scholarly journals The Risk of Newly Diagnosed Cancer in Patients with Rheumatoid Arthritis by TNF Inhibitor Use: A Nationwide Cohort Study

2021 ◽  
Author(s):  
Boyoon Choi ◽  
Hyun Jin Park ◽  
Yun-Kyoung Song ◽  
Yoon-Jeong Oh ◽  
In-Wha Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Risk ◽  
Cox Regression ◽  
Tnf Inhibitors ◽  
Tnf Inhibitor ◽  
Matched Cohort ◽  
Korean Patients ◽  
Study Results ◽  
The One ◽  
Risk Of Cancer

Abstract Background Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. Methods Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1,000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. Results Of the 22,851 patients in the before matching cohort, 4,592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1,000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820). Conclusions The use of TNF inhibitors was associated with a lower cancer incidence in Korean patients with RA. A further study linking claims and clinical data is needed to confirm our results.

scholarly journals Risk of Cancer Following the Use of N-Nitrosodimethylamine (NDMA) Contaminated Ranitidine Products: A Nationwide Cohort Study in South Korea

2021 ◽  
Vol 10 (1) ◽  
pp. 153
Author(s):  
Hong Jin Yoon ◽  
Jie-Hyun Kim ◽  
Gi Hyeon Seo ◽  
Hyojin Park
Keyword(s):  
Cohort Study ◽  
Cancer Risk ◽  
South Korea ◽  
Primary Study ◽  
Study Cohort ◽  
Matched Cohort ◽  
Cancer Outcomes ◽  
H2 Receptor Antagonist ◽  
Carcinogenic Agent ◽  
Risk Of Cancer

N-nitrosodimethylamine (NDMA), a known carcinogenic agent, was recently detected in some products of ranitidine. Several studies have investigated the detectability of NDMA, in drugs and their risks. However, only a few epidemiological studies have evaluated cancer risk from the use of such individual drugs. This study investigates the risk of cancer in ranitidine users. We conducted an observational population-based cohort study using the Health Insurance Review and Assessment databases, which contain information about the use of medicines in South Korea. The primary study cohort consisted of ranitidine users (n = 88,416). For controls, we enrolled users of famotidine, another H2-receptor antagonist in which no NDMA has been detected. A 4:1 matched cohort was constructed to compare cancer outcomes of the two groups. Our matched cohort comprised of 40,488 ranitidine users and 10,122 famotidine users. There was no statistical difference in the overall cancer risk between the ranitidine and famotidine groups (7.45% vs. 7.56%, HR 0.99, 95% CI 0.91–1.07, p = 0.716). Additionally, no significant differences were observed in the analysis of 11 single cancer outcomes. We found no evidence that exposure to NDMA through ranitidine increases the risk of cancer.

scholarly journals AB0115 COMPARISON OF ULTRASOUND FINDINGS BETWEEN TNF INHIBITORS AND NON-TNF INHIBITORS AT FIRST BIOLOGICS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1086.2-1087
Author(s):  
T. Okano ◽  
T. Koike ◽  
K. Inui ◽  
K. Mamoto ◽  
Y. Yamada ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Power Doppler ◽  
Tnf Inhibitors ◽  
Tnf Inhibitor ◽  
Significant Difference ◽  
The Us ◽  
Us Findings ◽  
Improvement Ratio

Background:In rheumatoid arthritis (RA), biologics treatment is one of the effective treatment options. Usually, there is no difference in therapeutic effect regardless of which biologics is used, but the effect for joint synovitis is unknown. Recently, ultrasound (US) has played a role of sensitive imaging modality in the diagnosis and follow-up of patients with RA.Objectives:The aim of this study was to compare the improvement of US findings between TNF inhibitors and non-TNF inhibitors at first biologics in patients with RA.Methods:Fifty-four RA patients who started the first biologics from September 2016 to December 2018 were included in this longitudinal study (SPEEDY study, UMIN000028260). All the patients were performed clinical examination, blood test and US examination at baseline, 4, 12, 24, 36 and 52 weeks. A US examination was performed at the bilateral first to fifth metacarpophalangeal (MCP) joints, first interphalangeal (IP) and second to fifth proximal interphalangeal (PIP) joints, wrist joints (three part of radial, medial and ulnar) and first to fifth metatarsophalangeal (MTP) joints, by using HI VISION Ascendus (Hitachi Medical Corporation, Japan) with a multifrequency linear transducer (18-6 MHz). The gray scale (GS) and power Doppler (PD) findings were assessed by the semi-quantitative method (0-3). GS score and PD score (both 0-108 points) were defined as the sum of each score. The change of disease activity and US findings were compared between TNF group and non-TNF group.Results:Among 54 cases, 32 patients were used TNF inhibitor and 22 were non-TNF inhibitor. Age and duration of RA were significantly higher in the non-TNF group, and MTX dose was significantly lower in the non-TNF group. The baseline inflammatory markers tended to be higher in the non-TNF group and the disease activity was also higher in the non-TNF group. However, the US findings showed no significant difference in both GS and PD between two groups at baseline. US improvement ratio was no difference between TNF group and non-TNF group at 4, 12, 24, 36 and 52 weeks in both GS and PD score. Regardless of the type of biologics, patients with long-term disease duration tended to have poor improvement in US synovial fingings.Table 1.Baseline patient and disease characteristicsTNF (n=32)non-TNF (n=22)P valueFemale patients, n (%)21 (65.6)16 (72.7)0.767Age (years)63.5±15.471.0±9.00.030Disease duration (years)6.5±8.213.0±11.70.032CRP (mg/dl)1.8±2.53.0±3.20.170DAS28-ESR5.0±1.45.8±1.20.022GS score26.1±18.831.8±21.10.313PD score17.6±11.423.1±14.60.150Figure 1.GS and PD improvement ratio at 4, 12, 24, 36 and 52 weeksConclusion:There was no difference in the US findings improvement between patients with TNF inhibitor and non-TNF inhibitor at first biologics in patients with RA.References:[1]Grassi W, Okano T, Di Geso L, Filippucci E. Imaging in rheumatoid arthritis: options, uses and optimization. Expert Rev Clin Immunol. 2015;11:1131-46.[2]Nishino A, Kawashiri SY, Koga T, et al. Ultrasonographic Efficacy of Biologic andTargeted Synthetic Disease-ModifyingAntirheumatic Drug Therapy in RheumatoidArthritis From a Multicenter RheumatoidArthritis Ultrasound Prospective Cohort in Japan. Arthritis Care Res (Hoboken). 2018;70:1719-26.Acknowledgements:We wish to thank Atsuko Kamiyama, Tomoko Nakatsuka for clinical assistant, Setsuko Takeda, Emi Yamashita, Yuko Yoshida, Rika Morinaka, Hatsue Ueda and Tomomi Iwahashi for their special efforts as a sonographer and collecting data.Disclosure of Interests:None declared

scholarly journals AB0302 USE OF TNF-INHIBITORS BEFORE, DURING AND THE FIRST YEAR AFTER PREGNANCY AMONG WOMEN WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1450.2-1450
Author(s):  
H. Bjørngaard ◽  
H. Koksvik ◽  
B. Jakobsen ◽  
M. Wallenius
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Post Partum ◽  
Tnf Inhibitors ◽  
Treat To Target ◽  
Inflammatory Rheumatic Diseases ◽  
Tnf Inhibitor ◽  
Rheumatic Arthritis ◽  
Quality Register ◽  
In Pregnancy

Background:Treat to target is a goal, also in pregnant women with Rheumatoid arthritis (1). There is increasing evidence on safe use with TNF inhibitors during pregnancy. Adjusted use of TNF inhibitors preconception and throughout pregnancy may stabilize disease activity and prevent flares (2). Low disease activity is also beneficial for the fetus.Objectives:To study the use of TNF-inhibitors among women with Rheumatic arthritis during and after pregnancy.Methods:RevNatus is a Norwegian, nationwide quality register that monitors treatment of inflammatory rheumatic diseases before, during and after pregnancy. Data from RevNatus in the period October 2017 to October 2019 was used to map the use of all types of TNF inhibitors among 208 women with rheumatoid arthritis, diagnosed by the ACR/EULAR criteria. The use of medication was reported at the time of visit in outpatient clinic. The frequency of use of TNF inhibitors registered at seven timepoints from pre-pregnancy to twelve months after delivery.Results:The use of medication was reported at each visit for all the women with rheumatoid arthritis. Most of the women were not using TNF inhibitors before and beyond conception. Most of the women continuing TNF inhibitors beyond conception used certolizumab or etanercept. Adalimumab and infliximab were used in pregnancy (tabell 1).Tabell 1.certoliz-umabetane-rceptadalim-umabgolim-umabinflixi-mabNo TNF-inhibitorBefore pregnancyn=10521% (22)9% (10)3% (3)1% (1)66% (69)1.trimestern=8119% (15)10% (8)71% (58)2.trimestern=8810% (9)10% (9)80% (70)3.trimestern=9111% (10)5% (5)83% (76)6 weeks post partum n=9622% (21)13% (13)1% (1)1% (1)63% (60)6 months post partum n=8824% (21)18% (16)4% (4)1% (1)53% (46)12 months post partum n=8421% (18)17% (15)7% (6)2% (2)53% (43)Conclusion:Most of the women with rheumatic arthritis were not treated with TNF inhibitors before or in pregnancy. Women with rheumatic arthritis that continuing treatment with TNF inhibitors through pregnancy were using certilozumab and etanercept.References:[1]Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. 2016;75(5):795-810.[2]van den Brandt S, Zbinden A, Baeten D, Villiger PM, Ostensen M, Forger F. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther. 2017;19(1):64.Disclosure of Interests:None declared

scholarly journals Changing Patterns of Tumor Necrosis Factor Inhibitor Use in 9074 Patients with Rheumatoid Arthritis

2009 ◽  
Vol 36 (5) ◽  
pp. 907-913 ◽  
Author(s):  
YUSUF YAZICI ◽  
SVETLANA KRASNOKUTSKY ◽  
JAIME P. BARNES ◽  
PATRICIA L. HINES ◽  
JASON WANG ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Dose Escalation ◽  
Tumor Necrosis ◽  
Randomized Clinical Trials ◽  
Tnf Inhibitors ◽  
Tnf Inhibitor ◽  
Insurance Claims ◽  
Claims Database ◽  
Necrosis Factor

Objective.Patients with rheumatoid arthritis (RA) commonly switch between tumor necrosis factor (TNF) inhibitors after failing to control disease activity. Much of the clinical data that support switching to a second TNF agent when one agent fails to work has come from small, short-term studies. We utilized a US insurance claims database to determine patterns of use such as dose escalation, time to discontinuation, and switching between TNF inhibitors in patients with RA.Methods.A retrospective analysis was performed using an insurance claims database in the US from 2000 to 2005. TNF inhibitor use, time to switch, dose escalation, and continuation times were analyzed in patients with RA.Results.Nine thousand seventy-four patients with RA started TNF inhibitors during the period 2000 to 2005. Etanercept was the most commonly used TNF inhibitor; infliximab had the highest duration of continuation, about 50% at 2 years. In addition, infliximab showed higher rates of dose escalation compared to etanercept and adalimumab. For all TNF inhibitors, time to switching decreased from 2000 to 2005.Conclusion.TNF inhibitor use patterns changed from 2000 to 2005, with more frequent changes among the different TNF inhibitors and a shorter duration of treatment before the change. Only about 50% of TNF inhibitors are still continued at 2 years, reflecting the difference between randomized clinical trials and real-world experience.

scholarly journals Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study

2016 ◽  
Vol 209 (5) ◽  
pp. 393-399 ◽  
Author(s):  
Ru-Yu Huang ◽  
Kun-Pin Hsieh ◽  
Wan-Wen Huang ◽  
Yi-Hsin Yang
Keyword(s):  
Bipolar Disorder ◽  
Cohort Study ◽  
Cancer Risk ◽  
Cox Regression ◽  
Glycogen Synthase ◽  
Control Group ◽  
Defined Daily Dose ◽  
Research Database ◽  
Hazard Ratios ◽  
Risk Of Cancer

BackgroundLithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer.AimsTo investigate the association between lithium and cancer risk in patients with bipolar disorder.MethodA retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer.ResultsCompared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554–0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516–1.125), 0.919 (95% CI 0.640–1.318) and 0.552 (95% CI 0.367–0.831), respectively.ConclusionsLithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose–response relationship for cancer risk reduction was observed.

scholarly journals SAT0134 COMPARATIVE RISK OF CANCER ASSOCIATED WITH FIRST-LINE DMARDS USE IN RHEUMATOID ARTHRITIS: REAL WORLD EVIDENCE FROM THE OHDSI NETWORK

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1004.1-1004
Author(s):  
T. Duarte-Salles ◽  
M. Recalde ◽  
J. Weaver ◽  
E. Burn ◽  
K. Marinier ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Risk ◽  
Full Time ◽  
First Line ◽  
Research Support ◽  
Site Specific ◽  
Hazard Ratios ◽  
Comparative Risk ◽  
Risk Of Cancer

Background:Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are recommended as first line treatment for rheumatoid arthritis (RA) patients, but limited information exists on the comparative risk of cancer associated with their use.Objectives:To compare the risk of incident overall (excluding non-melanoma skin) and site-specific cancers (colorectal, lung, lymphoma, leukaemia) associated with first-line use of csDMARDs in patients with RA.Methods:We conducted a multinational cohort study informed by data from 7 healthcare databases including claims and electronic medical records from 4 countries (SIDIAP-Spain, MDCR-US Optum-US, CCAE-US, IQVIA AMBEMR-US, IQVIA-Germany, THIN-UK) part of the Observational Health Data Sciences and Informatics (OHDSI) network. All patients aged ≥18 years who initiated methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), or leflunomide (LEF) as first-line monotherapy after a diagnosis of RA between 2005 to 2018 were eligible. Individuals with a prior diagnosis of another inflammatory arthropathy or cancer, or <1 year of follow-up were excluded. Patients were followed from 1-year after treatment initiation to the earliest of incident cancer, loss to follow-up, or 5-years. Cox proportional-hazard models for MTX against each other csDMARD were performed after propensity score stratification. A large set of negative control outcomes were analysed to calibrate hazard ratios (cHRs). Estimates were pooled where homogeneity across sources was adequate (I2<0.4).Results:Across the databases, 127,547 RA patients initiating csDMARD therapy were included in the analyses (MTX: 73,996, HCL: 36,381 SSZ: 9,383 LEF: 7,787). The pooled incidence rate of overall cancer for MTX was 22.8 per 1,000 person years. The pooled summary and source-specific estimated cHRs for overall cancer are shown below in Figure 1. While little difference was seen for HCQ and SSZ compared to MTX, LEF was consistently associated with a reduced cancer risk: pooled cHR (95% CI) 0.67 (0.59 to 0.76) and cHRs ranged from 0.53 (0.36 to 0.80) in CCAE-US to 0.84 (0.58 to 1.22) in SIDIAP-Spain. There were insufficient cases to look site-specific cancers within data sources, although pooled results suggest little risk difference in leukemia, lymphoma, colorectal, or lung cancers.Figure 1.Calibrated hazard ratios (cHRs) of overall cancer risk with their respective confidence intervals (95%CI) by study database. Database estimates not reported where adequate covariate balance not attained. Meta-analysis results not reported where I2>0.4.Conclusion:Compared to MTX users, patients treated with LEF had a lower risk of overall cancer. Risk of four specific cancers did not differ by first line csDMARD exposure.Disclosure of Interests: :Talita Duarte-Salles: None declared, Martina Recalde: None declared, James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Karine Marinier Employee of: Servier, Yesika Díaz: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

scholarly journals Distribution, Source Appropriation, and Human Health Risk Assessment of Polycyclic Aromatic Hydrocarbons due to Consumption of Callinectes amnicola from Woji Creek in Sambreiro River

2021 ◽  
Vol 21 (05) ◽  
pp. 245-253
Author(s):  
Owhonda Chikeru Ihunwo ◽  
Millicent Uzoamaka Ibezim-Ezeani
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Surface Water ◽  
Cancer Risk ◽  
Aromatic Hydrocarbons ◽  
Age Groups ◽  
Excess Cancer Risk ◽  
Study Results ◽  
Polycyclic Aromatic ◽  
Toxicity Equivalent ◽  
Risk Of Cancer

Crabs (Callinectes amnicola) and surface water sampled from the Sambreiro River, Rivers State of Nigeria, were analyzed for polycyclic aromatic hydrocarbons concentrations for four months (December (2019), January, February, and March (2020)). Excess cancer risk due to ingestion of the crabs was assessed for individuals of the age groups: 3 to < 6 years, 16 to < 21 years, 21 to < 50 years, and ≥ 50 years. Although concentrations in surface water (ΣPAH16 = 0.125±011 mg/L) were lower than in the previous study, results obtained revealed considerably higher concentrations of aromatic hydrocarbons in crab tissues (ΣPAH16=10.659±2.399 mg/kg). Hepatopancreas (ΣPAH16=6.590±0.266 mg/kg) accumulated the highest concentration of hydrocarbons followed by the gills (ΣPAH16=2.349±0.029 mg/kg), then the muscles (ΣPAH16=1.720±0.320 mg/kg). Source appropriation results revealed a combination of the petrogenic and pyrogenic contribution of hydrocarbons in the crab tissues. The trend for the toxicity equivalent quotient was hepatopancreas > muscles > gills; while the excess cancer risk exceeded for all age groups, suggesting that humans are at risk of cancer arising from the ingestion of crab species from this study location.

scholarly journals A Meta-Analysis of Association Between the MMP-13 rs2252070 Promoter Polymorphism and Cancer Risk

2021 ◽  
Author(s):  
Peng Yuan ◽  
Yudi Chen ◽  
Youzhao Ma ◽  
Chengjuan Zhang ◽  
Pengfei Ren ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Promoter Polymorphism ◽  
Cochrane Library ◽  
Cancer Tissue ◽  
Cancer Type ◽  
Environment Interaction ◽  
Study Results ◽  
Risk Of Cancer

Abstract Background Originally detected in breast cancer tissue, MMP-13 has been showed to be closely related to cancer development. Increasing evidence has also suggested that rs2252070, one of its SNP, can profoundly influence cancer risk by regulating the expression while the conclusion still remained controversial. Therefore, this meta-analysis was conducted to assess the carcinogenesis effect of this SNP quantitatively. Methods Studies about association between rs2252070 polymorphism and cancer risk by March 15, 2020 had been collected in PubMed, Web of Science, Cochrane Library and CNKI. R scripts and STATA software were applied to calculate estimates. Pooled ORs and corresponding 95% CIs were used to evaluate the strength of association. Results Twenty studies meeting pre-defined criteria were retrieved for the final statistical analysis, including 8,215 cancer patients and 8,480 healthy controls. The pooled estimates revealed no statistical significance for the association between this polymorphism and the risk of cancer in all 5 genetic models. Similarly, no significance had been detected in stratified analyses by region, cancer type, sample size and genotyping method. Conclusion The association between MMP-13 rs2252070 and carcinogenesis was not statistically significant. To elucidate this conclusion, future studies including gene-gene and gene-environment interaction are needed to verify the study results.

scholarly journals Drug-induced cutaneous vasculitis developing during Etanercept treatment for rheumatoid arthritis

2021 ◽  
Vol 97 (4) ◽  
pp. 113-119
Author(s):  
Maria N. Chamurlieva ◽  
Yulia L. Korsakova ◽  
Stefka G. Radenska-Lopovok ◽  
Tatiana V. Korotaeva
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Tnf Inhibitors ◽  
Cutaneous Vasculitis ◽  
Inflammatory Rheumatic Diseases ◽  
Tnf Inhibitor ◽  
Drug Induced ◽  
Etanercept Treatment ◽  
Increased Risk

Biological disease-modifying anti-rheumatic drugs (bDMARDs) are widely used for the treatment of chronic inflammatory rheumatic diseases. Since the introduction of tumor necrosis factor alpha (TNF-) inhibitors, the treatment of rheumatoid arthritis has been revolutionized. The approach of targeting TNF- has considerably improved the success of the treatment of rheumatoid arthritis. Their effectiveness has been extensively proven in randomized clinical trials and in clinical practice. Randomized clinical trials and post-marketing studies proved that patients undergoing TNF- inhibitors therapy are at increased risk of infectious disease, bacterial, viral, fungal, opportunistic, oncology and skin adverse effects such as psoriasis and angiitis of the skin. In this case report drug-induced cutaneous vasculitis developing during TNF- inhibitor (Etanercept) treatment for rheumatoid arthritis is described.

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