Frequentist Network Research Articles

Sex-Based Outcomes of Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention: A Pairwise and Network Meta-Analysis.

Although dual antiplatelet therapy (DAPT) improves the outcomes of patients undergoing percutaneous coronary intervention (PCI), sex-specific differences in efficacy and safety of DAPT remain unresolved. We compared sex differences for DAPT outcomes and DAPT durations (1-3 months [short-term], 6months [mid-term], and >12months [extended] vs. 12months). We searched databases through 31 December 2023 for trials reporting DAPT after PCI. The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), net adverse clinical and cerebrovascular events (NACCE), and any bleeding. Extracted data were pooled in a frequentist network and pairwise, random-effects meta-analysis. Twenty-two trials (99,591 participants, 25.2% female) were included. Female sex was significantly associated with a higher 1-year MACCE risk (hazard ratio 1.14 [95% confidence interval 1.02-1.28]) and bleeding (1.13 [1.00-1.28]), but not NACCE (1.12 [0.96-1.31]). In sub-analyses, the association between female sex and MACCE was related to use of clopidogrel as the second antiplatelet agent(1.11 [1.03-1.20]), whereas higher bleeding events were related to newer P2Y12 inhibitors (P2Y12i) (1.58 [1.01-2.46]). For DAPT duration, short-term DAPT followed by P2Y12i monotherapy was non-inferior for MACCE in females and males (0.95 [95% CI 0.83-1.10; and 0.96 [0.80-1.16]) but tended to be superior in males for NACCE versus 12-month DAPT (0.96 [0.91-1.01]); mid-term DAPT tended to be associated with a lower bleeding risk in males (0.43 [0.17-1.09]). Female sex is associated with higher MACCE and bleeding when newer P2Y12i agents are used. Short-term DAPT followed by P2Y12i monotherapy is safe and effective in both sexes undergoing PCI. PROSPERO ID: CRD42021278663.

OP70 Treating Patients With Hormone-Sensitive Cancer On Endocrine Therapy With Denosumab (Prolia®): A Systematic Review And Network Meta-Analysis

IntroductionPatients receiving endocrine therapy for hormone-sensitive cancers, such as men with prostate cancer (MPC) on hormone ablation therapy (HAT) and women with breast cancer (WBC) on adjuvant aromatase inhibitor therapy (AAIT), have an increased risk of developing osteoporosis. The aim of this study was to compare the safety and effectiveness of denosumab (Prolia®) with selective estrogen receptor modulators (SERMs) (raloxifene and bazedoxifene), bisphosphonates (zoledronate, ibandronate, alendronate, and risedronate), and placebo for the treatment of osteoporosis in patients receiving endocrine therapy for hormone-sensitive cancer.MethodsSystematic literature searches were conducted in three biomedical databases (PubMed, the Cochrane Library, and Embase) to identify randomized controlled trials (RCTs). Only RCTs that investigated MPC on HAT or WBC on AAIT allocated to denosumab, SERMs, bisphosphonates, or placebo were included. RCTs were appraised using the Cochrane Risk of Bias 2.0 tool. Frequentist network and pairwise meta-analyses were performed on predetermined outcomes of vertebral or nonvertebral fractures, treatment-related adverse events (AEs), bone mineral density (BMD), mortality, withdrawal due to treatment-related AEs, and serious AEs.ResultsA total of 14 RCTs (15 publications, 6,463 participants) were included. Relative to placebo, denosumab was found to prevent vertebral fractures in cancer patients receiving endocrine therapy. Moreover, denosumab, alendronate, and zoledronate increased femoral neck (FN) and lumbar spine (LS) BMD in MPC on HAT, compared with placebo, whereas denosumab, risedronate, and ibandronate improved LS and total hip BMD in WBC on AAIT. Similarly, denosumab and risedronate increased trochanteric BMD in WBC on AAIT, compared with placebo. In WBC on AAIT, only denosumab increased FN BMD relative to placebo.ConclusionsDenosumab was more effective than placebo in preventing vertebral fractures and improving BMD at the LS and FN in MPC on HAT, and in preventing vertebral fractures and improving FN, trochanteric, total hip, and LS BMD in WBC on AAIT. From a policy perspective, the continued reimbursement of denosumab needs to be reviewed.

Network analysis to evaluate complexities in relationships among fermentation variables measured within continuous culture experiments.

The objective of this study was to leverage a frequentist (ELN) and Bayesian learning (BLN) network analyses to summarize quantitative associations among variables measured in 4 previously published dual-flow continuous culture fermentation experiments. Experiments were originally designed to evaluate effects of nitrate, defaunation, yeast, and/or physiological shifts associated with pH or solids passage rates on rumen conditions. Measurements from these experiments that were used as nodes within the networks included concentrations of individual volatile fatty acids, mM and nitrate, NO3-,%; outflows of non-ammonia nitrogen (NAN, g/d), bacterial N (BN, g/d), residual N (RN, g/d), and ammonia N (NH3-N, mg/dL); degradability of neutral detergent fiber (NDFd, %) and degradability of organic matter (OMd, %); dry matter intake (DMI, kg/d); urea in buffer (%); fluid passage rate (FF, L/d); total protozoa count (PZ, cells/mL); and methane production (CH4, mmol/d). A frequentist network (ELN) derived using a graphical LASSO (least absolute shrinkage and selection operator) technique with tuning parameters selected by Extended Bayesian Information Criteria (EBIC) and a BLN were constructed from these data. The illustrated associations in the ELN were unidirectional yet assisted in identifying prominent relationships within the rumen that were largely consistent with current understanding of fermentation mechanisms. Another advantage of the ELN approach was that it focused on understanding the role of individual nodes within the network. Such understanding may be critical in exploring candidates for biomarkers, indicator variables, model targets, or other measurement-focused explorations. As an example, acetate was highly central in the network suggesting it may be a strong candidate as a rumen biomarker. Alternatively, the major advantage of the BLN was its unique ability to imply causal directionality in relationships. Because the BLN identified directional, cascading relationships, this analytics approach was uniquely suited to exploring the edges within the network as a strategy to direct future work researching mechanisms of fermentation. For example, in the BLN acetate responded to treatment conditions such as the source of N used and the quantity of substrate provided, while acetate drove changes in the protozoal populations, non-NH3-N and residual N flows. In conclusion, the analyses exhibit complementary strengths in supporting inference on the connectedness and directionality of quantitative associations among fermentation variables that may be useful in driving future studies.

Comparative efficacy of different concentrations of chlorhexidine for prevention of ventilator‐associated pneumonia in intensive care units: A systematic review and network meta‐analysis

AbstractBackgroundVentilator‐associated pneumonia is a common type of hospital‐acquired infection in critically ill patients. The implementation of effective oral care with chlorhexidine is known to be an effective intervention to prevent ventilator‐associated pneumonia. Nonetheless, no well‐supported evidence exists yet to rank the efficacy of various concentrations of chlorhexidine.AimTo compare the efficacy of different concentrations of chlorhexidine (0.12%, 0.20% and 2.0%) for prevention of ventilator‐associated pneumonia.Study DesignElectronic databases, as well as bibliographies, were systematically searched to find relevant studies published in English from inception until January 1, 2022. We included randomized controlled trials of mechanically ventilated adult patients in intensive care settings comparing at least two of the following treatments: 0.12% chlorhexidine, 0.2% chlorhexidine, 2.0% chlorhexidine, or placebo. The selected outcome was the incidence of ventilator‐associated pneumonia. A frequentist network meta‐analysis was performed. We ranked the concentrations of chlorhexidine for the selected outcome by p score (estimate of the probability of being the best treatment).ResultsWe included 19 trials with 3183 participants, conducted across nine countries. The use of 2.0% chlorhexidine and 0.12% chlorhexidine decreased the risk of ventilator‐associated pneumonia compared with placebo (OR 0.46, 95% CI = 0.28–0.75; OR 0.49, 95% CI = 0.33–0.71, respectively), whereas the effect resulting from 0.02% chlorhexidine remains unclear (OR 0.78, 95% CI = 0.54–1.13). Our network meta‐analysis ranked the 2.0% concentration as the most beneficial for ventilator‐associated pneumonia prevention (p score: 0.92).ConclusionThe 2.0% chlorhexidine and the 0.12% chlorhexidine reduce the risk of ventilator‐associated pneumonia in mechanically ventilated patients. According to the results of our network meta‐analysis, 2.0% chlorhexidine seems more beneficial. Chlorhexidine needs to be further evaluated in large‐scale controlled trials.Relevance to clinical practiceIn patients in intensive care units, and within the inevitable limitations of a network meta‐analysis, this study proposes that 2.0% chlorhexidine is superior to other chlorhexidine concentrations in terms of preventing ventilator‐associated pneumonia.

Systematic Review and Network Meta-Analysis Comparing Bifurcation Techniques for Percutaneous Coronary Intervention.

BackgroundBifurcation lesions account for 20% of all percutaneous coronary interventions and represent a complex subset which are associated with lower procedural success and higher rates of restenosis. The ideal bifurcation technique, however, remains elusive.Methods and ResultsExtensive search of the literature was performed to pull data from randomized clinical trials that met predetermined inclusion criteria. Conventional meta‐analysis produced pooled relative risk (RR) and 95% CI of 2‐stent technique versus provisional stent on prespecified outcomes. Both frequentist and Bayesian network meta‐analyses were performed to compare bifurcation techniques. A total of 8318 patients were included from 29 randomized clinical trials. Conventional meta‐analysis showed no significant differences in all‐cause mortality, cardiac death, major adverse cardiac events, myocardial infarction, stent thrombosis, target lesion revascularization, and target vessel revascularization between 2‐stent techniques and provisional stenting. Frequentist network meta‐analysis revealed that double kissing crush was associated with lower cardiac death (RR, 0.57; 95% CI, 0.38–0.84), major adverse cardiac events (RR, 0.50; 95% CI, 0.39–0.64), myocardial infarction (RR, 0.60; 95% CI, 0.39–0.90), stent thrombosis (RR, 0.50; 95% CI, 0.28–0.88), target lesion revascularization, and target vessel revascularization when compared with provisional stenting. Double kissing crush was also superior to other 2‐stent techniques, including T‐stent or T and protrusion, dedicated bifurcation stent, and culotte.ConclusionsDouble kissing crush was associated with lower risk of cardiac death, major adverse cardiac events, myocardial infarction, stent thrombosis, target lesion revascularization, and target vessel revascularization compared with provisional stenting and was superior to other 2‐stent techniques. Superiority of 2‐stent strategy over provisional stenting was observed in subgroup meta‐analysis stratified to side branch lesion length ≥10 mm.

Abstract 344: Comparing the Efficacy of Real-Time Audiovisual Feedback Devices and Active Compression-Decompression Devices in Out-of-Hospital Cardiac Arrest: A Network Meta-Analysis

Introduction: Nearly 350,000 out-of-hospital cardiac arrest (OHCA) cases occur annually in the United States, with a fatality rate nearing 90%. Quality of cardiopulmonary resuscitation (CPR) is known to significantly influence survival. Randomized controlled trials (RCT) on real-time audiovisual feedback (RTAVF) and active compression-decompression (ACD) devices show both provide substantial advantages to standard CPR. We conducted the first network meta-analysis comparing the efficacy of RTAVF and ACD devices in OHCA based on a literature review. Methods: Studies examining the efficacy of RTAVF or ACD devices to standard CPR by emergency medical personnel in OHCA cases were identified in PubMed, SCOPUS, Cochrane, Google Scholar, and Embase. Outcomes of interest were return of spontaneous circulation (ROSC), survival to hospital discharge (SHD), and favorable neurological recovery. Both a frequentist and Bayesian network meta-analysis were conducted. The p-values, P-scores and Surface under the Cumulative Ranking (SUCRA) scores were computed to analyze significance and effect size. Results: The search yielded 31 eligible studies (n = 35,575). RTAVF devices significantly improved ROSC (Risk Ratio (RR) 1.15, 95% CI: 1.09 - 1.22, p < 0.001, P-score > 0.999) and SHD (RR 1.16, 1.07 - 1.26, p < 0.001, P-score > 0.91), but did not significantly improve favorable neurological recovery (RR 1.05, 0.92 - 1.19, p > 0.05). ACD devices did not report significant improvement in either ROSC (RR 1.03, 0.99 - 1.08, p > 0.05) or SHD (RR 1.10, 0.99 - 1.21, p > 0.05), but did report significant benefits in favorable neurological outcome (RR 1.30, 1.07 - 1.58, p < 0.01, P-score > 0.97). Similar findings were also seen in SUCRA scores. Conclusion: We found RTAVF devices increased ROSC and SHD, while ACD devices increased favorable neurological recovery. Our meta-analysis supports the adoption of RTAVF devices, but an RCT directly comparing RTAVF with ACD devices is recommended.