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Abstract Convolutional neural networks (CNNs) may improve response prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to investigate the feasibility of a CNN using maximum intensity projection (MIP) images from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) baseline scans to predict the probability of time-to-progression (TTP) within 2 years and compare it with the International Prognostic Index (IPI), i.e. a clinically used score. 296 DLBCL 18F-FDG PET/CT baseline scans collected from a prospective clinical trial (HOVON-84) were analysed. Cross-validation was performed using coronal and sagittal MIPs. An external dataset (340 DLBCL patients) was used to validate the model. Association between the probabilities, metabolic tumour volume and Dmaxbulk was assessed. Probabilities for PET scans with synthetically removed tumors were also assessed. The CNN provided a 2-year TTP prediction with an area under the curve (AUC) of 0.74, outperforming the IPI-based model (AUC = 0.68). Furthermore, high probabilities (> 0.6) of the original MIPs were considerably decreased after removing the tumours (

Abstract Aim Clinical prediction models need to be validated. In this study, we used simulation data to compare various internal and external validation approaches to validate models. Methods Data of 500 patients were simulated using distributions of metabolic tumor volume, standardized uptake value, the maximal distance between the largest lesion and another lesion, WHO performance status and age of 296 diffuse large B cell lymphoma patients. These data were used to predict progression after 2 years based on an existing logistic regression model. Using the simulated data, we applied cross-validation, bootstrapping and holdout (n = 100). We simulated new external datasets (n = 100, n = 200, n = 500) and simulated stage-specific external datasets (1), varied the cut-off for high-risk patients (2) and the false positive and false negative rates (3) and simulated a dataset with EARL2 characteristics (4). All internal and external simulations were repeated 100 times. Model performance was expressed as the cross-validated area under the curve (CV-AUC ± SD) and calibration slope. Results The cross-validation (0.71 ± 0.06) and holdout (0.70 ± 0.07) resulted in comparable model performances, but the model had a higher uncertainty using a holdout set. Bootstrapping resulted in a CV-AUC of 0.67 ± 0.02. The calibration slope was comparable for these internal validation approaches. Increasing the size of the test set resulted in more precise CV-AUC estimates and smaller SD for the calibration slope. For test datasets with different stages, the CV-AUC increased as Ann Arbor stages increased. As expected, changing the cut-off for high risk and false positive- and negative rates influenced the model performance, which is clearly shown by the low calibration slope. The EARL2 dataset resulted in similar model performance and precision, but calibration slope indicated overfitting. Conclusion In case of small datasets, it is not advisable to use a holdout or a very small external dataset with similar characteristics. A single small testing dataset suffers from a large uncertainty. Therefore, repeated CV using the full training dataset is preferred instead. Our simulations also demonstrated that it is important to consider the impact of differences in patient population between training and test data, which may ask for adjustment or stratification of relevant variables.

Diagnostic accuracy studies are, like other clinical studies, at risk of bias due to shortcomings in design and conduct, and the results of a diagnostic accuracy study may not apply to other patient groups and settings. Readers of study reports need to be informed about study design and conduct, in sufficient detail to judge the trustworthiness and applicability of the study findings. The STARD statement (Standards for Reporting of Diagnostic Accuracy Studies) was developed to improve the completeness and transparency of reports of diagnostic accuracy studies. STARD contains a list of essential items that can be used as a checklist, by authors, reviewers and other readers, to ensure that a report of a diagnostic accuracy study contains the necessary information. STARD was recently updated. All updated STARD materials, including the checklist, are available at http://www.equator-network.org/reporting-guidelines/stard. Here, we present the STARD 2015 explanation and elaboration document. Through commented examples of appropriate reporting, we clarify the rationale for each of the 30 items on the STARD 2015 checklist, and describe what is expected from authors in developing sufficiently informative study reports. This article is the reprint with Russian translation of the original that can be observed here: Cohen JF, Korevaar DA, Altman DG, et al. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open 2016;6:e012799. doi: 10.1136/bmjopen-2016-012799

Abstract Background In The Netherlands, low back pain patients can consult physicians specialized in musculoskeletal (MSK) medicine. Previous studies have reported on the characteristics of patients consulting MSK physicians, and the treatment options used. There are no studies yet reporting on the course of Low Back Pain (LBP) after treatment by musculoskeletal (MSK) physicians in The Netherlands. Methods In an observational cohort study MSK physicians recorded data about all low back pain patients presenting for a first consultation. At baseline they recorded age, gender, type and duration of the main complaint, and concomitant complaints. At the end of treatment they recorded the type of treatment and the number of treatment sessions. Patients were recruited to answer questionnaires at baseline, and at 6-weekly intervals during a follow-up period of six months. Patient questionnaires included information about previous medical consumption, together with PROMs measuring the level of pain and functional status. Latent Class Growth Analysis (LCGA) was used to classify patients into different groups according to their pain trajectories. Baseline variables were evaluated as predictors of a favourable trajectory using logistic regression analyses, and treatment variables were evaluated as possible confounders. Results A total of 1377 patients were recruited, of whom 1117 patients (81%) answered at least one follow-up measurement. LCGA identified three groups of patients with distinct pain trajectories. A first group (N = 226) with high pain levels showed no improvement, a second group (N = 578) with high pain levels showed strong improvement, and a third group (N = 313) with mild pain levels showed moderate improvement. The two groups of patients presenting with high baseline pain scores were compared, and a multivariable model was constructed with possible predictors of a favourable course. Male gender, previous specialist visit, previous pain clinic visit, having work, a shorter duration of the current episode, and a longer time since the complaints first started were predictors of a favourable course. The multivariable model showed a moderate area under the curve (0.68) and a low explained variance (0.09). Conclusions In low back pain patients treated by musculoskeletal physicians in The Netherlands three different pain trajectories were identified. Baseline variables were of limited value in predicting a favourable course.

Abstract Purpose Correct identification of tumour receptor status is important for treatment decisions in breast cancer. [18F]FES PET and [18F]FDHT PET allow non-invasive assessment of the oestrogen (ER) and androgen receptor (AR) status of individual lesions within a patient. Despite standardised analysis techniques, interobserver variability can significantly affect the interpretation of PET results and thus clinical applicability. The purpose of this study was to determine visual and quantitative interobserver variability of [18F]FES PET and [18F]FDHT PET interpretation in patients with metastatic breast cancer. Methods In this prospective, two-centre study, patients with ER-positive metastatic breast cancer underwent both [18F]FES and [18F]FDHT PET/CT. In total, 120 lesions were identified in 10 patients with either conventional imaging (bone scan or lesions > 1 cm on high-resolution CT, n = 69) or only with [18F]FES and [18F]FDHT PET (n = 51). All lesions were scored visually and quantitatively by two independent observers. A visually PET-positive lesion was defined as uptake above background. For quantification, we used standardised uptake values (SUV): SUVmax, SUVpeak and SUVmean. Results Visual analysis showed an absolute positive and negative interobserver agreement for [18F]FES PET of 84% and 83%, respectively (kappa = 0.67, 95% CI 0.48–0.87), and 49% and 74% for [18F]FDHT PET, respectively (kappa = 0.23, 95% CI − 0.04–0.49). Intraclass correlation coefficients (ICC) for quantification of SUVmax, SUVpeak and SUVmean were 0.98 (95% CI 0.96–0.98), 0.97 (95% CI 0.96–0.98) and 0.89 (95% CI 0.83–0.92) for [18F]FES, and 0.78 (95% CI 0.66–0.85), 0.76 (95% CI 0.63–0.84) and 0.75 (95% CI 0.62–0.84) for [18F]FDHT, respectively. Conclusion Visual and quantitative evaluation of [18F]FES PET showed high interobserver agreement. These results support the use of [18F]FES PET in clinical practice. In contrast, visual agreement for [18F]FDHT PET was relatively low due to low tumour-background ratios, but quantitative agreement was good. This underscores the relevance of quantitative analysis of [18F]FDHT PET in breast cancer. Trial registration ClinicalTrials.gov , NCT01988324. Registered 20 November 2013, https://clinicaltrials.gov/ct2/show/NCT01988324?term=FDHT+PET&draw=1&rank=2 .

Abstract Background Decision-making about palliative care for metastatic colorectal cancer (mCRC) consists of many different treatment-related decisions, and there generally is no best treatment option. Decision support systems (DSS), e.g., prognostic calculators, can aid oncologists’ decision-making. DSS that contain features tailored to the needs of oncologists are more likely to be implemented in clinical practice. Therefore, our aim is to inventory colorectal cancer specialists’ unmet decision support needs. Methods We asked oncologists from the Dutch colorectal cancer group (DCCG), to participate in an online inventory questionnaire on their unmet decision support needs. To get more in-depth insight in required features of the DSS they need, we also conducted semi-structured telephone interviews. Results Forty-one oncologists started the inventory questionnaire, and 27 of them completed all items. Of all respondents, 18 were surgeons (44%), 22 were medical oncologists (54%), and 28 (68%) had more than 10 years of experience treating mCRC. In both the inventory questionnaire and interviews, respondents expressed a need for an overarching DSS incorporating multiple treatment options, and presenting both the treatment benefits and harms. Respondents found it relevant for other outcomes, such as cost-effectiveness of treatment or quality of life, to be incorporated in DSS. There was also a wish for DSS incorporating an up-to-date “personalized” overview of the ongoing trials for which a specific patient is eligible. Conclusions Experienced oncologists indicate that their treatment advice is currently almost solely based on the available clinical guidelines. They experience a lack of good quality DSS to help them personalize their treatment advice. New tools integrating multiple treatment options and providing a broad range of clinically relevant outcomes are urgently needed to stimulate and safeguard more personalized treatment decision-making.

Abstract Background To support healthcare professionals in dealing with ethically difficult situations, Clinical Ethics Support (CES) services like Moral Case Deliberation (MCD) are increasingly implemented. To assess the impact of CES, it is important to evaluate outcomes. Despite general claims about outcomes from MCD experts and some qualitative research, there exists no conceptual analysis of outcomes yet. Therefore, the aim of this study was to systematically define and categorize MCD outcomes. An additional aim was to compare these outcomes with the outcomes in the Euro-MCD Instrument from 2014, to further validate this Instrument. Methods The concept mapping method was used and involves qualitative and quantitative steps including brainstorming, individual structuring, computation of concept maps (by principal component analysis and cluster analysis), group interpretation and utilization. In total, 12 experienced MCD participants from a variety of professional backgrounds participated in two sessions. Results The focus group brainstorm resulted in a list of 85 possible MCD outcomes, of which a point map and concept maps were constructed. After a thorough discussion of each cluster, final consensus was reached on the names and position of 8 clusters of MCD outcomes: 1) Organisation and Policy; 2) Team development; 3) Personal development focused on the Other Person; 4) Personal development as Professional, focused on Skills; 5) Personal development as Professional, focused on Knowledge; 6) Personal development as an Individual; 7) Perception and Connection; and 8) Concrete action. Conclusions This study explored and categorized MCD outcomes in a concept mapping focus group. When comparing the results with the Euro-MCD Instrument, our study confirms that outcomes of MCD can be categorized in clusters referring to the organisational level, team development, personal development (both as an individual and a professional) and the concrete case-level. In developing CES evaluation tools, it is important to be explicit if an outcome refers to the individual or the team, to knowledge or skills, to the organisation or the specific case. The findings will be used in the further validation of the Euro-MCD Instrument. The current study further contributes to the field of evaluating CES in general and defining outcomes of MCD in particular.

Abstract Background Convalescence advice is often based on tradition and anecdote from health care providers, rather than being based on experiences from patients themselves. The aim of this study was to analyse recovery in terms of resumption of various daily activities including work, following different laparoscopic and abdominal surgery in order to optimize an expert-based guideline on convalescence recommendations. Methods This is a prospective cohort study conducted in nine general and one university hospital in the Netherlands. Women aged 18–65 years and scheduled for a hysterectomy (laparoscopic, vaginal, abdominal) and/or laparoscopic adnexal surgery (n = 304) were eligible to participate. Preoperatively, participants were provided with tailored expert-based convalescence recommendations on the graded resumption of several daily activities including sitting, standing, walking, climbing stairs, bending, lifting, driving, cycling, household chores, sport activities and return to work (RTW). Postoperatively, time until the resumption of these activities was tracked. Convalescence recommendations were considered correct when at least 25% and less than 50% of the women were able to resume an activity before or at the recommended recovery time. Results There was a wide variation in the duration until the resumption of daily activities within and between groups of patients undergoing different types of surgery. Recovery times lengthened with increasing levels of physical burden as well as with increasing levels of invasiveness of the surgery. For the majority of activities actual recovery times exceeded the recovery time recommended by the expert panel. Conclusions This study provided insight in the resumption of daily activities after gynecological surgery and the adequacy of an expert-based convalescence guideline in clinical practice. Patient data was used to optimize the convalescence recommendations. Trial registration Dutch trial registry, NTR2087 (August 2009) and NTR2933 (June 2011).

Abstract Background Various health care professionals apply Spinal Manipulative Treatment (SMT) in daily practice. While the characteristics of chiropractors and manual therapists and the characteristics of their patient populations are well described, there is little research about physicians who use SMT techniques. A distinct group of physicians in The Netherlands has been trained in musculoskeletal (MSK) medicine, which includes the use of SMT. Our objective was to describe the characteristics of these physicians and their patient population. Methods All registered MSK physicians were approached with questionnaires and telephone interviews to collect data about their characteristics. Data about patient characteristics were extracted from a web-based register. In this register physicians recorded basic patient data (age, gender, the type and duration of the main complaint, concomitant complaints and the type of referral) at the first consultation. Patients were invited to fill in web-based questionnaires to provide baseline data about previous treatments and the severity of their main complaint. Functional impairment was measured with Patient Reported Outcome Measures (PROMs). Results Questionnaires were sent to 138 physicians of whom 90 responded (65%). Most physicians were trained in MSK medicine after a career in other medical specialities. They reported to combine their SMT treatment with a variety of diagnostic and treatment options part of which were only permissible for physicians, such as prescription medication and injections. The majority of patients presented with complaints of long duration (62.1% > 1 year), most frequently low back pain (48.1%) or neck pain (16.9%), with mean scores of 6.0 and 6.2, respectively, on a 0 to10 numerical rating scale (NRS) for pain intensity. Mean scores on all PROMs showed moderate impairment. Patients most frequently reported previous treatment by physical therapists (68.1%), manual therapists (37.7%) or chiropractors (17.0%). Conclusion Our study showed that MSK physicians in The Netherlands used an array of SMT techniques. They embedded their SMT techniques in a broad array of other diagnostic and treatment options, part of which were limited to medical doctors. Most patients consulted MSK physicians with spinal pain of long duration with moderate functional impairment.

Background:. Measurements of scar quality are essential to evaluate the effectiveness of scar treatments and to monitor scars. A large number of scar scales and measurement devices have been developed, which makes instrument selection challenging. The aim of this study was to provide an overview of the content (ie, included items) of all outcome measurement instruments that measure scar quality in different types of scars (burn, surgical, keloid, and necrotizing fasciitis), and the frequency at which the instruments and included items are used. Methods:. A systematic search was performed in PubMed and Embase.com up to October 31, 2018. All original studies reporting on instruments that measured at least 1 characteristic of scar quality were included and the instrument’s content was extracted. Results:. We included 440 studies for data extraction. Included instruments (N = 909) were clinician-reported scales (41%), measurement devices (30%), patient-reported scales (26%), and combined clinician- and patient-reported scales (3%). The Observer scale of the Patient and Observer Scar Assessment Scale, the Cutometer, the Patient Scale of the Patient and Observer Scar Assessment Scale, and the modified Vancouver Scar Scale were the most often used instrument in each of these categories, respectively. The most frequent assessed items were thickness, vascularity, pigmentation, pliability, pain, and itch. Conclusion:. The results of this study lay the foundation for our future research, which includes an international Delphi study among many scar experts, and an international focus group study among scar patients, aiming to elucidate how scar quality must be defined and measured from both professional and patient perspectives.

BackgroundActive parent participation in neonatal care and collaboration between parents and professionals during infant hospitalization in the neonatal intensive care unit (NICU) is beneficial for infants and their parents. A tool is needed to support parents and to study the effects and implementation of parent-partnered models of neonatal care.MethodsWe developed and psychometrically evaluated a tool measuring active parent participation and collaboration in neonatal care within six domains: Daily Care, Medical Care, Acquiring Information, Parent Advocacy, Time Spent with Infant and Closeness and Comforting the Infant. Items were generated in focus group discussions and in-depth interviews with professionals and parents. The tool was completed at NICU-discharge by 306 parents (174 mothers and 132 fathers) of preterm infants. Subsequently, we studied structural validity with confirmatory factor analysis (CFA), construct validity, using the Average Variance Extracted and Heterotrait-Monotrait ratio of correlations, and hypothesis testing with correlations and univariate linear regression. For internal consistency we calculated composite reliability (CR). We performed multiple imputations by chained equations for missing data.ResultsA 31 item tool for parent participation and collaboration in neonatal care was developed. CFA revealed high factor loadings of items within each domain. Internal consistency was 0.558 to 0.938. Convergent validity and discriminant validity were strong. Higher scores correlated with less parent depressive symptoms (r = -0.141, 95%CI -0.240; -0.029, p = 0.0141), less impaired parent-infant bonding (r = -0.196, 95%CI -0.302; -0.056, pConclusionThe CO-PARTNER tool explicitly measures parents' participation and collaboration with professionals in neonatal care incorporating their unique roles in care provision, leadership, and connection to their infant. The tool consists of 31 items within six domains with good face, content, construct and structural validity.

ObjectivesTo assess the interobserver agreement in categories of electrocardiogram (ECG) abnormalities using the Minnesota Code criteria.MethodsWe used a random sample of 180 ECGs from people with type 2 diabetes. ECG abnormalities were classified and coded using the Minnesota ECG Classification. Each ECG was independently rated on several abnormalities by an experienced rater (rater 1) and by two cardiologists (raters 2 and 3) trained to apply the Minnesota codes on four Minnesota codes; 1-codes as an indication for myocardial infarction, 4 en 5-codes as an indication for ischemic abnormalities, 3-codes as an indication for left ventricle hypertrophy, 7-1-codes as an indication for ventricular conduction abnormalities, and 8-3-codes as an indication for atrial fibrillation / atrial flutter. After all pairwise tables were summed, the overall agreement, the specific positive and negative agreement were calculated with a 95% confidence interval (CI) for each abnormality. Also, Kappa's with a 95% CI were calculated.ResultsThe overall agreement (with 95% CI) were for myocardial infarction, ischemic abnormalities, left ventricle hypertrophy, conduction abnormalities and atrial fibrillation/atrial flutter respectively: 0.87 (0.84-0.91), 0.79 (0.74-0.84), 0.81 (0.76-0.85), 0.93 (0.90-0.95), 0.96 (0.93-0.97).ConclusionThis study shows that the overall agreement of the Minnesota code is good to excellent.

The Four-Dimensional Symptom Questionnaire (4DSQ) is a self-report instrument measuring distress, depression, anxiety and somatization. The questionnaire has been developed and validated in adult samples. It is unknown whether adolescents and emerging adults respond to the 4DSQ items in the same way as adults do. The objective of the study was to examine measurement equivalence of the 4DSQ across adolescents, emerging adults and adults. 4DSQ data were collected in a primary care psychotherapy practice (N = 1349). Measurement equivalence was assessed using differential item and test functioning (DIF and DTF) analysis in an item response theory framework. DIF was compared across the following groups: adolescents (age 10-17), emerging adults (age 18-25), and adults (age 26-40). DIF was found in 9 items (out of 50) across adolescents and adults, and in 4 items across emerging adults and adults. The item with the largest DIF was 'difficulty getting to sleep', which was less severe for adolescents compared to adults. A likely explanation is that adolescents have a high base rate for problems with sleep initiation. The effect of DIF on the scale scores (DTF) was negligible. Adolescents and emerging adults score some 4DSQ items differently compared to adults but this had practically no effect on 4DSQ scale scores. 4DSQ scale scores from adolescents and emerging adults can be interpreted in the same way as 4DSQ scores from adults.

AimTo assess the concurrent validity and discriminative ability of total, gross and fine motor (TM, GM and FM) scores of Dutch performance-based motor tests, the Baecke-Fassaert Motor Test (BFMT) and the 8- and 4-Skills Scan (SkSc) with the Movement Assessment Battery (MABC) for children at age 5.Method116 Dutch children (40.3% boys) were included. Spearman's rho correlations and area under the curves (AUC) were assessed.ResultsCorrelations between the TM scores of the tests were strong (absolute values from 0.58 to .65); the correlations between the GM scores and the FM scores between and within tests were weaker (absolute values from 0.30 to 0.45). Related to the cut-off (15th percentile) of the MABC, the AUC of the BFMT, 8- and 4-SkSc, the AUC was 0.853 (95% CI: 0.757-0.949), 0.905 (95% CI: 0.837-0.972) and 0.844 (95% CI: 0.730-0.957), respectively. At optimal cut-offs, the sensitivity and specificity of the BFMT, the 8- and 4-SkSc were 78.6 and 78.4%, 92.2 and 73.2%, 78.6 and 76.3%, respectively.ConclusionAll tests had a reasonably high discriminative ability, but validation with the MABC-2 and adaptations are needed to meet the requirements for screening (i.e. sensitivity ≥80% and specificity ≥90%). The relatively weak correlation between GM and FM scores implies that tests should be normalized and validated for GM and FM ability, separately.

BackgroundConsideration of older adults' quality of life (QoL) is becoming increasingly important in the evaluation, quality improvement and allocation of health and social care services. While numerous definitions and theories of QoL have been proposed, an overall synthesis of the perspective of older adults themselves is lacking.MethodsQualitative studies were identified in PubMed, Ebsco/Psycinfo and Ebsco/CINAHL, through a search on 28 November 2018. Articles needed to meet all of the following criteria: (i) focus on perceptions of QoL, (ii) older adults living at home as main participants, (iii) use of qualitative methodology, (iv) conducted in a Western country and (v) published in English (vi) not focused on specific patient groups. A thematic synthesis was conducted of the selected studies, using the complete 'findings/results' sections from the papers.ResultsWe included 48 qualitative studies representing the views of more than 3,400 older adults living at home in 11 Western countries. The QoL aspects identified in the synthesis were categorized into nine QoL domains: autonomy, role and activity, health perception, relationships, attitude and adaptation, emotional comfort, spirituality, home and neighbourhood, and financial security. The results showed that although different domains can be distinguished, these are also strongly connected.ConclusionQoL can be expressed in a number of domains and related subthemes that are important for older adults living at home. The findings further support that the concept of QoL should be seen as a dynamic web of intertwined domains.

In old age, sufficient protein intake is important to preserve muscle mass and function. Around 50% of older adults (65+ y) consumes ≤1.0 g/kg adjusted body weight (BW)/day (d). There is no rapid method available to screen for low protein intake in old age. Therefore, we aimed to develop and validate a short food questionnaire to screen for low protein intake in community-dwelling older adults. We used data of 1348 older men and women (56-101 y) of the LASA study (the Netherlands) to develop the questionnaire and data of 563 older men and women (55-71 y) of the HELIUS study (the Netherlands) for external validation. In both samples, protein intake was measured by the 238-item semi-quantitative HELIUS food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to predict protein intake ≤1.0 g/kg adjusted BW/d (based on the HELIUS FFQ). Candidate predictor variables were FFQ questions on frequency and amount of intake of specific foods. In both samples, 30% had a protein intake ≤1.0 g/kg adjusted BW/d. Our final model included adjusted body weight and 10 questions on the consumption (amount on average day or frequency in 4 weeks) of: slices of bread (number); glasses of milk (number); meat with warm meal (portion size); cheese (amount and frequency); dairy products (like yoghurt) (frequency); egg(s) (frequency); pasta/noodles (frequency); fish (frequency); and nuts/peanuts (frequency). The area under the receiver operating characteristic curve (AUC) was 0.889 (95% CI 0.870-0.907). The calibration slope was 1.03 (optimal slope 1.00). At a cut-off of ≤0.8 g/kg adjusted BW/d, the AUC was 0.916 (96% CI 0.897-0.936). Applying the regression equation to the HELIUS sample, the AUC was 0.856 (95% CI 0.824-0.888) and the calibration slope 0.92. Regression coefficients were therefore subsequently shrunken by a linear factor 0.92. To conclude, the short food questionnaire (Pro55+) can be used to validly screen for protein intake ≤1.0 g/kg adjusted BW/d in community-dwelling older adults. An online version can be found at www.proteinscreener.nl. External validation in other countries is recommended.

The network approach to psychopathology conceives mental disorders as sets of symptoms causally impacting on each other. The strengths of the connections between symptoms are key elements in the description of those symptom networks. Typically, the connections are analysed as linear associations (i.e., correlations or regression coefficients). However, there is insufficient awareness of the fact that differences in variance may account for differences in connection strength. Differences in variance frequently occur when subgroups are based on skewed data. An illustrative example is a study published in PLoS One (2013;8(3):e59559) that aimed to test the hypothesis that the development of psychopathology through "staging" was characterized by increasing connection strength between mental states. Three mental states (negative affect, positive affect, and paranoia) were studied in severity subgroups of a general population sample. The connection strength was found to increase with increasing severity in six of nine models. However, the method used (linear mixed modelling) is not suitable for skewed data.We reanalysed the data using inverse Gaussian generalized linear mixed modelling, a method suited for positively skewed data (such as symptoms in the general population).The distribution of positive affect was normal, but the distributions of negative affect and paranoia were heavily skewed. The variance of the skewed variables increased with increasing severity. Reanalysis of the data did not confirm increasing connection strength, except for one of nine models.Reanalysis of the data did not provide convincing evidence in support of staging as characterized by increasing connection strength between mental states. Network researchers should be aware that differences in connection strength between symptoms may be caused by differences in variances, in which case they should not be interpreted as differences in impact of one symptom on another symptom.

The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT) model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA). Items were calibrated using the graded response model (GRM), an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF) for language (Dutch vs. English) was examined. Reliability was evaluated based on standard errors and Cronbach's alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF), good reliability (Cronbach's alpha = 0.98), and good construct validity (Pearson correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed.

The constructs optimism, pessimism, hope, treatment credibility and treatment expectancy are associated with outcomes of medical treatment. While these constructs are grounded in different theoretical models, they nonetheless show some conceptual overlap. The purpose of this study was to examine whether currently available measurement instruments for these constructs capture the conceptual differences between these constructs within a treatment setting.Patients undergoing Total Hip and Total Knee Arthroplasty (THA and TKA) (Total N = 361; 182 THA; 179 TKA), completed the Life Orientation Test-Revised for optimism and pessimism, the Hope Scale, the Credibility Expectancy Questionnaire for treatment credibility and treatment expectancy. Confirmatory factor analysis was used to examine whether the instruments measure distinct constructs. Four theory-driven models with one, two, four and five latent factors were evaluated using multiple fit indices and Δχ2 tests, followed by some posthoc models.The results of the theory driven confirmatory factor analysis showed that a five factor model in which all constructs loaded on separate factors yielded the most optimal and satisfactory fit. Posthoc, a bifactor model in which (besides the 5 separate factors) a general factor is hypothesized accounting for the commonality of the items showed a significantly better fit than the five factor model. All specific factors, except for the hope factor, showed to explain a substantial amount of variance beyond the general factor.Based on our primary analyses we conclude that optimism, pessimism, hope, treatment credibility and treatment expectancy are distinguishable in THA and TKA patients. Postdoc, we determined that all constructs, except hope, showed substantial specific variance, while also sharing some general variance.