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Background Acute type B aortic dissection is a cardiovascular emergency with considerable mortality and morbidity risk. Male–female differences have been observed in cardiovascular disease; however, literature on type B aortic dissection is scarce. Methods and Results A retrospective cohort study was conducted including all consecutive patients with acute type B aortic dissection between 2007 and 2017 in 4 tertiary hospitals using patient files and questionnaires for late morbidity. In total, 384 patients were included with a follow‐up of 6.1 (range, 0.02–14.8) years, of which 41% (n=156) were female. Women presented at an older age than men (67 [interquartile range (IQR), 57–73] versus 62 [IQR, 52–71]; P=0.015). Prior abdominal aortic aneurysm (6% versus 15%; P=0.009), distally extending dissections (71 versus 85%; P=0.001), and clinical malperfusion (18% versus 32%; P=0.002) were less frequently observed in women. Absolute maximal descending aortic diameters were smaller in women (36 [IQR: 33–40] mm versus 39 [IQR, 36–43] mm; P

Abstract The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are associated with QT prolongation, which increases the risk of serious arrhythmia. Consequently, regulatory agencies issued safety warnings in 2011. This study aimed to investigate the risk of serious arrhythmia following initiation of citalopram or escitalopram compared to other SSRIs and the risk in the periods before and after the warnings were issued. We conducted a series of nationwide cohort studies emulating a target trial using Danish healthcare register data from January 1, 2002, to December 31, 2016. We included patients (aged ≥65 years) who filled an SSRI prescription with a 1‐year washout period before the index date. The outcome was an event of serious arrhythmia. Individuals were followed for a maximum of 6 months using an intention‐to‐treat approach. Log‐binomial regression analyses were performed, estimating risk ratios (RRs) and 95% confidence intervals (CIs) adjusting for age and sex, comorbidities, and comedications with propensity scores. Dose–response effects were not investigated because dosage instructions were not available. We included 167,366 (146,014 individuals), 40,113 (37,069 individuals), and 50,281 (44,754 individuals) person‐trials of citalopram, escitalopram, and other SSRIs, respectively. In total, there were 228 events of serious arrhythmia. No difference in risk was observed in the entire study period for either citalopram (0.87 [0.62–1.22]) or escitalopram (0.85 [0.53–1.40]). We identified lower point estimates after the safety warning, RR 0.54 (95% CI 0.31–0.93) for citalopram and 0.58 (0.20–1.63) for escitalopram. Initiation of citalopram and escitalopram was not associated with an increased risk of serious arrhythmia. However, lower point estimates were observed after the safety warning.

Abstract Background Limited real‐world studies are available comparing infection risk between biologics for psoriasis. Objectives The primary aim was to determine the differential effect of currently available biologics on the risk of respiratory tract infections (RTI) among psoriasis patients in a real‐world setting. Secondary aims were to explore the differential risk of all types of serious infections (SI) between biologics and to provide an early overview of SARS‐CoV‐2 infections during the pre‐vaccine era. Methods Crude incidence rates of RTI and SI were calculated per 100 patient‐years (PY) per biologic using prospective BioCAPTURE data. Negative Binomial Regression modeling was used to explore the risk of RTI. Frailty Cox proportional hazards modeling was used to estimate hazard ratios for the risk of the first SI. Confounders adjusted for both models were selected by a directed acyclic graph. A post hoc exploratory analysis of SARS‐CoV‐2 infection incidence rates during 2020 was performed. Results We included 714 patients with 1325 treatment episodes (3607.7PY between 2005 and 2020), in which 2224 RTI and 63 SI occurred. Among RTI, 1.3% were serious. The crude incidence rates were 61.7 (95% confidence interval [CI]: 59.1–64.3) per 100PY for RTI, and 1.8 (95% CI: 1.4–2.2) per 100PY for SI. Confounder adjusted analyses showed no differential risk of RTI between adalimumab, etanercept, infliximab, ustekinumab, secukinumab, ixekizumab and guselkumab. For SI, no differential risk was found between biologics either. Extended single‐center data showed 3.8 (95% CI: 2.2–6.1) SARS‐CoV‐2 infections per 100PY in 2020. Conclusions Confounder adjusted analyses showed no differential risks of RTI or SI between included biologics (adalimumab, etanercept, infliximab, ustekinumab, secukinumab, ixekizumab and guselkumab) in a prospective psoriasis patients cohort. In general, absolute numbers of all types of SI were low.

Abstract Background Countries are adapting their health and social care systems to better meet the needs of growing populations with (multiple) chronic conditions. To guide this process, assessment of the ‘patient experience’ is becoming increasingly important. For this purpose, the Person‐Centred Coordinated Care Experience Questionnaire (P3CEQ) was developed in the United Kingdom, and translated into several languages. Aim This study aimed to assess the internal and construct validity of the Dutch P3CEQ to capture the experience of person‐centred coordinated care of people with chronic conditions in the Netherlands. Participants and Methods Adults with chronic conditions (N = 1098) completed the Dutch P3CEQ, measures of health literacy and patient activation, and reported the use and perceived quality of care services. Data analysis included Principal Component and reliability analysis (internal validity), analysis of variance and Student's T‐tests (construct validity). Results The two‐component structure found was pretty much the same as in the UK validation study. Sociodemographic correlates also resembled those found in the United Kingdom. Women, persons who were less educated, less health‐literate or less activated experienced less person‐centred coordinated care. P3CEQ scores correlated positively with general practitioner performance scores and quality ratings of the total care received. Conclusion The Dutch P3CEQ is a valid instrument to assess the experience of person‐centred coordinated care among people with chronic conditions in the Netherlands. Awareness of inequity and more attention to communication skills in professional training are needed to ensure that care professionals better recognize the needs of women, lower educated or less health‐literate persons, and improve their experiences of care. Patient Contribution The P3CEQ has been developed in collaboration with a range of stakeholders. Eighteen persons with (multiple) chronic conditions participated as patient representatives and codesign experts in (four) codesign workshops. Other patient representatives participated in cognitive testing of the English‐language instrument. The usability of the P3CEQ to capture the experience of person‐centred coordinated care of older persons has been examined by interviewing 228 older European service users, including 13 living in the Netherlands, as part of the SUSTAIN project. More than a thousand persons with chronic conditions participated in the validation study of the Dutch P3CEQ.

Abstract Permafrost regions are experiencing increasing air temperatures, accelerating the thawing process, and thickening the active layer in summer. This can accelerate the release of greenhouse gasses into the atmosphere from the organic carbon stored in the permafrost. The long‐term thawing rates of permafrost below the active layer are governed by the soil thermal properties, the heat capacity, and thermal conductivity, which vary due to differences in grain sizes and distribution and organic matter content. Using nine column experiments comprised of fully saturated synthetic permafrost samples exposed to freeze–thaw cycles, the relative contributions of a range of soil grain sizes and organic matter contents on the soil thermal properties were investigated. The columns were subjected to a freeze and thaw cycle while soil temperatures were recorded in profiles. To infer the thermal properties from these experimental data, a numerical heat transfer model was used. The best fit between the observations and a batch of 5544 numerical models was used to find optimum values for permafrost thermal properties. The optimized heat capacity varied between 500 and 650 (J/m3 K) and thermal conductivity between 2.45 and 3.55 (W/m K). These optimized parameters were subsequently used to model a 100‐year permafrost active layer thaw scenario under warming air temperatures. Variations in the optimized thermal properties resulted in a time difference in thawing depth of 10–15 years and thawing depths varied between 9 and 10 m between the different optimized thermal properties at the end of the 100‐year scenario.

Objectives The aim of this study was to establish the prognostic value of the epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on local control in patients with early stage supraglottic laryngeal squamous cell carcinoma (LSCC) treated with radiotherapy only. Study design Retrospective cohort study. Methods Immunohistochemical staining for EGFR and PTEN was performed on pretreatment biopsies of a selected well‐defined homogeneous group of 52 patients with T1–T2 supraglottic LSCC treated with radiotherapy between 1990 and 2008. Kaplan–Meier analysis and univariate and multivariate Cox Regression analyses were performed to correlate clinical data and expression levels of EGFR and PTEN with local control. Results Kaplan–Meier survival analysis and Cox Regression analysis showed a significant association between PTEN expression and local control (hazard ratio [HR] = 3.26, 95% confidence interval [CI] = 1.14–9.33, P = .027) and between lymph node status and local control (HR = 3.60, 95% CI = 1.26–10.31, P = .017). Both were independent prognostic factors in a multivariate analysis (HR = 3.28, 95% CI = 1.14–9.39, P = .027 and HR = 3.62, 95% CI = 1.26–10.37, P = .017, respectively). There was no significant association between EGFR expression and local control (HR = 1.32, 95% CI = 1.17–10.14, P = .79). Conclusion This study showed an association between both high PTEN expression and the presence of lymph node metastasis and deteriorated local control in early stage supraglottic LSCC treated with radiotherapy. Level of Evidence NA

Major efforts are made to characterize the presence of microRNA (miRNA) and messenger RNA in blood plasma to discover novel disease-associated biomarkers. MiRNAs in plasma are associated to several types of macromolecular structures, including extracellular vesicles (EV), lipoprotein particles (LPP) and ribonucleoprotein particles (RNP). RNAs in these complexes are recovered at variable efficiency by commonly used EV- and RNA isolation methods, which causes biases and inconsistencies in miRNA quantitation. Besides miRNAs, various other non-coding RNA species are contained in EV and present within the pool of plasma extracellular RNA. Members of the Y-RNA family have been detected in EV from various cell types and are among the most abundant non-coding RNA types in plasma. We previously showed that shuttling of full-length Y-RNA into EV released by immune cells is modulated by microbial stimulation. This indicated that Y-RNAs could contribute to the functional properties of EV in immune cell communication and that EV-associated Y-RNAs could have biomarker potential in immune-related diseases. Here, we investigated which macromolecular structures in plasma contain full length Y-RNA and whether the levels of three Y-RNA subtypes in plasma (Y1, Y3 and Y4) change during systemic inflammation. Our data indicate that the majority of full length Y-RNA in plasma is stably associated to EV. Moreover, we discovered that EV from different blood-related cell types contain cell-type-specific Y-RNA subtype ratios. Using a human model for systemic inflammation, we show that the neutrophil-specific Y4/Y3 ratios and PBMC-specific Y3/Y1 ratios were significantly altered after induction of inflammation. The plasma Y-RNA ratios strongly correlated with the number and type of immune cells during systemic inflammation. Cell-type-specific “Y-RNA signatures” in plasma EV can be determined without prior enrichment for EV, and may be further explored as simple and fast test for diagnosis of inflammatory responses or other immune-related diseases.