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BMJ Open Apr 2022This study aimed to determine the benefits of adjuvant therapy in patients with resected biliary tract cancer (BTC) and identify the optimal adjuvant treatment scheme. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to determine the benefits of adjuvant therapy in patients with resected biliary tract cancer (BTC) and identify the optimal adjuvant treatment scheme.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Studies comparing different adjuvant therapies in patients with BTC were searched in PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases from inception to December 2021. Additionally, the references were manually searched for the related literature.
MATERIALS AND METHODS
Eligible studies were identified, and data were extracted independently by two authors. A random-effects network meta-analysis was performed using R software. The pooled outcomes of overall survival (OS) and disease-free survival (DFS) were measured using the combined HRs with 95% CIs.
RESULTS
Nineteen eligible studies reporting three types of adjuvant therapies were included in our network meta-analysis. Adjuvant radiotherapy (ART, HR 0.62; 95% CI 0.42 to 0.93), adjuvant chemoradiotherapy (ACRT; HR 0.71; 95% CI 0.54 to 0.83) and adjuvant chemotherapy (ACT; HR 0.84; 95% CI 0.68 to 0.98) were more effective in prolonging OS than that of observation, with no significant difference between the three adjuvant therapies. Moreover, the improvement in DFS was also found in ACRT and ACT compared with that of observation (HR 0.60; 95% CI 0.45 to 0.75; HR 0.82; 95% CI 0.68 to 0.97, respectively). Furthermore, ACRT obtained a slightly better DFS benefit compared with that of ACT (HR 0.73; 95% CI 0.53 to 0.95).
CONCLUSIONS
Our primary results demonstrated that, compared with that of observation, ACRT and ACT after radical resection could provide better OS and DFS benefits in patients with BTC. However, ART only showed improvement in OS, but not in DFS. Due to the lack of head-to-head studies of ACT, ACRT and ART, the above results need to be further verified by prospective randomised controlled trials.
Topics: Biliary Tract Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Network Meta-Analysis; Prospective Studies; Treatment Outcome
PubMed: 35440445
DOI: 10.1136/bmjopen-2021-051421 -
Journal of Parkinson's Disease 2022Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy.
OBJECTIVE
We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa.
METHODS
We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups.
RESULTS
Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = -71.39, -28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments.
CONCLUSION
Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.
Topics: Antiparkinson Agents; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Dyskinesias; Humans; Levodopa; Oxadiazoles; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 35180134
DOI: 10.3233/JPD-213057 -
PloS One 2021Irritable bowel syndrome (IBS) affects children's quality of life and learning. The purpose of this research was to systematically evaluate the efficacy of probiotic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Irritable bowel syndrome (IBS) affects children's quality of life and learning. The purpose of this research was to systematically evaluate the efficacy of probiotic adjuvant therapy for IBS in children.
METHODS
The Web of Science, PubMed, Cochrane Library, EMBASE and Clinical Trials databases were electronically searched for randomized controlled trials (RCTs) published prior to January 2021 exploring the use of probiotic adjuvant therapy for IBS in children. Strict screening and quality evaluations of the eligible articles were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using RevMan 5.4.1 and STATA 16 software. Finally, the risk of bias in the included studies was assessed with the RCT bias risk assessment tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (5.1.0).
RESULTS
A total of nine RCTs were included. In children, probiotics significantly reduced the abdominal pain score (I2 = 95%, SMD = -1.15, 95% (-2.05, -0.24), P = 0.01) and Subject's Global Assessment of Relief (SGARC) score (I2 = 95%, MD = -3.84, 95% (-6.49, -1.20), P = 0.004), increased the rate of abdominal pain treatment success (I2 = 0%, RR = 3.44, 95% (1.73, 6.87), P = 0.0005) and abdominal pain relief (I2 = 40%, RR = 1.48, 95% (0.96, 2.28), P = 0.08), and reduced the frequency of abdominal pain (I2 = 2%, MD = -0.82, 95% (-1.57, -0.07), P = 0.03). However, we found that it might not be possible to relieve abdominal pain by increasing the daily intake of probiotics.
CONCLUSIONS
Probiotics are effective at treating abdominal pain caused by IBS in children, however, there was no significant correlation between abdominal pain and the amount of probiotics ingested. More attention should be given to IBS in children, and a standardized evaluation should be adopted.
Topics: Abdominal Pain; Adjuvants, Pharmaceutic; Child; Humans; Irritable Bowel Syndrome; Placebos; Probiotics; Publication Bias; Risk Assessment; Treatment Outcome
PubMed: 34358238
DOI: 10.1371/journal.pone.0255160 -
Cancers Nov 2021Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subset of lung carcinoma with poor overall survival. (Review)
Review
BACKGROUND
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subset of lung carcinoma with poor overall survival.
METHODS
A systematic review following a meta-analysis of studies was performed to identify the effect of different selections of chemotherapy in LCNEC. Articles providing overall survival data for adjuvant chemotherapy or palliative chemotherapy for LCNEC were eligible. The odds ratio (OR) of mortality at one or two years after chemotherapy was evaluated.
RESULTS
A total of 16 reports were finally included in the quantitative synthesis, involving a total of 5916 LCNEC patients. Adjuvant chemotherapy was administered to 1303 patients, and palliative chemotherapy was administered to 313 patients using either a small cell lung cancer (SCLC) or a non-small cell lung cancer (NSCLC) regimen. The OR for adjuvant chemotherapy was 0.73 (95% confidence interval (CI): 0.59 to 0.89, = 0.002). The SCLC regimen showed an OR of 0.52 (95% CI: 0.11 to 2.38, = 0.40) after one year, and 0.32 (95% CI: 0.11 to 0.89, = 0.03) after two years, compared with the NSCLC regimen.
CONCLUSIONS
Adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma improved the outcome after surgery. The SCLC regimen showed better survival than the NSCLC regimen as palliative chemotherapy.
PubMed: 34885057
DOI: 10.3390/cancers13235948 -
Urologic Oncology Nov 2021Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies... (Meta-Analysis)
Meta-Analysis
PURPOSE
Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC.
MATERIALS AND METHODS
The MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade.
RESULTS
Five trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81-0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83-1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10-6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22-12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity.
CONCLUSIONS
The findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.
Topics: Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Kidney Neoplasms; Male; Protein Kinase Inhibitors
PubMed: 34400065
DOI: 10.1016/j.urolonc.2021.07.022 -
Evidence-based Complementary and... 2021There was limited evidence of treatments aiming at aged coronary artery disease (CAD) patients. Yanyu decoction (YD) has been used as adjuvant therapy in aged patients... (Review)
Review
BACKGROUND
There was limited evidence of treatments aiming at aged coronary artery disease (CAD) patients. Yanyu decoction (YD) has been used as adjuvant therapy in aged patients with stable CAD and might be a new treatment worthy of recommendation for CAD patients. This study was to evaluate the combined effects of YD plus conventional pharmaceutical treatment (CPT) on senile patients with stable CAD.
METHODS
This review was designed according to the PRISMA (Preferred Reported Items for Systematic Reviews and Meta-Analysis) recommendations. A literature search was conducted in seven electronic databases from their inception until August 2020. Primary outcomes of interest were adverse cardiovascular events, including cardiac mortality, acute myocardial infarction (AMI), and unstable angina (UA). The secondary outcomes were blood lipids and hemorheology. Studies were pooled to calculate the risk ratio or weighted mean difference and corresponding 95% confidence interval.
RESULTS
Five studies recruiting 848 aged patients with stable CAD were included. Patients receiving YD as an adjuvant have fewer adverse cardiovascular events, including cardiac mortality, AMI, and UA. Besides, YD plus CPT has a better effect on reducing triglycerides, low-density lipoprotein cholesterol, and improving high-density lipoprotein cholesterol. Moreover, significant effects of YD plus CPT for reducing blood viscosity, plasma viscosity, and platelet aggregation rate were found compared with CPT alone.
CONCLUSION
YD plus CPT showed better efficacy than CPT on reducing adverse cardiovascular events and improving hemorheology and blood lipids for aged patients with stable CAD. Our findings may suggest YD as an adjuvant natural-based treatment for CAD. However, more rigorous and larger trials are essential to validate our results, and further consideration of CAD studies specific to aged patients is needed.
PubMed: 33959186
DOI: 10.1155/2021/6615035 -
Evidence-based Complementary and... 2022Yunnan Baiyao (YNBY) is a traditional Chinese medicine used to treat bleeding. We evaluated the efficacy of YNBY plus conventional pharmaceutical treatment (CPT) versus... (Review)
Review
BACKGROUND
Yunnan Baiyao (YNBY) is a traditional Chinese medicine used to treat bleeding. We evaluated the efficacy of YNBY plus conventional pharmaceutical treatment (CPT) versus CPT alone in patients with hemoptysis.
METHODS
A total of eight electronic databases were searched. The outcomes in the included studies were effective rate, hemoptysis volume, duration of hemoptysis and hospitalization, number of cases requiring endotracheal intubation, and adverse events (AEs). The studies were used to calculate risk ratios (RRs) or mean differences (MDs) with corresponding 95% confidence intervals. Risk of bias for included trials was assessed using the Cochrane risk of bias tool.
RESULTS
Thirteen RCTs were analyzed consisting of a total of 1379 patients. Treatment with YNBY + CPT had a greater effective rate than CPT alone (RR: 1.18; 95% CI: 1.13 to 1.23; < 0.001; = 0%), a lower hemoptysis volume (MD: -107.37; 95% CI: -121.69 to -93.06; < 0.001; = 0%), a shorter duration of hemoptysis (MD: -2.70; 95% CI: -2.96 to 2.43; < 0.001; = 0%) and hospitalization (MD: -2.38; 95% CI: -2.93 to -1.83; < 0.001; = 9%), and a reduction in the incidence of AEs (RR: 0.34; 95% CI: 0.23 to 0.51; < 0.001; = 0%). YNBY + CPT treatment provided no significant difference in reducing the number of cases requiring endotracheal intubation compared to CPT alone (RR: 0.49; 95% CI: 0.15 to 1.60; =0.24; = 0%).
CONCLUSION
YNBY plus CPT showed better efficacy than CPT for patients with hemoptysis. Our study provides medical evidence for the efficacy and safety of YNBY for hemoptysis.
PubMed: 35242198
DOI: 10.1155/2022/4931284 -
Children (Basel, Switzerland) Oct 2020Children and adolescents with severe burns require medical and nursing interventions, associated with pain. As immersive virtual reality (VR) gained prominence as... (Review)
Review
Children and adolescents with severe burns require medical and nursing interventions, associated with pain. As immersive virtual reality (VR) gained prominence as non-pharmacological adjuvant analgesia, we conducted a systematic review and meta-analysis on the efficacy of full immersive VR on pain experienced during dressing changes in hospitalized children and adolescents with severe burns. This exercise included quality and risk of bias assessment. The systematic review resulted in eight studies and 142 patients. Due to missing data, four studies were excluded from the meta-analysis. Fixed effects meta-analysis of the four included studies (n = 104) revealed a large effect size (ES) (Standardized Mean Difference = 0.94; 95% Confidence Interval = 0.62, 1.27; Z = 5.70; < 0.00001) for adjuvant full immersive VR compared to standard care (SC). In conclusion, adjuvant full immersive VR significantly reduces pain experienced during dressing changes in children and adolescents with burns. We therefore recommend implementing full immersive VR as an adjuvant in this specific setting and population. However, this requires further research into the hygienic use of VR appliances in health institutions. Furthermore, due to the high cost of the hardware, a cost-benefit analysis is required. Finally, research should also verify the long term physical and psychological benefits of VR.
PubMed: 33105581
DOI: 10.3390/children7110194 -
Critical Reviews in Oncology/hematology Jan 2022To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated... (Meta-Analysis)
Meta-Analysis Review
Chemotherapy is superior to checkpoint inhibitors after radical surgery for urothelial carcinoma: a systematic review and network meta-analysis of oncologic and toxicity outcomes.
OBJECTIVE
To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated with radical surgery for urothelial carcinoma (UC).
METHODS
We used the Bayesian approach in the network meta-analysis of different therapy regimens compared to observation or placebo.
RESULTS
Nine studies comprised of 2,444 patients met the eligibility criteria. In bladder UC, chemotherapy, atezolizumab, and nivolumab did not improve disease progression compared to observation/placebo. In upper tract UC (UTUC), chemotherapy was significantly associated with a lower likelihood of disease progression compared to observation/placebo, while atezolizumab and nivolumab were not. Based on the analysis of the treatment ranking, adjuvant chemotherapy appeared as the best treatment approach in both bladder UC and UTUC. The risk of adverse events with ICIs was comparable to that of observation/placebo.
CONCLUSION
Our analysis suggests a superior oncologic benefit to adjuvant chemotherapy over ICIs in patients treated with radical surgery for both bladder UC and UTUC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Carcinoma, Transitional Cell; Humans; Network Meta-Analysis; Urinary Bladder Neoplasms
PubMed: 34902554
DOI: 10.1016/j.critrevonc.2021.103570 -
JAMA Network Open Oct 2019The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial.
OBJECTIVES
To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach.
DATA SOURCES
PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019.
STUDY SELECTION
Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC.
DATA EXTRACTION AND SYNTHESIS
Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model.
MAIN OUTCOMES AND MEASURES
Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS).
RESULTS
A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC.
CONCLUSIONS AND RELEVANCE
These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.
Topics: Adult; Chemoradiotherapy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Randomized Controlled Trials as Topic
PubMed: 31626318
DOI: 10.1001/jamanetworkopen.2019.13619