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Gynecologic Oncology Apr 2021To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic oncology.
METHODS
A systematic literature search was performed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science for all peer-reviewed cohort studies and controlled trials on ERAS involving gynecologic oncology patients. Abstracts, commentaries, non-controlled studies, and studies without specific data on gynecologic oncology patients were excluded. Meta-analysis was performed on the primary endpoint of LOS. Subgroup analyses were performed based on risk of bias of the studies included, number of ERAS elements, and ERAS compliance. Secondary endpoints were readmission rate, complications, and cost.
RESULTS
A total of 31 studies (6703 patients) were included: 5 randomized controlled trials, and 26 cohort studies. Meta-analysis of 27 studies (6345 patients) demonstrated a decrease in LOS of 1.6 days (95% confidence interval, CI 1.2-2.1) with ERAS implementation. Meta-analysis of 21 studies (4974 patients) demonstrated a 32% reduction in complications (OR 0.68, 95% CI 0.55-0.83) and a 20% reduction in readmission (OR 0.80, 95% CI 0.64-0.99) for ERAS patients. There was no difference in 30-day postoperative mortality (OR 0.61, 95% CI 0.23-1.6) for ERAS patients compared to controls. No difference in the odds of complications or reduction in LOS was observed based on number of included ERAS elements or reported compliance with ERAS interventions. The mean cost savings for ERAS patients was $2129 USD (95% CI $712 - $3544).
CONCLUSIONS
ERAS protocols decrease LOS, complications, and cost without increasing rates of readmission or mortality in gynecologic oncology surgery. This evidence supports implementation of ERAS as standard of care in gynecologic oncology.
Topics: Cytoreduction Surgical Procedures; Enhanced Recovery After Surgery; Female; Genital Neoplasms, Female; Gynecologic Surgical Procedures; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33388155
DOI: 10.1016/j.ygyno.2020.12.035 -
Lancet (London, England) May 2020Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y inhibitor versus aspirin for secondary prevention. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y inhibitor versus aspirin for secondary prevention.
METHODS
In this systematic review and meta-analysis, all randomised trials comparing P2Y inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I index. This study is registered with PROSPERO (CRD42018115037).
FINDINGS
A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I=0%), and vascular death (OR 0·97 [0·86-1·09]; I=0%) did not differ between patients who received a P2Y inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I=3·9%) did not differ between patients who received a P2Y inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y inhibitor used.
INTERPRETATION
Compared with aspirin monotherapy, P2Y inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality.
FUNDING
Italian Ministry of Education.
Topics: Aged; Aspirin; Atherosclerosis; Cerebrovascular Disorders; Clopidogrel; Coronary Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine
PubMed: 32386592
DOI: 10.1016/S0140-6736(20)30315-9 -
EBioMedicine Apr 2023The cytokine interleukin-2 (IL-2) can stimulate both effector immune cells and regulatory T (Treg) cells. The ability of selectively engaging either of these effects has...
BACKGROUND
The cytokine interleukin-2 (IL-2) can stimulate both effector immune cells and regulatory T (Treg) cells. The ability of selectively engaging either of these effects has spurred interest in using IL-2 for immunotherapy of cancer and autoimmune diseases. Thus, numerous IL-2-based biologic agents with improved bias or delivery towards effector immune cells or Treg cells have been developed. This study systematically reviews clinical results of improved IL-2-based compounds.
METHODS
We searched the ClinicalTrials.gov database for registered trials using improved IL-2-based agents and different databases for available results of these studies.
FINDINGS
From 576 registered clinical trials we extracted 36 studies on different improved IL-2-based compounds. Adding another nine agents reported in recent literature reviews and based on our knowledge totalled in 45 compounds. A secondary search for registered clinical trials of each of these 45 compounds resulted in 141 clinical trials included in this review, with 41 trials reporting results.
INTERPRETATION
So far, none of the improved IL-2-based compounds has gained regulatory approval for the treatment of cancer or autoimmune diseases. NKTR-214 is the only compound completing phase 3 studies. The PIVOT IO-001 trial testing the combination of NKTR-214 plus Pembrolizumab compared to Pembrolizumab monotherapy in metastatic melanoma missed its primary endpoints. Also the PIVOT-09 study, combining NKTR-214 with Nivolumab compared to Sunitinib or Cabozantinib in advanced renal cell carcinoma, missed its primary endpoint. Trials in autoimmune diseases are currently in early stages, thus not allowing definite conclusions on efficacy.
FUNDING
This work was supported by public funding agencies.
Topics: Humans; Antineoplastic Agents; Interleukin-2; Carcinoma, Renal Cell; Kidney Neoplasms; Immunotherapy; Autoimmune Diseases
PubMed: 37004361
DOI: 10.1016/j.ebiom.2023.104539 -
Cardiovascular Diabetology Nov 2023Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia.
METHODS
PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867).
RESULTS
Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy.
CONCLUSIONS
The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Cholesterol; Myocardial Infarction; Gout; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38017541
DOI: 10.1186/s12933-023-02022-z -
PloS One 2023Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.
METHODS
We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.
CONCLUSIONS
As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.
Topics: Adult; Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Angiotensin Receptor Antagonists; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Kidney Failure, Chronic; Angiotensins; Diabetes Mellitus
PubMed: 37917640
DOI: 10.1371/journal.pone.0293183 -
Clinical Cancer Research : An Official... Aug 2022Because of the increased number of sequential treatments used for advanced hepatocellular carcinoma (HCC), there is a need for surrogate endpoints of overall survival... (Meta-Analysis)
Meta-Analysis
PURPOSE
Because of the increased number of sequential treatments used for advanced hepatocellular carcinoma (HCC), there is a need for surrogate endpoints of overall survival (OS). We analyze whether objective response (OR) is an independent predictor and surrogate endpoint of OS.
PATIENTS AND METHODS
A systematic review of randomized clinical trials (RCT) in advanced HCC published between 2010 and 2020 was conducted to explore OS surrogacy of OR by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). In parallel, RCTs exploring the impact of OR on OS in a time-dependent multivariate analysis were integrated in a meta-analysis.
RESULTS
Of 65 RCTs identified in advanced HCC, we analyzed 34 studies including 14,056 patients that reported OS and OR by either RECIST (n = 23), mRECIST (n = 5), or both (n = 6). When exploring surrogacy, the trial-level correlation between OR odds ratio and OS HR was R = 0.677 by mRECIST and R = 0.532 by RECIST. Meta-analysis of five RCTs assessing predictors of survival in multivariate analysis found that patients with OR by mRECIST presented a pooled HR for OS of 0.44 (95% confidence interval, 0.27-0.70; P < 0.001) compared with nonresponders. Responses to atezolizumab-bevacizumab had a greater impact on OS than tyrosine kinase inhibitor responses.
CONCLUSIONS
OR-mRECIST is an independent predictor of OS in patients with advanced HCC. Although correlation of OR-mRECIST and OS is better than with OR-RECIST, the level of surrogacy is modest. Thus, it can be used as endpoint in proof-of-concept phase II trials, but the data do not support its use as a primary endpoint of phase III investigations assessing systemic therapies.
Topics: Antineoplastic Agents; Biomarkers; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Randomized Controlled Trials as Topic; Response Evaluation Criteria in Solid Tumors; Survival Analysis
PubMed: 34907081
DOI: 10.1158/1078-0432.CCR-21-3135 -
Digestive Diseases and Sciences Jun 2023We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary...
BACKGROUND AND AIMS
We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
METHODS
Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs.
RESULTS
Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes.
CONCLUSIONS
There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.
Topics: Humans; Young Adult; Adult; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Pruritus; Fibric Acids; Quality of Life
PubMed: 36933112
DOI: 10.1007/s10620-023-07862-z -
BMJ Open Respiratory Research Feb 2024Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.
DESIGN
Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.
DATA SYNTHESIS
The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.
RESULTS
A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DL (95% CI 2.05 to 6.79, I=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.
CONCLUSIONS
There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.
PROSPERO REGISTRATION NUMBER
CRD42023423223.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Lung Diseases, Interstitial; Lung; Mycophenolic Acid; Enzyme Inhibitors; Observational Studies as Topic
PubMed: 38413120
DOI: 10.1136/bmjresp-2023-002163 -
Digestive and Liver Disease : Official... Oct 2023Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard results in heterogeneity in second-line treatment research and clinical practice.
AIMS
This study aimed to explore which UDCA treatment response endpoint serves as the most accurate predictive model of long-term outcome.
METHODS
A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding validations) were performed.
RESULTS
Sixteen individual UDCA treatment response endpoints and 96 external validations were found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores are currently most robustly validated in external populations. The results show that the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase and total bilirubin normalization has been suggested as a new therapeutic target.
CONCLUSIONS
The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation of second-line therapies (obeticholic acid and fibrates). However, in the wake of the recent findings, alkaline phosphatase and total bilirubin normalization should be the primary outcome in trial research in PBC.
Topics: Humans; Ursodeoxycholic Acid; Liver Cirrhosis, Biliary; Cholagogues and Choleretics; Alkaline Phosphatase; Treatment Outcome; Bilirubin; Cholangitis
PubMed: 36593158
DOI: 10.1016/j.dld.2022.12.010 -
European Journal of Vascular and... Dec 2023Currently, there is no consensus on the optimal management of Paget-Schroetter syndrome (PSS). The objective was to summarise the current evidence for management of PSS... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Currently, there is no consensus on the optimal management of Paget-Schroetter syndrome (PSS). The objective was to summarise the current evidence for management of PSS with explicit attention to the clinical outcomes of different management strategies.
DATA SOURCES
The Cochrane, PubMed, and Embase databases were searched for reports published between January 1990 and December 2021.
REVIEW METHODS
A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines. The primary endpoint was the proportion of symptom free patients at last follow up. Secondary outcomes were success of initial treatment, recurrence of thrombosis or persistent occlusion, and patency at last follow up. Meta-analyses of the primary endpoint were performed for non-comparative and comparative reports. The quality of evidence was assessed using the GRADE approach.
RESULTS
Sixty reports were included (2 653 patients), with overall moderate quality. The proportions of symptom free patients in non-comparative analysis were: anticoagulation (AC), 0.54; catheter directed thrombolysis (CDT) + AC, 0.71; AC + first rib resection (FRR), 0.80; and CDT + FRR, 0.96. Pooled analysis of comparative reports confirmed the superiority of CDT + FRR compared with AC (OR 13.89, 95% CI 1.08 - 179.04; p = .040, I 87%, very low certainty of evidence), AC + FRR (OR 2.29, 95% CI 1.21 - 4.35; p = .010, I 0%, very low certainty of evidence), and CDT + AC (OR 8.44, 95% CI 1.12 - 59.53; p = .030, I 63%, very low certainty of evidence). Secondary endpoints were in favour of CDT + FRR.
CONCLUSION
Non-operative management of PSS with AC alone results in persistent symptoms in 46% of patients, while 96% of patients managed with CDT + FFR were symptom free at end of follow up. Superiority of CDT + FRR compared with AC, CDT + AC, and AC + FRR was confirmed by meta-analysis. The overall quality of included reports was moderate, and the level of certainty was very low.
Topics: Humans; Upper Extremity Deep Vein Thrombosis; Thrombolytic Therapy; Treatment Outcome; Decompression, Surgical
PubMed: 37678659
DOI: 10.1016/j.ejvs.2023.08.065