Disseminated Intravascular Coagulation in Anaphylaxis.

Anaphylaxis is a life-threatening condition that involves severe cutaneous, respiratory, and cardiovascular symptoms. Disseminated intravascular coagulation (DIC) is an acquired, widespread activation of coagulation that can be caused by infectious conditions (e.g., sepsis) and noninfectious conditions. The onset of DIC following anaphylaxis is not commonly known, and information regarding the pathomechanism linking anaphylaxis to DIC is scarce. Further, demographic and clinical data in anaphylaxis-induced DIC are still missing to this day. Triggered by a case of anaphylaxis-induced DIC that seamlessly transitioned to lethal sepsis-induced DIC, we aimed to characterize the patient population affected by anaphylaxis-induced DIC by performing a review of existing literature and expand the discussion to underlying mechanisms. The overall mortality of the patient cohort (n = 30) identified by the literature review was 50%. All patients that died either suffered a bleeding event or a thrombotic event. The majority of patients (n = 25/30; 83%) had bleeding events; thrombotic events were only reported in nonsurvivors (n = 9/15 or 60% of nonsurvivors; vs. n = 0/15 in survivors; p < 0.001). Nonsurvivors of anaphylaxis-induced DIC were on average 25 years older than survivors (p = 0.068). In conclusion, DIC can complicate anaphylaxis and is expected to contribute to poor microvascular perfusion after anaphylaxis. Particularly, elderly patients with known cardiovascular disease and patients who develop thrombotic events are susceptible to lethal outcomes. As a rare and largely uncharacterized disease entity, further research is needed to investigate the link between DIC and anaphylaxis and to potentially identify better treatment strategies.

Immigration bias among medical students: a randomized controlled trial.

BACKGROUND AND IMPORTANCE: Racial bias is found in both physicians and medical students. Immigrants in many parts of the world face challenges similar to racial minorities. Identification of immigrants might however be more subtle than identification by race, and currently, no data are available on a possible bias against the large minority group of migrants in Europe. DESIGN: Randomized control trial. SETTINGS AND PARTICIPANTS: Second-year medical students were randomized into four groups to watch a video of either a male or female patient with pain, with or without immigrant status. INTERVENTION: Students were asked whether they would administer pain medication (primary outcome). OUTCOME MEASURES AND ANALYSIS: Immigrant status, patient's gender, student's gender, age, and language skills were covariates in a logistic regression model. Secondary outcomes included pain medication potency and the student's rating of the patient's pain intensity. MAIN RESULTS: We recruited 607 students [337 females (56%), 387 (64%) between 18 and 22 years old]. Analgesia was administered in 95% (n = 576). Immigrant status was not associated with the probability of receiving pain medication [95 vs. 95%, odds ratio (OR) 0.81, 95% confidence interval (CI) 0.39-1.70, P  = 0.58]. Immigrants received high-potency analgesia less often (26 vs. 33%, OR 0.69, 95% CI 0.50-0.96, P  = 0.03). Female students administered pain medication more frequently (96 vs. 93%, OR 2.29, 95% CI 1.05-5.02, P  = 0.04), and rated the patients' pain higher (mean numeric rating scale 7.7, SD 0.9 vs. 7.4, SD 1.0, OR 1.36, 95% CI 1.16-1.60, P  < 0.001). CONCLUSION: Medical students showed no immigration bias with regard to administering pain medication but were less likely to choose high-potency analgesia in immigrants. We also found a gender difference in pain management. These results demonstrate the importance of including knowledge about immigration bias in medical training.

A moodle course to substitute resuscitation teaching in a medical curriculum during the COVID-19 pandemic: A prospective pilot study.

Background: Face-to-face medical education was restricted during the COVID-19 pandemic, leading to alternative teaching methods. Moodle® (Modular Object-Oriented Dynamic Learning Environment) - an online course format - has not yet been sufficiently evaluated for its feasibility and effectiveness in teaching cardiopulmonary resuscitation. Methods: Medical students in the eighth semester took part in a Moodle® course teaching basic life support, the ABCDE-approach, airway management, and advanced life support. The content was presented using digital background information and interactive videos. A multiple-choice test was conducted at the beginning and at the end of the course. Subjective ratings were included as well. Results: Out of 594 students, who were enrolled in the online course, 531 could be included in this study. The median percentage of correctly answered multiple-choice test questions increased after completing the course [78.9%, interquartile range (IQR) 69.3-86.8 vs. 97.4%, IQR 92.1-100, p < 0.001]. There was no gender difference in the median percentage of correctly answered questions before (female: 79.8%, IQR 70.2-86.8, male: 78.1%, IQR 68.4-86.8, p = 0.412) or after (female: 97.4%, IQR 92.1-100, male: 96.5%, IQR 92.6-100, p = 0.233) the course. On a 5-point Likert scale, 78.7% of students self-reported ≥4 when asked for a subjective increase in knowledge. Noteworthy, on a 10-point Likert scale, male students self-reported their higher confidence in performing CPR [female 6 (5-7), male 7 (6-8), p < 0.001]. Conclusion: The Moodle® course led to a significant increase in theoretical knowledge. It proved to be a feasible substitute for face-to-face courses - both objectively and subjectively.

The use of personal protection equipment does not negatively affect paramedics' attention and dexterity: a prospective triple-cross over randomized controlled non-inferiority trial.

BACKGROUND: The COVID-19 pandemic led to widespread use of personal protection equipment (PPE), including filtering face piece (FFP) masks, throughout the world. PPE. Previous studies indicate that PPE impairs neurocognitive performance in healthcare workers. Concerns for personnel safety have led to special recommendations regarding basic life support (BLS) in patients with a potential SARS-CoV-2 infection, including the use of PPE. Established instruments are available to assess attention and dexterity in BLS settings, respectively. We aimed to evaluate the influence of PPE with different types of FFP masks on these two neuropsychological components of EMS personnel during BLS. METHODS: This was a randomized controlled non-inferiority triple-crossover study. Teams of paramedics completed three 12-min long BLS scenarios on a manikin after having climbed three flights of stairs with equipment, each in three experimental conditions: (a) without pandemic PPE, (b) with PPE including a FFP2 mask with an expiration valve and (c) with PPE including an FFP2 mask without an expiration valve. The teams and intervention sequences were randomized. We measured the shift in concentration performance using the d2 test and dexterity using the nine-hole peg test (NHPT). We compared results between the three conditions. For the primary outcome, the non-inferiority margin was set at 20 points. RESULTS: Forty-eight paramedics participated. Concentration performance was significantly better after each scenario, with no differences noted between groups: d2 shift control versus with valve - 8.3 (95% CI - 19.4 to 2.7) points; control versus without valve - 8.5 (- 19.7 to 2.7) points; with valve versus without valve 0.1 (- 11.1 to 11.3) points. Similar results were found for the NHPT: + 0.3 (- 0.7 to 1.4), - 0.4 (- 1.4 to 0.7), 0.7 (- 0.4 to 1.8) s respectively. CONCLUSION: Attention increases when performing BLS. Attention and dexterity are not inferior when wearing PPE, including FFP2 masks. PPE should be used on a low-threshold basis.

The von Willebrand factor A-1 domain binding aptamer BT200 elevates plasma levels of von Willebrand factor and factor VIII: a first-in-human trial.

Von Willebrand factor (VWF) and factor VIII (FVIII) circulate in a noncovalent complex in blood and promote primary hemostasis and clotting, respectively. A new VWF A1-domain binding aptamer, BT200, demonstrated good subcutaneous bioavailability and a long half-life in non-human primates. This first-in-human, randomized, placebo-controlled, doubleblind trial tested the hypothesis that BT200 is well tolerated and has favorable pharmacokinetic and pharmacodynamic effects in 112 volunteers. Participants received one of the following: a single ascending dose of BT200 (0.18-48 mg) subcutaneously, an intravenous dose, BT200 with concomitant desmopressin or multiple doses. Pharmacokinetics were characterized, and the pharmacodynamic effects were measured by VWF levels, FVIII clotting activity, ristocetin-induced aggregation, platelet function under high shear rates, and thrombin generation. The mean half-lives ranged from 7-12 days and subcutaneous bioavailability increased dose-dependently exceeding 55% for doses of 6-48 mg. By blocking free A1 domains, BT200 dose-dependently decreased ristocetin-induced aggregation, and prolonged collagen-adenosine diphosphate and shear-induced platelet plug formation times. However, BT200 also increased VWF antigen and FVIII levels 4-fold (P<0.001), without increasing VWF propeptide levels, indicating decreased VWF/FVIII clearance. This, in turn, increased thrombin generation and accelerated clotting. Desmopressin-induced VWF/FVIII release had additive effects on a background of BT200. Tolerability and safety were generally good, but exaggerated pharmacology was seen at saturating doses. This trial identified a novel mechanism of action for BT200: BT200 dose-dependently increases VWF/FVIII by prolonging half-life at doses well below those which inhibit VWF-mediated platelet function. This novel property can be exploited therapeutically to enhance hemostasis in congenital bleeding disorders.

Can we predict the severe course of COVID-19 - a systematic review and meta-analysis of indicators of clinical outcome?

BACKGROUND: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. METHODS: This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. RESULTS: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). DISCUSSION: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.

Successful treatment of vaccine-induced prothrombotic immune thrombocytopenia (VIPIT).

Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV-19 vaccine (AstraZeneca) have been reported. The term vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high-dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet-activating properties of ChAdOx1 nCoV-19 vaccine induced antibodies. Here, we report a case of a 62-year-old woman who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work-up, thrombocytopenia, low fibrinogen, elevated D-dimer, and positivity in the platelet factor 4/heparin-enzyme-immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non-heparin anticoagulation, high-dose IVIG, and prednisolone, laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications.

Optimal duration and combination of antiplatelet therapies following percutaneous coronary intervention: a meta-analysis.

INTRODUCTION: The ideal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) is still unknown. In this meta-analysis, we aimed to compare very short-term (1-3 months), short-term (6 months), standard-term (12 months) and long-term (>12 months) DAPT durations for efficacy and safety. METHODS: Overall DAPT comparisons were classified as "any shorter-term"/"any longer-term" DAPT. The primary outcome was a composite of major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke and cardiovascular death). The primary safety outcome was major bleeding. RESULTS: Twenty-six studies comprising 103.394 patients were included. Compared with standard-term DAPT duration, very short-term DAPT duration with subsequent drop of aspirin (RR 1.06, 95% CI, 0.95-1.18, p = 0.26) or drop of the P2Y12 inhibitor (RR 0.92, 95% CI, 0.72-1.16, p = 0.47) was not associated with a higher risk of MACE. Any longer-term compared with any shorter-term DAPT durations led to a significantly lower risk of MACE (RR 0.88, 95% CI, 0.81-0.96, p = 0.002), but a significantly higher risk of BARC 3-5 major bleeding events (RR 1.63, 95% CI, 1.22-2.17, p = 0.001). In the ACS subgroup receiving prasugrel or ticagrelor but not clopidogrel, any longer-term DAPT duration was associated with a significantly lower risk of MACE compared to any shorter-term DAPT duration (RR 0.84, 95% CI, 0.77-0.92, p = 0.0001). CONCLUSION: DAPT may be shortened to 1-3 months in patients with low ischemic but high bleeding risk followed by aspirin or P2Y12 monotherapy. Prasugrel or ticagrelor based DAPT may be extended to >12 months in case of high ischemic and low bleeding risk. PROSPERO REGISTRATION NO: CRD42020163719.

The use of personal protection equipment does not impair the quality of cardiopulmonary resuscitation: A prospective triple-cross over randomised controlled non-inferiority trial.

AIM: Prior studies suggest that the use of personal protective equipment might impair the quality of critical care. We investigated the influence of personal protective equipment on out-of-hospital cardiopulmonary resuscitation. METHODS: Randomised controlled non-inferiority triple-crossover study. Forty-eight emergency medical service providers, randomized into teams of two, performed 12 min of basic life support (BLS) on a manikin after climbing 3 flights of stairs. Three scenarios were completed in a randomised order: Without personal protective equipment, with personal protective equipment including a filtering face piece (FFP) 2 mask with valve, and with personal protective equipment including an FFP2 mask without valve. The primary outcome was mean depth of chest compressions with a pre-defined non-inferiority margin of 3.5 mm. Secondary outcomes included other measurements of CPR quality, providers' subjective exhaustion levels, and providers' vital signs, including end-tidal CO2. RESULTS: Differences regarding the primary outcome were well below the pre-defined non-inferiority margins for both control vs. personal protective equipment without valve (absolute difference 1 mm, 95% CI [-1, 2]) and control vs. personal protective equipment with valve (absolute difference 1 mm, [-0.2, 2]). This was also true for secondary outcomes regarding quality of chest compressions and providers' vital signs including etCO2. Subjective physical strain after BLS was higher in the personal protective equipment groups (Borg 4 (SD 3) without valve, 4 (SD 2) with valve) than in the control group (Borg 3 (SD 2)). CONCLUSION: PPE including masks with and without expiration valve is safe for use without concerns regarding the impairment of CPR quality.

The ISTH DIC score predicts outcome in non-septic patients admitted to a cardiovascular intensive care unit.

BACKGROUND: The International Society of Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score is widely used to predict mortality in critically ill - typically septic - patients. The objective of this study was to investigate whether the ISTH DIC-2001 and DIC-2018 score can be used to predict the 30-day mortality in non-septic patients in an intensive care unit (ICU). METHODS: In this single-center, prospective observational study we included all patients ≥18 years of age who were admitted to a medical ICU with a focus on cardiovascular diseases between August 2012 and 2013. The DIC-2001 and DIC-2018 scores were calculated on admission (DIC-2001-0h and DIC-2018-0h) and 72 hours thereafter (DIC-2001-72h and DIC-2018-72h) and were classified as overt when ≥ 5 for DIC-2001 and ≥ 4 for DIC-2018. RESULTS: A total of 233 patients were included in this study. Excluding septic patients and patients after routine surgery/procedures, we calculated the DIC score for 167 patients (32.4% female; median age 64.9 years). Overt DIC-2001-0h, DIC-2018-0h and overt DIC-2001-72h scores were associated with a significantly higher 30-day mortality rate (52.9% vs. 25.0%, 46.2% vs 21.2%, and 57.1% vs. 23.7%; p < 0.04). The DIC-2001 scores and the DIC-2018-0h score significantly predicted the 30-day mortality. CONCLUSION: This study suggests that the DIC score may be applied to non-septic ICU populations, and indicates that it is a useful tool for mortality prediction, regardless of the underlying disease.