Fatigue

From Wikipedia the free encyclopedia

Fatigue
Other namesExhaustion, weariness, tiredness, lethargy, listlessness
SpecialtyInternal medicine and most other specialities
TreatmentAvoid known stressors, avoid unhealthy habits such as: drug use, excessive alcohol consumption, smoking; healthy diet, exercise regularly, medication, staying hydrated, and vitamins

Fatigue describes a state of tiredness (which is not sleepiness) or exhaustion.[1] In general usage, fatigue often follows prolonged physical or mental activity. When fatigue occurs independently of physical or mental exertion, or does not resolve after rest or sleep, it may have other causes, such as a medical condition.[2]

Fatigue (in a medical context) is complex and its cause is often unknown.[3] Fatigue is associated with a wide variety of conditions including autoimmune disease, organ failure, chronic pain conditions, mood disorders, heart disease, infectious diseases, and post-infectious-disease states.[4]

Fatigue (in the general usage sense of normal tiredness) can include both physical and mental fatigue. 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]

Definition[edit]

Fatigue in a medical context is used to cover experiences of low energy that are not caused by normal life.[10][11]

Distinguishing features of such fatigue include

  • not linking fatigue to an obvious cause,
  • lack of improvement with rest,
  • variability in severity,
  • unpredictability, and
  • fatigue being more profound/overwhelming, and having extensive impact on daily living.[12]

Correlation of the quantum of fatigue with the severity of an underlying disease is often not present.[12]

Fatigue is multi-faceted and broadly defined, which makes understanding the cause of its manifestations especially difficult in conditions with diverse pathology including autoimmune diseases.[13]

A 2021 review proposed a definition for fatigue as a starting point for discussion: "A multi-dimensional phenomenon in which the biophysiological, cognitive, motivational and emotional state of the body is affected resulting in significant impairment of the individual's ability to function in their normal capacity".[12]

Another definition is that fatigue is "a significant subjective sensation of weariness, increasing sense of effort, mismatch between effort expended and actual performance, or exhaustion independent from medications, chronic pain, physical deconditioning, anaemia, respiratory dysfunction, depression, and sleep disorders.".[14]

Terminology[edit]

The use of the term "fatigue" in medical contexts may carry inaccurate connotations from the more general usage of the same word. More accurate terminology may also be needed to cover variants within the umbrella term of fatigue.[15]

Comparison with other terms[edit]

Tiredness[edit]

Tiredness which is a normal result of work, mental stress, anxiety, overstimulation and understimulation, jet lag, active recreation, boredom, or lack of sleep is not considered medical fatigue. This is the tiredness described in MeSH Descriptor Data.[16]

Sleepiness[edit]

Fatigue is generally considered a longer-term condition than sleepiness (somnolence).[17] Although sleepiness can be a symptom of a medical condition, it usually results from lack of restful sleep, or lack of stimulation.[18] Fatigue is often described as an uncomfortable tiredness, whereas sleepiness can be comfortable and inviting.

Classification[edit]

By type[edit]

Uni- or multi-dimensional[edit]

It is disputed whether there are different dimensions of fatigue, such as peripheral (muscle) and central (mental) fatigue, or whether fatigue is a uni-dimensional phenomenon that influences different aspects of human life.[19][20]

A 2021 review considered that different 'types/subsets' of fatigue may exist and that patients normally present with more than one such 'type/subset". These different "types/subsets" of fatigue may be different dimensions of the same symptom, and the relative manifestations of each may depend on the relative contribution of different mechanisms. Inflammation may be the root causal mechanism in many cases.[12]

Physical[edit]

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.[21] 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.[22] The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system.[23] During motor activity, serotonin released in synapses that contact motor neurons promotes muscle contraction.[24] 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.[25]

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.[26]

Mental[edit]

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, though the validity of the concept is disputed. 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.[27]

Decreased attention can also be described as a more or less decreased level of consciousness.[28] 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.[citation needed]

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

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 being awake over 20 hours is the equivalent of driving with a blood-alcohol concentration level of 0.08%.[29]

Neurological fatigue[edit]

People with multiple sclerosis experience a form of overwhelming 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" or "lassitude".[30][31]

People with autoimmune diseases including inflammatory rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and primary Sjögren's syndrome, experience similar fatigue.[32][33][34]

By timescale[edit]

Acute[edit]

Acute fatigue is that which is temporary and self-limited. Acute fatigue is most often caused by an infection such as the common cold and can be cognized as one part of the sickness behavior response occurring when the immune system fights an infection.[35]

Other common causes of acute fatigue include depression and chemical causes, such as dehydration, poisoning, low blood sugar, or mineral or vitamin deficiencies.

Prolonged[edit]

Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month.[medical citation needed]

Chronic[edit]

Chronic fatigue is a self-reported fatigue lasting at least 6 consecutive months. Chronic fatigue may be either persistent or relapsing.[36] Chronic fatigue is a symptom of many chronic illnesses and of idiopathic chronic fatigue.

By effect[edit]

Fatigue can have significant negative impacts on quality of life.[37][38] Profound and debilitating fatigue is the most common complaint reported among individuals with autoimmune disease, such as systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, celiac disease, chronic fatigue syndrome, and rheumatoid arthritis.[12]

Fatigue that dissociates by quantum with disease activity represents a large health economic burden and unmet need to patients and to society.[12]

Measurement[edit]

Fatigue is currently measured by many different self-measurement surveys.[39] There is no consensus on best practice,[40] and the existing surveys do not capture the intermittent nature of some forms of fatigue.

Nintendo announced plans for a device to possibly quantitatively measure fatigue in 2014,[41] but the project was stopped in 2016.[42]

Causes[edit]

Undiagnosed[edit]

The cause of fatigue is often undiagnosed.[43]

Idiopathic chronic fatigue[edit]

Idiopathic chronic fatigue is chronic fatigue not caused by a known proximate cause such as a discrete medical condition, drug or alcohol use.

Medications[edit]

Fatigue may 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.

Drug use[edit]

Caffeine and alcohol can cause fatigue.[44]

Sleep deprivation[edit]

Sleep deprivation and disruption is associated with subsequent fatigue. [45][46]

Obesity[edit]

Obesity appears to correlate with greater fatigue incidence.[47]

Psychological stress and conditions[edit]

Depression and adverse life events have been associated with fatigue.[32]

Association with diseases[edit]

Fatigue is often associated with diseases and conditions. Some major categories of conditions that often list fatigue as a symptom include:

Primary vs. secondary[edit]

In some areas it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and ordinary or secondary fatigue, caused by a range of causes including exertion and also secondary impacts on a person of having a disease (such as disrupted sleep).[62][63][64][65][66] The ICD definition of fatigue [67] captures both types of fatigue; it includes fatigue that "occur[s] in the absence of... exertion... as a symptom of health conditions."

Mechanisms[edit]

The mechanisms that cause fatigue are not well understood.[13] Several mechanisms may be in operation within a patient,[68] with the relative contribution of each mechanism differing over time.[12]

Inflammation[edit]

Inflammation distorts neural chemistry, brain function and functional connectivity across a broad range of brain networks,[69] and has been linked to many types of fatigue.[48][70] Findings implicate neuroinflammation in the etiology of fatigue in autoimmune and related disorders.[32][48] Low-grade inflammation may cause an imbalance between energy availability and expenditure.[71] Cytokines are small protein molecules that modulate immune responses and inflammation (as well as other functions) and may have causal roles in fatigue.[72][73] The inflammation model may have difficulty in explaining the "unpredictability" and "variability" (i.e. appearing intermittently during the day, and not on all days) of the fatigue associated with inflammatory rheumatic diseases and autoimmune diseases (such as multiple sclerosis).[32]

Heat shock proteins[edit]

A small 2016 study found that primary Sjögren's syndrome patients with high fatigue, when compared with those with low fatigue, had significantly higher plasma concentrations of HSP90α, and a tendency to higher concentrations of HSP72.[74]

Reduced brain connectivity[edit]

Fatigue has been correlated with reductions in structural and functional connectivity in the brain.[75] This has included in post-stroke,[76] MS,[77] NMOSD and MOG,[14] and ME/CFS.[78] This was also found for fatigue after brain injury,[79] including a significant linear correlation between self-reported fatigue and brain functional connectivity.[80] (Areas of the brain for which there is evidence of relation to fatigue are the thalamus and middle frontal cortex,[80] fronto-parietal and cingulo-opercular,[79] and default mode network, salience network, and thalamocortical loop areas.[75][81])

Prevalence[edit]

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

2023 guidance stated fatigue prevalence is between 4.3% and 21.9%. Prevalence is higher in women than men.[82]

2021 German study found that fatigue was the main or secondary reason for 10–20% of all consultations with a primary care physician.[83]

Diagnosis[edit]

The overall goal in diagnosis is to identify and rule out any treatable conditions. This is done by considering

  • the person's medical history, any other symptoms present.
  • evaluation of the qualities of the fatigue itself. Identifiable patterns to the fatigue can include being more tired at certain times of day, whether fatigue increases throughout the day, and whether fatigue is reduced after taking a nap.
  • sleep patterns. These can be examined by enquiring about 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.
  • substance use disorders, and use of caffeine and alcohol.
  • poor diet.
  • lack of physical exercise (which paradoxically increases fatigue).

Further tests may include

A 2009 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.[85]

2023 guidance stated

  • In the primary care setting, a medical or psychiatric diagnosis is found in at least two-thirds of patients.
  • The most common diagnoses are viral illness, upper respiratory infection, iron-deficiency anaemia, acute bronchitis, adverse effects of a medical agent in the proper dose, and depression or other mental disorder (such as panic disorder, and somatisation disorder).
  • The origin of fatigue may be central (brain-derived) or peripheral (usually a neuromuscular origin). It may be attributed to Physical illness, Psychological (e.g., psychiatric disorder), social (e.g., family problems), and physiological factors (e.g., old age), Occupational illness (e.g., workplace stress).
  • When unexplained, clinically evaluated chronic fatigue can be separated into ME/CFS and idiopathic chronic fatigue.[82]

Treatment and Management[edit]

Management may include the following;

Review of existing medications[edit]

Medications may be evaluated for side effects that contribute to fatigue[86][87][better source needed] and the interactions of medications are complex.[non-primary source needed][88]

Lifestyle changes[edit]

Fatigue may be reduced by reducing obesity, caffeine and alcohol intake,[89] pain and sleep disturbance, and by improving mental well-being.[90][12]

Medications used to treat fatigue[edit]

The UK NICE recommends consideration of amantadine, modafinil and SSRIs for MS fatigue.[91] Psychostimulants such as methylphenidate, amphetamines, and modafinil have been used in the treatment of fatigue related to depression,[92][93][94][95] and medical illness such as chronic fatigue syndrome[96][97] and cancer.[93][98][99][100][101][102][103] They have also been used to counteract fatigue in sleep loss[104] and in aviation.[105]

Vagus nerve stimulation[edit]

A small study showed possible efficacy of vagus nerve stimulation for fatigue reduction in Sjogren's patients.[106]

Mental health tools[edit]

CBT has been found useful.[107]

Possible purposes of fatigue[edit]

Evolutionary purposes[edit]

It has been posited that fatigue had evolutionary benefits in making more of the body's resources available for healing processes, such as immune responses, and in limiting disease spread by tending to reduce social interactions.[68]

Body resource management purposes[edit]

Fatigue has been posited as a bio-psycho-physiological state reflecting the body's overall strategy in resource (energy) management. Fatigue may occur when the body wants to limit resource utilisation ("rationing") in order to conserve energy for a particular need, including a threat. This need may be a current or future anticipated need.[12]

See also[edit]

References[edit]

  1. ^ "10 medical reasons for feeling tired". nhs.uk. 3 October 2018. Retrieved 24 November 2021.
  2. ^ "ICD-11 for Mortality and Morbidity Statistics". icd.who.int.
  3. ^ 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.
  4. ^ 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.
  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. ^ a b 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. S2CID 12221961.
  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. ^ "Fatigue". Mayo Clinic.
  11. ^ Cancer terms
  12. ^ a b c d e f g h i Davies K, Dures E, Ng W (January 15, 2021). "Fatigue in inflammatory rheumatic diseases: current knowledge and areas for future research". Nature Reviews Rheumatology. 17 (11): 651–664. doi:10.1038/s41584-021-00692-1. PMID 34599320. S2CID 238233411 – via eprints.ncl.ac.uk.
  13. ^ a b Zielinski MR, Systrom DM, Rose NR (2019). "Fatigue, Sleep, and Autoimmune and Related Disorders". Frontiers in Immunology. 10: 1827. doi:10.3389/fimmu.2019.01827. PMC 6691096. PMID 31447842.
  14. ^ a b https://academic.oup.com/braincomms/article/5/3/fcad107/7103314[bare URL]
  15. ^ Hubbard AL, Golla H, Lausberg H (2020). "What's in a name? That which we call Multiple Sclerosis Fatigue". Multiple Sclerosis (Houndmills, Basingstoke, England). 27 (7): 983–988. doi:10.1177/1352458520941481. PMC 8142120. PMID 32672087.
  16. ^ "MeSH Browser". meshb.nlm.nih.gov.
  17. ^ 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.
  18. ^ 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.
  19. ^ Roald Omdal, Svein Ivar Mellgren, Katrine Brække Norheim (July 2021). "Pain and fatigue in primary Sjögren's syndrome". Rheumatology. 6 (7): 3099–3106. doi:10.1093/rheumatology/kez027. PMID 30815693.
  20. ^ Gerber LH, Weinstein AA, Mehta R, Younossi ZM (July 28, 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.
  21. ^ "Weakness and fatigue". Webmd. Healthwise Inc. Retrieved 2 January 2013.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ 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.
  26. ^ 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.
  27. ^ 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.
  28. ^ Giannini AJ (1991). "Fatigue, Chronic". In Taylor RB (ed.). Difficult Diagnosis 2. Philadelphia: W.B. Saunders Co. p. 156. ISBN 978-0-7216-3481-4. OCLC 954530793.
  29. ^ "Drowsy Driving is Impaired Driving". National Safety Council. Retrieved 31 January 2019.
  30. ^ 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.
  31. ^ 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.
  32. ^ a b c d Davies K, Dures E, Ng W (November 2021). "Fatigue in inflammatory rheumatic diseases: current knowledge and areas for future research". Nature Reviews Rheumatology. 17 (11): 651–664. doi:10.1038/s41584-021-00692-1. PMID 34599320. S2CID 238233411.
  33. ^ a b Zielinski MR, Systrom DM, Rose NR (2019). "Fatigue, Sleep, and Autoimmune and Related Disorders". Frontiers in Immunology. 10: 1827. doi:10.3389/fimmu.2019.01827. PMC 6691096. PMID 31447842.
  34. ^ Baumer K (March 23, 2015). "Fatigue Survey Results Released". Autoimmune Association.
  35. ^ Piraino B, Vollmer-Conna U, Lloyd A (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.
  36. ^ 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.
  37. ^ Hemmett L, Holmes J, Barnes M, Russell N (October 2004). "What drives quality of life in multiple sclerosis?". QJM. 97 (10): 671–676. doi:10.1093/qjmed/hch105. PMID 15367738.
  38. ^ Mæland E, Miyamoto ST, Hammenfors D, Valim V, Jonsson MV (2021). "Understanding Fatigue in Sjögren's Syndrome: Outcome Measures, Biomarkers and Possible Interventions". Frontiers in Immunology. 12: 703079. doi:10.3389/fimmu.2021.703079. PMC 8267792. PMID 34249008.
  39. ^ Machado MO, Kang NC, Tai F, Sambhi RD, Berk M, Carvalho AF, Chada LP, Merola JF, Piguet V, Alavi A (September 2021). "Measuring fatigue: a meta-review". International Journal of Dermatology. 60 (9): 1053–1069. doi:10.1111/ijd.15341. hdl:11343/276722. PMID 33301180. S2CID 228087205.
  40. ^ "Fatigue Survey Results Released". 23 March 2015.
  41. ^ "Nintendo's first health care device will be sleep and fatigue tracker". The Japan Times. Reuters. 30 October 2014. Retrieved 29 June 2017.
  42. ^ "Nintendo presses snooze button on planned sleep-tracking device". 4 February 2016.
  43. ^ "Medically unexplained symptoms". 19 October 2017.
  44. ^ "Tiredness and fatigue". 26 April 2018.
  45. ^ Panel on Research Methodologies and Statistical Approaches to Understanding Driver Fatigue Factors in Motor Carrier Safety and Driver (August 12, 2016). "Consequences of Fatigue from Insufficient Sleep". Commercial Motor Vehicle Driver Fatigue, Long-Term Health, and Highway Safety: Research Needs. National Academies Press (US) – via www.ncbi.nlm.nih.gov.
  46. ^ Kayser KC, Puig VA, Estepp JR (February 25, 2022). "Predicting and mitigating fatigue effects due to sleep deprivation: A review". Frontiers in Neuroscience. 16. doi:10.3389/fnins.2022.930280. PMC 9389006. PMID 35992930.
  47. ^ Lim W, Hong S, Nelesen R, Dimsdale JE (25 April 2005). "The Association of Obesity, Cytokine Levels, and Depressive Symptoms With Diverse Measures of Fatigue in Healthy Subjects". Archives of Internal Medicine. 165 (8): 910–915. doi:10.1001/archinte.165.8.910. PMID 15851643.
  48. ^ a b c 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.
  49. ^ "Autoimmune Fatigue: The Staggering Symptoms Beyond "Feeling Tired"". 5 March 2013.
  50. ^ 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.
  51. ^ "Fatigue is a common feature of the anti-nuclear antibody (ANA)-positive systemic autoimmune rheumatic diseases (SARDs), including systemic lupus erythematosus (SLE), Sjogren's disease (SjD), systemic sclerosis (SSc), dermatomyositis, and mixed connective tissue disease."
  52. ^ Hafiz W, Nori R, Bregasi A, Noamani B, Bonilla D, Lisnevskaia L, Silverman E, Bookman AA, Johnson SR, Landolt-Marticorena C, Wither J (November 4, 2019). "Fatigue severity in anti-nuclear antibody-positive individuals does not correlate with pro-inflammatory cytokine levels or predict imminent progression to symptomatic disease". Arthritis Research & Therapy. 21 (1): 223. doi:10.1186/s13075-019-2013-9. PMC 6827224. PMID 31685018.
  53. ^ A 2015 US survey found that 98% of people with autoimmune diseases experienced fatigue, 89% said it was a "major issue", 68% said "fatigue is anything but normal. It is profound and prevents [them] from doing the simplest everyday tasks." and 59% said it was "probably the most debilitating symptom of having an AD." https://autoimmune.org/fatigue-survey-results-released/
  54. ^ "Fatigue after brain injury".
  55. ^ "What is cancer fatigue? | Coping physically | Cancer Research UK".
  56. ^ "Long-term effects of coronavirus (Long COVID)". 7 January 2021.
  57. ^ a b 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): S1. doi:10.1186/1471-244X-9-S1-S1. PMC 2766938. PMID 19857242.
  58. ^ Williams ZJ, Gotham KO (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
  59. ^ a b c d e Friedman HH (2001). Problem-oriented Medical Diagnosis. Lippincott Williams & Wilkins. pp. 4–5. ISBN 978-0-7817-2909-3.
  60. ^ 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.
  61. ^ 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.
  62. ^ "Fatigue in Patients with Multiple Sclerosis".
  63. ^ 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.
  64. ^ 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.
  65. ^ Hartvig Honoré P (June 2013). "Fatigue". European Journal of Hospital Pharmacy. 20 (3): 147–148. doi:10.1136/ejhpharm-2013-000309. S2CID 220171226.
  66. ^ Newland P, Starkweather A, Sorenson M (2016). "Central fatigue in multiple sclerosis: a review of the literature: The Journal of Spinal Cord Medicine: Vol 39, No 4". The Journal of Spinal Cord Medicine. 39 (4): 386–399. doi:10.1080/10790268.2016.1168587. PMC 5102292. PMID 27146427.
  67. ^ "ICD-11 for Mortality and Morbidity Statistics". icd.who.int.
  68. ^ a b Korte SM, Straub RH (November 15, 2019). "Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms". Rheumatology. 58 (Suppl 5): v35–v50. doi:10.1093/rheumatology/kez413. PMC 6827268. PMID 31682277.
  69. ^ Korte SM, Straub RH (November 2019). "Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms". Rheumatology. 58 (Suppl 5): v35–v50. doi:10.1093/rheumatology/kez413. PMC 6827268. PMID 31682277.
  70. ^ Omdal R (June 2020). "The biological basis of chronic fatigue: neuroinflammation and innate immunity". Current Opinion in Neurology. 33 (3): 391–396. doi:10.1097/WCO.0000000000000817. PMID 32304437. S2CID 215819309.
  71. ^ Lacourt TE, Vichaya EG, Chiu GS, Dantzer R, Heijnen CJ (2018). "The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure". Frontiers in Behavioral Neuroscience. 12: 78. doi:10.3389/fnbeh.2018.00078. PMC 5932180. PMID 29755330.
  72. ^ Karshikoff B, Sundelin T, Lasselin J (2017). "Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms". Frontiers in Immunology. 8: 21. doi:10.3389/fimmu.2017.00021. PMC 5247454. PMID 28163706.
  73. ^ A small study showed possible efficacy of VNS for Sjogren's fatigue https://www.sciencedirect.com/science/article/pii/S1094715922012636 and inflammation has been suggested as a possible VNS mechanism (https://en.wikipedia.org/wiki/Vagus_nerve_stimulation#Reducing_inflammation).
  74. ^ Bårdsen K, Nilsen MM, Kvaløy JT, Norheim KB, Jonsson G, Omdal R (2016). "Heat shock proteins and chronic fatigue in primary Sjögren's syndrome". Innate Immunity. 22 (3): 162–167. doi:10.1177/1753425916633236. PMC 4804286. PMID 26921255.
  75. ^ a b Qi P, Ru H, Gao L, Zhang X, Zhou T, Tian Y, Thakor N, Bezerianos A, Li J, Sun Y (April 1, 2019). "Neural Mechanisms of Mental Fatigue Revisited: New Insights from the Brain Connectome". Engineering. 5 (2): 276–286. doi:10.1016/j.eng.2018.11.025.
  76. ^ Schaechter JD, Kim M, Hightower BG, Ragas T, Loggia ML (February 28, 2023). "Disruptions in Structural and Functional Connectivity Relate to Poststroke Fatigue". Brain Connectivity. 13 (1): 15–27. doi:10.1089/brain.2022.0021. PMC 9942175. PMID 35570655.
  77. ^ Cruz Gómez ÁJ, Ventura Campos N, Belenguer A, Ávila C, Forn C (October 22, 2013). "Regional Brain Atrophy and Functional Connectivity Changes Related to Fatigue in Multiple Sclerosis". PLOS ONE. 8 (10): e77914. Bibcode:2013PLoSO...877914C. doi:10.1371/journal.pone.0077914. PMC 3805520. PMID 24167590.
  78. ^ Gay CW, Robinson ME, Lai S, O'Shea A, Craggs JG, Price DD, Staud R (February 1, 2016). "Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses". Brain Connectivity. 6 (1): 48–56. doi:10.1089/brain.2015.0366. PMC 4744887. PMID 26449441.
  79. ^ a b Ramage AE, Ray KL, Franz HM, Tate DF, Lewis JD, Robin DA (January 30, 2021). "Cingulo-Opercular and Frontoparietal Network Control of Effort and Fatigue in Mild Traumatic Brain Injury". Frontiers in Human Neuroscience. 15. doi:10.3389/fnhum.2021.788091. PMC 8866657. PMID 35221951.
  80. ^ a b Nordin LE, Möller MC, Julin P, Bartfai A, Hashim F, Li T (February 16, 2016). "Post mTBI fatigue is associated with abnormal brain functional connectivity". Scientific Reports. 6 (1): 21183. Bibcode:2016NatSR...621183N. doi:10.1038/srep21183. PMC 4754765. PMID 26878885.
  81. ^ Borghetti L, Rhodes LJ, Morris MB (September 30, 2022). "Fatigue Leads to Dynamic Shift in Fronto-parietal Sustained Attention Network". Proceedings of the Human Factors and Ergonomics Society Annual Meeting. 66 (1): 606–610. doi:10.1177/1071181322661056. S2CID 253205546 – via CrossRef.
  82. ^ a b "Evaluation of fatigue - Differential diagnosis of symptoms | BMJ Best Practice US". bestpractice.bmj.com.
  83. ^ Maisel P, Baum E, Donner-Banzhoff N (August 30, 2021). "Fatigue as the Chief Complaint". Deutsches Ärzteblatt International. 118 (33–34): 566–576. doi:10.3238/arztebl.m2021.0192. PMC 8579431. PMID 34196270.
  84. ^ Davis CP (11 September 2017). Doerr S (ed.). "Fatigue". eMedicineHealth. Archived from the original on 7 March 2010.
  85. ^ 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.
  86. ^ 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.
  87. ^ "What to do when medication makes you sleepy". 8 March 2016.
  88. ^ 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.
  89. ^ See causal factors section
  90. ^ Geenen R, Dures E (November 1, 2019). "A biopsychosocial network model of fatigue in rheumatoid arthritis: a systematic review". Rheumatology. 58 (Suppl 5): v10–v21. doi:10.1093/rheumatology/kez403. PMC 6827269. PMID 31682275.
  91. ^ "Recommendations | Multiple sclerosis in adults: management | Guidance | NICE". www.nice.org.uk. June 22, 2022.
  92. ^ 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.
  93. ^ a b 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.
  94. ^ 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.
  95. ^ 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.
  96. ^ 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.
  97. ^ 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. S2CID 37482754.
  98. ^ 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.
  99. ^ 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.
  100. ^ 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.
  101. ^ 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. Bibcode:2014PLoSO...984391G. doi:10.1371/journal.pone.0084391. PMC 3885551. PMID 24416225.
  102. ^ 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.
  103. ^ 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.
  104. ^ 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.
  105. ^ 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.
  106. ^ Tarn J, Evans E, Traianos E, Collins A, Stylianou M, Parikh J, Bai Y, Guan Y, Frith J, Lendrem D, Macrae V, McKinnon I, Simon BS, Blake J, Baker MR, Taylor JP, Watson S, Gallagher P, Blamire A, Newton J, Ng W (1 April 2023). "The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome". Neuromodulation: Technology at the Neural Interface. 26 (3): 681–689. doi:10.1016/j.neurom.2022.08.461. ISSN 1094-7159. PMID 37032583.
  107. ^ "Self-help tips to fight tiredness". nhs.uk. January 27, 2022.

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