-
Current Pharmacology Reports Jun 2016Compared with controlled terminologies (, MedDRA, CTCAE, and WHO-ART), the community-based Ontology of AEs (OAE) has many advantages in adverse event (AE)...
Compared with controlled terminologies (, MedDRA, CTCAE, and WHO-ART), the community-based Ontology of AEs (OAE) has many advantages in adverse event (AE) classifications. The OAE-derived Ontology of Vaccine AEs (OVAE) and Ontology of Drug Neuropathy AEs (ODNAE) serve as AE knowledge bases and support data integration and analysis. The Immune Response Gene Network Theory explains molecular mechanisms of vaccine-related AEs. The OneNet Theory of Life treats the whole process of a life of an organism as a single complex and dynamic network (, OneNet). A new "OneNet effectiveness" tenet is proposed here to expand the OneNet theory. Derived from the OneNet theory, the author hypothesizes that one human uses one single genotype-rooted mechanism to respond to different vaccinations and drug treatments, and experimentally identified mechanisms are manifestations of the OneNet blueprint mechanism under specific conditions. The theories and ontologies interact together as semantic frameworks to support integrative pharmacovigilance research.
PubMed: 27458549
DOI: 10.1007/s40495-016-0055-0 -
Journal For Immunotherapy of Cancer Jul 2021Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation....
BACKGROUND
Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation. However, less is known about adverse effects of these drugs in the eye.
METHODS
Two adverse event databases were retrospectively reviewed. The two databases consisted of a routine adverse event database and a serious adverse event database of expeditiously submitted reports. Patients with any malignancy who had ocular adverse events while on PD-1/PD-L1 inhibitor treatment were included. Patients received nivolumab, pembrolizumab, atezolizumab or durvalumab alone or in combination with other anticancer agents per each trial's protocol. Databases were queried up to May 19, 2020.
RESULTS
In the routine adverse event database, 272 adverse events from 213 patients were reported and in the serious adverse event reporting database, 59 ocular adverse events from 47 patients were reported. A lower estimate of the prevalance from the routine adverse event database showed 259/7727 patients on study treatment arms reporting ocular adverse events (3.3% prevalence). Excluding trials that do not report lower grade adverse events to the routine adverse event database results in a higher end estimate of 242/3255 patients on study treatment arms reporting ocular adverse events (7.4% prevalence). Ocular events occurred early after drug initiation (routine database: median 6 weeks, IQR 0-16, serious adverse events database: median 11 weeks, IQR 6-21). The median Common Terminology Criteria for Adverse Events grade was grade 1 (mild) (IQR 1-2) and grade 2 (moderate) (IQR 2-3) for the routine database and the serious adverse events database, respectively. In-depth analysis of the serious adverse event reports revealed varying degrees of clinical workup, with 30/47 patients (64%) receiving ophthalmological evaluation and 16/47 (34%) of patients having to delay or discontinue treatment. However, 16/47 (34%) patients experienced resolution and 14/47 (30%) patients experienced at least some improvement.
CONCLUSIONS
This is one of the largest analyses of ocular adverse events in patients treated with PD-1/PD-L1 inhibitors in the USA. We found ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, can be severe enough to cause treatment discontinuation/delay, and may not always be appropriately evaluated by eye specialists. Standardized plans for ophthalmology evaluation and management of ocular toxicities are needed in studies of patients treated with PD-1/PD-L1 inhibitors.
Topics: Adult; Aged; Eye Diseases; Humans; Immune Checkpoint Inhibitors; Middle Aged; Programmed Cell Death 1 Receptor; Retrospective Studies
PubMed: 34226280
DOI: 10.1136/jitc-2020-002119 -
Frontiers in Pharmacology 2023Molnupiravir, an urgently approved drug during the Coronavirus Disease 2019 (COVID-19) pandemic, serves as the basis for our study, which relies on the Food and Drug...
Molnupiravir, an urgently approved drug during the Coronavirus Disease 2019 (COVID-19) pandemic, serves as the basis for our study, which relies on the Food and Drug Administration Adverse Event Reporting System (FAERS). The objective is to extract adverse event (AE) signals associated with molnupiravir from the FAERS database, thereby providing a reference for post-marketing monitoring of adverse events. Specifically, we extracted individual case safety reports (ICSRs) from the database, focusing on cases with COVID-19 indications and molnupiravir identified as the primary suspect drug. Descriptive analysis of the extracted data was performed, followed by four disproportionality analyses using the reporting odds ratio (ROR) method. These analyses were conducted across four levels, encompassing overall data, reports by health professionals, as well as age and gender differentiations, ensuring the robustness of the analysis results. In total, 116,576 ICSRs with COVID-19 indications and 2,285 ICSRs with molnupiravir as the primary suspect were extracted. Notably, after excluding cases with unknown age or gender, a higher proportion of molnupiravir-related ICSRs were observed among individuals aged 65 years and older (70.07%) and women (54.06%). The most frequently reported adverse events and AE signals were associated with gastrointestinal disorders, as well as skin and subcutaneous tissue disorders. Moreover, individuals aged 65 years and older exhibited a higher risk of cardiac disorders, hepatobiliary disorders, renal and urinary disorders, and vascular disorders. In conclusion, this study found molnupiravir demonstrated a lower risk of serious adverse events compared to other RNA antiviral drugs like remdesivir in patients under 65 years old. However, close monitoring of its safety is still necessary for elderly patients aged 65 years and above. Further studies are warranted to continuously assess the safety profile of molnupiravir as its usage increases, especially in high risk populations.
PubMed: 38026949
DOI: 10.3389/fphar.2023.1253799 -
The Journal of Pediatrics Jan 2022To determine the frequency, type, and severity of adverse events (AEs) during intrahospital transport of newborn infants and to identify associated factors. (Observational Study)
Observational Study
OBJECTIVE
To determine the frequency, type, and severity of adverse events (AEs) during intrahospital transport of newborn infants and to identify associated factors.
STUDY DESIGN
We conducted a prospective observational study in a tertiary care academic neonatal unit. All patients hospitalized in the neonatal unit and undergoing intrahospital transport between June 1, 2015, and May 31, 2017 were included. Transports from other hospitals and the delivery room were not included.
RESULTS
Data from 990 intrahospital transports performed in 293 newborn infants were analyzed. The median postnatal age at transport was 13 days (Q1-Q3, 5-44). Adverse events occurred in 25% of transports (248/990) and were mainly related to instability of cardiovascular and respiratory systems, agitation, and temperature control. Adverse events were associated with no harm in 207 transports (207/990, 21%), mild harm in 37 transports (37/990, 4%), and moderate harm in 4 transports (4/990, 0.4%). There was no severe or lethal adverse event. Hemodynamic support with catecholamines, the presence of a central venous catheter, and a longer duration of transport were independent predictors for the occurrence of adverse events during transport.
CONCLUSIONS
Intrahospital transports of newborns are associated with a substantial proportion of adverse events of low-to-moderate severity. Our data have implications to inform clinical practice, for benchmarking and quality improvement initiatives, and for the development of specific guidelines.
Topics: Critical Illness; Female; Humans; Infant, Newborn; Male; Patient Safety; Patient Transfer; Prospective Studies; Switzerland
PubMed: 34480917
DOI: 10.1016/j.jpeds.2021.08.074 -
Adverse event reporting in studies of penetrating acupuncture during pregnancy: a systematic review.Acta Obstetricia Et Gynecologica... May 2015Acupuncture within pregnancy has frequently been investigated, often finding this to be more effective than standard care. However, the adverse event severity, types and... (Review)
Review
BACKGROUND
Acupuncture within pregnancy has frequently been investigated, often finding this to be more effective than standard care. However, the adverse event severity, types and occurrence are unclear.
OBJECTIVE
To investigate the quality of reporting adverse events and to attempt to identify occurrence, type and severity of adverse events in acupuncture and non-acupuncture groups.
DATA SOURCES
MEDLINE, CINAHL, Allied and Complementary Medicine Database, and Physiotherapy Evidence Database (PEDro) were searched for relevant studies between 2000 and 2014.
STUDY SELECTION
Seventeen studies using penetrating acupuncture and making comment on adverse events experienced were included. Quality appraisal of the selected publications was performed using either the PEDro scale or the Downs and Black checklist. Quality of reporting was evaluated against STRICTA and CONSORT guidelines, with data on adverse events extracted in accordance with CONSORT and Good Clinical Practice adverse event guidelines.
RESULTS
Overall quality of reporting of adverse events was poor, with information describing the adverse events often lacking in detail. A number of trends were noted: adverse events occurring within a treatment session was 3-17% in the acupuncture groups and 4-25% in the non-acupuncture groups. The percentage of women affected by an adverse event was between 14 and 17% in the acupuncture groups and between 15 and 19% in non-acupuncture groups.
CONCLUSIONS
Adverse event reporting within acupuncture trials is generally poor. The trends noted were that adverse events do occur, but would appear to be largely minor and comparable to non-acupuncture-related interventions.
Topics: Acupuncture Therapy; Female; Humans; Pregnancy; Pregnancy Complications; Research Design
PubMed: 25603694
DOI: 10.1111/aogs.12587 -
Medicina (Kaunas, Lithuania) Nov 2023: One type of immune-related adverse event caused by immune checkpoint inhibitors (ICIs) is pituitary-related adverse events. The management of pituitary-related adverse...
: One type of immune-related adverse event caused by immune checkpoint inhibitors (ICIs) is pituitary-related adverse events. The management of pituitary-related adverse events is important because they can be fatal if not treated promptly. Therefore, this study was conducted to investigate the onset of pituitary-related adverse events using the Japanese Adverse Drug Report (JADER) database. : Cases registered in the JADER database from 2004 to 2019 were used. The target drugs were ipilimumab, nivolumab, pembrolizumab, avelumab, atezolizumab, and durvalumab, and the target adverse events were the high-level terms "Anterior pituitary hypofunction," "Anterior pituitary hyperfunction," "Posterior pituitary disorder," and "Pituitary neoplasm" in the Medical Dictionary for Regulatory Activities, Japanese version (MedDRA/J). The information component (IC) was used for signal detection and IC delta (ICΔ) was used for women-related signals. Onset timing and patterns were analyzed using the Weibull distribution. : Signals were detected with ipilimumab, nivolumab, pembrolizumab, and atezolizumab in "Anterior pituitary hypofunction," with ICs and 95% credible intervals (95%CrI) of 5.53 (5.30-5.69), 4.96 (4.79-5.08), 4.04 (3.76-4.25), and 2.40 (1.53-3.00). Significant signals were detected in women, except for atezolizumab. Additionally, the time of onset was classified as the wear-out failure type. Inverse signals were detected with ipilimumab and nivolumab in "Posterior pituitary disorder," with ICs (95%CrI) of -1.24 (-2.80--0.26), and -0.89 (-1.64--0.37). : Anterior pituitary hypofunction is likely to occur with the long-term administration of ipilimumab, nivolumab, and pembrolizumab. Further investigation is needed to determine the differences in the tendencies to detect signals in the anterior and posterior pituitaries between ipilimumab and nivolumab.
Topics: Female; Humans; East Asian People; Immune Checkpoint Inhibitors; Ipilimumab; Nivolumab; Pituitary Diseases
PubMed: 38004012
DOI: 10.3390/medicina59111963 -
Journal of the American College of... Feb 2014The aim of this study was to determine the associations between statin use and major adverse cardiovascular and cerebrovascular events (MACCE) and amputation-free...
OBJECTIVES
The aim of this study was to determine the associations between statin use and major adverse cardiovascular and cerebrovascular events (MACCE) and amputation-free survival in critical limb ischemia (CLI) patients.
BACKGROUND
CLI is an advanced form of peripheral arterial disease associated with nonhealing arterial ulcers and high rates of MACCE and major amputation. Although statin medications are recommended for secondary prevention in peripheral arterial disease, their effectiveness in CLI is uncertain.
METHODS
We reviewed 380 CLI patients who underwent diagnostic angiography or therapeutic endovascular intervention from 2006 through 2012. Propensity scores and inverse probability of treatment weighting were used to adjust for baseline differences between patients taking and not taking statins.
RESULTS
Statins were prescribed for 246 (65%) patients. The mean serum low-density lipoprotein (LDL) level was lower in patients prescribed statins (75 ± 28 mg/dl vs. 96 ± 40 mg/dl, p < 0.001). Patients prescribed statins had more baseline comorbidities including diabetes, coronary artery disease, and hypertension, as well as more extensive lower extremity disease (all p values <0.05). After propensity weighting, statin therapy was associated with lower 1-year rates of MACCE (stroke, myocardial infarction, or death; hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.28 to 0.99), mortality (HR: 0.49, 95% CI: 0.24 to 0.97), and major amputation or death (HR: 0.53, 95% CI: 0.35 to 0.98). Statin use was also associated with improved lesion patency among patients undergoing infrapopliteal angioplasty. Patients with LDL levels >130 mg/dl had increased HRs of MACCE and mortality compared with patients with lower levels of LDL.
CONCLUSIONS
Statins are associated with lower rates of mortality and MACCE and increased amputation-free survival in CLI patients.
Topics: Aged; Aged, 80 and over; Amputation, Surgical; Cardiovascular Diseases; Critical Illness; Extremities; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemia; Limb Salvage; Male; Middle Aged; Registries; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 24315911
DOI: 10.1016/j.jacc.2013.09.073 -
Journal of Medical Internet Research Dec 2021Existing systems to document adverse drug events often use free text data entry, which produces nonstandardized and unstructured data that are prone to...
BACKGROUND
Existing systems to document adverse drug events often use free text data entry, which produces nonstandardized and unstructured data that are prone to misinterpretation. Standardized terminology may improve data quality; however, it is unclear which data standard is most appropriate for documenting adverse drug event symptoms and diagnoses.
OBJECTIVE
This study aims to compare the utility, strengths, and weaknesses of different data standards for documenting adverse drug event symptoms and diagnoses.
METHODS
We performed a mixed methods substudy of a multicenter retrospective chart review. We reviewed the research records of prospectively diagnosed adverse drug events at 5 Canadian hospitals. A total of 2 pharmacy research assistants independently entered the symptoms and diagnoses for the adverse drug events using four standards: Medical Dictionary for Regulatory Activities (MedDRA), Systematized Nomenclature of Medicine (SNOMED) Clinical Terms, SNOMED Adverse Reaction (SNOMED ADR), and International Classification of Diseases (ICD) 11th Revision. Disagreements between research assistants regarding the case-specific utility of data standards were discussed until a consensus was reached. We used consensus ratings to determine the proportion of adverse drug events covered by a data standard and coded and analyzed field notes from the consensus sessions.
RESULTS
We reviewed 573 adverse drug events and found that MedDRA and ICD-11 had excellent coverage of adverse drug event symptoms and diagnoses. MedDRA had the highest number of matches between the research assistants, whereas ICD-11 had the fewest. SNOMED ADR had the lowest proportion of adverse drug event coverage. The research assistants were most likely to encounter terminological challenges with SNOMED ADR and usability challenges with ICD-11, whereas least likely to encounter challenges with MedDRA.
CONCLUSIONS
Usability, comprehensiveness, and accuracy are important features of data standards for documenting adverse drug event symptoms and diagnoses. On the basis of our results, we recommend the use of MedDRA.
Topics: Canada; Drug-Related Side Effects and Adverse Reactions; Humans; Retrospective Studies
PubMed: 34890351
DOI: 10.2196/27188 -
Journal of Cannabis Research May 2023There is an expanding unregulated market for a psychotropic compound called ∆-Tetrahydrocannabinol (delta-8-THC) that is being derived from hemp, but a summary of...
BACKGROUND
There is an expanding unregulated market for a psychotropic compound called ∆-Tetrahydrocannabinol (delta-8-THC) that is being derived from hemp, but a summary of adverse events related to delta-8-THC has not been publicly reported.
METHODS
This case series assessed adverse events reported by delta-8-THC users on the Reddit forum r/Delta8 and compared these to delta-8-THC AEs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). Delta-8-THC and cannabis AEs reported in FAERS were also compared. The r/Delta8 forum was selected because it includes a large sample of 98,700 registered individuals who publicly discuss their experiences using delta-8-THC. All r/Delta8 posts were obtained from August 20, 2020, through September 25, 2022. A random sample of r/Delta8 posts was drawn (n = 10,000) and filtered for posts in which delta-8-THC users reported an adverse event (n = 335). FAERS reports that listed delta-8-THC (N = 326) or cannabis (N = 7076) as a suspect product active ingredient were obtained. Adverse events claimed to result from delta-8-THC use were coded using Medical Dictionary for Regulatory Activities to system organ class and preferred term categories.
RESULTS
The absolute number of delta-8-THC adverse event reports (N = 2184, 95% CI = 1949-2426) and serious adverse event reports (N = 437; 95% CI = 339-541) on r/Delta 8 were higher than the adverse event reports (N = 326) and serious adverse event reports (N = 289) to FAERS. Psychiatric disorders were the most frequently cited system organ class in r/Delta8 adverse event reports, mentioned in 41.2% (95% CI = 35.8%-46.3%) of reports, followed by respiratory, thoracic and mediastinal disorders (29.3%, 95% CI = 25.1%-34.0%) and nervous system disorders (23.3%, 95% CI = 18.5%-27.5%). Anxiety (16.4%, 95% CI = 12.8-20.6), Cough (15.5%, 95% CI = 11.9-20.0) and Paranoia (9.3%, 95% CI = 6.3-12.5) were the most frequently cited preferred terms in adverse event reports. The overall prevalence of AEs reported for cannabis and delta-8-THC on FAERS were also similar when analyzed by system organ class (Pearson's r = 0.88).
CONCLUSIONS
The findings of this case series suggest that most of the adverse events reported by delta-8-THC users are like those reported during acute cannabis intoxication. This finding suggests that health care professionals follow similar treatment and management protocols, and that jurisdictions should clarify whether delta-8-THC can be sold as a hemp product.
PubMed: 37217977
DOI: 10.1186/s42238-023-00191-y -
Cardiovascular Therapeutics 2023Alirocumab and evolocumab, as protein convertase subtilisin kexin type 9 (PCSK9) inhibitors, have been reported to reduce cardiovascular risk. This meta-analysis is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alirocumab and evolocumab, as protein convertase subtilisin kexin type 9 (PCSK9) inhibitors, have been reported to reduce cardiovascular risk. This meta-analysis is aimed at updating the safety data of PCSK9 inhibitors.
METHODS
We assessed the relative risk for all treatment-related adverse events, serious adverse events, diabetes-related adverse events, and neurocognitive and neurologic adverse events with PCSK9 inhibitors compared to controls (placebo or ezetimibe). In addition, we conducted a meta-analysis to quantitatively integrate and estimate the adverse event rates in long-term studies.
RESULTS
There were no significant differences between PCSK9 inhibitors and controls in the relative risk analysis. In a subgroup analysis of each PCSK9 inhibitor, alirocumab treatment significantly reduced the risk of serious adverse events compared to control treatment (risk ratio (RR) = 0.937; 95% confidence interval (CI), 0.896-0.980), but no significant difference was observed with evolocumab treatment (RR = 1.003; 95% CI, 0.963-1.054). Moreover, alirocumab treatment afforded a significant reduction in the risk of diabetes-related adverse events compared to control treatment (RR = 0.9137; 95% CI, 0.845-0.987). The overall incidence (event rate) of long-term adverse events was 75.1% (95% CI, 71.2%-78.7%), and the incidence of serious long-term event rate was 16.2% (95% CI, 11.6%-22.3%).
CONCLUSIONS
We suggest that alirocumab and evolocumab are generally safe and well tolerated and that their addition to background lipid-lowering therapy is not associated with an increased risk of adverse events or toxicity.
Topics: Humans; Antibodies, Monoclonal; Anticholesteremic Agents; Cardiovascular Diseases; PCSK9 Inhibitors; Subtilisin
PubMed: 36704607
DOI: 10.1155/2023/7362551