Undocumented Safety Signals of Imatinib: Pharmacovigilance Insights from the FDA Adverse Event Reporting System (FAERS) and Implications for Clinical Practice

Undocumented Safety Signals of Imatinib: Pharmacovigilance Insights from the FDA Adverse Event Reporting System (FAERS) and Implications for Clinical Practice | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Undocumented Safety Signals of Imatinib: Pharmacovigilance Insights from the FDA Adverse Event Reporting System (FAERS) and Implications for Clinical Practice Tianqin Xia, Bo Shu, Yuan Peng, Baiqiang Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6289043/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Aims To evaluate the safety profile of Imatinib using the FAERS database, identifying both documented and undocumented adverse events. Methods FAERS data Q1 2004 to Q1 2024 were analyzed via disproportionality analysis (ROR, PRR, BCPNN, EBGM) to quantify drug-AE associations. Results A total of 56,364 patients (170,659 AE occurrences) were included. Imatinib exhibited expected AEs (e.g., nausea, diarrhea) consistent with labels, alongside novel signals such as pubertal failure (ROR = 452.74), large intestine fibroma (ROR = 431.18), ototoxicity, and pregnancy complications. Severe outcomes comprised 84.24% of reports (34.44% death), with 38.08% of AEs occurring > 360 days post-treatment. Malignant neoplasm progression showed strong association (ROR = 8.33). Conclusions The study reveals undocumented safety risks of Imatinib, highlighting the need for long-term monitoring of rare and insidious toxicities. Limitations of spontaneous reporting systems were acknowledged. Imatinib FAERS disproportionality analysis pharmacovigilance malignant neoplasm progression Figures Figure 1 Figure 2 Figure 3 Introduction In 2001, imatinib, the first kinase inhibitor, was approved by the U.S. Food and Drug Administration (FDA)( 1 ). Imatinib inhibits the Abelson (ABL) tyrosine kinase, which is expressed as a dysregulated fusion protein, BCR-ABL, in nearly all chronic myeloid leukemia (CML) cases( 2 ). This oncogenic fusion protein arises from a chromosomal rearrangement that juxtaposes the breakpoint cluster region protein (BCR) gene with the Abelson (ABL) gene, forming the Philadelphia chromosome. The phase 3 International Randomized Study of Interferon and STI571 (IRIS) demonstrated superior efficacy and tolerability of imatinib (400 mg once daily) compared to interferon alfa plus cytarabine in newly diagnosed chronic-phase chronic myeloid leukemia (CML). At the 18-month follow-up, the imatinib arm achieved a significantly higher complete cytogenetic response rate (0% Philadelphia chromosome-positive metaphases: 76.2% (95% CI, 72.5–79.9) vs. 14.5% (95% CI, 10.5–18.5); P < 0.001) and a greater probability of freedom from disease progression to accelerated phase or blast crisis (96.7% vs. 91.5%; P < 0.001). These results established imatinib as a first-line therapy with enhanced therapeutic activity and reduced toxicity in early CML management( 3 ). Imatinib has fundamentally transformed the treatment of chronic myeloid leukemia (CML), resulting in significant improvements in patient prognosis( 4 ). In the United States, the age-adjusted annual mortality rate for CML patients decreased from 0.9 per 100,000 individuals in 1996 to 0.4 per 100,000 in 2006( 5 ). Similar trends of reduced mortality have been observed in CML patients across other global regions( 6 , 7 ). Although imatinib has undoubtedly provided substantial benefits for many cancer patients, these agents are not curative. Most merely delay tumor progression, as advanced malignancies develop escape pathways to evade targeted inhibition, leading to adverse effects and drug resistance. Thus, investigating and analyzing the real-world safety profile of imatinib remains critically important. The FDA Adverse Event Reporting System (FAERS), a prototypical public spontaneous reporting system, collates post-marketing safety reports and clinical study data related to FDA-approved drugs and therapeutic biologics, both within and outside the United States. It has been extensively employed for pharmacovigilance signal detection( 8 ). Our study leveraged comprehensive disproportionality analyses of imatinib-associated adverse events (AEs) extracted from FAERS data. By rigorously evaluating signal strengths within real-world evidence, this approach provides a robust framework for assessing the efficacy and safety of imatinib therapy, facilitating effective AE detection and management. Through this analysis, our research aims to elucidate imatinib’s safety profile and contribute evidence on its adverse events. This endeavor not only advances our understanding of imatinib-related risks but also underscores the necessity of continuous post-marketing drug safety surveillance. Ultimately, this pharmacovigilance study seeks to inform clinical practice, guide therapeutic decision-making, and enhance patient safety. Methodology Study design and data sources This study analyzed adverse events (AEs) associated with imatinib using data from the FDA Adverse Event Reporting System (FAERS). The raw data spanned 84 quarters (Q1 2004 to Q4 2024), encompassing 18,613,992 background patients (55,357,463 AE occurrences), with 56,364 patients (170,659 AE occurrences) specifically linked to imatinib. To address inherent limitations of spontaneous reporting systems, such as duplicate or withdrawn reports, rigorous data cleaning was performed following FDA guidelines. Duplicate reports were removed by sorting the DEMO table fields (PRIMARYID, CASEID, FDA_DT) and retaining the entry with the highest FDA_DT for identical CASEIDs; if CASEID and FDA_DT matched, the entry with the largest PRIMARYID was retained. Post-2019 quarterly deletion lists were further utilized to exclude invalid reports.Statistical methods were applied to identify adverse drug reactions (ADRs). AEs related to imatinib were categorized into preferred terms (PTs) and system organ classes (SOCs) based on the hierarchical structure of the Medical Dictionary for Regulatory Activities (MedDRA). The data screening workflow is illustrated in Fig. 1 . Statistical analysis A disproportionality analysis was conducted to identify potential drug-adverse event (AE) associations in pharmacovigilance. Four algorithms were applied: the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN)( 9 , 10 ), and multi-item gamma Poisson shrinker (MGPS). These methods compare the proportional reporting rates of AEs between imatinib and all other drugs( 11 ). Four algorithms were employed to quantify imatinib-associated AE signals, with their equations and decision criteria detailed in Supplementary Table 1 . Signal detection rules were applied at both the system organ class (SOC) and preferred term (PT) levels. A signal was flagged at the SOC level if at least one of the four indices met the predefined criteria, while PT-level signals required concurrent satisfaction of all four criteria( 12 , 13 ). Higher scores across these parameters generally indicated stronger disproportionality( 14 ). Statistical analyses were performed using SAS software (version 9.4), as recommended by the FDA. Raw ASCII data downloaded from the FDA website were imported into SAS, deduplicated following FDA-recommended protocols, and subsequently analyzed. Results General characteristics In the FAERS database, 56,364 patients were identified with 170,659 adverse events (AEs) attributed to imatinib, averaging 3.02 AEs per individual. Females accounted for 24,179 cases (42.9%), males 27,808 (49.34%), and 4,377 (7.77%) had unspecified gender. Age data were available for 28,962 patients (mean age = 59 ± 14 years). Patients aged < 18 years (n = 1,180, 2.09%), 18–44 years (n = 5,721, 10.15%), 45–64 years (n = 10,954, 19.43%), and ≥ 65 years (n = 11,107, 19.71%) comprised the cohorts. The highest reporting year was 2014 (n = 5,131, 9.10%). Most reports originated from consumers (39.98%), with the United States of America contributing the majority (n = 16,962, 30.09%). The primary indication was chronic myeloid leukemia (n = 25,664, 45.53%). Severe outcomes constituted 84.24% of reports, predominantly death (n = 19,409, 34.44%) and other serious outcomes (n = 24,861, 44.11%) (Table 1 ). AE occurrence time (excluding unspecified medication dates) peaked at 0–30 days (24.22%) and > 360 days (38.08%) (Fig. 2 ). Table 1 Characteristics of cases of Imatinib usage. Characteristics Number of events (%) Gender Female(%) 24179(42.90) Male(%) 27808(49.34) Not Specified(%) 4377( 7.77) Age <18(%) 1180( 2.09) 18–44(%) 5721(10.15) 45–64(%) 10954(19.43) 65≤(%) 11107(19.71) NotSpecified(%) 27402(48.62) Report year 2006(%) 624( 1.11) 2007(%) 683( 1.21) 2008(%) 658( 1.17) 2009(%) 671( 1.19) 2010(%) 707( 1.25) 2011(%) 1128( 2.00) 2012(%) 1678( 2.98) 2013(%) 3174( 5.63) 2014(%) 5131( 9.10) 2015(%) 3456( 6.13) 2016(%) 3402( 6.04) 2017(%) 3244( 5.76) 2018(%) 3602( 6.39) 2019(%) 3950( 7.01) 2020(%) 4153( 7.37) 2021(%) 4835( 8.58) 2022(%) 4174( 7.41) 2023(%) 3355( 5.95) 2024(%) 2847( 5.05) Reporter Consumer(%) 22532(39.98) Not Specified(%) 8( 0.01) Other health-professional(%) 4202( 7.46) Pharmacist(%) 7146(12.68) Physician(%) 6954(12.34) Reported countries(TOP ten) United States of America(%) 16962(30.09) Not Specified(%) 14162(25.13) India(%) 4315( 7.66) Japan(%) 2799( 4.97) France(%) 1618( 2.87) China(%) 1540( 2.73) United Kiongdom(%) 1200( 2.13) Germany(%) 1125( 2.00) Canada(%) 867( 1.54) Italy(%) 835( 1.48) Indications(TOP ten) Chronic myeloid leukaemia(%) 25664(45.53) Product used for unknown indication(%) 7978(14.15) Gastrointestinal stromal tumour(%) 7640(13.55) Not Specified(%) 7082(12.56) Acute lymphocytic leukaemia(%) 1866( 3.31) Leukaemia(%) 339( 0.60) Gastric cancer(%) 338( 0.60) Neoplasm malignant(%) 315( 0.56) Soft tissue sarcoma(%) 247( 0.44) Philadelphia positive chronic myeloid leukaemia(%) 230( 0.41) Serious report Serious(%) 47481(84.24) Non-Serious(%) 8883(15.76) Outcome Life-Threatening(%) 1233( 2.19) Hospitalization - Initial or Prolonged(%) 10187(18.07) Disability(%) 737( 1.31) Death(%) 19409(34.44) Congenital Anomaly(%) 90( 0.16) Required Intervention to Prevent Permanent Impairment/Damage(%) 65( 0.12) Other(%) 24861(44.11) Imatinib-associated AEs affected multiple organ systems The top four involved categories were general disorders and administration site conditions (40,355, 23.65%), gastrointestinal disorders (17,125, 10.03%), neoplasms benign/malignant/unspecified (15,433, 9.04%), and investigations (14,428, 8.45%) (Table 2 ). Table 2 Organ system-specific distribution of AEs associated with Imatinib. System Organ Class Number of events (%) General disorders and administration site conditions 40355(23.65) Gastrointestinal disorders 17125(10.03) Neoplasms benign, malignant and unspecified (incl cysts and polyps) 15433(9.04) Investigations 14428(8.45) Nervous system disorders 8402(4.92) Infections and infestations 8210(4.81) Respiratory, thoracic and mediastinal disorders 7705(4.51) Skin and subcutaneous tissue disorders 7302(4.28) Musculoskeletal and connective tissue disorders 7277(4.26) Blood and lymphatic system disorders 6997(4.10) Injury, poisoning and procedural complications 6353(3.72) Cardiac disorders 4724(2.77) Eye disorders 4255(2.49) Metabolism and nutrition disorders 3929(2.30) Renal and urinary disorders 3189(1.87) Vascular disorders 2707(1.59) Psychiatric disorders 2698(1.58) Surgical and medical procedures 2399(1.41) Hepatobiliary disorders 2246(1.32) Immune system disorders 1184(0.69) Pregnancy, puerperium and perinatal conditions 693(0.41) Ear and labyrinth disorders 690(0.40) Reproductive system and breast disorders 637(0.37) Congenital, familial and genetic disorders 581(0.34) Product issues 571(0.33) Endocrine disorders 407(0.24) Social circumstances 162(0.09) Disproportionality Analysis of Imatinib AEs Using the reporting odds ratio (ROR) method, the top 50 preferred terms (PTs) by signal frequency and strength were ranked (Fig. 3 ). The most frequent signals included: Death (n = 15,667; ROR (95% CI) = 7.34 (7.22–7.46)), Nausea (n = 3,000; ROR = 1.39 (1.34–1.44)), Diarrhoea (n = 2,532; ROR = 1.46 (1.40–1.52)), Malignant neoplasm progression (n = 2,177; ROR = 8.33 (7.98–8.69)) and Vomiting (n = 2,000; ROR = 1.57 (1.50–1.64)). The strongest signals (highest ROR) were: Blast crisis in myelogenous leukaemia (n = 762; ROR = 612.66 (542.99–691.27)), Pubertal failure (n = 7; ROR = 452.74 (143.69–1426.52)), Large intestine fibroma (n = 4; ROR = 431.18 (96.50–1926.58)), Slit-lamp tests abnormal (n = 5; ROR = 404.23 (108.55–1505.38)) and Chromosome analysis abnormal (n = 124; ROR = 326.24 (254.21–418.68)). A four-algorithm integrated analysis (Table 3 ) ranked the most frequent signals as: 1. Death (n = 15,667; ROR = 7.34 (7.22–7.46); PRR = 6.76; IC = 2.73; EBGM = 6.64). 2. Nausea (n = 3,000; ROR = 1.39 (1.34–1.44); PRR = 1.38; IC = 0.47; EBGM = 1.38). 3. Diarrhoea (n = 2,532; ROR = 1.46 (1.40–1.52); PRR = 1.45; IC = 0.54; EBGM = 1.45). 4. Drug ineffective (n = 2,436; ROR = 0.67 (0.64–0.69); PRR = 0.67; IC = -0.57; EBGM = 0.67). 5. Malignant neoplasm progression (n = 1,519; ROR = 8.33 (7.98–8.69); PRR = 8.23; IC = 3.01; EBGM = 8.05). By signal strength (ROR lower limit, Table 4 ), the top signals were: 1. Blast crisis in myelogenous leukaemia (ROR = 612.66 (542.99–691.27); PRR = 609.93; IC = 7.73; EBGM = 211.98). 2. Pubertal failure (ROR = 452.74 (143.69–1426.52); PRR = 452.72; IC = 7.56; EBGM = 189.22). 3. Large intestine fibroma (ROR = 431.18 (96.50–1926.58); PRR = 431.17; IC = 7.53; EBGM = 185.36). 4. Slit-lamp tests abnormal (ROR = 404.23 (108.55–1505.38); PRR = 404.22; IC = 7.49; EBGM = 180.21). 5. Chromosome analysis abnormal (ROR = 326.24 (254.21–418.68); PRR = 326.00; IC = 7.35; EBGM = 162.84). Table 3 The top 50 PTs with the highest signal frequency for Imatinib positivity in ROR、PRR、BCPNN and MGPS. Preferred Terms Case ROR(95% CI) PRR(Chi-Square) IC(IC-2SD) EBGM(EBGM05) Death 15667 7.34(7.22–7.46) 6.76(76349.7) 2.73(2.71) 6.64(6.53) Nausea 3000 1.39(1.34–1.44) 1.38(322.91) 0.47(0.41) 1.38(1.33) Diarrhoea 2532 1.46(1.40–1.52) 1.45(359.28) 0.54(0.48) 1.45(1.39) Drug ineffective 2436 0.67(0.64–0.69) 0.67(401.06) -0.57(-0.63) 0.67(0.65) Malignant neoplasm progression 2177 8.33(7.98–8.69) 8.23(13510.6) 3.01(2.94) 8.05(7.72) Fatigue 2069 0.97(0.93–1.01) 0.97(1.68) -0.04(-0.10) 0.97(0.93) Vomiting 2000 1.57(1.50–1.64) 1.56(408.76) 0.64(0.58) 1.56(1.49) Rash 1691 1.37(1.30–1.44) 1.36(165.40) 0.45(0.38) 1.36(1.30) Anaemia 1565 2.96(2.81–3.11) 2.94(1991.60) 1.55(1.47) 2.92(2.78) Pyrexia 1541 1.61(1.53–1.69) 1.61(352.04) 0.68(0.61) 1.60(1.52) Dyspnoea 1479 0.94(0.90–0.99) 0.94(4.93) -0.08(-0.16) 0.94(0.90) Malaise 1434 1.16(1.10–1.22) 1.16(31.61) 0.21(0.14) 1.16(1.10) Muscle spasms 1327 2.59(2.46–2.74) 2.58(1278.40) 1.36(1.28) 2.57(2.43) Chronic myeloid leukaemia 1321 148.19(138.83-158.18) 147.05(131731) 6.66(6.47) 101.40(94.99) Drug resistance 1262 19.26(18.19–20.39) 19.12(20472.1) 4.18(4.08) 18.11(17.11) Gastrointestinal stromal tumour 1214 296.39(274.18–320.40) 294.29(185784) 7.27(7.00) 154.55(142.97) Drug intolerance 1174 4.75(4.48–5.03) 4.72(3401.40) 2.22(2.13) 4.67(4.41) Pneumonia 1149 1.23(1.16–1.30) 1.23(47.72) 0.29(0.21) 1.22(1.16) Asthenia 1125 1.08(1.02–1.14) 1.08(6.36) 0.11(0.02) 1.08(1.02) Haemoglobin decreased 1013 3.53(3.32–3.75) 3.51(1805.31) 1.80(1.71) 3.49(3.28) Pleural effusion 965 5.73(5.37–6.10) 5.70(3677.19) 2.49(2.39) 5.62(5.27) Pain 944 0.55(0.51–0.58) 0.55(355.89) -0.87(-0.96) 0.55(0.51) Oedema peripheral 934 2.69(2.52–2.87) 2.68(980.65) 1.42(1.32) 2.67(2.50) Neoplasm malignant 930 5.18(4.86–5.53) 5.16(3072.46) 2.35(2.25) 5.09(4.77) Headache 924 0.53(0.50–0.56) 0.53(385.72) -0.91(-1.01) 0.53(0.50) Second primary malignancy 909 43.58(40.66–46.71) 43.36(33170.8) 5.26(5.10) 38.35(35.78) Abdominal pain 885 1.39(1.30–1.48) 1.39(95.58) 0.47(0.37) 1.39(1.30) Thrombocytopenia 858 2.83(2.65–3.03) 2.82(1003.82) 1.49(1.39) 2.81(2.63) Arthralgia 831 0.74(0.69–0.79) 0.74(77.10) -0.44(-0.54) 0.74(0.69) Disease progression 830 2.59(2.42–2.77) 2.58(800.54) 1.36(1.26) 2.57(2.40) Platelet count decreased 819 2.79(2.60–2.99) 2.78(927.87) 1.47(1.36) 2.77(2.58) Oedema 804 5.46(5.09–5.86) 5.44(2869.84) 2.42(2.31) 5.37(5.01) Blast crisis in myelogenous leukaemia 762 612.66(542.99-691.27) 609.93(160510) 7.73(7.24) 211.98(187.88) White blood cell count increased 743 6.91(6.42–7.43) 6.88(3659.59) 2.76(2.64) 6.76(6.28) Decreased appetite 741 1.11(1.03–1.19) 1.11(7.82) 0.15(0.04) 1.11(1.03) Dizziness 697 0.50(0.47–0.54) 0.50(341.79) -0.99(-1.09) 0.51(0.47) Therapy non-responder 686 4.62(4.28–4.98) 4.60(1909.14) 2.19(2.07) 4.55(4.22) Pain in extremity 685 0.82(0.76–0.89) 0.82(25.98) -0.28(-0.39) 0.82(0.76) Myalgia 679 1.44(1.33–1.55) 1.44(90.11) 0.52(0.41) 1.44(1.33) White blood cell count decreased 673 2.24(2.08–2.42) 2.23(456.91) 1.15(1.04) 2.23(2.06) Fluid retention 667 0.72(0.67–0.78) 0.72(70.40) -0.46(-0.58) 0.72(0.67) Fall 667 4.75(4.40–5.13) 4.74(1939.50) 2.23(2.11) 4.68(4.34) Pruritus 642 0.61(0.57–0.66) 0.62(155.02) -0.70(-0.81) 0.62(0.57) Weight decreased 638 0.82(0.76–0.89) 0.82(24.03) -0.28(-0.39) 0.82(0.76) Abdominal pain upper 629 1.12(1.04–1.22) 1.12(8.47) 0.17(0.05) 1.12(1.04) Pancytopenia 609 4.04(3.73–4.37) 4.03(1369.33) 2.00(1.87) 3.99(3.68) Neutropenia 608 1.66(1.53–1.79) 1.65(156.91) 0.72(0.60) 1.65(1.52) Cough 575 0.75(0.70–0.82) 0.76(45.64) -0.40(-0.52) 0.76(0.70) Abdominal discomfort 561 1.20(1.10–1.30) 1.20(18.60) 0.26(0.14) 1.20(1.10) Sepsis 559 1.81(1.67–1.97) 1.81(200.97) 0.85(0.73) 1.80(1.66) Table 4 The top 50 PTs with the highest signal intensity for Imatinib positivity in ROR、PRR、BCPNN and MGPS. Preferred Terms Case ROR(95% CI) PRR(Chi-Square) IC(IC-2SD) EBGM(EBGM05) Blast crisis in myelogenous leukaemia 762 612.66(542.99-691.27) 609.93(160510) 7.73(7.24) 211.98(187.88) Pubertal failure 7 452.74(143.69-1426.52) 452.72(1314.62) 7.56(1.65) 189.22(60.05) Large intestine fibroma 4 431.18(96.50-1926.58) 431.17(735.72) 7.53(0.64) 185.36(41.48) Slit-lamp tests abnormal 5 404.23(108.55-1505.38) 404.22(893.82) 7.49(1.05) 180.21(48.39) Chromosome analysis abnormal 124 326.24(254.21-418.68) 326.00(20007.2) 7.35(5.83) 162.84(126.89) Gastrointestinal stromal tumour 1214 296.39(274.18–320.40) 294.29(185784) 7.27(7.00) 154.55(142.97) Chronic myeloid leukaemia (in remission) 9 291.05(118.27-716.28) 291.04(1369.14) 7.26(2.12) 153.65(62.43) Cytogenetic analysis abnormal 444 274.19(241.62-311.16) 273.48(65309.1) 7.22(6.64) 148.63(130.97) Chronic myeloid leukaemia transformation 183 270.51(222.28–329.20) 270.22(26740.2) 7.21(6.10) 147.66(121.34) Chordoma 42 266.37(177.06-400.75) 266.31(6087.72) 7.19(4.53) 146.49(97.37) Chronic eosinophilic leukaemia 9 264.59(109.64-638.53) 264.58(1299.79) 7.19(2.12) 145.97(60.49) Cytogenetic response 4 258.71(69.47-963.44) 258.70(570.45) 7.17(0.70) 144.17(38.71) Philadelphia chromosome negative 4 258.71(69.47-963.44) 258.70(570.45) 7.17(0.70) 144.17(38.71) C-kit gene mutation 7 251.52(93.67-675.39) 251.51(982.48) 7.15(1.69) 141.91(52.85) Philadelphia chromosome positive 210 202.96(170.79-241.19) 202.71(25909.4) 6.97(6.06) 124.99(105.18) Blood thrombin 3 194.03(46.37-811.91) 194.02(360.06) 6.93(0.23) 121.64(29.07) Chronic myeloid leukaemia recurrent 180 186.76(155.45-224.38) 186.56(21067.9) 6.89(5.92) 118.67(98.78) Acute aortic syndrome 4 184.79(54.09-631.26) 184.79(465.29) 6.88(0.73) 117.95(34.53) Erythrocyanosis 5 179.66(60.21-536.09) 179.65(571.04) 6.86(1.13) 115.85(38.82) Gene mutation identification test positive 134 168.74(136.93-207.94) 168.61(14674.9) 6.80(5.65) 111.17(90.21) Chronic myeloid leukaemia 1321 148.19(138.83-158.18) 147.05(131731) 6.66(6.47) 101.40(94.99) Necrotising panniculitis 15 147.00(79.84-270.64) 146.99(1495.27) 6.66(2.97) 101.37(55.06) Oral pigmentation 21 115.11(69.96-189.42) 115.10(1751.77) 6.41(3.44) 85.15(51.75) Gelatinous transformation of the bone marrow 5 107.79(39.18–296.60) 107.79(396.75) 6.34(1.16) 81.09(29.47) Wallerian degeneration 4 107.79(34.76-334.23) 107.79(317.40) 6.34(0.78) 81.09(26.15) Polymerase chain reaction positive 72 102.61(78.71-133.77) 102.57(5497.84) 6.29(4.87) 78.11(59.92) Loss of CAR T-cell persistence 5 95.11(35.09-257.81) 95.11(359.78) 6.20(1.16) 73.72(27.20) Ankle brachial index decreased 5 95.11(35.09-257.81) 95.11(359.78) 6.20(1.16) 73.72(27.20) Transdifferentiation of neoplasm 11 91.21(46.71–178.10) 91.21(765.50) 6.16(2.45) 71.36(36.55) Heavy chain disease 5 89.83(33.35-241.95) 89.83(343.71) 6.14(1.16) 70.52(26.18) Blast cell crisis 66 89.33(68.02-117.33) 89.30(4515.59) 6.13(4.72) 70.19(53.45) Lymphoblast count increased 3 88.19(24.60-316.14) 88.19(203.20) 6.12(0.31) 69.51(19.39) HCoV-HKU1 infection 4 86.24(28.62-259.83) 86.23(266.04) 6.09(0.79) 68.29(22.66) Trisomy 8 13 84.08(45.68-154.78) 84.08(846.95) 6.06(2.70) 66.93(36.36) Clear cell sarcoma of soft tissue 4 80.85(27.03-241.83) 80.84(252.34) 6.02(0.80) 64.87(21.69) Pulse waveform abnormal 5 77.00(29.03–204.20) 76.99(302.91) 5.96(1.17) 62.38(23.52) Gastric antral vascular ectasia 83 76.72(60.39–97.47) 76.69(5011.60) 5.96(4.82) 62.18(48.94) Tyrosine kinase mutation 4 76.09(25.60-226.14) 76.09(239.95) 5.95(0.80) 61.79(20.79) Sarcomatosis 3 74.63(21.27-261.89) 74.62(177.06) 5.93(0.32) 60.82(17.33) Clonal evolution 18 71.87(43.12-119.77) 71.86(1029.07) 5.88(3.14) 58.98(35.39) Oncologic complication 159 70.89(59.70-84.16) 70.82(8978.67) 5.86(5.17) 58.28(49.08) Vulval cancer stage III 3 69.30(19.91-241.14) 69.29(166.29) 5.84(0.33) 57.24(16.45) Right ventricular diastolic collapse 7 68.60(30.35-155.07) 68.59(384.67) 5.83(1.71) 56.77(25.11) Polymerase chain reaction 19 67.53(41.19-110.71) 67.52(1030.06) 5.81(3.20) 56.03(34.17) Oligoasthenozoospermia 3 64.68(18.72-223.41) 64.67(156.73) 5.76(0.33) 54.06(15.65) Carotid intima-media thickness increased 6 62.59(26.11-150.03) 62.59(304.66) 5.72(1.46) 52.60(21.95) Allogenic bone marrow transplantation therapy 8 57.49(27.10-121.96) 57.49(377.02) 5.61(1.91) 48.96(23.08) Bone marrow necrosis 31 55.09(37.64–80.63) 55.08(1406.49) 5.56(3.72) 47.21(32.26) Myelocytosis 11 54.73(28.89-103.69) 54.72(496.20) 5.55(2.38) 46.95(24.78) Leukaemic infiltration 16 52.80(31.13–89.57) 52.80(698.93) 5.51(2.90) 45.53(26.84) Discussion This study represents the first comprehensive and systematic pharmacovigilance investigation utilizing the FDA Adverse Event Reporting System (FAERS) database to analyze post-marketing AEs associated with imatinib. The primary objective was to meticulously characterize, describe, and analyze imatinib-related AEs reported to date. The findings presented herein provide valuable and accurate insights into the safety profile of imatinib in real-world clinical settings. This study revealed that AEs associated with imatinib occurred slightly more frequently in males (49.34%) than females (42.9%), aligning with epidemiological trends( 15 ). The majority of affected patients (39.14%) were aged ≥ 45 years, reflecting the predominant demographic of CML and GIST populations( 16 ). Consumers submitted 39.98% of reports, consistent with the spontaneous reporting nature of the FAERS database( 17 ). Severe AEs accounted for 84.24% of imatinib-related reports, likely attributable to its mechanism as a multi-target Abl kinase inhibitor, which modulates critical biological pathways( 18 , 19 ). The high mortality rate (34.44% of outcomes) may stem from life-threatening complications such as tumor progression or organ failure. Notably, 38.08% of AEs occurred > 360 days post-treatment, underscoring the necessity for long-term safety monitoring.At the SOC level, the most frequent categories included General disorders and administration site conditions, Gastrointestinal disorders, and Neoplasms benign, consistent with labeled safety profiles. Common PTs such as nausea, diarrhea, vomiting, and malignant neoplasm progression were frequently reported, corroborating clinical trial findings( 20 , 21 ). While most AEs in our analysis were largely consistent with safety data from drug labeling and clinical trials, we identified previously unreported significant AE signals not explicitly documented in regulatory trials. These included new-onset benign tumors (e.g., lipomas, fibromas) or neoplasms of uncertain behavior. The FDA labeling for imatinib primarily focuses on its therapeutic efficacy against existing malignancies (e.g., GIST, CML) and known complications (e.g., tumor hemorrhage), but does not explicitly address the potential induction of or association with new benign or unclassified neoplasms during treatment( 22 ).The insidious toxicities associated with long-term medication require particular attention, such as sciatica, joint ankylosis, and even ischemic necrosis of the femoral head observed in the musculoskeletal system, while the FDA label merely mentions "musculoskeletal pain" without specifying severity or chronic consequences( 23 ). Severe dermatological reactions like exfoliative dermatitis and acute generalized exanthematous pustulosis are inadequately characterized in product labeling despite documented progression risks in clinical cases( 24 , 25 ). We advocate for enhanced long-term monitoring, particularly targeting musculoskeletal toxicity, metabolic syndrome, and other insidious risks, with recommendations including regular bone density assessments and systematic skin reaction evaluations. This call emphasizes the necessity to bridge labeling-practice discrepancies through proactive surveillance mechanisms. Under the SOC "Investigations," PTs encompassed non-specific enzymatic elevations (e.g., alkaline phosphatase (ALP), lactate dehydrogenase ( 26 )) or structural organ changes identified via imaging. While the FDA label lists abnormal liver function as a monitoring parameter, it does not classify "investigation abnormalities" as standalone adverse reactions, potentially underestimating their impact on clinical decision-making( 27 , 28 ). For the SOC "Pregnancy, Puerperium, and Perinatal Conditions," cases accounted for 0.41% of reports, yet the ROR method detected 13 positive signals (1.07%). Specific PTs included fetal developmental anomalies and gestational complications (e.g., miscarriage, preterm delivery). The FDA currently warns only of "embryo-fetal toxicity" and recommends contraception but lacks explicit risk data on imatinib use during pregnancy( 29 , 30 ). This underscores the need for enhanced monitoring of pregnancy-exposed patients and research into imatinib’s potential effects on placental function or fetal organogenesis. Within the psychiatric disorders (SOC), "psychiatric symptoms" accounted for 1.58% of reports, with specific PTs including depression, anxiety, and cognitive impairment. Notably, the FDA-approved label for imatinib does not list psychiatric symptoms as common or severe adverse reactions, only mentioning that impaired driving ability may be associated with fatigue( 31 , 32 ). Further investigation is warranted to determine whether imatinib crosses the blood-brain barrier to directly alter neurotransmitter activity or synergizes with the psychological burden inherent to chronic illness. The FDA-approved label for imatinib does not currently acknowledge ototoxicity-related risks. However, our study identified signals in the Ear and Labyrinth Disorders System Organ Class (SOC), including preferred terms (PTs) such as tinnitus, hearing impairment, and vestibular dysfunction( 33 ). This finding underscores the need for proactive monitoring of vestibular function in patients undergoing long-term imatinib therapy, particularly among elderly individuals or those with comorbid renal impairment. This study leverages the inherent advantages of large-scale real-world investigations and sophisticated data mining techniques. However, several limitations necessitate careful consideration. The FAERS database, as a spontaneous reporting system, may introduce analytical biases due to incomplete or inaccurate data collection across countries and healthcare professionals, including reporting bias and indication bias, with challenges in distinguishing adverse events caused by the drug versus disease progression. Additionally, adverse events with extremely low incidence rates associated with imatinib might lack statistical significance in disproportionality analyses, potentially leaving undetected safety signals. The specificity of attributing adverse events to imatinib is further limited by confounding from concomitant medications. Finally, while disproportionality analysis identifies statistical significance based on signal strength, it cannot fully eliminate confounding effects from polypharmacy. Conclusion This study conducted a real-world pharmacovigilance analysis of Imatinib using the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis (ROR, PRR, BCPNN, EBGM) was applied to evaluate adverse events (AEs) from 2004 to 2024. Results confirmed expected AEs (e.g., nausea, diarrhea) aligned with drug labels, while identifying undocumented signals such as pubertal failure (ROR = 452.74), large intestine fibroma (ROR = 431.18), ototoxicity, and pregnancy complications. Severe outcomes accounted for 84.24% of reports (34.44% death), with 38.08% of AEs occurring > 360 days post-medication. The study underscores the need for vigilant monitoring of long-term toxicities (e.g., bone metabolism disorders, psychiatric effects) and rare AEs to enhance patient safety. Declarations Data availability statement The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author. Ethics statement There are no ethical issues involved in this study Author contributions Tianqin Xia contributed to the design of the study protocol. Bo Shu performed the statistical analysis. Yuan Peng drew the picture. Baiqiang Wang contributed to the writing of the study protocol and made the final corrections to this manuscript. Tianqin Xia finally corrected the manuscript. All authors read and approved the final manuscript. Funding No Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher’s note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. 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Pye SM, Cortes J, Ault P, Hatfield A, Kantarjian H, Pilot R, et al. The effects of imatinib on pregnancy outcome. Blood. 2008;111(12):5505-8. Robertson HF, Milojkovic D, Butt N, Byrne J, Claudiani S, Copland M, et al. Expectations and outcomes of varying treatment strategies for CML presenting during pregnancy. British Journal of Haematology. 2024;205(3):947-55. Tian XF, Wang CT, Yu BA, Fan YX, Zhang L, Zhang X. 9.4 T static magnetic field ameliorates imatinib mesylate-induced toxicity and depression in mice. European Journal of Nuclear Medicine and Molecular Imaging. 2023;50(2):314-27. Phillips KM, Pinilla-Ibarz J, Sotomayor E, Lee MR, Jim HSL, Small BJ, et al. Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison. Supportive Care in Cancer. 2013;21(4):1097-103. Lin HW, Roberts DS, Kay J, Stankovic KM. Sensorineural Hearing Loss following Imatinib (Gleevec) Administration. Otolaryngology-Head and Neck Surgery. 2012;146(2):335-7. Additional Declarations No competing interests reported. Supplementary Files SupplementTable1.doc Supplement Table1. Calculation table Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 30 Apr, 2025 Reviews received at journal 24 Apr, 2025 Reviews received at journal 02 Apr, 2025 Reviewers agreed at journal 27 Mar, 2025 Reviewers agreed at journal 27 Mar, 2025 Reviewers invited by journal 27 Mar, 2025 Editor assigned by journal 26 Mar, 2025 Submission checks completed at journal 26 Mar, 2025 First submitted to journal 23 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6289043","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":439016563,"identity":"a992d0b5-d48d-4dc9-891f-232c5eb54da6","order_by":0,"name":"Tianqin Xia","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Tianqin","middleName":"","lastName":"Xia","suffix":""},{"id":439016564,"identity":"bf48718b-e51d-476c-89f2-a9d35fc64377","order_by":1,"name":"Bo Shu","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Shu","suffix":""},{"id":439016565,"identity":"3e3ed7dd-3f28-4840-a4d6-597970486371","order_by":2,"name":"Yuan Peng","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Peng","suffix":""},{"id":439016566,"identity":"a2ef4361-9fa2-4124-9bac-3c0a0633d1e1","order_by":3,"name":"Baiqiang Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsElEQVRIiWNgGAWjYBACeWbmAwc+GNjU9xOtxbCdLfHgjII0xpkNROs5z6N8mOfDYcYNB4jVwdjMw3BwhkEas/Hx5A0MPyq2EdbCzswL9gub2ZlnBYw9Z24TYwtfAsgWHrMbOQbMjG1EaGE4zGMAQhLGM0jVYmAgQawWw2Y2sMMSJIB+OUiUX+T5Dx/+8OGPTQJ/e/LGBz8qiHEYAiQYHCBJPVgLqTpGwSgYBaNghAAA+7hA9odeqfYAAAAASUVORK5CYII=","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":true,"prefix":"","firstName":"Baiqiang","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-03-23 15:08:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6289043/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6289043/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80710067,"identity":"060bea7b-2026-43fe-b267-60edba4751f1","added_by":"auto","created_at":"2025-04-16 08:58:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":176548,"visible":true,"origin":"","legend":"\u003cp\u003eMultistep process of data extraction, processing, and analysis from the Food and Drug Administration adverse event reporting system database.\u003c/p\u003e","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6289043/v1/31e9784a6551105cfabc9367.png"},{"id":80710066,"identity":"f9e87cbc-62d5-4b71-9f16-7e00f5bd8a66","added_by":"auto","created_at":"2025-04-16 08:58:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":31446,"visible":true,"origin":"","legend":"\u003cp\u003eTime to event report distribution of AE reports.\u003c/p\u003e","description":"","filename":"fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6289043/v1/4632539b5adb65843f91b521.png"},{"id":80711248,"identity":"10ae8daa-b1a1-4248-94a7-99d4e65ba125","added_by":"auto","created_at":"2025-04-16 09:06:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":534675,"visible":true,"origin":"","legend":"\u003cp\u003eThe top 50 PT results for Imatinib positivity in ROR. (A)The highest signal frequency. (B) The highest signal intensity.\u003c/p\u003e","description":"","filename":"fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-6289043/v1/25c0a216de80abb768ee6660.png"},{"id":80712301,"identity":"86fc976d-b94c-46c4-9aaa-cc20af54eadb","added_by":"auto","created_at":"2025-04-16 09:14:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1936134,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6289043/v1/0342a8ac-593e-47e0-b4fd-eb1d6c0e064b.pdf"},{"id":80710071,"identity":"55182f63-e98a-4c92-96a5-00d1e0a66d52","added_by":"auto","created_at":"2025-04-16 08:58:22","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":100864,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplement Table1\u003c/strong\u003e. Calculation table\u003c/p\u003e","description":"","filename":"SupplementTable1.doc","url":"https://assets-eu.researchsquare.com/files/rs-6289043/v1/4945e89570ed02976d61437c.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Undocumented Safety Signals of Imatinib: Pharmacovigilance Insights from the FDA Adverse Event Reporting System (FAERS) and Implications for Clinical Practice","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn 2001, imatinib, the first kinase inhibitor, was approved by the U.S. Food and Drug Administration (FDA)(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Imatinib inhibits the Abelson (ABL) tyrosine kinase, which is expressed as a dysregulated fusion protein, BCR-ABL, in nearly all chronic myeloid leukemia (CML) cases(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This oncogenic fusion protein arises from a chromosomal rearrangement that juxtaposes the breakpoint cluster region protein (BCR) gene with the Abelson (ABL) gene, forming the Philadelphia chromosome.\u003c/p\u003e \u003cp\u003eThe phase 3 International Randomized Study of Interferon and STI571 (IRIS) demonstrated superior efficacy and tolerability of imatinib (400 mg once daily) compared to interferon alfa plus cytarabine in newly diagnosed chronic-phase chronic myeloid leukemia (CML). At the 18-month follow-up, the imatinib arm achieved a significantly higher complete cytogenetic response rate (0% Philadelphia chromosome-positive metaphases: 76.2% (95% CI, 72.5\u0026ndash;79.9) vs. 14.5% (95% CI, 10.5\u0026ndash;18.5); \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a greater probability of freedom from disease progression to accelerated phase or blast crisis (96.7% vs. 91.5%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These results established imatinib as a first-line therapy with enhanced therapeutic activity and reduced toxicity in early CML management(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eImatinib has fundamentally transformed the treatment of chronic myeloid leukemia (CML), resulting in significant improvements in patient prognosis(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In the United States, the age-adjusted annual mortality rate for CML patients decreased from 0.9 per 100,000 individuals in 1996 to 0.4 per 100,000 in 2006(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Similar trends of reduced mortality have been observed in CML patients across other global regions(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough imatinib has undoubtedly provided substantial benefits for many cancer patients, these agents are not curative. Most merely delay tumor progression, as advanced malignancies develop escape pathways to evade targeted inhibition, leading to adverse effects and drug resistance. Thus, investigating and analyzing the real-world safety profile of imatinib remains critically important.\u003c/p\u003e \u003cp\u003eThe FDA Adverse Event Reporting System (FAERS), a prototypical public spontaneous reporting system, collates post-marketing safety reports and clinical study data related to FDA-approved drugs and therapeutic biologics, both within and outside the United States. It has been extensively employed for pharmacovigilance signal detection(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Our study leveraged comprehensive disproportionality analyses of imatinib-associated adverse events (AEs) extracted from FAERS data. By rigorously evaluating signal strengths within real-world evidence, this approach provides a robust framework for assessing the efficacy and safety of imatinib therapy, facilitating effective AE detection and management. Through this analysis, our research aims to elucidate imatinib\u0026rsquo;s safety profile and contribute evidence on its adverse events. This endeavor not only advances our understanding of imatinib-related risks but also underscores the necessity of continuous post-marketing drug safety surveillance. Ultimately, this pharmacovigilance study seeks to inform clinical practice, guide therapeutic decision-making, and enhance patient safety.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and data sources\u003c/h2\u003e \u003cp\u003eThis study analyzed adverse events (AEs) associated with imatinib using data from the FDA Adverse Event Reporting System (FAERS). The raw data spanned 84 quarters (Q1 2004 to Q4 2024), encompassing 18,613,992 background patients (55,357,463 AE occurrences), with 56,364 patients (170,659 AE occurrences) specifically linked to imatinib. To address inherent limitations of spontaneous reporting systems, such as duplicate or withdrawn reports, rigorous data cleaning was performed following FDA guidelines. Duplicate reports were removed by sorting the DEMO table fields (PRIMARYID, CASEID, FDA_DT) and retaining the entry with the highest FDA_DT for identical CASEIDs; if CASEID and FDA_DT matched, the entry with the largest PRIMARYID was retained. Post-2019 quarterly deletion lists were further utilized to exclude invalid reports.Statistical methods were applied to identify adverse drug reactions (ADRs). AEs related to imatinib were categorized into preferred terms (PTs) and system organ classes (SOCs) based on the hierarchical structure of the Medical Dictionary for Regulatory Activities (MedDRA). The data screening workflow is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eA disproportionality analysis was conducted to identify potential drug-adverse event (AE) associations in pharmacovigilance. Four algorithms were applied: the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN)(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), and multi-item gamma Poisson shrinker (MGPS). These methods compare the proportional reporting rates of AEs between imatinib and all other drugs(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Four algorithms were employed to quantify imatinib-associated AE signals, with their equations and decision criteria detailed in \u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e. Signal detection rules were applied at both the system organ class (SOC) and preferred term (PT) levels. A signal was flagged at the SOC level if at least one of the four indices met the predefined criteria, while PT-level signals required concurrent satisfaction of all four criteria(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Higher scores across these parameters generally indicated stronger disproportionality(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Statistical analyses were performed using SAS software (version 9.4), as recommended by the FDA. Raw ASCII data downloaded from the FDA website were imported into SAS, deduplicated following FDA-recommended protocols, and subsequently analyzed.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eGeneral characteristics\u003c/h2\u003e \u003cp\u003eIn the FAERS database, 56,364 patients were identified with 170,659 adverse events (AEs) attributed to imatinib, averaging 3.02 AEs per individual. Females accounted for 24,179 cases (42.9%), males 27,808 (49.34%), and 4,377 (7.77%) had unspecified gender. Age data were available for 28,962 patients (mean age\u0026thinsp;=\u0026thinsp;59\u0026thinsp;\u0026plusmn;\u0026thinsp;14 years). Patients aged\u0026thinsp;\u0026lt;\u0026thinsp;18 years (n\u0026thinsp;=\u0026thinsp;1,180, 2.09%), 18\u0026ndash;44 years (n\u0026thinsp;=\u0026thinsp;5,721, 10.15%), 45\u0026ndash;64 years (n\u0026thinsp;=\u0026thinsp;10,954, 19.43%), and \u0026ge;\u0026thinsp;65 years (n\u0026thinsp;=\u0026thinsp;11,107, 19.71%) comprised the cohorts. The highest reporting year was 2014 (n\u0026thinsp;=\u0026thinsp;5,131, 9.10%). Most reports originated from consumers (39.98%), with the United States of America contributing the majority (n\u0026thinsp;=\u0026thinsp;16,962, 30.09%). The primary indication was chronic myeloid leukemia (n\u0026thinsp;=\u0026thinsp;25,664, 45.53%). Severe outcomes constituted 84.24% of reports, predominantly death (n\u0026thinsp;=\u0026thinsp;19,409, 34.44%) and other serious outcomes (n\u0026thinsp;=\u0026thinsp;24,861, 44.11%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). AE occurrence time (excluding unspecified medication dates) peaked at 0\u0026ndash;30 days (24.22%) and \u0026gt;\u0026thinsp;360 days (38.08%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of cases of Imatinib usage.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of events (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24179(42.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27808(49.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Specified(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4377( 7.77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;18(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1180( 2.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;44(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5721(10.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u0026ndash;64(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10954(19.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e65\u0026le;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11107(19.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNotSpecified(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27402(48.62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReport year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2006(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e624( 1.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2007(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e683( 1.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2008(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e658( 1.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2009(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e671( 1.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2010(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e707( 1.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2011(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1128( 2.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2012(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1678( 2.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2013(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3174( 5.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2014(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5131( 9.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2015(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3456( 6.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2016(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3402( 6.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2017(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3244( 5.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3602( 6.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2019(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3950( 7.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2020(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4153( 7.37)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4835( 8.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4174( 7.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2023(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3355( 5.95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2024(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2847( 5.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReporter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsumer(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22532(39.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Specified(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8( 0.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther health-professional(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4202( 7.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacist(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7146(12.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6954(12.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReported countries(TOP ten)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States of America(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16962(30.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Specified(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14162(25.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndia(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4315( 7.66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2799( 4.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrance(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1618( 2.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChina(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1540( 2.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited Kiongdom(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1200( 2.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGermany(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1125( 2.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e867( 1.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItaly(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e835( 1.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndications(TOP ten)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic myeloid leukaemia(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25664(45.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct used for unknown indication(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7978(14.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal stromal tumour(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7640(13.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Specified(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7082(12.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute lymphocytic leukaemia(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1866( 3.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukaemia(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e339( 0.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastric cancer(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e338( 0.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoplasm malignant(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e315( 0.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSoft tissue sarcoma(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e247( 0.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhiladelphia positive chronic myeloid leukaemia(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e230( 0.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerious report\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerious(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47481(84.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Serious(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8883(15.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife-Threatening(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1233( 2.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization - Initial or Prolonged(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10187(18.07)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisability(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e737( 1.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19409(34.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital Anomaly(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90( 0.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequired Intervention to Prevent Permanent Impairment/Damage(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65( 0.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24861(44.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eImatinib-associated AEs affected multiple organ systems\u003c/h3\u003e\n\u003cp\u003eThe top four involved categories were general disorders and administration site conditions (40,355, 23.65%), gastrointestinal disorders (17,125, 10.03%), neoplasms benign/malignant/unspecified (15,433, 9.04%), and investigations (14,428, 8.45%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOrgan system-specific distribution of AEs associated with Imatinib.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystem Organ Class\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of events (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40355(23.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17125(10.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15433(9.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvestigations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14428(8.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNervous system disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8402(4.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfections and infestations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8210(4.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory, thoracic and mediastinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7705(4.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7302(4.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal and connective tissue disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7277(4.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6997(4.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjury, poisoning and procedural complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6353(3.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4724(2.77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEye disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4255(2.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetabolism and nutrition disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3929(2.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal and urinary disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3189(1.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2707(1.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychiatric disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2698(1.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical and medical procedures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2399(1.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatobiliary disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2246(1.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmune system disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1184(0.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy, puerperium and perinatal conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e693(0.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEar and labyrinth disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e690(0.40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReproductive system and breast disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e637(0.37)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital, familial and genetic disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e581(0.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct issues\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e571(0.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e407(0.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocial circumstances\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e162(0.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDisproportionality Analysis of Imatinib AEs\u003c/h2\u003e \u003cp\u003eUsing the reporting odds ratio (ROR) method, the top 50 preferred terms (PTs) by signal frequency and strength were ranked (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The most frequent signals included: Death (n\u0026thinsp;=\u0026thinsp;15,667; ROR (95% CI)\u0026thinsp;=\u0026thinsp;7.34 (7.22\u0026ndash;7.46)), Nausea (n\u0026thinsp;=\u0026thinsp;3,000; ROR\u0026thinsp;=\u0026thinsp;1.39 (1.34\u0026ndash;1.44)), Diarrhoea (n\u0026thinsp;=\u0026thinsp;2,532; ROR\u0026thinsp;=\u0026thinsp;1.46 (1.40\u0026ndash;1.52)), Malignant neoplasm progression (n\u0026thinsp;=\u0026thinsp;2,177; ROR\u0026thinsp;=\u0026thinsp;8.33 (7.98\u0026ndash;8.69)) and Vomiting (n\u0026thinsp;=\u0026thinsp;2,000; ROR\u0026thinsp;=\u0026thinsp;1.57 (1.50\u0026ndash;1.64)). The strongest signals (highest ROR) were: Blast crisis in myelogenous leukaemia (n\u0026thinsp;=\u0026thinsp;762; ROR\u0026thinsp;=\u0026thinsp;612.66 (542.99\u0026ndash;691.27)), Pubertal failure (n\u0026thinsp;=\u0026thinsp;7; ROR\u0026thinsp;=\u0026thinsp;452.74 (143.69\u0026ndash;1426.52)), Large intestine fibroma (n\u0026thinsp;=\u0026thinsp;4; ROR\u0026thinsp;=\u0026thinsp;431.18 (96.50\u0026ndash;1926.58)), Slit-lamp tests abnormal (n\u0026thinsp;=\u0026thinsp;5; ROR\u0026thinsp;=\u0026thinsp;404.23 (108.55\u0026ndash;1505.38)) and Chromosome analysis abnormal (n\u0026thinsp;=\u0026thinsp;124; ROR\u0026thinsp;=\u0026thinsp;326.24 (254.21\u0026ndash;418.68)). A four-algorithm integrated analysis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) ranked the most frequent signals as: 1. Death (n\u0026thinsp;=\u0026thinsp;15,667; ROR\u0026thinsp;=\u0026thinsp;7.34 (7.22\u0026ndash;7.46); PRR\u0026thinsp;=\u0026thinsp;6.76; IC\u0026thinsp;=\u0026thinsp;2.73; EBGM\u0026thinsp;=\u0026thinsp;6.64). 2. Nausea (n\u0026thinsp;=\u0026thinsp;3,000; ROR\u0026thinsp;=\u0026thinsp;1.39 (1.34\u0026ndash;1.44); PRR\u0026thinsp;=\u0026thinsp;1.38; IC\u0026thinsp;=\u0026thinsp;0.47; EBGM\u0026thinsp;=\u0026thinsp;1.38). 3. Diarrhoea (n\u0026thinsp;=\u0026thinsp;2,532; ROR\u0026thinsp;=\u0026thinsp;1.46 (1.40\u0026ndash;1.52); PRR\u0026thinsp;=\u0026thinsp;1.45; IC\u0026thinsp;=\u0026thinsp;0.54; EBGM\u0026thinsp;=\u0026thinsp;1.45). 4. Drug ineffective (n\u0026thinsp;=\u0026thinsp;2,436; ROR\u0026thinsp;=\u0026thinsp;0.67 (0.64\u0026ndash;0.69); PRR\u0026thinsp;=\u0026thinsp;0.67; IC = -0.57; EBGM\u0026thinsp;=\u0026thinsp;0.67). 5. Malignant neoplasm progression (n\u0026thinsp;=\u0026thinsp;1,519; ROR\u0026thinsp;=\u0026thinsp;8.33 (7.98\u0026ndash;8.69); PRR\u0026thinsp;=\u0026thinsp;8.23; IC\u0026thinsp;=\u0026thinsp;3.01; EBGM\u0026thinsp;=\u0026thinsp;8.05). By signal strength (ROR lower limit, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), the top signals were: 1. Blast crisis in myelogenous leukaemia (ROR\u0026thinsp;=\u0026thinsp;612.66 (542.99\u0026ndash;691.27); PRR\u0026thinsp;=\u0026thinsp;609.93; IC\u0026thinsp;=\u0026thinsp;7.73; EBGM\u0026thinsp;=\u0026thinsp;211.98). 2. Pubertal failure (ROR\u0026thinsp;=\u0026thinsp;452.74 (143.69\u0026ndash;1426.52); PRR\u0026thinsp;=\u0026thinsp;452.72; IC\u0026thinsp;=\u0026thinsp;7.56; EBGM\u0026thinsp;=\u0026thinsp;189.22). 3. Large intestine fibroma (ROR\u0026thinsp;=\u0026thinsp;431.18 (96.50\u0026ndash;1926.58); PRR\u0026thinsp;=\u0026thinsp;431.17; IC\u0026thinsp;=\u0026thinsp;7.53; EBGM\u0026thinsp;=\u0026thinsp;185.36). 4. Slit-lamp tests abnormal (ROR\u0026thinsp;=\u0026thinsp;404.23 (108.55\u0026ndash;1505.38); PRR\u0026thinsp;=\u0026thinsp;404.22; IC\u0026thinsp;=\u0026thinsp;7.49; EBGM\u0026thinsp;=\u0026thinsp;180.21). 5. Chromosome analysis abnormal (ROR\u0026thinsp;=\u0026thinsp;326.24 (254.21\u0026ndash;418.68); PRR\u0026thinsp;=\u0026thinsp;326.00; IC\u0026thinsp;=\u0026thinsp;7.35; EBGM\u0026thinsp;=\u0026thinsp;162.84).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe top 50 PTs with the highest signal frequency for Imatinib positivity in ROR、PRR、BCPNN and MGPS.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreferred Terms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eROR(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRR(Chi-Square)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIC(IC-2SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEBGM(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15667\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.34(7.22\u0026ndash;7.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.76(76349.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.73(2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.64(6.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.39(1.34\u0026ndash;1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.38(322.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.47(0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.38(1.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhoea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2532\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.46(1.40\u0026ndash;1.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.45(359.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.54(0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.45(1.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug ineffective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2436\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.67(0.64\u0026ndash;0.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.67(401.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.57(-0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.67(0.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant neoplasm progression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.33(7.98\u0026ndash;8.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.23(13510.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.01(2.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8.05(7.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.97(0.93\u0026ndash;1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.97(1.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.04(-0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.97(0.93)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.57(1.50\u0026ndash;1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.56(408.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.64(0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.56(1.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRash\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.37(1.30\u0026ndash;1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.36(165.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.45(0.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.36(1.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1565\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.96(2.81\u0026ndash;3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.94(1991.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.55(1.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.92(2.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePyrexia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1541\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.61(1.53\u0026ndash;1.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.61(352.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.68(0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.60(1.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspnoea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1479\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.94(0.90\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.94(4.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.08(-0.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.94(0.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalaise\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.16(1.10\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.16(31.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.21(0.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.16(1.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscle spasms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1327\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.59(2.46\u0026ndash;2.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.58(1278.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.36(1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.57(2.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic myeloid leukaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e148.19(138.83-158.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e147.05(131731)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.66(6.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e101.40(94.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.26(18.19\u0026ndash;20.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19.12(20472.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.18(4.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e18.11(17.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal stromal tumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e296.39(274.18\u0026ndash;320.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e294.29(185784)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.27(7.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e154.55(142.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug intolerance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.75(4.48\u0026ndash;5.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.72(3401.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.22(2.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.67(4.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.23(1.16\u0026ndash;1.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.23(47.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.29(0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.22(1.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.08(1.02\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.08(6.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.11(0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.08(1.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.53(3.32\u0026ndash;3.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.51(1805.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.80(1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.49(3.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePleural effusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e965\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.73(5.37\u0026ndash;6.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.70(3677.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.49(2.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.62(5.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e944\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.55(0.51\u0026ndash;0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.55(355.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.87(-0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.55(0.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOedema peripheral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e934\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.69(2.52\u0026ndash;2.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.68(980.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.42(1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.67(2.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoplasm malignant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.18(4.86\u0026ndash;5.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.16(3072.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.35(2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.09(4.77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e924\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.53(0.50\u0026ndash;0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.53(385.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.91(-1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.53(0.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond primary malignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e909\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43.58(40.66\u0026ndash;46.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43.36(33170.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.26(5.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e38.35(35.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e885\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.39(1.30\u0026ndash;1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.39(95.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.47(0.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.39(1.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e858\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.83(2.65\u0026ndash;3.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.82(1003.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.49(1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.81(2.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthralgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.74(0.69\u0026ndash;0.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.74(77.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.44(-0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.74(0.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease progression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.59(2.42\u0026ndash;2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.58(800.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.36(1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.57(2.40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e819\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.79(2.60\u0026ndash;2.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.78(927.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.47(1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.77(2.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOedema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e804\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.46(5.09\u0026ndash;5.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.44(2869.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.42(2.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.37(5.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlast crisis in myelogenous leukaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e762\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e612.66(542.99-691.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e609.93(160510)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.73(7.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e211.98(187.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite blood cell count increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.91(6.42\u0026ndash;7.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.88(3659.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.76(2.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.76(6.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased appetite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e741\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.11(1.03\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.11(7.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.15(0.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.11(1.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.50(0.47\u0026ndash;0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.50(341.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.99(-1.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.51(0.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTherapy non-responder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e686\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.62(4.28\u0026ndash;4.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.60(1909.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.19(2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.55(4.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain in extremity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e685\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.82(0.76\u0026ndash;0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.82(25.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.28(-0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.82(0.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e679\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.44(1.33\u0026ndash;1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.44(90.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.52(0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.44(1.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite blood cell count decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e673\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.24(2.08\u0026ndash;2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.23(456.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.15(1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.23(2.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluid retention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e667\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.72(0.67\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.72(70.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.46(-0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.72(0.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e667\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.75(4.40\u0026ndash;5.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.74(1939.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.23(2.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.68(4.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61(0.57\u0026ndash;0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62(155.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.70(-0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.62(0.57)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e638\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.82(0.76\u0026ndash;0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.82(24.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.28(-0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.82(0.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain upper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.12(1.04\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.12(8.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.17(0.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.12(1.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e609\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.04(3.73\u0026ndash;4.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.03(1369.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.00(1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.99(3.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e608\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.66(1.53\u0026ndash;1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.65(156.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.72(0.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.65(1.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e575\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.75(0.70\u0026ndash;0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76(45.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.40(-0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.76(0.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal discomfort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.20(1.10\u0026ndash;1.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.20(18.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.26(0.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.20(1.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e559\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.81(1.67\u0026ndash;1.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.81(200.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.85(0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.80(1.66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe top 50 PTs with the highest signal intensity for Imatinib positivity in ROR、PRR、BCPNN and MGPS.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreferred Terms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eROR(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRR(Chi-Square)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIC(IC-2SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEBGM(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlast crisis in myelogenous leukaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e762\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e612.66(542.99-691.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e609.93(160510)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.73(7.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e211.98(187.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePubertal failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e452.74(143.69-1426.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e452.72(1314.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.56(1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e189.22(60.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLarge intestine fibroma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e431.18(96.50-1926.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e431.17(735.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.53(0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e185.36(41.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlit-lamp tests abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e404.23(108.55-1505.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e404.22(893.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.49(1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e180.21(48.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChromosome analysis abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e326.24(254.21-418.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e326.00(20007.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.35(5.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e162.84(126.89)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal stromal tumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e296.39(274.18\u0026ndash;320.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e294.29(185784)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.27(7.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e154.55(142.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic myeloid leukaemia (in remission)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e291.05(118.27-716.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e291.04(1369.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.26(2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e153.65(62.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCytogenetic analysis abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e274.19(241.62-311.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e273.48(65309.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.22(6.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e148.63(130.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic myeloid leukaemia transformation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e270.51(222.28\u0026ndash;329.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e270.22(26740.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.21(6.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e147.66(121.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChordoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e266.37(177.06-400.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e266.31(6087.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.19(4.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e146.49(97.37)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic eosinophilic leukaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e264.59(109.64-638.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e264.58(1299.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.19(2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e145.97(60.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCytogenetic response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e258.71(69.47-963.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e258.70(570.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.17(0.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e144.17(38.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhiladelphia chromosome negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e258.71(69.47-963.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e258.70(570.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.17(0.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e144.17(38.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-kit gene mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e251.52(93.67-675.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e251.51(982.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.15(1.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e141.91(52.85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhiladelphia chromosome positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e202.96(170.79-241.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e202.71(25909.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.97(6.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e124.99(105.18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood thrombin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e194.03(46.37-811.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e194.02(360.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.93(0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e121.64(29.07)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic myeloid leukaemia recurrent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186.76(155.45-224.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e186.56(21067.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.89(5.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e118.67(98.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute aortic syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e184.79(54.09-631.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e184.79(465.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.88(0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e117.95(34.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eErythrocyanosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179.66(60.21-536.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e179.65(571.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.86(1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e115.85(38.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGene mutation identification test positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e168.74(136.93-207.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e168.61(14674.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.80(5.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e111.17(90.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic myeloid leukaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148.19(138.83-158.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e147.05(131731)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.66(6.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e101.40(94.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNecrotising panniculitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147.00(79.84-270.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e146.99(1495.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.66(2.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e101.37(55.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral pigmentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115.11(69.96-189.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e115.10(1751.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.41(3.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e85.15(51.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGelatinous transformation of the bone marrow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107.79(39.18\u0026ndash;296.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e107.79(396.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.34(1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e81.09(29.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWallerian degeneration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107.79(34.76-334.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e107.79(317.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.34(0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e81.09(26.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolymerase chain reaction positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102.61(78.71-133.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e102.57(5497.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.29(4.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e78.11(59.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of CAR T-cell persistence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.11(35.09-257.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.11(359.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.20(1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e73.72(27.20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnkle brachial index decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.11(35.09-257.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.11(359.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.20(1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e73.72(27.20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransdifferentiation of neoplasm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.21(46.71\u0026ndash;178.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e91.21(765.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.16(2.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e71.36(36.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeavy chain disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.83(33.35-241.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e89.83(343.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.14(1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e70.52(26.18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlast cell crisis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.33(68.02-117.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e89.30(4515.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.13(4.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e70.19(53.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphoblast count increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88.19(24.60-316.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e88.19(203.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.12(0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e69.51(19.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCoV-HKU1 infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86.24(28.62-259.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e86.23(266.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.09(0.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e68.29(22.66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrisomy 8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.08(45.68-154.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e84.08(846.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.06(2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e66.93(36.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClear cell sarcoma of soft tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.85(27.03-241.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80.84(252.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.02(0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e64.87(21.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse waveform abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.00(29.03\u0026ndash;204.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e76.99(302.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.96(1.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e62.38(23.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastric antral vascular ectasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.72(60.39\u0026ndash;97.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e76.69(5011.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.96(4.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e62.18(48.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTyrosine kinase mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.09(25.60-226.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e76.09(239.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.95(0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e61.79(20.79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSarcomatosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.63(21.27-261.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e74.62(177.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.93(0.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e60.82(17.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClonal evolution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.87(43.12-119.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e71.86(1029.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.88(3.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e58.98(35.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOncologic complication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e159\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.89(59.70-84.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70.82(8978.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.86(5.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e58.28(49.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVulval cancer stage III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.30(19.91-241.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e69.29(166.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.84(0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e57.24(16.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight ventricular diastolic collapse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.60(30.35-155.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e68.59(384.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.83(1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e56.77(25.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolymerase chain reaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.53(41.19-110.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e67.52(1030.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.81(3.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e56.03(34.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligoasthenozoospermia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.68(18.72-223.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64.67(156.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.76(0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e54.06(15.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarotid intima-media thickness increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.59(26.11-150.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e62.59(304.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.72(1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e52.60(21.95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAllogenic bone marrow transplantation therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.49(27.10-121.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57.49(377.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.61(1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e48.96(23.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone marrow necrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.09(37.64\u0026ndash;80.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e55.08(1406.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.56(3.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e47.21(32.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyelocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.73(28.89-103.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e54.72(496.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.55(2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e46.95(24.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukaemic infiltration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.80(31.13\u0026ndash;89.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52.80(698.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.51(2.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e45.53(26.84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study represents the first comprehensive and systematic pharmacovigilance investigation utilizing the FDA Adverse Event Reporting System (FAERS) database to analyze post-marketing AEs associated with imatinib. The primary objective was to meticulously characterize, describe, and analyze imatinib-related AEs reported to date. The findings presented herein provide valuable and accurate insights into the safety profile of imatinib in real-world clinical settings.\u003c/p\u003e \u003cp\u003eThis study revealed that AEs associated with imatinib occurred slightly more frequently in males (49.34%) than females (42.9%), aligning with epidemiological trends(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The majority of affected patients (39.14%) were aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years, reflecting the predominant demographic of CML and GIST populations(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Consumers submitted 39.98% of reports, consistent with the spontaneous reporting nature of the FAERS database(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Severe AEs accounted for 84.24% of imatinib-related reports, likely attributable to its mechanism as a multi-target Abl kinase inhibitor, which modulates critical biological pathways(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The high mortality rate (34.44% of outcomes) may stem from life-threatening complications such as tumor progression or organ failure. Notably, 38.08% of AEs occurred\u0026thinsp;\u0026gt;\u0026thinsp;360 days post-treatment, underscoring the necessity for long-term safety monitoring.At the SOC level, the most frequent categories included General disorders and administration site conditions, Gastrointestinal disorders, and Neoplasms benign, consistent with labeled safety profiles. Common PTs such as nausea, diarrhea, vomiting, and malignant neoplasm progression were frequently reported, corroborating clinical trial findings(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile most AEs in our analysis were largely consistent with safety data from drug labeling and clinical trials, we identified previously unreported significant AE signals not explicitly documented in regulatory trials. These included new-onset benign tumors (e.g., lipomas, fibromas) or neoplasms of uncertain behavior. The FDA labeling for imatinib primarily focuses on its therapeutic efficacy against existing malignancies (e.g., GIST, CML) and known complications (e.g., tumor hemorrhage), but does not explicitly address the potential induction of or association with new benign or unclassified neoplasms during treatment(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).The insidious toxicities associated with long-term medication require particular attention, such as sciatica, joint ankylosis, and even ischemic necrosis of the femoral head observed in the musculoskeletal system, while the FDA label merely mentions \"musculoskeletal pain\" without specifying severity or chronic consequences(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Severe dermatological reactions like exfoliative dermatitis and acute generalized exanthematous pustulosis are inadequately characterized in product labeling despite documented progression risks in clinical cases(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). We advocate for enhanced long-term monitoring, particularly targeting musculoskeletal toxicity, metabolic syndrome, and other insidious risks, with recommendations including regular bone density assessments and systematic skin reaction evaluations. This call emphasizes the necessity to bridge labeling-practice discrepancies through proactive surveillance mechanisms.\u003c/p\u003e \u003cp\u003eUnder the SOC \"Investigations,\" PTs encompassed non-specific enzymatic elevations (e.g., alkaline phosphatase (ALP), lactate dehydrogenase (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)) or structural organ changes identified via imaging. While the FDA label lists abnormal liver function as a monitoring parameter, it does not classify \"investigation abnormalities\" as standalone adverse reactions, potentially underestimating their impact on clinical decision-making(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFor the SOC \"Pregnancy, Puerperium, and Perinatal Conditions,\" cases accounted for 0.41% of reports, yet the ROR method detected 13 positive signals (1.07%). Specific PTs included fetal developmental anomalies and gestational complications (e.g., miscarriage, preterm delivery). The FDA currently warns only of \"embryo-fetal toxicity\" and recommends contraception but lacks explicit risk data on imatinib use during pregnancy(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). This underscores the need for enhanced monitoring of pregnancy-exposed patients and research into imatinib\u0026rsquo;s potential effects on placental function or fetal organogenesis. Within the psychiatric disorders (SOC), \"psychiatric symptoms\" accounted for 1.58% of reports, with specific PTs including depression, anxiety, and cognitive impairment. Notably, the FDA-approved label for imatinib does not list psychiatric symptoms as common or severe adverse reactions, only mentioning that impaired driving ability may be associated with fatigue(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Further investigation is warranted to determine whether imatinib crosses the blood-brain barrier to directly alter neurotransmitter activity or synergizes with the psychological burden inherent to chronic illness.\u003c/p\u003e \u003cp\u003eThe FDA-approved label for imatinib does not currently acknowledge ototoxicity-related risks. However, our study identified signals in the Ear and Labyrinth Disorders System Organ Class (SOC), including preferred terms (PTs) such as tinnitus, hearing impairment, and vestibular dysfunction(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). This finding underscores the need for proactive monitoring of vestibular function in patients undergoing long-term imatinib therapy, particularly among elderly individuals or those with comorbid renal impairment.\u003c/p\u003e \u003cp\u003eThis study leverages the inherent advantages of large-scale real-world investigations and sophisticated data mining techniques. However, several limitations necessitate careful consideration. The FAERS database, as a spontaneous reporting system, may introduce analytical biases due to incomplete or inaccurate data collection across countries and healthcare professionals, including reporting bias and indication bias, with challenges in distinguishing adverse events caused by the drug versus disease progression. Additionally, adverse events with extremely low incidence rates associated with imatinib might lack statistical significance in disproportionality analyses, potentially leaving undetected safety signals. The specificity of attributing adverse events to imatinib is further limited by confounding from concomitant medications. Finally, while disproportionality analysis identifies statistical significance based on signal strength, it cannot fully eliminate confounding effects from polypharmacy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study conducted a real-world pharmacovigilance analysis of Imatinib using the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis (ROR, PRR, BCPNN, EBGM) was applied to evaluate adverse events (AEs) from 2004 to 2024. Results confirmed expected AEs (e.g., nausea, diarrhea) aligned with drug labels, while identifying undocumented signals such as pubertal failure (ROR\u0026thinsp;=\u0026thinsp;452.74), large intestine fibroma (ROR\u0026thinsp;=\u0026thinsp;431.18), ototoxicity, and pregnancy complications. Severe outcomes accounted for 84.24% of reports (34.44% death), with 38.08% of AEs occurring\u0026thinsp;\u0026gt;\u0026thinsp;360 days post-medication. The study underscores the need for vigilant monitoring of long-term toxicities (e.g., bone metabolism disorders, psychiatric effects) and rare AEs to enhance patient safety.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no ethical issues involved in this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTianqin Xia contributed to the design of the study protocol. Bo Shu performed the statistical analysis. Yuan Peng drew the picture. Baiqiang Wang contributed to the writing of the study protocol and made the final corrections to this manuscript. Tianqin Xia finally corrected the manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublisher\u0026rsquo;s note\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCohen P. Protein kinases - the major drug targets of the twenty-first century? Nature Reviews Drug Discovery. 2002;1(4):309-15.\u003c/li\u003e\n\u003cli\u003eWitte ON, Dasgupta A, Baltimore D. Abelson murine leukaemia virus protein is phosphorylated in vitro to form phosphotyrosine. Nature. 1980;283(5750):826-31.\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. New England Journal of Medicine. 2003;348(11):994-1004.\u003c/li\u003e\n\u003cli\u003eKantarjian H, O\u0026apos;Brien S, Jabbour E, Garcia-Manero G, Quintas-Cardama A, Shan J, et al. 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Otolaryngology-Head and Neck Surgery. 2012;146(2):335-7.\u003c/li\u003e\n\u003c/ol\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":"european-journal-of-clinical-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcl","sideBox":"Learn more about [European Journal of Clinical Pharmacology](http://link.springer.com/journal/228)","snPcode":"228","submissionUrl":"https://submission.nature.com/new-submission/228/3","title":"European Journal of Clinical Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Imatinib, FAERS, disproportionality analysis, pharmacovigilance, malignant neoplasm progression","lastPublishedDoi":"10.21203/rs.3.rs-6289043/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6289043/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eTo evaluate the safety profile of Imatinib using the FAERS database, identifying both documented and undocumented adverse events.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFAERS data Q1 2004 to Q1 2024 were analyzed via disproportionality analysis (ROR, PRR, BCPNN, EBGM) to quantify drug-AE associations.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 56,364 patients (170,659 AE occurrences) were included. Imatinib exhibited expected AEs (e.g., nausea, diarrhea) consistent with labels, alongside novel signals such as pubertal failure (ROR\u0026thinsp;=\u0026thinsp;452.74), large intestine fibroma (ROR\u0026thinsp;=\u0026thinsp;431.18), ototoxicity, and pregnancy complications. Severe outcomes comprised 84.24% of reports (34.44% death), with 38.08% of AEs occurring\u0026thinsp;\u0026gt;\u0026thinsp;360 days post-treatment. Malignant neoplasm progression showed strong association (ROR\u0026thinsp;=\u0026thinsp;8.33).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe study reveals undocumented safety risks of Imatinib, highlighting the need for long-term monitoring of rare and insidious toxicities. Limitations of spontaneous reporting systems were acknowledged.\u003c/p\u003e","manuscriptTitle":"Undocumented Safety Signals of Imatinib: Pharmacovigilance Insights from the FDA Adverse Event Reporting System (FAERS) and Implications for Clinical Practice","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 08:58:17","doi":"10.21203/rs.3.rs-6289043/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-30T06:08:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-24T11:48:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-02T15:15:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319261285662154541799195895868053956227","date":"2025-03-27T12:11:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261032432507032131104702427249784275785","date":"2025-03-27T11:22:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-27T10:54:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-26T09:48:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-26T09:45:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Clinical Pharmacology","date":"2025-03-23T15:00:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcl","sideBox":"Learn more about [European Journal of Clinical Pharmacology](http://link.springer.com/journal/228)","snPcode":"228","submissionUrl":"https://submission.nature.com/new-submission/228/3","title":"European Journal of Clinical Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f2c17694-ada7-44b9-9e5f-6dbc976ee187","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-06-20T09:53:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-16 08:58:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6289043","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6289043","identity":"rs-6289043","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}