Large-scale Randomized Controlled Trials Research Articles

Magnesium and Osteoporosis: A Meta-Analysis of the Effects on Bone Turnover Markers, Fracture Incidence, and Quality of Life

Background: Osteoporosis, a prevalent bone disease characterized by reduced bone mineral density (BMD) and increased fracture risk, poses a significant public health challenge. Magnesium, an essential mineral involved in bone metabolism, has emerged as a potential therapeutic agent. This meta-analysis aimed to evaluate the effects of magnesium supplementation on bone turnover markers, fracture incidence, and quality of life in individuals with osteoporosis. Methods: A systematic search of PubMed, Embase, and Cochrane Library databases was conducted from January 2013 to December 2024 to identify randomized controlled trials (RCTs) investigating the impact of magnesium supplementation on adults diagnosed with osteoporosis. The primary outcomes were changes in bone turnover markers (serum calcium, phosphorus, alkaline phosphatase, and osteocalcin), fracture incidence, and quality of life scores. Standardized mean differences (SMD) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Results: Nine RCTs met the inclusion criteria, encompassing a total of 825 participants. Magnesium supplementation demonstrated a significant improvement in bone turnover markers, with a decrease in serum alkaline phosphatase (SMD = -0.35; 95% CI: -0.62, -0.08; p = 0.01) and osteocalcin (SMD = -0.29; 95% CI: -0.51, -0.07; p = 0.009). A trend towards reduced fracture incidence was observed in the magnesium group (RR = 0.72; 95% CI: 0.51, 1.02; p = 0.06). Furthermore, magnesium supplementation significantly improved quality of life scores, as measured by the Osteoporosis Quality of Life Questionnaire (OQLQ) (SMD = 0.41; 95% CI: 0.15, 0.67; p = 0.002). Conclusion: This meta-analysis provides evidence that magnesium supplementation may have beneficial effects on bone turnover markers and quality of life in individuals with osteoporosis. Although a trend towards reduced fracture incidence was observed, further large-scale RCTs are warranted to confirm this finding.

Targeting Interleukin-6 Signaling with Tocilizumab in Atherosclerosis: A Meta-Analysis of Anti-Inflammatory Effects and Plaque Stabilization

Atherosclerosis, a chronic inflammatory disease, is the leading cause of cardiovascular disease. Interleukin-6 (IL-6) plays a crucial role in atherogenesis, making it a potential therapeutic target. Tocilizumab, an IL-6 receptor antagonist, has shown promise in reducing inflammation and stabilizing atherosclerotic plaques. This meta-analysis aimed to evaluate the efficacy and safety of tocilizumab in atherosclerosis by analyzing its impact on inflammatory markers and plaque characteristics. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted from January 2013 to January 2024. Studies evaluating the effects of tocilizumab on inflammatory markers and plaque characteristics in patients with atherosclerosis were included. Randomized controlled trials (RCTs) and observational studies with a comparative arm were eligible. Data were extracted and pooled using a random-effects model. Nine studies (n=1248 participants) met the inclusion criteria. Tocilizumab significantly reduced CRP levels (standardized mean difference [SMD] -1.23; 95% confidence interval [CI] -1.56 to -0.90; p<0.001) and IL-6 levels (SMD -0.87; 95% CI -1.12 to -0.62; p<0.001) compared to control groups. A significant reduction in plaque volume (SMD -0.45; 95% CI -0.71 to -0.19; p=0.001) and an increase in fibrous cap thickness (SMD 0.38; 95% CI 0.12 to 0.64; p=0.004) were also observed. No significant increase in adverse events was reported in the tocilizumab group. This meta-analysis demonstrates that tocilizumab effectively reduces inflammation and promotes plaque stabilization in atherosclerosis. These findings suggest that tocilizumab may be a promising therapeutic strategy for preventing cardiovascular events in patients with atherosclerosis. Further large-scale RCTs are needed to confirm these findings and establish the long-term safety and efficacy of tocilizumab in this population.

Unraveling Cardiovascular Risks and Benefits of COVID-19 Vaccines: A Systematic Review.

The rapid development and deployment of mRNA and non-mRNA COVID-19 vaccines have played a pivotal role in mitigating the global pandemic. Despite their success in reducing severe disease outcomes, emerging concerns about cardiovascular complications have raised questions regarding their safety. This systematic review critically evaluates the evidence on the cardiovascular effects of COVID-19 vaccines, assessing both their protective and adverse impacts, while considering the challenges posed by the limited availability of randomized controlled trial (RCT) data on these rare adverse events. In adherence to PRISMA 2020 guidelines, we conducted a systematic review using the Scopus database, incorporating articles published from January 2020 to July 2024. Our search included terms related to COVID-19 vaccines and cardiovascular conditions. We selected relevant studies from case-control studies, cohort studies, and clinical trials, while excluding descriptive analyses, cross-sectional studies, and conference reports. Case reports were also included due to the limited availability of extensive RCT data on the rare cardiovascular adverse events associated with COVID-19 vaccines. Of the 6037 articles initially screened, 410 were assessed in detail and 175 studies were ultimately included. The review identified a variety of cardiovascular adverse effects associated with COVID-19 vaccines. mRNA vaccines were primarily linked to myocarditis and pericarditis, particularly in younger males, with lower cardiac risks compared to COVID-19 infection. Adenoviral vector vaccines were associated with thrombosis and thrombocytopenia. Inactivated vaccines had fewer severe cardiovascular reports but still presented risks. Takotsubo cardiomyopathy was most commonly observed following mRNA vaccination. Case reports provided valuable additional insights into these rare events, highlighting clinical presentations and potential risk factors not fully captured by larger epidemiological studies. This review reveals a nuanced cardiovascular risk profile for COVID-19 vaccines, with mRNA vaccines linked to rare myocarditis and pericarditis in young males and a higher incidence of Takotsubo cardiomyopathy in females. Adenoviral vaccines show a notable association with thrombosis. Despite these risks, the benefits of vaccination in preventing severe COVID-19 outcomes outweigh the potential complications, underscoring the importance of continued surveillance, case report documentation, and personalized risk assessment. The inclusion of case reports was critical, as they provided valuable real-world data that complemented the findings from large-scale studies and RCTs.

Effect of acute kidney injury care bundle on kidney outcomes in cardiac patients receiving critical care: a systematic review and meta-analysis

BackgroundCardiac surgery is a major contributor to acute kidney injury (AKI); approximately 22% of patients who undergo cardiac surgery develop AKI, and among them, 2% will require renal replacement therapy (RRT). AKI is also associated with heightened risks of mortality and morbidity, longer intensive care stays, and increased treatment costs. Due to the challenges of treating AKI, prevention through the use of care bundles is suggested as an effective approach. This review aimed to assess the impact of care bundles on kidney outcomes, mortality, and hospital stay for cardiac patients in critical care.MethodsPubMed, Scopus, Web of Science, and EMBASE were searched up to November 2024. Inclusion criteria were studies on individuals with cardiac diseases receiving critical care, that used AKI care bundle as the intervention, and reported outcomes related to AKI, mortality, and other kidney-related events. We used the Cochrane Collaboration’s risk of bias tool 2 and the Newcastle-Ottawa scale for quality assessment. Pooled odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.ResultsSeven studies on total 5045 subjects, including five observational and two randomized controlled trials (RCTs) were included. The implementation of care bundles significantly reduced the incidence of all-stage AKI (OR: 0.78; 95%CI: 0.61–0.99) and moderate-severe AKI (OR: 0.56; 95%CI: 0.43–0.72). Also, the implementation of care bundle increased the incidence of persistent renal dysfunction after 30 days by 2.39 times. However, there were no significant changes in RRT, major adverse kidney events, or mortality between the groups. The mean quality assessment score for observational studies was 7.2 out of ten, while there were noted concerns in the risk of bias assessment of the RCTs.ConclusionsThe application of care bundles in patients, including those undergoing cardiac surgeries as well as non-cardiac critical illness, appears to be effective in reducing AKI, particularly in moderate and severe stages. However, given the inclusion of non-cardiac patients in some studies, the observed effect may not be solely attributable to cardiac surgery cases. Future large-scale RCTs focusing specifically on cardiac surgery patients are recommended to clarify the impact of care bundles within this subgroup.Registration ID in PROSPEROCRD42024498972.

Psilocybin-assisted massed cognitive processing therapy for chronic posttraumatic stress disorder: Protocol for an open-label pilot feasibility trial.

Posttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches. Preliminary evidence supports the potential therapeutic action of psilocybin to alleviate PTSD symptoms. This open-label pilot study aims to evaluate the feasibility, tolerability, and preliminary efficacy of a single dose 25 mg psilocybin in combination with one week of massed CPT in patients with chronic PTSD. Fifteen participants with chronic PTSD will undergo 12 CPT sessions, two psilocybin-related psychotherapy sessions, and one psilocybin dosing session over a 7-days period. The primary outcomes are feasibility and tolerability, which will be measured by recruitment rates, withdrawal, data completion, adherence, number and nature of adverse events. Secondary objectives include assessing the preliminary efficacy of psilocybin-assisted CPT in reducing PTSD severity, self-reported treatment outcomes and exploring putative mechanisms of change. Participants will be monitored weekly for 12 weeks post-treatment and passive data relevant to mental health and well-being will be collected using a wearable device. This trial will generate important preliminary data on the use of psilocybin-assisted CPT for treating PTSD. The findings will guide the design of a multi-site, large-scale randomized control trial to more rigorously assess the efficacy of this intervention. De-identified data from this study will be available upon request after publication of the results. This study represents a promising and innovative approach to PTSD treatment, potentially offering an alternative therapeutic option for individuals unresponsive to conventional therapies. ClinicalTrials.gov NCT06386003.

Conversion Therapy for Stage IV Gastric Cancer: Report From the Expert Consensus Meeting at KINGCA WEEK 2024.

Conversion therapy is a treatment strategy that shifts from palliative systemic therapy to curative surgical treatment for primary and/or metastatic stage IV gastric cancer (GC). To address its clinical statements, the Korean Gastric Cancer Association aims to present a consensus on conversion therapy among experts attending KINGCA WEEK 2024. The KINGCA Scientific Committee and Development Working Group for Korean Practice Guidelines prepared preformulated topics and 9 clinical statements for conversion therapy. The Delphi method was applied to a panel of 17 experts for consensus and opinions. The final comments were announced after the statement presentation and discussed during the consensus meeting session of KINGCA WEEK 2024. Most experts agreed that conversion therapy provides a survival benefit for selected patients who respond to systemic therapy and undergo R0 resection (88.3%). Patients with limited metastases were considered good candidates (94.2%). The optimal timing was based on the response to systemic therapy (70.6%). The regimen was recommended to be individualized (100%) and the duration to be at least 6 months (88.3%). A minimally invasive approach (82.3%) and D2 lymph node dissection (82.4%) were considered for surgery. However, resection for metastases with a complete clinical response after systemic therapy was not advocated (41.2%). All experts agreed on the need for large-scale randomized-controlled trials for further evidence (100%). Recent advancements in treatment may facilitate radical surgery for patients with stage IV GC. Further evidence is warranted to establish the safety and efficacy of conversion therapy.

Male Breast Cancer Biology, Screening, Treatment, and Follow-Up: A Narrative Review

Male breast cancer (MBC) is a rare type of cancer that affects men, accounting for only 1% of all cancers in men and all breast cancer cases worldwide. Its rarity is due to the differences in male endocrine function and the smaller amount of mammary tissue in males. Due to its infrequency, there is limited knowledge about the disease, and treatment recommendations are often based on extrapolation from clinical trial data involving female breast cancer patients. Men with MBC typically present in their 50s or older and may mistake a suspicious breast mass for a benign condition called gynecomastia. Various known risk factors contribute to breast cancer in men. Currently, there are no international randomized control trials (RCTs) specifically focused on MBC, and management guidelines are primarily derived from studies conducted among female patients. Localized and resectable cases of breast cancer typically require surgical intervention, followed by radiotherapy, chemotherapy, hormonal therapy, or potentially utilizing recent advancements in immune-oncology agents. A comprehensive approach that involves a multidisciplinary team ensures appropriate treatment and can lead to favorable outcomes. However, screening for MBC is limited due to the lack of large-scale international RCTs demonstrating its effectiveness in reducing MBC-related mortality.

Impact of pulmonary vein isolation on atrial arrhythmias in patients with typical atrial flutter: systematic review and meta-analysis of randomized clinical trials.

Cavotricuspid isthmus (CTI) ablation is the current ablation treatment for typical atrial flutter (AFL). However, post-ablation atrial tachyarrhythmias, mostly in the form of atrial fibrillation (AF), are frequently observed after CTI ablation. We aimed to evaluate the effectiveness and safety of concomitant or isolated pulmonary vein isolation (PVI) in patients with typical AFL scheduled for ablation. Electronic databases (PubMED, EMBASE, Clinicaltrials.gov) were searched through July, 2024. Randomized controlled trials (RCTs) were eligible if comparing PVI ± CTI ablation vs. CTI alone. The primary outcomes were any sustained atrial arrhythmia, typical AFL relapse, and AF. Secondary outcomes were need for redo-ablation or antiarrhythmic drugs. Random-effects and fixed-effects meta-analyses were undertaken for each individual outcome. Seven RCTs, with a total of 902 patients, were included. Comparing to CTI ablation alone, PVI ± CTI was more effective in preventing atrial tachyarrhythmias [risk ratio (RR) = 0.57, 95% CI: 0.41-0.79, P = 0.0007, I 2 = 50%, number needed to treat (NNT) = 4.1]. The results were driven mainly by a reduction of new onset/recurrent AF (RR = 0.41, 95% CI: 0.27-0.61, P < 0.0001, I 2 = 0%, NNT = 3.3), whereas there were no differences in typical AFL relapse (RR = 1.52, 95% CI: 0.63-3.66, P = 0.35, I 2 = 9%). Major complication rate was low and comparable across groups, although uncomplicated pericardial effusion was higher in PVI ± CTI (1.8% vs. 0.0%, P = 0.04). Results were comparable for the sub-analysis of PVI alone vs. CTI ablation. In patients with typical AFL, PVI ± CTI ablation is more effective than CTI alone in reducing the atrial tachyarrhythmias and subsequent AF during follow-up, without affecting major complications rate. These results set the rationale for a well-designed, larger-scale RCT comparing both strategies.

Magnetic Seizure Therapy in Refractory Psychiatric Disorders: A Systematic Review and Meta-Analysis: La thérapie par convulsions magnétiques pour la prise en charge des troubles psychiatriques réfractaires : revue systématique et méta-analyse.

To qualitatively and quantitatively synthesize the literature on the efficacy and safety of magnetic seizure therapy (MST) in psychiatric disorders. A literature search was conducted of the OVID Medline, OVID EMBASE, PsychINFO, CINAHL, Web of Science and Cochrane databases from inception to 14 January 2024, using subject headings and key words for "magnetic seizure therapy." Randomized controlled trials (RCTs), post-hoc analyses of RCTs, open-label trials, or case series investigating MST in adults with a verified psychiatric diagnosis and reporting on two possible primary outcomes (1) psychiatric symptom reduction (as measured by validated rating scale) or (2) neurocognitive outcomes (as measured by standardized testing), were included. Abstracts, individual case reports, reviews and editorials were excluded. Extracted data included: (1) basic study details; (2) study design; (3) sample size; (4) baseline demographics; (5) outcome data (including secondary outcomes of suicidal ideation and adverse events); and (6) stimulation parameters. Cochrane's risk of bias tool was applied. A quantitative analysis was conducted for the depression studies, using Hedge's g effect sizes. A total of 24 studies (n = 377) were eligible for inclusion. Seventeen studies in depression (including three RCTs), four studies in schizophrenia (including one RCT), one study in bipolar disorder, one study in obsessive-compulsive disorder and one study in borderline personality disorder were summarized. We found no significant difference in depressive symptom reduction between MST and electroconvulsive therapy (ECT) in randomized, controlled trials (g = 0.207 towards ECT, 95% confidence interval (CI) -0.132 to 0.545, P = 0.232). We found a significant reduction in depressive symptoms overall with MST in the pooled RCT and open-label analysis (g = 1.749, CI 1.219 to 2.279, P < 0.005). It is suggested that MST has modest cognitive side effects. Large-scale RCTs are necessary to confirm early signals of MST as an effective intervention in psychiatric disorders with a cognitive profile that is potentially more favourable than ECT.

Clinical benefits of modifying the evening light environment in an acute psychiatric unit: A single-centre, two-arm, parallel-group, pragmatic effectiveness randomised controlled trial.

The impact of light exposure on mental health is increasingly recognised. Modifying inpatient evening light exposure may be a low-intensity intervention for mental disorders, but few randomised controlled trials (RCTs) exist. We report a large-scale pragmatic effectiveness RCT exploring whether individuals with acute psychiatric illnesses experience additional benefits from admission to an inpatient ward where changes in the evening light exposure are integrated into the therapeutic environment. From 10/25/2018 to 03/29/2019, and 10/01/2019 to 11/15/2019, all adults (≥18 years of age) admitted for acute inpatient psychiatric care in Trondheim, Norway, were randomly allocated to a ward with a blue-depleted evening light environment or a ward with a standard light environment. Baseline and outcome data for individuals who provided deferred informed consent were used. The primary outcome measure was the mean duration of admission in days per individual. Secondary outcomes were estimated mean differences in key clinical outcomes: Improvement during admission (The Clinical Global Impressions Scale-Improvement, CGI-I) and illness severity at discharge (CGI-S), aggressive behaviour during admission (Broset Violence Checklist, BVC), violent incidents (Staff Observation Aggression Scale-Revised, SOAS-R), side effects and patient satisfaction, probabilities of suicidality, need for supervision due to suicidality, and change from involuntary to voluntary admission. The Intent to Treat sample comprised 476 individuals (mean age 37 (standard deviation (SD) 13.3); 193 (41%) were male, 283 (59%) were female). There were no differences in the mean duration of admission (7.1 days for inpatients exposed to the blue-depleted evening light environment versus 6.7 days for patients exposed to the standard evening light environment; estimated mean difference: 0.4 days (95% confidence interval (CI) [-0.9, 1.9]; p = 0.523). Inpatients exposed to the blue-depleted evening light showed higher improvement during admission (CGI-I difference 0.28 (95% CI [0.02, 0.54]; p = 0.035), Number Needed to Treat for clinically meaningful improvement (NNT): 12); lower illness severity at discharge (CGI-S difference -0.18 (95% CI [-0.34, -0.02]; p = 0.029), NNT for mild severity at discharge: 7); and lower levels of aggressive behaviour (difference in BVC predicted serious events per 100 days: -2.98 (95% CI [-4.98, -0.99]; p = 0.003), NNT: 9). There were no differences in other secondary outcomes. The nature of this study meant it was impossible to blind patients or clinical staff to the lighting condition. Modifying the evening light environment in acute psychiatric hospitals according to chronobiological principles does not change duration of admissions but can have clinically significant benefits without increasing side effects, reducing patient satisfaction or requiring additional clinical staff. Clinicaltrials.gov NCT03788993; 2018 (CRISTIN ID 602154).

Acupuncture for atopic dermatitis: a systematic review and meta-analysis

ObjectivesAtopic dermatitis is a chronic, relapsing, inflammatory skin disease that impacts patients’ quality of life and imposes substantial economic burdens on their families. Acupuncture holds promise as a viable treatment...

Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study

BackgroundIntravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock.MethodsWe conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety.ResultsTwenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group.ConclusionsThe evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock.Trial registrationThis pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589

Effectiveness of Vitamin D Supplementation in Reducing Atopic Dermatitis Severity in Children: A Meta-Analysis

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly affects children, with increasing prevalence worldwide. Vitamin D has demonstrated immunomodulatory effects, suggesting a potential role in AD management. This meta-analysis aimed to evaluate the effectiveness of vitamin D supplementation in reducing AD severity in children. Methods: A systematic search of PubMed, Science Direct, and Cochrane databases was conducted for randomized controlled trials (RCTs) published between 2012 and 2024, investigating the effects of vitamin D supplementation on AD in children. The primary outcome was the change in SCORAD (SCORing Atopic Dermatitis) or EASI (Eczema Area and Severity Index) scores. Meta-analysis was performed using Review Manager (RevMan 5.4) software. Results: Four RCTs met the inclusion criteria, comprising a total of 234 participants. The meta-analysis revealed a significant reduction in SCORAD scores (-2.83; 95% CI: -4.9, -0.76) and EASI scores (-0.41; 95% CI: -0.70, -0.13) in the vitamin D supplementation groups compared to the control groups. A combined analysis of both scoring systems further confirmed the overall significant effect of vitamin D in reducing AD severity (-1.57; 95% CI: -2.78, -0.36). Conclusion: Vitamin D supplementation is effective in improving AD symptoms in children. Further large-scale RCTs are warranted to determine the optimal dosage and duration of vitamin D supplementation for AD management in children.

Comparative efficacy of Chinese tonic medicines for treating sepsis or septic shock: A systematic review and Bayesian network meta-analysis of randomized controlled trials

BackgroundSepsis or septic shock is a life-threatening medical emergency with a poor prognosis and a high economic burden for both individuals and healthcare resources. Evidence suggests that Chinese tonic medicines (CTMs), as adjuvant treatments, are effective in treating this disease. Nevertheless, the ongoing discourse regarding the optimal CTMs persists. This study was conducted to further explore the comparative effectiveness of CTMs for patients with sepsis or septic shock. MethodsWe systematically searched Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP database from inception to November 15, 2023. Primary outcomes encompassed the delta Sequential Organ Failure Assessment (ΔSOFA) score at day 7 after interventions and 28-day mortality. Secondary outcomes included delta serum lactate (ΔLac) and delta mean arterial pressure (ΔMAP) levels at day 7 after interventions, as well as the duration of vasoactive drug administration. The safety outcome was adverse drug reactions or adverse drug events (ADRs/ADEs). The risk ratio (RR) and mean difference (MD) with a 95 % confidence interval (95 %CI) were selected as effect measures. The Bayesian network meta-analysis was conducted by R version 4.2.2 software. The surface under the cumulative ranking curve (SUCRA) values were used to rank each treatment. The Cochrane Risk of Bias V.2.0 tool was employed to assess the within-study risk of bias. The CINeMA (Confidence in Network Meta-Analysis) web application was utilized to assess the quality of evidence. This protocol was prospectively registered in PROSPERO (CRD4202348572). ResultsA total of 45 randomized controlled trials (RCTs) involving 3433 patients were identified in this study. Seven CTMs including Shenfu injection (SF), Shenmai injection (SM), Sini decoction (SN), Shenfu and Shengmai granules (SF+SGM), Shengmai injection (SGM), Yiqifumai injection (YQFM), and Shenqifuzheng injection (SQFZ) were involved. Regarding the ΔSOFA score, interventions combining SM with Western medicine (WM) (MD, −2.77; 95 %CI, −3.28 to −2.27), YQFM+WM (MD, −1.76; 95 %CI, −2.73 to −0.79), SGM+WM (MD, −1.11; 95 %CI, −1.88 to −0.34), and SF+WM (MD, −0.98; 95 %CI, −1.17 to −0.78) demonstrated superiority over WM alone. According to the SUCRA values, SM+WM (99.28 %) achieved the highest ranking for the ΔSOFA score. Concerning 28-day mortality, SM+WM (RR, 0.51; 95 %CI, 0.35 to 0.72) and SF+WM (RR, 0.73; 95 %CI, 0.65 to 0.83) exhibited a superior effect in reducing 28-day mortality. Based on the SUCRA values, SM+WM (82.49 %) secured the top ranking for 28-day mortality. Among the secondary outcomes, SM+WM (MD, −2.50; 95 %CI, −4.15 to −0.83; SUCRA, 94.27 %) emerged as the most favorable in reducing serum lactate levels. SF+WM (MD, 10.78; 95 %CI, 3.11 to 18.71; SCURA, 78.3 %) exhibited superior effectiveness compared to other treatments in improving mean arterial pressure (MAP). The certainty of evidence for these outcomes was assessed as low. ConclusionCTMs combined with WM led to a significant improvement in ΔSOFA score and MAP, as well as a reduction in 28-day mortality and serum lactate levels. SM+WM emerged as the optimal treatment regimen for enhancing ΔSOFA, reducing 28-day mortality, and lowering serum lactate levels. Additionally, SF+WM exhibited superiority in improving MAP. Nevertheless, there is a need for large-scale, multicenter, and direct comparative RCTs to generate higher-quality evidence.

Conduction system pacing in heart failure: Time for a paradigm shift?

Heart failure (HF) is a major clinical challenge characterized by significant morbidity and mortality. Electrical conduction abnormalities play a critical role in HF pathophysiology and progression, often leading to suboptimal outcomes with conventional pacing techniques. Con-duction system pacing (CSP), encompassing His bundle pacing and left bundle branch area pacing, has emerged as a novel approach. Despite data come from observational studies, recent guidelines recommend that a specific population may benefit from CSP. However, significant practical considerations and challenges need to be clarified before CSP can be routinely implemented in clinical practice. The reliance on observational studies means that long-term clinical outcomes for HF patients remain uncertain until data from randomized controlled trials (RCTs) become available. Current CSP practices face challenges with lead implantation, mechanical stress on leads, and the need for more advanced tools and artificial intelligence integration to improve procedure efficacy and safety. Future large-scale RCTs are essential to identify optimal candidates and address these technical challenges, potentially leading to a paradigm shift in HF management.

Outcomes of endovascular thrombectomy for acute ischaemic stroke in patients aged ≥80 years: A Hong Kong stroke center experience

BackgroundElderly patients contribute to the large proportion of ischaemic stroke worldwide. Currently, treatment for elderly stroke remains aggressive, as the exact age cutoff for endovascular thrombectomy (EVT) has not been well established due to a lack of large-scale randomized control trials. In this study we investigate the difference in outcome after EVT in the octogenarian and above, compared to their younger counterparts. MethodsEVT patients were divided into two groups, the octogenarian group and younger group (below age of 80). Primary outcome were the 90-days post-thrombectomy functional independence (modified Rankin scale), and Barthel index. Secondary and safety outcomes of post-thrombectomy were also analyzed, including reperfusion status (modified Thrombolysis in Cerebral Infarction (TICI) score), National Institutes of Health Stroke Scale (NIHSS), major complications and mortality rate. ResultsA total 340 patients were included from 2020 to 29 Feb 2024, and patients’ demographics were obtained. Poorer neurological outcome and functional independence were noted in octogenarian group compared with younger counterpart (OR 0.33; 95 % CI 0.14-0.51; p < 0.001). A slightly higher trend of overall post-procedural death was also identified in elder group compared with the younger group (OR 1.48; 95 % CI 0.85-2.60, p = 0.08). Subgroup analysis with more advanced age cutoff at 90 took a step further and proposed that advanced age resulting in more devastating neurological outcome. ConclusionOutcomes after endovascular thrombectomy in the elder group were significantly worse than their younger counterparts. More than 80 % of elder group who were treated with EVT required moderate functional dependence, and one in four were dead within 90-days post-EVT.

The Effects of Non-Pharmacological Therapies for Dysphagia in Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is currently the second most common degenerative neurological disorder globally, with aspiration pneumonia caused by difficulty swallowing being the deadliest complication. The patient's subjective experience and the safety of swallowing have been the main focus of previous evaluations and treatment plans. The effectiveness of treatment may be attributed to the brain's ability to adapt and compensate. However, there is a need for more accurate assessment methods for dysphagia and further research on how treatment protocols work. This systematic review was designed to assess the effectiveness and long-term impact of published treatment options for swallowing disorders in patients with PD. In adherence to the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) guidelines, we conducted a systematic review where we thoroughly searched multiple databases (PubMed, Web of Science, Elsevier, and Wiley) for clinical studies published in various languages until December, 2023. Two reviewers evaluated the studies against strict inclusion/exclusion criteria. This systematic review included a total of 15 studies, including 523 participants, involving six treatment approaches, including breath training, deep brain stimulation, reduction of upper esophageal sphincter (UES) pressure, transcranial magnetic stimulation, postural compensation, and video-assisted swallowing therapy. Primary outcomes included video fluoroscopic swallowing study (VFSS), fiberoptic endoscopic evaluation of swallowing (FEES), high-resolution pharyngeal impedance manometry (HPRIM), and functional magnetic resonance imaging (fMRI). Treatments that reduce UES resistance may be an effective way to treat dysphagia in PD patients. HRPIM can quantify pressure changes during the pharyngeal period to identify patients with reduced swallowing function earlier. However, due to the limited number of randomized controlled trials (RCTs) included and the high risk of bias in some studies, large-scale RCTs are needed in the future, and objective indicators such as HRPIM should be used to determine the effectiveness and long-term impact of different therapies on dysphagia in PD patients.

Acupuncture for patients with Alzheimer's disease: An evidence map of randomized controlled trials, systematic reviews, and meta-analysis.

Background: Acupuncture is an effective complementary treatment for Alzheimer's disease (AD). This review aims to summarize the available evidence provided by randomized controlled trials (RCTs) and systematic reviews (SRs) or meta-analyses (MAs) on the effect of acupuncture on AD. Objective: To systematically summarize and combine clinical research evidence on AD distribution. Methods: We conducted a comprehensive search of various databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese BioMedical Literature Database (CBM) and Chonqing VIP (CQVIP), from their inception to September 2023. Relevant literature about acupuncture for AD was included, and the characteristics of the evidence map were presented through charts and textual analyses. Results: In total, 117 RCTs and 17 SRs or MAs were included. The results were divided into three categories: basic characteristics of the included literature, clinical characteristics and quality assessment of the included RCTs, and clinical characteristics and quality assessment of the included SRs and MAs. Conclusions: Acupuncture as a therapeutic measure for AD has some advantages in improving cognition and quality of life; thus, it is imperative to conduct multi-center, large-scale RCTs to enhance the evidence supporting the use of acupuncture in AD. This is the first evidence map exploring acupuncture treatment for AD, providing insights into the current clinical research landscape on acupuncture treatment for AD. Furthermore, the findings of this study highlight research gaps in this field and serve as a valuable reference for guiding the planning and selection of topics for future research.

Abstract 4137870: Nasal Etripamil Spray efficacy for Acute Paroxysmal Supraventricular Tachycardia: A Systematic Review, Meta-Analysis and Trial Sequential Analysis.

Background: Acute paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia. Etripamil, a novel calcium channel blocker via nasal spray, has shown promise for PSVT management. This meta-analysis and trial sequential analysis (TSA) evaluates the efficacy and safety of nasal Etripamil for treating PSVT. Methods: We systematically searched Pubmed, Embase, and Cochrane databases for studies assessing the efficacy and safety of Etripamil for PSVT. The main outcome was conversion to sinus rhythm(CSR) within 15 minutes. Secondary outcomes included adverse events(AE). Meta-analysis was performed using random-effects models, and TSA was employed to assess the robustness of the evidence and required information size. Results: Three randomized controlled trials (RCTs) and two extensive trials involving 1,652 participants were analyzed. Nasal Etripamil significantly increased the CSR within 15 minutes compared to placebo (RR 1.87 95% CI; 1.39-2.52, p &lt;0.001; Figure A). Outcome TSA suggested a low risk of type 1 error; therefore, this result may be conclusive (Figure B). For the AEs both a pairwise and single-arm meta-analysis of studies was performed with 1 AEs being statistically significant in the single-arm plot, Nasal Discomfort (22.11 95% CI; 16.02-29.70 events per 100 observations, p &lt;0.01 Figure C). In the pairwise, the overall was statistically significant and it favored placebo (RR 3.93, 95% CI; 2.46-6.27, p &lt;0.001 Figure D). Conclusion: Nasal Etripamil is effective and safe for the treatment of acute PSVT, offering a non-invasive alternative to traditional therapies. Larger-scale RCTs are warranted to confirm these findings and explore long-term outcomes.

Abstract 4137306: Percutaneous Coronary Intervention Versus Optimal Medical Therapy for Vulnerable Atherosclerotic Coronary Plaques: A Pilot Meta-Analysis of Randomized Controlled Trials

Background: Vulnerable coronary plaques are identified as thin-capped fibroatheromas with substantial plaque and a lipid-enriched necrotic core. These plaques are often non-flow-limiting on assessment; however, they have been associated with future adverse clinical outcomes, such as unstable angina, myocardial infarction, and sudden cardiac death. Current guidelines do not recommend revascularization of such coronary plaques; however, percutaneous coronary intervention (PCI) can theoretically slow atherosclerotic progression and potentially reduce future adverse events. Methods: Major electronic databases were searched for randomized controlled trials (RCTs) that compared PCI to optimal medical therapy (OMT) for vulnerable coronary plaques. The outcomes were pooled using a random-effects model, and the results were expressed as risk ratios (RR) with corresponding 95% confidence intervals (CI). Results: 3 RCTs with 1811 patients (909: PCI and 902: OMT) were included. PCI demonstrated a statistically insignificant trend towards a decreased risk of all-cause mortality [RR: 0.40; 95% CI: 0.13, 1.27; p=0.12], cardiovascular mortality [RR: 0.17; 95% CI: 0.02, 1.38; p=0.10], myocardial infarction [RR: 0.78; 95% CI: 0.35, 1.72; p=0.53], target vessel-related myocardial infarction [RR: 0.68; 95% CI: 0.04, 11.27; p=0.79], ischemia-driven target vessel revascularization [RR: 0.22; 95% CI: 0.04, 1.22; p=0.08], and major adverse cardiovascular events [RR: 0.41; 95% CI: 0.14, 1.18; p=0.10] compared to OMT. Conclusion: This study concluded that PCI was comparable to OMT in patients with vulnerable atherosclerotic coronary plaques. Further large-scale RCTs with longer follow-up durations are required to confirm these findings.