Classification Of Adverse Events Research Articles

Harms Reporting in Randomized Controlled Trials Underpinning the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines for Distal Radius Fractures

The purpose of this study was to measure the harms-related reporting among randomized controlled trials (RCTs) cited as supporting evidence for the American Academy of Orthopaedic Surgeons clinical practice guidelines regarding the management of distal radius fractures. We adhered to the guidance for reporting metaresearch and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines throughout the course of this investigation. We used the American Academy of Orthopaedic Surgeons clinical practice guidelines for distal radius fractures available on Orthoguidelines.org. A linear regression analysis was conducted to model the relationship between the year of publication and the total Consolidated Standards of Reporting Trials percentage adherence over time. Thirty-five RCTs were included in the final sample. The average number of Consolidated Standards of Reporting Trials Extension for Harms items adequately reported across all included RCTs was 9.2 (9.2/18, 50.9%). None of the included trials adequately reported all 18 items. Ten items had a compliance of more than 50% (10/18, 55.6%), 4 items had a compliance of 20%-50% (4/18, 22.2%), and 4 items had a compliance of less than 20% (4/18, 22.2%). The results of the linear regression model showed no significant improvement in Consolidated Standards of Reporting Trials Harms reporting over time. Adverse events are incompletely reported among RCTs cited as supporting evidence for American Academy of Orthopaedic Surgeons clinical practice guidelines for the management of distal radius fractures. Given our findings, specific attention should be paid to improving the standardization of the classification of adverse events to facilitate ease in the reporting process.

MP61-11 RETZIUS-SPARING ROBOT-ASSISTED RADICAL PROSTATECTOMY AFTER PREVIOUS TRANS-URETHRAL RESECTION OF THE PROSTATE: ASSESSMENT OF FUNCTIONAL AND ONCOLOGICAL OUTCOMES

You have accessJournal of UrologyCME1 Apr 2023MP61-11 RETZIUS-SPARING ROBOT-ASSISTED RADICAL PROSTATECTOMY AFTER PREVIOUS TRANS-URETHRAL RESECTION OF THE PROSTATE: ASSESSMENT OF FUNCTIONAL AND ONCOLOGICAL OUTCOMES Stefano Tappero, Enrico Vecchio, Erika Palagonia, Giorgia Granelli, Marco Martiriggiano, Ofir Maltzman, Alberto Olivero, Silvia Secco, Aldo Massimo Bocciardi, Antonio Galfano, and Paolo Dell'oglio Stefano TapperoStefano Tappero More articles by this author , Enrico VecchioEnrico Vecchio More articles by this author , Erika PalagoniaErika Palagonia More articles by this author , Giorgia GranelliGiorgia Granelli More articles by this author , Marco MartiriggianoMarco Martiriggiano More articles by this author , Ofir MaltzmanOfir Maltzman More articles by this author , Alberto OliveroAlberto Olivero More articles by this author , Silvia SeccoSilvia Secco More articles by this author , Aldo Massimo BocciardiAldo Massimo Bocciardi More articles by this author , Antonio GalfanoAntonio Galfano More articles by this author , and Paolo Dell'oglioPaolo Dell'oglio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003319.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To date, no data exist concerning functional and oncological outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) in patients previously treated with trans-urethral resection of the prostate (p-TURP) for benign prostate obstruction. The current study aimed to address the impact of p-TURP on immediate and 12-months urinary continence recovery (UCR), as well as perioperative outcomes and surgical margins after RS-RARP. METHODS: Patients treated with RS-RARP for prostate cancer at a single high-volume European institution were identified and stratified according to p-TURP. Intraoperative and postoperative complications were reported according to EAU guidelines standardized methodology. Univariable and multivariable logistic, Poisson log-linear and Cox regression models were performed. RESULTS: Of 1,386 RS-RARP patients, 99 (7%) had history of p-TURP. According to EAU intraoperative adverse events classification (EAUiaiC), the most common intraoperative complications were EAUiaiC grade 1 (n=26/31, 84%). The most common postoperative complications were Clavien-Dindo grade 2 (n=67/174, 39%), and the most common reason of readmission was infected lymphocele (n=8/16, 50%). Between p-TURP and no-TURP patients no differences were detected in terms of rates of intraoperative complications (2 vs 2%), in-hospital postoperative complications (12 vs 11%), and readmissions (1 vs 1%; all p values≥0.8). At catheter removal, the rates of immediate UCR were 40 vs 67% in p-TURP vs no-TURP patients (p<0.001). At 12 months from RS-RARP, the rates of UCR were 68 vs 94% in p-TURP vs no-TURP patients (p<0.001). At multivariable logistic and Cox regression models, p-TURP was independently associated, respectively, with lower immediate (odds ratio [OR]: 0.32, p<0.001) and 12-months UCR (hazard ratio: 0.54, p<0.001). At multivariable Poisson analyses, p-TURP predicted longer operative time (rate ratio: 1.08, p<0.001) but not longer length of stay or time to catheter removal (p values>0.05). Positive surgical margins rates were 23 vs 17% in p-TURP vs no-TURP patients (p=0.1), which translated in a non significant multivariable OR of 1.14 (p=0.58). CONCLUSIONS: RS-RARP in patients with history of TURP for BPO may be longer and associated with worse urinary continence recovery both at bladder catheter removal and at subsequent time-points. In the current series, p-TURP patients harbored low complication rates, and surgical margins rates comparable to their no-TURP counterparts. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e856 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stefano Tappero More articles by this author Enrico Vecchio More articles by this author Erika Palagonia More articles by this author Giorgia Granelli More articles by this author Marco Martiriggiano More articles by this author Ofir Maltzman More articles by this author Alberto Olivero More articles by this author Silvia Secco More articles by this author Aldo Massimo Bocciardi More articles by this author Antonio Galfano More articles by this author Paolo Dell'oglio More articles by this author Expand All Advertisement PDF downloadLoading ...

Efficacy and safety of allergen-specific immunotherapy in children

Atopic diseases are one of the most common chronic diseases in children and adolescents. They lead to a significant deterioration in the quality of life of patients and their families. The only strategy for the treatment of atopic diseases that has a disease-modifying effect is allergen-specific immunotherapy. The purpose of this review is to summarize the literature data on the practical aspects of allergen-specific immunotherapy use in children and adolescents with allergic rhinoconjunctivitis and atopic bronchial asthma. An analysis of scientific articles has shown that allergen-specific immunotherapy can reduce the severity of symptoms of allergic rhinoconjunctivitis and/or atopic bronchial asthma and reduce the amount of pharmacotherapy, as well as reduce the risk of bronchial asthma developing in patients with allergic rhinoconjunctivitis. The current evidence of the preventive effect of allergen-specific immunotherapy in relation to the development of new sensitizations in monosensitized patients is unconvincing, and, according to many authors, new randomized clinical trials are needed. According to most experts, allergen-specific immunotherapy should be started in children from 5 years of age in the presence of proven immunoglobulin E-mediated sensitization to one or more allergens, carried out for at least 3 years, using preparations in which the presence of major allergens is documented. At the same time, both subcutaneous and sublingual administration of allergens has comparable effectiveness. Allergen-specific immunotherapy is a safe and well-tolerated treatment for children, but currently there is no generally accepted classification of possible adverse events, as well as a standardized and uniform system for assessing their severity.

Radiation-induced Fistulas in Patients With Prior Pelvic Radiotherapy for Prostate Cancer: A Systematic Review and Meta-analysis

ObjectiveTo systematically aggregate and summarize existing data on fistula prevalence among patients with a history of pelvic radiotherapy for prostate cancer. Materials and MethodsWe queried PubMed, Embase, and Web of Science on October 7, 2020 for peer-reviewed publications pertaining to radiation-induced fistulas in the pelvis. For meta-analysis, we used the random-effects model. We used the I2 statistic to quantify heterogeneity and the Newcastle-Ottawa Scale to assess risk of bias. ResultsOur final meta-analysis included 6 cohort studies with a total of 7665 patients exposed to pelvic radiotherapy between 1967 and 2013. Median follow-up time was 35.5 months (IQR 33.5-57.5). Pooled prevalence of radiation-induced fistula across all 6 cohort studies was 0.2% (95% CI: 0.1-0.4, I2 = 0.000%, P < .608). In subgroup analysis, we did not detect significant heterogeneity in fistula prevalence in patients who were re-irradiated (0.3%, 95% CI: 0.1-0.4; P = .762) or patients on concurrent chemotherapy (0.4%, 95% CI: -0.3 -1.2; P = .664) compared to those receiving their first course of radiotherapy alone. No randomized controlled trials met inclusion criteria due to ambiguous and inconsistent reporting language for fistula occurrence. ConclusionThere is limited published literature reporting fistula as an adverse event of prostate cancer radiotherapy, especially in the medium and long-term period. Patients undergoing pelvic radiotherapy for prostate cancer appear at low short-term risk for developing fistulas. Adverse event reporting in randomized controlled trials merits greater granularity where fistulas should be reported with specificity rather than aggregating into broad categories of genitourinary or gastrointestinal adverse events.

Classification, diagnosis and clinical strategy of congenital coronary artery disease in children.

Some of the congenital coronary artery diseases in children have potential life-threatening complications. In addition to anatomical classification, the peadiatricians should pay more attention to the risk of adverse cardiac events classification; and then, they can eventrually make the personalized guidance suggestions and treatment decisions according to different diseases.

Clavien-Dindo, comprehensive complication index and classification of intraoperative adverse events: a uniform and holistic approach in adverse event registration for (deep) endometriosis surgery.

What is the additional value of the comprehensive complication index (CCI) and ClassIntra system (classification for intraoperative adverse events (ioAEs)) in adverse event (AE) reporting in (deep) endometriosis (DE) surgery compared to only using the Clavien-Dindo (CD) system? The CCI and ClassIntra are useful additional tools alongside the CD system for a complete and uniform overview of the total AE burden in patients with extensive surgery (such as DE), and with this uniform data registration, it is possible to provide greater insight into the quality of care. Uniform comparison of AEs reported in the literature is hampered by scattered registration. In endometriosis surgery, the usage of the CD complication system and the CCI is internationally recommended; however, the CCI is not routinely adapted in endometriosis care and research. Furthermore, a recommendation for ioAEs registration in endometriosis surgery is lacking, although this is vital information in surgical quality assessments. A prospective mono-center study was conducted with 870 surgical DE cases from a non-university DE expertise center between February 2019 and December 2021. Endometriosis cases were collected with the EQUSUM system, a publicly available web-based application for registration of surgical procedures for endometriosis. Postoperative adverse events (poAEs) were classified with the CD complication system and CCI. Differences in reporting and classifying AEs between the CCI and the CD were assessed. ioAEs were assessed with the ClassIntra. The primary outcome measure was to assess the additional value toward the CD classification with the introduction of the CCI and ClassIntra. In addition, we report a benchmark for the CCI in DE surgery. A total of 870 DE procedures were registered, of which 145 procedures with one or more poAEs, resulting in a poAE rate of 16.7% (145/870), of which in 36 cases (4.1%), the poAE was classified as severe (≥Grade 3b). The median CCI (interquartile range) of patients with poAEs was 20.9 (20.9-31.7) and 33.7 (33.7-39.7) in the group of patients with severe poAEs. In 20 patients (13.8%), the CCI was higher than the CD because of multiple poAEs. There were 11 ioAEs reported (11/870, 1.3%) in all procedures, mostly minor and directly repaired serosa injuries. This study was conducted at a single center; thus, trends in AE rates and type of AEs could differ from other centers. Furthermore, no conclusion could be drawn on ioAEs in relation to the postoperative course because the power of this database is not robust enough for that purpose. From our data, we would advise to use the Clavien-Dindo classification system together with the CCI and ClassIntra for a complete overview of AE registration. The CCI appeared to provide a more complete overview of the total burden of poAEs compared to only reporting the most severe poAEs (as with CD). If the use of the CD, CCI, and ClassIntra is widely adapted, uniform data comparison will be possible at (inter)national level, providing better insight into the quality of care. Our data could be used as a first benchmark for other DE centers to optimize information provision in the shared decision-making process. No funding was received for this study. The authors have no conflicts of interest to declare. N/A.

Analysis of reported adverse events of pipeline stents for intracranial aneurysms using the FDA MAUDE database.

Flow diverting stents (FDS) are a validated device in the treatment of intracranial aneurysms, allowing for minimally invasive intervention. However, after its approval for use in the United States in 2011, post-market surveillance of adverse events is limited. This study aims to address this critical knowledge gap by analyzing the FDA Manufacturer and User Facility Device Experience (MAUDE) database for patient and device related (PR and DR) reports of adverse events and malfunctions. Using post-market surveillance data from the MAUDE database, PR and DR reports from January 2012-December 2021 were extracted, compiled, and analyzed with R-Studio version 2021.09.2. PR and DR reports with insufficient information were excluded. Raw information was organized, and further author generated classifications were created for both PR and DR reports. A total of 2203 PR and 4017 DR events were recorded. The most frequently reported PR adverse event categories were cerebrovascular (60%), death (11%), and neurological (8%). The most frequent PR adverse event reports were death (11%), thrombosis/thrombus (9%) cerebral infarction (8%), decreased therapeutic response (7%), stroke/cerebrovascular accident (6%), intracranial hemorrhage (5%), aneurysm (4%), occlusion (4%), headache (4%), neurological deficit/dysfunction (3%). The most frequent DR reports were activation/positioning/separation problems (52%), break (9%), device operates differently than expected (4%), difficult to open or close (4%), material deformation (3%), migration or expulsion of device (3%), detachment of device or device component (2%). Post-market surveillance is important to guide patient counselling and identify adverse events and device problems that were not identified in initial trials. We present frequent reports of several types of cerebrovascular and neurological adverse events as well as the most common device shortcomings that should be explored by manufacturers and future studies. Although inherent limitations to the MAUDE database are present, our results highlight important PR and DR complications that can help optimize patient counseling and device development.

Phase II trial of maximal ablative irradiation because of encasement (MAIBE) for patients with potentially resectable locally advanced pancreatic cancer.

710 Background: For patients with localized but not immediately resectable pancreatic adenocarcinoma (PDAC), the role for local therapy remains undefined. Phase II MAIBE trial studied ablative radiation (A-RT) followed by consideration of surgery for patients with locally advanced pancreatic cancer (LAPC) who remain unresectable after induction chemotherapy. Methods: Participants with histologically confirmed PDAC judged unresectable by multidisciplinary review using NCCN definition after completing 3-6 months of mFOLFIRINOX (FFX) or Gemcitabine/Nab-paclitaxel (GN) were eligible. They received hypofractionated A-RT (either 67.5Gy in 15 fractions or 75Gy in 25 fractions based on anatomy) with concurrent capecitabine followed by consideration of resection within 1-3 months. Primary endpoints included resectability (80% power to detect resectability improvement from 15% in historical controls to 30% with α = 0.05) and overall survival (OS) from A-RT. Secondary endpoints included safety of surgical resection after ablative RT using 90-day Clavien-Dindo Classification of adverse events (AE). Results: Between 6/2018 and 4/2022, 47 eligible participants underwent A-RT. Median age was 67 (range, 50-80) years, 24 (51%) were male with a median tumor size of 3.95 (1.6 – 8.3) cm and CA19-9 of 92 ( &lt; 1-1601) U/mL. Forty-four patients (94%) received at least 1 cycle of FFX with a median duration of chemotherapy (FFX or GN) of 3.5 months (1.0 – 9.4). Sixteen (34%) underwent a laparoscopy and 12 (26%) underwent a resection (Pancreaticoduodenectomy, N = 11; distal pancreatectomy, N = 1) at a median time of 3.2 months (1.9-16.9 months) from start of A-RT. The rate of resection satisfied our prespecified boundary of 11. R0 rate was 58.3%. Two-year OS from A-RT for the entire cohort was 38.9% (95% CI, 21.9 – 55.6%), including 37.1% (18.5 - 55.8%) in non-surgical and 39.4% (7.0- 72.1%) in surgical groups. There were no deaths within 90 days of surgery and 9 surgical AEs were recorded in 6 participants, including grade 1 (n = 1), grade 2 (n = 5), grade 3 (n = 2) and grade unknown (n = 1). Conclusions: In patients with LAPC and no metastatic disease after 3-6 months of chemotherapy, A-RT results in a favorable rate of resection without excess surgical toxicity. Promising 2-year OS rates were noted in both resected and non-resected patients. Clinical trial information: NCT03523312 .

Classification of Adverse Events in Adult Surgery.

Successful surgery combines quality (achievement of a positive outcome) with safety (avoidance of a negative outcome). Outcome assessment serves the purpose of quality improvement in health care by establishing performance indicators and allowing the identification of performance gaps. Novel surgical quality metric tools (benchmark cutoffs and textbook outcomes) provide procedure-specific ideal surgical outcomes in a subgroup of well-defined low-risk patients, with the aim of setting realistic and best achievable goals for surgeons and centers, as well as supporting unbiased comparison of surgical quality between centers and periods of time. Validated classification systems have been deployed to grade adverse events during the surgical journey: (1) the ClassIntra classification for the intraoperative period; (2) the Clavien-Dindo classification for the gravity of single adverse events; and the (3) Comprehensive Complication Index (CCI) for the sum of adverse events over a defined postoperative period. The failure to rescue rate refers to the death of a patient following one or more potentially treatable postoperative adverse event(s) and is a reliable proxy of the institutional safety culture and infrastructure. Complication assessment is undergoing digital transformation to decrease resource-intensity and provide surgeons with real-time pre- or intraoperative decision support. Standardized reporting of complications informs patients on their chances to realize favorable postoperative outcomes and assists surgical centers in the prioritization of quality improvement initiatives, multidisciplinary teamwork, surgical education, and ultimately, in the enhancement of clinical standards.

Inter-Rater Agreement of the Classification of Intraoperative Adverse Events (ClassIntra) in Abdominal Surgery.

Adverse events in surgical patients can occur preoperatively, intraoperatively, and postoperatively. Universally accepted classification systems are not yet available for intraoperative adverse events (iAEs). ClassIntra has recently been developed and validated as a tool for grading iAEs that occur between skin incision and skin closure irrespective of the origin, that is, surgery, anesthesia, or organizational. The aim of this study is to assess the inter-rater agreement of ClassIntra and assess its predictive value for postoperative complications in elective abdominal surgery. This study is a secondary use of data from the LAParotomy or LAParoscopy and ADhesiolysis (LAPAD) study, with detailed data on incidence and management of intra-operative and post-operative complications. Data were collected in a cohort of elective abdominal surgeries. Two teams graded all recorded events in the LAPAD study according to ClassIntra. Cohen Kappa coefficient was calculated to determine inter-rater agreement. Uni- and multivariable linear regression was used to assess the predictive value of the ClassIntra grades for postoperative complications. IAEs were rated in 333 of 755 (44%) surgeries by team 1, and in 324 of 755 (43%) surgeries by team 2. Cohen kappa coefficient for ClassIntra grades was 0.87 [95% confidence interval (CI) 0.84-0.90]. Discrepancies in grading were most frequent for intraoperative bleeding and adhesions' associated injuries. At least 1 postoperative complication was observed in 278 (37%) patients. The risk of a postoperative complications increased with every increase in severity grade of ClassIntra. Intraoperative hypotension [mean difference (MD) 23.41, 95% CI 12.93-33.90] and other organ injuries (MD 18.90, 95% CI -4.22 - 42.02) were the strongest predictors for postoperative complications. ClassIntra has an almost perfect inter-rater agreement for the classification of iAEs. An increasing grade of ClassIntra was associated with a higher incidence of postoperative complications. Discrepancies in grading related to common complications in abdominal procedures mostly consisted of intraoperative bleeding and adhesion-related injuries. Grading of interoperative events in abdominal surgery might further improve by consensus regarding the definitions of a number of frequent events.

Technical and Clinical Complications of Cosmetic Tattooing.

Cosmetic tattooing and medical tattooing of the face share basic principles and to some degree types and spectrum of technical and clinical complications known from decorative tattooing of other parts of the body. Cosmetic tattoos recently have grown exponentially in popularity in industrialized countries all over the world. The different complications and their clinical symptoms, pathophysiology, diagnosis, treatment, and prevention are analyzed versus culprit pigments and updated. Eyeliner tattooing is associated with special complications because of the subtle anatomy and the closeness to the eye, and the risk of meibomian gland damage. The spectrum of cosmetic tattoo complications includes early-onset complications (infections particularly with herpes simplex, healing issues, aesthetic and technical mistakes with regret), and late-onset complications (color fading and color shift, "blowout" pigment escape to surrounding skin, papules, nodules, granulomas associated with sarcoidosis, allergic reactions in lip tattoos with lichenoid dermatitis, eye irritation, and fibrosis and scaring especially after microblading); miscellaneous complications include severe burn sensation in tattoos during magnetic resonance imaging later in life. Corneal tattooing and subconjunctival/episcleral tattooing performed on medical indication by ophthalmologists, and for decoration by tattooists carry special risk of intraocular complications. It is recommended for the purpose of research harmonization that terms and diagnostic classification of tattoo adverse events follow the system introduced by the Tattoo Clinic of Copenhagen and already accepted in specialized tattoo clinics in other centers.

Application of "Human Factor Analysis and Classification System" (HFACS) Model to the Prevention of Medical Errors and Adverse Events: A Systematic Review.

Hospitals, as one of most important subsectors in human societies, are responsible for providing safe and effective medical services to clients. But sometimes these hospitals are the source of injury and death in patients by creating medical errors. In this systematic review study, the application of human factor analysis and classification system (HFACS) method in the classification of medical errors was investigated. Major electronic databases including Scopus, Web of Science, and MEDLINE were searched. All studies that investigated the application of HFACS method for coding, causation, and classification of medical errors and adverse events conducted from 2001 until February 2021 were included. A total of 108 articles were found. Due to duplication, 18 studies were removed from the review list. After reading the titles and abstracts, 50 of these publications were excluded because they had objectives different from this review. The remaining 40 publications were retrieved for further assessment. Of these, 28 publications were excluded because it did not meet the inclusion criteria. Finally, 12 articles remained for the final systematic review. We found that in 65% of the selected studies, preconditions for unsafe acts have been the major causal level of medical errors and adverse events. In the majority of the studies, communication and coordination, adverse mental states, physical environment, crew resource management, and technological environment have also been recognized as the most important causal categories in this study. As a result, to prevent medical errors and adverse events, the main focus should be on controlling the preconditions for unsafe acts including personnel factors, operator conditions, and environmental factors.

An Effective Approach for Multiclass Classification of Adverse Events Using Machine Learning

An Effective Approach for Multiclass Classification of Adverse Events Using Machine Learning

Automated Detection of Patient Harm: Implementation and Prospective Evaluation of a Real-Time Broad-Spectrum Surveillance Application in a Hospital With Limited Resources.

This study aimed to prospectively validate an application that automates the detection of broad categories of hospital adverse events (AEs) extracted from a basic hospital information system, and to efficiently mobilize resources to reduce the level of acquired patient harm. Data were collected from an internally designed software, extracting results from 14 triggers indicative of patient harm, querying clinical and administrative databases including all inpatient admissions (n = 8760) from October 2019 to June 2020. Representative samples of the triggered cases were clinically validated using chart review by a consensus expert panel. The positive predictive value (PPV) of each trigger was evaluated, and the detection sensitivity of the surveillance system was estimated relative to incidence ranges in the literature. The system identified 394 AEs among 946 triggered cases, associated with 291 patients, yielding an overall PPV of 42%. Variability was observed among the trigger PPVs and among the estimated detection sensitivities across the harm categories, the highest being for the healthcare-associated infections. The median length of stay of patients with an AE showed to be significantly higher than the median for the overall patient population. This application was able to identify AEs across a broad spectrum of harm categories, in a real-time manner, while reducing the use of resources required by other harm detection methods. Such a system could serve as a promising patient safety tool for AE surveillance, allowing for timely, targeted, and resource-efficient interventions, even for hospitals with limited resources.

1119. Covid-19 Mab Use in High-Risk Pediatric Patients

Abstract Background Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. Methods Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild COVID disease at Cincinnati Children’s Hospital Medical Center from 5/1/2020 through 3/1/2022 were identified retrospectively. In accordance with the FDA EUA, patients were eligible for monoclonal antibody administration if they were ≥12 years of age, weighed ≥40kg, and were at high risk of progressing to severe disease or hospitalization. Results Ninety-four patients received monoclonal antibody therapy, of which 14 (13.5%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (51.9%) received casirivimab-imdevimab, and 26 (25%) received sotrovimab. Ten patients (10.6%) experienced one or more adverse events. Of those, 2 (14.3%) received either bamlanivimab or bamlanivimab-etesivimab, 7 (12.9%) received casirivimab-imdevimab, and 1 (3.8%) received sotrovimab. Most common symptoms include rash, nausea, and throat irritation (table R1), the majority (90%) of which were mild, either self-resolving with infusion cessation (60%) or persistent but requiring no medical intervention (30%) (table R2). Of the patients who experienced adverse events, only 1 (10%) received medical intervention - epinephrine. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 15 patients (15.9%) required additional medical care for ongoing COVID symptoms (table R3). Eight (53.3%) of these were either hospitalized or received escalation of care while already in the hospital. Table R1. Infusion-related adverse events. Of note, several patients had more than one symptom. Table R2. Classification of adverse events by grade and monoclonal antibody. Grade I events are defined as mild and generally not bothersome. Grade II events are defined as moderate: bothersome, but not dangerous. Grade III events are defined as medically significant, but not immediately life-threatening, and often require medical intervention. Table R3. Patients who required additional medical care for ongoing COVID-19 symptoms within 90 days of receiving a monoclonal antibody. Conclusion Overall, monoclonal antibodies are safe, largely well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations. Disclosures Grant Schulert, MD, PhD, Novartis: Advisor/Consultant Paul Spearman, MD, CyanVac: Grant/Research Support|Meissa Vaccines: Grant/Research Support Grant C. Paulsen, MD, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lara A. Danziger-Isakov, MD, Ansun BioPharma: Contracted clinical research|Astellas: Contracted clinical research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted clinical research|Pfizer: Contracted clinical research|Takeda: Grant/Research Support|Takeda: Contracted clinical research|Viracor: Grant/Research Support.

Your clinical pharmacist can save your life, the impact of pharmacist's intervention.

Patient safety and adverse event analysis are of paramount importance in the management of patient medication, given the significant economic burden they place on a country's healthcare system. Medication errors fall into the category of preventable adverse drug therapy events and are therefore of key importance from a patient safety perspective. Our study aims to identify the types of medication errors associated with the medication dispensing process and to determine whether automated individual medication dispensing with pharmacist intervention significantly reduces medication errors, thereby increasing patient safety, compared to traditional, ward base medication dispensing (by a nurse). A prospective, quantitative, double-blind point prevalence study was conducted in three inpatient internal medicine wards of Komló Hospital in February 2018 and 2020. We analyzed data from comparisons of prescribed and non-prescribed oral medications in 83 and 90 patients per year aged 18 years or older with different diagnoses treated for internal medicine on the same day and in the same ward. In the 2018 cohort, medication was traditionally dispensed by a ward nurse, while in the 2020 cohort, it used automated individual medication dispensing with pharmacist intervention. Transdermally administered, parenteral and patient-introduced preparations were excluded from our study. We identified the most common types of errors associated with drug dispensing. The overall error rate in the 2020 cohort was significantly lower (0.9%) than in the 2018 cohort (18.1%) (p < 0.05). Medication errors were observed in 51% of patients in the 2018 cohort, i.e. 42 patients, of which 23 had multiple errors simultaneously. In contrast, in the 2020 cohort, a medication error occurred in 2%, i.e. 2 patients (p < 0.05). When evaluating the potential clinical consequences of medication errors, in the 2018 cohort, the proportion of potentially significant errors was 76.2% and potentially serious errors 21.4%, whereas in the 2020 cohort, only three medication errors were identified in the potentially significant category due to pharmacist intervention, which was significantly lower (p < 0.05). Polypharmacy was detected in 42.2% of patients in the first study and in 12.2% (p < 0.05) in the second study. Automated individual medication dispensing with pharmacist intervention is a suitable method to increase the safety of hospital medication, reduce medication errors, and thus improve patient safety.

Complications and Adverse Events of Gonadal Vein Embolization with Coils.

Background: The efficacy and safety of gonadal vein embolization (GVE) with coils in the treatment of pelvic venous disease (PeVD) has not been fully investigated, and the outcomes after GVE do not always meet expectations of both doctors and patients. The study was aimed at assessing the incidence and causes of the complications after GVE with coils in patients with PeVD. Methods: This retrospective cohort study included 150 female patients with PeVD who underwent GVE with coils in 2000-2020. A total of 4975 patients with chronic pelvic pain (CPP) were examined, of which 1107 patients had the PeVD-related CPP and 305 underwent surgical or endovascular interventions on the gonadal veins. Complication rates were evaluated 30 days after GVE and classified according to the Society for Interventional Radiology (SIR) adverse event classification system. The pain severity before and after GVE was assessed using a visual analogue scale (VAS). All patients underwent duplex ultrasound after GVE, while patients with persisting pain syndrome and suspected perforation of the gonadal vein were also evaluated using computed tomographic venography. Results: At 30 days after GVE, the CPP was decreased in 109 (72.6%) patients (from 8.2 ± 1.5 at baseline to 1.7 ± 0.8 scores, p = 0.0001) and persisted in 41 (27.4%) patients (mean change from 8.1 ± 0.7 at baseline to 7.8 ± 0.4 scores; p = 0.71). Post-embolic syndrome (PES) occurred in 22% of patients and was completely resolved in 1 month after GVE. The efficacy of GVE in the CPP relief after resolving PES was 94.6%. The GVE complications were identified in 52 (34.6%) patients. Minor complications included access-site hematoma (4%) and allergic reactions (1.3%), and major complications included protrusion of coils (5.3%), thrombosis of the parametrial/uterine veins (21.3%) and deep veins of the calf (2.7%). Conclusions: Gonadal vein embolization with coils in the treatment of PeVD is associated with the development of specific complications and adverse events. The most common complication was pelvic vein thrombosis. Post-embolization syndrome should be considered as an adverse event of this procedure.

Safety and Tolerability of Pirtobrutinib Monotherapy in Patients with B-Cell Malignancies Who Were Previously Intolerant to a Covalent BTK Inhibitor: Results from the Phase 1/2 BRUIN Study

Background: Covalent (c) Bruton tyrosine kinase inhibitors (BTKi) have markedly improved outcomes in several B-cell malignancies. Despite this progress, treatment discontinuation due to cBTKi intolerance remains a significant barrier, ultimately limiting efficacy. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, inhibits both wildtype and C481-mutant BTK with equal low nM potency, and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. Pirtobrutinib is well tolerated and has demonstrated promising efficacy in patients (pts) with poor-prognosis B-cell malignancies following prior therapy, including prior cBTKi (Mato et al. Lancet, 2021). Here, we evaluated the safety and tolerability of pirtobrutinib monotherapy specifically in pts with relapsed/refractory (R/R) B-cell malignancies who were intolerant to a prior cBTKi. Methods: For this analysis, pts with R/R B-cell malignancies enrolled to the multicenter phase 1/2 BRUIN study (NCT03740529) with documented intolerance to prior cBTKi were analyzed. Intolerance was defined as having discontinued any prior cBTKi due to persistent/recurrent adverse events as assessed by the physician, in the absence of progressive disease. Pirtobrutinib monotherapy was administered once daily in 28-day cycles until disease progression or discontinuation due to toxicity. Analyses were performed descriptively. Results: As of 31 January 2022, 566 pts (CLL/SLL, n=276; MCL, n=150; other NHL, n=140) treated with pirtobrutinib had received a prior cBTKi-containing regimen (prior lines of cBTKi containing regimens: 1 regimen, n=454; 2 regimens, n=93; ≥3 regimens, n=19). Among these 566 pts, 123 (22%) pts (CLL/SLL, n=79; MCL, n=20; other NHL, n=24) discontinued a prior cBTKi due to toxicity. This cBTKi intolerant cohort had received one or more of the following: ibrutinib (n=118, 96%), acalabrutinib (n=29, 24%), or zanubrutinib (n=6, 5%). At the time of enrollment to BRUIN, the median age for pts with prior cBTKi intolerance was 70 years (IQR: 64-75), and ECOG PS was 0, 1 and 2 in 58%, 35%, and 7% of pts, respectively. The most common adverse events (AEs) leading to prior cBTKi discontinuation were cardiac disorders [n=40, 33%; primarily atrial fibrillation (n=31, 25%)], infections (n=13, 11%), neutropenia (n=12, 10%), rash (n=12, 10%), bleeding/hemorrhage (n=11, 9%), arthralgias/myalgias (n=10, 8%), gastrointestinal disorders [n=9, 7%; diarrhea (n=6, 5%)], and fatigue (n=8, 7%). In these 123 pts with prior cBTKi intolerance, median time on pirtobrutinib treatment was 11 months (IQR, 4-18), with 63% (n=78) of pts remaining on pirtobrutinib at the time of data cut-off date. Of the 45 pts who had discontinued pirtobrutinib, the majority did so for progressive disease (62%, n=28). Overall, 9 (7%) pts discontinued pirtobrutinib for AEs which showed no particular pattern. Discontinuations related to pirtobrutinib occurred in 4 pts (1 each) including: myalgia, neutropenia, rash maculo-papular, and staphylococcal sepsis, and discontinuations unrelated to pirtobrutinib occurred in 5 pts (1 each) including: anxiety, abdominal pain and blood alkaline phosphatase increase, chronic respiratory failure, pneumonia, and COVID-19 and dyspnea. Treatment-emergent adverse events (TEAEs) on pirtobrutinib were manageable with dose reductions in 10 pts (8%) primarily due to neutropenia (n=6). The median pirtobrutinib relative dose intensity was 98% (IQR, 92-100). Pirtobrutinib TEAEs recurring in the same patient and same AE category as those leading to prior cBTKi intolerance are listed in the Table. Overall recurrence of a grade ≥3 pirtobrutinib TEAE in the same patient and category as that leading to prior cBTKi discontinuation was observed in only 13% (n=16/123) of pts. Conclusions: Pirtobrutinib monotherapy was safe and well-tolerated in the majority of pts with B-cell malignancies with documented intolerance to prior cBTKi therapy. Most pts did not experience high-grade recurrence of the AE that led to discontinuation of the prior cBTKi, and among those who did, none discontinued pirtobrutinib for this AE. Pirtobrutinib may be an important consideration to extend the benefit of BTK inhibition among pts with intolerance to a prior cBTKi. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immune-related generalised oedema – A new category of adverse events with immune checkpoint inhibitors

BackgroundGeneralised oedema was occasionally reported associated with immune checkpoint inhibitors (ICPIs). The purpose of this study is to investigate immune-related generalised oedema (ir-GE) drug related to ICPI, through frequency, clinical and pathological characteristics, and patient's outcome. Patients and methodsObjectives of the study were to report on ir-GE associated with ICPI to define frequency, associated signs and symptoms, pathological characteristics, severity, and response to corticosteroids. To be included in the study, adult patients had to have ir-GE related to ICPI with certain or likely link, without any other known causes of generalised oedema. The study design was observational, over the period 2014–2020, from pharmacovigilance databases in France, including the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC) registry. Calculation of the frequency of ir-GE was restricted to the prospective REISAMIC registry. ResultsOver 6633 screened patients, 20 had ir-GE confirmed drug related to ICPI. Based on the prospective REISAMIC registry, the frequency of ir-GE was 0.19% of ICPI-treated patients (3 cases out of 1598 screened patients). The 20 patients with ir-GE had a median (range) age of 62 (26–81) years, most frequent tumour types were melanoma (n = 9; 45%) and lung cancer (n = 6; 30%). The most frequent localisations of oedema were peripheral (n = 17; 85%), pleural (n = 13; 65%), and peritoneal (n = 10; 50%). Polyserositis was observed in 11 (55%) patients. The median (range) weight gain per patient was 9 (2–30) kg. Associated signs and symptoms met criteria for capillary leak syndrome (n = 4; 20%), sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) (n = 3; 15%), or subcutaneous autoimmune syndrome (n = 2; 10%). Corticosteroids were administered to 15 patients; of them, 10 (67%) improved clinically after corticosteroids. Based on CTCAEV5.0, the highest severity of ir-GE was grade ≥4 in 11 (55%) patients and four (20%) patients died due to ir-GE. ConclusionsGeneralised immune system-related oedema is a new category of adverse event with immune checkpoint inhibitors and is often associated with a life-threatening condition. The pathophysiology may in some cases be related to endothelial dysfunctions, such as SOS/VOD or capillary leak syndrome.

Drug Adverse Event Detection Using Text-Based Convolutional Neural Networks (TextCNN) Technique

With the rapid advancement in healthcare, there has been exponential growth in the healthcare records stored in large databases to help researchers, clinicians, and medical practitioner’s for optimal patient care, research, and trials. Since these studies and records are lengthy and time consuming for clinicians and medical practitioners, there is a demand for new, fast, and intelligent medical information retrieval methods. The present study is a part of the project which aims to design an intelligent medical information retrieval and summarization system. The whole system comprises three main modules, namely adverse drug event classification (ADEC), medical named entity recognition (MNER), and multi-model text summarization (MMTS). In the current study, we are presenting the design of the ADEC module for classification tasks, where basic machine learning (ML) and deep learning (DL) techniques, such as logistic regression (LR), decision tree (DT), and text-based convolutional neural network (TextCNN) are employed. In order to perform the extraction of features from the text data, TF-IDF and Word2Vec models are employed. To achieve the best performance of the overall system for efficient information retrieval and summarization, an ensemble strategy is employed, where predictions of the selected base models are integrated to boost the robustness of one model. The performance results of all the models are recorded as promising. TextCNN, with an accuracy of 89%, performs better than the conventional machine learning approaches, i.e., LR and DT with accuracies of 85% and 77%, respectively. Furthermore, the proposed TextCNN outperforms the existing adverse drug event classification approaches, achieving precision, recall, and an F1 score of 87%, 91%, and 89%, respectively.