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1.  Fatigue in the Danish general population. Influence of sociodemographic factors and disease 
OBJECTIVE—To measure the levels of fatigue in the general population, and to examine how disease and sociodemographic factors influence fatigue.
DESIGN—Cross sectional questionnaire study in the Danish general population.
SUBJECTS—A random, age stratified sample of 1608 people aged 20-77 with an equal gender distribution (response rate 67%).
MAIN OUTCOME MEASURES—Five fatigue scales from the questionnaire Multidimensional Fatigue Inventory: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation and Mental Fatigue.
RESULTS—Fatigue scores were skewed towards absence of fatigue. The General Fatigue and Physical Fatigue scales showed the highest fatigue levels while the Reduced Motivation scale showed lowest levels. Gender differences in fatigue scores were small, but the variability among women was higher—that is, more women had high scores. A multiple linear regression analysis showed that respondents of low social status and respondents with a depression had high fatigue scores on all scales, independent of other factors. Chronic somatic disease had an independent direct effect on Mental Fatigue, but for the rest of the scales, the effect of somatic disease depended on age, gender and/or whether the person was living alone. For example, General and Physical Fatigue decreased with age among healthy people, whereas scores on these scales increased with age among those with a somatic disease.
CONCLUSIONS—Physical and mental diseases play essential parts for the level of fatigue and as modulators of the associations between sociodemographic factors and fatigue. These interactions should be taken into account in future research on fatigue and sociodemographic factors and when data from clinical studies are compared with normative data from the general population.


Keywords: fatigue; general population
doi:10.1136/jech.54.11.827
PMCID: PMC1731588  PMID: 11027196
2.  Effects of glatiramer acetate on fatigue and days of absence from work in first-time treated relapsing-remitting multiple sclerosis 
Objectives
Treatment of multiple sclerosis patients with glatiramer acetate has been demonstrated a beneficial effect on disease activity. The objective of this prospective naturalistic study was to evaluate the impact of glatiramer acetate on fatigue and work absenteeism.
Methods
291 treatment-naïve patients with relapsing remitting multiple sclerosis were included and treated with glatiramer acetate for twelve months. Relapse rates, disability, fatigue symptoms, days of absence from work and adverse events were monitored. Fatigue was measured with the MFIS scale and with a visual analogue scale.
Results
Total MFIS scores decreased by 7.6 ± 16.4 from 34.6 to 27.0 (p ≤ 0.001). Significant reductions were observed on all three subscales of the MFIS. Fatigue symptoms, assessed using a visual analogue scale, decreased by 1.04 ± 2.88 cm from 4.47 cm to 3.43 cm (p ≤ 0.001). The proportion of patients absent from work at least once was reduced by a factor of two from 65.1% to 30.1% (p ≤ 0.001). Tolerance to treatment was rated as very good or good in 78.3% of patients. Adverse effects, most frequently local injection site reactions, were reported in 15.1% of patients.
Conclusion
Treatment with glatiramer acetate was associated with a significant improvement in fatigue symptoms and a marked reduction in absence from work. Treatment was well-tolerated. Such benefits are of relevance to overall patient well-being.
doi:10.1186/1477-7525-6-67
PMCID: PMC2542355  PMID: 18775064
3.  Fatigue as a predictor of sickness absence: results from the Maastricht cohort study on fatigue at work 
Occupational and Environmental Medicine  2003;60(Suppl 1):i71-i76.
Objectives: To investigate whether there is a relationship between fatigue and sickness absence. Two additional hypotheses were based on the theoretical distinction between involuntary, health related absence and voluntary, attitudinal absence. In the literature, the former term is usually used to describe long term sickness absence, the latter relates to short term sickness absence. In line with this, the first additional hypothesis was that higher fatigue would correspond with a higher risk of long term, primarily health related absence. The second additional hypothesis was that higher fatigue would correspond with a higher risk of short term, primarily motivational absence.
Methods: A multidimensional fatigue measure, as well as potential sociodemographic and work related confounders were assessed in the baseline questionnaire of the Maastricht cohort study on fatigue at work. Sickness absence was objectively assessed on the basis of organisational absence records and measured over the six months immediately following the baseline questionnaire. In the first, general hypothesis the effect of fatigue on time-to-onset of first sickness absence spell during follow up was investigated. For this purpose, a survival analysis was performed. The effect of fatigue on long term sickness absence was tested by a logistic regression analysis. The effect of fatigue on short term sickness absence was investigated by performing a survival analysis with time-to-onset of first short absence spell as an outcome.
Results: It was found that higher fatigue decreased the time-to-onset of the first sickness absence spell. Additional analyses showed that fatigue was related to long term as well as to short term sickness absence. The effect of fatigue on the first mentioned outcome was stronger than the effect on the latter outcome. Potential confounders only weakened the effect of fatigue on long term absence.
Conclusions: Fatigue was associated with short term but particularly with long term sickness absence. The relation between fatigue and future sickness absence holds when controlling for work related and sociodemographic confounders. Fatigue as measured with the Checklist Individual Strength can be used as a screening instrument to assess the likelihood of sickness absence in the short term.
doi:10.1136/oem.60.suppl_1.i71
PMCID: PMC1765725  PMID: 12782750
4.  Need for recovery from work related fatigue and its role in the development and prediction of subjective health complaints 
Occupational and Environmental Medicine  2003;60(Suppl 1):i62-i70.
Aims: To present the available empirical evidence for the assumed position of the concept of work related fatigue as: (1) short term effect of the working day; and (2) an intermediate variable between work demands and the development of subjective health complaints and sickness absence.
Methods: Results from six single occupation studies, conducted between 1996 and 2002, are presented. Work demands (working hours, decision latitude, break control/autonomy, and mental, emotional, and physical demands) were assessed through validated scales. Work related fatigue was represented and assessed by means of the need for recovery after working time scale in all studies. Subjective health complaints and duration of sickness absence were quantified with the same instruments in most studies as well. Both cross sectional studies (four) as well as prospective studies (two; up to two years follow up) were performed. Cross sectional data of 3820 workers, in total, were available. Prospective data were accessible for 1200 workers in industry and health care. Models were tested with stepwise multiple regression analyses.
Results: Strong associations between work demands and need for necovery were found in different occupations. The variance explained in need for recovery by work demands, age, and (baseline) need for recovery ranged between 14% and 48% in both types of studies. The amount of explained variance by work demands, age, and (baseline) need for recovery in subjective health complaints ranged between 24% and 58% in the different occupations. The prospective data showed the prognostic value of need for recovery in relation to subjective health complaints (in terms of psychosomatic complaints, emotional exhaustion, or sleep problems) and duration of future sickness absence.
Conclusions: The hypothesised role for work related fatigue as a link in the causal string of events, that is assumed to exist between repeated adverse work demands and the development of work related stress reactions, (psychological) overload and, eventually, health problems, was confirmed.
doi:10.1136/oem.60.suppl_1.i62
PMCID: PMC1765724  PMID: 12782749
5.  Associations between fatigue attributions and fatigue, health, and psychosocial work characteristics: a study among employees visiting a physician with fatigue 
Occupational and Environmental Medicine  2003;60(Suppl 1):i99-i104.
Aims: To study associations between characteristics of employees active at work and making a fatigue related visit to the general practitioner (GP) or occupational physician (OP) in terms of fatigue, physical health problems, mental health problems, psychosocial work characteristics, and attributions of their fatigue complaints.
Methods: Self report questionnaires from the Maastricht Cohort Study Fatigue at Work were used to measure fatigue (Checklist Individual Strength, Maslach Burnout Inventory–General Survey), physical health problems (chronic illness), mental health problems (Hospital Anxiety and Depression Scale), psychosocial work characteristics (Job Content Questionnaire), and fatigue attributions (somatic, psychological, none) in employees who made a fatigue related visit to the GP or OP over a six month period.
Results: In employees visiting only the GP, fatigue was an important reason to visit in one of seven (13.9%) employees. These fatigue related visits were in particular associated with high fatigue levels and mental health problems. A psychological fatigue attribution was reported by 41.8%, a somatic fatigue attribution by 44.0%. On a multivariate level, mental health problems showed the strongest association with psychological fatigue attributions, over and beyond fatigue itself. No associations were found between fatigue attributions and psychosocial work characteristics. Attributional patterns appeared to be different between visitors of the GP and the OP.
Conclusions: Fatigue is a common reason among employees to consult a GP. Asking employees for their own fatigue attributions in terms of somatic or psychological causes may be useful for the GP—and possibly also the OP—to gather information about underlying health problems in employees active at work and making a fatigue related visit.
doi:10.1136/oem.60.suppl_1.i99
PMCID: PMC1765717  PMID: 12782755
6.  The definition of disabling fatigue in children and adolescents 
BMC Family Practice  2005;6:33.
Background
Disabling fatigue is the main illness related reason for prolonged absence from school. Although there are accepted criteria for diagnosing chronic fatigue in adults, it remains uncertain as to how best to define disabling fatigue and Chronic Fatigue Syndrome (CFS) in children and adolescents. In this population-based study, the aim was to identify children who had experienced an episode of disabling fatigue and examine the clinical and demographic differences between those individuals who fulfilled a narrow definition of disabling fatigue and those who fulfilled broader definitions of disabling fatigue.
Methods
Participants (aged 8–17 years) were identified from a population-based twin register. Parent report was used to identify children who had ever experienced a period of disabling fatigue. Standardised telephone interviews were then conducted with the parents of these affected children. Data on clinical and demographic characteristics, including age of onset, gender, days per week affected, hours per day spent resting, absence from school, comorbidity with depression and a global measure of impairment due to the fatigue, were examined. A narrow definition was defined as a minimum of 6 months disabling fatigue plus at least 4 associated symptoms, which is comparable to the operational criteria for CFS in adults. Broader definitions included those with at least 3 months of disabling fatigue and 4 or more of the associated symptoms and those with simply a minimum of 3 months of disabling fatigue. Groups were mutually exclusive.
Results
Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were completed on 99 of the 129 participants (77%) who had experienced fatigue. There were no significant differences in demographic and clinical characteristics or levels of impairment between those who fulfilled the narrower definition and those who fulfilled the broader definitions. The only exception was the reported number of days per week that the child was affected by the fatigue. All groups demonstrated evidence of substantial impairment associated with the fatigue.
Conclusion
Children and adolescents who do not fulfil the current narrow definition of CFS but do suffer from disabling fatigue show comparable and substantial impairment. In primary care settings, a broader definition of disabling fatigue would improve the identification of impaired children and adolescents who require support.
doi:10.1186/1471-2296-6-33
PMCID: PMC1192794  PMID: 16091130
7.  The factors associated with the burnout syndrome and fatigue in Cypriot nurses: a census report 
BMC Public Health  2012;12:457.
Background
Fatigue and burnout are two concepts often linked in the literature. However, regardless of their commonalities they should be approached as distinct concepts. The current and ever-growing reforms regarding the delivery of nursing care in Cyprus, stress for the development of ways to prevent burnout and effectively manage fatigue that can result from working in stressful clinical environments.
Methods
To explore the factors associated with the burnout syndrome in Cypriot nurses working in various clinical departments. A random sampling method taking into account geographical location, specialty and type of employment has been used.
Results
A total of 1,482 nurses (80.4% were females) working both in the private and public sectors completed and returned an anonymous questionnaire that included several aspects related to burnout; the MBI scale, questions related to occupational stress, and questions pertaining to self reported fatigue. Two-thirds (65.1%) of the nurses believed that their job is stressful with the majority reporting their job as stressful being female nurses (67.7%). Twelve point eight percent of the nurses met Maslach’s criteria for burnout. The prevalence of fatigue in nurses was found 91.9%. The prevalence of fatigue was higher in females (93%) than in males (87.5%) (p = 0.003). As opposed to the burnout prevalence, fatigue prevalence did not differ among the nursing departments (p = 0.166) and among nurses with a different marital status (p = 0.553). Burnout can be associated adequately knowing if nurses find their job stressful, their age, the level of emotional exhaustion and depersonalization. It has been shown that the fatigue may be thought of as a predictor of burnout, but its influence is already accounted by emotional exhaustion and depersonalization.
Conclusion
The clinical settings in Cyprus appear as stress generating environment for nurses. Nurses working both in the private and public sector appear to experience low to severe burnout. Self-reported fatigue interferes to the onset of emotional exhaustion and depersonalization.
doi:10.1186/1471-2458-12-457
PMCID: PMC3506490  PMID: 22716044
Burnout syndrome; Nurses; Fatigue; Maslach’s burnout scale
8.  Post-Infectious Fatigue 
Canadian Family Physician  1987;33:1217-1219.
Post-infectious fatigue or post-infectious neuromyasthenia (PIN) is an illness characterized by persisting fatigue and disability after apparent acute infections. In most cases the illness is attributed to a chronic Epstein-Barr virus infection. Symptoms include weakness and fatigue in the absence of physical findings or significant laboratory abnormalities. These patients are frequently depressed and have considerable disability resulting in prolonged loss of time from work. The illness may be persistent or can be relapsing, but often lingers for two years or more. There is no effective therapy. Pin is probably caused by an acute infection occurring in patients who are psychologically susceptible. They require emotional support, reassurance and explanation.
PMCID: PMC2218522  PMID: 21263931
post-infections neurasthenia; chronic Epstein-Barr virus
9.  Development of the chronic fatigue syndrome in severely fatigued employees: predictors of outcome in the Maastricht cohort study 
Study objective: To identify risk factors of the development of the chronic fatigue syndrome (CFS), the persistence or recurrence of fatigue, or recovery from fatigue in a large sample of fatigued employees.
Design: Analyses were based on the Maastricht cohort study (MCS), a prospective population based cohort study among more than 12 000 employees. Multiple regression models were used to identify predictors of CFS-like caseness (meeting research criteria for CFS), non-CFS fatigue caseness, or no fatigue caseness.
Setting: The working population in the Netherlands.
Participants: 1143 employees with medically unexplained fatigue were followed up prospectively for 44 months.
Main results: At 44 month follow up, 8% of the employees were CFS-like cases (none of who reported to have received a CFS diagnosis), 40% were non-CFS fatigue cases, and 52% were no longer fatigue cases. Factors that predicted CFS-like caseness compared with non-CFS fatigue caseness were high age, exhaustion, female sex, low education, and visits to the general practitioner. Factors that predicted CFS-like caseness compared with no fatigue caseness were fatigue, exhaustion, low education, visits to the GP and occupational physician, and bad self rated health. Factors that predicted non-CFS fatigue caseness compared with no fatigue caseness were fatigue, low self perceived activity, exhaustion, anxious mood, and bad self rated health.
Conclusions: Unexplained fatigue among employees in some instances is a precursor of the development of CFS. The prognostic role of self rated health suggests that prevention and treatment of chronic fatigue should be aimed at changing the perception of health or illness. Less clear is the role of health care seeking or receiving a CFS diagnosis.
doi:10.1136/jech.2003.017939
PMCID: PMC1763327  PMID: 15365116
10.  Cognitive impairment in patients with chronic fatigue: a preliminary study. 
Subjective impairment of memory and concentration is a frequent complaint in sufferers from chronic fatigue. To study this, 65 general practice attenders identified as having chronic fatigue were administered a structured psychiatric interview and a brief screening battery of cognitive tests. Subjective cognitive impairment was strongly related to psychiatric disorder, especially depressed mood, but not fatigue, anxiety, or objective performance. Simple tests of attention and concentration showed some impairment but this was influenced by both fatigue and depression. Subjects with high levels of fatigue performed less well on a memory task requiring cognitive effort, even in the absence of depression. There was no evidence for mental fatiguability. The relationship between depression, fatigue, and cognitive function requires further research.
PMCID: PMC1015065  PMID: 8331359
11.  Effectiveness of a minimal psychological intervention to reduce mild to moderate depression and chronic fatigue in a working population: the design of a randomized controlled trial 
BMC Public Health  2013;13:129.
Background
In a working population, common mental complaints like depressed mood and chronic fatigue are highly prevalent and often result in further deterioration of mental health and consequently absence from work. In a large occupational health setting, we will evaluate the (cost-) effectiveness of a Minimal Psychological Intervention (MPI), in reducing symptoms of depression and chronic fatigue in a working population. The MPI is also evaluated regarding its appreciation by worker, nurse, and occupational health physician (process evaluation). The tailor-made intervention is administered by nurses, who are trained in the principles of cognitive behavioural therapy and self-management.
Methods/design
The presented WoPaCoM study (Work Participation of Workers with Common Mental complaints) is a two-armed randomized controlled trial, comparing MPI with usual care. A total number of 124 workers suffering from (chronic) mental fatigue or mild to moderate depression will be included. A stratified and block randomization will be applied, stratifying by customer organisation, income, and gender, using a block size of four. It will include a baseline measurement and subsequently follow up measurements after 4, 6 and 12 months. The primary outcome measures are symptoms of either fatigue (using the Checklist Individual Strength) and/or depression (using the Beck Depression Inventory) and secondary outcome measures include sickness absence, self efficacy, costs and quality of life. Analysis will include both univariate and multivariate techniques and data will be analysed according to the intention to treat principle.
Discussion
Patient recruitment in an occupational setting proves to be complicated and time consuming. Shift work for instance proved to be an obstacle for making appointments for consultation with the nurse. Furthermore, economic developments might have created job insecurity which negatively influenced participation in the study, with workers being anxious to be detected as having psychological problems. Additionally, long-term follow-up in a working population is time-consuming and continuously engages occupational health staff and administrative personnel to control the process of data gathering. However, if the intervention proves to be effective, occupational medicine will have a manageable option for treatment of workers who are at risk of loss of productivity or sickness absence.
Trial registration
Nederlands Trialregister NTR3162
doi:10.1186/1471-2458-13-129
PMCID: PMC3579682  PMID: 23402525
12.  Chronic fatigue syndrome after Giardia enteritis: clinical characteristics, disability and long-term sickness absence 
BMC Gastroenterology  2012;12:13.
Background
A waterborne outbreak of Giardia lamblia gastroenteritis led to a high prevalance of long-lasting fatigue and abdominal symptoms. The aim was to describe the clinical characteristics, disability and employmentloss in a case series of patients with Chronic Fatigue Syndrome (CFS) after the infection.
Methods
Patients who reported persistent fatigue, lowered functional capacity and sickness leave or delayed education after a large community outbreak of giardiasis enteritis in the city of Bergen, Norway were evaluated with the established Centers for Disease Control and Prevention criteria for CFS. Fatigue was self-rated by the Fatigue Severity Scale (FSS). Physical and mental health status and functional impairment was measured by the Medical Outcome Severity Scale-short Form-36 (SF-36). The Hospital Anxiety and Depression Scale (HADS) was used to measure co-morbid anxiety and depression. Inability to work or study because of fatigue was determined by sickness absence certified by a doctor.
Results
A total of 58 (60%) out of 96 patients with long-lasting post-infectious fatigue after laboratory confirmed giardiasis were diagnosed with CFS. In all, 1262 patients had laboratory confirmed giardiasis. At the time of referral (mean illness duration 2.7 years) 16% reported improvement, 28% reported no change, and 57% reported progressive course with gradual worsening. Mean FSS score was 6.6. A distinctive pattern of impairment was documented with the SF-36. The physical functioning, vitality (energy/fatigue) and social functioning were especially reduced. Long-term sickness absence from studies and work was noted in all patients.
Conclusion
After giardiasis enteritis at least 5% developed clinical characteristics and functional impairment comparable to previously described post-infectious fatigue syndrome.
doi:10.1186/1471-230X-12-13
PMCID: PMC3292445  PMID: 22316329
13.  Work schedules and fatigue: a prospective cohort study 
Occupational and Environmental Medicine  2003;60(Suppl 1):i47-i53.
Aims: (1) To describe the prevalence of fatigue among employees in different work schedules (day work, three-shift, five-shift, and irregular shift work); (2) to investigate whether different work schedules are related to increasing fatigue over time, while taking into account job title and job characteristics; and (3) to study fatigue among shift workers changing to day work.
Methods: Data from nine consecutive four-monthly self administered questionnaires from the Maastricht Cohort Study on Fatigue at work (n = 12 095) were used with 32 months of follow up. Day and shift workers were matched on job title.
Results: The prevalence of fatigue was 18.1% in day workers, 28.6% in three-shift, 23.7% in five-shift, and 19.1% in irregular shift workers. For three-shift and five-shift workers substantial higher fatigue levels were observed compared to day workers at baseline measurement. In the course of fatigue over the 32 months of follow up there were only small and insignificant differences between employees in different work schedules. However, among employees fatigued at baseline, fatigue levels decreased faster over time among five-shift workers compared to fatigued day workers. Shift workers changing to day work reported substantially higher fatigue levels prior to change, compared to those remaining in shift work.
Conclusions: Substantial differences in fatigue existed between day and shift workers. However, as no considerable differences in the course of fatigue were found, these differences have probably developed within a limited time span after starting in a shift work job. Further, evidence was found that fatigue could be an important reason for quitting shift work and moving to day work. Finally, in the relation between work schedules and fatigue, perceived job characteristics might play an important role.
doi:10.1136/oem.60.suppl_1.i47
PMCID: PMC1765732  PMID: 12782747
14.  The Effect of Operating Time on Surgeons' Muscular Fatigue 
INTRODUCTION
A study was completed to determine if operating has an effect on a surgeon's muscular fatigue.
SUBJECTS AND METHODS
Six head and neck surgery consultants, two ENT registrars, 20 normal controls from two tertiary referral centres in the West Midlands participated in the study. Electromyography (EMG) measurements were taken throughout a day of operating and fatigue indices were compared to controls performing desk work.
RESULTS
The percentage changes in mean frequency of muscular contractions were examined; there was no significant difference in fatigue levels between consultants and registrars. Operating led to an increase in fatigue in all subjects, compared to no increase in controls performing desk work. It was also found that the brachioradialis muscle is used more than the mid-deltoid muscle and, hence, fatigues at a faster rate.
CONCLUSIONS
Surgeons should be aware that their muscular fatigue levels will increase as an operation progresses; therefore, if possible, more complex parts of the operation should be performed as early as possible, or, in the case of a very long operation, a change in surgeon may be necessary.
doi:10.1308/003588408X321710
PMCID: PMC2727807  PMID: 18990280
Muscular fatigue; Surgery; Electromyography
15.  Fatigue is a Brain-Derived Emotion that Regulates the Exercise Behavior to Ensure the Protection of Whole Body Homeostasis 
An influential book written by A. Mosso in the late nineteenth century proposed that fatigue that “at first sight might appear an imperfection of our body, is on the contrary one of its most marvelous perfections. The fatigue increasing more rapidly than the amount of work done saves us from the injury which lesser sensibility would involve for the organism” so that “muscular fatigue also is at bottom an exhaustion of the nervous system.” It has taken more than a century to confirm Mosso’s idea that both the brain and the muscles alter their function during exercise and that fatigue is predominantly an emotion, part of a complex regulation, the goal of which is to protect the body from harm. Mosso’s ideas were supplanted in the English literature by those of A. V. Hill who believed that fatigue was the result of biochemical changes in the exercising limb muscles – “peripheral fatigue” – to which the central nervous system makes no contribution. The past decade has witnessed the growing realization that this brainless model cannot explain exercise performance. This article traces the evolution of our modern understanding of how the CNS regulates exercise specifically to insure that each exercise bout terminates whilst homeostasis is retained in all bodily systems. The brain uses the symptoms of fatigue as key regulators to insure that the exercise is completed before harm develops. These sensations of fatigue are unique to each individual and are illusionary since their generation is largely independent of the real biological state of the athlete at the time they develop. The model predicts that attempts to understand fatigue and to explain superior human athletic performance purely on the basis of the body’s known physiological and metabolic responses to exercise must fail since subconscious and conscious mental decisions made by winners and losers, in both training and competition, are the ultimate determinants of both fatigue and athletic performance.
doi:10.3389/fphys.2012.00082
PMCID: PMC3323922  PMID: 22514538
fatigue; central nervous system; central governor model; anticipation; feedback; feedforward; brain; skeletal muscle
16.  ASCPRO Recommendations for the Assessment of Fatigue as an Outcome in Clinical Trials 
Context
Development of pharmacologic and behavioral interventions for cancer-related fatigue (CRF) requires adequate measures of this symptom. A guidance document from the Food and Drug Administration offers criteria for the formulation and evaluation of patient-reported outcome measures used in clinical trials to support drug or device labeling claims.
Methods
An independent working group, ASCPRO (Assessing Symptoms of Cancer Using Patient-Reported Outcomes), has begun developing recommendations for the measurement of symptoms in oncology clinical trials. The recommendations of the Fatigue Task Force for measurement of CRF are presented here.
Results
There was consensus that CRF could be measured effectively in clinical trials as the sensation of fatigue or tiredness, impact of fatigue/tiredness on usual functioning or as both sensation and impact. The ASCPRO Fatigue Task Force constructed a definition and conceptual model to guide measurement of CRF. ASCPRO recommendations do not endorse a specific fatigue measure but clarify how to evaluate and implement fatigue assessments in clinical studies. The selection of a CRF measure should be tailored to the goals of the research. Measurement issues related to various research environments were also discussed.
Conclusion
There exist in the literature good measures of CRF for clinical trials with strong evidence of clarity and comprehensibility to patients, content and construct validity, reliability, sensitivity to change in conditions in which one would expect them to change (assay sensitivity), and sufficient evidence to establish guides for interpreting changes in scores. Direction for future research is discussed.
doi:10.1016/j.jpainsymman.2010.02.006
PMCID: PMC2909842  PMID: 20538190
Cancer-related fatigue; self-report measures; clinical trials; patient-reported outcomes
17.  Is fatigue all in your head? A critical review of the central governor model 
The central governor model has recently been proposed as a general model to explain the phenomenon of fatigue. It proposes that the subconscious brain regulates power output (pacing strategy) by modulating motor unit recruitment to preserve whole body homoeostasis and prevent catastrophic physiological failure such as rigor. In this model, the word fatigue is redefined from a term that describes an exercise decline in the ability to produce force and power to one of sensation or emotion. The underpinnings of the central governor model are the refutation of what is described variously as peripheral fatigue, limitations models, and the cardiovascular/anaerobic/catastrophe model. This argument centres on the inability of lactic acid models of fatigue to adequately explain fatigue. In this review, it is argued that a variety of peripheral factors other than lactic acid are known to compromise muscle force and power and that these effects may protect against “catastrophe”. Further, it is shown that a variety of studies indicate that fatigue induced decreases in performance cannot be adequately explained by the central governor model. Instead, it is suggested that the concept of task dependency, in which the mechanisms of fatigue vary depending on the specific exercise stressor, is a more comprehensive and defensible model of fatigue. This model includes aspects of both central and peripheral contributions to fatigue, and the relative importance of each probably varies with the type of exercise.
doi:10.1136/bjsm.2005.023028
PMCID: PMC2564297  PMID: 16799110
fatigue; electromyography; exercise; metabolism
18.  Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis 
BMC Neurology  2010;10:43.
Background
Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice.
Methods/Design
This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change.
Discussion
This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research.
Trial registration
Current Controlled Trials ISRCTN76517470
doi:10.1186/1471-2377-10-43
PMCID: PMC2905353  PMID: 20553617
19.  Prediction of sickness absence: development of a screening instrument 
Objectives
To develop a concise screening instrument for early identification of employees at risk for sickness absence due to psychosocial health complaints.
Methods
Data from the Maastricht Cohort Study on “Fatigue at Work” were used to identify items to be associated with an increased risk of sickness absence. The analytical procedures univariate logistic regression, backward stepwise linear regression, and multiple logistic regression were successively applied. For both men and women, sum scores were calculated, and sensitivity and specificity rates of different cut‐off points on the screening instrument were defined.
Results
In women, results suggested that feeling depressed, having a burnout, being tired, being less interested in work, experiencing obligatory change in working days, and living alone, were strong predictors of sickness absence due to psychosocial health complaints. In men, statistically significant predictors were having a history of sickness absence, compulsive thinking, being mentally fatigued, finding it hard to relax, lack of supervisor support, and having no hobbies. A potential cut‐off point of 10 on the screening instrument resulted in a sensitivity score of 41.7% for women and 38.9% for men, and a specificity score of 91.3% for women and 90.6% for men.
Conclusions
This study shows that it is possible to identify predictive factors for sickness absence and to develop an instrument for early identification of employees at risk for sickness absence. The results of this study increase the possibility for both employers and policymakers to implement interventions directed at the prevention of sickness absence.
doi:10.1136/oem.2005.024521
PMCID: PMC2078122  PMID: 16698807
screening instrument; prediction; sickness absence
20.  Chronic fatigue syndrome‐like caseness as a predictor of work status in fatigued employees on sick leave: four year follow up study 
Objective
To assess whether CFS‐like caseness (meeting the criteria for chronic fatigue syndrome (CFS)) predicts work status in the long term.
Methods
Prospective study in a sample of fatigued employees absent from work. Data were collected at baseline and four years later, and included CFS‐like caseness and work status (inactive work status and full work incapacity).
Results
CFS‐like cases at baseline were three times more likely to be unable to work at follow up than fatigued employees who did not meet CFS criteria at baseline (ORs 3–3.3). These associations grew even stronger when demographic and clinical confounders were controlled for (ORs 3.4–4.4).
Conclusion
A CFS‐like status (compared to non‐CFS fatigue) proved to be a strong predictor of an inactive work status and full work incapacity in the long term. Since little is known about effective interventions that prevent absenteeism and work incapacity or facilitate return to work in subjects with chronic fatigue, there is a great need for powerful early interventions that restore or preserve the ability to work, especially for workers who meet criteria for CFS.
doi:10.1136/oem.2005.023176
PMCID: PMC2078121  PMID: 16698810
fatigue syndrome, chronic; work; absenteeism; prognosis
21.  Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome 
Nutrition Journal  2009;8:4.
Disturbances in intestinal microbial ecology and in the immune system of the host have been implicated as a part of the pathogenesis in chronic fatigue syndrome. Probiotic lactic acid producing bacteria have been shown to prevent and alleviate gastrointestinal disturbances and to normalize the cytokine profile which might be of an advantage for patients suffering from chronic fatigue syndrome. The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity in CFS patients. Fifteen patients fulfilling the criteria set by international researchers in the field at the US Centre for Disease Control and Prevention in 1994 for chronic fatigue syndrome, were included in the study. The patients had high fatigue severity scores and high disability scores. During the first two weeks baseline observations without treatment were assessed, succeeded by four weeks of intake of a probiotic product and a four-week follow-up period. The fatigue, health and physical activity was assessed by the use of the Visual Analogue Scales and the SF-12 Health Survey. Faecal samples were collected and the normal microflora was analysed. Neurocognitive functions improved during the study period while there were no significant changes in fatigue and physical activity scores. No major changes occurred in the gastrointestinal microflora. At the end of the study 6 of 15 patients reported that they had improved according to the assessment described. The findings in this study that improvement of health is possible to achieve should encourage further studies with interventions with probiotics in patients with CFS.
doi:10.1186/1475-2891-8-4
PMCID: PMC2642862  PMID: 19171024
22.  An epidemiological approach to study fatigue in the working population: the Maastricht Cohort Study 
Occupational and Environmental Medicine  2003;60(Suppl 1):i32-i39.
In 1998, a large scale prospective cohort study of prolonged fatigue in the working population was started in the Netherlands. The ultimate goal of this Maastricht Cohort Study was to identify risk factors involved in the aetiology and natural course of prolonged fatigue in the working population and to develop preventive measures and treatments that can be used in occupational health settings. In this paper, a conceptual model for epidemiological research on prolonged fatigue is presented. This model is the basis for the Maastricht Cohort Study. Alongside the model and design, the characteristics of the study population, the prevalence and one year cumulative incidence of prolonged fatigue, as well as its relation with secondary health outcomes (psychological distress, need for recovery, and burnout) are presented. Furthermore, model, design, and the presented results are discussed.
doi:10.1136/oem.60.suppl_1.i32
PMCID: PMC1765733  PMID: 12782745
23.  Psychometric and Clinical Assessment of the 10-item Reduced Version of the Fatigue Scale –Child Instrument 
Fatigue is one of the most debilitating conditions associated with cancer and anticancer therapy. The lack of reliable and valid self-report instruments has prevented accurate assessment of fatigue in pediatric oncology patients. The purpose of this study was to identify the most sensitive and specific score, i.e., the “cut score,” on the Fatigue Scale–Child (FS-C) to identify those children with high cancer-related fatigue in need of clinical intervention. We first used Rasch methods to identify the items on the FS-C that distinguished children with high cancer-related fatigue from other children; our findings indicated that the FS-C needed to be reduced from 14 items to 10 items. We then assessed the 10-item FS-C for its psychometric properties and applied the receiver operating characteristics (ROC) curve analysis to the FS-C responses from 221 children (aged 7–12 years) receiving anticancer treatment. The cut score identified with 75% sensitivity and 73.5% specificity was 12; 73 (33%) patients scored 12 or higher. Findings from this validated instrument provide a needed guide for clinicians to interpret fatigue scores and provide clinical interventions for this debilitating condition to their pediatric patients with cancer.
doi:10.1016/j.jpainsymman.2009.07.015
PMCID: PMC2941159  PMID: 20303031
Pediatric; oncology; fatigue; patient-reported outcome; Rasch; ROC
24.  Predictors of the Trajectories of Self-Reported Attentional Fatigue in Women With Breast Cancer Undergoing Radiation Therapy 
Oncology Nursing Forum  2010;37(4):423-432.
PURPOSE/OBJECTIVES
To examine how attentional fatigue changed from the time of simulation to four months after the completion of radiation therapy (RT) and to investigate whether specific variables predicted initial levels and trajectories of attentional fatigue.
DESIGN
Descriptive, longitudinal study.
SETTINGS
Two RT departments.
SAMPLE
73 women with breast cancer who received primary or adjuvant RT.
METHODS
Participants completed questionnaires prior to, during, and after RT. Descriptive statistics and hierarchical linear modeling were used for data analysis.
MAIN RESEARCH VARIABLES
Attentional fatigue; demographic, clinical, and symptom characteristics.
FINDINGS
Large amounts of inter-individual variability were found in the trajectories of attentional fatigue. At baseline, higher levels of attentional fatigue were associated with younger age, not working, a higher number of comorbidities, and higher levels of trait anxiety. The trajectory of attentional fatigue improved over time for women with a higher body mass index at baseline.
CONCLUSIONS
This study is the first to identify predictors of inter-individual variability in attentional fatigue in women with breast cancer undergoing RT. These predictors need to be considered in the design of future correlational and interventional studies.
IMPLICATIONS FOR NURSING
Nurses could use knowledge of these predictors to identify patients at risk for higher levels of attentional fatigue. In addition, nurses could use this information to educate their patients about how attentional fatigue may change during and following a course of RT for breast cancer.
doi:10.1188/10.ONF.423-432
PMCID: PMC3312014  PMID: 20591802
25.  Decrease in eccentric hamstring strength in runners in the Tirol Speed Marathon 
British Journal of Sports Medicine  2006;40(10):850-852.
Background
The local muscular endurance of knee flexors, during eccentric work in particular, is important in preventing or delaying kinematic changes associated with fatigue during treadmill running. This result, however, may not be transferable to overground running.
Objective
To test the hypothesis that overground running is associated with eccentric hamstring fatigue.
Methods
Thirteen runners (12 male and one female) performed an isokinetic muscle test three to four days before and 18 hours after a marathon. Both legs were tested. The testing protocol consisted of concentric and eccentric quadriceps and hamstring contractions.
Results
There were no significant differences between peak torque before and after the race, except that eccentric peak hamstring torque (both thighs) was reduced.
Conclusion
Overground running (running a marathon) is associated with eccentric hamstring fatigue. Eccentric hamstring fatigue may be a potential risk factor for knee and soft tissue injuries during running. Eccentric hamstring training should therefore be introduced as an integral part of the training programme of runners.
doi:10.1136/bjsm.2006.028175
PMCID: PMC2465081  PMID: 16825267
fatigue; concentric; eccentric; hamstring; musculoskeletal injury

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