Fatigue may be a symptom of almost any medical condition. For the purpose of this topic, the differentials discussed concentrate on people presenting with fatigue or where fatigue is the only symptom. Conditions in which fatigue may not necessarily be an initial complaint, but is still regarded as a markedly significant and debilitating symptom, are also included.
Summary
Definition
There are numerous definitions and classifications of fatigue, reflecting the multitude of interpretations, depending on being a patient, a physician, a biologist, or a physiologist. A common and practical definition defined fatigue as a sensation of exhaustion during or after usual activities, or a feeling of inadequate energy to begin these activities.[1]
Epidemiology
Primary-care-based surveys have shown that between 11% and 33% of patients report significant fatigue, resulting in approximately 7 million office visits per year in the US. Fatigue is also a common complaint in the general population, with a prevalence between 4.3% and 21.9%.[2] [3] [4] [5] [6] [7]
In the primary care setting, a medical or psychiatric diagnosis is found in the majority of patients presenting with fatigue (at least two-thirds).[8] [9] [10] [11] [12] A Dutch study identified a specific diagnosis in 63% of patients presenting to a general practitioner with general weakness or tiredness for any length of time.[11] One study identified the most common diagnoses, in descending order, as viral illness, upper respiratory infection, iron-deficiency anemia, acute bronchitis, adverse effects of a medical agent in the proper dose, and depression or other mental disorder.[13] The most frequent psychiatric illnesses included major depression, panic disorder, and somatization disorder. A systematic review and meta-analysis of studies reporting on the differential diagnosis of tiredness in primary care found serious somatic disease was a rare cause. The prevalences of the following causes were found to be: anemia (2.8%); malignancy (0.6%); serious somatic disease (4.3%); depression (18.5%).[14]
Classification
Fatigue can be divided into categories based on origin, attribution, and duration of symptoms. The origin of fatigue may be:
- Central (brain-derived)
- Peripheral (usually a neuromuscular origin).
It may be attributed to:[8]
- 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).
The duration of symptoms may refer to:
- Recent fatigue (symptoms lasting <1 month)
- Prolonged fatigue (symptoms lasting >1 month)
- Chronic fatigue (symptoms lasting >6 months).
When unexplained, clinically evaluated chronic fatigue can be separated into chronic fatigue syndrome (also known as myalgic encephalomyelitis [ME]) and idiopathic chronic fatigue.[18] [19] Chronic fatigue syndrome represents a small subset of those who report actual chronic fatigue. Even in patients with fatigue of 6 months or longer in duration, the prevalence is <40%. European studies have shown that patients with fatigue lasting longer than 6 months were given a diagnosis of chronic fatigue syndrome in up to one third of cases.[9] [13] [20] [21] [22] The US Institute of Medicine has clustered several key symptoms associated with chronic fatigue syndrome, and has proposed the term "systemic exertion intolerance disease" (SEID) as an alternative to chronic fatigue syndrome.[23]
Last updated
Citations
National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. Oct 2021 [internet publication].[Full Text]
Centers for Disease Control and Prevention. Myalgic encephalomyelitis/chronic fatigue syndrome, etiology and pathophysiology. Jul 2018 [internet publication].[Full Text]
Cornuz J, Guessous I, Favrat B. Fatigue: a practical approach to diagnosis in primary care. CMAJ. 2006 Mar 14;174(6):765-7.[Abstract][Full Text]
Hamilton W, Watson J, Round A. Investigating fatigue in primary care. BMJ. 2010;341:c4259.[Abstract]
1. Chen MK. The epidemiology of self-perceived fatigue among adults. Prev Med. 1986 Jan;15(1):74-81.[Abstract]
2. Hickie IB, Hooker AW, Hadzi-Pavlovic D, et al. Fatigue in selected primary care settings: sociodemographic and psychiatric correlates. Med J Aust. 1996 May 20;164(10):585-8.[Abstract]
3. Wessely S, Chalder T, Hirsch S, et al. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. Am J Public Health. 1997 Sep;87(9):1449-55.[Abstract][Full Text]
4. Kroenke K, Wood DR, Mangelsdorff AD, et al. Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA. 1988 Aug 19;260(7):929-34.[Abstract]
5. Skapinakis P, Lewis G, Meltzer H. Clarifying the relationship between unexplained chronic fatigue and psychiatric morbidity: results from a community survey in Great Britain. Int Rev Psychiatry. 2003 Feb-May;15(1-2):57-64.[Abstract]
6. Steele L, Dobbins JG, Fukuda K, et al. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998 Sep 28;105(3A):83S-90S.[Abstract]
7. Galland-Decker C, Marques-Vidal P, Vollenweider P. Prevalence and factors associated with fatigue in the Lausanne middle-aged population: a population-based, cross-sectional survey. BMJ Open. 2019 Aug 24;9(8):e027070.[Abstract][Full Text]
8. Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet. 2006 Jan 28;367(9507):346-55.[Abstract]
9. Wessely S, Chalder T, Hirsch S, et al. Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting. Am J Psychiatry. 1996 Aug;153(8):1050-9.[Abstract]
10. Cathebras PJ, Robbins JM, Kirmayer LJ, et al. Fatigue in primary care: prevalence, psychiatric comorbidity, illness behavior, and outcome. J Gen Intern Med. 1992 May-Jun;7(3):276-86.[Abstract]
11. Okkes IM, Oskam SK, Lamberts H. The probability of specific diagnoses for patients presenting with common symptoms to Dutch family physicians. J Fam Pract. 2002 Jan;51(1):31-6.[Abstract]
12. Walker EA, Katon WJ, Jemelka RP. Psychiatric disorders and medical care utilization among people in the general population who report fatigue. J Gen Intern Med. 1993 Aug;8(8):436-40.[Abstract]
13. Bates DW, Schmitt W, Buchwald D, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993 Dec 27;153(24):2759-65.[Abstract]
14. Stadje R, Dornieden K, Baum E, et al. The differential diagnosis of tiredness: a systematic review. BMC Fam Pract. 2016 Oct 20;17(1):147.[Abstract][Full Text]
15. Bensing JM, Hulsman RL, Schreurs KM. Gender differences in fatigue: biopsychosocial factors relating to fatigue in men and women. Med Care. 1999 Oct;37(10):1078-83.[Abstract]
16. Verdon F, Burnand B, Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003 May 24;326(7399):1124.[Abstract][Full Text]
17. Vaucher P, Druais PL, Waldvogel S, et al. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012 Aug 7;184(11):1247-54.[Abstract]
18. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9.[Abstract]
19. Reid S, Chalder T, Cleare A, et al. Chronic fatigue syndrome. BMJ. 2000 Jan 29;320(7230):292-6.[Abstract][Full Text]
20. Buchwald D, Umali P, Umali J, et al. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med. 1995 Jul 15;123(2):81-8.[Abstract]
21. Darbishire L, Ridsdale L, Seed PT. Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract. 2003 Jun;53(491):441-5.[Abstract][Full Text]
22. Ridsdale L, Evans A, Jerrett W, et al. Patients with fatigue in general practice: a prospective study. BMJ. 1993 Jul 10;307(6896):103-6.[Abstract][Full Text]
23. Institute of Medicine. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, DC: The National Academies Press; 2015.
24. Ohayon MM. Prevalence of DSM-IV diagnostic criteria of insomnia: distinguishing insomnia related to mental disorders from sleep disorders. J Psychiatr Res. 1997 May-Jun;31(3):333-46.[Abstract]
25. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.
26. National Institute for Health and Care Excellence. Obstructive sleep apnoea/hypopnoea syndrome and obesity hypoventilation syndrome in over 16s. Aug 2021 [internet publication].[Full Text]
27. Hornyak M, Kopasz M, Berger M, et al. Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome. J Clin Psychiatry. 2005 Sep;66(9):1139-45.[Abstract]
28. Cuellar NG, Strumpf NE, Ratcliffe SJ. Symptoms of restless legs syndrome in older adults: outcomes on sleep quality, sleepiness, fatigue, depression, and quality of life. J Am Geriatr Soc. 2007 Sep;55(9):1387-92.[Abstract]
29. Lawrie SM, Pelosi AJ. Chronic fatigue syndrome in the community. Prevalence and associations. Br J Psychiatry. 1995 Jun;166(6):793-7.[Abstract]
30. Krayenbuehl PA, Battegay E, Breymann C, et al. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood. 2011 Sep 22;118(12):3222-7.[Abstract][Full Text]
31. Favrat B, Balck K, Breymann C, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women--PREFER a randomized, placebo-controlled study. PLoS One. 2014 Apr 21;9(4):e94217.[Abstract][Full Text]
32. Drexler H, Coats AJ. Explaining fatigue in congestive heart failure. Annu Rev Med. 1996;47:241-56.[Abstract]
33. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016 Jul 14;37(27):2129-200.[Abstract][Full Text]
34. McSweeney JC, Cody M, O'Sullivan P, et al. Women's early warning symptoms of acute myocardial infarction. Circulation. 2003 Nov 25;108(21):2619-23.[Abstract][Full Text]
35. Blakeman JR, Stapleton SJ. An integrative review of fatigue experienced by women before and during myocardial infarction. J Clin Nurs. 2018 Mar;27(5-6):906-16.[Abstract][Full Text]
36. Khan NA, Daskalopoulou SS, Karp I, et al. Sex differences in acute coronary syndrome symptom presentation in young patients. JAMA Intern Med. 2013 Nov 11;173(20):1863-71.[Abstract]
37. Crea F, Battipaglia I, Andreotti F, et al. Sex differences in mechanisms, presentation and management of ischaemic heart disease. Atherosclerosis. 2015 Jul;241(1):157-68.[Abstract]
38. Canaris GJ, Manowitz NR, Mayor G, et al. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000 Feb 28;160(4):526-34.[Abstract]
39. Biondi B, Cappola AR, Cooper DS. Subclinical Hypothyroidism: A Review. JAMA. 2019 Jul 9;322(2):153-60.[Abstract][Full Text]
40. Levy-Marchal C, Patterson CC, Green A, et al. Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study. European and Diabetes. Diabetologia. 2001 Oct;44(suppl 3):B75-80.[Abstract]
41. Lovas K, Loge JH, Husebye ES. Subjective health status in Norwegian patients with Addison's disease. Clin Endocrinol (Oxf). 2002 May;56(5):581-8.[Abstract]
42. Biermasz NR, van Thiel SW, Pereira AM, et al. Decreased quality of life in patients with acromegaly despite long-term cure of growth hormone excess. J Clin Endocrinol Metab. 2004 Nov;89(11):5369-76.[Abstract][Full Text]
43. Wallymahmed ME, Foy P, MacFarlane IA. The quality of life of adults with growth hormone deficiency: comparison with diabetic patients and control subjects. Clin Endocrinol (Oxf). 1999 Sep;51(3):333-8.[Abstract]
44. Aronson MD, Komaroff AL, Pass TM, et al. Heterophil antibody in adults with sore throat: frequency and clinical presentation. Ann Intern Med. 1982 Apr;96(4):505-8.[Abstract]
45. Barroso J. A review of fatigue in people with HIV infection. J Assoc Nurses AIDS Care. 1999 Sep-Oct;10(5):42-9.[Abstract]
46. Crook H, Raza S, Nowell J, et al. Long covid-mechanisms, risk factors, and management. BMJ. 2021 Jul 26;374:n1648.[Abstract][Full Text]
47. Chen C, Haupert SR, Zimmermann L, et al. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review. J Infect Dis. 2022 Nov 1;226(9):1593-607.[Abstract][Full Text]
48. Nadelman RB, Nowakowski J, Forseter G, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med. 1996 May;100(5):502-8.[Abstract]
49. Cairns V, Godwin J. Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol. 2005 Dec;34(6):1340-5.[Abstract][Full Text]
50. Berende A, ter Hofstede HJ, Vos FJ, et al. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. N Engl J Med. 2016 Mar 31;374(13):1209-20.[Abstract][Full Text]
51. Monto AS, Gravenstein S, Elliott M, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000 Nov 27;160(21):3243-7.[Abstract][Full Text]
52. Revol B, Jullian-Desayes I, Tamisier R, et al. Ticagrelor and Central Sleep Apnea. J Am Coll Cardiol. 2018 May 22;71(20):2378-9.[Abstract][Full Text]
53. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury - current exposures and clinical manifestations. N Engl J Med. 2003 Oct 30;349(18):1731-7.[Abstract]
54. Leikin JB, Karydes HC, Whiteley PM, et al. Outpatient toxicology clinic experience of patients with hip implants. Clin Toxicol (Phila). 2013 May;51(4):230-6.[Abstract]
55. Breslin E, van der Schans C, Breukink S, et al. Perception of fatigue and quality of life in patients with COPD. Chest. 1998 Oct;114(4):958-64.[Abstract]
56. Guyatt GH, Berman LB, Townsend M, et al. A measure of quality of life for clinical trials in chronic lung disease. Thorax. 1987 Oct;42(10):773-8.[Abstract][Full Text]
57. Wijkstra PJ, Van Altena R, Kraan J, et al. Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home. Eur Respir J. 1994 Feb;7(2):269-73.[Abstract][Full Text]
58. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-731.[Full Text]
59. Alsina-Restoy X, Torres-Castro R, Caballería E, et al. Pulmonary rehabilitation in sarcoidosis: a systematic review and meta-analysis. Respir Med. 2023 Nov-Dec;219:107432.[Abstract]
60. Atkins C, Wilson AM. Managing fatigue in sarcoidosis - a systematic review of the evidence. Chron Respir Dis. 2017 May;14(2):161-73.[Abstract][Full Text]
61. Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med. 2002 Jan 17;346(3):180-8.[Abstract]
62. Jelsness-Jørgensen LP, Bernklev T, Lundin KEA. Fatigue as an Extra-Intestinal Manifestation of Celiac Disease: A Systematic Review. Nutrients. 2018 Nov 3;10(11):.[Abstract][Full Text]
63. Goldblatt J, Taylor PJ, Lipman T, et al. The true impact of fatigue in primary biliary cirrhosis: a population study. Gastroenterology. 2002 May;122(5):1235-41.[Abstract]
64. Foster GR, Goldin RD, Thomas HC. Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis. Hepatology. 1998 Jan;27(1):209-12.[Abstract]
65. Witt-Sullivan H, Heathcote J, Cauch K, et al. The demography of primary biliary cirrhosis in Ontario, Canada. Hepatology. 1990 Jul;12(1):98-105.[Abstract]
66. Grimstad T, Norheim KB. Fatigue in inflammatory bowel disease. [in nor]. Tidsskr Nor Laegeforen. 2016 Nov;136(20):1721-4.[Abstract][Full Text]
67. Han CJ, Yang GS. Fatigue in Irritable Bowel Syndrome: A Systematic Review and Meta-analysis of Pooled Frequency and Severity of Fatigue. Asian Nurs Res (Korean Soc Nurs Sci). 2016 Mar;10(1):1-10.[Abstract][Full Text]
68. Laupacis A, Muirhead N, Keown P, et al. A disease-specific questionnaire for assessing quality of life in patients on hemodialysis. Nephron. 1992;60(3):302-6.[Abstract]
69. McCann K, Boore JR. Fatigue in persons with renal failure who require maintenance haemodialysis. J Adv Nurs. 2000 Nov;32(5):1132-42.[Abstract]
70. Krupp LB, Pollina DA. Mechanisms and management of fatigue in progressive neurological disorders. Curr Opin Neurol. 1996 Dec;9(6):456-60.[Abstract]
71. Karlsen K, Larsen JP, Tandberg E, et al. Fatigue in patients with Parkinsons disease. Mov Disord. 1999 Mar;14(2):237-41.[Abstract]
72. Beiske AG, Svensson E. Fatigue in Parkinson's disease: a short update. Acta Neurol Scand Suppl. 2010;(190):78-81.[Abstract]
73. Staub F, Bogousslavsky J. Fatigue after stroke: a major but neglected issue. Cerebrovasc Dis. 2001 Aug;12(2):75-81.[Abstract]
74. Cumming TB, Yeo AB, Marquez J, et al. Investigating post-stroke fatigue: An individual participant data meta-analysis. J Psychosom Res. 2018 Oct;113:107-12.[Abstract][Full Text]
75. van der Werf SP, Jongen PJ, Lycklama a Nijeholt GJ, et al. Fatigue in multiple sclerosis: interrelations between fatigue complaints, cerebral MRI abnormalities and neurological disability. J Neurol Sci. 1998 Oct 8;160(2):164-70.[Abstract]
76. Vercoulen JH, Hommes OR, Swanink CM, et al. The measurement of fatigue in patients with multiple sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects. Arch Neurol. 1996 Jul;53(7):642-9.[Abstract]
77. Colombo B, Martinelli Boneschi F, Rossi P, et al. MRI and motor evoked potential findings in nondisabled multiple sclerosis patients with and without symptoms of fatigue. J Neurol. 2000 Jul;247(7):506-9.[Abstract]
78. Krupp LB, LaRocca NG, Muir J, et al. A study of fatigue in systemic lupus erythematosus. J Rheumatol. 1990 Nov;17(11):1450-2.[Abstract]
79. Omdal R, Waterloo K, Koldingsnes W, et al. Fatigue in patients with systemic lupus erythematosus: the psychosocial aspects. J Rheumatol. 2003 Feb;30(2):283-7.[Abstract]
80. Riemsma RP, Rasker JJ, Taal E, et al. Fatigue in rheumatoid arthritis: the role of self-efficacy and problematic social support. Br J Rheumatol. 1998 Oct;37(10):1042-6.[Abstract]
81. Stone P, Richardson A, Ream E, et al. Cancer-related fatigue: inevitable, unimportant and untreatable? Results of a multi-centre patient survey. Cancer Fatigue Forum. Ann Oncol. 2000 Aug;11(8):971-5.[Abstract]
82. Levy M. Cancer fatigue: a review for psychiatrists. Gen Hosp Psychiatry. 2008 May-Jun;30(3):233-44.[Abstract]
83. Cella D, Lai JS, Chang CH, et al. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002 Jan 15;94(2):528-38.[Abstract][Full Text]
84. Harter M, Reuter K, Aschenbrenner A, et al. Psychiatric disorders and associated factors in cancer: results of an interview study with patients in inpatient, rehabilitation and outpatient treatment. Eur J Cancer. 2001 Jul;37(11):1385-93.[Abstract]
85. National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. Oct 2021 [internet publication].[Full Text]
86. Muller AE, Tveito K, Bakken IJ, et al. Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched. J Transl Med. 2020 Dec 14;18(1):484.[Abstract][Full Text]
87. Huth TK, Eaton-Fitch N, Staines D, et al. A systematic review of metabolomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID). J Transl Med. 2020 May 13;18(1):198.[Abstract][Full Text]
88. Centers for Disease Control and Prevention. Myalgic encephalomyelitis/chronic fatigue syndrome, etiology and pathophysiology. Jul 2018 [internet publication].[Full Text]
89. Miller RR, Uyaguari-Diaz M, McCabe MN, et al. Metagenomic Investigation of Plasma in Individuals with ME/CFS Highlights the Importance of Technical Controls to Elucidate Contamination and Batch Effects. PLoS One. 2016;11(11):e0165691.[Abstract][Full Text]
90. Bombardier CH, Buchwald D. Chronic fatigue, chronic fatigue syndrome, and fibromyalgia. Disability and health-care use. Med Care. 1996 Sep;34(9):924-30.[Abstract]
91. Cornuz J, Guessous I, Favrat B. Fatigue: a practical approach to diagnosis in primary care. CMAJ. 2006 Mar 14;174(6):765-7.[Abstract][Full Text]
92. Lane TJ, Matthews DA, Manu P. The low yield of physical examinations and laboratory investigations of patients with chronic fatigue. Am J Med Sci. 1990 May;299(5):313-8.[Abstract]
93. Ridsdale L, Evans A, Jerrett W, et al. Patients who consult with tiredness: frequency of consultation, perceived causes of tiredness and its association with psychological distress. Br J Gen Pract. 1994 Sep;44(386):413-6.[Abstract][Full Text]
94. Hamilton W, Watson J, Round A. Investigating fatigue in primary care. BMJ. 2010;341:c4259.[Abstract]
95. Wright J, O'Connor KM. Fatigue. Med Clin North Am. 2014 May;98(3):597-608.[Abstract]
96. Yu DS, Lee DT, Man NW. Fatigue among older people: a review of the research literature. Int J Nurs Stud. 2010 Feb;47(2):216-28.[Abstract]
97. Guidelines and Protocols Advisory Committee, British Columbia Medical Services Commission. Iron deficiency: diagnosis and management. April 2019 [internet publication].[Full Text]
98. Ebell MH, Belden JL. Clinical inquiries. What is a reasonable initial approach to the patient with fatigue? J Fam Pract. 2001 Jan;50(1):16-7.[Abstract]
99. Kroenke K, Spitzer RL, Williams JB. The patient health questionnaire-2: validity of a two-item depression screener. Med Care. 2003 Nov;41(11):1284-92.[Abstract]
100. Spitzer RL, Williams JB, Kroenke K, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA. 1994 Dec 14;272(22):1749-56.[Abstract]
101. Jackson JL, Houston JS, Hanling SR, et al. Clinical predictors of mental disorders among medical outpatients. Arch Intern Med. 2001 Mar 26;161(6):875-9.[Abstract][Full Text]
102. Spitzer RL, Kroenke K, Williams JB; Patient Health Questionnaire Primary Care Study Group. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. JAMA. 1999 Nov 10;282(18):1737-44.[Abstract][Full Text]
103. Ewing JA. Detecting alcoholism: the CAGE questionnaire. JAMA. 1984 Oct 12;252(14):1905-7.[Abstract]
104. Babor TF, Higgins-Biddle JC, Saunders JB, et al. The alcohol use disorders identification test: guidelines for use in primary care. 2nd ed. World Health Organization. Department of Mental Health and Substance Dependence. Geneva, Switzerland: WHO; 2001.[Full Text]
105. Violani C, Devoto A, Lucidi F, et al. Validity of a short insomnia questionnaire: the SDQ. Brain Res Bull. 2004 Jun 30;63(5):415-21.[Abstract]
106. Nguyen AT, Baltzan MA, Small D, et al. Clinical reproducibility of the Epworth Sleepiness Scale. J Clin Sleep Med. 2006 Apr 15;2(2):170-4.[Abstract]
107. Rosenthal LD, Dolan DC. The Epworth sleepiness scale in the identification of obstructive sleep apnea. J Nerv Ment Dis. 2008 May;196(5):429-31.[Abstract]
108. Whitehead L. The measurement of fatigue in chronic illness: a systematic review of unidimensional and multidimensional fatigue measures. J Pain Symptom Manage. 2009 Jan;37(1):107-28.[Abstract]
109. Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer. 1999 Mar 1;85(5):1186-96.[Abstract]
110. Krupp LB, LaRocca NG, Muir-Nash J, et al. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3.[Abstract]
111. Hann DM, Jacobsen PB, Azzarello LM, et al. Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory. Qual Life Res. 1998 May;7(4):301-10.[Abstract]
112. Belza B, Miyawaki CE, Liu M, et al. A Systematic Review of Studies Using the Multidimensional Assessment of Fatigue Scale. J Nurs Meas. 2018 Apr 1;26(1):36-75.[Abstract][Full Text]
113. Kalra L, Hamlyn AN, Jones BJ. Blue sclerae: a common sign of iron deficiency? Lancet. 1986 Nov 29;2(8518):1267-9.[Abstract]
114. Prabhakar VK, Shalet SM. Aetiology, diagnosis, and management of hypopituitarism in adult life. Postgrad Med J. 2006 Apr;82(966):259-66.[Abstract][Full Text]
115. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the Multicenter Criteria Committee. Arthritis Rheum. 1990 Feb;33(2):160-72.[Abstract]
116. Centers for Disease Control and Prevention. Signs and symptoms of untreated Lyme disease. Jan 2021 [internet publication] [Full Text]
117. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032.[Abstract][Full Text]
118. Anton RF, Moak DH. Carbohydrate-deficient transferrin and gamma-glutamyltransferase as markers of heavy alcohol consumption: gender differences. Alcohol Clin Exp Res. 1994 Jun;18(3):747-54.[Abstract]
119. Hanna FWF, Issa BG, Kevil B, et al. Investigating cortisol excess or deficiency: a practical approach. BMJ. 2019 Nov 26;367:l6039.[Abstract][Full Text]
120. Oelkers W. Hyponatremia and inappropriate secretion of vasopressin (antidiuretic hormone) in patients with hypopituitarism. N Engl J Med. 1989 Aug 24;321(8):492-6.[Abstract]
121. Centers for Disease Control and Prevention. Evaluating and caring for patients with post-COVID conditions: interim guidance. Jun 2021 [internet publication].[Full Text]
122. National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing the long-term effects of COVID-19. Jan 2024 [internet publication].[Full Text]
123. Mulrow CD, Williams JW Jr, Gerety MB, et al. Case-finding instruments for depression in primary care settings. Ann Intern Med. 1995 Jun 15;122(12):913-21.[Abstract]
124. Rushton DH, Norris MJ, Dover R, et al. Causes of hair loss and the developments in hair rejuvenation. Int J Cosmet Sci. 2002 Feb;24(1):17-23.[Abstract]
125. Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron deficiency and its potential relationship to hair loss. J Am Acad Dermatol. 2006 May;54(5):824-44.[Abstract]
126. American Academy of Sleep Medicine. International classification of sleep disorders - third edition, text revision (ICSD-3-TR). Westchester, IL: American Academy of Sleep Medicine; 2023.
127. Gibson GJ. Obstructive sleep apnoea syndrome: underestimated and undertreated. Br Med Bull. 2005 Mar 29;72:49-65.[Abstract][Full Text]
128. American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events. Feb 2023 [internet publication].[Full Text]
129. Erratum: Evaluation and management of obesity hypoventilation syndrome. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2019 Nov 15;200(10):1326.[Full Text]
130. Mokhlesi B, Masa JF, Brozek JL, et al. Evaluation and management of obesity hypoventilation syndrome. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2019 Aug 1;200(3):e6-24.[Abstract][Full Text]
131. Mokhlesi B, Tulaimat A, Faibussowitsch I, et al. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. 2007 Jun;11(2):117-24.[Abstract]
132. Sivam S, Yee B, Wong K, et al. Obesity hypoventilation syndrome: early detection of nocturnal-only hypercapnia in an obese population. J Clin Sleep Med. 2018 Sep 15;14(9):1477-84.[Abstract][Full Text]
133. American Diabetes Association Professional Practice Committee. 2. Diagnosis and classification of diabetes: standards of care in diabetes-2024. Diabetes Care. 2024 Jan 1;47(suppl 1):S20-42.[Abstract][Full Text]
134. Centers for Disease Control and Prevention. Influenza signs and symptoms and the role of laboratory diagnostics. October 2016 [internet publication].[Full Text]
135. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5.[Abstract][Full Text]
136. Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in northern Germany: a clinical review. Chest. 2002 Apr;121(4):1177-82.[Abstract][Full Text]
137. Weir MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985 Oct;79(4):467-78.[Abstract][Full Text]
138. Baydur A. The spectrum of extrapulmonary tuberculosis. West J Med. 1977 Apr;126(4):253-62.[Abstract][Full Text]
139. Nataraj G, Kurup S, Pandit A, et al. Correlation of fine needle aspiration cytology, smear and culture in tuberculous lymphadenitis: a prospective study. J Postgrad Med. 2002 Apr-Jun;48(2):113-6.[Abstract][Full Text]
140. Centers for Disease Control and Prevention. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. Jan 2009 [internet publication].[Full Text]
141. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].[Full Text]
142. Bjerrum S, Schiller I, Dendukuri N, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019 Oct 21;10(10):CD011420.[Abstract][Full Text]
143. Dickstein G, Shechner C, Nicholson WE, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab. 1991 Apr;72(4):773-8.[Abstract]
144. Mead P, Petersen J, Hinckley A. Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):703.[Abstract][Full Text]
145. Hedman K, Lappalainen M, Seppala I, et al. Recent primary toxoplasma infection indicated by a low avidity of specific IgG.J Infect Dis. 1989 Apr;159(4):736-40.[Abstract]
146. Perazella MA, Reilly RF. Chronic kidney disease: a new classification and staging system. Hospital Physician. 2003 Mar;39:18-45.
147. Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4.[Abstract][Full Text]
148. Smeenk R, Brinkman K, van den Brink H, et al. Antibodies to DNA in patients with systemic lupus erythematosus: their role in the diagnosis, the follow-up and the pathogenesis of the disease. Clin Rheumatol. 1990 Mar;9(1 suppl 1):100-10.[Abstract]
149. Eaton RB, Schnneider G, Schur PH. Enzyme immunoassay for antibodies to native DNA. Specificity and quality of antibodies. Arthritis Rheum. 1983 Jan;26(1):52-62.[Abstract]
