Eligible Randomized Controlled Trials Research Articles

Critical quality appraisal of randomized controlled trials with traditional Chinese medicines for the coronavirus disease 2019

ObjectiveTraditional Chinese medicines (TCM) play an indispensable role during the pandemic of coronavirus disease 2019 (COVID-19), with an increasing number of randomized controlled trials (RCTs) designed and performed to evaluate the efficacy and safety of TCM for COVID-19. This study aimed to critically appraise the quality of currently available RCTs of TCM for COVID-19. MethodsRCTs of TCM for COVID-19 were searched from three databases by two investigators and selected according to pre-established inclusion and exclusion criteria. General information of included studies was presented by applying descriptive statistics. The methodological and reporting quality of eligible RCTs was critically evaluated based on the risk of bias assessment tool 2 (RoB2) and CONSORT Extension for TCM (CONSORT-CHM Formulas 2017), respectively. The differences of risks and main general information were compared between RCTs published in English and Chinese journals. Microsoft Excel 2019 and SPSS were used for the statistical analysis. A result with p < 0.05 was considered statistically significant. ResultsThis study finally included 64 RCTs with a total of 10858 participants investigating TCM for COVID-19. All 64 RCTs were evaluated as moderate-to-low RoB including 27 RCTs with high bias, 26 RCTs with some concerns, and 11 with low bias. Results of reporting quality appraisal by CONSORT-CHM Formulas 2017 showed that 61 (95%) RCTs reported more than 18 (50%) items, and 14 (22%) RCTs reported more than 26 (70%) items among all 38 items. Forty-two RCTs were approved by ethics committees and 47 RCTs reported the informed consent information. Twenty-five RCTs and 39 RCTs provided information on trial registration and funding resources, respectively. The quality of 44 RCTs published in Chinese was significantly worse than that of 20 RCTs published in English, especially in the following considerations including the overall RoB, ethics approved, informed consent, trial register, and reporting quality with CONSORT-CHM Formulas 2017. ConclusionThe overall quality of RCTs investigating TCM for COVID-19 was appraised as moderate-to-high that was substandard and needs to be continuously improved, especially for RCTs published in Chinese, in the future.

Assessment of corticospinal tract remodeling based on diffusion tensor imaging in the treatment of motor dysfunction after ischemic stroke by acupuncture: A meta-analysis.

To investigate the efficacy of acupuncture in improving motor dysfunction after ischemic stroke (IS) and to investigate the effect of acupuncture on corticospinal tract (CST) remodeling using diffusion tensor imaging. Published literature on the effect of acupuncture on CST remodeling after IS using diffusion tensor imaging in the form of randomized controlled trials (RCTs) were systematically retrieved and screened from Cochrane Library, Web of Science, PubMed, Embase, CNKI, CBM, VIP, and Wanfang databases from inception to December 2022. The methodological quality of the included studies was critically and independently evaluated by 2 reviewers using the Cochrane Risk of Bias Assessment Tool for RCTs. The correlated data were extracted using the pre-designed form, and all analyses were performed using Reviewer Manager version 5.4. Eleven eligible RCTs involving 459 patients were eventually included. The combined evidence results showed that the acupuncture group significantly improved patients' National Institute of Health stroke scale, Fugl-Meyer Assessment Scale, and Barthel index compared with conventional medical treatment. The acupuncture group significantly promoted remodeling of the CST, as reflected by an increase in fractional anisotropy (FA) throughout the CST [MD = 0.04, 95% CI (0.02, 0.07), P = .001], and in addition, subgroup analysis showed that the acupuncture group significantly improved FA in the infarct area compared with conventional medical treatment at around 4 weeks [MD = 0.04, 95% CI (0.02, 0.06), P = .0002] and FA of the affected cerebral peduncle [MD = 0.03, 95% CI (0.00, 0.07), P = .02]. Also, compared with conventional medical treatment, the acupuncture group significantly increased average diffusion coefficient of the affected cerebral peduncle [MD = -0.21, 95% CI (-0.28, -0.13), P < .00001]. The results of the meta-analysis suggest that acupuncture therapy can improve the clinical manifestations of motor dysfunction in patients after IS and advance a possibly beneficial effect on CST remodeling. However, due to the number and quality of eligible studies, these findings need to be further validated in more standardized, rigorous, high-quality clinical trials.

Effects of exercise on bone mineral density in middle-aged and older men: A comprehensive meta-analysis.

To determine the effect of exercise on bone mineral density (BMD) in middle-aged and older men. We searched three electronic databases up to March 21, 2022. A systematic review of the literature according to the PRISMA statement included (1) randomised controlled trials (RCTs), with (2) at least one exercise group as an intervention versus a control group, (3) men aged ≥ 45years old, and (4) areal BMD of the lumbar spine (LS) and/or femoral neck (FN) and/or total hip (TH) and/or trochanter region. Mean differences (MD) for BMD changes at the LS, FN, TH, and trochanter were defined as outcome measures. A total of 10 eligible RCTs were included (N = 555 participants). Exercise significantly improved BMD, and the summarised MD was 0.02 (95% CI: 0.00 to 0.05) for LS BMD, 0.01 (95% CI: 0.00 to 0.02) for FN BMD, 0.01 (95% CI: 0.00 to 0.01) for TH BMD, and 0.03 (95% CI: 0.00 to 0.05) for trochanter BMD. Subgoup analyses showed the improvement effect was statistically significant in trials with longer duration and higher intensity in LS (≥ 12 months: MD, 0.01, 95% CI:0.00 to 0.03; higher intensity: MD, 0.01, 95% CI:0.00 to 0.03) and FN (≥ 12months: MD, 0.02, 95% CI:0.01 to 0.02; higher intensity: MD, 0.01, 95% CI:0.01 to 0.02). Our results suggested a relatively mild, improvement effect of exercise on LS and proximal femur BMD. Exercise has the potential to be an effective way to avert bone loss in middle-aged and older men.

Comparative efficacy of mind-body exercise for depression in breast cancer survivors: A systematic review and network meta-analysis.

As pharmacotherapy often leads to adverse reactions, mind-body exercise (MBE) treatments have become a more popular option for treating depression in people living with breast cancer (BC). However, the most effective type of MBE treatment for this population remains unclear. The aim of this systematic review and network meta-analysis (NMA) was to compare the efficacy of the different MBE modes for depression in people with BC. A systematic search for randomized controlled trials (RCTs) from inception to March 25, 2023, was conducted in the following database: EMBASE, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine, OpenGrey, and ClinicalTrials.gov. A traditional meta-analysis was conducted using the random-effects model to directly assess the effectiveness of various MBE interventions. Stata 16.0 software was used for performing the NMA. The NMA was performed in 32 eligible RCTs including 2361 participants. The efficacy of MBE treatments on depression was ranked as the following: Liuzijue (surface under the cumulative ranking curve [SUCRA] = 95.4%) > Tai chi (SUCRA = 76.9%) > yoga (SUCRA = 55.0%) > Baduanjin (SUCRA = 53.9%) > Pilates (SUCRA = 38.6%) > dance (SUCRA = 30.2%) > Qigong (SUCRA = 28.1%) > control (SUCRA = 21.9%). Our research showed that Liuzijue and Tai chi might be the most significantly effective MBE intervention for mitigating depression among BC survivors. Healthcare professionals could consider recommending Liuzijue and Tai Chi as a complementary therapy for BC survivors who experience depression.

The effects of pomegranate consumption on inflammatory and oxidative stress biomarkers in adults: a systematic review and meta-analysis.

Several studies have shown the effects of pomegranate on oxidative stress and inflammation biomarkers, while some studies showed no effects of pomegranate on these biomarkers. Therefore, we aimed to evaluate the effects of pomegranate consumption on C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor α (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in adults. A systematic literature search was performed using databases, including PubMed, Web of Science, and Scopus, up to May 2023 to identify eligible randomized controlled trials (RCTs). Heterogeneity tests of the included trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. Of 3811 records, 33 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced CRP (WMD: -0.50mg/l; 95% CI -0.79 to -0.20; p = 0.001), IL-6 (WMD: -1.24ng/L 95% CI -1.95 to -0.54; p = 0.001), TNF-α (WMD: -1.96pg/ml 95%CI -2.75 to -1.18; p < 0.001), and MDA (WMD: -0.34nmol/ml 95%CI -0.42 to -0.25; p < 0.001). Pooled analysis of 13 trials revealed that pomegranate consumption led to a significant increase in TAC (WMD: 0.26mmol/L 95%CI 0.03 to 0.49; p = 0.025). Overall, the results demonstrated that pomegranate consumption has beneficial effects on oxidative stress and inflammatory biomarkers in adults. Therefore, pomegranate can be consumed as an effective dietary approach to attenuate oxidative stress and inflammation in patients with cardiovascular diseases. CRD42023406684.

Endovenous ablation for venous leg ulcers.

Venous leg ulcers (VLUs) are a serious manifestation of chronic venous disease affecting up to 3% of the adult population. This typically recalcitrant and recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The longstanding mainstay treatment for VLUs is compression therapy. Surgical removal of incompetent veins reduces the risk of ulcer recurrence. However, open surgery is an unpopular option amongst people with VLU, and many people are unsuitable for it. The efficacy of the newer, minimally-invasive endovenous techniques has been established in uncomplicated superficial venous disease, and these techniques can also be used in the management of VLU. When used with compression, endovenous ablation aims to further reduce pressure in the veins of the leg, which may impact ulcer healing. To determine the effects of superficial endovenous ablation on the healing and recurrence of venous leg ulcers and the quality of life of people with venous ulcer disease. In April 2022 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scrutinised reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions on the language of publication, but there was a restriction on publication year from 1998 to April 2022 as superficial endovenous ablation is a comparatively new technology. Randomised controlled trials (RCTs) comparing endovenous ablative techniques with compression versus compression therapy alone for the treatment of VLU were eligible for inclusion. Studies needed to have assessed at least one of the following primary review outcomes related to objective measures of ulcer healing such as: proportion of ulcers healed at a given time point; time to complete healing; change in ulcer size; proportion of ulcers recurring over a given time period or at a specific point; or ulcer-free days. Secondary outcomes of interest were patient-reported quality of life, economic data and adverse events. Two reviewers independently assessed studies for eligibility, extracted data, carried out risk of bias assessment using the Cochrane RoB 1 tool, and assessed GRADE certainty of evidence. The previous version of this review found no RCTs meeting the inclusion criteria. In this update, we identified two eligible RCTs and included them in a meta-analysis. There was a total of 506 participants with an active VLU, with mean durations of 3.1 months ± 1.1 months in the EVRA trial and 60.5 months ± 96.4 months in the VUERT trial. Both trials randomised participants to endovenous treatment and compression or compression alone, however the compression alone group in the EVRA trial received deferred endovenous treatment (after ulcer healing or from six months). There is high-certainty evidence that combined endovenous ablation and compression compared with compression therapy alone, or compression with deferred endovenous treatment, improves time to complete ulcer healing (pooled hazard ratio (HR) 1.41, 95% CI 1.36 to 1.47; I2 = 0%; 2 studies, 466 participants). There is moderate-certainty evidence that the proportion of ulcers healed at 90 days is probably higher with combined endovenous ablation and compression compared with compression therapy alone or compression with deferred endovenous treatment (risk ratio (RR) 1.14, 95% CI 1.00 to 1.30; I2 = 0%; 2 studies, 466 participants). There is low-certainty evidence showing an unclear effect on ulcer recurrence at one year in people with healed ulcers with combined endovenous treatment and compression when compared with compression alone or compression with deferred endovenous treatment (RR 0.29, 95% CI 0.03 to 2.48; I2 = 78%; 2 studies, 460 participants). There is also low-certainty evidence that the median number of ulcer-free days at one year may not differ (306 (interquartile range (IQR) 240 to 328) days versus 278 (IQR 175 to 324) days) following combined endovenous treatment and compression when compared with compression and deferred endovenous treatment; (1 study, 450 participants). There is low-certainty evidence of an unclear effect in rates of thromboembolism between groups (RR 2.02, 95% CI 0.51 to 7.97; I2 = 78%, 2 studies, 506 participants). The addition of endovenous ablation to compression is probably cost-effective at one year (99% probability at GBP 20,000/QALY; 1 study; moderate-certainty evidence). Endovenous ablation of superficial venous incompetence in combination with compression improves leg ulcer healing when compared with compression alone. This conclusion is based on high-certainty evidence. There is moderate-certainty evidence to suggest that it is probably cost-effective at one year and low certainty evidence of unclear effects on recurrence and complications. Further research is needed to explore the additional benefit of endovenous ablation in ulcers of greater than six months duration and the optimal modality of endovenous ablation.

Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials.

The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles. A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR). We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]). The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity. After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.

Bariatric surgery, novel glucose-lowering agents, and insulin for type 2 diabetes and obesity: Bayesian network meta-analysis of randomized controlled trials.

This network meta-analysis aimed to compare the effects of bariatric surgery, novel glucose-lowering agents (SGLT2i, GLP1RA, DPP4i), and insulin for patients with type 2 diabetes mellitus (T2DM) and obesity. Four databases were searched from inception to April 2023 to identify randomized controlled trials (RCTs) comparing bariatric surgery, SGLT2i, GLP1RA, DPP4i, insulin, and/or placebo/usual care among patients with T2DM and obesity in the achievement of HbA1c < 7.0 per cent within one year, and 12-month changes in HbA1c and body weight. A total of 376 eligible RCTs (149 824 patients) were analysed. Bariatric surgery had significantly higher rates of achieving HbA1c < 7.0 per cent than SGLT2i (RR = 2.46, 95 per cent c.i. = 1.28, 4.92), DPP4i (RR = 2.59, 95 per cent c.i. = 1.36, 5.13), insulin (RR = 2.27, 95 per cent c.i. = 1.18, 4.58) and placebo/usual care (RR = 4.02, 95 per cent c.i. = 2.13, 7.93), but had no statistically significant difference from GLP1RA (RR = 1.73, 95 per cent c.i. = 0.91, 3.44), regardless of oral (RR = 1.33, 95 per cent c.i. = 0.66, 2.79) or injectable (RR = 1.75, 95 per cent c.i. = 0.92, 3.45) administration. Significantly more GLP1RA patients achieved HbA1c < 7.0 per cent than other non-surgical treatments. Bariatric surgery had the greatest reductions in HbA1c (∼1 per cent more) and body weight (∼15 kg more) at 12 months. Among novel glucose-lowering medications, GLP1RA was associated with greater reductions in HbA1c than SGLT2i (-0.39 per cent, 95 per cent c.i. = -0.55, -0.22) and DPP4i (-0.51 per cent, 95 per cent c.i. = -0.64, -0.39) at 12 months, while GLP1RA (-1.74 kg, 95 per cent c.i. = -2.48, -1.01) and SGLT2i (-2.23 kg, 95 per cent c.i. = -3.07, -1.39) showed greater reductions in body weight than DPP4i at 12 months. Bariatric surgery showed superiority in glycaemic control and weight management compared to non-surgical approaches. GLP1RA administered by oral or injectable form demonstrated reduced HbA1c and body weight at 12 months, and was preferable over other non-surgical treatments among patients with T2DM and obesity. CRD42020201507.

Efficacy and safety of oral immunotherapy for peanut, cow's milk, and hen's egg allergy: A systematic review of randomized controlled trials.

Oral immunotherapy (OIT) is a promising treatment for food allergies; however, safety is a concern. We synthesized evidence from the best randomized controlled trials (RCTs) on efficacy/safety of OIT for desensitization (DS) and remission (sustained unresponsiveness (SU)) in IgE mediated allergy to peanut, hen's eggs, and cow's milk. BODY: We searched Pubmed, EMBASE, and Cochrane databases (Until Oct 22) identifying 16 eligible RCTs published in English measuring food allergy by food challenge at the beginning and at the end of the study. The Cochrane Risk of Bias tool was used to assess study quality. We found 18 eligible studies. There was evidence of efficacy for DS for all allergens: peanut (RR 11.32; 95% CI 5.93, 21.60, I2 49%, 8 studies); hen's egg (RR 4.67; 2.66, 8.21, I2 0%, 5 studies); cow's milk (RR 13.98; 3.51, 55.65, I2 0%, 4 studies) and evidence for SU for peanut (RR 7.74; 2.90, 20.69, I2 0%, 3 studies) and hen's egg (RR 6.91; 1.67, 28.57, I2 0%, 2 studies). Allergic events were increased with intervention, and risk of adrenaline use increased for peanut RR 2.96; 1.63, 5.35, I2 0%, 8 studies; egg RR 1.71; 0.42, 6.92, I2 0%, 6 studies; and milk RR 8.45; 2.02, 35.27, I2 0%, 4 studies. We found strong evidence that peanut, hen's egg, and cow's milk OIT can induce DS and some evidence for remission. There was a high risk of allergic reactions. Generalizability to the entire food allergic population is not known.

The effect of dietary approaches to stop hypertension and ketogenic diets intervention on serum uric acid concentration: a systematic review and meta-analysis of randomized controlled trials

Hyperuricemia as a risk factor for metabolic diseases is proved to be profoundly modified by dietary approaches. This systematic review and meta-analysis of randomized control trials (RCT) was conducted to investigate the effect of two nutritional interventions; dietary approaches to stop hypertension (DASH) diet and ketogenic diet (KD) on serum uric acid (UA) concentrations. Our systematic search was for RCTs in which KD or DASH diet were assigned to adults for at least 2 weeks or more. Until March 2023 in Embase, Web of Science, PubMed, and Scopus databases, 10 eligible RCTs that intervened with DASH diet (n = 4) or KD (n = 6) and had provided laboratory data on serum UA were found. Summary effect was calculated by random-effects model. Results from the meta-analysis of the 4 DASH diet RCTs with a total of 590 participants revealed significant decrease in serum UA after at least 4 weeks of interventions (mean difference (MD) = ‒0.25; 95% CI ‒0.4 to ‒0.1 mg/dL; p < 0.01; I2 = 0%). The pooled meta-analysis of the 6 included RCTs of KD reporting data of 267 participants showed no significant changes in serum UA (MD = 0.26; 95% CI ‒0.47 to 0.98 mg/dL, I2 = 95.32%). However, a non-significant reduction of UA in the subgroup analysis of very low-calorie KD (VLCKD) studies (MD = ‒0.04; 95% CI ‒0.29 to 0.22, I2 = 0%) was obtained. DASH diet has an ameliorating effect on serum UA and may be recommended for hyperuricemia states such as gout. In addition, we have shown that serum UA level following KD remained unchanged. Although, in view of the heterogeneity across the studies, further investigations are needed to determine the effect of KD and VLKD on serum UA concentrations.

Effect of zinc supplementation on blood sugar control in the overweight and obese population: A systematic review and meta-analysis of randomized controlled trials

BackgroundAlthough overweight and obese people have a higher risk of type 2 diabetes incidence than normal-weight individuals, the efficacy of zinc supplementation in blood sugar control in overweight and obese people remained unknown. This meta-analysis attempted to address this issue. MethodsDatabases including PubMed, Embase, and the Cochrane Library were searched from inception until May 2022 to identify randomized controlled trials (RCTs) investigating the effects of zinc supplementation among participants who were overweight or obese without language restriction. It is a random-effect meta-analysis that analyzed the impact of zinc supplementation on fasting glucose (FG) (i.e., primary outcome) and other variables including fasting insulin (FI), homeostasis model assessment-insulin resistance index (HOMA-IR), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and 2-hour postprandial glucose (2 h- PG). ResultsAnalysis of 12 eligible RCTs involving 651 overweight/obese participants demonstrated that zinc supplementation significantly improves FG (weighted mean difference [WMD]: −8.57 mg/dL; 95% confidence interval [CI]: −14.04 to −3.09 mg/dL, p = 0.002), HOMA-IR (WMD: −0.54; 95% CI: −0.78 to −0.30, p < 0.001), HbA1c (WMD: −0.25%; 95% CI: −0.43% to −0.07%, p = 0.006), and 2 h-PG (WMD: −18.42 mg/dL; 95% CI: −25.04 to −11.79 mg/dL, p < 0.001) compared to those in the control group. After conducting subgroup analyses, we found that the primary outcome, FG, showed more significant results in the subgroups with Asia, Zinc supplementation alone, higher dose (≥30 mg) and patients with diabetes. ConclusionOur meta-analysis indicated that zinc supplementation benefits blood sugar control in overweight and obese populations, with an especially significant reduction in FG.

P-169 In vitro fertilization versus intrauterine insemination with ovarian stimulation for unexplained infertility: A Collaborative Meta-analysis with Individual Participant Data

Abstract Study question In couples with unexplained infertility, does IVF increase cumulative live birth rate and reduce multiple pregnancy rate compared to intrauterine insemination with ovarian stimulation (IUI-OS)? Summary answer There were no significant differences in cumulative live birth and multiple pregnancy rates between IVF and IUI-OS in couples with unexplained infertility. What is known already IVF and IUI-OS are widely used in managing unexplained infertility, especially in couples with a poor prognosis for natural conception. Although several randomized controlled trials (RCTs) have compared IVF versus IUI-OS, it remains inconclusive regarding which approach is more effective. Some of the RCTs did not define a time limit for follow up and others made the comparison on a per-cycle basis which provides a biased estimate in favour of IVF. Study design, size, duration We performed an individual participant data meta-analysis (IPD-MA) that synthesised available individual-level data comparing IVF and IUI-OS in unexplained infertility. We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register of RCTs and included eligible RCTs that completed data collection before June 2021. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. Participants/materials, setting, methods RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were included. The primary effectiveness outcome was cumulative live birth, defined by time to pregnancy leading to live birth. The primary safety outcome was the number of multiple pregnancies per participant. IPD were checked and standardised before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool. The analysis followed the intention-to-treat principle, and a two-stage IPD meta-analysis was performed. Main results and the role of chance Of eight potentially eligible RCTs, four shared individual-level data of 933 couples, of which 550 couples were allocated to IVF and 383 couples to IUI-OS. Two RCTs had a low risk of bias, one had some concerns, and one had a high risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 couples, 50.3% vs 43.2%, HR 1.10, 95% CI 0.54 to 2.21, I2 = 68.7%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than in IUI-OS (3 RCTs, 923 couples, 3.8% vs 5.2%, OR 0.78, 95% CI 0.41 to 1.50, I2 = 0.0%). Clinical pregnancy (4 RCTs, 933 couples, OR 1.09, 95% CI of 0.78 to 1.53, I2 = 14.3%) and pregnancy loss (3 RCTs, 760 couples, OR 0.97, 95% CI 0.55 to 1.72, I2 = 0.0%) were comparable between IVF and IUI-OS. There were no significant differences in neonatal outcomes between the two interventions on gestational age and birth weight. Limitations, reasons for caution Four RCTs did not share IPD which may introduce the risk of data availability bias. Only two included RCTs collected data on neonatal outcomes. Three of the included RCTs predominantly or only included couples with poor prognosis of natural conception which limits generalisability. Wider implications of the findings IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility, especially for those with a poor prognosis of natural conception. The associated costs of interventions and the preference of couples are important in clinical decision-making. Trial registration number not applicable

The effects of Capsicum annuum supplementation on lipid profiles in adults with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

The electiveness of Capsicum annuum supplementation in controlling dyslipidemia in adults has been unclear. Therefore, this meta-analysis focuses on the relationship between C. annuum supplementation and lipid profile in adults with metabolic syndrome (MetS) and related disorders. PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched up to March 2021. Only randomized controlled trials (RCTs) studying the administration of C. annuum compared to control on lipid markers in adults with MetS and related disorders were examined. Pooled effect sizes were reported as weighted mean differences (WMDs) and 95% confidence intervals (CIs). The results of four eligible RCTs showed that C. annuum supplementation could significantly reduce total cholesterol (TC) (WMD: -4.98 mg/dL, 95% CI: -7.08 to -2.88, p ≤ 0.001) levels, but did not regulate triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations. In summary, the present findings suggest the beneficial effects of C. annuum supplementation on the reduction of plasma levels of TC. However, to draw a firm link between C. annuum supplementation and lipid profile, more trials with adequate sample sizes, specifically in subjects with dyslipidemia are warranted.

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials.

Steroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens. Literature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method. Eight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01-1.32, P = 0.04), especially in patients with severe (grade III-IV or grade C-D) aGVHD (RR = 1.26, 95% CI = 1.04-1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05-1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy. Adding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487.

Conservative and Surgical Modalities in the Management of Pediatric Parapneumonic Effusion and Empyema: A Living Systematic Review and Network Meta-Analysis

The optimal treatment for community-acquired childhood pneumonia complicated by empyema remains unclear. In children with parapneumonic effusion or empyema, do hospital length of stay and other key clinical outcomes differ according to the treatment modality used? A living systematic review of randomized controlled trials (RCTs) was conducted by searching the Cochrane Central Register of Controlled Trials, Embase, Latin American and Caribbean Health Sciences Literature, Ovid MEDLINE, and Web of Science Core Collection databases. Eligible RCTs included patients aged< 18 years and compared two of the following treatment modalities: antibiotics alone, chest tube insertion with or without fibrinolytics, video-assisted thoracoscopic surgery (VATS), and decortication via thoracotomy. A network meta-analysis was performed to evaluate treatment effects on hospital length of stay (LOS), the primary outcome. Eleven trials including a total of 590 patients were selected for the network meta-analysis. Compared with a chest tube alone, a chest tube with fibrinolytics, thoracotomy, and VATS were all associated with shorter LOS, with a mean difference of 5.05days (95%CI, 2.46-7.64), 6.33days (95%CI, 3.17-9.50), and 5.86days (95%CI, 3.38-8.35), respectively. No substantial differences in LOS were observed between the latter three interventions. None of the 11 RCTs compared antibiotics alone vsother types of treatment. Most trials reported peri-procedural complications and the need for reintervention, but the descriptions differed significantly between trials, preventing meta-analysis. In trials reporting health care-associated costs, fibrinolytics had cost advantages compared with VATS. Short- and long-term morbidity and mortality were very low, regardless of the treatment modality. The results of this network meta-analysis showed that a chest tube alone was associated with a longer LOS compared with other treatment modalities. The lower cost associated with a chest tube plus fibrinolytics warrants consideration when choosing between treatment options, given similar LOS and clinical outcomes compared with the other modalities.

#4368 THE PERSISTENT UNDERREPRESENTATION OF PEOPLE WITH CHRONIC KIDNEY DISEASE IN CARDIOVASCULAR TRIALS: A SYSTEMATIC REVIEW AND EVIDENCE MAP

Abstract Background and Aims People with chronic kidney disease (CKD) have a markedly higher risk for cardiovascular disease. Systematic underrepresentation of people with CKD in cardiovascular randomised controlled trials (RCTs) limits evidence to guide cardiovascular risk management (CVRM). In this systematic review we aimed to identify evidence gaps regarding CVRM medication for people with CKD and evaluated the prevalence of exclusion of people with CKD from cardiovascular RCTs. Method We searched Clinicaltrials.gov through the Cochrane Central Register of Controlled Trials from inception until October 2021. Eligible studies were randomised controlled trials (RCTs) that investigate the efficacy of guideline-recommended CVRM medications on (cardiovascular) mortality, cardiovascular morbidity, and end-stage kidney disease in adults with a history of cardiovascular disease or one or more major risk factors for cardiovascular disease. Two reviewers independently determined the eligibility of references and extracted data. Outcomes were an overview of studies that report results for people with CKD, evidence gaps in results, and the rate of exclusion of people with CKD. Results We included 1180 of the 2794 eligible RCTs involving 2,158,869 participants (mean age 63±6 years, 36% female). Overall, 841 (71%) RCTs excluded (subgroups of) people with CKD based on heterogenous exclusion criteria. Since 2000, this prevalence has increased from 70% to 75%. Of included RCTs, only 157 (13%) reported results for people with CKD (again in heterogenous subgroups). The prevalence of RCTs with results for people with CKD has increased since 2000 from 10% to 23%. Nevertheless, significant evidence gaps remain for most CVRM interventions, particularly for those with an eGFR &amp;lt;30 ml/min/1.73m2 (22 RCTs), and people who are treated with dialysis (14 RCTs) or received a kidney transplant (1 RCTs). Conclusion The majority of cardiovascular RCTs continues to exclude (subgroups of) people with CKD and this has only increased over the years. Although more RCTs report results for people with CKD, evidence gaps for the efficacy most CVRM medications persist, particularly for those with severe CKD.

Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.

We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.

Interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews.

Interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews.

The impact of dance‐movement interventions on psychological health in older adults: A systematic review and meta‐analysis of randomized controlled trials

AbstractBackgroundGood psychological health is proposed as a key factor in the protection against Alzheimer’s disease (AD) and age‐related cognitive decline1. Multimodal motor, cognitive, sensory, and social enrichment as induced by dance‐movement interventions (DMI) could promote psychological health in the older population. This systematic review and meta‐analysis investigated the impact of DMI compared to control intervention (active/passive) on psychological health in older adults.MethodsA systematic search of three databases (PubMed, Web of Science, PsycInfo; screenings: April and November 2021) was conducted following PRISMA guidelines. Criteria included randomized controlled trials (RCTs) evaluating the effects of DMI (minimum 4 weeks’ duration) on health‐related psychological outcomes (primary outcome) and global cognitive functioning (secondary outcome) among non‐demented older adults (≥ 55 years of age). A random‐effects meta‐analysis with robust variance estimation was carried out. This review was registered with PROSPERO (CRD42021265112).ResultsData of 13 eligible primary RCTs (n = 943, n‐DMI = 474, n‐control = 469) were synthesized. Overall heterogeneity of results and risk of bias across RCTs were high. DMI had a small positive impact on psychological health compared to control (g = 0.31; 95% Confidence Interval (CI): [0.09, 0.53]; p = .01, I2 = 62.55). Separation of psychological health into positive and negative outcomes and particularly social and emotional aspects showed similar trends favouring DMI compared to control (see Figure 1). Analysis of secondary outcomes indicated a positive effect of DMI on global cognitive functioning (g = 0.48; 95%CI: [0.03, 0.93], p = .04, I2 = 82.44). Exploratory subgroup analyses suggested that the implementation of longer intervention durations and psychotherapeutic elements increase the psychological health benefits of DMI.ConclusionMultimodal interventions, as specifically offered by DMI, may serve as an effective tool to promote psychological health together with cognitive functioning in older adults. High‐quality future trials are needed to expand evidence on the particular aspects of psychological health and identify underlying neurophysiological correlates. We will present a protocol for a prospective RCT to assess the impact of a DMI on psychological, cognitive and brain health outcomes in the older population at increased risk of AD.References1Livingston G, et al. Lancet 2020.

Meta-analysis of the effectiveness of heparin in suppressing physiological myocardial FDG uptake in PET/CT.

The present meta-analysis aims to investigate the effectiveness of heparin administration in suppressing physiological myocardial 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT), as its role in this regard has not been well investigated. PRISMA guidelines were used to interrogate the PubMed, Embase, Cochrane library, Web of Knowledge, and www.clinicaltrail.gov databases from the earliest records to March 2023. The final analysis included five randomized controlled trials (RCTs). Meta-analysis was conducted to compare the effectiveness of unfractionated heparin (UFH) administration versus non-UFH administration, and subgroup analysis based on fixed and variable fasting durations was conducted. Effect sizes were pooled using a random-effects model, and the pooled odds ratios (ORs) were calculated. Five eligible RCTs with a total of 910 patients (550 with heparin, 360 without heparin) were included. The forest plot analysis initially indicated no significant difference in the suppression of myocardial FDG uptake between the UFH and non-UFH groups (OR 2.279, 95% CI 0.593 to 8.755, p = 0.23), with a high degree of statistical heterogeneity (I2 = 91.16%). Further subgroup analysis showed that the fixed fasting duration group with UFH administration had statistically significant suppression of myocardial FDG uptake (OR 4.452, 95% CI 1.221 to 16.233, p = 0.024), while the varying fasting duration group did not show a significant effect. According to the findings of our meta-analysis, we suggest that intravenous administration of UFH can be considered as a supplementary approach to suppress myocardial FDG uptake.