Adverse Event Information Research Articles

Detection of Vaccine Adverse Events Before Package Insert Revisions Using a Japanese Spontaneous Reporting System.

The usefulness of disproportionality analysis for the pharmacovigilance of vaccines in the Japanese Adverse Drug Event Report (JADER) database is yet to be proven. This study aimed to verify whether significant disproportionality could be detected before adding new vaccine adverse event information to package inserts. Information on package insert revisions related to vaccine adverse drug events from January 2013 to March 2023 was extracted from the Pharmaceuticals and Medical Devices Agency website. This period was set as the maximum period for which early disproportionalities could be detected by the latest JADER database (April 2004 to December 2022). From JADER data, 15 revision histories (10 types of vaccines) of package inserts were identified, and 823,662 cases were obtained. Of the 15, 12 (80%) adverse events were identified as significant disproportionalities before package insert revisions were made. Nine of the 15 (60%) events were identified as significant disproportionalities earlier than at least 12 months. These findings suggest that the JADER database may detect vaccine adverse events earlier than package insert revisions, indicating its usefulness for the safety surveillance of vaccines.

Statistical methods for exploring spontaneous adverse event reporting databases for drug-host factor interactions

BackgroundDrug toxicity does not affect patients equally; the toxicity may only exert in patients who possess certain attributes of susceptibility to specific drug properties (i.e., drug-host interaction). This concept is crucial for personalized drug safety but remains under-studied, primarily due to methodological challenges and limited data availability. By monitoring a large volume of adverse event reports in the postmarket stage, spontaneous adverse event reporting systems provide an unparalleled resource of information for adverse events and could be utilized to explore risk disparities of specific adverse events by age, sex, and other host factors. However, well-formulated statistical methods to formally address such risk disparities are currently lacking.MethodsIn this paper, we present a statistical framework to explore spontaneous adverse event reporting databases for drug-host interactions and detect risk disparities in adverse drug events by various host factors, adapting methods for safety signal detection. We proposed four different methods, including likelihood ratio test, normal approximation test, and two tests using subgroup ratios. We applied our proposed methods to simulated data and Food and Drug Administration (FDA) Adverse Event Reporting Systems (FAERS) and explored sex-/age-disparities in reported liver events associated with specific drug classes.ResultsThe simulation result demonstrates that two tests (likelihood ratio, normal approximation) can detect disparities in adverse drug events associated with host factors while controlling the family wise error rate. Application to real data on drug liver toxicity shows that the proposed method can be used to detect drugs with unusually high level of disparity regarding a host factor (sex or age) for liver toxicity or to determine whether an adverse event demonstrates a significant unbalance regarding the host factor relative to other events for the drug.ConclusionThough spontaneous adverse event reporting databases require careful data processing and inference, the sheer size of the databases with diverse data from different countries provides unique resources for exploring various questions for drug safety that are otherwise impossible to address. Our proposed methods can be used to facilitate future investigation on drug-host interactions in drug toxicity using a large number of reported adverse events.

Inclusion of Participants with CKD and Other Kidney-Related Considerations during Clinical Drug Development: Landscape Analysis of Anticancer Agents Approved from 2015 to 2019.

The US Food and Drug Administration has prioritized efforts to expand availability of therapies, including anticancer agents, for patients with CKD. US Food and Drug Administration Guidance recommends inclusion of study participants with CKD in clinical trials, improving pharmacokinetic characterization in people with decreased GFR, and using contemporary GFR assessment methods during drug development. We performed a landscape analysis of anticancer agents approved from 2015 to 2019 to evaluate inclusion of study participants with CKD and GFR assessment methods used during drug development and subsequent translation to kidney-related safety and dosing data in product labeling. Oncology drugs approved from 2015 to 2019 and associated pivotal trials were identified. We evaluated inclusion of study participants with CKD in pivotal trials and pharmacokinetic analyses, investigated GFR assessment methods used for pivotal trial eligibility and renal pharmacokinetic analyses, and identified kidney-related adverse drug event and dosing information. A total of 55 drugs and 74 pivotal trials were included. Of the pivotal trials, 95% contained kidney-related eligibility criteria, including 68% with GFR-based eligibility. The median lower limit of GFR required for inclusion was 45 ml/min or ml/min per 1.73 m 2 . Pharmacokinetic analyses were performed in CKD stages 4-5 and hemodialysis for only 29% and 6% of drugs, respectively. Estimated creatinine clearance was used in over 60% and 80% of pivotal trials and pharmacokinetic analyses, respectively. Reporting of kidney-related adverse drug events was highly variable. Product labeling for 49% of drugs contained no kidney dosing information. Study participants with CKD continue to be excluded from anticancer drug development, and GFR estimation in pivotal trials and renal pharmacokinetic analyses remains imprecise and heterogeneous. Furthermore, kidney-related safety and dosing information is scarcely and inconsistently presented.

Data mining techniques for detecting signals of adverse drug reaction of cardiac therapy drugs based on Jinan adverse event reporting system database: a retrospective study

ObjectiveCardiac therapy drugs are widely used in the treatment of heart disease. However, the concern regarding adverse events (AEs) of cardiac therapy drugs have been rising. This study aimed to...

Off-Label Magnetic Resonance Imaging (MRI) in Patients with Persistent Pain with Spinal Cord Stimulators: A Case Series.

Advances in spinal cord stimulator (SCS) technology and increasing prevalence of magnetic resonance imaging (MRI) diagnostic testing require empirical evidence describing the presence of MRI-related SCS adverse events related to off-label use of imaging. MRI safety recommendations vary based on the type of stimulator used with scant availability regarding adverse events associated with off-label MRI use. The aim of this case series is to describe the type and frequency of adverse events associated with off-label MRI use in patients with implanted SCSs. Convenient samples of records of patients who had SCS and subsequently underwent MRI were included. Descriptive data including patient demographics, stimulator information, and frequency of adverse events were described. Sixty-nine individuals with implanted SCSs were included. The total number of scans was 78. Sixty-two percent of the sample was female. Over 92% of the MRI scans were considered off-label and the overall adverse event rate for off-label use was 9.72%. No serious adverse events were reported. Seven clinical adverse events were reported, all of which were related to the spinal cord stimulation and resolved. This case series demonstrates that individuals implanted with SCSs experienced no serious adverse events associated with off-label MRI use. While these results represent a convenient sample, they provide important preliminary information about using MRI when medically necessary for patients with older spinal cord stimulator models. Specifically, these data demonstrate that the rate of observed adverse events related to MRI was low and suggest that the benefits of acquiring these images for pain management may outweigh the risks of not acquiring MRI for appropriate pain management.

Beyond fear: A longitudinal investigation of emotions and risk of a vasovagal reaction in first-time whole-blood donors.

Fear is a recognized predictor of vasovagal reactions (VVRs) in blood donors. However, less is known about the role of other emotions, including positive emotions, that donors might experience. The aim of this study was to identify the emotions experienced in center that predict onsite VVRs, and to determine at what point during the donation appointment, the experience of these emotions is most influential. A sample of 442 first-time whole-blood donors (57.7% female; mean ± SD age 30.7 ± 11.7 years) completed a survey in the waiting area and before venepuncture in the donation chair to assess their current emotional experience. The survey data were matched with routinely-collected demographic, donation, and donor adverse event information. A generalized estimating equations model was used to identify emotions associated with the occurrence of a VVR. A total of 56 (12.7%) participants experienced a VVR. The occurrence of a VVR was significantly associated with lower love/closeness/trust (OR: 0.53, 95%CI: 0.34-0.82) and higher scared/fearful/afraid (OR: 1.96, 95%CI: 1.18-3.25) states. Significant interaction effects suggested that the effect of scared/fearful/afraid decreased while stressed/nervous/overwhelmed increased from the waiting area to before venepuncture on the likelihood of a VVR. To effectively reduce donor VVR risk, blood collection agencies need to address a broader range of emotions at different points during the donation process.

Reporting of the safety from allergic rhinitis trials registered on ClinicalTrials.gov and in publications: An observational study

BackgroundIncomplete and inconsistent reporting of adverse events (AEs) through multiple sources can distort impressions of the overall safety of the medical interventions examined as well as the benefit-risk relationship. We aimed to assess completed allergic rhinitis (AR) trials registered in ClinicalTrials.gov for completeness and consistency of AEs reporting comparing ClinicalTrials.gov and corresponding publications.MethodsWe retrospectively examined completed randomised controlled trials on AR registered in ClinicalTrials.gov on or after 9/27/2009 to trials updated with results on or before 12/31/2021 along with any corresponding publications. Complete reporting of AEs in ClinicalTrials.gov were summarised in tables describing AE information, and complete reporting in publications was an explicit statement of serious AE, death or other AE. Difference in completeness, number, or description of AEs between ClinicalTrials.gov and publication was classified as inconsistent reporting of AEs.ResultsThere were 99 registered trials with 45 (45.5%) available publications. All published trials completely reported AEs in ClinicalTrials.gov, and 21 (46.7%) in publications (P < .001). In 43 (95.6%) publications, there was at least one inconsistency in the reporting of AEs (P < .001). 8 (17.8%) publications had different number of serious AEs (P = .003), 36 (80.0%) of other AEs (P < .001) while deaths reporting was inconsistent in 8 (57.1%) publications (P = .127).ConclusionThe reporting of AEs from AR trials is complete in ClinicalTrials.gov and incomplete and inconsistent in corresponding publications. There is a need to improve the reporting of AEs from AR trials in corresponding publications, and thus to improve patient safety.

Mid-term Results of the Treatment of Isolated Dissection of the Celiac Artery: A Comparative Analysis of Endovascular Versus Conservative Therapy

Objectives: Endovascular treatment (EVT) is an alternative method used to treat isolated dissection of the celiac artery (IDCA). However, only a few mid-term results have been reported. This study aimed to analyze and compare the outcomes of endovascular and non-operative therapies for IDCA. Methods: Data from a cohort of consecutive IDCA patients enrolled in the study hospital between April 2012 and September 2020 were retrospectively reviewed. Demographic information, imaging features, treatment modalities, and follow-up results of celiac artery remodeling and adverse events were collected and analyzed. Results: A total of 87 patients were enrolled in the study. Stents were deployed in 68 patients, and non-operative treatment (blood pressure control and pain management) was continued in the remaining 19 patients who did not receive stenting; among these 19 patients, EVT failed in 6. The mean follow-up period was 37.3 (range, 10–85 months) and 44.0 (range, 9–80 months) months in the EVT and non-operative groups, respectively. During follow-up, the overall complete remodeling (absence of residual dissection with no false lumen or no intramural thrombus) rate was significantly higher in the EVT group than in the non-operative group (87.3% vs 7.1%, p<0.001). The incomplete remodeling (improved true lumen with malabsorption or partial thrombosis of the false lumen) rate was not significantly different between the EVT and non-operative groups (6.3% vs 14.3%; p=0.2984). Meanwhile, the adverse event-free survival rates were 89.0%, 67.0%, and 67.0% at 1, 3, and 5 years, respectively, in the EVT group compared with 39.7% and 29.8% at 1 and 3 years in the non-operative group (p<0.0001). Conclusions: EVT for IDCA may be considered an effective management option with a favorable clinical success rate, an encouraging complete remodeling rate, and a satisfactory adverse event-free survival rate. However, further evaluation with a long-term follow-up is required. Clinical Impact Endovascular intervention for isolated dissection of the celiac artery has attracted inadequate attention. In this retrospective study with comparative analysis of endovascular versus conservative therapy for isolated dissection of the celiac artery patients, a better complete remodeling rate and a higher adverse event-free survival rate were observed in the endovascular treatment (EVT) group during follow-up, indicating that EVT could be an effective management option for isolated dissection of the celiac artery.

Step-up titration dosing (TD) of carfilzomib (K) is associated with prolonged duration of therapy and improved treatment outcomes compared to standard dosing (SD) in patients with multiple myeloma (MM).

e20016 Background: K is a 2nd-generation proteasome inhibitor (PI) approved for the treatment of multiple myeloma (MM). K-based regimens are associated with higher rates of CV toxicity compared with other PIs. We conducted a retrospective analysis to assess incidence of CV adverse events (AE) and outcomes of MM patients (pts) treated with K using a step-up TD schedule compared to SD protocol. Methods: A retrospective chart review was performed of MM pts treated with K at The Ohio State University Comprehensive Cancer Center (OSUCCC) from 1/1/13 to 9/1/19. Pt demographics, disease and K-related characteristics, CV AE, and follow-up information were collected. Pts were excluded if treated at both local center and at OSUCCC, not K-naïve when receiving treatment at OSUCCC, received a single dose of K while inpatient with no intent to continue treatment outpatient, or had a treatment plan entered but never received it. Results: Of the 166 pt charts analyzed, 36 were treated using a TD method (ex. step-wise C1D1 20mg/m2, C1D8 27mg/m2, C1D15 36mg/m2, for goal C2D1 56mg/m2 onwards) and 130 pts were treated using a standard dosing method (ex. C1D1 20mg/m2 and C1D8 56mg/m2 onwards). Pre-existing CV risk factors were similar between the two groups. There was a slight difference in baseline renal function (TD: median CrCl 94mL/min, SD: 76mL/min; p=0.01) and prior PI use (TD: 86.1%, SD: 95%; p=0.048) between the two groups. In pts treated with TD, hypertension (HTN) developed earlier compared with SD (p=0.02). There was a lower incidence of onset of dyspnea in the TD group compared to SD group (16.7% vs 36.2%, respectively; p=0.03). There were no differences in incidence of HTN, congestive heart failure, ischemic heart disease, arrythmias, or pulmonary HTN. The median number of cycles administered to titrated pts was 7 (range: 2-56) compared to 3 (range: 1-44) for standard pts (p&lt;0.001). There was no statistical difference in CV AE being the cause for treatment discontinuation between the two groups. The overall response rate (ORR) was higher in the TD group compared to the SD group (63.9% vs 42.8%, respectively; p=0.04). Five-year overall survival (OS) was improved in patients treated with TD than with SD (43.8% vs 17.5%, respectively; p&lt;0.001). By multivariable analysis, TD was associated with improved OS compared to SD (HR 0.47; 95% CI 0.29-0.77-3.58; P=0.003). Conclusions: A simple modification of K titration dosing improved the tolerability of MM therapy without compromising efficacy. Although there were no differences in AE being the cause of treatment discontinuation between the two groups, an improvement in duration of therapy, ORR, and OS was observed in the TD group. As a result, TD is the standard-of-care dosing for MM pts treated with K at the OSUCCC. Prospective trials are needed to confirm the safety and efficacy of this dosing regimen.

Inadequate reporting quality of registered genome editing trials: an observational study

BackgroundTo assess registration completeness and safety data of trials on human genome editing (HGE) reported in primary registries and published in journals, as HGE has safety and ethical problems, including the risk of undesirable and unpredictable outcomes. Registration transparency has not been evaluated for clinical trials using these novel and revolutionary techniques in human participants.MethodsObservational study of trials involving engineered site-specific nucleases and long-term follow-up observations, identified from the WHO ICTRP HGE Registry in November 2020 and two comprehensive reviews published in the same year. Registration and adverse events (AEs) information were collected from public registries and matching publications. Published data were extracted in May 2021.ResultsAmong 81 eligible trials, most were recruiting (51.9%) phase 1 trials (45.7%). Five trials were withdrawn. Most trials investigated CAR T cells therapies (45.7%) and used CRISPR/Cas9 (35.8%) ex vivo (88.9%). Among 12 trials with protocols both registered and published, eligibility criteria, sample size, and secondary outcome measures were consistently reported for less than a half. Three trials posted results in ClinicalTrials.gov, and one reported serious AEs.ConclusionsIncomplete registration and published data give emphasis to the need to increase the transparency of HGE trials. Further improvements in registration requirements, including phase 1 trials, and a more controlled publication procedure, are needed to augment the implementation of this promising technology.

The evidence behind the use of LASER for genitourinary syndrome of menopause, vulvovaginal atrophy, urinary incontinence and lichen sclerosus: A state-of-the-art review.

In recent years, LASER has been introduced as a minimally invasive treatment for a broad range of vaginal and vulvar symptoms and diseases. However, the efficacy and safety of vaginal and vulvar LASER has continuously been questioned. The aim of this study is to create an overview of the current literature and discuss the controversies within the use of LASER for genitourinary syndrome of menopause, vulvovaginal atrophy, urinary incontinence and lichen sclerosus. A search string was built in PubMed. The search was commenced on August 25, 2021 and closed on October 27, 2021. Two authors screened the studies in Covidence for inclusion according to the eligibility criteria in the protocol. The data were extracted from the studies and are reported in both text and tables. This review included 114 papers, of which 15 were randomized controlled trials (RCTs). The effect of LASER as a vaginal treatment was investigated for genitourinary syndrome of menopause in 36 studies (six RCTs), vulvovaginal atrophy in 34 studies (four RCTs) and urinary incontinence in 30 studies (two RCTs). Ten studies (three RCTs) investigated the effect of vulvar treatment for lichen sclerosus. Half of the included RCTs, irrespective of indication, did not find a significant difference in improvement in women treated with vaginal CO2 or Er:YAG LASER compared with their respective controls. However, most non-comparative studies reported significant improvement after exposure to vaginal or vulvar LASER across all indications. Included studies generally had a short follow-up period and only a single RCT followed their participants for more than 6 months post treatment. Adverse events were reported as mild and transient and 99 studies including 51 094 patients provided information of no serious adverse events. In conclusion, this review found that the effect of vaginal and vulvar LASER decreases with higher study quality where potential biases have been eliminated. We therefore stress that all patients who are treated with vaginal or vulvar LASER should be carefully monitored and that LASER for those indications as a treatment should be kept on a research level until further high-quality evidence is available.

Safety of Global SARS-CoV-2 Vaccines, a Meta-Analysis.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines were developed in only a short amount of time and were widely distributed. We conducted this meta-analysis to understand the safety of SARS-CoV-2 vaccines. (2) Methods: We searched the corresponding literature published from 1 January 2020 to 20 October 2021. Information of adverse events (AEs) of each selected work was collected. The quality and bias of studies was evaluated, and meta-analysis was carried out by using Stata 17.0. (3) Results: Totally, 11,451 articles were retrieved, and 53 of them were included for analysis. The incidence rate of AEs was 20.05–94.48%. The incidence rate of vascular events increased after viral vector vaccination, while the incidence rate of vascular events decreased after mRNA vaccination. Viral vector vaccine had a higher AE rate compared to mRNA vaccines and inactivated vaccines. In most circumstances, the incidence of AEs was higher in older people, female and after the second dose. The sensitivity of meta-analysis was acceptable; however, the literature was subject to a certain publication bias. (4) Conclusions: The safety of SARS-CoV-2 vaccines was acceptable. The incidence of allergic symptoms and cardiovascular and cerebrovascular symptoms was low. Viral vector vaccine had a higher risk of leading to thrombosis events. The understanding of SARS-CoV-2 vaccine AEs should be enhanced, so as to promote the vaccination.

Adverse drug events in AYUSH interventions for cervical and lumbar spondylosis

Abstract Introduction: The prevalence of musculoskeletal disorders ranges between 20%–33% and also varies by age and diagnosis. In India, low back and neck pain are important leading contributors to the disability burden irrespective of gender. Many Ayurveda, Yoga and naturopathy, Unani, Siddha and Sowa-rigpa and Homeopathy (AYUSH) interventions used for the treatment of cervical and lumbar spondylosis conditions due to its availability and accessibility. Even though it's widely practiced, there is no documentation of adverse events of AYUSH interventions for cervical and lumbar spondylosis. The primary objective of this systematic review is to synthesize evidence of adverse events attributable to pharmacological and non-pharmacological AYUSH interventions for cervical and lumbar spondylosis. Methods: We will conduct a systematic search in all standard biomedical databases and AYUSH system portals to identify and retrieve both the published and unpublished research articles. We will include all study designs such as the randomized and non-randomized controlled trials (RCTs), cross-sectional studies, prospective and retrospective cohort studies, case-control studies, case series, and case studies. They should have reported the Adverse events of AYUSH systems of interventions for cervical and lumbar spondylosis. Using predefined search strategy with suitable medical subject headings terms and field terms, we will retrieve all the relevant articles from PubMed, Embase, Scopus, Google Scholar, ProQuest, AYUSH research portal, Digital Helpline for Ayurveda Research Articles, Shodhganga and reports of National Pharmacovigilance Centres. We will include the articles that are in English language. Data synthesis will be conducted using meta-analysis. Results: The systematic review will provide adverse events information attributable to pharmacological and non-pharmacological AYUSH interventions for cervical and lumbar spondylosis. Discussion: We will generate a report on the frequency and types of adverse drug events among patients with lumbar and cervical spondylosis treated with AYUSH system and characteristics of adverse event such as type and nature of medications. This study may help Indian AYUSH pharmacovigilance centres to develop methods to improve quality of data on adverse events. Systematic review registration number: PROSPERO CRD42020167433 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020167433)

Clinical Characteristics and Perioperative Complication Profiles of COVID-19-Positive Patients Undergoing Hip Fracture Surgery.

Introduction:The coronavirus 2019 (COVID-19) pandemic disease has imposed an unprecedented degree of stress on healthcare systems. This study aimed to understand whether COVID-19 positivity is associated with an increased risk of adverse outcomes after geriatric hip fracture surgery.Methods:From a national administrative claims data set, patients who underwent hip fracture surgery from April 1, 2020, to December 1, 2020 were selected for analysis. COVID-19–positive status was assessed by the emergency International Classification of Diagnoses, 10th Revision, COVID-19 code within 2 weeks before the surgery. Demographic, comorbidity, and 30-day postoperative adverse event information were extracted. Logistic regression before and after 10:1 propensity matching was performed to identify patient risk factors associated with the occurrence of postoperative adverse events.Results:Of 42,002 patients who underwent hip fracture surgery, 678 (1.61%) were identified to be positive for COVID-19 infection. No significant differences in age, sex, and procedure type were found between COVID-19–positive and COVID-19–negative groups, but the COVID-19–positive patients demonstrated a higher incidence of several comorbidities. These differences were no longer significant after matching. After matching, the COVID-19–positive group had a higher incidence of any, serious, and minor adverse events (P < 0.001 for all). Controlling for preoperative variables, COVID-19 positivity was associated with an increased risk of experiencing any adverse events (odds ratio [OR] = 1.62, 95% confidence interval [95% CI] = [1.37 to 1.92], P < 0.001), serious adverse events (OR = 1.66, 95% CI = [1.31 to 2.07], P < 0.001), and minor adverse events (OR = 1.59, 95% CI = [1.34 to 1.89], P < 0.001).Discussion:After matching and controlling for confounding variables, COVID-19–positive hip fracture patients had increased odds of multiple postoperative events. Clinicians caring for this vulnerable geriatric population should be mindful of this risk to improve the care for these patients during the ongoing global pandemic.

United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA).

Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels.

Safety and Effectiveness of Intravenous Artesunate for Treatment of Severe Malaria in the United States-April 2019 Through December 2020.

Severe malaria can be deadly and requires treatment with intravenous artesunate (IVAS). The Centers for Disease Control and Prevention provided IVAS starting 1 April 2019 for all patients with severe malaria in the United States. This study describes the safety and effectiveness of IVAS in these patients. Patients meeting criteria for severe malaria April 2019-December 2020 who received IVAS were included. Demographic, clinical, laboratory, adverse event, and outcome information were collected. Clinical presentation, time to reach 1% and 0% parasitemia, adverse events, and death were described using proportions, medians, interquartile range (IQR), and tests of significance for differences in proportions. Of 280 patients included, the majority were male (61.4%), Black (75.0%), with a median age of 35 years (IQR: 15.8-53.9). Most had Plasmodium falciparum (83.6%) with median parasitemia of 8.0% (IQR: 4.6-13.2). Of 170 patients with information, 159 (93.5%) reached ≤1% parasitemia by the third IVAS dose with a median time of 17.6 hours (IQR: 10.8-28.8), and 0% parasitemia in a median of 37.2 hours (IQR 27.2-55.2). Patients with parasite densities >10% and those requiring adjunct therapy had significantly higher parasite clearance times. Adverse events associated with IVAS were reported in 4.8% (n = 13 of 271). Eight patients had post-artesunate delayed hemolysis that resolved. There were 5 (1.8%) deaths, all attributable to severe malaria. IVAS is a safe and effective drug for the treatment of severe malaria in the United States; timely administration can be lifesaving.

The characteristics and trend of adverse events following immunization reported by information system in Jiangsu province, China, 2015\u20132018

ObjectiveAdverse events following immunization is an important factor influencing public trust in vaccination. Publicizing its incidence timely can increase public trust. The aim of this study is to describe the incidence and characteristics of adverse events following immunization in Jiangsu province of China from 2015 to 2018.MethodsAll information of adverse events following immunization (AEFIs) was gained from Jiangsu Province Vaccination Integrated Service Management Information System. The reported AEFI trend was analyzed using Chi-square test.ResultsA total of 77,980 AEFI cases were reported through the AEFI system; Among which, 77,731 were classified as non-serious AEFI cases and 249 were serious AEFI cases. The male to female ratio was 1.31:1, cases less than 7 years old accounted for 97.7%. The total estimated AEFI rate was 62.70/100,000 doses. By severity, 60.75/100,000, 4.46/100,000 and 0.11/100,000 AEFI cases were common vaccine reaction, rare vaccine reaction, and serious rare vaccine reaction, respectively. The top two serious AEFI were thrombocytopenic purpura and febrile. The incidence rates showed the increasing trend and the linear trend of the increasing incidence rates passed the significant test at 0.05 levels.ConclusionThe sensitivity of AEFI monitoring in Jiangsu Province is increasing and higher than the national average and most countries. The majority of AEFI cases were common adverse reactions, while the serious vaccine reactions caused by vaccines were extremely low. To elevate the sensitivity of AEFI surveillance may reduce the incidence of developing serious AEFI cases.

Prognostic value of copeptin in patients with acute myocardial infarction treated with percutaneous coronary intervention: a prospective cohort study.

BackgroundIschemic myocardial injury leads to neurohormonal system activation and increased release of copeptin. Although diagnostic value of copeptin has been widely described, data on its prognostic performance in patients with myocardial infarction is inconclusive. The aim of this study was to asses if elevated copeptin concentration provides prognostic information for long-term adverse cardiac events in a cohort of first acute myocardial infarction patients treated with percutaneous coronary intervention.MethodsCopeptin concentration was assessed in a cohort of 100 consecutive patients (39% women; mean age 63±7 years) presenting with first acute myocardial infarction and subjected to percutaneous coronary intervention. Samples were collected at the time of admission and on the 4th/5th day of hospitalisation. All patients were followed-up prospectively for 12 months for the occurrence of major adverse cardiovascular events defined as reinfarction, unscheduled coronary revascularisation and all-cause death.ResultsElevated copeptin concentration on the 4th/5th day of hospitalisation was identified as a predictor of major adverse cardiovascular events (P=0.0445). The increase between copeptin level on admission and on day 4th/5th was associated with the requirement for unscheduled coronary revascularisation in receiver operating characteristics (ROC) analysis (AUC =0.639; 95% CI: 0.504–0.773; P=0.0430). In a multivariate analysis, copeptin concentration on the 4th/5th day of hospitalisation and left ventricular ejection fraction assessed by transthoracic echocardiography, were the only predictors for major adverse cardiac events during follow-up (P=0.024 and P=0.001, respectively).ConclusionsCopeptin seems to be a prognostic marker in patients with first myocardial infarction treated with percutaneous coronary intervention.

Preoperative ventricular late potentials and the risk of adverse events in patients with obstructive hypertrophic cardiomyopathy undergoing septal myectomy.

Ventricular late potentials (VLPs) detected by signal-averaged electrocardiogram are considered as an indicator of electrical instability in diseased myocardium. Little information exists about the VLPs and their effects on clinical prognosis in patients with obstructive hypertrophic cardiomyopathy (OHCM) undergoing septal myectomy. Patients with OHCM who underwent septal myectomy from January 2019 to December 2019 were prospectively enrolled. All patients underwent signal-averaged electrocardiogram. Patients were subsequently divided into two groups based on the presence or absence of VLPs. All patients were followed up after surgery to obtain information of survival status and adverse events, including all-cause mortality, congestive heart failure requiring hospitalization, new-onset stroke, and unexplained syncope. In total, 128 patients (47.5±12.8 years, 57.8% male) were enrolled. There were 21 (16.4%) individuals in the VLPs-positive group and 107 (83.6%) individuals in the VLPs-negative group. There were no statistically significant differences in non-sustained ventricular tachycardia and late gadolinium enhancement on cardiovascular magnetic resonance images between the two groups. Eight adverse events were reported at the 14.9±4.1 months follow-up. The rates of adverse events in groups of VLPs-positive and VLPs-negative were 23.8% (5/21) and 2.8% (3/107) of cases, respectively. These events included three patients hospitalized for heart failure, two who experienced ischemic strokes, and three with unexplained syncope, respectively. Patients in the VLPs-positive group had a higher risk of adverse events than those in the VLPs-negative group (P<0.001). The presence of positive VLPs (hazard ratio =9.095, 95% confidence intervals: 2.080-39.776, P=0.003) was a strong independent risk factor of adverse events by multivariate Cox regression analysis. Cardiac function Class III or IV, as defined by the New York Heart Association classification, was also an independent risk factor of adverse events (hazard ratio =13.756, 95% confidence intervals: 1.667-113.510, P=0.015). VLPs may increase the risk of adverse events in patients with OHCM after septal myectomy, which may be used as a screening test for further risk stratification.

Adverse events in non-small cell lung cancer patients receiving immune checkpoint inhibitors: A single center, real-world study in China.

e21081 Background: Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in non-small cell lung cancer (NSCLC), whereas they also can cause various adverse events (AEs). We reported the incidences, spectrum and severity of AEs in real-life practice after the approval of ICIs in Chinese NSCLC patients. Methods: In this single center, retrospective study, anonymized electronic medical record data were collected from the dedicated lung cancer immunotherapy outpatient clinic of Guangdong Provincial People’s Hospital through the LinkDoc database. The patients (≥18 years old) with pathologically diagnosed metastatic NSCLC who receiving ICIs between 1 June 2019 and 31 December 2020 were included. The immune-related adverse events (irAEs) were diagnosed and assessed by oncologists. All AEs were classified and graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE V5.0). Results: A total of 203 patients with a median age of 60.5 years were included in this study. Most patients were male (81.8%), smokers (49.8%), non-squamous histological type (51.7%). 61.1% of patients visited the outpatient clinic more than once. Pembrolizumab and Nivolumab were given to the majority of patients (80.8%). 114 patients (56.2%) received single-agent and 89 patients (43.8%) received combination therapy. The median duration of ICIs therapy was 271.2 days. In our study, 68.0% of patients experienced any-grade AEs, and 19.7% experienced grade≥3 AEs. The most commonly AEs were abnormal laboratory findings (57.1%), blood and lymphatic system disorders (25.1%), and respiratory disorders (19.7%). All of 93 patients (45.8%) experienced irAEs and 6 patients (8.4%) developed grade≥3 irAEs. The most frequent irAEs included blood and lymphatic system disorders (25.1%), hepatobiliary disorders (17.7%), and cardiac disorders (9.9%). Cough (3.4%), sputum (2.5%), and pain (2.0%) were the most frequent AEs which received treatment. Conclusions: Our results showed 68.0% and 45.8% patients experienced AEs and irAEs, respectively. The AEs and irAEs were primarily low grade. This study also demonstrated the information of AEs could be well collected and managed through our dedicated lung cancer immunotherapy outpatient clinic. [Table: see text]