Documentation of ethically relevant information in out-of-hospital resuscitation is rare: a Danish nationwide observational study of 16,495 out-of-hospital cardiac arrests

Abstract Background Decision-making in out-of-hospital cardiac arrest should ideally include clinical and ethical factors. Little is known about the extent of ethical considerations and their influence on prehospital resuscitation. We aimed to determine the transparency in medical records regarding decision-making in prehospital resuscitation with a specific focus on ethically relevant information and consideration in resuscitation providers’ documentation. Methods This was a Danish nationwide retrospective observational study of out-of-hospital cardiac arrests from 2016 through 2018. After an initial screening using broadly defined inclusion criteria, two experienced philosophers performed a qualitative content analysis of the included medical records according to a preliminary codebook. We identified ethically relevant content in free-text fields and categorised the information according to Beauchamp and Childress’ four basic bioethical principles: autonomy, non-maleficence, beneficence, and justice. Results Of 16,495 medical records, we identified 759 (4.6%) with potentially relevant information; 710 records (4.3%) contained ethically relevant information, whereas 49 did not. In general, the documentation was vague and unclear. We identified four kinds of ethically relevant information: patients’ wishes and perspectives on life; relatives’ wishes and perspectives on patients’ life; healthcare professionals’ opinions and perspectives on resuscitation; and do-not-resuscitate orders. We identified some “best practice” examples that included all perspectives of decision-making. Conclusions There is sparse and unclear evidence on ethically relevant information in the medical records documenting resuscitation after out-of-hospital cardiac arrests. However, the “best practice” examples show that providing sufficient documentation of decision-making is, in fact, feasible. To ensure transparency surrounding prehospital decisions in cardiac arrests, we believe that it is necessary to ensure more systematic documentation of decision-making in prehospital resuscitation

Documentation of ethically relevant information in out-of-hospital resuscitation is rare: a Danish nationwide observational study of 16,495 out-of-hospital cardiac arrests

Abstract Background Decision-making in out-of-hospital cardiac arrest should ideally include clinical and ethical factors. Little is known about the extent of ethical considerations and their influence on prehospital resuscitation. We aimed to determine the transparency in medical records regarding decision-making in prehospital resuscitation with a specific focus on ethically relevant information and consideration in resuscitation providers’ documentation. Methods This was a Danish nationwide retrospective observational study of out-of-hospital cardiac arrests from 2016 through 2018. After an initial screening using broadly defined inclusion criteria, two experienced philosophers performed a qualitative content analysis of the included medical records according to a preliminary codebook. We identified ethically relevant content in free-text fields and categorised the information according to Beauchamp and Childress’ four basic bioethical principles: autonomy, non-maleficence, beneficence, and justice. Results Of 16,495 medical records, we identified 759 (4.6%) with potentially relevant information; 710 records (4.3%) contained ethically relevant information, whereas 49 did not. In general, the documentation was vague and unclear. We identified four kinds of ethically relevant information: patients’ wishes and perspectives on life; relatives’ wishes and perspectives on patients’ life; healthcare professionals’ opinions and perspectives on resuscitation; and do-not-resuscitate orders. We identified some “best practice” examples that included all perspectives of decision-making. Conclusions There is sparse and unclear evidence on ethically relevant information in the medical records documenting resuscitation after out-of-hospital cardiac arrests. However, the “best practice” examples show that providing sufficient documentation of decision-making is, in fact, feasible. To ensure transparency surrounding prehospital decisions in cardiac arrests, we believe that it is necessary to ensure more systematic documentation of decision-making in prehospital resuscitation

Development of decision support system for the diagnosis of arthritis pain for rheumatic fever patients: Based on the fuzzy approach

Developing a Decision Support System (DSS) for Rheumatic Fever (RF) is complex due to the levels of vagueness, complexity and uncertainty management involved, especially when the same arthritis symptoms can indicate multiple diseases. It is this inability to describe observed symptoms precisely that necessitates our approach to developing a Decision Support System (DSS) for diagnosing arthritis pain for RF patients using fuzzy logic. In this paper we describe how fuzzy logic could be applied to the development of a DSS application that could be used for diagnosing arthritis pain (arthritis pain for rheumatic fever patients only) in four different stages, namely: Fairly Mild, Mild, Moderate and Severe. Our approach employs a knowledge-base that was built using WHO guidelines for diagnosing RF, specialist guidelines from Nepal and a Matlab fuzzy tool box as components to the system development. Mixed membership functions (Triangular and Trapezoidal) are applied for fuzzification and Mamdani-type is used for the fuzzy reasoning process. Input and output parameters are defined based on the fuzzy set rules

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC):can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20–365 from study allocation and (ii) days alive and without exacerbation within days 20–365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142. Registered on August 25, 2017. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06720-z

XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53

Additional file 1. Table S1: Clinicopathologic and molecular characteristics of DLBCL patients with high or low XPO1 expression. Table S2: Significantly differentially expressed genes between XPO1high and XPO1low DLBCL patients with concurrent TP53 mutation and high MYC expression. Figure S1: Biomarker study for XPO1 and selinexor. (A–B) XPO1high expression showed significant adverse prognostic impact in the ABC subtype but not the GCB subtype of DLBCL. (C) XPO1high expression showed a trend of unfavorable prognostic effect on PFS in MYC-rearranged (MYC-R+) DLBCL. (D) XPO1high expression was associated with significantly poorer survival in DLBCL patients with wild type (Wt) TP53. (E) ABC-DLBCL and GCB-DLBCL cells showed similar sensitivity to the cytotoxicity of selinexor. (F) TP53 mutation (Mut-TP53) significantly reduced the anti-lymphoma efficacy of selinexor in HGBCL-DH cells. IC50 values were calculated by GraphPad Prism 8 based on the cell viability data after 72-hour treatment

Male breast cancer in BRCA1 and BRCA2 mutation carriers : pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)). Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.Peer reviewe

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes