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The Cochrane Database of Systematic... Jul 2023Potential benefits of rapamycin or rapalogs for treating people with tuberous sclerosis complex (TSC) have been shown. Currently everolimus (a rapalog) is only approved... (Review)
Review
BACKGROUND
Potential benefits of rapamycin or rapalogs for treating people with tuberous sclerosis complex (TSC) have been shown. Currently everolimus (a rapalog) is only approved for TSC-associated renal angiomyolipoma and subependymal giant cell astrocytoma (SEGA), but not other manifestations of TSC. A systematic review needs to establish evidence for rapamycin or rapalogs for various manifestations in TSC. This is an updated review.
OBJECTIVES
To determine the effectiveness of rapamycin or rapalogs in people with TSC for decreasing tumour size and other manifestations and to assess the safety of rapamycin or rapalogs in relation to their adverse effects.
SEARCH METHODS
We identified relevant studies from the Cochrane-Central-Register-of-Controlled-Trials (CENTRAL), Ovid MEDLINE and ongoing trials registries with no language restrictions. We searched conference proceedings and abstract books of conferences. Date of the last searches: 15 July 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs of rapamycin or rapalogs in people with TSC.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias of each study; a third review author verified the extracted data and risk of bias decisions. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
The current update added seven RCTs, bringing the total number to 10 RCTs (with 1008 participants aged 3 months to 65 years; 484 males). All TSC diagnoses were by consensus criteria as a minimum. In parallel studies, 645 participants received active interventions and 340 placebo. Evidence is low-to-high certainty and study quality is mixed; mostly a low risk of bias across domains, but one study had a high risk of performance bias (lack of blinding) and three studies had a high risk of attrition bias. Manufacturers of the investigational products supported eight studies. Systemic administration Six studies (703 participants) administered everolimus (rapalog) orally. More participants in the intervention arm reduced renal angiomyolipoma size by 50% (risk ratio (RR) 24.69, 95% confidence interval (CI) 3.51 to 173.41; P = 0.001; 2 studies, 162 participants, high-certainty evidence). In the intervention arm, more participants in the intervention arm reduced SEGA tumour size by 50% (RR 27.85, 95% CI 1.74 to 444.82; P = 0.02; 1 study; 117 participants; moderate-certainty evidence) ,and reported more skin responses (RR 5.78, 95% CI 2.30 to 14.52; P = 0.0002; 2 studies; 224 participants; high-certainty evidence). In one 18-week study (366 participants), the intervention led to 25% fewer seizures (RR 1.63, 95% CI 1.27 to 2.09; P = 0.0001) or 50% fewer seizures (RR 2.28, 95% CI 1.44 to 3.60; P = 0.0004); but there was no difference in numbers being seizure-free (RR 5.30, 95% CI 0.69 to 40.57; P = 0.11) (moderate-certainty evidence). One study (42 participants) showed no difference in neurocognitive, neuropsychiatry, behavioural, sensory and motor development (low-certainty evidence). Total adverse events (AEs) did not differ between groups (RR 1.09, 95% CI 0.97 to 1.22; P = 0.16; 5 studies; 680 participants; high-certainty evidence). However, the intervention group experienced more AEs resulting in withdrawal, interruption of treatment, or reduced dose (RR 2.61, 95% CI 1.58 to 4.33; P = 0.0002; 4 studies; 633 participants; high-certainty evidence and also reported more severe AEs (RR 2.35, 95% CI 0.99 to 5.58; P = 0.05; 2 studies; 413 participants; high-certainty evidence). Topical (skin) administration Four studies (305 participants) administered rapamycin topically. More participants in the intervention arm showed a response to skin lesions (RR 2.72, 95% CI 1.76 to 4.18; P < 0.00001; 2 studies; 187 participants; high-certainty evidence) and more participants in the placebo arm reported a deterioration of skin lesions (RR 0.27, 95% CI 0.15 to 0.49; 1 study; 164 participants; high-certainty evidence). More participants in the intervention arm responded to facial angiofibroma at one to three months (RR 28.74, 95% CI 1.78 to 463.19; P = 0.02) and three to six months (RR 39.39, 95% CI 2.48 to 626.00; P = 0.009; low-certainty evidence). Similar results were noted for cephalic plaques at one to three months (RR 10.93, 95% CI 0.64 to 186.08; P = 0.10) and three to six months (RR 7.38, 95% CI 1.01 to 53.83; P = 0.05; low-certainty evidence). More participants on placebo showed a deterioration of skin lesions (RR 0.27, 95% CI 0.15 to 0.49; P < 0.0001; 1 study; 164 participants; moderate-certainty evidence). The intervention arm reported a higher general improvement score (MD -1.01, 95% CI -1.68 to -0.34; P < 0.0001), but no difference specifically in the adult subgroup (MD -0.75, 95% CI -1.58 to 0.08; P = 0.08; 1 study; 36 participants; moderate-certainty evidence). Participants in the intervention arm reported higher satisfaction than with placebo (MD -0.92, 95% CI -1.79 to -0.05; P = 0.04; 1 study; 36 participants; low-certainty evidence), although again with no difference among adults (MD -0.25, 95% CI -1.52 to 1.02; P = 0.70; 1 study; 18 participants; low-certainty evidence). Groups did not differ in change in quality of life at six months (MD 0.30, 95% CI -1.01 to 1.61; P = 0.65; 1 study; 62 participants; low-certainty evidence). Treatment led to a higher risk of any AE compared to placebo (RR 1.72, 95% CI 1.10, 2.67; P = 0.02; 3 studies; 277 participants; moderate-certainty evidence); but no difference between groups in severe AEs (RR 0.78, 95% CI 0.19 to 3.15; P = 0.73; 1 study; 179 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Oral everolimus reduces the size of SEGA and renal angiomyolipoma by 50%, reduces seizure frequency by 25% and 50% and implements beneficial effects on skin lesions with no difference in the total number of AEs compared to placebo; however, more participants in the treatment group required a dose reduction, interruption or withdrawal and marginally more experienced serious AEs compared to placebo. Topical rapamycin increases the response to skin lesions and facial angiofibroma, an improvement score, satisfaction and the risk of any AE, but not severe adverse events. With caution regarding the risk of severe AEs, this review supports oral everolimus for renal angiomyolipoma, SEGA, seizure, and skin lesions, and topical rapamycin for facial angiofibroma.
Topics: Adult; Male; Humans; MTOR Inhibitors; Sirolimus; Everolimus; Angiofibroma; Angiomyolipoma; Tuberous Sclerosis; Astrocytoma; Kidney Neoplasms
PubMed: 37432030
DOI: 10.1002/14651858.CD011272.pub3 -
Photodiagnosis and Photodynamic Therapy Dec 2023Objective To investigate the effect of low-level laser and photodynamic therapy on the oral health, and periodontal tissue of fixed orthodontic patients and the effect... (Meta-Analysis)
Meta-Analysis
Objective To investigate the effect of low-level laser and photodynamic therapy on the oral health, and periodontal tissue of fixed orthodontic patients and the effect of using photobiomodulation methods compared to routine plaque removal methods and the amount of plaque in fixed orthodontic patients. Method and materials First, the title and summary of related articles were collected by using the search strategy electronic databases PUBMED, EMBASE, Cochrane's CENTRAL, Scopus, ISI and all the articles that were published from the beginning to February 2023 were evaluated. The title, abstracts and full texts of all the relevant studies were reviewed respectively, and those meeting the criteria were entered into our study. Finally, the quality of the studies was examined and the results of the studies were pooled by means of random effects inverse variance meta-analysis. Results Eighteen randomized studies, conducted between 2015 and December 2022, were selected for meta-analysis. Five studies were conducted as split-mouth, twelve as parallel-group, and one as a cross-over design. Among the studies, five examined the effects of low-level laser therapy and twelve assessed the effects of photodynamic therapy. The meta-analysis revealed that photodynamic therapy significantly reduced probing depth compared to scaling (MD=-0.2 mm, P<0.001), though the difference does not seem to be clinically significant. But no significant differences between photodynamic therapy and scaling or low-level laser therapy and control groups in terms of plaque index, or bleeding on probing, gingival crevicular fluid volume, gingival recession, clinical attachment loss, bacterial load and concentrations of inflammatory substances across multiple follow-up periods. Conclusion Moderate evidence indicates that photodynamic therapy (PDT) is comparable to conventional methods in improving oral health, as measured by periodontal indices, inflammatory proteins, bacterial colonies, and white spot lesions, making it a suitable alternative. Limited evidence suggests low-level laser therapy (LLLT) may improve oral health, particularly addressing caries, but further research is needed.
Topics: Humans; Photochemotherapy; Low-Level Light Therapy; Oral Health; Photosensitizing Agents; Orthodontics; Dental Scaling
PubMed: 37604216
DOI: 10.1016/j.pdpdt.2023.103759 -
BMC Bioinformatics Oct 2023Recent advancements in computing power and state-of-the-art algorithms have helped in more accessible and accurate diagnosis of numerous diseases. In addition, the...
BACKGROUND
Recent advancements in computing power and state-of-the-art algorithms have helped in more accessible and accurate diagnosis of numerous diseases. In addition, the development of de novo areas in imaging science, such as radiomics and radiogenomics, have been adding more to personalize healthcare to stratify patients better. These techniques associate imaging phenotypes with the related disease genes. Various imaging modalities have been used for years to diagnose breast cancer. Nonetheless, digital breast tomosynthesis (DBT), a state-of-the-art technique, has produced promising results comparatively. DBT, a 3D mammography, is replacing conventional 2D mammography rapidly. This technological advancement is key to AI algorithms for accurately interpreting medical images.
OBJECTIVE AND METHODS
This paper presents a comprehensive review of deep learning (DL), radiomics and radiogenomics in breast image analysis. This review focuses on DBT, its extracted synthetic mammography (SM), and full-field digital mammography (FFDM). Furthermore, this survey provides systematic knowledge about DL, radiomics, and radiogenomics for beginners and advanced-level researchers.
RESULTS
A total of 500 articles were identified, with 30 studies included as the set criteria. Parallel benchmarking of radiomics, radiogenomics, and DL models applied to the DBT images could allow clinicians and researchers alike to have greater awareness as they consider clinical deployment or development of new models. This review provides a comprehensive guide to understanding the current state of early breast cancer detection using DBT images.
CONCLUSION
Using this survey, investigators with various backgrounds can easily seek interdisciplinary science and new DL, radiomics, and radiogenomics directions towards DBT.
Topics: Humans; Female; Deep Learning; Radiographic Image Enhancement; Breast; Breast Neoplasms; Mammography
PubMed: 37884877
DOI: 10.1186/s12859-023-05515-6 -
The American Journal of Sports Medicine Sep 2023Superior labrum anterior to posterior (SLAP) lesions are targeted on physical examination using a variety of provocative maneuvers. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Superior labrum anterior to posterior (SLAP) lesions are targeted on physical examination using a variety of provocative maneuvers.
PURPOSE/HYPOTHESIS
The purpose was to conduct a systematic review on the performance of physical examination maneuvers in diagnosing SLAP lesions and to perform a meta-analysis comparing the sensitivity and specificity of these examinations both individually and in combination. The null hypothesis stated that there would be no significant difference in the sensitivity or specificity of the included physical examination tests, neither individually nor in combination.
STUDY DESIGN
Meta-analysis and systematic review; Level of evidence, 4.
METHODS
A systematic review was performed with the inclusion criteria of studies that reported either the sensitivities and specificities or the number of true-positive, true-negative, false-positive, or false-negative results for at least 1 maneuver for identifying SLAP lesions. A meta-analysis was performed to determine the sensitivity and specificity of individual maneuvers. Additional analysis determined the performance of these maneuvers when combined in series and parallel. In series, all must be present to be considered positive. In parallel, any single positive test forces the overall combination to be considered positive. Only tests that were included in ≥3 studies were considered in the meta-analysis and those included in ≥4 studies were considered in the combination analysis.
RESULTS
Overall, 862 studies were identified, 18 of which were included in the systematic review and meta-analysis. The physical examinations included were the O'Brien (n = 16), speed (n = 8), Yergason (n = 6), anterior slide (n = 8), crank (n = 7), Jobe (n = 5), dynamic labral shear (n = 3), Kim 2 (n = 3), and biceps groove tenderness tests (n = 3). All combinations of 2 to 5 maneuvers in both series and parallel were considered. The O'Brien and crank test combination was the most sensitive 2-test combination in both parallel and series. The Yergason and anterior slide test combination was the most specific 2-test combination in parallel and series.
CONCLUSION
This systematic review and meta-analysis reports an updated meta-analysis considering the sensitivity and specificity of common physical examination maneuvers used in the diagnosis of SLAP lesions and considers these values for tests in both series and parallel combinations. The present analysis demonstrates improved specificities when tests are considered in series and improved sensitivities when considered in parallel combination.
Topics: Humans; Shoulder Injuries; Sensitivity and Specificity; Physical Examination; Shoulder; Shoulder Joint; Arthroscopy
PubMed: 35997579
DOI: 10.1177/03635465221100977 -
Clinical and Translational Science May 2024No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and... (Review)
Review
No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and primary end points (PEs) of phase II and III trials intended to modify the natural course of the disease in patients with RMS. The purpose of the study is to explore trends/topics and discussion points in clinical trial design and PE, comparing them to regulatory guidelines and expert recommendations. Three trial registration systems, ClinicalTrials.gov, the EU Clinical Trials Register, and the Japan Registry of Clinical Trials, were used and 60 trials were evaluated. The dominant clinical trial design was a randomized controlled parallel-arms trial and other details were as follows: in adult phase III confirmatory trials (n = 32), active-controlled double-blind trial (DBT) (53%) and active-controlled open-label assessor-masking trial (16%); in adult phase II dose-finding trials (n = 9), placebo- and active-controlled DBT (44%), placebo-controlled DBT (22%), and placebo-controlled add-on DBT (22%); and in pediatric phase III confirmatory trials (n = 8), active-controlled DBT (38%) and active-controlled open-label non-masking trial (25%). The most common PEs were as follows: in adult confirmatory trials, annual relapse rate (ARR) (56%) and no evidence of disease activity-3 (NEDA-3) (13%); in adult dose-finding trials, the cumulative number of T1 gadolinium-enhancing lesions (56%), combined unique active lesions (22%), and overall disability response score (22%); and in pediatric confirmatory trials, ARR (38%) and time to first relapse (25%). It was suggested that some parts of the regulatory guidelines and expert recommendations need to be revised.
Topics: Humans; Clinical Trials, Phase III as Topic; Clinical Trials, Phase II as Topic; Adult; Multiple Sclerosis, Relapsing-Remitting; Child; Research Design; Endpoint Determination; Randomized Controlled Trials as Topic
PubMed: 38708586
DOI: 10.1111/cts.13794 -
NeuroImage. Clinical 2024Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.
OBJECTIVE
We performed a systematic review and meta-analysis on the use of QSM in MS.
METHODS
Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.
RESULTS
After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.
CONCLUSIONS
We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Gray Matter; Brain
PubMed: 38582068
DOI: 10.1016/j.nicl.2024.103598 -
European Archives of Psychiatry and... Oct 2023The application of transcranial direct current stimulation (tDCS) at home for the treatment of major depressive disorder (MDD) is the subject of current clinical trials....
UNLABELLED
The application of transcranial direct current stimulation (tDCS) at home for the treatment of major depressive disorder (MDD) is the subject of current clinical trials. This is due to its positive safety profile, cost-effectiveness, and potential scalability for a wide outreach in clinical practice. Here, we provide a systematic review of the available studies and also a report on the results of a randomized controlled trial (RCT) on tDCS at home for the treatment of MDD. This trial had to be prematurely terminated due to safety concerns. The HomeDC trial is a double-blinded, placebo-controlled, parallel-group study. Patients with MDD (DSM-5) were randomized to active or sham tDCS. Patients conducted tDCS at home for 6 weeks with 5 sessions/week (30 min at 2 mA) anode over F3, cathode over F4. Sham tDCS resembled active tDCS, with ramp-in and ramp-out periods, but without intermittent stimulation. The study was prematurely terminated due to an accumulation of adverse events (AEs, skin lesions), so that only 11 patients were included. Feasibility was good. Safety monitoring was not sufficient enough to detect or prevent AEs within an appropriate timeframe. Regarding antidepressant effects, the reduction in depression scales over time was significant. However, active tDCS was not superior to sham tDCS in this regard. Both the conclusions from this review and the HomeDC trial show that there are several critical issues with the use of tDCS at home that need to be addressed. Nevertheless the array of transcranial electric simulation (TES) methods that this mode of application offers, including tDCS, is highly interesting and warrants further investigation in high quality RCTs.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov .
TRIAL REGISTRATION NUMBER
NCT05172505. Registration date: 12/13/2021, https://clinicaltrials.gov/ct2/show/NCT05172505 . *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers) **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https://doi.org/10.1136/bmj.n71 . For more information, visit: http://www.prisma-statement.org/.
Topics: Humans; Transcranial Direct Current Stimulation; Pilot Projects; Treatment Outcome; Depressive Disorder, Major; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 37191697
DOI: 10.1007/s00406-023-01620-y -
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 -
Pediatric Dermatology 2024Pediatric dermatitis and nonaccidental trauma (NAT) may have overlapping cutaneous presentations, posing a risk of misdiagnosis and subsequent emotional distress and...
BACKGROUND/OBJECTIVES
Pediatric dermatitis and nonaccidental trauma (NAT) may have overlapping cutaneous presentations, posing a risk of misdiagnosis and subsequent emotional distress and further harm. Through a systematic literature review, we reviewed pediatric (<18 years old) patients investigated for both dermatitis and NAT.
METHODS
EMBASE and MEDLINE databases were searched. English publications with original data involving pediatric patients investigated for both dermatitis and NAT were included. Nonhuman studies and incomplete articles/conference abstracts were excluded. Data extracted included the first author, year of publication, study design, participant count, sex of the population, age of the population, cutaneous presentation, timing of presentation, Child Protective Services involvement, and case relation to dermatitis and NAT.
RESULTS
This review included 21 case reports or series encompassing 29 patients. Among 26 patients initially investigated as NAT (26.9% involving Child Protective Services), final diagnoses included irritant contact dermatitis (53.8%), phytophotodermatitis (30.8%), allergic contact dermatitis (7.7%), perianal infectious dermatitis (3.8%), and atopic dermatitis (3.8%). Three patients initially diagnosed with nontraumatic dermatitis were later found to be victims of physical (2/3; 66.7%) or sexual abuse (1/3; 33.3%).
CONCLUSIONS
Effective history-taking and physical examinations should encompass a history of laxative use, contact with furocoumarin-containing plants/fruit, parallel family/peer cutaneous presentations, caregiver involvement, financial burden, patient discomfort, birthmark assessment, and lesions aligning with diaper borders or toilet seats. Limitations of this review include potential underreporting and the inclusion of low-quality study designs and evidence.
Topics: Child; Humans; Adolescent; Child Abuse; Laxatives; Dermatitis, Phototoxic; Dermatitis, Atopic; Diagnostic Errors
PubMed: 38400817
DOI: 10.1111/pde.15556