The Comparison Of Four Methods In Diagnosis And 10-day Sequential Therapy In Clinical Research Of Helicobacter Pylori Infection In Children

Objective1. To investigate the detection rate of Helicobacter pylori(H.pylori) in children with gastroduodenal disease.2. To evaluate the clinical values of four methods including H.pylori culture,¹³C urea breath test(¹³C-UBT),histological examination and rapid urease test(RUT) in diagnosis of H.pylori infection in children.Subjects and Methods1. Subjects:1.1 1132 children were the ones who needed undergoing endoscopy due to digestive disorders.According to the inclusion criteria, 142 patients were enrolled in this study, including 87 boys and 55 girls,the ratio of the boys and the girls was 1.58:1, the average age was 7.3 years, range 3¹4years. 74 cases were diagnosed as chronic superficial gastritis, 62 cases as chronic superficial gastritis with duodenal inflammation and 6 cases as duodenal ulcer by endoscopy.1.2 Inclusion criteria:â‘ None of the patients had recieved antibiotics, proton pump inhibitors, H2-receptor antagonists or nonsteroidal anti-inflammatory durgs in one month before undergoing gastroscope;â‘¡All included patients were done ¹³C-UBT the day before gastroscope;â‘¢All the patients included were underwent RUT, histological detection and H.pylori culture. 1.3 Exclusion ctiteria: the patient who had not done all the checkings were excluded.1.4 Diagnostic criteria[1]: H.pylori culture was positive or any two results that was RUT and ¹³C-UBT and histological detection positive confirmed H.pylori positive.2. Methods2.1 ¹³C-UBT: according to delta over baseline(DOB) to judge the results,DOB values≥4.0 were positive, <4.0 were negative.2.2 3 mucosal biopsies specimens were take from gastric antral mucosa in the diameter of 5 cm, one for rapid urease reaction, one placed in 10% formaldehyde and sent to pathology within 4h for histological examination, and one stored in 4℃refrigerator and sent to the laboratory within 2h for H.pylori culture.3. Statistical analysis: Data were analyzed by SPSS version 13.0. Data for different groups were analyzed usingχ2 test and Fisher exact test. Difference was considered statistically significantly for P value less than 0.05(P<0.05). Evaluate its reliability and accuracy according to calculate its sensitivity and specificity.Results1. The prevalence rate of H.pylori1.1 With H.pylori research diagnostic criteria as the diagnostic criteria , 76 cases were detected H.pylori positive in 142 cases ,which the prevalence was 53.5% (76/142). 29, 41 and 6 cases were detected H.pylori positive in 74 cases of chronic superficial gastritis and 62 cases of chronic superficial gastritis with duodenal inflammation and 6 cases of duodenal ulcer, which the prevalence rate of H.pylori were 39.2%, 66.1% and 100% respectively.1.2 The prevalence rate of H.pylori of chronic superficial gastritis and chronic superficial gastritis with duodenal inflammation was significantly different(χ2=9.802,P=0.002<0.05). The prevalence rate of H.pylori of chronic superficial gastritis and duodenal ulcer was significantly different(χ²=8.340,P=0.005<0.05). The prevalence rate of H.pylori of chronic superficial gastritis with duodenal inflammation and duodenal ulcer was not significantly different(χ2=2.940,P=0.166>0.05).2. With"total positive rate"as the diagnostic criteria, the clinical value of four methodsThe sensitivity of the four methods which were H.pylori culture and ¹³C-UBT and histological examination and RUT respectively were 97.4%, 94.7%, 84.2%, 89.5%, while the specificity and accuracy of the four methods were 100%, 98.5%, 97.0%, 81.8% and 98.6%,96.5%,90.1%,85.9% respectively, while the false positive rate and the false negative rate were 0%, 1.5%, 3.0%, 18.2% and 2.6%, 96.5%, 5.8%, 10.5% respectively.3. The"bacterial culture"as the diagnostic criteria, the clinical value of the other three methodsThe sensitivity of the other three methods which ¹³C-UBT and histological examination and RUT respectively was 97.3%, 85.1%, 89.2%, while the specificity and accuracy of the three methods were 98.5%, 95.6%, 19.4% and 97.9%, 90.1%, 84.5% respectively, while the false positive rate and the false negative rate were 1.5%, 4.4%, 20.6% and 2.7%, 14.9%, 10.8% respectively. The Kappa value were 0.985, 0.803 and 0.688.Conclusion1. The H.pylori infection was the mainly cause of duodenal ulcer and chronic superficial gastritis with duodenal inflammation of gastroduodenal disease in children.2. H.pylori culture was still the"gold standard"as the detection of H.pylori. The clinical application of H.pylori culture should be paid more attentions.3. The ¹³C-UBT was reliable in testing H.pylori infection for the children over three years old who did not want to do gastroscopy.4. The histopathology biopsy for testing H.pylori infection results negative could be excluded without H.pylori infection.5. The RUT could not be a single method to diagnose the children with H.pylori infection. ObjectiveTo compare the clinical effect of 10-day sequential therapy which was made up with omeprazole,clarithromycin,amoxicillin-clavulanate and metronidazole and 7 days, 10 days and 14 days triple therapy which were made up with omeprazole, clarithromycin, amoxicillin-clavulanate for the eradication of children's Helicobacter pylori infection.To find a best H.pylori eradication program that was higher eradication rate and better compliance and more economical.Subjects and Methods1.Subjects: 2287 children were the ones who needed undergoing endoscopy due to recurrent abdominal pain(not associated with diarrhea and changed in bowel habits) in March to December 2009. 214 patients were enrolled in this study, including 135 boys and 79 girls, range 3¹4years. According to the randomized principle, all the cases were divided into four groups. 10-day sequential therapy group had 54 cases including 33 boys and 21 girls, the ratio of the boys and the girls was 1.57:1, mean age was 8.33±3.12 years; 7 days triple therapy group had 53 cases including 34 boys and 19 girls,the ratio of the boys and the girls was 1.56:1, mean age was 7.46±2.83 years; 10 days triple therapy group had 55 cases including 35 boys and 20 girls,the ratio of the boys and the girls was 1.75:1, mean age was 7.75±3.58 years; 14 days triple therapy group had 52 cases including 33 boys and 19 girls,the ratio of the boys and the girls was 1.74:1, mean age was 7.23±2.80 years. The gender and age of the four groups were not statistically significant(P>0.05). According to ethical standards, the legal guardians of all children were signed on informed consent before the examination and trentment.Inclusion criteria:â‘ none of the patients had recieved antibiotics, proton pump inhibitors, H2-receptor antagonists or nonsteroidal anti-inflammatory durgs in one month before undergoing gastroscope;â‘¡all the patients had drug-free allergy;â‘¢none of the patients had acute gastrointestinal illness;â‘£none of the patients had serious organ damage;⑤all the patients were H.pylori positive.Excluding criteria:â‘ poor compliance(defined as 2 days straight without taking drugs);â‘¡the patient who had exacerbations or complications;â‘¢the patient who can not tolerate the side effects occurred;â‘£t he patient occurred other diseases that interfered the observation during the treatment;⑤the patient who referral not on time or lost.Diagnostic and Eradication criteria[23]: H.pylori culture was positive or any two results that was RUT and 13C-UBT and histological detection positive confirmed H.pylori positive. 4 weeks later after withdrawal, all the patients had ¹³C-UBT which negative result was H.pylori eradication.Methods1. Diagnosis: 3 mucosal biopsies specimens were take from gastric antral mucosa in the diameter of 5 cm, one for rapid urease reaction, one for histological examination, and one for H.pylori culture. H.pylori culture positive or both histopathology and rapid urease test positive were H.pylori infection positive.2. Treatment: 214 cases were randomly divided into four groups. 10-day sequential therapy group accepted omeprazole plus amoxicillin-clavulanate for five days and omeprazole, clarithromycin and metronidazole for the remaining five days. The 7 days, 10 days and 14 days triple therapy group all received omeprazole, amoxicillin-clavulanate and clarithromycin for 7 days, 10 days, 14 days ,respectively.All drugs were given twice daily. Doses were used: omeprazole 0.8-1.0mg / (kg?d), amoxicillin-clavulanic acid 50 mg / (kg ? d), clarithromycin 20mg / (kg ? d),metronidazole 20 mg / (kg ? d). metronidazole 20 mg / (kg ? d). During treatment and 4 weeks withdrawal, all children were not taking other drugs, and strict Dining with the family.3. Clinical judgement: 4 weeks later after withdrawal, all patients had 13C-UBT which negative result was H.pylori eradication. Asked and recorded in detail about whether the patients had side effects including nausea and vomiting, diarrhea, rash, dizziness, headache or abdominal pain relief including abdominal pain disappeared or improved or invalid.4. Statistical analysis: Data were analyzed by SPSS version 13.0. Measurement data was with mean±standard deviation. Data for different groups were analyzed using variance F test, or SNK-q test. The eradication rates of each group were analyzed by intention to treat analysis (ITT) and by per-protocol analysis (PP), data usingχ2 test or Fisher exact test. Difference was considered statistically significantly for P value less than 0.05(P<0.05). Difference was considered statistically significantly for P value less than 0.05(P<0.05).Results1. 214 cases were diagnosed with chronic superficial gastritis with duodenal inflammation by endoscopy. All patients underwent RUT and histological examination, which all patients were diagnosed H.pylori positive by RUT and 197 cases were positive by pathological examination. 135 patients had H.pylori culture which were 122 cases positive.The H.pylori culture positive but pathological examination negative were 17 cases and the H.pylori culture negative but pathological examination positive were 13 cases.2. H.pylori eradication rate: H.pylori eradication rate was achieved in 85.2% and 90.2%, in 66.0% and 71.4%, in 60.0% and 67.3%,and in 78.8% and82.0% of patients following the 10-day sequential regimen, 7-day or 10-day or 14-day triple therapy at intention-to-treat and per protocol analyses, respectively. By ITT analysis, there was significantly different between the 10-day sequential therapy group and 7-day or 10-day triple therapy group(P<0.05), while no significant difference emerged between the 10-day sequential therapy group and 14-day triple therapy group(P>0.05).The results of the ITT analysis and the PP analysis were the same.3. The relief rate of abdominal pain: No significant difference emerged among the four groups about the relief rate of abdominal pain(P>0.05).4. The incidence rate of adverse reactions: There were no significant difference between the 10-day sequential therapy group and 7-day or 10-day triple therapy group(P>0.05),while the significant difference emerged between the 10-day sequential therapy group and 14-day triple therapy group(P<0.05).5. Cost-Effectiveness analysis: The Cost-Effectiveness ratio (C/E) of 10-day sequential therapy group and 7 days, 10 days, 14 days triple therapy group were 343.58,458.33,694.65 and 798.17 respectively. The Increase cost-effectiveness ratio of 7 days, 10 days, 14 days triple therapy group were 92.23, 688.17 and 4202.32.Conclusion1. The H.pylori eradication rate of 7 days and 10 days triple therapy were lower and not satisfactory. We did not recommended using them.2. The H.pylori eradication rate of the 10-day sequential therapy and 14 days triple therapy were the same, but the former had shorter treatment, fewer adverse events, better compliance and more economical.