Fatigue

Fatigue
Other names: Exhaustion, weariness, tired, lethargy, languidness, languor, lassitude, listlessness, injuries, sleepy
SpecialtyInternal medicine, family practice, psychiatry, psychology
TreatmentAvoid known stressors, avoid unhealthy habits such as: drug use, excessive alcohol consumption, smoking; healthy diet, exercise regularly, medication, staying hydrated, and vitamins

Fatigue is a feeling of extreme exhaustion; either physical, mental or both.[1] It generally does not resolve with rest or sleep.[2] It is frequently used interchangeably with lethargy.[3]

In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve after rest or sleep, or occurs independently of physical or mental exertion, it may be a symptom of a medical condition that may become severe or progressive.[4]

Physical fatigue results from muscle fatigue brought about by intense physical activity.[5][6][7] Mental fatigue results from prolonged periods of cognitive activity which impairs cognitive ability. Mental fatigue can manifest as sleepiness, lethargy, or directed attention fatigue.[8] Mental fatigue can also impair physical performance.[9]

Classification

Fatigue can be a feature of a mental disorder such as depression; may be associated with conditions of chronic pain such as fibromyalgia; it may also feature in conditions of chronic low-level inflammation, and be a disease-related symptom in many other conditions.[10] Fatigue often has no known cause, and is recognised as being very complex in nature.[11] Fatigability describes a susceptibility to fatigue.[12]

Physical

Physical fatigue, or muscle fatigue, is the temporary physical inability of muscles to perform optimally. The onset of muscle fatigue during physical activity is gradual, and depends upon an individual's level of physical fitness – other factors include sleep deprivation and overall health.[13] Physical fatigue can be caused by a lack of energy in the muscle, by a decrease of the efficiency of the neuromuscular junction or by a reduction of the drive originating from the central nervous system, and can be reversed by rest.[14] The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system.[15] During motor activity, serotonin released in synapses that contact motor neurons promotes muscle contraction.[16] During high level of motor activity, the amount of serotonin released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the axonal initial segment of motor neurons with the result that nerve impulse initiation and thereby muscle contraction are inhibited.[17]

Muscle strength testing can be used to determine the presence of a neuromuscular disease, but cannot determine its cause. Additional testing, such as electromyography, can provide diagnostic information, but information gained from muscle strength testing alone is not enough to diagnose most neuromuscular disorders.[18]

People with multiple sclerosis experience a form of overwhelming lassitude or tiredness that can occur at any time of the day, for any duration, and that does not necessarily recur in a recognizable pattern for any given patient, referred to as "neurological fatigue", and often as "multiple sclerosis fatigue".[19][20]

Mental

Mental fatigue is a temporary inability to maintain optimal cognitive performance. The onset of mental fatigue during any cognitive activity is gradual, and depends upon an individual's cognitive ability, and also upon other factors, such as sleep deprivation and overall health. Mental fatigue has also been shown to decrease physical performance.[8] It can manifest as somnolence, lethargy, directed attention fatigue, or disengagement. Research also suggests that mental fatigue is closely linked to the concept of ego depletion. For example, one pre-registered study of 686 participants found that after exerting mental effort, people are likely to disengage and become less interested in exerting further effort.[21] Decreased attention can also be described as a more or less decreased level of consciousness.[22] In any case, this can be dangerous when performing tasks that require constant concentration, such as operating large vehicles. For instance, a person who is sufficiently somnolent may experience microsleep. However, objective cognitive testing can be used to differentiate the neurocognitive deficits of brain disease from those attributable to tiredness.

The perception of mental fatigue is believed to be modulated by the brain's reticular activating system (RAS).

Fatigue impacts a driver's reaction time, awareness of hazards around them and their attention. Drowsy drivers are three times more likely to be involved in a car crash and if they are awake over 20 hours, is the equivalent of driving with a blood-alcohol concentration level of 0.08%.[23]

Primary vs secondary

In some areas it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and secondary fatigue, caused by more general impacts on the person of having the disease.[24][25][26][27]

Causes

Fatigue is a normal result of work, mental stress, anxiety, overstimulation and understimulation, jet lag, active recreation, boredom, lack of sleep or disease.

Acute

Causes of acute fatigue include depression; chemical causes, such as dehydration, poisoning, low blood sugar, or mineral or vitamin deficiencies. Fatigue is different from drowsiness, where a patient feels that sleep is required.

Temporary fatigue is likely to be a minor illness like the common cold as one part of the sickness behavior response that happens when the immune system fights an infection.[28]

Prolonged

Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month.

Chronic

Chronic fatigue is a self-reported fatigue lasting at least six consecutive months. Chronic fatigue may be either persistent or relapsing.[29] Chronic fatigue is a symptom of many diseases and conditions. Some major categories of conditions that feature fatigue include:

Fatigue may also be a side effect of certain medications (e.g., lithium salts, ciprofloxacin); beta blockers, which can induce exercise intolerance; and many cancer treatments, particularly chemotherapy and radiotherapy.

Inflammation

Inflammation has been linked to many types of fatigue.[30] Findings implicate neuroinflammation in the etiology of fatigue in autoimmune and related disorders.[30]

Diagnosis

Minor dark circles, in addition to a hint of eye bags, a combination which is suggestive of sleep deprivation and/or mental fatigue.

One study concluded about 50% of people who have fatigue receive a diagnosis that could explain the fatigue after a year with the condition. In those people who have a possible diagnosis, musculoskeletal (19.4%) and psychological problems (16.5%) are the most common. Definitive physical conditions were only found in 8.2% of cases.[40]

If a person with fatigue decides to seek medical advice, the overall goal is to identify and rule out any treatable conditions. This is done by considering the person's medical history, any other symptoms that are present, and evaluating of the qualities of the fatigue itself. The affected person may be able to identify patterns to the fatigue, such as being more tired at certain times of day, whether fatigue increases throughout the day, and whether fatigue is reduced after taking a nap.

Because disrupted sleep is a significant contributor to fatigue, a diagnostic evaluation considers the quality of sleep, the emotional state of the person, sleep pattern, and stress level. The amount of sleep, the hours that are set aside for sleep, and the number of times that a person awakens during the night are important. A sleep study may be ordered to rule out a sleep disorder.

Depression and other psychological conditions can produce fatigue, so people who report fatigue are routinely screened for these conditions, along with substance use disorders, poor diet, and lack of physical exercise, which paradoxically increases fatigue.

Basic medical tests may be performed to rule out common causes of fatigue. These include blood tests to check for infection or anemia, a urinalysis to look for signs of liver disease or diabetes mellitus, and other tests to check for kidney and liver function, such as a comprehensive metabolic panel.[41] Other tests may be chosen depending on the patient's social history, such as an HIV test or pregnancy test.

Comparison with sleepiness

Fatigue is generally considered a more long-term condition than sleepiness (somnolence).[42] Although sleepiness can be a symptom of a medical condition, it usually results from lack of restful sleep, or a lack of stimulation.[43] Chronic fatigue, on the other hand, is a symptom of a greater medical problem in most cases. It manifests in mental or physical weariness and inability to complete tasks at normal performance.[44] Both are often used interchangeably and even categorized under the description of 'being tired.' Fatigue is often described as an uncomfortable tiredness, whereas sleepiness is comfortable and inviting.

Measurement

Fatigue can be quantitatively measured. Devices to measure medical fatigue have been developed by Japanese companies, among them Nintendo (cancelled).[45] Nevertheless, such devices are not in common use outside Japan.

Management

Medications are reviewed as some have side effects that may contribute to fatigue[46][47] and the interactions of medications are complex.[48]

Psychostimulants such as methylphenidate, amphetamines, and modafinil have been used in the treatment of fatigue related to depression,[49][50][51][52] chronic fatigue syndrome,[53][54] and medical illness such as cancer.[55][50][56][57][58][59][60] They have also been used to counteract fatigue in sleep loss[61] and in aviation.[62]

See also

References

  1. Japp, Alan G.; Robertson, Colin; Wright, Rohana J.; Reed, Matthew J.; Robson, Andrew (2018). "13. Fatigue". Macleod's Clinical Diagnosis (2nd ed.). Elsevier. pp. 130–135. ISBN 978-0-7020-6962-8. Archived from the original on 2022-11-15. Retrieved 2022-11-16.
  2. "10 medical reasons for feeling tired". nhs.uk. 3 October 2018. Archived from the original on 24 November 2021. Retrieved 24 November 2021.
  3. Claud, Regnard (2004). "Fatigue, lethargy, drowsiness and weakness". Helping The Patient with Advanced Disease (1st ed.). ISBN 9781315376363. Archived from the original on 2022-11-16. Retrieved 2022-11-16.
  4. "ICD-11 for Mortality and Morbidity Statistics". icd.who.int. Archived from the original on 2018-08-01. Retrieved 2022-11-12.
  5. Gandevia SC (February 1992). "Some central and peripheral factors affecting human motoneuronal output in neuromuscular fatigue". Sports Medicine. 13 (2): 93–98. doi:10.2165/00007256-199213020-00004. PMID 1561512. S2CID 20473830.
  6. Hagberg M (July 1981). "Muscular endurance and surface electromyogram in isometric and dynamic exercise". Journal of Applied Physiology. 51 (1): 1–7. doi:10.1152/jappl.1981.51.1.1. PMID 7263402.
  7. Hawley JA, Reilly T (June 1997). "Fatigue revisited". Journal of Sports Sciences. 15 (3): 245–246. doi:10.1080/026404197367245. PMID 9232549.
  8. 1 2 Marcora SM, Staiano W, Manning V (March 2009). "Mental fatigue impairs physical performance in humans". Journal of Applied Physiology. 106 (3): 857–864. CiteSeerX 10.1.1.557.3566. doi:10.1152/japplphysiol.91324.2008. PMID 19131473.
  9. Martin K, Meeusen R, Thompson KG, Keegan R, Rattray B (September 2018). "Mental Fatigue Impairs Endurance Performance: A Physiological Explanation". Sports Med. 48 (9): 2041–2051. doi:10.1007/s40279-018-0946-9. PMID 29923147. S2CID 49317682.
  10. Finsterer J, Mahjoub SZ (August 2014). "Fatigue in healthy and diseased individuals". Am J Hosp Palliat Care. 31 (5): 562–575. doi:10.1177/1049909113494748. PMID 23892338. S2CID 12582944.
  11. Haß U, Herpich C, Norman K (September 2019). "Anti-Inflammatory Diets and Fatigue". Nutrients. 11 (10): 2315. doi:10.3390/nu11102315. PMC 6835556. PMID 31574939.
  12. "Medical Definition of Fatigability". www.merriam-webster.com. Archived from the original on 21 November 2021. Retrieved 21 November 2021.
  13. "Weakness and fatigue". Webmd. Healthwise Inc. Archived from the original on 30 December 2012. Retrieved 2 January 2013.
  14. Gandevia SC (October 2001). "Spinal and supraspinal factors in human muscle fatigue". Physiological Reviews. 81 (4): 1725–1789. doi:10.1152/physrev.2001.81.4.1725. PMID 11581501.
  15. Davis JM, Alderson NL, Welsh RS (August 2000). "Serotonin and central nervous system fatigue: nutritional considerations". The American Journal of Clinical Nutrition. 72 (2 Suppl): 573S–578S. doi:10.1093/ajcn/72.2.573S. PMID 10919962.
  16. Perrier JF, Delgado-Lezama R (August 2005). "Synaptic release of serotonin induced by stimulation of the raphe nucleus promotes plateau potentials in spinal motoneurons of the adult turtle". The Journal of Neuroscience. 25 (35): 7993–7999. doi:10.1523/JNEUROSCI.1957-05.2005. PMC 6725458. PMID 16135756.
  17. Cotel F, Exley R, Cragg SJ, Perrier JF (March 2013). "Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation". Proceedings of the National Academy of Sciences of the United States of America. 110 (12): 4774–4779. Bibcode:2013PNAS..110.4774C. doi:10.1073/pnas.1216150110. PMC 3607056. PMID 23487756.
  18. Enoka RM, Duchateau J (January 2008). "Muscle fatigue: what, why and how it influences muscle function". The Journal of Physiology. 586 (1): 11–23. doi:10.1113/jphysiol.2007.139477. PMC 2375565. PMID 17702815.
  19. Hubbard AL, Golla H, Lausberg H (June 2021). "What's in a name? That which we call Multiple Sclerosis Fatigue". Multiple Sclerosis. 27 (7): 983–988. doi:10.1177/1352458520941481. PMC 8142120. PMID 32672087.
  20. Mills RJ, Young CA, Pallant JF, Tennant A (February 2010). "Development of a patient reported outcome scale for fatigue in multiple sclerosis: The Neurological Fatigue Index (NFI-MS)". Health and Quality of Life Outcomes. 8: 22. doi:10.1186/1477-7525-8-22. PMC 2834659. PMID 20152031.
  21. Lin H, Saunders B, Friese M, Evans NJ, Inzlicht M (May 2020). "Strong Effort Manipulations Reduce Response Caution: A Preregistered Reinvention of the Ego-Depletion Paradigm". Psychological Science. 31 (5): 531–547. doi:10.1177/0956797620904990. PMC 7238509. PMID 32315259.
  22. Giannini AJ (1991). "Fatigue, Chronic". In Taylor RB (ed.). Difficult Diagnosis 2. Philadelphia: W.B. Saunders Co. p. 156. ISBN 978-0721634814. OCLC 954530793.
  23. "Drowsy Driving is Impaired Driving". National Safety Council. Archived from the original on 1 February 2019. Retrieved 31 January 2019.
  24. "Fatigue in Patients with Multiple Sclerosis". Archived from the original on 2022-06-16. Retrieved 2022-11-12.
  25. Chalah MA, Riachi N, Ahdab R, Créange A, Lefaucheur JP, Ayache SS (2015). "Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation". Frontiers in Cellular Neuroscience. 9: 460. doi:10.3389/fncel.2015.00460. PMC 4663273. PMID 26648845.
  26. Gerber LH, Weinstein AA, Mehta R, Younossi ZM (July 2019). "Importance of fatigue and its measurement in chronic liver disease". World Journal of Gastroenterology. 25 (28): 3669–3683. doi:10.3748/wjg.v25.i28.3669. PMC 6676553. PMID 31391765.
  27. Hartvig Honoré P (June 2013). "Fatigue". European Journal of Hospital Pharmacy. 20 (3): 147–148. doi:10.1136/ejhpharm-2013-000309. S2CID 220171226.
  28. Piraino, B.; Vollmer-Conna, U.; Lloyd, A.R. (2012-05-01). "Genetic associations of fatigue and other symptom domains of the acute sickness response to infection". Brain, Behavior, and Immunity. 26 (4): 552–558. doi:10.1016/j.bbi.2011.12.009. ISSN 0889-1591. PMC 7127134. PMID 22227623.
  29. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A (December 1994). "The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group". Annals of Internal Medicine. 121 (12): 953–959. doi:10.7326/0003-4819-121-12-199412150-00009. PMID 7978722. S2CID 510735.
  30. 1 2 3 Zielinski MR, Systrom DM, Rose NR (August 2019). "Fatigue, Sleep, and Autoimmune and Related Disorders". Frontiers in Immunology. 10: 1827. doi:10.3389/fimmu.2019.01827. PMC 6691096. PMID 31447842.
  31. Strober LB (2015). "Fatigue in multiple sclerosis: a look at the role of poor sleep". Frontiers in Neurology. 6: 21. doi:10.3389/fneur.2015.00021. PMC 4325921. PMID 25729378.
  32. "Signs and Symptoms of Anxiety Disorders". Healthline. 2021-08-25. Archived from the original on 2021-12-01. Retrieved 2021-12-01.
  33. 1 2 Avellaneda Fernández A, Pérez Martín A, Izquierdo Martínez M, Arruti Bustillo M, Barbado Hernández FJ, de la Cruz Labrado J, et al. (October 2009). "Chronic fatigue syndrome: aetiology, diagnosis and treatment". BMC Psychiatry. 9 Suppl 1 (Suppl 1): S1. doi:10.1186/1471-244X-9-S1-S1. PMC 2766938. PMID 19857242.
  34. Williams, Zachary J.; Gotham, Katherine O. (2021-10-03), Current and Lifetime Somatic Symptom Burden Among Transition-aged Autistic Young Adults, Cold Spring Harbor Laboratory, doi:10.1101/2021.10.02.21264461, S2CID 238252764
  35. 1 2 3 4 5 Friedman HH (2001-01-01). Problem-oriented Medical Diagnosis. Lippincott Williams & Wilkins. pp. 4–5. ISBN 978-0781729093. Archived from the original on 2022-11-16. Retrieved 2022-11-12.
  36. Arpino C, Carrieri MP, Valesini G, Pizzigallo E, Rovere P, Tirelli U, et al. (1999). "Idiopathic chronic fatigue and chronic fatigue syndrome: a comparison of two case-definitions". Annali dell'Istituto Superiore di Sanità. 35 (3): 435–441. PMID 10721210.
  37. Carrico AW, Jason LA, Witter E, Torres-Harding S (2004). "Disability in Chronic Fatigue Syndrome and Idiopathic Chronic Fatigue". Review of Disability Studies. 1 (1). Archived from the original on 2020-07-31. Retrieved 2022-11-12.
  38. Whitehead WE, Palsson O, Jones KR (April 2002). "Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?". Gastroenterology. 122 (4): 1140–1156. doi:10.1053/gast.2002.32392. PMID 11910364. Archived from the original on 2022-07-04. Retrieved 2022-11-12.
  39. Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG (February 2007). "Review article: fructose malabsorption and the bigger picture". Alimentary Pharmacology & Therapeutics. 25 (4): 349–363. doi:10.1111/j.1365-2036.2006.03186.x. PMID 17217453. S2CID 11487905.
  40. Nijrolder I, van der Windt D, de Vries H, van der Horst H (November 2009). "Diagnoses during follow-up of patients presenting with fatigue in primary care". CMAJ. 181 (10): 683–687. doi:10.1503/cmaj.090647. PMC 2774363. PMID 19858240.
  41. Davis CP (11 September 2017). Doerr S (ed.). "Fatigue". eMedicineHealth. Archived from the original on 7 March 2010.
  42. Shen J, Barbera J, Shapiro CM (February 2006). "Distinguishing sleepiness and fatigue: focus on definition and measurement". Sleep Medicine Reviews. 10 (1): 63–76. doi:10.1016/j.smrv.2005.05.004. PMID 16376590.
  43. Hoddes E, Zarcone V, Smythe H, Phillips R, Dement WC (July 1973). "Quantification of sleepiness: a new approach". Psychophysiology. 10 (4): 431–436. doi:10.1111/j.1469-8986.1973.tb00801.x. PMID 4719486.
  44. Mayou R (January 1999). "Chronic fatigue and its syndromes". BMJ. 318 (7176): 133A. doi:10.1136/bmj.318.7176.133a. PMC 1114599. PMID 9880310.
  45. "Nintendo's first health care device will be sleep and fatigue tracker". The Japan Times. Reuters. 30 October 2014. Archived from the original on 31 July 2020. Retrieved 29 June 2017.
  46. Siniscalchi A, Gallelli L, Russo E, De Sarro G (October 2013). "A review on antiepileptic drugs-dependent fatigue: pathophysiological mechanisms and incidence". European Journal of Pharmacology. 718 (1–3): 10–16. doi:10.1016/j.ejphar.2013.09.013. PMID 24051268.
  47. "What to do when medication makes you sleepy". 8 March 2016. Archived from the original on 9 November 2021. Retrieved 12 November 2022.
  48. Phansalkar S, van der Sijs H, Tucker AD, Desai AA, Bell DS, Teich JM, et al. (May 2013). "Drug-drug interactions that should be non-interruptive in order to reduce alert fatigue in electronic health records". Journal of the American Medical Informatics Association. 20 (3): 489–493. doi:10.1136/amiajnl-2012-001089. PMC 3628052. PMID 23011124.
  49. Candy M, Jones L, Williams R, Tookman A, King M (April 2008). "Psychostimulants for depression". Cochrane Database Syst Rev (2): CD006722. doi:10.1002/14651858.CD006722.pub2. PMID 18425966.
  50. 1 2 Hardy SE (February 2009). "Methylphenidate for the treatment of depressive symptoms, including fatigue and apathy, in medically ill older adults and terminally ill adults". Am J Geriatr Pharmacother. 7 (1): 34–59. doi:10.1016/j.amjopharm.2009.02.006. PMC 2738590. PMID 19281939.
  51. Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, Mulder R, Porter R, Singh A, Murray G (March 2016). "Stimulants for depression: On the up and up?". Aust N Z J Psychiatry. 50 (3): 203–207. doi:10.1177/0004867416634208. PMID 26906078. S2CID 45341424.
  52. Bahji A, Mesbah-Oskui L (September 2021). "Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis". J Affect Disord. 292: 416–423. doi:10.1016/j.jad.2021.05.119. PMID 34144366.
  53. Van Houdenhove B, Pae CU, Luyten P (February 2010). "Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy?". Expert Opin Pharmacother. 11 (2): 215–223. doi:10.1517/14656560903487744. PMID 20088743. S2CID 34827174.
  54. Valdizán Usón JR, Idiazábal Alecha MA (June 2008). "Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate". Expert Rev Neurother. 8 (6): 917–927. doi:10.1586/14737175.8.6.917. PMID 18505357.
  55. Masand PS, Tesar GE (September 1996). "Use of stimulants in the medically ill". Psychiatr Clin North Am. 19 (3): 515–547. doi:10.1016/s0193-953x(05)70304-x. PMID 8856815.
  56. Breitbart W, Alici Y (August 2010). "Psychostimulants for cancer-related fatigue". J Natl Compr Canc Netw. 8 (8): 933–942. doi:10.6004/jnccn.2010.0068. PMID 20870637.
  57. Minton O, Richardson A, Sharpe M, Hotopf M, Stone PC (April 2011). "Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis". J Pain Symptom Manage. 41 (4): 761–767. doi:10.1016/j.jpainsymman.2010.06.020. PMID 21251796.
  58. Gong S, Sheng P, Jin H, He H, Qi E, Chen W, Dong Y, Hou L (2014). "Effect of methylphenidate in patients with cancer-related fatigue: a systematic review and meta-analysis". PLOS ONE. 9 (1): e84391. doi:10.1371/journal.pone.0084391. PMC 3885551. PMID 24416225.
  59. Yennurajalingam S, Bruera E (2014). "Review of clinical trials of pharmacologic interventions for cancer-related fatigue: focus on psychostimulants and steroids". Cancer J. 20 (5): 319–324. doi:10.1097/PPO.0000000000000069. PMID 25299141. S2CID 29351114.
  60. Dobryakova E, Genova HM, DeLuca J, Wylie GR (2015). "The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders". Front Neurol. 6: 52. doi:10.3389/fneur.2015.00052. PMC 4357260. PMID 25814977.
  61. Bonnet MH, Balkin TJ, Dinges DF, Roehrs T, Rogers NL, Wesensten NJ (September 2005). "The use of stimulants to modify performance during sleep loss: a review by the sleep deprivation and Stimulant Task Force of the American Academy of Sleep Medicine". Sleep. 28 (9): 1163–1187. doi:10.1093/sleep/28.9.1163. PMID 16268386.
  62. Ehlert AM, Wilson PB (March 2021). "Stimulant Use as a Fatigue Countermeasure in Aviation". Aerosp Med Hum Perform. 92 (3): 190–200. doi:10.3357/AMHP.5716.2021. PMID 33754977. S2CID 232325161.
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