-
JAMA Oncology Jul 2019Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.
OBJECTIVE
To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.
DATA SOURCES
PubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018.
STUDY SELECTION
Published clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included.
DATA EXTRACTION AND SYNTHESIS
Trial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis.
MAIN OUTCOMES AND MEASURES
Incidences of treatment-related adverse events and differences between different drugs and cancer types.
RESULTS
This systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).
CONCLUSIONS AND RELEVANCE
Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Clinical Trials as Topic; Humans; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 31021376
DOI: 10.1001/jamaoncol.2019.0393 -
Quality & Safety in Health Care Jun 2008Adverse events in hospitals constitute a serious problem with grave consequences. Many studies have been conducted to gain an insight into this problem, but a general... (Review)
Review
INTRODUCTION
Adverse events in hospitals constitute a serious problem with grave consequences. Many studies have been conducted to gain an insight into this problem, but a general overview of the data is lacking. We performed a systematic review of the literature on in-hospital adverse events.
METHODS
A formal search of Embase, Cochrane and Medline was performed. Studies were reviewed independently for methodology, inclusion and exclusion criteria and endpoints. Primary endpoints were incidence of in-hospital adverse events and percentage of preventability. Secondary endpoints were adverse event outcome and subdivision by provider of care, location and type of event.
RESULTS
Eight studies including a total of 74 485 patient records were selected. The median overall incidence of in-hospital adverse events was 9.2%, with a median percentage of preventability of 43.5%. More than half (56.3%) of patients experienced no or minor disability, whereas 7.4% of events were lethal. Operation- (39.6%) and medication-related (15.1%) events constituted the majority. We present a summary of evidence-based interventions aimed at these categories of events.
CONCLUSIONS
Adverse events during hospital admission affect nearly one out of 10 patients. A substantial part of these events are preventable. Since a large proportion of the in-hospital events are operation- or drug-related, interventions aimed at preventing these events have the potential to make a substantial difference.
Topics: Data Interpretation, Statistical; Health Services Research; Hospitals; Humans; Medical Errors; Risk Management
PubMed: 18519629
DOI: 10.1136/qshc.2007.023622 -
British Journal of Clinical Pharmacology Feb 2021To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin. (Review)
Review
AIMS
To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin.
METHODS
A systematic literature review was performed on 5 databases from inception up to 31 December 2019. These interactions were classified depending on the likelihood of interaction and supporting evidences.
RESULTS
A total of 149 articles describing 78 herbs, food or dietary supplements were reported to interact with warfarin. These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics. Twenty unique herb and dietary supplements also reported to result in minor bleeding events, such as purpura and gum bleeding as well as major events such as intracranial bleeding that led to death.
CONCLUSION
While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs. These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St. John's Wort, sushi and smoking tobacco. Patients should be counselled to continue to seek advice from their healthcare professionals when starting any new herbs, food or supplement.
Topics: Dietary Supplements; Ginkgo biloba; Herb-Drug Interactions; Humans; Phytotherapy; Warfarin
PubMed: 32478963
DOI: 10.1111/bcp.14404 -
BMJ (Clinical Research Ed.) Mar 2019To assess the benefits and harms of spinal manipulative therapy (SMT) for the treatment of chronic low back pain. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefits and harms of spinal manipulative therapy (SMT) for the treatment of chronic low back pain.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES
Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, Physiotherapy Evidence Database (PEDro), Index to Chiropractic Literature, and trial registries up to 4 May 2018, including reference lists of eligible trials and related reviews.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials examining the effect of spinal manipulation or mobilisation in adults (≥18 years) with chronic low back pain with or without referred pain. Studies that exclusively examined sciatica were excluded, as was grey literature. No restrictions were applied to language or setting.
REVIEW METHODS
Two reviewers independently selected studies, extracted data, and assessed risk of bias and quality of the evidence. The effect of SMT was compared with recommended therapies, non-recommended therapies, sham (placebo) SMT, and SMT as an adjuvant therapy. Main outcomes were pain and back specific functional status, examined as mean differences and standardised mean differences (SMD), respectively. Outcomes were examined at 1, 6, and 12 months. Quality of evidence was assessed using GRADE. A random effects model was used and statistical heterogeneity explored.
RESULTS
47 randomised controlled trials including a total of 9211 participants were identified, who were on average middle aged (35-60 years). Most trials compared SMT with recommended therapies. Moderate quality evidence suggested that SMT has similar effects to other recommended therapies for short term pain relief (mean difference -3.17, 95% confidence interval -7.85 to 1.51) and a small, clinically better improvement in function (SMD -0.25, 95% confidence interval -0.41 to -0.09). High quality evidence suggested that compared with non-recommended therapies SMT results in small, not clinically better effects for short term pain relief (mean difference -7.48, -11.50 to -3.47) and small to moderate clinically better improvement in function (SMD -0.41, -0.67 to -0.15). In general, these results were similar for the intermediate and long term outcomes as were the effects of SMT as an adjuvant therapy. Evidence for sham SMT was low to very low quality; therefore these effects should be considered uncertain. Statistical heterogeneity could not be explained. About half of the studies examined adverse and serious adverse events, but in most of these it was unclear how and whether these events were registered systematically. Most of the observed adverse events were musculoskeletal related, transient in nature, and of mild to moderate severity. One study with a low risk of selection bias and powered to examine risk (n=183) found no increased risk of an adverse event (relative risk 1.24, 95% confidence interval 0.85 to 1.81) or duration of the event (1.13, 0.59 to 2.18) compared with sham SMT. In one study, the Data Safety Monitoring Board judged one serious adverse event to be possibly related to SMT.
CONCLUSION
SMT produces similar effects to recommended therapies for chronic low back pain, whereas SMT seems to be better than non-recommended interventions for improvement in function in the short term. Clinicians should inform their patients of the potential risks of adverse events associated with SMT.
Topics: Chronic Disease; Humans; Low Back Pain; Manipulation, Spinal; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 30867144
DOI: 10.1136/bmj.l689 -
The American Journal of Emergency... Feb 2022Intrahospital transport of critically ill patients is often necessary for diagnostic procedures, therapeutic procedures, or admission to the intensive care unit. The aim... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Intrahospital transport of critically ill patients is often necessary for diagnostic procedures, therapeutic procedures, or admission to the intensive care unit. The aim of this study was to investigate and describe safety and adverse events during intrahospital transport of critically ill patients.
MATERIAL AND METHODS
A systematic search was performed of MEDLINE and the Cochrane Central Register of Controlled Trials for studies published up to June 3, 2020, and of the International Clinical Trials Platform Search Portal and ClinicalTrials.gov for ongoing trials. We selected prospective and retrospective cohort studies published in English on intrahospital transport of critically ill patients, and then performed a meta-analysis. The primary outcome was the incidence of all adverse events that occurred during intrahospital transport. The secondary outcomes were death due to intrahospital transport or life-threatening adverse events, minor events in vital signs, adverse events related to equipment, durations of ICU and hospital stay, and costs.
RESULTS
A total of 12,313 intrahospital transports and 1898 patients from 24 studies were included in the meta-analysis. Among 24 studies that evaluated the primary outcome, the pooled frequency of all adverse events was 26.2% (95% CI: 15.0-39.2) and the heterogeneity among these studies was high (I2 = 99.5%). The pooled frequency of death due to intrahospital transport and life-threatening adverse events was 0% and 1.47% each, but heterogeneity was also high.
CONCLUSIONS
Our findings suggest that adverse events can occur during intrahospital transport of critically ill patients, and that the frequency of critical adverse events is relatively low. The results of this meta-analysis could assist in risk-benefit analysis of diagnostic or therapeutic procedures requiring intrahospital transport of critically ill patients.
TRIAL REGISTRATION
UMIN000040963.
Topics: Adolescent; Adult; Aged; Critical Care; Critical Illness; Humans; Middle Aged; Patient Transfer; Risk Factors; Safety; Young Adult
PubMed: 34861515
DOI: 10.1016/j.ajem.2021.11.021 -
Drug Safety Dec 2019Children admitted to paediatric and neonatal intensive care units may be at high risk from medication errors and preventable adverse drug events.
INTRODUCTION
Children admitted to paediatric and neonatal intensive care units may be at high risk from medication errors and preventable adverse drug events.
OBJECTIVE
The objective of this systematic review was to review empirical studies examining the prevalence and nature of medication errors and preventable adverse drug events in paediatric and neonatal intensive care units.
DATA SOURCES
Seven electronic databases were searched between January 2000 and March 2019.
STUDY SELECTION
Quantitative studies that examined medication errors/preventable adverse drug events using direct observation, medication chart review, or a mixture of methods in children ≤ 18 years of age admitted to paediatric or neonatal intensive care units were included.
DATA EXTRACTION
Data on study design, detection method used, rates and types of medication errors/preventable adverse drug events, and medication classes involved were extracted.
RESULTS
Thirty-five unique studies were identified for inclusion. In paediatric intensive care units, the median rate of medication errors was 14.6 per 100 medication orders (interquartile range 5.7-48.8%, n = 3) and between 6.4 and 9.1 per 1000 patient-days (n = 2). In neonatal intensive care units, medication error rates ranged from 4 to 35.1 per 1000 patient-days (n = 2) and from 5.5 to 77.9 per 100 medication orders (n = 2). In both settings, prescribing and medication administration errors were found to be the most common medication errors, with dosing errors the most frequently reported error subtype. Preventable adverse drug event rates were reported in three paediatric intensive care unit studies as 2.3 per 100 patients (n = 1) and 21-29 per 1000 patient-days (n = 2). In neonatal intensive care units, preventable adverse drug event rates from three studies were 0.86 per 1000 doses (n = 1) and 0.47-14.38 per 1000 patient-days (n = 2). Anti-infective agents were commonly involved with medication errors/preventable adverse drug events in both settings.
CONCLUSIONS
Medication errors occur frequently in critically ill children admitted to paediatric and neonatal intensive care units and may lead to patient harm. Important targets such as dosing errors and anti-infective medications were identified to guide the development of remedial interventions.
Topics: Adolescent; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Medication Errors; Prevalence
PubMed: 31410745
DOI: 10.1007/s40264-019-00856-9 -
Critical Care (London, England) Apr 2021It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine the incidence of local anatomic adverse events associated with PIV vasopressor administration in patients of any age cared for in any acute care environment.
METHODS
MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials, and the Database of Abstracts of Reviews of Effects were searched without restriction from inception to October 2019. References of included studies and related reviews, as well as relevant conference proceedings were also searched. Studies were included if they were: (1) cohort, quasi-experimental, or randomized controlled trial study design; (2) conducted in humans of any age or clinical setting; and (3) reported on local anatomic adverse events associated with PIV vasopressor administration. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or the Joanna Briggs Institute checklist for prevalence studies where appropriate. Incidence estimates were pooled using random effects meta-analysis. Subgroup analyses were used to explore sources of heterogeneity.
RESULTS
Twenty-three studies were included in the systematic review, of which 16 and 7 described adults and children, respectively. Meta-analysis from 11 adult studies including 16,055 patients demonstrated a pooled incidence proportion of adverse events associated with PIV vasopressor administration as 1.8% (95% CI 0.1-4.8%, I = 93.7%). In children, meta-analysis from four studies and 388 patients demonstrated a pooled incidence proportion of adverse events as 3.3% (95% CI 0.0-10.1%, I = 82.4%). Subgroup analyses did not detect any statistically significant effects associated with stratification based on differences in clinical location, risk of bias or design between studies, PIV location and size, or vasopressor type or duration. Most studies had high or some concern for risk of bias.
CONCLUSION
The incidence of adverse events associated with PIV vasopressor administration is low. Additional research is required to examine the effects of PIV location and size, vasopressor type and dose, and patient characteristics on the safety of PIV vasopressor administration.
Topics: Catheterization, Peripheral; Drug-Related Side Effects and Adverse Reactions; Humans; Vasoconstrictor Agents
PubMed: 33863361
DOI: 10.1186/s13054-021-03553-1 -
Frontiers in Immunology 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious adverse events. Rituximab, omalizumab, and dupilumab should be explored as alternative treatment options to improve outcomes.
OBJECTIVE
To systematically review the rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid.
METHODS
A PubMed, Embase, Web of Science, and Cochrane library search were conducted on March 10, 2022. A total of 75 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
Use of rituximab (n=122), omalizumab (n=53) and dupilumab (n=36) were reported in 211 patients with BP. Rituximab led to complete remission in 70.5% (n=86/122) and partial remission in 23.8% (n=29/122) of patients within 5.7 months, with a recurrence rate of 20.5% (n=25/122). 9.0% (n=11/122) of patients died and infection (6.6%, n=8/122) was the most common adverse event. Omalizumab led to complete remission in 67.9% (n=36/53) and partial remission in 20.8% (n=11/53) of patients within 6.6 months, with a recurrence rate of 5.7% (n=3/53). 1.9% (n=1/53) of patients died and thrombocytopenia (1.9%, n=1/53) was observed as the most common adverse event. Dupilumab led to complete remission in 66.7% (n=24/36) and partial remission in 19.4% (n=7/36) of patients within 4.5 months of treatment without any reported adverse events, with a recurrence rate of 5.6% (n=2/36).
CONCLUSIONS
Rituximab, omalizumab, and dupilumab have similar clinical benefits for BP patients. However, rituximab resulted in higher recurrence rates, adverse events, and mortality rates.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316454.
Topics: Antibodies, Monoclonal, Humanized; Humans; Omalizumab; Pemphigoid, Bullous; Rituximab; Treatment Outcome
PubMed: 35769474
DOI: 10.3389/fimmu.2022.928621 -
Clinical Breast Cancer Dec 2023Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Camptothecin; Neutropenia; Anemia; Receptor, ErbB-2
PubMed: 37775347
DOI: 10.1016/j.clbc.2023.09.005 -
Air Medical Journal 2023Neonatal transports are an essential component of regionalized medical systems. Neonates who are unstable after birth require transport to a higher level of care by...
OBJECTIVE
Neonatal transports are an essential component of regionalized medical systems. Neonates who are unstable after birth require transport to a higher level of care by neonatal transport teams. Data on adverse events on neonatal transports are limited. The aim of this study was to identify, evaluate, and summarize the findings of all relevant studies on adverse events on neonatal transports.
METHODS
We identified 38 studies reporting adverse events on neonatal transports from January 1, 2000, to December 31, 2019. The adverse events were distributed into 5 categories: vital sign abnormalities, laboratory value abnormalities, equipment challenges, system challenges, cardiopulmonary resuscitation, and transport-related mortality.
RESULTS
Most of the evidence surrounds vital sign abnormalities during transport (n = 28 studies), with hypothermia as the most frequently reported abnormal vital sign. Fourteen studies addressed laboratory abnormalities, 12 reported on events related to equipment issues, and 4 reported on system issues that lead to adverse events on transport. Of the 38 included studies, 12 included mortality related to transport as an outcome, and 4 reported on cardiopulmonary resuscitation during transport. There were significant variations in samples, definitions of adverse events, and research quality.
CONCLUSION
Adverse events during neonatal transport have been illuminated in various ways, with vital sign abnormalities most commonly explored in the literature. However, considerable variation in studies limits a clear understanding of the relative frequencies of each type of adverse event. The transport safety field would benefit from more efforts to standardize adverse event definitions, collect safety data prospectively, and pool data across larger care systems.
Topics: Humans; Infant, Newborn; Benchmarking; Patient Transfer; Neonatology
PubMed: 37356892
DOI: 10.1016/j.amj.2023.05.001