Relevant Randomized Controlled Trials Research Articles

Industry affiliation does not predict outcomes of randomized controlled trials for mesenchymal stem cells in knee osteoarthritis

BackgroundThis research aims to determine the influence of industry on the outcomes of randomized controlled trials (RCTs) for Mesenchymal Stem Cell (MSC) treatments in knee osteoarthritis (OA). MethodsPubMed, Scopus, and Web of Science were searched from 2010 onwards using the terms “knee osteoarthritis” and “mesenchymal stem cells”. After identifying relevant RCTs, studies were categorized as industry-affiliated or non-industry-affiliated. They were also classified as favorable if they achieved statistically significant (p < 0.05) results with MSC injections compared to control. Chi-squared tests were employed to analyze the relationship between industry affiliation and study outcome. ResultsPost exclusion criteria, 38 studies were analyzed. Of these, there were 20 (52.6%) industry affiliated (IA) and 18 (47.4%) non-industry affiliated (NIA) studies. Among the 20 IA studies, 17 (85.0%) reported favorable outcomes for MSC treatment arm, with the remaining 3 (15.0%) showing analogous (no difference between treatment arms) results. For the 18 NIA studies, 15 (83.3%) were favorable, and 3 (16.6%) were analogous. No significant difference in outcomes was observed between IA and NIA studies (p = 0.888). Analysis of patient reported outcomes also revealed no significant difference. Of note, studies using allogeneic MSCs were more likely to be IA than studies using autologous MSCs (p = 0.005) ConclusionThis study demonstrated no strong association between industry affiliation and the outcomes of RCTs for MSC treatments in knee OA. Despite this, the potential influence of industry ties should always be considered when applying study findings to new treatment modalities for patient care.

Chronic exercise effects on overall depression severity and distinct depressive symptoms in older adults: A protocol of a systematic and meta-analytic review.

There is high evidence that chronic exercise benefits overall depression severity in older adults. However, late-life depression is characterized by considerable heterogeneity in clinical manifestation emphasizing the need for more individualized exercise intervention programs. Therefore, the objective of the proposed review is to investigate the effects of chronic exercise on overall depression severity and on different symptoms of depression in randomized controlled trials (RCTs) including older adults with a mean age of at least 60 years, and by considering the moderating effects of intervention characteristics and individual characteristics. This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). We will use the Population-Intervention-Comparator-Outcomes-Study design (PICOS) criteria for study inclusion and will search the following database sources for relevant RCTs: Web of Science, Academic Search Complete, CINAHL, APA Psycinfo, SPORTDiscuss, Cochrane. Two independent reviewers will conduct the study selection, data extraction, and quality assessment. Disagreement will be solved by a third reviewer. Primary outcome will be changes in overall depression severity and secondary outcomes will encompass changes in symptoms of depression as defined by the DSM-5, such as sleep quality, fatigue, anxiety, mood, apathy, changes in weight, information processing speed, and executive functions, from baseline until the end of the intervention and to any available intermediary measurement or follow up. Meta-analysis will be undertaken to synthesize the effects of chronic exercise on primary and secondary outcomes. Subgroup analysis will investigate the moderating effects of intervention characteristics (frequency, intensity, duration, type of exercise, cognitive demand, social interactions, exercise supervision, behavioral change techniques, compliance, study design, dropout-rate, type of control group) and individual characteristics (age, sex, education, functional capacity, global cognition, population) on primary and secondary outcomes. Additionally, we plan to assess quality of evidence and publication bias, and to carry out sensitivity analysis. The results of the proposed review are anticipated to have a substantial impact on research and clinical practice. On the one hand, the review's conclusions could form the foundation for developing evidence-based recommendations for individualized exercise programs that alleviate depression in older adults. On the other hand, by revealing research gaps, the review results could encourage the formulation of research questions for further RCTs. This protocol has been published in the Prospero repository (PROSPERO 2022 CRD42022361418, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361418).

Efficacy and safety of transcutaneous auricular vagus nerve stimulation (ta-VNS) in the treatment of tinnitus: protocol for an updated systematic review and meta-analysis

IntroductionWith an increasing incidence and significant effects on patients, tinnitus has become a major disease burden. There is a dearth of therapies with established efficacy for tinnitus. Transcutaneous auricular vagus...

Abstract PO2-04-07: Efficacy and Safety of First-line Therapy in Patients with HER-2 positive Advanced Breast Cancer:A network Meta-analysis of Randomized Controlled Trials

Abstract Background: The numerous but conflicting first-line treatment regimens for Her-2 positive advanced breast cancer necessitate a comprehensive evaluation to inform clinical decision-making. In this study, we conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions. Methods: We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts published by ASCO, SABCS. NMA was performed using R software, STATA and Review Manager 5.4 to calculate and analyze the primary endpoint progression free survival (PFS), as well as the secondary endpoints of overall survival (OS), objective response rate (ORR) and adverse events (AE) higher than grade 3. Results: Out of the 8,603 manuscripts retrieved, we included 30 RCTs involving 12,045 patients in our analysis. Regarding PFS, the combination of trastuzumab with TKI was more favorable than dual-target therapy (hazard ratio=0.54, 95% [CI]: 0.40–0.72), and combination chemotherapy was superior to monotherapy (HR=0.66, 0.53-0.83). It is important to note that the addition of anthracycline did not result in improved PFS (HR=1.27, 0.87-1.86). For the HR+HER2+ population, dual-target plus endocrine therapy was more effective than single-target plus endocrine therapy (HR=0.65, 0.53-0.80). Monotherapy combined with dual-target therapy significantly improved OS and ORR compared to monotherapy with single-target therapy (HR=0.69, 0.56-0.84; OR=1.89, 1.34-2.65). A comprehensive analysis of both PFS and AE higher than grade 3 indicated that monotherapy plus dual-target therapy struck a balanced approach between effectiveness and toxicity compared to other regimens. Conclusions: Monotherapy plus dual-target therapy remains the optimal choice among all first-line treatment options for advanced breast cancer. The combination of trastuzumab with TKI demonstrated a significant improvement in PFS, but further data are warranted to confirm the survival benefit. Figure 1. Network diagrams of PFS, OS, ORR and adverse events higher than grade 3 in eligible experimental arms. Figure 2. Forest plot of PFS, OS, ORR and adverse events higher than grade 3 in eligible experimental arms. (A): PFS of HER2+ for experimental arms. (B): PFS of HR+ and HER2+ for experimental arms. (C): OS of HER2+ for experimental arms. (D): ORR of HER2+ for experimental arms. (E): Adverse events higher than grade 3 of HER2+ for experimental arms. Figure 3. Each endpoint ranking for experimental arms. (SUCRA, surface under the cumulative ranking) (A): PFS ranking for experimental arms. (B): OS ranking for experimental arms. (C): ORR ranking for experimental arms. (D): Adverse events higher than grade 3 ranking for experimental arms. (E): Experimental arms ordered by their overall probability as the best treatment in terms of both efficacy and safety Citation Format: Junxiao Wang, Yushuai Yu, Jie Zhang, Chuangui Song. Efficacy and Safety of First-line Therapy in Patients with HER-2 positive Advanced Breast Cancer:A network Meta-analysis of Randomized Controlled Trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-07.

Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.

Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.

Comparative efficacy of immune checkpoint inhibitors combined with chemotherapy in patients with advanced driver-gene negative non-small cell lung cancer: A systematic review and network meta-analysis

ObjectiveTo evaluate the efficacy of different combinations of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) in the treatment of advanced non-small cell lung cancer (NSCLC). MethodsWe obtained relevant randomized controlled trials (RCTs) from databases such as PubMed, Embase, Web of Science, and The Cochrane Library up to May 31, 2023. The analysis of clinical prognostic factors was performed using R 4.2.3 and STATA 15.0. The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events of grade 3–5 severity (Grade ≥3 TRAE). ResultsA total of 17 randomized controlled trials (RCTs) were conducted between 2012 and 2023, involving 7792 patients. These trials evaluated 11 different treatment methods. The results of these trials showed that in terms of overall survival (OS) and progression-free survival (PFS), the combination of tislelizumab with chemotherapy and the combination of camrelizumab with chemotherapy were particularly effective. Moreover, when compared with other combination therapies, pembrolizumab combined with chemotherapy showed superiority in terms of disease control rate (DCR) and objective response rate (ORR). Subgroup analyses further demonstrated that the addition of immune checkpoint inhibitors (ICIs) to chemotherapy significantly improved PFS and OS in patients without liver metastasis and in those with brain metastasis. Additionally, carboplatin-based combination therapy was found to confer favorable survival benefits in terms of PFS, while cisplatin-based combination therapy showed the most favorable outcomes in terms of OS. The results of subgroup analyses for overall survival (OS) showed that the combination of immunotherapy and chemotherapy yielded positive outcomes in specific subgroups. These subgroups were characterized by PD-L1 Tumor Proportion Score (TPS) of 50 % or higher, usage of anti-PD-1 medications, age below 65, male gender, smoking history, and non-squamous cell carcinoma histology. Superior effectiveness was demonstrated only in extending the progression-free survival (PFS) of female patients and patients with squamous carcinoma. Meanwhile, other patient cohorts did not show the same level of improvement. ConclusionsTislelizumab, camrelizumab or pembrolizumab combined with chemotherapy may be the optimal first-line treatment strategies for NSCLC.

Comparative efficacy of telehealth interventions on promoting cancer screening: A network meta-analysis of randomized controlled trials.

Cancer screening is a pivotal method for reducing mortality from disease, but the screening coverage is still lower than expected. Telehealth interventions demonstrated significant benefits in cancer care, yet there is currently no consensus on their impact on facilitating cancer screening or on the most effective remote technology. A network meta-analysis was conducted to detect the impact of telehealth interventions on cancer screening and to identify the most effective teletechnologies. Six English databases were searched from inception until July 2023 to yield relevant randomized controlled trials (RCTs). Two individual authors completed the literature selection, data extraction, and methodological evaluations using the Cochrane Risk of Bias tool. Traditional pairwise analysis and network meta-analysis were performed to identify the overall effects and compare different teletechnologies. Thirty-four eligible RCTs involving 131,644 participants were enrolled. Overall, telehealth interventions showed statistically significant effects on the improvement of cancer screening. Subgroup analyses revealed that telehealth interventions were most effective for breast and cervical cancer screening, and rural populations also experienced benefits, but there was no improvement in screening for older adults. The network meta-analysis indicated that mobile applications, video plus telephone, and text message plus telephone were associated with more obvious improvements in screening than other teletechnologies. Our study identified that telehealth interventions were effective for the completion of cancer screening and clarified the exact impact of telehealth on different cancer types, ages, and rural populations. Mobile applications, video plus telephone, and text message plus telephone are the three forms of teletechnologies most likely to improve cancer screening. More well-designed RCTs involving direct comparisons of different teletechnologies are needed in the future. Telehealth interventions should be encouraged to facilitate cancer screening, and the selection of the optimal teletechnology based on the characteristics of the population is also necessary.

Development of the Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology: a qualitative synthesis of interventions in randomised controlled trials.

Community-based services to sustain independence for older people have varying configurations. A typology of these interventions would improve service provision and research by providing conceptual clarity and enabling the identification of effective configurations. We aimed to produce such a typology. We developed our typology by qualitatively synthesising community-based complex interventions to sustain independence in older people, evaluated in randomised controlled trials (RCTs), in four stages: (i) systematically identifying relevant RCTs; (ii) extracting descriptions of interventions (including control) using the Template for Intervention Description and Replication; (iii) generating categories of key intervention features and (iv) grouping the interventions based on these categories. PROSPERO registration: CRD42019162195. Our search identified 129 RCTs involving 266 intervention arms. The Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology comprises 14 action components and 5 tailoring components. Action components include procedures for treating patients or otherwise intended to directly improve their outcomes; regular examples include formal homecare; physical exercise; health education; activities of daily living training; providing aids and adaptations and nutritional support. Tailoring components involve a process that may result in care planning, with multiple action components being planned, recommended or prescribed. Multifactorial action from care planning was the most common tailoring component. It involves individualised, multidomain assessment and management, as in comprehensive geriatric assessment. Sixty-three different intervention types (combinations) were identified. Our typology provides an empirical basis for service planning and evidence synthesis. We recommend better reporting about organisational aspects of interventions and usual care.

A meta-analysis investigating the efficacy and safety of allergen-specific immunotherapy in the management of respiratory allergies

Background This meta-analysis aimed to evaluate the effectiveness and adverse effects of specific immunotherapy (SIT) in the management of respiratory allergens, including allergic asthma, rhinitis, and related disorders, based on a review of current literature up to November 8, 2022. Methods We conducted a search of databases, including PubMed, Embase, Cochrane, and Web of Science, to identify relevant randomized controlled trials (RCTs) assessing respiratory allergy-specific immunotherapy. We employed the Consolidated Standards of Reporting Trials (CONSORT) Statement to select RCTs that adhered to rigorous reporting standards. Specifically, we focused on double-blind placebo-controlled (DBPC) trials and open studies involving both adults and children, considering factors such as dosage, inclusion criteria, allergens, and primary outcome measurements. Results A total of 25 meta-analyses were included in this study. Among them, 14 evaluated sublingual-specific allergen immunotherapy (SLIT), 4 assessed subcutaneous allergen immunotherapy (SCIT), 4 explored both sublingual and subcutaneous immunotherapy, and 3 investigated intralymphatic immunotherapy. The outcomes of these meta-analyses indicated a reduction in medication scores in 20 cases and a decrease in symptom scores in 23 cases. Additionally, six studies reported on changes in IgE levels, seven studies focused on IgG4, four studies examined FEV1 (forced expiratory volume in 1 s), and eight studies reported on symptom and medication scores. Furthermore, 11 studies reported on differences in adverse reactions. Conclusion The results of our meta-analysis suggest that specific immunotherapy, while associated with some adverse effects, effectively reduces the symptoms of asthma and rhinitis. Therefore, we recommend its use in the treatment of respiratory allergies.

Effectiveness of Vitamin D and Alpha-Lipoic Acid in COVID-19 Infection: A Literature Review.

Over three years since the World Health Organization (WHO) declared COVID-19 a pandemic, it is still a global burden. Vaccines against COVID-19, caused by SARS-CoV-2, are available and effective for preventing disease. However, their protective effects are not 100%. Currently, the U.S. Food and Drug Administration (FDA) has only approved a limited number of inpatient treatments for COVID-19, such as remdesivir, baricitinib, and tocilizumab. These medications have indications and contraindications applicable to a select patient population. Finding additional effective therapies that are widely available with limited risk could be vital in optimizing treatment strategies for this viral illness. Some vitamins and supplements have been identified as potential options for managing COVID-19. Vitamin D (VD) deficiency has been associated with respiratory tract infections. Moreover, alpha-lipoic acid (ALA) is a powerful antioxidant and helps reduce inflammatory responses in many pathologic conditions. This review aims to analyze the current evidence regarding the effectiveness of VD and alpha-lipoic acid in COVID-19 infection in both outpatient and hospitalized patients. Relevant randomized controlled trials (RCTs) were identified via the PubMed database from January 1, 2021, to December 31, 2023. Inclusion criteria were as follows: the study design was a randomized controlled trial (RCT), the usage of a constant dose during the intervention period without any additional boluses, and a research ethics committee approved it. Exclusion criteria included a lack of an outcome or apparent intervention, additional boluses, or a single-dose regimen in all the interventional groups. There were 11 studies with a total sample size of 35,717 patients that met the criteria for this review. A total of 10 RCTs examined the efficacy of VD, and one RCT that reviewed the efficacy of ALA was identified. All of the articles investigated the use of VD or ALA during the treatment of COVID-19. The endpoints of each study varied, including length of stay in hospital, viral load, SARS-CoV-2 infection rate, mechanical ventilation, inflammatory markers, clinical symptoms, Sequential Organ Failure Assessment (SOFA) score, and mortality. In 8/10 VD supplementation trials, significant differences were identified between the interventional and placebo groups in the aforementioned parameters. In 2/10 VD supplementation trials, no significant differences were identified. The ALA supplementation RCT found no differences between the interventional and placebo groups in the SOFA score and 30-day all-cause mortality rate. The current literature suggests that VD can potentially reduce the SARS-CoV-2 infection rate, oxygen requirements, inflammatory markers, clinical symptoms, and mortality. Regarding ALA, although there was a suggestion of benefit, it was not statistically significant. Common limitations among the different studies included relatively small sample sizes, different geographical patient locations among studies, and differences in dosages. Trials investigating the effects of higher doses of VD supplementation on SARS-CoV-2 infection should be conducted. More research is needed to define best practices and optimal dosing protocols for the use of VD in COVID-19.

Efficacy of rTMS combined with cognitive training in TBI with cognition disorder: a systematic review and meta-analysis.

Post-traumatic brain injury cognitive disorder(PTBICD) is one of the common symptoms of TBI survivors, severely limiting their life and rehabilitation progress. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate cognition in a non-invasive manner while there are inconsistencies in previous studies. A comprehensive systematic review of rTMS treatment in patients with PTBICD is warranted. To evaluate the efficacy and safety of rTMS + cognitive training(CT) in enhancing cognitive function among PTBICD patients. A comprehensive search was conducted in PubMed, EMBASE, Cochrane Library, WOS, CNKI, Wan Fang, VIP and CBM, to identify relevant randomized controlled trials(RCTs) published before December 20, 2023. The primary outcomes measured changes in global cognitive scales, while the secondary outcomes focused on improvements in attention, memory, event-related potentials, and activities of daily living. Meta-analysis of data was carried out using Stata 14.0. Fourteen studies including 820 PTBICD patients were included. The results showed that rTMS + CT significantly improved MoCA[WMD = 3.47, 95%CI (2.56, 4.38)], MMSE[WMD = 3.79, 95%CI (2.23, 5.35)], RBMT[WMD = 1.53, 95%CI (0.19, 2.87)], LOTCA[WMD = 5.68, 95%CI (3.11, 8.24)], and promoted MBI[WMD = 7.41, 95%CI (5.90, 8.92)] as well as reduced correlated potential P300 latency[WMD = -20.77, 95%CI (-38.08, -3.45)] and amplitude[WMD = 0.81, 95%CI (0.57, 1.06)] in PTBICD compared to sham rTMS or CT, while adverse reaction ratio was higher than that of control group [RR = 1.67, 95%CI (1.00, 2.77)]. The results demonstrated that rTMS + CT can improve the cognitive function, mental state and daily activity ability of PTBICD patients. Systematic Review Registration: [PROSPERO], identifier [No. CRD42024520596].

The efficacy and safety of perioperative glucocorticoid for total knee arthroplasty: a systematic review and meta-analysis

BackgroundAn increasing number of individuals undergo total knee arthroplasty (TKA), which can result in pain, limited motor function and adverse complications such as infection, nausea and vomiting. Glucocorticoids have been shown anti-inflammatory and antiemetic effects, but can also elevate blood glucose levels and increase the risk of wound infection. Thus, it is essential to investigate the efficacy and safety of glucocorticoid usage in TKA.MethodA comprehensive systematic search of PubMed, Medline, EMBASE, Cochrane databases, to identify relevant randomized controlled trials (RCTs) of glucocorticoid application in TKA. The primary outcomes assessed were the postoperative pain assessment. Secondary outcomes included the range of motion in knee joint, levels of inflammatory cytokines, adverse complications, and the length of hospital stay.ResultsThirty-six randomized controlled trials were included in the final analysis. The glucocorticoid group exhibited significant reduction in the resting VAS scores on postoperative days 1, 2 (POD1, 2)and postoperative 3 months (POM3), as well as decreased morphine consumption on POD1 and increased range of motion (ROM) in knee joint on POD1, 3. Additionally, the glucocorticoid group exhibited decreased levels of postoperative inflammatory cytokines and the incidence of PONV along with a shorter length of hospital stay. The blood glucose concentration was significantly increased in the glucocorticoid group on POD1 compared with the control group. While the blood glucose on POD2 and occurrence of postoperative adverse complications were similar between two groups including wound infection and venous thrombosis. The periarticular injection analgesia (PIA) group demonstrated lower VAS scores on POD2 comparing to the systemic administration (SA) group according to two studies. However, there was no significant difference of the resting VAS on POD1 and POD2 between PIA and SA group across all studies.ConclusionPerioperative glucocorticoids treatment in TKA significantly reduced short-term pain score and opioid-use which was probably not patient relevant. The application of glucocorticoids in TKA implied a beneficial trend in analgesic, anti-inflammatory, and antiemetic effects, as well as improved range of motion and shortened hospital stay. While it will not increase the risk of continued high glucose, postoperative wound infection and venous thrombosis.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. PROSPERO CRD42023391562.

Effects of intermittent overload doses of oral vitamin D3 on serum 25(OH)D concentrations and the incidence rates of fractures, falls, and mortality in elderly individuals: A systematic review and meta-analysis.

Vitamin D is commonly used to prevent and treat osteoporosis, with studies indicating its potential to reduce fractures, falls, and mortality. However, meta-analyses present inconsistent findings regarding its efficacy, particularly reflecting significant variability in data and outcomes related to various dosing regimens. In this meta-analysis, we assessed the impact of high-dose intermittent oral administration of vitamin D3 on serum 25(OH)D levels, fractures, falls, and mortality among elderly individuals. We included 14 randomized controlled trials (RCTs) and employed Review Manager 5.4 for statistical analysis. Our findings indicate that intermittent monthly administration of vitamin D3 (over 800 IU per day) significantly raised serum 25(OH)D levels at all timepoints after six months, maintaining levels above 75 nmol/L throughout the year. This regimen showed no increase in all-cause mortality, with a risk ratio (95% CI) of 0.95 (0.87-1.04). Likewise, it did not significantly reduce the risks of falls and fractures, with risk ratios of 1.02 (0.98-1.05) and 0.95 (0.87-1.04) respectively. Although one-year intermittent administration significantly increased the concentration of 25(OH)D in serum, further research is needed to determine if this method would increase the incidence of falls. Therefore, it is not recommended at this stage due to the lack of demonstrated safety in additional relevant RCTs. This study had been registered on PROSPERO (CRD42022363229).

The Effectiveness of Virtual Reality on Anxiety and Pain Management in Patients Undergoing Cardiac Procedures: A Systematic Review and Meta-Analysis.

Cardiac procedure-related anxiety and pain can adversely affect outcomes and lead to patient dissatisfaction. Virtual reality (VR) offers a promising alternative to traditional therapies for improving patient experience. Our objective is to synthesize evidence and assess the effectiveness of VR in reducing cardiac procedure-related anxiety and pain compared to standard of care. We conducted a comprehensive search across various online databases, including MEDLINE, EMBASE, CINAHL, Web of Sciences, and COCHRANE, to identify relevant randomized controlled trials (RCTs) focusing on VR, cardiac procedures, anxiety, and pain. We utilized a random-effect model to generate effect estimates reported as standardized mean differences (SMD) with a 95% confidence interval. Our review comprised 10 studies with a total of 621 participants (intervention arm: 301, control arm: 320). Overall, among the seven studies evaluating anxiety outcomes, no significant difference in anxiety reduction was observed between the intervention and control groups (standardized mean difference (SMD) -0.62, 95% CI -1.61, 0.37, p=0.22). However, studies using the same anxiety assessment tool demonstrated a significant improvement in the VR arm (SMD -1.01, 95% CI -1.98, -0.04, p=0.04). Conversely, the narrative synthesis of four studies examining pain revealed mixed results. Our findings suggest no significant difference in anxiety reduction between the VR and control groups. Future studies should employ standardized tools for assessing and reporting anxiety and pain to better understand the potential of VR in enhancing patient experience during cardiac procedures.

Comparison of safety and efficacy of different positions in percutaneous nephrolithotomy: a network Meta-analysis.

Various new positions for percutaneous nephrolithotomy (PCNL) were proposed to reduce the limitations of the traditional position. This study was aimed to evaluate the efficacy and safety of the different PCNL positions. PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) up to April 18, 2023. We collected five common surgical positions used for PCNL: oblique supine position (OSP), supine position (SP), flank position (FP), split-leg oblique supine/flank position (SLP), and prone position (PP). Paired and network meta-analysis were conducted to compare relevant outcomes, including complications, operative time, stone free rates, hospital stay and hemoglobin loss among these different positions. The study included 17 RCTs with a total of 1841 patients. The result demonstrated that SLP significantly outperformed in terms of decreasing operation time (FP vs SLP MD- MD-41.65; OSP vs SLP MD 28.97; PP vs SLP MD 34.94), hospital stay, and hemoglobin loss. Ranking probabilities showed SLP had highest stone-free rate. Prone position was more likely to occur complications than others. Based on SMAA model, the benefit-risk analysis suggested the SLP was the optimal position in PCNL. For PCNL, the split-leg, flank, supine, and oblique supine positions are as secure as the prone position. Further RCTs are necessary to confirm the outstanding safety and efficacy of split-leg position. Besides, the position should be selected regard for the patient's demands, the surgeon's preference and learning curve.

Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). This systematic review was undertaken to compare these approaches in children. We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

Association between testosterone replacement therapy and cardiovascular outcomes: A meta-analysis of 30 randomized controlled trials.

The Cardiovascular safety of testosterone replacement therapy (TRT) among men with hypogonadism is not well established to date. Hence, we sought to evaluate the cardiovascular disease (CVD) outcomes among patients receiving testosterone therapy by using all recently published randomized controlled trials. We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until September 30th, 2023. A total of 30 randomized trials with 11,502 patients were included in the final analysis. The mean age was ranging from 61.61 to 61.82years. Pooled analysis of primary and secondary outcomes showed that the incidence of any CVD events (OR, 1.12 (95%CI: 0.77-1.62), P=0.55), stroke (OR, 1.01 (95%CI: 0.68-1.51), P=0.94), myocardial infarction (OR, 1.05 (95%CI: 0.76-1.45), P=0.77), all-cause mortality (OR, 0.94 (95%CI: 0.76-1.17), P=0.57), and CVD mortality (OR, 0.87 (95%CI: 0.65-1.15), P=0.31) was comparable between TRT and placebo groups. Our analysis indicates that for patients with hypogonadism, testosterone replacement therapy does not increase the CVD risk and all-cause mortality.

Impact of nutritional support routes on mortality in acute pancreatitis: A network meta-analysis of randomized controlled trials.

Nutritional administration in acute pancreatitis (AP) management has sparked widespread discussion, yet contradictory mortality results across meta-analyses necessitate clarification. The optimal nutritional route in AP remains uncertain. Therefore, this study aimed to compare mortality among nutritional administration routes in patients with AP using consistency model. This study searched four major databases for relevant randomized controlled trials (RCTs). Two authors independently extracted and checked data and quality. Network meta-analysis was conducted for estimating risk ratios (RRs) with 95% confidence interval (CI) based on random-effects model. Subgroup analyses accounted for AP severity and nutrition support initiation. A meticulous search yielded 1185 references, with 30 records meeting inclusion criteria from 27 RCTs (n=1594). Pooled analyses showed the mortality risk reduction associated with nasogastric (NG) (RR=0.34; 95%CI: 0.16-0.73) and nasojejunal (NJ) feeding (RR=0.46; 95%CI: 0.25-0.84) in comparison to nil per os. Similarly, NG (RR=0.45; 95%CI: 0.24-0.83) and NJ (RR=0.60; 95%CI: 0.40-0.90) feeding also showed lower mortality risk than total parenteral nutrition. Subgroup analyses, stratified by severity, supported these findings. Notably, the timing of nutritional support initiation emerged as a significant factor, with NJ feeding demonstrating notable mortality reduction within 24 and 48h, particularly in severe cases. For severe AP, both NG and NJ feeding appear optimal, with variations in initiation timings. NG feeding does not appear to merit recommendation within the initial 24h, whereas NJ feeding is advisable within the corresponding timeframe following admission. These findings offer valuable insights for optimizing nutritional interventions in AP.

Efficacy, Safety, and Cost-effectiveness of Bezlotoxumab in Preventing Recurrent Clostridioides difficile Infection : Systematic Review and Meta-analysis.

Clostridioides difficile infection (CDI) remains a global health challenge. Bezlotoxumab (BEZ) is a monoclonal antibody against C. difficile toxin B. Two randomized controlled trials (RCTs), MODIFY I and II, confirmed BEZ efficacy in preventing recurrent Clostridioides difficile infection (rCDI). However, there are safety concerns about its use in patients with a history of congestive heart failure. Observational studies have since been conducted, and it is important to explore the consistency of BEZ efficacy, cost-effectiveness, and its safety utilizing these real-world data. We performed a systematic review and meta-analysis to pool the rate of rCDI in patients receiving BEZ and explore its efficacy and safety in preventing rCDI compared with control. We searched PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through April 2023 for relevant RCTs or observational studies assessing BEZ in preventing rCDI. Single-arm studies describing experience with BEZ in preventing rCDI were also included for proportion meta-analysis. A proportion meta-analysis with a random-effects model was used to pool the rCDI rate with its corresponding 95% CI. In a meta-analysis of efficacy, we generated the relative risk (RR) to compare BEZ versus control in preventing rCDI. Thirteen studies including 2 RCTs and 11 observational studies totaling 2337 patients, of which 1472 received BEZ, were included in the analysis. Of the constituent studies, 5 (1734 patients) compared BEZ versus standard-of-care (SOC). Pooled rate of rCDI in patients receiving BEZ was 15.8% (95% CI: 14%-17.8%), and was 28.9% (95% CI: 24%-34.4%) in the SOC. BEZ significantly reduced rCDI risk compared with SOC [RR=0.57 (95% CI: 0.45-0.72, I2 =16%)]. There was no difference in the overall mortality or heart failure risk. Of the 9 included cost-effectiveness analyses, 8 demonstrated BEZ+SOC cost-effectiveness compared with SOC alone. Our meta-analysis comprising real-world data revealed lower rCDI in patients receiving BEZ and supported its efficacy and safety when added to SOC therapy. The results were consistent across various subgroups. Available cost-effectiveness analyses mostly support BEZ+SOC cost-effectiveness compared with SOC alone.