-
International Immunopharmacology Aug 2022High speed of COVID-19 vaccination has raised some concerns about the safety of the new vaccines. It is of a great importance to perform a review of the safety and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High speed of COVID-19 vaccination has raised some concerns about the safety of the new vaccines. It is of a great importance to perform a review of the safety and efficacy of the COVID-19 vaccines.
METHODS
Two International electronic databases (PubMed, ISI) were searched for clinical trials reporting efficacy and safety of COVID-19 vaccines compared to control group. Pooled risk ratio (RR) for total, systemic and local adverse events following immunization was calculated for different vaccine modalities.
RESULTS
The pooled RRs of total adverse reactions for Inactivated, mRNA, and vector vaccines were 1.46 (95% CI: 1.19-1.78), 2.01 (95% CI: 1.82 - 2.23), and 1.65 (95% CI: 1.31 - 2.32) respectively. The pooled RR for occurrence of systemic adverse reactions following immunization for different vaccine modalities was 1.13 (95% CI: 0.79 - 1.61), 1.53 (95% CI 1.08 - 2.16), 1.58 (95% CI: 1.13 - 1.90), 0.72 (95% CI: 0.34 - 1.55), and 1.62 (95% CI: 1.39 - 1.89) for inactivated vaccine, mRNA, vector, DNA, and protein subunit vaccines respectively. The pooled RR of local adverse event following immunization with inactivated vaccine, mRNA vaccine, vector vaccine, DNA vaccine, and protein subunit vaccine was 2.18 (95% CI: 1.32 - 3.59), 4.96 (95% CI: 4.02 - 6.11), 1.48 (95% CI: 0.88-2.50) 1.04 (95% CI: 0.12-8.75), and 4.09 (95% CI: 2.63-6.35) respectively.
CONCLUSION
mRNA vaccines are associated with greater risk of adverse events following immunization. However, at the present moment the benefits of all types of vaccines approved by WHO, still outweigh the risks of them and vaccination if available, is highly recommended.
Topics: COVID-19; COVID-19 Vaccines; Humans; Protein Subunits; RNA, Messenger; Vaccination; Vaccines, Inactivated; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35671640
DOI: 10.1016/j.intimp.2022.108906 -
Neurosurgery Sep 2023Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared.
OBJECTIVE
To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET.
METHODS
We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence.
RESULTS
Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: -11.6 (95% CI: -13.3, -9.9); SRS-T: -10.3 (95% CI: -14.2, -6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume.
CONCLUSION
Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.
Topics: Humans; Essential Tremor; Magnetic Resonance Imaging; Radiosurgery; Thalamus; Treatment Outcome; Tremor; Ultrasonic Surgical Procedures; Network Meta-Analysis
PubMed: 37010324
DOI: 10.1227/neu.0000000000002462 -
Therapeutic Advances in Gastroenterology 2023Vonoprazan, a novel acid-suppressive drug, is non-inferior to proton pump inhibitors (PPIs) for the management of gastric acid-related diseases. However, the safety of...
BACKGROUND
Vonoprazan, a novel acid-suppressive drug, is non-inferior to proton pump inhibitors (PPIs) for the management of gastric acid-related diseases. However, the safety of vonoprazan has not been systematically evaluated yet.
OBJECTIVES
To elucidate the incidence and type of adverse events (AEs) in patients taking vonoprazan.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES AND METHODS
PubMed, EMBASE, and Cochrane Library databases were searched for all studies reporting the safety of vonoprazan. The incidences of any AEs, drug-related AEs, serious AEs, AEs leading to drug discontinuation, and common AEs were pooled. Odds ratios (ORs) were calculated to compare the incidence of AEs between patients taking vonoprazan and PPIs.
RESULTS
Seventy-seven studies were included. The pooled incidences of any AEs, drug-related AEs, serious AEs, and AEs leading to drug discontinuation were 20, 7, 1, and 1%, respectively. The incidences of any AEs (OR = 0.96, = 0.66), drug-related AEs (OR = 1.10, = 0.44), serious AEs (OR = 1.14, = 0.36), and AEs leading to drug discontinuation (OR = 1.09, = 0.55) were not significantly different between patients taking vonoprazan and PPIs. In subgroup analyses, patients with peptic ulcer disease (PUD) had higher incidences of any AEs, serious AEs, and AEs leading to drug discontinuation than those with gastroesophageal reflux disease (GERD), () infection, and artificial ulcer after gastric endoscopic submucosal dissection (ESD), but patients with infection had a higher incidence of drug-related AEs than those with PUD, GERD, and artificial ulcer after gastric ESD. The incidence of AEs was higher in patients taking long-term use of vonoprazan than those taking short-term use of vonoprazan.
CONCLUSION
Vonoprazan is well tolerated and shows similar safety compared to PPIs. The safety of vonoprazan may be primarily influenced by its indications and duration.
REGISTRATION
PROSPERO CRD42022314982.
PubMed: 37113190
DOI: 10.1177/17562848231167858 -
A Systematic Review and Meta-Analysis of Outcomes and Adverse Events for Juxtafacet Cysts Treatment.International Journal of Spine Surgery Feb 2022Different procedures have been used for the treatment of lumbar juxtafacet cysts (JFCs). Recently, full-endoscopic cyst excision has been suggested as a reasonable...
BACKGROUND
Different procedures have been used for the treatment of lumbar juxtafacet cysts (JFCs). Recently, full-endoscopic cyst excision has been suggested as a reasonable alternative. We performed a meta-analysis to assess the overall rates of favorable outcomes and adverse events for each available treatment and determine the outcome and complication rates concerning spine stability.
METHODS
Multiple databases were searched for English-language studies involving adult patients with lumbar JFCs who had been followed for more than 6 months. Outcomes included the proportion of patients with a satisfactory outcome. Adverse events included recurrence and revision rates as well as intraoperative complications. We further stratified the analysis based on the spine's condition (degenerative listhesis vs without degenerative listhesis).
RESULTS
A total of 43 studies, including 2226 patients, were identified. Over 80% of patients experienced satisfactory improvement after surgical excision but only 66.2% after percutaneous cyst rupture and aspiration. Overall, recurrence and revision rates were almost double in patients with preoperative degenerative listhesis at the cyst level, especially in the minimally invasive group (2.1% vs 31.3% and 6.8% vs 13.1%, respectively). The rate of full-endoscopic satisfactory outcomes was approximately 90%, with low rates of adverse events (<2%).
CONCLUSION
We analyzed the outcome and adverse event rates for each kind of available treatment for JFC. Full endoscopy has outcomes and rates of adverse events that overlap with open and minimally invasive approaches.
LEVEL OF EVIDENCE
2A.
PubMed: 35217587
DOI: 10.14444/8181 -
Hemodialysis International.... Jan 2023We conducted a systematic review of studies investigating lock solutions for use in non-tunneled hemodialysis catheters.
BACKGROUND
We conducted a systematic review of studies investigating lock solutions for use in non-tunneled hemodialysis catheters.
METHODS
We searched PubMed and Cochrane databases from inception to June 11, 2021. Study inclusion criteria were: randomized trial or observational study, adults (>18 years), with acute kidney injury (AKI); and temporary non-tunneled catheters. We recorded bleeding events, catheter dysfunction and complications.
RESULTS
Of 649 studies identified, 6 were included (4 randomized, 1 non-randomized trial, 1 retrospective cohort study; sample sizes 78-1496 patients). Citrate was compared to heparin in 4 studies, to saline in 1, and ethanol versus saline in 1. Event-free survival of non-tunneled catheters did not differ between groups. Catheter-related infections and adverse events were less frequent with citrate locks, but reached statistical significance in only two studies.
CONCLUSION
Existing data are too heterogeneous to enable recommending one type of catheter lock over any other for non-tunneled hemodialysis catheters.
Topics: Adult; Humans; Retrospective Studies; Central Venous Catheters; Renal Dialysis; Catheterization; Heparin; Catheter-Related Infections; Citric Acid; Citrates; Catheters, Indwelling; Observational Studies as Topic
PubMed: 36203330
DOI: 10.1111/hdi.13047 -
Journal of Psychiatric Research May 2024Neuromodulatory interventions are relatively novel and approaches to studying harms and tolerability have varied. Using a checklist based on guidelines from Good... (Review)
Review
Neuromodulatory interventions are relatively novel and approaches to studying harms and tolerability have varied. Using a checklist based on guidelines from Good Clinical Practice and the Harms Extension of the CONSORT (Consolidated Standards of Reporting Trials) Statement, we identified how adverse events are measured, assessed, and reported in studies evaluating neuromodulation for the treatment of mental and neurodevelopmental disorders among children and adolescents. A systematic literature review identified 56 experimental and quasi-experimental studies evaluating transcranial magnetic stimulation (TMS), transcranial alternating (tACS) or direct (tDCS) current stimulation, transcranial pulse stimulation (TPS), and vagus or trigeminal nerve stimulation (VNS or TNS). For 22 studies (39%), the types of adverse events to be monitored were identified, and for 31 studies (55%), methods for collecting adverse event data were described. Methods for assessing adverse events were less commonly described with 23 studies (41%) having details on assessing event severity, and 11 studies (20%) having details on assessing event causality. Among 31 studies with reported results, headache, skin irritation, and general pain or discomfort were the most reported across studies. Seizure, untoward medical occurrences, and intracranial bleeding, edema, or other intracranial pathology were considered serious events, but these events were not reported as occurring in any results-based papers. Taken together, the findings from this review indicate that most studies of pediatric neuromodulatory interventions did not include descriptions of adverse event monitoring and evaluation. Comprehensive event monitoring and reporting across studies can significantly augment the current knowledge base.
PubMed: 38761518
DOI: 10.1016/j.jpsychires.2024.05.035 -
Vaccines Apr 2022We conducted a systematic review and a meta-analysis to assess the risk of serious adverse events in the elderly after yellow fever vaccination compared to the... (Review)
Review
We conducted a systematic review and a meta-analysis to assess the risk of serious adverse events in the elderly after yellow fever vaccination compared to the non-elderly population. We searched multiple databases and grey literature, and we selected research without language and publication date restrictions. Studies were analyzed in a descriptive way and meta-analyzed and expressed in terms of prevalence ratio and risk ratio with a 95% confidence interval, depending on the degree of heterogeneity found. A total of 18 studies were included and 11 were meta-analyzed. The results obtained through the meta-analysis showed a risk of serious adverse events after yellow fever vaccination three times higher for the elderly when compared to the non-elderly population and five times higher for persons > 70 years. In relation to adverse event types, viscerotropic disease associated with the yellow fever vaccine had a risk that was six times higher when compared to the population < 60 years. The evidence found supports that the vaccine indication in individuals > 60 years of age should be based on a careful analysis of individual benefit-risk assessments. The results found suggest a higher risk of events for individuals > 70 years, especially for viscerotropic and neurotropic disease associated with YFV contraindicating the use of the YFV in this age group.
PubMed: 35632466
DOI: 10.3390/vaccines10050711 -
The Cochrane Database of Systematic... Jul 2022Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.
OBJECTIVES
To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).
SEARCH METHODS
We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February 2022.
SELECTION CRITERIA
We included RCTs that compared HSCT to immunomodulators in the treatment of SSc.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence using standard Cochrane methods.
MAIN RESULTS
We included three RCTs evaluating: non-myeloablative non-selective HSCT (10 participants), non-myeloablative selective HSCT (79 participants), and myeloablative selective HSCT (36 participants). The comparator in all studies was cyclophosphamide (123 participants). The study examining non-myeloablative non-selective HSCT had a high risk of bias given the differences in baseline characteristics between the two arms. The other studies had a high risk of detection bias for participant-reported outcomes. The studies had follow-up periods of one to 4.5 years. Most participants had severe disease, mean age 40 years, and the duration of disease was less than three years. Efficacy No study demonstrated an overall mortality benefit of HSCT when compared to cyclophosphamide. However, non-myeloablative selective HSCT showed overall survival benefits using Kaplan-Meier curves at 10 years and myeloablative selective HSCT at six years. We graded our certainty of evidence as moderate for non-myeloablative selective HSCT and myeloablative selective HSCT. Certainty of evidence was low for non-myeloablative non-selective HSCT. Event-free survival was improved compared to cyclophosphamide with non-myeloablative selective HSCT at 48 months (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.16 to 0.74; moderate-certainty evidence). There was no improvement with myeloablative selective HSCT at 54 months (HR 0.54 95% CI 0.23 to 1.27; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not report event-free survival. There was improvement in functional ability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI, scale from 0 to 3 with 3 being very severe functional impairment) with non-myeloablative selective HSCT after two years with a mean difference (MD) of -0.39 (95% CI -0.72 to -0.06; absolute treatment benefit (ATB) -13%, 95% CI -24% to -2%; relative percent change (RPC) -27%, 95% CI -50% to -4%; low-certainty evidence). Myeloablative selective HSCT demonstrated a risk ratio (RR) for improvement of 3.4 at 54 months (95% CI 1.5 to 7.6; ATB -37%, 95% CI -18% to -57%; RPC -243%, 95% CI -54% to -662%; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; low-certainty evidence). The non-myeloablative non-selective HSCT trial did not report HAQ-DI results. All transplant modalities showed improvement of modified Rodnan skin score (mRSS) (scale from 0 to 51 with the higher number being more severe skin thickness) favoring HSCT over cyclophosphamide. At two years, non-myeloablative selective HSCT showed an MD in mRSS of -11.1 (95% CI -14.9 to -7.3; ATB -22%, 95% CI -29% to -14%; RPC -43%, 95% CI -58% to -28%; moderate-certainty evidence). At 54 months, myeloablative selective HSCT at showed a greater improvement in skin scores than the cyclophosphamide group (RR 1.51, 95% CI 1.06 to 2.13; ATB -27%, 95% CI -6% to -47%; RPC -51%, 95% CI -6% to -113%; moderate-certainty evidence). The NNTB was 4 (95% CI 3 to 18). At one year, for non-myeloablative non-selective HSCT the MD was -16.00 (95% CI -26.5 to -5.5; ATB -31%, 95% CI -52% to -11%; RPC -84%, 95% CI -139% to -29%; low-certainty evidence). No studies reported data on pulmonary arterial hypertension. Adverse events In the non-myeloablative selective HSCT study, there were 51/79 serious adverse events with HSCT and 30/77 with cyclophosphamide (RR 1.7, 95% CI 1.2 to 2.3), with an absolute risk increase of 26% (95% CI 10% to 41%), and a relative percent increase of 66% (95% CI 20% to 129%). The number needed to treat for an additional harmful outcome was 4 (95% CI 3 to 11) (moderate-certainty evidence). In the myeloablative selective HSCT study, there were similar rates of serious adverse events between groups (25/34 with HSCT and 19/37 with cyclophosphamide; RR 1.43, 95% CI 0.99 to 2.08; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not clearly report serious adverse events.
AUTHORS' CONCLUSIONS
Non-myeloablative selective and myeloablative selective HSCT had moderate-certainty evidence for improvement in event-free survival, and skin thicknesscompared to cyclophosphamide. There is also low-certainty evidence that these modalities of HSCT improve physical function. However, non-myeloablative selective HSCT and myeloablative selective HSCT resulted in more serious adverse events than cyclophosphamide; highlighting the need for careful risk-benefit considerations for people considering these HSCTs. Evidence for the efficacy and adverse effects of non-myeloablative non-selective HSCT is limited at this time. Due to evidence provided from one study with high risk of bias, we have low-certainty evidence that non-myeloablative non-selective HSCT improves outcomes in skin scores, forced vital capacity, and safety. Two modalities of HSCT appeared to be a promising treatment option for SSc though there is a high risk of early treatment-related mortality and other adverse events. Additional research is needed to determine the effectiveness and adverse effects of non-myeloablative non-selective HSCT in the treatment of SSc. Also, more studies will be needed to determine how HSCT compares to other treatment options such as mycophenolate mofetil, as cyclophosphamide is no longer the first-line treatment for SSc. Finally, there is a need for a greater understanding of the role of HSCT for people with SSc with significant comorbidities or complications from SSc that were excluded from the trial criteria.
Topics: Adult; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Randomized Controlled Trials as Topic; Scleroderma, Systemic
PubMed: 35904231
DOI: 10.1002/14651858.CD011819.pub2 -
Clinical Epigenetics Jul 2023To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).
METHODS
We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022.
RESULTS
A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events.
CONCLUSION
IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.
Topics: Humans; Prospective Studies; DNA Methylation; Leukemia, Myeloid, Acute; Enzyme Inhibitors; Mutation
PubMed: 37434249
DOI: 10.1186/s13148-023-01529-2