Cost-Effectiveness Analysis Of Plant Versus Antibiotic Regimens In Treating Patients With Helicobacter Pylori (H. Pylori) Infection In The South Of Iran

Cost-Effectiveness Analysis Of Plant Versus Antibiotic Regimens In Treating Patients With Helicobacter Pylori (H. Pylori) Infection In The South Of Iran | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost-Effectiveness Analysis Of Plant Versus Antibiotic Regimens In Treating Patients With Helicobacter Pylori (H. Pylori) Infection In The South Of Iran Hossein Faramarzi, Zahra Khajoei, Farhad Lotfi, Mehdi Rezaee, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1377344/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Helicobacter pylori infection is highly prevalent worldwide and affects more than half of the world's population. A variety of treatment regimens to eliminate H. pylori infection have been evaluated, but choosing the best treatment method that results in the most eradication at the lowest cost is one of the challenges facing physicians. Therefore, the present study aimed at analyzing the cost-effectiveness of using different methods to treat H. pylori in southern Iran. Methods: This study was a cost-effectiveness analysis conducted on 132 patients with H. pylori who referred to Shahid Motahari Clinic in Shiraz. The study was carried out in 2020 to evaluate two drug treatment strategies, including antibiotics (pantoprazole 40 mg, Bismuth subcitrate 108 mg, tetracycline 500 mg, and metronidazole 200 and 400 mg) and plants (Supermint Barij soft capsules 20 mg, Alium S garlic tablets 400 mg, and Green Teadin (green tea) tablets 500 mg). The patients were randomly divided into two groups, 64 of whom received an antibiotic regimen and 68 patients given a plant regimen. The success rate of clinical trials in each treatment method was determined as the clinical outcome. This study was conducted from a community perspective and therefore, direct and indirect costs were included. A data collection form was also used to collect the cost and effectiveness data. In addition, a one-way sensitivity analysis was performed to measure the robustness of the results. The data were analyzed using TreeAge Pro 2011 and Excel 2016 software. Results: The results showed that antibiotic treatment was cheaper and more effective than plant treatment and was the dominant strategy. The mean costs in the antibiotics and plant groups were $446.14 and $477.81, respectively, and the effectiveness was 0.625% and 0.382%. In addition, the one-way sensitivity analysis confirmed the robustness of the study results. Conclusion: The results showed that the use of antibiotics was a cost-effective and dominant strategy compared to plant treatment and could be suggested as a better alternative to a wide range of patients with Helicobacter pylori infection. Cost-Effectiveness Economic Evaluation Helicobacter pylori Antibiotic plant Figures Figure 1 Figure 2 Figure 3 Introduction Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide[ 1 ], the prevalence of which among adults in developed countries is 20–40%[ 2 , 3 ]. However, the infection rate reaches 90% in the first 5 years of life in developing countries[ 4 ]. As the most common infectious agent, H. pylori is involved in a variety of common gastrointestinal disorders including gastritis, duodenal ulcer, peptic ulcer, adenocarcinoma, and gastric lymphoma[ 5 ], and is also involved in about 89% of non-cardiac gastric cancers in the world[ 6 ]. In addition, it can lead to many diseases of non-digestive origin, such as cardiovascular disease, autoimmunity, Parkinson's, obesity, and allergic disorders[ 7 ]. Therefore, preventing or eradicating bacterial infections can help avoid these diseases. Nowadays, the biggest challenge in eradicating H. pylori infection is the low tolerance of patients for medical treatments, antibiotic resistance and side effects, and the high cost of antibiotic treatment[ 8 ]. Various treatment regimens containing several antimicrobial compounds have already been examined to eliminate H. pylori infection[ 9 – 11 ]. The failure of single drug methods has led to the development of drug regimens with a combination of three or four drugs, the most common of which is triple therapy. This treatment regimen includes a proton pump or inhibitor bismuth and two antibiotics, i.e. amoxicillin and clarithromycin[ 12 , 13 ]. Early studies suggested that eradication with triple therapy was cost-effective, and resistance to some strains was seen in more than 50% of the patients. However, triple therapy has shown a gradual decrease in efficacy (eradication rate of < 80%) in recent years[ 14 ]. It also has side effects such as metallic taste in the mouth, increased sensitivity to light, constipation, and diarrhea[ 15 ]. The use of a four-drug regimen containing omeprazole, bismuth, and two antibiotics (Metronidazole and Tetracycline) was associated with 80% eradication and was recommended as a first-line treatment in areas with high resistance (over 15%) to Metronidazole and Clarithromycin in the patients who did not respond to the three-drug regimen containing Metronidazole or Clarithromycin[ 16 , 17 ]. The four-drug regimen is not only very expensive [ 14 ]but in many cases leads to treatment discontinuation before the end of the treatment course due to the complications such as seizures and polyneuropathy in the patients who use metronidazole for a long time[ 18 ]. Despite various treatment methods, recurrence of the disease has been reported in a number of cases after treatment completion. Therefore, the use of plants and herbal medicines may be beneficial due to their numerous medicinal effects[ 19 ]. Today, the antimicrobial effects of many plant species (e.g. garlic) on H. pylori infection have been investigated and proposed as a way of increasing the efficacy of H. pylori treatment[ 20 ]. The results of a study showed that adding garlic extract to the standard anti-H. Pylori infection regimen increased its eradication rate from 52.6–75.8%[ 21 ], and long-term consumption of garlic reduced the risk of gastric and colon cancers[ 22 ]. However, the results of a study by McNulty et al. did not show a significant relationship between garlic consumption and eradication of H. pylori infection[ 23 ]. Thus, considering the high prevalence of gastrointestinal diseases in the world, especially gastric adenocarcinoma and its relationship with H. pylori, choosing the best treatment method that causes the highest eradication rate at the lowest cost is one of the challenges facing physicians[ 24 ]. Therefore, the present study aimed to analyze the cost-effectiveness of using different H. Pylori treatment methods in Shahid Motahari Clinic in Shiraz in 2020. Methods Overview This prospective cost-effectiveness study was conducted on 132 H. pylori patients who referred to Shahid Motahari Clinic in Shiraz (referral clinic) in order to examine two drug treatment strategies including antibiotics and plants in 2020. The patients were randomly divided into two groups of receiving antibiotic (n = 64) and plant (n = 68) regimens. The antibiotic group was given a drug regimen including pantoprazole 40 mg twice a day, bismuth subcitrate 108 mg and tetracycline 500 mg 4 times a day, and metronidazole 200 mg three times daily and 400 mg once overnight for 14 days[ 15 ]. The plant receiving group was given Supermint Barij soft capsules 20 mg, Alium S garlic tablets 400 mg[ 25 ], and Green Teadin (green tea) tablets 500 mg three times a day for 14 days[ 26 ]. A decision tree model was used to estimate the cost and effectiveness results. The cost data were collected from a community perspective, and direct and indirect costs were included in the study. The success rate of clinical trials in each treatment method was determined as the effectiveness outcome. A data collection form was also used to collect the cost and effectiveness data. The results were presented in the form of incremental cost-effectiveness ratio (ICER). Furthermore, the one-way sensitivity analysis was performed to measure the effects of parameter uncertainty in the model. The data were analyzed using TreeAge Pro 2011 and Excel 2016 software. Inclusion And Exclusion Criteria The inclusion criteria were as follows: the patients with dyspepsia who had a positive antigen stool test result; not taking antibiotics for at least 4 weeks before the start of the study; no history of allergies to mint, green tea, and garlic pills; and no use of other adjunctive therapy or medicinal plants for at least two weeks before the start of the study. The exclusion criteria were liver disease, gallstones or biliary obstruction, any gastrointestinal risk symptoms that required endoscopic examination (e.g., weight loss, anemia, severe gastrointestinal symptoms, recurrent vomiting, dysphagia, and gastrointestinal bleeding), not taking the drugs for at least one day, and not taking daily doses. Treatment Costs In this study, the costs were collected from a community perspective. Therefore, they included direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs). The DMCs included the costs of medication, tests, doctor visits, and hospitalization, which would include the side effect cost of each treatment method and the use of a subsequent method in case of the failure of the initial treatment. The DMC data were collected from the patients' medical records as well as the opinions of clinical experts in this field. The DNMCs included transportation costs (intra-city and intercity) as well as food and accommodation costs for the patient and companions to receive medical services. The ICs also included the mean days of absence from work of the patients and companions and reduced productivity lost due to illness, disability, and death. The DNMC and IC data were collected based on the patients' self-report through face-to-face interviews or telephone calls. The human capital approach was used to calculate the IC[ 27 , 28 ]. In addition, all costs were calculated based on the tariffs of 2020 and converted into international dollars (purchasing power parity (PPP)) at the exchange rate of 1 dollar = 22057 Rials[ 29 ]. Model Structure Figure 1 shows a schematic diagram of the decision tree model for antibiotic versus plant treatment strategies. The success and failure of the drugs and their side effects were plotted for each strategy in order to select the best. In addition, the costs and effectiveness of each strategy were entered into the model separately. Insert Fig. 1 here: Cost-effectiveness Analysis The model was designed in Tree-age software and the extracted data were entered into it. The costs, effectiveness, and cost-effectiveness of the two drugs were then calculated and their ICERs were estimated using the following equation. $$ICER=\frac{cost plant-cost Antibiotics}{Effectiveness plant-Effectiveness Antibiotics}$$ Sensitivity Analysis The one-way sensitivity analysis was performed to investigate the effects of parameter uncertainty on the results. To this end, some key parameters such as cost and utility were changed by 20% for each drug strategy and the results were presented in the form of a Tornado Diagram. In addition, due to the lack of a cost-effectiveness threshold in Iran and as proposed by the World Health Organization (WHO), the threshold of one to three times the per capita GDP was considered for developing countries[ 30 ]. The GDP in Iran was $ 12547 in 2019 (1* GDP)[ 31 ], using which the threshold of willingness to pay (WTP) was $ 37641 (3* GDP) in the country[ 32 ]. Results A total of 132 patients with H.pylori were included in the study. Table 1 provides descriptive results including the data on gender, age, employment status, and education. As shown in Table 2 , DMCs accounted for the highest costs in both groups ( $ 204.18 PPP in antibiotic and $ 210.47 PPP in plant treatments). On the other hand, the lowest costs were associated to indirect costs with an average value of $ 111.81 PPP in the antibiotic and $ 119.83 PPP in the plant methods. Overall, the mean total cost of antibiotic treatment ( $ 446.14 PPP) was lower than plant treatment ( $ 477.81 (PPP)). Table 1 Demographic variables among patients between two groups of plant and antibiotic Variable plant antibiotic Number Percent Number Percent sex Female 41 60.29 36 56.25 Male 27 39.71 28 43.75 Total 68 100 64 100 Age (year) 20–30 15 22.05 6 9.38 31–40 21 30.88 24 37.5 41–50 14 20.59 20 31.25 51–60 10 14.71 12 18.75 61–70 7 10.3 1 1.56 71–80 1 1.47 1 1.56 Total 68 100 64 100 Patients employment unemployed 35 51.5 34 53.13 Employed 2 3 5 7.81 Self employed 13 19.1 13 20.31 Retired 1 1.4 4 4.69 Daily worker 17 25 9 14.06 Total 68 100 64 100 Patient Education Illiterate 13 19.12 8 12.5 Fifth elementary 25 36.77 15 23.43 High school drop-out 9 13.23 7 10.94 High school diploma 10 14.7 18 28.13 Two year collage degree 3 4.41 5 7.81 Bachelor degree 8 11.77 11 17.19 TOTAL 68 100 64 100 Table 2 Estimated mean Direct medical and non-medical costs, Indirect costs, and Total costs per patient by Dollar in plant and antibiotic groups Type of Service Plant Antibiotic Mean SD Mean SD Direct medical cost visit 49.96 9.34 45.33 9.33 Drugs 64.86 23.57 72.03 26.73 Tests 95.18 17.8 86.35 17.79 Other services 0.47 1.9 0.47 1.31 Total 210.47 52.61 204.18 55.16 Direct non-medical cost Transport 100.39 92.95 85.67 70 Foods 30.4 40.88 29.37 39.46 Accommodation 16.72 26.25 15.11 33.19 Total 147.51 160.08 130.15 142.65 Indirect cost Time spent by the patient’s accompany and patient 119.83 67.39 111.81 58.62 Total cost Direct Medical Costs 210.47 52.61 204.18 55.16 Direct Non-medical Costs 147.51 160.08 130.15 142.65 Indirect Costs 119.83 67.39 111.81 58.62 Total Costs 477.81 280.08 446.14 256.43 According to Table 3 and Fig. 2 , the results of the cost-effectiveness analysis showed that the calculated effectiveness of antibiotic and plant strategies were 62.5% and 38.24%, respectively, and the costs were $ 446.14 and $ 457.81 PPP, respectively. Thus, antibiotic treatment was less costly and more effective, and therefore, a more cost-effective option and a dominant strategy. Table 3 Comparison between cost and effectiveness in plant and antibiotic groups Strategy name Effectiveness Cost (PPP $ ) ICER Plant 0.382 -0.243 457.81 11.67 -48.024 Antibiotic 0.625 446.14 * ICER = Incremental cost effectiveness ratio Uncertainty Analysis The effects of uncertainty were studied using the one-way sensitivity analysis, and the value of each variable changed by 20%. Figure 3 presents the results of the one-way sensitivity analysis in the form of a tornado diagram. The changes in many parameters did not have significant effects on the study results. However, ICER had the highest sensitivity to plant cost and the lowest sensitivity to the effectiveness of plant treatment in the patients with H. pylori. In fact, plant price was a determining parameter in ICER for the patients with H.pylori. Discussion The present research is in fact the first economic evaluation study that compared the cost-effectiveness of using antibiotic and plant treatments in patients with H. pylori in Iran. The results showed that antibiotic treatment was more cost-effective than plant treatment. Few studies have been conducted in this field. Using cost and effectiveness data to compare the cost-effectiveness of different H. pylori eradication regimens in the patients with gastric ulcer or chronic gastritis, Sancar et al (2006) concluded that the use of a 4-drug regimen was more cost-effective than other treatment regimens, and the eradication rate and cost-effectiveness ratio for the 4-drug treatment was 90% (€ 158.7)[ 33 ], confirming the results of the present study. In contrast, Yousef-Nezhad et al. (2017) showed that H. pylori treatment with alternative therapies using herbal compounds had less toxicity and side effects and was more cost-effective and less costly than drug treatments[ 34 ]. Bokaeian et al (2013) also showed that the use of medicinal plants was cheaper than chemical drugs and easily accessible[ 35 ]. This is inconsistent with the results of the present study. In this study, using the antibiotic regimen including four types of antibiotics (pantoprazole, bismuth, tetracycline, and metronidazole) (0.625) was more effective than using the plant regimen (0.382). The results of the studies by Jun-Ling Ma et al. (2012) and Wei-cheng et al (2006) in China showed that treatment with amoxicillin and omeprazole reduced the incidence of H. pylori infection and gastric cancer by 39%, but long-term use of garlic and vitamins was not associated with a statistically significant reduction in the incidence of H. pylori infection and gastric cancer mortality [ 36 , 37 ]. Kaviani et al. (2001) in Iran examined the two-week treatment with amoxicillin, metronidazole, bismuth, and ranitidine to eradicate Helicobacter pylori and reported 73% of effectiveness[ 38 ]. The results of a study by Nijevitch et al. (2007) in Russia indicated that a triple-therapy including bismuth subcitrate, nifuratel, and amoxicillin was 86% successful in eradicating H. pylori infection in childhood[ 39 ]. Hojo et al. (2001) stated that eradication rate of Helicobacter pylori with a drug regimen containing amoxicillin, metronidazole, bismuth, and omeprazole was 39%[ 40 ]. A study carried out by Tireno et al. in 1999 reported 75% potency of omeprazole, amoxicillin, and clarithromycin in eradicating Helicobacter pylori during two weeks[ 41 ]. The results of the study by Rahimian et al. (2013) in Shahrekord suggested that the combination of garlic and peppermint extracts, in comparison with metronidazole, was unsuccessful in eradicating H. pylori infection, and metronidazole could still be used as an effective drug in the treatment of the disease[ 25 ]. Graham et al. (1999) in the United States showed that the use of herbal medicines such as garlic and pepper had no effect on Helicobacter pylori compared to a drug regimen such as bismuth[ 42 ]. The ineffectiveness of plant regimens and the use of garlic in the treatment of the patients with H. pylori infection was stated in other studies [ 23 , 42 – 44 ]. In contrast, the results of the study by Nagata et al. (2017) in China indicated the effectiveness of goshuyuto and the successful eradication of a resistant species of H. pylori infection with this medicinal plant compared to drug regimens[ 31 ]. Besides, Hajiagha mohammadi et al. (2015) in Qazvin stated that adding garlic extract to the standard anti-H. pylori regimen increased its eradication rate from 52.6–75.8%[ 21 ]. Some other studies also indicated the effectiveness of plant regimens, especially garlic extract and green tea alone or in combination with other treatments such as proton pump inhibitors and antibiotics in the real stomach environment [ 24 , 45 – 48 ], which are not in line with the results of this study. According to the results of the one-way sensitivity analysis, the ICER was negative and the highest sensitivity was to the cost of the plant regimen, but considering that in the cost-effectiveness sensitivity analysis the ICER remained negative, it could be said that the results of the study were robust enough. Therefore, the results showed that the sensitivity analysis did not change the status of the antibiotic regimen as the most effective treatment, and this is a sign of the robustness of the study results. One strength of this study is the inclusion of total costs, including DMCs, DNMCs, and ICs. In addition, this is the first economic evaluation study in Iran addressing the cost-effectiveness of using antibiotic and plant treatment methods in patients with H.pylori. Among the limitations of this study are the relatively small sample size and the possibility or impossibility of generalizing the results to other geographical areas. Conclusion According to the results of this study, antibiotic treatment was a cost-effective strategy compared to plant treatment and could be suggested as a good alternative to a wide range of patients with H. pylori infection. It could also be used as the first priority for the treatment of the patients in the country. List Of Abbreviations H. pylori: Helicobacter pylori, ICER: Incremental Cost-Effectiveness Ratio, DMC: Direct Medical Costs, DNMC: Direct Non-Medical Costs, IC: Indirect Costs, WHO: World Health Organization, PPP: Purchasing Power Parity, GDP: Gross Domestic Product, PSA: Probabilistic Sensitivity Analysis, WTP: Willingness to Pay Declarations Ethics approval and consent to participate All data are collected and handled in accordance with the relevant privacy protection guidelines. According to Iran law, the study did not fall under the remit of the Medical Research Involving Human Subjects Act and no approval by a medical ethics committee was necessary. Verbal consent was obtained from respondents who completed a questionnaire anonymously, and their response expressed their willingness to participate. Written consent was obtained from participants to the cognitive interviews Consent for publication: All participants completed a consent form, stating that they were well-informed about the Content of questionnaires and that they agreed upon the publication of anonymized data. Availability of data and material: The data used in this study are not publicly available because the participants were promised that the raw data would remain confidential. However, they are available from the corresponding author on reasonable request. Competing interests: The authors declare that there is no conflict of interest regarding the publication of this paper. Funding: This research was supported by Shiraz University of Medical Sciences (Iran) through grant No 1323 and was approved by the ethics committee with the code of IR.SUMS.REC.1398.1323. The funder had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication . Authors' contributions: Conception and design: H.F., Z.Kh., F.L., M.E., Kh.K.; Material preparation and data collection: H.F., Z.Kh., F.L., M.R., M.E, Kh.K. ; Data analysis: Z.Kh.; Interpretation of data: H.F., Z.Kh., F.L., M.R., M.E, Kh.K; The frst draft of the manuscript was written by M.E.; Supervision: Kh.K. All authors read and approved the fnal manuscript. Acknowledgements: The researchers would like to thank Shiraz University of Medical Sciences, especially Shahid Motahari Clinic and thank the studied patients for their kind cooperation with the researchers in collecting data. References Hekmatdoost, A., et al., The effect of garlic consumption on Helicobacter pylori treatment using urea breath test: a randomized clinical trial . 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Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"","lastName":"Khajoei","suffix":""},{"id":85917172,"identity":"ed1d80fe-64ae-4757-8e54-baf75711876f","order_by":2,"name":"Farhad Lotfi","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Farhad","middleName":"","lastName":"Lotfi","suffix":""},{"id":85917173,"identity":"0a056594-036f-4f48-826b-08c8c9f7279f","order_by":3,"name":"Mehdi Rezaee","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mehdi","middleName":"","lastName":"Rezaee","suffix":""},{"id":85917174,"identity":"90c94b6d-6d48-41b6-b694-eeca8d03b353","order_by":4,"name":"Mehrnoosh Emadi","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mehrnoosh","middleName":"","lastName":"Emadi","suffix":""},{"id":85917175,"identity":"d88bdff5-d02c-4210-8956-76b3a15f779f","order_by":5,"name":"Khosro Keshavarz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIie3RIQvCQBTA8XcMZtlYPTmZX2Fj3X2VHYOzWCyCGFx6Rqvg9xCDQRjMcpiFK15Zsti85jBYxKnNcL/0OPhz9zgAy/pDlLoApHjM5Pw8zr5MnOjnxKVfPay7Rq7NdsCX60M9NbhJoVOeQe/eJ6xXlYkvc746ZkL5qHjhiQiy+n0S0iEygk4CEipFUDVbjJpd9q3JwhicJ31JcGxQpRBc2hNGRQU+lmEkHbcZFCnoh1u6K5EzHw9hLF2HeUfFkdbRvi2hJxFfDc68UHb09TZRaRDkWt9aklfNP8FPgWVZlvXqDqC8TyUMWG4sAAAAAElFTkSuQmCC","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Khosro","middleName":"","lastName":"Keshavarz","suffix":""}],"badges":[],"createdAt":"2022-02-20 05:29:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1377344/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1377344/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":18685255,"identity":"4eca4234-1c42-4847-bddf-c3073186898b","added_by":"auto","created_at":"2022-02-28 13:53:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":117457,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of the decision tree structure\u0026nbsp;to compare two plant and antibiotic treatments in patients with Helicobacter pylori infection\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1377344/v1/67902b18b4d9e7fa138d8c55.png"},{"id":18685254,"identity":"d657f661-0cc4-4a35-9467-97bcb0c95797","added_by":"auto","created_at":"2022-02-28 13:53:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":15690,"visible":true,"origin":"","legend":"\u003cp\u003eA cost-effectiveness Analysis for the plant\u0026nbsp;and antibiotic treatments in patients with Helicobacter pylori infection\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1377344/v1/b6b8b7314af65eb4dd50e443.png"},{"id":18685312,"identity":"8781ff6d-3437-49b3-b2ed-fa0626e5d413","added_by":"auto","created_at":"2022-02-28 13:56:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":9572,"visible":true,"origin":"","legend":"\u003cp\u003eTornado diagram for the cost-effectiveness of plant and antibiotic treatments in patients with Helicobacter pylori infection\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1377344/v1/ebe6668849d2338da655c3bb.png"},{"id":26158834,"identity":"180c05d4-0075-4564-b129-ff16329073ce","added_by":"auto","created_at":"2022-09-07 07:30:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":483409,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1377344/v1/b8e94569-e84c-406c-967a-a697779847e5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eCost-Effectiveness Analysis Of Plant Versus Antibiotic Regimens In Treating Patients With Helicobacter Pylori (H. Pylori) Infection In The South Of Iran\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHelicobacter pylori (H. pylori) is the most common bacterial infection worldwide[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the prevalence of which among adults in developed countries is 20\u0026ndash;40%[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the infection rate reaches 90% in the first 5 years of life in developing countries[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As the most common infectious agent, H. pylori is involved in a variety of common gastrointestinal disorders including gastritis, duodenal ulcer, peptic ulcer, adenocarcinoma, and gastric lymphoma[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and is also involved in about 89% of non-cardiac gastric cancers in the world[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In addition, it can lead to many diseases of non-digestive origin, such as cardiovascular disease, autoimmunity, Parkinson's, obesity, and allergic disorders[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Therefore, preventing or eradicating bacterial infections can help avoid these diseases.\u003c/p\u003e \u003cp\u003eNowadays, the biggest challenge in eradicating H. pylori infection is the low tolerance of patients for medical treatments, antibiotic resistance and side effects, and the high cost of antibiotic treatment[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Various treatment regimens containing several antimicrobial compounds have already been examined to eliminate H. pylori infection[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The failure of single drug methods has led to the development of drug regimens with a combination of three or four drugs, the most common of which is triple therapy. This treatment regimen includes a proton pump or inhibitor bismuth and two antibiotics, i.e. amoxicillin and clarithromycin[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Early studies suggested that eradication with triple therapy was cost-effective, and resistance to some strains was seen in more than 50% of the patients. However, triple therapy has shown a gradual decrease in efficacy (eradication rate of \u0026lt;\u0026thinsp;80%) in recent years[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. It also has side effects such as metallic taste in the mouth, increased sensitivity to light, constipation, and diarrhea[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The use of a four-drug regimen containing omeprazole, bismuth, and two antibiotics (Metronidazole and Tetracycline) was associated with 80% eradication and was recommended as a first-line treatment in areas with high resistance (over 15%) to Metronidazole and Clarithromycin in the patients who did not respond to the three-drug regimen containing Metronidazole or Clarithromycin[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The four-drug regimen is not only very expensive [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]but in many cases leads to treatment discontinuation before the end of the treatment course due to the complications such as seizures and polyneuropathy in the patients who use metronidazole for a long time[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite various treatment methods, recurrence of the disease has been reported in a number of cases after treatment completion. Therefore, the use of plants and herbal medicines may be beneficial due to their numerous medicinal effects[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Today, the antimicrobial effects of many plant species (e.g. garlic) on H. pylori infection have been investigated and proposed as a way of increasing the efficacy of H. pylori treatment[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The results of a study showed that adding garlic extract to the standard anti-H. Pylori infection regimen increased its eradication rate from 52.6\u0026ndash;75.8%[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and long-term consumption of garlic reduced the risk of gastric and colon cancers[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, the results of a study by McNulty et al. did not show a significant relationship between garlic consumption and eradication of H. pylori infection[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Thus, considering the high prevalence of gastrointestinal diseases in the world, especially gastric adenocarcinoma and its relationship with H. pylori, choosing the best treatment method that causes the highest eradication rate at the lowest cost is one of the challenges facing physicians[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Therefore, the present study aimed to analyze the cost-effectiveness of using different H. Pylori treatment methods in Shahid Motahari Clinic in Shiraz in 2020.\u003c/p\u003e"},{"header":"Methods Overview","content":"\u003cp\u003eThis prospective cost-effectiveness study was conducted on 132 H. pylori patients who referred to Shahid Motahari Clinic in Shiraz (referral clinic) in order to examine two drug treatment strategies including antibiotics and plants in 2020. The patients were randomly divided into two groups of receiving antibiotic (n\u0026thinsp;=\u0026thinsp;64) and plant (n\u0026thinsp;=\u0026thinsp;68) regimens. The antibiotic group was given a drug regimen including pantoprazole 40 mg twice a day, bismuth subcitrate 108 mg and tetracycline 500 mg 4 times a day, and metronidazole 200 mg three times daily and 400 mg once overnight for 14 days[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The plant receiving group was given Supermint Barij soft capsules 20 mg, Alium S garlic tablets 400 mg[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and Green Teadin (green tea) tablets 500 mg three times a day for 14 days[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA decision tree model was used to estimate the cost and effectiveness results. The cost data were collected from a community perspective, and direct and indirect costs were included in the study. The success rate of clinical trials in each treatment method was determined as the effectiveness outcome. A data collection form was also used to collect the cost and effectiveness data. The results were presented in the form of incremental cost-effectiveness ratio (ICER). Furthermore, the one-way sensitivity analysis was performed to measure the effects of parameter uncertainty in the model. The data were analyzed using TreeAge Pro 2011 and Excel 2016 software.\u003c/p\u003e\n\u003ch2\u003eInclusion And Exclusion Criteria\u003c/h2\u003e\n\u003cp\u003eThe inclusion criteria were as follows: the patients with dyspepsia who had a positive antigen stool test result; not taking antibiotics for at least 4 weeks before the start of the study; no history of allergies to mint, green tea, and garlic pills; and no use of other adjunctive therapy or medicinal plants for at least two weeks before the start of the study. The exclusion criteria were liver disease, gallstones or biliary obstruction, any gastrointestinal risk symptoms that required endoscopic examination (e.g., weight loss, anemia, severe gastrointestinal symptoms, recurrent vomiting, dysphagia, and gastrointestinal bleeding), not taking the drugs for at least one day, and not taking daily doses.\u003c/p\u003e\n\u003ch2\u003eTreatment Costs\u003c/h2\u003e\n\u003cp\u003eIn this study, the costs were collected from a community perspective. Therefore, they included direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs).\u003c/p\u003e \u003cp\u003eThe DMCs included the costs of medication, tests, doctor visits, and hospitalization, which would include the side effect cost of each treatment method and the use of a subsequent method in case of the failure of the initial treatment. The DMC data were collected from the patients' medical records as well as the opinions of clinical experts in this field.\u003c/p\u003e \u003cp\u003eThe DNMCs included transportation costs (intra-city and intercity) as well as food and accommodation costs for the patient and companions to receive medical services.\u003c/p\u003e \u003cp\u003eThe ICs also included the mean days of absence from work of the patients and companions and reduced productivity lost due to illness, disability, and death. The DNMC and IC data were collected based on the patients' self-report through face-to-face interviews or telephone calls. The human capital approach was used to calculate the IC[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In addition, all costs were calculated based on the tariffs of 2020 and converted into international dollars (purchasing power parity (PPP)) at the exchange rate of 1 dollar\u0026thinsp;=\u0026thinsp;22057 Rials[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\n\u003ch2\u003eModel Structure\u003c/h2\u003e\n\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows a schematic diagram of the decision tree model for antibiotic versus plant treatment strategies. The success and failure of the drugs and their side effects were plotted for each strategy in order to select the best. In addition, the costs and effectiveness of each strategy were entered into the model separately.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eInsert Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here:\u003c/p\u003e\n\u003ch2\u003eCost-effectiveness Analysis\u003c/h2\u003e\n\u003cp\u003eThe model was designed in Tree-age software and the extracted data were entered into it. The costs, effectiveness, and cost-effectiveness of the two drugs were then calculated and their ICERs were estimated using the following equation.\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$ICER=\\frac{cost plant-cost Antibiotics}{Effectiveness plant-Effectiveness Antibiotics}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch2\u003eSensitivity Analysis\u003c/h2\u003e\n\u003cp\u003eThe one-way sensitivity analysis was performed to investigate the effects of parameter uncertainty on the results. To this end, some key parameters such as cost and utility were changed by 20% for each drug strategy and the results were presented in the form of a Tornado Diagram. In addition, due to the lack of a cost-effectiveness threshold in Iran and as proposed by the World Health Organization (WHO), the threshold of one to three times the per capita GDP was considered for developing countries[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The GDP in Iran was \u003cspan\u003e$\u003c/span\u003e 12547 in 2019 (1* GDP)[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], using which the threshold of willingness to pay (WTP) was \u003cspan\u003e$\u003c/span\u003e 37641 (3* GDP) in the country[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 132 patients with H.pylori were included in the study. Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e provides descriptive results including the data on gender, age, employment status, and education. As shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, DMCs accounted for the highest costs in both groups (\u003cspan\u003e$\u003c/span\u003e 204.18 PPP in antibiotic and \u003cspan\u003e$\u003c/span\u003e 210.47 PPP in plant treatments). On the other hand, the lowest costs were associated to indirect costs with an average value of \u003cspan\u003e$\u003c/span\u003e 111.81 PPP in the antibiotic and \u003cspan\u003e$\u003c/span\u003e 119.83 PPP in the plant methods. Overall, the mean total cost of antibiotic treatment (\u003cspan\u003e$\u003c/span\u003e 446.14 PPP) was lower than plant treatment (\u003cspan\u003e$\u003c/span\u003e 477.81 (PPP)).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic variables among patients between two groups of plant and antibiotic\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eantibiotic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePercent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePercent\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003esex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"7\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u0026ndash;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u0026ndash;40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u0026ndash;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u0026ndash;60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u0026ndash;70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71\u0026ndash;80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cp\u003ePatients\u003c/p\u003e\n \u003cp\u003eemployment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eunemployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEmployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSelf employed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetired\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDaily worker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"7\"\u003e\n \u003cp\u003ePatient Education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIlliterate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFifth elementary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh school drop-out\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh school diploma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTwo year collage degree\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBachelor degree\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTOTAL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEstimated mean Direct medical and non-medical costs, Indirect costs, and Total costs per patient by Dollar in plant and antibiotic groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eType of Service\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePlant\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAntibiotic\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eDirect medical cost\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evisit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTests\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther services\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e210.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e204.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eDirect non-medical cost\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransport\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFoods\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccommodation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e147.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndirect cost\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime spent by the patient\u0026rsquo;s accompany and patient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal cost\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDirect Medical Costs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e210.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e204.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDirect Non-medical Costs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e147.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndirect Costs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal Costs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e477.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e280.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e446.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e256.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAccording to Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, the results of the cost-effectiveness analysis showed that the calculated effectiveness of antibiotic and plant strategies were 62.5% and 38.24%, respectively, and the costs were \u003cspan\u003e$\u003c/span\u003e 446.14 and \u003cspan\u003e$\u003c/span\u003e 457.81 PPP, respectively. Thus, antibiotic treatment was less costly and more effective, and therefore, a more cost-effective option and a dominant strategy.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison between cost and effectiveness in plant and antibiotic groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStrategy name\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEffectiveness\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCost (PPP\u003cspan\u003e$\u003c/span\u003e)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eICER\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e-0.243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e457.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e11.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e-48.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntibiotic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e446.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\u003csup\u003e*\u003c/sup\u003e ICER\u0026thinsp;=\u0026thinsp;Incremental cost effectiveness ratio\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch2\u003eUncertainty Analysis\u003c/h2\u003e\n\u003cp\u003eThe effects of uncertainty were studied using the one-way sensitivity analysis, and the value of each variable changed by 20%. Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e presents the results of the one-way sensitivity analysis in the form of a tornado diagram. The changes in many parameters did not have significant effects on the study results. However, ICER had the highest sensitivity to plant cost and the lowest sensitivity to the effectiveness of plant treatment in the patients with H. pylori. In fact, plant price was a determining parameter in ICER for the patients with H.pylori.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present research is in fact the first economic evaluation study that compared the cost-effectiveness of using antibiotic and plant treatments in patients with H. pylori in Iran. The results showed that antibiotic treatment was more cost-effective than plant treatment. Few studies have been conducted in this field. Using cost and effectiveness data to compare the cost-effectiveness of different H. pylori eradication regimens in the patients with gastric ulcer or chronic gastritis, Sancar et al (2006) concluded that the use of a 4-drug regimen was more cost-effective than other treatment regimens, and the eradication rate and cost-effectiveness ratio for the 4-drug treatment was 90% (\u0026euro; 158.7)[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], confirming the results of the present study. In contrast, Yousef-Nezhad et al. (2017) showed that H. pylori treatment with alternative therapies using herbal compounds had less toxicity and side effects and was more cost-effective and less costly than drug treatments[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Bokaeian et al (2013) also showed that the use of medicinal plants was cheaper than chemical drugs and easily accessible[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This is inconsistent with the results of the present study.\u003c/p\u003e \u003cp\u003eIn this study, using the antibiotic regimen including four types of antibiotics (pantoprazole, bismuth, tetracycline, and metronidazole) (0.625) was more effective than using the plant regimen (0.382).\u003c/p\u003e \u003cp\u003eThe results of the studies by Jun-Ling Ma et al. (2012) and Wei-cheng et al (2006) in China showed that treatment with amoxicillin and omeprazole reduced the incidence of H. pylori infection and gastric cancer by 39%, but long-term use of garlic and vitamins was not associated with a statistically significant reduction in the incidence of H. pylori infection and gastric cancer mortality [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Kaviani et al. (2001) in Iran examined the two-week treatment with amoxicillin, metronidazole, bismuth, and ranitidine to eradicate Helicobacter pylori and reported 73% of effectiveness[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The results of a study by Nijevitch et al. (2007) in Russia indicated that a triple-therapy including bismuth subcitrate, nifuratel, and amoxicillin was 86% successful in eradicating H. pylori infection in childhood[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Hojo et al. (2001) stated that eradication rate of Helicobacter pylori with a drug regimen containing amoxicillin, metronidazole, bismuth, and omeprazole was 39%[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. A study carried out by Tireno et al. in 1999 reported 75% potency of omeprazole, amoxicillin, and clarithromycin in eradicating Helicobacter pylori during two weeks[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe results of the study by Rahimian et al. (2013) in Shahrekord suggested that the combination of garlic and peppermint extracts, in comparison with metronidazole, was unsuccessful in eradicating H. pylori infection, and metronidazole could still be used as an effective drug in the treatment of the disease[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Graham et al. (1999) in the United States showed that the use of herbal medicines such as garlic and pepper had no effect on Helicobacter pylori compared to a drug regimen such as bismuth[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe ineffectiveness of plant regimens and the use of garlic in the treatment of the patients with H. pylori infection was stated in other studies [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. In contrast, the results of the study by Nagata et al. (2017) in China indicated the effectiveness of goshuyuto and the successful eradication of a resistant species of H. pylori infection with this medicinal plant compared to drug regimens[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Besides, Hajiagha mohammadi et al. (2015) in Qazvin stated that adding garlic extract to the standard anti-H. pylori regimen increased its eradication rate from 52.6\u0026ndash;75.8%[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Some other studies also indicated the effectiveness of plant regimens, especially garlic extract and green tea alone or in combination with other treatments such as proton pump inhibitors and antibiotics in the real stomach environment [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan additionalcitationids=\"CR46 CR47\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e], which are not in line with the results of this study.\u003c/p\u003e \u003cp\u003e According to the results of the one-way sensitivity analysis, the ICER was negative and the highest sensitivity was to the cost of the plant regimen, but considering that in the cost-effectiveness sensitivity analysis the ICER remained negative, it could be said that the results of the study were robust enough. Therefore, the results showed that the sensitivity analysis did not change the status of the antibiotic regimen as the most effective treatment, and this is a sign of the robustness of the study results.\u003c/p\u003e \u003cp\u003eOne strength of this study is the inclusion of total costs, including DMCs, DNMCs, and ICs. In addition, this is the first economic evaluation study in Iran addressing the cost-effectiveness of using antibiotic and plant treatment methods in patients with H.pylori. Among the limitations of this study are the relatively small sample size and the possibility or impossibility of generalizing the results to other geographical areas.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e According to the results of this study, antibiotic treatment was a cost-effective strategy compared to plant treatment and could be suggested as a good alternative to a wide range of patients with H. pylori infection. It could also be used as the first priority for the treatment of the patients in the country.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eH. pylori: Helicobacter pylori, ICER: Incremental Cost-Effectiveness Ratio, DMC: Direct Medical Costs, DNMC: Direct Non-Medical Costs, IC: Indirect Costs, WHO: World Health Organization, PPP: Purchasing Power Parity, GDP: Gross Domestic Product, PSA: Probabilistic Sensitivity Analysis, WTP: Willingness to Pay\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data are collected and handled in accordance with the relevant privacy protection guidelines. According to Iran law, the study did not fall under the remit of the Medical Research Involving Human Subjects Act and no approval by a medical ethics committee was necessary. Verbal consent was obtained from respondents who completed a questionnaire anonymously, and their response expressed their willingness to participate. Written consent was obtained from participants to the cognitive interviews\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants completed a consent form, stating that they were well-informed about the Content of questionnaires and that they agreed upon the publication of anonymized data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used in this study are not publicly available because the participants were promised that the raw data would remain confidential. However, they are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest regarding the publication of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by Shiraz University of Medical Sciences (Iran) through grant No\u0026nbsp;1323\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eand was approved by the ethics committee with the code of\u0026nbsp;IR.SUMS.REC.1398.1323.\u0026nbsp;The funder had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design: H.F., Z.Kh., F.L., M.E., Kh.K.; Material preparation and data collection: H.F., Z.Kh., F.L., M.R., M.E, Kh.K. ; Data analysis: Z.Kh.; Interpretation of data: H.F., Z.Kh., F.L., M.R., M.E, Kh.K; The frst draft of the manuscript was written by M.E.; Supervision: Kh.K. All authors read and approved the fnal manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe researchers would like to thank Shiraz University of Medical Sciences, especially Shahid Motahari Clinic and thank the studied patients for their kind cooperation with the researchers in collecting data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHekmatdoost, A., et al., \u003cem\u003eThe effect of garlic consumption on Helicobacter pylori treatment using urea breath test: a randomized clinical trial\u003c/em\u003e. Journal of Nutritional Sciences and Dietetics, 2015: p.\u0026nbsp;21\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFennerty, M.B., \u003cem\u003eHelicobacter pylori: why it still matters in 2005\u003c/em\u003e. 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Applied and environmental microbiology, 2000. \u003cb\u003e66\u003c/b\u003e(5): p.\u0026nbsp;2269\u0026ndash;2273.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cost-Effectiveness, Economic Evaluation, Helicobacter pylori, Antibiotic, plant ","lastPublishedDoi":"10.21203/rs.3.rs-1377344/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1377344/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eHelicobacter pylori infection is highly prevalent worldwide and affects more than half of the world's population. A variety of treatment regimens to eliminate H. pylori infection have been evaluated, but choosing the best treatment method that results in the most eradication at the lowest cost is one of the challenges facing physicians. Therefore, the present study aimed at analyzing the cost-effectiveness of using different methods to treat H. pylori in southern Iran. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis study was a cost-effectiveness analysis conducted on 132 patients with H. pylori who referred to Shahid Motahari Clinic in Shiraz. The study was carried out in 2020 to evaluate two drug treatment strategies, including antibiotics (pantoprazole 40 mg, Bismuth subcitrate 108 mg, tetracycline 500 mg, and metronidazole 200 and 400 mg) and plants (Supermint Barij soft capsules 20 mg, Alium S garlic tablets 400 mg, and Green Teadin (green tea) tablets 500 mg). The patients were randomly divided into two groups, 64 of whom received an antibiotic regimen and 68 patients given a plant regimen. The success rate of clinical trials in each treatment method was determined as the clinical outcome. This study was conducted from a community perspective and therefore, direct and indirect costs were included. A data collection form was also used to collect the cost and effectiveness data. In addition, a one-way sensitivity analysis was performed to measure the robustness of the results. The data were analyzed using TreeAge Pro 2011 and Excel 2016 software. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe results showed that antibiotic treatment was cheaper and more effective than plant treatment and was the dominant strategy. The mean costs in the antibiotics and plant groups were $446.14 and $477.81, respectively, and the effectiveness was 0.625% and 0.382%. In addition, the one-way sensitivity analysis confirmed the robustness of the study results. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe results showed that the use of antibiotics was a cost-effective and dominant strategy compared to plant treatment and could be suggested as a better alternative to a wide range of patients with Helicobacter pylori infection. \u003c/p\u003e","manuscriptTitle":"Cost-Effectiveness Analysis Of Plant Versus Antibiotic Regimens In Treating Patients With Helicobacter Pylori (H. Pylori) Infection In The South Of Iran","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-02-28 13:53:47","doi":"10.21203/rs.3.rs-1377344/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e062e06-882b-48dc-a37f-e5d172023265","owner":[],"postedDate":"February 28th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-09-07T07:29:56+00:00","versionOfRecord":[],"versionCreatedAt":"2022-02-28 13:53:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1377344","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1377344","identity":"rs-1377344","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}