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Background: Minimally important changes (MIC) in scores help interpret results from health status instruments. Various distribution-based and anchor-based approaches have been proposed to assess MIC. Objectives: To describe and apply a visual method, called the anchor-based MIC distribution method, which integrates both approaches. Method: Using an anchor, patients are categorized as persons with an important improvement, an important deterioration, or without important change. For these three groups the distribution of the change scores on the health status instrument are depicted in a graph. We present two cut-off points for an MIC: the ROC cut-off point and the 95% limit cut-off point. Results: We illustrate our anchor-based MIC distribution method determining the MIC for the Pain Intensity Numerical Rating Scale in patients with low back pain, using two conceivable definitions of minimal important change on the anchor. The graph shows the distribution of the scores of the health status instrument for the relevant categories on the anchor, and also the consequences of choosing the ROC cut-off point or the 95% limit cut-off point. Discussion: The anchor-based MIC distribution method provides a general framework, applicable to all kind of anchors. This method forces researchers to choose and justify their choice of an appropriate anchor and to define minimal importance on that anchor. The MIC is not an invariable characteristic of a measurement instrument, but may depend, among other things, on the perspective from which minimal importance is considered and the baseline values on the measurement instrument under study. A balance needs to be struck between the practicality of a single MIC value and the validity of a range of MIC values. © 2006 Springer Science+Business Media B.V.

Objective. To establish the impact of knee joint laxity on the relationship between muscle strength and functional ability in osteoarthritis (OA) of the knee. Methods. A cross-sectional study of 86 patients with OA of the knee was conducted. Tests were performed to determine varus-valgus laxity, muscle strength, and functional ability. Laxity was assessed using a device that measures the angular deviation of the knee in the frontal plane. Muscle strength was measured using a computer-driven isokinetic dynamometer. Functional ability was assessed by observation (100-meter walking test) and self report (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]). Regression analyses were performed to assess the impact of joint laxity on the relationship between muscle strength and functional ability. Results. In regression analyses, the interaction between muscle strength and joint laxity contributed to the variance in both walking time (P = 0.002) and WOMAC score (P = 0.080). The slope of the regression lines indicated that the relationship between muscle strength and functional ability (walking time, WOMAC) was stronger in patients with high knee joint laxity. Conclusion. Patients with knee OA and high knee joint laxity show a stronger relationship between muscle strength and functional ability than patients with OA and low knee joint laxity. Patients with OA, high knee joint laxity, and low muscle strength are most at risk of being disabled.

BACKGROUND: Low back pain is a common medical and social problem associated with disability and absence from work. Knowledge on effective return to work (RTW) interventions is scarce.OBJECTIVE: To determine the effectiveness of graded activity as part of a multistage RTW programme.DESIGN: Randomised controlled trial.SETTING: Occupational healthcare.SUBJECTS: 112 workers absent from work for more than eight weeks due to low back pain were randomised to either graded activity (n = 55) or usual care (n = 57).INTERVENTION: Graded activity, a physical exercise programme aimed at RTW based on operant-conditioning behavioural principles.MAIN OUTCOME MEASURES: The number of days off work until first RTW for more then 28 days, total number of days on sick leave during follow up, functional status, and severity of pain. Follow up was 26 weeks.RESULTS: Graded activity prolonged RTW. Median time until RTW was equal to the total number of days on sick leave and was 139 (IQR = 69) days in the graded activity group and 111 (IQR = 76) days in the usual care group (hazard ratio = 0.52, 95% CI 0.32 to 0.86). An interaction between a prior workplace intervention and graded activity, together with a delay in the start of the graded activity intervention, explained most of the delay in RTW (hazard ratio = 0.86, 95% CI 0.40 to 1.84 without prior intervention and 0.39, 95% CI 0.19 to 0.81 with prior intervention). Graded activity did not improve pain or functional status clinically significantly.CONCLUSIONS: Graded activity was not effective for any of the outcome measures. Different interventions combined can lead to a delay in RTW. Delay in referral to graded activity delays RTW. In implementing graded activity special attention should be paid to the structure and process of care.

Changes in scores on health status questionnaires are difficult to interpret. Several methods to determine minimally important changes (MICs) have been proposed which can broadly be divided in distribution-based and anchor-based methods. Comparisons of these methods have led to insight into essential differences between these approaches. Some authors have tried to come to a uniform measure for the MIC, such as 0.5 standard deviation and the value of one standard error of measurement (SEM). Others have emphasized the diversity of MIC values, depending on the type of anchor, the definition of minimal importance on the anchor, and characteristics of the disease under study. A closer look makes clear that some distribution-based methods have been merely focused on minimally detectable changes. For assessing minimally important changes, anchor-based methods are preferred, as they include a definition of what is minimally important. Acknowledging the distinction between minimally detectable and minimally important changes is useful, not only to avoid confusion among MIC methods, but also to gain information on two important benchmarks on the scale of a health status measurement instrument. Appreciating the distinction, it becomes possible to judge whether the minimally detectable change of a measurement instrument is sufficiently small to detect minimally important changes.

OBJECTIVES: Longitudinal growth and bone mass accumulation are two important phenomena during puberty, resulting in attainment of peak bone mass (PBM) and final height. They are thought to be under strong genetic control, with the vitamin D receptor (VDR) gene being among the candidate genes. Bone metabolism markers are reported to be good predictors of longitudinal growth and bone mass increase. The purpose of this longitudinal study was to evaluate whether bone metabolism markers predict bone mass and height increase differently according to Fok1 VDR genotype throughout puberty in healthy adolescents.PATIENTS AND MEASUREMENTS: At the start of the study 130 girls were aged 10.8 (range 8.5-12.8) years and 125 boys were aged 11.8 (range 9.4-14.6) years at the first visit. Markers of bone formation and bone resorption were measured at the first visit, as well as height and sitting height (SH), and bone mineral content (BMC) of the lumbar spine, femur, arm and total body. All measurements were repeated after 2 years.RESULTS: A higher BMC of the femur, distal arm and total body was found in ff boys at the first visit, which was not related to higher levels of bone metabolism markers in this group. In girls, no differences between genotypes were seen in BMC (increase). However, concentrations of markers of bone formation [alkaline phosphatase (AP), bone-specific alkaline phosphatase (BAP), procollagen aminoterminal propeptide (PINP)] and bone resorption [type I carboxyterminal telopeptide (ICTP)] were higher in ff girls. Regression coefficients between bone metabolism markers and bone mass increase differed according to genotype and sex. A similar pattern was found for height and SH (increase), the latter as a representative of growth of the axial skeleton, mainly consisting of cancellous bone.CONCLUSIONS: Our data suggest that the predicting capacities of bone metabolism markers on bone mass (increase), height and SH (increase) are genotype dependent. Their use as predictors of final height or PBM therefore remains questionable without knowing the genotype.

Purpose To investigate normal-appearing white (NAWM) and cortical gray (NAGM) matter separately in multiple sclerosis (MS) in vivo using diffusion tensor imaging (DTI). Materials and Methods In 64 MS patients (12 primary progressive [PP], 38 relapsing remitting [RR], 14 secondary progressive [SP]) and 20 healthy controls, whole-brain apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were acquired. A stimulated echo acquisition mode (STEAM) DTI sequence was used with minimal geometrical distortion in comparison to echo-planar imaging (EPI). NAWM and NAGM were identified using conventional magnetic resonance (MR) images, allowing a cautious assessment of FA in cortex. Results Histogram analyses showed significant global FA decreases and ADC increases in MS NAWM compared to control WM. MS cortical NAGM had no significant global ADC increase, but FA was decreased significantly. In regional analyses, nearly all NAWM regions-of-interest (ROIs) had significantly increased ADC compared to controls, but FA was not changed. In nearly all cortical NAGM ROIs, ADC was significantly increased and FA significantly reduced. In multiple linear regression analyses in RR/SPMS patients, NAGM-ADC histogram peak height was associated more strongly with clinical disability than T2 lesion load. Conclusion Tissue damage occurs in both NAWM and cortical NAGM. The cortical damage appears to have more clinical impact than T2 lesions. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

In order to better understand the large variation in cerebrospinal fluid (CSF) tau and amyloid-beta(1-42) (Abeta42) in frontotemporal lobar degeneration (FTLD), relations between these biomarkers and clinical parameters, neuroimaging characteristics, and apolipoprotein E (ApoE) genotype were studied in 31 patients with FTLD, including 16 patients with the frontal variant and 15 with the temporal variant. CSF tau was highest in FTLD with predominant temporal involvement. In the frontal subgroup, CSF tau level was influenced by the number of ApoE epsilon3 alleles. In the temporal subgroup, CSF tau level was dependent on a combination of CSF Abeta42, age, disease duration, and disease severity. No relation with degree of atrophy or asymmetry on neuroimaging could be established. CSF Abeta42 variability remained unexplained. Future research could study the role of ApoE genotype and Abeta42 in FTLD, as well as establish measures for disease intensity.

Background Back pain (including neck pain) is one of the most prevalent health problems for which physicians are consulted. Back pain can decrease the quality of life considerably during a great part of the lives of those who suffer from it. At the same time it has an enormous economic impact, mainly through sickness absence and long-term disability. The objective of this paper is to compare the incidence of occupational disability as a result of back and neck pain in 1980–1985 to 1999–2000 and to explain the findings. Methods A descriptive study was performed at population level of changes in incidence of occupational disability as a result of back and neck pain. Statistics from the National Institute of Social Insurance in the Netherlands are used to calculate age and gender specific incidence rates for back pain diagnoses based on the ICD-classification. Incidence rate ratios stratified according to gender and adjusted for age were calculated to indicate changes over time. Results The incidence of occupational disability as a result of back pain decreased significantly by 37% (95% CI 37%–38%) in men and with 21% (95% CI 20%–24%) in women, after adjustment for age. For overall occupational disability as a result of all diagnoses this was 18% (95% CI 18%–19%) and 34% (95% CI 33%–35%) respectively. Changes were not homogeneous over diagnostic subcategories and age groups. Spondylosis decreased most in men by 59% (95% CI 57%–61%). The incidence of non-specific back pain and neck pain increased most by 196% (95% CI 164%–215%). Post-laminectomy syndrome increased over all age categories both for men (85%, 95% CI 61%–113%) and women (113%, 95% CI 65%–179%). Conclusion The decrease in occupational disability as a result of back pain was larger than the decrease in occupational disability over all diagnoses. However, time trends were not homogeneous over age-, nor over sex- nor back pain categories. Most of this decrease was due to general changes such as legal and economic changes. One of several additional explanations for a decrease is the changed view on management of back pain.

Background Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist. Method An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist. Discussion Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase.

Objective: To describe the activities and participation of children with cerebral palsy and to examine the relationship with personal factors and disease characteristics. Design: Cross-sectional study. Setting: Department of Rehabilitation Medicine of a University Medical Center in The Netherlands. Subjects: One hundred and ten children: 70 boys, 40 girls, mean (SD) age 11 years and 3 months (20 months). Outcome measures: Activities and participation, described in the domains of mobility, self-care, domestic life, social life and communication, measured with the Gross Motor Function Measure, the Pediatric Evaluation of Disability Inventory and the Vineland Adaptive Behavior Scales. Results: Multiple linear regression models showed that the Gross Motor Function Classification System (GMFCS) was strongly associated with mobility (explained variance 87-92%), self-care and domestic life. Apart from the GMFCS, cognitive impairment and limb distribution were less important but also significantly associated with self-care and domestic life (explained variance 65-81%). Cognitive impairment and epilepsy were the most important factors associated with social life and communication (explained variance 54-75%). Conclusion: Activities and participation can, to a large extent, be explained by only a few associated factors.

Background: Information on prognostic factors for duration of sick leave due to low-back pain (LBP) is growing. In this prospective cohort study prognostic factors for duration of sick leave and course of disability were identified in a very early stage of sick leave due to LBP in an occupational health care setting. Methods: A total of 615 workers calling in sick from work due to LBP at an occupational health service (OHS) of one institution completed a questionnaire. Duration of follow-up was 26 weeks. Prognostic factors were identified by means of Cox regression analysis and multiple linear regression analysis, and explained variance was calculated. Results: Median time to first return to work (RTW) was 5 days (Inter Quartile Range (IQR) = 2–12). Median time to lasting return to work (LRTW) was 6 days (IQR = 3–13). The final model for delayed RTW included self-reported expected duration of sick-leave, treatment by GP or specialist, care-seeking, diminished mobility, and the interaction between care-seeking and diminished mobility. The final model for LRTW included: self-reported expected duration of sick-leave, treatment by GP or specialist, care-seeking, the interaction between the self-reported expected duration of sick-leave and seeking care at OHS, complaints due to job stress, diminished mobility, and the interactions between expected duration of more then 10 days and seeking OP care and diminished mobility. Median total days on sick leave (TDSL) was 6 days (IQR = 3–13 days). The final model for TDSL included: age, expected duration of sick leave, treatment by GP or medical specialist, seeking OP care, complaints due to physical load, and diminished mobility. Explained variance (R 2) of these models ranged from 30 to 35%. Conclusions: Poor prognosis for duration of sick leave can be identified by means of a simple questionnaire administered on the first day of sick leave. Workers at high risk for longer duration of sick leave (all outcomes) expected to stay off work longer, were already being treated by a MD, sought OP care, and had diminished mobility. In case of delayed LRTW workers reported job stress as a possible cause of sick leave. Interactions were found in both RTW and LRTW between care-seeking and diminished mobility and in LRTW between expected duration of sick leave and seeking OP care. Older age increased TDSL with borderline significance.

Raloxifene is a selective estrogen receptor modulator that may delay the onset of mild cognitive impairment in elderly women. Effects of raloxifene treatment on mental performance in males remain to be investigated. In a previous functional magnetic resonance imaging (fMRI) study, we showed that raloxifene treatment enhanced brain activation in elderly males during encoding of new information (faces) into memory. The current study used fMRI in the same group of subjects to screen for effects of raloxifene treatment on brain function during face recognition. Healthy elderly males (n = 28; mean age 63.6 years, SD 2.4) were scanned at baseline and after 3 months of treatment with either raloxifene 120 mg (n = 14) or placebo (n = 14) in a randomized, double-blind, placebo-controlled study design. Functional data were analyzed in an event-related fashion with respect to correct hits and correct rejections using FSL software. Performance data were analyzed with respect to recognition accuracy, latency, and response bias. Functional effects of treatment were found on brain activation related to correct hits only. When compared to placebo treatment, raloxifene treatment enhanced brain activation in the left posterior parahippocampal area (Z = 3.9) and right inferior prefrontal cortex (Z = 3.5). Recognition accuracy scores remained stable in the raloxifene group, whereas the placebo group showed a small but significant decrease in accuracy scores (p = 0.02). No significant effects were found on response bias or latency. In conclusion, raloxifene treatment affects brain function during memory performance in a way that may reflect increased arousal during initial encoding, with downstream effects on brain function during retrieval of information. Behaviorally, such neurofunctional effects may actively block decreased memory performance as a result of context-dependency. The validity of these predictions can be tested in large-scale clinical trials.

BACKGROUND: Using cerebral microdialysis, baseline values for energy-related chemical markers have been reported in awake patients. Radionuclide studies have demonstrated a locally decreased metabolism, thought to be the result of brain retraction. These baseline values, however, may not be applicable to patients after surgical aneurysm repair following a subarachnoid hemorrhage (SAH). We assessed metabolic chemical marker levels in World Federation of Neurological Surgeons Committee (WFNS) grade I SAH patients after aneurysm surgery and compared them with previously reported baseline values.METHODS: In 5 WFNS grade I SAH patients, energy-related chemical marker levels were obtained using microdialysis in the area of brain retraction after aneurysm surgery. In addition, an [(18)F]2-deoxy-d-glucose positron emission tomography (FDG-PET) was performed.RESULTS: The FDG-PET showed a decrease of glucose metabolism in the frontotemporal area. Comparing the mean values for chemical markers of this study with reported baseline values, the most striking difference was a mild decrease of pyruvate and an increase of the lactate/pyruvate ratio. In individual patients, some markers indicated possible ischemia. A consistent pattern or ischemic profile for all markers, however, was not found.CONCLUSION: FDG-PET scanning confirmed postoperative metabolic changes found in previous studies. Mean interstitial chemical marker levels ranged from normal to mildly deviant compared with reference chemical marker levels for awake patients and are likely to be applicable in SAH patients after aneurysm repair.

Introduction: Vertebral deformities are a common consequence of osteoporosis and are known to decrease quality of life. The Qualeffo-41 is a quality-of-life questionnaire especially developed for measuring quality of life in patients with vertebral deformities. It consists of 41 questions arranged in five domains: pain, physical function, social function, general health perception, and mental function. The objectives of this study were: (1) to develop a shorter version of the Qualeffo-41 by removing redundant questions; and (2) to investigate the scale characteristics, reliability, and validity of this shorter version. Methods: The study was performed using data from the Qualeffo validation study and the Multiple Outcomes of Raloxifene Evaluation (MORE) study. The analyses were performed in patients with vertebral deformities (n=579). Factor analysis on polychoric correlations and an item response theory (IRT) model, i.e., the generalized partial credit model (GPCM), were used to create a shorter version of Qualeffo-41. Using GPCM, scoring weights were computed for all items. Results: Three items were removed from the data set because of too many missing values. Factor analysis identified three instead of five domains: (1) pain, (2) physical function, and (3) mental function. Five items had factor loadings

Purpose: To determine whether interdisciplinary team care, using the Rehabilitation Activities Profile (RAP) as a team tool, results in a better rehabilitation outcome. Method: A multilevel prospective cohort study, with a controlled before and after design. Eighteen rehabilitation teams in eight rehabilitation centres in the Netherlands and Belgium participated. Based on the level of implementation of the RAP, we compared three study groups. Consecutive adult patients (n = 933) with stroke, amputation of the lower limb, spinal cord injury, multiple sclerosis, or other neuromuscular disorders, were followed during inpatient or outpatient rehabilitation. Main outcome measures were Barthel Index, RAP-CPM (sum score of the domains communication, personal care and mobility), Nottingham Health Profile (NHP), length of rehabilitation (LOR) and discharge destination (home vs elsewhere). Results: Overall results show that scores on the Barthel Index, the RAP-CPM and the NHP improved, on average, by 18.4%, 12.7%, and 6.7%, respectively. However, treatment from a rehabilitation team that uses the RAP was associated with a significantly lower Barthel score, and small, non-significant effects on the RAP-CPM and the NHP. Partial use of the RAP resulted in non-significant, lower scores on these measures. With respect to discharge destination and LOR, there were also no significant differences between the three study groups, with the exception of a shorter outpatient rehabilitation period for the group in which partial use was made of the RAP. Conclusion: The RAP, at the current level of implementation, does not improve rehabilitation outcome.

AIMS: To study occurrence and effectiveness of ergonomic interventions on return-to-work applied for workers with low back pain (LBP).METHODS: A multinational cohort of 1631 workers fully sicklisted 3-4 months due to LBP (ICD-9 codes 721, 722, 724) was recruited from sickness benefit claimants databases in Denmark, Germany, Israel, Sweden, the Netherlands, and the United States. Medical, ergonomic, and other interventions, working status, and return-to-work were measured using questionnaires and interviews at three months, one and two years after the start of sickleave. Main outcome measure was time to return-to-work. Cox's proportional hazards model was used to calculate hazard ratios regarding the time to return-to-work, adjusted for prognostic factors.RESULTS: Ergonomic interventions varied considerably in occurrence between the national cohorts: 23.4% (mean) of the participants reported adaptation of the workplace, ranging from 15.0% to 30.5%. Adaptation of job tasks and adaptation of working hours was applied for 44.8% (range 41.0-59.2%) and 46.0% (range 19.9-62.9%) of the participants, respectively. Adaptation of the workplace was effective on return-to-work rate with an adjusted hazard ratio (HR) of 1.47 (95% CI 1.25 to 1.72; p < 0.0001). Adaptation of job tasks and adaptation of working hours were effective on return-to-work after a period of more than 200 days of sickleave with an adjusted HR of 1.78 (95% CI 1.42 to 2.23; p < 0.0001) and 1.41 (95% CI 1.13 to 1.76; p = 0.002), respectively.CONCLUSIONS: Results suggest that ergonomic interventions are effective on return-to-work of workers long term sicklisted due to LBP.

Objective: Measurement properties of questionnaires should be based on samples of populations on whom these measurements will be used. The purpose of this study is to establish an evidence based recommendation regarding the use of functional status questionnaires in patients following a lumbar disc surgery by a direct comparison of the reproducibility and responsiveness. Study Design and Setting: The measurement properties of six functional status questionnaires were assessed: 1) Roland-Morris Disability Questionnaire (RDQ-24), 2) Modified Roland-Morris Disability Questionnaire (MRDQ), 3) short Roland-Morris Disability Questionnaire (RM-18), 4) Physical Functioning scale, 5) Role Limitations-Physical scale of the SF-36, and 6) The Main Complaint (MC). Subjects (n 97) that still suffered residual complaints 6 weeks following a lumbar disc surgery completed the questionnaires before and 3 months after treatment. In a direct comparison the A) The test-retest reproducibility (Intraclass Correlation Coefficients [ICC] and the Standard Error of Measurement [SEM]) and B) 3 parameters of responsiveness (Minimal Detectable Change [MDC], Standardised Response Mean [SRM], and the Area Under the receiver operator characteristic Curve [AUC]) were assessed. Results: This study suggests the superiority of the 3 versions of the RDQ compared to the 3 other questionnaires. Comparing the 3 versions of the RDQ reveals no substantial differences thereby indicating that the 2 modified version of the RDQ hold no better measurement properties in this specific population. Conclusion: The use of the RDQ-24 for this specific post-surgery population is suggested. The optimal cut-off point of the RDQ-24 that minimizes the overall classification error was found to be 3.5 with a sensitivity of 94.6% and a specificity of 88.2%. 2004 Elsevier

Aims: To examine the dimensionality, internal consistency, and construct validity of a new physical workload questionnaire in employees with musculoskeletal complaints. Methods: Factor analysis was applied to the responses in three study populations with musculoskeletal disorders (n = 406, 300, and 557) on 26 items related to physical workload. The internal consistency of the resulting subscales was examined. It was hypothesised that physical workload would vary among different occupational groups. The occupations of all subjects were classified into four groups on the basis of expected workload (heavy physical load; long lasting postures and repetitive movements; both; no physical load). Construct validity of the subscales created was tested by comparing the subscale scores among these occupational groups. Results: The pattern of the factor loadings of items was almost identical for the three study populations. Two interpretable factors were found: items related to heavy physical workload loaded highly on the first factor, and items related to static postures or repetitive work loaded highly on the second factor. The first constructed subscale “heavy physical work” had a Cronbach’s α of 0.92 to 0.93 and the second subscale “long lasting postures and repetitive movements”, of 0.86 to 0.87. Six of eight hypotheses regarding the construct validity of the subscales were confirmed. Conclusions: The results support the internal structure, internal consistency, and validity of the new physical workload questionnaire. Testing this questionnaire in non-symptomatic employees and comparing its performance with objective assessments of physical workload are important next steps in the validation process.

Background and Purpose— The Motor Activity Log (MAL) is a semistructured interview for hemiparetic stroke patients to assess the use of their paretic arm and hand (amount of use [AOU]) and quality of movement [QOM]) during activities of daily living. Scores range from 0 to 5. The following clinimetric properties of the MAL were quantified: internal consistency (Cronbach α), test-retest agreement (Bland and Altman method), cross-sectional construct validity (correlation between AOU and QOM and with the Action Research Arm [ARA] test), longitudinal construct validity (correlation of change on the MAL during the intervention with a global change rating [GCR] and with change on the ARA), and responsiveness (effect size). Methods— Two baseline measurements 2 weeks apart and 1 follow-up measurement immediately after 2 weeks of intensive exercise therapy either with or without immobilization of the unimpaired arm (forced use) were performed in 56 chronic stroke patients. Results— Internal consistency was high (AOU: α=0.88; QOM: α=0.91). The limits of agreement were −0.70 to 0.85 and −0.61 to 0.71 for AOU and QOM, respectively. The correlation with the ARA score (Spearman ρ) was 0.63 (AOU and QOM). However, the improvement on the MAL during the intervention was only weakly related to the GCR and to the improvement on the ARA, Spearman ρ was between 0.16 and 0.22. The responsiveness ratio was 1.9 (AOU) and 2.0 (QOM). Conclusion— The MAL is internally consistent and relatively stable in chronic stroke patients not undergoing an intervention. The cross-sectional construct validity of the MAL is reasonable, but the results raise doubt about its longitudinal construct validity.

Osteopontin (OPN) has been identified as the most prominent cytokine-encoding gene expressed within multiple sclerosis (MS) lesions. Recently, we demonstrated that OPN plasma levels were elevated in active relapsing-remitting (RR) MS patients. In this longitudinal study, a trend was observed for OPN serum levels in relation to clinical exacerbations. Moreover, OPN protein levels were significantly elevated 1 month prior to increase of gadolinium (Gd)-enhancing lesion number, whereas no relation was observed between OPN levels and increase in Gd-enhancing lesion volume. Although no robust relation between OPN and disease activity was observed, these data suggest that OPN levels are elevated prior to increased disease activity in RR MS patients. © 2004 Elsevier B.V. All rights reserved. Chemicals / CAS: gadolinium, 7440-54-2; osteopontin, 106441-73-0; Cytokines; Osteopontin, 106441-73-0; SPP1 protein, human; Sialoglycoproteins

Objective. In previous studies, cranial electrostimulation (CES) had positive effects on sleep in depressed patients and in patients with vascular dementia. The present study examined the effects of low-frequency CES on the rest-activity rhythm and cortisol levels of patients with probable Alzheimer's disease (AD). Method. It was hypothesised that a decreased level of cortisol would parallel a positive effect of low-frequency CES on nocturnal restlessness. Sixteen AD patients were randomly assigned to an experimental group (n = 8) or a control group (n = 8). The experimental group was treated with CES, whereas the control group received sham stimulation, for 30 minutes a day, during 6 weeks. The rest-activity rhythm was assessed by actigraphy. Cortisol was measured repeatedly in the saliva throughout the day by means of salivette tubes. Results. Low-frequency CES did not improve the rest-activity rhythm in AD patients. Moreover, both groups showed an increase instead of a decrease in the level of cortisol. Conclusions: These preliminary results suggest that low-frequency CES has no positive effect on the rest-activity rhythm in AD patients. An alternative research design with high-frequency CES in AD is discussed. © 2003, SAGE Publications. All rights reserved.

Multiple sclerosis (MS) is a chronic disease of presumed autoimmune origin with a considerable polygenic influence. We have previously observed that a specific allele combination in genes of the interleukin-1 (IL-1) family influenced the progression rate in MS. We have considerably expanded our patient population (492 MS patients and 228 controls). In the present study, we investigated the role of the IL- 1A - 889, IL-1B - 511, IL-1B+3953 and IL-1RN VNTR gene polymorphisms in MS. In addition, we performed preliminary analyses on longitudinal magnetic resonance imaging (MRI) data. We found no associations between the polymorphisms and susceptibility to MS or clinical features. In addition, we observed no significant effect of the polymorphisms on brain or lesion volumes, Based on our data and those from the literature, one can conclude that there is currently no evidence to support a role for the IL-1 genes in MS.

Background It has been hypothesized (i) that pain and low vitality lead to an increase in avoidance of activities in persons with early symptomatic knee osteoarthritis (OA), and (ii) that avoidance of activities leads to an increase in activity limitations. Objectives The present study aimed to evaluate these hypotheses in a cross-sectional and longitudinal design. Methods Baseline, 2-year and 5-year follow-up data of 828 participants from the Cohort Hip and Cohort Knee (CHECK) study with early symptomatic knee OA were used. Knee pain, vitality, avoidance of activities and activity limitations were measured with reliable and validated instruments. Regression and autoregressive generalized estimating equations (GEE) models analyzed the cross-sectional and longitudinal associations between pain, vitality, avoidance of activities and activity limitations. The models were adjusted for age, gender, education level, body-mass index, comorbidity, and radiographic severity. Results (i) In cross-sectional analyses, greater knee pain and lower vitality were associated with higher levels of avoidance of activities. In longitudinal analyses, pain and vitality predicted a subsequent increase in avoidance of activities. (ii) In cross-sectional analyses, a higher level of avoidance of activities was associated with greater activity limitations. In longitudinal analyses, this relationship was marginally significant. Conclusions Knee pain and low vitality lead to a subsequent increase in avoidance of activities, already at an early stage of knee OA. Avoidance of activities is related to activity limitations: alternative measurement instruments and a longer follow-up may be required to establish the longitudinal relationship. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1194

Background Muscle weakness has been hypothesized as being an important factor in the development of activity limitations in knee osteoarthritis (OA). Longitudinal evidence to support this hypothesis is scarce in early knee OA. The direct association between change in muscle strength and change in activity limitations following exercise therapy in established knee OA was studied in randomized controlled trials 1–2 . These studies provided conflicting results. Objectives The aims of the study were: 1) to determine whether a decrease in muscle strength over three years is associated with an increase in activity limitations; and 2) to examine whether the longitudinal association between muscle strength and activity limitations is moderated by knee joint proprioception and laxity in early symptomatic knee OA. Methods A longitudinal cohort study with three-year follow-up. Subjects (N=146) with early symptomatic knee OA from the CHECK study. Measurements were performed at the second (T0) and fifth (T1) year of the Cohort Hip and Cohort Knee (CHECK) study. Muscle strength, proprioception and laxity were assessed using specifically designed measurement devices. Self-reported and performance-based activity limitations were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the get-up-and-go test, walk-test and stair-climb test. Statistical analyses included paired t- tests, Chi-square tests and regression analyses. In regression analyses, the association between muscle strength and activity limitations was adjusted for relative confounders. Results Overall, small 3-year changes in muscle strength and activity limitations were observed. A 3-year decrease in muscle strength was independently associated with an increase in performance-based activity limitations, on three measures. Proprioception and laxity did not moderate this association. Conclusions In patients with early knee OA, a decrease in muscle strength is associated with an increase in activity limitations. Our results are a step forward in understanding the role of muscle weakness in the development of activity limitations in knee OA. To establish the causal role of muscle weakness in activity limitations, further well-designed experimental studies are indicated. References Fitzgerald GK, White DK, Piva SR. Associations for change in physical and psychological factors and treatment response following exercise in knee osteoarthritis: an exploratory study. Arthritis Care Res (Hoboken). 2012;64(11):1673-80. Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients. Arch Phys Med Rehabil 2011;92(8):1185-93. Acknowledgements CHECK is funded by the Dutch Arthritis Association. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5026

Background We previously identified 5 clinically relevant phenotypes from a heterogeneous knee OA population (Osteoarthritis Initiative [OAI] cohort), which needs to be replicated for validation. Objectives The present study aims to replicate this phenotype identification for validation in a clinical setting using data from the Amsterdam Osteoarthritis (AMS-OA) cohort. Methods K-means clustering analysis was performed in 374 knee OA patients from the AMS-OA cohort, using 4 clinically relevant and easily obtainable patient characteristics or clustering variables: radiographic severity (Kellgren/Lawrence [K/L] grade), body mass index (BMI), upper leg muscle strength, and depression (from Hospital Anxiety and Depression Scale [HADS] questionnaire). The cluster solution with the highest Pseudo F value was considered the most adequate number of clusters or phenotypes in the dataset. This solution was compared with the original study. Results The most adequate number of phenotypes was 5, similar as in the original study. Moreover, the 5 identified phenotypes represented in general similar phenotypes compared to the original study, namely a “minimal joint disease phenotype”, a “strong muscle phenotype”, a “non-obese weak muscle phenotype” (although obesity was more prevalent compared to the original study), an “obese weak muscle phenotype”, and a “depressive phenotype” (although depression was less prevalent compared to the original study). Conclusions The identification of phenotypes from the OAI cohort could be replicated, except for two minor differences that are presumably attributable to differences in study population. The phenotype identification seems therefore a valid finding, with phenotypes possibly representing different etiological subtypes of knee OA in which phenotype-specific interventions may be needed. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3277

Doel Het ontwikkelen van een predictieregel om patiënten te identificeren die een hoog risico lopen op het ontwikkelen van werkverzuim langer dan 6 maanden door lage rugpijn. Methode Secundaire data-analyse in een cohort van 628 werknemers die 3 tot 6 weken verzuimen van het werk vanwege lage rugpijn. We onderzochten de relatie tussen een breed scala aan prognostische factoren, zoals: demografische, werk-, rugpijn- en psychosociaal gerelateerde factoren op werkverzuim langer dan 6 maanden. Relaties werden onderzocht door gebruik te maken van Cox regressie overlevingsanalyse en backward selectietechnieken (achterwaartse stapsgewijze regressie). Daarnaast werd een predictieregel ontwikkeld. Variabele en modelselectie en de kwaliteit van de predictieregel werden bepaald met behulp van bootstrappingtechnieken. Ook werden de testeigenschappen van de klinische predictieregel onderzocht. Resultaten Matige tot slechte arbeidstevredenheid, een hogere score op vermijdingsgedrag, een hogere pijnintensiteit, een langere klachtenduur en van het vrouwelijke geslacht zijn, waren gerelateerd aan een hoger risico op werkverzuim langer dan 6 maanden. De prestatie van de predictieregel liet zien dat de index voor discriminatie (c-index) en kalibratie (slope) respectievelijk 0,63 en 0,90 waren. De testeigenschappen van de regel voor verschillende afkapwaarden van risicoscores voor sensitiviteit, specificiteit, positief en negatief voorspellende waarden waren redelijk. Conclusie Onze predictieregel kan gebruikt worden door bedrijfsartsen en bedrijfsfysiotherapeuten om patiënten te identificeren die een hoog risico lopen op langdurig verzuim.

In this article, the authors investigated the effect of maternal smoking during pregnancy on behavioral problems, which were not mediated by lower birth weight, in offspring at 3 y of age. The authors used the Child Behavior Checklist for ages 2-3 y (CBCL/2-3; Achenbach, Edelbrock and Howell) to assess behavioral problems in 1,377 2- to 3-y-old healthy twin pairs. Soon after the birth of twins, the authors collected pre- and perinatal information, including smoking habits of the mother during pregnancy. The question "Did you smoke during pregnancy?" could be answered by choosing one of three possible options: (1) never, (2) sometimes, or (3) regularly. The authors analyzed the effect of maternal smoking on the Child Behavioral Checklist total score and on several subscale scores for first- and second-born twins separately, and they adjusted for the possible confounding effects of birth weight, socioeconomic status, maternal age, and having been breast- or bottle-fed. There was a significant effect of maternal smoking on so-called externalizing behavior problems (oppositional, aggressive, overactive), but not on internalizing behavior problems (withdrawn, depressed, anxious), in both first- and second-born twins. The authors primarily attributed the enhanced externalizing problems to increased aggression. Although boys had higher externalizing (and aggression) scores than girls, the effect of maternal smoking was the same for boys and girls. The authors also discuss whether maternal smoking causes externalizing behavior problems.

Background Radiographic damage is one of the key outcomes for research in rheumatoid arthritis (RA). The optimal method to read radiographs, i.e. blind or unblind to sequence, is unknown. Sequence-blinded reading may be less efficient, but unblinded reading may cause bias. Objectives This study evaluated the difference between blinded and unblinded sequence reading in a series of radiographs with 11 years follow up. In addition, the influence of the starting point of the series was evaluated. Methods Two experienced readers independently and repeatedly read digitized radiographs of 62 patients at time points 0, 2, 5, 8 and 11 years of follow-up from the COBRA follow-up database according to the Sharp/van der Heijde method (SvH). These films were selected based on quality and distribution of damage progression (results from previous readings) to optimally represent low or high damage at baseline, and low or high damage progression. Readers were aware of the study question, but unaware of the number of repeated readings; the order of the films was randomized for every repeated reading. A statistical linear mixed model was fitted to the data, including all main effects and all first order interactions between method of reading, length of a series (2-3 years or 8-9 years), incorporation of baseline, baseline damage, progression, time point, as well as two second order interactions. Efficiency was calculated with standard errors (SE) of progression rates between unblinded (1) and blinded (2) reading as: (SE 1 /SE 2 ) 2 . Results In this dataset mean yearly progression rate (averaged over all iterations) was 3,1. Compared to blinded sequence reading, unblinded reading resulted in a slightly but significantly increased progression rate of 0.43 points per year (p=0.008) and a lower standard error of the mean total progression rate of 0.67 (compared to 0.77 for blinded reading). Over 11 years, this results in a small difference in progression of about 5 points, but a highly relevant difference of 25% of patients needed in a study to find a difference in radiological outcome between treatment groups. Sensitivity analyses in the subset of short series that more closely resembles trial datasets (follow up 2-3 years) reveals a range of 10-55% increased efficiency for unblinded vs blinded reading. Knowledge of the baseline radiograph influences the results of the other readings. When the baseline radiograph is read, the estimation of the progression rate is significantly higher (2 points per year, p Conclusions Unless the assessment of repair is the aim of the study, unblinded reading of radiographs should be preferred above blinded reading, due to the high similarity of the numerical results even over a long follow up period, but decreased variability around the estimation of the progression rate. Increased efficiency translates into smaller sample sizes, or increased power to detect small differences. In addition, unblinded reading more closely resembles the routine clinical situation. For studies with long term follow up the same two readers should read all radiographs including baseline. Disclosure of Interest None Declared

Clinicians are interested in observer variation in terms of the probability of other raters (interobserver) or themselves (intraobserver) obtaining the same answer. Cohen's κ is commonly used in the medical literature to express such agreement in categorical outcomes. The value of Cohen's κ, however, is not sufficiently informative because it is a relative measure, while the clinician's question of observer variation calls for an absolute measure. Using an example in which the observed agreement and κ lead to different conclusions, we illustrate that percentage agreement is an absolute measure (a measure of agreement) and that κ is a relative measure (a measure of reliability). For the data to be useful for clinicians, measures of agreement should be used. The proportion of specific agreement, expressing the agreement separately for the positive and the negative ratings, is the most appropriate measure for conveying the relevant information in a 2 × 2 table and is most informative for clinicians.

Objectives To investigate the effectiveness of the Stay@Work Participatory Ergonomics program (PE) aimed at prevention of low back pain (LBP) and neck pain (NP). Methods Departments were randomly allocated to either the intervention (PE) or control group (no PE). During a 6-h meeting, working groups composed and prioritised ergonomic measures aimed at preventing LBP and NP. Subsequently, working groups were requested to implement the prioritised ergonomic measures in their departments. Data was collected using questionnaires at baseline, and after 3, 6, 9, and 12 months of follow-up. The primary outcomes were LBP and NP prevalence; secondary outcomes were pain intensity and duration. Additionally, the course of LBP and NP (transitions from no symptoms to symptoms as well as from symptoms to no symptoms) was modelled. Results Randomisation resulted in 19 intervention departments (n=1472 workers) and 18 control departments (n=1575 workers). After 12 months the intervention was neither more effective than the control group in reducing the prevalence of LBP and NP nor in reducing pain intensity and pain duration. PE did not increase the probability of preventing LBP (OR 1.23; 95% CI 0.97 to 1.57) or NP (1.01; 0.74 to 1.40). However, PE significantly increased the probability of recovering from LBP (1.41; 1.01 to 1.96), but not from NP (0.95; 0.72 to 1.26). Conclusions PE did not reduce LBP and NP prevalence, pain intensity and pain duration, and was neither effective in preventing LBP and NP nor in recovering from NP. However, PE was more effective in recovering from LBP.

Background The number and volume of abnormalities on baseline brain magnetic resonance images in patients with initial findings suggestive of multiple sclerosis are known to predict outcome in terms of disability. However, no long-term data exist on specific locations or types of lesions. Objective To assess the long-term predictive value of baseline magnetic resonance imaging parameters, including location of lesions and gadolinium-enhancing and hypointense lesions in patients with initial findings suggestive of multiple sclerosis for the occurrence of clinically relevant disability as defined by an Expanded Disability Status Scale score of 3. Patients After a median follow-up period of 8.7 years, the medical records of 42 patients were reviewed and assessed for time until patients received an Expanded Disability Status Scale score of 3. Magnetic resonance imaging parameters were dichotomized according to maximum accuracy and then used to calculate hazard ratios using the Cox model for proportional hazard ratios. Results Conversion to clinically definite multiple sclerosis was observed in 26 patients (62%), of whom 14 (54%) progressed to an Expanded Disability Status Scale score of 3. Two or more infratentorial lesions best predicted long-term disability (hazard ratio, 6.3). Gadolinium-enhancing and hypointense T1-weighted lesions did not show prognostic value. Conclusion Infratentorial lesions are related to long-term prognosis for patients with initial findings suggestive of multiple sclerosis and thus may help to identify patients at high risk for earlier occurrence of clinically relevant disability.

Cattell suggested constructing scales on the basis of components analysis by assigning weights 1 to variables with high positive loadings on the components and -1 to variables with high negative loadings on the components. This strategy is compared with other strategies of scale construction, which assign weights 1 or -1 to variables with high weights for the components. The latter strategies appear to yield scales which have higher correlations with the corresponding component scores and lower correlations among them, but also are less homogeneous then scales constructed by the former strategy. It is concluded that the former strategy, which is very popular among practitioners, can continue to be used if homogeneity of scales is preferred to orthogonality of scales.

An algorithm is presented for the best least-squares fitting correlation matrix approximating a given missing value or improper correlation matrix. The proposed algorithm is based upon a solution for Mosier's oblique Procrustes rotation problem offered by ten Berge and Nevels. A necessary and sufficient condition is given for a solution to yield the unique global minimum of the least-squares function. Empirical verification of the condition indicates that the occurrence of non-optimal solutions with the proposed algorithm is very unlikely. A possible drawback of the optimal solution is that it is a singular matrix of necessity. In cases where singularity is undesirable, one may impose the additional nonsingularity constraint that the smallest eigenvalue of the solution be δ, where δ is an arbitrary small positive constant. Finally, it may be desirable to weight the squared errors of estimation differentially. A generalized solution is derived which satisfies the additional nonsingularity constraint and also allows for weighting. The generalized solution can readily be obtained from the standard “unweighted singular” solution by transforming the observed improper correlation matrix in a suitable way.

The aim of this study was to examine the school functioning of 8- to 18-year-old children born after in vitro fertilization (IVF). We compared 233 children born after IVF to 233 matched control children born spontaneously from parents with fertility problems on measures of education level, general cognitive ability, school performance (need for extra help, repeating a grade, special education), and rates of learning and developmental disorders. No differences were found between IVF and control children on these measures of school functioning. More than 60% of adolescents at secondary school attended high academic levels (with access to high school or university). We conclude that children and adolescents born after IVF show good academic achievement and general cognitive ability. They do not experience any more educational limitations than the naturally conceived children and adolescents of the control group. The tendency of reassuring school functioning already found in younger IVF children has been shown to continue at secondary school age. © 2008 The Author(s).

Methods for orthogonal Procrustes rotation and orthogonal rotation to a maximal sum of inner products are examined for the case when the matrices involved have different numbers of columns. An inner product solution offered by Cliff is generalized to the case of more than two matrices. A nonrandom start for a Procrustes solution suggested by Green and Gower is shown to give better results than a random start. The Green-Gower Procrustes solution (with nonrandom start) is generalized to the case of more than two matrices. Simulation studies indicate that both the generalized inner product solution and the generalized Procrustes solution tend to attain their global optima within acceptable computation times. A simple procedure is offered for approximating simple structure for the rotated matrices without affecting either the Procrustes or the inner product criterion.

Background: Worldwide, millions of people are suffering from dementia and this number is rising. An index of quality of life (QoL) can describe the impact a disease or treatment has on a person's wellbeing. QoL comprises many variables, including physical health and function, and mental health and function. QoL is related to masticatory ability and physical activity. Animal studies show that disruption of mastication due to loss of teeth or a soft diet leads to memory loss and learning problems. Since these are common complaints in dementia, it is hypothesized that improvement of masticatory function and normalization of diet consistency can increase QoL in elderly persons suffering from dementia. Therefore, the goal of the present study is to examine whether an increase in masticatory activity, achieved by increased food consistency and enhancement of masticatory function through improved oral health care has a positive effect on QoL, including cognition, mood, activities of daily living (ADL), and circadian rhythm in elderly persons with dementia.Methods and design: The described study is a prospective longitudinal matched cluster randomized single-blind multicenter study. Participants are elderly persons living in the Netherlands, suffering from dementia and receiving psychogeriatric care. An intervention group will receive improved oral health care and a diet of increased consistency. A control group receives care as usual. Participants will be assessed four times; outcome variables besides QoL are cognition, mood, independence, rest-activity rhythm, blood pressure, and masticatory function.Discussion: This research protocol investigates the effect of an intervention executed by daily caregivers. The intervention will increase masticatory activity, which is achieved by three different actions, (providing oral health care, increasing food consistency, or a combination of both). There is a certain amount of variety in the nature of the interventions due to local differences in nursing homes. This might be a scientific weakness in the study design; however, a practical implementation of any findings will be subject to the same factors, making this study design clinically relevant.Trial registration: NTR1561. © 2013 Weijenberg et al.; licensee BioMed Central Ltd.