Testosterone, free testosterone, and free androgen index in women: Reference intervals, biological variation, and diagnostic value in polycystic ovary syndrome.

OBJECTIVE: The objective of our study was to determine reference intervals and biologic variation for testosterone (T), free testosterone (fT), and free androgen index (FAI) in women with accurate methods and to test the discriminative value of these parameters in a polycystic ovary syndrome (PCOS)-population. METHODS: Serum was obtained daily during a normal menstrual cycle from 25 healthy women (677 data-points). A single serum sample was obtained from 44 PCOS-patients. T was measured by LC­MS/MS and by Architect® 2nd generation T Immunoassay. Sex hormone-binding globulin was measured to calculate fT and FAI. Results: Reference intervals which were established in healthy women with an ovulatory menstrual cycle were T = 0.3-1.6 nmol/L and 0.5-2.0 nmol/L, fT = 5.2-26 pmol/L and 7.2-33 pmol/L, and FAI = 0.4-2.9 and 0.6-4.4, by LC-MS/MS and immunoassay, respectively. T, fT and FAI were higher in PCOS patients than in controls (p b 0.0001). The areas under the curve of receiver operator characteristic (ROC) plots were not different for T, fT, or FAI when T was measured by LC­MS/MS versus immunoassay based on prediction of PCOS. FAI and fT were the strongest predictors of PCOS. CONCLUSIONS: When based upon the appropriate reference intervals and ROC analysis, LC-MS/MS and second generation immunoassay have equivalent clinical utility for the diagnosis of PCOS.

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.

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.

Diffusion-weighted imaging of the head and neck in healthy subjects: reproducibility of ADC values in different MRI systems and repeat sessions.

BACKGROUND AND PURPOSE: DWI is typically performed with EPI sequences in single-center studies. The purpose of this study was to determine the reproducibility of ADC values in the head and neck region in healthy subjects. In addition, the reproducibility of ADC values in different tissues was assessed to identify the most suitable reference tissue. MATERIALS AND METHODS: We prospectively studied 7 healthy subjects, with EPI and TSE sequences, on 5 MR imaging systems at 3 time points in 2 institutions. ADC maps of EPI (with 2 b-values and 6 b-values) and TSE sequences were compared. Mean ADC values for different tissues (submandibular gland, sternocleidomastoid muscle, spinal cord, subdigastric lymph node, and tonsil) were used to evaluate intra- and intersubject, intersystem, and intersequence variability by using a linear mixed model. RESULTS: On 97% of images, a region of interest could be placed on the spinal cord, compared with 87% in the tonsil. ADC values derived from EPI-DWI with 2 b-values and calculated EPI-DWI with 2 b-values extracted from EPI-DWI with 6 b-values did not differ significantly. The standard error of ADC measurement was the smallest for the tonsil and spinal cord (standard error of measurement = 151.2 × 10(-6) mm/s(2) and 190.1 × 10(-6) mm/s(2), respectively). The intersystem difference for mean ADC values and the influence of the MR imaging system on ADC values among the subjects were statistically significant (P < .001). The mean difference among examinations was negligible (ie, <10 × 10(-6) mm/s(2)). CONCLUSIONS: In this study, the spinal cord was the most appropriate reference tissue and EPI-DWI with 6 b-values was the most reproducible sequence. ADC values were more precise if subjects were measured on the same MR imaging system and with the same sequence. ADC values differed significantly between MR imaging systems and sequences.

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.

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.

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.

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.

Cytoreductive surgery and HIPEC for peritoneal metastases combined with curative treatment of colorectal liver metastases: Systematic review of all literature and meta-analysis of observational studies.

OBJECTIVE: Assess the overall outcome in colorectal cancer (CRC) patients that present with a combination of peritoneal metastases (PM) and liver metastases (CRLM) after curative resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the current literature. METHODS: A systematic literature search according to the PRISMA guidelines was conducted using the PubMed database of the U.S. National library of Medicine using the keywords: colorectal cancer, liver metastasis, extra-hepatic, peritoneal metastases, peritoneal carcinomatosis, cytoreductive surgery (CRS), HIPEC and combinations hereof. Papers focussing on CRS and HIPEC for PM combined with curative treatment of CRLM were included, provided sufficient information on survival outcomes could be extracted. Duplicate publications were excluded. Meta-analysis was performed using the method described by Tierney et al. RESULTS: After screening and full-text assessment of 39 papers, six articles were included containing data on combined PM and CRLM in patients treated with curative resection of both sites and HIPEC or early postoperative intraperitoneal chemotherapy (EPIC). Three articles provided enough statistical information for meta-analysis. Pooled hazard ratio (HR) was extracted from survival curves and was 1.24 (CI 0.96-1.60). A comparison was made with patients presenting with isolated PM undergoing CRS and HIPEC and with patients with disseminated disease undergoing (modern) systemic chemotherapy. CONCLUSIONS: In the absence of randomized controlled studies, we found in this systematic review and meta-analysis of patients with a combination of colorectal metastases in the liver as well as in the peritoneum show a trend towards a lower overall survival after curative resection and HIPEC, when compared to patients with isolated peritoneal metastases after CRS and HIPEC (pooled HR1.24, CI 0.96-1.60). However, patients with metastatic CRC show a tendency towards increased median overall survival after CRS and HIPEC combined with resection of liver metastases when compared to treatment with modern systemic chemotherapy.

Retinoblastoma: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis.

BACKGROUND AND PURPOSE: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features. MATERIALS AND METHODS: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2-70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ(5min) and κ(17min), respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1. RESULTS: The median value of κ(5min) was 1.28 (range, 0.87-2.07) and correlated positively with MVD (P = .008). The median value of κ(17min) was 1.33 (range, 0.35-3.08) and correlated negatively with tumor necrosis (P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ(5min) and 0.91 for κ(17min). CONCLUSIONS: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

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.

Diffusion-weighted MR imaging in head and neck cancer: comparison between half-fourier acquired single-shot turbo spin-echo and EPI techniques.

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

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.

The predictive value of 3D time-of-flight MR angiography in assessment of brain arteriovenous malformation obliteration after radiosurgery.

BACKGROUND AND PURPOSE: The purpose of radiosurgery of bAVMs is complete angiographic obliteration of its nidus. We assessed the diagnostic accuracy of 1.5T T2-weighted MR imaging and TOF-MRA images for detecting nidus obliteration after radiosurgery. MATERIALS AND METHODS: The pre- and postradiosurgery MR images and DSA images from 120 patients who were radiosurgically treated for a bAVM were re-evaluated by 2 observers for patency of the nidus (preradiosurgery) and obliteration (postradiosurgery: final follow-up MR imaging), by using a 3-point scale of confidence. Consensus reading of the DSA after radiosurgery was considered the criterion standard for obliteration. Sensitivity, specificity, PPVs, and NPVs, and overall diagnostic performance by using ROC were determined. RESULTS: Mean bAVM volume during radiosurgery was 3.4 mL (95% CI, 2.6-4.3 mL). Sixty-six patients (55%) had undergone previous endovascular embolization. The mean intervals between radiosurgery and follow-up MR imaging and for DSA, respectively, were 35.6 months (95% CI, 32.3-38.9 months) and 42.1 months (95% CI, 40.3-44.0 months). With ROC, an area under curve of 0.81-0.83 was found. PPVs of final follow-up MR-imaging for definitive obliteration varied between 0.89 [corrected] and 0.95. NPV was 0.52 [corrected] . An average false-positive rate, meaning overestimation of nidus obliteration of 0.10 [corrected] and an average false-negative rate, meaning underestimation of nidus obliteration of 0.42 [corrected] were found. CONCLUSIONS: MRA is insufficient to diagnose obliteration in the follow-up of bAVMs after radiosurgery. A remaining nidus diameter <10 mm seems to be the major limiting factor for reliable assessment of obliteration. We highly recommend follow-up DSA for definitive diagnosis of complete obliteration.

Single-shot turbo spin-echo diffusion-weighted imaging for retinoblastoma: initial experience.

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

Modeling MR imaging enhancing-lesion volumes in multiple sclerosis: application in clinical trials.

BACKGROUND AND PURPOSE: Although the number of enhancing lesions is the typical outcome measure of choice in clinical trials in MS, a potentially more sensitive and statistically more powerful outcome measure is the volume of enhancing lesions. In this study, we assessed the distribution and statistical power of the volume of enhancing brain lesions as an outcome measure by means of their required sample size, and we compared the results with the number of enhancing lesions. MATERIAL AND METHODS: First, a literature search was performed to compare the effects of treatment on the number and volume of enhancing lesions. Then, a statistical model was proposed to describe the distribution of the volume of enhancing lesions in 2 datasets of patients with RRMS, and sample sizes for enhancing-lesion volume as primary outcome measure were calculated. RESULTS: A mixture of the binomial and Weibull distribution was determined to model enhancing-lesion volumes in patients. Sample size calculations for enhancing-lesion volumes showed that approximately 94 patients per arm would be required to detect a combination of 20% decrease in lesion volume and 20% increase in patients without enhancing lesions, whereas calculations for enhancing-lesion counts showed that approximately 129 patients would be required to detect a 50% decrease. CONCLUSIONS: The mixture of the binomial and Weibull distribution is a suitable approach in modeling new enhancing-lesion volumes in MS and yielded feasible sample size estimates for clinical trials, showing lesion volumes to be an advantageous outcome measure compared with lesion counts in terms of statistical power.

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.