Safety and Efficacy of Bhutanese Traditional Herbal Drug Formulary for Gastritis-Related Problems (SEDRU): a Nationwide Observational Study

Safety and Efficacy of Bhutanese Traditional Herbal Drug Formulary for Gastritis-Related Problems (SEDRU): a Nationwide Observational Study | 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 Safety and Efficacy of Bhutanese Traditional Herbal Drug Formulary for Gastritis-Related Problems (SEDRU): a Nationwide Observational Study Dorji Gyeltshen, Thinley Dorji, Krit Pongpirul, Tharpala Tharpala This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4815044/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Background Gastritis-related symptoms, often manifesting as stomach disorders, are among the top ten diseases diagnosed and treated in traditional medicinal units (TMU) in Bhutan. This study evaluated the safety and potential efficacy of the currently used medications for stomach disorders in Bhutan. Methods This prospective observational study was conducted across all 63 TMUs in Bhutan over a six-month period in 2019. Patients presenting with gastritis-related symptoms were enrolled and monitored throughout the study. Adverse reactions were assessed using the Naranjo algorithm. The Severity of Dyspepsia Assessment (SODA) scores, both overall and recipe-specific, were recorded at baseline and at weekly follow-up visits. The changes in SODA scores over time were analyzed using repeated measures ANOVA to assess the efficacy of the herbal treatments. Results A total of 152 patients were included in the study, with baseline information available for 109 patients. Follow-up data were collected for 100 patients at one week, 88 patients at two weeks, 72 patients at three weeks, and 51 patients at four weeks. The most common prescribed herbal drugs were Sedru 5, Ruta 6 and Zhijay 6 . The baseline SODA score averaged 54.4 (± 8.8), which decreased progressively to 50.0 (± 8.3) at week 1, 46.9 (± 8.0) at week 2, 42.7 (± 12.0) at week 3 and 38.9 (± 13.7) at week 4, with a statistically significant improvements (p < 0.001). Nine adverse drug events were reported, but there were no definite adverse drug reactions. Patient satisfaction with the traditional formulations also showed a significant improvement. Conclusion The study found significant improvements in both pain and non-pain symptoms of gastritis, as well as patient satisfaction, with the use of traditional Bhutanese herbal medicines. The absense of definite adverse drug reactions indicates a favorable safety profile for these treatments. This study marks the first time the traditional medicine system in Bhutan has adopted scientific measures to promote evidence-based clinical practice, demonstrating a significant step forward in integrating traditional knowledge with modern research methodologies. Trial registration : Thai Clinical Trials Registry TCTR20180430004 dated 30 April 2018. Gastritis Dyspepsia Health status Traditional medicinal units Evidence-Based Medicine Complementary Therapies Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Background Traditional Medicine ( Sowa Rigpa ) is an integral part of Bhutan’s healthcare system and is recognized in the National Health Policy 2011. Practiced for over two thousand years in Bhutan and several countries in the Himalayan region [ 1 ], Sowa Rigpa is now gaining acceptance in Western countries as well. This traditional medicine system is based on balancing five inner elements (air, earth, water, fire, and space) within the three psycho-physical ‘humours’ (bile, phlegm, and wind) [ 2 , 3 ]. Imbalances or disturbances caused by diet, injury, or environmental stress can lead to disease and death. Diagnosis in Sowa Rigpa involves a detailed history and physical examination focusing on the tongue, pulse, and urine. Currently, these traditional medicines are produced by the state-owned Menjong Sorig Pharmaceuticals and included in the National Essential Medicines List [ 4 ]. They are distributed free of charge through Traditional Medicine Units (TMUs) in all primary, secondary and tertiary hospitals across Bhutan. With the adoption of patient safety measures, traditional medicines are now also subject to evidence-based medicine standards. Stomach disorders are among the top ten diseases treated in TMUs in Bhutan [ 5 ]. Gastritis, a major component of these disorders, had an incidence rate of over 827 cases per 10,000 population in 2017 [ 6 ]. In Sowa Rigpa , gastritis-related illnesses are referred to as pho-rlung , with a prevalence of gastritis-related symptoms estimated at 8.4% [ 7 ]. Traditional herbal drugs like Sedru 4, 5, 8 ; Ru-ta 6 and Zhijay 6 are commonly prescribed for gastritis, along with other traditional therapies. The traditional herbal drug formulary (THDF) of Bhutan combines various ingredients prescribed in the Fourth Medical Tantra, chosen for their possession of curative power due to its characteristics ( yon-ten ), natural potency ( ngo-bu nus-pa ), and taste ( ro ). While no research has been conducted on Bhutanese traditional medicine recipes for gastritis, numerous studies have examined their components. For instance, pomegranate ( Punica granatum Linn : Sedru) [ 8 ], cinnamon ( Cinnamomum verum ) [ 9 ] and long pepper ( Piper longum ) [ 10 ] are noted for their anti-inflammatory properties in the gastrointestinal tract and have been proven safe in other traditional medicine systems. The term gastritis-related illness is considered the most linguistically compatible with Bhutanese traditional medicine concepts. Nonetheless, the symptoms described by Bhutanese patients, in the absense of gastroscopic evidence, often suggest functional dyspepsia, a condition that is not well defined either. Among the 16 symptom-based Functional Dyspepsia Patient-Reported Outcome (PRO) instruments (range: 4 to 42 total items) identified in a recent literature review [ 11 ], the 17-item SODA score was optimal for capturing the wind and phlegm disorders described by Bhutanese patients, making it suitable for this study [ 12 ]. The objectives of this study were to monitor the safety and potential efficacy of the currently used THDFs in Bhutan for the treatment of gastritis-related illnesses and to introduce the documentation of standard clinical outcome measures as a simplified medical recording approach among traditional medicine practitioners. The specific PRO objectives were to explore whether the translated SODA score could reflect the changes of clinical symptoms of Bhutanese patients with gastritis-related illnesses and which of the 17 items is/are most responsive to each THDF. By addressing these objectives, this study aims to provide valuable insights into the safety and efficacy of traditional herbal drugs used in Bhutan and promote the integration of evidence-based practices in traditional medicine. Methods Study design This was a prospective observational study (Clinical Study Phase II/III) according to the World Health Organization framework for research and evaluation of Traditional Medicine [ 13 ]. Study setting Bhutan is the small Himalayan Kingdom where the practice of traditional medicine has remained preserved as practiced for thousands of years. Known as Sowa Rigpa , the science of healing was formally integrated into the healthcare system of Bhutan in 1968 [ 4 ]. Traditional Medicine is a complete package in Bhutan – its human resources are trained within Bhutan and all medicines are produced within the country. Traditional Medicine is popular and much sought after as an alternative medicine even in current digital and information age in Bhutan and several other countries. As of 2023, Bhutan had 81 TMUs, which share facilities with allopathic hospitals, including the National Traditional Medicine Hospital located in Thimphu. The administration of these units falls under the National Medical Services. There are two categories of traditional medicine practitioners. Those trained for six years and with degree holders are called drungtsho ; they can prescribe drugs and perform surgical procedures. Those trained for three years are called menpa ; they dispense drugs and perform supportive work. Pho-rlung has its operational definition and diagnosis according to the Sowa Rigpa system. The traditional medicine practitioner has several drugs at his disposition. Sedru 5, Sedru dangnay, Ruta 6, and Zhijay 6 are available at all hospital levels. The rest of the drugs are available only in the tertiary and secondary centers. After the formal integration of traditional medicine in the healthcare system of Bhutan, there has been continued effort to make it relevant and accessible to people through its improved quality services. In an effort to better document patient’s history, clinical assessment, and prescription practice pattern before and after the traditional medicine treatment, the Department of Traditional Medicine Services, Royal Government of Bhutan has introduced several validated tools such as the Severity of Disease Assessment (SODA) [ 14 ] and the Naranjo algorithm [ 15 ] to detect adverse drug reactions to traditional medicines in 2018. Sample size and sampling method This study included all adults age at least 18 years old with gastritis-related problems (wind and phlegm disorders) diagnosed by any licensed traditional medicine practitioner. No formal sample size was calculated. As both SODA score and the Naranjo’s algorithm were translated, language requirement was not a PRO-specific barrier to the study entry. This study excluded patients with severe gastrointestinal problems with blood in the vomitus, blood in the stools, melena (tarry black stools), recent weight loss of more than 5% of body weight in the last six months; patients with concomitant bile disorders ( thri-shes che-ba ); and known allergy to the components of the medicine. Treatment regimens prescribed by TM physicians All those patients who were treated for gastritis-related illnesses with the medicines Sedru 4, Sedru 5, Sedru 8, Sedru dangnay, Sedru nyikhil, Ruta 6 , and Zhijay 6 were be assessed by the treating traditional medicine practitioners by filling SODA 1, 2, 3 and 4 at the end of therapy for the respective week. The composition of these recipes is presented in Supplementary Table 1. All of these drugs are manufactured by the Menjong Sorig Pharmaceuticals—the only drug manufacturing company for traditional medicine in the country. This state-owned company follows standard guidelines in the collection and storage of ingredients and the Good Manufacturing Practices for production. For the purpose of this study, medicines were prescribed weekly and symptoms assessed weekly with the SODA score [ 14 ]. The patients were followed up for a period of four weeks after which the care for the patients may continue depending upon the physician’s advice. Physicians were allowed to practice in their natural environment. The choices of drugs, duration of therapy, change of regimen, the combination of drugs, stopping the regimen, switching of the regimen, the combination with allopathic medicines and referral to allopathic medicine were all allowed and data were collected on those parameters. Sedru 4, Sedru 5, Sedru 8, Sedru dangnay, Sedru nyikhil, Ruta 6 , and Zhijay 6 were formulated as a pill of 500 mg. Sedru 4, 5, Sedru nyikhil, Ruta 6 and Zhijay 6 were prescribed as 1500 mg BD while Sedru 8 was prescribed 1500 mg in the evening and Sedru dangnay as 1500 mg in the morning [ 16 ]. The prescription of the treatment regimens were up to the clinical indication according to the principles of gSo-ba Rig-pa . There was no randomization of patients to specific treatment arms. In the event the patient developed severe gastrointestinal problems with blood in the vomitus, blood in the stools, melena (tarry black stools), recent weight loss of more than 5% of body weight in six months, the patient was referred to an allopathic doctor as per the Standard Operating Procedure of the Department of Traditional Medicine Services, Royal Government of Bhutan [ 16 ]. The treating traditional medicine practitioner encouraged their patients to comply on the dose and timing of medicines, completion of treatment course and come for next consultation review. The patients were allowed to take allopathic medicines at the same time as the traditional medicine. Outcome assessment Primary Outcome: Safety / Adverse Drug Reaction (ADR) were assessed by using the Naranjo’s algorithm [ 15 ] at four weekly time points (Week 1,2,3,4) after the treatment commenced. Secondary Outcome: Gastritis-like symptoms were assessed by using the SODA scores [ 14 ] as part of the routine evaluation done by the traditional medicine practitioners before starting the treatment and at five weekly time points (Week 0, 1, 2, 3, 4) after the treatment was started. Both total, scale, and itemized scores were evaluated in terms of the weekly changes from baseline. Traditional medicine practitioners were trained in using the Dzongkha version of the SODA score and the Naranjo’s algorithm to ensure accurate and consistent data collection. If patients concurrently took allopathic medicines along with traditional medicine, information on the allopathic medicines was also collected to account for potential interactions and confounding factors. Data collection tool The patient characteristics collected were age, sex and the patient’s medical nature that included the nature of wind, bile, and phlegm. Only those patients who consented to allow his or her de-identified data to be used for this study were extracted. The SODA score is the PRO instrument used in this study. It contains 17 items in three scales: pain symptoms (6 items; range 2–47 points), non-pain symptoms (7 items; 7 to 35 points), and satisfaction (4 items; 2 to 23 points) [ 10 ]. It has good criterion validity as well as high Cronbach’s alpha reliability for the pain symptoms (0.97), non-pain symptoms (0.90), and the satisfaction scales (0.92) [ 10 ]. The Guyatt’s responsiveness indices (the ability of a scale to detect a minimal amount of change considered important by patients or physicians) were large for the pain symptoms (0.98) and satisfaction (0.87) but small for the non-pain symptoms (0.24). The traditional medicine practitioners who participated in this study were trained to use the translated SODA score. A manual in Dzongkha language was also provided. The SODA score [ 14 ] and the Naranjo’s algorithm [ 15 ] were translated from English into Dzongkha by an English-speaking Bhutanese medical doctor whose mother tongue was Dzongkha. The score was then translated back to English by another English-speaking Bhutanese traditional medicine practitioner whose mother tongue was Dzongkha and has no knowledge of the score. The score was pre-tested on ten randomly selected patients who were also debriefed and interviewed. Their inputs were used to create the final version of the score. Data collection period Data of patients who were treated for the period of June to December 2019 were extracted. Patients were recruited from June to December 2019. The follow up of the last group of patients ended in January 2020. The data monitoring committee comprised of one coordinating centre representative (TD), one sponsor representative (DG), and one non-Bhutanese investigator (KP). DG was responsible for checking the data completeness and removing any data that could be used for identifying the patients and the sites. TD and KP were responsible for the data analysis, writing of the report, and submitting the report for publication. The adverse drug reaction was the primary outcome of this study and was assessed by using the Naranjo’s algorithm [ 15 ] at four weekly time points (Week 1, 2, 3, 4) after the treatment was started. Data entry and analysis The data collection forms were coded and a data documentation sheet was prepared. The data was double entered and validated in EpiData version 3.1 (EpiData Association, Odense, Denmark). Descriptive statistics is used for presenting the patient and clinical characteristics. The changes of overall and recipe-specific SODA scores at baseline and at each of the follow-up visits is compared by using repeated measures ANOVA. STATA version 18 was used for all data analyses. Ethics considerations This study was conducted in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use – Good Clinical Practice (ICH-GCP) guidelines. The study protocol was reviewed and approved by the Research Ethics Board of Health (REBH), Ministry of Health, Bhutan via letter no REBH/Approval/2018/089 dated 08 January 2019. Consent to prescribe the traditional medicines was obtained by the prescribing traditional medicine practitioners as part of standard clinical practice. For the purpose of this study, additional consent was sought from patients to allow their de-identified data to be extracted and used for analysis. Results A total of 152 patient were followed up in this observational study. Baseline information was available for 109 patients, with follow-up data for 100 patients at one week, 88 at two weeks, 72 at three weeks, and 51 at four weeks. The mean age of the study participants was 44.5 (± 14.8) years, and 97 (65.5%) were females. The basic details of the study participants are shown in Table 1 . The number of patients who received traditional medicines and those who co-consumed allopathic medicines are shown in Table 2 . Table 1 The basic details of the study participants with stomach disorders who were treated with traditional medicines in Bhutan, 2019 Basic characteristics n (%) Total 152 100 Age group (years) 1 ≥ 18–24 10 6.7 25–34 30 20.0 35–44 47 31.3 45–54 25 16.7 55–64 20 13.3 ≥ 65 18 12.0 Sex 2 Female 97 65.5 Male 51 34.5 Elemental nature of patient (according to Sowa Rigpa ) 3 Lung 17 12.4 Thripa 4 2.9 Beyken 16 11.7 Lung-Thri 24 17.5 Bey-Thri 20 14.6 Bey-Lung 52 38.0 Duepa 4 2.9 Level of hospital 4 National Traditional Medicine Hospital/ Regional referral hospital 3 2.1 District/General hospital 74 51.0 Primary Health Centres 68 46.9 1 missing = 2 2 missing = 4 3 missing = 15 4 missing = 7 Table 2 Bhutanese traditional medicines prescribed and co-consumption of allopathic medicines among patients with stomach disorders in Bhutan, 2019 Medicine group Week 1 Week 2 Week 3 Week 4 n (%) n (%) n (%) n (%) Number of patients 100 (100.0) 88 (100.0) 72 (100.0) 51 (100.0) Bhutanese Traditional Medicines for stomach disorder 1 Sedru 4 10 (10.0) 7 (8.0) 8 (11.1 5 (9.8) Sedru 5 99 (99.0) 88 (100.0) 72 (100.0) 48 (94.1) Sedru 8 7 (7.0) 7 (8.0) 8 (11.1) 7 13.7) Sedru dangnay 35 (35.0) 35 (39.8) 30 (41.7) 14 (27.5) Sedru nyikhil 13 (13.0) 15 (17.0) 11 (15.3) 4 (7.8) Ruta 6 90 (90.0) 75 (85.2) 72 (100.0) 45 (88.2) Zhijay 6 76 (76.0) 72 (81.8) 67 (93.1) 39 (76.5) Co-consumption of any allopathic medicine 1 4 (100.0) 7 (100.0) 5 (100.0) 4 (100.0) Ranitidine 2 (50.0) 2 (28.6) 1 (20.0) 1 (25.0) Omeprazole 1 (25.0) 1 (14.2) 2 (40.0) 1 (25.0) Antacid 1 25.0 2 (28.6) - - - - Losartan 1 (25.0) 1 (14.2) 1 (20.0) 1 (25.0) Hydrochlorothiazide 1 (25.0) 1 (14.2) 1 (20.0) 1 (25.0) Amitriptyline - - 1 (14.2) - - - - Vitamin B - - 1 (14.2) - - 1 (25.0) Vitamin C - - 1 (14.2) - - - - Ibuprofen - - - - 1 (20.0) - - Dicyclomine - - - - 1 (20.0) - - 1 Multiple responses were allowed Severity of dyspepsia assessment (SODA) Over the course of the follow-up, there was a significant improvement in the overall SODA score, as well as in pain intensity, non-pain symptoms, and satisfaction scores (Table 3 and Fig. 1). The overall SODA score at baseline was 54.4 (± 8.8) and decreased to 50.0 (± 8.3) at Week 1, 46.9 (± 8.0) at Week 2, 42.7 (± 12.0) at Week 3 and 38.9 (± 13.7) at Week 4 (p < 0.001). The pain intensity score significantly decreased from 26.5 (± 5.6) at baseline to 23.7 (± 5.4) at Week 1, 21.3 (± 5.5) at Week 2, 17.7 (± 8.5) at Week 3, and 14.4 (± 10.3) at Week 4 (p < 0.001). The non-pain symptom score significantly decreased from 16.4 (± 3.6) at baseline to 14.2 (± 3.4) at Week 1, 12.6 (± 3.5) at Week 2, 11.4 (± 3.6) at Week 3, and 10.3 (± 3.6) at Week 4 (p < 0.001). The patient satisfaction score increased from 11.5 (± 3.4) at baseline to 12.2 (± 3.6) at Week 1, 13.2 (± 3.8) at Week 2, 13.2 (± 3.8) at Week 3, and 14.5 (± 5.0) at Week 4 (p < 0.001). Table 3 The details of Severity of Dyspepsia Assessment of patients at baseline and on weekly followed in SEDRU study, Bhutan, 2019 SODA domain Baseline Week 1 Week 2 Week 3 Week 4 P value Pain intensity score 26.5 (± 5.6) 23.7 (± 5.4) 21.3 (± 5.5) 17.7 (± 8.5) 14.4 (± 10.3) < 0.001 Non-pain symptom score 16.4 (± 3.6) 14.2 (± 3.4) 12.6 (± 3.5) 11.4 (± 3.6) 10.3 (± 3.6) < 0.001 Satisfaction score 11.5 (± 3.4) 12.2 (± 3.6) 13.2 (± 3.8) 13.2 (± 3.8) 14.5 (± 5.0) < 0.001 Total score 54.4 (± 8.8) 50.0 (± 8.3) 46.9 (± 8.0) 42.7 (± 12.0) 38.9 (± 13.7) < 0.001 Trends of SODA scores, pain intensity, non-pain symptoms, and satisfaction scores for specific traditional medicines (Sedru 4, Sedru 5, Sedru 8, Sedru dangnay, Sedru nyikhil, Ruta 6 , and Zhijay 6) over four weeks are shown in Figs. 2–8. Adverse events to SEDRU drugs A total of 9 adverse events were reported in this study. According to the Naranjo’s algorithm, there was only one probable ADR, one possible ADR and the rest were doubtful (Table 4 ). Table 4 Naranjo’s score for the adverse reactions among patients who received the SEDRU group of medicines, Bhutan, 2019. Naranjo’s core n (%) Definite ADR (score ≥ 9) 0 (0) Probable ADR (score 5–8) 1 (11.1) Possible ADR (score 1–4) 1 (11.1) Doubtful ADR (score 0) 7 (77.8) Supplementary Table 1. Composition of the Seven Bhutanese Traditional Herbal Drug Recipes studied in the SEDRU study, 2019 Discussion The traditional medicine system prevalent in Bhutan has, for the first time, adopted scientific measures to promote evidence-based clinical practice. This prospective study focused on the gastritis-related symptoms, which are among the top ten disease burdens in the country. The study demonstrated a progressive improvement in the overall dyspepsia assessment score and all three of its domains: pain symptoms, non-pain symptoms, and overall satisfaction. Although this study primarily reports empirical assessments of prescription practices and patient-reported efficacy of these traditional medicines, the findings provided a baseline for further exploration of the efficacy of these herbal formulations. Given that Sedru 5, Ruta 6 and Zhijay 6 were more commonly used, ensuring their production and availability at all hospital levels is essential. Sedru 5 contains ingredients such as pomegranate, cardamom, cinnamon, long pepper and ginger. Ruta 6 includes Saussurea lappa , long pepper, Justicia gendarussa , pomegranate, cardamom and gooseberry. Zhijay 6 consists of Inula, soapstone, soda, ginger, agerstroemia and Rheum palmatum . The use of pomegranate peel extract in sachets of 2.5 g twice a day after meals for 28 days has been reported to improve dyspepsia symptoms and Gastrointestinal Symptom Rating Scale [ 17 ]. Polyphenolics, flavonoids, anthocyanosides, alkaloids, lignans, and triterpenes found in pomegranate ( Punica granatum L.) have been evaluated for their effects in managing cancer and metabolic syndrome [ 17 ]. Additionally, various plant products and extracts have been evaluated for improving dyspepsia symptoms [ 18 ]. Many herbal preparations contain ingredients common in traditional formulations reported from several countries [ 18 ]. With growing interest in finding efficacious therapeutic agents for functional dyspepsia, empirical findings from this study provide valuable opportunities for drug discovery. This study also demonstrated significant improvement in patient satisfaction with the use of these traditional medicines. This factor is important not only for treating a single pho-rlung disease but also for the overall acceptance of Traditional Medicine among the 21st -century population of Bhutan. Traditional Medicine services remain popular among the public across all age groups, with high patient satisfaction reported [ 19 ]. For the first time in Bhutan’s Traditional Medicine system, changes in symptoms in response to commonly prescribed traditional medicine drugs were formally observed and documented using standardized and validated tools. The SODA questionnaire and the case record forms were introduced by the Department of Traditional Medicine Services to improve documentation. Although the use of such forms required training, the quality of data generated for this study demonstrates that such forms can be adopted as part of the system. The chosen tool is relatively simple and resulted in good compliance, as anticipated. The Naranjo’s algorithm reported only 10 cases of adverse drug reactions, out of which only one case was a “probable” ADR. This demonstrates that the six drug formulations studied in this study is safe. The use of the Naranjo algorithm to assess adverse drug reactions in the traditional medicine system is the first time in Bhutan. The acceptance of these forms in the traditional medicine system is a reflection of strong leadership to make Bhutanese Traditional Medicine relevant to modern times. This form helps to document ADRs and assess the strength of relationship between the drug and the ADR. This form will remain an important part of the Traditional Medicine System. It was also realised that for the data collected through Naranjo algorithm to be of future use, a national centre for reporting and assessment of ADRs in Traditional Medicine should be established. This centre requires individuals who understand the intricate considerations of the Traditional Medicine system as well as good understanding of pharmacology and chemistry. Establishment of such data repository will serve to house data that will contribute to making Traditional Medicine practices evidence-based. This national level project aimed to introduce modern research culture and build the research capacity of traditional medicine practitioners. Educated in the national language Dzongkha, practitioners face barriers in conveying traditional medicine concepts scientifically in English. Selecting a standard PRO instrument is critical to balancing scientific integrity and acceptability. The forward-and-back translation of PRO instruments and the adoption of such practices demonstrate the resolve of the Traditional Medicine System to remain relevant in the 21st century and beyond. Limitations This study was planned as a nationwide initiative involving all TMUs in Bhutan. However, data could only be collected from select centres, which resulted in a smaller sample size than initially intended. Despite the reduced sample size, the findings are promising and provide valuable insights into the safety and efficacy of traditional herbal medicines for gastritis-related problems. Conclusion The traditional medicine system in Bhutan has made significant strides by adopting scientific measures to promote evidence-based clinical practice. This prospective study focused on gastritis-related symptoms, one of the top ten disease burdens in the country. The study demonstrated progressive improvement in the overall dyspepsia assessment score and all three of its domains: pain symptoms, non-pain symptoms, and overall satisfaction. The use of standardized and validated tools such as the SODA questionnaire and the Naranjo algorithm has facilitated the formal observation and documentation of symptom changes in response to traditional medicine. The quality of data generated demonstrates that these tools can be successfully integrated into the traditional medicine system, resulting in good compliance. Given the common use of Sedru 5 , Ruta 6 , and Zhijay 6 , ensuring their production and availability at all hospital levels is essential. The study also highlighted the safety of these traditional medicines, with minimal adverse drug reactions reported. The findings from this study, despite the smaller sample size, provide a baseline for further exploration of the efficacy of traditional herbal formulations. The significant improvement in patient satisfaction underscores the importance of Traditional Medicine in Bhutan's healthcare system. This study marks an important step toward integrating traditional knowledge with modern research methodologies, ensuring the continued relevance of Traditional Medicine in the 21st century and beyond. Abbreviations ANOVA An alysis o f Va riance PRO P atient- R eported O utcome REBH R esearch E thics B oard of H ealth SODA S everity o f D yspepsia A ssessment TMU T raditional M edicine U nit THDF T raditional H erbal D rug F ormulary Declarations Ethics approval and consent to participate The study protocol was reviewed and approved by the Research Ethics Board of Health (REBH), Ministry of Health, Bhutan via letter no REBH/Approval/2018/089 dated 08 January 2019. Consent to prescribe the traditional medicines was obtained by the prescribing traditional medicine practitioners as part of standard clinical practice. For the purpose of this study, additional consent was sought from patients to allow their de-identified data to be extracted and used for analysis. Consent for publication Not applicable Availability of data and materials The complete dateaset is available from the corresponding author on request. Competing interests The authors declare no competing interests. Funding There was no funding for this study. Authors' contributions DG, TD and KP were involved in Conceptualization, Methodology, Software, Validation, Formal analysis, Writing – original draft, Writing – review and editing. DG and TD were involved in Resources and Data Curation. Acknowledgements We would like to than Ugyen Thinley, Pelden Zangpo, Dorji Wangchuck, Tsheltrim Dorji, Terpola and all other Traditional Medicine practitioners, and the Department of Traditional Medicine Services, Ministry of Health, Bhutan for their contribution in the development and implementation of this study. References McKay A, Wangchuk D. Traditional Medicine in Bhutan. Asian Med. 2005;1:204–18. Dorji T, Melgaard B. Medical History of Bhutan: A chronicle of health and disease from Bon times to today. 2nd edition. Centre for Research Initiatives; 2018. Wangchuk P, Wangchuk D, Aagaard-Hansen J. Traditional Bhutanese medicine (gSo-Ba Rig-Pa): an integrated part of the formal health care services. 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SODA (severity of dyspepsia assessment): a new effective outcome measure for dyspepsia-related health. J Clin Epidemiol. 2001;54:755–65. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45. Department of Traditional Medicine Services. Standard Operating Procedures for Traditional Medicine Services. Thimphu: Department of Traditional Medicine Services, Ministry of Health, Bhutan; 2015. Gupte PA, Mahajan MP, Revadkar Kole MS, Mandlecha AH, Tatke PA, Naharwar VA, et al. Efficacy and acceptability of pomegranate effervescent granules in patients suffering from acid peptic disorders. Indian J Pharmacol. 2022;54:7–12. Báez G, Vargas C, Arancibia M, Papuzinski C, Franco JV. Non-Chinese herbal medicines for functional dyspepsia. Cochrane database Syst Rev. 2023;6:CD013323. Chogyel T, Lhendup N, Dorji UD, Choeda T. Patient Satisfaction Survey in Traditional Medicine Units in Bhutan, 2023: a cross-sectional survey. Bhutan Sorig J. 2024;1:23–8. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 31 Jul, 2024 Submission checks completed at journal 31 Jul, 2024 First submitted to journal 27 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4815044","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":335149630,"identity":"9a328440-c6b4-464d-93b3-897b6dd9ae61","order_by":0,"name":"Dorji Gyeltshen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYDCCAxAqAYgNGBh4JOTAgg8IaklAaDEGCyYQr4WBIbEBZikuwHf7jNnDrz/q8vgZmDc+rpCxSJ8fdvgh0BY7Od0G7Fokz+WYG8skHC6WbGArNjzDI5G78XaaAVBLsrHZAexaDM7wmElLJBxI3HCAx0yyAaRldgJIy4HEbfi11MG1pBvOTv9AUIvkhwRmuJYEeekc/LZInmErk2ZIO5w4sxnoF6AWww3SOQUHEgxw+4XvDPM2yR82dYn97M0bHzb21MnLz07f/OFDhZ0cLi0gwMwDJoGYsQfoVLBKA9zKQYDxB5wJZMk34Fc9CkbBKBgFIw8AANnIXpWDAqt3AAAAAElFTkSuQmCC","orcid":"","institution":"National Traditional Medicine Hospital","correspondingAuthor":true,"prefix":"","firstName":"Dorji","middleName":"","lastName":"Gyeltshen","suffix":""},{"id":335149631,"identity":"bb69818e-06f7-48fa-a39c-2a14f3320646","order_by":1,"name":"Thinley Dorji","email":"","orcid":"","institution":"Central Regional Referral Hospital","correspondingAuthor":false,"prefix":"","firstName":"Thinley","middleName":"","lastName":"Dorji","suffix":""},{"id":335149633,"identity":"9a757955-8352-4826-b4d6-202cd2738f72","order_by":2,"name":"Krit Pongpirul","email":"","orcid":"","institution":"Chulalongkorn University","correspondingAuthor":false,"prefix":"","firstName":"Krit","middleName":"","lastName":"Pongpirul","suffix":""},{"id":335149638,"identity":"7ea83367-2f9b-412d-b4df-5bbac9dfcfa8","order_by":3,"name":"Tharpala Tharpala","email":"","orcid":"","institution":"National Traditional Medicine Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tharpala","middleName":"","lastName":"Tharpala","suffix":""}],"badges":[],"createdAt":"2024-07-28 03:53:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4815044/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4815044/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":64005697,"identity":"8da6d488-4ebd-4850-9c6e-45e5c1e637df","added_by":"auto","created_at":"2024-09-04 21:39:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":93346,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among patients with stomach disorders who were treated with Bhutanese traditional medicines (\u003cem\u003eSedru4, Sedru5, Sedru8, Sedru dangnay, Sedru nyikhil, Ruta6, and Zhijay6\u003c/em\u003e), Bhutan, 2019\u003c/p\u003e\n\u003cp\u003e(a) Decrease in overall Severity of Dyspepsia Assessment score\u003c/p\u003e\n\u003cp\u003e(b) Decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) Decrease in non-pain score\u003c/p\u003e\n\u003cp\u003e(d) Increase in satisfaction score\u003c/p\u003e","description":"","filename":"Slide1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/019acad5973f17270f320881.jpg"},{"id":64006175,"identity":"d6cd72d2-782b-4f3a-80f7-bf3e98e67a11","added_by":"auto","created_at":"2024-09-04 21:47:38","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84234,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among those who were prescribed \u003cem\u003eSedru 4 \u003c/em\u003e(a) Decrease in overall SODA score\u003c/p\u003e\n\u003cp\u003e(b) Decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) Decrease in non-pain score over first week\u003c/p\u003e\n\u003cp\u003e(d) Increase in satisfaction score till first week\u003c/p\u003e","description":"","filename":"Slide2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/7b4e2058f1d30f016efa10d0.jpg"},{"id":64005705,"identity":"6351f065-22af-46dc-96b8-a8161d5b52ed","added_by":"auto","created_at":"2024-09-04 21:39:38","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":93588,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among those who were prescribed \u003cem\u003eSedru 5\u003c/em\u003e (a) Decrease in overall SODA score\u003c/p\u003e\n\u003cp\u003e(b) Decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) Decrease in non-pain score\u003c/p\u003e\n\u003cp\u003e(d) Slight increase in satisfaction score\u003c/p\u003e","description":"","filename":"Slide3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/ffbd00218461673a4dfbf164.jpg"},{"id":64005706,"identity":"6ca6ae22-1c2f-41f9-bb26-8a5bd5d5d188","added_by":"auto","created_at":"2024-09-04 21:39:38","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":95750,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among those who were prescribed \u003cem\u003eSedru 8\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e(a) Increase in overall score seen in Week 2 compared to week 1\u003c/p\u003e\n\u003cp\u003e(b) Slight decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) No significant difference in non-pain score\u003c/p\u003e\n\u003cp\u003e(d) Slight increase in satisfaction score\u003c/p\u003e","description":"","filename":"Slide4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/0e244c91c5d5f82fc82dbe79.jpg"},{"id":64005700,"identity":"1dc11e10-0bd0-4886-92f5-79ca95efb0fa","added_by":"auto","created_at":"2024-09-04 21:39:38","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":93297,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among those who were prescribed \u003cem\u003eSedru dangnay\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e(a) Decrease in overall SODA score\u003c/p\u003e\n\u003cp\u003e(b) Decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) Decrease in non-pain score\u003c/p\u003e\n\u003cp\u003e(d) Not much increase in satisfaction\u003c/p\u003e","description":"","filename":"Slide5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/a4ca89a06ae2b6e33f5824b0.jpg"},{"id":64005704,"identity":"309054ad-28e0-493b-a248-0d9990a0fc86","added_by":"auto","created_at":"2024-09-04 21:39:38","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":92010,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among those who were prescribed \u003cem\u003eSedru nyikhil\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e(a) Slight decrease in overall SODA score\u003c/p\u003e\n\u003cp\u003e(b) Slight decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) Decrease in non-pain score\u003c/p\u003e\n\u003cp\u003e(d) Slight increase in satisfaction score after Week 2\u003c/p\u003e","description":"","filename":"Slide6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/d64d879444f11748bc6fe42f.jpg"},{"id":64005701,"identity":"b659b946-5f68-4e4f-a406-2ede32f90c65","added_by":"auto","created_at":"2024-09-04 21:39:38","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":92104,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among those who were prescribed \u003cem\u003eRuta 6\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e(a) Decrease in overall SODA score\u003c/p\u003e\n\u003cp\u003e(b) Decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) Decrease in non-pain score\u003c/p\u003e\n\u003cp\u003e(d) Increase in satisfaction score\u003c/p\u003e","description":"","filename":"Slide7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/c945c083306d4a0f792676bb.jpg"},{"id":64006178,"identity":"b13e5fb5-ad5d-46eb-9a5d-b03488ff68ef","added_by":"auto","created_at":"2024-09-04 21:47:38","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":81385,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported outcomes among those who were prescribed \u003cem\u003eZhijay 6\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e(a) Decrease in overall SODA score\u003c/p\u003e\n\u003cp\u003e(b) Decrease in pain score\u003c/p\u003e\n\u003cp\u003e(c) No increase in non-pain score\u003c/p\u003e\n\u003cp\u003e(d) No increase in satisfaction score\u003c/p\u003e","description":"","filename":"Slide8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/4062e7599ad97bcaaf56c95e.jpg"},{"id":64007121,"identity":"6bb70389-4a1a-425f-b470-c7701d185c51","added_by":"auto","created_at":"2024-09-04 21:55:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1520797,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/3ac3270a-7278-4d6a-9ca6-46af93e5e933.pdf"},{"id":64005698,"identity":"8ea22ffb-13a3-4b66-9e57-32edd333f318","added_by":"auto","created_at":"2024-09-04 21:39:38","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19508,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4815044/v1/838a7b9ecffe63d59251d398.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety and Efficacy of Bhutanese Traditional Herbal Drug Formulary for Gastritis-Related Problems (SEDRU): a Nationwide Observational Study","fulltext":[{"header":"Background","content":"\u003cp\u003eTraditional Medicine (\u003cem\u003eSowa Rigpa\u003c/em\u003e) is an integral part of Bhutan\u0026rsquo;s healthcare system and is recognized in the National Health Policy 2011. Practiced for over two thousand years in Bhutan and several countries in the Himalayan region [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], \u003cem\u003eSowa Rigpa\u003c/em\u003e is now gaining acceptance in Western countries as well. This traditional medicine system is based on balancing five inner elements (air, earth, water, fire, and space) within the three psycho-physical \u0026lsquo;humours\u0026rsquo; (bile, phlegm, and wind) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Imbalances or disturbances caused by diet, injury, or environmental stress can lead to disease and death. Diagnosis in \u003cem\u003eSowa Rigpa\u003c/em\u003e involves a detailed history and physical examination focusing on the tongue, pulse, and urine.\u003c/p\u003e \u003cp\u003eCurrently, these traditional medicines are produced by the state-owned Menjong Sorig Pharmaceuticals and included in the National Essential Medicines List [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. They are distributed free of charge through Traditional Medicine Units (TMUs) in all primary, secondary and tertiary hospitals across Bhutan. With the adoption of patient safety measures, traditional medicines are now also subject to evidence-based medicine standards.\u003c/p\u003e \u003cp\u003eStomach disorders are among the top ten diseases treated in TMUs in Bhutan [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Gastritis, a major component of these disorders, had an incidence rate of over 827 cases per 10,000 population in 2017 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In \u003cem\u003eSowa Rigpa\u003c/em\u003e, gastritis-related illnesses are referred to as \u003cem\u003epho-rlung\u003c/em\u003e, with a prevalence of gastritis-related symptoms estimated at 8.4% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Traditional herbal drugs like \u003cem\u003eSedru 4, 5, 8\u003c/em\u003e; \u003cem\u003eRu-ta 6\u003c/em\u003e and \u003cem\u003eZhijay 6\u003c/em\u003e are commonly prescribed for gastritis, along with other traditional therapies.\u003c/p\u003e \u003cp\u003eThe traditional herbal drug formulary (THDF) of Bhutan combines various ingredients prescribed in the Fourth Medical Tantra, chosen for their possession of curative power due to its characteristics (\u003cem\u003eyon-ten\u003c/em\u003e), natural potency (\u003cem\u003engo-bu nus-pa\u003c/em\u003e), and taste (\u003cem\u003ero\u003c/em\u003e). While no research has been conducted on Bhutanese traditional medicine recipes for gastritis, numerous studies have examined their components. For instance, pomegranate (\u003cem\u003ePunica granatum Linn\u003c/em\u003e: Sedru) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], cinnamon (\u003cem\u003eCinnamomum verum\u003c/em\u003e) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and long pepper (\u003cem\u003ePiper longum\u003c/em\u003e) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] are noted for their anti-inflammatory properties in the gastrointestinal tract and have been proven safe in other traditional medicine systems.\u003c/p\u003e \u003cp\u003eThe term gastritis-related illness is considered the most linguistically compatible with Bhutanese traditional medicine concepts. Nonetheless, the symptoms described by Bhutanese patients, in the absense of gastroscopic evidence, often suggest functional dyspepsia, a condition that is not well defined either. Among the 16 symptom-based Functional Dyspepsia Patient-Reported Outcome (PRO) instruments (range: 4 to 42 total items) identified in a recent literature review [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], the 17-item SODA score was optimal for capturing the wind and phlegm disorders described by Bhutanese patients, making it suitable for this study [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe objectives of this study were to monitor the safety and potential efficacy of the currently used THDFs in Bhutan for the treatment of gastritis-related illnesses and to introduce the documentation of standard clinical outcome measures as a simplified medical recording approach among traditional medicine practitioners. The specific PRO objectives were to explore whether the translated SODA score could reflect the changes of clinical symptoms of Bhutanese patients with gastritis-related illnesses and which of the 17 items is/are most responsive to each THDF. By addressing these objectives, this study aims to provide valuable insights into the safety and efficacy of traditional herbal drugs used in Bhutan and promote the integration of evidence-based practices in traditional medicine.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis was a prospective observational study (Clinical Study Phase II/III) according to the World Health Organization framework for research and evaluation of Traditional Medicine [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting\u003c/h2\u003e \u003cp\u003eBhutan is the small Himalayan Kingdom where the practice of traditional medicine has remained preserved as practiced for thousands of years. Known as \u003cem\u003eSowa Rigpa\u003c/em\u003e, the science of healing was formally integrated into the healthcare system of Bhutan in 1968 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Traditional Medicine is a complete package in Bhutan \u0026ndash; its human resources are trained within Bhutan and all medicines are produced within the country. Traditional Medicine is popular and much sought after as an alternative medicine even in current digital and information age in Bhutan and several other countries.\u003c/p\u003e \u003cp\u003eAs of 2023, Bhutan had 81 TMUs, which share facilities with allopathic hospitals, including the National Traditional Medicine Hospital located in Thimphu. The administration of these units falls under the National Medical Services. There are two categories of traditional medicine practitioners. Those trained for six years and with degree holders are called \u003cem\u003edrungtsho\u003c/em\u003e; they can prescribe drugs and perform surgical procedures. Those trained for three years are called \u003cem\u003emenpa\u003c/em\u003e; they dispense drugs and perform supportive work.\u003c/p\u003e \u003cp\u003e \u003cem\u003ePho-rlung\u003c/em\u003e has its operational definition and diagnosis according to the \u003cem\u003eSowa Rigpa\u003c/em\u003e system. The traditional medicine practitioner has several drugs at his disposition. \u003cem\u003eSedru 5, Sedru dangnay, Ruta 6, and Zhijay 6\u003c/em\u003e are available at all hospital levels. The rest of the drugs are available only in the tertiary and secondary centers.\u003c/p\u003e \u003cp\u003eAfter the formal integration of traditional medicine in the healthcare system of Bhutan, there has been continued effort to make it relevant and accessible to people through its improved quality services. In an effort to better document patient\u0026rsquo;s history, clinical assessment, and prescription practice pattern before and after the traditional medicine treatment, the Department of Traditional Medicine Services, Royal Government of Bhutan has introduced several validated tools such as the Severity of Disease Assessment (SODA) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and the Naranjo algorithm [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] to detect adverse drug reactions to traditional medicines in 2018.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSample size and sampling method\u003c/h2\u003e \u003cp\u003eThis study included all adults age at least 18 years old with gastritis-related problems (wind and phlegm disorders) diagnosed by any licensed traditional medicine practitioner. No formal sample size was calculated. As both SODA score and the Naranjo\u0026rsquo;s algorithm were translated, language requirement was not a PRO-specific barrier to the study entry.\u003c/p\u003e \u003cp\u003eThis study excluded patients with severe gastrointestinal problems with blood in the vomitus, blood in the stools, melena (tarry black stools), recent weight loss of more than 5% of body weight in the last six months; patients with concomitant bile disorders (\u003cem\u003ethri-shes che-ba\u003c/em\u003e); and known allergy to the components of the medicine.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTreatment regimens prescribed by TM physicians\u003c/h2\u003e \u003cp\u003eAll those patients who were treated for gastritis-related illnesses with the medicines \u003cem\u003eSedru 4, Sedru 5, Sedru 8, Sedru dangnay, Sedru nyikhil, Ruta 6\u003c/em\u003e, and \u003cem\u003eZhijay 6\u003c/em\u003e were be assessed by the treating traditional medicine practitioners by filling SODA 1, 2, 3 and 4 at the end of therapy for the respective week. The composition of these recipes is presented in Supplementary Table\u0026nbsp;1. All of these drugs are manufactured by the Menjong Sorig Pharmaceuticals\u0026mdash;the only drug manufacturing company for traditional medicine in the country. This state-owned company follows standard guidelines in the collection and storage of ingredients and the Good Manufacturing Practices for production.\u003c/p\u003e \u003cp\u003eFor the purpose of this study, medicines were prescribed weekly and symptoms assessed weekly with the SODA score [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The patients were followed up for a period of four weeks after which the care for the patients may continue depending upon the physician\u0026rsquo;s advice. Physicians were allowed to practice in their natural environment. The choices of drugs, duration of therapy, change of regimen, the combination of drugs, stopping the regimen, switching of the regimen, the combination with allopathic medicines and referral to allopathic medicine were all allowed and data were collected on those parameters.\u003c/p\u003e \u003cp\u003e \u003cem\u003eSedru 4, Sedru 5, Sedru 8, Sedru dangnay, Sedru nyikhil, Ruta 6\u003c/em\u003e, and \u003cem\u003eZhijay 6\u003c/em\u003e were formulated as a pill of 500 mg. \u003cem\u003eSedru 4, 5, Sedru nyikhil, Ruta 6\u003c/em\u003e and \u003cem\u003eZhijay 6\u003c/em\u003e were prescribed as 1500 mg BD while \u003cem\u003eSedru 8\u003c/em\u003e was prescribed 1500 mg in the evening and \u003cem\u003eSedru dangnay\u003c/em\u003e as 1500 mg in the morning [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The prescription of the treatment regimens were up to the clinical indication according to the principles of \u003cem\u003egSo-ba Rig-pa\u003c/em\u003e. There was no randomization of patients to specific treatment arms.\u003c/p\u003e \u003cp\u003eIn the event the patient developed severe gastrointestinal problems with blood in the vomitus, blood in the stools, melena (tarry black stools), recent weight loss of more than 5% of body weight in six months, the patient was referred to an allopathic doctor as per the Standard Operating Procedure of the Department of Traditional Medicine Services, Royal Government of Bhutan [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe treating traditional medicine practitioner encouraged their patients to comply on the dose and timing of medicines, completion of treatment course and come for next consultation review. The patients were allowed to take allopathic medicines at the same time as the traditional medicine.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eOutcome assessment\u003c/h2\u003e \u003cp\u003ePrimary Outcome: Safety / Adverse Drug Reaction (ADR) were assessed by using the Naranjo\u0026rsquo;s algorithm [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] at four weekly time points (Week 1,2,3,4) after the treatment commenced.\u003c/p\u003e \u003cp\u003eSecondary Outcome: Gastritis-like symptoms were assessed by using the SODA scores [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] as part of the routine evaluation done by the traditional medicine practitioners before starting the treatment and at five weekly time points (Week 0, 1, 2, 3, 4) after the treatment was started. Both total, scale, and itemized scores were evaluated in terms of the weekly changes from baseline.\u003c/p\u003e \u003cp\u003eTraditional medicine practitioners were trained in using the Dzongkha version of the SODA score and the Naranjo\u0026rsquo;s algorithm to ensure accurate and consistent data collection. If patients concurrently took allopathic medicines along with traditional medicine, information on the allopathic medicines was also collected to account for potential interactions and confounding factors.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData collection tool\u003c/h2\u003e \u003cp\u003eThe patient characteristics collected were age, sex and the patient\u0026rsquo;s medical nature that included the nature of wind, bile, and phlegm. Only those patients who consented to allow his or her de-identified data to be used for this study were extracted.\u003c/p\u003e \u003cp\u003eThe SODA score is the PRO instrument used in this study. It contains 17 items in three scales: pain symptoms (6 items; range 2\u0026ndash;47 points), non-pain symptoms (7 items; 7 to 35 points), and satisfaction (4 items; 2 to 23 points) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. It has good criterion validity as well as high Cronbach\u0026rsquo;s alpha reliability for the pain symptoms (0.97), non-pain symptoms (0.90), and the satisfaction scales (0.92) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The Guyatt\u0026rsquo;s responsiveness indices (the ability of a scale to detect a minimal amount of change considered important by patients or physicians) were large for the pain symptoms (0.98) and satisfaction (0.87) but small for the non-pain symptoms (0.24). The traditional medicine practitioners who participated in this study were trained to use the translated SODA score. A manual in Dzongkha language was also provided.\u003c/p\u003e \u003cp\u003eThe SODA score [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and the Naranjo\u0026rsquo;s algorithm [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] were translated from English into Dzongkha by an English-speaking Bhutanese medical doctor whose mother tongue was Dzongkha. The score was then translated back to English by another English-speaking Bhutanese traditional medicine practitioner whose mother tongue was Dzongkha and has no knowledge of the score. The score was pre-tested on ten randomly selected patients who were also debriefed and interviewed. Their inputs were used to create the final version of the score.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eData collection period\u003c/h2\u003e \u003cp\u003eData of patients who were treated for the period of June to December 2019 were extracted. Patients were recruited from June to December 2019. The follow up of the last group of patients ended in January 2020.\u003c/p\u003e \u003cp\u003eThe data monitoring committee comprised of one coordinating centre representative (TD), one sponsor representative (DG), and one non-Bhutanese investigator (KP). DG was responsible for checking the data completeness and removing any data that could be used for identifying the patients and the sites. TD and KP were responsible for the data analysis, writing of the report, and submitting the report for publication.\u003c/p\u003e \u003cp\u003eThe adverse drug reaction was the primary outcome of this study and was assessed by using the Naranjo\u0026rsquo;s algorithm [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] at four weekly time points (Week 1, 2, 3, 4) after the treatment was started.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eData entry and analysis\u003c/h2\u003e \u003cp\u003eThe data collection forms were coded and a data documentation sheet was prepared. The data was double entered and validated in EpiData version 3.1 (EpiData Association, Odense, Denmark). Descriptive statistics is used for presenting the patient and clinical characteristics. The changes of overall and recipe-specific SODA scores at baseline and at each of the follow-up visits is compared by using repeated measures ANOVA. STATA version 18 was used for all data analyses.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEthics considerations\u003c/h2\u003e \u003cp\u003e This study was conducted in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use \u0026ndash; Good Clinical Practice (ICH-GCP) guidelines. The study protocol was reviewed and approved by the Research Ethics Board of Health (REBH), Ministry of Health, Bhutan via letter no REBH/Approval/2018/089 dated 08 January 2019. Consent to prescribe the traditional medicines was obtained by the prescribing traditional medicine practitioners as part of standard clinical practice. For the purpose of this study, additional consent was sought from patients to allow their de-identified data to be extracted and used for analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 152 patient were followed up in this observational study. Baseline information was available for 109 patients, with follow-up data for 100 patients at one week, 88 at two weeks, 72 at three weeks, and 51 at four weeks. The mean age of the study participants was 44.5 (\u0026plusmn;\u0026thinsp;14.8) years, and 97 (65.5%) were females. The basic details of the study participants are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The number of patients who received traditional medicines and those who co-consumed allopathic medicines are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe basic details of the study participants with stomach disorders who were treated with traditional medicines in Bhutan, 2019\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasic characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group (years)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;18\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u0026ndash;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u0026ndash;44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u0026ndash;54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e55\u0026ndash;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElemental nature of patient (according to \u003cem\u003eSowa Rigpa\u003c/em\u003e)\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLung\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eThripa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBeyken\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLung-Thri\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBey-Thri\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBey-Lung\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDuepa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel of hospital\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNational Traditional Medicine Hospital/\u003c/p\u003e \u003cp\u003eRegional referral hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistrict/General hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary Health Centres\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e1\u003c/sup\u003emissing = 2\u003c/p\u003e \u003cp\u003e\u003csup\u003e2\u003c/sup\u003emissing = 4\u003c/p\u003e \u003cp\u003e\u003csup\u003e3\u003c/sup\u003emissing = 15\u003c/p\u003e \u003cp\u003e\u003csup\u003e4\u003c/sup\u003emissing = 7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBhutanese traditional medicines prescribed and co-consumption of allopathic medicines among patients with stomach disorders in Bhutan, 2019\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMedicine group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eWeek 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eWeek 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eWeek 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eWeek 4\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBhutanese Traditional Medicines for stomach disorder\u003c/b\u003e\u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSedru 4\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(9.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSedru 5\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(99.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(94.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSedru 8\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSedru dangnay\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(27.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSedru nyikhil\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(7.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRuta 6\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(85.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(88.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eZhijay 6\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(76.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(81.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(93.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(76.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCo-consumption of any allopathic medicine\u003c/b\u003e\u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRanitidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOmeprazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntacid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLosartan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydrochlorothiazide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmitriptyline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIbuprofen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDicyclomine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e1\u003c/sup\u003eMultiple responses were allowed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSeverity of dyspepsia assessment (SODA)\u003c/h2\u003e \u003cp\u003eOver the course of the follow-up, there was a significant improvement in the overall SODA score, as well as in pain intensity, non-pain symptoms, and satisfaction scores (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;1). The overall SODA score at baseline was 54.4 (\u0026plusmn;\u0026thinsp;8.8) and decreased to 50.0 (\u0026plusmn;\u0026thinsp;8.3) at Week 1, 46.9 (\u0026plusmn;\u0026thinsp;8.0) at Week 2, 42.7 (\u0026plusmn;\u0026thinsp;12.0) at Week 3 and 38.9 (\u0026plusmn;\u0026thinsp;13.7) at Week 4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The pain intensity score significantly decreased from 26.5 (\u0026plusmn;\u0026thinsp;5.6) at baseline to 23.7 (\u0026plusmn;\u0026thinsp;5.4) at Week 1, 21.3 (\u0026plusmn;\u0026thinsp;5.5) at Week 2, 17.7 (\u0026plusmn;\u0026thinsp;8.5) at Week 3, and 14.4 (\u0026plusmn;\u0026thinsp;10.3) at Week 4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The non-pain symptom score significantly decreased from 16.4 (\u0026plusmn;\u0026thinsp;3.6) at baseline to 14.2 (\u0026plusmn;\u0026thinsp;3.4) at Week 1, 12.6 (\u0026plusmn;\u0026thinsp;3.5) at Week 2, 11.4 (\u0026plusmn;\u0026thinsp;3.6) at Week 3, and 10.3 (\u0026plusmn;\u0026thinsp;3.6) at Week 4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The patient satisfaction score increased from 11.5 (\u0026plusmn;\u0026thinsp;3.4) at baseline to 12.2 (\u0026plusmn;\u0026thinsp;3.6) at Week 1, 13.2 (\u0026plusmn;\u0026thinsp;3.8) at Week 2, 13.2 (\u0026plusmn;\u0026thinsp;3.8) at Week 3, and 14.5 (\u0026plusmn;\u0026thinsp;5.0) at Week 4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe details of Severity of Dyspepsia Assessment of patients at baseline and on weekly followed in SEDRU study, Bhutan, 2019\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSODA domain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWeek 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWeek 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eWeek 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWeek 4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain intensity score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.5 (\u0026plusmn;\u0026thinsp;5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.7 (\u0026plusmn;\u0026thinsp;5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.3 (\u0026plusmn;\u0026thinsp;5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.7 (\u0026plusmn;\u0026thinsp;8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.4 (\u0026plusmn;\u0026thinsp;10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-pain symptom score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.4 (\u0026plusmn;\u0026thinsp;3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.2 (\u0026plusmn;\u0026thinsp;3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.6 (\u0026plusmn;\u0026thinsp;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.4 (\u0026plusmn;\u0026thinsp;3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.3 (\u0026plusmn;\u0026thinsp;3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSatisfaction score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.5 (\u0026plusmn;\u0026thinsp;3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.2 (\u0026plusmn;\u0026thinsp;3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.2 (\u0026plusmn;\u0026thinsp;3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.2 (\u0026plusmn;\u0026thinsp;3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.5 (\u0026plusmn;\u0026thinsp;5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e54.4 (\u0026plusmn;\u0026thinsp;8.8)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e50.0 (\u0026plusmn;\u0026thinsp;8.3)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e46.9 (\u0026plusmn;\u0026thinsp;8.0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e42.7 (\u0026plusmn;\u0026thinsp;12.0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e38.9 (\u0026plusmn;\u0026thinsp;13.7)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTrends of SODA scores, pain intensity, non-pain symptoms, and satisfaction scores for specific traditional medicines \u003cem\u003e(Sedru 4, Sedru 5, Sedru 8, Sedru dangnay, Sedru nyikhil, Ruta 6\u003c/em\u003e, and \u003cem\u003eZhijay 6)\u003c/em\u003e over four weeks are shown in Figs.\u0026nbsp;2\u0026ndash;8.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events to SEDRU drugs\u003c/h2\u003e \u003cp\u003eA total of 9 adverse events were reported in this study. According to the Naranjo\u0026rsquo;s algorithm, there was only one probable ADR, one possible ADR and the rest were doubtful (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNaranjo\u0026rsquo;s score for the adverse reactions among patients who received the SEDRU group of medicines, Bhutan, 2019.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNaranjo\u0026rsquo;s core\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDefinite ADR (score\u0026thinsp;\u0026ge;\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbable ADR (score 5\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(11.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePossible ADR (score 1\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(11.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDoubtful ADR (score 0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(77.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eSupplementary Table\u0026nbsp;1. Composition of the Seven Bhutanese Traditional Herbal Drug Recipes studied in the SEDRU study, 2019\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe traditional medicine system prevalent in Bhutan has, for the first time, adopted scientific measures to promote evidence-based clinical practice. This prospective study focused on the gastritis-related symptoms, which are among the top ten disease burdens in the country. The study demonstrated a progressive improvement in the overall dyspepsia assessment score and all three of its domains: pain symptoms, non-pain symptoms, and overall satisfaction. Although this study primarily reports empirical assessments of prescription practices and patient-reported efficacy of these traditional medicines, the findings provided a baseline for further exploration of the efficacy of these herbal formulations.\u003c/p\u003e \u003cp\u003eGiven that \u003cem\u003eSedru 5, Ruta 6\u003c/em\u003e and \u003cem\u003eZhijay 6\u003c/em\u003e were more commonly used, ensuring their production and availability at all hospital levels is essential. \u003cem\u003eSedru 5\u003c/em\u003e contains ingredients such as pomegranate, cardamom, cinnamon, long pepper and ginger. \u003cem\u003eRuta 6\u003c/em\u003e includes \u003cem\u003eSaussurea lappa\u003c/em\u003e, long pepper, \u003cem\u003eJusticia gendarussa\u003c/em\u003e, pomegranate, cardamom and gooseberry. \u003cem\u003eZhijay 6\u003c/em\u003e consists of Inula, soapstone, soda, ginger, agerstroemia and \u003cem\u003eRheum palmatum\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eThe use of pomegranate peel extract in sachets of 2.5 g twice a day after meals for 28 days has been reported to improve dyspepsia symptoms and Gastrointestinal Symptom Rating Scale [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Polyphenolics, flavonoids, anthocyanosides, alkaloids, lignans, and triterpenes found in pomegranate (\u003cem\u003ePunica granatum\u003c/em\u003e L.) have been evaluated for their effects in managing cancer and metabolic syndrome [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, various plant products and extracts have been evaluated for improving dyspepsia symptoms [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Many herbal preparations contain ingredients common in traditional formulations reported from several countries [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. With growing interest in finding efficacious therapeutic agents for functional dyspepsia, empirical findings from this study provide valuable opportunities for drug discovery.\u003c/p\u003e \u003cp\u003eThis study also demonstrated significant improvement in patient satisfaction with the use of these traditional medicines. This factor is important not only for treating a single \u003cem\u003epho-rlung\u003c/em\u003e disease but also for the overall acceptance of Traditional Medicine among the 21st -century population of Bhutan. Traditional Medicine services remain popular among the public across all age groups, with high patient satisfaction reported [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor the first time in Bhutan\u0026rsquo;s Traditional Medicine system, changes in symptoms in response to commonly prescribed traditional medicine drugs were formally observed and documented using standardized and validated tools. The SODA questionnaire and the case record forms were introduced by the Department of Traditional Medicine Services to improve documentation. Although the use of such forms required training, the quality of data generated for this study demonstrates that such forms can be adopted as part of the system. The chosen tool is relatively simple and resulted in good compliance, as anticipated.\u003c/p\u003e \u003cp\u003eThe Naranjo\u0026rsquo;s algorithm reported only 10 cases of adverse drug reactions, out of which only one case was a \u0026ldquo;probable\u0026rdquo; ADR. This demonstrates that the six drug formulations studied in this study is safe. The use of the Naranjo algorithm to assess adverse drug reactions in the traditional medicine system is the first time in Bhutan. The acceptance of these forms in the traditional medicine system is a reflection of strong leadership to make Bhutanese Traditional Medicine relevant to modern times. This form helps to document ADRs and assess the strength of relationship between the drug and the ADR. This form will remain an important part of the Traditional Medicine System. It was also realised that for the data collected through Naranjo algorithm to be of future use, a national centre for reporting and assessment of ADRs in Traditional Medicine should be established. This centre requires individuals who understand the intricate considerations of the Traditional Medicine system as well as good understanding of pharmacology and chemistry. Establishment of such data repository will serve to house data that will contribute to making Traditional Medicine practices evidence-based.\u003c/p\u003e \u003cp\u003eThis national level project aimed to introduce modern research culture and build the research capacity of traditional medicine practitioners. Educated in the national language Dzongkha, practitioners face barriers in conveying traditional medicine concepts scientifically in English. Selecting a standard PRO instrument is critical to balancing scientific integrity and acceptability. The forward-and-back translation of PRO instruments and the adoption of such practices demonstrate the resolve of the Traditional Medicine System to remain relevant in the 21st century and beyond.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study was planned as a nationwide initiative involving all TMUs in Bhutan. However, data could only be collected from select centres, which resulted in a smaller sample size than initially intended. Despite the reduced sample size, the findings are promising and provide valuable insights into the safety and efficacy of traditional herbal medicines for gastritis-related problems.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe traditional medicine system in Bhutan has made significant strides by adopting scientific measures to promote evidence-based clinical practice. This prospective study focused on gastritis-related symptoms, one of the top ten disease burdens in the country. The study demonstrated progressive improvement in the overall dyspepsia assessment score and all three of its domains: pain symptoms, non-pain symptoms, and overall satisfaction.\u003c/p\u003e \u003cp\u003eThe use of standardized and validated tools such as the SODA questionnaire and the Naranjo algorithm has facilitated the formal observation and documentation of symptom changes in response to traditional medicine. The quality of data generated demonstrates that these tools can be successfully integrated into the traditional medicine system, resulting in good compliance.\u003c/p\u003e \u003cp\u003eGiven the common use of \u003cem\u003eSedru 5\u003c/em\u003e, \u003cem\u003eRuta 6\u003c/em\u003e, and \u003cem\u003eZhijay 6\u003c/em\u003e, ensuring their production and availability at all hospital levels is essential. The study also highlighted the safety of these traditional medicines, with minimal adverse drug reactions reported.\u003c/p\u003e \u003cp\u003eThe findings from this study, despite the smaller sample size, provide a baseline for further exploration of the efficacy of traditional herbal formulations. The significant improvement in patient satisfaction underscores the importance of Traditional Medicine in Bhutan's healthcare system. This study marks an important step toward integrating traditional knowledge with modern research methodologies, ensuring the continued relevance of Traditional Medicine in the 21st century and beyond.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eANOVA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cu\u003eAn\u003c/u\u003ealysis \u003cu\u003eo\u003c/u\u003ef \u003cu\u003eVa\u003c/u\u003eriance\u003c/p\u003e\n\u003cp\u003ePRO\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cu\u003eP\u003c/u\u003eatient-\u003cu\u003eR\u003c/u\u003eeported \u003cu\u003eO\u003c/u\u003eutcome\u003c/p\u003e\n\u003cp\u003eREBH\u0026nbsp;\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cu\u003eR\u003c/u\u003eesearch \u003cu\u003eE\u003c/u\u003ethics \u003cu\u003eB\u003c/u\u003eoard of \u003cu\u003eH\u003c/u\u003eealth\u003c/p\u003e\n\u003cp\u003eSODA\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cu\u003eS\u003c/u\u003eeverity \u003cu\u003eo\u003c/u\u003ef \u003cu\u003eD\u003c/u\u003eyspepsia \u003cu\u003eA\u003c/u\u003essessment\u003c/p\u003e\n\u003cp\u003eTMU\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cu\u003eT\u003c/u\u003eraditional \u003cu\u003eM\u003c/u\u003eedicine \u003cu\u003eU\u003c/u\u003enit\u003c/p\u003e\n\u003cp\u003eTHDF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cu\u003eT\u003c/u\u003eraditional \u003cu\u003eH\u003c/u\u003eerbal \u003cu\u003eD\u003c/u\u003erug \u003cu\u003eF\u003c/u\u003eormulary\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was reviewed and approved by the Research Ethics Board of Health (REBH), Ministry of Health, Bhutan via letter no REBH/Approval/2018/089 dated 08 January 2019. Consent to prescribe the traditional medicines was obtained by the prescribing traditional medicine practitioners as part of standard clinical practice. For the purpose of this study, additional consent was sought from patients to allow their de-identified data to be extracted and used for analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe complete dateaset is available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDG, TD and KP were involved in Conceptualization, Methodology, Software, Validation, Formal analysis, Writing \u0026ndash; original draft, Writing \u0026ndash; review and editing. DG and TD were involved in Resources and Data Curation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to than Ugyen Thinley, Pelden Zangpo, Dorji Wangchuck, Tsheltrim Dorji, Terpola and all other Traditional Medicine practitioners, and the Department of Traditional Medicine Services, Ministry of Health, Bhutan for their contribution in the development and implementation of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcKay A, Wangchuk D. Traditional Medicine in Bhutan. Asian Med. 2005;1:204\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDorji T, Melgaard B. Medical History of Bhutan: A chronicle of health and disease from Bon times to today. 2nd edition. Centre for Research Initiatives; 2018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWangchuk P, Wangchuk D, Aagaard-Hansen J. Traditional Bhutanese medicine (gSo-Ba Rig-Pa): an integrated part of the formal health care services. Southeast Asian J Trop Med Public Health. 2007;38:161\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTenzin K, Dorji T, Gyeltshen T. Taking Traditional Medicine (Sowa Rigpa) research from Bhutan to the world. Bhutan Sorig J. 2024;1:1\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingye J, Wangchuk D, Chophel K, Chophel T, Dorji T, Dorji N, et al. Demographic and disease profile of patients availing Traditional Medicine services in Bhutan: a cross-sectional study. Bhutan Sorig J. 2024;1:19\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinistry of Health. Annual Health Bulletin. 2017. Thimphu: Ministry of Health, Royal Government of Bhutan; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee K, Kwon C, Yeniova A\u0026Ouml;, Koyanagi A, Jacob L, Smith L, et al. Global prevalence of functional dyspepsia according to Rome criteria, 1990\u0026ndash;2020: a systematic review and meta-analysis. Sci Rep. 2024;14:4172.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColombo E, Sangiovanni E, Dell\u0026rsquo;Agli M. A review on the anti-inflammatory activity of pomegranate in the gastrointestinal tract. Evidence-based Complement Altern Med. 2013;2013.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRanasinghe P, Pigera S, Premakumara GAS, Galappaththy P, Constantine GR, Katulanda P. Medicinal properties of \u0026lsquo;true\u0026rsquo; cinnamon (Cinnamomum zeylanicum): a systematic review. BMC Complement Altern Med. 2013;13:275.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeghwal M, Goswami TK. Piper nigrum and Piperine: An Update. Phyther Res. 2013;27:1121\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaylor F, Reasner DS, Carson RT, Deal LS, Foley C, Iovin R, et al. Development of a Symptom-Based Patient-Reported Outcome Instrument for Functional Dyspepsia: A Preliminary Conceptual Model and an Evaluation of the Adequacy of Existing Instruments. Patient. 2016;9:409\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalvert M, Kyte D, Mercieca-Bebber R, Slade A, Chan A-W, King MT, et al. Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension. JAMA. 2018;319:483\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine. World Health Organization; 2000.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRabeneck L, Cook KF, Wristers K, Souchek J, Menke T, Wray NP. SODA (severity of dyspepsia assessment): a new effective outcome measure for dyspepsia-related health. J Clin Epidemiol. 2001;54:755\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDepartment of Traditional Medicine Services. Standard Operating Procedures for Traditional Medicine Services. Thimphu: Department of Traditional Medicine Services, Ministry of Health, Bhutan; 2015.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGupte PA, Mahajan MP, Revadkar Kole MS, Mandlecha AH, Tatke PA, Naharwar VA, et al. Efficacy and acceptability of pomegranate effervescent granules in patients suffering from acid peptic disorders. Indian J Pharmacol. 2022;54:7\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026aacute;ez G, Vargas C, Arancibia M, Papuzinski C, Franco JV. Non-Chinese herbal medicines for functional dyspepsia. Cochrane database Syst Rev. 2023;6:CD013323.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChogyel T, Lhendup N, Dorji UD, Choeda T. Patient Satisfaction Survey in Traditional Medicine Units in Bhutan, 2023: a cross-sectional survey. Bhutan Sorig J. 2024;1:23\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gastritis, Dyspepsia, Health status, Traditional medicinal units, Evidence-Based Medicine, Complementary Therapies","lastPublishedDoi":"10.21203/rs.3.rs-4815044/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4815044/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eGastritis-related symptoms, often manifesting as stomach disorders, are among the top ten diseases diagnosed and treated in traditional medicinal units (TMU) in Bhutan. This study evaluated the safety and potential efficacy of the currently used medications for stomach disorders in Bhutan.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective observational study was conducted across all 63 TMUs in Bhutan over a six-month period in 2019. Patients presenting with gastritis-related symptoms were enrolled and monitored throughout the study. Adverse reactions were assessed using the Naranjo algorithm. The Severity of Dyspepsia Assessment (SODA) scores, both overall and recipe-specific, were recorded at baseline and at weekly follow-up visits. The changes in SODA scores over time were analyzed using repeated measures ANOVA to assess the efficacy of the herbal treatments.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 152 patients were included in the study, with baseline information available for 109 patients. Follow-up data were collected for 100 patients at one week, 88 patients at two weeks, 72 patients at three weeks, and 51 patients at four weeks. The most common prescribed herbal drugs were \u003cem\u003eSedru 5, Ruta 6\u003c/em\u003e and \u003cem\u003eZhijay 6\u003c/em\u003e. The baseline SODA score averaged 54.4 (\u0026plusmn;\u0026thinsp;8.8), which decreased progressively to 50.0 (\u0026plusmn;\u0026thinsp;8.3) at week 1, 46.9 (\u0026plusmn;\u0026thinsp;8.0) at week 2, 42.7 (\u0026plusmn;\u0026thinsp;12.0) at week 3 and 38.9 (\u0026plusmn;\u0026thinsp;13.7) at week 4, with a statistically significant improvements (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Nine adverse drug events were reported, but there were no definite adverse drug reactions. Patient satisfaction with the traditional formulations also showed a significant improvement.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe study found significant improvements in both pain and non-pain symptoms of gastritis, as well as patient satisfaction, with the use of traditional Bhutanese herbal medicines. The absense of definite adverse drug reactions indicates a favorable safety profile for these treatments. This study marks the first time the traditional medicine system in Bhutan has adopted scientific measures to promote evidence-based clinical practice, demonstrating a significant step forward in integrating traditional knowledge with modern research methodologies.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003e: Thai Clinical Trials Registry TCTR20180430004 dated 30 April 2018.\u003c/p\u003e","manuscriptTitle":"Safety and Efficacy of Bhutanese Traditional Herbal Drug Formulary for Gastritis-Related Problems (SEDRU): a Nationwide Observational Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-04 21:39:33","doi":"10.21203/rs.3.rs-4815044/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2024-07-31T14:13:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-31T14:11:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Complementary Medicine and Therapies","date":"2024-07-28T03:51:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"41f03568-60e9-464d-bbeb-542df8c19317","owner":[],"postedDate":"September 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-09-04T21:39:33+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-04 21:39:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4815044","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4815044","identity":"rs-4815044","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}