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Cardio-oncology (London, England) Jul 2022Reports of cardiac adverse events from oncology clinical trials often are at variance with reports derived from clinical observations or data-base reviews. These... (Review)
Review
Reports of cardiac adverse events from oncology clinical trials often are at variance with reports derived from clinical observations or data-base reviews. These differences may lead to confusion, as different levels of risks abound in the literature, and the true cardiac risk of using some agents is uncertain. Additionally, such discrepancies may lead to the creation of over-cautious surveillance algorithms. Reasons for these reported differences are complex and often reflect subtleties in the criteria for individual patient evaluation. Both clinical trial data and real-world data have potential flaws that make reconciliation problematic. Importantly, however, both provide crucial information regarding the risk of adverse events. Major factors contribute to these differences including different tools used to diagnose events, and how those tools are interpreted. Additionally, differences in the populations of clinical trial participants and real-world populations play a crucial role. This paper looks at these differences and provides a perspective intended to help clinicians interpret reported variations in event rates derived from highly scrutinized clinical trials and broader real-world data.
PubMed: 35854393
DOI: 10.1186/s40959-022-00139-w -
Evidence-based Complementary and... 2019Traditional Japanese Kampo medicines have been integrated into the Japanese national health-care system. In Japan, the Ministry of Health, Labor, and Welfare's website...
OBJECTIVES
Traditional Japanese Kampo medicines have been integrated into the Japanese national health-care system. In Japan, the Ministry of Health, Labor, and Welfare's website discloses adverse drug-event data that have been obtained from medical personnel reports investigated by the Pharmaceutical and Medical Devices Agency. Using these data, we investigated adverse events associated with ethical Kampo formulations.
METHODS
Reports of adverse events associated with ethical Kampo formulations from the domestic adverse-event data were obtained from July 30, 2003, to March 31, 2018. Adverse events were then categorized, and the relationships between categories of adverse events and crude drugs were analyzed.
RESULTS
There were 4,232 reported adverse events associated with ethical Kampo formulations. The numbers of events by category were as follows: events related to liver injury, 1,193; lung injury, 1,177; pseudoaldosteronism, 889; mesenteric phlebosclerosis, 223; drug eruption, 185; and others, 565. Among events related to both liver injury and lung injury, approximately 70% were suspected to be induced by Kampo formulations containing Scutellariae Radix. The pseudoaldosteronism-related events, which are induced by Glycyrrhizae Radix, included several events related to muscle injury, heart failure, and arrhythmia. Events related to mesenteric phlebosclerosis, believed to be induced by long-term use of Kampo formulas containing Gardeniae Fructus, increased remarkably during the study period. Among the events related to drug eruption, approximately 35% were suspected to be induced by Kampo formulations containing Ephedrae Herba.
CONCLUSION
Kampo medicines may cause various adverse events. The present results provide valuable information regarding adverse events associated with Kampo medicines from the viewpoint of patient safety.
PubMed: 31118950
DOI: 10.1155/2019/1643804 -
European Journal of Pediatric Surgery :... Apr 2023Successful surgery combines quality (achievement of a positive outcome) with safety (avoidance of a negative outcome). Outcome assessment serves the purpose of quality...
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.
Topics: Humans; Adult; Postoperative Complications; Benchmarking; Quality Improvement; Surgeons; Severity of Illness Index
PubMed: 36720250
DOI: 10.1055/s-0043-1760821 -
Resuscitation Aug 2013To review literature reporting adverse events and physiological instability in order to develop frameworks that describe and define clinical deterioration in... (Review)
Review
OBJECTIVES
To review literature reporting adverse events and physiological instability in order to develop frameworks that describe and define clinical deterioration in hospitalised patients.
METHODS
Literature review of publications from 1960 to August 2012. Conception and refinement of models to describe clinical deterioration based on prevailing themes that developed chronologically in adverse event literature.
RESULTS
We propose four frameworks or models that define clinical deterioration and discuss the utility of each. Early attempts used retrospective chart review and focussed on the end result of deterioration (adverse events) and iatrogenesis. Subsequent models were also retrospective, but used discrete complications (e.g. sepsis, cardiac arrest) to define deterioration, had a more clinical focus, and identified the concept of antecedent physiological instability. Current models for defining clinical deterioration are based on the presence of abnormalities in vital signs and other clinical observations and attempt to prospectively assist clinicians in predicting subsequent risk. However, use of deranged vital signs in isolation does not consider important patient-, disease-, or system-related factors that are known to adversely affect the outcome of hospitalised patients. These include pre-morbid function, frailty, extent and severity of co-morbidity, nature of presenting illness, delays in responding to deterioration and institution of treatment, and patient response to therapy.
CONCLUSION
There is a need to develop multiple-variable models for deteriorating ward patients similar to those used in intensive care units. Such models may assist clinician education, prospective and real-time patient risk stratification, and guide quality improvement initiatives that prevent and improve response to clinical deterioration.
Topics: Critical Illness; Early Medical Intervention; Health Status Indicators; Hospital Mortality; Hospitalization; Humans; Inpatients; Intensive Care Units; Models, Theoretical; Monitoring, Physiologic; Risk Assessment; Safety Management
PubMed: 23376502
DOI: 10.1016/j.resuscitation.2013.01.013 -
Preventive Medicine Reports Dec 2021Although medical error has been estimated as a major cause of death in the US, the capability of current diagnostic coding systems and standard death certificates to...
Although medical error has been estimated as a major cause of death in the US, the capability of current diagnostic coding systems and standard death certificates to capture these events has been criticized. This register-based study aimed to scrutinize medical adverse event deaths (i.e., deaths due to adverse events occurring within the healthcare practice, avoidable or unavoidable, including late complications and sequelae of such events) in the US National Vital Statistics 2018 mortality dataset. Individual-level data on underlying and multiple causes of death according to the tenth revision of the International Classification of Diseases (ICD-10) coding system were extracted together with the decedents' sex, age, ethnicity and education level. Adverse event deaths were identified by ICD-10 codes Y40-Y84 and Y88. The dataset comprised a total of 2 846 305 certified deaths. An adverse event ICD-10 code was used as the underlying cause of death in 0.16% (n = 4620) of the cases, and appeared on the list of multiple causes in 1.13% (n = 32 226) of the cases. Odds for adverse event death were higher among younger than elderly individuals, among those of black than white ethnicity, and among individuals with higher education level. The present data indirectly support previous evidence that a large number of adverse events remain underrecognized or misclassified. Future analyses are needed to reveal the root causes behind underreporting and to analyze whether it occurs at random or in a systematic way.
PubMed: 34976638
DOI: 10.1016/j.pmedr.2021.101574 -
International Journal of Health Care... 2014Adverse events and patient care-related adverse events are a challenging universal problem, among elder residents of geriatric facilities. The aim of this study was to...
PURPOSE
Adverse events and patient care-related adverse events are a challenging universal problem, among elder residents of geriatric facilities. The aim of this study was to examine which types of adverse events are characteristic of the geriatric center studied and which of the nursing staff reported this event.
DESIGN/METHODOLOGY/APPROACH
Data were retrieved from the computerized adverse event management system at a large geriatric center in central Israel, and all adverse events reported over the past three years were examined.
FINDINGS
The study findings indicate that the most common type of adverse event was falls. Older nurses with greater seniority in the facility show a higher tendency to report adverse events. In addition, registered nurses were found to report more often than practical nurses.
PRACTICAL IMPLICATIONS
This study highlights the important role that nurses can play in reporting and reducing adverse events. The role of the nurse is becoming increasingly complex, especially in geriatric facilities, which serve people with complex mental and physical states who are more susceptible to adverse events to begin with.
ORIGINALITY/VALUE
Despite the large number of adverse events, few studies have been undertaken on adverse events in geriatrics in general, and in nursing homes and long-term facilities in particular. Answers to these questions will enable improvement in the quality of care provided and ensure a safe care environment for residents. Systematically examining types of adverse events and the characteristics of those who do and do not report them, can contribute to improvement of processes in the healthcare system in general, and in the facility in particular. Additionally, efficient investigation can improve the behavior of those who enable adverse events.
Topics: Accidental Falls; Aged; Documentation; Drug-Related Side Effects and Adverse Reactions; Equipment Failure; Female; Homes for the Aged; Humans; Male; Middle Aged; Nurses; Nursing Homes; Patient Safety; Quality of Health Care; Violence
PubMed: 24745135
DOI: 10.1108/IJHCQA-05-2012-0051 -
BMC Medical Informatics and Decision... Jul 2017To identify safety signals by manual review of individual report in large surveillance databases is time consuming; such an approach is very unlikely to reveal complex...
BACKGROUND
To identify safety signals by manual review of individual report in large surveillance databases is time consuming; such an approach is very unlikely to reveal complex relationships between medications and adverse events. Since the late 1990s, efforts have been made to develop data mining tools to systematically and automatically search for safety signals in surveillance databases. Influenza vaccines present special challenges to safety surveillance because the vaccine changes every year in response to the influenza strains predicted to be prevalent that year. Therefore, it may be expected that reporting rates of adverse events following flu vaccines (number of reports for a specific vaccine-event combination/number of reports for all vaccine-event combinations) may vary substantially across reporting years. Current surveillance methods seldom consider these variations in signal detection, and reports from different years are typically collapsed together to conduct safety analyses. However, merging reports from different years ignores the potential heterogeneity of reporting rates across years and may miss important safety signals.
METHOD
Reports of adverse events between years 1990 to 2013 were extracted from the Vaccine Adverse Event Reporting System (VAERS) database and formatted into a three-dimensional data array with types of vaccine, groups of adverse events and reporting time as the three dimensions. We propose a random effects model to test the heterogeneity of reporting rates for a given vaccine-event combination across reporting years. The proposed method provides a rigorous statistical procedure to detect differences of reporting rates among years. We also introduce a new visualization tool to summarize the result of the proposed method when applied to multiple vaccine-adverse event combinations.
RESULT
We applied the proposed method to detect safety signals of FLU3, an influenza vaccine containing three flu strains, in the VAERS database. We showed that it had high statistical power to detect the variation in reporting rates across years. The identified vaccine-event combinations with significant different reporting rates over years suggested potential safety issues due to changes in vaccines which require further investigation.
CONCLUSION
We developed a statistical model to detect safety signals arising from heterogeneity of reporting rates of a given vaccine-event combinations across reporting years. This method detects variation in reporting rates over years with high power. The temporal trend of reporting rate across years may reveal the impact of vaccine update on occurrence of adverse events and provide evidence for further investigations.
Topics: Adverse Drug Reaction Reporting Systems; Data Mining; Humans; Patient Safety; Signal Detection, Psychological; Vaccines
PubMed: 28699543
DOI: 10.1186/s12911-017-0472-y -
Paediatric Drugs 2009Tizanidine is an imidazoline with central alpha(2)-adrenoceptor agonist activity at both spinal and supraspinal levels, which is indicated as a short-acting drug for the...
BACKGROUND
Tizanidine is an imidazoline with central alpha(2)-adrenoceptor agonist activity at both spinal and supraspinal levels, which is indicated as a short-acting drug for the management of spasticity. Despite being used in pediatric populations, there is no adequate information or well controlled studies to document the safety and efficacy of tizanidine in this group.
OBJECTIVE
To evaluate the safety of tizanidine in the pediatric population. We compared spontaneous adverse event reports in the Acorda Therapeutics worldwide clinical adverse event database for children (< or = 16 years; n = 99) and adults (>16 years; n = 1153) who had received tizanidine and for whom at least one adverse event was reported, and performed a retrospective chart review of the safety of tizanidine in children (< or = 16 years; n = 76) at a large US pediatric neurology practice. Causality of adverse events in our worldwide clinical adverse event database were neither assessed nor assigned by the company.
RESULTS
When adverse events from the clinical adverse event database were collapsed into the 25 Medical Dictionary for Regulatory Activities (MedDRA; version 9.0) organ system classes, five classes were more frequent in adults (general disorders and administration site conditions [p = 0.0006], hepatobiliary disorders [p = 0.0031], nervous system disorders [p = 0.0108], skin and subcutaneous disorders [p = 0.0063], and vascular disorders [p = 0.0029]), while one class was more frequent in children (psychiatric disorders [p < 0.0001]). The most common adverse event classes in children were psychiatric disorders (52.5%) followed by nervous system disorders (29.3%), and gastrointestinal disorders (16.2%), whereas the most common adverse event classes in adults were nervous system disorders (42.4%), general disorders and administration site conditions (28.6%), and gastrointestinal disorders (21.3%). Serious adverse events were substantially less frequent in children than adults (19.2% vs 45.9%) in the clinical adverse event database. In the pediatric practice chart review, the incidence of adverse events in the MedDRA psychiatric disorders class was very similar (52.6%) to that for children in the clinical adverse event database, while the next most common classes were gastrointestinal disorders (14.5%), and nervous system disorders (13.2%). There were three deaths in children across the databases, including one from accidental exposure and two from cardiac events; the relationship of cardiac events in relation to tizanidine or other causes was difficult to assess with the limited available information.The major causes of death in adults were related to suicide or overdose. Minor, transient liver transaminase increases were occasionally reported; the effect of tizanidine could not be ruled out.
CONCLUSION
The overall safety of tizanidine in the pediatric group appeared good; however, the adverse event profile differed from that in adults. This difference most likely reflects the off-label use of tizanidine as adjunctive treatment for attention disorders and autism. The frequency and nature of adverse events in adults were consistent with the tizanidine prescribing information as reported for its approved indication, i.e. management of spasticity.
Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Child; Child, Preschool; Clonidine; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Retrospective Studies; Young Adult
PubMed: 19877725
DOI: 10.2165/11316090-000000000-00000 -
British Journal of Clinical Pharmacology Mar 2021Medication harm has negative clinical and economic consequences, contributing to hospitalisation, morbidity and mortality. The incidence ranges from 4 to 14%, of which...
AIMS
Medication harm has negative clinical and economic consequences, contributing to hospitalisation, morbidity and mortality. The incidence ranges from 4 to 14%, of which up to 50% of events may be preventable. A predictive model for identifying high-risk inpatients can guide a timely and systematic approach to prioritisation. The aim of this study is to develop and internally validate a risk prediction model for prioritisation of hospitalised patients at risk of medication harm.
METHODS
A retrospective cohort study was conducted in general medical and geriatric specialties at an Australian hospital over six months. Medication harm was identified using International Classification of Disease (ICD-10) codes and the hospital's incident database. Sixty-eight variables, including medications and laboratory results, were extracted from the hospital's databases. Multivariable logistic regression was used to develop the final risk model. Performance was evaluated using area under the receiver operative characteristic curve (AuROC) and clinical utility was determined using decision curve analysis.
RESULTS
The study cohort included 1982 patients with median age 74 years, of which 136 (7%) experienced at least one adverse medication event(s). The model included: length of stay, hospital re-admission within 12 months, venous or arterial thrombosis and/or embolism, ≥ 8 medications, serum sodium < 126 mmol/L, INR > 3, anti-psychotic, antiarrhythmic and immunosuppressant medications, and history of medication allergy. Validation gave an AuROC of 0.70 (95% CI: 0.65-0.74). Decision curve analysis identified that the AIME may be clinically useful to help guide decision making in practice.
CONCLUSION
We have developed a predictive model with reasonable performance. Future steps include external validation and impact evaluation.
Topics: Aged; Area Under Curve; Australia; Cohort Studies; Humans; Inpatients; Retrospective Studies
PubMed: 32986855
DOI: 10.1111/bcp.14560 -
Frontiers in Physiology 2014New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by...
PURPOSE
New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse event co-occurrences.
METHODS
We analyzed the similarity of adverse event profiles of 2347 patients extracted from EMRs from a mental health center in Denmark. The patients were clustered based on their adverse event profiles and the similarities were presented as a network. The set of adverse events in each main patient cluster was evaluated. Co-occurrences of adverse events in patients (p-value < 0.01) were identified and presented as well.
RESULTS
We found that each cluster of patients typically had a most distinguishing adverse event. Examination of the co-occurrences of adverse events in patients led to the identification of potentially interesting adverse event correlations that may be further investigated as well as provide further patient stratification opportunities.
CONCLUSIONS
We have demonstrated the feasibility of a novel approach in pharmacovigilance to stratify patients based on fine-grained adverse event profiles, which also makes it possible to identify adverse event correlations. Used on larger data sets, this data-driven method has the potential to reveal unknown patterns concerning adverse event occurrences.
PubMed: 25249979
DOI: 10.3389/fphys.2014.00332