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To determine content validity, structural validity, construct validity and reliability of an internet-based questionnaire designed for assessment of publication pressure experienced by medical scientists. The Publication Pressure Questionnaire (PPQ) was designed to assess psychological pressure to publish scientific papers. Content validity was evaluated by collecting independent comments from external experts (n = 7) on the construct, comprehensiveness and relevance of the PPQ. Structural validity was assessed by factor analysis and item response theory (IRT) using the generalized partial credit model. Pearson’s correlation coefficients were calculated to assess potential correlations with the emotional exhaustion and depersonalization subscales of the Maslach Burnout Inventory (MBI). Single test reliability (lambda2) was obtained from the IRT analysis. Content validity was satisfactory. Confirmatory factor analysis did not support the presence of three initially assumed separate domains of publication pressure (i.e., personally experienced publication pressure, publication pressure in general, pressure on position of scientist). After exclusion of the third domain (six items), we performed exploratory factor analysis and IRT. The goodness-of-fit statistics for the IRT assuming a single dimension were satisfactory when four items were removed, resulting in 14 items of the final PPQ. Correlations with the emotional exhaustion and depersonalization scales of the MBI were 0.34 and 0.31, respectively, supporting construct validity. Single test administration reliability lambda2 was 0.69 and 0.90 on the test scores and expected a posteriori scores, respectively. The PPQ seems a valid and reliable instrument to measure publication pressure among medical scientists.

It has been hypothesized that pain and low vitality lead to an increase in avoidance of activities in persons with early symptomatic knee osteoarthritis (OA), and that avoidance of activities leads to an increase in activity limitations. The present study aimed to evaluate these hypotheses.Baseline, 2-year, and 5-year followup data of 828 participants from the Cohort Hip and Cohort Knee Study with early symptomatic knee OA were used. Autoregressive generalized estimating equations and linear regression models were used to analyze the longitudinal and cross-sectional associations between self-reported knee pain, vitality, pain-related avoidance of activities, and activity limitations. The models were adjusted for the covariates age, sex, education level, body mass index, comorbidity, radiographic severity, and hip pain.In longitudinal analyses, knee pain and vitality predicted a subsequent increase in avoidance of activities. Pain-related avoidance of activities predicted a subsequent increase in activity limitations; however, this relationship lost statistical significance (P = 0.089) after adjustment for covariates. Cross-sectional analyses showed strong relationships between knee pain, low vitality, pain-related avoidance of activities, and activity limitations at all time points.In persons with early symptomatic knee OA, knee pain and low vitality lead to a subsequent increase in avoidance of activities. Pain-related avoidance of activities is related to activity limitations at inception of symptoms, but also years later. Therefore, it can be recommended to monitor and target avoidance of activities at various stages of the disease.

Despite increasing interest in visual and hearing impairment in the older population, little attention has been paid to concurrent hearing and vision loss, also known as dual sensory loss. The aim of the present study was to investigate the prevalence of comorbid hearing disability and hearing aid ownership in visually impaired older adults.In a cross-sectional survey, a self-report hearing disability screener was administered to 1396 visually impaired patients (aged ≥ 50 years) of outpatient low vision rehabilitation centers in the Netherlands and Belgium.Of all participants, 44.8% (95% CI 42.2-47.5) had insufficient or poor hearing; the prevalence increased quadratically with age. Of all dual sensory impaired participants, 31.2% in the Netherlands and 55.7% in Belgium did not own hearing aids.The high prevalence of dual sensory loss calls for more awareness of related problems in these patients. Differences between the Netherlands and Belgium regarding hearing aid ownership might be due to different criteria used for hearing aid referral and insurance policies. For patients with dual sensory loss, specialized care implemented in low vision rehabilitation seems warranted.

OBJECTIVES: Nonpolypoid colorectal neoplasms (NP-CRNs) are proposed as a major contributor to the occurrence of interval cancers, but their underlying biology remains controversial. We conducted a systematic review and meta-analysis to clarify the major biological events in NP-CRNs. METHODS: We systematically searched for studies examining molecular characteristics of NP-CRNs. We performed random effect meta-analyses. We measured the heterogeneity among studies using I 2 and possible publication bias using funnel plots. RESULTS: Fifty-three studies on KRAS, APC, or BRAF mutations, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), or DNA promoter hypermethylation were included. We observed less KRAS mutations (summary odds ratio (OR) 0.30, confidence interval (CI) = 0.19-0.46, I-2 = 77.4 %, CI = 70.1-82.9) and APC mutations (summary OR 0.42, CI = 0.24-0.72, I-2 = 22.6 %, CI = 0.0-66.7) in NP-CRNs vs. protruded CRNs, whereas BRAF mutations were more frequent (summary OR 2.20, CI = 1.01-4.81, I-2 = 0 %, CI = 0-70.8), albeit all with large heterogeneity. Less KRAS mutations were especially found in NP-CRNs subtypes: depressed CRNs (summary OR 0.12, CI = 0.05-0.29, I-2 = 0 %, CI = 0-67.6), non-granular lateral spreading tumors (LSTs-NG) (summary OR 0.61, CI = 0.37-1.0, I 2 = 0 %, CI = 0-74.6), and early nonpolypoid carcinomas (summary OR 0.11, CI = 0.06-0.19, I-2 = 0 %, CI = 0-58.3). MSI frequency was similar in NP-CRNs and protruded CRNs (summary OR 0.99, CI = 0.21-4.71, I-2 = 70.3 %, CI = 38.4-85.7). Data for promoter hypermethylation and CIMP were inconsistent, precluding meaningful conclusions. CONCLUSIONS: This meta-analysis provides indications that NP-CRNs are molecularly different from protruded CRNs. In particular, some subtypes of NP-CRNs, the depressed and LST-NG, are featured by less KRAS mutations than polypoid CRNs. Prospective, multicenter studies are needed to clarify the molecular pathways underlying nonpolypoid colorectal carcinogenesis and potential implications for surveillance intervals.

Twin family data can cast light on the longstanding problem about the influences of genes and environment on the etiology of left-handedness. Therefore, hand preference was assessed in 1700 adolescent twin pairs and their parents. Left-handedness (LH) appeared not significantly enhanced among twins compared to the general population. In addition the following observations were made: (1) Significant more LH in first born twins than in second born twins. (2) Significant higher left-handedness association in MZmm pairs compared to DZmm pairs and not or may be marginally so in MZff versus DZff pairs. These results, combined with the observations that (a) left-handed fathers increase the probability of LH in sons but not in daughters; (b) LH in mothers increases LH prevalence in both sons and daughters to the same degree; and (c) very low birth weight, corrected for the effect of gestational age, increases LH prevalence in first born twins only, make an environmental explanation more likely. The possibility that exposure to prenatal male hormones — to which low birth weight and high birth stress children are more vulnerable — might be a crucial condition for the etiology of LH, is discussed.

Background A lack of non-technical skills is increasingly recognised as an important underlying cause of adverse events in healthcare. The nature and number of things professionals communicate to each other can be perceived as a product of their use of non-technical skills. This paper describes the development and reliability of an instrument to measure and quantify the use of non-technical skills by direct observations of explicit professional oral communication (EPOC) in the clinical situation. Methods In an iterative process we translated, tested and refined an existing checklist from the aviation industry, called self, human interaction, aircraft, procedures and environment, in the context of healthcare, notably emergency departments (ED) and intensive care units (ICU). The EPOC comprises six dimensions: assertiveness, working with others; task-oriented leadership; people-oriented leadership; situational awareness; planning and anticipation. Each dimension is specified into several concrete items reflecting verbal behaviours. The EPOC was evaluated in four ED and six ICU. Results In the ED and ICU, respectively, 378 and 1144 individual and 51 and 68 contemporaneous observations of individual staff members were conducted. All EPOC dimensions occur frequently, apart from assertiveness, which was hardly observed. Intraclass correlations for the overall EPOC score ranged between 0.85 and 0.91 and for underlying EPOC dimensions between 0.53 and 0.95. Conclusions The EPOC is a new instrument for evaluating the use of non-technical skills in healthcare, which is reliable in two highly different settings. By quantifying professional behaviour the instrument facilitates measurement of behavioural change over time. The results suggest that EPOC can also be translated to other settings.

Background: Body-mass index (BMI) and depressed mood are both positively associated with pain and activity limitations in knee osteoarthritis (OA), and are interrelated. The aims of the present study were: 1) to assess whether BMI and depressed mood are independently associated with knee pain and activity limitations; and 2) to compare the relative contributions of BMI and depressed mood to knee pain and activity limitations. Methods. A cross-sectional study in 294 patients with clinical knee OA. Regression analyses were performed with knee pain or activity limitations (self-reported and performance-based) as dependent variables, and BMI and depressed mood as independent variables. All analyses were adjusted for age, gender, marital status, education level, radiographic OA and comorbidity. Dominance analyses were performed to examine the relative contributions of BMI and depressed mood to knee pain and activity limitations. Results: BMI and depressed mood were positively and independently associated with knee pain and activity limitations. BMI and depressed mood explained small parts (3.0% and 2.3%, respectively) of variance in knee pain. BMI explained a substantial part of variance in both self-reported (9.8%) and performance-based (20.4%) activity limitations, while depressed mood explained a small part of variance (3.1% in self-reported and 2.6% in performance-based activity limitations). Conclusions: In patients with knee OA both BMI and depressed mood seem to be independently associated with knee pain and activity limitations. The contribution of BMI to activity limitations is most substantial, thereby offering a relevant target for interventions. © 2013 Holla et al.; licensee BioMed Central Ltd.

PURPOSE: To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other magnetic resonance (MR) imaging markers. MATERIALS AND METHODS: The institutional review board approved the study; all subjects gave written informed consent. Upper cervical cord cross-sectional area (UCCA), brain and spinal cord lesion loads, and brain atrophy were measured in 440 patients with MS (311 with relapsing-remitting [RR] MS, 92 with secondary-progressive [SP] MS, and 37 with primary-progressive [PP] MS) studied in two centers. Disability was scored with the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (TWT), and the nine-hole peg test. UCCA was compared between groups with the Mann-Whitney U test. Correlations were assessed with the Spearman ρ test. Multivariate associations between UCCA and clinical and other MR imaging parameters, including number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord, were assessed by using multiple linear regression, adjusted for study center site. RESULTS: The UCCA in patients with SP MS (median, 79 mm(2); interquartile range, 72.4-84.9 mm(2)) and PP MS (median, 77.3 mm(2); interquartile range, 69-82.5 mm(2)) was significantly smaller (P < .001) than that in patients with RR MS (median, 84 mm(2); interquartile range, 78.7-89.3 mm(2)). UCCA was inversely correlated with EDSS score, TWT, and nine-hole peg test findings (ρ ≤ -0.29, P < .001 for all comparisons). UCCA, number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord were found to be significant explanatory factors for clinical disability (R(2) = 0.564). The UCCA and the number of hypointense brain lesions on T1-weighted images were the strongest MR imaging parameters for explaining physical disability, as measured with the EDSS. CONCLUSION: Spinal cord abnormalities have a strong effect on clinical disability in MS. MR imaging-derived UCCA was found to be the most significant spinal cord parameter for explaining EDSS score.

BACKGROUND: Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly prevalent in knee OA, have been suggested to play an important role. No study has focussed on the association between proprioceptive accuracy and meniscal abnormalities in knee OA. OBJECTIVE: To explore the association between reduced proprioceptive accuracy and medial meniscal abnormalities in a clinical sample of knee OA subjects. METHODS: Cross-sectional study in 105 subjects with knee OA. Knee proprioceptive accuracy was assessed by determining the joint motion detection threshold in the knee extension direction. The knee was imaged with a 3.0 T magnetic resonance (MR) scanner. Number of regions with medial meniscal abnormalities and the extent of abnormality in the anterior and posterior horn and body were scored according to the Boston-Leeds Osteoarthritis Knee Score (BLOKS) method. Multiple regression analyzes were used to examine whether reduced proprioceptive accuracy was associated with medial meniscal abnormalities in knee OA subjects. RESULTS: Mean proprioceptive accuracy was 2.9degree + 1.9degree. Magnetic resonance imaging (MRI)-detected medial meniscal abnormalities were found in the anterior horn (78%), body (80%) and posterior horn (90%). Reduced proprioceptive accuracy was associated with both the number of regions with meniscal abnormalities (P < 0.01) and the extent of abnormality (P = 0.02). These associations were not confounded by muscle strength, joint laxity, pain, age, gender, body mass index (BMI) and duration of knee complaints. CONCLUSION: This is the first study showing that reduced proprioceptive accuracy is associated with medial meniscal abnormalities in knee OA. The study highlights the importance of meniscal abnormalities in understanding reduced proprioceptive accuracy in persons with knee OA. Copyright 2013 Osteoarthritis Research Society International. All rights reserved

Background: Dual sensory loss (DSL) has a negative impact on health and wellbeing and its prevalence is expected to increase due to demographic aging. However, specialized care or rehabilitation programs for DSL are scarce. Until now, low vision rehabilitation does not sufficiently target concurrent impairments in vision and hearing. This study aims to 1) develop a DSL protocol (for occupational therapists working in low vision rehabilitation) which focuses on optimal use of the senses and teaches DSL patients and their communication partners to use effective communication strategies, and 2) describe the multicenter parallel randomized controlled trial (RCT) designed to test the effectiveness and cost-effectiveness of the DSL protocol. Methods/design. To develop a DSL protocol, literature was reviewed and content was discussed with professionals in eye/ear care (interviews/focus groups) and DSL patients (interviews). A pilot study was conducted to test and confirm the DSL protocol. In addition, a two-armed international multi-center RCT will evaluate the effectiveness and cost-effectiveness of the DSL protocol compared to waiting list controls, in 124 patients in low vision rehabilitation centers in the Netherlands and Belgium. Discussion. This study provides a treatment protocol for rehabilitation of DSL within low vision rehabilitation, which aims to be a valuable addition to the general low vision rehabilitation care. Trial registration. Netherlands Trial Register (NTR) identifier: NTR2843. © 2013 Vreeken et al.; licensee BioMed Central Ltd.

Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were investigated. Subjects with MCI were selected from the Development of Screening Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study (n = 156) and the single-center VU medical center (n = 172). At follow-up, area under the curve was highest for automated atlas-based hippocampal measurement (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65) and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal measurements correlated with CSF total tau and phosphorylated tau, not with beta-amyloid 1-42. MTA-score and lateral ventricle volume correlated with CSF beta-amyloid 1-42. We can conclude that volumetric hippocampal measurements are the best predictors of AD conversion in subjects with MCI. (c) 2013 Elsevier Inc. All rights reserved. (Less)

We studied the predictive value of cognitive performance, vascular risk factors, apolipoprotein E (APOE) genotype, and structural brain changes on MRI, on progression to dementia in post hoc analyses of 426 placebo patients (mean age 71 years; 55% women) with mild cognitive impairment (MCI) who participated in a previously published large multi-center clinical trial (Gal-Int-11). The ADAS-cog/MCI test, the New York University Paragraph Recall Test, and the Digit Symbol Coding Test were available at baseline, as were vascular risk factors and APOE genotype. Medial temporal lobe atrophy (MTA), white matter hyperintensities (WMH) and lacunes were assessed on MRI. Over two years of follow-up, 81 patients (19%) converted to dementia, while 345 patients (81%) remained stable. Results of Cox proportional-hazards regression analysis showed that higher age, worse cognitive test performance, presence of an APOE e4 allele, and higher MTA scores on MRI increased the risk of progression to dementia in univariate analyses. Vascular risk factors, and WMH and lacunes on MRI, were not associated with progression to dementia. Lower performance on the ADAS-cog/MCI test (HR 1.08 per point increase; 95% CI 1.06-1.10) and Delayed recall test (HR 0.76 per point increase; 95% CI 0.68-0.85), as well as higher MTA scores on MRI (HR 1.33 per point increase; 95% CI 1.00-1.77) were independent predictors of progression to dementia in a step-wise Cox proportional-hazards model with age and gender forced into the model. We conclude that global cognitive function, episodic memory performance, and MTA on MRI independently predict progression to dementia in patients with MCI. © 2013 - IOS Press and the authors. All rights reserved.

Background The M1 muscarinic acetylcholine receptor (M1ACh-R) is a G protein-coupled receptor that can occur in interconvertible coupled and uncoupled states. It is enriched in the basal ganglia, hippocampus, olfactory bulb, and cortical areas, and plays a role in motor and cognitive functions. Muscarinic M1 agonists are potential therapeutic agents for cognitive disorders. The aim of this study was to evaluate [11C]AF150(S) as a putative M1ACh-R agonist PET ligand, which, owing to its agonist properties, could provide a tool to explore the active G protein-coupled receptor. Methods Regional kinetics of [11C]AF150(S) in rat brain were measured using a high-resolution research tomograph, both under baseline conditions and following pre-treatment with various compounds or co-administration of non-radioactive AF150(S). Data were analysed by calculating standard uptake values and by applying the simplified reference tissue model (SRTM). Results [11C]AF150(S) was rapidly taken up in the brain, followed by a rapid clearance from all brain regions. Analysis of PET data using SRTM revealed a binding potential (BPND) of 0.25 for the striatum, 0.20 for the hippocampus, 0.16 for the frontal cortical area and 0.15 for the posterior cortical area, all regions rich in M1ACh-R. BPND values were significantly reduced following pre-treatment with M1ACh-R antagonists. BPND values were not affected by pre-treatment with a M3ACh-R antagonist. Moreover, BPND was significantly reduced after pre-treatment with haloperidol, a dopamine D2 receptor blocker that causes an increase in extracellular acetylcholine (ACh). The latter may compete with [11C]AF150(S) for binding to the M1ACh-R; further pharmacological agents were applied to investigate this possibility. Upon injection of the highest dose (49.1 nmol kg−1) of [11C]AF150(S) diluted with non-radioactive AF150(S), brain concentration of AF150(S) reached 100 nmol L−1 at peak level. At this concentration, no sign of saturation in binding to M1ACh-R was observed. Conclusions The agonist PET ligand [11C]AF150(S) was rapidly taken up in the brain and showed an apparent specific M1ACh-R-related signal in brain areas that are rich in M1ACh-R. Moreover, binding of the agonist PET ligand [11C]AF150(S) appears to be sensitive to changes in extracellular ACh levels. Further studies are needed to evaluate the full potential of [11C]AF150(S) for imaging the active pool of M1ACh-R in vivo.

Objective To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS). Design From eight MAGNIMS (MAGNetic resonance Imaging in MS) centres, we retrospectively included 261 MS patients with MR imaging at baseline and after 1–2 years, and Expanded Disability Status Scale (EDSS) scoring at baseline and after 10 years. Annualised whole brain atrophy, central brain atrophy rates and T2 lesion volumes were calculated. Patients were categorised by baseline diagnosis as primary progressive MS (n=77), clinically isolated syndromes (n=18), relapsing–remitting MS (n=97) and secondary progressive MS (n=69). Relapse onset patients were classified as minimally impaired (EDSS=0–3.5, n=111) or moderately impaired (EDSS=4–6, n=55) according to their baseline disability (and regardless of disease type). Linear regression models tested whether whole brain and central atrophy, lesion volumes at baseline, follow-up and lesion volume change predicted 10 year EDSS and MS Severity Scale scores. Results In the whole patient group, whole brain and central atrophy predicted EDSS at 10 years, corrected for imaging protocol, baseline EDSS and disease modifying treatment. The combined model with central atrophy and lesion volume change as MRI predictors predicted 10 year EDSS with R 2 =0.74 in the whole group and R 2 =0.72 in the relapse onset group. In subgroups, central atrophy was predictive in the minimally impaired relapse onset patients (R 2 =0.68), lesion volumes in moderately impaired relapse onset patients (R 2 =0.21) and whole brain atrophy in primary progressive MS (R 2 =0.34). Conclusions This large multicentre study points to the complementary predictive value of atrophy and lesion volumes for predicting long term disability in MS.

Objective: To compare the predictive accuracy of beta-amyloid (A beta)1-42 and total tau in CSF, hippocampal volume (HCV), and APOE genotype for Alzheimer disease (AD)-type dementia in subjects with amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI). Methods: We selected 399 subjects with aMCI and 226 subjects with naMCI from a multicenter memory clinic-based cohort. We measured CSF A beta 1-42 and tau by ELISA (n = 231), HCV on MRI (n = 388), and APOE epsilon 4 (n = 523). Follow-up was performed annually up to 5 years. Outcome measures were progression to AD-type dementia and cognitive decline. Results: At least 1 follow-up was available for 538 subjects (86%). One hundred thirty-two subjects with aMCI (38%) and 39 subjects with naMCI (20%) progressed to AD-type dementia after an average follow-up of 2.5 years. CSF A beta 1-42, tau, A beta 1-42/tau ratio, HCV, and APOE epsilon 4 predicted AD-type dementia in each MCI subgroup with the same overall diagnostic accuracy. However, CSF A beta 1-42 concentration was higher and hippocampal atrophy less severe in subjects with naMCI compared with aMCI. This reduced the sensitivity but increased the specificity of these markers for AD-type dementia in subjects with naMCI. Conclusions: AD biomarkers are useful to predict AD-type dementia in subjects with aMCI and naMCI. However, biomarkers might not be as sensitive for early diagnosis of AD in naMCI compared with aMCI. This may have implications for clinical implementation of the National Institute on Aging and Alzheimer's Association criteria. Neurology (R) 2013; 80:1124-1132

Background: In clinical settings, it is important for health care providers to measure different aspects of functioning in older adults with joint pain and comorbidity. Besides the use of distinct measures, it could also be attractive to have one general measure of functioning that incorporates several distinct measures, but provides one summary score to quantify overall level of functioning, for example for the identification of older adults at risk of poor functional outcome. Therefore, we selected four measures of functioning: Physical Functioning (PF), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and participation, and tested the possibility to aggregate these measures into one general measure of functioning. Methods. A prospective cohort study of older adults (≥65 years) with joint pain and comorbidity provided baseline data (n = 407) consisting of PF (PF subscale, RAND-36; 10 items), ADL (KATZ index; 6 items), IADL (Lawton index; 7 items) and participation (KAP; 6 items). We tested two models with confirmatory factor analysis: first, a bifactor model with all four measures and second, a bifactor model with PF, ADL and IADL and a correlated but distinct subgroup factor for participation. Several model fit indexes and reliability coefficients, such as explained common variance (ECV) and omegas were computed for both models. Results: The first model fitted the data well, but the reliability analysis indicated multidimensionality and unique information in the subgroup factor participation. The second model showed similar model fits, but better reliability; ECV = 0.67, omega-t = 0.94, low omega-s = 0.18-0.22 on the subgroup factors and high omega of 0.82 on participation, which all were in favour of the second model. Conclusions: The results indicate that PF, ADL and IADL could be aggregated into one general measure of functioning, whereas participation should be considered as a distinct measure. © 2013 Hermsen et al.; licensee BioMed Central Ltd.

Objective To describe foot-related health care use over time in a cohort of rheumatoid arthritis (RA) patients in an outpatient secondary care center for rheumatology and rehabilitation in The Netherlands. Methods A total of 1,087 patients with recent-onset RA from 1995 to September 2010 were included in the study. All foot-related visits to the podiatrist, rehabilitation physician, orthopedic surgeon, and the multidisciplinary foot-care clinic were registered and described. Logistic regression techniques for longitudinal data were used to analyze the course of foot-related health care use. Results A total of 32.9% of patients visited a podiatrist in secondary care during the course of their disease. For most patients, a visit to the podiatrist took place during the first year after diagnosis. This was followed by a significant decrease in visits in the ensuing years. Nine percent of patients visited the rehabilitation physician with foot symptoms, with peak prevalences between year 10 and 11 and during year 14 of followup. The orthopedic surgeon was visited by 5.3% of patients with foot symptoms, with a significant increase in visits over time. The multidisciplinary foot-care clinic was visited by 7.5% of patients. This was significantly associated with visits to the rehabilitation physician. Conclusion In an outpatient secondary care center in The Netherlands, RA patients with foot symptoms visited the podiatrist in an early stage of the disease. When foot symptoms worsened, patients visited the rehabilitation physician, who subsequently referred patients to the multidisciplinary foot-care clinic for therapeutic footwear. The orthopedic surgeon was the final step in the management of foot symptoms. © 2013 by the American College of Rheumatology.

Background Proxy respondents, partners of multiple sclerosis (MS) patients, can provide valuable information on the MS patients' disease. In an earlier publication we found relatively good agreement on patient reported outcomes (PROs) measuring physical impact and functioning, but we found large differences on (neuro)psychological scales. Objective We aim to identify patient and proxy related variables explaining differences between patients' and proxies' ratings on five PROs. Methods We report on data from 175 MS patients and proxy respondents. Regression analyses were performed, using as dependent variable the mean differences on five scales: Physical and Psychological scale of the Multiple Sclerosis Impact Scale (MSIS-29), the Multiple Sclerosis Walking Scale (MSWS), Guy's Neurological Disability Scale (GNDS) and the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ). The independent variables were patient, proxy and disease related variables. Results Caregiver strain was significantly related to differences between patient and proxy scores for all five PROs. A higher level of patient anxiety on the HADS was linked to larger differences on all PROs except the GNDS. In addition, cognitive functioning, proxy depression, walking ability, proxy gender and MS related disability were contributing to the discrepancies. Conclusion We found several patient and proxy factors that may contribute to discrepancies between patient and proxy scores on MS PROs. The most important factor is caregiver burden. © 2013 Elsevier B.V.

Background: Communicating effectively with palliative care patients has been acknowledged to be somewhat difficult, but little is known about the effect that training general practitioners (GPs) in specific elements of communication in palliative care might have. We hypothesized that GPs exposed to a new training programme in GP-patient communication in palliative care focusing on availability of the GP for the patient, current issues the GP should discuss with the patient and anticipation by the GP of various scenarios (ACA), would discuss more issues and become more skilled in their communication with palliative care patients. Methods. In this controlled trial among GPs who attended a two-year Palliative Care Peer Group Training Course in the Netherlands only intervention GPs received the ACA training programme. To evaluate the effect of the programme a content analysis (Roter Interaction Analysis System) was performed of one videotaped 15-minute consultation of each GP with a simulated palliative care patient conducted at baseline, and one at 12 months follow-up. Both how the GP communicated with the patient ('availability') and the number of current and anticipated issues the GP discussed with the patient were measured quantitatively. We used linear mixed models and logistic regression models to evaluate between-group differences over time. Results: Sixty-two GPs were assigned to the intervention and 64 to the control group. We found no effect of the ACA training programme on how the GPs communicated with the patient or on the number of issues discussed by GPs with the patient. The total number of issues discussed by the GPs was eight out of 13 before and after the training in both groups. Conclusion: The ACA training programme did not influence how the GPs communicated with the simulated palliative care patient or the number of issues discussed by the GPs in this trial. Further research should evaluate whether this training programme is effective for GPs who do not have a special interest in palliative care and whether studies using outcomes at patient level can provide more insight into the effectiveness of the ACA training programme. Trial registration. Current Controlled Trials ISRCTN56722368. © 2013 Slort et al.; licensee BioMed Central Ltd.

Background: Patients with dementia frequently do not receive adequate palliative care which may relate to poor understanding of the natural course of dementia. We hypothesized that understanding that dementia is a progressive and terminal disease is fundamental to a focus on comfort in dementia, and examined how family and professional caregivers' understanding of the nature of the disease was associated with patients' comfort during the dying process.Methods: We enrolled 372 nursing home patients from 28 facilities in The Netherlands in a prospective observational study (2007 to 2010). We studied both the families and the physicians (73) of 161 patients. Understanding referred to families' comprehension of complications, prognosis, having been counseled on these, and perception of dementia as " a disease you can die from" (5-point agreement scale) at baseline. Physicians reported on this perception, prognosis and having counseled on this. Staff-assessed comfort with the End-of-Life in Dementia - Comfort Assessment in Dying (EOLD-CAD) scale. Associations between understanding and comfort were assessed with generalized estimating equations, structural equation modeling, and mediator analyses.Results: A family's perception of dementia as " a disease you can die from" predicted higher patient comfort during the dying process (adjusted coefficient -0.8, 95% confidence interval (CI): -1.5; -0.06 point increment disagreement). Family and physician combined perceptions (-0.9, CI: -1.5; -0.2; 9-point scale) were also predictive, including in less advanced dementia. Forty-three percent of the families perceived dementia as a disease you can die from (agreed completely, partly); 94% of physicians did. The association between combined perception and higher comfort was mediated by the families' reporting of a good relationship with the patient and physicians' perception that good care was provided in the last week.Conclusions: Awareness of the terminal nature of dementia may improve patient comfort at the end of life. Educating families on the nature of dementia may be an important part of advance care planning. © 2013 van der Steen et al.; licensee BioMed Central Ltd.

OBJECTIVE: To determine the association of postural control with muscle strength, proprioception, self-reported knee instability and activity limitations in patients with knee osteoarthritis. METHODS: A total of 284 patients with knee osteoarthritis from the Amsterdam Osteoarthritis cohort were included. Postural control was assessed using the One-Leg Stand Test (OLST), in which the patients were asked to stand on one leg for 30 s. Muscle strength (isokinetic dynamometer), proprioception (joint motion detection threshold) and self-reported knee instability (episodes of buckling, shifting or giving way) were also assessed. Activity limitations were assessed using the Get Up and Go (GUG) test, the walking up-down stairs test, and Western Ontario and McMaster University Osteoarthritis Index - Physical Function subscale. Regression analyses were used to assess the associations. RESULTS: Muscle weakness (p = 0.02) and proprioceptive inaccuracy (p

Objective: To determine the course of daily functioning in patients with multiple sclerosis in the 10 years after their definite diagnosis. Methods: A long-term prospective follow-up study including an incidence cohort of 156 patients with multiple sclerosis. Participants were examined systematically, beginning immediately after definite diagnosis, then at the following timepoints: 6 months, 1, 2, 3, 6 and 10 years. The various domains of daily functioning were assessed with the Expanded Disability Status Scale, the Functional Independence Measure, and the Medical Outcome Study Short Form-36 (SF-36). Results: Neurological disability and physical functioning worsened significantly, with a time course dependent on whether a patient had multiple sclerosis of the relapse onset type or non-relapse onset type. Cognitive and social functioning worsened significantly over time, but with the same (accelerated) rate of change in both the RO and NRO groups. Scores on SF-36 mental health, SF-36 role physical, and SF-36 general health changed only slightly. Conclusion: In the first 10 years after definite diagnosis, patients with multiple sclerosis showed a more pronounced decline in physical functioning than in cognitive and social functioning. There was no time-related decline in mental health, social role due to physical limitations, or general health. © 2013 The Authors.

Age at exam (years) 75.0 (72.5-78.5) 75.9 (70.0-80.5) 73.7 (68.5-80.0) 0.78 Education (years) 14.0 (13.0-16.5) 16.0 (14.0-18.0) 15.5 (12.0-17.0) 0.06 Gender (% male) 47.8% 59% 56% 0.57 APOE4 (% APOE4 positive) 13% 55.2% 76%

Background: To test a previous report of improved performance of the FSL/ Siena whole brain atrophy algorithm by using non default settings at both 3T and 1.5T. Methods: As part of the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, high quality MPRAGE (a T1 weighted 3D MRI sequence) from 200 subjects visit pairs is available to compare the reproducibility of brain atrophies over 12 to 18 month intervals at both 3T and 1.5T. This is because in ADNI all subjects received back-to-back (BTB) MPRAGEs with the second MRPAGE acquisition starting within seconds of the completion of the first. Also as part of ADNI, 131 subjects received BTB scans at multiple time points and two field strengths of 3T and 1.5T. For this study FSL/Siena was applied to the 200 subject visit pairs for 88 different combinations of options and the two field strengths requiring a total of 9 core years of calculations. For each combination of options and field strengths Siena's BTB reproducibility was quantified as the median of the absolute value of the difference between the BTB percentage brain volume change (PBVC) yielded by Siena. Results: For Siena option combinations -B (bias field correction and neck cleanup turned on) and f = 0.1 to 0.3 (which selects the fractional intensity threshold) provided the smallest reproducibility of 0.26 to 0.27 for 1.5T. However, bootstrapping provided a 95% confidence interval on the reproducibility up to 0.29. Options that often yielded poor reproducibilities included the -S option (eye and optic nerve cleanup turned on) and f > = 0.5. The range of the 3T results made an optimal option combination less clear. For the 69 subjects with two visit pairs each, no significant correlation was found between the BTB differences of the 0 to 12 month and 6 to 18 month visit pairs bearing out their treatment in this analysis as independent measures. Conclusions: For the ADNI MPRAGEs at 1.5T the -B option with f = 0.3 will likely yield the best BTB PBVC reproducibility for Siena - supporting the previous report and differing from the Siena default value of f = 0.5. For 3T the optimum choice is less clear.

Purpose: Quality of care for long-term care (LTC) residents with dementia at the end-of-life is often evaluated using standardized instruments that were not developed for or thoroughly tested in this population. Given the importance of using appropriate instruments to evaluate the quality of care (QOC) and quality of dying (QOD) in LTC, we compared the validity and reliability of ten available instruments commonly used for these purposes. Methods: We performed prospective observations and retrospective interviews and surveys of family (n = 70) and professionals (n = 103) of LTC decedents with dementia in the Netherlands. Results: Instruments within the constructs QOC and QOD were highly correlated, and showed moderate to high correlation with overall assessments of QOC and QOD. Prospective and retrospective ratings using the same instruments differed little. Concordance between family and professional scores was low. Cronbach's alpha was mostly adequate. The EOLD-CAD showed good fit with pre-assumed factor structures. The EOLD-SWC and FPCS appear most valid and reliable for measuring QOC, and the EOLD-CAD and MSSE for measuring QOD. The POS performed worst in this population. Conclusions: Our comparative study of psychometric properties of instruments allows for informed selection of QOC and QOD measures for LTC residents with dementia. © The Author(s) 2011.

Alzheimer's disease (AD) is a common cause of mild cognitive impairment (MCI). However, the time between the diagnosis of MCI and the diagnosis of dementia is highly variable. In this study we investigated which known risk factors and biomarkers of AD pathology were associated with rapid progression from MCI to dementia. Of the 203 subjects with MCI, 91 progressed to AD-type dementia and were considered to have MCI-AD at baseline. Subjects with MCI-AD were older, more frequently female and carrier of the APOE-epsilon 4 allele, had lower scores on the Mini-Mental State Examination (MMSE), more medial temporal lobe atrophy (MTA) and lower levels of A beta(1-42) and increased levels of t-tau and p-tau in the cerebrospinal fluid (CSF) compared to subjects without AD-type dementia at follow up. Of the 91 subjects with MCI-AD, we had data available of CSF (n = 56), MTA (n = 76), and APOE-genotype (n = 63). Among the subjects with MCI-AD, MTA (hazard ratio (HR) 2.2, p = 0.004) and low MMSE score (HR 2.0 p = 0.007) were associated with rapid progression to dementia. High CSF t-tau (HR 1.7, p = 0.07) and p-tau (1.7, p = 0.08) tended to be associated with rapid progression to dementia. CSF A beta(1-42), APOE status, age, gender, and educational level were not associated with time to dementia. Our findings implicate a different role for biomarkers in diagnosis and prognosis of MCI-AD. While amyloid markers can be used to identify MCI-AD, injury markers may predict rapid progression to dementia.

Trilateral retinoblastoma (TRb) is a rare disease associating intraocular retinoblastoma with intracranial primitive neuroectodermal tumor. Treatment is difficult and prognosis is poor. This multicenter study evaluates clinical findings and MR imaging characteristics of associated intracranial tumors in Rb patients. Clinical data of 17 patients (16 TRb and 1 quadrilateral Rb patients) included time intervals between Rb and TRb diagnosis and presence of baseline brain-imaging (BBI). Two reviewers reviewed all images individually and one reviewer per center evaluated their images. Consensus was reached during a joint scoring session. Studies were reviewed for tumor location, size and imaging characteristics (signal intensity (SI) on T1- and T2-weighted images, enhancement pattern and cystic appearance). Of 18 intracranial tumors, 78 % were located in the pineal gland and 22 % suprasellar. All tumors showed well-defined borders with mostly heterogenous enhancement (72 %) and isointense SI on T1- (78 %) and T2-weighted images (72 %) compared to gray matter. The majority of pineal TRbs showed a cystic component (57 %). TRb detected synchronously with the intraocular tumors on BBI (n = 7) were significantly smaller (P = 0.02), and mainly asymptomatic than TRb detected later on (n = 10). Overall, 5-year-survival of TRb patients detected on BBI was 67 % (95 % CI 29–100 %) compared to 11 % (95 % CI 0–32 %) for the group with delayed diagnosis. TRb mainly develops in the pineal gland and frequently presents with a cystic appearance that could be misinterpreted as benign pineal cysts. Routine BBI in all newly diagnosed Rb patients can detect TRb at a subclinical stage.

Background Important health benefits can be achieved when physical activity in children from low socio-economic status is promoted and sedentariness is limited. By specifying the mediating mechanisms of existing interventions one can improve future physical activity interventions. This study explored potential mediators of the long-term effect of the school-based multicomponent JUMP-in intervention on sport participation, outdoor play and screen time in Dutch primary schoolchildren from disadvantaged neighborhoods. Methods In total, 600 primary schoolchildren (aged 9.8 ± 0.7, 51% girls, 13% Dutch ethnicity, 35% overweight) from 9 intervention and 10 control schools were included in the analyses. JUMP-in was developed using Intervention Mapping, and targeted psychological and environmental determinants of physical activity. Outcome behaviors were self-reported sport participation, outdoor play, TV-viewing behavior and computer use. Potential mediators were self-reported psychological, social and physical environmental factors. Results JUMP-in was effective in improving sport participation after 20 months, but not in improving outdoor play, or reducing TV-viewing or computer time. JUMP-in was not effective in changing hypothesized mediators so no significant mediated effects could be identified. However, changes in self-efficacy, social support and habit strength were positively associated with changes in sport participation, and changes in social support, self-efficacy, perceived planning skills, enjoyment and habit strength were positively associated with changes in outdoor play. Changes in enjoyment was positively associated with changes in TV-viewing while parental rules were negatively associated. Having a computer in the bedroom and enjoyment were positively associated with changes in computer use, while changes in parental rules were negatively associated. Conclusions Besides a significant positive effect on sports participation, no significant intervention effect on outdoor play, screen time or any of the potential mediators was found. This suggest that other (unmeasured) factors operated as mediating mechanisms of the intervention, that we used unsuccessful intervention strategies, that the strategies were inappropriately implemented, or that children are unable to accurately recall past activities and cognitions. Additionally, the school setting might not be the sole channel to influence leisure time activities. Still, several personal and environmental constructs were found to be relevant in predicting change in sport participation, outdoor play and screen behavior and seem to be potential mediators. Future interventions are recommended including more effective strategies targeting these relevant constructs, addressing different constructs (e.g. pedagogic skills of parents), and focusing on different implementation settings. Trail registration ISRCTN17489378

Purpose: To identify the risk factors for the onset of arm-wrist-hand and neck-shoulder symptoms among office workers and to estimate the relative contribution of these risk factors by calculating Population Attributable Fractions (PAFs). Methods: A prospective cohort study was conducted among 1951 office workers with a follow-up duration of 2 years. Data on self-reported risk factors were collected at baseline and after 1 year of follow-up. Every 3 months, the occurrence of upper extremity symptoms was assessed using questionnaires. PAFs for individual risk factors were estimated based on Rate ratios (RRs) obtained from Poisson regression using Generalized Estimation Equations. Results: Previous disabling symptoms were identified as the most important risk factor for the onset of arm-wrist-hand and neck-shoulder symptoms. Modifiable risk factors for arm-wrist-hand symptoms with relatively large PAFs were: at least 4 h per day of self-reported computer use at work, high level of overcommitment, and low task variation and for neck-shoulder symptoms: supporting the arms during keyboard use and at least 4 h per day of self-reported mouse use at work. Compared to having 0 or 1 risk factor, the RR for arm-wrist-hand symptoms increased to 6.2 (95% CI 3.7-10.5) for having 5-7 potentially modifiable risk factors and for neck-shoulder symptoms to 3.0 (95% CI 2.1-4.4) for having 4 or 5 potentially modifiable risk factors. Conclusion: Preventive interventions at the population level should be aimed at changing modifiable risk factors with large PAFs. At the individual level, preventive interventions should be aimed at changing multiple modifiable risk factors simultaneously. © Springer-Verlag 2011.

BACKGROUND AND PURPOSE: Several studies have reported on the clinical utility of DWI in head and neck cancer, but none of these studies compared HASTE with EPI-DWI in patients with head and neck cancer. The aim of our study was to compare detection and delineation of primary tumors and lymph nodes by using HASTE and EPI-DWI techniques in patients with HNSCC. MATERIALS AND METHODS: Twelve patients with HNSCC and a total of 12 primary tumors and 77 visualized lymph nodes on MR imaging underwent DWI by using both EPI-based and HASTE techniques. Interobserver agreement for detection, delineation, and ADC values of primary tumors and lymph nodes was assessed by 2 radiologists, and artifacts for both DWI techniques were described. RESULTS: The number of lesions (primary tumors and lymph nodes) identified on pretreatment EPI-DWI was higher compared with pretreatment HASTE-DWI, with means of total lesions of 88.5 and 69.0, respectively. Delineation of lesions was also better on pretreatment EPI-DWI compared with pretreatment HASTE-DWI, with means of well-delineated lesions of 80.5 and 27.5, respectively. Both EPI- and HASTE-DWI showed good interobserver agreement between radiologists of ADC values in lesions with ICC values of 0.79 and 0.92, respectively. Intraobserver agreement for ADC values in lesions assessed with EPI- versus HASTE-DWI techniques was low, with ICC values of 0.31 and 0.42, respectively. Significant interobserver disagreement concerning detection was only seen with HASTE-DWI, and none of the DWI techniques showed significant interobserver disagreements regarding delineation. EPI-DWI was more prone to susceptibility artifacts than HASTE-DWI: Ninety-one percent of primary tumors and 16% of lymph nodes were affected by susceptibility artifacts on pretreatment EPI-DWI, whereas these artifacts were not seen on HASTE-DWI. CONCLUSIONS: Primary tumors and lymph nodes are more easily visualized on EPI-DWI compared with HASTE-DWI. EPI-DWI has geometric distortion, however, which has a negative effect on interobserver agreement of ADC values.

BACKGROUND AND PURPOSE: The purpose of radiosurgery of bAVMs is complete angiographic obliteration of its nidus. We assessed the diagnostic accuracy of 1.5T T2-weighted MR imaging and TOF-MRA images for detecting nidus obliteration after radiosurgery. MATERIALS AND METHODS: The pre- and postradiosurgery MR images and DSA images from 120 patients who were radiosurgically treated for a bAVM were re-evaluated by 2 observers for patency of the nidus (preradiosurgery) and obliteration (postradiosurgery: final follow-up MR imaging), by using a 3-point scale of confidence. Consensus reading of the DSA after radiosurgery was considered the criterion standard for obliteration. Sensitivity, specificity, PPVs, and NPVs, and overall diagnostic performance by using ROC were determined. RESULTS: Mean bAVM volume during radiosurgery was 3.4 mL (95% CI, 2.6–4.3 mL). Sixty-six patients (55%) had undergone previous endovascular embolization. The mean intervals between radiosurgery and follow-up MR imaging and for DSA, respectively, were 35.6 months (95% CI, 32.3–38.9 months) and 42.1 months (95% CI, 40.3–44.0 months). With ROC, an area under curve of 0.81–0.83 was found. PPVs and NPVs of final follow-up MR imaging for definitive obliteration varied between 0.85 and 0.95 and 0.55 and 0.62. An average false-positive rate, meaning overestimation of nidus obliteration, of 0.08 and an average false-negative rate, meaning underestimation of nidus obliteration of 0.48, were found. CONCLUSIONS: MRA is insufficient to diagnose obliteration in the follow-up of bAVMs after radiosurgery. A remaining nidus diameter

Contains fulltext : 109807.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To evaluate the effectiveness of integrated, multidisciplinary care as compared with usual care for patients with moderate to severe, chronic hand eczema after 26 weeks of follow-up. BACKGROUND: This study was designed as a randomized, controlled trial. METHODS: Patients who visited one of the participating hospitals were randomized to integrated care or usual care. Integrated care was carried out by a multidisciplinary team, and integrated clinical and occupational care to optimize treatment, and the patient's quality of life and social functioning. Outcome variables were clinical assessment of hand eczema with the Hand Eczema Severity Index (HECSI) (primary outcome), quality of life, patient's global assessment of hand eczema, and sick leave. RESULTS: Average improvement on the HECSI was 22.4 points in the intervention group and 11.7 points in the control group. The mean difference in improvement on the HECSI between both groups after 26 weeks was 10.7 points in favour of the integrated care group (standard error 5.3, 95% confidence interval 0.3-21.1, p = 0.044). No differences in improvement between the groups were found for any of the other outcomes. CONCLUSIONS: The integrated care programme significantly improved clinical outcome measures as compared with usual care, and was effective for treating patients with chronic hand eczema. 01 april 2012

Objectives: Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology. Methods: We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimer9s Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of β-amyloid 1−42 (Aβ 1–42 ) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of APOE genotype, CSF total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) and hippocampal volume on time to AD-type dementia using Cox proportional hazards models and on decline on the Mini-Mental State Examination (MMSE) using linear mixed models. Results: We included 110 subjects with MCI with abnormal CSF Aβ 1–42 and a mean MMSE score of 26.3 ± 2.8. During a mean follow-up of 2.2 ± 1.0 (range 0.4–5.0) years, 63 subjects (57%) progressed to AD-type dementia. Abnormal CSF t-tau (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1–4.6, p = 0.03) and CSF p-tau (HR 3.5, 95% CI 1.3–9.2, p = 0.01) concentration and hippocampal atrophy (HR 2.5, 95% CI 1.1–5.6, p = 0.02) predicted time to dementia. For subjects with both abnormal t-tau concentration and hippocampal atrophy, HR was 7.3 (95% CI 1.0–55.9, p = 0.06). Furthermore, abnormal CSF t-tau and p-tau concentrations and hippocampal atrophy predicted decline in MMSE score. Conclusions: In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline.

BackgroundPatients with knee osteoarthritis patients have problems with walking, and tend to walk slower. An important aim of knee arthroplasty is functional recovery, which should include a post-operative increase in walking speed. Still, there are several problems with measuring walking speed in groups of knee osteoarthritis patients. Nevertheless, test-retest reliability of walking speed measurements is high, and when the same investigators monitor the same subjects, it should be possible to assess the walking speed effects of knee arthroplasty. The present study reports a meta-analysis of these effects.MethodsA total of 16 independent pre-post arthroplasty comparisons of walking speed were identified through MEDLINE, Web of Science, and PEDro, in 12 papers, involving 419 patients.ResultsFor 0.5–5 months post-operatively, heterogeneity was too large to obtain a valid estimate of the overall effect-size. For 6–12 and 13–60 months post-operatively, heterogeneity was absent, low, or moderate (depending on estimated pre-post correlations). During these periods, subjects walked on average 0.8 standard-deviations faster than pre-operatively, which is a large effect. Meta-regression analysis revealed significant effects of time and time squared, suggesting initial improvement followed by decline.ConclusionThis meta-analysis revealed a large effect of arthroplasty on walking speed 6–60 months post-operatively. For the first 0.5–5 months, heterogeneity of effect-sizes precluded a valid estimate of short-term effects. Hence, patients may expect a considerable improvement of their walking speed, which, however, may take several months to occur. Meta-regression analysis suggested a small decline from 13 months post-operatively onwards.

Kempen JCE, de Groot V, Knol DL, Lankhorst GJ, Beckerman H. Self-reported fatigue and energy cost during walking are not related in patients with multiple sclerosis. Objectives To determine whether there is a relationship between self-reported fatigue and the energy cost of walking (ECw), and how self-reported fatigue and ECw relate to physical functioning in patients with multiple sclerosis (MS). Design Cross-sectional cohort study, using structural equation modeling. Setting Home environment and at a university medical center. Participants Patients (N=75) were obtained from a longitudinal study on outcome measurement and functional prognosis in early MS. Patients were included if they were able to walk for 6 minutes without being assisted by a person. The age range was between 28.0 and 69.7 years and the median Expanded Disability Status Scale was 2.5 (range, 1.0–6.5). Interventions Not applicable. Main Outcome Measures Self-reported fatigue was measured with the Fatigue Severity Scale, the vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and a visual analog scale. Physical functioning was determined with the physical functioning subscale of the SF-36, fast walking speed, and comfortable walking speed. The ECw (J·kg −1 ·m −1 ) was measured with the energy cost of the walking test. Results The relationship between ECw and latent variable fatigue had a β=−.188 ( P =.236), that between ECw and physical functioning (SF-36 physical functioning) had a β=−.344 ( P =.001), and that between fatigue and physical functioning had a β=−.448 ( P =.000). Conclusions Fatigue and ECw are not related in patients with MS with mild to moderate walking problems. ECw and fatigue are independent determinants of physical functioning.

PURPOSE To investigate the effectiveness of training in the use of closed-circuit television (CCTV) on reading performance in visually impaired patients. METHODS In a multicenter masked randomized controlled trial, 122 patients were randomized either to a treatment group that received usual delivery instructions from the CCTV supplier combined with concise outpatient standardized training, or to a control group that received delivery instructions only. The main outcome measure was reading performance, which was obtained by measuring reading acuity, reading speed, reading errors, column-tracking time, and technical reading, approximately two weeks after patients had received their CCTV and 3 months later. Videotapes of all measurements were rated by two investigators. Training effects were analyzed with linear mixed modeling. RESULTS There were no statistically significant differences in results between the treatment and control group. However, introducing a CCTV increased reading acuity (mean difference [MD] 0.93 logRAD; P < 0.01) and maximum reading speed (MD 15 wpm; P < 0.01), and decreased the number of errors (MD 0.33; P = 0.04), compared to reading without CCTV. Average reading speed (P = 0.05), number of errors (P = 0.04), and column-tracking time (P = 0.01) improved over time. CONCLUSIONS Prescribing a CCTV and the delivery instructions by the supplier seemed sufficient to improve reading performance. Additional training in the use of this device did not result in further improvement. Based on these results, outpatient low-vision rehabilitation centers may consider reallocating part of the training resources into other evidence-based rehabilitation programs. (trialregister.nl number, NTR1031.).

Background: To determine which short-term changes on clinical scales including the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg test (9HPT) and Guy’s Neurological Disability Scale (GNDS) are most predictive of long-term outcome of disability as rated by the EDSS in progressive multiple sclerosis (MS). Methods: From a longitudinal database, all progressive patients, both primary (PP) and secondary (SP), were selected on the basis of at least two complete examinations being available within a time interval of 1–2 years (short-term change). All patients who fulfilled the selection criteria were invited for a third visit after an interval of at least 3 years (long-term outcome). We used ordinal logistic regression to see which early changes were most predictive of the long-term EDSS. Results: 181 patients fulfilled the selection criteria. Early change on EDSS and T25FW were the best predictors of long-term EDSS; both were significant predictors in a ‘single predictor’ model. Early EDSS change was a slightly stronger single predictor (R2 0.38, Wald χ2 42.65, p < 0.001) compared with early T25FW change (R2 0.27, Wald χ2 12.35, p < 0.001). Adding early T25FW change to early EDSS change in a ‘combined predictor’ model improved prediction ( p = 0.036). Conclusion: Both early change on EDSS and T25FW predict long-term EDSS with comparable strength. Early change on T25FW adds significant independent information and improves the prediction model with early EDSS change only. Therefore we support the use of early T25FW examinations in future clinical trials in progressive MS.

Background: In many retrospective studies and large clinical trials, high‐resolution, good‐contrast 3DT1 images are unavailable, hampering detailed analysis of brain atrophy. Ventricular enlargement then provides a sensitive indirect measure of ongoing central brain atrophy. Validated automated methods are required that can reliably measure ventricular enlargement and are robust across magnetic resonance (MR) image types. Aim: To validate the automated method VIENA for measuring the percentage ventricular volume change (PVVC) between two scans. Materials and Methods: Accuracy was assessed using four image types, acquired in 15 elderly patients (five with Alzheimer's disease, five with mild cognitive impairment, and five cognitively normal elderly) and 58 patients with multiple sclerosis (MS), by comparing PVVC values from VIENA to manual outlining. Precision was assessed from data with three imaging time points per MS patient, by measuring the difference between the direct (one‐step) and indirect (two‐step) measurement of ventricular volume change between the first and last time points. The stringent concordance correlation coefficient (CCC) was used to quantify absolute agreement. Results: CCC of VIENA with manual measurement was 0.84, indicating good absolute agreement. The median absolute difference between two‐step and one‐step measurement with VIENA was 1.01%, while CCC was 0.98. Neither initial ventricular volume nor ventricular volume change affected performance of the method. Discussion: VIENA has good accuracy and good precision across four image types. VIENA therefore provides a useful fully automated method for measuring ventricular volume change in large datasets. Conclusion: VIENA is a robust, accurate, and precise method for measuring ventricular volume change. Hum Brain Mapp 35:1101–1110, 2014. © 2013 Wiley Periodicals, Inc.

BACKGROUND AND PURPOSE: Retinoblastoma may exhibit variable hyperintensities on DWI, resulting in different values in the ADC maps, depending on their histology and cellularity. However, EP-based DWI has susceptibility artifacts and image distortions, which make DWI of the orbit a challenging technique. The aim of this study was to investigate the feasibility of single-shot turbo spin-echo (HASTE) DWI in the evaluation of children with retinoblastoma and to assess the value of ADC maps in differentiating viable and necrotic tumor tissue. MATERIALS AND METHODS: Two radiologists assessed conventional MR images, DWI, and ADC maps of 17 patients with retinoblastoma (n = 17 eyes). Non-EP DWI was performed by using a HASTE sequence with b-values of 0 and 1000 s/mm(2). ADC values were measured for enhancing and nonenhancing tumor tissue. ADC maps were compared with histopathologic findings regarding tumor differentiation and viability. RESULTS: On DWI, vital tumor tissue showed hyperintensity with negligible intensity of surrounding vitreous. The difference in mean (range) ADC values between enhancing (1.03 [0.72–1.22] × 10(−3) mm(2) s(−1)) and nonenhancing (1.47 [0.99–1.80] × 10(−3) mm(2) s(−1)) parts of retinoblastoma was statistically significant (P < .0005). Nonenhancing tumor parts showed a significantly lower ADC compared with vitreous (2.67 [2.24–3.20]×10(−3) mm(2) s(−1)) (P < .0005) and subretinal fluid (2.20 [1.76–2.96] × 10(−3) mm(2) s(−1)) (P < .0005). Histopathologically, low ADC values (enhancing tumor part) correlated to viable tumor tissue, whereas intermediate ADC values (nonenhancing tumor parts) correlated to necrotic tumor tissue. CONCLUSIONS: HASTE DWI allowed adequate characterization of retinoblastoma, and ADC is a helpful tool to differentiate viable and necrotic tumor tissue and might be valuable in monitoring the response to eye-preserving therapies.

Introduction Technical developments and advances in medical knowledge mean that new measurement instruments are still appearing in all fields of medicine. Think about recent developments such as functional MRI and DNA microarrays. Furthermore, existing instruments are continuously being refined and existing technologies are being applied beyond their original domains. The current attention to patient-oriented medicine has shifted interest from pathophysiological measurements to impact on functioning, perceived health and quality of life (QOL). Patient-reported outcomes (PROs) have therefore gained importance in medical research. It is clear that the measurement instruments used in various medical disciplines differ greatly from each other. Therefore, it is evident that details of the development of measurement instruments must be specific to each discipline. However, from a methodological viewpoint, the basic steps in the development of all these measurement instruments are the same. Moreover, basic requirements with regard to measurement properties, which have to be considered in evaluating the adequacy of a new instrument, are similar for all measurement instruments. Chapters 3 and 4 are written from the viewpoint of developers of measurement instruments. When describing the different steps we have the development of PROs in mind. However, at various points in this chapter we will give examples to show analogies with other measurement instruments in medicine.

Introduction Systematic reviews are made for many different types of studies, such as randomized clinical trials (RCTs), observational studies and diagnostic studies. Researchers, doctors and policy-makers use the results and conclusions of systematic reviews for research purposes, development of guidelines, and evidence-based patient care and policy-making. It saves them a considerable amount of time in searching for literature, and reading and interpreting the relevant articles. For the same purposes, more and more systematic reviews of studies focusing on the measurement properties of measurement instruments are being published. The aim of such reviews is to find all the existing evidence of the properties of one or more measurement instruments, to evaluate the strength of this evidence, and come to a conclusion about the best instrument available for a particular purpose. They may also result in a recommendation for additional research.