Recent Randomized Clinical Trials Research Articles

Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders: A Systematic Review and Meta-Analysis.

Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking. To compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients. MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses. Using these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria. Following the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The primary outcome, pooled pre-post placebo effect sizes (dav) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate. A total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses (Q = 88.5; df = 8; P < .001), with major depressive disorder (dav = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder (dav = 1.23; 95% CI, 1.06-1.41) exhibiting the largest dav. Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed dav between 0.68 and 0.92, followed by OCD (dav = 0.65; 95% CI, 0.51-0.78) and schizophrenia (dav = 0.59; 95% CI, 0.41-0.76). This systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.

Bronchiectasis management in adults: state of the art and future directions.

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find "treatable traits" and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent randomised clinical trials.

Use of medical therapy and risk of clinical events according to frailty in heart failure patients-A real-life cohort study.

Although recent randomized clinical trials have demonstrated the advantages of heart failure (HF) therapy in both frail and not frail patients, there is insufficient information on the use of HF therapy based on frailty status in a real-world setting. The aim was to examine how frailty status in HF patients associates with use of HF therapy and with clinical outcomes. Patients with new-onset HF between 2014 and 2021 were identified using the nationwide Danish registers. Patients across the entire range of ejection fraction were included. The associations between frailty status (using the Hospital Frailty Risk Score) and use of HF therapy and clinical outcomes (all-cause mortality, HF hospitalization, and non-HF hospitalization) were evaluated using multivariable-adjusted Cox models adjusting for age, sex, diagnostic setting, calendar year, comorbidities, pharmacotherapy, and socioeconomic status. Of 35 999 participants (mean age 69.1 years), 68% were not frail, 26% were moderately frail, and 6% were severely frail. The use of HF therapy was significantly lower in frailer patients. The hazard ratio (HR) for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation was 0.74 (95% confidence interval 0.70-0.77) and 0.48 (0.43-0.53) for moderate frailty and severe frailty, respectively. For beta-blockers, the corresponding HRs were 0.74 (0.71-0.78) and 0.51 (0.46-0.56), respectively, and for mineralocorticoid receptor antagonists, 0.83 (0.80-0.87) and 0.58 (0.53-0.64), respectively. The prevalence of death and non-HF hospitalization increased with frailty status. The HR for death was 1.55 (1.47-1.63) and 2.32 (2.16-2.49) for moderate and severe frailty, respectively, and the HR for non-HF hospitalization was 1.37 (1.32-1.41) and 1.82 (1.72-1.92), respectively. The association between frailty status and HF hospitalization was not significant (HR 1.08 [1.02-1.14] and 1.08 [0.97-1.20], respectively). In real-world HF patients, frailty was associated with lower HF therapy use and with a higher incidence of clinical outcomes including mortality and non-HF hospitalization.

Therapeutic Hypothermia Compared with Normothermia in Adults with Traumatic Brain Injury; Functional Outcome, Mortality, and Adverse Effects: A Systematic Review and Meta-Analysis.

The main focus of traumatic brain injury (TBI) management is prevention of secondary injury. Therapeutic hypothermia (TH), the induction of a targeted low core body temperature, has been explored as a potential neuroprotectant in TBI. The aim of this article is to synthesize the available clinical data comparing the use of TH with the use of normothermia in TBI. A systematic search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized clinical trials including one or more outcome of interest associated with TH use in TBI. Independent reviewers evaluated quality of the studies and extracted data on patients with TBI undergoing TH treatment compared with those undergoing normothermia treatment. Pooled estimates, confidence intervals (CIs), and risk ratios (RRs) or odds ratios were calculated for all outcomes. A total of 3,909 patients from 32 studies were eligible for analysis. Pooled analysis revealed a significant benefit of TH on mortality and functional outcome (RR 0.81, 95% CI 0.68-0.96, I2 = 41%; and RR 0.77; 95% CI 0.67-0.88, I2 = 68%, respectively). However, subgroup analysis based on risk of bias showed that only studies with a high risk of bias maintained this benefit. When divided by cooling method, reduced poor functional outcome was seen in the systemic surface cooling and cranial cooling groups (RR 0.68, 95% CI 0.59-0.79, I2 = 35%; and RR 0.44, 95% CI 0.29-0.67, I2 = 0%), and no difference was seen for the systemic intravenous or gastric cooling group. Reduced mortality was only seen in the systemic surface cooling group (RR 0.63, 95% CI 0.53-0.75, I2 = 0%,); however, this group had mostly high risk of bias studies. TH had an increased rate of pneumonia (RR 1.24, 95% CI 1.10-1.40, I2 = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09-2.44, I2 = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05-3.01, I2 = 21%). Once separated by low and high risk of bias, we saw no difference in these complications in the groups with low risk of bias. Overall quality of the evidence was moderate for mortality, functional outcome, and pneumonia and was low for coagulation abnormalities and cardiac arrhythmias. With the addition of several recent randomized clinical trials and a thorough quality assessment, we have provided an updated systematic review and meta-analysis that concludes that TH does not show any benefit over normothermia in terms of mortality and functional outcome.

Timing of fractional flow reserve-guided complete revascularization in patients with ST-segment elevation myocardial infarction with multivessel disease: Rationale and design of the OPTION-STEMI trial

Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA. The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least one non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into two groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis were revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025. The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD. URL: https://www. gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457.

Empagliflozin and Dapagliflozin Therapies Favorably Alter QRS-T Angle and Cardiac Repolarization Parameters in Patients with Heart Failure.

Recent randomized clinical trials demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduces the risk of cardiac mortality due to sudden cardiac death and progressive pump failure in patients with heart failure (HF). Mechanisms underlying the potential anti-arrhythmic effects of SGLT2is are not well understood. We aimed to examine the effect of SGLT2i treatment on the frontal-plane QRS-T (f[QRS-T]) angle, a novel marker of myocardial repolarization and an independent predictor of adverse cardiac outcomes. The study included 106 patients with HF with reduced ejection fraction (HFrEF) who received an SGLT2i, empagliflozin, or dapagliflozin. All study participants underwent screening 12-lead electrocardiography (ECG) before and ∼90 days after treatment. We compared ECG repolarization parameters before and after treatment. During study enrollment, there were statistically significant decreases in the Tp-e/QT ratio (P ≤ .0001), Tp-e/corrected QT ratio (P = .0002), Tp-e interval (P < .0001), and f(QRS-T) angle (P = .04) in response to SGLT2i therapy. In addition, study participants experienced an improvement in functional capacity (2.06 ± 0.6 vs. 1.82 ± 0.6, P = .0001) and reduced N-terminal pro-b-type natriuretic peptide values. In this retrospective cohort study, SGLT2i therapy was associated with improved cardiac repolarization parameters in patients with HFrEF. More comprehensive studies are needed to evaluate the impact of SGLT2i on cardiac repolarization and its potential relation to cardiac arrhythmia and sudden cardiac death risk.

Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: results of two harmonized randomized clinical trials.

Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements and any dose response relationships require further elucidation. A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events and 24-hour red cell transfusion requirements were compared between TXA and placebo groups. Regression analyses were utilized to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics and shock severity across a broad spectrum of injured patients. Dose response relationships were similarly characterized based upon grams of prehospital TXA administered. A total of 1744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR: 5-26). TXA was independently associated with a lower risk of 28-day mortality (HR: 0.72, 95% CI 0.54, 0.96, p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR: 0.78, 95% CI 0.63, 0.96, p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (β: -0.31, 95% CI -0.61, -0.01, p = 0.04) with a dose-response relationship (β: -0.24, 95% CI -0.45, -0.02, p = 0.03). There was no independent association of prehospital TXA administration on VTE, seizure, or stroke. In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit, lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship. Therapeutic/Care Management; Level III.

Proteomic Associations of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) in Heart Failure With Preserved Ejection Fraction.

NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels are variably elevated in heart failure with preserved ejection fraction (HFpEF), even in the presence of increased left ventricular filling pressures. NT-proBNP levels are prognostic in HFpEF and have been used as an inclusion criterion for several recent randomized clinical trials. However, the underlying biologic differences between HFpEF participants with high and low NT-proBNP levels remain to be fully understood. We measured 4928 proteins using an aptamer-based proteomic assay (SOMAScan) in available plasma samples from 2 cohorts: (1) Participants with HFpEF enrolled in the PHFS (Penn Heart Failure Study; n=253); (2) TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) participants in the Americas (n=218). We assessed the relationship between SOMAScan-derived plasma NT-proBNP and levels of other proteins available in the SOMAScan assay version 4 using robust linear regression, with correction for multiple comparisons, followed by pathway analysis. NT-proBNP levels exhibited prominent proteome-wide associations in PHFS and TOPCAT cohorts. Proteins most strongly associated with NT-proBNP in both cohorts included SVEP1 (sushi, von Willebrand factor type-A, epidermal growth factor, and pentraxin domain containing 1; βTOPCAT=0.539; P<0.0001; βPHFS=0.516; P<0.0001) and ANGPT2 (angiopoietin 2; βTOPCAT=0.571; P<0.0001; βPHFS=0.459; P<0.0001). Canonical pathway analysis demonstrated consistent associations with multiple pathways related to fibrosis and inflammation. These included hepatic fibrosis and inhibition of matrix metalloproteases. Analyses using cut points corresponding to estimated quantitative concentrations of 360 pg/mL (and 480 pg/mL in atrial fibrillation) revealed similar proteomic associations. Circulating NT-proBNP levels exhibit prominent proteomic associations in HFpEF. Our findings suggest that higher NT-proBNP levels in HFpEF are a marker of fibrosis and inflammation. These findings will aid the interpretation of NT-proBNP levels in HFpEF and may guide the selection of participants in future HFpEF clinical trials.

Patent Foramen Ovale Percutaneous Closure: Evolution and Ongoing Challenges.

Patent foramen ovale (PFO) concerns nearly a quarter of the general population and incidence may reach up to 50% in patients with cryptogenic stroke. Recent randomized clinical trials confirmed that percutaneous closure of PFO-related stroke reduces the risk of embolic event recurrence. PFO also comes into play in other pathogenic conditions, such as migraine, decompression sickness or platypnea-orthodeoxia syndrome, where the heterogeneity of patients is high and evidence for closure is less well-documented. In this review, we describe the current indications for PFO percutaneous closure and the remaining challenges, and try to provide future directions regarding the technique and its indications.

Hematological Response to Frontline Treatment in Lower Risk Myelodysplastic Syndromes (LRMDS) Is Associated with Better Overall Survival

Background The majority of LRMDS patients (pts) (70%) do not progress but unfortunately succumb to complications related to cytopenia, namely anemia and red blood cell transfusion dependency (RBC-TD) or their interplay with co-morbidities. RBC-TD is associated with worse outcome reflecting bone marrow failure and long-term sequela of RBC-TD. There is growing evidence that response to treatment and RBC transfusion independence (TI) are associated with favorable outcome. In lieu of 2 recent randomized clinical trials demonstrating efficacy of luspatercept &amp; imetelstat in LRMDS, we assessed the impact of response to sequential lines of treatment in LR-MDS on overall survival (OS) to guide our treatment choices and to determine whether erythroid stimulating agents (ESA) should still be our 1 st line of therapy. Methods We included LRMDS pts (IPSS-R very low &amp; low) from Moffitt Database who received ESA as frontline therapy (FL) and assessed subsequently outcomes with second line (SL) therapy (SOC or clinical trial). We excluded MDS/MPN and del5q pts. We also excluded all pts who eventually progressed to either higher risk MDS or AML to better reflect the majority LRMDS in that disease state. We assessed details of FL and SL. Pts who received FL &amp; SL were then divided into 4 groups based on response to FL and SL therapy: group 1 (no/no), group 2 (no/yes) with response only to SL, group 3 (yes/no) response to FL only, and group 4 (yes/yes) with response to both lines of therapy. Response was defined as hematological improvement (HI) with ≥1.5 g/dl Hgb increase in non-TD pts and RBC-TI in TD pts at baseline for at least for 8 weeks. We compared median OS (mOS) among those groups. Results There were 603 LRMDS pts who met eligibility criteria and received ESA as FL (Table-1); 43% were RBC-TD, mean serum EPO was 132 (n=211 pts), 69% received epoetin, 17% darbepoetin and 14% with G-CSF. HI was observed in 42% of pts with no difference among ring sideroblasts (RS) +/- (46% vs 40%, p =.12). Response was higher among non-RBC-TD (52% vs 31%, p&amp;lt; .001). The median time to start ESA was 1.2 mo (0-249). The median time on ESA therapy was 11 mo (.4-213). 331 pts (55%) received SL which included HMA 43% (n= 142), lenalidomide 39% (n=130), luspatercept 7% (n=24), ATG 2% (n=8), investigational agent 4% (n=14), and other 4% (n=13) . The HI rate was 27% (91/331). No difference in HI based on RS nor RBC-TD was observed. The median duration on SL treatment was 6 mo (.1-93). 170 pts (28%) received 3 rd line of therapy with 7% HI, 88 pts (15%) received 4 th line of therapy with 3% HI and 39 pts (7%) had 5 th line of therapy with 2% HI. Among the 331 pts who received at least FL and SL, pts were divided into 4 groups based on response to (methods, table-2), the mOS was 114 mo among Yes/Yes response group, 103 mo among yes/no group, 97 mo no/yes and 64 mo among no/no ( P=.007; Figure-1). Response to FL was significantly associated with better OS after adjusting for RS (HR .74 ,95% CI .55-.99, p=.043). Conclusions Only half of patients who receive ESA as FL therapy for LRMDS received any subsequent therapies. Response rates were highest with ESA as FL than any SL therapy. HI with FL and/or SL is associated with improved OS. Lack of response to first line of therapy is associated with worse OS. Responses beyond SL were rarely observed. Identifying and moving agents with high HI rate as FL therapy and or selecting option based on predictors of best chance of response to a specific treatment as FL may lead to better overall survival.

Alberta Stroke Program Early Computed Tomography Score, Infarct Core Volume, and Endovascular Therapy Outcomes in Patients With Large Infarct

Endovascular therapy (EVT) demonstrated better outcomes compared with medical management in recent randomized clinical trials (RCTs) of patients with large infarct. To compare outcomes of EVT vs medical management across different strata of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and infarct core volume in patients with large infarct. This prespecified secondary analysis of subgroups of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) RCT included patients from 46 stroke centers across China between October 2, 2020, and May 18, 2022. Participants were enrolled within 24 hours of symptom onset and had ASPECTS of 3 to 5 or 0 to 2 and infarct core volume of 70 to 100 mL. Patients were divided into 3 groups: ASPECTS of 3 to 5 with infarct core volume less than 70 mL, ASPECTS of 3 to 5 with infarct core volume of 70 mL or greater, and ASPECTS of 0 to 2. Endovascular therapy or medical management. The primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. There were 455 patients in the trial; median age was 68 years (IQR, 60-73 years), and 279 (61.3%) were male. The treatment effect did not vary significantly across the 3 baseline imaging subgroups (P = .95 for interaction). The generalized odds ratio for the shift in the 90-day mRS distribution toward better outcomes with EVT vs medical management was 1.40 (95% CI, 1.06-1.85; P = .01) in patients with ASPECTS of 3 to 5 and infarct core volume less than 70 mL, 1.22 (95% CI, 0.81-1.83; P = .23) in patients with ASPECTS of 3 to 5 and infarct core volume of 70 mL or greater, and 1.59 (95% CI, 0.89-2.86; P = .09) in patients with ASPECTS of 0 to 2. In this study, no significant interaction was found between baseline imaging status and the benefit of EVT compared with medical management in patients with large infarct core volume. However, estimates within subgroups were underpowered. A pooled analysis of large core trials stratified by ASPECTS and infarct core volume strata is warranted. ClinicalTrials.gov Identifier: NCT04551664.

Abstract 13308: Characteristics of Participants Enrolled in a Randomized Controlled Trial Evaluating Vitamin D Normalization on Major Adverse Cardiovascular-Related Events: The Target-D Trial

Background: Many observational studies have reported associations between low 25-hydroxyvitamin D (25[OH] vit D) levels and adverse cardiovascular (CV) outcomes. Recent randomized clinical trials have not found vitamin (vit) D 3 supplementation to reduce CV risk. However, these trials gave “blanket” doses regardless of 25[OH] vit D level, with none having "treated to target". We are performing the first study where subjects are prescribed vit D 3 supplementation based on individual 25[OH] vit D levels. Methods: The purpose of Target-D (NCT: 02996721) is to determine if achieving 25[OH] vit D levels &gt;40 ng/mL among myocardial infarction (MI) patients will result in a reduction of adverse CV events. Subjects meeting study criteria from April 2017 to May 2023 were randomized to receive standard of care or clinical management of 25[OH] vit D levels. The treatment arm received targeted vit D 3 supplementation based on a dosing algorithm. Target-D is an event-driven trial that will conclude when 104 primary outcome events (composite of death, MI, heart failure hospitalization, and stroke) have occurred. Results: The study consort diagram is shown in Figure. Patient characteristics are shown in Table. Baseline 25[OH] vit D levels were 26.8±12.7 (median: 25) and were similar between arms (Table). Among those randomized to the treatment arm with a 25[OH] vit D levels &lt; 40, 58.5% of patients began vit D 3 dosing at 5000 IU. Conclusions: Average baseline 25[OH] vit D levels were deficient in Target-D participants. The discrepancy in findings between observational and randomized trials of vit D may be due to the inability of vit D 3 supplementation doses to achieve therapeutic 25[OH] vit D thresholds. Target-D will evaluate if it is the level of serum 25[OH] vit D achieved that provides CV benefit and not necessarily the vit D 3 supplementation dose that is received. It is anticipated that the number of events needed for this event-driven trial will be achieved by May 2024.

Endovascular Treatment in Acute Basilar Artery Occlusion Stroke: A Brief Practice Update From the Society of Vascular and Interventional Neurology

Background The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee established the “Brief Practice Update” format to provide up‐to‐date recommendations on focused relevant clinical questions. In this Brief Practice Update, we review current evidence and provide recommendations for endovascular treatment (EVT) in patients with acute large‐vessel occlusion of the basilar artery. Methods The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee conducted a systematic review, including the recent randomized clinical trials of EVT for acute ischemic stroke attributable to basilar artery occlusion, and summarized relevant data to provide recommendations for clinical practice. The Guidelines and Practice Standards quality committee reviewed the findings to ensure adherence to the Society of Vascular and Interventional Neurology internal evidence evaluation guidelines before review by the Society of Vascular and Interventional Neurology board members for societal endorsement. Results Evidence favors EVT for basilar artery occlusion in comparison to medical management alone in patients with moderate to severe stroke. We formulated the level of evidence and the class of recommendation in the context of 5 clinical questions. Conclusions In this brief practice statement, we share general recommendations on EVT for acute ischemic stroke attributable to large‐vessel occlusion of the basilar artery. Recent randomized controlled trials, Basilar Artery Occlusion Chinese Endovascular (BAOCHE) trial and Endovascular Treatment for Acute Basilar‐Artery Occlusion (ATTENTION), and a meta‐analysis of all randomized controlled trials support EVT in patients with moderate to severe basilar artery occlusion stroke symptoms.

Impact of group antenatal care on fetal and maternal outcomes, systematic literature review and meta-analysis of recent randomized clinical trials

Impact of group antenatal care on fetal and maternal outcomes, systematic literature review and meta-analysis of recent randomized clinical trials

Acute heart failure: current pharmacological treatment and perspectives.

Acute heart failure (AHF) represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Symptoms and clinical signs of AHF (e.g. dyspnoea, orthopnoea, oedema, jugular vein distension, and variation of body weight) are mostly related to systemic venous congestion secondary to various mechanisms including extracellular fluids, increased ventricular filling pressures, and/or auto-transfusion of blood from the splanchnic into the pulmonary circulation. Thus, the initial management of AHF patients should be mostly based on decongestive therapies on admission followed, before discharge, by rapid implementation of guideline-directed oral medical therapies for heart failure. The therapeutic management of AHF requires the identification and rapid diagnosis of the disease, the diagnosis of the cause (or triggering factor), the evaluation of severity, the presence of comorbidities, and, finally, the initiation of a rapid treatment. The most recent guidelines from ESC and ACC/AHA/HFSA have provided updated recommendations on AHF management. Recommended pharmacological treatment for AHF includes diuretic therapy aiming to relieve congestion and achieve optimal fluid status, early and rapid initiation of oral therapies before discharge combined with a close follow-up. Non-pharmacological AHF management requires risk stratification in the emergency department and non-invasive ventilation in case of respiratory failure. Vasodilators should be considered as initial therapy in AHF precipitated by hypertension. On the background of recent large randomized clinical trials and international guidelines, this state-of-the-art review describes current pharmacological treatments and potential directions for future research in AHF.

Cold snare polypectomy compared to cold forceps polypectomy for endoscopic resection of guideline defined diminutive polyps: A systematic review and meta-analysis of randomized trials.

International guidelines recommend cold snare polypectomy (CSP) for polyps < 10mm in size. However, recent randomized clinical trials (RCTs) showed conflicting results for the use of cold forceps polypectomy (CFP) vs. CSP for the resection of diminutive colorectal polyps (DCPs) (≤ 5mm), especially for polyps ≤ 3mm. Herein we compared CFP with CSP for patients with DCPs in this meta-analysis of RCTs. We systematically searched the Cochrane Library, PubMed and EMBASE databases from inception to November 24, 2022, (Registration number INPLASY2022110135). The primary endpoint was DCP complete resection rate. The secondary endpoints were mean polypectomy time, polyp retrieval rate and complications. Seven RCTs involving 1023 DCPs were included. The complete resection rate (91.6% vs. 94.7%) for CFP was not significantly lower for polyps ≤ 5mm (relative risk [RR] = 1.03; 95% confidence interval [CI]: 0.98-1.07). Sub-group analysis showed that the complete resection rate (88.7% vs. 92.4%) for CFP was not significantly lower for DCPs > 3mm (RR = 1.04; 95%CI: 0.97-1.12). Another sub-group analysis showed that the complete resection rate (97.0% vs. 96.3%) was similar for polyps ≤ 3mm for CFP vs. CSP (RR = 1.00; 95%CI: 0.98-1.03). The mean polypectomy time was not different between CFP and CSP (95%CI: -11.86-10.18). The polyp retrieval rate (100% vs. 96.9%) was not significantly higher for CFP (RR = 1.02; 95%CI: 0.98-1.07). There were no reported complications in the included studies. The overall study quality was moderate except for the removal of polyps ≤ 5mm (low-quality evidence). CFP was comparable to CSP for theresection of polyps ≤ 3mm; however, caution should be taken for DCPs > 3mm because of the low complete resection rate (< 90%).

Dual Antiplatelet Therapy or Antiplatelet Plus Anticoagulant Therapy in Patients with Peripheral and Chronic Coronary Artery Disease: An Updated Review.

Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particularly vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a difficult outcome to target, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD; however, the optimal intensity of such therapy is still a topic of debate, particularly in the post-acute and long-term setting. Recent well-powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and selection of patients is a key issue. The aim of this review is, therefore, to discuss and summarize the most up-to-date available evidence for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both types of atherosclerotic disease and comparing a higher- versus a lower-intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improve precision medicine.

Management of Coronary Artery Disease in Older Adults: Recent Advances and Gaps in Evidence.

Coronary artery disease (CAD) is highly prevalent in older adults, yet its management remains challenging. Treatment choices are made complex by the frailty burden of older patients, a high prevalence of comorbidities and body composition abnormalities (e.g., sarcopenia), the complexity of coronary anatomy, and the frequent presence of multivessel disease, as well as the coexistence of major ischemic and bleeding risk factors. Recent randomized clinical trials and epidemiological studies have provided new data on optimal management of complex patients with CAD. However, frail older adults are still underrepresented in the literature. This narrative review aims to highlight the importance of assessing frailty as an aid to guide therapeutic decision-making and tailor CAD management to the specific needs of older adults, taking into account age-related pharmacokinetic and pharmacodynamic changes, polypharmacy, and potential drug interactions. We also discuss gaps in the evidence and offer perspectives on how best in the future to optimize the global strategy of CAD management in older adults.

Twenty-Four-Month Blood Pressure Results After Renal Denervation Using Endovascular Ultrasound.

BACKGROUND Renal denervation has proven its efficacy to lower blood pressure in comparison to sham treatment in recent randomized clinical trials. Although there is a large body of evidence for the durability and safety of radiofrequency-based renal denervation, there are a paucity of data for endovascular ultrasound-based renal denervation (uRDN). We aimed to assess the long-term efficacy and safety of uRDN in a single-center cohort of patients. METHODS AND RESULTS Data from 2 previous studies on uRDN were pooled. Ambulatory 24-hour blood pressure measurements were taken before as well as 3, 6, 12, and 24 months after treatment with uRDN. A total of 130 patients (mean age 63±9 years, 24% women) underwent uRDN. After 3, 6, 12, and 24 months, systolic mean 24-hour ambulatory blood pressure values were reduced by 10±12, 10±14, 8±15, and 10±15 mm Hg, respectively, when compared with baseline (P<0.001). Corresponding diastolic values were reduced by 6±8, 6±8, 5±9, and 6±9 mm Hg, respectively (P<0.001). Periprocedural adverse events occurred in 16 patients, and all recovered without sequelae. CONCLUSIONS In this single-center study, uRDN effectively lowered blood pressure up to 24 months after treatment.

Placebo and nocebo responses in painful diabetic neuropathy: systematic review and meta-analysis.

This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical trials (RCTs) on painful diabetic neuropathy (PDN), updating the previous literature by a decade. Four databases were searched for PDN trials published in the past 20 years, testing oral medications, adopting a parallel-group design. Magnitude of placebo or nocebo responses, Cochrane risk of bias, heterogeneity, and moderators were evaluated. Searches identified 21 studies (2425 placebo-treated patients). The overall mean pooled placebo response was -1.54 change in the pain intensity from baseline [95% confidence interval (CI): -1.52, -1.56, I2 = 72], with a moderate effect size (Cohen d = 0.72). The pooled placebo 50% response rate was 25% [95% CI: 22, 29, I2 = 50%]. The overall percentage of patients with adverse events (AEs) in the placebo arms was 53.3% [95% CI: 50.9, 55.7], with 5.1% [95% CI: 4.2, 6] of patients dropping out due to AEs. The year of study initiation was the only significant moderator of placebo response (regression coefficient = -0.06, [95% CI: -0.10, -0.02, P = 0.007]). More recent RCTs tended to be longer, bigger, and to include older patients (N = 21, rs = 0.455, P = 0.038, rs = 0.600, P = 0.004, rs = 0.472, P = 0.031, respectively). Our findings confirm the magnitude of placebo and nocebo responses, identify the year of study initiation as the only significant moderator of placebo response, draw attention to contextual factors such as confidence in PDN treatments, patients' previous negative experiences, intervention duration, and information provided to patients before enrollment.