Clinical phenotypes in patients with knee osteoarthritis: a study in the Amsterdam osteoarthritis cohort.

OBJECTIVE: To identify and validate previously established phenotypes of knee osteoarthritis (OA) based on similarities in clinical patient characteristics. METHODS: Knee OA patients (N = 551) from the Amsterdam OA (AMS-OA) cohort provided data. Four clinical patient characteristics were assessed: upper leg muscle strength, body mass index (BMI), radiographic severity (Kellgren/Lawrence [KL] grade), and depressive mood (the Hospital Anxiety and Depression Scale [HADS] questionnaire). Cluster analysis was performed to identify the optimal number of phenotypes. Differences in clinical characteristics between the phenotypes were analyzed with ANOVA. RESULTS: Cluster analysis identified five phenotypes of knee OA patients: "minimal joint disease phenotype", "strong muscle strength phenotype", "severe radiographic OA phenotype", "obese phenotype", and "depressive mood phenotype". CONCLUSIONS: Among patients with knee OA, five phenotypes were identified based on four clinical characteristics. To a high degree, the results are a replication of earlier findings in the OA Initiative, indicating that these five phenotypes seem a stable, valid, and clinically relevant finding.

What drives MRI-measured cortical atrophy in multiple sclerosis?

BACKGROUND: Cortical atrophy, assessed with magnetic resonance imaging (MRI), is an important outcome measure in multiple sclerosis (MS) studies. However, the underlying histopathology of cortical volume measures is unknown. OBJECTIVE: We investigated the histopathological substrate of MRI-measured cortical volume in MS using combined post-mortem imaging and histopathology. METHODS: MS brain donors underwent post-mortem whole-brain in-situ MRI imaging. After MRI, tissue blocks were systematically sampled from the superior and inferior frontal gyrus, anterior cingulate gyrus, inferior parietal lobule, and superior temporal gyrus. Histopathological markers included neuronal, axonal, synapse, astrocyte, dendrite, myelin, and oligodendrocyte densities. Matched cortical volumes from the aforementioned anatomical regions were measured on the MRI, and used as outcomes in a nested prediction model. RESULTS: Forty-five tissue blocks were sampled from 11 MS brain donors. Mean age at death was 68±12 years, post-mortem interval 4±1 hours, and disease duration 35±15 years. MRI-measured regional cortical volumes varied depending on anatomical region. Neuronal density, neuronal size, and axonal density were significant predictors of GM volume. CONCLUSIONS: In patients with long-standing disease, neuronal and axonal pathology are the predominant pathological substrates of MRI-measured cortical volume in chronic MS.

Longitudinal changes and seasonal variations in serum 25-hydroxyvitamin D levels in different age groups: results of the Longitudinal Aging Study Amsterdam.

UNLABELLED: Vitamin D levels remained fairly stable during ageing with increasing levels in persons aged 55-65 years old and decreasing levels in persons aged 65-88 years old. The seasonal variation was larger than the longitudinal change. Our findings implicate that vitamin D supplementation becomes more important in older age groups and during wintertime. INTRODUCTION: Longitudinal changes in serum 25-hydroxyvitamin D (25-OHD) levels during aging have not been studied extensively. Two studies showed increasing serum 25-OHD levels. One of these studies suggested that there might be decreasing levels in persons aged 65 years and older. The objectives of the current study are the following: (1) to examine longitudinal changes in serum 25-OHD levels in different age groups and (2) to describe the seasonal variation in different age groups. METHODS: Data of the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study, were used. Two different cohorts were included: (1) younger cohort: aged 55-65 years old at baseline, n = 738, follow-up of 6 years and (2) older cohort: aged 65-88 years old at baseline, n = 1,320, follow-up of 13 years. RESULTS: At baseline, average levels were 56.5 nmol/L in the younger cohort and 51.1 nmol/L in the older cohort. In the younger cohort, a longitudinal increase in the mean serum 25-OHD levels of 4 nmol/L in 6 years was observed; in the older cohort, a longitudinal decrease in the mean serum 25-OHD levels of 4 nmol/L in 13 years was observed. The seasonal variation was ±12 nmol/L in the younger cohort and ±7 nmol/L in the older cohort. CONCLUSIONS: Long-term serum 25-OHD levels remained fairly stable during aging with slightly increasing levels in persons aged 55-65 years old and slightly decreasing levels in persons aged 65-88 years old. On average, the seasonal variation was larger than the longitudinal change. Our findings implicate that vitamin D supplementation becomes more important in older age groups and during wintertime.

Mediators of physical exercise for improvement in cancer survivors' quality of life.

OBJECTIVE: Mediating mechanisms of a 12-week group-based exercise intervention on cancer survivors' quality of life (QoL) were examined to inform future exercise intervention development. METHODS: Two hundred nine cancer survivors ≥ 3 months posttreatment (57% breast cancer) aged 49.5 (± 10.4) years were assigned to physical exercise (n = 147) or wait-list control (n = 62). QoL, fatigue, emotional distress, physical activity, general self-efficacy and mastery were assessed at baseline and post-intervention using questionnaires. Path analysis was conducted using Mplus to explore whether improved physical activity, general self-efficacy and mastery mediated the effects of exercise on fatigue and distress and consequently QoL. RESULTS: The intervention was associated with increased physical activity (ß = 0.46, 95% confidence interval (CI) = 0.14;0.59), general self-efficacy (ß = 2.41, 95%CI = 0.35;4.73), and mastery (ß = 1.75, 95%CI = 0.36;2.78). Further, the intervention had both a direct effect on fatigue (ß = -1.09, 95%CI = -2.12;0.01), and an indirect effect (ß = -0.54, 95%CI = -1.00;-0.21) via physical activity (ß = -0.29, 95%CI = -0.64;-0.07) and general self-efficacy (ß = -0.25, 95%CI = -0.61;-0.05). The intervention had a borderline significant direct effect on reduced distress (ß = -1.32, 95%CI = -2.68;0.11), and a significant indirect effect via increased general self-efficacy and mastery (ß = -1.06, 95%CI = -1.89;-0.38). Reductions in fatigue (ß = -1.33, 95%CI =-1.85;-0.83) and distress (ß = -0.86, 95%CI = -1.25;-0.52) were associated with improved QoL. Further, increased physical activity was directly associated with improved QoL (ß = 3.37, 95%CI = 1.01;5.54). CONCLUSION: The beneficial effect of group-based physical exercise on QoL was mediated by increased physical activity, general self-efficacy and mastery, and subsequent reductions in fatigue and distress. In addition to physical activity, future interventions should target self-efficacy and mastery. This may lead to reduced distress and fatigue, and consequently improved QoL of cancer survivors.

A personalised eHealth programme reduces the duration until return to work after gynaecological surgery: results of a multicentre randomised trial.

OBJECTIVE: To evaluate the effectiveness of an eHealth intervention on recovery and return to work, after gynaecological surgery. DESIGN: Randomised multicentre trial that ran from March 2010 until September 2011. SETTING: Secondary care in seven general and university hospitals in The Netherlands. POPULATION: A cohort of 215 women (aged 18-65 years) who had a hysterectomy and/or laparoscopic adnexal surgery for a benign indication. METHODS: The women were randomly assigned to the intervention group (n = 110) or the control group (n = 105). The intervention group received an eHealth programme that provided personalised tailor-made pre- and postoperative instructions on the resumption of daily activities, including work, and tools to improve self-empowerment and to identify recovery problems. The control group was provided with access to a control website. MAIN OUTCOME MEASURES: The primary outcome was the duration of sick leave until a full sustainable return to work. Secondary outcome measures were quality of life, general recovery, and pain intensity. RESULTS: In intention-to-treat analysis the eHealth intervention was effective on time to return to work (hazard ratio 1.43; 95% confidence interval 1.003-2.040; P = 0.048). The median duration of sick leave until a full sustainable return to work was 39 days (interquartile range 20-67 days) in the intervention group and 48 days (interquartile range 21-69 days) in the control group. After 26 weeks pain intensity was lower (visual analogue scale, cumulative odds ratio 1.84; 95% confidence interval 1.04-3.25; P = 0.035) and quality of life was higher (Rand-36 health survey, between-group difference 30, 95% confidence interval 4-57; P = 0.024) in the intervention group, compared with the control group. CONCLUSIONS: The use of the eHealth intervention by women after gynaecological surgery results in a faster return to work, with a higher quality of life and less pain.

Measurement properties of the Client-centered Care Questionnaire (CCCQ): factor structure, reliability and validity of a questionnaire to assess self-reported client-centeredness of home care services in a population of frail, older people.

BACKGROUND: The increasing and specific use of home care services by frail, older people asks for the evaluation of the client-centeredness of these services. To our knowledge, no instrument that measures client-centeredness of home care from this group's unique perspective exists. We therefore tested the factor structure, reliability, content validity and acceptability of the Client-centered Care Questionnaire (CCCQ), an existing instrument developed for general home care users, in a population of frail, older people in the Netherlands. METHODS: We used data from a 2-year clinical trial. STUDY POPULATION: frail, older people who received home care. Data were collected at baseline (n = 600) and 24-month measurements (n = 389); retest data (n = 67) were collected 7-14 days after the 24-month measurements. ANALYSES: We performed confirmatory factor analysis, investigated reliability and validity parameters and assessed acceptability. RESULTS: The factor analysis yielded a bifactor model with essential unidimensionality. Internal consistency was high (omega total .88). We found a test-retest reliability of total test scores of .81; the standard error of measurement was 2.61 (total score range 15-75) and the limits of agreement were -7.03 and 7.86. We rejected three out of four hypotheses for construct validity. CONCLUSIONS: The CCCQ is sufficiently unidimensional to permit the use of total test scores. We found acceptable reliability values, but considered our results on construct validity inconclusive. Respondents found the CCCQ questions challenging to answer, which is indicative of a high degree of respondent burden. Future instruments that measure client-centeredness of home care from the frail, older client's perspective should therefore be tailored to the specific circumstances of this population.

The assessment of publication pressure in medical science; validity and reliability of a Publication Pressure Questionnaire (PPQ).

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The PPQ seems a valid and reliable instrument to measure publication pressure among medical scientists.

The association between reduced knee joint proprioception and medial meniscal abnormalities using MRI in knee osteoarthritis: results from the Amsterdam osteoarthritis cohort.

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 2.9° ± 1.9°. 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.

Optimizing parameter choice for FSL-Brain Extraction Tool (BET) on 3D T1 images in multiple sclerosis.

BACKGROUND: Brain atrophy studies often use FSL-BET (Brain Extraction Tool) as the first step of image processing. Default BET does not always give satisfactory results on 3DT1 MR images, which negatively impacts atrophy measurements. Finding the right alternative BET settings can be a difficult and time-consuming task, which can introduce unwanted variability. AIM: To systematically analyze the performance of BET in images of MS patients by varying its parameters and options combinations, and quantitatively comparing its results to a manual gold standard. METHODS: Images from 159 MS patients were selected from different MAGNIMS consortium centers, and 16 different 3DT1 acquisition protocols at 1.5 T or 3T. Before running BET, one of three pre-processing pipelines was applied: (1) no pre-processing, (2) removal of neck slices, or (3) additional N3 inhomogeneity correction. Then BET was applied, systematically varying the fractional intensity threshold (the "f" parameter) and with either one of the main BET options ("B" - bias field correction and neck cleanup, "R" - robust brain center estimation, or "S" - eye and optic nerve cleanup) or none. For comparison, intracranial cavity masks were manually created for all image volumes. FSL-FAST (FMRIB's Automated Segmentation Tool) tissue-type segmentation was run on all BET output images and on the image volumes masked with the manual intracranial cavity masks (thus creating the gold-standard tissue masks). The resulting brain tissue masks were quantitatively compared to the gold standard using Dice overlap coefficient (DOC). Normalized brain volumes (NBV) were calculated with SIENAX. NBV values obtained using for SIENAX other BET settings than default were compared to gold standard NBV with the paired t-test. RESULTS: The parameter/preprocessing/options combinations resulted in 20,988 BET runs. The median DOC for default BET (f=0.5, g=0) was 0.913 (range 0.321-0.977) across all 159 native scans. For all acquisition protocols, brain extraction was substantially improved for lower values of "f" than the default value. Using native images, optimum BET performance was observed for f=0.2 with option "B", giving median DOC=0.979 (range 0.867-0.994). Using neck removal before BET, optimum BET performance was observed for f=0.1 with option "B", giving median DOC 0.983 (range 0.844-0.996). Using the above BET-options for SIENAX instead of default, the NBV values obtained from images after neck removal with f=0.1 and option "B" did not differ statistically from NBV values obtained with gold-standard. CONCLUSION: Although default BET performs reasonably well on most 3DT1 images of MS patients, the performance can be improved substantially. The removal of the neck slices, either externally or within BET, has a marked positive effect on the brain extraction quality. BET option "B" with f=0.1 after removal of the neck slices seems to work best for all acquisition protocols.

Proxy measurements in multiple sclerosis: agreement on different patient-reported outcome scales.

BACKGROUND: Patient-reported outcome (PRO) scales are often used in multiple sclerosis (MS) research. Full understanding of items can be influenced by disease worsening, mood disturbances and cognitive problems of the MS patient. Earlier research with the Multiple Sclerosis Impact Scale (MSIS-29) showed that proxy respondents (i.e. partners of patients) can provide useful information. OBJECTIVE: To determine agreement between patients and proxy respondents on different MS PRO scales. METHODS: 139 Patients and partners completed the MSIS-29 (Physical and Psychological scale), Multiple Sclerosis Walking Scale (MSWS-12), Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) and Guy's Neurological Disability Scale (GNDS). We calculated the mean difference and intra-class correlation coefficients (ICC) on scale level and weighted kappas (κ(w)) on item level. RESULTS: On all scales, except MSNQ, the partner score was higher. ICCs were good for MSWS, GNDS and MSIS Physical, and moderate for MSNQ and MSIS Psychological. κ(w) was excellent for MSWS items, fair to good for GNDS, MSIS Physical and MSIS Psychological items, and poor for MSNQ items. CONCLUSION: Partners of patients with MS can be a useful source of information for several PRO scales, especially when the focus is on physical functioning. For psychological functioning this seems to be less reliable.

Sunlight exposure or vitamin D supplementation for vitamin D-deficient non-western immigrants: a randomized clinical trial.

UNLABELLED: Vitamin D deficiency is very common in non-western immigrants. In this randomized clinical trial, vitamin D 800 IU/day or 100,000 IU/3 months were compared with advised sunlight exposure. Vitamin D supplementation was more effective than advised sunlight exposure in improving vitamin D status and lowering parathyroid hormone levels. INTRODUCTION: Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 25 nmol/l) is common among non-western immigrants. It can be treated with vitamin D supplementation or sunlight exposure. METHODS: To determine whether the effect of vitamin D(3) supplementation (daily 800 IU or 100,000 IU/3 months) or sunlight exposure advice is similar with regard to serum 25(OH)D and parathyroid hormone (PTH) concentrations. Randomized clinical trial in 11 general practices in The Netherlands. Non-western immigrants, aged 18-65 years (n = 232) and serum 25(OH)D < 25 nmol/l were randomly assigned to supplementation (daily 800 IU or 100,000 IU/3 months) or advice for sunlight exposure for 6 months (March-September). Blood samples were collected at baseline, during treatment (3 months, 6 months), and at follow-up (12 months). Statistical analysis was performed with multilevel regression modelling. RESULTS: The intention-to-treat analysis included 211 persons. Baseline serum 25(OH)D was 22.5 ± 11.1 nmol/l. After 6 months, mean serum 25(OH)D increased to 53 nmol/l with 800 IU/day, to 50.5 nmol/l with 100,000 IU/3 months, and to 29.1 nmol/l with advised sunlight exposure (supplementation vs sunshine p < 0.001). Serum PTH decreased significantly in all groups after 3 months, more in the supplementation groups than in the advised sunlight group (p < 0.05). There was no significant effect on physical performance and functional limitations. CONCLUSION: Vitamin D supplementation is more effective than advised sunlight exposure for treating vitamin D deficiency in non-western immigrants.

Factor structure of Guy's Neurological Disability Scale in a sample of Dutch patients with multiple sclerosis.

BACKGROUND: Guy's Neurological Disability Scale (GNDS) is designed to assess disability (i.e. activity limitations) in patients with multiple sclerosis. It contains 12 functional domains, each indicating a level of disability. Four domain scores and a total score can be calculated. OBJECTIVE: The aim of this study was to evaluate the structural validity of the GNDS in a Dutch population who were definitely diagnosed as having multiple sclerosis. METHODS: Data of 974 patients were available. The structural validity of the GNDS was evaluated by confirmatory item factor analysis (CIFA). Two first-order models and two bifactor models were investigated. RESULTS: The best fitted model was a bifactor model with a general factor underlying all items, and 10 items loading on 3 group factors. Cronbach's alpha on the general factor (0.78) and on the group factor spinal-plus (0.74) were satisfying. Cronbach's alpha on the group factors mental (0.56) and bulbar (0.48) were low. Reliability based on CIFA was 0.85. CONCLUSION: Results showed a clear factor structure of the GNDS. It justifies the use of the total score of the GNDS. In addition, three sub-scale scores could be used.

Community walking can be assessed using a 10-metre timed walk test.

BACKGROUND: A decline in mobility is a common feature of multiple sclerosis (MS). Community walking scales are used to categorize patients in their ability to move independently. The first purpose of this study was to determine which specific gait speed corresponded with the categories of the Modified Functional Walking Categories (MFWC). The second purpose was to determine the Minimally Important Change (MIC) in absolute gait speed using the MFWC and Expanded Disability Status Scale (EDSS) as external criteria. METHOD: MS patients were measured six times in 6 years. Gait velocity was measured with the 10-metre timed walk test (10-m TWT), the severity of MS was determined with the EDSS, and community walking was assessed with the MFWC. For each category of the MFWC, Receiver Operating Characteristic (ROC) curves were used to find the best possible cut-off point on the 10-m TWT. The MIC in absolute gait speed was determined using a change of one category on the MFWC or one point on the EDSS. RESULTS: A strong relationship was found between gait speed and the MFWC; all areas under the ROC curves (AUCs) were between 0.74 and 0.86. The MIC in absolute gait speed could not be determined, because the AUCs were below the threshold of 0.70 and changes in gait speed were small. CONCLUSIONS: Gait speed is related to community walking, but an MIC in absolute gait speed could not be determined using a minimally important change on the MFWC or the EDSS as external criteria.

Lesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis.

Magnetization transfer ratio (MTR) is a sensitive parameter to quantify the integrity of myelinated white matter in patients with multiple sclerosis. Lesional MTR decreases in the acute phase due to demyelination, and subsequently shows recovery depending on the degree of remyelination in the absence of axonal loss. Recovery of average lesion MTR therefore might prove a viable outcome measure to assess the effect of remyelinating agents. Our objective was to determine the required sample size for phase II multicentre clinical trials using the recovery of average lesion MTR as primary outcome measure. With 7-monthly MRI scans, the MTR evolution of 349 new enhancing lesions before and after enhancement was assessed in 32 MS patients from 5 centres. Multilevel models were fitted to the data yielding estimates for the variance components, which were applied in power calculations. Sample sizes were determined for placebo-controlled, multicentre trials using lesional MTR recovery post-enhancement as primary outcome measure. Average lesion MTR decreased slightly in the build-up to enhancement, decreased dramatically during enhancement and showed recovery in the period after cessation. The power calculations showed that for a power of 80%, approximately 136 patients per trial (mean number of 6 lesions per patient) are required to detect a 30% increase in lesional MTR post-enhancement compared with placebo, whereas 48 subjects are required to detect a 50% increase in lesional MTR compared with placebo. Recovery of lesion MTR is a feasible outcome measure for future multicentre clinical trials measuring the effect of remyelinating agents.

Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis.

INTRODUCTION: Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure. METHODS: One hundred thirty-five relapsing-remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline. RESULTS: A significant atrophy occurred over 6 months (PBVC = -0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population. CONCLUSION: Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power.

Does patient feedback improve the consultation skills of general practice trainees? A controlled trial.

CONTEXT: This study aimed to assess if an additional patient feedback training programme leads to better consultation skills in general practice trainees (GPTs) than regular communication skills training, and whether process measurements (intensity of participation in the programme) predict the effect of the intervention. METHODS: We carried out a controlled trial in which two sub-cohorts of GPTs were allocated to an intervention group (n = 23) or a control group (n = 30), respectively. In 2006, allocated first-year GPTs in the VU University Medical Centre attended a patient feedback training programme in addition to the regular communication skills training. The control group attended only regular communication skills training. Trainees were assessed by simulated patients who visited the practices and videotaped the consultations at baseline and after 3 months. The videotapes were randomly assigned to eight trained staff members. The MAAS-Global Instrument (range 0-6) was used to assess (a change in) trainee consultation skills. RESULTS: were analysed using a multi-level, linear mixed-model analysis. Results Data on 50 GPTs were available for the follow-up analysis. Both intervention group and control group GPTs improved their consultation skills: mean MAAS-Global scores for all participants were 3.29 (standard deviation [SD] 0.75) at baseline and 3.54 (SD 0.66) at follow-up (P = 0.047). The improvement in MAAS-Global scores in the intervention group did not differ significantly from the improvement in the control group. The analysis showed a trend for intensity of participation in the patient feedback programme to predict greater improvement in MAAS-Global scores. DISCUSSION: Although the baseline scores were already in the high range, consultation skills in both groups improved significantly. This is reassuring for current teaching methods. The patient feedback programme did not improve consultation skills more than regular communication skills training. However, a subgroup of GPTs who participated intensively in the programme did improve their consultation skills further in comparison with the less motivated subgroup.

Information processing, attention and visual-motor function of adolescents born after in vitro fertilization compared with spontaneous conception.

BACKGROUND: Adverse conditions during prenatal life are associated with changes in physical and mental functioning in later life, as shown in children born preterm or small for gestational age. While recently in IVF children cardiometabolic differences have been demonstrated, there might also be risks for disturbance in cognitive functions. Therefore, this study examined information processing, attention and visual-motor function in pubertal IVF children compared with spontaneously conceived controls from subfertile parents. Results of these cognitive functions were then related to cardiometabolic measures to explore whether both can be explained by changes in fetal programming due to IVF. METHODS: A total of 139 IVF and 143 control adolescents underwent various neuropsychological tests to measure information processing, attention and visual-motor function. The results were then related to data on blood pressure and glucose levels previously obtained from the same groups. RESULTS: No differences between IVF and control adolescents were found in the various test results for information processing and attention. A slight difference was found between the groups for motor speed, but these scores were within the normal range for the test. No direct relation was found between cognitive measures and cardiometabolic outcome. CONCLUSIONS: Comparison of IVF adolescents and controls revealed no disturbances in information processing, attention and visual-motor function. In addition, these cognitive functions were not directly related to cardiometabolic outcome. Therefore, these results do not support the hypothesis that cognition is influenced by IVF conception or an altered programming of metabolic systems due to IVF, and indicate that cognitive abilities in IVF children, as measured by the tasks assessed, appear to develop normally.

White matter hyperintensities and medial temporal lobe atrophy in clinical subtypes of mild cognitive impairment: the DESCRIPA study.

BACKGROUND: Clinical subtypes of mild cognitive impairment (MCI) may represent different underlying aetiologies. METHODS: This European, multicentre, memory clinic based study (DESCRIPA) of non-demented subjects investigated whether MCI subtypes have different brain correlates on MRI and whether the relation between subtypes and brain pathology is modified by age. Using visual rating scales, medial temporal lobe atrophy (MTA) (0-4) and white matter hyperintensities (WMH) (0-30) were assessed. RESULTS: Severity of MTA differed between MCI subtypes (p<0.001), increasing from a mean of 0.8 (SD 0.7) in subjective complaints (n = 77) to 1.3 (0.8) in non-amnestic MCI (n = 93), and from 1.4 (0.9) in single domain amnestic MCI (n = 70) to 1.7 (0.9) in multiple domain amnestic MCI (n = 89). The association between MCI subtype and MTA was modified by age and mainly present in subjects >70 years of age. Severity of WMH did not differ between MCI subtypes (p = 0.21). However, the combination of MTA and WMH differed between MCI subtypes (p = 0.02) CONCLUSION: We conclude that MCI subtypes may have different brain substrates, especially in older subjects. Isolated MTA was mainly associated with amnestic MCI subtypes, suggesting AD as the underlying cause. In non-amnestic MCI, the relatively higher prevalence of MTA in combination with WMH may suggest a different pathophysiological origin.

A search for new MRI criteria for dissemination in space in subjects with a clinically isolated syndrome.

The International Panel on the Diagnosis of Multiple Sclerosis (MS) incorporated the Barkhof/Tintoré (B/T) magnetic resonance criteria into their diagnostic scheme to provide evidence of dissemination in space of central nervous system lesions, a prerequisite for diagnosing MS in patients who present with clinically isolated syndromes (CIS). Although specific for MS, the B/T criteria were criticised for their low sensitivity and relative complexity in clinical use. We used lesion characteristics at onset from 349 CIS patients in logistic regression and recursive partitioning modelling in a search for simpler and more sensitive criteria, while maintaining current specificity. The resulting models, all based on the presence of periventricular and deep white matter lesions, performed roughly in agreement with the B/T criteria, but were unable to provide higher diagnostic accuracy based on information from a single scan. Apparently, findings from contrast-enhanced and follow-up magnetic resonance scans are needed to improve the diagnostic algorithm.

Lack of interferon-beta bioactivity is associated with the occurrence of relapses in multiple sclerosis.

BACKGROUND: Treatment failure to Interferon-beta (IFNbeta) in multiple sclerosis (MS) can only partly be explained by anti-IFNbeta neutralising antibodies (NAb). Myxovirus resistance protein A (MxA) mRNA, reflecting IFNbeta bioactivity, is studied as an alternative biomarker for IFNbeta therapy response. Although absent IFNbeta bioactivity is associated with NAb and NAb are associated with reduced drug efficacy, the direct relationship between IFNbeta bioactivity and clinical disease activity is largely unknown. METHODS: We enrolled 126 consecutive relapsing-remitting MS patients on IFNbeta treatment. MxA mRNA expression was assessed 4 h after IFNbeta injection. Biological response status was determined after 3 months, by combined measurement of MxA mRNA expression and induction (MxA mRNA expression after/before IFNbeta injection). Patients were considered biological non-responders when both MxA mRNA expression and MxA mRNA induction were negative. RESULTS: Biological non-responders showed a significantly higher annualised relapse rate and smaller proportion relapse-free patients compared with biological responders (relapse rate 0.81 vs. 0.37; proportion relapse free 37% vs. 67%). CONCLUSIONS: Our results suggest that a lack of IFNbeta bioactivity is associated with the occurrence of relapses and therefore can be useful as a biomarker for unresponsiveness to IFNbeta.