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Objective: This study examined depressive symptomatology (DS) across the academic year in first-year undergraduate students and the influence of DS on anxiety, stress, body esteem, physical activity, and sleep. Participants: Participants were first-year undergraduate students (N= 164). Methods: Participants completed validated self-report measures each quarter. A repeated measures ANCOVA was conducted to examine changes in DS over time. Students were categorized as reporting subclinical (SCD) or clinical (CD) depressive symptoms. A repeated measures MANCOVA was conducted to examine the effect of time and DS groups on primary outcomes. Results: No significant main effects of time were observed for outcomes. Significant between-subjects effects were observed with CD participants reporting significantly higher anxiety and stress and lower sleep than SCD participants. Conclusions: First-year undergraduates with CD may have increased risk for negative markers of psychological and physical health outcomes. Universities should prioritize the psychological and physical health of their first-year students.

Study Question: What is the prevalence of pre-eclampsia (PE) in pregnancies after oocyte donation (OD) compared to natural conception (NC) and to IVF with autologous oocytes (AO)?Summary Answer: Overall the prevalence of PE after OD was 4-5 times higher than after NC and 2-3 times higher than after IVF with AO.What Is Known Already: The indication for OD is expanding to lesbian women requesting shared lesbian motherhood. Previous reviews have shown that the risk of PE is higher in pregnancies after OD than after NC and after IVF with AO. Classification on the severity of PE is lacking as is the relationship with known risk factors such as maternal age and multiple gestations. Furthermore the actual prevalence of PE in pregnancies resulting from OD is not known.Study Design, Size, Duration: A systematic review and meta-analysis was conducted. A literature search was performed using the following databases: PubMed, EMBASE and CINAHL, OpenGrey and Greynet from January 1980 through July 2020.Participants/materials, Setting, Methods: We included retrospective and prospective cohort studies. The study population consisted of pregnancies after OD and NC or IVF and data had to be available about prevalence of PE. We compared the risk of (severe) PE in OD versus NC and IVF pregnancies, subgrouped by plurality and maternal age. We calculated individual and pooled odds ratios (OR) and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2.Main Results and the Role Of Chance: In total, 27 studies comprising of 7089 OD pregnancies, 1 139 540 NC pregnancies and 72 742 IVF pregnancies were available for analysis. The risks of PE and severe PE was increased in OD pregnancies compared to NC pregnancies (pooled OR of all subgroups: 5.09, 95% CI: 4.29-6.04; I2 = 19% and OR: 7.42, 95% CI: 4.64-11.88; I2 = 49%, respectively). This suggests that compared to a PE risk of 2.9% with NC, the risk with OD was between 11.5% and 15.4%. Compared to a severe PE risk of 0.5% with NC, the risk with OD was between 2.3% and 5.6%. The pooled adjusted OR for PE was 3.24 (95% 2.74-3.83) for OD versus NC pregnancies. The risks of PE and severe PE were also increased in OD pregnancies compared to IVF pregnancies (pooled OR of all subgroups: 2.97, 95% CI: 2.49-3.53; I2 = 51% and OR: 2.97, 95% CI: 2.15-4.11; I2 = 0%, respectively). This suggests that compared to a PE risk of 5.9% with IVF, the risk with OD was between 13.5% and 18.0%. Compared to a severe PE risk of 3.3% with IVF, the risk with OD was between 6.8% and 12.2%. The pooled adjusted OR for PE was 2.67 (95% 2.28-3.13) for OD versus IVF. The pooled prevalence of PE in singleton pregnancies after OD was 10.7% (95% CI 6.6-15.5) compared to 2.0% (95% CI 1.0-3.1) after NC and 4.1% (95% CI 2.7-5.6) after IVF. The prevalence in multiple pregnancies was 27.8% (95% CI 23.6-32.2) after OD, 7.5% (95% CI 7.2-7.8) after NC and 9.7% (95% CI 6.2-13.9) after IVF.Limitations, Reasons For Caution: The precise definition of PE is still a matter of debate. The different criteria could have affected the prevalence estimate.Wider Implications Of the Findings: Nearly one in six women will suffer PE after OD. Although it is uncertain whether these risks are consistent for lesbian couples undergoing shared motherhood, we feel that women who can conceive naturally could be advised to reconsider. In women with primary ovarian insufficiency, we feel that factors that may increase risk of PE ever further, such as double embryo transfer, should be avoided whenever possible.Study Funding/competing Interest(s): No funding or competing interests.Registration Number: CRD42020166899. [ABSTRACT FROM AUTHOR]

Background: Inflammation is increasingly recognised as a treatment target in hand osteoarthritis, and therefore correct measurement of local inflammation is essential. This study aimed to assess ultrasound scoring of synovitis and the additional value of the Global OMERACT/EULAR Ultrasound Synovitis Score (GLOESS) in hand osteoarthritis., Methods: Data from the randomised, double-blinded Hand Osteoarthritis Prednisolone Efficacy (HOPE) trial were used. The HOPE trial included patients with painful, inflammatory hand OA, treated with prednisolone or placebo (1:1). Ultrasound was performed in 30 hand joints at weeks 0, 6 and 14. Effusion, synovial thickening and Doppler signal were measured, the GLOESS was calculated from the latter two. Joint tenderness on palpation was assessed semiquantitatively (0-3), soft swelling as present/absent. Changes in ultrasound scores, and their association with change in joint tenderness or soft swelling, were investigated using generalised estimating equations. Effect sizes were calculated., Results: Of 92 included patients 79% were women, with mean (SD) age 63.9 (8.8) and body mass index 27.2 (4.6). Synovial thickening was the most prevalent. All ultrasound scores were strongly associated with joint tenderness and soft swelling cross-sectionally. There was no association of change in ultrasound scores with change in tenderness, but there was with change in soft tissue swelling. Synovial thickening and the GLOESS responded to treatment (effect size -0.39 (-0.72 to -0.07), -0.39 (-0.71 to -0.07), respectively)., Discussion: Various ultrasound scores were associated with joint tenderness and soft swelling. The GLOESS and synovial thickening were both responsive to treatment, but GLOESS was not superior to synovial thickening alone., Competing Interests: Competing interests: MK reports the following, all outside the current study. Grant from IMI-APPROACH. Royalties or licences from Wolters Kluwer and Springer Verlag, paid to the institution. Fees for consulting/advisory boards by Pfizer, UCB, CHDR, GSK, Novartis and Peptinov, all paid to the institution. Payment or honoraria for lectures or presentations from Novartis, paid to the institution. Roles on the OARSI board (member), EULAR council (member advocacy committee EULAR) and presidency of the Dutch Society for Rheumatology. For the current study, MK reports funding from the Dutch Arthritis Society, paid to the institution. The other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aimed to characterize hand osteoarthritis (OA) patients with deteriorating or improving hand pain, and to investigate patients achieving good clinical outcome after four years., Methods: We used four year annual Australian/Canadian hand osteoarthritis index (AUSCAN) pain subscale (range 0-20) measurements from the HOSTAS cohort (hand OA patients). Pain changes were categorized as deterioration, stable and improvement using the Minimal Clinical Important Improvement (MCII). Good clinical outcome was categorized using the Patient Acceptable Symptom State (PASS). Associations between baseline characteristics (patient and disease characteristics, coping styles, illness perceptions) and outcomes were investigated using multinomial or binary logistic regression, adjusted for baseline pain, age, sex and BMI., Results: 356 patients (83% female, mean age 60.6 years, mean AUSCAN 9.1) were analyzed. Pain improved for 38%, deteriorated for 30% and remained stable for 32% over four years. Four year pain development followed annual trends. At baseline, 44% of patients reached PASS, 49% at follow-up. Higher BMI, coping through comforting cognitions and illness comprehension were positively associated with pain deterioration. Higher AUSCAN function score, mental wellbeing and illness consequences were negatively associated with pain improvement. Employment (positively) and emotional representations (negatively) were associated with both improvement and deterioration. Higher baseline AUSCAN function, tender joint count and symptoms attributed to hand OA were associated negatively with PASS after four years., Conclusions: The pain course of hand OA patients is variable, not inevitably worsening, and various factors may play a role. Whether modification of these risk factors can influence pain outcomes requires further investigation., (This article is protected by copyright. All rights reserved.)

Objectives: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features., Methods: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria., Results: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts., Conclusions: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology., Competing Interests: Competing interests: IKH reports personal fees from Novartis and GSK; research grants from Pfizer and IMI-APPROACH (both paid to the institution); and unpaid role as secretary general of OARSI, all outside of the submitted work. AA reports institutional research grants from AstraZeneca and Oxford Immunotech; and personal fees from UpToDate (royalty), Springer (royalty), Cadilla Pharmaceuticals (lecture fees), NGM Bio (consulting), Limbic (consulting) and Inflazome (consulting), all outside of the submitted work. FB reports shares of 4P Pharma and 4Moving Biotech; personal fees from Boehringer Ingelgeim, Galapagos, Gilead, GSK, Merck Sereno, MSD, Novartis, Pfizer, Roche, Sanofi, Servier and Viatris; and research grant from TRB Chemedica, all outside the submitted work.Sita Bierma-Zeinstra reports research grants from Dutch Arthritis Association, EU Horizon, EU ERC and ZonMW (paid to institution), personal fees from Pfizer, Infirst healthcare, and paid role as deputy editor of Osteoarthritis and Cartilage, all outside of the submitted work.Krysia Dziedzic reports research grants from National Institute for Health and Care Research (NIHR); royalty/licence for Textbook for Rheumatology Therapists; payment for lecture at Australian Rheumatology Association Conference in May 2022; Implementation Advisor Fellows and Scholars Programme National Institute for Health and Care Excellence (UK 2019-22), Steering group member of NICE Implementation subgroup and Steering group member of OARSI Joint Effort initiative, all paid to institution and outside of the submitted work.Martin Englund reports personal fees from Cellcolabs AB (Sweden) and Key2 Compliance (Sweden), outside of the submitted work. Ying Ying Leung reports grants from National Medical Research Council (NMRC/CSA-INV/0022/2017), and personal fees from AbbVie, DKSH, Janssen, Novartis and Pfizer, outside of the submitted work. EM reports personal fees from Expanscience, Keyrus Life Science, Pierre Fabre, Rottapharm, MEDA-Mylan, Sublimed, TRB Chemedica, outside the submitted work. RR reports personal fees from from Novartis, AbbVie, Pfizer, MSD, Janssen, Lilly; support for attending EULAR, ACR and SIR; advisory board for Janssen, Novartis and Abbvie, outside of the submitted work. TAS reports grants and personal fees from AbbVie and Roche, and personal fees from Sanofi, Takeda and Novartis, outside the submitted work. ZS reports personal fees from AbbVie, Pfizer, Roche, Novartis, Lilly, Gedeon Richter, Sobi/Galapagos, outside of the submitted work. RW reports institutional research grants from Pfizer and Amgen, unrelated to this work, and is a Senior Clinical Investigator of the Research Foundation Flanders (Belgium) (FWO) (1803023N). MK reports consulting fees from Abbvie, Pfizer, Kiniksa, Flexion, Galapagos, Jansen, CHDR, Novartis and UCB (all paid to institution), outside of the submitted work. DF, JJE, MH-E, GH-B, CH, MLI, HJ, TK, CDM, MM, RHM, VR, MJPFR, FVG, LAS, CM, EG and HL report no conflicts of interest., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: The Health Assessment Questionnaire-Disability Index is an important outcome measure reflecting functional disability, but knowledge on its course over time in patients with systemic sclerosis is scarce. Therefore, we investigated the long-term course of the Health Assessment Questionnaire-Disability Index and its association with baseline characteristics in systemic sclerosis patients., Methods: Systemic sclerosis patients, fulfilling the European League Against Rheumatism and the American College of Rheumatology 2013 criteria, were included from the Leiden Combined Care in Systemic Sclerosis cohort with annual assessments including the Scleroderma Health Assessment Questionnaire-Disability Index (range = 0-3). The course of the Health Assessment Questionnaire-Disability Index was evaluated over the total follow-up (baseline to last available Health Assessment Questionnaire-Disability Index) and between yearly visits. Based on a minimal clinical important difference of 0.22, courses were categorized into worsening, stable or improvement. The course of the Health Assessment Questionnaire-Disability Index over time was evaluated with linear mixed models. Baseline characteristics were compared between patients with a worsening or improvement of the Health Assessment Questionnaire-Disability Index over the total follow-up period with logistic regression analyses., Results: A total of 517 systemic sclerosis patients were included, with a median follow-up of 7 years (interquartile range = 4-9; 2649 visits) and a baseline Health Assessment Questionnaire-Disability Index of 0.625 (interquartile range = 0.125-1.25). On group level, the Health Assessment Questionnaire-Disability Index is stable with an annual increase of 0.019 (95% confidence interval = 0.011 to 0.027). Looking at subgroups, patients >65 years or who died/were physically unable to come during follow-up had a worse mean Health Assessment Questionnaire-Disability Index. In individual courses from baseline to the last follow-up, the proportions of patients with a clinically meaningful worsening, stable or improved Health Assessment Questionnaire-Disability Index were 35%, 42% and 23%, respectively. Patients with immunosuppressants (odds ratio = 0.5, 95% confidence interval = 0.3 to 0.9) or gastrointestinal involvement (odds ratio = 0.6, 95% confidence interval = 0.4 to 0.9) at baseline showed a reduced chance of worsening of the Health Assessment Questionnaire-Disability Index over the total follow-up period., Conclusion: Over time, the average course of the Health Assessment Questionnaire-Disability Index was stable in systemic sclerosis patients. However, individual courses vary, with worsening occurring in one-third. Worsening occurred less often in individuals using immunosuppressants or with gastrointestinal involvement at baseline., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2023.)

Objectives: To investigate pain, pain trajectories and their determinants in hand osteoarthritis (OA)., Methods: Data from the HOSTAS (Hand OSTeoArthritis in Secondary care) consisting of consecutive hand OA patients were used. Australian Canadian Osteoarthritis Hand Index (AUSCAN) pain was measured yearly for four years. Patients with complete AUSCAN at ≥2 time points were eligible for longitudinal analysis. Associations between variables of interest and baseline AUSCAN pain were investigated with linear regression. Development of pain over time was modelled using latent class growth analysis (LCGA). Associations of LCGA classes with variables of interest were analysed using multinomial logistic regression adjusted for baseline pain., Results: A total of 484/538 patients [mean (s.d.) age 60.8 (8.5) years, 86% women, mean (s.d.) AUSCAN pain 9.3 (4.3)] were eligible for longitudinal analysis. Sex, marital and working status, education, disease duration and severity, anxiety and depression scores, lower health-related quality of life (HR-QoL), specific illness perceptions and coping styles were associated with baseline pain. LCGA yielded three classes, characterized by average pain levels at baseline; average pain remained stable over time within classes. Classes with more pain were positively associated with BMI, tender joint count, symptom duration, hand function scores and depression scores, negatively with physical HR-QoL, and education level., Conclusion: Baseline pain was associated with patient and disease characteristics, and psychosocial factors. LCGA showed three pain trajectories in hand OA patients, with different baseline pain levels and stable pain over time. Classes were distinguished by BMI, education level, disease severity, depression and HR-QoL., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Ubiquitin and ubiquitin-like conjugation cascades consist of dedicated E1, E2, and E3 enzymes with E3s providing substrate specificity. Mass spectrometry-based approaches have enabled the identification of more than 6500 SUMO2/3 target proteins. The limited number of SUMO E3s provides the unique opportunity to systematically study E3 substrate wiring. We developed SUMO-activated target traps (SATTs) and systematically identified substrates for eight different SUMO E3s, PIAS1, PIAS2, PIAS3, PIAS4, NSMCE2, ZNF451, LAZSUL (ZNF451-3), and ZMIZ2. SATTs enabled us to identify 427 SUMO1 and 961 SUMO2/3 targets in an E3-specific manner. We found pronounced E3 substrate preference. Quantitative proteomics enabled us to measure substrate specificity of E3s, quantified using the SATT index. Furthermore, we developed the Polar SATTs web-based tool to browse the dataset in an interactive manner. Overall, we uncover E3-to-target wiring of 1388 SUMO substrates, highlighting unique and overlapping sets of substrates for eight different SUMO E3 ligases.

Objective: Surgical denervation has been proposed as a treatment for pain in hand osteoarthritis (OA). This review aimed to summarise the available evidence and to propose a research agenda., Methods: A systematic literature search was performed up to September 2022. Two investigators independently identified studies that reported on denervation for OA of the proximal interphalangeal, distal interphalangeal, metacarpophalangeal or carpometacarpal joints. Quality of studies was assessed and study characteristics, patient characteristics, details of the surgical technique and outcomes of the surgery were extracted., Results: Of 169 references, 17 articles reporting on 384 denervations in 351 patients were selected. Sixteen case series reported positive outcomes with respect to pain, function and patient satisfaction. One non-randomised clinical trial reported no difference in outcome when comparing denervation of the first carpometacarpal (CMC I) joint to trapeziectomy. Adverse events were frequent, with sensory abnormalities occurring the most, followed by the need for revision surgery. All studies had significant risk of bias., Conclusion: Surgical denervation for pain in hand OA shows some promise, but the available evidence does not allow any conclusions of efficacy and higher-quality research is needed. Techniques should be harmonised and more data regarding how denervation compares to current usual care, other denervation methods or placebo in terms of outcomes and adverse events are needed., Competing Interests: Competing interests: MK reports the following, all outside the current study: Grants from IMI-APPROACH and the Dutch Arthritis Society, paid to the institution. Royalties or licences from Wolters Kluwer and Springer Verlag, paid to the institution. Fees for consulting/advisory boards by Abbvie, Kiniksa, Galapagos, CHDR, Novartis, UCB, all paid to the institution. Payment or honoraria for lectures or presentations from Galapagos and Jansen, paid to the institution. Roles on the OARSI board (member), EULAR council (member advocacy committee EULAR) and presidency of the Dutch Society for Rheumatology. For the current study, MK reports funding from SKMS, paid to the institution., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pain is common in hand osteoarthritis (OA) and multiple types may occur. We investigated the prevalence, associated patient characteristics, influence on health-related quality of life (HR-QoL) and response to anti-inflammatory treatment of neuropathic-like pain in inflammatory hand OA., Methods: Data were analysed from a 6-week, randomized, double-blind, placebo-controlled trial investigating prednisolone treatment in 92 patients with painful inflammatory hand OA. Neuropathic-like pain was measured with the painDETECT questionnaire. Associations between baseline characteristics and baseline neuropathic-like pain were analysed with ordinal logistic regression, association of baseline neuropathic-like pain symptoms with baseline HR-QoL with linear regression, painDETECT and visual analogue scale (VAS) change from baseline to week 6 and interaction of painDETECT with prednisolone efficacy on VAS pain change from baseline to week 6 with generalized estimating equations (GEE)., Results: Of 91 patients (79% female, mean age 64) with complete painDETECT data at baseline, 53% were unlikely to have neuropathic-like pain, 31% were indeterminate and 16% were likely to have neuropathic-like pain. Neuropathic-like pain was associated with female sex, less radiographic damage and more comorbidities. Patients with neuropathic-like pain had lower HR-QoL (PCS-6.5 [95% CI -10.4 to -2.6]) than those without. Neuropathic-like pain symptoms remained under prednisolone treatment and no interaction was seen between painDETECT and prednisolone efficacy on VAS pain., Conclusions: In this study, 16% of inflammatory hand OA patients had neuropathic-like pain. They were more often female, had more comorbidities and had lower QoL than those without. Neuropathic-like pain symptoms remained despite prednisolone treatment and did not seem to affect the outcome of prednisolone treatment., Significance: Pain is the dominant symptom in hand OA, with an unclear aetiology. In this study, we found that neuropathic-like pain may play a role in hand OA, that it showed associations with female sex, younger age and more comorbidities and that it lowered health-related quality of life in hand OA. Neuropathic-like pain in hand OA seems resistant to prednisolone therapy but did not seem to interfere with the treatment of inflammatory pain with prednisolone., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.)

Purpose: Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients., Methods: Forty-four long-term controlled acromegaly patients (aged 62.6 ± 12.6 years; 56.8% female) were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0-35): unlikely (≤ 12), indeterminate (13-18) and likely (≥ 19). HR-QoL (physical component score (PCS), and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses., Results: Self-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL (PCS: r = - 0.46, P = 0.003; MCS: r = - 0.37, P = 0.018), and SF-36 pain scores (r = - 0.63, P < 0.0001). Female sex was a risk factor for NP-like symptoms., Conclusions: Pain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted., (© 2021. The Author(s).)

Diminished trust in professionals has resulted in professional pain among many of them. Professionals feel obstructed by external stakeholders such as policymakers and insurance companies who do not understand the reality in which professionals work. Protests by professionals against this type of disciplining have been diminishing for a long time, and some professionals have even collaborated with these stakeholders. In many professions, this has resulted in so-called 'voluntary servitude'. For instance, it has been stated that the majority of professionals in health care deviate from their standards of professional behaviour to a greater or lesser degree. This attitude of distrust towards professionals unjustly injures their professional pride. In this paper the concept of professional pride is explained and the authors argue why this is crucial for good healthcare.