Effectiveness of a positive psychology and mindfulness-based app on mental health for parents of children with a neurodevelopmental disorder: study protocol of a pragmatic international randomized controlled trial.

INTRODUCTION: Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called "Adappt," aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences. METHOD: A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with "Adappt." DISCUSSION: Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care. TRIAL REGISTRATION: This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework ( https://osf.io/5znqv ).

Test-Retest Reliability of the Generalized Pain Questionnaire in Patients with Rheumatoid Arthritis and Preliminary Reference Values for Non-Clinical and Several Clinical Samples.

Introduction: Generalized pain hypersensitivity is a characteristic feature in many different types of chronic pain. Recently, a 7-item self-reported Generalized Pain Questionnaire (GPQ) was developed to evaluate the presence and severity of generalized pain hypersensitivity in chronic pain patients. Here, we evaluate the test-retest reliability of the GPQ and report on preliminary reference values for various patient groups and healthy subjects. Methods: Eighty-five patients diagnosed with Rheumatoid Arthritis (RA) completed the GPQ twice over a 2-week interval. Relative and absolute indicators of reliability were determined using data of 69 patients (81.2% retest response rate). Using readily available datasets, preliminary reference data were established in two nonclinical populations (NCP1; N = 30 and NCP2; N = 111), and for patients diagnosed with RA (N = 114), gout (N = 97), fibromyalgia (N=98), or neuropathy (N = 25), or participants in a pain rehabilitation program (N = 33). Results: Total GPQ scores had an ICC of 0.78 (95% CI: 0.67 to 0.86). While no systematic or proportional differences were found for the GPQ total score; two (near-)significant systematic differences were observed for the individual questions. The standard error of measurement and minimal detectable change were 2.22 and 6.2, respectively. Mean ± SD scores were found to be 0.8 ± 1.2 (NCP1), 4.0 ± 4.6 (NCP2), 6.4 ± 5.5 (Gout), 6.5 ± 5.1 (RA), 8.1 ± 4.5 (Neuropathy), 13.6 ± 4.0 (Rehabilitation) and 16.0 ± 5.0 (Fibromyalgia). Discussion: This study shows that the GPQ has acceptable reliability to be used as a tool to evaluate the presence and intensity of generalized pain hypersensitivity. The absolute measures of reliability and the preliminary reference values reported here aid in the interpretation of future studies with the GPQ.

Further evaluation of inflammatory and non-inflammatory aspects of pain in rheumatoid arthritis patients.

Objective: A high discrepancy between the number of tender and swollen joints (e.g. ΔTSJ ≥ 7) has previously been used as an indication for the presence of changes in central mechanisms in patients with moderate-to-high disease activity. In this study, we explored whether the ΔTSJ can also be used to obtain insights into the underlying pain mechanisms in patients with on average well-controlled disease activity. Methods: A 2 year retrospective analysis of routinely obtained 28-joint DAS (DAS28) components was performed on 45 patients with low inflammatory activity at the group level. All patients underwent pressure pain threshold (PPT) and electrical pain threshold (EPT) measurements and completed four self-report questionnaires [short-form 36 (SF-36v2); central sensitization inventory (CSI); generalized pain questionnaire (GPQ); and the pain catastrophizing scale (PCS)]. Results: Patients with a ΔTSJ ≥ 3 at least once in the past 2 years showed significantly lower EPT and PPT values and higher levels of pain and disability on the SF-36v2 compared with the ΔTSJ < 3 group. Furthermore, GPQ scores were significantly higher in those with ΔTSJ ≥ 3, while CSI and PCS scores were similar. Conclusion: These findings suggest that in patients in the ΔTSJ ≥ 3 group, mechanisms other than inflammation (only) underlie the pain. Moreover, our findings suggest that among the multiple potential underlying psychological mechanisms, pain catastrophizing (as measured by the PCS) and psychological hypervigilance (as measured by the CSI) do not play an important role. These findings could be useful in the clinical management of the patient. Depending on the dominant mechanism underlying the (persistent) pain, patients might respond differently to treatment.

Objectively assessed long-term wearing patterns and predictors of wearing orthopaedic footwear in people with diabetes at moderate-to-high risk of foot ulceration: a 12 months observational study.

BACKGROUND: Orthopaedic footwear can only be effective in preventing diabetic foot ulcers if worn by the patient. Robust data on long-term wearing time of orthopaedic footwear are not available, and needed to gain more insights into wearing patterns and associated factors (i.e. participants' demographic, disease-related characteristics, and footwear usability). We aimed to objectively assess long-term wearing patterns and identify factors associated with wearing orthopaedic footwear in people with diabetes at moderate-to-high risk of ulceration. METHODS: People diagnosed with diabetes mellitus type 1 and 2 with loss of protective sensation and/or peripheral artery disease and prescribed with orthopaedic footwear were included and followed for 12 months. The primary outcome was mean daily wearing time, continuously measured using a temperature sensor inside the footwear (Orthotimer®). Adherence to wearing orthopaedic footwear was calculated as percentage of wearing time of a total assumed 16 h out-of-bed daytime, where adherence < 60% was a pre-determined non-adherent threshold. Wearing time patterns were assessed by calculating participants' wearing (in)consistency. One-way analyses of variance tested for wearing time differences between subgroups, weekdays, and weekend days. Factors potentially associated with wearing time were collected by questionnaires and medical files. Univariately associated factors were included in multivariate linear regression analysis. RESULTS: Sixty one participants were included (mean (SD) age: 68.0 (7.4) years; females: n = 17; type 2 diabetes mellitus: n = 54). Mean (SD) overall daily wearing time was 8.3 (6.1) hours/day. A total of 40 (66%) participants were non-adherent. Participants with a consistent wearing pattern showed higher daily wearing times than participants with an inconsistent pattern. Mean (SD) wearing times were 12.7 (4.3) vs 3.6 (4.8) hours/day, respectively (P < 0.001). Mean (SD) wearing time was significantly higher (P < 0.010) during weekdays (8.7 (6.0) hours/day) compared to Saturday (8.0 (6.1) hours/day) and Sunday (6.9 (6.2) hours/day). In the multivariate model (R2 = 0.28), "satisfaction with my wear of orthopaedic footwear" was positively associated (P < 0.001) with wearing time. The other seven multivariate model factors (four demographic variables and three footwear usability variables) were not associated with wearing time. CONCLUSIONS: Only one out of three people at moderate to high risk of foot ulceration were sufficiently adherent to wearing their orthopaedic footwear. Changing people's wearing behaviour to a more stable pattern seems a potential avenue to improve long-term adherence to wearing orthopaedic footwear. Investigated factors are not associated with daily wearing time. Based on these factors the daily wearing time cannot be estimated in daily practice. TRIAL REGISTRATION: Netherlands Trial Register NL7710. Registered: 6 May 2019.

Exploring mental health dynamics during eating disorder treatment: A psychometric network study with panel data.

To explore mental health associations during eating disorder (ED) treatment. Based on the dual-continua model of mental health, general and ED-specific psychopathology, as well as emotional, psychological, and social well-being were considered as mental health domains.Network analyses with panel data were applied to explore within- (temporal and contemporaneous networks) and between-person effects in a sample of 1250 female ED patients during 12 months of outpatient treatment. The associations between the domains and their centrality were examined. Autoregressive and cross-lagged effects were also estimated.ED psychopathology was the most central domain in the temporal network. ED psychopathology changes predicted further ED psychopathology changes and small changes in the other domains. Weak bi-directional associations were found between changes in the well-being domains and general psychopathology. In contrast to the temporal network, ED psychopathology was the least central and psychological well-being the most central domain in the contemporaneous and between-subjects networks. This suggests a central role of psychological well-being for experiencing mental health within time points.ED psychopathology may change relatively independent from other mental health domains. Well-being domains may be considered as more stable aspects of mental health.

A multicomponent positive psychology intervention for euthymic patients with bipolar disorder to improve mental well-being and personal recovery: A pragmatic randomized controlled trial.

OBJECTIVE: Mental well-being and personal recovery are important treatment targets for patients with bipolar disorder (BD). The goal of this study was to evaluate the effectiveness of an 8-week group multicomponent positive psychology intervention (PPI) for euthymic patients with BD as an adjunct to treatment as usual (TAU) compared to TAU alone. METHODS: Patients with BD were randomized to receive TAU (n = 43) or the PPI in addition to TAU (n = 54). The primary outcome was well being measured with the Mental Health Continuum-Short Form. Personal recovery was measured with the Questionnaire about the Process of Recovery. Data were collected at baseline, mid-treatment, post-treatment and 6- and 12-month follow-up. Life chart interviews were conducted at 12 months to retrospectively assess recurrence of depression and mania. RESULTS: Significant group-by-time interaction effects for well-being and personal recovery were found favouring the PPI. At post-treatment, between-group differences were significant for well-being (d = 0.77) and personal recovery (d = 0.76). Between-group effects for well-being were still significant at 6-month follow-up (d = 0.72). Effects on well-being and personal recovery within the intervention group were sustained until 12-month follow-up. Survival analyses showed no significant differences in time to recurrence. CONCLUSIONS: The multicomponent PPI evaluated in this study is effective in improving mental well-being and personal recovery in euthymic patients with BD and would therefore be a valuable addition to the current treatment of euthymic BD patients. The fact that the study was carried out in a pragmatic RCT demonstrates that this intervention can be applied in a real-world clinical setting.

Impact of adverse drug reactions on the treatment pathways of early rheumatoid arthritis patients: a prospective observational cohort study.

BACKGROUND: Several patient characteristics may be of influence on treatment pathways of rheumatoid arthritis (RA) patients in clinical practice. The aim of this study is to analyze treatment pathways of early RA patients stratified for gender and adverse drug reaction (ADR) occurrence. RESEARCH DESIGN AND METHODS: Treatment pathways of patients included in the DREAM-RA treat-to-target cohort I between 16th of July 2006-30th of April 2020 were assessed. Treatment pathways were visualized in Sankey diagrams. Follow-up time, duration per treatment and the number of treatments received were stratified for gender and ADR occurrence and analyzed. Independent t-tests and chi-square tests were performed where applicable. RESULTS: Treatment pathways of 372 patients (follow-up: 2488.4 years, mean 6.7 ± 3.7 years) were analyzed. The Sankey diagrams visualize that treatment pathways became increasingly varied and complex over time. No significant differences were found when comparing female patients and male patients. However, the average treatment duration was shorter in patients with ADRs (1.8 vs. 2.7 years, p < 0.05), and the number of treatments higher (3.5 vs. 2.5, p < 0.05). CONCLUSIONS: Treatment pathways increase in complexity over time. Differences were found between patients with and without ADRs, with patients that experience ADRs receiving more and shorter treatments.

The Traumatic Grief Inventory-Clinician Administered: A psychometric evaluation of a new interview for ICD-11 and DSM-5-TR prolonged grief disorder severity and probable caseness.

BACKGROUND: There is a need for an interview-based measure to assess Prolonged Grief Disorder (PGD) included in the text revision of the fifth Diagnostic and Statistical Manual for Mental Disorder (DSM-5-TR) and 11th edition of the International Classification of Disease (ICD-11). We evaluated the psychometric properties of the Traumatic Grief Inventory-Clinician Administered (TGI-CA); a new interview measuring DSM-5-TR and ICD-11 PGD severity and probable caseness. METHODS: In 211 Dutch and 222 German bereaved adults, the: (i) factor structure, (ii) internal consistency, (iii) test-retest reliability, (iv) measurement invariance across subgroups (e.g., differing in language), (v) prevalence of probable caseness, (vi) convergent validity, and (vii) known-groups validity were examined. RESULTS: Confirmatory factor analyses (CFAs) showed acceptable fit for the unidimensional model for DSM-5-TR and ICD-11 PGD. Omega values indicated good internal consistency. Test-retest reliability was high. Multi-group CFAs demonstrated configural and metric invariance for DSM-5-TR and ICD-11 PGD criteria for all group-comparisons; for some we found support for scalar invariance. Rates of probable caseness for DSM-5-TR PGD were lower than ICD-11 PGD. Optimal agreement in probable caseness was reached when increasing the number of accessory symptoms for ICD-11 PGD from 1+ to 3+. Convergent and known-groups validity was demonstrated for both criteria-sets. LIMITATIONS: The TGI-CA was developed to assess PGD severity and probable caseness. Clinical diagnostic interviews for PGD are needed. CONCLUSIONS: The TGI-CA seems a reliable and valid interview for DSM-5-TR and ICD-11 PGD symptomatology. More research in larger and more diverse samples is needed to further test its psychometric properties.

The impact of health literacy: associations with disease activity and medication prescription in patients with rheumatoid arthritis.

OBJECTIVE: The aim of this study was to explore the longitudinal associations between health literacy profiles and disease activity and medication prescription in patients with RA. METHODS: Patients with RA who previously completed the Health Literacy Questionnaire (HLQ) and were assigned 1 of 10 distinct health literacy profiles based on cluster analysis were further aggregated into three groups: 'several health literacy limitations', 'some health literacy limitations' and 'good health literacy'. Linear mixed modelling (LMM) was used to analyse the association between health literacy groups and disease activity over the course of 1 year. Chi-squared tests and logistic regression analyses were used to compare medication prescriptions between the groups. RESULTS: A total of 108 patients with RA were included. LMM showed a significant effect of health literacy group on disease activity over time (P = 0.010). Patients with 'good health literacy' had significantly lower disease activity over time [28-joint DAS with ESR (DAS28-ESR) = 2.4] than patients with 'several health literacy limitations' (DAS28-ESR = 3.1), independent of age, gender and education level. Patients with 'good health literacy' were most often prescribed a biologic DMARD (50%), whereas patients with 'some health literacy limitations' more commonly received a conventional synthetic DMARD only [72.7%; odds ratio (OR) 4.24], and patients with 'several health literacy limitations' were more often prescribed prednisolone (52.4%; OR 3.56). CONCLUSION: Significant differences in longitudinal disease activity and medication prescription were observed between groups with different health literacy levels. These results stress the importance of insights into the role of health literacy in treatment and outcomes in patients with RA.

First-time adverse drug reactions, survival analysis, and the share of adverse drug reactions in treatment discontinuation in real-world rheumatoid arthritis patients: a comparison of first-time treatment with adalimumab and etanercept.

BACKGROUND: This study aims to compare nature and frequency of adverse drug reactions (ADRs), time to first ADR, drug survival, and the share of ADRs in treatment discontinuation of first-time treatment with adalimumab (ADA) and etanercept (ETN) in real-world RA patients. RESEARCH DESIGN AND METHODS: Retrospective, single-center cohort study including naïve patients treated between January 2003-April 2020. Time to first ADR and drug survival of first-time treatment were studied using Kaplan-Meier and Cox-regression models up to 10 years, with 2- and 5-year post-hoc sensitivity analysis. Nature and frequencies of first-time ADRs and causes of treatment discontinuation were assessed. RESULTS: In total, 416 patients (ADA: 255, ETN: 161, 4865 patient years) were included, of which 92 (22.1%) experienced ADR(s) (ADA: 59, 23.1%; ETN: 33, 20.4%). Adjusted for age, gender and concomitant conventional DMARD use, ADA was more likely to be discontinued than ETN up to 2-, 5- and 10-year follow-up (adjusted HRs 1.63; 1.62; 1.59 (all p<0.001)). ADRs were the second reason of treatment discontinuation (ADA 20.7%, ETN 21.4%). CONCLUSIONS: Despite seemingly different nature and frequencies, ADRs are the second reason of treatment discontinuation for both bDMARDs. Furthermore, 2-, 5-, and 10-year drug survival is longer for ETN compared to ADA.

Physical and mental fatigue in post-COVID syndrome and their associations over time: A small-sample ESM-study to explore fatigue, quality of sleep and behaviours.

OBJECTIVE: Post-COVID syndrome leaves millions of people with severe fatigue, yet little is known about its nature in daily life. In this exploratory study, momentary associations between physical and mental fatigue, quality of sleep and behaviours over two weeks in patients with post-COVID syndrome were assessed. METHOD: Data on fatigue levels, quality of sleep and behaviours was collected for 14 consecutive days using the experience sampling method in ten ex-hospitalised patients with post-COVID syndrome. RESULTS: Multilevel linear regression modelling showed strong associations between physical and mental fatigue (ß = 0.61, p ≤0.001), significant both between and within individuals. Sleeping more hours at night was associated with less physical and mental fatigue the following day (ß = -0.35, p = .001; ß = -0.27, p = .008). Strenuous relaxation (B = 0.45, p ≤0.001; B = 0.28, p = .004) and social contacts (B = -0.33, p = .003; B = -0.22, p = .02) were associated with physical and mental fatigue at the same measurement point. Performing household chores decreased physical and mental fatigue (B = -0.29, p = .02; B = -0.30, p = .006) two hours later on the same day, whereas eating and drinking increased physical fatigue (B = 0.20, p = .05) two hours later on the same day. CONCLUSION: Physical fatigue and mental fatigue were strongly associated and revealed fluctuations in fatigue levels between individuals, which might suggest potentially different post-COVID subgroups. Indications for potential risk and beneficial behaviours for fatigue were found.

Continuous effectiveness and safety after a hospital-wide switch to adalimumab biosimilar: An observational study in rheumatoid arthritis patients.

The objective of this study was to examine the maintenance of effect and safety after a hospital-wide switch for economic reasons from adalimumab originator Humira® to biosimilar Amgevita® in real-world rheumatoid arthritis (RA) patients and patient satisfaction with the switch. We conducted a single-center retrospective observational study of RA patients on the course of their disease activity (DAS28, ESR, and CRP), health-related quality of life (SF-36), and functional disability (HAQ-DI) before and up to 1 year after the switch, supplemented with a cross-sectional survey on satisfaction and experienced side effects approximately 18 months after the switch. Treatment outcomes were analyzed with linear mixed modeling and generalized estimating equations. Of 52 RA patients sufficient data were available. Disease activity levels, the proportion of patients in remission, and SF-36 and HAQ-DI scores did not significantly change from before the switch. Overall, patients were satisfied with the switch. Three patients (7.9%) stopped the biosimilar due to side effects. In conclusion, switching to the adalimumab biosimilar did not result in increased disease activity or worse patient-reported outcomes. Also, there was no apparent evidence of increased side effects. Patients themselves were mostly satisfied with the switching experience.

The effectiveness of a web-based Dutch parenting program to prevent overweight in children 9-13 years of age: Results of a two-armed cluster randomized controlled trial.

INTRODUCTION: Although parental support is an important component in programs designed to prevent overweight in children, current programs pay remarkably little attention to the role of parenting. We therefore developed a web-based parenting program entitled "Making a healthy deal with your child". This e-learning program can be incorporated into existing overweight prevention programs. The aim of this study was to determine the effectiveness of this e-learning program. MATERIALS AND METHODS: The effectiveness was examined in a two-armed cluster randomized controlled trial. The participants were 475 parent-child dyads of children 9-13 years of age in the Netherlands who participated in an existing schoolclass-based overweight prevention program. At the school grade level, parents were randomly assigned to either the intervention or the control condition. Measurements were taken from both parents and children at baseline, and 5 and 12 months after baseline. Primary outcomes included the child's dietary and sedentary behavior, and level of physical activity. Secondary outcomes included general parenting style, specific parenting practices, and parental self-efficacy. Linear mixed effects models and generalized linear mixed effects models were conducted in R. RESULTS: Intention-to-treat analyses and completers only revealed no significant effects between the intervention and control condition on energy balance-related behaviors of the child and parenting skills after correction for multiple testing. The parents' mean satisfaction with the e-learning program (on a 10-point scale) was 7.0±1.1. CONCLUSIONS: Although parents were generally satisfied with the parenting program, following this program had no significant beneficial effects regarding the children's energy balance-related behaviors or the parenting skills compared to the control condition. This program may be more beneficial if used by high-risk groups (e.g. parents of children with unhealthy energy balance-related behaviors and/or with overweight) compared to the general population, warranting further study.

Disentangling between- and within-person associations of psychological distress and mental well-being: An experience sampling study examining the dual continua model of mental health among university students.

The dual continua model assumes that psychological distress and mental well-being are two related, yet distinct dimensions of mental health. Previous studies did convincingly show the distinctiveness of these two dimensions using mainly cross-sectional research. Despite the importance to distinguish between- and within-person associations in psychological theories, to date, no study specifically distinguished between- and within-person associations for the relationship between distress and well-being. Therefore, the objective of this study was to validate whether the dual continua model actually holds when examined within individuals. Intensive longitudinal data were collected through experience sampling. The sample included 25 university students (mean age = 23.50 years, 56% female), who completed a baseline questionnaire as well as momentary measures of psychological distress and mental well-being three times per day for two weeks. 1,014 timepoints were analyzed using multilevel models and person-mean centering was applied to distinguish between- and within person associations. A significant moderate negative between-person association was found for the relationship between psychological distress and mental well-being (ß = -.363, marginal R 2 = 0.15, p < .001). The within-person association was also significant and similar in magnitude (ß = -.432, marginal R 2 = 0.18, p < .001) at the group level. Individual within-person associations between distress and well-being varied substantially, but were negative for almost all participants. This study is an important step towards validating the applicability and universality of this widely used model. The current findings provide preliminary evidence that the dual continua model does not only hold between people, but also on the level it is actually used for, namely within individual people.

Fatigue is associated with disease activity in some, but not all, patients living with rheumatoid arthritis: disentangling "between-person" and "within-person" associations.

BACKGROUND: Previous research has shown an unclear and inconsistent association between fatigue and disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to explore differences in "between-person" and "within-person" associations between disease activity parameters and fatigue severity in patients with established RA. METHODS: Baseline and 3-monthly follow-up data up to one-year were used from 531 patients with established RA randomized to stopping (versus continuing) tumor necrosis factor inhibitor treatment enrolled in a large pragmatic trial. Between- and within-patient associations between different indicators of disease activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], swollen and tender joint count [ SJC and TJC], visual analog scale general health [VAS-GH]) and patient-reported fatigue severity (Bristol RA Fatigue Numerical Rating Scale) were disaggregated and estimated using person-mean centering in combination with repeated measures linear mixed modelling. RESULTS: Overall, different indices of disease activity were weakly to moderately associated with fatigue severity over time (ß's from 0.121 for SJC to 0.352 for VAS-GH, all p's < 0.0001). Objective markers of inflammation (CRP, ESR and SJC) were associated weakly with fatigue within patients over time (ß's: 0.104-0.142, p's < 0.0001), but not between patients. The subjective TJC and VAS-GH were significantly associated with fatigue both within and between patients, but with substantially stronger associations at the between-patient level (ß's: 0.217-0.515, p's < 0.0001). Within-person associations varied widely for individual patients for all components of disease activity. CONCLUSION: Associations between fatigue and disease activity vary largely for different patients and the pattern of between-person versus within-person associations appears different for objective versus subjective components of disease activity. The current findings explain the inconsistent results of previous research, illustrates the relevance of statistically distinguishing between different types of association in research on the relation between disease activity and fatigue and additionally suggest a need for a more personalized approach to fatigue in RA patients. Trial registration Netherlands trial register, Number NTR3112.

Neuropsychiatric adverse drug reactions associated with low dose methotrexate in rheumatoid arthritis patients.

BACKGROUND: Neuropsychiatric adverse drug reactions (NPADRs) are not commonly associated with low dose methotrexate (LDMTX) in patients with rheumatoid arthritis (RA). RESEARCH DESIGN AND METHODS: In this case series assessment, we described the nature and frequency of NPADRs with LDMTX in the Dutch DREAM-RA registry, including causality of NPADRs, the impact on further LDMTX treatment and the impact on patient reported Health Related Quality of Life (HRQoL). RESULTS: A total of 71 NPADRs (frequency 6.8%) associated with LDMTX were captured in the DREAM-RA registry. NPADRs were registered for 62 (5.9%) out of 1048 patients with 10.9 NPADRs per 1000 patient years. Headache, dizziness and depression were most frequently reported. The causality was considered probable for 67 NPADRs (94.4%) and definite for 1 NPADR (1.4%). NPADRs led to LDMTX withdrawal in 34 cases (47.9%) and was not restarted in 16 cases (47.1%). Median mental HRQoL was significantly decreased around the occurrence of the NPADR and remained significantly lower after the event. Median physical HRQoL was not significantly affected. CONCLUSIONS: Knowledge on the nature, frequency and impact of the demonstrated NPADRs during LDMTX therapy will enhance attention toward these potential ADRs allowing better risk assessment and communication to patients.

Performance of 3 Composite Measures for Disease Activity in Peripheral Spondyloarthritis.

OBJECTIVE: To investigate concurrent validity and discrimination of the Disease Activity Index for Psoriatic Arthritis (DAPSA) score, Psoriatic Arthritis Disease Activity Score (PASDAS), and Ankylosing Spondylitis Disease Activity Score (ASDAS) in peripheral spondyloarthritis (pSpA) in clinical practice. METHODS: Data from a Dutch registry for SpA (SpA-Net) were used. Predefined hypotheses on concurrent validity of the composite measures with 15 other outcome measures of disease activity, physical function, and health-related quality of life were tested. Concurrent validity was considered acceptable if ≥ 75% of the hypotheses were confirmed. Discrimination was assessed by stratifying patients in DAPSA, PASDAS, and ASDAS predefined disease activity states and studying mean differences in health outcomes by 1-way ANOVA. Further, the concordance in disease activity states was determined. All analyses were repeated in subgroups with and without psoriasis (PsO). RESULTS: DAPSA, PASDAS, and ASDAS scores were available for 191, 139, and 279 patients with pSpA, respectively. The concurrent validity and discrimination of all composite measures were acceptable, as the strength of correlations were as hypothesized in ≥ 75% of the studied correlations. With increasing disease activity states, scores in nearly all outcome measures worsened significantly. The DAPSA, PASDAS, and ASDAS classified 22%, 56%, and 48% of the patients, respectively, in the 2 highest disease activity states. Stratified analyses for concomitant PsO revealed no relevant subgroup differences. CONCLUSION: The performance of DAPSA, PASDAS, and ASDAS in pSpA was acceptable, and independent of concomitant PsO. Due to discrepancy in classification, the validity of existing thresholds for disease activity states warrants further study in pSpA.

Generalized pain hypersensitivity and associated factors in gout.

OBJECTIVES: Previous studies have indicated that a sizeable proportion of patients with inflammatory arthritis present with features characteristic of central pain sensitization. However, this has not yet been examined in patients with gout. The objective of this study was to explore the presence of generalized pain hypersensitivity and associated factors in patients with diagnosed gout. METHODS: A cross-sectional survey was performed in outpatients with crystal proven gout using the generalized pain questionnaire (GPQ) to screen for the presence of generalized pain hypersensitivity. Additional self-reported socio-demographic and medical information was collected and several patient-reported outcome measures were completed. Univariable logistic regressions and multivariable LASSO regression analysis with 10-fold cross-validation was used to explore relationships with patient characteristics, clinical features and PROMs. RESULTS: Of the 97 included patients (84.5% male; mean (s.d.) age: 68.9 ± 11.9 years), 20 patients (20.6%, 95% CI: 13.0, 30.0) reported possible generalized pain hypersensitivity defined as a GPQ score ≥11 (range: 0-28; mean (s.d.) GPQ: 6.3 ± 5.3). Lower age, concomitant fibromyalgia and more experienced difficulties in performing their social role were independently associated with generalized pain hypersensitivity. Notably, use of urate lowering therapy was significantly lower in those with generalized pain hypersensitivity. CONCLUSIONS: Generalized pain hypersensitivity appears to be quite common in gout, despite its more intermittent nature compared with other inflammatory arthritides. As this kind of pain does not respond well to regular treatment, screening for non-inflammatory pain may be important for improving pain management in gout.

Responsible Relations: A Systematic Scoping Review of the Therapeutic Alliance in Text-Based Digital Psychotherapy.

Introduction: Developing a good therapeutic alliance is considered essential for the responsible delivery of psychotherapy. Text-based digital psychotherapy has become increasingly common, yet much remains unclear about the alliance and its importance for delivering mental health care via a digital format. To employ text-based digital therapies responsibly, more insight is needed into the type and strength of the therapeutic alliance online. Methods: A systematic scoping review was performed searching four databases: Scopus, PsycINFO, Web of Science, and Wiley Online Library. A total of 23 studies were selected and data was extracted and tabulated to explore the characteristics of studies on text-based psychotherapy, measurements of the therapeutic alliance and associations of the alliance with treatment outcome. Results: The therapeutic alliance in text-based digital interventions was studied with a variety of client groups, though mostly for clients diagnosed with anxiety and/or depression issues. Treatment modalities were predominantly internet-based cognitive behavioral therapy (ICBT) and tailored platforms for distinct client groups (e.g., PTSD). Almost all treatments used asynchronous text-based communication, such as e-mails and integrated messaging functions, which were mainly used to give feedback on tasks. For measurements, a version of the Working Alliance Inventory (WAI) was used in most studies. Measurements with the WAI or WAI- short form indicated a good therapeutic alliance with a weighted mean score of 5.66 (on a scale of 1 to 7) and a weighted standard deviation of 0.84. Relations between the therapeutic alliance and treatment outcomes were mostly positive, with many studies reporting significant associations (n = 8 out of 10) or significant effects of the therapeutic alliance on treatment outcomes (n = 5 out of 6). Discussion: Our scoping review suggests that a good therapeutic alliance can be established in digital psychotherapy through text-based communication, and shows support for a positive relationship between the alliance and treatment outcomes. These findings illustrate that text-based online psychotherapy can be a responsible treatment option as far as the establishment of the therapeutic alliance is concerned. However, current measures of the therapeutic alliance might miss important aspects of the alliance in digital treatment, such as the presence of empathy or compassion.