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Update - Week 40, 2018
Curated by Peter Lansberg,
a Dutch lipidologist and educator, and
reviewed by prof. Philip Barter, Past President of the
International Atherosclerosis Society.
The IAS Statin Newsletter will keep you up-to-date with all recent statin publications, using a curated approach to select relevant articles.

Key publications

Evaluation effects of statins in dialysis requiring AKI
The Taiwanese National Health Insurance Research Database (NHIRD) is a valuable source of retrospective, observational data in a wide range of (Chinese) patients. In this recent analysis the authors examined the impact of statin use on survival in patients that were diagnosed with acute kidney injury (AKI) and required dialysis. Between January 1, 2000, and December 31, 2012 6091 patients were hospitalized for AKI-D; patients were followed up until December 31st, 2013. In total data of 1271 statin users was compared to 4820 patients that did not use statins using a propensity score matching model. In hospital and 1-year mortality were the predefined outcomes of this analysis. Death occurred in 492 of 1271 statin users (38.7%) and 2365 of 4820 statin nonusers (49.1%) after 1-year follow-up; HR: 0.79 (0.69-0.9; P<.001). For in hospital mortality benefits of statin use were observed as well; HR: 0.84 (0.71-0.99; P=.04). Results were very similar in a broad range of subgroups and seemed to be dose as well as adherence dependent. In patients that were compliant benefits outweighed the intention to treat analysis outcomes HR: 0.44 (0.36-0.53; P<0.001 vs 0.79 (0.69-0.9; <P,0.001), respectively. The authors concluded that statin use in patients with AKI-D proofed to be beneficial showing significant reduction in hospital and 1-year mortality rates, but before definite conclusions can be drawn, additional clinical trials are warranted.
Wu CL, Kor CT, Chang CC et al. Association of Statin Use With Mortality After Dialysis-Requiring Acute Kidney Injury: A Population-Based Cohort Study. Mayo Clinic proceedings 2018; 93:1474-1483. http://www.ncbi.nlm.nih.gov/pubmed/?term=30286832
Bridging the knowledge gap: using statins in (very) elderly patients?
With our aging population the benefits or harms of statins in elderly, and especially in the very elderly patients (> 80years), becomes a clinically very relevant question. Clinical trials did not include large numbers of elderly patients. Resulting that there remains unanswered question. To discuss and address this knowledge gap the National Institute on Aging and the National Heart, Lung and Blood Institute convened a multidisciplinary expert panel from July 31 to August 1, 2017 to review existing evidence on the uses of statins in a primary prevention setting of patients >75 years. The expert panel decided that we lack evidence in elderly especially in those with concomitant frailty, polypharmacy, comorbidities, cognitive impairment. They also noted a lack of proper tools to evaluate CVD risk in the very elderly and a scarcity on relevant clinical outcomes, including muscle symptoms, cognitive function and new onset diabetes, in this patient category. Prospective, traditional, placebo-controlled, randomized clinical trials (RCTs) and pragmatic RCTs are needed to bridge this critical knowledge gap.  A better representation of (very) elderly patients in future clinical trials need to be considered; Large healthcare networks registries can be queried to confirm appropriate power for death and cardiovascular outcomes for future RCTs.
Singh S, Zieman S, Go AS et al. Statins for Primary Prevention in Older Adults-Moving Toward Evidence-Based Decision-Making. J Am Geriatr Soc 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30277567
Exploring the statin legacy effect

In this meta-analysis of the major large primary and secondary prevention statin trials, post-trial long-term benefits of statin therapy is evaluated. Included were 8 trials (3 primary prevention and 5 secondary prevention studies) with a post-trial follow-up of 1.6 -15.1 years. During the prolonged follow up 13 781 post-trial deaths including 6 685 CVD deaths were recorded. Overall there was a significant benefit on total mortality (P=0.01) but not for CVD deaths. In the pooled analysis of the primary prevention trials, risk of CVD mortality was reduced, HR=0.87 (0.79-0.95, p=0.003) and significantly improved total mortality benefit, HR=0.90 (0.85-0.96; P<0.001), as well. One of the main limitations of this report is that the findings are based on aggregate data and not individual data. The earlier the better strategy to reduce long term reduce CVD risk has not been tested in RCT and it is unlikely that such a very large and expensive trial will be effectuated. Indirect evidence from post-trial follow-up of the large statin trials, as was attempted in this meta-analysis, is the most realistic strategy to explore the legacy effect hypothesis for statins in the future.
Nayak A, Hayen A, Zhu L et al. Legacy effects of statins on cardiovascular and all-cause mortality: a meta-analysis. BMJ Open 2018; 8:e020584. http://www.ncbi.nlm.nih.gov/pubmed/?term=30287603
Understanding statin induced pro-diabetogenic effects
The pro-diabetogenic effects of statins remain poorly understood. In this small trial the effects of simvastatin were studied in 20 male subjects; 10 considered pre-diabetics (HbA1C 5.7± 0.1%) and 10 were healthy individuals (HbA1C 5.1 ± 0.1%). The aim was to study the effects of simvastatin on skeletal muscles (biopsies) capacity to oxidize lipids and expression of the major proteins regulating lipid uptake, synthesis, lipolysis, and storage. Simvastatin use was associated with impaired glucose tolerance, but no differences could be discerned in fat oxidation at rest or during exercise. Changes were observed in muscle protein content with lower concentrations of CD36, lipoprotein lipase and diacylglycerol acyltransferase (DGAT) 1 as well as DGAT 2 in simvastatin treated individuals. The authors concluded that changes in muscle lipid uptake and lipid synthesis play an important role in the observed simvastatin induced insulin resistance. A reduced capacity to synthesize FA and diacylglycerol (DAG) into triacylglycerol results into decreased lipid synthesis capacity and subsequently accumulation of lipotoxic intermediates (FA and DAG) in skeletal muscle, inducing impaired glucose tolerance.
Larsen S, Vigelso A, Dandanell S et al. Simvastatin-Induced Insulin Resistance May Be Linked to Decreased Lipid Uptake and Lipid Synthesis in Human Skeletal Muscle: the LIFESTAT Study. Journal of diabetes research 2018; 2018:9257874. http://www.ncbi.nlm.nih.gov/pubmed/?term=30276217
Achieving LDL-C targets differs between STEMI, NSTEMI and UA patients
Predicting which patients are less likely to attain guideline dictated LDL-c targets as well persist using their prescribed statin dose, can help healthcare professionals to improve long term lipid management and reduce (recurrent) cardiovascular complications. In this single academic institute retrospective study, the investigators evaluated hospital e-records. Patients presented with a first acute coronary syndrome were aged between 31 and 82 years, diagnosed with STEMI (N=260), NSTEMI (N=560), and UA (N=206) between February 2014 and December 2016. All patients survived at least 6 months and were prescribed atorvastatin or rosuvastatin. During the hospital admission 72% underwent percutaneous coronary interventions, 18.3% were managed medically, and 5.7% received coronary artery bypass grafting. LDL-c plasma concentrations were significantly reduced in in all 3 groups (P<0.001). The number of patients attaining ACC/AHA guideline dictated LDL-c targets were significantly higher In the STEMI group, than in the NSTEMI and UA groups. Percentage of patients achieving targets vs those that did not were 41.1% vs 22%; 43.3% vs 57%; 15.6% vs 21% (P<.001), in STEMI, NSTEMI and UA respectively. The authors concluded that STEMI patients were more likely to achieve LDL-c treatment goals compared to NSTEMI and UA patients. Physicians should aim to achieve LDL-c targets in UAE and NSTEMI patients, in a similar fashion as STEMI patients, as well as encourage all to persist in using high dose high intensity statins lifelong.
Guntekin U, Tosun V, Kilinc AY et al. ST segment elevation myocardial infarction (STEMI) patients are more likely to achieve lipid-lowering treatment goals: A retrospective analysis of patients presenting with first acute coronary syndromes. Medicine (Baltimore) 2018; 97:e12225. http://www.ncbi.nlm.nih.gov/pubmed/?term=30278492
Relevant publications
  1. Ye S, Leppin AL, Chan AY et al. An Informatics Approach to Implement Support for Shared Decision Making for Primary Prevention Statin Therapy. MDM policy & practice 2018; 3:2381468318777752. http://www.ncbi.nlm.nih.gov/pubmed/?term=30288449
  2. Woo Y, Shin JS, Shim CY et al. Effect of fenofibrate in 1113 patients at low-density lipoprotein cholesterol goal but high triglyceride levels: Real-world results and factors associated with triglyceride reduction. PLoS One 2018; 13:e0205006. http://www.ncbi.nlm.nih.gov/pubmed/?term=30286170
  3. Iughetti L, Predieri B, Bruzzi P, Balli F. Approaches to dyslipidemia treatment in children and adolescents. Expert review of endocrinology & metabolism 2008; 3:615-633. http://www.ncbi.nlm.nih.gov/pubmed/?term=30290407
  4. Vohnout B, Fabryova L, Klabnik A et al. Treatment pattern of familial hypercholesterolemia in Slovakia: Targets, treatment and obstacles in common practice. Atherosclerosis 2018; 277:323-326. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270066
  5. Thompson W, Pottegard A, Nielsen JB et al. Correction to: How Common is Statin Use in the Oldest Old? Drugs Aging 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30284119
  6. Tern PJW, Kujawiak I, Saha P et al. Site and Burden of Lower Limb Atherosclerosis Predicts Long-term Mortality in a Cohort of Patients With Peripheral Arterial Disease. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30287208
  7. Tai MH, Shepherd J, Bailey H et al. Real-world treatment patterns of PCSK9 inhibitors among patients with dyslipidemia in Germany, Spain, and United Kingdom. Current medical research and opinion 2018:1-17. http://www.ncbi.nlm.nih.gov/pubmed/?term=30289004
  8. Botha TC, Pilcher GJ, Wolmarans K et al. Statins and other lipid-lowering therapy and pregnancy outcomes in homozygous familial hypercholesterolaemia: A retrospective review of 39 pregnancies. Atherosclerosis 2018; 277:502-507. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270091
  9. Sawami K, Tanaka A, Nakamura T et al. Multiple potency of ezetimibe in a patient with macroproteinuric chronic kidney disease and statin-intolerant dyslipidemia. Journal of cardiology cases 2018; 17:204-207. http://www.ncbi.nlm.nih.gov/pubmed/?term=30279893
  10. Poropat G, Archibugi L, Korpela T et al. Statin use is not associated with an increased risk of acute pancreatitis-A meta-analysis of observational studies. United European gastroenterology journal 2018; 6:1206-1214. http://www.ncbi.nlm.nih.gov/pubmed/?term=30288283
  11. Moniri NH, Momary KM, McMahon T, Nayee E. Statin-Associated Achilles Tendon Rupture and Reproducible Bilateral Tendinopathy on Repeated Exposure. Mayo Clinic proceedings 2018; 93:1531-1532. http://www.ncbi.nlm.nih.gov/pubmed/?term=30286837
  12. Li YH, Chao TH, Liu PY et al. Lipid Lowering Therapy for Acute Coronary Syndrome and Coronary Artery Disease: Highlights of the 2017 Taiwan Lipid Guidelines for High Risk Patients. Acta Cardiologica Sinica 2018; 34:371-378. http://www.ncbi.nlm.nih.gov/pubmed/?term=30271086
  13. Lee OS, Zhang J, Jung SH et al. High-Intensity Statin Therapy Is "Too Much," Thus Not Indicated for Very Elderly Patients. Pulse (Basel, Switzerland) 2018; 6:19-31. http://www.ncbi.nlm.nih.gov/pubmed/?term=30283750
  14. Khariton Y, Patel KK, Chan PS et al. Guideline-directed statin intensification in patients with new or worsening symptoms of peripheral artery disease. Clin Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30284297
  15. Han JS, Kim K, Jung Y et al. Metabolic Alterations Associated with Atorvastatin/Fenofibric Acid Combination in Patients with Atherogenic Dyslipidaemia: A Randomized Trial for Comparison with Escalated-Dose Atorvastatin. Scientific reports 2018; 8:14642. http://www.ncbi.nlm.nih.gov/pubmed/?term=30279504
  16. Basu S, Sussman JB, Hayward RA. Black-White Cardiovascular Disease Disparities After Target-Based Versus Personalized Benefit-Based Lipid and Blood Pressure Treatment. MDM policy & practice 2017; 2:2381468317725741. http://www.ncbi.nlm.nih.gov/pubmed/?term=30288429
  17. Vrablik M, Raslova K, Vohnout B et al. Real-life LDL-C treatment goals achievement in patients with heterozygous familial hypercholesterolemia in the Czech Republic and Slovakia: Results of the PLANET registry. Atherosclerosis 2018; 277:355-361. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270071
  18. van Delden XM, Huijgen R, Wolmarans KH et al. LDL-cholesterol target achievement in patients with heterozygous familial hypercholesterolemia at Groote Schuur Hospital: Minority at target despite large reductions in LDL-C. Atherosclerosis 2018; 277:327-333. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270067
  19. Truong TH, Kim NT, Nguyen MNT et al. Homozygous familial hypercholesterolaemia in Vietnam: Case series, genetics and cascade testing of families. Atherosclerosis 2018; 277:392-398. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270076
  20. Sinha P, Delucchi KL, Thompson BT et al. Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive care medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30291376
  21. Shek A, Alieva R, Kurbanov R et al. Burden of familial heterozygous hypercholesterolemia in Uzbekistan: Time is muscle. Atherosclerosis 2018; 277:524-529. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270094
  22. Schmidt N, Dressel A, Grammer TB et al. Lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients with familial hypercholesterolemia in Germany: The CaReHigh Registry. Atherosclerosis 2018; 277:314-322. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270065
  23. Sarsam S, Berry A, Degheim G et al. Real-world use of PCSK9 inhibitors: A single-center experience. J Int Med Res 2018:300060518800595. http://www.ncbi.nlm.nih.gov/pubmed/?term=30280628
  24. Sanja M, Jozsef P, Sanja PG et al. Cytokines and statin therapy in chronic obstructive pulmonary disease patients. Scandinavian journal of clinical and laboratory investigation 2018:1-6. http://www.ncbi.nlm.nih.gov/pubmed/?term=30278779
  25. Rosas Saldarriaga D, Berrouet Mejia MC. Atorvastatin-Associated DRESS Syndrome. American journal of therapeutics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30272596
  26. Roder ME, Hildebrandt P, Storgaard H, Heitmann M. [Cholesterol-lowering treatment with PCSK9-inhibitors]. Ugeskrift for laeger 2018; 180. http://www.ncbi.nlm.nih.gov/pubmed/?term=30274588
  27. Nicholls SJ, Nelson AJ. Monitoring the Response to Statin Therapy: One Scan at a Time. JACC. Cardiovascular imaging 2018; 11:1485-1486. http://www.ncbi.nlm.nih.gov/pubmed/?term=30286908
  28. Meyer D, Merkel M. [Hyperlipidemia: What role do PCSK9 inhibitors play?]. Deutsche medizinische Wochenschrift (1946) 2018; 143:1430-1434. http://www.ncbi.nlm.nih.gov/pubmed/?term=30286489
  29. Liu Z, Lai CH, Zhang X et al. Simvastatin ameliorates total liver ischemia/reperfusion injury via KLF2-mediated mechanism in rats. Clin Res Hepatol Gastroenterol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30274910
  30. Liang Z, Li W, Yang S et al. Tangier disease may cause early onset of atherosclerotic cerebral infarction: A case report. Medicine (Baltimore) 2018; 97:e12472. http://www.ncbi.nlm.nih.gov/pubmed/?term=30278532
  31. Latkovskis G, Saripo V, Gilis D et al. Latvian registry of familial hypercholesterolemia: The first report of three-year results. Atherosclerosis 2018; 277:347-354. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270070
  32. Lalic K, Rajkovic N, Popovic L et al. The effects of 3-year statin therapy and the achievement of LDL cholesterol target values in familial hypercholesterolemia patients: An experience from Serbia. Atherosclerosis 2018; 277:298-303. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270062
  33. Kuhlman AB, Morville T, Dohlmann TL et al. Coenzyme Q10 does not improve peripheral insulin sensitivity in statin-treated men and women; the LIFESTAT study. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30273493
  34. Kayikcioglu M, Tokgozoglu L, Dogan V et al. What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)? Atherosclerosis 2018; 277:341-346. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270069
  35. Jang HJ, Kim HS, Kim JH, Lee J. The Effect of Statin Added to Systemic Anticancer Therapy: A Meta-Analysis of Randomized, Controlled Trials. Journal of clinical medicine 2018; 7. http://www.ncbi.nlm.nih.gov/pubmed/?term=30287761
  36. J BS, Holleman RG, Youles B, Lowery JC. Quality Improvement and Personalization for Statins: the QUIPS Quality Improvement Randomized Trial of Veterans' Primary Care Statin Use. Journal of general internal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30284172
  37. Iacocca MA, Wang J, Sarkar S et al. Whole-Gene Duplication of PCSK9 as a Novel Genetic Mechanism for Severe Familial Hypercholesterolemia. Can J Cardiol 2018; 34:1316-1324. http://www.ncbi.nlm.nih.gov/pubmed/?term=30269829
  38. Husain I, Khan S, Khan S et al. Unfolding the pleiotropic facades of rosuvastatin in therapeutic intervention of myriads of neurodegenerative disorders. Clin Exp Pharmacol Physiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30290001
  39. Harada PH, Miname MH, Bensenor IM et al. Familial hypercholesterolemia prevalence in an admixed racial society: Sex and race matter. The ELSA-Brasil. Atherosclerosis 2018; 277:273-277. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270058
  40. Goncalves RSG, Dantas AT, Pereira MC et al. Statins Inhibit Cytokines in a Dose-Dependent Response in Patients with Systemic Sclerosis. Inflammation 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30288636
  41. Ghasemi A, Ghashghai Z, Akbari J et al. Topical atorvastatin 1% for prevention of skin toxicity in patients receiving radiation therapy for breast cancer: a randomized, double-blind, placebo-controlled trial. Eur J Clin Pharmacol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30291370
  42. Farnier M. [New guidelines on dyslipidemia management]. Presse medicale (Paris, France : 1983) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30274915
  43. Dumitrescu A, Mosteoru S, Vinereanu D et al. Preliminary data of familial hypercholesterolemia (FH) patients in Romania. Atherosclerosis 2018; 277:304-307. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270063
  44. Crum J, Wilson J, Sabbagh M. Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia? Alzheimer's research & therapy 2018; 10:104. http://www.ncbi.nlm.nih.gov/pubmed/?term=30285877
  45. Choi GJ, Park HK, Kim DS et al. Effect of statins on experimental postoperative adhesion: a systematic review and meta-analysis. Scientific reports 2018; 8:14754. http://www.ncbi.nlm.nih.gov/pubmed/?term=30283040
  46. Chemaly P, Nallet O, Delarche N et al. [Screening for familial hypercholesterolemia from low-density lipoprotein cholesterol levels at admission in the coronary care unit]. Annales de cardiologie et d'angeiologie 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30290906
  47. Bogovic P, Lusa L, Stupica D et al. Impact of pre-existing treatment with statins on the course and outcome of tick-borne encephalitis. PLoS One 2018; 13:e0204773. http://www.ncbi.nlm.nih.gov/pubmed/?term=30286159
  48. Beliard S, Boccara F, Cariou B et al. High burden of recurrent cardiovascular events in heterozygous familial hypercholesterolemia: The French Familial Hypercholesterolemia Registry. Atherosclerosis 2018; 277:334-340. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270068
  49. Barter PJ, Cochran BJ, Rye KA. CETP inhibition, statins and diabetes. Atherosclerosis 2018; 278:143-146. http://www.ncbi.nlm.nih.gov/pubmed/?term=30278356
  50. Alver M, Palover M, Saar A et al. Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia. Genetics in medicine : official journal of the American College of Medical Genetics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270359
Miscellaneous publications
  1. Zdybel M, Chodurek E, Pilawa B. Effect of simvastatin in different concentrations on free radicals in A-2058 human melanoma malignum cells-EPR studies. Journal of cellular biochemistry 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30277600
  2. Yang N, Dong B, Yang J et al. Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats. Arquivos brasileiros de cardiologia 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30281685
  3. Xia Y, Xie Y, Yu Z et al. The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery. Cell 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30270039
  4. Ren C, Li S, Liu K et al. Enhanced oxidative stress response and neuroprotection of combined limb remote ischemic conditioning and atorvastatin after transient ischemic stroke in rats. Brain circulation 2017; 3:204-212. http://www.ncbi.nlm.nih.gov/pubmed/?term=30276326
  5. Nunez-Garcia M, Gomez-Santos B, Saenz de Urturi D et al. Atorvastatin provides a new lipidome improving early regeneration after partial hepatectomy in osteopontin deficient mice. Scientific reports 2018; 8:14626. http://www.ncbi.nlm.nih.gov/pubmed/?term=30279550
  6. Nezic L, Skrbic R, Amidzic L et al. Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-kappaB/p65 Expression. Scientific reports 2018; 8:14652. http://www.ncbi.nlm.nih.gov/pubmed/?term=30279549
  7. Irwin JC, Fenning AS, Ryan KR, Vella RK. Validation of a clinically-relevant rodent model of statin-associated muscle symptoms for use in pharmacological studies. Toxicology and applied pharmacology 2018; 360:78-87. http://www.ncbi.nlm.nih.gov/pubmed/?term=30268577
  8. Wang L, Wang Y, Yu L et al. Direct Differentiation of Stereoisomers of Ezetimibe/Ambrisentan/Atorvastatin and their Mechanism Study by Electrospray Ionization Quadurupole Time-of-Flight Mass Spectrometry. Journal of mass spectrometry : JMS 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30276925
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