Vincent de Groot

How to measure comorbidity. a critical review of available methods.

The object of this article was to systematically review available methods to measure comorbidity and to assess their validity and reliability. A search was made in Medline and Embase, with the keywords comorbidity and multi-morbidity, to identify articles in which a method to measure comorbidity was described. The references of these articles were also checked, and using a standardized checklist the relevant data were extracted from these articles. An assessment was made of the content, concurrent, predictive and construct validity, and the reliability. Thirteen different methods to measure comorbidity were identified: one disease count and 12 indexes. Data on content and predictive validity were available for all measures, while data on construct validity were available for nine methods, data on concurrent validity, and interrater reliability for eight methods, and data on intrarater reliability for three methods. The Charlson Index is the most extensively studied comorbidity index for predicting mortality. The Cumulative Illness Rating Scale (CIRS) addresses all relevant body systems without using specific diagnoses. The Index of Coexisting Disease (ICED) has a two-dimensional structure, measuring disease severity and disability, which can be useful when mortality and disability are the outcomes of interest. The Kaplan Index was specifically developed for use in diabetes research. The Charlson Index, the CIRS, the ICED and the Kaplan Index are valid and reliable methods to measure comorbidity that can be used in clinical research. For the other indexes, insufficient data on the clinimetric properties are available.

Physical Activity Behavior of People With Multiple Sclerosis: Understanding How They Can Become More Physically Active

Background People with multiple sclerosis (MS) are less physically active than those without the disease. Understanding the modifiable factors that are related to physical inactivity is important for developing effective physical activity programs. Objective The objectives of this study were to determine levels of physical activity and to determine factors related to the physical activity behavior of adults with MS by use of the Physical Activity for People With a Disability (PAD) model. The PAD model combines the International Classification of Functioning, Disability and Health framework of disability and theoretical models of physical activity behavior. Design This investigation was a cross-sectional study. Methods The study participants were 106 people who had MS and who, since their definite diagnosis, had been participating in a prospective cohort study. Physical activity was assessed with the Short Questionnaire to Assess Health-Enhancing Physical Activity. The independent roles of disease characteristics and demographic, cognitive-behavioral, and environmental factors were determined using questionnaires for which reliability and validity have been established. Results The median total level of physical activity of participants with MS (mean age=42.8 years, median Expanded Disability Status Scale score=3, disease duration=6 years) was 10.68 metabolic equivalents × h/d (interquartile range=3.69–16.57). On average, participants spent 30 h/wk on activities with metabolic equivalents of 2 or more (interquartile range=10.7–45.0 h/wk). The regression models predicting physical activity behavior on the basis of demographic (29.4%) and disease-related (28.3%) variables explained more variance than the models based on cognitive-behavioral (12.0%) and environmental (9.1%) variables. Combining significant variables yielded a final regression model that explained 37.2% of the variance in physical activity. Significant determinants were disease severity, a disability pension, and having children to care for. Limitations Changes in physical activity behavior were not measured. Conclusions Participants with MS were less active if their disease was more severe, if they received a disability pension, or if they had children to care for. The PAD model was helpful in understanding the physical activity behavior of participants with MS.

Polypropylene ankle foot orthoses to overcome drop-foot gait in central neurological patients: A mechanical and functional evaluation

The aim of this study was to assess the functional effects and mechanical contribution of Ankle Foot Orthoses (AFO) prescribed to overcome drop-foot gait. We hypothesized that poor functional effects of the AFO relate to insufficient mechanical contribution of the AFO during the swing phase, or unwanted constraining of the ankle during the stance phase. In seven patients with Stroke or Multiple Sclerosis, we determined changes in energy cost of walking resulting from wearing an AFO, as a measure of the functional effects. In addition, an instrumented gait analysis was performed, and the mechanical AFO properties were measured, to calculate the mechanical contribution of the AFO. The AFO was sufficiently stiff to effectively support the foot in swing, without hampering the ankle during stance. For the whole group, there was a significant improvement in walking speed and energy cost (12%). However, the AFO had no functional benefit in terms of a reduced energy cost of walking for three patients, who coherently demonstrated no pathological plantar flexion during swing without their AFO. We conclude that functional benefit from the AFO was only found when the mechanical AFO characteristics met the need to support the patients‘ mechanical deficiencies.

Challenges in multi-plex and mono-plex platforms for the discovery of inflammatory profiles in neurodegenerative diseases

Pro and anti-inflammatory cytokines are involved in disease onset and pathophysiology of multiple sclerosis, Alzheimers disease and Parkinsons disease. It is likely that panels of multiple cytokines provide a good reflection of disease status and can be used as biological markers in body fluids. Different multi-plex platforms, Luminex-xMAP and Meso Scale Discovery, are able to detect multiple analytes in the same sample at the same time. In this literature based review, we offer an overview of the multi-plex platforms and compare them with the golden standard ELISA in their ability to accurately and sensitively detect cytokines in cerebrospinal fluid (CSF) and blood (serum/plasma). The detectability and levels of cytokines in multiple sclerosis, Alzheimers disease and Parkinsons disease are promising but also show discrepancies between studies. The current immuno-assays lack sensitivity for detection of various cytokines that have low concentrations of cytokines in CSF and blood, and therefore technical improvements are needed. With such improvements the use of large panels of cytokines as inflammatory profiles may offer additional value in diagnosis, prognosis and therapeutic response in neurodegenerative diseases.

Studies examining the efficacy of ankle foot orthoses should report activity level and mechanical evidence

Ankle Foot Orthoses (AFOs) to promote walking ability are a common treatment in patients with neurological or muscular diseases. However, guidelines on the prescription of AFOs are currently based on a low level of evidence regarding their efficacy. Recent studies aiming to demonstrate the efficacy of wearing an AFO in respect to walking ability are not always conclusive. In this paper it is argued to recognize two levels of evidence related to the ICF levels. Activity level evidence expresses the gain in walking ability for the patient, while mechanical evidence expresses the correct functioning of the AFO. Used in combination for the purpose of evaluating the efficacy of orthotic treatment, a conjunct improvement at both levels reinforces the treatment algorithm that is used. Conversely, conflicting outcomes will challenge current treatment algorithms and the supposed working mechanism of the AFO. A treatment algorithm must use relevant information as an input, derived from measurements with a high precision. Its result will be a specific AFO that matches the patients needs, specified by the mechanical characterization of the AFO footwear combination. It is concluded that research on the efficacy of AFOs should use parameters from two levels of evidence, to prove the efficacy of a treatment algorithm, i.e., how to prescribe a well-matched AFO.

Effectiveness of cognitive behavioral therapy for the treatment of fatigue in patients with multiple sclerosis: A systematic review and meta-analysis

BACKGROUND Fatigue is a frequently occurring symptom of multiple sclerosis (MS) that limits social participation. OBJECTIVE To systematically determine the short and long-term effects of cognitive behavioral therapy (CBT) for the treatment of MS-related fatigue. DATA SOURCES Pubmed, Cochrane, EMBASE, Psychology and Behavioral Sciences Collection, ERIC, PsychINFO, Cinahl, PsycARTICLES, and relevant trial registers were searched up to February 2016. In addition, references from retrieved articles were examined. STUDY SELECTION Studies were included if participants had MS, fatigue was a primary outcome measure, the intervention was CBT, and the design was a randomized controlled trial. The search was performed by two independent reviewers, three CBT experts determined whether interventions were CBT. DATA EXTRACTION Data on patient and study characteristics and fatigue were systematically extracted using a standardized data extraction form. Two independent reviewers assessed risk of bias using the Cochrane Collaboration risk of bias tool. In the event of disagreement, a third reviewer was consulted. DATA SYNTHESIS Of the 994 identified studies, 4 studies were included in the meta-analysis, comprising 193 CBT-treated patients and 210 patients who underwent a control treatment. Meta-analyses of these studies showed that CBT treatment had a positive short-term effect on fatigue (standardized mean difference [SMD]=-0.47; 95% confidence interval [CI]=-0.88; -0.06; I2=73%). In addition, three studies showed a long-term positive effect of CBT (SMD=-0.30; CI -0.51; -0.08; I2=0%). CONCLUSIONS This review found that the use of CBT for the treatment of fatigue in patients with MS has a moderately positive short-term effect. However, this effect decreases with cessation of treatment.

Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines?

Objective. To investigate the pathophysiological role of pro- and anti-inflammatory cytokines in primary multiple sclerosis-related fatigue. Methods. Fatigued and non-fatigued patients with multiple sclerosis (MS) were recruited and their cytokine profiles compared. Patients with secondary fatigue were excluded. Fatigue was assessed with the self-reported Checklist Individual Strength (CIS20r), subscale fatigue. A CIS20r fatigue cut-off score of 35 was applied to differentiate between non-fatigued (CIS20r fatigue ≤34) and fatigued (CIS20r fatigue ≥35) patients with MS. Blood was collected to determine the serum concentrations of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12p70, IL-17, TNFα, and IFN-γ) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). We controlled for the confounding effect of age, gender, duration of MS, disease severity, type of MS, and use of immunomodulatory drugs. Results. Similar cytokine levels were observed between MS patients with (n = 21) and without fatigue (n = 14). Adjusted multiple regression analyses showed a single significant positive relationship, that of IL-6 with CIS20r fatigue score. The explained variance of the IL-6 model was 21.1%, once adjusted for the confounding effect of age. Conclusion. The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS. Trial Registrations. ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628.

The effectiveness of aerobic training, cognitive behavioural therapy, and energy conservation management in treating MS-related fatigue: the design of the TREFAMS-ACE programme

BackgroundTREFAMS is an acronym for TReating FAtigue in Multiple Sclerosis, while ACE refers to the rehabilitation treatment methods under study, that is, Aerobic training, Cognitive behavioural therapy, and Energy conservation management. The TREFAMS-ACE research programme consists of four studies and has two main objectives: (1) to assess the effectiveness of three different rehabilitation treatment strategies in reducing fatigue and improving societal participation in patients with MS; and (2) to study the neurobiological mechanisms of action that underlie treatment effects and MS-related fatigue in general.Methods/DesignAmbulatory patients (n = 270) suffering from MS-related fatigue will be recruited to three single-blinded randomised clinical trials (RCTs). In each RCT, 90 patients will be randomly allocated to the trial-specific intervention or to a low-intensity intervention that is the same for all RCTs. This low-intensity intervention consists of three individual consultations with a specialised MS-nurse. The trial-specific interventions are Aerobic Training, Cognitive Behavioural Therapy, and Energy Conservation Management. These interventions consist of 12 individual therapist-supervised sessions with additional intervention-specific home exercises. The therapy period lasts 16 weeks. All RCTs have the same design and the same primary outcome measures: fatigue - measured with the Checklist Individual Strength, and participation - measured with the Impact on Participation and Autonomy questionnaire. Outcomes will be assessed 1 week prior to, and at 0, 8, 16, 26 and 52 weeks after randomisation. The assessors will be blinded to allocation. Pro- and anti-inflammatory cytokines in serum, salivary cortisol, physical fitness, physical activity, coping, self-efficacy, illness cognitions and other determinants will be longitudinally measured in order to study the neurobiological mechanisms of action.DiscussionThe TREFAMS-ACE programme is unique in its aim to assess the effectiveness of three rehabilitation treatments. The programme will provide important insights regarding the most effective treatment for MS-related fatigue and the mechanisms that underlie treatment response. A major strength of the programme is that the design involves three almost identical RCTs, enabling a close comparison of the treatment strategies and a strong overall meta-analysis. The results will also support clinical practice guidelines for the treatment of MS-related fatigue.Trial registrationsCurrent Controlled Trials ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628

Indications and effects of botulinum toxin A for obstetric brachial plexus injury: a systematic literature review

Aim  To give an overview of indications for the use of botulinum toxin A (BoNT‐A) treatment for children with obstetric brachial plexus injury (OBPI), and to present the best available evidence of the effectiveness of this treatment.

Physical and Cognitive Functioning After 3 Years Can Be Predicted Using Information From the Diagnostic Process in Recently Diagnosed Multiple Sclerosis

OBJECTIVE To predict functioning after 3 years in patients with recently diagnosed multiple sclerosis (MS). DESIGN Inception cohort with 3 years of follow-up. At baseline, predictors were obtained from medical history taking, neurologic examination, and magnetic resonance imaging (MRI). SETTING Neurology outpatient clinic. PARTICIPANTS Patients with MS (N=156); 146 with complete follow-up. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Inability to walk at least 500 m, impaired dexterity, cognitive impairments, incontinence, inability to drive a car or use public transportation, social dysfunction, and reliance on a disability pension. RESULTS Clinical prediction rules were constructed for the models that were well calibrated (sufficient agreement between predicted and observed outcomes, based on visual inspection of calibration curves) and that showed sufficient discrimination (area under the receiver operation characteristic curve >.70) after internal bootstrap validation. The models for the inability to walk at least 500 m, impaired dexterity, and cognitive impairments were well calibrated. Discrimination was sufficient for all 7 models, except the one predicting social dysfunction (.67). The inability to walk at least 500 m was predicted by the perceived ability to walk, impairment of the cerebellar tract, and the number of MRI lesions in the spinal cord. Impaired dexterity was predicted by the perceived ability to use the hands, impairments of the pyramidal, cerebellar, and sensory tracts, and the T2-weighted infratentorial lesion load. Cognitive impairment was predicted by age, gender, the perceived ability to concentrate, and the T2-weighted supratentorial lesion load. CONCLUSIONS Inability to walk at least 500 m, impaired dexterity, and cognitive impairments can be predicted with predictors that are derived from medical history taking, neurologic examination, and MRI shortly after a definite diagnosis of MS has been made.