for 10 days). Eradication wasconfirmed by 13C-urea breath test or histology 4-6 weeks after treatment. Adverse eventsand adherence to treatment were evaluated. Results: Ninety two patients (39F/53M, aged18-83, mean 54years, 38.2% smokers, 28.9% with ulcer disease) allocated to concomitantand 95 (43F/52M, aged 20-94, mean 51.7years, 33.7% smokers, 21.7% with ulcer disease)to sequential treatment. Positive (159/180, 88%) cultures revealed 35.7% resistance tometronidazole, 23.9% to clarithromycin, 8.2% to both and 9.4% to levofloxacin. Eradicationrates were, respectively, 89.1% (82/92) versus 80% (76/95) by intention to treat (p=0.1)and 93.1% (82/88) versus 82.6% (76/92) per protocol (p=0.03). Adherence to treatmentwas overall 98% (95%CI 95,9-99,6) and comparable among regimens. Eradication ratesaccording to resistances were: 37/37, 100% and 40/42, 95.2% for dual sensitive strains (p=0.4), 18/18, 100% and 19/25, 76% for metronidazole single resistant strains (p=0.032), 9/12, 75% and 9/12, 75% for clarithromycin single resistant strains (p=1), and 7/9, 77.7%and 1/4, 25% for dual resistance strains (p=0.2) for concomitant and sequential regimensrespectively. Treatment related side effects were reported in 45% of patients, without differ-ences among treatment arms, and no treatment discontinuation. Conclusions: Concomitanttreatment has a significant advantage over sequential therapy. Noteworthy, it is overcoming90% eradication rate in per protocol analysis regardless of the high clarithromycin resistanceof the group. This difference is probably due to the lower efficacy of sequential thanconcomitant regimen on metronidazole resistant strains. Both regimens were well toleratedand safe for the patients.

Su1185

Can We Achieve the Same Results From Repetitive Testing of 13CO2 BreathSamples for the Diagnosis of Helicobacter pylori?Tsachi Tsadok Perets, Einav Shporn, Dalal Hamouda, Yaron Niv, Ram Dickman

Background: Long-term storage does not affect the stability of breath test samples for thediagnosis of Helicobacter pylori (H.pylori) infection. Unfortunately, results from repetitivetesting of 13CO2 of the same breath samples are not available. Aim: To evaluate therepeatability of 13CO2 concentrations in the same breath sample over time. Methods:Consecutive breath samples for the diagnosis of H.pylori were collected in duplicates, beforeand after administration of 75 mg urea-13C dissolved in 50 ml of orange juice. Results wereexpressed as delta 13CO2 (d13CO2) and a cut-off value above 3.5 parts per thousand wasused to define a positive test. A total of 202 positive breath samples were used for theanalysis of repeatability and precision. Each sample was analyzed in a mass spectrometer 7days after collection, and in intervals of 7 days for an additional 3 weeks, for a total durationof 1 month. Assessment of repeatability and precision was obtained by comparing thed13CO2 of the first run to the results of the three subsequent d13CO2 runs.. All sampleswere stored at room temperature. Results: In the second run, 200/202 (99%) samples were

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