OBSERVATIONS IN CONTROLLING HELICOBACTER PYLORI BETWEEN TRIPLE REGIME AND SEQUENTIAL REGIME

Objective: To compare conventional triple regime and sequential regime in controlling of Helicobacter Pylori. Methods: The study was conducted at Medical OPD Military Hospital, Rawalpindi for six months. The consecutive (nonprobability sampling) technique was used. All patients fulfilling inclusion criteria and diagnosed according to operational definition of Helicobacter Pylori infection were selected. All the information was entered, assessed and results were obtained through SPSS. Results: According to our study the cases mean age was 36.23±10.87 years, ratio between male, female was 1.07:1. Overall efficacy achieved in 289 (67.21%) patients (124 in set A and 165 in set B). So according to results sequential therapy has got much higher results as compared to triple therapy group. Conclusion: It has been proved in our study that the sequential regime has got significantly better results than conventional triple regime in the management of Helicobacter Pylori eradication


INTRODUCTION
Helicobacter Pylori is spiral, gram negative bacteria with many flagella for mobility. Its prevalence in the world is more than 50% and is much higher in developing countries 1 . 81% of adult population is infected with it in Pakistan 2 . It is associated with different diseases including peptic ulcer formation, atrophic gastritis, dyspepsia, gastric cancer and gastric lymphoma. Early control is required for prevention of these diseases and their complications 3 . Triple regime in the most widely used therapy in Helicobacter pylori infection control. But its efficacy has reduced by the time below 80% due to drug resistance which is unacceptable 3,4 . So to overcome the resistance and to improve the results, sequential regimen was introduced with 98% eradication rate 5 . The target of this trial was to see the effectiveness of sequential and triple therapy in Helicobacter Pylori infection amongst local population as till date no such study is conducted in local population. This study may enable us to choose better eradication regimen for this highly prevalent pathogen. Helicobacter pylori (H. pylori): Australian scientists Barry Marshall and Robin Warren discovered it in 1982 in patients of chronic gastritis and gastric ulcers. So it was also thought that it led to the development of duodenal ulcers and related diseases. But most of the human beings having it are asymptomatic and perhaps it may be the part of natural stomach ecology. 6 It is present in the gastrointestinal tract of more than 50% of world population and is more common in underdeveloped countries. It has been suggested that it has developed power to attack the lining of stomach mucosa. [7][8] Helicobacter pylori in stomach mucosa 8 oral--oral and feco--oral are its commonest ways of spread, Parents and siblings play a primary role in its transmission 9. Infection has shown accumulation of neutrophils, mast cell, lymphocytes in gastric mucosa and is supposed to cause dysplastic and metaplastic alterations. Its gastric mucosal attachment has resulted in lowering the levels of cells glutathione, which is required for the mucosal repair and in immunity. It may lead to the production of autoantibodies with further increase in parietal cells atrophy 10. Signs and symptoms of H. pylori: Patients usually have no symptoms incase present these are due to acute gastritis like abdominal pain or nausea 11,12. In case of chronic gastritis symptoms can be pain in stomach, feeling of nausea, vomiting and rarely dark stool. 13 Its patients are in 20% risk of peptic ulcer and 1-2% risk of gastric cancer. 14,15 Hypothesis: Sequential regime is better than triple regime.

Operational Definitions Helicobacter pylori infection
Positive H. Pylori stool antigen in symptomatic patients having dyspepsia. Helicobacter pylori stool antigen was detected via immunochromatography monoclonal antibodies method.

Efficacy:
In this study the efficacy was eradication of infection by sequential regime and triple regime in 4 weeks' time having stool antigen negative to H. pylori.

Triple therapy
Amoxicillin 1gm 2 times daily 10 days Clarithromycin 500 mg 2 times daily 10 days Omeprazole 20 mg 2 times daily 10 days Sequential therapy Amoxicillin 1gm 2 times daily 5 days Omeprazole 20 mg 2 times daily 5 days

Followed by
Clarithromycin 500 mg 2 times daily 5 days Metronidazole 400 mg 2 times daily 5 days Omeprazole 20 mg 2 times daily 5 days

METHODS:
It was randomized control trial study conducted at Medical OPD Military Hospital, Rawalpindi. Its duration was 6 months According to WHO guidelines, following are calculations for sample size: • Level of significance is equal to 5%.
• Power of test is equal to 80%. • Anticipated population in set 'A' is equal to 85.9% . • Anticipated population in set 'B' is equal to 75% .
• 215 patients sample size in each group (total 430 patients) Consecutive (nonprobability sampling).  Table 1 According to the study good results obtained in 157 male patients (69 in set A and 88 in set B) and in female cases good results obtained in 132 patients (55 in set A and 77 in set B). Table 2 Chi value =17.73 Value of p = 0

DISCUSSION
This study was conducted at Medical OPD MH Rawalpindi. Managing H. pylori infection is still a headache for physicians because no current drug therapy has been successful to control it in all infected individuals. Old triple therapy was advised as first-line therapy previously . 16 Then the sequential therapy was introduced and its efficacy was compared with triple regimes. Different comparative studies were conducted and it was found that results were better for sequential regime. [17][18] 20 In recently different studies that were carried out in Korea, sequential therapy had a better control rate against triple regime. [21][22] Regarding making a choice as a first line management option in controlling H. pylori sequential regime has shown much better results. Also, a large number of data was analyzed and sequential regimen was shown to have better control than either of the seven-days and ten-days triple regimes, with a control rate of 93.7%, 75.9% and 79.6%, respectively. [23][24] It was found that Such strains of H. pylori that are resistant to clarithromycin, Sequential therapy was found better in controlling them and the efficacy was 83.9% and for triple regime it was 35.1%, respectively. 25

CONCLUSION
So, our study proves that the sequential therapy is better than conventional triple therapy in the management of Helicobacter Pylori.

ETHICAL APPROVAL
The study was approved by the Ethical Review Committee of Military Hospital, Rawalpindi, dated September, 2020.