Effectiveness of a blended booster programme for the long-term outcome of cognitive behavioural therapy for MS-related fatigue: A randomized controlled trial.

BACKGROUND: Cognitive behavioural therapy (CBT) reduces MS-related fatigue. However, studies on the long-term effects show inconsistent findings. OBJECTIVE: To evaluate whether a blended booster programme improves the outcome of CBT for MS-related fatigue on fatigue severity at 1-year follow-up. METHOD: A multicentre randomized clinical trial in which 126 patients with MS were allocated to either a booster programme or no booster programme (control), after following 20-week tailored CBT for MS-related fatigue. Primary outcome was fatigue severity assessed with the Checklist Individual Strength fatigue subscale 1 year after start of treatment (T52). Mixed model analysis was performed by a statistician blinded for treatment-allocation to determine between-group differences in fatigue severity. RESULTS: Fatigue severity at 1-year follow-up did not differ significantly between the booster (N = 62) and control condition (N = 64) (B = -2.01, 95% confidence interval (CI) = -4.76 to 0.75). No significant increase in fatigue severity was found at T52 compared with directly post-treatment (T20) in both conditions (B = 0.44, 95% CI = -0.97 to 1.85). CONCLUSION: Effects of CBT were sustained up to 1 year in both conditions. The booster programme did not significantly improve the long-term outcome of CBT for MS-related fatigue. TRIAL REGISTRATION: Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782.

Online vestibular rehabilitation for chronic vestibular syndrome: 36-month follow-up of a randomised controlled trial in general practice.

BACKGROUND: Vestibular rehabilitation (VR) is the preferred treatment for chronic vestibular symptoms such as dizziness and vertigo. An internet-based programme was developed to increase uptake of VR. The authors have previously reported that internet-based VR resulted in a clinically relevant decrease of vestibular symptoms for up to 6 months, compared with usual care. AIM: To evaluate long-term outcomes of internet-based VR in patients with chronic vestibular syndrome. DESIGN AND SETTING: A randomised controlled trial was conducted in Dutch general practice involving 322 participants aged ≥50 years with chronic vestibular syndrome. Participants were randomised to stand-alone VR, blended VR (with physiotherapy support), and usual care. Usual care participants were allowed to cross over to stand-alone VR 6 months after randomisation. METHOD: Participants were approached 36 months after randomisation. The primary outcome was the presence of vestibular symptoms as measured by the vertigo symptom scale-short form (VSS-SF). Secondary outcomes were dizziness-related impairment, anxiety, depressive symptoms, and healthcare utilisation. RESULTS: At 36-month follow-up, 65% of participants filled in the VSS-SF. In the usual care group, 38% of participants had crossed over to VR at 6 months. There were no significant differences in vestibular symptoms between VR groups and usual care (mean difference = -0.8 points, 95% confidence interval [CI] = -2.8 to 1.2, for stand-alone VR; -0.3, 95% CI = -2.2 to 1.7, for blended VR). In VR groups, clinically relevant improvement compared with baseline was maintained over time. CONCLUSION: Internet-based VR provides a maintained improvement of vestibular symptoms for up to 36 months in patients with chronic vestibular syndrome.

Pharmacokinetics of oral and subcutaneous methotrexate in red and white blood cells in patients with early rheumatoid arthritis: the methotrexate monitoring trial.

OBJECTIVE: To investigate the pharmacokinetics of methotrexate polyglutamate (MTX-PG) accumulation in red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) in patients with early rheumatoid arthritis (RA) after oral and subcutaneous MTX treatment. METHODS: In a clinical prospective cohort study (Methotrexate Monitoring study), newly diagnosed patients with RA were randomised for oral or subcutaneous MTX. At 1, 2, 3 and 6 months after therapy initiation, blood was collected and RBCs and PBMCs were isolated. MTX-PG1-6 concentrations were determined by mass spectrometry methods using stable isotopes of MTX-PG1-6 as internal standards. RESULTS: 43 patients (mean age: 58.5 years, 77% female) were included. PBMCs and RBCs revealed disparate pharmacokinetic profiles in both absolute MTX-PG accumulation levels and distribution profiles. Intracellular MTX-PG accumulation in PBMCs was significantly (p<0.001) 10-fold to 20-fold higher than RBCs at all time points, regardless of the administration route. MTX-PG distribution in PBMCs was composed of mostly MTX-PG1 (PG1>PG2>PG3). Remarkably, the distribution profile in PBMCs remained constant over 6 months. RBCs accumulated mainly MTX-PG1 and lower levels of MTX-PG2-5 at t=1 month. After 3 months, MTX-PG3 was the main PG-moiety in RBCs, a profile retained after 6 months of MTX therapy. Subcutaneous MTX administration results in higher RBC drug levels than after oral administration, especially shortly after treatment initiation. CONCLUSIONS: This is the first study reporting disparate MTX-PG accumulation profiles in RBCs versus PBMCs in newly diagnosed patients with RA during 6 months oral or subcutaneous MTX administration. This analysis can contribute to improved MTX therapeutic drug monitoring for patients with RA. TRIAL REGISTRATION NUMBER: NTR 7149.

Effectiveness of electronic drug monitoring feedback to increase adherence in patients with RA initiating a biological DMARD: a randomised clinical trial.

OBJECTIVE: Medication non-adherence in rheumatoid arthritis (RA) is associated with disease flares, increased disability and increased costs. This study assessed the effectiveness of electronic monitoring feedback (EMF) on medication adherence in patients with RA starting with or switching to a new biological disease-modifying antirheumatic drug (bDMARD). METHODS: In this randomised controlled trial, bDMARD starters were assigned to the intervention or control group and followed for 1 year. The intervention group received a needle container with a Medication Event Monitoring System (MEMS) cap registering patient's adherence to injections. Scores were calculated every 3 months with MEMS and motivational interviewing feedback was given. The control group received usual care. Effectiveness of EMF on adherence was measured with the medication possession ratio (MPR). RESULTS: 104 consecutive intervention patients were included and 102 controls. MPR was 0.95 (SD: 0.10) and 0.90 (0.16) after 12 months (B: 0.036, 95% CI: 0.001 to 0.007, p=0.045). bDMARD-naive patients receiving EMF achieved low disease activity (LDA) sooner compared with the control group, adjusted for baseline DAS (HR: 1.68, 95% CI: 1.00 to 2.81, p=0.050). Side effects and DAS28 were similar. CONCLUSION: EMF increased adherence for patients with RA starting with or switching to a bDMARD. Especially bDMARD-naive patients achieved LDA sooner compared with the control group, which holds promise for the future.

Treatment alliance and needs of care concerning religiousness and spirituality: A follow-up study among psychiatric inpatients.

BACKGROUND: Patient satisfaction with religious/spiritual (R/S) care during mental health treatment has been associated with a better treatment alliance. AIMS: To investigate the longitudinal relations between (un)met R/S care needs and treatment alliance/compliance over a 6-month period. METHOD: 201 patients in a Christian (CC) and a secular mental health clinic completed a questionnaire (T0) containing an R/S care needs questionnaire, the Working Alliance Inventory (WAI) and the Service Engagement Scale (SES). After 6 months 136 of them took part in a follow-up (T1). Associations were analysed using hybrid linear mixed models and structural equation modelling. RESULTS: R/S care needs decreased over time, but a similar percentage remained unanswered (e.g. 67% of the needs on R/S conversations in a secular setting). Over a 6-month period, met R/S care needs were associated with a higher WAI score (ß = .25; p < .001), and unmet R/S care needs with lower WAI score (ß = -.36; p < .001), which were mainly between subjects effects. Patients reporting a high score of unmet R/S care at baseline, reported a decrease in SES over time (ß = -.13; p < .05). CONCLUSIONS: Satisfaction with R/S care among mental health patients is related to a better treatment alliance. When unmet R/S care needs persist, they precede a decrease in treatment compliance. Mental health professionals are recommended to assess the presence of R/S care needs and consider possibilities of R/S care especially in the first weeks of treatment.

Intention-to-treat analysis when only a baseline value is available.

OBJECTIVES: How to perform an intention to treat (ITT) analysis when a patient has a baseline value but no follow-up measurements is problematic. The purpose of this study was to compare different methods that deal with this problem, i.e. no imputation (standard and alternative mixed model analysis), single imputation (i.e. baseline value carried forward), and multiple imputation (selective and non-selective). STUDY DESIGN AND SETTING: We used a simulation study with different scenarios regarding 1) the association between missingness and the baseline value, 2) whether the patients did or did not receive the treatment, and 3) the percentage of missing data, and two real life data sets. RESULTS: Bias and coverage were comparable between the two mixed model analyses and multiple imputation in most situations including the real life data examples. Only in the situation when the patients in the treatment group were simulated not to have received the treatment, selective imputation using this information outperformed all other methods. CONCLUSIONS: In most situations a standard mixed model analysis without imputation is appropriate as ITT analysis. However, when patients with missing follow-up data allocated to the treatment group did not received treatment, it is advised to use selective imputation, using this information, although the results should be interpreted with caution.

The association between freezing of gait, fear of falling and anxiety in Parkinson's disease: a longitudinal analysis.

Aim: We studied the longitudinal associations between freezing of gait (FoG), fear of falling (FoF) and anxiety, and how these associations are influenced by confounding factors. Materials & methods: We analyzed longitudinal motor and nonmotor measurements from 153 Parkinson's disease patients. Possible confounding factors were divided into three subgroups: demographics, disease characteristics, medication use and adverse effects of medication. Results: All crude associations between FoG, FoF and anxiety were significant and remained so after adjusting for confounders. When analyzing FoF and anxiety together as independent variables, the association between FoG and FoF remained, and the association between FoG and anxiety diminished. Conclusion: We confirm the complex interactions between motor and nonmotor symptoms in Parkinson's disease, and plead for a multidisciplinary approach.

Inguinal hernia in girls: A retrospective analysis of over 1000 patients.

BACKGROUND: In girls with inguinal hernia, timing of surgical repair to prevent ovarian strangulation and screening for Androgen Insensitivity Syndrome (AIS) remain controversial. This study assesses the incidence of ovarian strangulation and AIS, and its associated risk factors. METHODS: Electronic patient records were used to study girls aged 0-15 years who underwent inguinal hernia repair between 2000 and 2017. Patients with incomplete data were excluded. Risk factors were identified using logistic regression. RESULTS: This study includes 1084 girls (median (IQR) age: 133.5 (14-281) weeks) who underwent 1132 hernia repairs (1015 unilateral, 117 bilateral) within a median (IQR) time interval of 12 (6-23) days following diagnosis. Hernia sac intraoperatively contained ovary in 235 (21.7%) patients, ovary was strangulated in 14 (6%). Risk factors for ovarian strangulation were younger gestational age (OR 0.49), higher birthweight (OR 32.18), and first presentation at the emergency department (OR 13.07). However data were partly missing. Ectopic testis was found in seven (0.6%) patients. Metachronous contralateral inguinal hernia and ipsilateral recurrence developed in 6.1% and 0.3%, respectively. CONCLUSIONS: Ovarian hernia was diagnosed in 21.7%, and ovary was strangulated in 6%. No definite conclusions can be drawn regarding risk factors for strangulation and timing of surgery in girls with irreducible ovarian hernia. LEVEL OF EVIDENCE: Level III.

Online Self-Management Support for Family Caregivers Dealing With Behavior Changes in Relatives With Dementia (Part 2): Randomized Controlled Trial.

BACKGROUND: Online contacts with a health professional have the potential to support family caregivers of people with dementia. OBJECTIVE: The goal of the research was to study the effects of an online self-management support intervention in helping family caregivers deal with behavior changes of a relative with dementia. The intervention-involving among others personal email contacts with a dementia nurse-was compared with online interventions without these email contacts. METHODS: A randomized controlled trial was conducted with 81 family caregivers of people with dementia who live at home. Participants were randomly assigned to a (1) major self-management support intervention consisting of personal email contacts with a specialist dementia nurse, online videos, and e-bulletins; (2) medium intervention consisting only of online videos and e-bulletins; or (3) minor intervention consisting of only the e-bulletins. The primary outcome was family caregivers' self-efficacy in dealing with behavior changes of the relative with dementia. Secondary outcomes were family caregivers' reports of behavior problems in the people with dementia and the quality of the relationship between the family caregiver and the person with dementia. Measurements were performed at the baseline and at 6 (T1) and 12 weeks (T2) after the baseline. A mixed-model analysis was conducted to compare the outcomes of the 3 intervention arms. RESULTS: Family caregivers participating in the major intervention involving email contacts showed no statistically significant differences in self-efficacy after the intervention compared with the minor intervention involving only e-bulletins (difference -0.02, P=.99). In the adjusted analysis, the medium intervention (involving videos and e-bulletins) showed a negative trend over time (difference -4.21, P=.09) and at T1 (difference -4.71, P=.07) compared with the minor intervention involving only e-bulletins. No statistical differences were found between the intervention arms in terms of the reported behavior problems and the quality of the relationship between the family caregiver and the person with dementia. CONCLUSIONS: The expectation that an online self-management support intervention involving email contacts would lead to positive effects and be more effective than online interventions without personal email contacts was not borne out. One explanation might be related to the fact that not all family caregivers who were assigned to that intervention actually made use of the opportunity for personal email contact. The online videos were also not always viewed. To obtain more definite conclusions, future research involving extra efforts to reach higher use rates is required. TRIAL REGISTRATION: Netherlands Trial Registry NTR6237; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6237 (Archived by WebCite at http://www.webcitation.org/6v0S4fxTC). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.8365.

Palliative care provision in long-term care facilities differs across Europe: Results of a cross-sectional study in six European countries (PACE).

BACKGROUND: While the need for palliative care in long-term care facilities is growing, it is unknown whether palliative care in this setting is sufficiently developed. AIM: To describe and compare in six European countries palliative care provision in long-term care facilities and to assess associations between patient, facility and advance care planning factors and receipt and timing of palliative care. DESIGN: Cross-sectional after-death survey regarding care provided to long-term care residents in Belgium, England, Finland, Italy, the Netherlands and Poland. Generalized estimating equations were used for analyses. SETTING/PARTICIPANTS: Nurses or care assistants who are most involved in care for the resident. RESULTS: We included 1298 residents in 300 facilities, of whom a majority received palliative care in most countries (England: 72.6%-Belgium: 77.9%), except in Poland (14.0%) and Italy (32.1%). Palliative care typically started within 2 weeks before death and was often provided by the treating physician (England: 75%-the Netherlands: 98.8%). A palliative care specialist was frequently involved in Belgium and Poland (57.1% and 86.7%). Residents with cancer, dementia or a contact person in their record more often received palliative care, and it started earlier for residents with whom the nurse had spoken about treatments or the preferred course of care at the end of life. CONCLUSION: The late initiation of palliative care (especially when advance care planning is lacking) and palliative care for residents without cancer, dementia or closely involved relatives deserve attention in all countries. Diversity in palliative care organization might be related to different levels of its development.

Fronto-limbic disconnection in patients with multiple sclerosis and depression.

BACKGROUND: The biological mechanism of depression in multiple sclerosis (MS) is not well understood. Based on work in major depressive disorder, fronto-limbic disconnection might be important. OBJECTIVE: To investigate structural and functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS (nDMS) patients. METHODS: In this retrospective study, 22 moderate-to-severe DMS patients (disease duration 8.2 ± 7.7 years), 21 nDMS patients (disease duration 15.3 ± 8.3 years), and 12 healthy controls underwent neuropsychological testing and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM), gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC) between limbic and frontal areas were measured and compared between groups. Regression analysis was performed to relate MRI measures to the severity of depression. RESULTS: Compared to nDMS patients, DMS patients (shorter disease duration) had lower WM volume ( p < 0.01), decreased FA of the uncinate fasciculus ( p < 0.05), and lower FC between the amygdala and frontal regions ( p < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala could explain 48% of variance in the severity of depression. No differences in cognition were found. CONCLUSION: DMS patients showed more pronounced (MS) damage, that is, structural and functional changes in temporo-frontal regions, compared to nDMS patients, suggestive of fronto-limbic disconnection.

Bone Safety During the First Ten Years of Gender-Affirming Hormonal Treatment in Transwomen and Transmen.

Concerns about the effects of gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender people exist, particularly regarding the decrease in estrogen concentrations in transmen. Although it is known that HT is safe for BMD in the short term, long-term follow-up studies are lacking. Therefore this study aimed to investigate the change in BMD during the first 10 years of HT, to determine whether HT is safe and if assessing BMD during HT is necessary. A follow-up study was performed in adult transgender people receiving HT at the VU University Medical Center Amsterdam between 1998 and 2016. People were included if they were HT naive and had a dual-energy X-ray absorptiometry (DXA) scan at the start of HT. Follow-up DXA scans performed after 2, 5, and/or 10 years of HT were used for analyses. The course of BMD of the lumbar spine during the first 10 years of HT was analyzed using multilevel analyses. A total of 711 transwomen (median age 35 years; IQR, 26 to 46 years) and 543 transmen (median age 25 years; IQR, 21 to 34 years) were included. Prior to the start of HT, 21.9% of transwomen and 4.3% of transmen had low BMD for age (Z-score < -2.0). In transwomen lumbar spine BMD did not change (+0.006; 95% CI, -0.005 to +0.017), but lumbar spine Z-score increased by +0.22 (95% CI, +0.12 to +0.32) after 10 years of HT. Also in transmen lumbar spine BMD did not change (+0.008; 95% CI, -0.004 to +0.019), but lumbar spine Z-score increased by +0.34 (95% CI, +0.23 to +0.45) after 10 years of HT. This study showed that HT does not have negative effects on BMD, indicating that regularly assessing BMD during HT is not necessary. However, a high percentage of low BMD was found prior to HT, especially in transwomen. Therefore, evaluation of BMD before start of HT may be considered. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Improved diabetes medication convenience and satisfaction in persons with type 2 diabetes after switching to insulin glargine 300 U/mL: results of the observational OPTIN-D study.

OBJECTIVE: Insulin glargine 300 (Gla-300) provides less hypoglycemia risk and more flexibility in injection time. The extent to which these effects translate into improved patient-reported outcomes (PROs) is unknown, and is the subject of this observational study. RESEARCH DESIGN AND METHODS: Adults with type 2 diabetes treated with basal insulin for at least 6 months initiating Gla-300 were included. Data were collected at baseline (start Gla-300) and at 3-month and 6-month follow-up. Patients and physicians gave reasons for switching to Gla-300 at baseline and the extent to which Gla-300 fulfilled their expectations at 6 months. Mixed model analyses examined PRO changes over time, with emotional well-being (WHO-5 Well-Being Index) as the primary outcome. The secondary outcomes were hypoglycemia incidence, hemoglobin A1c (HbA1c), hypoglycemia worries (worry subscale of the Hypoglycemia Fear Survey), diabetes distress (short form of the Dutch version of the Problem Areas In Diabetes Scale), diabetes medication convenience (Diabetes Medication System Rating Questionnaire (DMSRQ)), sleep quality and duration (Pittsburgh Sleep Quality Index), and adherence (Summary of Diabetes Self-Care Activities). RESULTS: 162 patients participated: 53.70% were men, the mean age was 65.54 years (9.05), baseline mean HbA1c was 7.87% (1.15) (62.48 mmol/mol (12.61)), and mean diabetes duration was 15.14 years (6.65). Mean WHO-5 Well-Being Index scores improved non-significantly from 61.94 (19.52) at baseline (T0) to 63.83 (19.67) at 6 months (T2). Mean DMSRQ scores improved significantly from 32.96 (9.02) (T0) to 36.70 (8.85) (T2) (p<0.001). Dose (less volume) was a switching reason in 69.60% of patients and 63% of physicians, and flexibility in 33.30% and 24.70%, respectively. Gla-300 fulfilled the expectations or even better than expected in 92.30% of patients and 88.90% of physicians. CONCLUSION: In a relatively well-controlled sample of adults with type 2 diabetes, switching to Gla-300 improves diabetes medication convenience.

Effectiveness of a digital platform-based implementation strategy to prevent work stress in a healthcare organization: a 12-month follow-up controlled trial.

Objectives Healthcare workers frequently deal with work stress. This is a risk factor for adverse mental and physical health effects. The objective of this study was to investigate the effectiveness of a digital platform-based implementation strategy - compared to a control group - on stress, work stress determinants (ie. psychosocial work factors) and the level of implementation among healthcare workers. Methods By way of matching, 30 teams from a healthcare organization were assigned to the experimental (15 teams; N=252) or wait-list control (15 teams; N=221) group. The experimental group received access to the strategy for 12 months. They were asked to complete the 5-step protocol within six months. The primary outcome was stress (DASS-21) and secondary outcomes were psychological demands, social support, autonomy, and the level of implementation. Questionnaire-based data were collected at baseline, and at 6- and 12-months follow-up. Linear mixed model analyses were used to test differences between the two groups. Results In total, 210 participants completed the baseline questionnaire and at least one follow-up questionnaire. There was a significant effect of the strategy on stress in favor of the experimental group [B=-0.95, 95% confidence interval (CI) -1.81 - -0.09]. No statistically significant differences were found for any secondary outcomes. Conclusions The strategy showed potential for primary prevention of work stress, mainly explained by an increase in stress in the control group that was prevented in the experimental group. More research is necessary to assess the full potential of the strategy.

Prediction models to identify workers at risk of sick leave due to low-back pain in the Dutch construction industry.

Objective The aim of this study was to develop a prediction model based on variables measured in occupational health checks to identify non-sick listed workers at risk of sick leave due to non-specific low-back pain (LBP). Methods This cohort study comprised manual (N=22 648) and non-manual (N=9735) construction workers who participated in occupational health checks between 2010 and 2013. Occupational health check variables were used as potential predictors and LBP sick leave was recorded during 1-year follow-up. The prediction model was developed with logistic regression analysis among the manual construction workers and validated in non-manual construction workers. The performance of the prediction model was evaluated with explained variances (Nagelkerke's R-square), calibration (Hosmer-Lemeshow test), and discrimination (area under the receiver operating curve, AUC) measures. Results During follow-up, 178 (0.79%) manual and 17 (0.17%) non-manual construction workers reported LBP sick leave. Backward selection resulted in a model with pain/stiffness in the back, physician-diagnosed musculoskeletal disorders/injuries, postural physical demands, feeling healthy, vitality, and organization of work as predictor variables. The Nagelkerke's R-square was 3.6%; calibration was adequate, but discrimination was poor (AUC=0.692; 95% CI 0.568-0.815). Conclusions A prediction model based on occupational health check variables does not identify non-sick listed workers at increased risk of LBP sick leave correctly. The model could be used to exclude the workers at the lowest risk on LBP sick leave from costly preventive interventions.

Passive imputation and parcel summaries are both valid to handle missing items in studies with many multi-item scales.

Previous studies showed that missing data in multi-item scales can best be handled by multiple imputation of item scores. However, when many scales are used, the number of items will become too large for the imputation model to reliably estimate imputations. A solution is to use passive imputation or a parcel summary score that combine and consequently reduce the number of variables in the imputation model. The performance of these methods was evaluated in a simulation study and illustrated in an example. Passive imputation, which updated scale scores from imputed items, and parcel summary scores that use the average over available item scores were compared to using all items simultaneously, imputing total scores of scales and complete-case analysis. Scale scores and coefficient estimates from linear regression were compared to "true" parameters on bias and precision. Passive imputation and using parcel summaries showed smaller bias and more precision than imputing total scores and complete-case analyses. Passive imputation or using parcel summary scores are valid missing data solutions in studies that include many multi-item scales.

Effectiveness of energy conservation management on fatigue and participation in multiple sclerosis: A randomized controlled trial.

BACKGROUND: Fatigue is a frequently reported and disabling symptom in multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness of an individual energy conservation management (ECM) intervention on fatigue and participation in persons with primary MS-related fatigue. METHODS: A total of 86 severely fatigued and ambulatory adults with a definite diagnosis of MS were randomized in a single-blind, two-parallel-arm randomized clinical trial to the ECM group or the information-only control group in outpatient rehabilitation departments. Blinded assessments were carried out at baseline and at 8, 16, 26 and 52 weeks after randomization. Primary outcomes were fatigue (fatigue subscale of Checklist Individual Strength - CIS20r) and participation (Impact on Participation and Autonomy scale - IPA). RESULTS: Modified intention-to-treat analysis was based on 76 randomized patients (ECM, n = 36; MS nurse, n=40). No significant ECM effects were found for fatigue (overall difference CIS20r between the groups = -0.81; 95% confidence interval (CI), -3.71 to 2.11) or for four out of five IPA domains. An overall unfavourable effect was found in the ECM group for the IPA domain social relations (difference between the groups = 0.19; 95% CI, 0.03 to 0.35). CONCLUSION: The individual ECM format used in this study did not reduce MS-related fatigue and restrictions in participation more than an information-only control condition.

Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial.

BACKGROUND: Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely fatigued patients with multiple sclerosis (MS) is lacking. OBJECTIVE: To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue. METHODS: Patients ( N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or control intervention. Primary outcomes were perceived fatigue (Checklist Individual Strength (CIS20r) fatigue subscale) and societal participation. An improvement of ⩾8 points on the CIS20r fatigue subscale was considered clinically relevant. Outcomes were assessed by a blinded observer at baseline, 2, 4, 6 and 12 months. RESULTS: Of the 89 patients that started treatment (median Expanded Disability Status Scale (interquartile range), 3.0 (2.0-3.6); mean CIS20r fatigue subscale (standard deviation (SD)), 42.6 (8.0)), 43 received aerobic training and 46 received the control intervention. A significant post-intervention between-group mean difference (MD) on the CIS20r fatigue subscale of 4.708 (95% confidence interval (CI) = 1.003-8.412; p = 0.014) points was found in favour of aerobic training that, however, was not sustained during follow-up. No effect was found on societal participation. CONCLUSION: Aerobic training in MS patients with severe fatigue does not lead to a clinically meaningful reduction in fatigue or societal participation when compared to a low-intensity control intervention.

Cognitive behavioral therapy positively affects fatigue in patients with multiple sclerosis: Results of a randomized controlled trial.

BACKGROUND: Fatigue is a common symptom in multiple sclerosis (MS) and often restricts societal participation. Cognitive behavioral therapy (CBT) may alleviate MS-related fatigue, but evidence in literature is inconclusive. OBJECTIVE: To evaluate the effectiveness of CBT to improve MS-related fatigue and participation. METHODS: In a multi-center, assessor-masked, randomized controlled trial, participants with severe MS-related fatigue were assigned to CBT or control treatment. CBT consisted of 12 individual sessions with a psychologist trained in CBT, the control treatment consisted of three consultations with a MS nurse, both delivered over 16 weeks. Assessments were at baseline, 8, 16 (i.e. post-intervention), 26, and 52 weeks post-baseline. Primary outcomes were the Checklist Individual Strength-fatigue subscale (CIS20r fatigue) and the Impact on Participation and Autonomy questionnaire (IPA). Data were analyzed according to the intention-to-treat principle, using mixed-model analysis. RESULTS: Between 2011 and 2014, 91 patients were randomized (CBT: n = 44; control: n = 47). Between-group analysis showed a positive post-intervention effect for CBT on CIS20r fatigue (T16: -6.7 (95% confidence interval (CI) = -10.7; -2.7) points) that diminished during follow-up (T52: 0.5 (95% CI = -3.6; 4.4)). No clinically relevant effects were found on societal participation. CONCLUSION: Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect over the long term.