- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02358343
A Trial of Sertraline vs. CBT for End-stage Renal Disease Patients With Depression {ASCEND} (ASCEND)
ASCEND: A Trial of Sertraline vs. CBT for End-stage Renal Disease Patients With Depression
Patients whose kidneys fail generally require dialysis treatments to sustain life. The ability of patients to make major adjustments in their lives for dialysis is hampered by depression that affects almost one-quarter of such individuals. There are no studies that have adequately tested whether treatment of depression is effective in dialysis patients and if there is any difference between the response to the two most commonly available forms of treatment, psychotherapy and anti-depressant drug therapy.
To fill this important gap in the investigators knowledge, the investigators propose to undertake (1) a randomized controlled clinical trial of 200 patients to test whether an engagement interview will result in a higher proportion of dialysis patients accepting treatment for depression; and (2) a randomized controlled clinical trial of 120 patients to determine whether there is any difference in the likelihood of improvement of depressive symptoms with psychotherapy or drug therapy among dialysis patients with depression. Patients in these studies will be enrolled from among individuals receiving care in 50 dialysis facilities in three metropolitan areas - Seattle, Dallas, and Albuquerque. The research proposal has been developed with the support of patients, caregivers, and stakeholders to ensure that the findings from the study are relevant to them and can be readily implemented in day-to-day clinical practice. Hence, the engagement interview and psychotherapy will be delivered in a dialysis facility to ease the burden on patients, and the dose of the study drug will be changed in partnership with the study participants. In addition to depressive symptoms, the effect of treatment on other meaningful outcomes such as fatigue and sleep will be determined.
The two forms of treatment for depression being tested in this clinical trial are very different from each other and patients differ with regards to the treatment option preferable and/or available to them. Successful completion of the clinical trial will provide patients, caregivers, and other stakeholders with the information that they would need when faced with a diagnosis of depression in patients undergoing hemodialysis. This will allow patients to select evidence-based treatments to improve outcomes that are relevant to them.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New Mexico
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Albuquerque, New Mexico, United States, 87131
- University of New Mexico
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Texas
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Dallas, Texas, United States, 75390
- University of Texas Southwestern
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Washington
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Seattle, Washington, United States, 98195
- University of Washington
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 21 years;
- Undergoing thrice-weekly maintenance HD for ≥ 3 months;
- Able to speak either English or Spanish;
- BDI-II score ≥ 15; and
- Meets diagnostic criteria for either current major depressive episode or dysthymia on the MINI.
Exclusion Criteria:
- Active suicidal intent;
- Ongoing psychotherapy or current treatment with certain anti-depressant drugs;
- Evidence of cognitive impairment on Mini-Cog;
- Present or past psychosis or bipolar disorder I or II on the MINI;
- Alcohol or substance abuse diagnosed on the MINI or history of such abuse in the past three months;
- Life expectancy < 3 months, in the judgment of the site principal investigator;
- Anticipated to receive living related donor kidney transplantation within 3 months;
- Pregnancy, or lactation, or women of childbearing age not willing to use adequate birth control;
- Clinical and/or laboratory evidence of chronic liver disease;
- History of significant active bleeding in the past three months, such as hospitalization for gastrointestinal bleeding;
- Current use of class I anti-arrhythmic medications (e.g., propafenone, flecainide), pimozide, monoamine oxidase inhibitors, reserpine, guanethidine, cimetidine, tri-cyclic anti-depressants, triptans, tramadol, linezolid, tryptophan, and St. John's wort; and
- Known hypersensitivity to sertraline.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Engagement Interview
Subjects will be randomly assigned to engagement interview or a control visit.Trained CBT therapists at each of the three sites will conduct the engagement interview.
The session will be aimed at improving the acceptance of the diagnosis of depression by patients and treatment for the same.
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An Engagement Interview will comprise a one-on-one session with the patient, during which the health-care provider will use reflective statements and non-judgmental listening techniques, will explore barriers to treatment, and will help patient articulate ambivalence about engaging in treatment.
This session will be enhanced with a 40-minute DVD that the subject will watch with the therapist in the dialysis facility.
The subject will be encouraged to take the DVD home with them and watch it with their family members as well.
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No Intervention: Control Visit
Subjects will be randomly assigned to engagement interview or a control visit.
Individuals assigned to control visit will be scheduled for a follow-up discussion with a member of the research team.
During this session, they will be informed of the diagnosis of major depression or dysthymia, the options for treatment available through the clinical trial, and alternatives should they decline participation in the clinical trial.
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Active Comparator: Cognitive Behavioral Therapy
The subjects will be randomly assigned to individual CBT or sertraline drug therapy using block randomization. Individuals will undergo 10 CBT sessions of 60 minutes each, by a trained therapist in the dialysis facility (8 weekly sessions; then every other week x 2). The CBT will be administered while the patient is undergoing HD; however, alternative arrangements will be made upon individual patient's preferences. |
Cognitive Behavioral Therapy (CBT) is a short-term psychotherapy that will focus on how the individual is thinking, behaving, and communicating today rather than on their childhood experience.
The therapist will assist the patient in identifying specific distortions (cognitive assessment) and biases in thinking and will provide guidance on how to change this thinking.
During the course of intervention, study subjects will undergo assessment of severity of depressive symptoms using Quick Inventory of Depressive Symptoms - Self-Report (QIDS-SR) every two weeks for the first six weeks (weeks 0, 2, 4, and 6) and every three weeks for the next six weeks (weeks 9 and 12).
Other Names:
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Active Comparator: Antidepressant Drug Therapy
The subjects will be randomly assigned to individual CBT or sertraline drug therapy using block randomization.
Anti-Depressant Drug Therapy will be delivered with sertraline, a selective serotonin reuptake inhibitor, and the dose will be titrated using the Measurement Based Care Protocol.
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The site investigators will prescribe sertraline drug at a starting dose of 25 mg oral tablets.
Dose titration will be implemented using standardized assessments of depressive symptoms and drug side effects; and the research team and the patient make joint decisions to maintain, increase, or decrease the dose.
This will help establish the highest effective but tolerable dose tailored for each patient.
The QIDS-SR scale will be used to assess the clinical response for dose titration.
The FIBSER scale will be used to assess side effects and the degree to which they interfere with day-to-day functions.
The participant-specific dose at week 6, up to a maximum of 200 mg/d, will be continued for the remaining 6 weeks.
Other Names:
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No Intervention: Observational Cohort
Subjects who (1) are not willing to participate in the clinical trial and (2) do not find any treatment acceptable outside the clinical trial will be invited to participate in the prospective observational cohort for serial assessment of depressive symptoms.These subjects will only undergo assessment of severity of depressive symptoms at weeks 0, 6, and 12 using QIDS-C.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Initiated Depression Treatment
Time Frame: within four weeks of engagement interview or control visit
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The primary measure of efficacy of the Engagement Interview will be the number of patients undergoing hemodialysis with co-morbid depression who initiate treatment for the condition. This will be defined as one of the following:
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within four weeks of engagement interview or control visit
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QIDS-C Score
Time Frame: Week 12 of treatment
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The Quick Inventory of Depressive Symptomatology Clinician-rated (QIDS-C) scale ranges from 0-27, higher scores indicate worse depression.
The primary measure of efficacy of Intervention will be the mean difference in QIDS-C score at Week 12 between treatment groups.
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Week 12 of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Accepted Depression Treatment
Time Frame: within two weeks of engagement interview or control visit
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The secondary measure of efficacy of the Engagement Interview will be the % of patients undergoing hemodialysis with co-morbid depression who are willing to accept treatment. This will be measured by the patient's intent and will be defined as one of the following:
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within two weeks of engagement interview or control visit
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BDI-II
Time Frame: Week 12
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Beck Depression Inventory-II, range 0-63, higher scores indicate worse depression
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Week 12
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GAD-7
Time Frame: Week 12
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Generalized Anxiety Disorder 7-item Scale, range 0-21, higher scores indicate worse anxiety
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Week 12
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Sheehan Disability Scale
Time Frame: Week 12
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range 0-30, higher scores indicate worse disability
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Week 12
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SF-36 Energy/Vitality
Time Frame: Week 12
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Energy/vitality subscale of the 36-Item Short Form Health Survey, range 0-100, higher scores indicate better energy/vitality
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Week 12
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Global Quality of Life Scale
Time Frame: Week 12
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range 0-10, higher scores indicate better quality of life
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Week 12
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Satisfaction With Life Scale
Time Frame: Week 12
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range 1-35, higher scores indicate better satisfaction
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Week 12
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Perceived Social Support
Time Frame: Week 12
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Multi-Dimensional Scale of Perceived Social Support, range 1-7, higher scores indicate better social support
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Week 12
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PSQI
Time Frame: Week 12
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Pittsburgh Sleep Quality Index, range 0-21, higher scores indicate worse sleep quality
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Week 12
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Exercise
Time Frame: Week 12
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Single item activity measure, range 1-6, higher indicates less activity
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Week 12
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Percentage of Dialysis Treatment Sessions Skipped and/or Shortened
Time Frame: Over 12 Weeks
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Treatment Adherence with Dialysis as defined by the percentage of all dialysis sessions skipped and/or requested by the patient to be shortened by ≥ 10 minutes over the 12-week intervention period.
Dialysis sessions missed due to hospitalization will not be included as a skipped treatment.
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Over 12 Weeks
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Percent Inter-dialytic Weight Gain
Time Frame: Week 12
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Treatment Adherence with Fluid Intake as defined by inter-dialytic weight gain (as % of post-dialysis weight) during Week 12 of the study
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Week 12
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Serum Phosphorus Level
Time Frame: Week 12
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Treatment Adherence with Diet and/or Medications as defined by Serum phosphorus level measured as a part of routine clinical care during the third month of participation in the study.
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Week 12
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Rajnish Mehrotra, MD, University of Washington
Publications and helpful links
General Publications
- Weisbord SD, Fried LF, Mor MK, Resnick AL, Unruh ML, Palevsky PM, Levenson DJ, Cooksey SH, Fine MJ, Kimmel PL, Arnold RM. Renal provider recognition of symptoms in patients on maintenance hemodialysis. Clin J Am Soc Nephrol. 2007 Sep;2(5):960-7. doi: 10.2215/CJN.00990207. Epub 2007 Aug 8.
- Cukor D, Ver Halen N, Asher DR, Coplan JD, Weedon J, Wyka KE, Saggi SJ, Kimmel PL. Psychosocial intervention improves depression, quality of life, and fluid adherence in hemodialysis. J Am Soc Nephrol. 2014 Jan;25(1):196-206. doi: 10.1681/ASN.2012111134. Epub 2013 Oct 10.
- Weisbord SD, Fried LF, Arnold RM, Fine MJ, Levenson DJ, Peterson RA, Switzer GE. Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients. J Am Soc Nephrol. 2005 Aug;16(8):2487-94. doi: 10.1681/ASN.2005020157. Epub 2005 Jun 23.
- Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003 Sep 1;54(5):573-83. doi: 10.1016/s0006-3223(02)01866-8. Erratum In: Biol Psychiatry. 2003 Sep 1;54(5):585.
- Wisniewski SR, Rush AJ, Balasubramani GK, Trivedi MH, Nierenberg AA; STARD Investigators. Self-rated global measure of the frequency, intensity, and burden of side effects. J Psychiatr Pract. 2006 Mar;12(2):71-9. doi: 10.1097/00131746-200603000-00002.
- Duarte PS, Miyazaki MC, Blay SL, Sesso R. Cognitive-behavioral group therapy is an effective treatment for major depression in hemodialysis patients. Kidney Int. 2009 Aug;76(4):414-21. doi: 10.1038/ki.2009.156. Epub 2009 May 20.
- Davison SN, Jhangri GS. The impact of chronic pain on depression, sleep, and the desire to withdraw from dialysis in hemodialysis patients. J Pain Symptom Manage. 2005 Nov;30(5):465-73. doi: 10.1016/j.jpainsymman.2005.05.013.
- Hedayati SS, Bosworth HB, Kuchibhatla M, Kimmel PL, Szczech LA. The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients. Kidney Int. 2006 May;69(9):1662-8. doi: 10.1038/sj.ki.5000308.
- Kimmel PL, Peterson RA, Weihs KL, Simmens SJ, Alleyne S, Cruz I, Veis JH. Multiple measurements of depression predict mortality in a longitudinal study of chronic hemodialysis outpatients. Kidney Int. 2000 May;57(5):2093-8. doi: 10.1046/j.1523-1755.2000.00059.x.
- Hedayati SS, Bosworth HB, Briley LP, Sloane RJ, Pieper CF, Kimmel PL, Szczech LA. Death or hospitalization of patients on chronic hemodialysis is associated with a physician-based diagnosis of depression. Kidney Int. 2008 Oct;74(7):930-6. doi: 10.1038/ki.2008.311. Epub 2008 Jun 25.
- System, U.S.R.D., US Department of Public Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, 2012.
- Glassman AH, O'Connor CM, Califf RM, Swedberg K, Schwartz P, Bigger JT Jr, Krishnan KR, van Zyl LT, Swenson JR, Finkel MS, Landau C, Shapiro PA, Pepine CJ, Mardekian J, Harrison WM, Barton D, Mclvor M; Sertraline Antidepressant Heart Attack Randomized Trial (SADHEART) Group. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002 Aug 14;288(6):701-9. doi: 10.1001/jama.288.6.701. Erratum In: JAMA 2002 Oct 9;288(14):1720.
- Cukor D, Rosenthal DS, Jindal RM, Brown CD, Kimmel PL. Depression is an important contributor to low medication adherence in hemodialyzed patients and transplant recipients. Kidney Int. 2009 Jun;75(11):1223-1229. doi: 10.1038/ki.2009.51. Epub 2009 Feb 25.
- Kutner NG, Zhang R, McClellan WM, Cole SA. Psychosocial predictors of non-compliance in haemodialysis and peritoneal dialysis patients. Nephrol Dial Transplant. 2002 Jan;17(1):93-9. doi: 10.1093/ndt/17.1.93.
- Atalay H, Solak Y, Biyik M, Biyik Z, Yeksan M, Uguz F, Guney I, Tonbul HZ, Turk S. Sertraline treatment is associated with an improvement in depression and health-related quality of life in chronic peritoneal dialysis patients. Int Urol Nephrol. 2010 Jun;42(2):527-36. doi: 10.1007/s11255-009-9686-y. Epub 2009 Dec 2.
- Cukor D, Coplan J, Brown C, Peterson RA, Kimmel PL. Course of depression and anxiety diagnosis in patients treated with hemodialysis: a 16-month follow-up. Clin J Am Soc Nephrol. 2008 Nov;3(6):1752-8. doi: 10.2215/CJN.01120308. Epub 2008 Aug 6.
- Hedayati SS, Minhajuddin AT, Toto RD, Morris DW, Rush AJ. Validation of depression screening scales in patients with CKD. Am J Kidney Dis. 2009 Sep;54(3):433-9. doi: 10.1053/j.ajkd.2009.03.016. Epub 2009 Jun 3.
- Mehrotra R, Cukor D, Unruh M, Rue T, Heagerty P, Cohen SD, Dember LM, Diaz-Linhart Y, Dubovsky A, Greene T, Grote N, Kutner N, Trivedi MH, Quinn DK, Ver Halen N, Weisbord SD, Young BA, Kimmel PL, Hedayati SS. Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial. Ann Intern Med. 2019 Mar 19;170(6):369-379. doi: 10.7326/M18-2229. Epub 2019 Feb 26.
- Hedayati SS, Daniel DM, Cohen S, Comstock B, Cukor D, Diaz-Linhart Y, Dember LM, Dubovsky A, Greene T, Grote N, Heagerty P, Katon W, Kimmel PL, Kutner N, Linke L, Quinn D, Rue T, Trivedi MH, Unruh M, Weisbord S, Young BA, Mehrotra R. Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND). Contemp Clin Trials. 2016 Mar;47:1-11. doi: 10.1016/j.cct.2015.11.020. Epub 2015 Nov 24.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Urologic Diseases
- Renal Insufficiency
- Renal Insufficiency, Chronic
- Depression
- Depressive Disorder
- Kidney Diseases
- Kidney Failure, Chronic
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Sertraline
- Antidepressive Agents
Other Study ID Numbers
- 48647
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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