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Archivos Espanoles de Urologia May 2024This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor... (Meta-Analysis)
Meta-Analysis Comparative Study
PURPOSE
This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor injection for overactive bladder syndrome (OAB).
METHODS
This systematic review is registered with PROSPERO (CRD42021237964). A licensed librarian surveyed Medline, EMBASE, Scopus, and Google Scholar databases to conduct a comprehensive search. Studies comparing suburothelial and intradetrusor techniques of OnabotA injection for OAB were included, along with clinical and urodynamic variables and complications. The studies were assessed for quality on the basis of Cochrane Collaboration guidelines and evaluated using statistical analysis via a random-effect model and I statistic. Data extraction and analysis were conducted using Covidence systematic review platform and Review Manager software.
RESULTS
Six studies with 299 patients were included in the systematic review, with four reporting that suburothelial injection of OnabotA was as effective as intradetrusor injection and two reporting intradetrusor injection to be more effective. The meta-analysis found no significant difference between the suburothelial and intradetrusor groups for mean daily catheter or voiding frequency (mean difference: 2.12 [95% confidence interval (CI): -1.61, 5.84]) and the mean number of urgency/urge incontinence episodes (mean difference: 0.08 [95% CI: -1.42, 1.57]). However, a significant heterogeneity was found among the studies. Only the mean volume at first detrusor contraction showed a significant difference, being higher for suburothelial injection (mean difference: 33.39 [95% CI: 0.16, 66.63]). No significant difference was noted for mean compliance, mean bladder capacity, and mean maximum detrusor pressure. Urinary tract infections (UTIs) ( = 0.24) and acute urinary retention ( = 0.92) showed no significant difference between the two groups. The risk of bias varied among the studies.
CONCLUSIONS
Suburothelial injection of OnabotA is as effective as intradetrusor injection in improving OAB symptoms, and it has similar complication rates. A higher mean volume of the first detrusor contraction was found in a urodynamic study with suburothelial injection.
Topics: Botulinum Toxins, Type A; Humans; Urinary Bladder, Overactive; Adult; Urinary Bladder, Neurogenic; Injections
PubMed: 38840279
DOI: 10.56434/j.arch.esp.urol.20247704.50 -
The Cochrane Database of Systematic... Jun 2024Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss and disability worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is an effective treatment option that helps to prevent vision loss or to improve visual acuity in people with neovascular AMD, treatment imposes a significant financial burden on patients and healthcare systems. A biosimilar is a biological product that has been developed to be nearly identical to a previously approved biological product. The use of biosimilars may help reduce costs and so may increase patient access to effective biologic medicines with similar levels of safety to the drugs on which they are based.
OBJECTIVES
To assess the benefits and harms of anti-VEGF biosimilar agents compared with their corresponding anti-VEGF agents (i.e. the reference products) that have obtained regulatory approval for intravitreal injections in people with neovascular AMD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries together with reference checking and contact with study authors to identify studies that are included in the review. The latest search date was 2 June 2023.
ELIGIBILITY CRITERIA
We included randomized controlled trials (RCTs) that compared approved anti-VEGF biosimilars with their reference products for treating the eyes of adult participants (≥ 50 years) who had an active primary or recurrent choroidal neovascularization lesion secondary to neovascular AMD.
OUTCOMES
Our outcomes were: best-corrected visual acuity (BCVA), central subfield thickness (CST), vision-related quality of life, serious ocular and non-ocular adverse events (AE), treatment-emergent adverse events (TEAEs), anti-drug antibodies (ADAs), and serum concentrations of biosimilars and reference drugs.
RISK OF BIAS
We assessed the risk of bias (RoB) for seven outcomes reported in a summary of findings table by using the Cochrane RoB 2 tool.
SYNTHESIS METHODS
We synthesized results for each outcome using meta-analysis, where possible, by calculating risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for dichotomous outcomes and continuous outcomes, respectively. Where this was not possible due to the nature of the data, we summarized the results narratively. We used GRADE to assess the certainty of evidence for prespecified outcomes.
INCLUDED STUDIES
We included nine parallel-group multi-center RCTs that enrolled a total of 3814 participants (3814 participating eyes), with sample sizes that ranged from 160 to 705 participants per study. The mean age of the participants in these studies ranged from 67 to 76 years, and the proportion of women ranged from 26.5% to 58.7%. Ranibizumab (Lucentis) was the reference product in seven studies, and aflibercept (Eyelea) was the reference product in two others. All the included studies had been supported by industry. The follow-up periods ranged from 12 to 52 weeks (median 48 weeks). Five studies (56%) were conducted in multi-country settings across Europe, North America and Asia, two studies in India, and one each in Japan and the Republic of Korea. We judged all the included studies to have met high methodological standards.
SYNTHESIS OF RESULTS
With regard to efficacy, our meta-analyses demonstrated that anti-VEGF biosimilars for neovascular AMD resulted in little to no difference compared with the reference products for BCVA change at 8 to 12 weeks (MD -0.55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% CI -1.17 to 0.07; 8 studies, 3603 participants; high-certainty evidence) and the proportion of participants who lost fewer than 15 letters in BCVA at 24 to 48 weeks (RR 0.99, 95% CI 0.98 to 1.01; 7 studies, 2658 participants; moderate-certainty evidence). Almost all participants (96.6% in the biosimilar group and 97.0% in the reference product group) lost fewer than 15 letters in BCVA. The evidence from two studies suggested that there was no evidence of difference between biosimilars and reference products in vision-related quality of life measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) summary scores at 24 to 48 weeks (MD 0.82, 95% CI -0.70 to 2.35; 2 studies, 894 participants; moderate-certainty evidence). With regard to the safety profile, meta-analyses also revealed little to no difference between anti-VEGF biosimilars and the reference products for the proportion of participants who experienced serious ocular AEs (RR 1.24, 95% CI 0.68 to 2.26; 7 studies, 3292 participants; moderate-certainty evidence), and for TEAEs leading to investigational product discontinuation or death (RR 0.96, 95% CI 0.63 to 1.46; 8 studies, 3497 participants; moderate-certainty evidence). Overall, 1.4% of participants in the biosimilar group and 1.2% in the reference product group experienced serious ocular adverse events. The most frequently documented serious ocular AEs were retinal hemorrhage and endophthalmitis. Although the evidence is of low certainty due to imprecision, meta-analysis suggested that anti-VEGF biosimilars led to no difference compared with the reference products for cumulative incidence of ADAs (RR 0.84, 95% CI 0.58 to 1.22; 8 studies, 3066 participants; low-certainty evidence) or mean maximum serum concentrations (MD 0.42 ng/mL, 95% CI -0.22 to 1.05; subgroup of 3 studies, 100 participants; low-certainty evidence). We judged the overall risk of bias to be low for all studies.
AUTHORS' CONCLUSIONS
In our review, low to high certainty evidence suggests that there is little to no difference, to date, between the anti-VEGF biosimilars approved for treating neovascular AMD and their reference products in terms of benefits and harms. While anti-VEGF biosimilars may be a viable alternative to reference products, current evidence for their use is based on a limited number of studies - particularly for comparison with aflibercept - with sparse long-term safety data, and infrequent assessment of quality of life outcomes. Our effect estimates and conclusions may be modified once findings have been reported from studies that are currently ongoing, and studies of biosimilar agents that are currently in development.
FUNDING
Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. Takeshi Hasegawa and Hisashi Noma were supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239).
REGISTRATION
Protocol available via doi.org/10.1002/14651858.CD015804.
Topics: Aged; Humans; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide; Bevacizumab; Bias; Biosimilar Pharmaceuticals; Choroidal Neovascularization; Intravitreal Injections; Macular Degeneration; Randomized Controlled Trials as Topic; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A; Visual Acuity; Middle Aged; Male; Female
PubMed: 38829176
DOI: 10.1002/14651858.CD015804.pub2 -
International Journal of Chronic... 2024Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology.
RESEARCH METHODS
Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed.
RESULTS
A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =-4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure.
CONCLUSION
This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Drugs, Chinese Herbal; Network Pharmacology; Treatment Outcome; Randomized Controlled Trials as Topic; Lung; Anti-Inflammatory Agents; Middle Aged; Male; Aged; Female; Injections
PubMed: 38826697
DOI: 10.2147/COPD.S442281 -
Neurosurgical Focus Jun 2024The purpose of this systematic review was to evaluate empirical outcomes of studies in the literature that investigated effectiveness of intrathecal baclofen (ITB) in...
OBJECTIVE
The purpose of this systematic review was to evaluate empirical outcomes of studies in the literature that investigated effectiveness of intrathecal baclofen (ITB) in the treatment of multiple sclerosis (MS)-related spasticity (MSRS) based on various metrics. Since the first description of this route of baclofen delivery for MS patients by Penn and Kroin in 1984, numerous studies have contributed to the medical community's knowledge of this treatment modality. The authors sought to add to the literature a systematic review of studies over the last 2 decades that elucidates the clinical impact of ITB in treating MSRS with the following endpoints: impact on patient-centered outcomes, such as spasticity reduction (primary), complications (secondary), and dosing (secondary).
METHODS
The authors queried three databases (PubMed, Scopus, and Cochrane Library) using the following search terms: (intrathecal baclofen) AND (multiple sclerosis). The set inclusion criteria were as follows: 1) original, full-text article; 2) written in the English language; 3) published between and including the years 2000 and 2023; 4) discussion of pre- and post-ITB pump implantation outcomes (e.g., reduction in spasticity and improved comfort) in MSRS patients with long-term ITB treatment; and 5) contained a minimum of 5 MS patients. Data on study type, patient demographics, follow-up periods, primary outcomes, and secondary outcomes were extracted from the included studies.
RESULTS
The authors' search yielded 465 studies, of which 17 met inclusion criteria. Overall, they found evidence for the effectiveness of ITB in treating MSRS patients whose condition was refractory to oral medications, with significant reported changes in spasm frequency from pre- to postimplantation. They also found evidence supporting the positive impact of ITB on MSRS patients' quality of life. Moreover, the authors found that most complications were surgical rather than pharmacological. In addition, the average 1-year dose of ITB (reported in 7 of the included studies) was 191.93 μg/day, which is substantially lower than ITB doses reported in the literature for patients with central (non-MS) or spinal origins of spasticity at 1-year follow-up.
CONCLUSIONS
The evidence supports ITB as a clinically effective treatment for MSRS, particularly in patients in whom oral antispasmodics and physiotherapy have failed. This systematic review contributes a comprehensive synthesis of clinical benefits, complications, and dosing of ITB reported over the past 2 decades, which furthers an understanding of ITB's clinical utility in practice.
Topics: Baclofen; Humans; Multiple Sclerosis; Injections, Spinal; Muscle Spasticity; Muscle Relaxants, Central; Treatment Outcome
PubMed: 38823049
DOI: 10.3171/2024.3.FOCUS2464 -
International Wound Journal Jun 2024Recent randomised controlled trials (RCTs) have investigated the analgesic activity of sesame oil among patients with limb trauma; nevertheless, their findings are... (Meta-Analysis)
Meta-Analysis Review
Alleviating severity of limb trauma pain with coadministration of topical sesame oil and standard treatments: A GRADE-assessed systematic review and meta-analysis of randomised controlled trials.
Recent randomised controlled trials (RCTs) have investigated the analgesic activity of sesame oil among patients with limb trauma; nevertheless, their findings are inconsistent. Hence, this review aimed to clarify the impact of topical administration of sesame oil on acute pain of adult outpatients with minor limb trauma. The online databases (e.g., Scopus, PubMed, Web of Science) were searched up to 31 January 2024. The RCTs were included if they compared the effect of applying standard treatments plus topical sesame oil to administering standard treatments alone or with a placebo/sham treatment. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and the Cochrane Collaboration's risk of bias tool were applied to address the evidence quality and the study's methodological rigour, respectively. Four RCTs had the inclusion criteria, and their findings were pooled in a meta-analysis employing a random-effects approach. According to the pooled analysis, the reduction in mean change of the pain score from baseline to the second/third intervention day was significantly higher in favour of clients who received standard care plus daily massage of the trauma site with sesame oil compared to those who received a control condition (weighted mean difference: -1.10; 95% confidence interval [-1.62, -0.57]; p < 0.001). However, the evidence quality was moderate, and only two studies had good methodological rigour. Hence, more high-quality studies are needed to make a solid evidence-based conclusion about the favourable consequence of topical sesame oil on alleviating acute traumatic limb pain.
Topics: Humans; Randomized Controlled Trials as Topic; Sesame Oil; Administration, Topical; Pain Management; Adult; Female; Male; Analgesics; Pain Measurement; Middle Aged; Extremities
PubMed: 38822706
DOI: 10.1111/iwj.14907 -
BMC Pediatrics May 2024Agitation/delirium is commonly seen in children after anesthesia, and a proper dose of dexmedetomidine can prevent this complication. This study aimed to investigate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Agitation/delirium is commonly seen in children after anesthesia, and a proper dose of dexmedetomidine can prevent this complication. This study aimed to investigate the effects of different doses of Dexmedetomidine (DEX) on agitation/delirium and other complications in anesthetized children, providing clinical evidence for dose recommendations of DEX.
METHODS
This study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and EMBASE. Two independent researchers performed literature screening, data extraction, and assessed the methodological quality. Data analysis was conducted using R and STATA 16.0.
RESULTS
In the final analysis, 20 randomized controlled trials (RCTs) involving 2521 children were included. The results showed that in comparison to normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX significantly reduced the incidence of post-anesthetic emergence agitation in children with the most effective dose being 2 µg/kg (SUCRA = 0.91). Compared with normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX reduced patient's need for postoperative analgesia, with the most effective dose being 1.5 µg/kg (SUCRA = 0.78). However, 1 µg/kg DEX performed the best in reducing Pediatric Anaesthesia Emergence Delirium (PAED) Scale score (SUCRA = 0.88).
CONCLUSION
Compared with normal saline, intranasal administration of 2 µg/kg DEX and 1.5 µg/kg DEX are the optimal doses to reduce the incidence of agitation and the need for postoperative pain relief in children under general anesthesia. Given effectiveness and safety, intranasal use of 1 µg/kg DEX appears to be the most effective dosage for anesthetized children.
Topics: Dexmedetomidine; Humans; Administration, Intranasal; Child; Hypnotics and Sedatives; Dose-Response Relationship, Drug; Parents; Emergence Delirium; Psychomotor Agitation; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 38822315
DOI: 10.1186/s12887-024-04832-w -
The Journal of Evidence-based Dental... Jun 2024Effectiveness of intra-articular injections of sodium hyaluronate, corticosteroids, platelet-rich plasma on temporomandibular joint osteoarthritis: a systematic review... (Meta-Analysis)
Meta-Analysis
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION
Effectiveness of intra-articular injections of sodium hyaluronate, corticosteroids, platelet-rich plasma on temporomandibular joint osteoarthritis: a systematic review and network meta-analysis of randomized controlled trials. Xie Y, Zhao K, Ye G, Yao X, Yu M, Ouyang H. J Evid Based Dent Pract. 2022 Sep;22(3):101720. doi:10.1016/j.jebdp.2022.101720.
SOURCE OF FUNDING
National Natural Science Foundation of China (nos. T2121004, 81630065).
TYPE OF STUDY/DESIGN
Systematic review with network meta-analysis of data.
Topics: Humans; Injections, Intra-Articular; Osteoarthritis; Temporomandibular Joint Disorders; Hyaluronic Acid; Platelet-Rich Plasma; Randomized Controlled Trials as Topic; Adrenal Cortex Hormones; Network Meta-Analysis
PubMed: 38821656
DOI: 10.1016/j.jebdp.2024.101985 -
The Bone & Joint Journal Jun 2024Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and... (Meta-Analysis)
Meta-Analysis
AIMS
Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months.
METHODS
This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included.
RESULTS
In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months.
CONCLUSION
Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes.
Topics: Humans; Injections, Intra-Articular; Osteoarthritis, Hip; Hyaluronic Acid; Platelet-Rich Plasma; Treatment Outcome; Anesthetics, Local; Randomized Controlled Trials as Topic; Viscosupplements; Network Meta-Analysis; Pain Measurement
PubMed: 38821500
DOI: 10.1302/0301-620X.106B6.BJJ-2023-1272.R1 -
Journal of Robotic Surgery May 2024Subretinal injection (SI) is a novel drug delivery method, directly to retina for treatment of various eye disease. However, manual injection requires surgical... (Review)
Review
Subretinal injection (SI) is a novel drug delivery method, directly to retina for treatment of various eye disease. However, manual injection requires surgical experience and precision due to physiological factors. Robots offer solution to this issue, by reducing hand tremor and increased accuracy. This systematic review analyzes current status on robot-assisted SI compared to conventional techniques. Systematic search across 5 databases was conducted to identify studies comparing manual and robot-assisted SI procedures. Extracted data included robotic systems, complications, and success rates. Four studies, including one human trial, two ex vivo porcine eye studies, and one artificial eye model study were included in the synthesis. The findings show early advantages of robot-assisted SI. Compared to traditional interventions, robot procedures result in reduced tremor, what potentially lowers the risk of complications, including retinal tears and reflux. The first in-human randomized trial showed encouraging results, with no significant differences in surgical times or complications between robot-assisted and manual SI. However, major limitation of robot-assisted procedures is longer procedure time. Robot-assisted SI holds promise by offering increased precision and stability, reducing human error and potentially improving clinical outcomes. Challenges include cost, availability, and learning curve. Overall, early stage of robot-assisted SI suggests advantages in precision, complication reduction, and potentially improved drug delivery. Further research in human randomized trials is needed to fully assess its full-scale clinical application.
Topics: Humans; Animals; Retina; Drug Delivery Systems; Robotic Surgical Procedures; Swine; Injections, Intraocular
PubMed: 38819533
DOI: 10.1007/s11701-024-01991-x -
PloS One 2024This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment. (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVES
This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment.
METHODS
A computerized search through PubMed/MEDLINE, SCOPUS, and the Cochrane Library was conducted to find relevant papers. We used the "netmeta" and "meta" packages for network meta-analysis (NMA) in RStudio 1.2.5019 (2009-2019 RStudio, Inc.) to conduct all of our statistical tests.
RESULTS
Seven articles (n = 2,006 patients) were included. The fixed-effect size showed that TC 1% bis in die (BID) showed potential effectiveness in reducing the inflammatory and non-inflammatory lesion count compared to placebo (Standardized mean difference, SMD = -0.27, 95% CI: -0.36 to -0.17) and (SMD = -0.31, 95% CI: -0.41 to -0.22), respectively. The random-effect size showed that TC 1% BID was significantly associated with a 12-week treatment success compared to placebo (Odds ratio, OR = 2.44, 95% CI: 1.12 to 5.30). Spironolactone 200 mg was associated with a significant reduction in total lesion count (SMD = -4.46, 95% CI: -5.60 to -3.32).
CONCLUSION
TC appears to reduce both inflammatory and non-inflammatory lesion count and may lead to treatment success. Spironolactone at 200 mg showed potential effectiveness in terms of total lesion count reduction. These results suggest that both TC and Spironolactone could be beneficial in treating patients with acne vulgaris.
Topics: Acne Vulgaris; Humans; Spironolactone; Network Meta-Analysis; Treatment Outcome; Administration, Topical; Cortodoxone; Propionates
PubMed: 38814916
DOI: 10.1371/journal.pone.0298155