Acromegaly management in the Nordic countries: A Delphi consensus survey.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Efficacy of high-intensity aerobic exercise on cognitive performance in people with multiple sclerosis: A randomized controlled trial.

BACKGROUND: Cognitive impairment is highly prevalent in multiple sclerosis (MS). Progressive aerobic exercise (PAE) represents a promising approach toward preservation or even improvement of cognitive performance in people with MS (pwMS). OBJECTIVE: To investigate the effects of PAE on the cognitive domains of information processing, learning and memory, and verbal fluency in pwMS. METHODS: This randomized controlled trial included an exercise (n = 43, 24 weeks of supervised PAE, followed by self-guided physical activity) and a waitlist group (n = 43, 24 weeks of habitual lifestyle, followed by supervised PAE). Assessments included the Brief Repeatable Battery of Neuropsychological tests (BRB-N), self-reported mood, and cardiorespiratory fitness. Published reference data were used to compute Z-scores for BRB-N scores. Cognitive impairment was defined as one or more Z-scores ⩽ -1.5SD. RESULTS: No between-group changes in the total group were observed in BRB-N scores following PAE. In the cognitively impaired subgroup (43% of the total group) the between-group point estimate suggested a potential clinical relevant improvement in the Symbol Digit Modalities Test (95% CI overlapping zero). Cardiorespiratory fitness increased in the total group and the cognitively impaired subgroup. CONCLUSION: In the present representative MS group, 24 weeks of supervised PAE had no effect on any cognitive domain in the total group but potentially improved processing speed in the cognitively impaired subgroup.

Differential effects and discriminative validity of motor and cognitive tasks varying in difficulty on cognitive-motor interference in persons with multiple sclerosis.

BACKGROUND: Cognitive-motor interference (CMI) has been well recognized in persons with multiple sclerosis (pwMS); however, there are limited data on effects of task difficulty. OBJECTIVE: Examine (1) the effects of motor and cognitive tasks varying in difficulty on the magnitude of CMI and (2) the discriminative validity of CMI between pwMS and healthy controls (HC). METHODS: Nine cognitive-motor dual-task (DT) conditions (combinations of three cognitive and three walking tasks) were examined. Outcome measures were DT-performance and dual-task cost (DTC) of gait parameters and correct answers. Task differences and overall group-effects were analysed by mixed model analysis, plus the Wilcoxon signed-rank tests or multivariate analysis of variances (MANOVAs), respectively. RESULTS: Task effects were examined in 82 pwMS (Expanded Disability Status Scale (EDSS): 3.3 ± 1.0) and discriminative validity in a subsample (35 pwMS and 33 HC). Motor-DTC and DT-performance were affected by difficulty of both the cognitive task (p < 0.001) and the walking condition (p ⩽ 0.002), while cognitive-DTC only varied between cognitive tasks with a large difference in difficulty (p ⩽ 0.005) and not between walking conditions (p ⩾ 0.125). None of the DTCs differed between groups. CONCLUSION: CMI, and especially motor performance, is affected by difficulty of the DT. Although pwMS performed worse on the tasks than HC, none of the DT-conditions showed a discriminative DTC.

The rate of neuropsychological assessments in multiple sclerosis has increased-A retrospective study in a Finnish Central Hospital.

OBJECTIVE: To investigate possible changes in the rate of conducted neuropsychological assessments and rehabilitation process for patients with multiple sclerosis (pwMS) during the last two decades. The change in the rate of vocational rehabilitation process was also evaluated. BACKGROUND: Cognitive deficits are frequent among pwMS and negatively affect patients' working ability and quality of life. Preliminary evidence suggests that neuropsychological rehabilitation positively affects cognitive symptoms. Vocational approaches are widely recommended for pwMS. METHODS: A retrospective survey of all multiple sclerosis (MS) patients diagnosed and treated at the Department of Neurology in Kanta-Häme Central Hospital over the period 1988-2013 was conducted using hospital records. The rate of neuropsychological assessment and rehabilitation processes as well as vocational rehabilitation processes were evaluated. RESULTS: A total of 417 pwMS were identified. A neuropsychological assessment was performed for 104 (24.9%) of these patients, of whom 21 (20.2%) were evaluated between 1988 and 1999 and 83 (79.8%) between 2000 and 2013. Of the 417 patients, eight (1.9%) received neuropsychological rehabilitation, each of these after the year 2000. Only 25 (6.0%) of the 417 pwMS received vocational rehabilitation. Fourteen (56.0%) of the 25 patients received vocational rehabilitation between 1988 and 1999 and 11 (44.0%) between 2000 and 2013. CONCLUSIONS: Neuropsychological assessment has been a rarity in MS in Finland, but a marked increase in frequency has occurred since the year 2000. Although understanding of MS-related cognitive impairment and its impact on working ability has increased, the rate of neuropsychological and vocational rehabilitation has remained low.

Assessing data protection and governance in health information systems: a novel methodology of Privacy and Ethics Impact and Performance Assessment (PEIPA).

BACKGROUND: Data processing of health research databases often requires a Data Protection Impact Assessment to evaluate the severity of the risk and the appropriateness of measures taken to comply with the European Union (EU) General Data Protection Regulation (GDPR). We aimed to define and apply a comprehensive method for the evaluation of privacy, data governance and ethics among research networks involved in the EU Project Bridge Health. METHODS: Computerised survey among associated partners of main EU Consortia, using a targeted instrument designed by the principal investigator and progressively refined in collaboration with an international advisory panel. Descriptive measures using the percentage of adoption of privacy, data governance and ethical principles as main endpoints were used for the analysis and interpretation of the results. RESULTS: A total of 15 centres provided relevant information on the processing of sensitive data from 10 European countries. Major areas of concern were noted for: data linkage (median, range of adoption: 45%, 30%-80%), access and accuracy of personal data (50%, 0%-100%) and anonymisation procedures (56%, 11%-100%). A high variability was noted in the application of privacy principles. CONCLUSIONS: A comprehensive methodology of Privacy and Ethics Impact and Performance Assessment was successfully applied at international level. The method can help implementing the GDPR and expanding the scope of Data Protection Impact Assessment, so that the public benefit of the secondary use of health data could be well balanced with the respect of personal privacy.

Predictors of Participation and Autonomy in People With Multiple Sclerosis.

IMPORTANCE: Because multiple sclerosis (MS) affects many life areas, it is important to know how participation and autonomy are associated with the perceived impact of MS on everyday life. OBJECTIVE: To investigate how perceived quality of life, disease impact, gender, and disease severity predict participation and autonomy in people with MS. DESIGN: Cross-sectional study in which structural equation modeling was used to evaluate relationships between measured variables. SETTINGS: Outpatient clinics in three areas and one inpatient rehabilitation center in Finland. PARTICIPANTS: Convenience sample of 194 people with MS. OUTCOMES AND MEASURES: Participants completed the Impact on Participation and Autonomy (IPA), the World Health Organization Quality of Life-Brief measure (WHOQOL-BREF), and the Multiple Sclerosis Impact Scale (MSIS-29). The Expanded Disability Status Scale (EDSS) was administered by a neurologist. RESULTS: The final model showed good fit to the data. All the goodness-of-fit indexes except χ² supported the model, χ²(30, N = 194) = 46.729, p < .026; comparative fit index = .983; Tucker-Lewis index = .969; root mean square error of approximation = .054; standardized root mean square residual = .039. Quality of life (WHOQOL-BREF) and the impact of multiple sclerosis (MSIS-29) were the main predictors of participation and autonomy. Disease severity influenced only the IPA Autonomy Indoors domain. Gender was not associated with participation and autonomy. CONCLUSION AND RELEVANCE: Experiences of participation and autonomy appear to be closely associated with perceived quality of life and impact of the disease. Findings support the importance of assessing participation and autonomy and planning interventions using this information. WHAT THIS ARTICLE ADDS: The IPA appears to be an appropriate measure for assessing participation and autonomy and planning occupational therapy interventions for people with MS. In particular, environmental factors affecting participation and autonomy should be considered when planning interventions to promote participation and autonomy.

Hemoglobin level and lipoprotein particle size.

BACKGROUND: Alterations in lipoprotein size are associated with increased cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk of atherosclerosis and was previously associated with obesity, metabolic syndrome, and insulin resistance. No previous studies have investigated an association between hemoglobin concentration and lipoprotein particle size. METHODS: We conducted a population-based, cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) born in Pieksämäki, Finland, who were categorized into five age groups. The concentrations and sizes of lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Larger very low density lipoprotein (VLDL) particle diameter was associated with higher hemoglobin concentrations in men (p = 0.003). There was a strong relationship between smaller high density lipoprotein (HDL) particle size and higher hemoglobin concentration in both men and women as well as with smaller low density lipoprotein (LDL) particle size and higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p = 0.008). VLDL particle concentration had a moderate positive correlation with hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed a statistical trend suggesting increasing particle concentration with increasing hemoglobin levels (r = 0.08; p = 0.05). CONCLUSION: Higher hemoglobin levels are associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and increasing amounts of larger VLDL and smaller LDL particles. This suggests that a higher hemoglobin concentration is associated with an unfavorable lipoprotein particle profile that is part of states that increase cardiovascular disease risk like diabetes and metabolic syndrome.

Neuropsychological rehabilitation does not improve cognitive performance but reduces perceived cognitive deficits in patients with multiple sclerosis: a randomised, controlled, multi-centre trial.

BACKGROUND: There is preliminary evidence on the positive effects of neuropsychological rehabilitation on cognition in multiple sclerosis (MS), but the generalisability of the findings is limited by methodological problems. OBJECTIVE: The aim of the present study was to determine the effects of strategy-oriented neuropsychological rehabilitation on MS. METHODS: A total of 102 relapsing-remitting MS patients with subjective and objective attentional deficits were randomised into an intervention and a control group. Neuropsychological assessments were performed at baseline, at three months immediately after the intervention, and at six months. Patients in the intervention group received neuropsychological rehabilitation once a week in 60-minute sessions for 13 consecutive weeks. The control group received no intervention. RESULTS: Neuropsychological rehabilitation including computer-based attention and working memory retraining, psychoeducation, strategy learning and psychological support did not improve cognitive performance but had a positive effect on perceived cognitive deficits. The intervention group perceived significantly fewer deficits than the control group both immediately after the intervention and at six months. The personal rehabilitation goals were also well achieved. CONCLUSIONS: Strategy-oriented neuropsychological rehabilitation did not improve cognitive performance but reduced perceived cognitive deficits in MS.

Neuropsychological rehabilitation for multiple sclerosis.

BACKGROUND: This is an update of the Cochrane review 'Neuropsychological rehabilitation for multiple sclerosis' (first published in The Cochrane Library 2011, Issue 11).Cognitive deficits are a common manifestation of multiple sclerosis (MS) and have a significant effect on the patient's quality of life. Alleviation of the harmful effects caused by these deficits should be a major goal of MS research and practice.  OBJECTIVES: To assess the effects of neuropsychological/cognitive rehabilitation on health-related factors, such as cognitive performance and emotional well-being in patients with MS. SEARCH METHODS: The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Search Co-ordinator searched their Specialised Register which, among other sources, contains trials from CENTRAL (The Cochrane Library 2013, Issue 2), MEDLINE, EMBASE, CINAHL, LILACS, PEDro and clinical trials registries (28 May 2013). We contacted authors of the studies for additional information. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials evaluating the effects of neuropsychological rehabilitation in MS compared to other interventions or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors individually judged the eligibility of the included studies, assessed risk of bias and extracted data. We combined results quantitatively in meta-analyses according to the intervention type: 1) cognitive training and 2) cognitive training combined with other neuropsychological rehabilitation methods. MAIN RESULTS: Twenty studies (986 participants; 966 MS participants and 20 healthy controls) fulfilled the inclusion criteria. The mean age of the participants was 44.6 years, mean length of education was 12.3 years and 70% of the participants were women. Most of the participants had a relapsing-remitting course of disease. The mean Expanded Disability Status Scale score was 3.2 and the mean duration of disease was 14.0 years.On the basis of these studies, we found low-level evidence that neuropsychological rehabilitation reduces cognitive symptoms in MS. Cognitive training was found to improve memory span (standardised mean difference (SMD) 0.54, 95% confidence interval (CI) 0.20 to 0.88, P = 0.002) and working memory (SMD 0.33, 95% CI 0.09 to 0.57, P = 0.006). Cognitive training combined with other neuropsychological rehabilitation methods was found to improve attention (SMD 0.15, 95% CI 0.01 to 0.28, P = 0.03), immediate verbal memory (SMD 0.31, 95% CI 0.08 to 0.54, P = 0.008) and delayed memory (SMD 0.22, 95% CI 0.02 to 0.42, P = 0.03). There was no evidence of an effect of neuropsychological rehabilitation on emotional functions.The overall quality, as well as the comparability of the included studies, was relatively low due to methodological limitations and heterogeneity of interventions and outcome measures. Although most of the pooled results in the meta-analyses yielded no significant findings, 18 of the 20 studies showed some evidence of positive effects when the studies were individually analysed. AUTHORS' CONCLUSIONS: This review found low-level evidence for positive effects of neuropsychological rehabilitation in MS. The interventions and outcome measures included in the review were heterogeneous, which limited the comparability of the studies. New trials may therefore change the strength and direction of the evidence.

Global estimates of the burden of injury and illness at work in 2012.

This article reviews the present indicators, trends, and recent solutions and strategies to tackle major global and country problems in safety and health at work. The article is based on the Yant Award Lecture of the American Industrial Hygiene Association (AIHA) at its 2013 Congress. We reviewed employment figures, mortality rates, occupational burden of disease and injuries, reported accidents, surveys on self-reported occupational illnesses and injuries, attributable fractions, national economic cost estimates of work-related injuries and ill health, and the most recent information on the problems from published papers, documents, and electronic data sources of international and regional organizations, in particular the International Labor Organization (ILO), World Health Organization (WHO), and European Union (EU), institutions, agencies, and public websites. We identified and analyzed successful solutions, programs, and strategies to reduce the work-related negative outcomes at various levels. Work-related illnesses that have a long latency period and are linked to ageing are clearly on the increase, while the number of occupational injuries has gone down in industrialized countries thanks to both better prevention and structural changes. We have estimated that globally there are 2.3 million deaths annually for reasons attributed to work. The biggest component is linked to work-related diseases, 2.0 million, and 0.3 million linked to occupational injuries. However, the division of these two factors varies depending on the level of development. In industrialized countries the share of deaths caused by occupational injuries and work-related communicable diseases is very low while non-communicable diseases are the overwhelming causes in those countries. Economic costs of work-related injury and illness vary between 1.8 and 6.0% of GDP in country estimates, the average being 4% according to the ILO. Singapore's economic costs were estimated to be equivalent to 3.2% of GDP based on a preliminary study. If economic losses would take into account involuntary early retirement then costs may be considerably higher, for example, in Finland up to 15% of GDP, while this estimate covers various disorders where work and working conditions may be just one factor of many or where work may aggravate the disease, injury, or disorders, such as traffic injuries, mental disorders, alcoholism, and genetically induced problems. Workplace health promotion, services, and safety and health management, however, may have a major preventive impact on those as well. Leadership and management at all levels, and engagement of workers are key issues in changing the workplace culture. Vision Zero is a useful concept and philosophy in gradually eliminating any harm at work. Legal and enforcement measures that themselves support companies and organizations need to be supplemented with economic justification and convincing arguments to reduce corner-cutting in risk management, and to avoid short- and long-term disabilities, premature retirement, and corporate closures due to mismanagement and poor and unsustainable work life. We consider that a new paradigm is needed where good work is not just considered a daily activity. We need to foster stable conditions and circumstances and sustainable work life where the objective is to maintain your health and work ability beyond the legal retirement age. We need safe and healthy work, for life.

Patient-reported outcome measures for the assessment of stress in neurological patients: An integrative review.

Background: Patient stress is often overlooked in the care of patients with neurological problems. Nursing theorists have previously heralded stress assessment through conceptual clarification, while clinical nurses in the health care system hold an ideal position for implementation of assessment and coordination of support. Integrated with a hospital assessment and support scheme, recognition of stress as a target of systematic assessment can lead to improved clinical outcomes. Objective: The aim of the study was to describe and compare patient-reported outcome measures suitable for assessment of the stress response as symptoms in neurological patients. Design: This study is an integrative review and concept development of patient stress based on qualitative and quantitative analysis of available self-reporting instruments. Methods: Instruments were retreived with a systematic search from PubMed, CINAHL, PsychINFO and Web of Science reference databases on August 2, 2021. Search terms associated with the concept of stress symptoms were used. Instrument inclusion was done with the guidance of authoritative symptom inventories, with partial confirmation by a second author to mitigate bias. In the analysis, the instruments included in the review were quantitatively described and compared. Insights from the instrument composition led to clarification of our concept of stress response to further refine the list of instruments suitable for self-assessment of the stress status. This study was not registered. Results: Based on the inclusion criteria, 23 patient-reported outcome measures extending over a variety of stress concepts were included. The similarity of items among the instruments implied a symptom cluster delineated by 59 common symptom subclasses that were grouped together in a re-classification of instrument items. A comparative quantitative analysis prompted us to distinguish the concept of stress response from antecedent, consequent, and related concepts as a manifestation of mental, somatic, and behavioral domains. Ten instruments with items covering the three domains, each with unique qualities regarding number of items, measured spread, and letter count were described. Conclusions: Within an organizational framework, effective allotment among types of support can be founded on the patient's stress status and the stressors. The stress status manifests itself as a set of measurable symptoms. Optimal instruments for use in systematic clinical assessment of neurological patients' stress status should satisfy the suggested specification of the stress response with a minimal number of items and concise wording. Finding and including the relevant instruments for analysis were the main limitation of the study. Tweetable abstract: Stress of neurological patients needs to be assessed and addressed. We ranked 10 suitable instruments that can be useful in the assessment.

Global-, regional- and country-level estimates of the work-related burden of diseases and accidents in 2019.

OBJECTIVE: This study provides the global-, regional- and country-level estimates on the work-related burden of diseases and accidents for 2019, including deaths, disability adjusted life years (DALY) and economic losses. METHODS: Data on occupational illnesses and injuries from international organizations, institutions, and public websites were used. Risk ratios (RR) and population attributable fractions (PAF) for the risk factor-outcome pairs were derived from the literature. Estimated mortality and DALY for a group of seven major diseases covering 120 risk-outcome pairs attributable to work were calculated for 181 countries. RESULTS: Globally, 2.9 million deaths were attributed to work, with 2.58 million deaths due to work-related diseases and 0.32 million related to occupational injuries. Globally, work-related diseases with a long latency period are increasing, while the number of occupational injuries has decreased. Work-related circulatory diseases were the major cause of 912 000 deaths globally, followed by 843 000 work-related malignant neoplasms. In high-income, American, Eastern European and Western Pacific World Health Organization (WHO) regions, however, work-related malignant neoplasms comprised the biggest disease group. DALY attributable to work were estimated to be 180 million in 2019, with an associated economic loss of 5.8% of global GDP. New estimates of psychosocial factors increased the global loss. CONCLUSIONS: The burden of work-related diseases and injuries increased by 26% from 2.3 million annual deaths in 2014 to 2.9 million in 2019. The DALY attributable to work have also substantially increased from 123 million in 2014 to 180 million in 2019 (47% increase). We found large regional and country variations.

Clinical significance of CYP11B2 immunostaining in unilateral primary aldosteronism.

Objective: The associations between adrenal histopathology, lateralization studies, and surgical outcomes in primary aldosteronism remain poorly characterized. We examined the value of immunohistochemical analysis of CYP11B2 for evaluation of adrenalectomy outcomes after anatomical versus functional subtyping. Design: A retrospective multicenter study of 277 patients operated for primary aldosteronism who had an adrenalectomy sample available in the Finnish biobanks from 1 January 2000 to 31 December 2019. Adrenal slides from biobanks were analyzed centrally after CYP11B2 and CYP11B1 staining. Clinical data were obtained from patient registries. Histopathological diagnosis and cure after surgery were assessed as outcome measures. Results: Re-evaluation with CYP11B2 staining changed the histopathological diagnosis in 91 patients (33%). The presence of a CYP11B2-positive adenoma and the use of functional subtyping independently predicted clinical cure of primary aldosteronism. CYP11B2-positive <7 mm nodules were more frequent in patients without clinical cure, whereas CYP11B2-positive micronodules were common in all patients and had no impact on adrenalectomy outcomes. Small CYP11B2-positive nodules and micronodules were equally prevalent regardless of the subtyping method applied. Clinical cure rates were lower and CYP11B2-negative adenomas more common after adrenalectomy based on anatomical imaging than functional studies. Conclusions: Incorporating CYP11B2 staining in histopathological diagnosis enhances the prediction of surgical outcomes in primary aldosteronism. A finding of CYP11B2-positive adenoma is indicative of cure of primary aldosteronism, whereas smaller CYP11B2-positive nodules associate with poorer results at postoperative evaluation. Functional subtyping methods decrease the operations of CYP11B2-negative adenomas and are superior to anatomical imaging in identifying unilateral primary aldosteronism.

Behavioural symptoms and impairments in multiple sclerosis: a systematic review and meta-analysis.

Behavioural problems are not well recognized in multiple sclerosis (MS). In this review we aimed to evaluate the prevalence of behavioural symptoms and impairments in MS. A systematic search was carried out from MEDLINE, PsycINFO, Web of Science, CINAHL and COCHRANE. In total, 23 studies (1831 participants) were identified. Based on the literature search, behavioural symptoms and impairments are observed in MS. Aggression (23%), apathy (22%), euphoria (12%) and lack of insight (11%) were the most frequent symptoms, and adjustment disorder (17%) the most frequent impairment. Severe mental disorders are more infrequent than changes in behaviour, manner of reaction, and way of action. In conclusion the objective behavioural impairments and especially subjective symptoms are present in patients with MS. These manifestations should be taken into account in the diagnostics and treatment of the disease.

Fatigue and health-related quality of life depend on the disability status and clinical course in RRMS.

BACKGROUND: Fatigue is a prominent and disabling symptom of multiple sclerosis (MS), impairing quality of life. The disease course of relapsing remitting MS (RRMS) is individual. OBJECTIVES: We aimed to study the effects of demographic and clinical characteristics, as well as lifestyle risk factors on experienced fatigue and health-related quality of life (HRQoL) among RRMS patients, comparing benign and severe disease types. METHODS: Altogether 198 Finnish RRMS patients were recruited for this real-life cross-sectional study. Self-reported questionnaires were used to evaluate fatigue and HRQoL by using Fatigue Scale for Motor and Cognitive Functions and 15D health-related quality of life questionnaires. Patients were categorized into subgroups based on the current disability status measured by the Expanded Disability Status Scale (EDSS) cut-off value of 4.5, and by retrospective clinical course divided into benign and aggressive RRMS. RESULTS: All in all, 73% of the RRMS patients suffered from fatigue. Lower HRQoL had a strong correlation with more prominent fatigue (r = -0.719). Higher EDSS was associated with more prominent fatigue and lower HRQoL in the whole RRMS cohort. Older age at the disease onset was associated with more prominent fatigue and decreased HRQoL in the groups of aggressive RRMS and EDSS > 4.5. In the groups of EDSS ≤ 4.5 and benign RRMS, a higher number of used disease-modifying treatments (DMTs) was associated with more pronounced fatigue and reduced HRQoL. In addition, higher BMI was associated with lower HRQoL in patients with benign RRMS. Side effects (45 %) and lack of efficacy (26 %) were the most common reasons for discontinuing a DMT. Cessation due to side effects was the only reason that was significantly associated with more prominent fatigue and lower HRQoL. Use of nicotine products, gender, or disease duration were not associated with fatigue or HRQoL. CONCLUSIONS: Individuals with severe RRMS and higher EDSS scores are more prone to experience fatigue and lower HRQoL. In addition, fatigue and lower HRQoL are more commonly observed among RRMS patients with older age at disease onset and in those with multiple DMT switches.

Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study.

BACKGROUND: Increased ferritin concentrations are associated with metabolic syndrome (MetS). The association between ferritin as well as hemoglobin level and individual MetS components is unclear. Erythropoietin levels in subjects with MetS have not been determined previously. The aim of this study was to compare serum erythropoietin, ferritin, haptoglobin, hemoglobin, and transferrin receptor (sTFR) levels between subjects with and without MetS and subjects with individual MetS components. METHODS: A population based cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) from five age groups born in Pieksämäki, Finland who were invited to a health check-up in 2004 with no exclusion criteria. Laboratory analyzes of blood samples collected in 2004 were done during year 2010. MetS was defined by National Cholesterol Education Program criteria. RESULTS: 159 (53%) men and 170 (40%) women of study population met MetS criteria. Hemoglobin and ferritin levels as well as erythropoietin and haptoglobin levels were higher in subjects with MetS (p < 0.001, p = 0.018). sTFR level did not differ significantly between subjects with or without MetS. Hemoglobin level was significantly higher in subjects with any of the MetS components (p < 0.001, p = 0.002). Ferritin level was significantly higher in subjects with abdominal obesity or high TG or elevated glucose or low high density cholesterol component (p < 0.001, p = 0.002, p = 0.02). Erythropoietin level was significantly higher in subjects with abdominal obesity component (p = 0.015) but did not differ significantly between subjects with or without other MetS components. Haptoglobin level was significantly higher in subjects with blood pressure or elevated glucose component o MetS (p = 0.028, p = 0.025). CONCLUSION: Subjects with MetS have elevated hemoglobin, ferritin, erythropoietin and haptoglobin concentrations. Higher hemoglobin levels are related to all components of MetS. Higher ferritin levels associate with TG, abdominal obesity, elevated glucose or low high density cholesterol. Haptoglobin levels associate with blood pressure or elevated glucose. However, erythropoietin levels are related only with abdominal obesity. Higher serum erythropoietin concentrations may suggest underlying adipose tissue hypoxemia in MetS.

Brief International Cognitive Assessment for MS (BICAMS): international standards for validation.

An international expert consensus committee recently recommended a brief battery of tests for cognitive evaluation in multiple sclerosis. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory. Recognizing that resources for validation will vary internationally, the committee identified validation priorities, to facilitate international acceptance of BICAMS. Practical matters pertaining to implementation across different languages and countries were discussed. Five steps to achieve optimal psychometric validation were proposed. In Step 1, test stimuli should be standardized for the target culture or language under consideration. In Step 2, examiner instructions must be standardized and translated, including all information from manuals necessary for administration and interpretation. In Step 3, samples of at least 65 healthy persons should be studied for normalization, matched to patients on demographics such as age, gender and education. The objective of Step 4 is test-retest reliability, which can be investigated in a small sample of MS and/or healthy volunteers over 1-3 weeks. Finally, in Step 5, criterion validity should be established by comparing MS and healthy controls. At this time, preliminary studies are underway in a number of countries as we move forward with this international assessment tool for cognition in MS.

Self-reported Reasons for Changes in Performance of Daily Activities During a 2-Year Multidisciplinary Multiple Sclerosis Rehabilitation.

Background: Few multidisciplinary rehabilitation studies with a heterogeneous design have focused on individuals with multiple sclerosis (MS). This study compared subjective-reported changes in performance and satisfaction with daily activities among moderately and severely disabled individuals with MS during a 2-year, multidisciplinary, group-based, outpatient rehabilitation program comprising education in self-management and compensatory techniques, exercise, and guided peer support. Methods: Thirty-eight adults with moderate disability (Expanded Disability Status Scale [EDSS] score of 4.0-5.5, 74% women, mean age of 48) and 41 individuals with severe disability (EDSS 6.0-8.5, 63% women, mean age of 48) were assessed at baseline and after 12 and 21 months of outpatient rehabilitation using the Canadian Occupational Performance Measure (COPM). Group × time interactions were analyzed using mixed analysis of variance. Participants' explanations of reasons for changes in activity performance were collected via semistructured interviews and analyzed content. Results: Statistically significant improvements in COPM performance and satisfaction scores were reported in both groups from baseline to 21 months of rehabilitation. No significant between-group differences in improvement were observed. The self-reported reasons for improvement were mainly linked to environmental factors. Conclusions: The outpatient rehabilitation program, including 4 themes-cognition, mood, energy conservation, and body control-improved the self-reported performance of patients with MS with moderate and severe disabilities. Environmental factors warrant consideration during rehabilitation.

Neuropsychological rehabilitation for multiple sclerosis.

BACKGROUND: Cognitive deficits are a common manifestation in multiple sclerosis (MS) and have a wide effect on the patient's quality of life. Alleviation of the harmful effects caused by these deficits should be a major goal of MS research and practice. OBJECTIVES: The aim of this review was to evaluate the effects of neuropsychological/cognitive rehabilitation in MS by conducting a systematic review. SEARCH METHODS: A systematic literature search was carried out on reports drawn from Cochrane MS Group Specialised Register (To October 2010), Evidence-based medicine (EBM) reviews (To September 2010), MEDLINE (January 1950 to September 2010), EMBASE (1974 to September 2010), PsycINFO (January 1806 to September 2010), WEB OF SCIENCE (WOS) (January 1986 to September 2010), CINAHL (1982 to September 2010), and identified from the references in these reports. SELECTION CRITERIA: Randomised Controlled Trials (RCTs) and quasi-randomised trials evaluating the effects of neuropsychological rehabilitation in MS compared to other interventions or no intervention at all and employing neuropsychological rehabilitation methods and outcome measures were included. DATA COLLECTION AND ANALYSIS: Two review authors individually judged the relevance, risk of bias, and content of the included studies. Results were combined quantitatively with meta-analyses according to the intervention type: 1) Cognitive training and 2) Cognitive training combined with other neuropsychological rehabilitation methods. In addition, narrative presentation was used in reporting the results of those studies which were inappropriate to be included in the meta-analysis. MAIN RESULTS: Fourteen studies (770 MS patients) fulfilled the inclusion criteria. On the basis of these studies, low level evidence was found that neuropsychological rehabilitation reduces cognitive symptoms in MS. Cognitive training was found to improve memory span (standardised mean difference 0.54 (95% confidence interval 0.2 to 0.88, P = 0.002)), working memory (standardised mean difference 0.33 (95% confidence interval 0.09 to 0.57, P = 0.006)), and immediate visual memory (standardised mean difference 0.32 (95% confidence interval 0.04 to 0.6, P = 0.02)). There was no evidence of an effect of cognitive training combined with other neuropsychological rehabilitation methods on cognitive or emotional functions. The overall quality as well as the comparability of the included studies were relatively low due to methodological limitations and heterogeneity of outcome measures. Although most of the pooled results in the meta-analyses yielded no significant findings, twelve of the fourteen studies showed some evidence of positive effects when the studies were individually analysed. AUTHORS' CONCLUSIONS: The review indicates low level evidence for the positive effects of neuropsychological rehabilitation in MS. Interventions included in the review were heterogeneous. Consequently, clinical inferences can basically be drawn from single studies. Therefore, new trials may change the strength and direction of the evidence. To further strengthen the evidence, well-designed high quality studies are needed. In this systematic review, recommendations are given for improving the quality of future studies on the effects of neuropsychological rehabilitation in MS.

Risk factors for reduced survival after traumatic brain injury: a 30-year follow-up study.

PRIMARY OBJECTIVE: To evaluate risk factors for reduced survival in subjects with traumatic brain injury (TBI). PARTICIPANTS AND METHODS: A retrospective follow-up of three decades included 192 subjects with TBI. Cognitive testing was carried out on average 2 years after the injury (at mean age of 39.0 years), during the years 1966-1972. Cox's regression and logistic regression analyses were used and the survival of the subjects was compared with the general population using the standardized mortality ratio (SMR). RESULTS: Reduced survival was significantly associated with age at injury (p < 0.001) and vocational outcome (p = 0.003). Vocational outcome in turn was associated with age (p = 0.010), TBI severity (p < 0.001), cognitive impairment (p = 0.010), later TBIs (p = 0.007) and alcohol abuse (p = 0.015). Mortality in the younger patient group (age at death <40 years) was higher than in the general population (SMR 4.50, 95% CI = 2.02-10.01). CONCLUSIONS: A reduced working ability, influenced by age-, injury- and lifestyle-related factors, is associated with long-term survival after TBI. The mortality among younger patients is high, a finding which should be considered when planning the care after TBI.