Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers

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We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. Methods: In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. Results: Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.44–8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR, 5.80; 95% CI, 2.08–16.2), and heart disease (OR, 3.05; 95% CI, 1.11–8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR, 8.24; 95% CI, 2.36–28.7). Conclusion: In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration. Gastroenterology & Hepatology Gastroduodenal ulcer elderly prognosis activity of daily living Figures Figure 1 Figure 2 Background Hemorrhagic gastroduodenal ulcers (HGUs) are the most common cause of upper gastrointestinal bleeding. Although most HGUs can be safely treated with medications and/or endoscopic procedures [1], some patients with HGU have a poor prognosis owing to comorbidities [2] and medications for anticoagulation [3]. Indeed, mortality from HGU is still high, with reported rates up to 10% [4]. Several reports have evaluated the risk factors of mortality of HGU [5-9]. A previous systematic review has shown that older age, comorbidity, shock, and delayed treatment are independent risk factors of mortality [5]. Another study revealed that endoscopic features with a high-risk Forrest classification (Forrest I, IIa, and IIb) are prognostic indicators of mortality [6]. In addition to mortality, impairment of activities of daily living (ADL) is also a very important prognostic issue, particularly in elderly subjects, leading to longer hospitalization and higher treatment cost [10]. Moreover, lowering of ADL is closely correlated with mortality in elderly subjects [11]. Changes in ADL associated with disease outcome have been evaluated mainly in diseases that directly influence patients’ physical functions, such as hip fracture and stroke [12, 13]. In this regard, there have been no studies that have evaluated which risk factors of HGU are associated with impairment of ADL. This is important in both clinical care of patients who are identified to be at risk of ADL impairment after HGU and planning of clinical and social care services. This is especially relevant in care of the elderly since previous reports have revealed that advanced age is a risk factor of poor outcomes for HGU patients [5, 7, 8]. In this study, the risk factors of poor prognosis, including mortality and impairment of ADL, were examined in patients with HGU. In particular, the prognosis of elderly HGU patients ( > 75 years old) was evaluated in comparison to that of non-elderly (< 75 years old) patients, since previous reports have revealed that advanced age is a risk factor of poor outcomes for HGU patients [5, 7 ,8]. Methods Patients A retrospective cohort study was performed using the database of endoscopy and medical record reviews from Mitsui Memorial Hospital, a secondary emergency hospital in Tokyo, Japan, between August 2004 and December 2017. We extracted the data of patients who had evidence of gastroduodenal ulcers identified by endoscopy from the endoscopic database. Those who showed hemorrhagic implications with symptoms including black stool, hematemesis, and/or anemia in medical records were included. If patients experienced two or more episodes of HGU during the study period, the first episode alone was included in the analysis. Patients who were confirmed as malignant ulcers by pathological diagnosis were excluded. Those with lower ADL on admission due to comorbidities including malignancy and dementia were not excluded because we focused on each patient’s change of ADL, but patients who had resided in care facilities before hospitalization were excluded when examining the impairment of ADL. In this study, both gastric and duodenal ulcers were included in HGUs because management of these diseases is similar including gastric acid inhibition, endoscopic hemostasis, and eradication of Helicobacter pylori [14]. Our policy for management of HGU was as follows. Endoscopic hemostasis was generally performed for HGU with Forrest I or IIa according to the Forrest classification [15]. If the index endoscopic hemostasis was unsuccessful with bleeding continuing, surgery or angioembolization was considered. The second look endoscopy was done before start of eating for patients with high-risk HGU such as large size and Forrest I or II. EGD for biopsy to rule out gastric cancer was also performed. The following clinical factors were evaluated as they have been shown to be associated with the severity of bleeding or prognosis of HGU [5, 6]. Endoscopic features and need for interventional endoscopic procedures were collected from endoscopic database. The information of comorbidities, symptoms, and medications were reviewed with medical records. The evaluated endoscopic features included locations of HGU (fundus, gastric body, gastric angle, antral zone, anterior wall of duodenal bulb, posterior wall of duodenal bulb, and second portion of duodenum), type of hemorrhage using the Forrest classification [15], size of ulcer ( > 20 mm or not), and the number of ulcers ( > 2 ulcers or not). Interventional endoscopic procedures indicate endoscopic hemostasis including clipping, argon plasma coagulation, heat probe, sprinkling of thrombin, injection of hypertonic saline-epinephrine solution, and injection of epinephrine. The following comorbidities were recorded: heart disease, pulmonary disease, stroke, diabetes mellitus, liver disease, renal disease, and history of gastroduodenal ulcers before the study period. The evaluated symptoms included black stool, syncope, and hematemesis. Medication use prior to hemorrhage was documented for anticoagulants, antiplatelets, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, corticosteroids, proton pump inhibitors (PPIs), and H2 receptor antagonists (H2RAs). This analysis defined patients > 75 years of age as elderly, and the clinical backgrounds and outcomes were compared between patients 75 years old. The primary outcomes were overall mortality, mortality within 30 days after occurrence of hemorrhage, and impairment of ADL. Admission to a care facility or the need for home adaptations such as a care bed, during the hospitalization period were defined as ADL decline. When estimating the impairment of ADL, 13 patients who resided in care facilities before hospitalization were excluded. The secondary outcomes were rebleeding, hospitalization periods, and need for transfusion. The Ethics Committee of Mitsui Memorial Hospital approved this retrospective study, which conformed to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013). For this type of study formal consent is not required. Statistical analysis Continuous data are presented as mean ± standard deviation, and categorical data as actual frequencies and percentages. Continuous data were compared with the Student’s t-test. Comparisons of categorical data between the groups were performed with the chi-square test or Fisher’s exact test as appropriate. Independent risk factors of primary outcomes were identified using multivariate logistic regression analysis based on parameters with p < 0.1 in univariate analysis. A p- value < 0.05 was considered statistically significant, and odds ratios (ORs) with 95% confidence intervals (CIs) were determined. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, EZR is a modified version of R commander designed to add statistical functions frequently used in biostatistics. Results Patient characteristics In total, 582 patients (425 men and 157 women; mean age, 66.6 ± 14.4 years) were diagnosed with HGU at least once during the study period, and the first episode of these patients were analyzed. Table 1 shows the evaluated clinical factors of all patients. The following variables were significantly higher in patients > 75 years old than patients 20 mm (33% vs. 23%, p = 0.02), comorbidities (heart disease [34% vs. 21%, p < 0.001], pulmonary disease [12% vs. 7%, p = 0.044], and stroke [14% vs. 5%, p < 0.001]), symptoms of hematemesis (36% vs. 24%, p = 0.0038), and antiplatelet use (38% vs. 19%, p < 0.001). Meanwhile, HGU in the anterior wall of duodenal bulb [14% vs. 25%, p = 0.0024], HGU with the Forrest classification IIa (27% vs. 37%, p = 0.02), and history of gastroduodenal ulcers [16% vs. 27%, p = 0.0023] were less likely observed in patients > 75 years old. Primary and secondary outcomes of patients 75 years old Table 2 shows the outcomes of the two groups. Overall mortality (8% vs. 4%, p = 0.048), impairment of ADL (7% vs. 1%, p < 0.001) and need for transfusion (67% vs. 51%, p 75 years old than in patients 75 years old had significantly longer hospitalization period (23.1 ± 28.2 days vs. 16.0 ± 29.3 days, p = 0.0056). Independent risk factors of primary outcomes in multivariate logistic regression analysis Multivariate analysis revealed that age ( > 75 years) (OR, 2.24; 95% CI, 1.06 –4.73), and renal disease (OR, 3.43; 95% CI, 1.44–8.14) were independent and significant risk factors for overall mortality. The risk factors of mortality within 30 days after hemorrhage were age ( > 75 years) (OR, 3.36; 95% CI, 1.19–9.44), need for interventional endoscopic procedures (OR, 3.84; 95% CI, 1.06–13.9), and renal disease (OR, 4.35; 95% CI, 1.42–13.4). Finally, the risk factors of impairment of ADL were use of PPI prior to hemorrhage (OR, 5.80; 95% CI, 2.08–16.2), heart disease (OR, 3.05; 95% CI; 1.11–8.43), and age ( > 75 years) (OR, 5.09; 95% CI, 1.73–15.0) (Figure 1). Independent risk factors of primary outcomes for elderly patients in multivariate logistic regression analysis The prognostic factors in elderly subjects were analyzed. The independent and significant risk factors for overall mortality were Forrest IIb (OR, 4.26; 95% CI, 1.17–15.5), and ulcer location of posterior wall of duodenal bulb (OR, 5.14; 95% CI, 1.18–22.5). The risk factors of mortality within 30 days after hemorrhage were need for interventional endoscopic procedure (OR, 9.65; 95% CI, 1.11–83.7), and location of posterior wall of duodenal bulb (OR, 11.9; 95% CI, 2.24–63.4). The risk factors of impairment of ADL were fundus ulcer (OR, 11.6; 95% CI, 1.47–91.7), and use of PPI prior to hemorrhage (OR, 8.24; 95% CI, 2.36–28.7) (Figure2). Discussion In this study, the risk factors of poor prognosis and impairment of ADL in patients with HGU were examined. Advanced age, comorbidities (renal disease and heart disease), need for interventional endoscopic procedures, and use of PPI prior to hemorrhage were identified as independent risk factors for worse outcomes. Moreover, we particularly focused on the impairment of ADL by HGU and found that PPI use prior to hemorrhage was a significant risk factor that impaired ADL both in overall subjects and in elderly subjects alone. Advanced age was a risk factor of overall mortality and mortality within 30 days after hemorrhage; this result is in line with several previous studies [5, 7, 8]. Advanced age was also an independent risk factor of impairment of ADL. Iwatsuka et al. showed that the elderly patients (> 70 years old) with gastrointestinal bleeding were less likely to return home after hospital discharge than non-elderly patients (< 70 years old) (5% vs. 21%, p < 0.001) [7]. However, their study included many types of gastrointestinal bleedings, from benign ulcers to malignant tumors. In contrast, we analyzed the risk factors of impairment of ADL in patients with HGU alone, and elderly subjects with gastrointestinal bleeding were at risk even with benign disease. The attribute of limited physiologic reserves, sarcopenia and frailty in elderly is probably responsible. In this regard, more attention should be paid to rehabilitation and prehabilitation for those subjects [16]. The need for interventional endoscopic procedures was a risk factor of mortality within 30 days after hemorrhage. Endoscopic procedures are generally performed for HGU with risky appearance, including Forrest I and II. In this regard, and consistent with our results, Lanie et al. showed that endoscopic features of Forrest I and II are prognostic indicators of mortality [6]. In contrast, Giese et al. showed that those Forrest scores are not significantly associated with death within 30 days, and rebleeding [17]. They discussed the discrepancy from Lanie’s results based on the timing of endoscopy, because they always performed endoscopy within 6 hours of admission. In our hospital, when severe bleeding is implied by symptoms, vital signs, laboratory data, medications, or comorbidities, EGD is performed as soon as possible after admission, but otherwise, EGD is performed electively. Earlier endoscopic interventions, regardless of the severity of HGU, might improve the prognosis of patients with HGU. In this regard, recent guidelines suggested stratifying patients based on the Blatchford score and adopting a risk-stratified management and recommended urgent inpatient endoscopy (≤ 12 hours of admission) in the high-risk group [18]. In this study, HGU patients with renal disease had worse prognosis, and similar results have also been reported previously [8, 19]. Renal disease in general is poor prognosticator for many diseases and pathologies. In particular, bleeding leads to acute on chronic kidney injury and hence drives poor outcomes [20]. This result may also be partly due to lower hemoglobin levels in patients with chronic kidney disease because anemia is reportedly the risk factor of mortality for patients with a higher risk of stroke or cardiovascular events [21, 22]. In addition, uremic platelet function impairment is a potential cause of the higher risk for ulcer bleeding complications [23]. Uremic platelet dysfunction involves von Willebrand factor with platelet membrane glycoproteins Ib and IIb to IIIa, which is not normalized after dialysis [24]. Furthermore, anticoagulation use during hemodialysis may contribute to the risk [19]. The presence of heart disease was one of the risk factors of impairment of ADL. It has been reported that when patients have some cardiac abnormality, such as valvular heart disease or underlying left ventricular dysfunction, severe anemia can cause hyper-output heart failure [25] resulting in long hospitalization and impairment of ADL. Eikelboom et al. revealed that there is a strong, consistent, temporal, and dose-related association between bleeding and poor prognosis in patients who have a history of acute coronary syndromes [26]. They discussed that major bleeding is likely to lead physicians to discontinue effective antithrombotic drugs such as aspirin, clopidogrel, heparin, low-molecular-weight heparin, and warfarin, which in turn could increase the risk of ischemic heart disease, stroke, and cardiovascular death. Furthermore, it is commonly known that heart disease is one of the risk factors of sarcopenia that could cause impairment of ADL. Consequently, sarcopenia in patients with HGU might affect the results [27, 28]. PPI use was identified as a risk factor of impairment of ADL. Most of the patients were prescribed PPI for the prevention of peptic ulcers caused by NSAIDs (21%) and antiplatelets (including aspirin) (47%) or due to a previous history of peptic ulcers (9%). A previous report showed that approximately 5% of patients with a history of ulcer bleeding who continued to take both NSAIDs and PPI still had recurrent ulcers after 6 months [29]. Another study revealed that 19%–26% of patients with similar situations had endoscopically assessed gastroduodenal ulcers at 6 months, and the risk factors of ulcer recurrence included age > 75 and comorbidity (heart diseases, stroke, cirrhosis, respiratory diseases, renal diseases, and diabetes) [30]. Thus, ulcer development as a result of NSAIDs under PPI treatment is not rare, and based on our results, such ulcers may result in poor clinical outcomes. Although the precise reasons are unknown, a possible risk of osteoporosis and dementia owing to taking PPIs may also be associated with the poor outcomes of PPI users [31, 32]. Moreover, the relatively low dose of PPIs in Japanese patients (e.g. esomeprazole 10–20 mg/day) could not sufficiently prevent the development of ulcers as a result of NSAIDs. In the elderly, the locations of HGU (fundus and the posterior wall of the duodenum) were identified as independent risk factors of worse outcomes, but the presence of comorbidities was not. Localization on the posterior wall of the duodenal bulb has been shown to be a risk factor for adverse outcome in bleeding peptic ulcers [33]. Furthermore, the morbidity rate of fundus ulcers in elderly people is known to be higher than that in non-elderly people [34]. The seriousness of ulcers or bleeding is likely to be associated with mortality for elderly patients. Indeed, Chow et al. reported that the risk of death was increased in elderly patients (age > 80) with features of severe bleeding (transfusion > 4 units, ulcer size > 2 cm, hematemesis, and melaena) at presentation [8]. In this regard, the finding that Forrest IIb was the risk of overall mortality was of interest. Although patients with Forrest I or Forrest IIa ulcer always received endoscopic hemostasis, those with Forrest IIb did not. The difference in treatment strategy between the stages of ulcers might contribute to the result [35]. The fact that comorbidities were not identified as a prognostic factor in the elderly is not surprising because most elderly patients have at least one comorbidity. The present study has several strengths. First, our study included a relatively high number of patients with a number of variables. Second, we evaluated each comorbidity separately instead of using the Charlson Comorbidities Index, which resulted in the identification of independent risk factors. This study has several limitations that should be recognized. First, this study was a retrospective and single center study and there could be some biases. In particular, relatively homogenous socio-cultural status and limited health infrastructure in our hospital might affect the results. Second, the patients in our study might have had more severe heart and renal diseases than patients in other studies because our hospital is a tertiary center of heart diseases and renal diseases in the eastern region of Tokyo. Third, we defined ADL impairment as admission to care facilities after hospital discharge or requirement of home modification for rehabilitation at home. Although a previous report applied similar definitions in the estimation of ADL [7], such definitions are not validated. In order to evaluate the changes of ADL more precisely, validated measurement scores such as the Pune-FAAT scale or the MDS-derived ADL scale should be used. Fourth, the patients’ information about ADL after discharge may be insufficient due to limited access. Finally, the characteristics of our patients did not include the Helicobacter pylori infection profile; however, as far as we know, no previous study has shown that Helicobacter pylori is a risk factor of poor prognosis of HGU. Conclusion Advanced age was a potent predictor of poor outcomes in patents with HGU, and additional risk factors of poor outcomes were different between overall HGU patients and elderly patients alone. The presence of comorbidities was a risk factor in the overall patients, and in particular heart disease was a risk of impairment of ADL. In elderly patients, the location of ulcers was associated with outcomes. Furthermore, PPI use prior to hemorrhage was a significant predictor of impairment of ADL, both in overall patients and in elderly patients alone. Although PPI use has generally been recommended for the prevention of ulcer development, such a policy may have room for reconsideration. Abbreviations ADL: activity of daily living, HGU: hemorrhagic gastroduodenal ulcers, EGD: esophagogastroduodenoscopy, PPI: proton pump inhibitor, NSAIDs: nonsteroidal anti-inflammatory drugs, OR: odds ratio, CI: confidence interval. Declarations Ethics approval and consent to participate The Ethics Committee of Mitsui Memorial Hospital approved this retrospective study, which conformed to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with 1964 Helsinki declaration and its amendments or comparable ethical standards. For this type of study formal consent is not required. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study was unfunded. Author contributions JA and NT conceived and designed the study. JA and JK analyzed the data. JA, JK, and NT wrote the paper. Finally, all authors, including KK, CS, SK, KF, MK, KT1, KK, TO, MS, and KT2, reviewed and approved the version of the manuscript. Acknowledgments Not applicable. References 1 Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ . 2005;330(7491):568. 2 Marmo R, Koch M, Cipolletta L et al. Predictive factors of mortality from nonvariceal upper gastrointestinal hemorrhage: Multicenter Study. Am J Gastroenterol. 2008;103(7):1639–1647. 3 Barada K, Abdul-Baki H, El Hajj II, Hashash JG, Green PH. Gastrointestinal bleeding in the setting of anticoagulation and antiplatelet therapy. J Clin Gastroenterol. 2009;43(1):5–12. 4 Rosenstock SJ, Møller MH, Larsson H, et al. Improving quality of care in peptic ulcer bleeding: Nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery. 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Baseline characteristics of HGU patients Characteristics Non-elderly (n = 390) Elderly (n = 192) P-value Patient number 390 192 Sex (Male/Female) 309/81 116/76 < 0.001 Age (mean ± SD) 59.2 ± 11.3 81.8 ± 5.0 < 0.001 Weekend hospitalization 90 (23%) 38 (20%) 0.43 Location of HGU Fundus 13 (3%) 5 (2%) 0.8 Gastric body 127 (33%) 90 (47%) 0.001 Gastric angle 72 (19%) 30 (16%) 0.47 Antral zone 51 (13%) 30 (16%) 0.48 Anterior wall of duodenal bulb 97 (25%) 26 (14%) 0.0024 Posterior wall of duodenal bulb 30 (8%) 12 (6%) 0.64 Second part of duodenum 6 (2%) 5 (3%) 0.52 Endoscopic features Forrest classifications Ia 32 (8%) 17 (9%) 0.92 Ib 65 (17%) 39 (20%) 0.34 IIa 145 (37%) 52 (27%) 0.02 IIb 38 (10%) 19 (10%) 1 IIc 27 (7%) 23 (12%) 0.059 III 83 (21%) 42 (22%) 0.96 Size > 20 mm 91 (23%) 63 (33%) 0.02 > 2 ulcers 167 (43%) 96 (50%) 0.12 Need for interventional endoscopic procedure 233 (60%) 98 (51%) 0.057 Comorbidities Heart disease 83 (21%) 66 (34%) < 0.001 Pulmonary disease 26 (7%) 23 (12%) 0.044 Stroke 18 (5%) 26 (14%) < 0.001 Diabetes 82 (21%) 34 (18%) 0.41 Liver disease 21 (5%) 19 (10%) 0.062 Renal disease 46 (12%) 18 (9%) 0.46 History of GU 107 (27%) 30 (16%) 0.0023 Symptoms Hematemesis 94 (24%) 69 (36%) 0.0038 Black stool 315 (81%) 144 (75%) 0.14 Syncope 15 (4%) 10 (5%) 0.59 Medications Anticoagulation 29 (7%) 23 (12%) 0.099 Antiplatelet 74 (19%) 73 (38%) < 0.001 NSAIDS 61 (16%) 43 (22%) 0.059 COX-2 inhibitor 3 (1%) 4 (2%) 0.23 Corticosteroids 14 (4%) 7 (4%) 1 PPI 42 (11%) 24 (13%) 0.63 H2RA 24 (6%) 14 (7%) 0.73 ADL: activity of daily living, COX: cyclooxygenase, GU: gastroduodenal ulcers, H2RA: histamine 2 receptor antagonist, NSAIDs: nonsteroidal anti-inflammatory drugs, PPI: proton pump inhibitor, SD: standard deviation. Table 2. Outcomes of patients Outcomes Non-elderly (n = 390) Elderly (n = 192) P-value Overall mortality 15 (4%) 15 (8%) 0.048 Mortality within 30 days after hemorrhage 7 (2%) 9 (5%) 0.058 Impairment of ADL 5 (1%) 13 (7%) < 0.001 Hospitalization period (days) 16.0 ± 29.3 23.1 ± 28.2 0.0056 Rebleeding 62 (16%) 28 (15%) 0.77 Transfusion 200 (51%) 128 (67%) < 0.001 ADL: activity of daily living. When estimating the impairment of ADL, 13 patients who had resided in care facilities before hospitalization were excluded. Cite Share Download PDF Status: Published Journal Publication published 06 Jan, 2021 Read the published version in BMC Gastroenterology → Version 4 posted Submission checks completed at journal 12 Dec, 2020 Editorial decision: Accept 10 Dec, 2020 Editor assigned by journal 02 Dec, 2020 Submission checks completed at journal 02 Dec, 2020 Editor invited by journal 02 Dec, 2020 You are reading this latest preprint version Show more versions 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-19921","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":6606017,"identity":"8ed2a8bb-f207-4297-9b3b-ddc710d935b3","order_by":0,"name":"Junya Arai","email":"","orcid":"https://orcid.org/0000-0002-4905-7046","institution":"Mitsui Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junya","middleName":"","lastName":"Arai","suffix":""},{"id":6606018,"identity":"2c61a852-8f16-45d2-9aa6-ea23d8e4ac86","order_by":1,"name":"Jun Kato","email":"","orcid":"","institution":"Mitsui Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Kato","suffix":""},{"id":6606019,"identity":"8385fb1c-00ee-4bd4-af48-7ce9625f96ec","order_by":2,"name":"Nobuo Toda","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYJACCYYKBh4Q4zCSEB7ABpI/w8DDQ5oWxjYGsDXMRDnKXL754I2f87bJ2POfMTxcUFGXx8De+4DBcgduLZZtbMmWvdtu8/BI5BgcnnHmcDEDz3EDBskzuLUYHOMxk+AFa+ExOMzbdiCxQSKNgUGyDb8Wyb9zgFr4z4C01BGnRZq3AaiFIQekhZkYLWnJ1jLHgFpupBUc5gH6hY3nGMMBvH45fPjgzTc1t+3Z+w9v/swDDDF+9jbGx5J4QgwDJAAjiuGwZAMpWkAE40dStIyCUTAKRsFwBwCOEkqaFUmBTAAAAABJRU5ErkJggg==","orcid":"","institution":"Mitsui Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Nobuo","middleName":"","lastName":"Toda","suffix":""},{"id":6606020,"identity":"6f762284-e178-4186-8952-e02c7cc6a18e","order_by":3,"name":"Ken Kurokawa","email":"","orcid":"","institution":"Mitsui Memorial 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10:47:12","currentVersionCode":4,"declarations":"","doi":"10.21203/rs.3.rs-19921/v4","doiUrl":"https://doi.org/10.21203/rs.3.rs-19921/v4","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-020-01580-w","type":"published","date":"2021-01-06T15:01:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":4575660,"identity":"0257735a-23e3-49cb-9ac0-6e34902fce10","added_by":"auto","created_at":"2020-12-29 15:59:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":70888,"visible":true,"origin":"","legend":"Independent risk factors of primary outcomes in multivariate logistic regression analysis\nADL: activity of daily living, PPI: proton pump inhibitor, OR: odds ratio, CI: confidence interval.\nWhen estimating the impairment of ADL, 13 patients who had resided in care facilities before hospitalization were excluded.\n","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-19921/v4/c0fcda40f690f830eacddca7.png"},{"id":4575561,"identity":"8bf16869-0b6a-47a4-a064-148d54e84a88","added_by":"auto","created_at":"2020-12-29 15:56:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":36794,"visible":true,"origin":"","legend":"Independent risk factors of primary outcomes for elderly patients in multivariate logistic regression analysis\nOR: odds ratio, CI: confidence interval.\nWhen estimating the impairment of ADL, 6 patients who had resided in care facilities before hospitalization were excluded.\n","description":"","filename":"fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-19921/v4/3a58a92d16d2bde0288a72fa.png"},{"id":13640591,"identity":"25c63d80-c86b-42a6-93bf-c3a0fc1f2ed8","added_by":"auto","created_at":"2021-09-17 09:00:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":478395,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-19921/v4/017cd238-72c3-46d0-94fa-85fa3788b8e0.pdf"}],"financialInterests":"","formattedTitle":"Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers","fulltext":[{"header":"Background","content":"\u003cp\u003eHemorrhagic gastroduodenal ulcers (HGUs) are the most common cause of upper gastrointestinal bleeding. Although most HGUs can be safely treated with medications and/or endoscopic procedures [1], some patients with HGU have a poor prognosis owing to comorbidities [2] and medications for anticoagulation [3]. Indeed, mortality from HGU is still high, with reported rates up to 10% [4].\u003c/p\u003e\n\u003cp\u003eSeveral reports have evaluated the risk factors of mortality of HGU [5-9]. A previous systematic review has shown that older age, comorbidity, shock, and delayed treatment are independent risk factors of mortality [5]. Another study revealed that endoscopic features with a high-risk Forrest classification (Forrest I, IIa, and IIb) are prognostic indicators of mortality [6].\u003c/p\u003e\n\u003cp\u003eIn addition to mortality, impairment of activities of daily living (ADL) is also a very important prognostic issue, particularly in elderly subjects, leading to longer hospitalization and higher treatment cost [10]. Moreover, lowering of ADL is closely correlated with mortality in elderly subjects\u0026nbsp;[11]. Changes in ADL associated with disease outcome have been evaluated mainly in diseases that directly influence patients\u0026rsquo; physical functions, such as hip fracture and stroke\u0026nbsp;[12, 13].\u0026nbsp;In this regard, there have been no studies that have evaluated which risk factors of HGU are associated with impairment of ADL. This is important in both clinical care of patients who are identified to be at risk of ADL impairment after HGU and planning of clinical and social care services. This is especially relevant in care of the elderly since previous reports have revealed that advanced age is a risk factor of poor outcomes for HGU patients [5, 7, 8].\u003c/p\u003e\n\u003cp\u003eIn this study, the risk factors of poor prognosis, including mortality and impairment of ADL, were examined in patients with HGU. In particular, the prognosis of elderly HGU patients (\u003cu\u003e\u0026gt;\u003c/u\u003e 75 years old) was evaluated in comparison to that of non-elderly (\u0026lt; 75 years old) patients, since previous reports have revealed that advanced age is a risk factor of poor outcomes for HGU patients [5, 7 ,8].\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective cohort study was performed using the database of endoscopy and medical record reviews from Mitsui Memorial Hospital, a secondary emergency hospital in Tokyo, Japan, between August 2004 and December 2017.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe extracted the data of patients who had evidence of gastroduodenal ulcers identified by endoscopy from the endoscopic database. Those who showed hemorrhagic implications with symptoms including black stool, hematemesis, and/or anemia in medical records were included. If patients experienced two or more episodes of HGU during the study period, the first episode alone was included in the analysis. Patients who were confirmed as malignant ulcers by pathological diagnosis were excluded. Those with lower ADL on admission due to comorbidities including malignancy and dementia were not excluded because we focused on each patient\u0026rsquo;s change of ADL, but\u0026nbsp;patients who had resided in care facilities before hospitalization were excluded when examining the impairment of ADL.\u0026nbsp;In this study, both gastric and duodenal ulcers were included in HGUs because management of these diseases is similar including gastric acid inhibition, endoscopic hemostasis, and eradication of \u003cem\u003eHelicobacter pylori\u003c/em\u003e [14].\u003c/p\u003e\n\u003cp\u003eOur policy for management of HGU was as follows. Endoscopic hemostasis was generally performed for HGU with Forrest I or IIa according to the Forrest classification\u0026nbsp;[15].\u0026nbsp;If the index endoscopic hemostasis was unsuccessful with bleeding continuing, surgery or angioembolization was considered.\u0026nbsp;The second look endoscopy was done before start of eating for patients with high-risk HGU such as large size and Forrest I or II.\u0026nbsp;EGD for biopsy to rule out gastric cancer was also performed.\u003c/p\u003e\n\u003cp\u003eThe following clinical factors were evaluated as they have been shown to be associated with the severity of bleeding or prognosis of HGU [5, 6].\u0026nbsp;Endoscopic features and need for interventional endoscopic procedures were collected from endoscopic database. The information of comorbidities, symptoms, and medications were reviewed with medical records.\u0026nbsp;The evaluated endoscopic features included locations of HGU (fundus, gastric body, gastric angle, antral zone, anterior wall of duodenal bulb, posterior wall of duodenal bulb, and second portion of duodenum), type of hemorrhage using the Forrest classification\u0026nbsp;[15], size of ulcer (\u003cu\u003e\u0026gt;\u003c/u\u003e 20 mm or not), and the number of ulcers (\u003cu\u003e\u0026gt;\u003c/u\u003e 2 ulcers or not). Interventional endoscopic procedures indicate endoscopic hemostasis including clipping, argon plasma coagulation, heat probe, sprinkling of thrombin, injection of hypertonic saline-epinephrine solution, and injection of epinephrine. The following comorbidities were recorded: heart disease, pulmonary disease, stroke, diabetes mellitus, liver disease, renal disease, and history of gastroduodenal ulcers before the study period. The evaluated symptoms included black stool, syncope, and hematemesis. Medication use prior to hemorrhage was documented for anticoagulants, antiplatelets, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, corticosteroids, proton pump inhibitors (PPIs), and H2 receptor antagonists (H2RAs).\u003c/p\u003e\n\u003cp\u003eThis analysis defined patients \u003cu\u003e\u0026gt;\u003c/u\u003e 75 years of age as elderly, and the clinical backgrounds and outcomes were compared between patients \u0026lt; 75 years old and those \u003cu\u003e\u0026gt;\u003c/u\u003e 75 years old. The primary outcomes were overall mortality, mortality within 30 days after occurrence of hemorrhage, and impairment of ADL. Admission to a care facility or the need for home adaptations such as a care bed, during the hospitalization period were defined as ADL decline. When estimating the impairment of ADL, 13 patients who resided in care facilities before hospitalization were excluded. The secondary outcomes were rebleeding, hospitalization periods, and need for transfusion.\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of Mitsui Memorial Hospital approved this retrospective study, which conformed to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013). For this type of study formal consent is not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous data are presented as mean \u0026plusmn;\u0026nbsp;standard deviation, and categorical data as actual frequencies and percentages. Continuous data were compared with the Student\u0026rsquo;s t-test. Comparisons of categorical data between the groups were performed with the chi-square test or Fisher\u0026rsquo;s exact test as appropriate. Independent risk factors of primary outcomes were identified using multivariate logistic regression analysis based on parameters with \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.1 in univariate analysis.\u003c/p\u003e\n\u003cp\u003eA \u003cem\u003ep-\u003c/em\u003evalue \u0026lt; 0.05 was considered statistically significant, and odds ratios (ORs) with 95% confidence intervals (CIs) were determined. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, EZR is a modified version of R commander designed to add statistical functions frequently used in biostatistics.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn total, 582 patients (425 men and 157 women; mean age, 66.6 \u0026plusmn; 14.4 years) were diagnosed with HGU at least once during the study period, and the first episode of these patients were analyzed. Table 1 shows the evaluated clinical factors of all patients. The following variables were significantly higher in patients \u003cu\u003e\u0026gt;\u003c/u\u003e 75 years old than patients \u0026lt; 75 years old: HGU in the gastric body [47% vs. 33%, \u003cem\u003ep\u003c/em\u003e = 0.001], HGU \u0026gt; 20 mm (33% vs. 23%, \u003cem\u003ep\u003c/em\u003e = 0.02), comorbidities (heart disease [34% vs. 21%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001], pulmonary disease [12% vs. 7%, \u003cem\u003ep\u003c/em\u003e = 0.044], and stroke [14% vs. 5%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001]), symptoms of hematemesis (36% vs. 24%, \u003cem\u003ep\u003c/em\u003e = 0.0038), and antiplatelet use (38% vs. 19%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). Meanwhile, HGU in the anterior wall of duodenal bulb [14% vs. 25%, \u003cem\u003ep\u003c/em\u003e = 0.0024], HGU with the Forrest classification IIa (27% vs. 37%, \u003cem\u003ep\u003c/em\u003e = 0.02), and history of gastroduodenal ulcers [16% vs. 27%, \u003cem\u003ep\u003c/em\u003e = 0.0023] were less likely observed in patients \u003cu\u003e\u0026gt;\u003c/u\u003e 75 years old.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary and secondary outcomes of patients \u0026lt; 75 years old versus those \u003cu\u003e\u0026gt;\u003c/u\u003e 75 years old\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 shows the outcomes of the two groups. Overall mortality (8% vs. 4%, \u003cem\u003ep\u003c/em\u003e = 0.048), impairment of ADL (7% vs. 1%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and need for transfusion (67% vs. 51%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) were frequently observed in patients \u003cu\u003e\u0026gt;\u003c/u\u003e 75 years old than in patients \u0026lt; 75 years old. In addition, patients \u003cu\u003e\u0026gt;\u003c/u\u003e 75 years old had significantly longer hospitalization period (23.1 \u0026plusmn; 28.2 days vs. 16.0 \u0026plusmn; 29.3 days, \u003cem\u003ep\u003c/em\u003e = 0.0056).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIndependent risk factors of primary outcomes in multivariate logistic regression analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultivariate analysis revealed that age (\u003cu\u003e\u0026gt;\u003c/u\u003e 75 years) (OR, 2.24; 95% CI, 1.06 \u0026ndash;4.73), and renal disease (OR, 3.43; 95% CI, 1.44\u0026ndash;8.14) were independent and significant risk factors for overall mortality. The risk factors of mortality within 30 days after hemorrhage were age (\u003cu\u003e\u0026gt;\u003c/u\u003e 75 years) (OR, 3.36; 95% CI, 1.19\u0026ndash;9.44), need for interventional endoscopic procedures (OR, 3.84; 95% CI, 1.06\u0026ndash;13.9), and renal disease (OR, 4.35; 95% CI, 1.42\u0026ndash;13.4). Finally, the risk factors of impairment of ADL were use of PPI prior to hemorrhage (OR, 5.80; 95% CI, 2.08\u0026ndash;16.2), heart disease (OR, 3.05; 95% CI; 1.11\u0026ndash;8.43), and age (\u003cu\u003e\u0026gt;\u003c/u\u003e 75 years) (OR, 5.09; 95% CI, 1.73\u0026ndash;15.0) (Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIndependent risk factors of primary outcomes for elderly patients in multivariate logistic regression analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe prognostic factors in elderly subjects were analyzed. The independent and significant risk factors for overall mortality were Forrest IIb (OR, 4.26; 95% CI, 1.17\u0026ndash;15.5), and ulcer location of posterior wall of duodenal bulb (OR, 5.14; 95% CI, 1.18\u0026ndash;22.5). The risk factors of mortality within 30 days after hemorrhage were need for interventional endoscopic procedure (OR, 9.65; 95% CI, 1.11\u0026ndash;83.7), and location of posterior wall of duodenal bulb (OR, 11.9; 95% CI, 2.24\u0026ndash;63.4). The risk factors of impairment of ADL were fundus ulcer (OR, 11.6; 95% CI, 1.47\u0026ndash;91.7), and use of PPI prior to hemorrhage (OR, 8.24; 95% CI, 2.36\u0026ndash;28.7) (Figure2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the risk factors of poor prognosis and impairment of ADL in patients with HGU were examined. Advanced age, comorbidities (renal disease and heart disease), need for interventional endoscopic procedures, and use of PPI prior to hemorrhage were identified as independent risk factors for worse outcomes. Moreover, we particularly focused on the impairment of ADL by HGU and found that PPI use prior to hemorrhage was a significant risk factor that impaired ADL both in overall subjects and in elderly subjects alone.\u003c/p\u003e\n\u003cp\u003eAdvanced age was a risk factor of overall mortality and mortality within 30 days after hemorrhage; this result is in line with several previous studies\u0026nbsp;[5, 7, 8]. Advanced age was also an independent risk factor of impairment of ADL. Iwatsuka et al. showed that the elderly patients (\u0026gt; 70 years old) with gastrointestinal bleeding were less likely to return home after hospital discharge than non-elderly patients (\u0026lt; 70 years old) (5% vs. 21%, p \u0026lt; 0.001)\u0026nbsp;[7]. However, their study included many types of gastrointestinal bleedings, from benign ulcers to malignant tumors. In contrast, we analyzed the risk factors of impairment of ADL in patients with HGU alone, and elderly subjects with gastrointestinal bleeding were at risk even with benign disease. The attribute of limited physiologic reserves, sarcopenia and frailty in elderly is probably responsible. In this regard, more attention should be paid to rehabilitation and prehabilitation for those subjects [16].\u003c/p\u003e\n\u003cp\u003eThe need for interventional endoscopic procedures was a risk factor of mortality within 30 days after hemorrhage. Endoscopic procedures are generally performed for HGU with risky appearance, including Forrest I and II. In this regard, and consistent with our results, Lanie et al. showed that endoscopic features of Forrest I and II are prognostic indicators of mortality\u0026nbsp;[6]. In contrast, Giese et al. showed that those Forrest scores are not significantly associated with death within 30 days, and rebleeding\u0026nbsp;[17]. They discussed the discrepancy from Lanie\u0026rsquo;s results based on the timing of endoscopy, because they always performed endoscopy within 6 hours of admission. In our hospital, when severe bleeding is implied by symptoms, vital signs, laboratory data, medications, or comorbidities, EGD is performed as soon as possible after admission, but otherwise, EGD is performed electively. Earlier endoscopic interventions, regardless of the severity of HGU, might improve the prognosis of patients with HGU. In this regard, recent guidelines suggested stratifying patients based on the Blatchford score and adopting a risk-stratified management and recommended urgent inpatient endoscopy (\u0026le; 12\u0026thinsp;hours of admission) in the high-risk group [18]. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, HGU patients with renal disease had worse prognosis, and similar results have also been reported\u0026nbsp;previously\u0026nbsp;[8, 19]. Renal disease in general is poor prognosticator for many diseases and pathologies. In particular, bleeding leads to acute on chronic kidney injury and hence drives poor outcomes [20]. This result may also be partly due to lower hemoglobin levels in patients with chronic kidney disease because anemia is reportedly the risk factor of mortality for patients with a higher risk of stroke or cardiovascular events\u0026nbsp;[21, 22]. In addition, uremic platelet function impairment is a potential cause of the higher risk for ulcer bleeding complications\u0026nbsp;[23]. Uremic platelet dysfunction involves von Willebrand factor with platelet membrane glycoproteins Ib and IIb to IIIa, which is not normalized after dialysis\u0026nbsp;[24]. Furthermore, anticoagulation use during hemodialysis may contribute to the risk\u0026nbsp;[19].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The presence of heart disease was one of the risk factors of impairment of ADL. It has been reported that when patients have some cardiac abnormality, such as valvular heart disease or underlying left ventricular dysfunction, severe anemia can cause hyper-output heart failure\u0026nbsp;[25] resulting in long hospitalization and impairment of ADL. Eikelboom et al. revealed that there is a strong, consistent, temporal, and dose-related association between bleeding and poor prognosis in patients who have a history of acute coronary syndromes\u0026nbsp;[26]. They discussed that major bleeding is likely to lead physicians to discontinue effective antithrombotic drugs such as aspirin, clopidogrel, heparin, low-molecular-weight heparin, and warfarin, which in turn could increase the risk of ischemic heart disease, stroke, and cardiovascular death. Furthermore, it is commonly known that heart disease is one of the risk factors of sarcopenia that could cause impairment of ADL. Consequently, sarcopenia in patients with HGU might affect the results\u0026nbsp;[27, 28].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePPI use was identified as a risk factor of impairment of ADL. Most of the patients were prescribed PPI for the prevention of peptic ulcers caused by NSAIDs (21%) and antiplatelets (including aspirin) (47%) or due to a previous history of peptic ulcers (9%). A previous report showed that approximately 5% of patients with a history of ulcer bleeding who continued to take both NSAIDs and PPI still had recurrent ulcers after 6 months\u0026nbsp;[29].\u003csup\u003e\u0026nbsp;\u003c/sup\u003eAnother study revealed that 19%\u0026ndash;26% of patients with similar situations had endoscopically assessed gastroduodenal ulcers at 6 months, and the risk factors of ulcer recurrence included age \u003cu\u003e\u0026gt;\u003c/u\u003e 75 and comorbidity (heart diseases, stroke, cirrhosis, respiratory diseases, renal diseases, and diabetes)\u0026nbsp;[30]. Thus, ulcer development as a result of NSAIDs under PPI treatment is not rare, and based on our results, such ulcers may result in poor clinical outcomes. Although the precise reasons are unknown, a possible risk of osteoporosis and dementia owing to taking PPIs may also be associated with the poor outcomes of PPI users\u0026nbsp;[31, 32]. Moreover, the relatively low dose of PPIs in Japanese patients (e.g. esomeprazole 10\u0026ndash;20 mg/day) could not sufficiently prevent the development of ulcers as a result of NSAIDs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the elderly, the locations of HGU (fundus and the posterior wall of the duodenum) were identified as independent risk factors of worse outcomes, but the presence of comorbidities was not. Localization on the posterior wall of the duodenal bulb has been shown to be a risk factor for adverse outcome in bleeding peptic ulcers\u0026nbsp;[33]. Furthermore, the morbidity rate of fundus ulcers in elderly people is known to be higher than that in non-elderly people\u0026nbsp;[34]. The seriousness of ulcers or bleeding is likely to be associated with mortality for elderly patients. Indeed, Chow et al. reported that the risk of death was increased in elderly patients (age \u0026gt; 80) with features of severe bleeding (transfusion \u0026gt; 4 units, ulcer size \u0026gt; 2 cm, hematemesis, and melaena) at presentation\u0026nbsp;[8]. In this regard, the finding that Forrest IIb was the risk of overall mortality was of interest. Although patients with Forrest I or Forrest IIa ulcer always received endoscopic hemostasis, those with Forrest IIb did not. The difference in treatment strategy between the stages of ulcers might contribute to the result [35]. The fact that comorbidities were not identified as a prognostic factor in the elderly is not surprising because most elderly patients have at least one comorbidity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe present study has several strengths. First, our study included a relatively high number of patients with a number of variables. Second, we evaluated each comorbidity separately instead of using the Charlson Comorbidities Index, which resulted in the identification of independent risk factors.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This study has several limitations that should be recognized. First, this study was a retrospective and single center study and there could be some biases. In particular, relatively homogenous socio-cultural status and limited health infrastructure in our hospital might affect the results. Second, the patients in our study might have had more severe heart and renal diseases than patients in other studies because our hospital is a tertiary center of heart diseases and renal diseases in the eastern region of Tokyo. Third, we defined ADL impairment as admission to care facilities after hospital discharge or requirement of home modification for rehabilitation at home. Although a previous report applied similar definitions in the estimation of ADL\u0026nbsp;[7], such definitions are not validated. In order to evaluate the changes of ADL more precisely, validated measurement scores such as the Pune-FAAT scale or the MDS-derived ADL scale should be used. Fourth, the patients\u0026rsquo; information about ADL after discharge may be insufficient due to limited access. Finally, the characteristics of our patients did not include the \u003cem\u003eHelicobacter pylori\u0026nbsp;\u003c/em\u003einfection profile; however, as far as we know, no previous study has shown that \u003cem\u003eHelicobacter pylori\u0026nbsp;\u003c/em\u003eis a risk factor of poor prognosis of HGU.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAdvanced age was a potent predictor of poor outcomes in patents with HGU, and additional risk factors of poor outcomes were different between overall HGU patients and elderly patients alone. The presence of comorbidities was a risk factor in the overall patients, and in particular heart disease was a risk of impairment of ADL. In elderly patients, the location of ulcers was associated with outcomes. Furthermore, PPI use prior to hemorrhage was a significant predictor of impairment of ADL, both in overall patients and in elderly patients alone. Although PPI use has generally been recommended for the prevention of ulcer development, such a policy may have room for reconsideration.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eADL: activity of daily living, HGU: hemorrhagic gastroduodenal ulcers, EGD: esophagogastroduodenoscopy, PPI: proton pump inhibitor, NSAIDs: nonsteroidal anti-inflammatory drugs, OR: odds ratio, CI: confidence interval.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of Mitsui Memorial Hospital approved this retrospective study, which conformed to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with 1964 Helsinki declaration and its amendments or comparable ethical standards. For this type of study formal consent is not required.\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 datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was unfunded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJA and NT conceived and designed the study. JA and JK analyzed the data. JA, JK, and NT wrote the paper. Finally, all authors, including KK, CS, SK, KF, MK, KT1, KK, TO, MS, and KT2, reviewed and approved the version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1 Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. \u003cem\u003eBMJ\u003c/em\u003e. 2005;330(7491):568.\u003c/p\u003e\n\u003cp\u003e2 Marmo R, Koch M, Cipolletta L et al. Predictive factors of mortality from nonvariceal upper gastrointestinal hemorrhage: Multicenter Study. \u003cem\u003eAm J Gastroenterol. \u003c/em\u003e2008;103(7):1639\u0026ndash;1647.\u003c/p\u003e\n\u003cp\u003e3 Barada K, Abdul-Baki H, El Hajj II, Hashash JG, Green PH. 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Pathophysiology of anemia in heart failure. \u003cem\u003eHeart Fail Clin\u003c/em\u003e. 2010;6(3):279\u0026ndash;88.\u003c/p\u003e\n\u003cp\u003e26 Eikelboom JW, Mehta SR, Sonia S, et al. Adverse impact of bleeding on prognosis in patients with acute coronary syndrome. \u003cem\u003eCirculation\u003c/em\u003e. 2006;114:774\u0026ndash;782.\u003c/p\u003e\n\u003cp\u003e27 Cruz\u0026ndash;Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. \u003cem\u003eAge Aging\u003c/em\u003e. 2010;39(4):412\u0026ndash;423.\u003c/p\u003e\n\u003cp\u003e28 Collamati A, Marzetti E, Calvani R, et al. Sarcopenia in heart failure: Mechanisms and therapeutic strategies.\u003cem\u003e J Geriatr Cardiol\u003c/em\u003e. 2016;13(7):615\u0026ndash;624.\u003c/p\u003e\n\u003cp\u003e29 Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. \u003cem\u003eN Engl J Med.\u003c/em\u003e 2002;347:2104\u0026ndash;2110.\u003c/p\u003e\n\u003cp\u003e30 Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac plus omeprazole in high risk arthritis patients.\u003cem\u003e Gastroentel\u003c/em\u003e. 2004;127:1038\u0026ndash;1043.\u003c/p\u003e\n\u003cp\u003e31 Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: A meta\u0026ndash;analysis of 11 international studies.\u003cem\u003e Am J Med.\u003c/em\u003e 2011;124(6):519.\u003c/p\u003e\n\u003cp\u003e32 Haenisch B, von Holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors.\u003cem\u003e Eur Arch Psychiatry Clin Neurosci.\u003c/em\u003e 2015;153:971.\u003c/p\u003e\n\u003cp\u003e33 Kolkman JJ, Meuwissen SG. A review on treatment of bleeding peptic ulcer: A collaborative task of gastroenterologist and surgeon. \u003cem\u003eScand J Gastroenterol Suppl\u003c/em\u003e. 1996;218:16\u0026ndash;25.\u003c/p\u003e\n\u003cp\u003e34 Nakamura T. Gastric ulcers in the aged with special reference to the high located ulcers. \u003cem\u003eJpn J Gastroenterol Surg\u003c/em\u003e. 1982;15(11):1706\u0026ndash;1715.\u003c/p\u003e\n\u003cp\u003e35 Jensen DM, Kovacs TOG, Jutabha R, et al. Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots. Gastroenterology. 2002 Aug;123(2):407-13.\u003c/p\u003e\n"},{"header":"Tables","content":"\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eTable 1. Baseline characteristics of HGU patients\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCharacteristics\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eNon-elderly\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(n = 390)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eElderly\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(n = 192)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePatient number\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e390\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e192\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family: \"MS Mincho\";'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSex (Male/Female)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e309/81\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e116/76\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt; 0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAge (mean\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;SD)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e59.2\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;11.3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e81.8\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;5.0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt; 0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eWeekend hospitalization\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e90 (23%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e38 (20%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.43\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLocation of HGU\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family: \"MS Mincho\";'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Fundus\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e13 (3%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e5 (2%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Gastric body\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e127 (33%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e90 (47%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Gastric angle\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e72 (19%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e30 (16%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.47\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Antral zone\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e51 (13%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e30 (16%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.48\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Anterior wall of duodenal bulb\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e97 (25%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e26 (14%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.0024\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Posterior wall of duodenal bulb\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e30 (8%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e12 (6%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.64\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Second part of duodenum\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e6 (2%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e5 (3%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.52\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eEndoscopic features\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family: \"MS Mincho\";'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Forrest classifications\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family: \"MS Mincho\";'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026nbsp; Ia\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e32 (8%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e17 (9%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.92\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026nbsp; Ib\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e65 (17%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e39 (20%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.34\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026nbsp; IIa\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e145 (37%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e52 (27%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.02\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026nbsp; IIb\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e38 (10%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e19 (10%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026nbsp; IIc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e27 (7%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e23 (12%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.059\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026nbsp; III\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e83 (21%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e42 (22%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.96\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;text-indent:5.25pt;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;Size \u0026gt; 20 mm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e91 (23%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e63 (33%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.02\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026gt; 2 ulcers\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e167 (43%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e96 (50%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eNeed for interventional endoscopic procedure\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e233 (60%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e98 (51%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.057\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eComorbidities\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family: \"MS Mincho\";'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Heart disease\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e83 (21%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e66 (34%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt; 0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Pulmonary disease\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e26 (7%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e23 (12%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.044\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Stroke\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e18 (5%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e26 (14%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt; 0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Diabetes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e82 (21%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e34 (18%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.41\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Liver disease\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e21 (5%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e19 (10%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.062\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Renal disease\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e46 (12%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e18 (9%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.46\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; History of GU\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e107 (27%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e30 (16%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.0023\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSymptoms\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family: \"MS Mincho\";'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Hematemesis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e94 (24%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e69 (36%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.0038\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Black stool\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e315 (81%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e144 (75%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Syncope\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e15 (4%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e10 (5%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.59\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMedications\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family: \"MS Mincho\";'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Anticoagulation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e29 (7%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e23 (12%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.099\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Antiplatelet\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e74 (19%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e73 (38%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt; 0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; NSAIDS\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e61 (16%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e43 (22%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.059\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; COX-2 inhibitor\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e3 (1%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e4 (2%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.23\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; Corticosteroids\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e14 (4%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e7 (4%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; PPI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e42 (11%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e24 (13%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.63\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 233.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; H2RA\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e24 (6%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e14 (7%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.73\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eADL: activity of daily living, COX: cyclooxygenase, GU: gastroduodenal ulcers, H2RA: histamine 2 receptor antagonist, NSAIDs: nonsteroidal anti-inflammatory drugs, PPI: proton pump\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003einhibitor, SD: standard deviation.\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eTable 2. Outcomes of patients\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 163.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eOutcomes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eNon-elderly (n = 390)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eElderly (n = 192)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 163.05pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eOverall mortality\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e15 (4%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.2pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e15 (8%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.55pt;border: none;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.048\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 163.05pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMortality within 30 days after hemorrhage\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:113.4pt;padding:0in 5.4pt 0in 5.4pt;height:18.75pt;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e7 (2%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;padding:0in 5.4pt 0in 5.4pt;height:18.75pt;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e9 (5%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:49.55pt;padding:0in 5.4pt 0in 5.4pt;height:18.75pt;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.058\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 163.05pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eImpairment of ADL\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e5 (1%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.2pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e13 (7%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.55pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt; 0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 163.05pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eHospitalization period (days)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e16.0\u0026nbsp;\u003c/span\u003e\u003cspan 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style='font-family:\"Times New Roman\",serif;'\u003eTransfusion\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e200 (51%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e128 (67%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt; 0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eADL: activity of daily living.\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eWhen estimating the impairment of ADL, 13 patients who had resided in care facilities before hospitalization were excluded.\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gastroduodenal ulcer, elderly, prognosis, activity of daily living","lastPublishedDoi":"10.21203/rs.3.rs-19921/v4","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-19921/v4","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eImpairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The\u003cstrong\u003e \u003c/strong\u003eclinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Advanced age (\u0026gt; 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.44–8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR, 5.80; 95% CI, 2.08–16.2), and heart disease (OR, 3.05; 95% CI, 1.11–8.43) for the impairment of ADL. Analysis of elderly (\u0026gt; 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR, 8.24; 95% CI, 2.36–28.7).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.\u003c/p\u003e","manuscriptTitle":"Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers","msid":"","msnumber":"","nonDraftVersions":[{"code":4,"date":"2020-12-29 15:55:52","doi":"10.21203/rs.3.rs-19921/v4","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2020-12-12T14:58:29+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-12-11T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-12-03T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-12-02T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-12-02T23:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":3,"date":"2020-12-16 18:47:14","doi":"10.21203/rs.3.rs-19921/v3","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-10-29 18:49:45","doi":"10.21203/rs.3.rs-19921/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-11-30T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-11-13T00:00:00+00:00","index":2,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nDear Authors\nMany thanks for including changes within manuscript as per comments.\nI agree to keep age as 75 yr cut off with sound reasons provided.\n\nThanks\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **none**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-11-06T00:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nPEER REVIEWER ASSESSMENTS:\n\nOBJECTIVE - Full research articles: is there a clear objective that addresses one or several testable research questions? (Brief or other article types: is there a clear objective?)\nYes - there is a clear objective\n\nDESIGN - Is the current approach (including controls and analysis protocols) appropriate for the objective?\nYes - the approach is appropriate\n\nEXECUTION - Are the experiments and analyses performed with sufficient technical rigor to allow confidence in the results?\nYes - experiments and analyses were performed appropriately\n\nSTATISTICS - Is the use of statistics in the manuscript appropriate?\nYes - appropriate statistical analyses have been used in the study\n\nINTERPRETATION - Is the current interpretation/discussion of the results reasonable and not overstated?\nYes - the author's interpretation is reasonable\n\nOVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently for you to now recommend the work as a technically sound contribution? If not, can further revisions be made to make the work technically sound?\nYes - current version is technically sound\n\nPEER REVIEWER COMMENTS:\n\nGENERAL COMMENTS: * Have the authors responded adequately to each of the questions or concerns you raised in your comments?\nYes.\n\n* Have they also made changes to reflect their responses in the manuscript itself?\nYes changes have been made. I suggest some further minor edits for clarity:\nAbstract.\n\"Necessity to look for care facilities to admit or requirement of home modifications\nduring the hospitalization period was defined as ADL decline.\" Suggest 'Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline'\nBackground. No further comments.\nMethods.\nLine 29 'Patients who *had* confirmed malignant ulcers confirmed by …'\nPlease edit this sentence for clarity: \"Necessity to look for care facilities\nto admit or requirement of home modifications, such as preparing caring bed,\narrangement of home visiting nurses and doctors, etc, during the hospitalization\nperiod were defined as ADL decline.\" \nSuggest: Admission to a care facility or the need for home adaptations such as a care bed, during the hospitalization period were defined as ADL decline'\nResults.\nThe summary titles for each paragraph are helpful as are the forest plots for OR. The section part of this section is very much improved by the addition of data from Table 1 and Table 2.\nDiscussion. No further comments.\n* What is your overall impression of the revised manuscript?\nSuitable for publication, at the discretion of the editor with some minor edits for clarity.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **This reviewer has been recruited by a partner organization, Research Square. Reviewers with declared or apparent competing interests are not utilized for these reviews. This reviewer has agreed to publication of their comments online under a Creative Commons Attribution License attributed to Research Square and was paid a small honorarium for completing the review within a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-11-05T01:00:00+00:00","index":2,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-11-05T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-11-05T00:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-10-21T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-10-20T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-10-20T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-04-06 17:38:06","doi":"10.21203/rs.3.rs-19921/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-09-23T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-09-17T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nPEER REVIEWER ASSESSMENTS:\n\nOBJECTIVE - Full research articles: is there a clear objective that addresses a testable research question(s) (brief or other article types: is there a clear objective)?\nNo - there are minor issues\n\nDESIGN - Is the current approach (including controls and analysis protocols) appropriate for the objective?\nNo - there are minor issues\n\nEXECUTION - Are the experiments and analyses performed with technical rigor to allow confidence in the results?\nYes - experiments and analyses were performed appropriately\n\nSTATISTICS - Is the use of statistics in the manuscript appropriate?\nYes - appropriate statistical analyses have been used in the study\n\nINTERPRETATION - Is the current interpretation/discussion of the results reasonable and not overstated?\nYes - the author's interpretation is reasonable\n\nOVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound? If not, can revisions be made to make the work technically sound?\nProbably - with minor revisions\n\nPEER REVIEWER COMMENTS:\n\nGENERAL COMMENTS:\n* What is your overall impression of the study?\nInteresting with some novel results relevant to care of older people and service planning.\n\n* What have the authors done well?\nProvided an analysis of risk factors for impairment of daily living after haemorrhagic ulcer, using retrospective methods. Analyses are appropriate.\n\n* In what ways does it not meet best practice?\nThe report of the study needs some additional detail and re-organisation of some of the text to improve readability.\n\nREQUESTED REVISIONS:\nObjective - minor issues. These are issues of clarity in reporting rather than conduct of the research, please see my notes about the Abstract and methods, in particularly the statements concerning specification of the risk factors and the outcomes of interest in the report.\nDesign - minor issues. Only in that the study is of retrospective design and in a single centre, which is discussed in the Discussion section as a potential limitation.\nExecution - appropriate, but some additional detail needs to be given in the report for clarity.\nStatistics - appropriate.\nInterpretation - reasonable\nFurther details are provided below on a section by section basis.\n\n\n\nAbstract\n\nImpairment of activities of daily living (ADL) due to haemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. The Background then goes on cite several studies in which mortality and hospitalization have ben studied. It might be better just to state that the authors evaluated Impairment of activities of daily living (ADL) due to haemorrhagic gastroduodenal ulcer in the abstract and expand on the lack of data other than mortality, hospitalizations and healthcare costs in the Background, i.e. please make the case for the novelty of this work in the Background section.\nState risk factors and outcomes to be evaluated more clearly.\nThe retrospective design of this study should be stated in the abstract.\nBackground.\nPlease see notes below regarding the choice of risk factors and outcomes. The Background does not state why this research is novel and important for clinical care and service planning. A minor edit to state this clearly would improve the relevance of the paper.\ne.g. 'Although previous studies have evaluated the risk factors for mortality of HGU, and impairment of ADL has been evaluated in other disease, to date there have been no studies that have evaluate which risk factors of HGU are associated with impairment of ADL. This is important in both clinical care of patients who are identified to be at risk of ADL impairment after HGU and for planning of clinical and social care services. This is especially relevant in care of the elderly since previous reports have revealed that advanced age is a risk factor of poor outcomes for HGU patients (refs) '\n\nMethods\nHow was the review conducted - by case notes, how were data extracted, was a pro forma used and how was this developed (why were the data items chosen)? Who performed the data extraction? How were data stored, collated, verified? Please provide these details.\nInclusion and exclusion criteria. Please state these, e.g. co morbidities, residence in care facilities.\nHow was ADL assessed? How were these data obtained once the patient had left hospital care? The paper states that \"Impairment of ADL was defined as admission to care facilities after hospital discharge or the requirement of home modification for rehabilitation at home.\" However, there is wide variation in having minor adaptations in the home (which may have been needed for reasons unrelated to HGU e.g. arthritis, and a full care package delivered in residential care. This introduces uncertainty in the interpretation authors' of the results for ADL and at the very least, there should be some discussion of this in the Discussion section.\nState risk factors - on reading this section data items are specified but it is not clear how these were chosen as 'risk factors' (Were these chosen a priori ? ). The reasons for these choices of risk factor and outcome should be stated in the methods. It seems reasonable to select these risk factors and outcomes of importance based on what is known from clinical practice, but some background (with references) and reasons should be provided in the paper. The information is present in the Background to some extent but there is no logical train of reasoning between the existing knowledge and risk factors and outcomes chosen. Some editing of the paper would solve this.\nI am glad to see ethical approval stated clearly.\n\nStatistical analysis\nStatistics used appear to be appropriate, although a detailed opinion should be sought from a medical statistician.\nOR appears to be appropriate, given that the total number of exposed people is not available, OR here is used as a measure of the strength of association between exposure and outcome. Odds however are difficult for non specialists to use and it would be helpful if there was an interpretation of the results in terms of e.g. 'elderly patients who had pre-existing renal disease were x % more likely to die within 30 days …'\n\nResults\nThis section is clear enough, but the presentation of results could be better - at present the format is rather dense and numerical. I accept that that is the nature of the results, but the message is not easy to determine. A summary paragraph providing the main results would be helpful, stating the clinical factors from Table 1 and the results for the main outcomes of interest from Table 2. This information appears throughout the Discussion and moving does this information to the Results section would improve the readability.\nTables - all fine - possibly the OR could be plotted rather than being presented as a table?\nIt is unclear why patients who resided in care facilities were included in the initial data analyses, but later excluded. Since they were already experiencing disruption to ADL presumably, these patients should have been excluded and the inclusion/exclusion criteria should have been stated in the methods section (e.g.. malignancies, pre-existing dementia).\n\nDiscussion\nThe Discussion is good, as each finding is compared and contrasted with what is already known. However please see my note above about summarising these results in the text of the Results section, before moving on to discuss the findings in the Discussion.\nA minor observation is that the results focus on both mortality and impairment of ADL. This is not reflected in the title of the paper, or the abstract.\nThe limitations and strengths section is good.\nThe conclusion section is good, and this work is novel in that it has identified that location and PPI use are predicators of impairment of ADL.\nADDITIONAL REQUESTS/SUGGESTIONS:\nNone , but please see my notes above.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **This reviewer has been recruited by a partner organization, Research Square. Reviewers with declared or apparent competing interests are not utilized for these reviews. This reviewer has agreed to publication of their comments online under a Creative Commons Attribution License attributed to Research Square and was paid a small honorarium for completing the review within a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-09-11T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-06-08T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\n1. In method section you state that you only included index ulcer case in patient with multiple ulcer related admission. Than you state that you collected patients with history of gastroduodenal ulcers. Both are paradoxical statements. Modify this. I include both statements below for your reference.\n\n\nIf patients experienced two or more episodes of HGU during the study period, the first episode alone was included in the analysis.\nThe following comorbidities were recorded: heart disease, pulmonary disease, brain stroke, diabetes mellitus, liver disease, renal disease, and history of gastroduodenal ulcers.\n\nMy point is if you include only the first episode, than how can that patient have a 'history of ulcer'!\n\n2. \"brain stroke' - make it 'stroke'.\n\n3. Why did you define 75 as elderly and not above 70? I know it is a bit of hassle to redo the stats again etc but I suggest consider 70 yrs as elderly. Or else cite a reference for 75 years as elderly to support. Your own citation 7 also reports 70 years. So overall it makes more sense for 70 years and not 75 years.\n\n4. Delete the following statement - All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with 1964 Helsinki declaration and its amendments or comparable ethical standards -- This is not relevant.\n\n5. The statement in second paragraph of results, authors need to tell significant difference for what variable is for which group of patients. Authors have to clarify rather than just report difference. The following statement - \"Significant differences were found between patients \u003c 75 years old and those \u003e 75 years old in terms of the location of HGU (gastric body [33% vs. 47%, p = 0.001], anterior wall of duodenal bulb\n[25% vs. 14%, p = 0.0024]), Forrest classification IIa (37% vs. 27%, p = 0.02), HGU size (\u003e 20 mm) (23% vs. 33%, p = 0.02), comorbidities (heart disease [21% vs. 34%, p \u003c 0.001], pulmonary disease [7% vs. 12%, p = 0.044], brain stroke [5% vs. 14%, p \u003c 0.001], and history of gastroduodenal ulcers [27% vs. 16%, p = 0.0023]), symptoms of hematemesis (24% vs. 36%, p = 0.0038), and antiplatelet use (19% vs. 38%, p \u003c 0.001). \" - needs to be revised accordingly.\n\n6. Same issue with paragraph 3 statement based on table 2 - authors have to tell what is for \u003c75 and what is for above 75.\n\n7. Your focus is on 'elderly'. Elderly have limited physiologic reserves, sarcopenia and frailty. This all has to be added to enhance the discussion. Consider citation of a recent paper on prehabilitation and parts on ageing and sarcopenia are relevant to enhance discussion - Mohan R, et al. Prehabilitation in elderly patients scheduled for liver resection and protocol for Recovery Of Surgery in Elderly. Hepatoma Res 2020;6:13. http://dx.doi.org/10.20517/2394-5079.2019.53. This discussion should be in second paragraph as such.\n\n8. Third paragraph which includes 'interventional procedure - early endoscopy'. This paragraph you need to cite a recent paper on WSES guidelines. It is essential to enhance discussion. As you have rightly pointed, timing of endoscopy determines outcomes. Consider adding the citation - Tarasconi A, Coccolini F, Biffl WL, et al. Perforated and bleeding peptic ulcer: WSES guidelines. World J Emerg Surg. 2020;15:3. Published 2020 Jan 7. doi:10.1186/s13017-019-0283-9.\n\n9. Agree that renal dysfunction is associated with poor outcomes in patients with perforated and bleeding ulcer. Please include that this in general is poor prognosticator for many diseases and pathologies. In particular bleeding leads to acute on chronic kidney injury and hence drives poor outcomes. Consider citation of - Chung KT, Shelat VG. Perforated peptic ulcer - an update. World J Gastrointest Surg. 2017;9(1):1‐12. doi:10.4240/wjgs.v9.i1.1.\n\n10. You are right. Low dose of omeprazole doesn't help with ulcer prevention. Further, if patient develops ulcer despite PPI, they tend to be recalcitrant. Good point.\n\n11. You discuss mortality and ulcer hemostasis: I have 3 comments and querries:\nA. What is your local strategy for hemostasis based on Forrest classification. Do you do hemostasis for Forrest 2b and 2c lesions? Do you dislodge the clot? Please state this in protocol / methods.\nB. Once hemostasis is done, do you perform routine endoscopy to check? Do you perform routine endoscopy or reserve endoscopy 'on demand'? i.e. only do when there is rebleeding. Please clarify this aspect in method section and consider citation of - Ho, M.L., Ahmed, S. \u0026 Shelat, V.G. Outcomes of Salvage Emergency Surgery for Bleeding Peptic Ulcer. Indian J Surg (2020). https://doi.org/10.1007/s12262-020-02358-w.\nC. What are your indications for surgery or angioembolization? Include a brief 1-2 statement in method section.\n\n12. In the method section also add the rationale for considering gastric and duodenal ulcers togather. I agree. We treat them both the same way i.e. ppi, endoscopy etc and do H Pylori eradication for both. Hence for clinical reasons, they both can be grouped togather. This is clarified in citation - Anbalakan K, Chua D, Pandya GJ, Shelat VG. Five year experience in management of perforated peptic ulcer and validation of common mortality risk prediction models - are existing models sufficient? A retrospective cohort study. Int J Surg. 2015;14:38‐44. doi:10.1016/j.ijsu.2014.12.022. Add this.\n\n13. Also, this is acute presentation, but there could be some role of in hospital rebabilitation or prehabilitation for selected elderly patients. COnsider adding this in discussion - Mohan R, et al. Prehabilitation in elderly patients scheduled for liver resection and protocol for Recovery Of Surgery in Elderly. Hepatoma Res 2020;6:13. http://dx.doi.org/10.20517/2394-5079.2019.53\n\n14. You also need to add socio-cultural diversity and health infrastructure in hospital - These determines the discharge destination.\n\n15. lastly you need to explain why Forrest 2b predicts mortality but not Forrest 1 and Forrest 2a lesions which are theoretically more severe? Please formulate some logical reasoning and explain in discussion. \n\nThanks* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **none**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. 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