Relevant Randomized Controlled Trials Research Articles

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.

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.

Effects of calcitonin on lumbar spinal stenosis.

Systematic review and meta-analysis. There is some controversy about the effects of calcitonin (CT) on lumbar spinal stenosis (LSS). This systematic review and meta-analysis is to assess the strength of the evidence supporting the use of CT in the treatment of patients with LSS. We performed an electronic search depicting randomized controlled trials (RCTs) through 4 databases from the date of database creation to January 2023. 3 different researchers conducted independent literature screening, data extractions, and quality assessments. The outcome measures included visual analogue scale (VAS), walking distance, and oswestry disability index (ODI). Meta-analysis and trial sequence analysis (TSA) were carried out using RevMan 5.4, Stata 16.0, and TSA 0.9. GRADE 3.6 was used to evaluate the evidence quality. We accepted 9 studies with 496 participants. The meta-analysis revealed that CT offered no significant improvement in VAS, walking distance, or ODI in patients with LSS. There is no evidence that CT has a benefit in patients with LSS, either alone or in combination with other treatments, or depending on the route of administration, according to the systematic review and meta-analysis of relevant RCTs.

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 one second), and eight studies reported on symptom and medication scores. Furthermore, eleven 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.

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.

Effectiveness of Nonpharmacological Measures on Improving Headache Score, Strength, Pain, and Quality of Life in Cervicogenic Headaches: A Systematic Review.

Cervicogenic headache (CGH) is a common condition affecting a significant portion of the population and is effectively managed through various interventions, including nonpharmacological approaches. Physical therapy plays a crucial role in CGH management, with numerous studies supporting its effectiveness. This systematic review aimed to evaluate the effectiveness of specific nonpharmacological physical therapy interventions for CGH. A comprehensive search was conducted across various databases (PubMed, Medline, PEDro, and Cochrane Library) for randomized controlled trials (RCTs) published between January 2017 and January 2023 investigating the effectiveness of specific nonpharmacological physical therapy interventions for CGH. We employed manual searches to capture potentially missed studies. Independent reviewers screened all studies based on predefined eligibility criteria. Extracted data included methodology, specific interventions, outcome measures (headache score, strength, pain, and quality of life (QOL)), and study conclusions. Eight RCTs were identified as meeting all inclusion criteria and were thus included in the data synthesis. The findings from these trials revealed a diverse range of nonpharmacological physical therapy interventions, including but not limited to manual therapy, exercise therapy, and multimodal approaches. Specifically, the interventions demonstrated significant improvements in headache scores, strength, pain levels, and overall QOL among individuals with CGH. These results underscore the multifaceted benefits of physical therapy in managing CGH and highlight its potential as a comprehensive treatment option. This review identified eight relevant RCTs investigating nonpharmacological interventions for CGH. Despite the promising findings, this review acknowledges several limitations, including the limited sample size and the heterogeneity of interventions across studies. These limitations emphasize the necessity for further research to elucidate optimal intervention strategies and refine treatment protocols. Nevertheless, the comprehensive analysis presented herein reinforces the pivotal role of physical therapy in not only alleviating pain but also enhancing function and improving the QOL for individuals suffering from CGH.

Quality reporting of randomized controlled trials on SGLT2 inhibitors for heart failure: a comprehensive assessment

Randomised controlled trials (RCTs) provide clinicians with the best evidence of the effectiveness of an intervention, and complete and transparent trial reports help to critically assess and use trial results. The objective of our study was to assess the quality of reporting in RCTs of sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for heart failure (HF) and identify factors associated with improved reporting quality. Two researchers conducted a comprehensive search in four databases (PubMed, Web of Science, EMBASE, and Cochrane). The quality of each report was assessed using a 25-point Overall Quality Score (OQS) based on the guidelines provided in the 2010 Consolidated Standards for Reporting of Trials (CONSORT) statement. We included a total of 58 relevant RCTs. The median OQS in the 2010 CONSORT statement was 15 (range 7.5–24). The missing items were primarily found in the 'Methods' and 'Results' sections of the 2010 CONSORT statement. Multivariate regression modeling revealed that a more recent publication year, high impact factor, and large sample size were significant predictors of OQS improvement. The findings suggest that the overall quality of reported RCTs of SGLT2 inhibitors in HF is unsatisfactory, which reduces their potential usefulness.

Use of electrical stimulation for accelerated orthodontics in humans: a systematic review and meta-analysis.

The main objective of this systematic review is to comprehensively evaluate all the relevant studies to evaluate the effectiveness of electrical stimulation to accelerate orthodontic tooth movement in human patients. Using a suitable search strategy, various databases like PubMed, CENTRAL, Scopus and Google Scholar were surveyed for relevant randomized controlled trials (RCTs); after which a hand search of related orthodontic journals was completed. The risk of bias of studies was checked using Cochrane's ROB-2 tool. The quality of evidence of the included studies was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Rate of orthodontic tooth movement was compared and thus efficiency of electrical stimulation to accelerate tooth movement was assessed. Meta-analysis was done on 2 studies out of the 4; rate of orthodontic tooth movement was compared at two time periods after start of treatment (3rd month and 5th month) with standardized mean difference (SMD) as summary estimate, with p < 0.05 denoting statistical significance. Publication bias was checked using a funnel plot. Via exploration of the online databases and hand searching,1080 studies were found after removing duplicates. After full text assessment, 13 studies in total were selected that used electrical stimulation, out of which 4 studies were included in the qualitative analysis as they met the inclusion criteria. The meta-analysis was done for 3rd month and 5th month with SMD as 0.69(-1.26-0.12) and 1.64(-3.44-0.16), respectively. The strength of evidence in the meta-analysis is moderate. There was no publication bias as shown by funnel plot. The studies included showed increased risk of selection and performance bias. Also due to the limited number of studies available, there was difficulty in reaching definitive conclusions. The meta-analysis showed a significant difference among the control and experimental group for the 3rd month. Even though a positive correlation is found between electrical stimulation and acceleration of orthodontic tooth movement, it is advised to conduct further studies, particularly with human participants, to establish a more conclusive outcome. This review has received no funding. The protocol for the study was registered in the Prospective Registration of Systematic Review (PROSPERO)(CRD42023495077).

Effects of ketogenic diet on weight loss parameters among obese or overweight patients with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trails.

To evaluate how effective a low carbohydrate ketogenic diet (KD) is for changing key physical measurements such as weight, waist circumference (WC), body mass index (BMI), and fat mass (FM) in women with polycystic ovary syndrome (PCOS) who were obese or overweight. Several online databases, including PubMed, Scopus, EMBASE, Cochrane Library, and Web of Science (WOS), were searched systematically to find relevant randomized controlled trials (RCTs) up until June 2023. The Q-test and I2 statistics were used to assess the level of heterogeneity among the included studies. The data were then combined using either a fixed or random effects model and presented as a weighted mean difference (WMD) along with a 95% confidence interval (CI). Of the 682 citations, 11 RCTs were included. The pooled results showed a significant decrease in the WMD of weight levels [WMD = -9.13 kg; 95% CI, -11.88, -6.39, P < 0.001; I2 = 87.23%] following KD. Moreover, KD significantly reduced BMI levels [WMD = -2.93 kg/m2; 95% CI, -3.65, -2.21, P < 0.001; I2 = 78.81%] compared to the controls. Patients with PCOS received KD demonstrated significant decrease in WC [WMD = -7.62 cm; 95% CI, -10.73, -4.50, P < 0.001; I2 = 89.17%] and FM [WMD = -5.32 kg; 95% CI, -7.29, -3.36, P < 0.001; I2 = 83.97%]. KD was associated with lower weight loss (WL) parameters, including weight, BMI, WC, and FM, in obese or overweight women with PCOS, highlighting the significance of physicians and nurses in taking care of the nutritional needs of overweight/obese patients with PCOS.

Cognitive approaches in the rehabilitation of upper limbs function in children with cerebral palsy: a systematic review and meta-analysis.

Cerebral palsy (CP) is the predominant cause of children disability. It is characterized by motor, sensory, and postural deficits due to a non-progressive injury to the developing central nervous system. In recent years, new rehabilitation techniques targeting the central representations of motor patterns have been introduced: the most used are action observation therapy (AOT), motor imagery (MI), and mirror therapy (MT). Aim of this study is to assess the effectiveness of these cognitive strategies on the recovery of upper limb motor functions in children with CP. This study was designed as a systematic review and meta-analysis, registered in PROSPERO (CRD42023403794). For the report and methodological definitions of this study, the recommendations of the PRISMA protocol and the Cochrane collaboration, were followed. A total of 3 electronic databases (PubMed, Scopus, and Web of Science) were searched for relevant Randomized Control Trials (RCT) using the combinations of terms "cerebral palsy" AND "action observation" OR "motor imagery" OR "mirror therapy" OR "cognitive therapy." A meta-analysis was carried out to compare cognitive and conventional approaches and combine direct and indirect effects. A random-effects meta-analysis model was used to derive pooled effect estimates. Out of 328 records, 12 RCTs were analyzed in this systematic review published from 2012 to 2022, and included 375 children, of whom 195 received cognitive therapies, and 180 underwent conventional rehabilitation. AOT was the most investigated (RCTs N.=7), and showed significant results in the recovery of upper limb motor functions, albeit the meta-analysis demonstrated a non-significant difference in Melbourne Unilateral Upper limb Scale (MUUL) (95% CI: -7.34, 12); in Assisting Hand Assessment (AHA) (95% CI: -4.84, 10.74), and in AbilHand-Kids Questionnaire (95% CI: -1.12, 1.45). Five RCTs investigated MT showing significant improvements in grip and dexterity; none used MI as intervention therapy. Cognitive therapies provided with encouraging results in the recovery of upper limb motor functions, although not a clinical effect in bimanual or unimanual performance; they could represent a valid therapeutic solution integrated to conventional rehabilitation in the treatment of upper limb motor impairment in children with CP.