Roos Colman

Objectives: Oral disorders are an important disability driver in adults aged 70 and older, who often experience greater tooth loss and higher levels of untreated oral disease than younger persons. Despite the importance of regular dental visits, older adults attend dental services less frequently, facing several barriers. This study aimed to evaluate whether a low‐threshold dental screening could increase the likelihood that older adults (≥ 65 years) contact a dental professional. Methods: A total of 194 community‐dwelling adults aged ≥ 65 years without a dental check‐up in the past 12 months were randomized (1:1) in a two‐arm, single‐blinded, controlled superiority trial. The intervention group received an oral screening, personalized oral health information, referral letters for a dentist and general practitioner, and a list of nearby dentists. The control group received only general oral hygiene flyers and a list of nearby dentists. The primary outcome was whether participants contacted a dental professional within 4 months following the intervention. Oral hygiene practices (i.e., tooth brushing frequency and use of brushing materials) were evaluated as secondary outcomes. Results: No evidence for an effect of the intervention on contact with a dental professional was found (risk difference = −0.01 (95% CI: −0.12; 0.10)). Within 4 months, 14% of control group participants and 12% of those in the intervention group reported contacting a dental professional, mostly due to urgent issues (e.g., pain or broken teeth), rather than the intervention itself. Among those who did not seek care ( n = 133), 79% cited a lack of perceived need. Furthermore, no intervention effect was found regarding oral hygiene practices. Conclusion: Motivating older adults to attend preventive professional dental care remains challenging. Greater integration of oral health into primary care, along with early‐life promotion of positive oral health behaviours, is essential.

Systemic glucocorticosteroids (sGCS) are widely used in the treatment of chronic inflammatory airway diseases such as rhinitis, rhinosinusitis and asthma. It is well‐known that systemic use is linked to multiple adverse effects (AEs) both in the short‐ and the long‐term. However, less is known about the safety of multiple short courses of sGCS. Currently there is no established agreement on the acceptable cumulative exposure to sGCS, considering the potential for various AEs. This systematic review and meta‐analysis evaluated sGCS‐related AEs in both upper and lower inflammatory airway disease, with a particular focus on short‐ and long‐term risks. We further evaluated whether a dose–response relationship existed between the daily and cumulative dosages of sGCS and the occurrence of those AEs. Our meta‐analysis confirmed that cumulative dosages between 500 mg and 1 g prednisolone‐equivalent significantly increase the risk of most AEs, with risks increasing with incremental dose. These findings underscore the importance of: (a) judicious sGCS prescription and need for steroid stewardship, due to their potential for short‐ and long‐term complications, occurring even with repeated short courses, and (b) prioritization of steroid‐sparing approaches (e.g., biologicals) to avoid reaching a cumulative dose of 500 mg.

STUDY QUESTION: Is there evidence of a plateau in the cumulative live birth rate (cLBR) after a certain number of consecutive transfers of untested embryos? SUMMARY ANSWER: In our cohort of 11 463 women, the cLBR continues to increase with each additional transfer of an untested embryo, reaching 68.3% after six blastocyst transfers and 78.0% after 10 blastocyst transfers. WHAT IS KNOWN ALREADY: While cumulative success rates in ART are rising, implantation failure remains a persistent challenge. The actual frequency of recurrent implantation failure (RIF) and whether RIF surpasses the inherent implantation potential of transferred embryos remains a matter of debate. A recent study reported a cLBR of 98% after five euploid blastocyst transfers, suggesting that most implantation failures are likely embryonic rather than endometrial. However, it remains unclear how these findings can be extrapolated to patients who did not undergo preimplantation genetic testing for aneuploidy (PGT-A). While theoretical models estimate cumulative implantation probabilities based on published blastocyst euploidy rates by female age, real-world data on cumulative success in routine clinical practice remain limited. STUDY DESIGN, SIZE, DURATION: This non-interventional retrospective cohort study included records of all completed IVF/ICSI cycles (including thus fresh and frozen–thawed transfers of one oocyte retrieval cycle) in women who underwent IVF/ICSI at the Ghent University Hospital between January 2010 and December 2022. After excluding treatments involving PGT, oocyte donation and surrogacy, or a mix of cleavage stage and blastocyst stage transfers, our dataset consisted of 11 463 women who underwent a total of 19 378 IVF/ICSI cycles, resulting in a total of 31 478 embryo transfers. PARTICIPANTS/MATERIALS, SETTING, METHODS: The number of embryos transferred (‘time’) until achieving live birth (‘event’) was analysed using a Kaplan–Meier approach with inverse probability weighting (IPW). Additionally, logistic regression analysis was conducted to assess the predictive value of the number of previously transferred embryos on the live birth rates (LBRs) of the second and subsequent transfers, adjusting for female age, quality of previously transferred embryos, and stage of embryos transferred (cleavage stage versus blastocyst stage). MAIN RESULTS AND THE ROLE OF CHANCE: Kaplan–Meier estimates using an IPW approach showed cLBRs increasing from 51.1% (95% CI: 49.2–53.0%) after a third, up to 68.3% (95% CI: 64.6–72.0%) after a sixth and even as high as 78.0% (95% CI: 69.5–86.5%) after a tenth blastocyst transfer, respectively. As maternal age increases, higher numbers of blastocysts are required to achieve the same cLBR. Moreover, no age category achieves an 80% cLBR until after the transfer of eight blastocysts. Maternal age has a considerable effect, as illustrated by cLBR after the fourth blastocyst transfer of 68.9% (95% CI: 65.8–71.8%) for 42 years, respectively. In the adjusted logistic regression analysis, the odds for achieving live birth are estimated to decrease for each additional embryo transferred; however, this effect is not statistically significant (OR = 0.91; 95% CI: 0.86–1.07). Female age, as expected, was a significant predictor of implantation rate with subsequent transfers (OR = 0.92; 95% CI: 0.91–0.93). Additionally, being assigned to a blastocyst transfer strategy rather than to a cleavage stage transfer strategy was also a significant predictor (OR = 1.34; 95% CI: 1.20–1.51), as was proportion of embryos classified as excellent or good quality based on predefined morphological criteria out of the total number of embryos previously transferred (OR = 1.21; 95% CI: 1.06—1.38). Implantation rate is also correlated with the response to stimulation (P = 0.016) and the blastocyst formation rate (P < 0.0001). There was no significant difference in LBR after an equal number of previously unsuccessful blastocyst transfers, depending on how many oocyte collection cycles it took to reach that number of blastocysts. LIMITATIONS, REASONS FOR CAUTION: The results are limited by the observational retrospective design, and while regression analyses were adjusted for potential confounding factors, residual confounding may persist, particularly given the considerable heterogeneity in treatments. We did not exclude patients with factors associated with less favourable reproductive outcomes because our goal was to evaluate actual clinical practice. WIDER IMPLICATIONS OF THE FINDINGS: Our data emphasize the potential for successful live birth even after multiple unsuccessful transfers. Factors such as age, embryo quality, response to ovarian stimulation, and rate of blastocyst formation influence outcomes. By addressing these multifaceted influences, our research provides valuable insights and a hopeful outlook for patients undergoing fertility treatment. STUDY FUNDING/COMPETING INTEREST(S): L.D. received a grant from the Agency for Innovation through Science (IWT SB-141441). The funder did not have any role in the study design; data collection, data analysis, and interpretation of data; the writing of the report; nor the decision to submit the paper for publication. 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. TRIAL REGISTRATION NUMBER: N/A.

Background: Cirrhosis is the main risk factor for the development of Hepatocellular carcinoma (HCC). Six-monthly screening with ultrasound is advocated for the surveillance of cirrhotic patients. We recently showed that a glycomics-based test (GlycoCirrhoTest [GCT]) can provide additional information regarding the risk of HCC development in cirrhotic patients. Aims: Independent clinical validation of the GCT for the assessment of the risk of HCC development in cirrhosis and exploration of additional clinical parameters to assess HCC risk. Methods: Validation study on serum samples of patients with established compensated cirrhosis (CHILD Pugh A & B) in a tertiary liver centre. Serum N-glycan profiling was performed and GCT was calculated at baseline. During the follow up period, patients were screened for the presence of HCC every 6 months with ultrasound. Results: A total of 198 cirrhotic patients were followed in clinical routine for the development of HCC. 29 patients developed HCC and one died during follow up. At baseline, the mean GCT value was significantly higher in patients who developed HCC within 3 years compared to patients who did not develop HCC (Welch’s t-test, p-value 3 years: 0.034). A high GCT at baseline was associated with increased HCC incidence with a HR of 5.8 (95% CI: 0.7 – 48), 4.8 (95% CI: 1.4 – 16) and 3.6 (95% CI: 1.2 – 11) at 3, 5 and 7 years post sampling respectively. Results from this study are in agreement with previous results ¹ , as shown in a meta-analysis. Moreover, we also identified albumin as an independent predictor for developing HCC in a multivariate analysis revealing that low albumin blood levels (< 4g/dL) are also associated with increased HCC incidence with a HR at 7 years of 2.3 (95% CI: 1.1 - 4.9). For subjects with both high GCT and low albumin we found a HR of 9.8 (95% CI: 3.5 to 27) at 7 years. Conclusions: GCT is a glycomics-based test that provides additional information for risk assessment of HCC development in cirrhosis. This information could be used to develop personalised HCC screening programs in cirrhotic patients according to the value of GCT. Serum albumin levels could provide additional and GCT-independent information which may add to the utility of the test.

Improvements in COVID-19 treatments, especially for the critically ill, require deeper understanding of the mechanisms driving disease pathology. The complement system is not only a crucial component of innate host defense but can also contribute to tissue injury. Although all complement pathways have been implicated in COVID-19 pathogenesis, the upstream drivers and downstream effects on tissue injury remain poorly defined. We demonstrate that complement activation is primarily mediated by the alternative pathway, and we provide a comprehensive atlas of the complement alterations around the time of respiratory deterioration. Proteomic and single-cell sequencing mapping across cell types and tissues reveals a division of labor between lung epithelial, stromal, and myeloid cells in complement production, in addition to liver-derived factors. We identify IL-6 and STAT1/3 signaling as an upstream driver of complement responses, linking complement dysregulation to approved COVID-19 therapies. Furthermore, an exploratory proteomic study indicates that inhibition of complement C5 decreases epithelial damage and markers of disease severity. Collectively, these results support complement dysregulation as a key druggable feature of COVID-19.

Purpose: This longitudinal survey study aimed to investigate the self-reported outcome measures of COVID-19 peritraumatic distress, depression, anxiety, stress, quality of life (QOL), and their associated factors in a cohort of cancer patients treated at a tertiary care hospital during the SARS-CoV-2 pandemic. Methods: Surveys were administered at four time points between 1 April 2020 and 18 September 2020. The surveys included the CPDI, DASS-21, and WHOQOL-BREF questionnaires. Results: Survey response rates were high (61.0% to 79.1%). Among the 355 participants, 71.3% were female, and the median age was 62.2 years (IQR, 53.9 to 69.1). The majority (78.6%) were treated with palliative intention. An important proportion of the participants reported symptoms of COVID-19 peritraumatic distress (34.2% to 39.6%), depression (27.6% to 33.5%), anxiety (24.9% to 32.7%), and stress (11.4% to 15.7%) at any time point during the study period. We did not find clinically meaningful mental health and QOL differences during the study period, with remarkably little change in between the pandemic’s first and second wave. We found no consistent correlates of mental health or QOL scores, including cancer type, therapy intention, and sociodemographic information. Conclusion: This cohort of cancer patients showed considerable resilience against mental health and QOL deterioration during the SARS-CoV-2 pandemic.

Treatment with golimumab monotherapy in early peripheral SpA (pSpA) results in higher rates of clinical remission compared with treatment in more longstanding disease. When reaching remission, treat-to-target recommendations suggest tapering of treatment. We therefore explored whether addition of MTX would permit discontinuation of golimumab in patients with pSpA in sustained clinical remission. After a 2-year extension phase with golimumab treatment, patients with pSpA reaching clinical remission in the CRESPA trial were offered a tapering strategy leading to discontinuation of golimumab and replacement by MTX monotherapy. Patients were prospectively followed to assess the rate of sustained biologic-free clinical remission. In case of relapse of arthritis, enthesitis or dactylitis under MTX monotherapy, golimumab was restarted. Of the original 60 pSpA patients, 25 entered the step-down strategy. Currently, only 4 patients (16%) are still in sustained remission under MTX monotherapy. In 21 patients (84%), golimumab was reinstalled because of relapse of disease activity (n = 19) or development of adverse events related to MTX (n = 2). Restarting golimumab treatment promptly restored clinical remission in all patients within 12 weeks. In patients with early pSpA achieving clinical remission after 2 years of golimumab treatment, step-down therapy to monotherapy with MTX led to high rates of clinical relapse. This underscores the overall weak efficacy of MTX in maintaining clinical remission in pSpA. ClinicalTrials.gov, https://clinicaltrials.gov, NCT01426815.

Objective To determine interrater variability in diagnosing individual muscle biopsy abnormalities and diagnosis. Methods We developed a scoring tool to analyze consensus in muscle biopsy reading of an ad hoc workgroup of international experts. Twenty-four samples from patients with suspected idiopathic inflammatory myopathy (IIM) were randomly selected, providing sections that were stained with standard histologic and immunohistochemical methods. Sections were made available on an online platform, and experts were queried about myopathologic features within 4 pathologic domains: muscle fibers, inflammation, connective tissue, and vasculature. A short clinical presentation of cases was included, and experts were asked to give a tentative diagnosis of polymyositis, dermatomyositis, inclusion-body myositis, antisynthetase syndrome–related myositis, immune-mediated necrotizing myopathy, nonspecific myositis, or other disease. Fleiss κ values, scoring interrater variability, showed the highest agreement within the muscle fiber and connective tissue domains. Results Despite overall low κ values, moderate agreement was achieved for tentative diagnosis, supporting the idea of using holistic muscle biopsy interpretation rather than adding up individual features. Conclusion The assessment of individual pathologic features needs to be standardized and harmonized and should be measured for sensitivity and specificity for subgroup classification. Standardizing the process of diagnostic muscle biopsy reading would allow identification of more homogeneous patient cohorts for upcoming treatment trials.

The risk of developing acute radiotherapy(RT)-induced side effects may increase with hypofractionated RT. To detect treatment-related side effects, patient-reported outcomes (PROs) might be more reliable than physician-reported outcomes. Therefore, we tried to evaluate the rate of agreement between urinary and gastrointestinal (GI) side effects and the prevalence of side effects reported by patients and by physicians.

Objective: New treatment algorithms using tumor necrosis factor (TNF) blockers in early stages of spondyloarthritis (SpA) induce high rates of clinical remission or low disease activity. It could be anticipated that such early intervention strategies in peripheral SpA may induce drug‐free remission. We undertook this study to evaluate drug‐free clinical remission after induction therapy with golimumab in patients with very early active peripheral SpA, and to identify patient characteristics that predict sustained drug‐free remission.Methods: Eligible patients were age ≥18 years and fulfilled the Assessment of SpondyloArthritis international Society criteria for peripheral SpA. All patients had symptom duration of 5).Conclusion: Anti‐TNF treatment in very early peripheral SpA results in a remarkably high rate of sustained clinical remission. More than 50% of patients continue to have remission of their disease after withdrawal of therapy, which highlights a defined window of opportunity permitting induction of drug‐free remission.