Conventional Meta-analysis Research Articles

Abstract TP24: C-Reactive Protein, and Homocysteine as a Predictors of Post Stroke Depression Among Stroke Patients: A Meta-Analysis and Meta Regression

Background: Post-stroke depression (PSD) is a common neuropsychiatric complication of stroke associated with poor functional outcome and increased mortality. Its pathophysiology is poorly understood, however, evidence suggests that neuroinflammation in reaction to the stroke could play a role in the development of PSD. Aim: To compare C-reactive protein (CRP), and homocysteine (Hcy) levels in post-stroke patients with and without PSD. Methods: We systematically searched all electronic databases from inception until May 30th 2023. We performed a conventional meta-analysis and adopted the DerSimonian and Laird random-effect model for the study variations [30]. Outcomes were reported as standard mean difference (SMD), and their corresponding 95% confidence interval (95% CI). Results: A total of 12 studies with 3,230 Patients were included in this analysis. The mean age of the overall cohort was 65.7 years with PSD patients appearing to be older than non-PSD patients (mean 68.3 years versus 63.1 years). In terms of gender distribution, there were more females in the PSD group compared with non-PSD groups (44.4% versus 40.7%). Compared to patients without post-stroke depression, it was found that patients with post-stroke depression had a higher levels of baseline CRP levels [SMD 0.16, (95% CI 0.08 to 0.25), p<0.001], and Hcy [SMD 0.14, (95% CI 0.05 to 0.22), p<0.001]. Meta-regression was performed using covariates including age, female gender, hypertension, diabetes mellitus, CAD, widowhood and family history of psychiatric disorder. For CRP there was no effect modifier, while for Hcy it was observed that a personal history of widowhood appeared as an only significant effect modifier (coefficient 1.998, p=0.038). Conclusion: Elevated baseline levels of CRP and Hcy were significantly higher in patients that developed PSD, suggesting that both could play a role in the pathophysiology of PSD and as a potential biomarker for diagnosing risk of depression post stroke.

The effectiveness of faecal collection devices in preventing moderate to severe incontinence-associated dermatitis: A systematic review and network meta-analysis.

Incontinence-associated dermatitis (IAD) is a common problem among critically ill patients with faecal incontinence (FI). However, there are few studies comparing the effects of different faecal collection devices impact the prevention of moderate to severe IAD in this patient population. This review aims to compare the effectiveness of various devices for collecting faecal matter in preventing moderate to severe IAD in critically ill patients suffering from FI through a network meta-analysis. We conducted a systematic search of PubMed, Embase, ProQuest, CENTRAL, CINAHL Plus with Full Text, China National Knowledge Infrastructure (CNKI), Wan fang, Wei Pu, and China Biomedicine (CBM) from their inception until May 4, 2023. The selected studies were randomized controlled trials (RCTs). Two researchers independently performed study selection and data extraction. We assessed the risk of bias using the Cochrane risk of bias tool Version 2.0. RevMan 5.4 was utilized for conventional pairwise meta-analysis of direct comparisons, while Stata16.0 was employed for network meta-analysis. A total of 14 studies, involving 1345 patients, were included in the analysis. Pairwise meta-analysis showed that an anal bag[odds ratio(OR): 0.07(0.03, 0.20)], a balloon catheter[(OR:0.30(0.15, 0.62)], and an anal bag connected to negative pressure and flushing [(OR: 0.09(0.01,0.68)] all reduced the incidence of moderate to severe IAD in critically ill patients compared with usual care measures, respectively. The cumulative rank probabilities indicated that moderate to severe IAD prevention was more effective when employing balloon catheters connected to negative pressure [surface under the cumulative ranking curve(SUCRA): 20.8%] and anal bags connected to negative pressure (SUCRA: 27.0%) among critically ill patients with FI. FI is a common problem among severely ill patients, and the reduction of moderate and severe IAD incidence is deemed essential. In this review, it is suggested that both balloon catheters connected to negative pressure and anal bags connected to negative pressure are associated with a higher effectiveness in preventing moderate and severe IAD. The findings of this review can assist healthcare professionals in the selection of suitable stool management devices for the prevention of moderate to severe IAD in critically ill patients with FI.

The Current State of Light-Duty Electric Vehicle Supply Equipment Costs: An Assessment of Contemporary Understanding

This study uses a hybrid meta-analysis and literature-review approach to understand the current state of knowledge regarding the costs of electric vehicle supply equipment (EVSE). We present a novel way to consider, categorize, and label measures of cost and show cost measure estimates from a sample of 13 recent studies. We find that in general, there is too much variation and too few commonly represented EVSE cost measures to reasonably provide aggregate figures for these measures. We propose a convention for presenting EVSE cost measures that includes the application (commercial or residential), the power level (Level 1, Level 2, DCFC [with further distinction based on rated power capacity]), and the type of cost measure (hardware, installation, operation, and total cost). We contend that providing researchers with standard cost measures will help to advance our knowledge of EVSE costs by ensuring that future work will use common metrics. Establishing common metrics will enable conventional meta-analyses that will make assessments of EVSE costs even more accessible. Additionally, common metrics will make tracking costs more reliable as the technology continues to evolve and become more ubiquitous.

Prognostic value of circulating tumor DNA in operable non-small cell lung cancer: a systematic review and reconstructed individual patient-data based meta-analysis

BackgroundThis reconstructed individual patient data (IPD)-based meta-analysis is aimed to summarize the current findings and comprehensively investigate the predictive value of circulating tumor DNA (ctDNA) in operable non-small cell lung cancer (NSCLC).MethodsPubMed, Cochrane and Embase were searched to include potentially eligible studies. The primary outcomes included progression-free survival (DFS) by ctDNA status at baseline, postoperative, and longitudinal timepoints. The IPD-based survival data was retracted and used in reconstructed IPD-based meta-analysis. Subgroup analysis was implemented based on the baseline characteristics.ResultsTotally, 28 studies were involved, including 15 full-length articles (1686 patients) for IPD-based synthesis and 20 studies for conventional meta-analysis. The IPD-based meta-analysis discovered that patients with positive ctDNA status at the baseline (hazard ratio, HR = 3.73, 95% confidential interval, CI: 2.95–4.72), postoperative (3.96, 2.19–7.16), or longitudinal timepoints (12.33, 8.72–17.43) showed significantly higher risk of recurrence. Patients with persistent ctDNA-negative status had the lowest recurrence rate, and the negative conversion of ctDNA from baseline to postoperative timepoints was correlated with elevated DFS. Subgroup analyses suggested that stage II–III patients with ctDNA-positive status may achieve preferable therapeutic outcomes.ConclusionsPlasm ctDNA monitoring shows excellent clinical significance at the tested timepoints. Perioperative conversion of ctDNA status may indicate the therapeutic effect of radical surgery. Postoperative adjuvant therapy may be determined according to the ctDNA status.Trail registrationCRD42022304445.

Is intradialytic oral nutritional supplementation safe and effective on clinical outcomes? A systematic review with conventional meta-analysis and network meta-analysis

determine the effect of intradialytic oral nutrition (ION) on clinical and safety outcomes. Systematic Review with conventional Meta-analysis, and a Network Meta-analysis (NMA) as sensitivity analysis. We searched on MEDLINE, LILACS, CENTRAL, and EMBASE in June 2020, and the last update was until August 2022. We selected observational and randomized controlled trials with ION for at least four weeks. Primary outcomes were all-cause mortality and quality of life (QoL); adverse events, physical performance, and appetite were secondary outcomes. Seven clinical trials and three observational studies were selected. Even when we did not obtain significant differences in physical performance and gastrointestinal symptoms, we identified a clinical improvement in the QoL's physical role, bodily pain, and physical performance domains. After pooling the data on mortality, a protection rate trend was observed in the ION group without statistical significance. The home-prepared ION was the best nutritional supplementation when assessing the appetite outcome through NMA. ION seems to have a protective trend in mortality risk; the current evidence is insufficient to establish a relationship with adverse events or other clinical outcomes. The lack of homogeneity in the trials makes it difficult to generalize these results. CRD42020186311.

The Effectiveness of Medial Branch Blocks and Radiofrequency Neurotomy in Managing Chronic Thoracic Pain: A Systematic Review and Meta-Analysis

BACKGROUND: Extensive research into potential sources of thoracic pain with or without referred pain into the chest wall has demonstrated that thoracic facet joints can be a potential source of pain confirmed by precise, diagnostic blocks. The objective of this systematic review and meta-analysis is to evaluate the effectiveness of medial branch blocks and radiofrequency neurotomy as a therapeutic thoracic facet joint intervention. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies of medial branch blocks and the radiofrequency neurotomy in managing thoracic pain utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed. A comprehensive literature search of multiple databases of RCTs and observational studies of medial branch blocks and radiofrequency neurotomy in managing chronic thoracic pain were identified from 1996 to December 2022 with inclusion of manual searches of the bibliography of known review articles and multiple databases. Methodologic quality and risk of bias assessment was also conducted. Evidence was synthesized utilizing principles of quality assessment and best evidence synthesis, with conventional and single meta-analysis. The primary outcome measure of success was 3 months of pain reduction for medial branch blocks and 6 months for radiofrequency thermoneurolysis for a single treatment. Short-term success was defined as up to 6 months and long-term was more than 6 months. RESULTS: This literature search yielded 11 studies meeting the inclusion criteria, of which 3 were RCTs and 8 were observational studies. Of the 3 RCTs, 2 of them assessed medial branch blocks and one trial assessed radiofrequency for thoracic pain. The evidence for managing thoracic pain with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 2 RCTs and 3 observational studies for medial branch blocks was Level II. For radiofrequency neurotomy, with the inclusion of one RCT of 20 patients in the treatment group and 5 observational studies, the evidence was Level III in managing thoracic pain. LIMITATIONS: There was a paucity of literature with RCTs and real-world pragmatic controlled trials. Even observational studies had small sample sizes providing inadequate clinically applicable results. In addition, there was heterogeneity of the available studies in terms of their inclusion and exclusion criteria, defining their endpoints and the effectiveness of the procedures. CONCLUSION: This systematic review and meta-analysis show Level II evidence of medial branch blocks and Level III evidence for radiofrequency neurotomy on a long-term basis in managing chronic thoracic pain. KEY WORDS: Chronic spinal pain, thoracic facet or zygapophysial joint pain, facet joint nerve blocks, medial branch blocks, controlled comparative local anesthetic blocks, diagnostic accuracy, radiofrequency neurotomy

Evidence Synthesis for Complex Interventions Using Meta-Regression Models.

A goal of evidence synthesis for trials of complex interventions is to inform the design or implementation of novel versions of complex interventions by predicting expected outcomes with each intervention version. Conventional aggregate data meta-analyses of studies comparing complex interventions have limited ability to provide such information. We argue that evidence synthesis for trials of complex interventions should forgo aspirations of estimating causal effects and instead model the response surface of study results to 1) summarize the available evidence and 2) predict the average outcomes of future studies or in new settings. We illustrate this modeling approach using data from a systematic review of diabetes quality improvement (QI) interventions involving at least 1 of 12 QI strategy components. We specify a series of meta-regression models to assess the association of specific components with the posttreatment outcome mean and compare the results to conventional meta-analysis approaches. Compared with conventional approaches, modeling the response surface of study results can better reflect the associations between intervention components and study characteristics with the posttreatment outcome mean. Modeling study results using a response surface approach offers a useful and feasible goal for evidence synthesis of complex interventions that rely on aggregate data.

Diagnostic Accuracy of ki-67 Labeling Index in Endoscopic Ultrasonography-Fine-Needle Aspiration Cytology and Biopsy of Pancreatic Neuroendocrine Neoplasms.

This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713-0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681-0.794) and 0.839 (95% CI, 0.738-0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590-0.917) and 0.998 (95% CI, 0.987-1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145-489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.

Insufficient information size and potentially false results in orthodontic meta-analyses using trial sequential analysis.

Meta-analysis (MA) is a common mathematical method used in systematic reviews (SRs) to gather data from different studies. MA may result in overestimation or underestimation of the effect due to systematic and random errors. Trial sequential analysis (TSA) has been used to overcome the limitations of conventional MA. The objective of this study was to re-evaluate the findings of orthodontic MAs using TSA to investigate the conclusiveness of the effect and to estimate the required information size (IS). Orthodontic SRs with MA published between 1 January 2013 and 31 December 2022 in the leading orthodontic journals were sourced. Data from arm-level MAs were extracted and re-entered in TSA software. A total of 180 papers were assessed against the inclusion criteria. Finally, 50 SRs with MAs were included. TSA found that almost half of the MAs with significant results demonstrated firm evidence of effect. While 38% of the significant MAs confirmed potentially spurious evidence of effect. In contrast, only one MA with insignificant findings showed a lack of effect. Furthermore, a larger number of patients were needed when the evidence of the effect was absent. TSA revealed that many orthodontic MAs have potentially false-positive results and have insufficient IS.

How to Keep the Balance between Red and Processed Meat Intake and Physical Activity Regarding Mortality: A Dose-Response Meta-Analysis.

Non-communicable diseases have become a major threat to public health, with cardiovascular diseases (CVDs) and cancer being the top two causes of death each year. Our objective is to evaluate the balanced association between the effect of red and processed meat intake on the risk of death and the effect of physical activity on the risk of mortality, where the risk of death includes all causes, CVDs, and cancers. We searched electronic databases, including PubMed, ISI Web of Science, Embase, and the Cochrane Library, for prospective studies reporting risk estimates for the association between the intake of red and processed meat, walking, and muscle-strengthening activity (MSA) and the risk of mortality from all causes, CVDs, and cancer. We extracted fully adjusted effect estimates from original studies and performed a summary analysis using the fixed and random-effect models. A conventional meta-analysis showed that red meat and processed meat were positively associated with the risk of mortality, and daily steps and MSA were negatively associated with the risk of death. Further analysis of the dose-response relationship showed that a risk reduction (20%) from 39.5 min/week of MSA or 4100 steps/d was equivalent to an increased risk of all-cause mortality from a daily intake of 103.4 g/d of red meat or 50 g/d of processed meat. The risk was further decreased as the number of steps per day increased, but the risk reversed when the MSA exceeded the threshold (39.5 min/week). Adherence to physical activity is an effective way to reduce the risk of mortality due to meat intake. However, the total intake of red meat and processed meat should be controlled, especially the latter. Walking is recommended as the main daily physical activity of choice, while MSAs are preferred when time is limited, but it should be noted that longer MSAs do not provide additional benefits.

Network meta-analysis of the treatment safety and efficacy of different energy systems in prostate vaporization.

Many clinical trials and meta-analyses have examined vaporization with different energy instruments has been recognized by the American Urological Association (AUA) and the European Association of Urology (EAU) as a promising treatment for benign prostate hyperplasia. However, there is still a lack of evidence for a network comparison between different vaporization devices. The PubMed, Embase, Cochrane and Web of Science databases were searched to identify randomized controlled trials (RCTs) of different energy systems for prostate vaporization. Pairwise and network meta-analyses (NMA) were performed to analyze the outcome regarding surgery time, complications, short-term maximum urine flow rate (Qmax), and long-term Qmax. The Stata software was used for paired meta-analysis. A Bayesian NMA model with ADDIS software was applied to achieve the indirect comparison of different energy systems. Node-splitting analysis and inconsistency factors were used to test inconsistency for closed-loop indirect comparison. Fifteen studies were included in this study, involving three types of energy systems used in prostate vaporization: diode laser (wavelength: 980nm, power: 200-300 W, mode: continuous), green-light laser (wavelength: 532nm, power: 80-180 W, mode: continuous), and bipolar plasma vaporization (bipolar electrode, power: 270-280 W, mode: pulsed). In the conventional paired meta-analysis, significantly better short-term efficacy was found in green light laser vaporization, while no significant difference was detected in other parameters. According to the results of the NMA, a greenlight laser is recommended for prostate vaporization rather than the other two systems. When considering operation time, overall complications, short-term Qmax, and long-term Qmax, there were no significant differences among green-light laser vaporization, diode laser vaporization, and bipolar vaporization in BPH treatment. However, according to the probability ranking and benefit-risk analysis results, the green-light laser might be the best energy system for prostate vaporization in BPH treatment.

P-768 A network meta-analysis yields new insights on the efficacy of different progestogen regimens for luteal support in fresh embryo in vitro fertilization

Abstract Study question How do seven progestogen regimens rank in their efficacy for achieving clinical pregnancy when used as luteal support in women undergoing fresh embryo transfer? Summary answer Given as luteal support and based on clinical pregnancy rate, intramuscular progesterone was most effective, followed by oral dydrogesterone and then micronized vaginal progesterone gel. What is known already A large number of randomized controlled trials (RCTs) have compared fresh in vitro fertilisation cycle luteal support with progestogens. A number of systematic reviews and conventional meta-analyses have likewise been published. A network meta-analysis integrates direct and indirect comparisons between treatments in a single analysis, and allows the ranking of treatments and the estimation of heterogeneity in both the effect of any given treatment and the inconsistency (‘incoherence') in the evidence from different pairs of treatments. Network meta-analyses can thus increase the precision and robustness of inferences from the literature on treatment effect estimates. Study design, size, duration A literature search was performed using BIOSIS, Embase, and MEDLINE and supplemented with manual searches to identify RCTs reporting the efficacy of progestogen regimens in luteal support during fresh embryo transfer. A single network meta-analysis was used to compare progestogen regimens, combining both direct and indirect evidence across the selected studies using the R package ‘netmeta’ and fixed and random effects models. The analysis was repeated and confirmed using SAS. Participants/materials, setting, methods Peer-reviewed full publications that compared individual progestogens (either with placebo or another progestogen) were included. Studies were excluded if they included frozen embryo transfers, used human chorionic gonadotropin or formulations not currently available for the indication, or if they did not report at least clinical pregnancy rate. Two authors (EK, QW) individually reviewed papers to collect data. Where doses differed between studies for an individual progestogen the doses were noted and the results combined. Main results and the role of chance Among studies from 1987–2022, 35 RCTs met the inclusion criteria, comprising 17,955 observations of 7 treatments plus placebo and resulting in 43 pairwise comparisons for the network meta-analysis of clinical pregnancy rate (the primary outcome). Based on the random effects model, the top three regimens versus placebo were intramuscular (IM) progesterone, Duphaston® (oral dydrogesterone), and Crinone® (micronized progesterone vaginal gel) (see Figure). Compared with placebo, only the top 3 ranking compounds had confidence intervals that excluded zero, with a risk difference to placebo (95% confidence interval) of 0.08 (0.01-0.14) for IM progesterone and 0.07 (0.01-0.13) for both Duphaston® and Crinone®. The P-score (fixed, random) ranking for the compounds was: IM progesterone 0.77, 0.79; Duphaston® 0.78, 0.69; Crinone® 0.65, 0.65; Cyclogest® (vaginal micronized progesterone) 0.58, 0.60; Endometrin® (vaginal micronized progesterone) 0.52, 0.54; Prolutex® (subcutaneous progesterone) 0.31, 0.36; Utrogestan® (vaginal micronized progesterone) 0.34, 0.31; and placebo 0.05, 0.06. Ranking was confirmed by SUCRA score (surface under the cumulative ranking curve). Studies were thoroughly reviewed to ensure similarity assumption. Homogeneity and consistency of the network were investigated and fulfilled. Exclusion of placebo-controlled studies did not impact the overall results or rankings. Limitations, reasons for caution Treatment duration was assumed identical across arms in each study and therefore was not included in this analysis. Most studies were single-centre with a small sample size. Methodological rigor was heterogenous between trials. Direct comparisons with placebo were only available for the top three compounds. Wider implications of the findings Three progestogen regimens showed a positive effect on clinical pregnancy rate versus placebo. Frequently used vaginal preparations do not lead the efficacy league table when the available direct and indirect comparative evidence is collated. Relevant efficacy differences likely exist between the available progesterone regimens. Trial registration number n/a

Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis.

In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties.

A model-based quantitative analysis of efficacy and associated factors of platelet rich plasma treatment for osteoarthritis.

While platelet rich plasma (PRP) has been extensively studied in treating osteoarthritis (OA), there has been an ongoing debate regarding the efficacy of PRP and the optimal subpopulation for PRP treatment remains unknown. The authors hereby aim to establish a pharmacodynamic model-based meta-analysis to quantitatively evaluate PRP efficacy, comparing with hyaluronic acid (HA) and identify relevant factors that significantly affect the efficacy of PRP treatment for OA. The authors searched for PubMed and the Cochrane Library Central Register of Controlled Trials of PRP randomized controlled trials (RCTs) for the treatment of symptomatic or radiographic OA from the inception dates to 15 July 2022. Participants' clinical and demographic characteristics and efficacy data, defined as Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale pain scores at each time point were extracted. A total of 45 RCTs (3829 participants) involving 1805 participants injected with PRP were included in the analysis. PRP reached a peak efficacy at ~ 2-3 months after injection in patients with OA. Both conventional meta-analysis and pharmacodynamic maximal effect models showed that PRP was significantly more effective than HA for joint pain and function impairment (additional decrease of 1.1, 0.5, 4.3, and 1.1 scores compared to HA treatment at 12 months for Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, function, and visual analog scale pain scores, respectively). Higher baseline symptom scores, older age (≥60 years), higher BMI (≥30), lower Kellgren-Lawrence grade (≤2) and shorter OA duration (<6 months) were significantly associated with greater efficacy of PRP treatment. These findings sugges t that PRP is a more effective treatment for OA than the more well-known HA treatment. The authors also determined the time when the PRP injection reaches peak efficacy and optimized the targeting subpopulation of OA. Further high-quality RCTs are required to confirm the optimal population of PRP in the treatment of OA.

Efficacy of post-first-line agents for advanced gastrointestinal stromal tumors following imatinib failure: A network meta-analysis.

Imatinib is the standard first-line treatment for advanced gastrointestinal stromal tumors (GISTs); however, most patients eventually develop imatinib resistance, leading to considerable clinical challenges. Few direct comparisons have been made between different post-first-line therapies on clinical efficacy in advanced GIST following imatinib failure. Databases including PubMed, Embase, Scopus, Google Scholars, and Cochrane Library from inception to February 2023 were retrieved for randomized controlled trials evaluating the clinical efficacy of different post-first-line agents for advanced GIST following imatinib failure. Network and conventional meta-analysis were carried out using Stata/MP 16.0. Ripretinib showed significant improvement in progression-free survival (PFS) rates from the 2nd to the 12th month compared to placebo, while there was virtually no evidence that the rest active agents had a significant benefit at the 12th month. Masitinib, ripretinib, sunitinib, regorafenib, and pimitespib exhibited significantly longer median PFS than placebo, and pairwise comparisons indicated there were no significant differences among masitinib, ripretinib, and sunitinib. These post-first-line agents decreased the risk of disease progression or death by 65% (HR = 0.35, 95% CI: 0.26-0.47) compared to placebo. Ripretinib and sunitinib came into effect earlier and exhibited more consistent overall survival (OS) rate improvements than masitinib and pimitespib, while pairwise comparisons revealed no significant differences in these four active agents concerning the improvement in OS rate. These post-first-line agents decreased the risk of death by 39% (HR = 0.61, 95% CI: 0.44-0.83) over placebo for advanced GIST following imatinib failure. The active agents in our analysis as post-first-line therapies are able to provide superior clinical efficacy, with improved PFS rate and OS rate at certain time points, as well as absolute values of PFS and OS for advanced GIST. Ripretinib might be the optimal recommendation as a post-first-line treatment for advanced GIST following imatinib failure.

Efficacy and moderators of short-term psychodynamic psychotherapy for depression: A systematic review and meta-analysis of individual participant data.

Short-term psychodynamic psychotherapy (STPP) is frequently used to treat depression, but it is unclear which patients might benefit specifically. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses and identify patient-level moderators. This IPD meta-analysis examined the efficacy and moderators of STPP for depression compared to control conditions. PubMed, PsycInfo, Embase, and Cochrane Library were searched September 1st, 2022, to identify randomized trials comparing STPP to control conditions for adults with depression. IPD were requested and analyzed using mixed-effects models. IPD were obtained from 11 of the 13 (84.6%) studies identified (n=771/837, 92.1%; mean age=40.8, SD=13.3; 79.3% female). STPP resulted in significantly lower depressive symptom levels than control conditions at post-treatment (d=-0.62, 95%CI [-0.76, -0.47], p<.001). At post-treatment, STPP was more efficacious for participants with longer rather than shorter current depressive episode durations. These results support the evidence base of STPP for depression and indicate episode duration as an effect modifier. This moderator finding, however, is observational and requires prospective validation in future large-scale trials.

Antipsychotic drugs and their effects on cognitive function: protocol for a systematic review, pairwise, and network meta-analysis

BackgroundThere is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning.MethodsIn our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings.DiscussionThis systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients’ and physicians’ decision-making processes based on the latest available evidence.Systematic review registrationPROSPERO CRD42022312483

Efficacy and Safety of Minimally Invasive Thyroid Surgery: A Network Meta-Analysis.

Minimally invasive and remote surgical approaches for thyroid tumors have been developed primarily for cosmetic benefit. However, conventional meta-analysis could not provide comparative data between new techniques. This network meta-analysis would be able to provide data for clinicians and patients to compare cosmetic satisfaction and morbidity by comparing surgical methods. The PubMed, EMBASE, MEDLINE, SCOPUS, Web of Science, Cochrane Trials, and Google Scholar. The nine interventions included minimally invasive video-assisted thyroidectomy (MIVA), endoscopic and robotic bilateral axillo-breast-approach thyroidectomy (EBAB and RBAB, respectively), endoscopic and robotic retro-auricular thyroidectomy (EPA and RPA, respectively), endoscopic or robotic transaxillary thyroidectomy (EAx and RAx, respectively), endoscopic and robotic transoral approaches (EO and RO, respectively), and a conventional thyroidectomy. We recorded the operative outcomes and perioperative complications; pairwise and network meta-analyses were performed. EO, RBAB, and RO were associated with good patient cosmetic satisfaction. EAx, EBAB, EO, RAx, and RBAB were associated with significantly more postoperative drainage than the other methods. Postoperatively, more flap problems and wound infections were found in the RO than control group, and more transient vocal cord palsy was found in the EAx and EBAB groups. MIVA ranked first in terms of operative time, postoperative drainage amount, postoperative pain, and hospitalization, but cosmetic satisfaction was low. EAx, RAx, and MIVA ranked higher than the other approaches in terms of operative bleeding. It was confirmed that minimally invasive thyroidectomy achieves high cosmetic satisfaction and is not inferior to conventional thyroidectomy in terms of surgical results or perioperative complications. Laryngoscope, 133:2470-2479, 2023.

Ethnic differences in response to atypical antipsychotics in patients with schizophrenia: individual patient data meta-analysis of randomised placebo-controlled registration trials submitted to the Dutch Medicines Evaluation Board.

Little is known about the effect of ethnicity on the response to antipsychotic medication in patients with schizophrenia. To determine whether ethnicity moderates the response to antipsychotic medication in patients with schizophrenia, and whether this moderation is independent of confounders. We analysed 18 short-term, placebo-controlled registration trials of atypical antipsychotic medications in patients with schizophrenia (N = 3880). A two-step, random-effects, individual patient data meta-analysis was applied to establish the moderating effect of ethnicity (White versus Black) on symptom improvement according to the Brief Psychiatric Rating Scale (BPRS) and on response, defined as >30% BPRS reduction. These analyses were corrected for baseline severity, baseline negative symptoms, age and gender. A conventional meta-analysis was performed to determine the effect size of antipsychotic treatment for each ethnic group separately. In the complete data-set, 61% of patients were White, 25.6% of patients were Black and 13.4% of patients were of other ethnicities. Ethnicity did not moderate the efficacy of antipsychotic treatment: pooled β-coefficient for the interaction between treatment and ethnic group was -0.582 (95% CI -2.567 to 1.412) for mean BPRS change, with an odds ratio of 0.875 (95% CI 0.510-1.499) for response. These results were not modified by confounders. Atypical antipsychotic medication is equally effective in both Black and White patients with schizophrenia. In registration trials, White and Black patients were overrepresented relative to other ethnic groups, limiting the generalisability of our findings.

The effect of age on task switching: updated and extended meta-analyses.

Cognitive flexibility is one of the crucial abilities for human survival. As people get older, whether their flexibility ability will be affected is one of the core research topics in aging research. Researchers have developed a task-switch paradigm in laboratories to mimic daily-life shifting task-set scenarios. However, the empirical evidence is equivocal. Considering every single study may have a biased sample; therefore, we hoped to combine smaller studies, making them into one extensive investigation, which may help show an actual effect. In the current study, we used two meta-analysis techniques, the Brinley plot (along with the State-trace plot) and conventional meta-analysis, to re-evaluate whether healthy aging influences cognitive flexibility. The results of the Brinley plot analysis showed no evidence of switch-specific age-related impairment as indexed by the local switch cost. Yet, older adults performed more slowly than younger adults across task conditions. The conventional meta-analysis further showed that the currently available findings were heterogenous and exhibited publication bias. Therefore, this study suggests that researchers should interpret their results cautiously while using a task-switching paradigm to address older adults' shifting abilities. More parametric variables must be considered and developed in a task-switching paradigm to enhance its sensitivity and reveal older adults' actual shifting ability.