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13MEDICAL SCIENCES
EFFICACY OF COMBINED TREATMENT USING HELICOBACTER PYLORI ERADICATION THERAPY WITH ANXIOLYTIC IN COMPARISON WITH ERADICATION THERAPY ALONE IN PATIENTS WITH FUNCTIONAL DYSPEPSIA: A RANDOMIZED TRIAL
Alianova T.
National Medical Bogomolets University, PhD student, MMed Solovyova G.
National Medical Bogomolets University, Department of internal medicine #3, professor, PhD
TaranA.
National Medical Bogomolets University, Department of therapy, infectious diseases, and dermatology ofpostgraduate education,
associate professor, PhD Aleksieieva V.
National Medical Bogomolets University, Department of therapy, infectious diseases, and dermatology ofpostgraduate education,
teaching assistant, PhD
Abstract
Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders that affects nearly 1030% of the population worldwide. Currently the problem of efficacious treatment of functional dyspepsia is not fully solved. Most of the previous trials recommended prokinetics and eradication therapy, however it was effective only in 15-30% of cases. Anxiolitics seems to increase the efficacy of treatment as they reduce signs of anxiety, which aggravate the dyspeptic symptoms. In previous trials buspirone (5-hydroxytryptamine 1A receptor agonist) showed the possibility to relax the proximal stomach in healthy individuals. Aim of the study: to assess the superiority of combined treatment using Helicobacter pylori eradication therapy with anxiolytic (buspirone) in comparison with eradication therapy (ET) in patients with functional dyspepsia. Material and methods: It was a randomized trial. Adult patients (18-45 years old) with confirmed diagnosis of FD according to Rome IV criteria were eligible to participate after the informed consent was signed. Exclusion criteria: presence of "red flag" symptoms or comorbidities that could explain the symptoms. All patients were tested for Helicobacter pylori. We used Likert 7-grade Scale to allocate the intensity of dyspeptic symptoms. To allocate patients randomly a numbered series of sealed envelopes were used. Subjects were divided into 4 groups: Group 1 (29 patients) - patient with PDS who received ET according to the Maastricht 5 (2017) with buspirone 10 mg, 3 times daily; Group 2 (29 patients) - patient with PDS who received ET only; Group 3 (20 patients) - patient with EPS who received ET with buspirone 10 mg, 3 times daily; Group 2 (17 patients) - patient with EPS who received ET only. Duration of therapy was 14 days. Patients were assessed on the 15th and 30th day after the treatment started. The superiority was qualified if there was more lasting decrease in symptoms severity. Results and conclusions: The groups were statistically comparable in age, sex, prolongation of symptoms and their severity. All patients had H. pylori positive tests. The combination of ET with anxiolytic (buspirone) demonstrates clinical and statistical superiority to ET alone in the patients with PDS and EPS showing more lasting regression of symptoms. The results in the group of patients with PDS were higher than in patients with EBS, however no statistical difference was evaluated.
Keywords: functional dyspepsia, postprandial distress syndrome, epigastric pain syndrome, anxiety, anxiolitics.
Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders. Extensive trials demonstrated that FD affects nearly 10-30% of the population worldwide [3, 4, 5]. In global studies it was evaluated that FD was diagnosed in 14-27.5% of European population, 12-28% of USA and Canadian inhabitants, 1828% of Asian population, up to 45% of men and women in Africa, and 24-39% of Australian inhabitants [2]. In 2012 the Ministry of Health of Ukraine published statistical data for Ukrainian population, according to which the prevalence rate of FD is 30-40%. Experts expect the real level to be significantly higher as around 50% of patients do not visit specialists, and so could not be included in official statistics [1].
Currently the problem of efficacious treatment of functional dyspepsia is not fully solved. Most of the previous trials recommended prokinetics and eradication therapy, however it was effective only in 15-30% of cases
[4].
Functional disorders were discovered to have multi-factorial pathophysiological factors. That was reflected in new Rome IV definition, which was released in May 2016.
They are: gastric emptying, impaired gastric accommodation, gastric and duodenal hypersensitivity to distention, acid, and the other intraluminal stimuli, duodenal low-grade inflammation, mucosal permeability, and food antigens, environmental exposures, psychological factors, and Helicobacter pylori infection [4]. It was previously demonstrated that the level of anxiety increases in patients with functional disorders [6].
Buspirone, a 5-hydroxytryptamine 1A receptor agonist, is one of the anxiolytics. In a randomized, doubleblind, placebo-controlled, crossover study of 17 patients it was demonstrated that buspirone relaxes the proximal stomach in healthy individuals [7].
Aim of the study: to assess the superiority of combined treatment using Helicobacter pylori eradication therapy with anxiolytic (buspirone) in comparison with eradication therapy (ET) in patients with functional dyspepsia.
Material and methods: We performed a randomized trial in which patients the patients with newly set diagnosis of FD participated. The study was done on the basis of Gastro center of the Clinic "Oberig" in Kyiv, Ukraine in the period from June 2016 till June 2019. We
compared the results of the patients with different types of FD - PDS and EPS depending on the type of therapy.
Diagnosis of FD was set if the patients had symptoms according to Rome IV criteria either for postprandial distress syndrome (PDS) (bothersome postprandial fullness or early satiety severe enough to affect daily life or ability to finish a regular-size meal for 3 or more days per week in the past 3 months, with at least a 6-month history) or for epigastric pain syndrome (EPS) (bothersome epigastric pain or epigastric burning 1 or more days per week in the past 3 months, with at least a 6-month history).
Patients with a prior organic upper or lower gastrointestinal diagnosis that might explain their symptoms, such as esophageal, pancreatic or bowel disease, were excluded. Patients with prior cancer, alcoholism or drug dependence recorded within 3 months before the FD was set, as well as pregnant women, were also excluded. Patients with red flag symptoms - onset in the age >45 years, persistent vomiting, signs of bleeding, iron deficiency anemia, family history of upper gastrointestinal cancer, progressive dysphagia and/or odynophagia - were not included into the analysis as well as cases with no details of medical history. We also excluded patients with presence of psychiatric or psychoactive use disorders with a history psychotropic treatment for the last 5 years.
All patients were tested for Helicobacter pylori using rapid one-step immunochromatographic assay for detection of monoclonal Helicobacter pylori antigen in stool
samples or in PCR for Helicobacter pylori DNA, or due to morphological method.
We used Likert 7-grade Scale to allocate the intensity of dyspeptic symptoms.
To allocate patients randomly a numbered series of sealed envelopes containing the number of the group assignments were used.
Four study groups were formed:
- Group 1 (29 patients) - patient with PDS who received ET according to the Maastricht 5 (2017) with buspirone 10 mg, 3 times daily;
- Group 2 (29 patients) - patient with PDS who received ET only;
- Group 3 (20 patients) - patient with EPS who received ET with buspirone 10 mg, 3 times daily;
- Group 2 (17 patients) - patient with EPS who received ET only.
Duration of therapy was 14 days. Patients were assessed on the 15th and 30th day after the treatment started. The superiority was qualified if there was more lasting decrease in symptoms severity, reduced level of anxiety.
Statistic processing of data was conducted according to the generally accepted standards using the statistical program Statistica 6.
Results and Discussion
There were no differences in age, sex, body mass index (BMI), and the duration of symptoms among all study groups. The details are provided in Table 1.
Table 1
Clinical anamnestic characteristics of study participants
Characteristic Study group p
Group 1 (n=29) Group 2 (n=29) Group 3 (n=20) Group 4 (n=17) p 1-2 p3-4
Age, years (M±SD) 35.7±7.7 34.2±6.1 33.0±4.5 34.0±5.5 0.119* 0.117*
Women/men, n 19/10 18/11 12/8 11/6 0.948# 0.882#
BMI, kg/m2 (M±SD) 21.1±1.9 20.9±1.8 21.0±1.8 22.1±2.9 0.507* 0.671*
Duration of symptoms, months (M±SD) 34.5±11.9 33.6±10.9 32.5±15.9 31.9±13.9 0.704* 0.892*
* - t-test; # - x2-test; no statistical significance of differences, p>0.05.
The effectiveness of treatment of the patients with PDS during the study is provided in the Table 2.
Table 2.
_The effectiveness of treatment of the patients with PDS___
Effectiveness of the treatment Study group OR (95% CI) p
Group 1 (n=29) Group 2 (n=29)
Dyspeptic symptoms decreased / are absent on Day 7, n (%) 15 (51.2 %) 9 (31.0 %) 0.4 (0.14-1.2) 0.110
Dyspeptic symptoms decreased / are absent on Day 15, n (%) 25 (86.2 %) 10 (34.5 %) 0.1 (0.02-0.3) <0.001*
Dyspeptic symptoms decreased / are absent on Day 30, n (%) 22 (75.7 %) 3 (10.3%) 0.04 (0.01-0.2) <0.001*
■ statistical significance of differences, p<0.05
According to the received results in Group 1 on the Day 7 51.2% of patients registered decrease in the intensity of dyspeptic symptoms of did not have any. In comparison, the same measure in the Group 2 was lower -31.0% - although there was no statistical difference evaluated (p=0.110).
On the Day 15 the results of the treatment effectiveness were significantly higher in the Group 1 (86.2%) than in the Group 2 (34.5%) - p <0.001.
On the Day 30 some of the treated subjects registered the recurrence of dyspeptic symptoms. The treatment was effective in 75.7% cases in the Group 1 and in 10.3% cases in the Group 2. The combined treatment was statistically more effective than ET alone - p <0.001.
The effectiveness of treatment of the patients with EPS during the study is provided in the Table 3.
Table 3.
The effectiveness of treatment of the patients with EPS
Effectiveness of the treatment Study group OR (95% CI) p
Group 3 (n=20) Group 4 (n=17)
Dyspeptic symptoms decreased / are absent on Day 7, n (%) 9 (45.0%) 3 (17.6%) 0.7 (0.18-2.5) 0.549
Dyspeptic symptoms decreased / are absent on Day 15, n (%) 13 (65.0%) 6 (35.3%) 0.2 (0.06-0.9) 0.020*
Dyspeptic symptoms decreased / are absent on Day 30, n (%) 11 (55.0%) 5 (29.4%) 0.2 (0.04-0.8) 0.031*
*
* - statistical significance of differences, p<0.05
According to the received results in Group 3 on the Day 7 45.0% of patients registered decrease in the intensity of dyspeptic symptoms of did not have any. In comparison, the same measure in the Group 4 was lower -17.6% - although no statistical difference was evaluated (p=0.549).
On the Day 15 the results of the treatment effectiveness were significantly higher in the Group 3 (65.0%) than in the Group 4 (35.3%) - p=0.020.
On the Day 30 some of the treated subjects registered the recurrence of dyspeptic symptoms. The treatment was effective in 55.0% cases in the Group 3 and in 29.4% cases in the Group 4. The combined treatment was statistically more effective than ET alone - p=0.031.
Treatment efficacy rates were higher in Group 1 than in Group 3. The results in these two groups on Day 7 did not differ statistically (p = 0.684), but the effectiveness of combined therapy in Group 1 on Day 15 and Day 30 increased more significantly than in Group 3. The risk of detecting dyspeptic symptoms in Group 1 in comparison with Group 3 on day 7 is reduced by 20% - OR = 0.8 (0.242.4), on Day 15 - by 70% OR = 0.3 (0, 07-1.2), on Day 30 the risk is lower by 60% - OR = 0.4 (0.11-1.3).
As a result, combined treatment with anxiolytic buspirone was more effective in reducing the intensity of dyspeptic symptom than eradication therapy alone, both in the group of patients with PDS and among patients with EBS on Day 15 and Day 30. Its efficacy was higher among patients with PDS than among patients with EBS, although not statistically significant. The effectiveness of eradication therapy alone did not differ in terms of the intensity of dyspeptic symptoms, depending on the type of FD.
There were no statistical differences evaluated for the effectiveness of eradication and amount and severity of adverse events in study groups (p>0.005).
Conclusions. Combined treatment with anxiolytic buspirone was more effective in reducing the intensity of dyspeptic symptom than eradication therapy alone, both in
the group of patients with PDS and among patients with EBS on Day 15 and Day 30. Its efficacy was higher among patients with PDS than in patients with EBS, although not statistically significant.
References
1. Наказ, М. О. З. "Укра!ни вщ 03.08. 2012 № 600 «Про затвердження та впровадження медико-техно-лопчних докуменлв 3i стандартизацп медично! допо-моги при диспепсп»." Ушфжований клшчний протокол первинно! медично! допомоги «Диспепшя». Адап-тована клшчна настанова «Ведення диспепсп у дорослих».
2. Aziz I., Palsson O.S., Tornblom H., et al. Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study. Lancet Gastroenterol Hepatol. 2018; 3(4): 252-262.
3. Chuah, Kee-Huat, and Sanjiv Mahadeva. "Functional dyspepsia." Clinical and Basic Neurogastroenterol-ogy and Motility. Academic Press, 2020. 281-292.
4. Drossman, Douglas A., and William L. Hasler. "Rome IV—functional GI disorders: disorders of gut-brain interaction." Gastroenterology 150.6 (2016): 12571261.
5. Mahadeva, Sanjiv, and Khean-Lee Goh. "Epidemiology of functional dyspepsia: a global perspective." World journal of gastroenterology vol. 12,17 (2006): 2661-6. doi:10.3748/wjg.v12.i17.2661.
6. Mak, A.D.P., et al. "Dyspepsia is strongly associated with major depression and generalised anxiety disor-der-a community study." Alimentary pharmacology & therapeutics 36.8 (2012): 800-810.
7. Tack, Jan, et al. "Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia." Clinical Gastroenterology and Hepatology 10.11 (2012): 1239-1245.
THE CAUSES OF POSTOPERATIVE INTRA-ABDOMINAL ABSCESSES IN CHILDREN AND
WAYS OF THEIR PREVENTION
Shamsiev A.
Samarkand state medical institute, Department of pediatric surgery, MD, professor
Yusupov Sh. Samarkand state medical institute, Head of the department ofpediatric surgery, MD, professor
Shakhriev A. Samarkand state medical institute, Department of pediatric surgery, MD, docent
Djalolov D. Samarkand state medical institute, 4th-year student of the faculty ofpediatrics
Abstract
In abdominal surgery and intensive care of children, the main problem is the treatment of patients with abdominal diseases caused by destructive processes in the organs and the development of peritonitis. Despite the identification and elimination of the source of infection, sanitation and drainage of the abdominal cavity, active detoxification and massive antibacterial therapy, every second patient develops manifestations of a systemic inflammatory reaction with signs of multiple organ failure, often leading to the development of abdominal sepsis, the mortality rate of which even with modern medical achievements ranges from 20% to 80%. Abdominal abscesses (AA) of various localization according to different authors make up from 10% to 44% of all intra-abdominal complications.
The causes of AA are very diverse. The existing literature provides contradictory statistical data on the etiology of AA. Many authors consider acute appendicitis to be the most common cause of AA, but some note that the frequency of intraperitoneal abscess formation after elective surgery prevails over that after emergency operations.
Among the reasons for the formation of AA, technical errors of the operation are of great importance, which can include shortcomings of operational equipment, inadequate sanitation and drainage of the abdominal cavity. Among
