Longitudinal determinants of employment status in people with relapsing-remitting multiple sclerosis.

Purpose: To investigate longitudinal relationships between employment status and disease-related, (neuro)psychological, and work-related factors in people with multiple sclerosis (MS). Methods: 170 employed people with MS underwent yearly neurological and neuropsychological examinations to assess MS-related disability and cognitive functioning. Additionally, they completed yearly questionnaires assessing depression, anxiety, fatigue, cognitive complaints, workplace support and coping. Multilevel models for change were fitted to examine progression of these factors over three years, and to assess possible relationships with change in employment status. Results: People with a deteriorated employment status after three years reported more depression (p=0.009), a higher impact of fatigue (p<0.001), more cognitive complaints (p<0.001) and less workplace support (p=0.001) at baseline than people with a stable employment status. There were no differences in progression over time of the examined variables between people with a stable or deteriorated employment status. Conclusion: More depression, a higher impact of fatigue, more cognitive complaints and less workplace support are predictive of a deteriorated employment status after three years in individuals with MS. How these factors progress over time is not different between those with a stable or deteriorated employment. MS-related disability, anxiety, objective cognition and coping were not related to a deterioration in employment status.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Subjective cognitive impairment is related to work status in people with multiple sclerosis.

Background: Unemployment is common among people with multiple sclerosis (pwMS) and has been associated with subjective cognitive difficulties, specifically in memory, attention, and executive functioning. However, longitudinal research on subjective cognitive difficulties and employment is scarce. Objective: We investigated whether subjective cognitive impairment (SCI), based on the clinical cut-off score of the MS Neuropsychological Screening Questionnaire (MSNQ), was associated with work status and negative work events (NWE) at baseline and after 2 years. Moreover, we investigated whether four MSNQ subdomains were related to work status and NWE. Methods: 287 participants (77.4% female, median age = 42 years) completed questionnaires on subjective cognitive functioning, depression, anxiety, and fatigue, and completed the Symbol Digit Modalities Test (SDMT). After baseline comparisons, logistic regression analyses were performed, with work status and NWE at baseline, and employment change and NWE change within 2 years after baseline as dependent variables. Independent variables included SCI and the MSNQ domains. Covariates anxiety, depression, fatigue, and SDMT were added. Results: SCI, depression and anxiety were associated with work status (Nagelkerke R 2 = .286), but only SCI was associated with employment change (Nagelkerke R 2 = .164). No predictors were associated with NWE at baseline or follow-up. In addition, no MSNQ subdomain was related to work status, employment change or NWE. Conclusion: Unemployed pwMS and pwMS with a deteriorated work status reported more cognitive difficulties after 2 years than employed pwMS or pwMS with a stable work status. In addition, depression, and anxiety were associated with work status.

Work difficulties in people with multiple sclerosis: The role of anxiety, depression and coping.

Background: Symptoms of anxiety and depression affect the daily life of people with multiple sclerosis (MS). This study examined work difficulties and their relationship with anxiety, depression and coping style in people with MS. Methods: 219 employed people with MS (median age = 43 years, 79% female) completed questionnaires on anxiety, depression, coping style, demographics and work difficulties, and underwent a neurological examination. Two regression analyses were performed with work difficulties as the dependent variable and either anxiety or depression as continuous independent variables. Coping style, age, gender, educational level, MS-related disability and disease duration were added as additional predictors, as well as interaction terms between coping style and either symptoms of depression or anxiety. Results: A significant model was found (F (10,205) = 13.14, p < 0.001, R 2 = 0.39) in which anxiety, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. The analysis of depression resulted in a significant model (F (10,205) = 14.98, p < 0.001, R 2 = 0.42) in which depression, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. None of the interaction effects were significant. Conclusions: Work difficulties were positively related to anxiety, depression, emotion- and avoidance-oriented coping and MS-related disability in workers with MS.

Self-reported occupational functioning in persons with relapsing-remitting multiple sclerosis: Does personality matter?

BACKGROUND: Multiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was to explore the contribution of personality traits in explaining occupational functioning in MS. METHODS: 241 participants with relapsing-remitting MS (78% female, median age: 42.0 years, median EDSS: 2.0) and 60 healthy controls (70% female, median age: 45.0 years) underwent neuropsychological and neurological examinations and completed questionnaires. Multivariate logistic and linear regression analyses were conducted to examine relations between personality traits and self-reported occupational functioning, while accounting for known correlates. RESULTS: Personality traits were not associated with self-reported occupational functioning when correcting for known correlates. A higher impact of fatigue (B = -0.05, p = .005 and B = -0.04, p = .009) and depression (B = -0.22, p = .008 and B = -0.21, p = .01) were associated with no paid job (R2 = 0.13) and considering to reduce work hours (R2 = 0.12). A higher impact of fatigue (B = -0.05, p = .008, ß = 0.46, p = .001 and ß = -0.36, p = .001) was associated with absenteeism from work (R2 = 0.15), more presenteeism (R2 = 0.35) and lower work ability (R2 = 0.25). A higher impact of fatigue (ß = 0.46, p = .001) and anxiety (ß = 0.25, p = .001) were associated with more work difficulties (R2 = 0.54). CONCLUSION: Personality traits did not explain additional variance in self-reported occupational functioning in persons with relapsing-remitting MS with mild disability. The impact of fatigue was the main and most consistent correlate of occupational functioning, often combined with depression or anxiety. Total explained variance of the models was limited, emphasizing the need to additionally examine other (contextual) factors when considering occupational challenges in MS.

Caregiver strain among life partners of persons with mild disability due to relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disorder of the central nervous system with an unpredictable disease course. Life partners often become caregivers, which can be both rewarding and challenging, as the caregiver's physical and mental health is often negatively affected. Previous studies on caregiver strain focused on caregivers of persons with MS with relatively high disability levels, while caregiver strain may already be experienced by life partners living with mildly disabled persons with MS. OBJECTIVE: The current study examines factors associated with caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS. METHODS: We included 173 persons with relapsing-remitting MS (79% female; mean age 42.8 years; 90% employed; median EDSS 2.0) and their life partners. The life partners completed questionnaires on caregiver strain and neuropsychiatric and cognitive functioning of the person with MS. The persons with MS completed questionnaires about demographics, fatigue, personality, physical, cognitive and neuropsychiatric functioning, and underwent neuropsychological and neurological examinations. A linear regression analysis was conducted to examine predictors of caregiver strain. RESULTS: 24% of the life partners experienced above average levels of caregiver strain. A multivariate linear regression analysis revealed that a higher age of the person with MS (ß = 0.16, p = 0.04), more physical disability (ß = 0.17 p = 0.04), more cognitive and neuropsychiatric problems of the person with MS as reported by the life partner (ß = 0.33, p = 0.001) and higher severity of neuropsychiatric symptoms as reported by the life partner (ß = 0.32, p = 0.001) were associated with higher caregiver strain (R2 = 0.49). CONCLUSION: Higher caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS was primarily associated with cognitive and neuropsychiatric problems of the person with MS.

The capability set for work - correlates of sustainable employability in workers with multiple sclerosis.

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014.

[Medicinal treatment of Bell's palsy: effect of prednisolone not sufficiently demonstrated]. / Medicamenteuze behandeling van bell-paralyse: effect van prednisolon onvoldoende aangetoond.

Bell's palsy is an acute idiopathic paralysis of the facial nerve. Antiviral drugs and corticosteroids have been suggested as treatment. Due to a lack of consistent, significant treatment effects in various studies, controversy has remained. Recently, a large randomised placebo-controlled, Scottish study concluded that corticosteroids significantly improve outcome in all patients with Bell's palsy. In our opinion the study had several considerable drawbacks. For instance, the results were not in accordance with the expected natural course. Also an analysis of the effect of treatment between patients with complete or incomplete Bell's palsy could not be made. A meta-analysis shows a significant effect of corticosteroids due to domination by the Scottish study. Therefore, we consider it inappropriate to treat all Bell's palsy patients with corticosteroids and patients with incomplete palsy should not be treated at all. More research is needed to clarify the role of corticosteroids in patients with complete Bell's palsy.

[Severe phenytoin intoxication in patients with hypoalbuminaemia]. / Ernstige fenytoïne-intoxicatie bij patiënten met hypoalbuminemie.

Two patients, a 35-year-old woman and a 60-year-old man, developed severe neurological side effects during treatment with phenytoin: disorientation, myoclonia, hallucinations and drowsiness in the first patient and a comatose state in the second. The woman had spina bifida, a ventriculoperitoneal drain because of hydrocephalus, recurrent urinary-tract infection, and a history of status epilepticus. The man suffered from diabetic ketoacidosis complicated by epileptic convulsions. In both patients, the total phenytoin concentration in the blood was within the therapeutic range of 8-20 mg/l. However, both had low serum albumin concentrations, below 25 g/l. Low serum albumin levels are associated with increased concentrations of the free fraction of phenytoin. Toxic levels of free phenytoin were found: 4 and 8 mg/l, respectively, while the therapeutic range is 0.5-2 mg/l. The first patient recovered after treatment with phenytoin was stopped, after which she was placed on a lower dosage; the second patient died. When prescribing phenytoin to patients with hypoalbuminaemia, one should be aware of the risk of intoxication due to a high level of free phenytoin and consequently an increased risk of severe neurological side effects.

Timing of aneurysm surgery in subarachnoid haemorrhage--an observational study in The Netherlands.

BACKGROUND: There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period. METHOD: In eight hospitals we identified 1,500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage. FINDINGS: We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition. CONCLUSIONS: In this observational study we found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling.

Treatment and outcome of severe intraventricular extension in patients with subarachnoid or intracerebral hemorrhage: a systematic review of the literature.

Severe intraventricular hemorrhage caused by extension from subarachnoid hemorrhage or intracerebral hemorrhage leads to hydrocephalus and often to poor outcome. We conducted a systematic review to compare conservative treatment, extraventricular drainage, and extraventricular drainage combined with fibrinolysis. We carried out a search in Medline of the literature between January 1966 and December 1998 and an additional hand-search from January 1990 to December 1998. Pharmaceutical companies were contacted to gather unpublished data. We reviewed the reference lists of all relevant articles. Two authors independently assessed eligibility of the studies and extracted data on characteristics of study design, patients, and treatment. Patients with primary intraventricular hemorrhage were excluded. Main outcome measures were death and poor outcome (defined as death or dependency) at the end of follow-up. No randomized clinical trial has yet been conducted so far, and we therefore reviewed only observational studies. The case fatality rate for conservative treatment (ten studies) was 78%. For extraventricular drainage (seven studies) it was 58% [relative risk versus conservative treatment (RR) 0.74; 95% confidence interval (CI) 0.55-0.99]. For extraventricular drainage with fibrinolytic agents (five studies) the case fatality rate was 6% (RR 0.08; 95% CI 0.02-0.24). The poor outcome rate for conservative treatment was 90%, that for extraventricular drainage 89% (RR 0.98; 95% CI 0.75-1.30) and that for extraventricular drainage with fibrinolytic agents 34% (RR 0.38; 95% CI 0.21-0.68). All RR values remained essentially the same after adjusting for age, sex, World Federation of Neurological Surgeons scale, study design, and year of publication for the studies that provided these data. Outcome is thus poor in patients with intraventricular extension of subarachnoid or intracerebral hemorrhage. This meta-analysis suggests that treatment with ventricular drainage combined with fibrinolytics may improve outcome for such patients, although this impression is derived only from an indirect comparison between observational studies. A randomized clinical trial is warranted.