Definitions Of Adverse Events Research Articles

Associations of early adverse events with clinical outcomes in patients with NSCLC treated with EGFR tyrosine kinase inhibitors.

e20551 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) constitute the primary treatment modality for EGFR-mutant non-small cell lung cancer (NSCLC). While efficacious, EGFR TKIs are associated with adverse events (AEs) like dermatologic toxicities, diarrhea, and stomatitis. This study examined the prognostic implications of these on-target AEs in NSCLC patients receiving EGFR TKI therapy. Methods: A retrospective cohort study was conducted, encompassing advanced NSCLC patients treated with first-line EGFR TKIs within two distinct healthcare delivery systems in Taiwan between June 2011 and December 2019. Patients were stratified by TKI type, and those who had received AE reliever medications within 180 days prior to EGFR TKI initiation were excluded. We examined correlations between AEs and key endpoints: time to next treatment (TTNT) and overall survival (OS). To minimize immortal time bias, a landmark analysis at 60 days post-treatment initiation was utilized. On-target AEs were identified based on the issuance of at least two prescriptions for AE management on different dates within this period. Multivariable Cox proportional hazards models were utilized to evaluate the association between AEs and clinical endpoints, and a random-effects meta-analysis was performed to combine findings from both institutions. Results: Our analysis included 1,605 patients on gefitinib, 848 on erlotinib, and 1,236 on afatinib. Despite potential variations in AE reporting due to prescribing behaviors, the incidence of AE within the first 60 days of treatment was highest for afatinib, particularly with diarrhea (76.7%) and stomatitis (14.9%), followed by erlotinib with notable skin reactions (49.4%). Gefitinib showed the lowest incidence rates across all examined AEs. Of note, afatinib-treated patients who experienced diarrhea within the initial 60 days demonstrated a statistically significant extension in OS (HR 0.75, 95% CI 0.60-0.92). No significant prognostic link was found for other AEs in afatinib users or any AEs among users of gefitinib and erlotinib. Sensitivity analyses, incorporating modified AE definitions, corroborated these outcomes. Conclusions: Identifying AEs via prescription records for symptom relief poses methodological challenges and introduces uncertainty. Nevertheless, the occurrence of diarrhea within the first 60 days of therapy emerged as a significant predictor of enhanced OS in EGFR-mutant NSCLC patients receiving afatinib. This finding suggests a potential prognostic implication. The correlation was not evident in patients treated with first-line gefitinib or erlotinib.

Assessing the safety of physical rehabilitation in critically ill patients: a Delphi study

BackgroundPhysical rehabilitation of critically ill patients is implemented to improve physical outcomes from an intensive care stay. However, before rehabilitation is implemented, a risk assessment is essential, based on robust safety data. To develop this information, a uniform definition of relevant adverse events is required. The assessment of cardiovascular stability is particularly relevant before physical activity as there is uncertainty over when it is safe to start rehabilitation with patients receiving vasoactive drugs.MethodsA three-stage Delphi study was carried out to (a) define adverse events for a general ICU cohort, and (b) to define which risks should be assessed before physical rehabilitation of patients receiving vasoactive drugs. An international group of intensive care clinicians and clinician researchers took part. Former ICU patients and their family members/carers were involved in generating consensus for the definition of adverse events. Round one was an open round where participants gave their suggestions of what to include. In round two, participants rated their agreements with these suggestions using a five-point Likert scale; a 70% consensus agreement threshold was used. Round three was used to re-rate suggestions that had not reached consensus, whilst viewing anonymous feedback of participant ratings from round two.ResultsTwenty-four multi-professional ICU clinicians and clinician researchers from 10 countries across five continents were recruited. Average duration of ICU experience was 18 years (standard deviation 8) and 61% had publications related to ICU rehabilitation. For the adverse event definition, five former ICU patients and one patient relative were recruited. The Delphi process had a 97% response rate. Firstly, 54 adverse events reached consensus; an adverse event tool was created and informed by these events. Secondly, 50 risk factors requiring assessment before physical rehabilitation of patients receiving vasoactive drugs reached consensus. A second tool was created, informed by these suggestions.ConclusionsThe adverse event tool can be used in studies of physical rehabilitation to ensure uniform measurement of safety. The risk assessment tool can be used to inform clinical practise when risk assessing when to start rehabilitation with patients receiving vasoactive drugs.Trial registration This study protocol was retrospectively registered on https://www.researchregistry.com/ (researchregistry2991).

Cardiovascular Eligibility Criteria and Adverse Event Reporting in Combined Immune Checkpoint and VEGF Inhibitor Trials

BackgroundCombination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors (VEGFIs) has improved cancer outcomes and is increasingly used. These drug classes are associated with cardiovascular toxicities when used alone, but heterogeneity in trial design and reporting may limit knowledge of toxicities in patients receiving these in combination. ObjectivesThe aim of this study was to assess consistency and clarity in definitions and reporting of cardiovascular eligibility criteria, baseline characteristics, and cardiovascular adverse events in ICI and VEGFI combination trials. MethodsA scoping review was conducted of phase 2 to 4 randomized controlled trials of ICI and VEGFI combination therapy for solid tumors. Trial cardiovascular eligibility criteria and baseline cardiovascular characteristic reporting in trial publications was assessed, and cardiovascular adverse event definitions and reporting criteria were also examined. ResultsSeventeen trials (N = 10,313; published 2018-2022) were included. There were multiple cardiovascular exclusion criteria in 15 trials. No primary trial publication reported baseline cardiovascular characteristics. Thirteen trials excluded patients with prior heart failure, myocardial infarction, hypertension, or stroke. There was heterogeneity in defining cardiovascular conditions. “Grade 1 to 4” cardiovascular adverse events were reported when incidence was ≥5% to 25% in 15 trials. Incident hypertension was recorded in all trials, but other cardiovascular events were not consistently reported. No trial specifically noted the absence of cardiovascular events. ConclusionsIn ICI and VEGFI combination trials, there is heterogeneity in cardiovascular exclusion criteria, reporting of baseline characteristics, and reporting of cardiovascular adverse events. This limits an optimal understanding of the incidence and severity of events relating to these combinations. Better standardization of these elements should be pursued. (Exclusions and Representation of Patients With Kidney Disease and Cardiovascular Disease in Drug Trials of the Novel Systemic Anti-Cancer Therapies VEGF-Signalling Pathway Inhibitors Alone or in Combination With Immune Checkpoint Inhibitors; CRD42022337942)

Safety Profile of Selective Serotonin Reuptake Inhibitors in Real-World Settings: A Pharmacovigilance Study Based on FDA Adverse Event Reporting System.

Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed agents to treat depression. Considering the growth in antidepressant prescription rates, SSRI-induced adverse events (AEs) need to be comprehensively clarified. This study was to investigate safety profiles and potential AEs associated with SSRIs using the Food and Drug Administration Adverse Event Reporting System (FAERS). A retrospective pharmacovigilance analysis was conducted using the FAERS database, with Open Vigil 2.1 used for data extraction. The study included cases from the marketing date of each SSRI (ie, citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) to April 30, 2023. We employed the reporting odds ratio and Bayesian confidence propagation neural network as analytical tools to assess the association between SSRIs and AEs. The Medical Dictionary for Regulatory Activities was used to standardize the definition of AEs. AE classification was achieved using system organ classes (SOCs). Overall, 427 655 AE reports were identified for the 6 SSRIs, primarily associated with 25 SOCs, including psychiatric, nervous system, congenital, familial, genetic, cardiac, and reproductive disorders. Notably, sertraline (n = 967) and fluvoxamine (n = 169) exhibited the highest and lowest signal frequencies, respectively. All SSRIs had relatively strong signals related to congenital, psychiatric, and nervous disorders. Most of our findings are consistent with those reported previously, but some AEs were not previously identified. However, AEs attributed to SSRIs remain ambiguous, warranting further validation. Applying data-mining methods to the FAERS database can provide additional insights that can assist in appropriately utilizing SSRIs.

Developing a research tool to detect iatrogenic adverse events in psychiatric health care by involving service users and health professionals.

Most health professionals working in psychiatric care will experience adverse events (AE) such as service user suicide or violence, during their career Norway lacks measures to capture potential iatrogenic injuries, such as risk assessment measures, to evaluate patient records for AEs in both inpatient and outpatient psychiatric clinics in hospitals WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: We have described an approach to the validation of a research tool between different national contexts; a process that went beyond language translation We have incorporated the understanding of health professionals and service users; to bring together the lifeworld of the patient with the professional definition of AEs, triggers and risk areas of AEs in a psychiatric context. The service users' experiences resulted in modifications to the tool. Applying the 'Global Trigger Tool-Psychiatry' in Norway and Sweden can help mental health nurses to prevent iatrogenic harm and reduce the occurrence of AEs through the identification of potential triggers. Implementing 'Global Trigger Tool-Psychiatry' might help mental health nurses to improve patient safety in Norway and Sweden. INTRODUCTION: There is little consensus on cross-cultural and cross-national adaptation of research instruments. To translate and validate a Swedish research tool (GTT-P) to detect iatrogenic adverse events in psychiatric health care by involving service users and health professionals in the process. The GTT-P, designed to identify events in patient records that were triggers for adverse events, was translated to Norwegian using a cross-cultural adaptation approach. This involved two focus groups with clinical staff, one of which involved service users, and a joint discussion at a Dialogue Conference to generate consensus on the definition of the triggers of potential adverse events identifiable in patient records. We highlight both the differences and commonalities in defining the nature of risks, the adverse events and the triggers of such events. The Dialogue Conference resulted in three modifications of the tool, based on service users' experiences. Service user involvement and co-production was essential for both the translation and adaptation of the research instrument. We have described an approach to the validation of a research tool between different national contexts; a process that went beyond language translation. This approach enables a more nuanced understanding of potential risks within a psychiatric context as it engages differences in the care delivery. Applying the GTT-P in hospital-based psychiatric care might help to identify processes that need to be changed in order to promote patient safety and a safer work environment for mental health nurses. When translating and validating the GTT-P from Swedish to Norwegian, we have considered the knowledge and experiences of both service users and health professionals. The application of the GTT-P can promote greater patient safety in hospital settings.

The Awareness and Experience About Endoscopic Adverse Events Among South Korean Endoscopists.

The number of endoscopic procedures and related adverse events is increasing. We investigated South Korean endoscopists' awareness and experience of endoscopic adverse events. We used Google Forms to conduct an online questionnaire survey among South Korean endoscopists from December 11 to 29, 2020. The survey comprised 30 questions developed by members of the Quality Management Committee of the Korean Society of Gastrointestinal Endoscopy. In total, 475 endoscopists participated in the survey. Of these, 454 (95.6%) were board-certified gastroenterologists and 255 (53.7%) had >10 years of endoscopy experience. Most participants had experienced serious adverse events requiring hospitalization (80.4%, 382/475); however, only 100 (21.1%) were aware of programs for the prevention and management of adverse endoscopic events in their affiliated endoscopy centers. Most participants (98.5%, 468/475) agreed with the need for education on medical accidents for healthcare workers. Responses were inconsistent regarding the definition of adverse events formulated by the 2010 American Society for Gastrointestinal Endoscopy Workshop. Most participants were not aware of the minimal standard terminology (76.6%, 364/475) and had not used it when writing endoscopy reports (88.8%, 422/475). Responses were inconsistent regarding which events to record in endoscopy records. Further discussion on the nationwide adverse-event reporting system and education program for adverse events related to endoscopy is needed to ensure the safety of patients and endoscopists.

Does Size Matter? On the Role of Stereotactic Radiosurgery for Large Vestibular Schwannomas as Seen in an Institutional Experience of Gamma Knife Radiosurgery for High-Grade Tumors.

Management of large vestibular schwannoma (VS) is controversial. Surgery has historically been the treatment of choice, but emerging literature suggests that definitive stereotactic radiosurgery is feasible. We report our institutional experience of control and morbidity outcomes treating Koos grade 3-4 VS with Gamma Knife radiosurgery (GKRS). An institutional review board-approved database compiled outcomes of Koos grade 3-4 VS treated by GKRS from March 2014 to January 2021 with >6 months' follow-up. Baseline symptoms per Common Terminology Criteria for Adverse Events definitions were recorded. Control rates, toxicities, and post-treatment volumetric changes were analyzed. Aggregate impairment scores (AIs) were defined by the sum of relevant Common Terminology Criteria for Adverse Events grades to categorize symptomatic burdens. Baseline and post-treatment AIs were tested for association with definitive versus adjuvant strategies. In total, 34 patients with Koos grade 3-4 VS were identified, 19 treated with definitive GKRS (GKRS-D) and 15 with adjuvant GKRS (GKRS-A). Median follow-up was 34.2 months for GKRS-D and 48.8 months for GKRS-A. Patients who received GKRS-A had greater AIs at presentation (3.73 vs. 2.11, P= 0.017). Irrespective of treatment approach, tumor control rates were 100% without instances of brainstem necrosis or shunt placement. Six of 19 patients who received GKRS-D had improved post-treatment AI, and 63% of patients who received GKRS-D and 66% of patients who received GKRS-A had tumor shrinkage >20%. In well-selected patients with Koos grade 3-4 VS, definitive stereotactic radiosurgery may be an appropriate strategy with excellent control and minimal toxicity. Our data suggest that the need for surgical decompression should be considered based on pretreatment symptom burden rather than tumor size.

(209) Moving Toward Uniform Criteria for Adverse Event Definitions Across Mechanical Circulatory Support

(209) Moving Toward Uniform Criteria for Adverse Event Definitions Across Mechanical Circulatory Support

Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis

3 months of weekly rifapentine plus isoniazid (3HP) and 4 months of daily rifampicin (4R) are recommended for tuberculosis preventive treatment. As these regimens have not been compared directly, we used individual patient data and network meta-analysis methods to compare completion, safety, and efficacy between 3HP and 4R. We conducted a network meta-analysis of individual patient data by searching PubMed for randomised controlled trials (RCTs) published between Jan 1, 2000, and Mar 1, 2019. Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease. Deidentified individual patient data from eligible studies were provided by study investigators and outcomes were harmonised. Methods for network meta-analysis were used to generate indirect adjusted risk ratios (aRRs) and risk differences (aRDs) with their 95% CIs. We included 17 572 participants from 14 countries in six trials. In the network meta-analysis, treatment completion was higher for people on 3HP than for those on 4R (aRR 1·06 [95% CI 1·02-1·10]; aRD 0·05 [95% CI 0·02-0·07]). For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 [2·12-4·21]; aRD 0·03 [0·02-0·05]) and for grade 3-4 adverse events (aRR 3·46 [2·09-6·17]; aRD 0·02 [0·01-0·03]). Similar increased risks with 3HP were observed with other definitions of adverse events and were consistent across age groups. No difference in the incidence of tuberculosis disease between 3HP and 4R was found. In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events. Although findings should be confirmed, the trade-off between completion and safety must be considered when selecting a regimen for tuberculosis preventive treatment. None. For the French and Spanish translations of the abstract see Supplementary Materials section.

Building Consensus for a Shared Definition of Adverse Events: A Case Study in the Profession of Dentistry.

To achieve high-quality health care, adverse events (AEs) must be proactively recognized and mitigated. However, there is often ambiguity in applying guidelines and definitions. We describe the iterative calibration process needed to achieve a shared definition of AEs in dentistry. Our alignment process includes both independent and consensus building approaches. We explore the process of defining dental AEs and the steps necessary to achieve alignment across different care providers. Teams from 4 dental institutions across the United States iteratively reviewed patient records after identification of charts using an automated trigger tool. Calibration across teams was supported through negotiated definition of AEs and standardization of evidence provided in review. Interrater reliability was assessed using descriptive and κ statistics. After 5 iterative cycles of calibration, the teams (n = 8 raters) identified 118 cases. The average percent agreement for AE determination was 82.2%. Furthermore, the average, pairwise prevalence and bias-adjusted κ (PABAK) was 57.5% (κ = 0.575) for determining AE presence. The average percent agreement for categorization of the AE type was 78.5%, whereas the PABAK was 48.8%. Lastly, the average percent agreement for categorization of AE severity was 82.2% and the corresponding PABAK was 71.7%. Successful calibration across reviewers is possible after consensus building procedures. Higher levels of agreement were found when categorizing severity (of identified events) rather than the events themselves. Our results demonstrate the need for collaborative procedures as well as training for the identification and severity rating of AEs.

Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta-analysis of randomized controlled trials.

BackgroundThe effects and safety of extracorporeal hemoadsorption with CytoSorb® in critically ill patients with inflammatory conditions are controversial.MethodsWe performed a systematic review with meta‐analysis and trial sequential analysis (TSA) of randomized‐controlled trials to assess the mortality and safety of CytoSorb® therapy in critically ill patients with inflammatory conditions. Electronic databases were searched up to April 2022. The primary outcome was mortality at longest follow‐up and secondary outcomes included various adverse event (AE) outcomes. Conflict of interest and funding of each trial were assessed. We calculated relative risk (RR) and 95% confidence interval (CI).ResultsFourteen published (n = 764) and 4 unpublished (n = 111) trials were included. Eight trials were performed in medical ICU patients and 10 in complex cardiac surgery. Ten trials had significant industrial funding or an author conflict of interest. Hemoadsorption with CytoSorb® was associated with higher mortality at latest follow‐up (16 trials, n = 807, 120 of 402 [29.85%] patients in the CytoSorb® group vs. 98 of 405 [24.20%] patients in the control group, RR = 1.24 [95% CI, 1.04–1.49], p = .02, [TSA‐adjusted CI, 0.92–1.68]) and at 30‐days or in‐hospital (11 trials, n = 727; RR = 1.41 [95% CI, 1.06–1.88], p = .02, [TSA‐adjusted CI, 0.44–4.62]). Only one trial reported the definition of adverse event, while detailed results were reported in 3 trials; the risk of adverse events was not higher with CytoSorb®. Certainty of evidence ranged from low to very low.ConclusionLow certainty of evidence showed that the use of CytoSorb® might increase mortality in critically ill patients with inflammatory conditions. Adverse events were frequent but underreported and not systematically evaluated. Industrial funding and conflict of interest were common. Considerable uncertainty about the findings does not allow firm conclusions and suggests a need for high‐quality randomized trials to clarify mortality and adverse events related to CytoSorb®.Editorial CommentHemoadsorption with CytoSorb® have been used in critically ill patients despite lack of high quality data from RCTs suggesting any patient‐important benefits. The findings from this systematic review and meta‐analysis suggests an increased risk of adverse events including mortality. With no apparent benefits and at the same time risk of harm, use of hemoadsorption with CytoSorb® in daily clinical practice cannot be recommended at this time.

Definition and classification for adverse events following spinal and peripheral joint manipulation and mobilization: A scoping review.

IntroductionSpinal and peripheral joint manipulation and mobilization are interventions used by many healthcare providers to manage musculoskeletal conditions. Although there are many reports of adverse events (or undesirable outcomes) following such interventions, there is no common definition for an adverse event or clarity on any severity classification. This impedes advances of patient safety initiatives and practice. This scoping review mapped the evidence of adverse event definitions and classification systems following spinal and peripheral joint manipulation and mobilization for musculoskeletal conditions in adults.MethodsAn electronic search of the following databases was performed from inception to February 2021: MEDLINE, EMBASE, CINAHL, Scopus, AMED, ICL, PEDro, Cochrane Library, Open Grey and Open Theses and Dissertations. Studies including adults (18 to 65 years old) with a musculoskeletal condition receiving spinal or peripheral joint manipulation or mobilization and providing an adverse event definition and/or classification were included. All study designs of peer-reviewed publications were considered. Data from included studies were charted using a standardized data extraction form and synthesised using narrative analysis.ResultsFrom 8248 identified studies, 98 were included in the final synthesis. A direct definition for an adverse event and/or classification system was provided in 69 studies, while 29 provided an indirect definition and/or classification system. The most common descriptors to define an adverse event were causality, symptom severity, onset and duration. Twenty-three studies that provided a classification system described only the end anchors (e.g., mild/minor and/or serious) of the classification while 26 described multiple categories (e.g., moderate, severe).ConclusionA vast array of terms, definition and classification systems were identified. There is no one common definition or classification for adverse events following spinal and peripheral joint manipulation and mobilization. Findings support the urgent need for consensus on the terms, definition and classification system for adverse events related to these interventions.

Cardiovascular toxicities associated with immune checkpoint inhibitors: An updated comprehensive disproportionality analysis of the FDA adverse event reporting system.

Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes for a wide range of cancers but can also lead to cardiovascular toxicities. This study was to scientifically and systematically explore the association between cardiovascular toxicities and immune checkpoint inhibitors (ICIs) and also to characterize the main features of ICI-related cardiovascular toxicities. From January 2012 to December 2020, data in the Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved for disproportionality analysis. The definition of adverse events (AEs) relied on the Medical Dictionary for Regulatory Activities (MedDRA). We used the reporting odds ratio (ROR) with 95% confidence intervals (CIs) to evaluate the association between ICIs and cardiovascular AEs. Clinical characteristics of patients with ICI-associated cardiovascular toxicities were collected, and the time to onset following different ICI regimens was further investigated. We identified a total of 13,713 ICI-associated cardiovascular toxicities which appeared to influence more men (56.90%) than women (36.79%), with a median age of 67 (interquartile range [IQR] 58-74) years. ICI-associated cardiovascular AEs were most frequently reported in lung, pleura, thymus and heart cancer patients (34.49%). Compared with the full database, ICI therapies were detected with pharmacovigilance of myocardial disorders (ROR: 2.64; 95% CI: 2.55-2.75) and pericardial disorders (ROR: 4.51; 95% CI: 4.30-4.74). Concerning myocardial and pericardial disorders, a significant increased ROR was found for all anti-PD-1 and anti-PD-L1 monotherapies, with the exception of anti-CTLA-4 monotherapies. Regarding cardiac arrhythmias, only tremelimumab among ICI monotherapies was associated with an increased ROR (1.92, 1.09-4.72; 4 cases). Compared with ICI monotherapy, ICI combination therapy detected an increase in cardiovascular toxicity spectrum, but did not prolong the onset time. We observed that the spectrum and risk of ICI-associated cardiovascular AEs differed between therapeutic regimens. The poor clinical outcome and early onset of these events should attract clinical attention.

We should abandon the Brighton Collaboration criteria for vaccine-associated anaphylaxis

We should abandon the Brighton Collaboration criteria for vaccine-associated anaphylaxis

The EHA Research Roadmap: Malignant Lymphoid Diseases.

The EHA Research Roadmap: Malignant Lymphoid Diseases.

The Influence of Surgeon Sex on Adverse Events Following Primary Total Hip Arthroplasty: A Register-Based Study of 11,993 Procedures and 200 Surgeons in Swedish Public Hospitals.

Stereotypes may prevail, but little is known about the influence that the sex of an orthopaedic surgeon may have on outcomes. In a recently published study, there were no differences in the rate of adverse events following total hip arthroplasties (THAs) performed by female or male orthopaedic surgeons. The objective of the present study was to investigate whether there was any difference in adverse events within 90 days following a primary THA performed by either a male or female surgeon in Sweden. A retrospective study was performed to evaluate primary THAs performed for osteoarthritis between 2008 and 2016 at 10 hospitals in western Sweden. Local hospital data were linked with the Swedish Hip Arthroplasty Register (SHAR) and with a regional patient register. Data collected from local hospitals and the SHAR included surgeon-related information (e.g., sex, annual volume, and level of training) and patient-related information (e.g., age, sex, and Elixhauser comorbidity index). Adverse events were retrieved from the regional patient register. The definition of adverse events followed the SHAR definition of adverse events. Mixed models were used to investigate the impact of surgeon sex on adverse events. A total of 11,993 primary THAs were performed by 200 surgeons, of whom 17.5% were women. The proportions of adverse events within 90 days were similar for female (6%) and male (7%) surgeons. No association was found between surgeon sex and adverse events (adjusted odds ratio, 0.72; 95% confidence interval, 0.52 to 1.00) when all surgeons (both attendings and residents) were included in the analysis. A sensitivity analysis that included attendings only yielded similar results (adjusted odds ratio, 0.88; 95% confidence interval, 0.60 to 1.29). Despite a small tendency toward lower rates of adverse events at 90 days after THAs performed by female surgeons, there was no significant association between surgeon sex and the risk of adverse events following THA. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Off-Pump Implantation of Left Ventricular Assist Devices - A Single Center Experience

<h3>Purpose</h3> In the past decades, survival after left ventricular assist device (LVAD) implantation has improved notably due to technical improvements of the implantable devices and refined peri- and postoperative patient management. It has been suggested that further benefits could be achieved by avoiding cardiopulmonary bypass and thus its associated negative effects such as systematic inflammatory response syndrome. Therefore, we evaluated safety and feasibility of off-pump LVAD implantation. <h3>Methods</h3> A retrospective analysis of our patient cohort in the time span from 2012 to 2019 was performed. During that time period a total of 275 adult LVAD implantations were done. Of those, 3 patients were excluded due to loss of follow-up giving a final patient population of 272 patients (HeartWare n=128, HeartMate II n=40, HeartMate III n=104). Primary outcomes of interest were 30-day, 90-day and one-year all-cause mortality; secondary outcomes included ICU length of stay, ventilation- and catecholamine support time and peri-operative complications stratified by implantation method. <h3>Results</h3> The overall population is mostly male (86%) with a medium age of 64 (IQR 14.5) and 63.2% of ischemic etiology. We identified 35 patients (12.9%) who received off-pump LVAD implantation. Baseline characteristics between off-pump and on-pump implanted patients did not differ in respect to INTERMACS levels, comorbidities or end-organ function at time of surgery. Off-pump implanted patients were implanted more commonly with an HVAD device (p=0.01) and in all cases via a less invasive surgical approach avoiding full sternotomy (p<0.001). However, this difference is explained by the different surgical technique when performing an off-pump implantation and the smaller size of the HVAD device. No significant differences in mortality were observed, neither in the first 30 days (6.8% vs. 2.9%, p=0.37), 90 days (13.9% vs. 11.4%, p=0.64) nor one year after LVAD implantation (28.3% vs. 22.9%, p=0.41). Also no differences in ICU length of stay, ventilation times or time on catecholamine support were observed. The occurrence of perioperative complications based on the INTERMACS adverse event definition was similar in both groups. <h3>Conclusion</h3> Off-pump LVAD implantation is safe and feasible, and the one-year survival rate is comparable to that of conventional on-pump implantation.

Myocarditis and pericarditis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data

Myocarditis and/or pericarditis (also known as myopericarditis) are inflammatory diseases involving the myocardium (with non-ischemic myocyte necrosis) and/or the pericardial sac. Myocarditis/pericarditis (MPC) may present with variable clinical signs, symptoms, etiologies and outcomes, including acute heart failure, sudden death, and chronic dilated cardiomyopathy. Possible undiagnosed and/or subclinical acute myocarditis, with undefined potential for delayed manifestations, presents further challenges for diagnosing an acute disease and may go undetected in the setting of infection as well as adverse drug/vaccine reactions.The most common causes of MPC are viral, with non-infectious, drug/vaccine associated hypersensitivity and/or autoimmune causes being less well defined and with potentially different inflammatory mechanisms and treatment responses. Potential cardiac adverse events following immunization (AEFIs) encompass a larger scope of diagnoses such as triggering or exacerbating ischemic cardiac events, cardiomyopathy with potential heart failure, arrhythmias and sudden death. The current published experience does not support a potential causal association with vaccines based on epidemiologic evidence of relative risk increases compared with background unvaccinated incidence. The only evidence supporting a possible causal association of MPC with a vaccine comes from case reports.Hypersensitivity MPC as a drug/vaccine induced cardiac adverse event has long been a concern for post-licensure safety surveillance, as well as safety data submission for licensure. Other cardiac adverse events, such as dilated cardiomyopathy, were also defined in the CDC definitions for adverse events after smallpox vaccination in 2006. In addition, several groups have attempted to develop and improve the definition and adjudication of post-vaccination cardiovascular events. We developed the current case definitions for myocarditis and pericarditis as an AEFI building on experience and lessons learnt, as well as a comprehensive literature review. Considerations of other etiologies and causal relationships are outside the scope of this document.

What Are Adverse Events in Mindfulness Meditation?

Mindfulness meditation has become a successful treatment of both physical and psychosocial ailments over the past decade. Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT) are now implemented in various clinical and hospital settings for the treatment of stress, depression, substance abuse, and chronic pain. However, given mindfulness meditation’s exponential rise in popularity, scientific and media reports have called for the evaluation of mindfulness meditation’s safety for those who participate in its programs. Studies have described adverse events, such as anxiety and pain, and more severe events like psychosis, that have been associated with mindfulness meditation. However, there has not been a consistent, systematic way to define and report adverse events in meditation randomized control trials. The objective of our viewpoint was to dispel the notion that these emotive feelings and sensations are adverse events due to mindfulness meditation. Instead, they are actually expected reactions involved in the process of achieving the true benefits of mindfulness meditation. For the more severe outcomes of meditation, for example, psychosis and mania, these events are confounded by other factors, such as the intensity and length of the meditative practices as well as psychological stressors and the psychiatric histories of those affected. Comparatively, mindfulness-based programs like MBSR and MBCT are shorter in duration and less intense. They are designed to be adapted to their participants’ needs as to not induce pain or panic. Mindfulness meditation teaches its students to learn how to deal with their minds and bodies instead of using maladaptive coping techniques. Thus, we urge that further research in mindfulness meditation consistently use the definition of adverse events as those which lead to severe outcomes or hospitalization.

Safety of SGLT2 Inhibitors: A Pharmacovigilance Study from 2013 to 2021 Based on FAERS.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are widely used in clinical practice for their demonstrated cardiorenal benefits, but multiple adverse events (AEs) have been reported. We aimed to describe the distribution of SGLT2i-related AEs in different systems and identify important medical event (IME) signals for SGLT2i. Methods: Data from the first quarter (Q1) of 2013–2021 Q2 in FAERS were selected to conduct disproportionality analysis. The definition of AEs and IMEs relied on the system organ classes (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA-version 24.0). Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to estimate the association between SGLT2is and IMEs. Results: A total of 57,818 records related to SGLT2i, with 22,537 SGLT2i-IME pairs. Most SGLT2i-related IMEs occurred in monotherapy (N = 21,408, 94.99%). Significant signals emerged at the following SOCs: “metabolism and nutrition disorders” (N = 9,103; IC025 = 4.26), “renal and urinary disorders” (3886; 1.20), “infections and infestations” (3457; 0.85). The common strong signals were observed in diabetic ketoacidosis, ketoacidosis, euglycaemic diabetic ketoacidosis and Fournier’s gangrene. Unexpected safety signals such as cellulitis, osteomyelitis, cerebral infarction and nephrolithiasis were detected. Conclusion: Our pharmacovigilance analysis showed that a high frequency was reported for IMEs triggered by SGLT2i monotherapy. Different SGLT2is caused different types and the association strengths of IMEs, while they also shared some specific PTs. Most of the results are generally consistent with previous studies, and more pharmacoepidemiological studies are needed to validate for unexpected AEs. Based on risk-benefit considerations, clinicians should be well informed about important medical events that may be aggravated by SGLT2is.