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Objectives: We aimed to compare various methods for imputing disease activity in longitudinally collected observational data of patients with axial spondyloarthritis (axSpA)., Methods: We conducted a simulation study on data from 8583 axSpA patients from ten European registries. Disease activity was assessed by the Axial Spondyloarthritis Disease Activity Score (ASDAS) and the corresponding low disease activity (LDA; ASDAS<2.1) state at baseline, 6 and 12 months. We focused on cross-sectional methods which impute missing values of an individual at a particular time point based on the available information from other individuals at that time point. We applied nine single and five multiple imputation methods, covering mean, regression and hot deck methods. The performance of each imputation method was evaluated via relative bias and coverage of 95% confidence intervals for the mean ASDAS and the derived proportion of patients in LDA., Results: Hot deck imputation methods outperformed mean and regression methods, particularly when assessing LDA. Multiple imputation procedures provided better coverage than the corresponding single imputation ones. However, none of the evaluated methods produced unbiased estimates with adequate coverage across all time points, with performance for missing baseline data being worse than for missing follow-up data. Predictive mean and weighted predictive mean hot deck imputation procedures consistently provided results with low bias., Conclusions: This study contributes to the available methods for imputing disease activity in observational research. Hot deck imputation using predictive mean matching exhibited the highest robustness and is thus our suggested approach., Competing Interests: Competing interests: SG: Novartis, UCB; MP: Novartis, UCB; SR: Novartis, UCB; MLH: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, Medac, MSD, Novartis, Nordforsk, Pfizer, Roche, Samsung Biopies, Sandoz; LL: Novartis, UCB; DdG: none; BM: Novartis; JKW: AbbVie, Amgen, Eli Lilly, Novartis, Pfizer; TO: MSD, UCB; JZ: Abbvie, AstraZeneca, Egis, Elli Lilly, Novartis, Sandoz, Sanofi, Sobi, UCB; BG: Abbvie, BMS, Pfizer, Sandoz; AGL: AbbVie, Janssen, Eli Lilly, Novartis, Pfizer, UCB; CC: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Ewopharma, Eli Lilly, Novartis, Pfizer, Sandoz, Sobi; DM: none; DA: none; SAP: Boehringer Ingelheim; TKK: AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, Grünenthal, Novartis, Pfizer, Sandoz, UCB; VR: Abbvie, BMS, Lilly, Novartis, Viatris; RP: Abbvie, Boehringer Ingelheim, Celltrion, Eli Lilly, Fresenius, Galapacos. Janssen, UCB; BG: none; OP: none; OR: none; RMD: none; ZR: Abbvie, Amgen, AstraZeneca, Biogen, Eli Lilly, Janssen, Lek, Medis, MSD, Novartis, Pfizer, Sanofi, Sobi, Swixx BioPharma; KPP: Abbvie, Boehringer Ingelheim, Eli Lilly, Medis, MSD, Lek, Novartis, Pfizer; KL: Abbvie, Johnson and Johnson, Novartis, Pfizer; FI: Abbvie, Amgen, AstraZeneca, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB; AC: none; MØ: Abbvie, Amgen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB; LMO: Novartis, UCB., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objective: To establish recommendations for thromboprophylaxis in patients with endogenous Cushing's syndrome (CS), addressing the elevated risk of venous thromboembolism (VTE) associated with hypercortisolism., Methods: A Delphi method was used, consisting of four rounds of voting and subsequent discussions. The panel included 18 international experts from 11 countries and 4 continents.Consensus was defined as ≥75% agreement among participants. Recommendations were structured into the following categories: thromboprophylaxis, perioperative management, and VTE treatment., Results: Consensus was reached on several critical areas, resulting in 14 recommendations. Key recommendations include: thromboprophylaxis should be considered at time of CS diagnosis and continued for three months after biochemical remission, provided there are no obvious contraindications. The standard weight-based prophylactic dose of low molecular weight heparin is the preferred agent for thromboprophylaxis in patients with CS. Additionally, perioperatively and around inferior petrosal sinus sampling, thromboprophylaxis should be reconsidered if not already initiated at diagnosis. For VTE treatment, extended thromboprophylaxis is advised continuing for three months after Cushing is resolved., Conclusion: These Delphi consensus-based recommendations aim to standardise care practices and enhance patient outcomes in CS by providing guidance on thromboprophylaxis, including its initiation and continuation across various disease states, as well as the preferred agents to use. The panel also highlighted key areas for further research, particularly regarding the use of direct oral anticoagulants in CS and the management of mild CS and mild autonomous cortisol secretion. Additionally, the optimal duration of anticoagulant prophylaxis following curative treatment remains uncertain., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: In patients with axial spondyloarthritis (axSpA) initiating secukinumab, we aimed to identify baseline (treatment start) predictors of achieving low disease activity (LDA) after 6 months, as measured by Axial Spondyloarthritis Disease Activity Score using C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), as well as treatment continuation after 12 months., Methods: From 11 European registries, patients with axSpA, who initiated secukinumab treatment in routine care, with available data on 6-month ASDAS and BASDAI assessments were included. Logistic regression analyses on multiply imputed baseline data were performed; potential baseline predictors included demographic, diagnosis, lifestyle, clinical and patient-reported variables., Results: In a pooled cohort of 1,174 patients with axSpA, 5 of 19 potential assessed variables were mutually predictive for achieving LDA by ASDAS-CRP and BASDAI: higher Physician Global Assessment score, non-current smoking, lack of prior exposure to biologic/targeted synthetic Disease-Modifying Anti-Rheumatic Drugs, lower Health Assessment Questionnaire scores and BASDAI scores. Moreover, radiographic axSpA and CRP ≤ 10mg/L were associated with achieving ASDAS-CRP LDA; HLA-B27 positivity and history of psoriasis with achieving BASDAI LDA; while earlier time of secukinumab initiation (2015-2017) was associated with treatment continuation., Conclusion: In this European real-world study of patients with axSpA initiating secukinumab, predictors of achieving LDA by ASDAS-CRP and BASDAI at 6 months and remaining on treatment at 12 months included both clinical, patient-reported and lifestyle factors, underscoring the complex mechanisms of real-world drug effectiveness.

Purpose: This study aimed to develop and validate a comprehensive polygenic risk score (PRS) for keratoconus, enhancing the predictive accuracy for identifying individuals at increased risk, which is crucial for preventing keratoconus-associated visual impairment such as post-Laser-assisted in situ keratomileusis (LASIK) ectasia., Methods: We applied a multi-trait analysis approach (MTAG) to genome-wide association study data on keratoconus and quantitative keratoconus-related traits and used this to construct PRS models for keratoconus risk using several PRS methodologies. We evaluated the predictive performance of the PRSs in two biobanks: Estonian Biobank (EstBB; 375 keratoconus cases and 17 902 controls) and UK Biobank (UKB: 34 keratoconus cases and 1000 controls). Scores were compared using the area under the curve (AUC) and odds ratios (ORs) for various PRS models., Results: The PRS models demonstrated significant predictive capabilities in EstBB, with the SBayesRC model achieving the highest OR of 2.28 per standard deviation increase in PRS, with a model containing age, sex and PRS showing good predictive accuracy (AUC = 0.72). In UKB, we found that adding the best-performing PRS to a model containing corneal measurements increased the AUC from 0.84 to 0.88 (P = 0.012 for difference), with an OR of 4.26 per standard deviation increase in the PRS. These models showed improved predictive capability compared to previous keratoconus PRS., Conclusion: The PRS models enhanced prediction of keratoconus risk, even with corneal measurements, showing potential for clinical use to identify individuals at high risk of keratoconus, and potentially help reduce the risk of post-LASIK ectasia., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Spondylolysis is defined as a defect or elongation in the pars interarticularis of the lumbar spine, either unilateral or bilateral. Growing children with bilateral spondylolysis may develop spondylolisthesis, i.e., forward slipping of the affected vertebra. The etiology of spondylolysis is regarded as a stress fracture due to repetitive loading associated with a genetic predisposition. Lumbar magnetic resonance imaging (MRI) shows an increased signal intensity before an actual fracture line develops. In low grade spondylolisthesis, two-thirds of children with acute pediatric spondylolysis will undergo bony union with early activity restriction. Health-related quality of life is improved in patients achieving bony union as compared with patients having non-union, of which one-fourth will additionally develop spondylolisthesis. In patients with high-grade spondylolisthesis, defined as a more than 50% forward slippage of the affected vertebra, spinal fusion is recommended to prevent further progression.

Objectives: To explore thresholds for the Psoriatic Arthritis (PsA) Impact of Disease questionnaire (PsAID12) score against disease activity measures in an observational setting, in patients with PsA., Methods: The baseline data from the ReFlaP observational, prospective, multicentre and international study was used (NCT03119805). Cutoffs for PsAID12 were determined against disease activity scores, defining disease impact states (ie remission, low impact, moderate impact and high impact). Statistics used to assess the optimal cutoff point included the Youden's index and the 75th percentile method, with external anchors (i.e. DAPSA, VDLA/MDA and single questions for both patients and physicians) serving as gold standards. The diagnostic performance of these cutoffs was evaluated using Receiver Operating Characteristic (ROC) curve analyses., Results: A total of 410 patients were analyzed. Mean (standard deviation, SD) PsAID12 score was 3.4 (SD 2.5). The prevalence of remission varied between 12.4% and 36.1%, while low disease activity ranged from 37.8% to 59.8%. PsAID12 performed well against external anchors, with high areas under the ROC curves ranging from 0.75-0.94. Using the DAPSA as external anchor, the proposed PsAID12 cutoffs were <1.7 for remission, ≥1.7 to ≤ 3.1 for low impact, >3.1 to < 4.8 for moderate impact, and ≥4.8 for high impact. Compared with composite scores, patient and physician opinions performed less stringent., Conclusion: This study established cutoffs for PsAID12 in a clinical practice observational population, corresponding to remission and varying levels of disease impact. However, these proposed cutoffs need further validation, and an expert consensus is essential to confirm the most accurate thresholds for future use., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction/aims: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care., Methods: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs)., Results: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death., Discussion: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Introduction: Ecosystem-centered healthcare innovations, such as digital health platforms, patient-centric records, and mobile health applications, depend on the semantic interoperability of health data. This ensures efficient, patient-focused healthcare delivery in a mobile world where citizens frequently travel for work and leisure. Beyond healthcare delivery, semantic interoperability is crucial for secondary health data use. This paper introduces a tool and techniques for achieving health data semantic interoperability, using reusable visual transformation components to create and validate transformation rules and maps, making them usable for domain experts with minimal technical skills., Methods: The tool and techniques for health data semantic interoperability have been developed and validated using Design Science, a common methodology for developing software artifacts, including tools and techniques., Results: Our tool and techniques are designed to facilitate the interoperability of Electronic Health Records (EHRs) by enabling the seamless unification of various health data formats in real time, without the need for extensive physical data migrations. These tools simplify complex health data transformations, allowing domain experts to specify and validate intricate data transformation rules and maps. The need for such a solution arises from the ongoing transition of the Estonian National Health Information System (ENHIS) from Clinical Document Architecture (CDA) to Fast Healthcare Interoperability Resources (FHIR), but it is general enough to be used for other data transformation needs, including the European Health Data Space (EHDS) ecosystem., Conclusion: The proposed tool and techniques simplify health data transformation by allowing domain experts to specify and validate the necessary data transformation rules and maps. Evaluation by ENHIS domain experts demonstrated the usability, effectiveness, and business value of the tool and techniques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bossenko, Randmaa, Piho and Ross.)

The purpose of this study is to evaluate childhood bacterial meningitis (BM): incidence, clinical presentation, causative pathogens, diagnostics, and outcome (neurological sequelae, hearing loss, and death). A retrospective review of all children aged ≤ 16 years and 1 month diagnosed with BM at a tertiary children's centre in the period 2010-2020. The Glasgow Outcome Scale (GOS) was used to assess outcome, with a GOS score of 1-4 considered to be an unfavourable outcome. Logistic regression univariate analysis was used to determine predefined risk factors for death, unfavourable outcome, and long-term neurological sequelae. Seventy-four patients (44 males) with a median age of 8.0 months (range 1 day to 16 years and 1 month) and 77 BM episodes were included in the study. The average incidence rate of BM was 2.2/100,000/year, the majority (91%) being community-acquired BM. Streptococcus pneumonia and Neisseria meningitidis were the most common pathogens 12/77 (16%) each. Neurological sequelae at discharge were present in 24 (34%) patients, unfavourable outcome in 19 (25%), and hearing loss (deafness) in two (3%) survivors of BM. Seven (9%) patients died. Long-term neurological sequelae were observed in 19/60 (32%), aphasia/dysphasia being the most common in 10 (17%) BM children. No independent risk factors were identified for long-term neurological sequelae in univariate analysis., Conclusion: The risk for a fatal course of BM is still remarkable. Neurological sequelae persisted in a substantial proportion of BM survivors in long-term follow-up, aphasia/dysphasia being the most common. Hearing loss (deafness) occurred in 3%. However, no specific risk factors predicting the long-term sequelae were found., What Is Known: • Streptococcus pneumonia and Neisseria meningitidis were the most common pathogens causing bacterial meningitis. • Risk for fatal course of bacterial meningitis (BM) remains remarkable despite advances in modern medicine., What Is New: • In long-term follow-up, 1/3 of BM children suffered from neurological sequelae in the 2010s, aphasia and dysphasia being the most common sequelae. • Hearing loss was diagnosed in only two (3%) children, whom of both were deaf., (© 2024. The Author(s).)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) still has a relatively high complication rate, underscoring the importance of high-quality training. Despite existing guidelines, real-world data on training conditions remain limited. This pan-European survey aims to systematically explore the perceptions surrounding ERCP training., Methods: A survey was distributed through the friends of United European Gastroenterology (UEG) Young Talent Group network to physicians working in a UEG member or associated states who regularly performed ERCPs., Results: Of 1035 respondents from 35 countries, 649 were eligible for analysis: 228 trainees, 225 trainers, and 196 individuals who regularly performed ERCP but were neither trainees nor trainers. The mean age was 43 years, with 72.1% identifying as male, 27.6% as female, and 0.3% as non-binary. The majority (80.1%) agreed that a structured training regimen is desirable. However, only 13.7% of trainees and 28.4% of trainers reported having such a structured program in their institutions. Most respondents (79.7%) supported the concept of concentrating training in centers meeting specific quality metrics, with 64.1% suggesting a threshold of 200 annual ERCPs as a prerequisite. This threshold revealed that 36.4% of trainees pursued training in lower-volume centers performing <200 ERCPs annually. As many as 70.1% of trainees performed <50 annual ERCPs, whereas only 5.0% of trainers performed <50 ERCPs annually. A low individual trainee caseload (<50 ERCPs annually) was more common in lower-volume centers than in higher-volume centers (82.9% vs. 63.4%)., Conclusions: The first pan-European survey investigating ERCP training conditions reveals strong support for structured training and the concentration of training efforts within centers meeting specific quality metrics. Furthermore, this survey exposes the low availability of structured training programs with many trainees practicing at lower-volume centers and 71% of all trainees having little hands-on exposure. These data should motivate to standardize ERCP training conditions further and ultimately improve patient care throughout Europe., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Objectives: In axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating secukinumab, we aimed to assess retention rates and proportions of patients achieving remission and low disease activity (LDA), according to disease activity measures and patient-reported outcomes at 24 and 48 months., Patients and Methods: Data on patients with axSpA and PsA who initiated secukinumab treatment were pooled from 13 European registries. Analyses were performed overall and stratified according to the number of previous biologic/targeted synthetic Disease-Modifying Antirheumatic Drugs (b/tsDMARDs, 0/1/≥ 2). Kaplan-Meier plots and Cox regression analyses were performed to assess and compare secukinumab retention rates. Comparisons of remission and LDA rates were performed by logistic regression analyses., Results: The overall 24-/48-month secukinumab retention rates were 61%/51% in 767 axSpA patients, and 64%/49% in 975 PsA patients, respectively. Compared to b/tsDMARD naïve patients, a higher risk of withdrawal from secukinumab was found for those with ≥ 2 prior b/tsDMARDs in axSpA and PsA, and 1 prior b/tsDMARD in axSpA. Generally, remission and LDA rates were numerically higher in b/tsDMARD naïve patients. After adjustment for confounders, statistically significantly higher remission and LDA rates were found for b/tsDMARD naïve patients compared to patients with ≥ 2 prior b/tsDMARDs at 24 months in axSpA and PsA., Conclusion: This large European real-world study demonstrates that 4-year secukinumab retention rates were approximately 50% in both axSpA and PsA. b/tsDMARD naïve patients had higher retention, remission and LDA rates than patients with prior b/tsDMARD exposure., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Real-world evidence is needed to inform treatment strategies for patients with PsA and axial SpA (axSpA) who have non-musculoskeletal manifestations (NMMs), various risk factors and comorbidities. International collaboration is required to ensure statistical power and to enhance generalizability. The first step forward is identifying which data are currently being collected. Across 17 registries participating in the European Spondyloarthritis Research Collaboration (EuroSpA), we aimed to map recording practices for NMMs, comorbidities and safety outcomes in patients with PsA and axSpA., Methods: Through a survey with 4,420 questionnaire items, we explored the recording practices of 58 pre-defined conditions (i.e. NMMs, comorbidities and safety outcomes) covering 10 disease areas. In all registries we mapped for each condition whether it was recorded, the recording procedure and the potential to identify it through linkage to other national registries., Results: Conditions were generally recorded at entry into the registry and clinical follow-up visits using a pre-specified list or a coding system. Most registries recorded conditions within the following disease areas: NMMs (number of registries, n  = 15-16), cardiovascular diseases ( n  = 10-14), gastrointestinal diseases ( n  = 12-13), infections ( n  = 10-13) and death ( n  = 14). Nordic countries had the potential for data linkage and generally had limited recording of conditions in their registry, while other countries had comprehensive recording practices., Conclusion: A wide range of conditions were consistently recorded across the registries. The recording practices of many conditions and disease areas were comparable across the registries. Our findings support the potential for future collaborative research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Myopia is a growing healthcare concern worldwide. Increasing evidence suggests that sleep and circadian rhythms may be associated with myopia. Furthermore, the risk factors of myopia have not been studied in the Estonian population to date. This study aimed to evaluate chronotype, lifestyle factors, and parental myopia in relation to myopia in Estonian secondary school students., Methods: Grade 10 students from three secondary schools in Tallinn, each with distinct focuses: one science-oriented, one arts-oriented, and one sports-oriented, were invited to participate. They underwent a comprehensive ocular examination, including cycloplegic autorefraction and ocular biometry. Chronotype was evaluated with the Morningness - Eveningness Questionnaire. Participants reported parental myopia and replied to a set of questions, separately for schooldays and free days, to indicate the amount of time they spent outdoors, doing near work and intermediate distance activities. Myopia was defined as cycloplegic SER ≤ - 0.50 D. Logistic regression analysis was performed to assess the association of the studied factors with myopia., Results: A total of 123 students (57% female) participated in the study, with a mean age of 16.71 years (standard deviation 0.41). In a multivariable regression model, having two myopic parents was associated with higher odds of myopia (OR 3.78, 95% CI 1.15 - 12.42). We found no association between myopia and chronotype. Notably, time spent outdoors and doing near work or intermediate distance work did not affect the likelihood of having myopia. We observed that students attending the sports-oriented school had lower odds of myopia than those attending the science-oriented school (OR 0.12, 95% CI 0.03-0.51)., Conclusion: Chronotype was not associated with myopia in our study sample. Consistent with previous reports, we identified parental myopia as a myopia risk factor. Interestingly, there was no association between myopia and time spent outdoors or near work. However, the odds of myopia varied depending on the school attended by the participants, which may reflect the educational load or lifestyle of participants in earlier childhood., (© 2024. The Author(s).)

Animal models are critical for understanding the initiation and progression of myopia, a refractive condition that causes blurred distance vision. The prevalence of myopia is rapidly increasing worldwide, and myopia increases the risk of developing potentially blinding diseases. Current pharmacological, optical, and environmental interventions attenuate myopia progression in children, but it is still unclear how this occurs or how these interventions can be improved to increase their protective effects. To optimize myopia interventions, directed mechanistic studies are needed. The mouse model is well-suited to these studies because of its well-characterized visual system and the genetic experimental tools available, which can be combined with pharmacological and environmental manipulations for powerful investigations of causation. This review describes aspects of the mouse visual system that support its use as a myopia model and presents genetic, pharmacological, and environmental studies that significantly contribute to our understanding of the mechanisms that underlie myopigenesis.

Background: The NORDeHEALTH project studies patient-accessible electronic health records (PAEHRs) in Estonia, Finland, Norway, and Sweden. Such country comparisons require an analysis of the sociotechnical context of these services. Although sociotechnical analyses of PAEHR services have been carried out in the past, a framework specifically tailored to in-depth cross-country analysis has not been developed., Objective: This study aims to develop and evaluate a method for a sociotechnical analysis of PAEHRs that advances a framework for sociotechnical analysis of eHealth solutions first presented by Sittig and Singh. This first article in a series presents the development of the method and a cross-country comparison of the contextual factors that enable PAEHR access and use., Methods: The dimensions of the framework for sociotechnical analysis were thoroughly discussed and extended in a series of workshops with international stakeholders, all being eHealth researchers focusing on PAEHRs. All countries were represented in the working group to make sure that important national perspectives were covered. A spreadsheet with relevant questions related to the studied services and the various dimensions of the sociotechnical framework was constructed and distributed to the 4 participating countries, and the project participants researched various national sources to provide the relevant data for the comparisons in the 10 sociotechnical dimensions., Results: In total, 3 dimensions were added to the methodology of Sittig and Singh to separate clinical content from features and functions of PAEHRs and demonstrate basic characteristics of the different countries regarding national and regional steering of health care and information and communications technology developments. The final framework contained the following dimensions: metadata; hardware and software computing infrastructure; features and functions; clinical content shared with patients; human-computer interface; people; workflow and communication; the health care organization's internal policies, procedures, and culture; national rules, regulations, and incentives; system measurement and monitoring; and health care system context. The dimensions added during the study mostly concerned background information needed for cross-country comparisons in particular. Several similarities were identified among the compared countries, especially regarding hardware and software computing infrastructure. All countries had, for example, one national access point, and patients are provided a PAEHR automatically. Most of the differences could be identified in the health care system context dimension. One important difference concerned the governing of information and communications technology development, where different levels (state, region, and municipality) were responsible in different countries., Conclusions: This is the first large-scale international sociotechnical analysis of services for patients to access their electronic health records; this study compared services in Estonia, Finland, Norway, and Sweden. A methodology for such an analysis was developed and is presented to enable comparison studies in other national contexts to enable future implementations and evaluations of PAEHRs., (©Jonas Moll, Isabella Scandurra, Annika Bärkås, Charlotte Blease, Maria Hägglund, Iiris Hörhammer, Bridget Kane, Eli Kristiansen, Peeter Ross, Rose-Mharie Åhlfeldt, Gunnar O Klein. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.08.2024.)

Direct-to-consumer testing (DTCT) refers to commercial laboratory tests initiated by laypersons without the involvement of healthcare professionals. As this market grows in size and variety of products, a clear definition of DTCT to ground the conceptualization of their harms and benefits is needed. We describe how three different modalities of DTCT (home self-testing, self-sampled tests, and direct access tests) present caveats to the traditional testing process ('brain-to-brain loop'), and how this might differ between medical vs. non-medical laboratories. We make recommendations for ways to improve quality and reduce errors with respect to DTCT. The potential benefits and harms of DTCT will invariably depend on the context and situation of individual consumers and the types of tests involved. Importantly, implications for both consumers and the healthcare system should be considered, such as the effects on improving health outcomes and reducing unnecessary testing and use of clinical resources. 'Consumer initiation' must be a central defining characteristic of DTCT, to clearly demarcate the key drawbacks as well as opportunities of this type of testing from a laboratory specialists' perspective. The concept of 'consumer initiated testing' should also help define DTCT regulation, and provide a locus of efforts to support consumers as the main decision-makers in the purchasing and conducting of these tests in the absence of clinician gatekeeping., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Digitization shall improve the secondary use of health care data. The Government of the Kingdom of Saudi Arabia ordered a project to compile the National Master Plan for Health Data Analytics, while the Government of Estonia ordered a project to compile the Person-Centered Integrated Hospital Master Plan., Objective: This study aims to map these 2 distinct projects' problems, approaches, and outcomes to find the matching elements for reuse in similar cases., Methods: We assessed both health care systems' abilities for secondary use of health data by exploratory case studies with purposive sampling and data collection via semistructured interviews and documentation review. The collected content was analyzed qualitatively and coded according to a predefined framework. The analytical framework consisted of data purpose, flow, and sharing. The Estonian project used the Health Information Sharing Maturity Model from the Mitre Corporation as an additional analytical framework. The data collection and analysis in the Kingdom of Saudi Arabia took place in 2019 and covered health care facilities, public health institutions, and health care policy. The project in Estonia collected its inputs in 2020 and covered health care facilities, patient engagement, public health institutions, health care financing, health care policy, and health technology innovations., Results: In both cases, the assessments resulted in a set of recommendations focusing on the governance of health care data. In the Kingdom of Saudi Arabia, the health care system consists of multiple isolated sectors, and there is a need for an overarching body coordinating data sets, indicators, and reports at the national level. The National Master Plan of Health Data Analytics proposed a set of organizational agreements for proper stewardship. Despite Estonia's national Digital Health Platform, the requirements remain uncoordinated between various data consumers. We recommended reconfiguring the stewardship of the national health data to include multipurpose data use into the scope of interoperability standardization., Conclusions: Proper data governance is the key to improving the secondary use of health data at the national level. The data flows from data providers to data consumers shall be coordinated by overarching stewardship structures and supported by interoperable data custodians., (©Janek Metsallik, Dirk Draheim, Zlatan Sabic, Thomas Novak, Peeter Ross. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.08.2024.)

Objectives: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe., Methods: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders)., Results: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates., Conclusion: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status., Competing Interests: Competing interests: SNC: Speaker fees BMS and GE, Research grant from Novartis (paid to the employer). SHR: Research grant from Novartis (paid to the employer). MO: Speaker and/or consultancy fees from AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB. Research grants from AbbVie, BMS, Merck, Novartis and UCB. MP: Research grant from Novartis (paid to the employer). Speaker fees: Sandoz. Brigitte Michelsen: Consulting fees from Novartis. Research grant from Novartis (paid to employer). KP: Consultancy fees: AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD and Novartis. Catalin Codreanu: Speaker and consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer. Adrian Ciurea: None. Bente Glintborg: Research grants from Pfizer, Abbvie, BMS, Sandoz. MJS: Speaker fees from AbbVie, AstraZeneca, Janssen, Lilly, Medac, Novartis, Pfizer. Ismail Sari: None. ZR: Speaker and consultancy fees from Abbvie, Novartis, Eli Lilly, Pfizer, Janssen, SOBI, Swixx BioPharma, AstraZeneca, Amgen, MSD, Medis, Biogen, Eli Lilly, Sanofi, Lek. BG: Speaker and consultancy fees from Novartis and Nordic-Pharma. GJM: Research grant from GSK. HR: Consulting and/or speaking fees from AbbVie, Celgene, Pfizer, UCB, Viatris. FI: None. Karin Laas: Speakers fees from AbbVie, Johnson and Johnson, Novartis, Pfizer. JKW: Speaker fees from AbbVie, Amgen. Research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer. MvdS: Consultant for Novartis, AbbVie, Eli Lilly UCB, Speakers fee: Novartis, UCB, Janssen, Grant/research support: UCB, Janssen, Novartis, Eli Lilly. Sella Aarrestad Provan: Consultancy fees and Research grants from Boehringer Ingelheim. IC: Speaker and/or consultancy fees from BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer, GSK. JZ: Speakers fees from AbbVie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, Sobi. CM: None. MJN: Speaker and/or consultancy fees from AbbVie, Amgen, Eli Lilly, Janssens, Novartis, Pfizer. Research grants from Novartis and Pfizer. AGL: Speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB. Research grant from Novartis. AB: Speaker and/or consultancy fees from AbbVie, Lilly, Janssen and Novartis. YE: None. Katja Perdan Pirkmajer: Speaker and/or consultancy fees from AbbVie, Novartis, MSD, Medis, Eli Lilly, Pfizer, Lek, Janssen and Boehringer Ingelheim. GG: None. GTJ: Speaker fee from Janssen. Research grants (paid to employer) from AbbVie, Pfizer, UCB, Amgen, GSK. A-MH: Grant/research support from MSD. MSC: None. SV: None. DdG: None. TKK: Speaker and/or consultancy fees from AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB and Grünenthal. LO-V: None. IvdH-B: Speaker and/or consultancy fees from AbbVie, UCB, MSD, Novartis, Lilly. Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie, UCB. Fees received for Lectures from BMS, AbbVie, Pfizer, MSD, UCB. MLH: Advisory Board AbbVie (No personal income, paid to institution). Prev. chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. Speaker for Pfizer, Medac, Sandoz (no personal income, institution). Research grants (institution) from AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk. LMO: Research grant from Novartis (paid to the employer)., (© 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.)

Introduction: This paper addresses the dilemmas of accessibility, comprehensiveness, and ownership related to health data. To resolve these dilemmas, we propose and justify a novel, globally scalable reference architecture for a Personal Health Data Space (PHDS). This architecture leverages decentralized content-addressable storage (DCAS) networks, ensuring that the data subject retains complete control and ownership of their personal health data. In today's globalized world, where people are increasingly mobile for work and leisure, healthcare is transitioning from episodic symptom-based treatment toward continuity of care. The main aims of this are patient engagement, illness prevention, and active and healthy longevity. This shift, along with the secondary use of health data for societal benefit, has intensified the challenges associated with health data accessibility, comprehensiveness, and ownership., Method: The study is structured around four health data use case scenarios from the Estonian National Health Information System (EHIS): primary medical use, medical emergency use, secondary use, and personal use. We analyze these use cases from the perspectives of accessibility, comprehensiveness, and ownership. Additionally, we examine the security, privacy, and interoperability aspects of health data., Results: The proposed architectural solution allows individuals to consolidate all their health data into a unified Personal Health Record (PHR). This data can come from various healthcare institutions, mobile applications, medical devices for home use, and personal health notes., Discussions: The comprehensive PHR can then be shared with healthcare providers in a semantically interoperable manner, regardless of their location or the information systems they use. Furthermore, individuals maintain the autonomy to share, sell, or donate their anonymous or pseudonymous health data for secondary use with different systems worldwide. The proposed reference architecture aligns with the principles of the European Health Data Space (EHDS) initiative, enhancing health data management by providing a secure, cost-effective, and sustainable solution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Klementi, Piho and Ross.)

The Nordic countries are, together with the United States, forerunners in online record access (ORA), which has now become widespread. The importance of accessible and structured health data has also been highlighted by policy makers internationally. To ensure the full realization of ORA's potential in the short and long term, there is a pressing need to study ORA from a cross-disciplinary, clinical, humanistic, and social sciences perspective that looks beyond strictly technical aspects. In this viewpoint paper, we explore the policy changes in the European Health Data Space (EHDS) proposal to advance ORA across the European Union, informed by our research in a Nordic-led project that carries out the first of its kind, large-scale international investigation of patients' ORA-NORDeHEALTH (Nordic eHealth for Patients: Benchmarking and Developing for the Future). We argue that the EHDS proposal will pave the way for patients to access and control third-party access to their electronic health records. In our analysis of the proposal, we have identified five key principles for ORA: (1) the right to access, (2) proxy access, (3) patient input of their own data, (4) error and omission rectification, and (5) access control. ORA implementation today is fragmented throughout Europe, and the EHDS proposal aims to ensure all European citizens have equal online access to their health data. However, we argue that in order to implement the EHDS, we need more research evidence on the key ORA principles we have identified in our analysis. Results from the NORDeHEALTH project provide some of that evidence, but we have also identified important knowledge gaps that still need further exploration., (©Maria Hägglund, Anna Kharko, Annika Bärkås, Charlotte Blease, Åsa Cajander, Catherine DesRoches, Asbjørn Johansen Fagerlund, Josefin Hagström, Isto Huvila, Iiris Hörhammer, Bridget Kane, Gunnar O Klein, Eli Kristiansen, Jonas Moll, Irene Muli, Hanife Rexhepi, Sara Riggare, Peeter Ross, Isabella Scandurra, Saija Simola, Hedvig Soone, Bo Wang, Maedeh Ghorbanian Zolbin, Rose-Mharie Åhlfeldt, Sari Kujala, Monika Alise Johansen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.06.2024.)

We recruited 48 neonates (50 vancomycin treatment episodes) in a prospective study to validate a model-informed precision dosing (MIPD) software. The initial vancomycin dose was based on a population pharmacokinetic model and adjusted every 36-48 h. Compared with a historical control group of 53 neonates (65 episodes), the achievement of a target trough concentration of 10-15 mg/L improved from 37% in the study to 62% in the MIPD group ( P = 0.01), with no difference in side effects., Competing Interests: The authors declare no conflict of interest.

Infertility, affecting ∼10% of men, is predominantly caused by primary spermatogenic failure (SPGF). We screened likely pathogenic and pathogenic (LP/P) variants in 638 candidate genes for male infertility in 521 individuals presenting idiopathic SPGF and 323 normozoospermic men in the ESTAND cohort. Molecular diagnosis was reached for 64 men with SPGF (12%), with findings in 39 genes (6%). The yield did not differ significantly between the subgroups with azoospermia (20/185, 11%), oligozoospermia (18/181, 10%), and primary cryptorchidism with SPGF (26/155, 17%). Notably, 19 of 64 LP/P variants (30%) identified in 28 subjects represented recurrent findings in this study and/or with other male infertility cohorts. NR5A1 was the most frequently affected gene, with seven LP/P variants in six SPGF-affected men and two normozoospermic men. The link to SPGF was validated for recently proposed candidate genes ACTRT1, ASZ1, GLUD2, GREB1L, LEO1, RBM5, ROS1, and TGIF2LY. Heterozygous truncating variants in BNC1, reported in female infertility, emerged as plausible causes of severe oligozoospermia. Data suggested that several infertile men may present congenital conditions with less pronounced or pleiotropic phenotypes affecting the development and function of the reproductive system. Genes regulating the hypothalamic-pituitary-gonadal axis were affected in >30% of subjects with LP/P variants. Six individuals had more than one LP/P variant, including five with two findings from the gene panel. A 4-fold increased prevalence of cancer was observed in men with genetic infertility compared to the general male population (8% vs. 2%; p = 4.4 × 10 -3 ). Expanding genetic testing in andrology will contribute to the multidisciplinary management of SPGF., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Purpose: Physical load during military training might increase the need for vitamin D; therefore, supplementation could be beneficial for 25(OH)D serum levels and physical performance., Methods: One hundred and twelve male conscripts were randomized into two vitamin D oil capsule supplementation groups: 55 participants in the 600 IU group and 57 in the 4000 IU group with a follow-up period from July 2021 to May 2022. Physical fitness tests were performed in July, October and May. Hand grip strength tests were performed in July, October and January. Blood serum (25(OH)D), parathyroid hormone PTH), calcium and ionized calcium (i-Ca) values were measured in July, October, January and May., Results: The 600 IU group had a lower ( p  < 0.001) value of 25(OH)D at all time points compared to the 4000 IU group, except at baseline. None of the subjects in the 600 IU group reached sufficient levels of 75 nmol/L of 25(OH)D in January and May. In May, 60% of participants in the 600 IU group and 30% in the 4000 IU group had 25(OH)D levels under 50 nmol/L. No significant differences in PTH or i-Ca values were found between the study groups at any time point. No significant differences at any time point were found in the physical fitness test or hand grip strength test between the groups., Conclusion: A 10-month vitamin D supplementation with 4000 IU decreased the incidence of vitamin D deficiency (<75 nmol/L) in young, male army conscripts during wintertime, but no differences in physical performance were found compared to 600 IU supplementation., Level of Evidence: Level I, Prospective randomized study., Competing Interests: Leho Rips: Consultant Orthopedic Surgeon of Estonian Defence Forces. Alar Toom, Rein Kuik, Marika Laidvere, Mart Kull, Helena Gapeyeva, and Madis Rahu: No conflict of interest. Ahti Varblane, Hanno Mölder, and Ragnar Kibur: Doctor of Estonian Defence Forces. Jüri‐Toomas Kartus: Lecturing for ConMed, Sweden., (© 2024 The Authors. Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Considering a lack of respective data, the primary objective of this study was to assess whether seasonal variation in vitamin D status (D-status) affects the extent of improvement in physical performance (PP) in conscripts during basic military training (BMT). D-status, PP and several blood parameters were measured repeatedly in conscripts whose 10-week BMT started in July (cohort S-C; n = 96) or in October (cohort A-C; n = 107). D-status during BMT was higher in S-C compared to A-C (overall serum 25(OH)D 61.4 ± 16.1 and 48.5 ± 20.7 nmol/L, respectively; p < 0.0001). Significant ( p < 0.05) improvements in both aerobic and muscular endurance occurred in both cohorts during BMT. Pooled data of the two cohorts revealed a highly reliable ( p = 0.000) but weak (R 2 = 0.038-0.162) positive association between D-status and PP measures both at the beginning and end of BMT. However, further analysis showed that such a relationship occurred only in conscripts with insufficient or deficient D-status, but not in their vitamin D-sufficient companions. Significant ( p < 0.05) increases in serum testosterone-to-cortisol ratio and decreases in ferritin levels occurred during BMT. In conclusion, a positive association exists between D-status and PP measures, but seasonal variation in D-status does not influence the extent of improvement in PP in conscripts during BMT.

RASopathies are syndromes caused by congenital defects in the Ras/mitogen-activated protein kinase (MAPK) pathway genes, with a population prevalence of 1 in 1,000. Patients are typically identified in childhood based on diverse characteristic features, including cryptorchidism (CR) in >50% of affected men. As CR predisposes to spermatogenic failure (SPGF; total sperm count per ejaculate 0-39 million), we hypothesized that men seeking infertility management include cases with undiagnosed RASopathies. Likely pathogenic or pathogenic (LP/P) variants in 22 RASopathy-linked genes were screened in 521 idiopathic SPGF patients (including 155 CR cases) and 323 normozoospermic controls using exome sequencing. All 844 men were recruited to the ESTonian ANDrology (ESTAND) cohort and underwent identical andrological phenotyping. RASopathy-specific variant interpretation guidelines were used for pathogenicity assessment. LP/P variants were identified in PTPN11 (two), SOS1 (three), SOS2 (one), LZTR1 (one), SPRED1 (one), NF1 (one), and MAP2K1 (one). The findings affected six of 155 cases with CR and SPGF, three of 366 men with SPGF only, and one (of 323) normozoospermic subfertile man. The subgroup "CR and SPGF" had over 13-fold enrichment of findings compared to controls (3.9% vs. 0.3%; Fisher's exact test, p = 5.5 × 10 -3 ). All ESTAND subjects with LP/P variants in the Ras/MAPK pathway genes presented congenital genitourinary anomalies, skeletal and joint conditions, and other RASopathy-linked health concerns. Rare forms of malignancies (schwannomatosis and pancreatic and testicular cancer) were reported on four occasions. The Genetics of Male Infertility Initiative (GEMINI) cohort (1,416 SPGF cases and 317 fertile men) was used to validate the outcome. LP/P variants in PTPN11 (three), LZTR1 (three), and MRAS (one) were identified in six SPGF cases (including 4/31 GEMINI cases with CR) and one normozoospermic man. Undiagnosed RASopathies were detected in total for 17 ESTAND and GEMINI subjects, 15 SPGF patients (10 with CR), and two fertile men. Affected RASopathy genes showed high expression in spermatogenic and testicular somatic cells. In conclusion, congenital defects in the Ras/MAPK pathway genes represent a new congenital etiology of syndromic male infertility. Undiagnosed RASopathies were especially enriched among patients with a history of cryptorchidism. Given the relationship between RASopathies and other conditions, infertile men found to have this molecular diagnosis should be evaluated for known RASopathy-linked health concerns, including specific rare malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Juchnewitsch, Pomm, Dutta, Tamp, Valkna, Lillepea, Mahyari, Tjagur, Belova, Kübarsepp, Castillo-Madeen, Riera-Escamilla, Põlluaas, Nagirnaja, Poolamets, Vihljajev, Sütt, Versbraegen, Papadimitriou, McLachlan, Jarvi, Schlegel, Tennisberg, Korrovits, Vigh-Conrad, O’Bryan, Aston, Lenaerts, Conrad, Kasak, Punab and Laan.)

Objectives: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates., Patients and Methods: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0-10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates., Results: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84-1.02])., Conclusion: In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Nysom Christiansen, Simon Horskjær Rasmussen, Lykke Midtbøll Ørnbjerg: research grant from Novartis; Marion Pons: research grant from Novartis and speaker fees from Sandoz; Brigitte Michelsen: research grant from Novartis and the centre for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) is funded as a Centre for Clinical Treatment Research by The Research Council of Norway (project 328,657); Bente Glintborg: research grants from Pfizer, Abbvie, BMS, Sandoz; Bjorn Gudbjornsson: consulting fees from Novartis and speaker fees from Novartis, Nordic-Pharma; Gerdur Grondal: none; Jiri Vencovsky: research grant from Abbvie, consulting fees from Abbvie, Argenx, Boehringer, Eli Lilly, Gilead, Octapharma, Pfizer, UCB and speaker fees from Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Werfen; Anne Gitte Loft: research grant from Novartis andspeaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, paid instructor from Pfizer; Ziga Rotar: consulting fees from Abbvie, Novartis, Eli Lilly, Pfizer, Janssen and speaker fees from Abbvie, Amgen, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen; Katja Perdan Pirkmajer: consulting fees from Abbvie, Novartis, Medis, Eli Lilly, Pfizer, Boehringer Ingelheim and speaker fees from Abbvie, Novartis, MSD, Medis, Eli Lilly, Pfizer, Lek, Janssen; Michael J. Nissen: research grant from Pfizer andconsulting and/or speaker fees from Abbvie, Eli Lilly, Janssens, Novartis, Pfizer; Jana Baranova: none; Gary J. Macfarlane: research grant from GSK; Gareth T.Jones: research grants from Abbvie, Pfizer, UCB, Amgen, GSK and speaker fees from Janssen; Florenzo Iannone: research grant from BMS, Galapagos, Pfizer and consulting and/or speakers fees from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB; Roberto Caporali: consulting and/or speaker fees from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB; Karin Laas: research grant from Abbvie, Johnson and Johnson, Novartis, Pfizer; Sigrid Vorobjov: none; Daniella Di Giuseppe: none; Tor Olofsson: none; Sella Aarrestad Provan: Research grant from Boehringer Ingelheim and consulting fees from Boehringer Ingelheim; Karen Minde Fagerli: none; Isabel Castrejon: consulting and speaker fees from BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer, GSK; Lucia Otero-Varela: None; Marleen Van de Sande: research grants from UCB, Janssen, Novartis, Eli Lilly, consulting fees from Novartis, Abbvie, Eli Lilly UCB and speaker fees from Novartis, UCB, Janssen; Irene van der Horst-Bruinsma: Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie, UCB. Fees received for lectures from BMS, AbbVie, Pfizer, MSD, UCB, consulting fees from Abbvie, UCB, MSD, Novartis, Lilly and speaker fees from UCB; Dan Nordström: research grant from MSD, consulting fees from Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB, and speaker fees from Novartis, Pfizer, UCB; Laura Kuusalo: consulting fees from Gilead, Pfizer and speaker fees from Abbvie, Lilly, Medac, Orion, Pfizer, UCB; Miguel Bernades: none; Merete Lund Hetland: Research grants from Novartis, Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk, consulting fees from Abbvie, chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies and speaker fees from Pfizer, Medac, Sandoz; Mikkel Østergaard: Research grant from Abbvie, BMS, Merck, Novartis and UCB and consulting and/or speaker fees from Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions., Methods: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS., Results: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes., Conclusion: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objectives: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries., Methods: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors., Results: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99)., Conclusion: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction : The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods : A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results : A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus , Streptococcus species, Enterococcus faecalis , Kingella kingae , Neisseria gonorrhoeae , and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion : The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting., Competing Interests: At least one of the (co-)authors is a member of the editorial board of Journal of Bone and Joint Infection. The peer-review process was guided by an independent editor, and the authors also have no other competing interests to declare., (Copyright: © 2024 Stéphanie Pascual et al.)

Human accuracy in diagnosing psychiatric disorders is still low. Even though digitizing health care leads to more and more data, the successful adoption of AI-based digital decision support (DDSS) is rare. One reason is that AI algorithms are often not evaluated based on large, real-world data. This research shows the potential of using deep learning on the medical claims data of 812,853 people between 2018 and 2022, with 26,973,943 ICD-10-coded diseases, to predict depression (F32 and F33 ICD-10 codes). The dataset used represents almost the entire adult population of Estonia. Based on these data, to show the critical importance of the underlying temporal properties of the data for the detection of depression, we evaluate the performance of non-sequential models (LR, FNN), sequential models (LSTM, CNN-LSTM) and the sequential model with a decay factor (GRU-Δt, GRU-decay). Furthermore, since explainability is necessary for the medical domain, we combine a self-attention model with the GRU decay and evaluate its performance. We named this combination Att-GRU-decay. After extensive empirical experimentation, our model (Att-GRU-decay), with an AUC score of 0.990, an AUPRC score of 0.974, a specificity of 0.999 and a sensitivity of 0.944, proved to be the most accurate. The results of our novel Att-GRU-decay model outperform the current state of the art, demonstrating the potential usefulness of deep learning algorithms for DDSS development. We further expand this by describing a possible application scenario of the proposed algorithm for depression screening in a general practitioner (GP) setting-not only to decrease healthcare costs, but also to improve the quality of care and ultimately decrease people's suffering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives : There is increasing evidence that patients with dysphagia often have limited access to suitable oral dosage forms, especially when administered via an enteral feeding tube (FT). In addition, there is a lack of clear and readily available information from drug manufacturers on how to administer medications to patients with dysphagia. This study aimed to develop a practical guide for healthcare professionals to increase the safe and effective administration of oral medications to patients with dysphagia. Materials and Methods : The data were collected from existing English databases and handbooks available to develop an easy-to-use tabular guideline presenting all relevant information using keywords and short expressions. The working group differentiated 514 formulation types, and the information was collected and added to the guideline separately. In addition, the instructions for the patients taking the medicines orally or via FT were described separately. Results : The guideline consisted of 24 keywords or short expressions developed by the working group and described the instructions to use them. The guideline contained 343 active pharmaceutical ingredients and 19 fixed-dose combinations. Conclusions : Knowledge about proper medication preparation and administration for patients with swallowing difficulties is limited but essential. It is crucial to encourage drug manufacturers to provide this information as a standard to ensure the safe and effective use of medications for all patient groups.

Background: In European axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) clinical registries, we aimed to investigate commonalities and differences in (1) set-up, clinical data collection; (2) data availability and completeness; and (3) wording, recall period, and scale used for selected patient-reported outcome measures (PROMs)., Methods: Data was obtained as part of the EuroSpA Research Collaboration Network and consisted of (1) an online survey and follow-up interview, (2) upload of real-world data, and (3) selected PROMs included in the online survey., Results: Fifteen registries participated, contributing 33,948 patients (axSpA: 21,330 (63%), PsA: 12,618 (37%)). The reported coverage of eligible patients ranged from 0.5 to 100%. Information on age, sex, biological/targeted synthetic disease-modifying anti-rheumatic drug treatment, disease duration, and C-reactive protein was available in all registries with data completeness between 85% and 100%. All PROMs (Bath Ankylosing Spondylitis Disease Activity and Functional Indices, Health Assessment Questionnaire, and patient global, pain and fatigue assessments) were more complete after 2015 (68-86%) compared to prior (50-79%). Patient global, pain and fatigue assessments showed heterogeneity between registries in terms of wording, recall periods, and scale., Conclusion: Important heterogeneity in registry design and data collection across fifteen European axSpA and PsA registries was observed. Several core measures were widely available, and an increase in data completeness of PROMs in recent years was identified. This study might serve as a basis for examining how differences in data collection across registries may impact the results of collaborative research in the future., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: We aimed to evaluate whether obese patients with psoriatic arthritis (PsA) were less likely to be in remission/low disease activity (LDA)., Methods: We used data from the ReFlaP, an international multi-centre cohort study (NCT03119805), which recruited consecutive adults with definite PsA (disease duration ≥ 2 years) from 14 countries. Demographics, clinical data, comorbidities, and patient-reported outcomes were collected. Remission/LDA was defined as Very Low Disease Activity (VLDA)/minimal disease activity (MDA), Disease Activity in PSoriatic Arthritis (DAPSA) ≤4/≤14, or by patients' opinion. Obesity was defined as physician-reported and/or body mass index ≥30 kg/m 2 . We evaluated the association between obesity and the presence of remission/LDA, with adjustment in multivariable regression models., Results: Among 431 patients (49.3% women), 136 (31.6%) were obese. Obese versus non-obese patients were older, more frequently women, had higher tender joint and enthesitis counts and worse pain, physical function and health-related quality of life. Obese patients were less likely to be in VLDA; DAPSA remission and MDA, with adjusted ORs of 0.31 (95% CI 0.13 to 0.77); 0.39 (95% CI 0.19 to 0.80) and 0.61 (95% CI 0.38 to 0.99), respectively. Rates of DAPSA-LDA and patient-reported remission/LDA were similar for obese and non-obese patients., Conclusion: PsA patients with comorbid obesity were 2.5-3 folds less likely to be in remission/LDA by composite scores compared with non-obese patients; however, remission/LDA rates were similar based on the patients' opinion. PsA patients with comorbid obesity may have different disease profiles and require individualised management., Competing Interests: Competing interests: YYL has received consulting fee and speaking fees from AbbVie, DKSH, Janssen, Novartis and Pfizer. LCC is an Editorial Board Member of RMD Open, she has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB; and has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. MdW has received fees for lectures or consultancy from Celgene, Eli Lilly, Pfizer and UCB. JSS received Research Grants for his institution from Abbvie, AstraZeneca, Lilly, Novartis and Roche, and honoraria for consultancies and/or speaking engagements from AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Lilly, Merck Sharp & Dohme, Novartis- Sandoz, Pfizer, R-Pharm, Samsung, Sanofi, and UCB. UK has received grants and research support and consultancy fees from AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, Grünenthal, GSK, Hexal, Janssen, MSD, Novartis, onkowoessen.de, Pfizer, Roche, UCB and Viatris. AB has received speakers’ fees and consulting fees from Abbvie, Amgen, Akros, Astra-Zeneca, Angellini, AlphaSigma, BMS, Berlin-Chemie, Biogen, Lilly, Mylan, MSD, Novartis, Pfizer, Roche, Sandoz, Teva, UCB, Zentiva; and was investigator in clinical trials sponsored by Akros, MSD, Sanofi, Pfizer, Astra-Zeneca, Novartis, BMS, GSK, Roche, UCB, Sandoz. LG has received research grants from Sandoz, UCB; consulting fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

New parents and their newborns are followed up after discharge either through home visits from midwives/nurses or using information and communication technology. This follow-up focuses on individual needs related to breastfeeding and infant feeding, practical advice on caring for babies, supporting and strengthening the new mother's knowledge and self-confidence concerning child development and parenting skills, and supporting the relationship between parents and baby. This systematic review aims to integrate available research results that describe new parents' experiences when health and care providers used telemedicine as a platform for follow-up after discharge from the childbirth department. This literature review was conducted following the PRISMA statement and was prospectively registered in PROSPERO CRD42021236912. The studies were identified through the following databases: AMED, Academic, EMBASE, Google Scholar, Ovid MEDLINE via PubMed, Cochrane database, and CINAHL. Results from these studies were compiled using thematic analysis. A total of 886 studies were identified. Screening resulted in eight studies that met the inclusion criteria. Thematic analysis produced the following themes: a) Flexibility and convenience of digital support, b) Digital literacy, c) Parents feeling safe with digital support, and d) Adequate substitute for physical meetings. New parents who live in a home environment with a relaxed atmosphere and around-the-clock digital support experience a sense of control, security, full attention, and encouragement. Digital follow up at home has proven effective because it can meet the support needs of new parents when necessary., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pajalic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations., Competing Interests: BM, research grant from Novartis (for the present manuscript, paid to employer), Centre for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) is funded as a Centre for Clinical Treatment Research by The Research Council of Norway (project 328657); MØ, Funding for the present manuscript from Novartis (paid to institution), The EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG, research grants from Abbvie, BMS, Merck, Novartis, UCB, consulting fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, UCB, support for attending meetings and/or travel from UCB; MJN, grant from Novartis (payment to institution), consulting fees from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), support for attending meetings and/or travel from Janssen, UCB (payment to institution), participation on a Data Safety Monitoring Board or Advisory Board from Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), scientific member of the SCQM registry and the EuroSpA collaboration (unpaid), ASAS-EULAR taskforce member (unpaid); AC, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Merck-Sharp & Dohme, Novartis; BMö, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Novartis, Pfizer, support for attending meetings and/or travel from Abbvie, Janssen, Novartis, Pfizer; LMØ, research grant from Novartis (for the present manuscript, paid to employer); JZ, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Eli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, support for attending meetings and/or travel from Abbvie, Pfizer, Astra Zeneca, participation on a data safety monitoring board or advisory board from Abbvie, UCB, Sobi; BGli, Research grants from Pfizer, AbbVie, BMS (payments made to institution); AM; payment for work done in relation to research questions for this project from the University of Aberdeen, speakers fees for educational events from Galapagos; KL, Honoraria for lectures from Pfizer, Abbvie, Novartis, Janssen, support for attending meetings from Abbvie, Pfizer; DN, Consulting fees from BMS, Lilly, MSD, Novartis, Pfizer, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, support for attending meetings and/or travel from Pfizer; BGu, consulting fees from Novartis, speaker bureaus from Novartis, Nordic Pharma; FI, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, BMS, Galapagos, Eli-Lilly, Pfizer, UCB, support for attending meetings and/or travel from Pfizer, UCB; PH, research grant (payments made to employer) from Novartis; TKK, consulting fees from AbbVie, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Grünenthal, Janssen, Sandoz, participation on a data safety monitoring board or advisory board from Abbvie, grants or contracts from AbbVie, BMS, Galapagos, Novartis, Pfizer, UCB; AMR, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Amgen, Novartis, support for attending meetings and/or travel from Amgen, Nordic, Theramex, grants or contracts from Novartis, Pfizer, Amgen, Astra Zeneca, Abbvie, MSD, Lilly, Boehringer Ingelheim; CC, None; ZR, Consulting fees from AbbVie, Janssen, Novartis, MSD and Lek Sandoz, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eli Lilly, Janssen, Abbvie, Pfizer, Boehringer Ingelheim, support for attending meetings and/or travel from Gedeon Richter, Pfizer, SOBI (payments made to employer), participation on data safety monitoring board or advisory board from Abbvie, Pfizer, Astra Zeneca, Janssen, Eli Lilly, Novartis and Boehringer Ingelheim; ICF, consulting fees from Pfizer, Galapagos, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Eli-Lilly, Gilead, Janssen, Novartis, MSD, Pfizer, GSK, support for attending meetings and/or travel from Pfizer, Eli-Lilly; JKW, Research support from Abbvie, Amgen, Eli Lilly, Novartis, Pfizer (unrelated to the present work, payment made to Lund University), speakers bureaus from Abbvie and Amgen (payed to Skåne University Hospital), acting co-chair of the Swedish Society for Rheumatology's working group annually updating Swedish treatment recommendations for axial spondyloarthritis and psoriatic arthritis (unpaid, fiduciary assignment); JV, support for the present manuscript from the Czech Ministry of Health–Conceptual Development of Research Organization 00023728 (Institute of Rheumatology), payment to institution, consulting fees from Eli Lilly, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Biogen, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, support for attending meetings and/or travel from Abbvie (payment to institution), participation on a data safety monitoring board or advisory board from Abbvie, Gilead, Pfizer, UCB, grants or contracts from Abbvie (payment to institution); AGL, Consulting fees from Jansen-Cilag A/S, Lilly Nordics, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis Healthcare A/S, Pfizer, support for attending meetings and/or travel from Pfizer, UCB, participation on a data safety monitoring board or advisory board from Jansen-Cilag A/S, Lilly Nordics, UCB; MH; None; SV, None; AMH, Research grant from MSD, grant for attending meeting from Janssen, Pfizer, support for travel cost from Janssen; GG, None; MS, support for the present manuscript from Lilly and Boehringer-Ingelheim, payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Pfizer, Boehringer-Ingelheim, GSK, participation on data safety or advisory board from Janssen-Cilag, support for attending meetings and/or travel from Janssen-Cilag; MvdS, Research support/grant from UCB, Eli Lilly, Novartis, Janssen (payments made to institution, AMR Medical Research BV), consulting fees from Novartis, UCB, Abbvie (payments made to institution), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, UCB, Janssen (payments made to institution), support for attending meetings and/or travel from UCB; EKK, None; MJS, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Lilly, Novartis, Pfizer, support for attending meetings and/or travel from Janssen, Viatris, Medac and receipt of equipment, materials, drugs, medical writing, gifts or other services from Vifor; CM, None; MT, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Amgen, Boehringer, Pfizer, Sanofi-Aventis, Roche, Lek-Sandoz, Janssen, Medis, Novartis, participation on data safety or advisory board from Astra Zeneca, Eli Lilly, Janssen, Boehringer, MSD, Novartis, Roche; FDG, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, payment for expert testimony from Abbvie, Galapagos, Janssen, and support for attending meetings and/or travel from Pfizer, Astra Zeneca; DDG, None; MLH, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Medac, Sandoz, research grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordstar (payment to institution). MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis., (© 2023 The Author(s).)

Background: Laparoscopic appendectomy (LA) is the standard treatment for acute appendicitis (AA) in general population. However, the safety of LA during pregnancy has remained a matter of debate. The purpose of this study was to compare surgical and obstetrical outcomes in pregnant women who underwent LA vs. open appendectomy (OA) for AA. We hypothesized that LA results in improved surgical and obstetric outcomes during pregnancy., Methods: Using a nationwide claim-based database in Estonia, a retrospective review of all cases of pregnant women undergoing OA or LA for AA from 2010 to 2020 was performed. Patient characteristics, surgical and obstetrical outcomes were analyzed. Primary outcomes were preterm delivery, fetal loss and perinatal mortality. Secondary outcomes included operative time, hospital length of stay (HLOS) and 30-day postoperative complications., Results: Overall, 102 patients were included of whom 68 (67%) underwent OA and 34 patients (33%) LA, respectively. Patients in LA cohort had a significantly shorter length of pregnancy in terms of gestational weeks when compared to OA cohort (12 weeks versus 17 weeks, p = 0.002). Most of the patients in their 3 rd trimester pregnancy were subjected to OA. Operative time in LA cohort was shorter than in OA cohort (34 min. versus 44 min., p = 0.038). HLOS in LA cohort was shorter than in OA cohort (2.1 days versus 2.9 days, p = 0.016). There were no differences between OA and LA cohorts in terms of surgical complications or obstetrical outcomes., Conclusions: Laparoscopic appendectomy for acute appendicitis was associated with a significantly shorter operative time and a shorter hospital length of stay while open and laparoscopic appendectomy cohorts experienced comparable obstetrical outcomes. Our findings support the laparoscopic approach for acute appendicitis in pregnancy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Despite the considerable progress made in assisted reproductive technologies (ART), the implantation rate of transferred embryos remains low and in many cases, the reasons for failure remain unclear. We aimed to determine the potential impact of female and male partners' reproductive tract microbiome composition on ART outcome., Material and Methods: The ART couples (n = 97) and healthy couples (n = 12) were recruited into the study. The smaller healthy group underwent a careful selection according to their reproductive and general health criteria. Both vaginal and semen samples were subjected to 16S rDNA sequencing to reveal the bacterial diversity and identify distinct microbial community types. Ethics statement The study was approved by the Ethics Review Committee on Human Research of Tartu University, Tartu, Estonia (protocol no. 193/T-16) on 31 May 2010. Participation in the research was voluntary. Written informed consent was obtained from all study participants., Results: The men with Acinetobacter-associated community who had children in the past, had the highest ART success rate (P < 0.05). The women with bacterial vaginosis vaginal microbiome community and with L. iners-predominant and L. gasseri-predominant microbiome had a lower ART success rate than women with the L. crispatus-predominant or the mixed lactic-acid-bacteria-predominant type (P < 0.05). The 15 couples where both partners had beneficial microbiome types had a superior ART success rate of 53%, when compared with the rest of the couples (25%; P = 0.023)., Conclusions: Microbiome disturbances in the genital tract of both partners tend to be associated with couple's infertility as well as lower ART success levels and may thus need attention before the ART procedure. The incorporation of genitourinary microbial screening as a part of the diagnostic evaluation process may become routine for ART patients if our results are confirmed by other studies., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Maternal mental health during the peripartum period is critically important to the wellbeing of mothers and their infants. Numerous studies and clinical trials have focused on various aspects of interventions and treatments for perinatal mental health from the perspective of researchers and medical health professionals. However, less is known about women's experiences of participating in perinatal mental health research, and the ethical issues that arise., Aim: To systematically review the literature on the ethical issues that emerge from pregnant and/or postpartum women's experiences of taking part in perinatal mental health-related research., Methods: Systematic review of nine bibliographic databases, from inception to July 2021. Qualitative, quantitative and mixed method studies were included if they reported on ethical issues experienced by perinatal women. Research ethical issues encompassed any issue relating to women's experiences of being offered study information, recruitment, consent, retention and respect for autonomy.Titles, abstracts and full text screening, appraisal of the methodological quality of included studies, and data extraction, were conducted independently by two reviewers., Ethical Considerations: Ethical approval was not required for this systematic review., Findings: A total of 9830 unique citations was retrieved. Six studies met the inclusion criteria. Studies were clinically and methodologically heterogenous, and only one was purposively designed to explore women's experiences. The key finding was the establishment of trust between the researcher and participant in all stages of the research process. Findings are presented according to recruitment and consent processes, participation and retention, and study follow-up and completion ., Conclusion: The establishment of trust between the researcher and perinatal women leads to a dynamic with research ethical implications relevant to all stages of perinatal mental health-related research. Further research on the research ethical issues experienced by perinatal women is required because of the limited literature., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To explore patient-defined flares in psoriatic arthritis (PsA), compared to an increase in disease activity in psoriatic arthritis (DAPSA) and to analyze the validity of a patient-reported flare question., Methods: ReFlap (NCT03119805) was a longitudinal study in 14 countries of consecutive patients with definite PsA. Patients were seen twice in the context of usual care, 4.5±2.2 months apart. Flares were reported by patients and physicians at the second visit using a single question. DAPSA worsening was defined as a change to a higher DAPSA category. Agreement between the definitions of worsening was calculated by prevalence adjusted bias adjusted kappa (PABAK). Validity of patient-reported flare was assessed by comparing patients with versus without flare and transition to flares., Results: In 222 patients, mean disease duration 10.8±8.3 years, 127 (58.8%) males: disease activity was low (mean DAPSA 11.5±14.0); 63.3% received a bDMARD. Patient-reported flares between the 2 visits were seen in 27% patients (for these patients, mean 2.2±3.7 flares per patient, mean duration 12.6±21.0 days per flare). Physician- reported flares were seen in 17.6% and worsening in DAPSA in 40.1% of patients. Agreement between definitions was moderate (PABAK=0.32-0.59). Patients in flare had significantly more active disease than patients not in flare for all outcomes (all P<0.001). At the patient-level, transition to flare state was associated to a worsening in disease activity and impact outcomes., Conclusions: Patient flares were frequent and were associated with active and symptomatic disease. These findings provide preliminary validation for patient-reported flares in PsA., (Copyright © 2022 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Hospital-acquired strains (HASs) and multiresistant strains in neonatal intensive care unit often harbour virulence and resistance mechanisms, carrying the risk of invasive infections. We describe colonisation with Enterobacteriaceae in neonates receiving early directed versus routine family-integrated care (FIC) within the first month of life., Methods: A prospective cohort study included neonates with a gestational age below 34 weeks. During the first period, neonates were admitted to an open bay unit with transfer to the single-family room if available; feeding with the mother's own breast milk (MOBM) was introduced within 24 hours, and skin-to-skin contact (SSC) within 5 days of life (the routine care group). During the second period, following a wash-in of 2 months, care in a single-family room within 48 hours, the introduction of MOBM within two and SSC in 48 hours were applied (the intervention group). Enterobacteriaceae isolated from neonatal stool, breast milk and parental skin swabs were genotyped, Simpson's Index of Diversity (SID) calculated, and extended-spectrum beta-lactamases (ESBL) detected., Results: In 64 neonate-parents' groups, 176 Enterobacteriaceae , 87 in routine care and 89 in the intervention group were isolated; 26 vs 18 were HAS and one vs three ESBL positive, respectively. In the intervention group compared with the routine care group, SSC and MOBM feeding was started significantly earlier (p<0.001); during the first week of life, time spent in SSC was longer (median hours per day 4.8 (4-5.1) vs 1.9 (1.4-2.6), p<0.001) and the proportion of MOBM in enteral feeds was higher (median (IQR) 97.8% (95.1-100) vs 95.1% (87.2-97.4), p=0.011). Compared with the routine care group, the intervention group had higher SID and a reduction of HAS by 33.1% (95% CI 24.4% to 42.4%) in time series analysis., Conclusions: Early implementation of FIC measures may hold the potential to increase diversity and reduce colonisation with HAS Enterobacteriaceae ., Competing Interests: Competing interests: No, there are no competing interests., (© 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: Ongoing education of health professionals in rheumatology (HPR) is critical for high-quality care. An essential factor is education readiness and a high quality of educational offerings. We explored which factors contributed to education readiness and investigated currently offered postgraduate education, including the European Alliance of Associations for Rheumatology (EULAR) offerings., Methods and Participants: We developed an online questionnaire, translated it into 24 languages and distributed it in 30 European countries. We used natural language processing and the Latent Dirichlet Allocation to analyse the qualitative experiences of the participants as well as descriptive statistics and multiple logistic regression to determine factors influencing postgraduate educational readiness. Reporting followed the Checklist for Reporting Results of Internet E-Surveys guideline., Results: The questionnaire was accessed 3589 times, and 667 complete responses from 34 European countries were recorded. The highest educational needs were 'professional development', 'prevention and lifestyle intervention'. Older age, more working experience in rheumatology and higher education levels were positively associated with higher postgraduate educational readiness. While more than half of the HPR were familiar with EULAR as an association and the respondents reported an increased interest in the content of the educational offerings, the courses and the annual congress were poorly attended due to a lack of awareness, comparatively high costs and language barriers., Conclusions: To promote the uptake of EULAR educational offerings, attention is needed to increase awareness among national organisations, offer accessible participation costs, and address language barriers., Competing Interests: Competing interests: VR, LS, MRRA, MB, CB, JC, TD, JdlT, AdT, AD, FE-L, RJOF, GEF, JG, KK, MLK, CM-B, AM, JM, RHM, ElM, ErM, CN-S: no competing interest to declare. RD: Speaker fees from Abbvie, Elly Lilly, EwoPharma, Sandoz, and Novartis, all outside the submitted work., (© 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: Teledermatoscopy accuracy has been examined in experimental settings and is recommended for primary care despite lacking real-world implementation evidence. A teledermatoscopy service has been provided in Estonia since 2013, where lesions are evaluated based on the patient's or general practitioner's suggestion., Objective: The management plan and diagnostic accuracy of a real-world store-and-forward teledermatoscopy service for melanoma diagnosis were evaluated., Methods: A retrospective study analyzed 4748 cases from 3403 patients using the service between October 16, 2017 and August 30, 2019 by matching country-wide databases. Management plan accuracy was calculated as the percentage of melanoma found that was managed correctly. Diagnostic accuracy parameters were sensitivity, specificity, and positive and negative predictive values., Results: Management plan accuracy for melanoma detection was 95.5% (95% CI, 77.2-99.9). Diagnostic accuracy showed a sensitivity of 90.48% (95% CI, 69.62-98.83) and a specificity of 92.57% (95% CI, 91.79-93.31)., Limitations: Matching the lesions was limited to SNOMED CT location standard precision. Diagnostic accuracy was calculated based on a combination of diagnosis and management plan data., Conclusion: Teledermatoscopy for detecting and managing melanoma in real-world clinical practice displays results comparable with those in experimental setting studies., Competing Interests: Dr Koop, Kruus, Hallik, Lehemets, Dr Ross, and Dr Kingo have declared financial interest in Dermtest OÜ, the company providing the software, which enables teledermatoscopy in Estonia. Drs Vettus, and Niin have no conflicts of interest to declare., (© 2023 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Background: The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in 11 languages (Dutch, English, German, Finnish, French, Italian, Polish, Portuguese, Persian, Swedish, Turkish). From other languages under validation, the Spanish and Estonian versions completed data acquisition and underwent further validation., Methods: The EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during the initial validation study), 2) item reduction and scale exploration (completed during the initial validation study), 3) confirmatory analyses and responsiveness of the Spanish and Estonian versions (completed during the initial validation study in seven other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory., Results: The internal consistency of the scale was confirmed in the Spanish and Estonian versions (Cronbach's Alpha>0.8). Responsiveness was good, with moderate to large effect sizes in both languages, and evidence of a statistically significant positive association between the EFAS Score and patient-reported improvement., Conclusions: The Spanish and Estonian EFAS Score versions were successfully validated in orthopaedic ankle and foot surgery patients, with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.net., (Copyright © 2023 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Retinal periphlebitis (RPP) is a long-known entity in patients with multiple sclerosis (MS) and has not been revisited in the context of recent developments in MS pathogenesis and heterogeneity. We present six cases of RPP in three female and three male MS patients. They all have relapsing-remitting MS and did not have or had minor ocular symptoms. It is important to perform a thorough retinal examination in patients with MS, as peripheral and sectorial lesions could be unseen. A better knowledge on the concomitant involvement of retinal veins contributes to the understanding of immunopathology, with potentially distinct autoantigenic targets. RPP might serve as a subphenotype marker that may influence treatment choices in MS. Further research is needed., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)