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The present study evaluated the impact of Urban Improv (UI), a theater-based youth violence prevention (YVP) program developed for inner-city youth, on three behavioral and psychological outcome domains: aggressive behaviors, prosocial behaviors, and scholastic attention and engagement. This study compared outcomes for 77 elementary school students in classrooms designated to receive UI with those of 63 students from matched control classrooms. Findings revealed that students who received UI were superior to matched controls on all outcome domains. Findings support UI as a promising practice for YVP with urban elementary school students and suggest that greater attention should be focused on application of theater-based programs in YVP. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the five-year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR-screening programme., Methods: Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013-2018. According to the worse eye at first screening, DR was classified (levels 0-4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication., Results: At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five-year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63-1.89, and HR 2.04, 95% CI 1.73-2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10-1.47, and HR 2.80, 95% CI 2.23-3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05-1.36, and HR 1.98, 95% CI 1.53-2.57)., Conclusion: In a study of all patients with type 1 diabetes from the Danish DR-screening programme, we identified duration of diabetes, systemic disease and use of anti-hypertensive treatment as consistent risk markers for incident and progressive DR., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Deep dermatophytosis is a rare condition in which dermatophytes invade deep into the skin. Predisposing factors include chronic superficial dermatophytosis, immunosuppression or the use of topical steroids. Clinical, mycological, and histological examination are crucial for accurate diagnosis. Microscopy and culture or molecular diagnostic are useful tools when identifying the causative dermatophyte species. Species-directed systemic antimycotic treatment is golden standard and require careful consideration of potential drug-drug interactions and monitoring for both efficacy and side effects, as argued in this review., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background The growth of biomedical literature presents challenges in extracting and structuring knowledge. Knowledge Graphs (KGs) offer a solution by representing relationships between biomedical entities. However, manual construction of KGs is labor-intensive and time-consuming, highlighting the need for automated methods. This work introduces BioKGrapher, a tool for automatic KG construction using large-scale publication data, with a focus on biomedical concepts related to specific medical conditions. BioKGrapher allows researchers to construct KGs from PubMed IDs. Methods The BioKGrapher pipeline begins with Named Entity Recognition and Linking (NER+NEL) to extract and normalize biomedical concepts from PubMed, mapping them to the Unified Medical Language System (UMLS). Extracted concepts are weighted and re-ranked using Kullback-Leibler divergence and local frequency balancing. These concepts are then integrated into hierarchical KGs, with relationships formed using terminologies like SNOMED CT and NCIt. Downstream applications include multi-label document classification using Adapter-infused Transformer models. Results BioKGrapher effectively aligns generated concepts with clinical practice guidelines from the German Guideline Program in Oncology (GGPO), achieving F 1 -Scores of up to 0.6. In multi-label classification, Adapter-infused models using a BioKGrapher cancer-specific KG improved micro F 1 -Scores by up to 0.89 percentage points over a non-specific KG and 2.16 points over base models across three BERT variants. The drug-disease extraction case study identified indications for Nivolumab and Rituximab. Conclusion BioKGrapher is a tool for automatic KG construction, aligning with the GGPO and enhancing downstream task performance. It offers a scalable solution for managing biomedical knowledge, with potential applications in literature recommendation, decision support, and drug repurposing., Competing Interests: The authors have no relevant interests to disclose., (© 2024 The Authors.)

Diabetic retinopathy (DR) is the most common complication in patients with diabetes, and screening for sight-threatening end-stages is indicated to avoid severe visual loss. Screening of DR is nationally implemented in Denmark according to evidence-based national guidelines, which includes the use of individualised screening intervals. Treatment is indicated for proliferative DR and diabetic macular oedema, and treatment modalities include retinal laser therapy, intravitreal angiostatic therapy, and vitrectomy. In this review, we summarise the current guidelines for screening and treatment of DR in Denmark., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Purpose: To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR-screening programme and non-diabetes adults., Methods: In this registry-based matched case-cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age- and sex-matched by five non-diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models., Results: Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20-1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08-1.30) as compared to non-diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72-0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR-levels 1-4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow-up (HR 1.23; 95% CI, 1.02-1.49)., Conclusion: In a nationwide matched case-cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objectives: Accurately acquiring and assigning different contrast-enhanced phases in computed tomography (CT) is relevant for clinicians and for artificial intelligence orchestration to select the most appropriate series for analysis. However, this information is commonly extracted from the CT metadata, which is often wrong. This study aimed at developing an automatic pipeline for classifying intravenous (IV) contrast phases and additionally for identifying contrast media in the gastrointestinal tract (GIT)., Materials and Methods: This retrospective study used 1200 CT scans collected at the investigating institution between January 4, 2016 and September 12, 2022, and 240 CT scans from multiple centers from The Cancer Imaging Archive for external validation. The open-source segmentation algorithm TotalSegmentator was used to identify regions of interest (pulmonary artery, aorta, stomach, portal/splenic vein, liver, portal vein/hepatic veins, inferior vena cava, duodenum, small bowel, colon, left/right kidney, urinary bladder), and machine learning classifiers were trained with 5-fold cross-validation to classify IV contrast phases (noncontrast, pulmonary arterial, arterial, venous, and urographic) and GIT contrast enhancement. The performance of the ensembles was evaluated using the receiver operating characteristic area under the curve (AUC) and 95% confidence intervals (CIs)., Results: For the IV phase classification task, the following AUC scores were obtained for the internal test set: 99.59% [95% CI, 99.58-99.63] for the noncontrast phase, 99.50% [95% CI, 99.49-99.52] for the pulmonary-arterial phase, 99.13% [95% CI, 99.10-99.15] for the arterial phase, 99.8% [95% CI, 99.79-99.81] for the venous phase, and 99.7% [95% CI, 99.68-99.7] for the urographic phase. For the external dataset, a mean AUC of 97.33% [95% CI, 97.27-97.35] and 97.38% [95% CI, 97.34-97.41] was achieved for all contrast phases for the first and second annotators, respectively. Contrast media in the GIT could be identified with an AUC of 99.90% [95% CI, 99.89-99.9] in the internal dataset, whereas in the external dataset, an AUC of 99.73% [95% CI, 99.71-99.73] and 99.31% [95% CI, 99.27-99.33] was achieved with the first and second annotator, respectively., Conclusions: The integration of open-source segmentation networks and classifiers effectively classified contrast phases and identified GIT contrast enhancement using anatomical landmarks., Competing Interests: Conflicts of interest and sources of funding: The Clinician Scientist Academy of the University Hospital Essen (UMEA), which is supported by the German Research Foundation (DFG) (FU 356/12-2), provided financial support to J.H., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to assess the influence of smoking on the subgingival metatranscriptomic profile of young patients affected by stage III/IV and generalized periodontal disease., Methodology: In total, six young patients, both smokers and non-smokers (n=3/group), who were affected by periodontitis were chosen. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for case-control reporting were followed. Periodontal clinical measurements and subgingival biofilm samples were collected. RNA was extracted from the biofilm and sequenced via Illumina HiSeq. Differential expression analysis used Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and differentially expressed genes were identified using the Sleuth package in R, with a statistical cutoff of ≤0.05., Results: This study found 3351 KEGGs in the subgingival biofilm of both groups. Smoking habits altered the functional behavior of subgingival biofilm, resulting in 304 differentially expressed KEGGs between groups. Moreover, seven pathways were modulated: glycan degradation, galactose metabolism, glycosaminoglycan degradation, oxidative phosphorylation, peptidoglycan biosynthesis, butanoate metabolism, and glycosphingolipid biosynthesis. Smoking also altered antibiotic resistance gene levels in subgingival biofilm by significantly overexpressing genes related to beta-lactamase, permeability, antibiotic efflux pumps, and antibiotic-resistant synthetases., Conclusion: Due to the limitations of a small sample size, our data suggest that smoking may influence the functional behavior of subgingival biofilm, modifying pathways that negatively impact the behavior of subgingival biofilm, which may lead to a more virulent community.

Automated medical image analysis systems often require large amounts of training data with high quality labels, which are difficult and time consuming to generate. This paper introduces Radiology Object in COntext version 2 (ROCOv2), a multimodal dataset consisting of radiological images and associated medical concepts and captions extracted from the PMC Open Access subset. It is an updated version of the ROCO dataset published in 2018, and adds 35,705 new images added to PMC since 2018. It further provides manually curated concepts for imaging modalities with additional anatomical and directional concepts for X-rays. The dataset consists of 79,789 images and has been used, with minor modifications, in the concept detection and caption prediction tasks of ImageCLEFmedical Caption 2023. The dataset is suitable for training image annotation models based on image-caption pairs, or for multi-label image classification using Unified Medical Language System (UMLS) concepts provided with each image. In addition, it can serve for pre-training of medical domain models, and evaluation of deep learning models for multi-task learning., (© 2024. The Author(s).)

Background: Periodontal disease is a biofilm-dependent chronic inflammatory condition triggered by a host response. Several factors impact systemic inflammation and could lead to changes in disease pathogenesis. Recently, studies have assessed the influence of nutritional patterns on the development of periodontitis. In the present cross-sectional study, we evaluated the dietary inflammatory profile on periodontal conditions, focusing on clinical, subgingival microbial, and cytokine assessment of individuals with periodontal health or gingivitis., Methods: One hundred patients with periodontal health or gingivitis were included. Plaque index (PI), Bleeding on probing (BoP), the probing depth (PD), and the clinical attachment level (CAL) for each patient were assessed. Nutritional data and the Dietary Inflammatory Index (DII) were recorded by two 24-h food recalls on non-consecutive days. Biofilm and gingival crevicular fluid (GCF) to assess the microbiome profile and inflammatory biomarkers were collected. Multiple regressions focused on the DII, age, and sex as predictors of periodontal conditions were done., Results: Age and moderate DII scores increased the risk of gingivitis by 1.64 and 3.94 times, respectively. Males with an elevated DII score had 27.15 times higher odds of being diagnosed with gingivitis and BoP (β = 6.54; p = 0.03). Elderly patients with a moderate or high DII score were less prone to gingivitis and increased BoP (p < 0.04) compared with younger subjects. Considering the DII, there were no differences in microbial alpha and beta diversity; however, distinct species abundance and a higher concentration of monocyte-chemoattractant protein-1 and interleukin 33 were seen in patients with a higher DII., Conclusion: A pro-inflammatory diet significantly contributes to periodontal inflammation, modulating inflammatory biomarkers and affecting the subgingival microbial community in healthy individuals., (© 2023 American Academy of Periodontology.)

Background: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model., Methods: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied., Results: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs., Conclusion: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden., (© 2024. The Author(s).)

Abstract: Platelet demand management (PDM) is a resource-consuming task for physicians and transfusion managers of large hospitals. Inpatient numbers and institutional standards play significant roles in PDM. However, reliance on these factors alone commonly results in platelet shortages. Using data from multiple sources, we developed, validated, tested, and implemented a patient-specific approach to support PDM that uses a deep learning-based risk score to forecast platelet transfusions for each hospitalized patient in the next 24 hours. The models were developed using retrospective electronic health record data of 34 809 patients treated between 2017 and 2022. Static and time-dependent features included demographics, diagnoses, procedures, blood counts, past transfusions, hematotoxic medications, and hospitalization duration. Using an expanding window approach, we created a training and live-prediction pipeline with a 30-day input and 24-hour forecast. Hyperparameter tuning determined the best validation area under the precision-recall curve (AUC-PR) score for long short-term memory deep learning models, which were then tested on independent data sets from the same hospital. The model tailored for hematology and oncology patients exhibited the best performance (AUC-PR, 0.84; area under the receiver operating characteristic curve [ROC-AUC], 0.98), followed by a multispecialty model covering all other patients (AUC-PR, 0.73). The model specific to cardiothoracic surgery had the lowest performance (AUC-PR, 0.42), likely because of unexpected intrasurgery bleedings. To our knowledge, this is the first deep learning-based platelet transfusion predictor enabling individualized 24-hour risk assessments at high AUC-PR. Implemented as a decision-support system, deep-learning forecasts might improve patient care by detecting platelet demand earlier and preventing critical transfusion shortages., (© 2023 by The American Society of Hematology.)

Spondylolysis is underdiagnosed and often missed in non-musculoskeletal abdominal CT imaging. Our aim was to assess the inter-reader agreement and diagnostic performance of a novel "Darth Vader sign" for the detection of spondylolysis in routine axial images. We performed a retrospective search in the institutional report archives through keyword strings for lumbar spondylolysis and spondylolisthesis. Abdominal CTs from 53 spondylolysis cases (41% female) and from controls ( n = 6) without spine abnormalities were identified. A total of 139 single axial slices covering the lumbar spine (86 normal images, 40 with spondylolysis, 13 with degenerative spondylolisthesis without spondylolysis) were exported. Two radiology residents rated all images for the presence or absence of the "Darth Vader sign". The diagnostic accuracy for both readers, as well as the inter-reader agreement, was calculated. The "Darth Vader sign" showed an inter-reader agreement of 0.77. Using the "Darth Vader sign", spondylolysis was detected with a sensitivity and specificity of 65.0-88.2% and 96.2-99.0%, respectively. The "Darth Vader sign" shows excellent diagnostic performance at a substantial inter-reader agreement for the detection of spondylolysis. Using the "Darth Vader sign" in the CT reading routine may be an easy yet effective tool to improve the detection rate of spondylolysis in non-musculoskeletal cases and hence improve patient care.

Background: Periodontitis Stage III-IV, Grade C (PerioC) is a severe form of Periodontitis. The individual genetic background has been shown to be an important etiopathogenic factor for the development of this disease in young, systemically healthy, and non-smokers patients. Recently, after exome sequencing of families with a history of the disease, PerioC was associated with three single nucleotide variations (SNVs) - rs142548867 (EEFSEC), rs574301770 (ZNF136), and rs72821893 (KRT25) - which were classified as deleterious or possibly harmful by prediction algorithms., Objective: Seeking to validate these findings in a cohort evaluation, this study aims to characterize the allele and genotypic frequency of the SNVs rs142548867, rs574301770, and rs72821893 in the Brazilian population with PerioC and who were periodontally healthy (PH)., Methodology: Thus, epithelial oral cells from 200 PerioC and 196 PH patients were harvested at three distinct centers at the Brazilian Southern region, their DNA were extracted, and the SNVs rs142548867, rs574301770, rs72821893 were genotyped using 5'-nuclease allelic discrimination assay. Differences in allele and genotype frequencies were analyzed using Fisher's Exact Test. Only the SNV rs142548867 (C > T) was associated with PerioC., Results: The CT genotype was detected more frequently in patients with PerioC when compared with PH subjects (6% and 0.5% respectively), being significantly associated with PerioC (odds ratio 11.76, p=0.02)., Conclusion: rs142548867 represents a potential risk for the occurrence of this disease in the Brazilian population.

Purpose: We aimed to investigate if diabetic retinopathy (DR), glaucoma and/or ocular hypertension (OHT) are prospectively linked, as previous studies have proposed cross-sectional associations, but longitudinal data from larger cohorts are lacking., Methods: We performed a bidirectional 5 years prospective, registry-based cohort study. We extracted data from national registers, including the Danish Registry of Diabetic Retinopathy, the Danish Civil Registration System, the Danish National Patient Register and the Danish National Prescription Registry. DR level was defined by the highest level of the two eyes. Glaucoma and/or OHT was defined by diagnostic codes (H40*) or at least three redeemed prescriptions of glaucoma medication (S01E*) within 1 year. We included 205 970 persons with diabetes and 1 003 170 age- and gender-matched non-diabetes controls. Exposures were level-specific DR (i) and glaucoma and/or OHT (ii), and outcomes were hazard ratios (HRs) for 5 years incident glaucoma and/or OHT (i) and DR (ii)., Results: Persons with diabetes were more likely to develop glaucoma and/or OHT (multivariable adjusted HR 1.11, 95% CI 1.06-1.15), but this did not depend on the level of DR. In persons with diabetes, those with glaucoma and/or OHT were more likely to develop DR (multivariable adjusted HR 1.12, 95% CI 1.03-1.23) within 5 years., Conclusion: In a national cohort, diabetes associated with a little higher risk of upcoming glaucoma and/or OHT, and, inversely, the presence of the latter predicted a higher risk of incident DR. Nevertheless, our data do not seem to justify including glaucoma evaluation in the national Danish DR-screening programme., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: An increasing shortage of donor blood is expected, considering the demographic change in Germany. Due to the short shelf life and varying daily fluctuations in consumption, the storage of platelet concentrates (PCs) becomes challenging. This emphasizes the need for reliable prediction of needed PCs for the blood bank inventories. Therefore, the objective of this study was to evaluate multimodal data from multiple source systems within a hospital to predict the number of platelet transfusions in 3 days on a per-patient level., Methods: Data were collected from 25,190 (42% female and 58% male) patients between 2017 and 2021. For each patient, the number of received PCs, platelet count blood tests, drugs causing thrombocytopenia, acute platelet diseases, procedures, age, gender, and the period of a patient's hospital stay were collected. Two models were trained on samples using a sliding window of 7 days as input and a day 3 target. The model predicts whether a patient will be transfused 3 days in the future. The model was trained with an excessive hyperparameter search using patient-level repeated 5-fold cross-validation to optimize the average macro F2-score., Results: The trained models were tested on 5,022 unique patients. The best-performing model has a specificity of 0.99, a sensitivity of 0.37, an area under the precision-recall curve score of 0.45, an MCC score of 0.43, and an F1-score of 0.43. However, the model does not generalize well for cases when the need for a platelet transfusion is recognized., Conclusion: A patient AI-based platelet forecast could improve logistics management and reduce blood product waste. In this study, we build the first model to predict patient individual platelet demand. To the best of our knowledge, we are the first to introduce this approach. Our model predicts the need for platelet units for 3 days in the future. While sensitivity underperforms, specificity performs reliably. The model may be of clinical use as a pretest for potential patients needing a platelet transfusion within the next 3 days. As sensitivity needs to be improved, further studies should introduce deep learning and wider patient characterization to the methodological multimodal, multisource data approach. Furthermore, a hospital-wide consumption of PCs could be derived from individual predictions., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

Purpose: The purpose of the study was to evaluate the prevalence and incidence of diabetic retinopathy (DR) along with associated markers in patients with type 2 diabetes in the Danish DR-screening programme., Methods: We included all persons with type 2 diabetes in the Danish Registry of Diabetic Retinopathy, who had attended at least one episode of DR screening in 2013-2018. DR was classified as levels 0-4 indicating increasing severity. Data were linked with various national health registries to retrieve information on diabetes duration, marital status, comorbidity and systemic medication., Results: Among 153 238 persons with type 2 diabetes, median age and duration of diabetes were 66.9 and 5.3 years and 56.4% were males. Prevalence and 5-year incidences of DR, 2-step-or-more progression of DR and progression to proliferative DR (PDR) were 8.8%, 3.8%, 0.7% and 0.2%, respectively. In multivariable models, leading markers of incident DR and progression to PDR were duration of diabetes (HR 1.98, 95% CI 1.87-2.09; HR 2.89, 95% CI 2.34-3.58 per 10 years of duration) and use of insulin (HR 1.88, 95% CI 1.76-2.01; HR 2.40, 95% CI 1.84-3.13), while the use of cholesterol-lowering medicine was a protecting marker (HR 0.87, 95% CI 0.81-0.93; HR 0.70, 95% CI 0.52-0.93). From 2013 to 2015, 3-year incidence rates of PDR decreased from 1.22 to 0.45 events per 1000 person-years., Conclusion: Nationally, among Danish individuals with type 2 diabetes attending DR screening, we identified duration of diabetes and use of insulin as the most important predictor for the development of DR, while cholesterol-lowering medicine was a protective factor., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate the proliferative diabetic retinopathy (PDR) progression rates and identify the demographic and clinical characteristics of patients who later developed PDR compared with patients who did not progress to that state., Design: A national 5-year register-based cohort study including 201 945 patients with diabetes., Subjects: Patients with diabetes who had attended the Danish national screening program (2013-2018) for diabetic retinopathy (DR)., Methods: We used the first screening episode as the index date and included both eyes of patients with and without subsequent progression of PDR. Data were linked with various national health registries to investigate relevant clinical and demographic parameters. The International Clinical Retinopathy Disease Scale was used to classify DR, with no DR as level 0, mild DR as level 1, moderate DR as level 2, severe DR as level 3, and PDR as level 4., Main Outcome Measures: Hazard ratios (HRs) for incident PDR for all relevant demographic and clinical parameters and 1-, 3-, and 5-year incidence rates of PDR according to baseline DR level., Results: Progression to PDR within 5 years was identified in 2384 eyes of 1780 patients. Proliferative diabetic retinopathy progression rates from baseline DR level 3 at 1, 3 and 5 years were 3.6%, 10.9%, and 14.7%, respectively. The median number of visits was 3 (interquartile range, 1-4). Progression to PDR was predicted in a multivariable model by duration of diabetes (HR, 4.66 per 10 years; 95% confidence interval [CI], 4.05-5.37), type 1 diabetes (HR, 9.61; 95% CI, 8.01-11.53), a Charlson Comorbidity Index score of > 0 (score 1: HR, 4.62; 95% CI, 4.14-5.15; score 2: HR, 2.28; 95% CI, 1.90-2.74; score ≥ 3: HR, 4.28; 95% CI, 3.54-5.17), use of insulin (HR, 5.33; 95% CI, 4.49-6.33), and use of antihypertensive medications (HR, 2.23; 95% CI, 1.90-2.61)., Conclusions: In a 5-year longitudinal study of an entire screening nation, we found increased risk of PDR with increasing baseline DR levels, longer duration of diabetes, type 1 diabetes, systemic comorbidity, use of insulin, and blood pressure-lowering medications. Most interestingly, we found lower risk of progression from DR level 3 to PDR compared with that in previous studies., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2023 by the American Academy of Ophthalmology. This is.)

Background: Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome is a bleeding disorder that can affect all parts of the body including the eyes. Different ocular abnormalities have been described in relation to HHT, but the pathogenesis of retinal involvement is still unknown. A few cases have described chorioretinal abnormalities primarily occurring in elderly patients. In this study, we present a unique case of a young female with known HHT and a series of retinal fundus images including optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) with macular telangiectasia-like lesions., Case Presentation: A young female genetically diagnosed with hereditary hemorrhagic telangiectasia (HHT), is regularly attending retinal screening since she is diagnosed with Type 1 diabetes. At one visit, abnormal retinal telangiectasia-like lesions in the macula, are observed. These abnormalities are monitored over an extended period of time with fundus imaging, and further investigated with OCT and OCTA. The patient has no visual complaints at any time and best-corrected visual acuity is 20/20 Snellen equivalent in both eyes., Conclusions: To the best of our knowledge, this is the first case to describe the occurrence of telangiectasia-like lesions in macula with secondary choriocapillaris atrophy in a patient diagnosed with HHT in such a young age., (© 2022. The Author(s).)

Purpose: Angiostatic agents have proven effective in the treatment of macular oedema in patients with branch retinal vein occlusion (BRVO). However, treatment is inconvenient and expensive, and novel treatment regimens are warranted. We aimed to evaluate if combination treatment of navigated central retinal laser and aflibercept lowered the treatment burden in these patients., Methods: Treatment-naïve patients with BRVO and macular oedema were included at two centres and randomized 1:1 to three monthly injections of 2.0 mg aflibercept with (Group A) or without (Group B) navigated central laser, followed by aflibercept as needed from month 4 through 12. Re-treatment need was evaluated, and secondary endpoints included functional and anatomical outcomes and safety evaluated by retinal microperimetry., Results: We evaluated 41 eyes of 41 patients with a mean age of 69.6 years. Baseline median best-corrected visual acuity (BCVA) was 70.0 letters, and median central retinal thickness (CRT) was 502 μm with no difference between Groups A (n = 21) and B (n = 20). Percentage of patients needing re-treatment after month three was 71% and 80% (p = 0.72). At month 12, groups did not differ in number of injections after loading (1 versus 2, p = 0.43), change in BCVA (+12.8 versus +15.1 letters, p = 0.48), CRT (-195 versus -181 μm, p = 0.82), or retinal sensitivity (+3.3 versus +4.1 dB, p = 0.67)., Conclusion: In treatment-naïve BRVO patients, addition of navigated central laser to aflibercept did not lower treatment burden or affect functional or anatomical outcomes. A low number of intravitreal injections were needed for successful outcome in both treatment arms., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective: To investigate aspects of image quality, feasibility and patient comfort in dedicated spiral breast computed tomography (B-CT) in a large patient cohort., Methods: This retrospective study was approved by the institutional review board. 2418 B-CT scans from 1222 women examined between 04/16/2019 and 04/13/2022 were analyzed. Patients evaluated their comfort during the examination, radiographers carrying out the scans evaluated the patient's mobility and usability of the B-CT device, whereas radiologists assessed lesion contrast, detectability of calcifications, breast coverage and overall image quality. For semi-quantitative assessment, a Likert-Scale was used and statistical significance and correlations were calculated using ANOVAs and Spearman tests., Results: Comfort, mobility and usability of the B-CT were rated each with either "no" or "negligible" complaints in >99%. Image quality was rated with "no" or "negligible complaints" in 96.7%. Lesion contrast and detectability of calcifications were rated either "optimal" or "good" in 92.6% and 98.4%. "Complete" and "almost complete" breast coverage were reported in 41.9%, while the pectoral muscle was found not to be covered in 56.0%. Major parts of the breast were not covered in 2.1%. Some variables were significantly correlated, such as age with comfort (ρ = -0.168, p < .001) and mobility (ρ = -0.172, p < .001) as well as patient weight with lesion contrast (ρ = 0.172, p < .001) and breast coverage (ρ = -0.109, p < .001)., Conclusions: B-CT provides high image quality and contrast of soft tissue lesions as well as calcifications, while covering the pre-pectoral areas of the breast remains challenging. B-CT is easy to operate for the radiographer and comfortable for the majority of women., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Migraine is a disease characterized by cerebral vasodilation. While diabetes has previously been associated with a lower risk of migraine, it is not known if diabetic retinopathy (DR), a retinal peripheral vascular occlusive disease, is a potential biomarker of protection against migraine. Therefore, we aimed to examine diabetic retinopathy as a marker of prevalent and 5-year incident migraine. In a national cohort, we compared patients with diabetes attending DR screening from The Danish National Registry of Diabetic Retinopathy (cases, n = 205,970) to an age- and gender-matched group of patients without diabetes (controls, n = 1,003,170). In the cross-sectional study, a multivariable model demonstrated a lower prevalence of migraine among cases compared with controls (OR 0.83, 95% CI 0.81-0.85), with a lower risk in cases with DR than in those without (OR 0.69, 95% CI 0.65-0.72). In the prospective study, a lower risk of incident migraine was found in a multivariable model in cases (HR 0.76, 95% CI 0.70-0.82), but this did not depend upon the presence of DR. To conclude, in a national study of more than 1.2 million people, patients screened for DR had a lower risk of present migraine, but DR was not a protective marker of incident migraine., (© 2022. The Author(s).)

Background: Initial results from the SCALA study demonstrated that training primary health care providers is an effective implementation strategy to increase alcohol screening in Colombia, Mexico and Peru, but did not show evidence of superior performance for the standard compared to the shorter training arm. This paper elaborates on those outcomes by examining the relationship of training-related process evaluation indicators with the alcohol screening practice., Methods: A mix of convergent and exploratory mixed-methods design was employed. Data sources included training documentation, post-training questionnaires, observation forms, self-report forms and interviews. Available quantitative data were compared on outcome measure - providers' alcohol screening., Results: Training reach was high: three hundred fifty-two providers (72.3% of all eligible) participated in one or more training or booster sessions. Country differences in session length reflected adaptation to previous topic knowledge and experience of the providers. Overall, 49% of attendees conducted alcohol screening in practice. A higher dose received was positively associated with screening, but there was no difference between standard and short training arms. Although the training sessions were well received by participants, satisfaction with training and perceived utility for practice were not associated with screening. Profession, but not age or gender, was associated with screening: in Colombia and Mexico, doctors and psychologists were more likely to screen (although the latter represented only a small proportion of the sample) and in Peru, only psychologists., Conclusions: The SCALA training programme was well received by the participants and led to half of the participating providers conducting alcohol screening in their primary health care practice. The dose received and the professional role were the key factors associated with conducting the alcohol screening in practice. Plain Language Summary: Primary health care providers can play an important role in detecting heavy drinkers among their consulting patients, and training can be an effective implementation strategy to increase alcohol screening and detection. Existing training literature predominantly focuses on evaluating trainings in high-income countries, or evaluating their effectiveness rather than implementation. As part of SCALA (Scale-up of Prevention and Management of Alcohol Use Disorders in Latin America) study, we evaluated training as implementation strategy to increase alcohol screening in primary health care in a middle-income context. Overall, 72.3% of eligible providers attended the training and 49% of training attendees conducted alcohol screening in practice after attending the training. Our process evaluation suggests that simple intervention with sufficient time to practice, adapted to limited provider availability, is optimal to balance training feasibility and effectiveness; that booster sessions are especially important in context with lower organizational or structural support; and that ongoing training refinement during the implementation period is necessary., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The cultural heritage community is increasingly exploring synchrotron radiation (SR) based techniques for the study of art and archaeological objects. When considering heterogeneous and complex micro-samples, such as those from paintings, the combination of different SR X-ray techniques is often exploited to overcome the intrinsic limitations and sensitivity of the single technique. Less frequently, SR X-ray analyses are combined with SR micro-photoluminescence or micro-Fourier Transform Infrared spectroscopy, which provide complementary information on the molecular composition, offering a unique integrated analysis approach. Although the spatial correlation between the maps obtained with different techniques is not straightforward due to the different volumes probed by each method, the combination of the information provides a greater understanding and insight into the paint chemistry. In this work, we discuss the advantages and disadvantages of the combination of X-ray techniques and SR-based photoluminescence through the study of two paint micro-samples taken from Pablo Picasso's Femme (1907). The painting contains two cadmium yellow paints (based on CdS): one relatively intact and one visibly degraded. SR micro-analyses demonstrated that the two Cd-yellow paints differ in terms of structure, chemical composition, and photoluminescence properties. In particular, on the basis of the combination of different SR measurements, we hypothesize that the degraded yellow is based on nanocrystalline CdS with high presence of Cd(OH)Cl. These two characteristics have enhanced the reactivity of the paint and strongly influenced its stability.

Issues: Numerous studies have examined the impact of the COVID-19 pandemic on alcohol use changes in Europe, with concerns raised regarding increased use and related harms., Approach: We synthesised observational studies published between 1 January 2020 and 31 September 2021 on self-reported changes in alcohol use associated with COVID-19. Electronic databases were searched for studies evaluating individual data from European general and clinical populations. We identified 646 reports, of which 56 general population studies were suitable for random-effects meta-analyses of proportional differences in alcohol use changes. Variations by time, sub-region and study quality were assessed in subsequent meta-regressions. Additional 16 reports identified were summarised narratively., Key Findings: Compiling reports measuring changes in overall alcohol use, slightly more individuals indicated a decrease than an increase in their alcohol use during the pandemic [3.8%, 95% confidence interval (CI) 0.00-7.6%]. Decreases were also reported more often than increases in drinking frequency (8.0%, 95% CI 2.7-13.2%), quantity consumed (12.2%, 95% CI 8.3-16.2%) and heavy episodic drinking (17.7%, 95% CI 13.6-21.8%). Among people with pre-existing high drinking levels/alcohol use disorder, high-level drinking patterns appear to have solidified or intensified., Implications: Pandemic-related changes in alcohol use may be associated with pre-pandemic drinking levels. Increases among high-risk alcohol users are concerning, suggesting a need for ongoing monitoring and support from relevant health-care services., Conclusion: Our findings suggest that more people reduced their alcohol use in Europe than increased it since the onset of the pandemic. However high-quality studies examining specific change mechanisms at the population level are lacking., (© 2022 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background: Paracetamol (acetaminophen) is a frequently used nonprescription analgesic with suggested endocrine-disrupting properties. Epidemiological evidence on the effect of paracetamol on male fecundity is sparse., Objectives: To investigate if the use of paracetamol as an oral nonprescription mild analgesic was associated with semen quality in young men., Materials and Methods: This cross-sectional study was based on data from the Fetal Programming of Semen Quality (FEPOS; 2017-2019) cohort of 1058 young men (18-21 years) included in the Danish National Birth Cohort. Participants completed a comprehensive online questionnaire on health behavior including analgesic use and provided a semen sample. Negative binomial regression models were used to estimate the percentage differences (adjusted mean ratios [aMR]) in semen quality characteristics according to paracetamol use (no; yes) and frequency of use (almost never; <1/month; ≥1/month; ≥1/week)., Results: In total, 28% of the 913 participants with available data reported the use of paracetamol within the last 6 months. We found a slightly higher total sperm count (aMR 1.13 95% CI [0.99-1.30]) in users compared to nonusers but other semen characteristics were unaffected. The frequency of use was suggestive of lower total sperm count and morphologically normal sperm cells primarily among users ≥1/week, however, CIs were wide., Discussion: We were unable to account for the underlying reason for paracetamol use, which may induce confounding by indication. Exposure misclassification due to recall is likely but probably nondifferential due to the participants' young age and unawareness of semen quality. Due to the rapid plasma half-life of paracetamol and few frequent users, it was not possible to conclude on potential high-dose effects., Conclusion: Our findings do not suggest any strong detrimental effect of paracetamol use on semen quality within this sample of young Danish men. However, the effects of high dose and frequent use cannot be excluded., (© 2021 American Society of Andrology and European Academy of Andrology.)

Introduction: Heavy drinking and depression frequently co-occur and make a substantial contribution to the global non-communicable disease burden. Positive evidence exists for the use of digital interventions with these conditions alone, but there has been limited assessment of combined approaches., Objective: A systematic review of the effectiveness of combined digital interventions for comorbid heavy drinking and major depression in community-dwelling populations., Methods and Analysis: Electronic databases were searched to October 2021 for randomised controlled trials that evaluated any personalised digital intervention for comorbid heavy drinking and depression. Primary outcomes were changes in quantity of alcohol consumed and depressive symptoms. Two reviewers independently assessed study eligibility, extracted data, and undertook risk of bias assessment. Due to the limited number and heterogeneity of studies identified, meta-analysis was not possible, therefore data were synthesised narratively., Results: Of 898 articles identified, 24 papers were reviewed in full, five of which met the inclusion criteria (N = 1503 participants). Three utilised web-based intervention delivery; two computer programmes delivered in a clinic setting. All involved multi-component interventions; treatment length varied from one to ten sessions. Four studies found no evidence for the superiority of combined digital interventions for comorbid heavy drinking and depression over therapist-delivered approaches, single condition interventions (including online), or assessment-only controls. Positive impacts of integrated online therapy compared to generalist online health advice were reported in a fifth study, but not maintained beyond the 1-month follow-up., Limitations: Few eligible, heterogeneous studies prevented meta-analysis., Conclusion: Limited evidence exists of the effectiveness of combined digital interventions for comorbid heavy drinking and depression in community dwelling populations., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Patients undergoing radical cystectomy are predominantly elderly with many comorbidities and high risk of complications. Studies on comorbidity and complications following cancer surgery are often based on data collected retrospectively from records. However, prospective registration is often considered a more valid source of information. Therefore, it is relevant to investigate if the amount and severity of complications and comorbidities is valid when using retrospective registration compared to a more meticulous prospective registration., Objective: To investigate the difference in registered comorbidities and complications between prospective and retrospective data collection in patients with bladder cancer undergoing radical cystectomy., Method: Seventy-three bladder cancer patients undergoing radical cystectomy were randomized to receive prospective or retrospective collection of data regarding comorbidities and complications. Data in the prospective arm was collected daily during hospitalization, 14-days after discharge and 90-days postoperatively. In the retrospective arm, medical records were reviewed retrospectively at 90-days. Comorbidities were compared using the Charlson Comorbidity Index (CCI) and complications were reported as overall, minor and major dependent on Clavien Dindo Classification (CDC). The primary endpoint was the difference in overall complication rate., Results: No statistically significant difference in CCI was observed with median [IQR] 2[0;3] and 1[0;2] ( p  = 0.21). No statistically significant difference was found regarding all, minor (CDC I-II) or major (CDC III-V) complications at all three time points., Conclusion: No statistically significant difference in comorbidity and complications between retrospectively and prospectively collected data was observed. We find that retrospective collected data is reliable when strict reporting guidelines are used in this single-centre study.

Pulmonary embolism response teams (PERT) aim to improve treatment of acute pulmonary embolism (PE). PERT focus on intermediate- and high-risk PE patients, but recent multicenter studies show that low-risk PE patients compose one in five of all PERT cases. Conversely, not all intermediate- and high-risk PE patients elicit a PERT activation. The factors leading to PERT activations remain unknown. This study aims to describe the patient characteristics associated with PERT activation for low-risk PE patients and characteristics precluding PERT activation for intermediate/high-risk PE patients. We analysed data from all patients with confirmed PE diagnosed in the Massachusetts General Hospital Emergency Department from August 2013 to February 2017 and cross-referred these data with patients who received a PERT activation and patients who did not. Patients were stratified into low-risk or intermediate/high-risk PE. Univariate analyses were performed within each risk group comparing patients with a PERT activation and patients without. Fifteen percent (56/374) of low-risk PE patients triggered a PERT activation. Patient characteristics associated with PERT activation were: (1) vascular disease, (2) pulmonary diseases, (3) thrombophilia, (4) current use of anticoagulants, (5) central PE and (6) concurrent DVT. Thirty-five percent (110/283) of intermediate/high-risk PE patients did not elicit a PERT activation. Patient characteristics precluding a PERT activation were: (1) vascular disease, (2) malignancies and (3) asymptomatic presentation. Low-risk PE patients with PERT activations had more extensive clot burden, complex comorbidities, or had failed anticoagulation treatment. Intermediate/high-risk PE patients without PERT activations tended to have malignancies or vascular disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alcohol measurement delivered by health care providers in primary health care settings is an efficacious and cost-effective intervention to reduce alcohol consumption among patients. However, this intervention is not yet routinely implemented in practice. Community support has been recommended as a strategy to stimulate the delivery of alcohol measurement by health care providers, yet evidence on the effectiveness of community support in this regard is scarce. The current study used a pre-post quasi-experimental design in order to investigate the effect of community support in three Latin American municipalities in Colombia, Mexico, and Peru on health care providers' rates of measuring alcohol consumption in their patients. The analysis is based on the first 5 months of implementation. Moreover, the study explored possible mechanisms underlying the effects of community support, through health care providers' awareness of support, as well as their attitudes, subjective norms, self-efficacy, and subsequent intention toward delivering the intervention. An ANOVA test indicated that community support had a significant effect on health care providers' rates of measuring alcohol consumption in their patients (F (1, 259) = 4.56, p = 0.034, η p 2  = 0.018). Moreover, a path analysis showed that community support had a significant indirect positive effect on providers' self-efficacy to deliver the intervention (b = 0.07, p = 0.008), which was mediated through awareness of support. Specifically, provision of community support resulted in a higher awareness of support among health care providers (b = 0.31, p < 0.001), which then led to higher self-efficacy to deliver brief alcohol advice (b = 0.23, p = 0.010). Results indicate that adoption of an alcohol measurement intervention by health care providers may be aided by community support, by directly impacting the rates of alcohol measurement sessions, and by increasing providers' self-efficacy to deliver this intervention, through increased awareness of support. Trial Registration ID: NCT03524599; Registered 15 May 2018; https://clinicaltrials.gov/ct2/show/NCT03524599., (© 2022. The Author(s).)

Background: The rise of investigative and commercially available cell therapy products adds a new dynamic to academic medical centers; that is, the management of patient-specific cell products. The scope of cell therapy has rapidly expanded beyond in-house collection and infusion of cell products such as bone marrow and peripheral blood transplant. The complexities and volumes of cell therapies are likely to continue to become more demanding. As patient-specific "living drugs," cell therapy products typically require material collection, product provenance, transportation and maintenance of critical quality attributes, including temperature and expiration dates. These requirements are complicated by variations in product-specific attributes, reporting requirements and interactions with industry not required of typical pharmaceuticals., Methods: To manage these requirements, the authors set out to establish a framework within the Immune, Progenitor and Cell Therapeutics Lab, the Current Good Manufacturing Practice facility responsible for cell manufacturing at Mayo Clinic Rochester housed within the Division of Transfusion Medicine. The authors created a work unit (biopharmaceutical unit) dedicated to addressing the specialized procedures required to properly handle these living drugs from collection to delivery and housing the necessary processes to more easily integrate externally manufactured cell therapies into clinical practice., Results: The result is a clear set of expectations defined for each step of the process, with logical documentation of critical steps that are concise and easy to follow., Conclusions: The authors believe this system is scalable for addressing the promised growth of cell therapy products well into the future. Here the authors describe this system and provide a framework that could be used by other centers to manage these important new therapies., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD)., Objective: To investigate diabetes and DR as a risk marker of present and incident AD., Methods: A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes., Results: At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59-0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81-0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08-1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18-1.53)., Conclusion: Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR.

Objectives: To investigate if oxygen could unload the right ventricle and improve right ventricle function in a porcine model mimicking intermediate-high risk acute pulmonary embolism., Design: Controlled, blinded, animal study., Setting: Tertiary university hospital, animal research laboratory., Subjects: Female, Danish pigs (n = 16, approximately 60 kg)., Interventions: Acute autologous pulmonary embolism was induced until doubling of baseline mean pulmonary arterial pressure. Group 1 animals (n = 8) received increasing Fio2 (40%, 60%, and 100%) for time intervals of 15 minutes returning to atmospheric air between each level of Fio2. In group 2 (n = 8), the effects of Fio2 40% maintained over 75 minutes were studied. In both groups, pulmonary vasodilatation from inhaled nitric oxide (40 parts per million) was used as a positive control., Measurements and Main Results: Effects were evaluated by biventricular pressure-volume loop recordings, right heart catheterization, and arterial and mixed venous blood gasses. Pulmonary embolism increased mean pulmonary arterial pressure from 15 ± 4 to 33 ± 6 mm Hg (p = 0.0002) and caused right ventricle dysfunction (p < 0.05) with troponin release (p < 0.0001). In group 1, increasing Fio2 lowered mean pulmonary arterial pressure (p < 0.0001) and pulmonary vascular resistance (p = 0.0056) and decreased right ventricle volumes (p = 0.0018) and right ventricle mechanical work (p = 0.034). Oxygenation was improved and pulmonary shunt was lowered (p < 0.0001). Maximal hemodynamic effects were seen at Fio2 40% with no additional benefit from higher fractions of oxygen. In group 2, the effects of Fio2 40% were persistent over 75 minutes. Supplemental oxygen showed the same pulmonary vasodilator efficacy as inhaled nitric oxide (40 parts per million). No adverse effects were observed., Conclusions: In a porcine model mimicking intermediate-high risk pulmonary embolism, oxygen therapy reduced right ventricle afterload and lowered right ventricle mechanical work. The effects were immediately present and persistent and were similar to inhaled nitric oxide. The intervention is easy and safe. The study motivates extended clinical evaluation of supplemental oxygen in acute pulmonary embolism., Competing Interests: Dr. Nielsen-Kudsk’s institution received funding from a Novo Nordic Research Foundation research grant (NNF17OC0024868). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare., Materials and Methods: Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status., Results: 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained., Conclusions: Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19., Competing Interests: The authors have declared that no competing interests exist.

Objective: The use of inferior vena cava (IVC) filters is controversial. However, the procedure is widely performed for secondary prophylaxis in patients with severe pulmonary embolism (PE), including those treated by a PE response team (PERT). In this study, we analyzed patient factors associated with the clinical decision to place an IVC filter in PERT patients., Methods: Data were collected on all Massachusetts General Hospital patients who had a PERT activation from October 1, 2012, to January 29, 2019. Data describing demographics, medical history, PE characteristics and treatment were collected at the time of PERT activation and prospectively for one year after PERT activation. Univariate and multivariable regression analyses were performed to determine factors associated with IVC filter placement., Results: We identified 834 patients, of whom 91 (10.9%) had an IVC filter placed in the first 7 days after PERT activation. The majority of patients receiving an IVC filter were male (55/91 [60.4%]; P =.096) with a mean age of 65 ± 15.0 years. Patients who received an IVC filter were less likely to have had a PERT referral from the Emergency Department (ED) (41/544 [7.5%]; P < .001) and more likely to have been referred from the intensive care unit (24/107 [22.43%]; P ≤ .001) compared with a floor referral. Patients who presented with syncope (15/86 [17.4%]; P = .040), a history of recent trauma (12/41 [29.3%]; P < .001), intracranial hemorrhage (11/39 [28.2%]; P = .002), a recent surgery or invasive procedure (30/188 [16.0%]; P = .012), a recent surgery (29/160 [18.1%]; P = .001) and a recent hospitalization (38/250 [15.2%]; P = .009) were more likely to have an IVC filter placed. Patients receiving an IVC filter were also more likely to have evidence of right heart dysfunction on a computed tomography pulmonary angiogram (61/359 [17.0%]; P < .001) and an echocardiogram (26/144 [18.1%]; P = .003). Compared with patients without an IVC filter, the 30-day venous thromboembolism recurrence rate was higher (4.7% vs 11.0%) in patients with IVC filters (10/45 [22.2%]; P = .023)., Conclusions: Factors associated with venous thromboembolism severity (eg, PERT referral from intensive care unit and right ventricular dysfunction) and an increased bleeding risk (eg, recent surgery or trauma) were associated with IVC filter placement among PERT patients., (Copyright © 2020 Society for Vascular Surgery. All rights reserved.)

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

Background: The haemodynamic response following acute, intermediate-risk pulmonary embolism is not well described. We aimed to describe the cardiovascular changes in the initial, critical phase 0-12 hours after acute pulmonary embolism in an in-vivo porcine model., Methods: Pigs were randomly allocated to pulmonary embolism ( n  = 6) or sham ( n  = 6). Pulmonary embolism was administered as autologous blood clots (20 × 1 cm) until doubling of mean pulmonary arterial pressure or mean pulmonary arterial pressure was greater than 34 mmHg. Sham animals received saline. Cardiopulmonary changes were evaluated for 12 hours after intervention by biventricular pressure-volume loop recordings, invasive pressure measurements, arterial and central venous blood gas analyses., Results: Mean pulmonary arterial pressure increased ( P  < 0.0001) and stayed elevated for 12 hours in the pulmonary embolism group compared to sham. Pulmonary vascular resistance and right ventricular arterial elastance (right ventricular afterload) were increased in the first 11 and 6 hours, respectively, after pulmonary embolism ( P  < 0.01 for both) compared to sham. Right ventricular ejection fraction was reduced ( P  < 0.01) for 8 hours, whereas a near-significant reduction in right ventricular stroke volume was observed ( P  = 0.06) for 4 hours in the pulmonary embolism group compared to sham. Right ventricular ventriculo-arterial coupling was reduced ( P  < 0.05) for 6 hours following acute pulmonary embolism despite increased right ventricular mechanical work in the pulmonary embolism group ( P  < 0.01) suggesting right ventricular failure., Conclusions: In a porcine model of intermediate-risk pulmonary embolism, the increased right ventricular afterload caused initial right ventricular ventriculo-arterial uncoupling and dysfunction. After approximately 6 hours, the right ventricular afterload returned to pre-pulmonary embolism values and right ventricular function improved despite a sustained high pulmonary arterial pressure. These results suggest an initial critical and vulnerable phase of acute pulmonary embolism before haemodynamic adaptation., (© The European Society of Cardiology 2020.)

Background: Inhaled nitric oxide (iNO) effectively reduces right ventricular afterload when administered in the immediate phase of acute pulmonary embolism (PE) in preclinical animal models. In a porcine model of intermediate-risk PE, we aimed to investigate whether iNO has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute PE., Methods: Anesthetized pigs ( n  = 18) were randomized into three subgroups. An acute PE iNO-group ( n  = 6) received iNO at 40 ppm at one, three, six, nine and 12 hours after onset of PE. Vehicle animals ( n  = 6) received PE, but no active treatment. A third group of sham animals ( n  = 6) received neither PE nor treatment. Animals were evaluated using intravascular pressures, respiratory parameters, biochemistry and intracardiac pressure-volume measurements., Results: The administration of PE increased mean pulmonary artery pressure (mPAP) (vehicle vs sham; 33.3 vs 17.7 mmHg, p  < 0.0001), pulmonary vascular resistance (vehicle vs sham; 847.5 vs 82.0 dynes, p  < 0.0001) and right ventricular arterial elastance (vehicle vs sham; 1.2 vs 0.2 mmHg/ml, p  < 0.0001). Significant mPAP reduction by iNO was preserved at 12 hours after the onset of acute PE (vehicle vs iNO; 0.5 vs -3.5 mmHg, p  < 0.0001). However, this response was attenuated over time ( p  = 0.0313). iNO did not affect the systemic circulation., Conclusions: iNO is a safe and effective pulmonary vasodilator both in the immediate and prolonged phase of acute PE in an in-vivo porcine model of intermediate-risk PE., (© The European Society of Cardiology 2020.)

Phoma stem canker (caused by the ascomycetes Leptosphaeria maculans and Leptosphaeria biglobosa) is an important disease of oilseed rape. Its effect on endophyte communities in roots and shoots and the potential of endophytes to promote growth and control diseases of oilseed rape (OSR) was investigated. Phoma stem canker had a large effect especially on fungal but also on bacterial endophyte communities. Dominant bacterial genera were Pseudomonas, followed by Enterobacter, Serratia, Stenotrophomonas, Bacillus and Staphylococcus. Achromobacter, Pectobacter and Sphingobacterium were isolated only from diseased plants, though in very small numbers. The fungal genera Cladosporium, Botrytis and Torula were dominant in healthy plants whereas Alternaria, Fusarium and Basidiomycetes (Vishniacozyma, Holtermaniella, Bjerkandera/Thanatephorus) occurred exclusively in diseased plants. Remarkably, Leptosphaeria biglobosa could be isolated in large numbers from shoots of both healthy and diseased plants. Plant growth promoting properties (antioxidative activity, P-solubilisation, production of phytohormones and siderophores) were widespread in OSR endophytes. Although none of the tested bacterial endophytes (Achromobacter, Enterobacter, Pseudomonas, Serratia and Stenotrophomonas) promoted growth of oilseed rape under P-limiting conditions or controlled Phoma disease on oilseed rape cotyledons, they significantly reduced incidence of Sclerotinia disease. In the field, a combined inoculum consisting of Achromobacter piechaudii, two pseudomonads and Stenotrophomonas rhizophila tendencially increased OSR yield and reduced Phoma stem canker.

Background: Screening for unhealthy alcohol use in routine consultations can aid primary health care (PHC) providers in detecting patients with hazardous or harmful consumption and providing them with appropriate care. As part of larger trial testing strategies to improve implementation of alcohol screening in PHC, this study investigated the motivational (role security, therapeutic commitment, self-efficacy) and organizational context (leadership, work culture, resources, monitoring, community engagement) factors that were associated with the proportion of adult patients screened with AUDIT-C by PHC providers in Colombia, Mexico and Peru. Additionally, the study investigated whether the effect of the factors interacted with implementation strategies and the country. Methods: Pen-and-paper questionnaires were completed by 386 providers at the start of their study participation (79% female, M age = 39.5, 37.6% doctors, 15.0% nurses, 9.6% psychologists, 37.8% other professional roles). They were allocated to one of four intervention arms: control group; short training only; short training in presence of municipal support; and standard (long) training in presence of municipal support. Providers documented their screening practice during the five-month implementation period. Data were collected between April 2019 and March 2020. Results: Negative binomial regression analysis found an inverse relationship of role security with the proportion of screened patients. Self-efficacy was associated with an increase in the proportion of screened patients only amongst Mexican providers. Support from leadership (formal leader in organization) was the only significant organizational context factor, but only in non-control arms. Conclusion: Higher self-efficacy is a relevant factor in settings where screening practice is already ongoing. Leadership support can enhance effects of implementation strategies.

Aim: The aim was to identify the prevalence of long-lasting pain among children with cerebral palsy (CP) and to investigate the association between pain and participation in physical leisure activities., Methods: This is a cross-sectional study based on data from the National Danish Clinical Quality Database of children with CP. The study population consisted of 960 children aged 2-11 years across all Gross Motor Function Classification System (GMFCS) levels. Data were collected at children's regular clinical visits in 2016 or 2017. Information about pain and participation in physical leisure activities were obtained. The association was estimated as odds ratios (OR) and 95% confidence intervals (95% CI) by logistic regression adjusted for age and sex., Results: We included data from 817 children (59% boys) median age 6 years, 52% classified as GMFCS level I. A total of 36% reported pain, and the most frequent pain locations were hips, feet and knees. Children reporting pain had lower odds for participation in physical leisure activities (OR 0.71, 95% CI 0.53-0.96)., Conclusion: A large proportion of children with CP reported pain. There is an indication that long-lasting pain influences participation in physical leisure activities. Pain-relieving interventions are important to decrease pain-related suffering and facilitate participation., (© 2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)