Absence Of Fatigue Research Articles

Fatigue and depression influence the prevalence of anxiety in patients with multiple sclerosis.

There is scarce information in Middle-Eastern Europe regarding the prevalence of anxiety in patients with multiple sclerosis (pwMS) and its association with different clinical-demographic factors. We aimed to determine the prevalence of anxiety in Hungarian MS patients and to analyze associated factors. We evaluated 260 PwMS with the STAI-5 anxiety questionnaire. Fatigue (FIS), depression (BDI-II) and cognition (BICAMS) were also measured. Patients underwent standard neurological evaluations to evaluate Expanded Disability Status Scale (EDSS), and also measured the fine motor skills of the hand with the 9-hole peg test (9HPT), and the walking distance with the 25-foot walking test (T25FW). We identified 23.1% (N = 60) of the patients with anxiety (only state, trait or both forms concurrently). According to our two univariate, multivariable logistic regression analysis, fatigue and depression are strongly associated with both state and trait anxiety. In the absence of fatigue, the odds of trait anxiety are 82% lower (OR: 0.18; 95% CI: 0.06-0.53; p = 0.002), while in the case of pwMS without depression, the odds are reduced by 81% (OR: 0.19; CI95%= 0.07-0.51, p = 0.001). This association with fatigue (OR: 0.33; CI95%= 0.13-0.85, p = 0.021) and depression (OR: 0.14; CI95%=0.06-0.35; p < 0.001) can also be statistically verified on state anxiety. Importantly, a significant association with state anxiety was found in SPSM patients as well (OR: 34.94; CI95%=2.55-479.61; p = 0.008). Anxiety was strongly associated with fatigue, depression, and secondary progressive disease form. These results emphasize the burden of psychiatric morbidity in pwMS.

DNA Methylation Levels of the ACE2 Promoter Are Not Associated with Post-COVID-19 Symptoms in Individuals Who Had Been Hospitalized Due to COVID-19.

It is known that SARS-CoV-2 can translocate via membrane ACE2 exopeptidase into the host cells, and thus hypomethylation of ACE2 possibly upregulates its expression, enhancing the risk of SARS-CoV-2 infection. This study investigated if DNA methylation levels of the ACE2 promoter are associated with the development of post-COVID-19 symptomatology in a cohort of COVID-19 survivors who had been previously hospitalized. Non-stimulated saliva samples were obtained from 279 (51.5 male, mean age: 56.5 ± 13.0 years old) COVID-19 survivors who were hospitalized during the first wave of the pandemic. A face-to-face interview in which patients described the presence of post-COVID-19 symptoms (defined as a symptom that started no later than three months after SARS-CoV-2 infection) that they suffered from to an experienced healthcare trainer was conducted. Methylation of five CpG dinucleotides in the ACE2 promoter was quantified using bisulfite pyrosequencing. The percentage of methylation (%) was associated with the presence of the following reported post-COVID-19 symptoms: fatigue, dyspnea at rest, dyspnea at exertion, brain fog, memory loss, concentration loss, or gastrointestinal problems. Participants were assessed a mean of 17.8 (SD: 5.3) months after hospitalization. At that time, 88.1% of the patients experienced at least one post-COVID-19 symptom (mean number for each patient: 3.0; SD: 1.9 post-COVID-19 symptoms). Dyspnea at exertion (67.3%), fatigue (62.3%), and memory loss (31.2%) were the most frequent post-COVID-19 symptoms in the sample. Overall, the analysis did not reveal any difference in the methylation of the ACE2 promoter in any of the CpG locations according to the presence or absence of fatigue, dyspnea at rest, dyspnea at exertion, memory loss, brain fog, concentration loss, and gastrointestinal problems. This study did not find an association between methylation of ACE2 promoter and the presence of post-COVID-19 fatigue, dyspnea, cognitive or gastrointestinal problems in previously hospitalized COVID-19 survivors.

Clinical Features and Predictors of Lethal Outcome in Tick-Borne Encephalitis: A Retrospective Study from Lithuania

Background. In Lithuania, the incidence rate of tick-borne encephalitis (TBE) increases and remains the highest in the whole Europe. Diverse clinical manifestations cause difficulties in diagnosing and treating this infectious disease. The aim of the study was to analyze clinical manifestations of the TBE and to indicate predictive variables for unfavorable outcome.&#x0D; Methods. A retrospective study of case histories of patients diagnosed with TBE and treated at the Vilnius University Hospital Santaros Klinikos in the years 2019-2021. Demographic variables, symptoms and clinical form of the disease, laboratory values, and aspects of treatment were recorded.&#x0D; Results. Six hundred and seven case histories were analyzed. Of these, 588 case histories were included in the final analysis. Men made up 56.97% of the population studied. The median age of the patients was 54 years (18-86). The median length of hospitalization was 9 days (1-50). Seventeen (2.89%) patients were immunized against TBE, the others were not immunized (401, 68.20%) or their immunization status was unknown (170, 28.91%). The most common symptoms were headache (509, 86.56%) followed by febrile fever (403, 68.54%), fatigue (400, 68.03%), and dizziness (394, 67.01%). The most prevalent clinical form of TBE cases was meningoencephalitis (387, 76.18%) followed by meningitis (88, 17.32%), meningoencephalomyelitis (29, 5.71%), and encephalitis (4, 0.79%). Patients with the meningoencephalomyelitic form of TBE less often had headache on admission, more often had diabetes, and had fewer lymphocytes in the CSF (all p&lt;0.05). Six patients (1.02%) died. The latter patients were significantly older (71 vs. 53 years, p=0.003), had higher protein concentration and cytosis in the CSF (1.04 vs. 0.70 g/L, p=0.006 and 422 vs. 84 cells per milliliter, p=0.003, respectively), whereas the percentage of lymphocytes in the CSF was lower (62% vs. 81%, p&lt;0.001). Univariate analysis showed that older age, absence of headache and fatigue, higher cytosis and percentage of neutrophils in the CSF may be prognostic variables for the lethal outcome of the disease. Multivariate analysis showed that the absence of fatigue and higher pleocytosis were significant predictors of unfavorable outcome.&#x0D; Conclusions. Clinical forms of TBE differ based on symptoms and laboratory values. Symptoms and laboratory results may prognose the outcome of the disease.

Impact of a passive upper-body exoskeleton on muscular activity and precision in overhead single and dual tasks: an explorative randomized crossover study.

Tasks performed at or above head height in industrial workplaces pose a significant challenge due to their association with musculoskeletal disorders. Upper-body exoskeletons have been identified as a potential solution for mitigating musculoskeletal loads and fighting against excessive muscular fatigue. However, the influence of such support on fine motor control, as well as on cognitive-motor interference, has received limited attention thus far. Therefore, this crossover randomized study aimed to investigate the impact of the use of a passive upper-body exoskeleton in the presence of muscular fatigue or not. Additionally, focusing on differences between single (ST) and dual (DT) industrial tasks consisting of overhead speed and accuracy exercises. In both scenarios, N = 10 participants (5 male/5 female) engaged in an overhead precision task using a nail gun to precisely target specific areas on three differently sized regions, based on Fitts' law paradigm (speed-accuracy trade-off task). This was done with and without the passive upper-body exoskeleton, before and immediately after a fatiguing exercise of shoulder and leg muscles. In addition, a second task (dual-task, DT) was carried out in which the occurrence of an auditory signal had to be counted. The main outcomes were muscular activation of the shoulder girdle as well as the time to perform speed-accuracy tasks of different difficulty indexes (calculated by means of Fitts' law). In the absence of fatigue, the exoskeleton did not affect the speed-accuracy trade-off management of participants in the single task, but it did in the dual-task conditions. However, after muscle fatigue, the speed-accuracy trade-off was differently affected when comparing its execution with or without the exoskeleton. In general, the dual task resulted in longer times to perform the different tasks, whether it was with or without the exoskeleton. Furthermore, the use of the exoskeleton decreased muscle activity, which is associated with less physical effort, but only significantly for the M. deltoideus and M. trapezius when compared by tasks. Overall, these study findings highlight the potential supportive effects of using an upper-body exoskeleton for industrial overhead tasks.

The association of serum carnitine levels with severity of fatigue in patients with multiple sclerosis: A pilot study.

Background: Fatigue is a common complaint of patients with multiple sclerosis (MS), adversely affecting their quality of life. There is a lot of evidence showing that carnitine deficiency is linked to fatigue development and severity in some conditions. This study aimed to evaluate the association between free L-carnitine serum levels and the severity of fatigue in patients with MS. Methods: This case-control study included 30 patients with relapsing-remitting MS (RRMS) in two age-matched equal-number groups according to the presence or absence of fatigue. Fatigue was scored using the valid questionnaire of Fatigue Severity Scale (FSS) and serum level of free L-carnitine was measured simultaneously. Finally, the association between serum level of free L-carnitine and fatigue severity was evaluated in patients with MS. Results: The mean value of FSS in patients with fatigue was 48.80 ± 8.55, which was nearly two-fold higher than the group without fatigue. We found a significant correlation between the serum level of free L-carnitine and FSS and showed that the patients with fatigue had a significantly lower serum level of free L-carnitine compared to patients without fatigue (P < 0.001). Conclusion: Present study demonstrated that patients with lower serum levels of free L-carnitine were more likely to experience fatigue. We recommend that a higher dietary intake of carnitine might be a useful complementary treatment for MS-related fatigue.

A74 URGENCY FOR BOWEL MOVEMENTS IS A HIGHLY DISCRIMINATORY SYMPTOM FOR ACTIVE DISEASE IN PERSONS WITH IBD (THE MANITOBA LIVING WITH IBD STUDY)

Abstract Background The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-reported measure used to assess IBD disease activity. Purpose We aimed to assess the prevalence of symptoms, and examine which symptoms are most associated with disease activity as measured by a symptom index and objective measure of inflammation. Method The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly Inflammatory Bowel Disease Symptom Inventory (IBDSI) surveys. Relative risks (RR) (with 95% confidence interval (CI)), positive and negative predictive values (PPV, NPV), and area under receiver operator curve (AUC) were reported for each symptom to predict active disease defined as: (1) active IBDSI, (2) self-reported flare, and (3) elevated fecal calprotectin (FCAL) (&amp;gt;250µg/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn’s disease (CD) and ulcerative colitis (UC)). Result(s) In total, 69.2% of participants were female; 64.7% had CD. Fatigue was the most prevalent symptom in both inactive and active disease, across all 3 disease measures (IBDSI: 24.5% and 75.1%, self-reported flare: 42.2% and 72.2%, FCAL: 46.0% and 60.6%). Absence of fatigue had a high NPV for active IBDSI and self-reporting a flare in both CD and UC. Urgency had a consistently strong NPV, RR and AUC across all three disease measures in both IBD subtypes and sexes. The number of loose/liquid bowel movements predicted elevated FCAL in UC (RR in men = 3.5, 95% CI 1.2-9.9, RR in women = 1.8, 95% CI 1.2-2.7, AUC in men = 0.73, 95% CI 0.59-0.84, AUC in women = 0.65, 95% CI 0.56-0.72), as did blood in stool in females with UC (RR = 1.8, 95% CI 1.2-2.7). In men with CD, excessive bowel gas (RR = 2.0, 95% CI 1.2-3.4) and urgency (RR = 3.9, 95% CI 1.6-9.3) best predicted an elevated FCAL. No symptom was strongly predictive of elevated FCAL in females with CD. Conclusion(s) Fatigue was the most prevalent symptom irrespective of disease activity. Urgency stood out as being consistently associated with disease activity, irrespective of the disease measure. Individual symptoms have different impacts on subjective (IBDSI) and objective (FCAL) measures in IBD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Sleep Disorders and Quality of Life in Patients With Cancer: Prospective Observational Study of the Rafael Institute.

Sleep disorders are a common occurrence in the general population. Yet today, it is clearly agreed that sleep disorders represent both a cancer risk factor and a biological consequence of the of the activation of the immuno-inflammatory system induced by cancer itself. The aim of this study was to assess the impact of sleep disorders on quality of life and identify the type of disorder and its causes in order to offer an adapted and personalized care plan. In a survey completed during the COVID-19 lockdown, 2000 hours of interviews were collected by remote consultations. During these calls, we administered a sleep questionnaire. This questionnaire was inspired by the STOP-BANG questionnaire and enquired about 6 items. The demographic details of each patient (eg, age and sex), the nature of the pathology, their past treatments, the ongoing cancer treatment, the mood, whether or not the patient is anxious or depressed, and the use of sleeping drug pills were analyzed. A univariate analysis was performed according to the presence or absence of fatigue. Chi-square test was applied to assess possible differences of variables' link to sleep disturbance between patients complaining of fatigue and those without fatigue. The same test was then used to analyze patients on hormone therapy and those with no hormone therapy for 2 types of cancer-breast cancer and prostate cancer. A total of 905 patients were prospectively included in this study. The average age was 66.7 (5 SD) years, and 606 (67%) patients were women; 142 patients declared being overweight. Breast cancer was the most frequently reported cancer. Nocturnal awakening was reported by 70% (n=633), fatigue by 50% (n=452), difficulty falling asleep by 38% (n=343), snoring reported by an independent observer in 38% (n=343), and apnea reported by an independent observer in 9% (n=81) of the patients. The univariate analysis showed that the feeling of tiredness was significantly greater in patients reporting difficulty falling asleep (P≥.99), pain (P<.001), and frequent awakening (P<.001), as well as in patients who were not receiving cancer treatment (P<.001). The univariate analysis showed that patients who were receiving breast cancer treatment and were under hormone therapy reported difficulty falling asleep (P=.04) and pain (P=.05). In a univariate analysis of patients treated for prostate cancer, being overweight was the only factor reported that had a statistically significant value. Our preliminary data support and are consistent with data in the literature regarding the importance of sleep disorders in oncology. This justifies the usefulness of a diagnosis and early treatment of sleep disorders in patients with cancer. The Rafael Institute sleep observatory will enable patients to be identified and treated.

Urgency for bowel movements is a highly discriminatory symptom of active disease in persons with IBD (the Manitoba Living with IBD study).

The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-reported measure used to assess IBD disease activity. There have yet to be more granular analyses on which symptoms are most associated with active disease. To assess the prevalence of symptoms, and to examine which are most associated with disease activity as measured by a symptom index and objective measure of inflammation METHODS: The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly IBDSI. Relative risks (RR) and predictive values (NPV and PPV) were reported for each symptom to predict active disease defined as active IBDSI, self-reported flare and elevated faecal calprotectin (FCAL) (>250 μg/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn's disease [CD] and ulcerative colitis [UC]). In total, 69.2% were female; 64.7% had CD. Fatigue was the most prevalent symptom in both inactive and active disease, across all three disease measures (IBDSI: 24.5% and 75.1%, self-reported flare: 42.2% and 72.2%, FCAL: 46.0% and 60.6%). The absence of fatigue had a high NPV for active IBDSI and self-reporting a flare in both CD and UC. Urgency had a consistently strong NPV and RR across all three disease measures in both IBD subtypes and sexes. The number of loose/liquid bowel movements predicted elevated FCAL in UC (RR males=3.5, 95% CI 1.2-9.9, RR females=1.8, 95% CI 1.2-2.7), as did blood in stool in UC females (RR=1.8, 95% CI 1.2-2.7). In males with CD, excessive bowel gas (RR=2.0, 95% CI 1.2-3.4) and urgency (RR=3.9, 95% CI 1.6-9.3) best predicted an elevated FCAL. No symptom was strongly predictive of an elevated FCAL in CD females. Urgency was consistently associated with disease activity, irrespective of the disease measure. Fatigue was the most prevalent symptom irrespective of disease activity measure. Individual symptoms have different impacts on subjective (IBDSI) and objective (FCAL) measures in IBD.

Associations of sleep duration with the incidence of needed support/long-term care certification according to presence or absence of sleep complaints in community-dwelling Japanese older adults

Background: Evidence on the variability of associations between sleep duration and incident disability according to the presence or absence of sleep complaints is limited. This study assessed the associations between sleep durations and disability incidence stratified by the presence or absence of sleep complaints.Methods: A total of 3,896 community-dwelling Japanese adults aged ≥65 years were observed for 37 months after the self-reporting of sleep duration and sleep complaints. Disability incidence was defined by the certification of needed support/long-term care according to the public long-term care insurance. A proportional hazards model was fitted to examine the association of sleep duration with incident disability according to the presence or absence of fatigue on awakening. Missing values of covariates were estimated using multiple imputations.Results: Long sleep duration was associated significantly with incident disability regardless of the presence or absence of fatigue on awakening; the age- and sex-adjusted hazard ratios were 1.62 (95% Confidence Interval, 1.02–2.56) and 1.35 (1.04–1.75), respectively. The elevated risks of long sleep durations without complaints disappeared after an adjustment for impairments of functional health, while that of long sleep duration with complaints disappeared after an adjustment for medical histories, especially stroke history.Conclusion: Long sleep duration was associated with disability incidence among community-dwelling older persons. The domains of health accounting for the association differed by the presence or absence of sleep complaints.

P294 On the way to disease control: Fatigue as part of a novel composite endpoint in an analysis of a prospective open label observation trial

Abstract Background Ambitious therapeutic goals in the therapy of inflammatory bowel disease need more stringent individual endpoints. Several definitions for composite endpoints are under evaluation to describe disease control. Most commonly symptomatic (PRO2) remission is combined with endoscopic response, histology and/or biomarker remission. Here we explore the addition of fatigues as a lead problem reported by patients with IBD as part of a composite endpoint. Methods We have conducted an interim analysis of an ongoing open label study of patients with Crohn’s disease (CD) and ulcerative colitis (UC) assigned to anti-TNF therapy, vedolizumab, ustekinumab or tofacitinib. Patients are scheduled for evaluations at start of the respective therapy and at weeks 2, 6, 14, 26 and 52. Endoscopies are conducted before therapy and at weeks 14 and 52. Clinical remission (CR) was defined as CDAI &amp;lt; 150 and reduction of partial Mayo score (pMayo) &amp;gt; 50% vs. baseline at week 14. All patients who are not in CR and/or no improvement in endoscopy at week 14 are assessed for a switch in the mechanism of action and observation schedules after a switch are reset to week 0. FACIT-F scores &amp;lt;30 was defined as clinically relevant fatigue. Results Fatigue was present in 52% patients (39/75) at baseline. 54% (25/46) of the patients achieved CR at week 14 while 46% (21/46) did not meet CR criteria (non-responder). Fatigue at baseline was persistent at week 14 in 12% (3/25) of CR responders, in contrast to 43 % (9/21) of non-responders. 64% (21/33) of all patients reached a combined endpoint of CR and absence of fatigue. If fatigue was present at baseline (n = 25), fatigue response was observed in 52% (13/25) of the patients, while CR was only reached in 40% (10/25) and the combined endpoint of CR and fatigue response in 24% (6/25) of the patients at week 14. In contrast, 71% (15/21) of patients without fatigue at baseline reached CR at week 14. Absence of fatigue at baseline thus increased the chance of CR at week 14, with an OR of 3.75 [1.031 – 11.50] (p = 0.0422 in Fisher’s exact test). Conclusion Fatigue is an important complaint strongly impacting the patients’ quality of life. A composite endpoint including fatigue and clinical remission (based on pMayo and CDAI) can be reached in a significant percentage of patients treated with biological therapies. Presence of fatigue at baseline might serve as a strong marker for clinical non-response at week 14. Further evaluation and replication of this novel composite endpoint will be conducted in our ongoing trial with a particular focus on inclusion of endoscopies and long-term outcome.

The Association of Fatigue With Decreasing Regularity of Locomotion During an Incremental Test in Trained and Untrained Healthy Adults

Fatigue is a key factor that affects human motion and modulates physiology, biochemistry, and performance. Prolonged cyclic human movements (locomotion primarily) are characterized by a regular pattern, and this extended activity can induce fatigue. However, the relationship between fatigue and regularity has not yet been extensively studied. Wearable sensor methodologies can be used to monitor regularity during standardized treadmill tests (e.g., the widely used Bruce test) and to verify the effects of fatigue on locomotion regularity. Our study on 50 healthy adults [27 males and 23 females; <40 years; five dropouts; and 22 trained (T) and 23 untrained (U) subjects] showed how locomotion regularity follows a parabolic profile during the incremental test, without exception. At the beginning of the trial, increased walking speed in the absence of fatigue is associated with increased regularity (regularity index, RI, a. u., null/unity value for aperiodic/periodic patterns) up until a peak value (RI = 0.909 after 13.8 min for T and RI = 0.915 after 13.4 min for U subjects; median values, n. s.) and which is then generally followed (after 2.8 and 2.5 min, respectively, for T/U, n. s.) by the walk-to-run transition (at 12.1 min for both T and U, n. s.). Regularity then decreases with increased speed/slope/fatigue. The effect of being trained was associated with significantly higher initial regularity [0.845 (T) vs 0.810 (U), p < 0.05 corrected], longer test endurance [23.0 min (T) vs 18.6 min (U)], and prolonged decay of locomotor regularity [8.6 min (T) vs 6.5 min (U)]. In conclusion, the monitoring of locomotion regularity can be applied to the Bruce test, resulting in a consistent time profile. There is evidence of a progressive decrease in regularity following the walk-to-run transition, and these features unveil significant differences among healthy trained and untrained adult subjects.

Evaluation of the Lake Louise Score for Acute Mountain Sickness and Its 2018 Version in a Cohort of 484 Trekkers at High Altitude.

Richalet, Jean-Paul, Chantal Julia, and François J. Lhuissier. Evaluation of the Lake Louise Score for acute mountain sickness and its 2018 version in a cohort of 484 trekkers at high altitude. High Alt Med Biol. 22:353-361, 2021. Background: The Lake Louise Score (LLS) is widely used in field studies and chamber studies for the diagnosis of Acute Mountain Sickness (AMS). This score aggregates symptoms that are nonspecific: headache, gastrointestinal symptoms, fatigue, dizziness and sleep disturbance can be due to a variety of causes unrelated to altitude hypoxia. The objectives of this study were to (1) reevaluate the need for a headache score >0 for the diagnosis of AMS, (2) evaluate the role of sleep disturbances, in relation with other symptoms, (3) evaluate the significance of dizziness. Materials and Methods: We analyzed LLS from 484 trekkers at high altitude. Among them, 212 suffered from moderate AMS (mAMS: 3 ≤ LLS < 6) and 115 from severe AMS (sAMS: LLS ≥ 6). Results: Cluster analysis of AMS revealed three main groups presenting the following symptoms: Group 1 includes 254 subjects who had less than 2 symptoms; Group 2 includes 137 subjects who had fatigue, sleep disturbance, and headache, corresponding to mAMS; Group 3 includes 93 subjects who had headache, fatigue, dizziness and sleep disturbance, corresponding to sAMS. A headache score of zero was found in 25% of mAMS and 5% of sAMS subjects. Only the absence of headache associated with the absence of fatigue was specific of absence of sAMS. In subjects with a dizziness score > 1, end-tidal partial pressure of carbon dioxide during a hypoxic exercise test was lower than that in subjects with a dizziness score < 2. Subjects with high ventilatory response to hypoxia may develop dizziness with high altitude exposure. Conclusion: (1) An isolated headache score > 0 should not be mandatory to define AMS, (2) sleep disruption contributes to the diagnosis of AMS, (3) gastrointestinal symptoms and dizziness are weaker contributors to the LLS, (4) dizziness might be linked to a hyperresponsiveness to hypoxia and not to AMS itself.

Tired of Being Ignored: Fatigue as a Presenting Symptom in Primary Hyperparathyroidism

BackgroundFatigue is a common presenting symptom in primary hyperparathyroidism (PHPT). Although fatigue alone is not currently an indication for parathyroidectomy, it can have a significant detrimental effect on quality of life. The purpose of this study was to determine if there are underlying differences in demographic or disease characteristics in patients with PHPT who present with fatigue compared with those who do not. MethodsWe reviewed a prospective database of 2197 patients undergoing parathyroidectomy for PHPT by three endocrine surgeons from 2001 to 2019. Patients were divided into two groups based on the presence or absence of fatigue as a presenting symptom. Objective measures of disease severity were then compared between groups. ResultsA total of 1379 (63%) patients presented with fatigue. Patients presenting with fatigue were more likely to be female and to have a prior fracture, lower preoperative serum calcium (Ca), and normocalcemic PHPT. There were no statistically significant differences between groups in age, body mass index, history of nephrolithiasis, or preoperative serum parathyroid hormone levels. Patients presenting with fatigue were also more likely to have smaller parathyroid glands and multiglandular disease. No statistically significant differences were detected in postoperative serum Ca and parathyroid hormone levels, or cure or recurrence rates. ConclusionsPatients with PHPT who report fatigue as a presenting symptom present with more complex disease as manifested by a higher incidence of multiglandular disease and normocalcemic PHPT. Despite this, surgical cure is equivalent to other patients. Therefore, fatigue should be a discrete indication for parathyroidectomy in PHPT.

Inability to increase the neural drive to muscle is associated with task failure during submaximal contractions.

We investigated changes in motor unit (MU) behavior and vasti-muscle contractile properties during sustained submaximal fatiguing contractions with a new time-domain tracking technique to understand the mechanisms responsible for task failure. Sixteen participants performed a nonfatiguing 15-s isometric knee extension at 50% of the maximum voluntary (MVC) torque, followed by a 30% MVC sustained contraction until exhaustion. Two grids of 64 surface electromyography electrodes were placed over vastus medialis and lateralis. Signals were decomposed into MU discharge times and the MUs from the 30% MVC sustained contraction were followed until task failure by overlapping decomposition intervals. These MUs were then tracked between 50% and 30% MVC. During the sustained fatiguing contraction, MUs of the two muscles decreased their discharge rate until ∼40% of the endurance time, referred to as the reversal time, and then increased their discharge rate until task failure. This reversal in firing behavior predicted total endurance time and was matched by opposite changes in twitch force (increase followed by a decrease). Despite the later increase in MU firing rates, peak discharge rates at task failure did not reach the frequency attained during a nonfatiguing 50% MVC contraction. These results show that changes in MU firing properties are influenced by adjustments in contractile properties during the course of the contraction, allowing the identification of two phases. Nevertheless, the contraction cannot be sustained, possibly because of progressive motoneuron inhibition/decreased excitability, as the later increase in firing rate saturates at a much lower frequency compared with a higher-force nonfatiguing contraction.NEW & NOTEWORTHY Motor unit firing and contractile properties during a submaximal contraction until failure were assessed with a new tracking technique. Two distinct phases in firing behavior were observed, which compensated for changes in twitch area and predicted time to failure. However, the late increase in firing rate was below the rates attained in absence of fatigue, which points to an inability of the central nervous system to sufficiently increase the neural drive to muscle with fatigue.

High Disease Burden Drives Indirect Costs in Employed Inflammatory Bowel Disease Patients: The WORK-IBD Study.

BackgroundWork productivity (WP) loss includes absence from work (absenteeism) and productivity loss while working (presenteeism), which leads to high indirect costs in inflammatory bowel disease (IBD). Prior health economic analyses predominantly focused on absenteeism. Here we focus on presenteeism and assess predictors of WP loss, fatigue, and reduced health-related quality of life (HRQL).MethodsEmployed IBD patients completed the following surveys: Work Productivity and Activity Impairment, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire. Predictors were assessed using uni- and multivariable regression analyses. Annual costs were calculated using percentages of WP loss, hourly wages, and contract hours.ResultsOut of 1590 invited patients, 768 (48%) responded and 510 (32%) were included. Absenteeism, presenteeism, and overall WP loss were reported by 94 (18%), 257 (50%), and 269 (53%) patients, respectively, resulting in mean (SD) annual costs of €1738 (5505), €5478 (8629), and €6597 (9987), respectively. Disease activity and active perianal disease were predictors of WP loss (odds ratio [OR] = 6.6; 95% confidence interval [CI], 3.6-12.1); OR = 3.7; 95% CI, 1.5-8.7). Disease activity and arthralgia were associated with fatigue (OR = 3.6; 95% CI, 1.9-6.8; OR = 1.8; 95% CI, 1.0-3.3)) and reduced HRQL (OR = 10.3; 95% CI, 5.9-17.9; OR = 2.3; 95 % CI, 1.4-3.8). Fatigue was the main reason for absenteeism (56%) and presenteeism (70%). Fatigue and reduced HRQL led to increased costs compared with absence of fatigue and normal HRQL (mean difference = €6630; 95% CI, €4977–€8283, P < 0.01; mean difference = €9575; 95% CI, €7767–€11,384, P < 0.01).ConclusionsDisease activity and disease burden lead to WP loss in approximately half of the employed IBD population, driving indirect costs. Fatigue is the most important reason for WP loss.

Vitamin D deficiency and its association with fatigue and quality of life in multiple sclerosis patients

Vitamin D deficiency is associated with the incidence and prevalence of a variety of neurologic disorders, including multiple sclerosis. However, available studies to date have not provided convincing evidence that vitamin D treatment improves fatigue and life quality in patients with multiple sclerosis. To assess the relationship of vitamin D deficiency with health-related quality-of-life issues and fatigue in multiple sclerosis patients. Vitamin D3 levels were measured in 149 multiple sclerosis patients. In patients with lower than 30 ng/mL levels, vitamin D was administered. Fatigue and health-related quality of life scores were measured at baseline and months 1, 3, 6, and 12 after the beginning of vitamin D3 administration. Among 149 patients, 90% were vitamin D deficient. After vitamin D supplementation, health-related quality of life and fatigue scores improved significantly. There was a direct association between health-related quality of life with absence of fatigue and vitamin D status at the end of study. The 90% frequency of multiple sclerosis patients with vitamin D deficiency, together with the significant association of vitamin D status with the absence of fatigue and improved physical and functional well-being, points to vitamin D supplementation as a potential therapy to enhance the patient's quality of life. This article emphasizes that vitamin D supplementation can improve clinical outcome in multiple sclerosis patients providing immune modulation and neuroprotection. Identification and correction of vitamin D deficiency has the potential to treat the related quality of life in patients with multiple sclerosis.

Fatigue induces long-lasting detrimental changes in motor-skill learning.

Fatigue due to physical exertion is a ubiquitous phenomenon in everyday life and especially common in a range of neurological diseases. While the effect of fatigue on limiting skill execution are well known, its influence on learning new skills is unclear. This is of particular interest as it is common practice to train athletes, musicians or perform rehabilitation exercises up to and beyond a point of fatigue. In a series of experiments, we describe how muscle fatigue, defined as degradation of maximum force after exertion, impairs motor-skill learning beyond its effects on task execution. The negative effects on learning are evidenced by impaired task acquisition on subsequent practice days even in the absence of fatigue. Further, we found that this effect is in part mediated centrally and can be alleviated by altering motor cortex function. Thus, the common practice of training while, or beyond, fatigue levels should be carefully reconsidered, since this affects overall long-term skill learning.

On the role of the amygdala for experiencing fatigue in patients with multiple sclerosis

BackgroundRecently, we proposed a model explaining the origin of fatigue in multiple sclerosis (MS) patients. This model assumes that the feeling of fatigue results from inflammation-induced information processing within interoceptive brain areas. ObjectivesTo investigate the association between self-reported cognitive fatigue and structural integrity of interoceptive brain areas in MS patients. Methods95 MS patients and 28 healthy controls participated in this study. All participants underwent diffusion tensor MRI and fractional anisotropy data were calculated for the amygdala, the stria terminalis and the corpus callosum, a non-interoceptive brain area. Based on the cognitive fatigue score of the Fatigue Scale for Motor and Cognition, patients were divided into moderately cognitively fatigued (cognitive fatigue score ≥ 28) and cognitively non-fatigued (cognitive fatigue score < 28) MS patients. Healthy controls were recruited as a third group. Repeated measures analyses of covariance, controlling for age, depression and brain atrophy, were performed to investigate whether the factor Group had a significant effect on the fractional anisotropy data. ResultsA significant effect of Group was observed for the amygdala (F = 3.389, p = 0.037). MS patients without cognitive fatigue presented lower values of the amygdala than MS patients with cognitive fatigue and healthy controls. For the stria terminalis and the corpus callosum, no main effect of Group was observed. ConclusionThe structural integrity of the amygdala in non-fatigued MS patients appears to be reduced. According to our model this might indicate that the absence of fatigue in non-fatigued MS patients might result from disturbed inflammation-induced information processing in the amygdala.

Patient\u2019s perspective of sustained remission in rheumatoid arthritis

BackgroundDuring the course of rheumatoid arthritis (RA), patients have profound negative effects on their patient-reported-outcomes (PRO); in addition, the impact of sustained remission (SR) on PROs may differ for each particular outcome. The objectives of this study were to identify SR from an inception cohort of RA patients and to examine the impact of SR in an ample spectrum of PROs.MethodsThe study was developed in a well characterized and ongoing cohort of RA patients with recent onset disease recruited from 2004 onwards. In November 2016, the cohort included 187 patients, of whom 145 had at least 30 months of follow-up, with complete rheumatic assessments at regular intervals in addition to a pain visual analogue scale (PVAS), overall disease-VAS (OVAS), health assessment questionnaire (HAQ), Short-Form 36v2 Survey (SF-36) and fatigue assessment. First SR was defined according to the DAS28 cut-offs (DAS28-SR) and ACR/EULAR 2011 Boolean definition (B-SR), if maintained for at least 12 consecutive months. The dependent t test and Mc Nemar’s tests were used for comparisons between related groups. Local IRB approval was obtained.ResultsMore patients achieved DAS28-SR than B-SR: 78 vs. 63, respectively. Fifty patients met both SR definitions. Follow-up to DAS28-SR was shorter than to B-SR and the duration of DAS28-SR was longer, p ≤ 0.023 for all comparisons.At SR, patients had PRO proxy to normal values; the percentage of patients with normal PRO varied from 97% (95% CI: 91–99) for HAQ to 50% (95% CI: 39–61) for absence of fatigue.In DAS28-SR patients, acute reactant phases within the normal range were detected very early (after 1.5–2.9 months). HAQ, PVAS, OVAS and SF-36 were scored within the normal range after 6–7 months. The absence of fatigue was detected at 8.7 months of follow-up, which was similar to DAS28-SR. In the 63 patients with B-SR, a similar pattern was observed. The follow-up to outcomes of the 50 patients who met both SR definitions was similar, but the absence of fatigue and physical component SF-36 normalization were achieved earlier in B-SR patients (p ≤ 0.02).ConclusionsThe impact of SR on PRO differs accordingly to each particular outcome.

The Effect of Cushioned Insoles on Tibial Acceleration During Running

Background: Running through fatigue has been found to place an excessive amount of stress to lower extrimities that may increase the risk of overuse injuries. Cushioned insoles are suggested to help attenuate shock and reduce impact forces caused by running. PURPOSE: To investigate the effect of implementing cushioned insoles on subjects before and after a fatigue protocol run to determine whether the insoles significantly lessened impacts. METHODS: Four male college students (age = 22.8± 4yr; weight = 80.2± 5kg; height = 187.3± 3cm) participated in the study. The participants were tested three times over a period of three weeks. During the first visit, lactate threshold speed (LTS) was assessed via blood samples (7.8±.5mph). During the second and third visits participants were randomly assigned to undergo incremental treadmill tests with and without insoles. The incremental runs included two rounds of seven 30-second bouts at stages -20% below to +40% above the LTS, with a 20 minute run at LTS in between the two trials. A triaxial accelerometer that was placed at each subject’s dominant tibial plateau recorded acceleration before and after the 20m run. Tibial acceleration (TA), stride length and frequency were calculated through Matlab. RESULTS: A two way repeated ANOVA (2 fatigue states by 2 insoles conditions) showed that there was a main effect of state (p=0.003) and a main effect of insole condition (p<0.001), as well as an interaction (p=0.044). Post hoc analysis revealed that TA was significantly lower during the non-fatigue control run with insoles when compared to the other conditions. Over the course of both pre- and post-fatigue incremental tests, stride length and frequency did not change. CONCLUSION: The findings indicate that insoles are an effective way to reduce tibial acceleration during running, but to a greater extent in the absence of fatigue (22% vs. 13%).