Critical Adverse Events Research Articles

Adverse event profile of albumin-bound paclitaxel: a real-world pharmacovigilance analysis.

Abraxane plays a crucial role in the treatment of various types of cancer, despite the considerable attention it has garnered for its adverse drug events (ADEs). Nevertheless, there is currently a significant lack of comprehensive real-world pharmacovigilance studies on the ADEs associated with Abraxane. We conducted a retrospective analysis of ADEs associated with Abraxane using data mining from the FAERS database, analyzing data from 2005 to 2023. In a real-world setting, we quantified and visualized the signals of these ADEs using four pharmacovigilance algorithms. The FAERS database identified a total of 10,230 adverse event reports associated with Abraxane. The study revealed that Abraxane-related adverse drug events involved 27 system organ classes (SOC), with the strongest signals associated with the lymphatic and hematological systems and hepatobiliary disorders. Additionally, we identified 70 significant Preferred Terms (PT) signals, which included some critical adverse events not highlighted in the product labeling, such as cystoid macular edema. Further analysis of the timing of adverse reactions showed a median onset time of 41days. Most adverse events (AEs) occurred within the first month of using Abraxane (43.5%), although some were still possible 1year after treatment (3.5%). Gender-specific analysis indicated that high-risk AEs differed between females (nausea, vomiting, and erythema) and males (febrile neutropenia, disseminated intravascular coagulation, and upper gastrointestinal bleeding). The examined results provide crucial recommendations for optimizing the administration of Abraxane, enhancing its effectiveness, and mitigating potential adverse effects. This knowledge will substantially facilitate the implementation of the substance in clinical settings.

Safe Penicillin Allergy Delabeling in Primary Care: A Systematic Review and Meta-Analysis

BackgroundTen % of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient de-labelling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and non-allergist de-labelling. ObjectiveTo assess the safety of de-labelling low-risk adults by means of dDC in primary care. MethodsWe searched MEDLINE, EMBASE and the Conchrane Library databases, from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal was performed by one reviewer and we pooled the results in a meta-analysis. ResultsOut of 2,138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated de-labelling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely de-labelled. Ten patients (<1%) developed an immediate reaction: three had self-limiting reactions, and seven needed antihistaminics, steroids, epinephrine and/or salbutamol. ConclusionNo serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of one recent report, these studies are of low to moderate quality. Non-specialist de-labelling is promising but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.

Optimizing the pharmacokinetics of an 211At-labeled RGD peptide with an albumin-binding moiety via the administration of an albumin-binding inhibitor

PurposeA probe for targeted alpha therapy (TAT) using the RGD peptide (Ga-DOTA-K([211At]APBA)-c(RGDfK) ([211At]1)) with albumin-binding moiety (ABM) was recently developed. [211At]1 highly accumulated in tumors and significantly inhibited tumor growth in U-87 MG tumor-bearing mice. However, high [211At]1 retention in blood may cause critical adverse events, such as hematotoxicity. Therefore, we attempted to accelerate the blood clearance of [211At]1 by competitively inhibiting the binding of [211At]1 to albumin to modulate the pharmacokinetics of the former.MethodsTo evaluate the effects of albumin-binding inhibitors in normal mice, sodium 4-(4-iodophenyl)butanoate at 2, 5, or 10 molar equivalents of blood albumin was administered at 1-h postinjection of [211At]1. The biodistribution of [211At]1, SPECT/CT imaging of [67Ga]Ga-DOTA-K(IPBA)-c(RGDfK) ([67Ga]2), and the therapeutic effects of [211At]1 were compared with or without IPBA administration in U-87 MG tumor-bearing mice.ResultsBlood radioactivity of [211At]1 was decreased in a dose-dependent manner with IPBA in normal mice. In U-87 MG tumor-bearing mice, the blood radioactivity and accumulation in nontarget tissues of [211At]1 were decreased by IPBA. Meanwhile, tumor [211At]1 accumulation was not changed at 3-h postinjection of IPBA. In SPECT/CT imaging of [67Ga]2, IPBA administration dramatically decreased radioactivity in nontarget tissues, and only tumor tissue was visualized. In therapeutic experiments, [211At]1 with IPBA injected-group significantly inhibited tumor growth compared to the control group.ConclusionIPBA administration (as an albumin-binding inhibitor) could modulate the pharmacokinetics and enhance the therapeutic effects of [211At]1.

Improving glycemic control: transitioning from dulaglutide to tirzepatide in patients with type 2 diabetes undergoing hemodialysis.

Background: Tirzepatide-a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist-is used to treat type 2 diabetes. However, the efficacy and safety of tirzepatide in patients undergoing hemodialysis remain unclear. Methods: We conducted a single-center retrospective study of patients with type 2 diabetes undergoing hemodialysis who were transitioned from dulaglutide to tirzepatide. We continuously monitored glucose levels in patients undergoing hemodialysis before and after switching from dulaglutide to tirzepatide. Results: Fourteen patients (mean age: 61.9 ± 9.9years, male: female = 11:3) were included in this study. After switching to tirzepatide, time in range increased to 50.8% from 42.7% (p = 0.02), time above range decreased to 37.8% from 48.4% (p = 0.02), and mean glucose levels decreased to 137.4mg/dL from 156.6mg/dL (p = 0.006). In contrast, there was no significant difference in time below range before and after tirzepatide administration (11.3% and 8.9%) (p = 0.75). Three patients experienced dyspepsia (21.4%), and one patient experienced nausea (7.1%); however, no critical adverse events were reported. Conclusion: Transitioning from dulaglutide to tirzepatide improved glycemic control without increasing hypoglycemia in patients undergoing hemodialysis for type 2 diabetes.

Management of Immune Thrombotic Thrombocytopenic Purpura without Therapeutic Plasma Exchange: Analysis of Efficacy and Safety Data

Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet recovery and survival. Methods: We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased post-first caplacizumab dose. An extensive efficacy and safety analysis of this approach was performed, in comparison with a control group of 59 patients with iTTP, receiving frontline caplacizumab treatment with TPE and immunosuppression (standard of care, SOC). The main outcome was time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, and iTTP-related deaths. Retrospective safety assessments with evaluation of treatment emergent adverse events (TEAE) were performed in both cohorts. Results: The median time to platelet count normalization was similar between the two cohorts (3 and 4 days; P = 0.31, see Figure 1). There were no significant differences in clinical response, exacerbations, refractoriness, or iTTP-related deaths (see Table 1). Four patients did not respond to the first dose of caplacizumab, and TPE was initiated. Cytomegalovirus infection, HIV/hepatitis B co-infection, and ovarian teratoma may have hindered immediate treatment response. Platelet count doubling and median platelet count change after first caplacizumab dose were unaffected by TPE. The median time to LDH normalization was 11 days in the TPE-free cohort. During overall follow-up at least one adverse event (TEAE) was observed in 11 patients (26.2%) in the TPE-free group and 15 patients (25.4%) in the SOC group (excluding adverse events of iTTP that were evaluated as outcome parameters) (see Table 1). There was one TTP-related death reported in the SOC group (1.7%). The cause of death in this patient was cerebral ischemia due to multiple strokes. Serious adverse events associated with therapeutic plasma exchange were observed in 3 patients (5.1%) exclusively in the SOC cohort. These included (1) in-hospital cardiac arrest (IHCA), (2) generalized seizure and supraventricular tachycardia and (3) a transfusion reaction with hypotension, rigors, pruritus and exanthema. Bleeding complications were reported without a significant difference and mainly comprised gingival bleeding and epistaxis. Two patients in the TPE-free cohort (4.8%) experienced major bleeding events, namely subdural hematoma requiring surgical intervention and gastrointestinal bleeding with mass transfusion. Spontaneous subdural hematoma occurred in one patient after 20 days of caplacizumab treatment. Gastrointestinal bleeding from a colon diverticulum occurred in another patient after a clinical response and resulted in a significant drop in hemoglobin and thrombocytes. Gastrointestinal bleeding worsened with concomitant factor XIII deficiency, which was reconstituted intravenously in addition to mass transfusion. Conclusion: Caplacizumab and immunosuppression, without TPE, rapidly controlled microvascular thrombosis and achieved a sustained clinical response in iTTP. The efficacy was similar to the control group, which received SOC. Standard iTTP treatment with TPE may lead to a prolonged hospital stay, including admission to the ICU, multiple sessions of daily TPE with associated risks, and the associated costs of plasma, equipment, nursing care, and medical supervision. The number of patients experiencing critical adverse events was comparable between groups. Bearing all restrictions of a retrospective cohort in mind, we did not identify a critical safety signal for TPE-free iTTP-treatment. However, TPE itself resulted in three life-threatening adverse events in the SOC cohort, including an in-hospital cardiac arrest. In conclusion, omitting TPE appears to be a viable choice for acute iTTP management that may reduce treatment burden without compromising patient outcomes or safety.

Anesthesia Risk Alert Program: A Proactive Safety Initiative.

Analyzing adverse events data collected over a three-year period on all anesthetic cases, North American Partners in Anesthesia (NAPA), a nationwide anesthesia practice, found a correlation between certain high-risk clinical factors and a number of critical events. Seeking to reduce the incidence of critical adverse events associated with these high-risk factors, the quality team of the NAPA Anesthesia Patient Safety Institute (NAPSI) developed the Anesthesia Risk Alert (ARA) program, which guides clinicians in proactively applying targeted risk mitigation interventions in five specific clinical scenarios. NAPSI is NAPA's Patient Safety Organization (PSO). ARA promotes a proactive (Safety II) approach to patient safety. The protocol incorporates innovative collaboration techniques to improve clinical decision-making, along with recommendations by professional medical societies. ARA risk mitigation strategies also adapt decision tools from other industries, such as red team/blue team methodology. Following implementation training to approximately 6,000 NAPA clinicians, ongoing compliance is tracked for the program's two components: screening patients for the five high-risk clinical scenarios and performing the associated mitigation strategy when one or more risk factor is identified. Since launching the ARA program in 2019, clinician compliance consistently exceeds 95%. Simultaneously, available data indicate that the incidence of selected adverse events has decreased. ARA, developed as a process improvement initiative to reduce patient harm in several vulnerable perioperative patient populations, demonstrates how proactive safety strategies can improve clinical outcomes and create better perioperative cultures. At various sites, NAPA anesthesia clinicians reported that ARA's collaboration strategies were transformative behaviors that extended beyond the operating room. Other health care providers may customize the lessons learned from ARA with a Safety II approach.

Comparison of Immediate and Long-term Outcomes of Stent vs. Grafts in Proximal LAD Lesions Complicated by TVD

Background: The management of triple-vessel disease (TVD) with proximal left anterior descending (PLAD) artery involvement remains a critical challenge in cardiology. Current guidelines advocate for both stent placement and graft surgery, yet evidence supporting the optimal approach is conflicting. Objective This study aims to compare the immediate and long-term outcomes of stent placement versus graft surgery in patients with TVD and PLAD involvement, focusing on all-cause mortality, myocardial infarction (MI), stroke, and major adverse cardiovascular and cerebrovascular events (MACCE). Methods: Conducted at Lady Reading Hospital, Peshawar, from January 2021 to December 2021, this research utilized data from the BEST and SYNTAX randomized controlled trials. The study included patients with at least one lesion causing ≥50% diameter stenosis in the PLAD. Primary outcomes included all-cause death, MI, stroke, and MACCE. Secondary outcomes encompassed cardiac death and all-cause revascularization. Statistical analyses were performed using IBM SPSS Statistics software, version 25, with significance set at a two-sided p-value of less than 0.05. Kaplan-Meier estimates and Cox proportional hazards models were applied for survival analysis, stratified by SYNTAX score. Results: The study encompassed 200 patients (110 in the stent group and 90 in the graft group). Graft surgery was associated with a significantly lower incidence of the combined endpoint of all-cause mortality, MI, and stroke (p &lt; 0.05), as well as reduced rates of MACCE, cardiac death, and all-cause revascularization compared to stent placement. In patients with low SYNTAX scores (≤22), graft surgery was linked with a reduced rate of MI. For those with intermediate to high SYNTAX scores (≥22), graft surgery showed superiority in reducing all-cause death, cardiac death, MI, all-cause revascularization, and MACCE. Conclusion: Graft surgery is superior to stent placement in reducing the incidence of critical adverse events in patients with TVD and PLAD involvement over a five-year follow-up period. These findings underscore the importance of personalized, evidence-based decision-making in the management of complex coronary artery disease.

Carbazole derivatives as promising competitive and allosteric inhibitors of human serotonin transporter: computational pharmacology

The human serotonin transporters (hSERTs) are neurotransmitter sodium symporters of the aminergic G protein-coupled receptors, regulating the synaptic serotonin and neuropharmacological processes related to neuropsychiatric disorders, notably, depression. Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and (S)-citalopram are competitive inhibitors of hSERTs and are commonly the first-line medications for major depressive disorder (MDD). However, treatment-resistance and unpleasant aftereffects constitute their clinical drawbacks. Interestingly, vilazodone emerged with polypharmacological (competitive and allosteric) inhibitions on hSERTs, amenable to improved efficacy. However, its application usually warrants adjuvant/combination therapy, another subject of critical adverse events. Thus, the discovery of alternatives with polypharmacological potentials (one-drug-multiple-target) and improved safety remains essential. In this study, carbazole analogues from chemical libraries were explored using docking and molecular dynamics (MD) simulation. Selectively, two IBScreen ligands, STOCK3S-30866 and STOCK1N-37454 predictively bound to the active pockets and expanded boundaries (extracellular vestibules) of the hSERTs more potently than vilazodone and (S)-citalopram. For instance, the two ligands showed docking scores of −9.52 and −9.59 kcal/mol and MM-GBSA scores of −92.96 and −65.66 kcal/mol respectively compared to vilazodone’s respective scores of −7.828 and −59.27 against the central active site of the hSERT (PDB 7LWD). Similarly, the two ligands also docked to the allosteric pocket (PDB 5I73) with scores of −8.15 and −8.40 kcal/mol and MM-GBSA of −96.14 and −68.46 kcal/mol whereas (S)-citalopram has −6.90 and −69.39 kcal/mol respectively. The ligands also conferred conformational stability on the receptors during 100 ns MD simulations and displayed interesting ADMET profiles, representing promising hSERT modulators for MDD upon experimental validation. Communicated by Ramaswamy H. Sarma

Outcomes of near-miss/adverse perioperative events during elective and emergency non-cardiac surgeries that required unplanned admissions to the intensive care unit of a tertiary care center: a retrospective cohort study

BackgroundThe near-miss/adverse events during elective and emergency non-cardiac surgeries requiring unplanned admissions to the intensive care unit (ICU) during the perioperative period are not known. Patients undergoing elective and emergency (E) noncardiac surgeries classified according to the American Society of Anesthesiologists physical status (ASA PS) (I–IV) were studied.ResultsFrom 01 January 2019 to 31 December 2020, 6584 patients above 18 years underwent non-cardiac surgeries at a tertiary care center in eastern India, of which 87.3% (n = 5754) were elective surgical cases, and 12.5% (n = 826) were emergency surgeries. 0.98% of the patients (n = 65) (26 men and 39 females) had serious adverse/near-miss events requiring unplanned admission to the ICU, of these, 50.7% (n = 33) were elective cases, in ASA PS I 12.3% (n = 8), ASA II 27.6% (n = 18) ASA III 9.2% (n = 6) and ASA IV 1.53% (n = 1) respectively and 49.3% (n = 32) were emergency cases in ASA PS I (E) 13.8% (n = 9) (13.8%), ASA II (E) 26.1% (n = 17), ASA III(E) 4.6% (n = 3) and ASA IV(E) 4.6% (n = 3) respectively. Near miss events were mainly due to (a) cardiac-related events seen in 37.5% (n = 25) patients, (b) hemorrhage seen in 25% (n = 16), and (c) airway-related issues seen in 16.1% (n = 11) patients respectively. The adverse events were mainly due to drug-related errors in 21.4% (n = 13) patients. 13.84% (n = 9) patients had died and 86.16% (n = 56) had survived due to the availability of critical care services.Emergency surgeries 25% (8 out of 32 patients) had a higher mortality rate due to adverse/near-miss events compared to elective surgeries which were 3.03% (1 out of 33 cases) respectively.ConclusionsEmergency non-cardiac surgeries were associated with higher rates of adverse/near-miss events. Early recognition and prompt management of critical adverse events during intraoperative and postoperative periods with the help of critical care facilities may improve clinical outcomes.

Early recognition of risk of critical adverse events based on deep neural decision gradient boosting.

Perioperative critical events will affect the quality of medical services and threaten the safety of patients. Using scientific methods to evaluate the perioperative risk of critical illness is of great significance for improving the quality of medical services and ensuring the safety of patients. At present, the traditional scoring system is mainly used to predict the score of critical illness, which is mainly dependent on the judgment of doctors. The result is affected by doctors' knowledge and experience, and the accuracy is difficult to guarantee and has a serious lag. Besides, the statistical prediction method based on pure data type do not make use of the patient's diagnostic text information and cannot identify comprehensive risk factor. Therefore, this paper combines the text features extracted by deep neural network with the pure numerical type features extracted by XGBOOST to propose a deep neural decision gradient boosting model. Supervised learning was used to train the risk prediction model to analyze the occurrence of critical illness during the perioperative period for early warning. We evaluated the proposed methods based on the real data of critical illness patients in one hospital from 2014 to 2018. The results showed that the critical disease risk prediction model based on multiple modes had faster convergence rate and better performance than the risk prediction model based on text data and pure data type. Based on the machine learning method and multi-modal data of patients, this paper built a prediction model for critical adverse events in patients, so that the risk of critical events can be predicted for any patient directly based on the preoperative and intraoperative characteristic data. At present, this work only classifies and predicts the occurrence of critical illness during or after operation based on the preoperative examination data of patients, but does not discuss the specific time when the patient was critical illness, which is also the direction of our future work.

Single-Stage Endovascular Thrombectomy and Stenting as the First-Line Strategy in the Treatment of Phlegmasia Cerulea Dolens Caused by Iliac Vein Lesions

Phlegmasia cerulea dolens (PCD) is a rare and serious complication of deep venous thrombosis and iliac vein lesions (IVLs) are the most common cause of PCD. The purpose of this study was to explore the safety and efficacy of single-stage endovascular thrombus removal and stenting to treat PCD caused by IVLs. Clinical data of 13 patients with PCD secondary to IVL were retrospectively analyzed. They underwent endovascular thrombus removal, including rheolytic thrombectomy, manual aspiration thrombectomy, and simultaneous iliac vein stenting after thrombus removal. The safety and efficacy of single-stage endovascular thrombectomy and stenting in the treatment of PCD were evaluated. The technical success rate was 100% (13/13). Postoperative symptoms were significantly relieved in all patients. There were no perioperative major bleeding complications or other critical adverse events. Two (15.4%) patients had slightly elevated serum creatinine concentration after surgery, which returned to normal before discharge. At the 12-month follow-up, the stent primary patency rate was 81.8% and there were no cases of severe post-thrombotic syndrome. Single-stage endovascular thrombectomy and stenting in PCD due to IVLs was minimally invasive, safe, and effective; it is recommended as a first-line treatment for PCD caused by IVLs.

Time to endoscopic vacuum therapy—lessons learned after > 150 robotic-assisted minimally invasive esophagectomies (RAMIE) at a German high-volume center

Objective of the studyIn esophageal surgery, anastomotic leak (AL) remains one of the most severe and critical adverse events after oncological esophagectomy. Endoscopic vacuum therapy (EVT) can be used to treat AL; however, in the current literature, treatment outcomes and reports on how to use this novel technique are scarce. The aim of this study was to evaluate the outcomes of patients with an AL after IL RAMIE and to determine whether using EVT as an treatment option is safe and feasible.Material and methodsThis study includes all patients who developed an Esophagectomy Complications Consensus Group (ECCG) type II AL after IL RAMIE at our center between April 2017 and December 2021. The analysis focuses on time to EVT, duration of EVT, and follow up treatments for these patients.ResultsA total of 157 patients underwent an IL RAMIE at our hospital. 21 patients of these (13.4%) developed an ECCG type II AL. One patient died of unrelated Covid-19 pneumonia and was excluded from the study cohort. The mean duration of EVT was 12 days (range 4–28 days), with a mean of two sponge changes (range 0–5 changes). AL was diagnosed at a mean of 8 days post-surgery (range 2–16 days). Closure of the AL with EVT was successful in 15 out of 20 patients (75%). Placement of a SEMS (Self-expandlable metallic stent) after EVT was performed in four patients due to persisting AL. Overall success rate of anastomotic sealing independently of the treatment modality was achieved in 19 out of 20 Patients (95%). No severe EVT-related adverse events occurred.ConclusionThis study shows that EVT can be a safe and effective endoscopic treatment option for ECCG type II AL.

Establishment of Membrane-Bound IgA1-Specific Antibody Possessing Antibody-Dependent Cellular Cytotoxicity Activity.

Therapeutic agents targeting B cells, such as rituximab, have been proven to be effective in several diseases. However, since this therapy targets the whole B cell population, there are still concerns about critical adverse events. Therefore, a new type of antibody that can specifically deplete a particular type of B cell may have the potential to become an efficient and safer therapy. Membrane-bound IgA1 (mIgA1) is expressed on soluble IgA1 (sIgA1) producing B cells and/or their precursor, B cells. Although most of the amino acid sequence in the N-terminal regions of the extracellular domains of mIgA1 and sIgA1 is shared, there is a membrane type-specific region, named the membrane-bound immunoglobulin isotype-specific (migis-α) region, at the membrane-proximal region of mIgA1. We hypothesized that the migis-α region would be a suitable antigen for therapeutic antibodies to target mIgA1-expressing B cells without binding to sIgA1, which may cause undesired adverse effects and poor pharmacokinetics (PK). We established two anti-migis-α monoclonal antibodies (mAbs), KM4641 and KM4644, by immunization of the synthetic peptide corresponding to an migis-α region. These mAbs both showed robust binding to mIgA1-expressing transfectant cells. As we expected, neither mAbs bound to sIgA1 and we found that the mAbs recognized different seven to eight amino acid sequences within the migis-α region. Furthermore, the rat-human chimeric type of both mAbs showed antibody-dependent cellular cytotoxicity against mIgA1-expressing transfectant cells. Taken together, this study showed that established mAbs have therapeutic potential in IgA-related diseases, such as IgA nephropathy.

Adverse events during intrahospital transport of critically ill patients: A systematic review and meta-analysis.

Intrahospital transport of critically ill patients is often necessary for diagnostic procedures, therapeutic procedures, or admission to the intensive care unit. The aim of this study was to investigate and describe safety and adverse events during intrahospital transport of critically ill patients. A systematic search was performed of MEDLINE and the Cochrane Central Register of Controlled Trials for studies published up to June 3, 2020, and of the International Clinical Trials Platform Search Portal and ClinicalTrials.gov for ongoing trials. We selected prospective and retrospective cohort studies published in English on intrahospital transport of critically ill patients, and then performed a meta-analysis. The primary outcome was the incidence of all adverse events that occurred during intrahospital transport. The secondary outcomes were death due to intrahospital transport or life-threatening adverse events, minor events in vital signs, adverse events related to equipment, durations of ICU and hospital stay, and costs. A total of 12,313 intrahospital transports and 1898 patients from 24 studies were included in the meta-analysis. Among 24 studies that evaluated the primary outcome, the pooled frequency of all adverse events was 26.2% (95% CI: 15.0-39.2) and the heterogeneity among these studies was high (I2=99.5%). The pooled frequency of death due to intrahospital transport and life-threatening adverse events was 0% and 1.47% each, but heterogeneity was also high. Our findings suggest that adverse events can occur during intrahospital transport of critically ill patients, and that the frequency of critical adverse events is relatively low. The results of this meta-analysis could assist in risk-benefit analysis of diagnostic or therapeutic procedures requiring intrahospital transport of critically ill patients. UMIN000040963.

Heterologous Vaccination for Preparing COVID-19 Pandemic

Infectious disease pandemics are characterized by extreme uncertainty. From the more predictable response to seasonal influenza, which occurs each year, we have learned the importance of effective universal vaccines and therapeutic agents to protect high-risk groups. Heterologous vaccination with different types of vaccines to prevent COVID-19 is already recommended for various reasons: shortages of mass vaccine supply; critical adverse events, and potential superior efficacy as a booster dose. However, very few studies have examined the efficacy and safety of heterologous vaccination with mixed types. This review discusses the efficacy of vaccines currently approved in the Republic of Korea, including heterologous vaccination options.

An Umbrella Review of Clinical Efficacy and Adverse Cardiac Events Associated with Hydroxychloroquine or Chloroquine with or Without Azithromycin in Patients with COVID-19.

ContextThe safety and efficacy of several repurposed drugs, including hydroxychloroquine and chloroquine, with or without azithromycin, were presumed to be miraculous in treating patients with COVID-19. However, as it later transpired, these therapeutic agents seem to be associated with critical adverse cardiac events.ObjectivesGiven the skepticism around the advantages and disadvantages of the aforementioned treatment strategies, the present study aimed to investigate the clinical efficacy and cardiac toxicity of hydroxychloroquine or chloroquine with or without azithromycin in the setting of COVID-19 infection.MethodThis was an umbrella review conducted on patients with COVID-19 who received hydroxychloroquine or chloroquine with or without azithromycin from January 2020 to November 2020. We systematically searched PubMed, Scopus, Cochrane, ProQuest, Web of Science, and Embase databases.ResultsThree studies (systematic review and meta-analysis) were analyzed to evaluate the arrhythmogenic potential of hydroxychloroquine or chloroquine with or without azithromycin in patients with COVID-19 and identify the clinical efficacy of such a combination.ConclusionsWe found no benefit for patients with COVID-19 who received hydroxychloroquine or chloroquine alone or in combination with azithromycin. Moreover, it is noteworthy that these medications, particularly when considering co-administration, could result in both statistically and clinically elevated risks of notorious arrhythmias, such as TdP.

Optimizing MObility for critically ill patiEnts undergoing Continuous Renal Replacement Therapy (MOvE CRRT): An audit of mobility interventions in the intensive care unit

BACKGROUND: CRRT is common in the ICU. This intervention has been shown to contribute to reduced mobilization due to fear of adverse events. This study sought to evaluate the degree of mobilization in patients receiving CRRT and to develop a procedure checklist to enhance mobilization in these patients. METHODS: A retrospective observational matched cohort audit of adult patients admitted to the General Systems ICU at the University of Alberta Hospital from April 1, 2015, and April 1, 2017 was conducted. A total of 50 CRRT patients were matched to 37 critically ill patients and their mobilization events compared. Data was analyzed descriptively. A protocolized mobilization procedure checklist was subsequently developed. RESULTS: Higher levels of mobility were achieved in patients not receiving CRRT. The highest level of mobility in CRRT patients was ambulation in 1 (2%), active mobilization in 17 (34%), passive mobilization in 13 (26%) and none in 19 (38%); whereas, in controls, the highest level of mobility was ambulatory in 22 (59%), active in 10 (27%), passive in 2 (5%) and none in 3 (8%). Four (8%) of the CRRT patients had a PT program delay attributed to CRRT. Adverse events were uncommon and unrelated to CRRT, occurring in 1 (2%) of CRRT patients and in 3 (8%) control patients. No critical adverse events occurred, and no CRRT was delayed or paused. Alarms limited or postponed treatment in 7 (14%) patients. CONCLUSIONS: Mobilization while on CRRT is feasible and safe. It is conducted less frequently and to a lesser degree when compared to similarly acute patients not receiving CRRT. A procedure checklist has been developed to improve mobilization while on CRRT that can be safely implemented in critically ill patients.

Technical Review of Developments in Endoscopic Ultrasound-Guided Hepaticogastrostomy.

Endoscopic ultrasound-guided biliary drainage has been developed as an alternative method for biliary drainage. EUS-guided hepaticogastrostomy (EUS-HGS) can be attempted via the trans-gastric route. These procedures are technically complex for two reasons. First, puncture of the intrahepatic bile duct via the trans-gastric route can be more difficult than that by other approaches because of the small diameter of the target site, and guidewire insertion or manipulation is challenging during EUS-HGS. Second, critical adverse events, such as stent migration into the abdominal cavity, could occur because of the greater mobility of the stomach compared to the duodenum. Therefore, endoscopists should be cautious when performing EUS-HGS. An advantage of EUS-HGS is that it can be performed in patients with complications such as duodenal bulb obstruction or surgically altered anatomy. Recent advances in technique and improvements in devices and stents for EUS-HGS have shown promise for improving the technical success rate of EUS-HGS and reducing the rate of adverse events. However, endoscopists should remain aware of the possibility of critical adverse events such as stent migration.

The Adjudication Process at ACTION - Providing Real-World High-Quality Data

Purpose Lack of both relevant clinical trials and real-world data (RWD) make it difficult to assess the effectiveness of any intervention in pediatric ventricular assist devices (VADs) population. Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry offers a means to capture RWD outside of traditional clinical trials. ACTION registry has introduced a standardized blinded adjudication process to provide VAD related adverse events (AEs) data with improved consistency and reliability. This study reviews the outcomes of the process at the end of its first year. Methods The ACTION adjudication committee, comprised of experts in the field, reviews all critical adverse events, including neurological dysfunction (ND), device malfunctions (DM) and events that lead to death, on a quarterly basis. The committee also reviews a randomly selected subset (15%) of major bleeding (MB) and major infection (MI). Pre-adjudication reports are sent to the centers to upload source documents to a secure portal. Documents are de-identified by the Data Coordinating Center (DCC) and are shared with the chair and two assigned adjudication reviewers. Each AE is presented by the assigned reviewers at a virtual meeting followed by a period of discussion and final adjudication. Committee recommendations are sent as post-adjudication reports to make necessary changes to the AE data entered in registry. Results Total of 658 AEs were reported in the registry through June 2020. Thus far, 182 (28%) AEs were adjudicated (59 Neuro AE, 48 events leading to death, 37 DM, and 38 randomly selected from other AEs). Majority of AEs [150 (82%)] were adjudicated as classified, however, 25 (14%) were classified as non-AEs (DMs = 22, MB = 2, ND = 1). Eight (4.5%) reported events were reclassified in different categories (MI = 2, ND = 4, Events leading to cause of death = 2). As a result of this process, 34 additional events (Events leading to cause of death = 21; Stroke = 4; Other neurological events = 3; Bleeding = 4; Infection = 1; Device malfunction = 1) were identified by the committee that were not originally reported to the registry. Conclusion ACTION adjudication process identified 18% misclassified and ∼5% unreported events, highlighting limitations of any registry data. However, an expert-led adjudication process with a follow-up DCC to site communications and training has the potential to improve the quality of RWD.

Adverse Events with the Pfizer-BioNTech COVID-19 Vaccine among Korean Healthcare Workers.

The Pfizer-BioNTech COVID-19 vaccine has shown excellent clinical effectiveness; however, adverse events of the vaccine remain a concern in Korea. We surveyed adverse events in 2498 healthcare workers vaccinated with the Pfizer-BioNTech COVID-19 vaccine at a university hospital. The survey was conducted using a diary card for 7 days following each injection. The questionnaire response rate was 75.1% (1876/2498) for the first dose and 73.8% (1840/2493) for the second dose. Among local reactions, pain was the most commonly reported (84.9% after the first dose and 90.4% after the second dose). After the second dose, two people visited the emergency room due to severe local pain, but no hospitalization or skin necrosis occurred. Among systemic reactions, fatigue was most frequently reported (52.8% after the first dose and 77.0% after the second dose), followed by myalgia (49.0% and 76.1%), headache (28.7% and 59.2%), chills (16.7% and 54.0%), and arthralgia (11.4% and 39.2%). One or more critical adverse events occurred in 0.2% and 0.7% of the vaccinees. Except for urticaria, more adverse events were reported after the second dose than after the first dose. In the future, adverse events should be investigated in older adults, and a future study with a longer observation period should be conducted.