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Journal of Extracellular Vesicles Jul 2024Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication... (Meta-Analysis)
Meta-Analysis
Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication system. Besides the use of EVs in biomarker studies and diagnostics, the potential of EV-therapeutics has been seen by many. They provide unique properties for disease therapy, including strong immune-modulatory actions, the possibility of engineering, low immunogenicity, and the capability of crossing biological barriers. Proof-of-concept of EV-therapeutics for various pathologies has been achieved in preclinical studies. However, clinical trials with EVs have only been emerging slowly. Here, we aim to provide a comprehensive overview of the current state-of-the-art concerning clinical studies using EVs in human therapy. By approaching the current knowledge in a systematic manner, we were able to include 21 reports for meta-analysis of safety and evaluation of efficacy outcomes. Overall, we have shown that EV-based therapy is safe with a low incidence of serious adverse events (SAE; 0.7% (95%-CI: 0.1-5.2%), and adverse events (AE; 4.4% (95%-CI: 0.7-22.2%). Subgroup analysis showed no significant difference in SAE when comparing autologous versus allogeneic administration, as well as engineered versus non-engineered EV products. A significantly higher number of AE was seen in autologous versus allogeneic administration. However, the clinical relevance remains questionable. Evaluation of the clinical outcomes of immunostimulatory, immunosuppressive or regenerative EV-therapies indicated improvement in the majority of treated patients. Despite these promising results, data need to be approached with caution due to a high heterogeneity in the EVs manufacturing methods, study design, and reporting of (S)AE. Overall, we conclude that EV-based therapy is safe and presents a promising opportunity in therapy. More efforts are needed in the standardization and harmonization of reporting of EV isolation and characterization data as well as in the reporting of (S)AE to allow inter-study comparison.
Topics: Humans; Extracellular Vesicles; Clinical Trials as Topic
PubMed: 38958077
DOI: 10.1002/jev2.12458 -
Psychiatry and Clinical Neurosciences Jul 2024Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile....
AIM
Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap.
METHODS
We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety).
RESULTS
The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups.
CONCLUSIONS
Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.
PubMed: 38957929
DOI: 10.1111/pcn.13709 -
Frontiers in Pharmacology 2024Natural products are widely used for primary insomnia (PI). This systematic review with trial sequential analysis (TSA) aimed to summarize evidence pertaining to the...
Natural products are widely used for primary insomnia (PI). This systematic review with trial sequential analysis (TSA) aimed to summarize evidence pertaining to the effectiveness and safety of Zao Ren An Shen (ZRAS) prescription, a commercial Chinese polyherbal preparation, for treating PI. Controlled clinical trials appraising ZRAS compared to controls or as an add-on treatment were systematically searched across seven databases until January 2024. Cochrane ROB 2.0 and ROBINS-I tools were adopted to determine risk of bias. Quality of evidence was assessed using the GRADE framework. We analyzed 22 studies, involving 2,142 participants. The effect of ZRAS in reducing Pittsburgh Sleep Quality Index scores was found to be comparable to benzodiazepines [ = 0.39, 95% (-0.12, 0.91), = 0.13] and superior to Z-drugs [ = -1.31, 95% (-2.37, -0.24), = 0.02]. The addition of ZRAS to hypnotics more significantly reduced polysomnographically-recorded sleep onset latency [ = -4.44 min, 95% (-7.98, -0.91), = 0.01] and number of awakenings [ = -0.89 times, 95% (-1.67, -0.10), = 0.03], and increased total sleep time [ = 40.72 min, 95% (25.14, 56.30), < 0.01], with fewer adverse events than hypnotics alone. TSA validated the robustness of these quantitative synthesis results. However, the quality of evidence ranged from very low to low. The limited data available for follow-up did not support meta-synthesis. While ZRAS prescription shows promising effectiveness in treating PI, the overall quality of evidence is limited. Rigorously-designed randomized control trials are warranted to confirm the short-term efficacy of ZRAS and explore its medium-to-long-term efficacy. (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=471497), identifier (CRD42023471497).
PubMed: 38957383
DOI: 10.3389/fphar.2024.1376637 -
Ethiopian Journal of Health Sciences Jan 2024Healthcare systems should ensure the provision of quality services to patients without harming them. However, the provision of services is occasionally accompanied by... (Review)
Review
BACKGROUND
Healthcare systems should ensure the provision of quality services to patients without harming them. However, the provision of services is occasionally accompanied by harm or complications, most of which are preventable. Most studies have focused on secondary healthcare rather than primary healthcare (PHC). Thus, this study aimed to identify various dimensions and components of patient safety in PHC worldwide.
METHODS
This systematic review study was conducted in November 2022 based on PRISMA reporting guidelines. Studies were retrieved from PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE and searched for English documents using the keywords "patient safety" and "PHC" from 2000 to 2022. Finally, two reviewers extracted the data independently and analyzed using thematic content analysis.
RESULTS
Overall, 23 out of the initially 4937 identified articles were selected for the final analysis based on the inclusion and exclusion criteria. Most of these studies used a qualitative-quantitative approach (61.9%, seven studies for both), and 64% had been conducted in European countries. Eventually, five dimensions and 22 components were identified for patient safety in PHC, including management measures, quality management, resources and technology, documents, and patient-related factors.
CONCLUSION
The patient safety dimensions and components identified in this research can help develop a clear definition of patient safety and its assessment standards and criteria in PHC. Considering that most previous studies on patient safety in PHC were conducted in European and developed countries, it is suggested that researchers conduct more studies in developing countries to fill this research gap.
Topics: Humans; Primary Health Care; Patient Safety; Quality of Health Care
PubMed: 38957341
DOI: 10.4314/ejhs.v34i1.9 -
Musculoskeletal Surgery Jul 2024Ankle fractures are common injuries that can significantly impact mobility and quality of life. Rehabilitation following ankle fracture treatment is crucial for... (Review)
Review
Ankle fractures are common injuries that can significantly impact mobility and quality of life. Rehabilitation following ankle fracture treatment is crucial for recovery, yet adherence to regimens remains a challenge. Behaviour Change Techniques (BCTs) have been suggested to improve adherence, but their effectiveness in ankle fracture rehabilitation is not well established. This review aimed to evaluate the effectiveness of BCTs in the rehabilitation of ankle fracture patients. We conducted a comprehensive search across multiple databases, including MEDLINE and EMBASE, focusing on Randomised Controlled Trials (RCTs) that incorporated BCTs into rehabilitation interventions. The effectiveness of BCTs on patient-reported outcomes (PROMs), quality of life, and adverse events was analysed. Nine RCTs met the inclusion criteria, encompassing a range of interventions that employed BCTs, most commonly including goal setting and instruction on how to perform behaviours, specifically physiotherapy exercises. The review found limited evidence supporting their effectiveness in improving PROMs. Only one study showed a significant positive effect, but it was deemed at high risk of bias. The lack of integration of behavioural theory in the design of rehabilitation interventions and the varied nature of the BCTs employed across studies may contribute to these findings. The use of BCTs in ankle fracture rehabilitation is prevalent, but this review highlights a significant gap their role of enhancing patient outcomes. Future research should incorporate a theory-based approach to intervention design, utilising a broader range of BCTs, to fully evaluate their potential in improving rehabilitation adherence and outcomes following ankle fracture .
PubMed: 38955960
DOI: 10.1007/s12306-024-00845-x -
Pain Management Nursing : Official... Jul 2024Morton's neuroma (MN) is one of the most frequent neurological pathologies in feet, affecting approximately 4% of the general population. The treatment of MN can be... (Review)
Review
BACKGROUND
Morton's neuroma (MN) is one of the most frequent neurological pathologies in feet, affecting approximately 4% of the general population. The treatment of MN can be surgical, conservative, and infiltrative, with different substances used in the injections for MN, as steroids, sclerosing solutions, and others. This review aims to evaluate the efficacy of current infiltrative therapy for Morton's neuroma and, additionally, to define adverse effects of this therapy.
MATERIAL AND METHODS
A literature search was performed in PubMed, Embase, CINHAL, Epistemonikos, Web of Science (WOS), SPORTSDiscus and Cochrane Library. This search involved the application of all types of infiltrative treatment applicable to MN. The search was limited to original data describing clinical outcomes and pain using the Visual Analogue pain Scale (VAS) or the Johnson Satisfaction Scale, between February and June 2023.
RESULTS
Twelve manuscripts were selected (six randomized controlled trials and six longitudinal observational studies) involving 1,438 patients. Capsaicin was reported to produce a VAS score reduction of 51.8%. Corticosteroids also reported a high level of efficacy. Alcohol and Hyaluronic Acid injections are well tolerated, but the effects of their application need further research. There were no serious adverse events.
CONCLUSIONS
Corticosteroids, sclerosant injections, hyaluronic acid and capsaicin have been shown to be effective in reducing the pain related to MN.
PubMed: 38955553
DOI: 10.1016/j.pmn.2024.06.005 -
Obstetrics and Gynecology Jul 2024To quantify the association between prophylactic radiologic interventions and perioperative blood loss during cesarean delivery in women with placenta accreta spectrum...
OBJECTIVE
To quantify the association between prophylactic radiologic interventions and perioperative blood loss during cesarean delivery in women with placenta accreta spectrum disorder through a systematic review and network meta-analysis.
DATA SOURCES
On January 3, 2023, a literature search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science. We also checked ClinicalTrials.gov retrospectively. Prophylactic radiologic interventions to reduce bleeding during cesarean delivery involved preoperative placement of balloon catheters, distal (internal or common iliac arteries) or proximal (abdominal aorta), or sheaths (uterine arteries). The primary outcome was volume of blood loss; secondary outcomes were the number of red blood cell units transfused and adverse events. Studies including women who received an emergency cesarean delivery were excluded.
METHODS OF STUDY SELECTION
Two authors independently screened citations for relevance, extracted data, and assessed the risk of bias of individual studies with the Cochrane Risk of Bias in Non-randomized Studies of Interventions tool.
TABULTATION, INTEGRATION, AND RESULTS
From a total of 1,332 screened studies, 50 were included in the final analysis, comprising 5,962 women. These studies consisted of two randomized controlled trials and 48 observational studies. Thirty studies compared distal balloon occlusion with a control group, with a mean difference in blood loss of -406 mL (95% CI, -645 to -167). Fourteen studies compared proximal balloon occlusion with a control group, with a mean difference of -1,041 mL (95% CI, -1,371 to -710). Sensitivity analysis excluding studies with serious or critical risk of bias provided similar results. Five studies compared uterine artery embolization with a control group, all with serious or critical risk of bias; the mean difference was -936 mL (95% CI, -1,522 to -350). Reported information on adverse events was limited.
CONCLUSION
Although the predominance of observational studies in the included literature warrants caution in interpreting the findings of this meta-analysis, our findings suggest that prophylactic placement of balloon catheters or sheaths before planned cesarean delivery in women with placenta accreta spectrum disorder may, in some cases, substantially reduce perioperative blood loss. Further study is required to quantify the efficacy according to various severities of placenta accreta spectrum disorder and the associated safety of these radiologic interventions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42022320922.
PubMed: 38954828
DOI: 10.1097/AOG.0000000000005662 -
Clinical Cardiology Jul 2024Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present study, we compared the efficacy of GLP-1 RAs in cardiovascular events between patients with and without diabetes.
METHODS
After finding eligible studies assessing the impact of GLP-1 RAs on cardiovascular events in patients with and without diabetes using a systematic search, we performed a meta-analysis on randomized-controlled trials (RCTs) comparing cardiovascular outcomes between patients taking GLP-1 RAs and placebo stratified by the presence or absence of diabetes. Relative risk (RR) and its 95% confidence interval (CI) were set as the reporting effect size using the random-effects model.
RESULTS
A total of 24 RCTs (50 033 with GLP-1 RAs and 44 514 with placebo) were included. Patients on GLP-1 RAs had lower risk of major adverse cardiovascular events (MACE) (RR 0.87, 95% CI 0.82-0.93), cardiovascular death (RR 0.88, 95% CI 0.82-0.94), myocardial infarction (MI) (RR 0.87, 95% CI 0.77-0.97), stroke (RR 0.86, 95% CI 0.80-0.92), and hospitalization for heart failure (RR 0.90, 95% CI 0.83-0.98). Both subgroups were shown to be effective in terms of MACE and mortality. Nondiabetic patients had decreased risk of hospitalization for heart failure and MI, whereas the diabetic subgroup had marginally nonsignificant efficacy.
CONCLUSION
The findings of this meta-analysis indicated that patients who are overweight/obese but do not have diabetes have a comparable reduction in the risk of adverse cardiovascular events as those with diabetes. These results need to be confirmed further by large-scale randomized trials in the future.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Cardiovascular Diseases; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Risk Factors; Risk Assessment; Treatment Outcome; Incretins; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38953365
DOI: 10.1002/clc.24314 -
Lung India : Official Organ of Indian... Jul 2024Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial...
BACKGROUND
Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) is a modality to obtain larger histological samples by inserting a cryoprobe into the mediastinal lesion. We aimed to study the diagnostic yield and safety of EBUS-TMC.
METHODS
We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. We then performed a meta-analysis to calculate the diagnostic yield of EBUS-TMC and compare it with EBUS-TBNA.
RESULTS
Following a systematic search, we identified 14 relevant studies (869 patients undergoing EBUS-TMC and EBUS-TBNA). We then performed a meta-analysis of the diagnostic yield of EBUS-TMC and EBUS-TBNA from studies wherein both procedures were performed. The pooled diagnostic yield of EBUS-TMC was 92% (95% confidence interval [CI], 89%-95%). The pooled diagnostic yield of EBUS-TBNA was 81% (95% CI, 77%-85%). The risk difference in yield was 11% (95% CI, 6%-15%, I2 = 0%) when EBUS-TMC and EBUS-TBNA were compared. The only complication reported commonly with EBUS-TMC was minor bleeding. The complication rate was comparable with EBUS-TBNA.
CONCLUSION
EBUS-TMC provides a greater diagnostic yield with a similar risk of adverse events compared to EBUS-TBNA. Future studies are required to clearly establish which patients are most likely to benefit from this modality.
PubMed: 38953193
DOI: 10.4103/lungindia.lungindia_606_23 -
American Journal of Clinical Oncology Jul 2024Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review...
OBJECTIVES
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population.
METHODS
We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data.
RESULTS
Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis.
CONCLUSIONS
T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.
PubMed: 38951994
DOI: 10.1097/COC.0000000000001126