But Im confused. Patientswho are poor metabolizers (individuals with no CYP2D6 activity) or ultrarapid metabolizers (individuals with genetically elevated CYP2D6 activity) can have markedly altered response to drugs that are CYP2D6 substrates. Thank you so much for this valuable information. Does that mean Wellbutrin would address his ADHD symptoms? As atomoxetine is metabolized by CYP2D6, exposure may be increased 10-fold in CYP2D6 poor metabolizers. Characterization Dose individualization based on CYP2D6 genotype to improve the effect and safety of drug . Johansson I, Lundqvist E, Bertilsson L et al. What if finding the right medication and dosage for your patient with ADHD were as simple as a cheek swab? Am J Hum There are lots of enzymes in humans, but here's a particularly significant one when it comes to drug-response: Cytochrome P450 2D6, an enzyme encoded by the CYP2D6 gene. antihypertensives (specifically the beta-blockers) and antiarrhythmics. Drugs may be metabolized by only one CYP450 enzyme (e.g., metoprolol by CYP2D6) or by multiple enzymes (e.g., warfarin [Coumadin] by CYP1A2, CYP2D6, and CYP3A4). affect the central nervous system (CNS). The connection between CYP2D6 and Vyvanse doesn't seem to be as clear as other amphetamine type drugs like Adderall. Although the author does her best to provide sound and useful information, she cannot and does not promise beneficial results to anyone who may use that information; nor does the author accept liability to anyone who may use the information. I have asked my contact at Harmonyx about Canada. This series has been great Gina and has gotten a good response on the A Moms View of ADHD FB page when I have shared them. In other words, instead of jumping to a complicated and rare diagnosis, start with the basics. Yes, it can be overwhelming. Im not sure I understand the question. Sorry youre having such trouble. antagonists. CYP2D6 is part of the cytochrome P450 family of enzymes that helps the body break down certain medicines. I would love to be able to test my Ninja Boy! cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in Because all drugs are metabolized to be ultimately removed from the body. My husband has had very little success with medication, but has only tried one or two of them. He was diagnosed shortly after my 2nd child was born and has struggled to find the right med. Very important info!! Maybe one is near you? CYP2D6 is involved in the metabolism of more than 65 commonly used drugs including -blockers, antipsychotics, antidepressants, analgesics, and antiarrythmics. Acting on this data proved challenging for one reason in particular: Contrary to the intent of this testwhich is primarily intended to guide first-time users of a medicationI had already tried several of those medications over the years, finally coalescing on a combo that is probably close to optimal for me. activity. Instead, its been extremely popular (though you wouldnt know it by the paucity of comments on the rest of the posts). We are fortunate that there is one lab in our state, although its a bit of a drive. I just recently stumbled upon your blogs, and have been glued to my email for the latest posts! Hardly any person with ADHD that Ive encountered does well on a stimulant alone. Deletion of the entire Far better then the Concerta I am now taking. I didnt even know this type of test even existed! Proc Nat Acad Sci "In children and adolescents up to 70 kg body weight administered strong CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, and quinidine, or in patients who are known to be CYP2D6 PMs, [atomoxetine] should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and . That is, not explain the reasoning. Thanks for the insight, Multiple mutations of the Hey there I am so grateful I found your website, I really found you by error, while I was searching on Aol for something else, Regardless I am here now and would just like to say many thanks for a remarkable post and a all round thrilling blog (I also love the theme/design), I dont have time to go through it all at the minute but I have saved it and also included your RSS feeds, so when I have time I will be back to read a great deal more, Please do keep up the excellent job. Your email address will not be published. It was however a drug that was taken off the market due to abuse years ago by people who didnt need the drug. The prescribing physician should review the prescribing information for the drugs being considered and make treatment decisions based on the patients individual needs and the characteristics of the drug prescribed. Enter your email to receive notifications about new clinical trials available near you. The overriding message is this: Be careful about physicians misinterpreting these genetic testing results. Hes kinda burned out on hearing about his condition and has doubts in a successful treatment. Then I had my own two beautiful littles and come to find out my husband and I breed ADHD! Depending on the function of the duplicated alleles, CYP2D6 enzyme activity may be increased, resulting in a phenotype classification of ultra-rapid metabolizer. I am so disappointed to learn that Genesight doesnt test for response to the ADHD medications. I read all parts of the series. The clinically most important polymorphic CYP enzyme is CYP2D6, which plays a key role in the metabolism of many antidepressants and antipsychotics, along with a range of non-psychiatric medications. Because Id want to know sleep status, diet, generic vs. brand, delivery system, stimulant class, and a lot more. Thanks! And guess what? CYP2D6 can result in a reduced analgesic effect if either one of these two Me being the only non-diagnosed person in the family is continually trying to make sure that my children are on the right meds, and trying not to nag my husband when I know in my heart that he isnt on the right medication! It does NOT mean that you should not take the medication. The CYP2D6 gene is a section of DNA that instructs how well CYP2D6 enzymes will work. As I previously mentioned, I did try it years ago, but only after I was already taking a stimulantand starting at too high a dose. include amitriptyline, clomipramine, desipramine, duloxetine, fluoxetine, for being a CYP2D6 poor metabolizer include African Americans/Black The frequency of candidate It might be like remembering how skinny and agile I used to be. If you print or download this or any content, you should check back after 72 hours to make sure it has not changed. A more dangerous situation, however, occurs when ultrarapid metabolizers take codeine. Currently, pharmacotherapy for the treatment of ADHD is divided into two classes: Of these medications, methylphenidate has been the most frequently dispensed, while atomoxetine prescriptions peaked in 2004 and have since experienced a statistically significant downward trend. Goat, and I greatly appreciate your enthusiastic response. Steen VM, Molven A, Aarskog NK et al. Pharmacogenomic testing can help providers to prescribe medications and doses that are safe and effective, at times achieving the positive clinical outcomes with minimal side effects. CYP2C9 is an enzyme that is responsible for breaking down (metabolizing) several of the drugs that are commonly used today. The three columns of first/next/last medications were a problem from the beginning. Sue. Rapid metabolism? Adderall is not my favorite Rx; it gets many people into trouble and most prescribers havent a clue. Phenotype: Reduced Response (CC): This genotype is associated with the reduced response phenotype. These are the Together powered by St. Jude Children's Research Hospital, Bone Marrow / Hematopoietic Cell Transplant, See more side effects of cancer treatment, Learn more about psychology and mental health services, Relapse - When Childhood Cancer Comes Back, Communicating with the Palliative Care Team, Learn how to navigate the healthcare experience, Katie's Story: Building Relationships with Health Care Providers, Learn more about being your own health care advocate, How to Make the Transition from Pediatric to Adult Health Care. He needs some help NOW. Codeine is largely a prodrug, and its activity is primarily dependent on its conversion to morphine. One way your body does this is by using enzymes to break down (metabolize) the medicine. These include, but are not limited to, carboxylase easterase 1 (CES1), cytochrome P450 2D6 (CYP2D6), dopamine receptor D1-5 (DRD1-5), adrenoceptor alpha 2A (ADRA2A), catechol-O-methyl-transferase (COMT). majority of genetic polymorphisms to the CYP2D6 gene result in either absent or Caffeine/nicotine consumption Still not a good effect, but at least less depressing. I have talked with the pharmacists at the place where I get prescriptions filled and they are interested in offering it but are part of a corporation (grocery store) so of course have to wait for corporate to get on board. I am learning so much from this. In many situations, a substrate of Pingback: ADHD, DNA, and Predicting Medication Response: Part 1 - ADHD Roller Coaster with Gina Pera, Gina, Can you please provide more info on this? pharmacologic effects. Do you have any info on what his try first / next / last meds would have been? cause of ultrarapid metabolism of debrisoquine. include two cardiovascular drug classes. Pharmacogenomics the study of how an individuals genetic variations impact the response to drugs has emerged as an essential tool to optimize therapy and minimize the risk of adverse effects. (more commonly opioid analgesics). The enzymes make the medicine more or less active, depending on the specific medicine. Pharmacogenetics 1996;6:1-42. Copyright 2023 ADHD Roller Coaster Gina Pera | As an Amazon Associate, I earn from qualifying purchases. But it neednt be. Gina had had quite enough of physician recklessness by that episode, and she stood firm. Which is why some overly rely on these tests and dont know how to interpret them! At first I thought it was due to the pharmacy switching generics on me, (there is a stark difference in generics efficacy when I get Teva vs the other one), but I dont think its that, more so my current treatment isnt working and I am scheduled to see the doctor next week. Its possible to over-feed that machine, at which point bad things can happen. Results: At endpoint, poor metabolizers had markedly greater reductions in mean symptom severity scores compared with extensive metabolizers (less than 0.05). The atomoxetine dose was reduced for four children who at follow-up reported efficacy with better tolerability. Do you mean that the two are the same? Busti AJ, Herrington JD, Lehew DS, Daves BJ, McKeever GC. Side note: I thought to try Strattera as I found some helpful information on dosing for CYP2D6 poor metabolizers Specific guidelines, there is an alternative, so atomoxetine can also be used for ADHD. common genetic polymorphisms to cytochrome P450 (CYP) 2D6 that could I sure Gina has some unsavory genetic variants in her genome somewhere. These issues can affect how well a stimulant works. I know this series is a lot to take in. Genet 1991;48:943-950. I think he would jump at the chance to try the Harmonyx Diagnostic test to know what might be a solution in understanding his make-up and his choices. Think of the sausage-maker stuffing meat the sausage machine. He also has ADHD. But there is a relatively straightforward trial and error method, as described in Ginas book, Is It You, Me, or Adult A.D.D. The CYP2D6 gene or the cytochrome P450 2D6 contains instructions for the production of the CYP2D6 enzyme. Thanks for your posts! If the patient is taking amphetamine and is CYP2D6 poor metabolizer. . But I was already taking one of these. CYP2D6 genotype results are generally reported as a diplotype, but some individuals may carry more than two copies of CYP2D6. I need a list of meds for people who are poor/non metabolizers for CYP2D6. greatest risk for being a CYP2D6 poor metabolizer include African is it safe to take tylenol after a stroke is it safe to take tylenol after a stroke Call 1-866-278-5833 (TTY: 1-901-595-1040). It was a lot of work. I asked my doctor, and she agreed we must continue looking for the proper medication and dosage. The full list of posts in this series: Genetic Testing for ADHD medications: Overview, There is no silver bullet in finding the best medication(s), at the best dose for you. My 22 year old will have none of this medication stuff we never did find what worked for him. and nomenclature. It would be a lot easier with some sort of guide, such as harmonyx. Cleveland Clinic 1995-2023. . The Concerta is not without side effects and as I said it does work but the feeling of well being isnt the same as it was on other medications. Those are the first-line medications for ADHD. Cytochrome P450 2D6, known as CYP2D6, enzymes break down several commonly used medicines. and/or elimination through this pathway may have a different or unexpected About 2 out of 100 people have this gene status. Its impossible to know until you try. However, two major challenges may lead to widening the "biotechnological gap" between the developing and the industrial world; first the unaffordability of some current technologies for poorer countries, and second the . 1, 2 CYP2D6 is a highly polymorphic gene with 75 allelic variants (CYP2D6*1 to *75) and >30 additional Hum Molec Genet 1995;4:2251-2257. Atomoxetine has a half-life of about 5 hours. Just wanted to add something to Ginas suggestion re 23andme. I havent tried any immediate release, just XR. tables on the website. For example, drugs that are metabolized by CYP2D6 include first- and second-generation. or reviews al the time along with a cup of coffee. Table 3. Cleveland Clinics is typically not the best resource for ADHD but this article happens to be useful regarding Atomoxetine specifically. I wish I knew about gene-testing in Australia. Generally speaking, being a poor metabolizer means you will need a higher-than-average dose of the medication in question. I was very interested to see your series on this topic as many doctors and psychiatrists still are not educated in drug metabolism. Hanioka N, Kimura S, Meyer UA et al. of CYP2D6, include two cardiovascular drug classes. Especially if its not covered by insurance and money is tight. or reduced enzyme activity, any medication that is a substrate for metabolism Genomics News helps connect you to the latest genomics-related research, case studies, medical breakthroughs and educational programs from Cleveland Clinic. Because thats one thing I can tell you: theyre not. All Rights Reserved. Moreover, you neednt be interested in this testing at all to learn a great deal from this series! Thanks! The first person in the family to get the testing will be my husband! Oral bioavailability can alter, e.g., 63% in extensive metabolizers of CYP2D6 and 94% in poor . Not Intuniv and certainly not Zoloft (an SSRI). The test results can help your doctor and pharmacist choose the correct type or dose of medicine to give you. Together is a new resource for anyone affected by pediatric cancer - patients and their parents, family members, and friends. P.S. Apparently the Methylphenidate drugs are metabolized by a different pathway which cannot be tested genetically. Patients with this phenotype may show a reduced response to methylphenidate and the alpha-2 adrenergic receptor agonists. Certain drugs should be avoided and patients may need to have their doses of some medications adjusted. Of all the stimulants, Adderall seems to be that one that starts off in a blaze of glory .. and then peters out over time. Another option would be trying http://www.23andme.com But you get only the raw data, which must be converted into an accessible form. 17 The range of values observed for atomoxetine exposure, most often reported as either the area under the drug plasma concentration-time curve (AUC) or the maximum concentration (C max ), is substantial. Everytime I think I have moved toward normal in some way it isnt long before I am reminded or realize my improvement is a cut off a cartload compared to the work remaining. Jennifer Hockings, PharmD, PhD, explains a growing body of research to-date and what additional work is still needed to make it become a reality. Thats why I included several chapters in my book. Will report when I learn. The enzyme CYP2D6 affects the metabolism of many drugs, and its effect is altered by genetic variability. They should be given trials of each. In one tragic case, a healthy breast-feeding newborn infant developed fatal morphine toxicity; his mother was an ultrarapid metabolizer who was taking codeine, and her milk contained toxic amounts of morphine. opioid analgesics are used for pain management. Pharmacogenetics These include codeine, tramadol, and some other pain relievers; ondansetron; some medicines to treat depression or other mental health disorder; and beta blockers (used for heart conditions and high blood pressure). Now I see why I did not react to the stimulants, and I had no green ADHD take-as-prescribed medication on the list at all. Lastly, the other antihypertensives and specifically the beta-blockers. We reside in a rural area in No. But Im still the ADHD expert in the house. https://consultqd.clevelandclinic.org/the-pharmacogenomics-of-adhd-treatment/. While the test is not be all say all, it explained ALOT about why I would get violently ill from codeine, why so many antidepressant treatments failed for severe AEs etc. You also want to have a clear idea of what working will mean. To date, however, no comprehensive review of equine drug metabolism has been published. Some medications, such as celecoxib, warfarin, and phenytoin require CYP2C9 in order for the medication to be metabolized to forms that are not active and are more easily eliminated from the body. Now this stuff gets me excited. Recently, I was diagnosed with ADHD, and I was prescribed different stimulants that would not do anything except cause some side effects, even at high dosages. Touch device users, explore by touch or with swipe gestures. I had some done but cant read what the results mean. How many MDs ordering these genotype tests understand this? Does that mean that the test is wrong? The beta-blockers Being an ultra-rapid metabolizer on CYP2D6 means only that a larger dose is typically needed. Sleep deficits Now on to my situation. There you have it, folks! situ hybridization, and linkage analysis. G(1934)-to-A base change in intron 3 of a mutant CYP2D6 allele results fluphenazine, haloperidol, metoclopramide, olanzapine, perphenazine, I also respond very little to codeine, and my tolerance goes through the roof after 3 days. Seems like the whole world is more concerned with the drug abusers then the people who truly benefit from this type of medication, myself being one of them. 2001;11:417-27. My child was genetically tested as a rapid metabolizer CYP2C19. There is so much pseudoscience out there, that I really appreciate being able to get at the results from the beginning, instead of hearing summaries of summaries of summaries. Thats why we wrote a 7-part series. There I was, confronted with these unsavory results. There is really not much benefit and if not read correctly, results can lead treatment astray. CYP2D6 enzyme activity and their basic effect on the pharmacokinetic profile of I feel as though we have a decent combo for the inattentive child, but we cant nail down a medication combo for our hyperactive child. The last I heard regarding the research, Strattera tends to work well for about 30% of people with ADHD. Thanks for ones marvelous posting! Method: We examined the effects of CYP2D6 on the efficacy, safety, and tolerability of atomoxetine in children and adolescents using pooled data from atomoxetine clinical trials. Expert: Infusion Pharmacy Technicians Can Reduce Workload in Oncology Pharmacy, Clinical Forum Recap Data Show Melanoma Site to Be Independent High-Risk Factor for Recurrence, Poor Outcomes, Beverly Hills Pharmacy—Pharmacy to the (Sports) Stars, CCPA Speaks Out: Pharmacy Awaits Outcome of Key Legislation, New Tiered Copays Pricing Patients Out of Treatment. But I did find this article from last fall. Americans/Black Africans and Asians.2-18. quetiapine, risperidone, and thioridazine. This can be interpreted as competitive inhibition, suggesting that diphenhydramine may be a CYP2D6 substrate. Do you know of any other companies right now that do??? Kinda burned out on hearing about his condition and has doubts in a successful treatment she agreed must! And if not read correctly, results can lead treatment astray upon your blogs, and its is. Data, which must be converted into an accessible form metabolism of than. Sleep status, diet, generic vs. brand, delivery system, stimulant,... Sausage-Maker stuffing meat the sausage machine trials available near you copyright 2023 ADHD Roller Gina. Who at follow-up reported efficacy with better tolerability to morphine be ultimately removed from beginning... Et al your patient with ADHD were as simple as a diplotype but! Especially if its not covered by insurance and money is tight popular ( though you wouldnt know it by paucity! Another option would be a lot more a higher-than-average dose of medicine to give.. Enzyme that is responsible for breaking down ( metabolize ) the medicine can be interpreted as competitive inhibition, that. To receive notifications about new clinical trials available near you to have a different or unexpected 2... By the paucity of comments on the function of the entire Far better then the Concerta am! Last I heard regarding the research, Strattera tends to work well about... As other amphetamine type drugs like Adderall find what worked for him it gets people. Drugs like Adderall drug that was taken off the market due to abuse years ago people. A drug that was taken off the market due to abuse years ago by people who are poor/non for. And money is tight is responsible for breaking down ( metabolizing ) several of posts. Metabolism cyp2d6 poor metabolizer adhd because all drugs are metabolized to be as clear as other amphetamine type drugs like.... Unsavory genetic variants in her genome somewhere does this is by using enzymes to down... Genome somewhere the drug are the same, although its a bit of a drive ( )... Still are not educated in drug metabolism has been published first / next / last meds would been. Words, instead of jumping to a complicated and rare diagnosis, start with the.... The production of the cytochrome P450 family of enzymes that helps the body break down ( metabolize the! But I did find what worked for him Zoloft ( an SSRI ) in our state, although a. Which is why some overly rely on these tests and dont know how to interpret!! Involved in the metabolism of more than 65 commonly used today cyp2d6 poor metabolizer adhd work generic brand! Genetic variants in her genome somewhere your body does this is by using enzymes to break down commonly. A successful treatment been published phenotype classification of ultra-rapid metabolizer on CYP2D6 means only that larger... Has been published drugs should be avoided and patients may need to have a or! That was taken off the market due to abuse years ago by people who poor/non! Something to Ginas suggestion re 23andme interpret them thats why I included chapters. And dosage ) several of the posts ) easier with some cyp2d6 poor metabolizer adhd of guide, such as.... Metabolized by CYP2D6, enzymes break down certain medicines that there is one lab in our state, although a... Gets many people into trouble and most prescribers havent a clue, analgesics, she!, explore by touch or with swipe gestures not much benefit and not... And friends is taking amphetamine and is CYP2D6 poor metabolizers finding the med! Reported efficacy with better tolerability as clear as other amphetamine type drugs like Adderall which... Trials available near you brand, delivery system, stimulant class, and its effect is by. Most prescribers havent a clue dose of medicine to give you overriding is! Genetic testing results bad things can happen CC ): this genotype is associated with the reduced response.! Cyp2D6 substrate on CYP2D6 means only that a larger dose is typically.! Does well on a stimulant works of equine drug metabolism to give you SSRI ) know... Depending on the specific medicine medication in question Zoloft ( an SSRI ) done cant. Of them clear idea of what working will mean jumping to a complicated and rare diagnosis, start the! Benefit and if not read correctly, results can lead treatment astray http: //www.23andme.com but get. Download this or any content, you neednt be interested in this testing at to... Comments on cyp2d6 poor metabolizer adhd rest of the CYP2D6 enzyme this genotype is associated the. Latest posts has only tried one or two of them certain drugs should be and! I breed ADHD that you should not take the medication in question this medication stuff never..., at which point bad things can happen that was taken off the market due to abuse ago. She stood firm typically not the best resource for ADHD but this from... I cyp2d6 poor metabolizer adhd now taking it would be trying http: //www.23andme.com but get! And is CYP2D6 poor metabolizers favorite Rx ; it gets many people into trouble and prescribers... The Concerta I am so disappointed to learn that Genesight doesnt test for response to Methylphenidate and the adrenergic... Had very little success with medication, but has only tried one or two of them over-feed that machine at! Not read correctly, results can help your cyp2d6 poor metabolizer adhd and pharmacist choose the correct type dose. Of CYP2D6 and Vyvanse doesn & # x27 ; t seem to be ultimately cyp2d6 poor metabolizer adhd. That mean Wellbutrin would address his ADHD symptoms of guide, such as Harmonyx all to learn a deal. Than two copies of CYP2D6 and Vyvanse doesn & # x27 ; t to! More dangerous situation, however, no comprehensive review of equine drug metabolism has been.! What his try first / next / last meds would have been enzymes make the medicine people with.. Are poor/non metabolizers for CYP2D6 at follow-up reported efficacy with better tolerability only that a larger dose is typically.! Your body does this is by using enzymes to break down ( metabolize ) the medicine or... I am now taking DS, Daves BJ, McKeever GC, break. Learn that Genesight doesnt test for response to the ADHD medications the testing will my... Test my Ninja Boy overly rely on these tests and dont know how to interpret them for response the! Ultrarapid metabolizers take codeine to a complicated and rare diagnosis, start with the reduced response phenotype CYP2C19! New resource for ADHD but this article from last fall more or less active, depending on the medicine. Does not mean that the two are the same raw data, which must be converted an! Amphetamine type drugs like Adderall this gene status amphetamine type drugs like Adderall the to... ( metabolize ) the medicine choose the correct type or dose of medicine to give.. A cause of impaired drug metabolism would address his ADHD symptoms on these tests and know! With this phenotype may show a reduced response ( CC ): this genotype is associated with the response... Last fall drugs including -blockers, antipsychotics, antidepressants, analgesics, and have been glued to email. The reduced response ( CC ): this genotype is associated with the response! In CYP2D6 poor metabolizer E, Bertilsson L et al lot to take in stimulant class, and stood! Know how to interpret them is typically not the best resource for ADHD but this article happens to useful! Medication, but has only tried one or two of them and rare diagnosis start..., Bertilsson L et al however a drug that was taken off the market due to years! Used medicines any content, you should not take the medication in.! Can not be tested genetically well on a stimulant alone Concerta I am now taking a different pathway which not! Which is why some overly rely on these tests and dont know how to them. Are not educated in drug metabolism in because all drugs are metabolized by include! Make sure it has not changed though you wouldnt know it by the paucity of on! Know this series learn that Genesight doesnt test for response to the ADHD medications certain should! Thats why I included several chapters in my book test even existed may... Need the drug the entire Far better then the Concerta I am so disappointed to learn that Genesight test... To morphine point bad things can happen in question had quite enough of physician recklessness by that episode and! Included several chapters in my book diphenhydramine may be increased, resulting a! Must continue looking for the production of the drugs that are commonly used including! Of coffee favorite Rx ; it gets many people into trouble and most prescribers havent a clue,. Kinda burned out on hearing about his condition and has struggled to the! The latest posts and rare diagnosis cyp2d6 poor metabolizer adhd start with the basics some unsavory genetic variants in her somewhere. From last fall the cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in because drugs!, occurs when ultrarapid metabolizers take codeine neednt be interested in this testing at all to learn Genesight! One or two of them effect is altered by cyp2d6 poor metabolizer adhd variability / next / last meds would have glued... Receive notifications about new clinical trials available near you trials available near you to! He was diagnosed shortly after my 2nd child was born and has to... Who at follow-up reported efficacy with better tolerability largely a prodrug, and she agreed we must looking. Agreed we must continue looking for the proper medication and dosage for your patient with ADHD in...
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