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Abstract Background Despite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment. For this reason, endoscopic stenting and/or bile duct decompression is the mainstay of treatment of these patients. Data on efficacy and safety of adding radiofrequency ablation (RFA) to biliary stenting is not conclusive. The aim of this multicenter, randomized trial is to evaluate the effect of intraductal RFA prior to bile duct stenting in patients with unresectable perihilar or ductal CCA undergoing palliative systemic therapy. Methods/Design ACTICCA-2 is a multicenter, randomized, controlled, open-label, investigator-initiated trial. 120 patients with perihilar or ductal CCA with indication for biliary stenting and systemic therapy will be randomized 1:1 to receive either RFA plus bile duct stenting (interventional arm) or bile duct stenting alone (control arm). Patients will be stratified by trial site and tumor location (perihilar vs. ductal). Both arms receive palliative systemic treatment according to the local standard of care determined by a multidisciplinary tumorboard. The primary endpoint is time to first biliary event, which is determined by an increase of bilirubin to > 5 mg/dl and/or the occurrence of cholangitis leading to premature stent replacement and/or disruption of chemotherapy. Secondary endpoints include overall survival, safety according to NCI CTCAE v5, quality of life assessed by questionnaires (EORTC QLQ-C30 and QLQ-BIL21), clinical event rate at 6 months after RFA and total days of over-night stays in hospital. Follow-up for the primary endpoint will be 6 months, while survival assessment will be continued until end of study (maximum follow-up 30 month). All patients who are randomized and who underwent endoscopic stenting will be used for the primary endpoint analysis which will be conducted using a cause-specific Cox proportional hazards model with a frailty for trial site and fixed effects for the treatment group, tumor location, and stent material. Discussion ACTICCA-2 is a multicenter, randomized, controlled trial to assess efficacy and safety of adding biliary RFA to bile duct stenting in patients with CCA receiving palliative systemic treatment. Trial registration The study is registered with ClinicalTrials.gov (NCT06175845) and approved by the local ethics committee in Hamburg, Germany (2024-101232-BO-ff). This manuscript reflects protocol version 1 as of January 9th, 2024. Graphical Abstract

This paper presents an investigation into the influence of repeating cycles of hydrothermal growth processes and rapid thermal annealing (HT+RTA) on the properties of CuO thin films. An innovative hydrothermal method ensures homogeneous single-phase films initially. However, their electrical instability and susceptibility to cracking under the influence of temperature have posed a challenge to their utilization in electronic devices. To address this limitation, the HT+RTA procedure has been developed, which effectively eliminated the issue. Comprehensive surface analysis confirmed the procedure’s ability to yield continuous films in which the content of organic compounds responsible for the formation of cracks significantly decreases. Structural analysis underscored the achieved improvements in the crystalline quality of the films. The implementation of the HT+RTA procedure significantly enhances the potential of CuO films for electronic applications. Key findings from Kelvin probe force microscopy analysis demonstrate the possibility of modulating the work function of the material. In addition, scanning capacitance microscopy measurements provided information on the changes in the local carrier concentration with each repetition. These studies indicate the increased usefulness of CuO thin films obtained from the HT+RTA procedure, which expands the possibilities of their applications in electronic devices.

BackgroundUnderstanding public opinions about emerging tobacco products is important to inform future interventions and regulatory decisions. Heated tobacco products (HTPs) are an emerging tobacco product category promoted by the tobacco industry as a “better alternative” to combustible cigarettes. Philip Morris International’s IQOS is leading the global HTP market and recently has been subject to important policy events, including the US Food and Drug Administration’s (FDA) modified-risk tobacco product (MRTP) authorization (July 2020) and the US import ban (November 2021). Although limited in their legal implications outside the United States, these policy events have been quoted in global news outlets and Philip Morris International’s promotional communications, showing how they may potentially impact global tobacco regulation. Given the impending return of IQOS to the US market, understanding how the policy events were received through social media discourse will provide valuable insights to inform global tobacco control policy. ObjectiveThis study aims to examine HTP-related social media discourse around important policy events. MethodsWe analyzed HTP-related posts on Twitter during the time period that included IQOS’s MRTP authorization in the United States and the US import ban, examining personal testimonial, news/information, and direct marketing/retail tweets separately. We also examined how the tweets discussed health and policy. A total of 10,454 public English tweets (posted from June 2020 to December 2021) were collected using HTP-related keywords. We randomly sampled 2796 (26.7%) tweets and conducted a content analysis. We used pairwise co-occurrence analyses to evaluate connections across themes. ResultsTweet volumes peaked around IQOS-related policy events. Among all tweets, personal testimonials were the most common (1613/2796, 57.7%), followed by news/information (862/2796, 30.8%) and direct marketing/retail (321/2796, 11%). Among personal testimonials, more tweets were positive (495/1613, 30.7%) than negative (372/1613, 23.1%), often comparing the health risks of HTPs with cigarettes (402/1613, 24.9%) or vaping products (252/1613, 15.6%). Approximately 10% (31/321) of the direct marketing/retail tweets promoted international delivery, suggesting cross-border promotion. More than a quarter of tweets (809/2796, 28.9%) discussed US and global policy, including misinterpretation about IQOS being a “safer” tobacco product after the US FDA’s MRTP authorization. Neutral testimonials mentioning the IQOS brand (634/1613, 39.3%) and discussing policy (378/1613, 23.4%) showed the largest pairwise co-occurrence. ConclusionsResults suggest the need for careful communication about the meaning of MRTP authorizations and relative risks of tobacco products. Many tweets expressed HTP-favorable opinions referring to reduced health risks, even though the US FDA has denied marketing of the HTP with reduced risk claims. The popularity of social media as an information source with global reach poses unique challenges in health communication and health policies. While many countries restrict tobacco marketing via the web, our results suggest that retailers may circumvent such regulations by operating overseas.

Aim: Late-onset Pompe disease is characterized by progressive loss of muscular and respiratory function. Until recently, standard of care was enzyme replacement therapy (ERT) with alglucosidase alfa. Secondgeneration ERTs avalglucosidase alfa (aval) and cipaglucosidase alfa with miglustat (cipa+mig) are now available. Without head-to-head trials comparing aval with cipa+mig, an indirect treatment comparison is informative and timely for understanding potential clinical differentiation. Materials & methods: A systematic literature review was performed to identify relevant studies on cipa+mig and aval. Using patient-level and aggregate published data from randomized controlled trials (RCTs) and phase I/II and open-label extension (OLE) trials, a multi-level network meta-regression was conducted, adjusting for various baseline covariates, including previous ERT duration, to obtain relative effect estimates on 6- minute walk distance (6MWD, meters [m]) and forced vital capacity (FVC, % predicted [pp]). Analyses of two networks were conducted: Network A, including only RCTs, and network B, additionally including single-arm OLE and phase I/II studies. Results: Network B (full evidence analysis) showed that cipa+mig was associated with a relative increase in 6MWD (mean difference 28.93 m, 95% credible interval [8.26– 50.11 m]; Bayesian probability 99.7%) and FVC (2.88 pp [1.07–4.71 pp]; >99.9%) compared with aval. The comparison between cipa+mig and aval became more favorable for cipa+mig with increasing previous ERT duration for both end points. Analysis of network A showed that cipa+mig was associated with a relative decrease in 6MWD(-10.02m[-23.62 to 4.00 m]; 91.8%) and FVC (-1.45 pp [-3.01 to 0.07 pp]; 96.8%) compared with aval. Conclusion: Cipa+mig showed a favorable effect versus aval when all available evidence was used in the analysis.

Abstract The purpose of this study was to determine the effect of hydration status on the change in sweat sodium (Na+), chloride (Cl−), and potassium (K+) concentrations during exercise‐heat stress. Fifteen subjects (Six female, nine male; 29 ± 9 y; 71 ± 14 kg) completed 90 min of cycling (81% HRmax) in the heat (~33°C, 42% rh) with fluid replacement to maintain euhydration (EUH) or without fluid to dehydrate to 2.4 ± 0.4% body mass loss (DEH). Sweat was collected from the forehead (FH), right scapula (SCAP), and left (LVFA) and right (RVFA) ventral forearms using the absorbent pad technique at the beginning (0–30 min) and end of exercise (60–90 min). Sweat was analyzed for Na+, Cl−, and K+ concentrations using ion chromatography. Data are reported as mean ± SD or median ± IQR. There were no differences (Paired t‐tests or Wilcoxon signed‐rank tests) between EUH and DEH in the change in sweat Na+ (FH: 24.3 ± 21.5 vs. 30.8 ± 22.4 mmol/L; SCAP: 9.7 ± 6.2 vs. 9.6 ± 8.2 mmol/L; LVFA: 7.5 ± 6.0 vs. 5.6 ± 5.9 mmol/L; RVFA: 8.2 ± 8.6 vs. 7.8 ± 5.2 mmol/L), sweat Cl−, or sweat K+ at any site (p = 0.07–0.99). The change in sweat electrolyte concentrations during 90 min of exercise in the heat was not significantly influenced by mild dehydration in recreational to moderately‐trained male and female athletes.

Background Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device‐detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device‐detected AF but with no ECG‐documented AF is unclear. Methods and Results This prespecified analysis of the NOAH‐AFNET 6 (Non‐Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device‐detected AF with and without a prior stroke or TIA in the randomized, double‐blind, double‐dummy NOAH‐AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device‐detected AF randomized in the NOAH‐AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time‐to‐event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient‐year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient‐year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient‐year]; no anticoagulation: 6 out of 131 [2.3% per patient‐year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). Conclusions Anticoagulation appears to have ambiguous effects in patients with device‐detected AF and a prior stroke or TIA in this hypothesis‐generating analysis of the NOAH‐AFNET 6 in the absence of ECG‐documented AF, partially due to a low rate of stroke without anticoagulation.

Abstract Due to growing interest in the investigation of exercise induced sweat biomarkers to assess an individual’s health and the increasing prevalence of tattoos in the world’s population, investigators sought to determine whether local sweat concentrations and excretion rates of epidermal growth factor (EGF), interleukin (IL) -1α, IL-6, IL-8, cortisol, glucose, blood urea nitrogen (BUN), and lactate differ between tattooed and contralateral non-tattooed skin during exercise. Sixteen recreational exercisers [female (50%)] (age = 25–48 years) with ≥ 1 unilateral permanent tattoo [median tattoo age = 6 years, IQR = 5] on the arm/torso completed an outdoor group fitness session. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate concentrations. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate excretion rate. Findings suggest that permanent tattoos older than 1 year may not impact local sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, and lactate concentrations or excretion rates during exercise. Clinical trial identifier NCT04920266 was registered on June 9, 2021.

Abstract Pulmonary embolism is a potentially fatal condition with increased mortality if anticoagulation is delayed. This study aimed to find influencing factors on the duration from requesting a computed tomography (CT) pulmonary angiography (CTPA) to performing a CTPA in suspected acute pulmonary embolism. In 1849 cases, automatically generated time data were extracted from the radiological information system. The impact of the distance to the scanner, case-related features (sector of patient care, triage), and workload (demand for CTs, performed CTs, available staff, hospital occupancy) were investigated retrospectively using multiple regression. The time to CTPA was shorter in cases from the emergency room (ER) than in inpatients and outpatients at distances below 160 m and 240 m, respectively. While requests from the ER were also performed faster than cases from regular wards (

Graphene is one of the most extensively studied 2D materials, exhibiting extraordinary mechanical and electronic properties. Although many years have passed since its discovery, manipulating single graphene layers is still challenging using standard resist-based lithography techniques. Recently, it has been shown that it is possible to etch graphene directly in water-assisted processes using the so-called focused electron-beam-induced etching (FEBIE), with a spatial resolution of ten nanometers. Nanopatterning graphene with such a method in one single step and without using a physical mask or resist is a very appealing approach. During the process, on top of graphene nanopatterning, we have found significant morphological changes induced in the SiO2 substrate even at low electron dose values (

The present work discusses the classification of distribution of values of impulses. We solve the problem in which random impulses occur before the vibrations caused by previous random impulses expire. The goal was to achieve a correct classification of three groups of distributions characteristic of three different processes: correct, transitory and flawed. The starting moment of the analysis as well as the length of time interval are the objects of study of this article. In order to determine the significance of the extracted features of the random time series under study, SHapley Additive exPlanations method was applied. The paper discussed the stage of study which is focused on finding the first three stochastic raw moments that allow for the most precise classification of distributions characterizing different processes in the shortest time. The analysis using the random forest classifier made it possible to distinguish the distributions characteristic for different types of processes, that is, it is possible to distinguish correct processes and transitory ones, etc. It is hardest to distinguish correct processes from one another, since they are highly similar to one another, but different from the other types.

Trillions of microbes comprise the human oral cavity, collectively acting as another bodily organ. Although research is several decades into the field, there is no consensus on how oral microbiomes differ in underrepresented groups such as Hispanic, Black, and Asian populations living in the United States. Here, using 16S ribosomal RNA sequencing, we examine the bacterial ecology of supragingival plaque from four quadrants of the mouth along with a tongue swab from 26 healthy volunteers from South Florida (131 total sequences after filtering). As an area known to be a unique amalgamation of diverse cultures from across the globe, South Florida allows us to address the question of how supragingival plaque microbes differ across ethnic groups, thus potentially impacting treatment regiments related to oral issues. We assess overall phylogenetic abundance, alpha and beta diversity, and linear discriminate analysis of participants based on sex, ethnicity, sampling location in the mouth, and gingival health. Within this cohort, we find the presence of common phyla such as Firmicutes and common genera such as Streptococcus. Additionally, we find significant differences across sampling locations, sex, and gingival health. This research stresses the need for the continued incorporation of diverse populations within human oral microbiome studies.

The COVID-19 pandemic suspended established practices that, in normal times, are seen as central to the functioning of education systems. For example, in England, school closures led to the cancellation of national examinations in 2020, and their attempted replacement with an algorithmic model. Following public outcry about what were seen as the unjust effects of the application of that model, there was a very public policy reversal, and examination grades were awarded on the basis of moderated teacher assessments or Centre Assessed Grades, resulting in substantial grade inflation. This paper draws on research that investigated the actors involved in examinations policy in this period and focuses especially on the sources of expertise and the kinds of knowledge that were mobilised--or not--in the decision to cancel examinations, to develop the algorithm and to revert to Centre Assessed Grades.

The upper respiratory tract, including the nasopharynx, is inhabited by many microbial species. Still, the nasopharyngeal microbiota (or microbiome) of pregnant women is not well understood and may be influenced by a number of factors, including place of residence. Many changes occur during pregnancy, and their association with the respiratory microbiota is important for the health of the mother and for the developing fetus. The aim of this study was to compare the colonisation of the nasopharyngeal cavity by culturable aerobic bacteria in the microbiota of women with a physiological pregnancy course according to rural or urban place of residence. Nasopharyngeal swabs were collected from 37 pregnant women (17 from rural and 20 from urban areas) to detect the colonisation of aerobically growing culturable bacteria. Isolates were identified using microbiological culture methods and the MALDI-TOF MS technique. Bacteria were colonisers of the nasopharynx cavity in all cases tested. Accordingly, 97.3% (36/37) of the pregnant women were colonised by Gram-positive bacteria, mainly coagulase-negative (CoNS) and -positive (CoPS) Staphylococcus spp. and Corynebacterium spp. in both the rural and urban groups. Gram-negative Klebsiella variicola, Proteus mirabilis and Pseudomonas congelans colonised only 17.6% (3/17) of rural women and Stenotrophomonas maltophilia only 5.0% (1/20) of the urban women. To summarise, all pregnant women were colonised with bacteria in the nasopharyngeal cavity. The majority from both rural and urban residences were colonised with Gram-positive bacteria only. Gram-negative bacteria were isolated mainly from samples in the rural group.

Abstract Background Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. Methods To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants’ attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled. Discussion Until today, no study has explored the interplay of pharmacological effects and patients’ expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively. Trial registration ClinicalTrials.gov (NCT05191277), January 13, 2022.

ObjectivesOpposed to other spectral CT techniques, fat quantification in dual-layer detector CT (dlCT) has only recently been developed. The impact of concomitant iron overload and dlCT-specific protocol settings such as the dose right index (DRI), a measure of image noise and tube current, on dlCT fat quantification was unclear. Further, spectral information became newly available Material and methodsPhantoms with 0 and 8mg/cm3 iron; 0 and 5mg/cm3 iodine; 0, 10, 20, 35, 50, and 100% fat and liver equivalent, respectively, were scanned with a dlCT (CT7500, Philips, the Netherlands) at 100kV/20DRI, 120kV/20DRI, 140kV/20DRI, and at 120kV/16DRI, 120kV/24DRI. Material decomposition was done for fat, liver, and iodine (A1); for fat, liver, and iron (A2); and for fat, liver, and combined reference values of iodine and iron (A3). All scans were analyzed with reference values from 120kV/20DRI. For statistics, the intraclass correlation coefficient (ICC) and Bland-Altman analyses were used.ResultsIn phantoms with iron and iodine, results were best for A3 with a mean deviation to phantom fat of 1.3±2.6% (ICC 0.999 [95%-confidence interval 0.996-1]). The standard approach A1 yielded a deviation of -2.5±3.0% (0.998[0.994-0.999]), A2 of 6.1±4.8% (0.991[0.974-0.997]). With A3 and changing tube voltage, the maximal difference between quantified fat and the phantom ground truth occurred at 100kV with 4.6±2.1%. Differences between scans were largest between 100kV and 140kV (2.0%[-7.1-11.2]). The maximal difference of changing DRI occurred between 16 and 24 DRI with 0.4%[-2.2-3.0].ConclusionFor dlCT fat quantification in the presence of iron, material decomposition with combined reference values for iodine and iron delivers the most accurate results. Tube voltage-specific calibration of reference values is advisable while the impact of the DRI on dlCT fat quantification is neglectable.

Background & Aims: Cirrhosis is associated with an increased surgical morbidity and mortality. Portal hypertension and the surgery type have been established as critical determinants of postoperative outcome. We aim to evaluate the hypothesis that preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with cirrhosis is associated with a lower incidence of in-house mortality/liver transplantation (LT) after surgery. Methods: A retrospective database search for the years 2010–2020 was carried out. We identified 64 patients with cirrhosis who underwent surgery within 3 months after TIPS placement and 131 patients with cirrhosis who underwent surgery without it (controls). Operations were categorised into low-risk and high-risk procedures. The primary endpoint was in-house mortality/LT. We analysed the influence of high-risk surgery, preoperative TIPS placement, age, sex, baseline creatinine, presence of ascites, Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD), American Society of Anesthesiologists (ASA), and model for end-stage liver disease (MELD) scores on in-house mortality/LT by multivariable Cox proportional hazards regression. Results: In both the TIPS and the control cohort, most patients presented with a Child-Pugh B stage (37/64, 58% vs. 70/131, 53%) at the time of surgery, but the median MELD score was higher in the TIPS cohort (14 vs. 11 points). Low-risk and high-risk procedures amounted to 47% and 53% in both cohorts. The incidence of in-house mortality/LT was lower in the TIPS cohort (12/64, 19% vs. 52/131, 40%), also when further subdivided into low-risk (0/30, 0% vs. 10/61, 16%) and high-risk surgery (12/34, 35% vs. 42/70, 60%). Preoperative TIPS placement was associated with a lower rate for postoperative in-house mortality/LT (hazard ratio 0.44, 95% CI 0.19–1.00) on multivariable analysis. Conclusions: A preoperative TIPS might be associated with reduced postoperative in-house mortality in selected patients with cirrhosis. Impact and implications: Patients with cirrhosis are at risk for more complications and a higher mortality after surgical procedures. A transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of cirrhosis, but it is unclear if it also helps to lower the risk of surgery. This study takes a look at complications and mortality of patients undergoing surgery with or without a TIPS, and we found that patients with a TIPS develop less complications and have an improved survival. Therefore, a preoperative TIPS should be considered in selected patients, especially if indicated by ascites.

Are there differences in divergent thinking and personality traits between students who attend art-based high schools and non-art-based high schools? The main goal of this exploratory study was to focus on this question and to explore the factors that might differentiate a sample of art and non-art high school students. We addressed these questions by exploring a convenience sample (N = 167) of students from art schools (N = 79) and students from non-art high schools (N = 88). We used three divergent-thinking measures (i.e., Sketches Test, Brick Uses Test, and Consequences Test) and the five-factor personality inventory (NEO-FFI) to explore potential differences. The results showed that the type of school was positively associated with fluency, flexibly, and originality and negatively with openness. We also explored differences using discriminant analysis. It was found that students who attended art high schools have a lower level of originality and a high level of flexibility and openness compared to students attending regular high schools. Our findings may indicate that these factors can help to understand the differences between art and non-art high school students.

Abstract Background In many clinical trials the study interest lies in the comparison of a treatment to a control group regarding a time to event endpoint like time to myocardial infarction, time to relapse, or time to a specific cause of death. Thereby, an event can occur before the primary event of interest that alters the risk for or prohibits observing the latter, i.e. a competing event. Furthermore, multi-center studies are often conducted. Hence, a cluster structure might be observed. However, commonly only the aspect of competing events or the aspect of the cluster structure is modelled within primary analysis, although both are given within the study design. Methods to adequately analyze data in such a design were recently described but were not systematically compared yet. Methods Within this work we provide a systematic comparison of four approaches for the analysis of competing events where a cluster structure is present based on a real life data set and a simulation study. The considered methods are the commonly applied cause-specific Cox proportional hazards model with a frailty, the Fine and Gray model for considering competing risks, and extensions of the latter model by Katsahian et al. and Zhou et al. Results Based on our simulation results, the model by Katsahian et al. showed the best performance in bias, square root of mean squared error, and power in nearly all scenarios. In contrast to the other three models this approach allows both unbiased effect estimation and prognosis. Conclusion The provided comparison and simulations help to guide applied researchers to choose an adequate method for the analysis of competing events where a cluster structure is present. Based on our simulation results the approach by Katsahian et al. can be recommended.

The study's main goal was to investigate the impact of various types of shocking content of provocative advertisements on brand recall and visual attention engagement. The experiment used the eye-tracker (iViewX RED500) to record the eye movements. Forty-one participants were divided into two groups. Provocative (drastic, religious, and erotic) advertisements were presented experimental group while the control group was shown modified illustrations without provocative content. The study revealed that the average fixation time and fixation counts on erotic element were significantly higher in provocative advertisements than in their non-provocative equivalents. Average fixations time on the brand was significantly greater in non-provocative advertisements than in erotic versions of these ads. It was found that the shocking element and brand were better remembered in provocative advertisements containing religious content than in their non-provocative equivalents. In contrast, these elements were less remembered in advertisements containing drastic content than in their non-provocative equivalents.

Abstract Background Career prospects in academic medicine are strongly linked to scientific authorship and this marker has been widely used as an indicator of gender equity in academia. However, direct comparisons of medical disciplines regarding their proportion of female physicians (FP) in different countries are missing. This study examines the gender parity and gender cooperation using first authorships (FA) and senior authorships (SA) of scientific publications in five medical disciplines and six different OECD countries over a 10-year time-trend. Methods Articles from three high-impact journals in each of the medical discipline radiology, urology, surgery, gynecology, and pediatrics from the years 2007/8 and 2017/18 were retrospectively reviewed. The gender and affiliation location of the FA and SA of original research articles and reviews were assigned and compared with the proportion of in each discipline for the United States of America, Canada, United Kingdom, France, Germany, and Japan. Mantel-Haenszel test and multinomial logistic regression models were used to calculate differences in proportions of women authors and FP and to assess trends and proportions of FA and SA. Results 30,803 articles were evaluated. Equally, with rising proportions of FP in all disciplines, the number of women authors increased across years. The shares of women FAs were either significantly higher (urology/surgery/gynecology) or balanced (pediatrics/radiology) compared to the proportion of FP. In contrast, the shares of women SA were balanced only in disciplines with a low proportion of FP (urology and surgery) and otherwise reduced. Women same-gender cooperation was as common as men same-gender cooperation and preferred over a women-led mixed gender cooperation in disciplines where this seemed to be practicable due to the high proportions of FP. Conclusion In contrast to FA, a significant disparity persists in SA, particularly in disciplines with a high proportion of FP. The discrepancy between FA and SA may reflect, among others, dropout from an academic career in early or mid-academic levels, for example, due to structural inequality; together with the findings on gender preference in authorship collaborations, this may inform future strategies for promoting equal career advancement for women physicians.

This study assessed the validity and reliability of the Pandemic Coping Scale (PCS), a new brief measure of coping with pandemic-related stressors.Methods The PCS was administered to N = 2316 German participants during the COVID-19 pandemic. Exploratory and confirmatory factor analysis was applied among random splits of the sample. Global goodness of fit (χ2, RMSEA, SRMR, CFI, TLI), local goodness of fit (factor loadings, communalities, factor reliability, discriminant validity) and additional test quality criteria (internal consistency, item discrimination and difficulty) were evaluated for a four-factor model vs. a four-factor model combined with a second-order general factor. Convergent and divergent validity were examined by Pearson correlations of the PCS subscales with the Brief-COPE subscales; criterion validity was evaluated by correlations with wellbeing (WHO-5), depressive (PHQ-9) and anxiety symptoms (GAD-2).Results Exploratory factor analysis suggested a four-factor solution (‘Healthy Lifestyle’, ‘Joyful Activities’, ‘Daily Structure’, ‘Prevention Adherence’). Confirmatory factor analysis showed a sufficient global fit for both specified models which did not differ in their fit to the data. Local goodness of fit indices showed moderate to large factor loadings and good factor reliabilities except for the subscale ‘Prevention Adherence’. Internal consistencies were good for the PCS total scale (α = .83), the ‘Healthy Lifestyle’ (α = .79) and the ‘Daily Structure’ (α = .86) subscales, acceptable for ‘Joyful Activities’ (α = .60), and low for ‘Prevention Adherence’ (α = .52). The four subscales evidenced convergent and divergent validity with the Brief-COPE subscales. The subscales ‘Healthy lifestyle’, ‘Joyful activities’ and ‘Daily structure’ showed criterion validity with wellbeing, depressive and anxiety symptoms.Conclusions The PCS is a reliable and valid measure to assess pandemic-specific coping behavior in the domains of ‘Healthy Lifestyle’, ‘Joyful Activities’, and ‘Daily Structure’. The PCS subscale ‘Prevention Adherence’ might be improved by adding items with varying item difficulties.

Abstract Background: The hospital ethical climate affects the quality of nursing care. A positive ethical climate is likely to reduce the proportion of those who consider leaving the profession, so it is necessary to develop tools which will enable assessment and analysis of the hospital ethical climate. The aim of this study was to examine selected psychometric properties of the Polish version of the Hospital Ethical Climate Survey, assess the hospital ethical climate perceived by nurses and midwives from Polish hospitals, and to determine its correlations with job-related variables. Methods: A cross-sectional study among 558 nurses and midwives working in hospitals in Poland. Results: The 21-item model showed acceptable model fitness between the hypothetical model of ethical climate and the data in the study. Five items with low factor loadings were removed from the study. The internal consistency was satisfactory (0.93). The mean score for the overall hospital ethical climate was 3.62. The highest mean score of hospital ethical climate in the present study was found in the ”peers” subscale and the lowest in the ”physicians” subscale. A positive correlation was found between overall hospital ethical climate and respondents’ satisfaction with work, salary, and working time. The hospital ethical climate was associated with problems found in nurses and midwives’ work, such as: limited time for direct face-to-face care, the lack of equipment and resources to provide high-quality health care, strained relations with hospital managers and other health care professionals, limitations to one’s own competences or those of other medical professionals, moral dilemmas related to patient care, the low prestige of nurses’/midwives‘ work, physical and mental burden, and the risk of making a mistake. Conclusion: The Polish 21-item version of the Hospital Ethical Climate Survey is a reliable tool. Correlations revealed that relationships with managers and physicians, and working conditions should be improved in order for the hospital ethical climate to improve.

Abstract Background The rational use of antibiotics is of great importance in health care. In primary care, acute respiratory infections are the most common cause of inappropriate antibiotic prescribing. Since existing studies aiming to optimize antibiotic use are usually based on the voluntary participation of physicians, general practitioners (GPs) with inappropriate prescribing behavior are underrepresented. For the first time in Germany, the ElektRA study will assess and compare the effects of three interventions on antibiotic prescribing rates for respiratory and urinary tract infections among high prescribers in primary care. Method ElektRA is a 4-arm cluster-randomized controlled trial among German GPs in nine regional Associations of Statutory Health Insurance Physicians. On their behalf, the Central Research Institute of Ambulatory Health Care in Germany (Zi) analyses all outpatient claims and prescription data. Based on this database, high antibiotic prescribing GPs are identified and randomized into four groups: a control group (N=2000) and three intervention arms. We test social norm feedback on antibiotic prescribing (N=2000), social norm feedback plus online training on rational prescribing practice and communication strategies (N=2000), and social norm feedback plus online peer-moderated training on rational antibiotic prescribing, communication strategies, and sustainable behavior change (N=1250). The primary outcome is the overall rate of antibiotic prescriptions. Outcomes are measured before intervention (T0, October 2020–September 2022) and over a period of 15 months (T1, October 2022 to December 2023) after randomization. Discussion The aim of the study is to implement individualized, low-threshold interventions to reduce antibiotic prescribing among high prescribers in primary care. If successful, a change in behavior among otherwise difficult-to-reach high prescribers will directly improve patient care. The increase in quality of care will ideally be achieved both in terms of the quantity of antibiotics used as well as the kind of substances prescribed. Also, if effective strategies for high prescribers are identified through this study, they can be applied not only to the antibiotics addressed in this study, but also to other areas of prescription management. Trial registration Current Controlled Trials ISRCTN95468513.