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1.  Chronic fatigue syndrome after Giardia enteritis: clinical characteristics, disability and long-term sickness absence 
BMC Gastroenterology  2012;12:13.
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.
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.
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.
After giardiasis enteritis at least 5% developed clinical characteristics and functional impairment comparable to previously described post-infectious fatigue syndrome.
PMCID: PMC3292445  PMID: 22316329
2.  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.
PMCID: PMC1763327  PMID: 15365116
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.
PMCID: PMC1765725  PMID: 12782750
4.  Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures 
PLoS Medicine  2006;3(12):e487.
A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (≥24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extended-duration shifts commonly worked by interns may contribute to the risk of medical errors being made, and perhaps to the risk of adverse events more generally. Our current study assessed whether extended-duration shifts worked by interns are associated with significant medical errors, adverse events, and attentional failures in a diverse population of interns across the United States.
Methods and Findings
We conducted a Web-based survey, across the United States, in which 2,737 residents in their first postgraduate year (interns) completed 17,003 monthly reports. The association between the number of extended-duration shifts worked in the month and the reporting of significant medical errors, preventable adverse events, and attentional failures was assessed using a case-crossover analysis in which each intern acted as his/her own control. Compared to months in which no extended-duration shifts were worked, during months in which between one and four extended-duration shifts and five or more extended-duration shifts were worked, the odds ratios of reporting at least one fatigue-related significant medical error were 3.5 (95% confidence interval [CI], 3.3–3.7) and 7.5 (95% CI, 7.2–7.8), respectively. The respective odds ratios for fatigue-related preventable adverse events, 8.7 (95% CI, 3.4–22) and 7.0 (95% CI, 4.3–11), were also increased. Interns working five or more extended-duration shifts per month reported more attentional failures during lectures, rounds, and clinical activities, including surgery and reported 300% more fatigue-related preventable adverse events resulting in a fatality.
In our survey, extended-duration work shifts were associated with an increased risk of significant medical errors, adverse events, and attentional failures in interns across the United States. These results have important public policy implications for postgraduate medical education.
During months in which medical interns worked extended shifts, the chances of their reporting at least one fatigue-related significant medical error increased more than 3-fold compared to months with no extended shifts.
Editors' Summary
In the United States, medical students who are doing their internship (first year of postgraduate clinical training) regularly work in the clinic for longer than 24 h at a time. It is already known that doctors or students who work for long shifts make more medical errors and are less able to pay attention to what they are doing. Many thousands of adverse medical events per year including, in the extreme, deaths of patients, are thought to result from medical errors, but it is not clear whether doctors or students working long shifts—as opposed to, for example, an increase in total number of hours worked—are the cause of many or any of these errors.
Why Was This Study Done?
This research group wanted to find out whether long shifts worked by interns had an effect on reported medical errors, and hence patient safety, and specifically whether any harm that happened to patients might otherwise have been preventable.
What Did the Researchers Do and Find?
The researchers contacted all US medical school graduates beginning their internships from one particular year-group by email, and asked each person whether they wanted to take part in a confidential survey. Individuals who agreed to participate were directed to a secure website to enter basic information about themselves and then to complete a form each month. On that form the interns gave information about their working hours, hours of sleep, and number of extended-duration shifts worked, and completed questions about medical errors in the past month. Then, for each intern in the study, researchers compared month by month the number of medical errors and the number of extended-duration shifts that had been worked. A total of 2,737 interns took part in the survey.
  Compared to months in which no extended-duration shifts were worked, in those months in which between one and four, and more than five extended-duration shifts were worked, the doctors were, respectively, three and seven times more likely to report at least one fatigue-related significant medical error. Similarly, fatigue-related adverse events increased by around seven and eight times, respectively, compared with months in which no extended-duration shifts were worked. Fatigue-related preventable adverse events associated with the death of the patient increased by ∼300% in interns working more than five extended-duration shifts per month; they were also more likely to fall asleep during lectures, rounds, and clinical activities, including surgery.
What Do These Findings Mean?
Guidelines for graduate medical education in the United States still allow up to nine marathon shifts (30 h at a stretch) per month, even though the total number of hours worked is capped. This study shows that the long shifts worked by interns are bad for patient safety, as they are more likely to cause harm that would not otherwise happen.
Additional Information.
Please access these Web sites via the online version of this summary at
The US Food and Drug Administration has resources on its website about medication errors
The National Sleep Foundation aims to improve public health and safety by achieving understanding of sleep and sleep disorders
Wikipedia (an internet encyclopedia anyone can edit) has a page about residency training in the United States
PMCID: PMC1705824  PMID: 17194188
5.  Changes in Lower Extremity Biomechanics Due to a Short-Term Fatigue Protocol 
Journal of Athletic Training  2013;48(3):306-313.
Noncontact anterior cruciate ligament injury has been reported to occur during the later stages of a game when fatigue is most likely present. Few researchers have focused on progressive changes in lower extremity biomechanics that occur throughout fatiguing.
To evaluate the effects of a sequential fatigue protocol on lower extremity biomechanics during a sidestep-cutting task (SS).
Controlled laboratory study.
Patients or Other Participants:
Eighteen uninjured female collegiate soccer players (age = 19.2 ± 0.9 years, height = 1.66 ± 0.5 m, mass = 61.6 ± 5.1 kg) volunteered.
The independent variable was fatigue level, with 3 levels (prefatigue, 50% fatigue, and 100% fatigue). Using 3-dimensional motion capture, we assessed lower extremity biomechanics during the SS. Participants alternated between a fatigue protocol that solicited different muscle groups and mimicked actual sport situations and unanticipated SS trials. The process was repeated until fatigue was attained.
Main Outcome Measure(s):
Dependent variables were hip- and knee-flexion and abduction angles and internal moments measured at initial contact and peak stance and defined as measures obtained between 0% and 50% of stance phase.
Knee-flexion angle decreased from prefatigue (−17° ± 5°) to 50% fatigue (−16° ± 6°) and to 100% fatigue (−14° ± 4°) (F2,34 = 5.112, P = .004). Knee flexion at peak stance increased from prefatigue (−52.9° ± 5.6°) to 50% fatigue (−56.1° ± 7.2°) but decreased from 50% to 100% fatigue (−50.5° ± 7.1°) (F2,34 = 8.282, P = 001). Knee-adduction moment at peak stance increased from prefatigue (0.49 ± 0.23 Nm/kgm) to 50% fatigue (0.55 ± 0.25 Nm/kgm) but decreased from 50% to 100% fatigue (0.37 ± 0.24) (F2,34 = 3.755, P = 03). Hip-flexion angle increased from prefatigue (45.4° ± 10.9°) to 50% fatigue (46.2° ± 11.2°) but decreased from 50% to 100% fatigue (40.9° ± 11.3°) (F2,34 = 6.542, P = .004). Hip flexion at peak stance increased from prefatigue (49.8° ± 9.9°) to 50% fatigue (52.9° ± 12.1°) but decreased from 50% to 100% fatigue (46.3° ± 12.9°) (F2,34 = 8.639, P = 001). Hip-abduction angle at initial contact decreased from prefatigue (−13.8° ± 6.6°) to 50% fatigue (−9.1° ± 6.5°) and to 100% fatigue (−7.8° ± 6.5°) (F2,34 = 11.228, P < .001). Hip-adduction moment decreased from prefatigue (0.14 ± 0.13 Nm/kgm) to 50% fatigue (0.08 ± 0.13 Nm/kgm) and to 100% fatigue (0.06 ± 0.05 Nm/kg) (F2,34 = 5.767, P = .007).
The detrimental effects of fatigue on sagittal and frontal mechanics of the hip and knee were visible at 50% of the participants' maximal fatigue and became more marked at 100% fatigue. Anterior cruciate ligament injury-prevention programs should emphasize feedback on proper mechanics throughout an entire practice and not only at the beginning of practice.
PMCID: PMC3655743  PMID: 23675789
anterior cruciate ligament; knee; fatiguing; kinematics; kinetics
6.  Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation 
BMC Geriatrics  2007;7:5.
Low grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons.
Forty elderly subjects (15 female and 25 male, mean age 75 ± 5 years) were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction), self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100), self rated physical functioning (domain of physical functioning on the MOS short-form) and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed.
In the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p < .05) and positively to circulating IL-6 (p < .05). When corrected for body weight, the relations of fatigue resistance with self-perceived fatigue became stronger and also apparent in the female. Grip strength and grip work were significantly related with several items of self-perceived fatigue and with physical functioning. These relations became more visible by means of higher correlation coefficients when grip strength and grip work were corrected for body weight.
Well functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained.
PMCID: PMC1820598  PMID: 17331228
7.  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
PMCID: PMC1731588  PMID: 11027196
8.  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.
PMCID: PMC1765717  PMID: 12782755
9.  Prediction of sickness absence: development of a screening instrument 
To develop a concise screening instrument for early identification of employees at risk for sickness absence due to psychosocial health complaints.
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.
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.
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.
PMCID: PMC2078122  PMID: 16698807
screening instrument; prediction; sickness absence
10.  Chronic fatigue syndrome: aetiology, diagnosis and treatment 
BMC Psychiatry  2009;9(Suppl 1):S1.
Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post-traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome.
PMCID: PMC2766938  PMID: 19857242
11.  Periostin Deficiency Increases Bone Damage and Impairs Injury Response to Fatigue Loading in Adult Mice 
PLoS ONE  2013;8(10):e78347.
Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn) is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn-/- and Postn+/+ mice after fatigue stimulus by axial compression of their tibia. In Postn+/+ mice, cracks number and surface (CsNb, CsS) increased 1h after fatigue, with a decrease in strength compared to non-fatigued tibia. At 15 days, CsNb had started to decline, while CtTV and CtBV increased in fatigued vs non-fatigued tibia, reflecting a woven bone response that was present in 75% of the fatigued bones. Cortical porosity and remodelling also prominently increased in the fatigued tibia of Postn+/+ mice. At 30 days, paralleling a continuous removal of cortical damage, strength of the fatigued tibia was similar to the non-fatigue tibia. In Postn-/- mice, cracks were detectable even in the absence of fatigue, while the amount of collagen crosslinks and tissue hardness was decreased compared to Postn+/+. Fatigue significantly increased CsNb and CsS in Postn-/-, but was not associated with changes in CtTV and CtBV, as only 16% of the fatigued bones formed some woven bone. Cortical porosity and remodelling did not increase either after fatigue in Postn-/- , and the level of damage remained high even after 30 days. As a result, strength remained compromised in Postn-/- mice. Contrary to Postn+/+ , which osteocytic lacunae showed a change in the degree of anisotropy (DA) after fatigue, Postn-/- showed no DA change. Hence periostin appears to influence bone materials properties, damage accumulation and repair, including local modeling/remodeling processes in response to fatigue. These observations suggest that the level of periostin expression could influence the propensity to fatigue fractures.
PMCID: PMC3805534  PMID: 24167618
12.  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.
PMCID: PMC1765732  PMID: 12782747
13.  The factors associated with the burnout syndrome and fatigue in Cypriot nurses: a census report 
BMC Public Health  2012;12:457.
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.
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.
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.
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.
PMCID: PMC3506490  PMID: 22716044
Burnout syndrome; Nurses; Fatigue; Maslach’s burnout scale
14.  The definition of disabling fatigue in children and adolescents 
BMC Family Practice  2005;6:33.
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.
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.
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.
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.
PMCID: PMC1192794  PMID: 16091130
15.  The relationship between fatigue and psychiatric disorders: Evidence for the concept of neurasthenia☆ 
Journal of Psychosomatic Research  2009;66(5):445-454.
Fatigue and psychiatric disorders frequently occur comorbidly and share similar phenomenological features. There has been debate as to whether chronic fatigue, or neurasthenia, should be considered an independent syndrome distinct from psychiatric disorders. We aimed to establish whether persistent fatigue can occur independently from psychiatric disorders and to test the hypothesis that fatigue without comorbid psychiatric symptoms has unique premorbid risk factors. We also aimed to investigate the psychological outcome of any individuals with fatigue.
The MRC National Survey of Health and Development was used to prospectively follow 5362 participants from birth. A sample of nonfatigued individuals without psychiatric disorder was selected at age 36 and followed until age 43 years (n=2714). At age 43, the presence of new onset fatigue and/or psychiatric disorder was assessed. Information on a number of potential premorbid risk factors was collected between ages 0 and 36 years. Individuals with fatigue but no comorbid psychiatric disorder were then followed up at age 53 years.
At age 43 years, 201 (7.4%) participants reported significant levels of new onset fatigue in the absence of comorbid psychiatric disorder. Despite the absence of case level psychiatric disorder, these individuals did report increased levels of some psychological symptoms. Excessive childhood energy (adjusted OR 2.63, 95% CI 1.55–4.48, P<.001) and being overweight at age 36 (adjusted OR 1.62, 95% CI 1.05–2.49, P=.03) were specific risk factors for fatigue without psychiatric disorder but not fatigue with comorbid psychiatric illness. Neuroticism was a risk factor for fatigue both with and without comorbid psychiatric disorder. Negative life events and a family history of psychiatric illness were only risk factors for fatigue when it occurred comorbidly with psychiatric illness.
A significant proportion of the adult population will suffer from fatigue without comorbid psychiatric disorder. While fatigue and psychiatric disorders share some risk factors, excessive energy in childhood and being overweight as an adult appear to be specific risk factors for fatigue. Our results confirm the significant overlap between fatigue and psychiatric disorders, while also providing evidence for neurasthenia as a separate diagnosis.
PMCID: PMC3500687  PMID: 19379961
Fatigue; Chronic fatigue; Neurasthenia; Psychiatric disorder; Mental disorder; Exercise; Body weight
16.  Work patterns and fatigue‐related risk among junior doctors 
To reduce fatigue‐related risk among junior doctors, recent initiatives in Europe and the USA have introduced limits on work hours. However, research in other industries has highlighted that other aspects of work patterns are important in generating fatigue, in addition to total work hours. The Australian Medical Association (AMA) has proposed a more comprehensive fatigue risk management approach.
To evaluate the work patterns of New Zealand junior doctors based on the AMA approach, examining relationships between different aspects of work and fatigue‐related outcomes.
An anonymous questionnaire mailed to all house officers and registrars dealt with demographics, work patterns, sleepiness, fatigue‐related clinical errors, and support for coping with work demands. Each participant was assigned a total fatigue risk score combining 10 aspects of work patterns and sleep in the preceding week.
The response rate was 63% (1366 questionnaires from doctors working ⩾40 hours a week). On fatigue measures, 30% of participants scored as excessively sleepy (Epworth Sleepiness Score >10), 24% reported falling asleep driving home since becoming a doctor, 66% had felt close to falling asleep at the wheel in the past 12 months, and 42% recalled a fatigue‐related clinical error in the past 6 months. Night work and schedule instability were independently associated with more fatigue measures than was total hours worked, after controlling for demographic factors, The total risk score was a significant independent risk factor for all fatigue measures, in a dose‐dependent manner (all p<0.01). Regular access to adequate supervision at work reduced the risk of fatigue on all measures.
To reduce fatigue‐related risk among junior doctors, account must be taken of factors in addition to total hours of work and duration of rest breaks. The AMA fatigue risk assessment model offers a useful example of a more comprehensive approach.
PMCID: PMC2078416  PMID: 17387138
fatigue; work patterns; fatigue risk management; national fatigue survey; junior doctors
17.  Implementing the 2009 Institute of Medicine recommendations on resident physician work hours, supervision, and safety 
Long working hours and sleep deprivation have been a facet of physician training in the US since the advent of the modern residency system. However, the scientific evidence linking fatigue with deficits in human performance, accidents and errors in industries from aeronautics to medicine, nuclear power, and transportation has mounted over the last 40 years. This evidence has also spawned regulations to help ensure public safety across safety-sensitive industries, with the notable exception of medicine.
In late 2007, at the behest of the US Congress, the Institute of Medicine embarked on a year-long examination of the scientific evidence linking resident physician sleep deprivation with clinical performance deficits and medical errors. The Institute of Medicine’s report, entitled “Resident duty hours: Enhancing sleep, supervision and safety”, published in January 2009, recommended new limits on resident physician work hours and workload, increased supervision, a heightened focus on resident physician safety, training in structured handovers and quality improvement, more rigorous external oversight of work hours and other aspects of residency training, and the identification of expanded funding sources necessary to implement the recommended reforms successfully and protect the public and resident physicians themselves from preventable harm.
Given that resident physicians comprise almost a quarter of all physicians who work in hospitals, and that taxpayers, through Medicare and Medicaid, fund graduate medical education, the public has a deep investment in physician training. Patients expect to receive safe, high-quality care in the nation’s teaching hospitals. Because it is their safety that is at issue, their voices should be central in policy decisions affecting patient safety. It is likewise important to integrate the perspectives of resident physicians, policy makers, and other constituencies in designing new policies. However, since its release, discussion of the Institute of Medicine report has been largely confined to the medical education community, led by the Accreditation Council for Graduate Medical Education (ACGME).
To begin gathering these perspectives and developing a plan to implement safer work hours for resident physicians, a conference entitled “Enhancing sleep, supervision and safety: What will it take to implement the Institute of Medicine recommendations?” was held at Harvard Medical School on June 17–18, 2010. This White Paper is a product of a diverse group of 26 representative stakeholders bringing relevant new information and innovative practices to bear on a critical patient safety problem. Given that our conference included experts from across disciplines with diverse perspectives and interests, not every recommendation was endorsed by each invited conference participant. However, every recommendation made here was endorsed by the majority of the group, and many were endorsed unanimously. Conference members participated in the process, reviewed the final product, and provided input before publication. Participants provided their individual perspectives, which do not necessarily represent the formal views of any organization.
In September 2010 the ACGME issued new rules to go into effect on July 1, 2011. Unfortunately, they stop considerably short of the Institute of Medicine’s recommendations and those endorsed by this conference. In particular, the ACGME only applied the limitation of 16 hours to first-year resident physicans. Thus, it is clear that policymakers, hospital administrators, and residency program directors who wish to implement safer health care systems must go far beyond what the ACGME will require. We hope this White Paper will serve as a guide and provide encouragement for that effort.
Resident physician workload and supervision
By the end of training, a resident physician should be able to practice independently. Yet much of resident physicians’ time is dominated by tasks with little educational value. The caseload can be so great that inadequate reflective time is left for learning based on clinical experiences. In addition, supervision is often vaguely defined and discontinuous. Medical malpractice data indicate that resident physicians are frequently named in lawsuits, most often for lack of supervision. The recommendations are: The ACGME should adjust resident physicians workload requirements to optimize educational value. Resident physicians as well as faculty should be involved in work redesign that eliminates nonessential and noneducational activity from resident physician dutiesMechanisms should be developed for identifying in real time when a resident physician’s workload is excessive, and processes developed to activate additional providersTeamwork should be actively encouraged in delivery of patient care. Historically, much of medical training has focused on individual knowledge, skills, and responsibility. As health care delivery has become more complex, it will be essential to train resident and attending physicians in effective teamwork that emphasizes collective responsibility for patient care and recognizes the signs, both individual and systemic, of a schedule and working conditions that are too demanding to be safeHospitals should embrace the opportunities that resident physician training redesign offers. Hospitals should recognize and act on the potential benefits of work redesign, eg, increased efficiency, reduced costs, improved quality of care, and resident physician and attending job satisfactionAttending physicians should supervise all hospital admissions. Resident physicians should directly discuss all admissions with attending physicians. Attending physicians should be both cognizant of and have input into the care patients are to receive upon admission to the hospitalInhouse supervision should be required for all critical care services, including emergency rooms, intensive care units, and trauma services. Resident physicians should not be left unsupervised to care for critically ill patients. In settings in which the acuity is high, physicians who have completed residency should provide direct supervision for resident physicians. Supervising physicians should always be physically in the hospital for supervision of resident physicians who care for critically ill patientsThe ACGME should explicitly define “good” supervision by specialty and by year of training. Explicit requirements for intensity and level of training for supervision of specific clinical scenarios should be providedCenters for Medicare and Medicaid Services (CMS) should use graduate medical education funding to provide incentives to programs with proven, effective levels of supervision. Although this action would require federal legislation, reimbursement rules would help to ensure that hospitals pay attention to the importance of good supervision and require it from their training programs
Resident physician work hours
Although the IOM “Sleep, supervision and safety” report provides a comprehensive review and discussion of all aspects of graduate medical education training, the report’s focal point is its recommendations regarding the hours that resident physicians are currently required to work. A considerable body of scientific evidence, much of it cited by the Institute of Medicine report, describes deteriorating performance in fatigued humans, as well as specific studies on resident physician fatigue and preventable medical errors.
The question before this conference was what work redesign and cultural changes are needed to reform work hours as recommended by the Institute of Medicine’s evidence-based report? Extensive scientific data demonstrate that shifts exceeding 12–16 hours without sleep are unsafe. Several principles should be followed in efforts to reduce consecutive hours below this level and achieve safer work schedules. The recommendations are: Limit resident physician work hours to 12–16 hour maximum shiftsA minimum of 10 hours off duty should be scheduled between shiftsResident physician input into work redesign should be actively solicitedSchedules should be designed that adhere to principles of sleep and circadian science; this includes careful consideration of the effects of multiple consecutive night shifts, and provision of adequate time off after night work, as specified in the IOM reportResident physicians should not be scheduled up to the maximum permissible limits; emergencies frequently occur that require resident physicians to stay longer than their scheduled shifts, and this should be anticipated in scheduling resident physicians’ work shiftsHospitals should anticipate the need for iterative improvement as new schedules are initiated; be prepared to learn from the initial phase-in, and change the plan as neededAs resident physician work hours are redesigned, attending physicians should also be considered; a potential consequence of resident physician work hour reduction and increased supervisory requirements may be an increase in work for attending physicians; this should be carefully monitored, and adjustments to attending physician work schedules made as needed to prevent unsafe work hours or working conditions for this group“Home call” should be brought under the overall limits of working hours; work load and hours should be monitored in each residency program to ensure that resident physicians and fellows on home call are getting sufficient sleepMedicare funding for graduate medical education in each hospital should be linked with adherence to the Institute of Medicine limits on resident physician work hours
Moonlighting by resident physicians
The Institute of Medicine report recommended including external as well as internal moonlighting in working hour limits. The recommendation is: All moonlighting work hours should be included in the ACGME working hour limits and actively monitored. Hospitals should formalize a moonlighting policy and establish systems for actively monitoring resident physician moonlighting
Safety of resident physicians
The “Sleep, supervision and safety” report also addresses fatigue-related harm done to resident physicians themselves. The report focuses on two main sources of physical injury to resident physicians impaired by fatigue, ie, needle-stick exposure to blood-borne pathogens and motor vehicle crashes. Providing safe transportation home for resident physicians is a logistical and financial challenge for hospitals. Educating physicians at all levels on the dangers of fatigue is clearly required to change driving behavior so that safe hospital-funded transport home is used effectively. Fatigue-related injury prevention (including not driving while drowsy) should be taught in medical school and during residency, and reinforced with attending physicians; hospitals and residency programs must be informed that resident physicians’ ability to judge their own level of impairment is impaired when they are sleep deprived; hence, leaving decisions about the capacity to drive to impaired resident physicians is not recommendedHospitals should provide transportation to all resident physicians who report feeling too tired to drive safely; in addition, although consecutive work should not exceed 16 hours, hospitals should provide transportation for all resident physicians who, because of unforeseen reasons or emergencies, work for longer than consecutive 24 hours; transportation under these circumstances should be automatically provided to house staff, and should not rely on self-identification or request
Training in effective handovers and quality improvement
Handover practice for resident physicians, attendings, and other health care providers has long been identified as a weak link in patient safety throughout health care settings. Policies to improve handovers of care must be tailored to fit the appropriate clinical scenario, recognizing that information overload can also be a problem. At the heart of improving handovers is the organizational effort to improve quality, an effort in which resident physicians have typically been insufficiently engaged. The recommendations are: Hospitals should train attending and resident physicians in effective handovers of careHospitals should create uniform processes for handovers that are tailored to meet each clinical setting; all handovers should be done verbally and face-to-face, but should also utilize written toolsWhen possible, hospitals should integrate hand-over tools into their electronic medical records (EMR) systems; these systems should be standardized to the extent possible across residency programs in a hospital, but may be tailored to the needs of specific programs and services; federal government should help subsidize adoption of electronic medical records by hospitals to improve signoutWhen feasible, handovers should be a team effort including nurses, patients, and familiesHospitals should include residents in their quality improvement and patient safety efforts; the ACGME should specify in their core competency requirements that resident physicians work on quality improvement projects; likewise, the Joint Commission should require that resident physicians be included in quality improvement and patient safety programs at teaching hospitals; hospital administrators and residency program directors should create opportunities for resident physicians to become involved in ongoing quality improvement projects and root cause analysis teams; feedback on successful quality improvement interventions should be shared with resident physicians and broadly disseminatedQuality improvement/patient safety concepts should be integral to the medical school curriculum; medical school deans should elevate the topics of patient safety, quality improvement, and teamwork; these concepts should be integrated throughout the medical school curriculum and reinforced throughout residency; mastery of these concepts by medical students should be tested on the United States Medical Licensing Examination (USMLE) stepsFederal government should support involvement of resident physicians in quality improvement efforts; initiatives to improve quality by including resident physicians in quality improvement projects should be financially supported by the Department of Health and Human Services
Monitoring and oversight of the ACGME
While the ACGME is a key stakeholder in residency training, external voices are essential to ensure that public interests are heard in the development and monitoring of standards. Consequently, the Institute of Medicine report recommended external oversight and monitoring through the Joint Commission and Centers for Medicare and Medicaid Services (CMS). The recommendations are: Make comprehensive fatigue management a Joint Commission National Patient Safety Goal; fatigue is a safety concern not only for resident physicians, but also for nurses, attending physicians, and other health care workers; the Joint Commission should seek to ensure that all health care workers, not just resident physicians, are working as safely as possibleFederal government, including the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality, should encourage development of comprehensive fatigue management programs which all health systems would eventually be required to implementMake ACGME compliance with working hours a “ condition of participation” for reimbursement of direct and indirect graduate medical education costs; financial incentives will greatly increase the adoption of and compliance with ACGME standards
Future financial support for implementation
The Institute of Medicine’s report estimates that $1.7 billion (in 2008 dollars) would be needed to implement its recommendations. Twenty-five percent of that amount ($376 million) will be required just to bring hospitals into compliance with the existing 2003 ACGME rules. Downstream savings to the health care system could potentially result from safer care, but these benefits typically do not accrue to hospitals and residency programs, who have been asked historically to bear the burden of residency reform costs. The recommendations are: The Institute of Medicine should convene a panel of stakeholders, including private and public funders of health care and graduate medical education, to lay down the concrete steps necessary to identify and allocate the resources needed to implement the recommendations contained in the IOM “Resident duty hours: Enhancing sleep, supervision and safety” report. Conference participants suggested several approaches to engage public and private support for this initiativeEfforts to find additional funding to implement the Institute of Medicine recommendations should focus more broadly on patient safety and health care delivery reform; policy efforts focused narrowly upon resident physician work hours are less likely to succeed than broad patient safety initiatives that include residency redesign as a key componentHospitals should view the Institute of Medicine recommendations as an opportunity to begin resident physician work redesign projects as the core of a business model that embraces safety and ultimately saves resourcesBoth the Secretary of Health and Human Services and the Director of the Centers for Medicare and Medicaid Services should take the Institute of Medicine recommendations into consideration when promulgating rules for innovation grantsThe National Health Care Workforce Commission should consider the Institute of Medicine recommendations when analyzing the nation’s physician workforce needs
Recommendations for future research
Conference participants concurred that convening the stakeholders and agreeing on a research agenda was key. Some observed that some sectors within the medical education community have been reluctant to act on the data. Several logical funders for future research were identified. But above all agencies, Centers for Medicare and Medicaid Services is the only stakeholder that funds graduate medical education upstream and will reap savings downstream if preventable medical errors are reduced as a result of reform of resident physician work hours.
PMCID: PMC3630963  PMID: 23616719
resident; hospital; working hours; safety
18.  Nutrition and its Relation to Mealtime Preparation, Eating, Fatigue and Mood Among Stroke Survivors After Discharge from Hospital - A Pilot Study 
The Open Nursing Journal  2008;2:15-20.
Eating difficulties and nutritional deficits are common among persons with acute stroke and during rehabilitation. Little is known about such problems after discharge from hospital. In addition the relationship between fatigue and nutritional status among stroke survivors living in the community remains to be explored. The aim of this pilot study was to describe mealtime preparation, eating, fatigue, mood and nutritional status among persons with stroke six months after discharge from hospital and to explore associations between these factors. Patients were interviewed six months poststroke. Standardised questions and methods were used. The mean age of the 89 respondents was 77.2 (SD 6.6) years, 44 were women and 45 men. Difficulties with swallowing, ingestion and energy to eat occurred among 27%, 20% and 7% respectively. Difficulties with cooking and buying food occurred among 57% and 56% respectively and 41% were at nutritional risk. Feeling full of energy less than some of the time was experienced by 61% while 15% had felt gloomy and sad at least some of the time during the previous four weeks. Considering activities of daily living (ADL), having a less favourable nutritional status was significantly predicted by difficulties with buying food, difficulties with ingestion and being a woman. Considering psychological state (mood and energy), having a less favourable nutritional status was significantly predicted by a lack of energy and high age. This study supports the occurrence of a nutritionally related fatigue by means of “lack of energy”. The associations between poor nutritional status and fatigue can work in both directions. Thus persons with fatigue are more prone to have poor nutritional status and those with poor nutritional status are at greater risk of fatigue. Besides fatigue also difficulties with buying food and ingestion are associated with nutritional risk. As nutritional deficits occur a long time after stroke onset it is important to assess aspects of mealtime preparation and the eating process and when necessary provide food delivery service and eating assistance in order to prevent a vicious circle of undernourishment and fatigue to develop.
PMCID: PMC2582825  PMID: 19319216
Fatigue; mood; mealtime preparation; eating; nutrition; stroke.
19.  Sleepiness and Safety: Where Biology Needs Technology 
Sleep and biological rhythms  2014;12(2):74-84.
Maintaining human alertness and behavioral capability under conditions of sleep loss and circadian misalignment requires fatigue management technologies due to: (1) dynamic nonlinear modulation of performance capability by the interaction of sleep homeostatic drive and circadian regulation; (2) large differences among people in neurobehavioral vulnerability to sleep loss; (3) error in subjective estimates of fatigue on performance; and (4) to inform people of the need for recovery sleep. Two promising areas of technology have emerged for managing fatigue risk in safety-sensitive occupations. The first involves preventing fatigue by optimizing work schedules using biomathematical models of performance changes associated with sleep homeostatic and circadian dynamics. Increasingly these mathematical models account for individual differences to achieve a more accurate estimate of the timing and magnitude of fatigue effects on individuals. The second area involves technologies for detecting transient fatigue from drowsiness. The Psychomotor Vigilance Test (PVT), which has been extensively validated to be sensitive to deficits in attention from sleep loss and circadian misalignment, is an example in this category. Two shorter-duration versions of the PVT recently have been developed for evaluating whether operators have sufficient behavioral alertness prior to or during work. Another example is online tracking the percent of slow eyelid closures (PERCLOS), which has been shown to reflect momentary fluctuations of vigilance. Technologies for predicting and detecting sleepiness/fatigue have the potential to predict and prevent operator errors and accidents in safety-sensitive occupations, as well as physiological and mental diseases due to inadequate sleep and circadian misalignment.
PMCID: PMC4061704  PMID: 24955033
Sleepiness; fatigue; vigilance; drowsiness; biomathematical models; Psychomotor Vigilance Test (PVT); PERCLOS; safety
20.  Prevalence, Incidence, and Classification of Chronic Fatigue Syndrome in Olmsted County, Minnesota, as Estimated Using the Rochester Epidemiology Project 
Mayo Clinic Proceedings  2012;87(12):1145-1152.
To estimate the prevalence and incidence of chronic fatigue syndrome in Olmsted County, Minnesota, using the 1994 case definition and describe exclusionary and comorbid conditions observed in patients who presented for evaluation of long-standing fatigue.
Patients and Methods
We conducted a retrospective medical record review of potential cases of chronic fatigue syndrome identified from January 1, 1998, through December 31, 2002, using the Rochester Epidemiology Project, a population-based database. Patients were classified as having chronic fatigue syndrome if the medical record review documented fatigue of 6 months' duration, at least 4 of 8 chronic fatigue syndrome–defining symptoms, and symptoms that interfered with daily work or activities. Patients not meeting all of the criteria were classified as having insufficient/idiopathic fatigue.
We identified 686 potential patients with chronic fatigue, 2 of whom declined consent for medical record review. Of the remaining 684 patients, 151 (22%) met criteria for chronic fatigue syndrome or insufficient/idiopathic fatigue. The overall prevalence and incidence of chronic fatigue syndrome and insufficient/idiopathic fatigue were 71.34 per 100,000 persons and 13.16 per 100,000 person-years vs 73.70 per 100,000 persons and 13.58 per 100,000 person-years, respectively. The potential cases included 482 patients (70%) who had an exclusionary condition, and almost half the patients who met either criterion had at least one nonexclusionary comorbid condition.
The incidence and prevalence of chronic fatigue syndrome and insufficient/idiopathic fatigue are relatively low in Olmsted County. Careful clinical evaluation to identify whether fatigue could be attributed to exclusionary or comorbid conditions rather than chronic fatigue syndrome itself will ensure appropriate assessment for patients without chronic fatigue syndrome.
PMCID: PMC3518652  PMID: 23140977
CFS, chronic fatigue syndrome; H-ICDA, H-ICDA: Hospital Adaptation of ICDA; ICD-9, International Classification of Diseases, Ninth Revision; ISF, insufficient/idiopathic fatigue; REP, Rochester Epidemiology Project
21.  The Effect of Acclydine in Chronic Fatigue Syndrome: A Randomized Controlled Trial 
PLoS Clinical Trials  2007;2(5):e19.
It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio).
A randomized, placebo-controlled, double-blind clinical trial.
Radboud University Nijmegen Medical Centre, The Netherlands.
Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals.
Acclydine or placebo for 14 wk.
Outcome measures:
Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis.
There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI −4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI −201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio −0.5 (95% CI −2.8 to +1.7, p = 0.63).
We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS.
Editorial Commentary
Background: Chronic fatigue syndrome is a complicated and poorly understood illness. People with the condition experience tiredness that carries on for a long period of time and does not get better with rest. Other symptoms include sleeping problems, muscle and joint pains, concentration difficulties, and headaches. The causes of chronic fatigue syndrome are not known. There is evidence for the effectiveness of certain behavioral interventions, such as exercise therapy and cognitive behavioral therapy, in improving certain symptoms. However, some doctors are concerned that a food supplement called Acclydine, derived from a plant called Solanum dulcamara, is being used and promoted as a treatment for chronic fatigue syndrome when there is little evidence about the efficacy or safety of this supplement.
The researchers here carried out a randomized trial in The Netherlands, recruiting adult patients who met the internationally accepted criteria for chronic fatigue syndrome. The participants were allocated by chance to receive either 14 weeks of treatment with Acclydine together with amino acid supplements or, alternatively, placebo versions of the Acclydine and amino acid tablets. The researchers then measured participants' responses with respect to two primary outcome measures. One of these was how tired participants felt, which was measured using a subscale on a questionnaire called the Checklist Individual Strength scale (CIS-fatigue). The other primary outcome measure was “functional impairment,” which examines how well someone carries out their daily life, using the Sickness Impact Profile (SIP-8) scale. The secondary outcome measures included physical activity levels, day-to-day fatigue levels, and the levels of insulin-like growth factor 1 (IGF1) in blood, a hormone that's thought by some researchers to be related to the severity of chronic fatigue.
What the trial shows: In the trial, 57 people were randomized to receive either Acclydine plus amino acid supplements, or placebo tablets. When comparing scores on the primary outcome measures at the end of the trial, the researchers did not see significant differences between the treatment and placebo groups. Similarly, the results for secondary outcome measures in this trial did not show any significant differences between the treatment and placebo groups.
Strengths and limitations: Strengths of this study include the fact that it is one of the few properly designed studies of a product for which claims have been made of effectiveness in chronic fatigue syndrome. The study was designed as a double-blind trial, in which participants and investigators (those collecting the outcome data) did not know whether an individual received Acclydine or placebo. This procedure should help to minimize bias in assessing outcomes. A key limitation of this study is the relatively small number of participants. However, the investigators considered it unlikely that a larger trial would detect a clinically meaningful effect of Acclydine on these outcome measures for patients with chronic fatigue syndrome.
Contribution to the evidence: Systematic reviews of interventions for the treatment of chronic fatigue syndrome have found evidence for the efficacy of exercise therapy and cognitive behavioral therapy. This trial shows no evidence of efficacy of Acclydine plus amino acid supplements for the treatment of chronic fatigue.
PMCID: PMC1876596  PMID: 17525791
22.  Chronic fatigue syndrome‐like caseness as a predictor of work status in fatigued employees on sick leave: four year follow up study 
To assess whether CFS‐like caseness (meeting the criteria for chronic fatigue syndrome (CFS)) predicts work status in the long term.
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).
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).
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.
PMCID: PMC2078121  PMID: 16698810
fatigue syndrome, chronic; work; absenteeism; prognosis
23.  Effects of glatiramer acetate on fatigue and days of absence from work in first-time treated relapsing-remitting multiple sclerosis 
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.
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.
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.
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.
PMCID: PMC2542355  PMID: 18775064
24.  Relationship between Comorbid Health Problems and Musculoskeletal Disorders Resulting in Musculoskeletal Complaints and Musculoskeletal Sickness Absence among Employees in Korea 
Safety and Health at Work  2015;6(2):128-133.
To investigate the relationship between musculoskeletal disorders and comorbid health problems, including depression/anxiety disorder, insomnia/sleep disorder, fatigue, and injury by accident, and to determine whether certain physical and psychological factors reduce comorbid health problems.
In total, 29,711 employees were selected from respondents of the Third Korean Working Conditions Survey and categorized into two groups: Musculoskeletal Complaints or Musculoskeletal Sickness Absence. Four self-reported health indicators (overall fatigue, depression/anxiety, insomnia/sleep disorder, and injury by accident) were selected as outcomes, based on their high prevalence in Korea. We used multiple logistic regression analysis to determine the relationship between comorbid health problems, musculoskeletal complaints, and sickness absence.
The prevalence of musculoskeletal complaints and musculoskeletal sickness absence due to muscular pain was 32.26% and 0.59%, respectively. Compared to the reference group, depression/anxiety disorder and overall fatigue were 5.2–6.1 times more prevalent in the Musculoskeletal Complaints Group and insomnia/sleep disorder and injury by accident were 7.6–11.0 times more prevalent in the Sickness Absence Group. When adjusted for individual and work-related physical factors, prevalence of all four comorbid health problems were slightly decreased in both groups.
Increases in overall fatigue and depression/anxiety disorder were observed in the Musculoskeletal Complaints Group, while increases in insomnia/sleep disorder and injury by accident were observed in the Sickness Absence Group. For management of musculoskeletal complaints and sickness absence in the workplace, differences in health problems between employees with musculoskeletal complaints and those with sickness absence as well as the physical and psychological risk factors should be considered.
PMCID: PMC4476197  PMID: 26106512
comorbid health problems; musculoskeletal complaints; musculoskeletal sickness absence
25.  Working conditions and fatigue in professional truck drivers at Israeli ports 
Injury Prevention  2005;11(2):110-114.
Background: Trucks represent 6% of all vehicles, but truck crashes account for 20% of road deaths in Israel, even though travel distances are usually short (<200 km) and overnight travel is uncommon.
Objective: To determine occupational and individual predictors of fatigue, falling asleep at the wheel, and involvement in crashes with injuries and deaths in truck drivers.
Setting and methods: We carried out field interviews of 160 port truck drivers regarding driver characteristics, workplace and driving conditions, employer-employee relations, medical conditions, sleep quality and fatigue, falling asleep at the wheel, and involvement in road crashes.
Results: One day before interview, 38.1% of the drivers had worked more than the 12 hour legal limit. More than 30% reported falling asleep at the wheel recently, and 13% had prior involvement in a sleep related crash. Sixty seven (41.9%) drivers said that their employer forced them to work beyond the legal 12 hour daily limit. Involvement in a crash with casualties was associated with poor sleep quality (adjusted OR = 2.9; p = 0.042) and frequent difficulty finding parking when tired (OR = 3.7; p = 0.049). Self assessment of fatigue underestimated fatigue from the Pittsburgh Sleep Quality Questionnaire. However fatigue occurred in many drivers without sleep problems and many crashes occurred without fatigue.
Conclusions: Prevention requires measures to reduce work stresses, screening drivers, speed control, and modal shifts. The work risks and adverse outcomes of truck drivers in large countries with long overnight journeys occur in a small country with small distances, relatively short work journeys, and little overnight travel.
PMCID: PMC1730197  PMID: 15805441

Results 1-25 (1161998)