Medical University of Vienna

Background Vaccination remains crucial for protection against severe SARS-CoV-2 infection, especially in aged population. Methods We evaluated, with a randomised controlled, adaptive, multicentre phase II study, the safety and immunogenicity of a 3rd vaccination dose (1st booster) in individuals ≥75 years (ClinicalTrials.gov Identifier: NCT05160766, EudraCT Number: 2021-004526-29). Participants were randomized to either a full-dose (100µg) of mRNA-1273 (Spikevax®) or 30 µg of BNT162b2 (Comirnaty®). The primary endpoint was the rate of 2-fold antibody titre increase 14 days post-vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA). Secondary endpoints included changes in neutralising capacity (ACE2 Virus Neutralisation Assay) against wild-type and 25 variants at 14 days and up to 12 months. Results Fifty-three volunteers were randomised between 8 November 2021 and 4 January 2022, with 52 receiving a COVID-19 vaccine as 1st booster. Fifty subjects (BNT162b2 n=25/mRNA-1273 n=25) were included in the analyses for immunogenicity after day 14. The primary endpoint of a 2-fold anti-RBD IgG titre increase 14 days post-vaccination was reached in all subjects. A 3rd full-dose mRNA-1273 vaccination provided higher anti-RBD IgG titres (GMT D14 7090 [95% CI 5688 – 8837] BNT162b2 vs. 10711 [95% CI 8003 – 14336] mRNA-1273). A pattern showing higher neutralising capacity of full-dose mRNA-1273 against Wuhan wild-type so as for 23/25 tested variants was observed. Conclusion Third doses of either BNT162b2 or mRNA-1273 provide substantial antibody increase 14 days post-vaccination, with full-dose mRNA providing higher antibody levels and an overall similar safety profile for ≥75 subjects. Additional booster doses should be prioritised, particularly in aged people and others at high-risk. In-depth data on waning of immune response is needed to assess duration of protection, and evaluation of vaccine-dosage for individuals at risk may be reconsidered. With the data on full-dose (100µg) mRNA-1273evaluation of vaccine-dosage for individuals at risk may be reconsidered, despite the small sample size. Disclosures Jannik Stemler, -, Ministry of Education and Research (BMBF): Grant/Research Support Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds

Background Twitter has become an invaluable resource for gaining insights into crucial developments in global healthcare communication. The hashtags (#) can be used to categorize tweets and gather conversations on a specific topic or to target a particular audience. Although the prevailing knowledge fund underlines the potential of digital networks to essentially influence the management of infectious diseases (ID), there has been no comprehensive analysis on the user information in the ID Twitter community, nor of the influence this hashtag has generated. The objective of our study was to evaluate the demographic data of #IDTwitter users, discern the most influential members and popular narratives in this realm, and ascertain the impact of the hashtag. Methods Using data from 28th June 2019 and 28th March 2023, an extensive analysis was conducted using the Symplur Signals research analytics tool. The analysis focused on the cumulative number of tweets, impressions, and unique users who shared tweets containing the hashtag #IDTwitter, with users categorized into specific healthcare stakeholder groups. The primary outcome measures were outreach and awareness measured by the number of tweets and impressions. Results The study observed the trends of #IDTwitter over a period of 45 months and found 441,650 tweets were shared by 92,734 users that generated a total of 1,833,037,732 impressions (views). Top five co-occurring hashtags were #IDtwitter, #MedTwitter, #MedEd, #COVID19, #TwitteRx. The top five countries reporting the greatest number of users of this hashtag were The United States of America (48326), Canada (4803), Mexico (3413), India (2759), Australia (2658). Various healthcare stakeholders’ categories were identified and three largest groups of contributors were Doctors (14.55%), Healthcare Providers (7.54%) and Researcher/Academic (3.70%). The top three influencers of this hashtag include two clinical pharmacists and one organization account. Country-wise distribution of Users of #IDTwitter The image shows the geographical distribution of the users who posted tweets containing #IDTwitter were shared (based on the locations at which the posting accounts were registered). Twitter is used worldwide for conversations regarding communicable diseases and their prevention, not only among the general public but also among students and professionals via online chat discussions and virtual rounds. Stakeholders of #IDTwitter Accounting for the percentage distribution of #IDTwitter-posting users in various healthcare stakeholders categories (data derived from Symplur Signals, with the classification being based on information provided in the Twitter biographies of the users- https://help.symplur.com/en/articles/103684-healthcare-stakeholder-segmentation). Twitter has become a quintessential tool for connecting people worldwide, and we can leverage this platform to our advantage by paying close attention to the topic and content of hashtag exchanges to combat misinformation related to matters like antibiotic usage or any epidemic infection on social media platforms. Top Co-occurring Hashtags The hashtags that generally appear alongside of #IDTwitter could provide an insight regarding the popular discussions involving #IDTwitter. Conclusion Our findings indicate that there is considerable interest in using #IDTwitter to promote relevant content and engage a geographically diverse audience. It underscores the vitality of professional voices in combating misinformation and we could definitely leverage this 'viral' hashtag for our advantage. Disclosures All Authors: No reported disclosures

Stereotactic radiosurgery effectively controls vestibular schwannoma (VS). However, in certain cases, microsurgical resection may be necessary for post-radiosurgery tumour progression. The characteristics and microsurgical challenges of uncommon cystic recurrences post-radiosurgery are rarely addressed. We retrospectively analysed 24 consecutive patients who underwent microsurgical intervention for recurrent VS post-radiosurgery by the senior author. Tumour recurrence post-radiosurgery occurred as solid growth in 19 patients (79%), while 5 patients (21%) developed large brainstem-compressing cysts. The median time interval for tumour recurrence post-radiosurgery was similar between cystic and non-cystic recurrent VS (30 vs. 25 months; p=0.08). Cystic recurrences occurred in primarily cystic VS in 3 patients, and new cysts developed in 2 patients with primarily solid VS. Intra-operatively, tumours were firm in 18 cases (75%) and strongly adhered to surrounding structures in 14 cases (58%). All cystic cases underwent cyst decompression, while complete resection of solid tumour components was avoided due to neurovascular adherence. At a mean follow-up of 42±39 months, 12 patients (50%) showed contrast-enhancing tumour residuals in follow-up imaging, including all cystic recurrent cases. Tumour residuals remained stable without requiring further intervention, except for one patient revealing malignant tumour transformation. House-Brackmann grade I/II was preserved in 15 patients (62%). Three patients (13%) developed new facial palsy, and two patients (8%) improved to House-Brackmann grade II. Cystic recurrences had a significantly higher frequency of tumour residuals compared to solid recurrences (100% vs. 37%; p=0.01) but similar rates of facial palsy (60% vs. 32%; p=0.24) Cyst development in VS post-radiosurgery is more common in primary cystic lesions but can also occur in rare cases of primary solid VS. Symptomatic cysts require microsurgical decompression. However, complete resection of the solid tumour component is not crucial for long-term tumour control and should be avoided if it risks neurological function in this delicate area.

Ceftaroline fosamil is a β-lactam antibiotic approved as a 600 mg twice daily dose (≤1 h infusion, ‘standard dosing’) or a 600 mg thrice daily dose (2 h infusion) to treat complicated skin and soft tissue infections caused by Staphylococcus aureus (minimum inhibitory concentration [MIC] 2–4 mg/L). We sought to systematically evaluate the relative impact of the three key components of the intensified dosing regimen (i.e. shortened dosing interval, prolonged infusion duration and increased total daily dose [TDD]) on the pharmacokinetic/pharmacodynamic (PK/PD) target attainment given different grades of bacterial susceptibility. A population PK model was developed using data from 12 healthy volunteers (EudraCT-2012-005134-11) receiving standard or intensified dosing. PK/PD target attainment (ƒT>MIC = 35% and 100%) after 24 h was compared following systematically varied combinations of the (1) dosing interval (every 12 h [q12h]→ every 8 h [q8h]); (2) infusion duration (1 h→2 h); and (3) individual and total daily dose (400→900 mg, i.e. TDD 1200→1800 mg), as well as for varying susceptibility of S. aureus (MIC 0.032–8 mg/L). A two-compartment model with linear elimination adequately described ceftaroline concentrations (n = 274). The relevance of the dosing components dosing interval/infusion duration/TDD for ƒT>MIC systematically changed with pathogen susceptibility. For susceptible pathogens with MIC ≤1 mg/L, shortened dosing intervals appeared as the main driver of the improved target attainment associated with the intensified dosing regimen, followed by increased TDD and infusion duration. For less susceptible pathogens, the advantage of q8h dosing and 2 h infusions declined, and increased TDD improved ƒT>MIC the most. The analysis calls to mind consideration of dose increases when prolonging the infusion duration in the case of low bacterial susceptibility.

To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS). The MIPA observational study database (7245 patients) was searched for patients aged 18–80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs). Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111). Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation. When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies. • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies.

Introduction This survey of international experts in obesity management was conducted to achieve consensus on standardized definitions and to identify areas of consensus and non-consensus in metabolic bariatric surgery (MBS) to assist in an algorithm of clinical practice guidelines for the management of obesity. Methods A three-round Delphi survey with 136 statements was conducted by 43 experts in obesity management comprising 26 bariatric surgeons, 4 endoscopists, 8 endocrinologists, 2 nutritionists, 2 counsellors, an internist, and a pediatrician spanning six continents over a 2-day meeting in Hamburg, Germany. To reduce bias, voting was unanimous, and the statements were neither favorable nor unfavorable to the issue voted or evenly balanced between favorable and unfavorable. Consensus was defined as ≥ 70% inter-voter agreement. Results Consensus was reached on all 15 essential definitional and reporting statements, including initial suboptimal clinical response, baseline weight, recurrent weight gain, conversion, and revision surgery. Consensus was reached on 95/121 statements on the type of surgical procedures favoring Roux-en-Y gastric bypass, sleeve gastrectomy, and endoscopic sleeve gastroplasty. Moderate consensus was reached for sleeve gastrectomy single-anastomosis duodenoileostomy and none on the role of intra-gastric balloons. Consensus was reached for MBS in patients > 65 and < 18 years old, with a BMI > 50 kg/m ² , and with various obesity-related complications such as type 2 diabetes, liver, and kidney disease. Conclusions In this survey of 43 multi-disciplinary experts, consensus was reached on standardized definitions and reporting standards applicable to the whole medical community. An algorithm for treating patients with obesity was explored utilizing a thoughtful multimodal approach. Graphical Abstract

Aim To compare outcomes of PJI in relation to treatment method versus classification using the JS-BACH system. Method Patients having surgery for EBJIS Criteria Confirmed PJI between 2010–2015 were included. Index surgical procedures were 1-stage or 2-stage revision or debridement and implant retention (DAIR). Patients completed the EuroQol EQ-5D-3L questionnaire and were followed clinically to a median of 4.7 years (IQR 2.7–6.7 years). Patients were stratified using the JS-BACH classification1 into either ‘Uncomplicated’, ‘Complex’ or having ‘Limited treatment options’, by two separate classifiers, blinded to clinical outcome. Results 216 patients met the inclusion criteria. There were 51 patients classified as Uncomplicated (23.6%), 127 (58.8%) as Complex and 38 (17.6%) having Limited treatment options. Patients underwent either DAIR (n=97), 1-stage (n=35) or 2-stage (n=84) revision. Patients classified as Uncomplicated PJI had the lowest risk of recurrence or treatment failure, regardless of index procedure performed. Complex patients were significantly more likely than Uncomplicated patients to have recurrence following 2-stage revision (Odds Ratio 1.85; p=0.040) or DAIR (OR 1.83; p=0.037), but not 1-stage revision (OR 0.518; p=0.675). Limited treatment option patients had the highest recurrence risk regardless of index procedure (1-stage: OR 2.5 p=0.036; 2-stage: OR 3.3 p=0.004; DAIR: OR 3.40 p=0.006). At one year after surgery, Uncomplicated patients had the highest EQ-index scores (a marker of Quality of Life), with all treatments (EQ-5D-3L mean index scores; Uncomp 0.773, Complex 0.512, Limited Options 0.310: p<0.01). Differences in patient-reported outcomes were greater between the JS-BACH classification groups than between any methods of treatment. Conclusions The JS-BACH classification effectively predicted outcome after three common PJI treatments. Comparing outcomes between treatments, without stratification of the patients, may be misleading as factors other than treatment method have a major effect on outcome. Classification may allow better allocation of individual treatments to provide optimal outcome for patients.

Introduction Non-specific low back pain is a common and clinically significant condition with substantial socioeconomic implications. Pulsed electromagnetic field (PEMF) therapy has shown benefits in pain reduction and improvement of physical function in patients with pain-associated disorders like osteoarthritis. However, studies had heterogeneous settings. The aim of this study was to assess the effects of PEMF on pain and function on patients with non-specific low back pain. Methods A systematic literature search of randomized controlled trials in PubMed, MEDLINE, EMBASE, Cochrane Library, and PEDro was performed (from inception until 15/5/2023). Outcome measures assessed pain and function. Results Nine randomized controlled trials with 420 participants ( n = 420) were included. The studies compared PEMF vs. placebo-PEMF, PEMF and conventional physical therapy vs. conventional physical therapy alone, PEMF and conventional physical therapy vs. placebo-PEMF and conventional physical therapy, PEMF vs. high-intensity laser therapy (HILT) vs. conventional physical therapy, and osteopathic manipulative treatment (OMT) and PEMF vs. PEMF alone vs. placebo-PEMF vs. OMT alone. Five of the nine included studies showed statistically significant pain reduction and improvement in physical function in comparison to their control groups ( p < 0.05). There was substantial heterogeneity among the groups of the study, with a wide range of duration (10–30 min), treatments per week (2–7/week), applied frequencies (3–50 Hz), and intensities (2mT–150mT). No serious adverse event had been reported in any study. The included studies showed solid methodological quality, with an overall score of 7.2 points according to the PEDro scale. Conclusion PEMF therapy seems to be a safe and beneficial treatment option for non-specific low back pain, particularly if used as an addition to conventional physical therapy modalities. Future research should focus on standardized settings including assessment methods, treatment regimens, frequencies, and intensities.

Aim Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). Method From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC). Results A total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001). Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043). Conclusions Due to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition.

Background The identification of novel biomarker which is highly specific and sensitive for periprosthetic joint (PJI) have the potential to improve diagnostic accuracy and ultimately improve patient outcomes. Thus, the aim of this systemic review is to identify and evaluate novel biomarkers for the preoperative diagnostics of PJI. Methods MEDLINE, EMBASE, PubMed and Cochrane Library databases identified from 1 st of January 2018 to 30 th of September. 2022. We used “periprosthetic joint infection” OR “prosthetic joint infection” OR “periprosthetic infection” as the diagnosis of interest and the target index applied AND “marker”. To focus on novel biomarkers already used biomarkers of the established PJI diagnostic criteria of MSIS, ICM and EBJIS were not included in the analysis. These three criteria were considered the reference standard during quality assessment. Results A total of 19 studies were included. In these, fourteen different novel biomarkers were analyzed. Fifteen studies (79%) had prospective designs and the other four (22%) were retrospective studies. Six studies (33%) included only periprosthetic knee infections and thirteen (67%) included periprosthetic knee and hip infections. Proteins were analyzed in most cases (nine studies), followed by molecules (three studies), exosome (two studies) as well as DNA (two studies), interleukin (one study) and lysosome (one study). One novel and promising marker that had been frequently analyzed is calprotectin. Conclusion No marker demonstrated higher sensitivity and specificity than already known parameters used for standardized treatment based on established PJI definitions. Further studies are needed to elucidate the benefit and usefulness of implementing new biomarkers in diagnostic PJI settings.

Introduction Non-specific low back pain (NLBP) is a common and clinically significant condition with substantial socioeconomic implications. Whole-body vibration therapy (WBVT) has shown effectiveness in improving pain and sensorimotor function (e.g., in osteoporosis) in previous studies. However, studies had heterogeneous settings. The aim of this study was to assess the effects of WBVT on pain, function, proprioception, and postural stability in patients with subacute and chronic NLBP. Methods A systematic literature search was conducted in the scientific databases PubMed, EMBASE, and PEDro (from inception until 17.05.2023). Only prospective controlled and uncontrolled studies were included. Outcome measures assessed were pain intensity, function (activities of daily living and physical function), proprioception, and postural stability. Results A total of 12 original articles ( n = 821) were included in the analysis. Ten of the studies were randomized controlled trials, one study had a crossover design, and one study had a one-group pre–post study design. The studies compared WBVT vs. no intervention, WBVT vs. basic physical therapy, WBVT vs. core stabilization exercises with and without respiratory resistance, WBVT vs. lumbar extension exercises, and WBVT vs. whole body electromyostimulation training. The treatment approaches varied in terms of duration (2–18 weeks), frequency (2–3 times per week, two applications with a 2-week break), vibration frequency (5–30 Hz), type of exercises (WBVT with or without static or dynamic exercises), and vibration direction (horizontal and vertical). Significant pain reduction was observed in all 10 studies that investigated pain levels. Significant improvement in daily activity function was reported in five of the six studies that investigated daily function, while improvement in physical function was observed in all four studies that investigated physical function. Improvement in proprioception was reported in all three studies that investigated proprioception, and significant improvement in postural stability was observed in four out of six studies that investigated postural stability. No adverse events or side effects related to WBVT were reported. Conclusion The majority of the included studies demonstrated significant pain reduction, improvement in physical and daily functioning, and enhanced proprioception. Improvement in postural stability was less consistent. WBVT appears to be a safe and effective treatment modality for subacute and chronic NLBP when used within a multimodal approach. Future research should focus on standardized settings including assessment methods, treatment regimens, frequencies, and intensities.

Objective The inclusion of patient research partners (PRPs) in research projects is increasingly recognised and recommended in rheumatology. The level of involvement of PRPs in translational research in rheumatology remains unknown, while in randomised clinical trials (RCTs), it has been reported to be 2% in 2020. Therefore, we aimed to assess the involvement of PRPs in recent translational studies and RCTs in rheumatology. Methods We conducted a scoping literature review of the 80 most recent articles (40 translational studies and 40 RCTs) from four target diseases: rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus and lower extremity osteoarthritis. We selected 20 papers from each disease, published up until 1 March 2023, in rheumatology and general scientific journals. In each paper, the extent of PRP involvement was assessed. Analyses were descriptive. Results Of 40 translational studies, none reported PRP involvement. Of 40 RCTs, eight studies (20%) reported PRP involvement. These trials were mainly from Europe (75%) and North America (25%). Most of them (75%) were non-industry funded. The type of PRP involvement was reported in six of eight studies: six studies reported PRP participation in the study design or design of the intervention and two of them in the interpretation of the results. All the trials reporting the number of PRPs (75%), involved at least two PRPs. Conclusion Despite a worldwide movement advocating for increased patient involvement in research, PRPs in translational research and RCTs in rheumatology are significantly under-represented. This limited involvement of PRPs in research highlights a persistent gap between the existing recommendations and actual practice.

The intermediate-conductance calcium-activated potassium channel K Ca 3.1 has been proposed to be a new potential target for glioblastoma treatment. This study analyzed the effect of combined irradiation and K Ca 3.1-targeting with TRAM-34 in the syngeneic, immune-competent orthotopic SMA-560/VM/Dk glioma mouse model. Whereas neither irradiation nor TRAM-34 treatment alone meaningfully prolonged the survival of the animals, the combination significantly prolonged the survival of the mice. We found an irradiation-induced hyperinvasion of glioma cells into the brain, which was inhibited by concomitant TRAM-34 treatment. Interestingly, TRAM-34 did neither radiosensitize nor impair SMA-560’s intrinsic migratory capacities in vitro. Exploratory findings hint at increased TGF-β1 signaling after irradiation. On top, we found a marginal upregulation of MMP9 mRNA, which was inhibited by TRAM-34. Last, infiltration of CD3 ⁺ , CD8 ⁺ or FoxP3 ⁺ T cells was not impacted by either irradiation or K Ca 3.1 targeting and we found no evidence of adverse events of the combined treatment. We conclude that concomitant irradiation and TRAM-34 treatment is efficacious in this preclinical glioma model.

Objective Children with medical complexity (CMC) are among the most vulnerable patient groups. This study aimed to evaluate their prevalence and risk factors for medication misunderstanding and potential harm (PH) at discharge. Design and setting Cross-sectional study at a tertiary care centre. Study population CMC admitted at Medical University of Vienna between May 2018 and January 2019. Intervention CMC and caregivers underwent a structured interview at discharge; medication understanding and PH for adverse events were assessed by a hybrid approach. Main outcome measures Medication misunderstanding rate; PH. Results For 106 included children (median age 9.6 years), a median number of 5.0 (IQR 3.0–8.0) different medications were prescribed. 83 CMC (78.3%) demonstrated at least one misunderstanding, in 33 CMC (31.1%), potential harm was detected, 5 of them severe. Misunderstandings were associated with more medications (r=0.24, p=0.013), new prescriptions (r=0.23, p=0.019), quality of medication-related communication (r=−0.21, p=0.032), low level of education (p=0.013), low language skills (p=0.002) and migratory background (p=0.001). Relative risk of PH was 2.27 times increased (95% CI 1.23 to 4.22) with new medications, 2.14 times increased (95% CI 1.10 to 4.17) with migratory background. Conclusion Despite continuous care at a tertiary care centre and high level of subjective satisfaction, high prevalence of medication misunderstanding with relevant risk for PH was discovered in CMC and their caregivers. This demonstrates the need of interventions to improve patient safety, with stratification of medication-related communication for high-risk groups and a restructured discharge process focusing on detection of misunderstandings (‘unknown unknowns’).

Significant sex-specific differences were described in the presentation, management and outcome of acute coronary syndrom (ACS) patients. Female ACS patients more often presented with noncardiac symptoms, which lead to significant time delays between symptom onset and treatment. Furthermore, multiple studies from various countries described that women with ACS were less likely to receive the medical or reperfusion therapy recommended by the respective guidelines, resulting in higher in-hospital mortality rates. The treating physicians and the patients need to be more aware of the described differences to ensure the best possible medical care for ACS patients, irrespective of sex.

We present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987. This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC.

Automated segmentation of cervical cells is a prerequisite for detection of cervical lesions. However, this segmentation is a highly challenging task since the cervical cells are highly overlapping forming clumps, resulting in irregular cytoplasmic boundaries. Nuclei detection is very crucial for individual cell segmentation because each cell is represented by its nuclei. But the presence of outliers like bad stains, mucus, blood, inflammatory substances, false nuclei, etc., makes nuclei detection a difficult task to accomplish. For this challenging task, it is difficult to extract discriminating features based on human knowledge. Thus, in this work, we have designed Pap-Net: a patch-based multi scale deep learning framework for nucleus segmentation from Pap smear images. Pap-Net obtained a precision and recall of 93.7 and 92.3%, respectively, on overlapping cervical cytology image segmentation challenge—ISBI-2014 dataset. Both the qualitative and quantitative analysis suggest that that Pap-Net is robust and can be used for nucleus segmentation in Pap smear cells.

Objectives: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. Methods: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members’ experience of fatigue in I-RMDs. Results: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals’ awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual’s needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. Conclusions: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.

Forests can foster mental health and well‐being. Yet, the contribution of forest biodiversity remains unclear, and experimental research is needed to unravel pathways of biodiversity–health linkages. Here, we assess the role of tree species richness, both actual and perceived, and how stress reduction and attention restoration can serve as potential mediating pathways to achieve positive mental health and well‐being outcomes. We conducted an experimental, multicentric field study in three peri‐urban forests in Europe, employing a mixed design with 223 participants, that comprised 20‐min stays in forests with either low, medium or high tree species richness or a built control. Participants' short‐term mental health and well‐being and saliva cortisol as a biomarker of stress were measured before and after the intervention. Forest visits for 20 min were found to be beneficial for participants' short‐term mental health, short‐term mental well‐being, subjective stress, subjective directed attention and perceived restorativeness compared with a built environment. No differences were found for the physiological stress indicator saliva cortisol, which decreased in both the forest and the built environments. Increased perceived biodiversity—possibly linked to structural forest attributes—was significantly associated with well‐being outcomes, while no association was found for differences in actual tree species richness. Structural equation modelling indicates that higher levels of perceived biodiversity had an indirect effect on short‐term mental health and well‐being through enhancing perceived restorativeness. While we found no evidence of actual tree species richness effects, perceived biodiversity was associated with positive short‐term mental health and well‐being outcomes. Understanding these biodiversity–health linkages can inform conservation management and help develop effective nature‐based interventions for promoting public health through nature visits. Read the free Plain Language Summary for this article on the Journal blog.

One sentence: The abducens or abducent nerve is CN VI and provides the motor innervation of the lateral rectus muscle.