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Healthcare (Basel, Switzerland) Mar 2019Adverse events are a common and for the most part unavoidable consequence of therapeutic intervention. Nevertheless, available tomes of such data now provide us with an...
Adverse events are a common and for the most part unavoidable consequence of therapeutic intervention. Nevertheless, available tomes of such data now provide us with an invaluable opportunity to study the relationship between human phenotype and drug-induced protein perturbations within a patient system. Deciphering the molecular basis of such adverse responses is not only paramount to the development of safer drugs but also presents a unique opportunity to dissect disease systems in search of novel response biomarkers, drug targets, and efficacious combination therapies. Inspired by the potential applications of this approach, we first examined adverse event circumstances reported in FAERS and then performed a molecular level interrogation of cancer patient adverse events to investigate the prevalence of drug-drug interactions in the context of patient responses. We discuss avoidable and/or preventable cases and how molecular analytics can help optimize therapeutic use of co-medications. While up to one out of three adverse events in this dataset might be explicable by iatrogenic, patient, and product/device related factors, almost half of the patients in FAERS received multiple drugs and one in four may have experienced effects attributable to drug interactions.
PubMed: 30893930
DOI: 10.3390/healthcare7010045 -
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 -
Expert Review of Vaccines Jul 2014While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal... (Review)
Review
While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Several community-based ontologies (including Vaccine Ontology, Ontology of Adverse Events and Ontology of Vaccine Adverse Events) have been developed to support vaccine and adverse event representation, classification, data integration, literature mining of host-vaccine interaction networks, and analysis of vaccine adverse events. The author further proposes minimal vaccine information standards and their ontology representations, ontology-based linked open vaccine data and meta-analysis, an integrative One Network ('OneNet') Theory of Life, and ontology-based approaches to study and apply the OneNet theory. In the Big Data era, these proposed strategies provide a novel framework for advanced data integration and analysis of fundamental biological networks including vaccine immune mechanisms.
Topics: Biological Ontologies; Brucella Vaccine; Computer Simulation; Data Interpretation, Statistical; Databases, Factual; Drug Design; Humans; Meningitis, Meningococcal; Meningococcal Vaccines; Neisseria meningitidis; Vaccines
PubMed: 24909153
DOI: 10.1586/14760584.2014.923762 -
Current Drug Safety 2022The Japan Pharmaceutical Association has conducted drug event monitoring to detect drug events related to pemafibrate. As there are a few studies on the safety of...
BACKGROUND
The Japan Pharmaceutical Association has conducted drug event monitoring to detect drug events related to pemafibrate. As there are a few studies on the safety of pemafibrate in clinical settings, a pilot study evaluating the association between drug use and detected events was performed in Japan.
AIMS
In this study, the association between detected events and the use of pemafibrate, utilizing pharmacy records maintained by community pharmacists, was investigated. We identified the newuser cohort using a test and active comparison drug and collected the baseline information. An active comparison group comprising new users was used to assess the events.
METHODS
A retrospective cohort study using questionnaires regarding baseline and event data was conducted by community pharmacists belonging to the Japan Pharmaceutical Association. The incidence of event and estimated hazard ratio were calculated using the Cox proportional hazards model that was adjusted for confounding factors, such as age and sex.
RESULTS
A total of 1294 patients using pemafibrate and 508 patients using fenofibrate were identified as new drug users. The most reported events involving suspected adverse reactions and add-on drugs were increased blood pressure and lipid-lowering effects with pemafibrate use, and nasopharyngitis, pruritus, dizziness, and lipid-lowering effects with fenofibrate use. No significant differences were found in commonly occurring events, except that an add-on anti-hypertensive drug has been used by pemafibrate users compared to fenofibrate users.
CONCLUSION
This study conducted by pharmacists can facilitate the safety assessment of newly marketed drugs, as few drug use investigations with a comparator are carried out by the Japanese authority for pharmaceutical companies. However, further research is required.
Topics: Benzoxazoles; Butyrates; Fenofibrate; Humans; Japan; Pharmaceutical Preparations; Pharmacists; Pilot Projects; Retrospective Studies
PubMed: 35209830
DOI: 10.2174/1574886317666220224142511 -
Journal of Vascular Surgery Jun 2022When introduced to a new procedure, physicians improve their performance and reduce their procedural adverse event rates rapidly during the initial cases and then...
BACKGROUND
When introduced to a new procedure, physicians improve their performance and reduce their procedural adverse event rates rapidly during the initial cases and then improvement slows, signaling that proficiency has been achieved. Determining when they have acquired proficiency has important implications for procedural innovation, education, credentialing, and patient safety. We analyzed the worldwide experience with transcarotid artery revascularization (TCAR), a hybrid approach to carotid revascularization, to identify the (1) procedural performance measures associated with clinical and technical adverse events; (2) target levels of performance measures that minimize adverse event rates; and (3) number of TCAR cases needed to achieve the target levels for the performance measures.
METHODS
The patient, lesion, and physician characteristics were collected for each TCAR procedure performed by each physician worldwide in an international quality assurance database. Four procedural performance measures were recorded for each procedure: flow-reversal time, fluoroscopy time, contrast volume, and total skin-to-skin time. Composite clinical adverse events (ie, transient ischemic attack, stroke, myocardial infarction, death) and composite technical adverse events (ie, aborted procedure, conversion to surgery, bleeding, dissection, cranial nerve injury, device failure), occurring within 24 hours were also recorded. Correlations between each performance measure and the clinical and technical adverse event rates were computed. The inflection points in the performance measures were identified at which no further improvements occurred in the adverse event rates. Finally, the minimum number of TCAR cases required to achieve the target performance measure levels was computed.
RESULTS
A total of 18,240 procedures performed by 1273 physicians were analyzed. Of the 18,240 patients, 34.9% were women and 62.5% were asymptomatic. The flow-reversal time correlated with clinical adverse events adjusted for age, sex, and symptomatic status (R = 0.91; P < .0001) and adjusted technical adverse events (R = 0.86; P < .0001). The skin-to-skin time correlated with adjusted technical adverse events (R = 0.92; P < .0001). A reduction in flow-reversal times to <13.1 minutes and the skin-to-skin time to <81 minutes did not translate into further improvements in the adverse event rates. A minimum of 26 TCAR cases was required to achieve the target flow-reversal time, and a minimum of 15 cases was required to achieve the target skin-to-skin time.
CONCLUSIONS
The flow-reversal time and skin-to-skin time are appropriate performance measures for establishing the level of expertise of physicians as they acquire skills to perform TCAR. A target time of ≤13.1 minutes for flow-reversal and 81 minutes for skin-to-skin time minimized the adverse event rates. Familiarity with the steps involved in performing TCAR was achieved after ≥15 cases, and minimizing clinical adverse events occurred after ≥26 cases.
Topics: Benchmarking; Carotid Arteries; Carotid Stenosis; Endovascular Procedures; Female; Humans; Learning Curve; Male; Retrospective Studies; Risk Factors; Stents; Stroke; Time Factors; Treatment Outcome
PubMed: 35063612
DOI: 10.1016/j.jvs.2021.12.073 -
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 -
Autism : the International Journal of... Feb 2021In this study, we looked at published research on interventions for young autistic children that did not involve administering medication. We were interested in...
In this study, we looked at published research on interventions for young autistic children that did not involve administering medication. We were interested in determining how often studies reported on whether adverse events (i.e. physical or psychological distress to the participants) or adverse effects (i.e. adverse events that are thought to be caused by the intervention) had occurred. We found that of the 150 reports we examined, only 11 mentioned adverse events. One of these studies reported adverse events occurred, and three reported that adverse effects occurred. We also reviewed the studies to examine the reasons that were given to explain why any participants dropped out of the intervention (termed "withdrawal"), to determine if any of these reasons could be considered adverse events or adverse effects. Fifty-four studies described reasons for withdrawal, and 10 of these studies had reasons that could be categorized as an adverse event, 8 studies had reasons that could be categorized as an adverse effect, and an additional 12 studies had reasons that were too vaguely described to determine whether they were adverse events or not. We recommend that autism intervention researchers develop more systematic methods of looking for and reporting adverse events and effects, so that professionals and families can be better informed when choosing to enroll their autistic children in interventions.
Topics: Autism Spectrum Disorder; Autistic Disorder; Child; Humans
PubMed: 33076682
DOI: 10.1177/1362361320965331 -
Frontiers in Pharmacology 2022Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in...
UNLABELLED
Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in the clinic, multiple Adverse Events (AE) are still reported each year.
OBJECTIVE
We aimed to characterize the distribution of Adverse Events associated with Triazole antifungal drugs in different systems and to identify Important Medical Events (IME) signals for Triazole antifungal drugs.
METHODS
The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was queried for Adverse Events related to Triazole antifungal drugs from 2012 to 2022. The Adverse Events caused by all other drugs and non-TAD antifungal drugs were analyzed as references. Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to evaluate the association between Triazole antifungal drugs and Important Medical Events. Visual signal spectrum is mapped to identify potential adverse reaction signals.
RESULTS
Overall, 10,262 Adverse Events were reported to be associated with Triazole antifungal drugs, of which 5,563 cases were defined as Important Medical Events. Common adverse drug reactions (ADR) mentioned in the instructions such as delirium and hypokalemia were detected, as well as unlabeled ADRs such as rhabdomyolysis and hepatitis fulminant. Cholestasis, drug-induced liver injury, QT interval prolongation and renal impairment have notable signals in all Triazole antifungal drugs, with 50 percent of patients developing a severe clinical outcome. Isavuconazole had the lowest signal intensity and demonstrated a superior safety profile.
CONCLUSION
Most results are generally consistent with previous studies and are documented in the prescribing instructions, but some IMEs are not included, such as hepatitis fulminant. Additional pharmaco-epidemiological or experimental studies are required to validate the small number of unlabeled ADRs. TAD-related Important Medical Eventshave a considerable potential to cause clinically serious outcomes. Clinical use of Triazole antifungal drugs requires more attention.
PubMed: 36588707
DOI: 10.3389/fphar.2022.1039867 -
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 -
Clinical Trials (London, England) Feb 2021Current adverse event reporting practices do not document longitudinal characteristics of adverse effects, and alternative methods are not easily interpretable and have...
BACKGROUND
Current adverse event reporting practices do not document longitudinal characteristics of adverse effects, and alternative methods are not easily interpretable and have not been employed by clinical trials. Introducing time parameters in the evaluation of safety that are comprehensive yet easily interpretable could allow for a better understanding of treatment quality. In this study, we developed and applied a novel adverse event reporting method based on longitudinal adverse event changes to aid describing, summarizing, and presenting adverse event profile. We termed it the "Adverse Event Load, Onset, and Maximum Grade" method.
METHODS
We developed two adverse event summary metrics to complement the traditional maximum grade report. Onset time indicates the time period in which the maximum grade for a specific adverse event occurred and was defined as "early" (i.e. maximum grade happened for the first time before 6 weeks) or "late" (i.e. after the 6 week). Adverse event load indicates the overall severity of a specific adverse event over the entire treatment. Higher adverse event load indicates a worse overall experience. These metrics can be calculated for adverse events with different maximum grades, in treatments with planned changes (e.g. dosage changes), using data sets with different number of adverse event data points between treatments (e.g. treatments with longer cycle lengths may have less adverse event data points) and on data sets with different adverse event data availability (e.g. cycle basis and patient-outcome reports). We tested the utility of this method using individual patient data from two major backbone therapies ("Irinotecan" and "Oxaliplatin") from the N9741 trial available in the Fondation ARCAD database (fondationarcad.org). We investigated profiles of diarrhea, neutropenia/leukopenia, and nausea/vomiting.
RESULTS
Our method provided additional information compared to traditional adverse event reports. For example, for nausea/vomiting, while patients in Irinotecan had a higher risk of experiencing maximum grade 3-4 (15.6% vs 7.6%, respectively; p < 0.001), patients in both groups experienced similar severity over time (adverse effect load = 0.102 and 0.096, respectively; p = 0.26), suggesting that patients in Oxaliplatin experienced a lower-grade but more persistent nausea/vomiting. For neutropenia/leukopenia, more patients in Irinotecan experienced their maximum grade for the first time early in the treatment compared to patients in Oxaliplatin (67.9% vs 41.7%; p < 0.001), regardless of maximum grade. Longitudinal information can help compare treatments or guide clinicians on choosing appropriate interventions for low-grade but persistent adverse event or early adverse event onset.
CONCLUSION
We developed an adverse event reporting method that provides clinically relevant information about treatment toxicity by incorporating two longitudinal adverse event metrics to the traditional maximum grade approach. Future research should establish clinical benchmarks for metrics included in this adverse event reporting method.
Topics: Adverse Drug Reaction Reporting Systems; Antineoplastic Agents; Clinical Trials as Topic; Female; Humans; Irinotecan; Male; Neoplasms; Oxaliplatin
PubMed: 32998522
DOI: 10.1177/1740774520959313