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Translational Cancer Research May 2024Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Combined anlotinib and immune checkpoint inhibitors (ICIs) therapy may have synergistic...
Efficacy and safety of anlotinib in combination with immune checkpoint inhibitors or not as advanced non-small cell lung cancer treatment: a systematic review and network meta-analysis.
BACKGROUND
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Combined anlotinib and immune checkpoint inhibitors (ICIs) therapy may have synergistic antitumor effects in NSCLC. This study aimed to comparing the efficacy and safety of anlotinib and ICIs treatment, monotherapy and combination in NSCLC.
METHODS
We performed a systematic review and network meta-analysis of 14 studies involving 4,308 NSCLC patients across four regimens: anlotinib, ICIs, anlotinib plus ICIs, and placebo. Efficacy outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety outcomes included treatment-related adverse events (TRAEs), TRAE grade three or higher (TRAE ≥3). Analyses were performed in RevMan 5.3 and R 3.5.1 (gemtc package). P<0.05 or effect estimate with 95% confidence interval (CI) that did not include 1 indicated statistical significance.
RESULTS
Fourteen publications involving 4,308 patients across four treatment regimens (anlotinib, ICIs, anlotinib plus ICIs, placebo) were included. For PFS, network meta-analysis showed all three interventions significantly improved PFS versus placebo. Anlotinib plus ICIs demonstrated the greatest PFS improvement [hazard ratio (HR) =0.24; 95% CI: 0.14, 0.36], followed by anlotinib (HR =0.37; 95% CI: 0.23, 0.58), and ICIs (HR =0.43; 95% CI: 0.27, 0.67). For OS, compared to placebo, anlotinib plus ICIs showed the greatest OS improvement (HR =0.52; 95% CI: 0.33, 0.74), followed by anlotinib (HR =0.66; 95% CI: 0.47, 0.95), and ICIs (HR =0.72; 95% CI: 0.54, 0.97). For ORR, anlotinib plus ICIs demonstrated the greatest improvement versus placebo [odds ratio (OR) =5.29; 95% CI: 3.32, 8.58], followed by anlotinib (OR =4.38; 95% CI: 2.42, 8.19), and ICIs (OR =2.17; 95% CI: 1.65, 2.89). For DCR, anlotinib plus ICIs showed the greatest improvement versus placebo (OR =13.32; 95% CI: 4.99, 45.09), followed by anlotinib (OR =5.56; 95% CI: 2.17, 14.38), and ICIs (OR =3.46; 95% CI: 1.29, 10.85). Compared to placebo, anlotinib was associated with the highest risk of TRAEs (OR =3.67, 95% CI: 1.12, 15.77), followed by ICIs (OR =1.83; 95% CI: 1.26, 2.69). Due to lack of data on anlotinib plus ICIs, no comparison was conducted. For grade ≥3 TRAEs, compared to placebo, anlotinib increased the risk (OR =3.67; 95% CI: 1.12, 15.77), while anlotinib plus ICIs (OR =2.45; 95% CI: 0.51, 11.6) and ICIs (OR =1.29; 95% CI: 0.33, 4.38) did not increase the risk.
CONCLUSIONS
Anlotinib combined with ICIs demonstrates improved efficacy over monotherapy for NSCLC treatment, without increased adverse events.
PubMed: 38881944
DOI: 10.21037/tcr-23-1483 -
Complementary Therapies in Medicine Jun 2024Obesity is associated with many chronic non-communicable diseases, including hypertension, diabetes, cardiovascular and cerebrovascular diseases, cancer, gallbladder...
INTRODUCTION
Obesity is associated with many chronic non-communicable diseases, including hypertension, diabetes, cardiovascular and cerebrovascular diseases, cancer, gallbladder disease, bone and joint disorders, skin diseases, fatty liver disease, etc. (Wharton et al., 2020) The recent report revealed that overweight and obesity were prevalent in 60 % of the adult population. Several studies have been published to determine the effect of Hibiscus sabdariffa Linn. on obesity treatment, but the findings are still inconclusive. The purpose of this study was to determine the efficacy and safety of H. sabdariffa Linn in the treatment of obesity.
METHODS
We searched PubMed, EMBASE, and CENTRAL from inception to February 2024. Randomized controlled trials (RCTs) were included if they explored the effect of H. sabdariffa on one of the following outcomes: body weight, body mass index (BMI), waist circumference, and waist-to-hip ratio. A random-effects model was used to meta-analyze the data. I was used to quantify statistical heterogeneity among the included RCTs. PROSPERO registered protocol: CRD42023408880.
RESULTS
A total of six RCTs with 339 participants were included. Four trials used H. sabdariffa extract in capsules as the intervention of interest compared to placebo, while the other two trials used H. sabdariffa tea compared to black or green tea. Our meta-analyses showed that the mean difference in weight reduction between H. sabdariffa and control was - 0.27 kg (95 % confidence interval (CI); - 1.98 to 1.42, I = 0.0 %). The mean differences for BMI and waist circumference reduction were - 0.06 kg/m (95 % CI; - 0.58 to 0.47, I = 0.0 %) and - 0.20 centimeters (95 % CI; - 2.06 to 1.66, I = 0.00 %). No safety concerns were reported in the included studies.
CONCLUSION
Our study did not show a clinical benefit of H. sabdariffa extract in obesity treatment. However, further high-quality RCTs with a longer treatment duration and a standard dose are still warranted.
PubMed: 38878905
DOI: 10.1016/j.ctim.2024.103063 -
Diabetology & Metabolic Syndrome Jun 2024Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is...
BACKGROUND
Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is thought to be lifestyle modification. Pharmacological therapy, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), were not well addressed in the literature and were only evaluated in trials as secondary and exploratory outcomes with a limited sample size. Here, GLP-1RAs are evaluated as a comprehensive therapy approach for patients with prediabetes.
METHODS
A comprehensive search of Web of Science, SCOPUS, PubMed, and Cochrane was performed on May 5, 2023, to retrieve randomized controlled trials (RCTs) comparing the effect of GLP-1RAs to placebo and/or lifestyle modification on prediabetes reversion to normoglycemia, prevention of overt diabetes, glycemic control, anthropometric parameters, and lipid profiles. Review Manager (RevMan) version 5.4 was used. The quality of RCTs was assessed using the revised version of the Cochrane Risk of Bias Tool. GRADE was performed to evaluate the certainty of evidence.
RESULTS
Twelve trials involving 2903 patients in the GLP-1RAs group and 1413 in the control group were included in the meta-analysis. Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43), P < 0.00001]. Significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL were observed in the GLP-1RAs arm (P < 0.05). However, higher incidences of gastrointestinal disorders were reported in the GLP-1RAs group (P < 0.05).
CONCLUSIONS
GLP-1RAs combined with lifestyle modification proved to be a more effective therapy for managing prediabetic patients than lifestyle modification alone, with a tolerable safety profile. Future guidelines should consider GLP-1RAs as an adjunct to lifestyle modification in the management of prediabetic patients to provide better management and improve treatment adherence.
PubMed: 38877565
DOI: 10.1186/s13098-024-01371-3 -
Complementary Therapies in Medicine Jun 2024The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials... (Review)
Review
OBJECTIVE
The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials (RCTs) to evaluate the effectiveness of GC on leptin levels.
METHODS
A thorough literature search was carried out using different online databases, including Scopus, Web of Science, PubMed, and Google Scholar, until May 25, 2024. Using random effects, weighted mean differences (WMDs) and corresponding 95 % confidence intervals (CIs) were computed. Standard procedures were followed to account for publication bias, study quality, and statistical heterogeneity.
RESULTS
In this meta-analysis, a total of eight eligible trials with 330 participants were ultimately included. Quality assessment showed that half of the included trials were considered to have fair quality, while the other half were deemed to have poor quality. Our analysis, with no indication of publication bias, showed a significantly decreased effect of GC on leptin compared with the placebo (WMD: -5.01 ng/ml; 95 % CI: -9.22 to -0.80, p = 0.02). However, significant heterogeneity was detected between studies (I =93.5 %, p < 0.001). The Hartung-Knapp adjustment did not affect our results. Subgroup analysis revealed that GC consumption represents the most effects in trials with sample size ≥ 50 (WMD: -3.63 ng/ml; 95 % CI [-5.51, -1.76], p < 0.001), and mean age of participants ≥ 30 years (WMD: -7.43 ng/ml; 95 % CI [-9.31, -5.56], p < 0.001).
CONCLUSIONS
The findings of the present study showed that leptin levels might decline following GC administration.
REGISTRATION NUMBER
CRD42023486370.
PubMed: 38876392
DOI: 10.1016/j.ctim.2024.103060 -
Frontiers in Cardiovascular Medicine 2024Several conflicting reviews have concluded that the use of loop diuretics is associated with poorer clinical and safety outcomes. Therefore, this study aimed to...
BACKGROUND
Several conflicting reviews have concluded that the use of loop diuretics is associated with poorer clinical and safety outcomes. Therefore, this study aimed to investigate the efficacy and safety of tolvaptan as an adjunct to conventional diuretic therapy in patients with acute heart failure (AHF).
METHODS
A comprehensive search was conducted on PubMed, Embase, ProQuest, EBSCO, and Cochrane Library until 24 May 2023 to identify randomized controlled trials that compared the effects of tolvaptan with conventional therapy and placebo in patients with AHF. The quality assessment of the included trials was conducted using the Cochrane risk of bias. A network meta-analysis (NMA) was conducted to examine the dosage effect of tolvaptan.
RESULT
A total of 17 studies with 18 reports, involving 10,039 patients, were selected. The tolvaptan add-on therapy significantly alleviated dyspnea [24 h: RR 1.16 (1.04, 1.29), 48 h: RR 1.18 (1.04, 1.33)], reduced body weight within 48 h [Asian group, MD -0.93 (-1.48, -0.38); non-Asian group, MD -2.76 (-2.88, -2.65)], reduced edema [RR 1.08 (1.02, 1.15)], increased serum sodium [non-Asian group, MD 3.40 (3.02, 3.78)], and resulted in a change in serum creatinine [MD -0.10 (-0.18, -0.01)]. No significant differences were observed in mortality and rehospitalization. The NMA suggested that an intermediate dosage (15 mg/day) might offer the best efficacy in reducing dyspnea within 24 h, reducing edema, increasing serum sodium, and lowering the incidence of worsening renal function (WRF).
CONCLUSION
In conclusion, the meta-analysis showed that tolvaptan contributed to the short-term alleviation of congestive symptoms, elevated sodium levels, and a lower incidence of WRF. However, no significant benefits were observed in long-term symptoms, rehospitalization rates, and mortality. An intermediate dosage of tolvaptan might be considered the optimal choice for various clinical outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42023420288).
PubMed: 38873266
DOI: 10.3389/fcvm.2024.1367442 -
Frontiers in Psychiatry 2024Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of...
Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.
BACKGROUND
Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear.
OBJECTIVE
To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators.
METHODS
We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression.
RESULTS
Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, 0.001), memory (g=0.31, 0.010), executive function (g=0.35, 0.001), working memory (g=0.26, 0.004), and processing speed (g=0.36, 0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency.
CONCLUSIONS
Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.
PubMed: 38863608
DOI: 10.3389/fpsyt.2024.1377257 -
Frontiers in Psychiatry 2024Anti-inflammatory agents have emerged as a potential new therapy for major depressive disorder (MDD). In this meta-analysis, our aim was to evaluate the antidepressant... (Review)
Review
BACKGROUND
Anti-inflammatory agents have emerged as a potential new therapy for major depressive disorder (MDD). In this meta-analysis, our aim was to evaluate the antidepressant effect of anti-inflammatory agents and compare their efficacy.
METHODS
We conducted a comprehensive search across multiple databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. The primary outcome measures of our meta-analysis were efficacy and acceptability, while the secondary outcome measures focused on remission rate and dropout rate due to adverse events. We used odds ratio (OR) and 95% confidence interval (95% CI) to present our results.
RESULTS
A total of 48 studies were included in our analysis. In terms of efficacy, anti-inflammatory agents demonstrated a significant antidepressant effect compared to placebo (OR = 2.04, 95% CI: 1.41-2.97, p = 0.0002). Subgroup analyses revealed that anti-inflammatory agents also exhibited significant antidepressant effects in the adjunctive therapy subgroup (OR = 2.17, 95% CI: 1.39-3.37, p = 0.0006) and in MDD patients without treatment-resistant depression subgroup (OR = 2.33, 95% CI: 1.53-3.54, p < 0.0001). Based on the surface under the cumulative ranking curve (SUCRA) value of network meta-analysis, nonsteroidal anti-inflammatory drugs (NSAIDs) (SUCRA value = 81.6) demonstrated the highest acceptability among the included anti-inflammatory agents.
CONCLUSION
In summary, our meta-analysis demonstrates that anti-inflammatory agents have significant antidepressant effects and are well-accepted. Furthermore, adjunctive therapy with anti-inflammatory agents proved effective in treating MDD. Among the evaluated anti-inflammatory agents, NSAIDs exhibited the highest acceptability, although its efficacy is comparable to placebo.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=422004), identifier CRD42023422004.
PubMed: 38863604
DOI: 10.3389/fpsyt.2024.1407529 -
Frontiers in Nutrition 2024Coaches and athletes are increasingly interested in understanding athletes' serum vitamin D levels, their impact on strength, physical performance, and athletic...
Effects of vitamin D3 supplementation on strength of lower and upper extremities in athletes: an updated systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Coaches and athletes are increasingly interested in understanding athletes' serum vitamin D levels, their impact on strength, physical performance, and athletic outcomes. Previous meta-analyses were reported with limited sample size and no significant overall effect was found. Hence, it is crucial to conduct a thorough and up-to-date systematic examination and meta-analysis to elucidate the potential advantages of supplementing with vitamin D3 in enhancing muscle strength for athletes.
METHODS
We performed a thorough investigation, spanning three databases (PubMed, EBSCO, and Cochrane Library), seeking randomized controlled trials (RCTs) in all languages. These trials delved into the influence of vitamin D3 supplementation on the changes of pre- and post-intervention muscle strength in healthy athletes. Our systematic examination and meta-analysis took into account serum 25(OH)D levels exceeding 30 ng/mL as a marker of adequacy.
RESULTS
Ten RCTs, comprising 354 athletes (185 in the vitamin D3 group and 169 in the placebo group), fulfilled the inclusion criteria. During the study, 36 athletes were lost to follow-up, leaving 318 athletes (166 in the vitamin D3 group and 152 in the placebo group) with documented complete results. In comparison with the placebo group, there is a significant increase between the changes of pre- and post-intervention serum 25(OH)D levels among athletes following a period of vitamin D3 supplementation (MD 14.76, 95% CI: 8.74 to 20.77, < 0.0001). Overall effect of four strength measurements including handgrip, one repetition maximum Bench Press (1-RM BP), vertical jump, and quadriceps contraction was not significantly improved (SMD 0.18, 95% CI: -0.02 to 0.37, = 0.08), but there was a significant increase in quadriceps contraction (SMD 0.57, 95% CI: 0.04 to 1.11, = 0.04).
CONCLUSION
This updated meta-analysis indicates the potential benefits of vitamin D supplementation for enhancing muscle strength in athletes when analyzing its quantitatively synthesized effects. With limited available studies for the quantitative synthesis, it cannot warrant significant overall enhancements in muscle strength when athletes attain adequate serum 25(OH)D levels through supplementation.
PubMed: 38860160
DOI: 10.3389/fnut.2024.1381301 -
Translational Psychiatry Jun 2024The treatment of suicidal ideation in patients with depression has been a major problem faced by psychiatric and emergency departments, and reasonable drug selection is... (Meta-Analysis)
Meta-Analysis
The treatment of suicidal ideation in patients with depression has been a major problem faced by psychiatric and emergency departments, and reasonable drug selection is particularly important. Ketamine has been shown to reduce suicidal ideation rapidly, but the strength of the effect is unclear and there is little evidence-based medical evidence to support this. We systematically searched all articles published on PubMed, Cochrane Library, Web of Science, CNKI and EMBASE. Stata 15 and R 4.1.3 were used for meta-analysis, and odds ratios were calculated in fixed effects or random effects models based on the heterogeneity test results. Our search resulted in 505 articles; we analyzed 14 studies, which included 1,380 participants. The 14 studies included 10 randomized controlled trial (RCT) studies and 4 single-arm studies. Our study suggests that, ketamine has a significant therapeutic effect on suicidal ideation throughout the treatment cycle. We performed network meta-analyses(NMA) and pairwise meta-analyses to compare the efficacy of ketamine in the reduction of suicidal ideation. There was a significant reduction in suicidal ideation within the first day after treatment (NMA ketamine day1 RR = 10.02, 95%CI = 4.24 to 23.68). In repeated treatment, the degree of recovery of suicidal ideation after the last dose was significantly greater than that after the first dose (RR = 0.56, 95%CI = 0.51 to 0.62). Recovery of suicidal ideation was also significantly better in the treatment end point than in the placebo group at the same time point (NMA ketamine day26 RR = 4.29, 95%CI = 1.41 to 13.08). This is the first network meta-analysis to demonstrate the role of ketamine in the alleviation of suicidal ideation. Our network meta-analysis also compared the effects of different drugs at different time points, which was not done in previous studies. This is of great reference significance for future drug research andrational drug use.
Topics: Ketamine; Humans; Suicidal Ideation; Antidepressive Agents; Depressive Disorder; Network Meta-Analysis; Treatment Outcome; Depression
PubMed: 38858391
DOI: 10.1038/s41398-024-02973-1 -
SAGE Open Medicine 2024Functional electrical stimulation is important for the rehabilitation of patients with chronic heart failure. This meta-analysis of randomized controlled trials compared... (Review)
Review
The effect of functional electrical stimulation of the legs on cardiopulmonary function and quality of life in patients with chronic heart failure: A systematic review and meta-analysis.
INTRODUCTION
Functional electrical stimulation is important for the rehabilitation of patients with chronic heart failure. This meta-analysis of randomized controlled trials compared the efficacy of functional electrical stimulation versus conventional exercise training or placebo in patients with chronic heart failure.
METHODS
Studies were searched through PubMed, Embase, and the Cochrane Library databases up to 1 November 2023. The outcomes were cardiopulmonary function index (6-minute walking distance), peak oxygen consumption, and Minnesota Heart Failure Life Questionnaire quality of life scores. A subgroup analysis was conducted according to the ejection fraction. The 95% confidence interval and mean difference represented the outcome of the effect size.
RESULTS
Seventeen studies involving 732 participants were included. Compared with the control, functional electrical stimulation significantly improved peak oxygen consumption (MD = 2.84 ml/kg/min, 95% Cl: 1.99-3.68 ml/kg/min), increased 6-minute walking distance (MD = 49.52 m, 95% Cl: 22.61-76.43 m), and improved the life quality scores (MD = -12.86, 95% Cl: -17.48 to -7.88). Compared with functional electrical stimulation, exercise training also improved peak oxygen consumption (MD = -0.94 ml/kg/min, 95% Cl: -1.36 to -0.52 ml/kg/min), and the quality of life (QoL, MD = 0.66, 95% Cl: 0.34-0.98, < 0.05, = 38%), but the result of 6-minute walking distance (MD = -6.97 m, 95% Cl: -18.32 to -4.38 m) did not show a difference. Further subgroup analysis showed that outcomes including the above, significantly improved under the functional electrical stimulationfor both HF patients with reduced ejection fraction and HF patients with preserved ejection fraction patients, but difference is insignificant of the results between groups of aerobic exercise and functional electrical stimulationacted on patients with HF patients with reduced ejection fraction.
CONCLUSIONS
Our study demonstrates that compared with placebo, functional electrical stimulation benefits the patients with chronic heart failure on cardiopulmonary function and quality of life. Furthermore, HF patients with reduced ejection fraction patients benefit more from functional electrical stimulation than HF patients with reduced ejection fraction patients. Therefore, functional electrical stimulation is a promising complementary therapy for patients with chronic heart failure.
PubMed: 38855004
DOI: 10.1177/20503121241245003