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Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness.

ABSTRACT: BACKGROUND:Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing-remitting MS patients showed a clinically meaningful decrease in fatigue over 1?year of treatment with natalizumab. OBJECTIVE:To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness. METHODS:Patients were assessed regarding fatigue, depression, and day-time sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analyzed. RESULTS:After 1?year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue. CONCLUSION:Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression.

SUBMITTER: Penner IK

PROVIDER: S-EPMC4337367 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness.

Penner Iris-Katharina IK Sivertsdotter Eva Catharina EC Celius Elisabeth G EG Fuchs Siegrid S Schreiber Karen K Berkö Sara S Svenningsson Anders A

Frontiers in neurology 20150223

<h4>Background</h4>Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing-remitting MS patients showed a clinically meaningful decrease in fatigue over 1 year of treatment with natalizumab.<h4>Objective</h4>To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness.<h4 ...[more]

PMID: 25755648

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Project description:BACKGROUND: Night work has been reported to be associated with various mental disorders and complaints. We investigated relationships between night work and anxiety, depression, insomnia, sleepiness and fatigue among Norwegian nurses. METHODS: The study design was cross-sectional, based on validated self-assessment questionnaires. A total of 5400 nurses were invited to participate in a health survey through the Norwegian Nurses' Organization, whereof 2059 agreed to participate (response rate 38.1%). Nurses completed a questionnaire containing items on demographic variables (gender, age, years of experience as a nurse, marital status and children living at home), work schedule, anxiety/depression (Hospital Anxiety and Depression Scale), insomnia (Bergen Insomnia Scale), sleepiness (Epworth Sleepiness Scale) and fatigue (Fatigue Questionnaire). They were also asked to report number of night shifts in the last 12 months (NNL). First, the parameters were compared between nurses i) never working nights, ii) currently working nights, and iii) previously working nights, using binary logistic regression analyses. Subsequently, a cumulative approach was used investigating associations between NNL with the continuous scores on the same dependent variables in hierarchical multiple regression analyses. RESULTS: Nurses with current night work were more often categorized with insomnia (OR = 1.48, 95% CI = 1.10-1.99) and chronic fatigue (OR = 1.78, 95% CI = 1.02-3.11) than nurses with no night work experience. Previous night work experience was also associated with insomnia (OR = 1.45, 95% CI = 1.04-2.02). NNL was not associated with any parameters in the regression analyses. CONCLUSION: Nurses with current or previous night work reported more insomnia than nurses without any night work experience, and current night work was also associated with chronic fatigue. Anxiety, depression and sleepiness were not associated with night work, and no cumulative effect of night shifts during the last 12 months was found on any parameters.

Project description:Interferon-alpha (IFN-?) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-? on immune cells in vivo and its relationship to IFN-?-induced behavioral changes.Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-? therapy (n=10) or at 12 weeks of IFN-? treatment (n=11).Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2'-5'-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-?-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-?-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-? signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-?-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-? and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression.Depression and fatigue during chronic IFN-? administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

Project description:BackgroundMany patients on maintenance dialysis experience significant sleepiness and fatigue. However, the influence of the hemodialysis (HD) day and circadian rhythms on patients' symptoms have not been well characterized. We sought to use ecological momentary assessment to evaluate day-to-day and diurnal variability of fatigue, sleepiness, exhaustion and related symptoms in thrice-weekly maintenance HD patients.MethodsSubjects used a modified cellular phone to access an interactive voice response system that administered the Daytime Insomnia Symptom Scale (DISS). The DISS assessed subjective vitality, mood, and alertness through 19 questions using 7- point Likert scales. Subjects completed the DISS 4 times daily for 7 consecutive days. Factor analysis was conducted and a mean composite score of fatigue-sleepiness-exhaustion was created. Linear mixed regression models (LMM) were used to examine the association of time of day, dialysis day and fatigue, sleepiness, and exhaustion composite scores.ResultsThe 55 participants completed 1,252 of 1,540 (81%) possible assessments over the 7 day period. Multiple symptoms related to mood (e.g., feeling sad, feeling tense), cognition (e.g., difficulty concentrating), and fatigue (e.g., exhaustion, feeling sleepy) demonstrated significant daily and diurnal variation, with higher overall symptom scores noted on hemodialysis days and later in the day. In factor analysis, 4 factors explained the majority of the observed variance for DISS symptoms. Fatigue, sleepiness, and exhaustion loaded onto the same factor and were highly intercorrelated. In LMM, mean composite fatigue-sleepiness-exhaustion scores were associated with dialysis day (coefficient and 95% confidence interval [CI] 0.21 [0.02 - 0.39]) and time of day (coefficient and 95% CI 0.33 [0.25 - 0.41]. Observed associations were minimally affected by adjustment for demographics and common confounders.ConclusionsMaintenance HD patients experience fatigue-sleepiness-exhaustion symptoms that demonstrate significant daily and diurnal variation. The variability in symptoms may contribute to poor symptom awareness by providers and greater misclassification bias of fatigue related symptoms in clinical studies.

Project description:Background and purposeThe considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging.Materials and methodsIn this explorative observational study, 25 patients with relapsing-remitting multiple sclerosis initiating natalizumab treatment were included and scanned every 6 months for 18 months. Additionally 18 matched patients with relapsing-remitting multiple sclerosis continuing treatment with interferon-β or glatiramer acetate were included along with 12 healthy controls. Imaging included short TE 2D-MR spectroscopic imaging with absolute metabolite quantification of total N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, and glutamate. Concentrations were determined for lesional white matter, normal-appearing white matter, and gray matter.ResultsAt baseline in both patient groups, lower concentrations of total N-acetylaspartate and creatine and phosphocreatine were found in lesional white matter compared with normal-appearing white matter and additionally lower glutamate in lesional white matter of patients receiving natalizumab. In those patients, a significant yearly metabolite increase was found for lesional white matter total N-acetylaspartate (7%, P < .001), creatine and phosphocreatine (6%, P = .042), and glutamate (10%, P = .028), while lesion volumes did not change. In patients receiving interferon-β/glatiramer acetate, no significant change was measured in lesional white matter for any metabolite, while whole-brain normalized lesion volumes increased.ConclusionsPatients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter. These increasing metabolite concentrations might be a sign of enhanced axonal metabolism.

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Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness.

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Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness.

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