Large Randomized Clinical Trials Research Articles

Pathogenic cardiomyopathy gene variants inform prognosis in atrial fibrillation: results from exome sequencing in over 17,000 patients in TIMI trials

Abstract Background Rare genetic variants in cardiomyopathy genes are associated with risk of atrial fibrillation (AF), even in the absence of overt ventricular dysfunction. Data on clinical outcomes for rare genetic variant carriers among patients with AF remain sparse. Purpose We aimed to study the prognostic implication of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with AF from large, well-phenotyped randomized clinical trials. Methods and results Rare variants were called using exome sequencing data in 5 large clinical trials from the TIMI study group (ENGAGE-AF, FOURIER, SAVOR, PEGASUS, DECLARE). PLP variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from the ClinVar database. In 17,190 patients with a history of AF, we identified 421 (2.4%) PLP variant carriers (age 67±10, 35% women) and 16,769 (97.6%) pts without PLP variants (age 70±9, 36% women). Among these individuals, we identified 265 DCM carriers (1.5%), 106 (0.6%) HCM carriers and 54 (0.3%) ARVC carriers. In this cohort, 9,275 (54%) had a history of heart failure (HF) and 2,991 (17.4%) prior ischemic stroke. Over 2.5 years median follow-up, 1,365 pts (7.9%) were hospitalized for HF, 599 (3.5%) had an ischemic stroke, and 1147 (6.7%) died of cardiovascular causes. In logistic regression analyses adjusting for age, sex, trial, and principal components of ancestry, PLP variants were significantly associated with a history of HF (OR 1.66, p<0.0001), most notably for DCM variants (OR 1.97, 1.48-2.62, p<0.0001). PLP variants were independently associated with incident HF admissions (adj HR 1.75, 1.39-2.29, p<0.0001), most notably for HCM (adj HR 2.59, 1.68-3.99, p<0.0001) and ARVC variants (adj HR 2.50, 1.34-4.66, p=0.004). The increased risk of HF admissions remained consistent in patients with (adj HR 1.49, 1.11-2.00, p=0.009) and those without (adj HR 1.88, 1.00-3.54, p=0.049) a history of HF. PLP variants were also associated with higher risk of cardiovascular death (adj HR 1.46, 1.06-2.02, p=0.02), most notably for DCM variants (adj HR 1.77, 1.21-2.58, p=0.003). In contrast, PLP variants were not associated with history of ischemic stroke at baseline (adj OR 0.99, p=0.96) nor with incident ischemic stroke (adj HR 0.95, p=0.84). Conclusion In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF and of cardiovascular death, but not stroke. These results, collected from large well-phenotyped randomized clinical trials, demonstrate an important prognostic implication for rare genetic variants for CMP in pts with AF.

Dapagliflozin versus empagliflozin and major adverse cardiovascular events in type 2 diabetes: a nationwide cohort study

Abstract Background Large randomized clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus (T2DM) at high risk of atherosclerotic cardiovascular disease. Whether these effects might differ between individual SGLT2-inhbitors remain unclear given the lack of head-to-head comparisons. Purpose To examine the association between treatment with dapagliflozin versus empagliflozin and the long-term rate of major adverse cardiovascular events (MACE) in patients with T2DM. Methods Using nationwide registries, all Danish residents with T2DM, who initiated treatment with dapagliflozin or empagliflozin from 2015 to 2020, were identified. Only treatment with dapagliflozin or empagliflozin was considered in the present analysis, since approximately 3% initiated treatment with other SGLT2-inhibitors (i.e., canagliflozin and ertugliflozin). Patients were followed from date of the first claimed prescription of dapagliflozin or empagliflozin until the outcome of interest, emigration, death, or end of study (December 31, 2021). The primary outcome was a composite endpoint of major adverse cardiovascular events (i.e., time to first heart failure hospitalisation, acute myocardial infarction (AMI), stroke, or all-cause mortality). The primary outcome was compared between the dapagliflozin and empagliflozin group, overall and in prespecified subgroups of interest, with multivariable Cox proportional hazards regression models. Results In total, 61,031 patients with T2DM initiated treatment with dapagliflozin (N=21,028; 34.5%) or empagliflozin (N=40,003; 65.5%). The median age of study population was 62.6 years (25th-75th percentile, 54.2-70.8 years), and 62.6% were men. There were no clinically significant differences between the dapagliflozin and empagliflozin group with respect to age, sex, and clinical characteristics. The median follow-up was 3.1 years (25th-75th percentile, 1.9-4.5 years). The adjusted long-term hazard ratios of the primary outcome, overall and in prespecified subgroups of interest, are displayed in the Figure. Compared with empagliflozin, treatment with dapagliflozin was not associated with a significantly different rate of the primary outcome (HR 1.02 [95% CI, 0.97-1.07]). The observed association was consistent across clinically relevant subgroups, including in patients with and without heart failure, chronic kidney disease, and atherosclerotic cardiovascular disease. Conclusion In a large, nationwide cohort of patients with T2DM, treatment with dapagliflozin was associated with a similar rate of major adverse cardiovascular outcomes compared with empagliflozin, and this association was consistent across clinically relevant subgroups. These findings suggest that the benefits of SGLT2-inhibitors can be characterized as a class-effect.

Improvements in Safety Outcomes Following Brief Healthcare-Based Intimate Partner Violence Interventions among Women Who Screen Positive for Intimate Partner Violence-Related Traumatic Brain Injuries.

Background: Traumatic brain injuries (TBIs) are a common consequence of experiencing intimate partner violence (IPV). IPV-related TBI contributes to adverse health outcomes among women, but it is unknown whether a history of IPV-related TBI negatively impacts safety outcomes following healthcare-based interventions for IPV. Methods: Using data from a larger randomized clinical trial, we explored the impact of IPV-related TBI status on safety-related outcomes in two healthcare-based IPV interventions. At baseline, 35% (n = 21) of the sample screened positive for IPV-related TBI history. We used repeated measures ANOVAs to examine differences in safety outcomes at post-treatment and 1-month follow-up based on treatment condition and IPV-related TBI status. Results: Significant interaction effects were found for safety outcomes, such that women with IPV-related TBI history experienced larger reductions in the frequency of physical IPV and similar reductions in sexual IPV across both treatment conditions compared to women without IPV-TBI (F(2, 102) = 10.88, p < 0.001; F(2, 98) = 3.93, p = 0.036). Conclusions: Findings suggest that brief healthcare-based IPV interventions may result in improvements in safety outcomes for women with a history of IPV-TBI. This highlights the continued need for implementation of promising IPV-focused interventions to promote safety and protect women from experiencing further IPV.

Cost-Effectiveness Ratio Analysis of LBBaP Versus BVP in Heart Failure Patients With LBBB.

For the initial treatment strategy for patients with cardiac resynchronization therapy (CRT) indications, whether to choose left bundle branch area pacing (LBBaP) or biventricular pacing (BVP) remains controversial. We aimed to investigate the cost-effectiveness ratio (CER) of LBBaP and BVP in heart failure (HF) patients with left bundle branch block (LBBB). This observational study included HF patients with LBBB who underwent successful LBBaP or BVP. The primary outcomes were echocardiographic response (left ventricular ejection fraction [LVEF] increase ≥5%), LVEF improvement, hospitalization costs, and CER (CER = cost/echocardiographic response rate). Secondary outcomes included other echocardiographic parameters, New York Heart Association (NYHA), N-terminal pro-B-type natriuretic peptide (NT-proBNP), pacemaker parameters, complications, ventricular arrhythmia (VA) events, HF hospitalization (HFH), and all-cause mortality. A total of 130 patients (85 LBBaP and 45 BVP) were included (65.6 ± 10.0 years, 70.77% men). The median follow-up period was 16(12,30), months. Compared with BVP, the LBBaP group showed a greater increase in LVEF (20.2%±11.8% vs. 10.5%±13.9%; p<0.001), higher echocardiographic response rate (86.1% vs. 57.8%; p<0.001), and lower hospitalization costs [$9707.7 (7751.2, 18,088.5) vs. $20,046.1 (18,840.1, 22,447.3); p<0.0001]. The CER was 112.7 and 346.8 in LBBaP and BVP, respectively. The incremental cost-effectiveness ratio (ICER = △cost/△echocardiographic response rate) was $-365.3/per 1% increase in effectiveness. LBBaP improved cardiac function more significantly than BVP. There were no significant differences in clinical outcomes. LBBaP-CRT is more cost-effective than BVP, offering greater LVEF improvement, higher echocardiographic response rates, lower hospitalization costs, and more significantly improved cardiac function. These findings need large randomized clinical trials for further confirmation.

The effectiveness of vedolizumab in advanced therapy-experienced ulcerative colitis patients: Real world data from the Inflammatory Bowel Disease of the Middle East (IBD-ME) Registry group.

Vedolizumab is an approved ulcerative colitis (UC) treatment. Multiple large randomized clinical trials have demonstrated the drug's efficacy and safety. However, real-world data from Middle Eastern countries are spare. The study aims to evaluate the clinical efficacy of vedolizumab (VDZ) therapy in advanced therapy experienced UC patients. A retrospective electronic chart review of a cohort study of 153 moderately to severely active UC patients who failed or were intolerant to TNF antagonists and received vedolizumab from two large tertiary care centers was performed. Rates of clinical response and remission were retrospectively evaluated at 3,6, and 12 months post VDZ therapy using Patient Simple Clinical Colitis Activity Index (P-SCCAI); clinical response was defined as a decrease in P-SCCAI ≥3, and clinical remission was defined as a P-SCCAI score of ≤3 points. Logistic regression analysis was used to identify predictors of response to vedolizumab. A total of 153 UC patients had sufficient data for analysis. Clinical remission rates were 61.9% for patients on vedolizumab every 8 weeks and 89.3% for those receiving every 4 (Q4) weeks dosing. A significant reduction in CRP and improvement of albumin post vedolizumab treatment were observed, and corticosteroids were stopped in most patients. In a multiple logistic regression analysis, several factors were found to influence the clinical effectiveness of VDZ in inducing remission. Female gender was associated with a higher likelihood of remission [OR =3.09, 95% CI = (1.05-9.13), P = 0.04]. Conversely, a greater number of biologics used prior to VDZ treatment was associated with a lower likelihood of remission [OR =0.418, 95% CI = (0.203-0.859), P = 0.017]. Patients with extensive disease (E3) had an increased likelihood of remission [OR =3.81, 95% CI = (1.32-10.97), P = 0.0129]. Additionally, a VDZ dosing frequency of Q4 weeks was associated with a significantly higher likelihood of remission [OR =6.08, 95% CI = (1.73-21.39), P = 0.0049]. No significant safety signals were reported. In this current real-world study, vedolizumab effectively achieved clinical response and remission in most advanced therapy experienced UC patients treated for up to 12 months. Future studies with larger sample sizes and more robust study designs should be conducted to further validate the results of this study.

Pharmacologic Therapy for Spinal Cord Injury.

Neuroprotective strategies aimed at preventing secondary neurologic injury following acute spinal cord injury remain an important area of clinical, translational, and basic science research. Despite recent advancement in the understanding of basic mechanisms of primary and secondary neurologic injury, few pharmacologic agents have shown consistent promise in improving neurologic outcomes following SCI in large randomized clinical trials. The authors review the existing literature and clinical guidelines for pharmacologic therapy investigated for managing acute SCI, including corticosteroids, GM-1 ganglioside (Sygen), Riluzole, opioid antagonists, Cethrin, minocycline, and vasopressors for mean arterial pressure augmentation. Therapies for managing secondary effects of SCI, such as bradycardia, are discussed. Current clinical trials for pharmacotherapy and cellular transplantation following acute SCI are also reviewed. Despite the paucity of current evidence for clinically beneficial post-SCI pharmacotherapy, future research efforts will hopefully elucidate promising therapeutic agents to improve neurologic function.

Exploring the Potential to Identify Early Development Pre-Atherosclerotic Disease in Pediatric Carotid Arteries

Objective: The aim of these analyses was to determine the potential development of increased carotid intima-media thickness (cIMT) and spectral Doppler velocity in a cohort of children who were eligible for federal nutrition support services. Materials and Methods: A secondary data analysis was conducted based on data collected during a larger randomized clinical trial. Data were pulled on 108 children, ages 8 to 11 years, who had both cIMT measures, as well as spectral Doppler data, at the level of measured intimae. Additional data such as vessel geometry, body mass index (BMI), and blood pressure (BP) were added to the analysis to provide additional descriptive data. Results: The posterior cIMT data provided the best visualization and measurements to assess the presence of early risk for atherosclerosis. In this cohort of 8- to 11-year-olds, the median spectral Doppler values did not exceed the published values for these ages, nor did their systolic blood pressure. In this group, 77 (71%) were classified as having a healthy BMI. However, the posterior cIMT data were compared to published measures of pediatric cIMT values and 60 children (55%) exceeded the expected mean thickness of 0.38 mm + 0.04 on the right and 58 (53%) on the left. Conclusion: The use of spectral Doppler to assess the risk of developing atherosclerosis may not be the best diagnostic tool, based on this cohort. The measurement of cIMT has the most promise to proper classify healthy appearing 8- to 11-year-olds, for early signs of diminished cardiovascular health.

Evolution of Medical and Surgical Management of Carotid Disease from Carotid Endarterectomy to Transfemoral Carotid Stenting to TCAR

Patients with carotid stenosis can be broadly classified into two categories: symptomatic and asymptomatic. While there is little disagreement about surgical management of symptomatic carotid stenosis, the optimal management strategy for the patients with asymptomatic carotid disease has undergone significant evolution over past five decades. With increasing focus on role of plaque morphology on the etiology of symptoms, there has been an increased focus on optimizing the medical management targeted at plaque stabilization, especially for the patients with asymptomatic carotid disease, while reserving the most aggressive surgical treatment options for the patients with symptomatic carotid stenosis. This review summarizes the scientific evidence based on multiple large clinical studies showing how the modern-day management of carotid stenosis has evolved. Multiple, large randomized clinical trials have established carotid endarterectomy (CEA) as the treatment of choice for symptomatic patients with symptomatic, >50% stenosis of carotid artery or those who have asymptomatic high grade carotid stenosis. With the advancements in endovascular techniques, the technique of Trans Femoral Carotid Artery Stenting (TF-CAS) was popularized, but after multiple, large randomized controlled trials demonstrated superiority of CEA, the indications for TF-CAS as the initial operation of choice for carotid disease for all patients have been reduced. In the past five years, the introduction of the newer technique of Trans Carotid Artery Revascularization (TCAR) has shown promising results with significant reduction in the incidence of perioperative complications as compared to CEA and TF-CAS, however, there have been no randomized controlled trials comparing TCAR to either CEA or TF-CAS. Moreover, with the developments in the medical field with introduction of several new medications which have been demonstrated to successfully change the plaque morphology, there has been a renewed interest in exploring if the indications for surgical management for the asymptomatic carotid disease should be revisited.

Semaglutide and blood pressure: an individual patient data meta-analysis.

Randomized clinical trials (RCTs) assessing semaglutide reported reductions of systolic blood pressure (SBP) in trial populations with baseline blood pressure in the normotensive range. This study aimed to determine whether this SBP reduction is greater in hypertensive groups. Individual patient data (IPD) from three RCTs examining the effect of semaglutide 2.4 mg on body weight over 68 weeks were included. Trial participants were categorized according to a hypertension diagnosis, treatment or baseline measurement (HTN), baseline SBP > 130 mmHg (HTN130) or >140 mmHg (HTN140), and those with apparent resistant hypertension (RH). The primary analysis compared the in-trial change in SBP in the semaglutide and placebo arms. Alterations of anti-hypertensive medications were quantified by treatment intensity score and compared between arms. These analyses were performed using analysis of covariance. Overall, 3136 participants were included. The difference in SBP change between the treatment (n = 2109) and placebo (n = 1027) groups was -4.95 mmHg [95% confidence interval (CI) -5.86 to -4.05] overall. This difference was -4.78 mmHg (95% CI -5.97 to -3.59) for HTN, -4.93 mmHg (95% CI -6.75 to -3.11) for HTN130, -4.09 mmHg (95% CI -7.12 to -1.06) for HTN140, and -3.16 mmHg (95% CI -8.69-2.37) for RH. Reduction in SBP was mediated substantially by weight loss. The anti-hypertensive treatment intensity score decreased for those on semaglutide compared to placebo (-0.51; 95% CI -0.71 to -0.32). This IPD analysis of three large RCTs found blood pressure reductions with semaglutide in participants with hypertension that were similar to those seen in all trial participants. This finding may in part be due to concurrent reductions to anti-hypertensive medications. These results suggest that semaglutide is a useful adjunctive treatment for patients with hypertension and obesity.

Stenting versus medical treatment alone for symptomatic intracranial artery stenosis: a preplanned pooled individual patient data analysis

BackgroundWhether the safety and efficacy of percutaneous transluminal angioplasty and stenting (PTAS) is significantly different from that of medical treatment alone for symptomatic intracranial arterial stenosis (ICAS) is debatable. A...

Ketamine for Critically Ill Patients with Severe Acute Brain Injury: A Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials.

Patients with severe acute brain injury have a high risk of a poor clinical outcome due to primary and secondary brain injury. Ketamine reportedly inhibits cortical spreading depolarization, an electrophysiological phenomenon that has been associated with secondary brain injury, making ketamine potentially attractive for patients with severe acute brain injury. The aim of this systematic review is to explore the current literature regarding ketamine for patients with severe acute brain injury. We systematically searched international databases for randomized clinical trials comparing ketamine by any regimen versus placebo, no intervention, or any control drug for patients with severe acute brain injury. Two authors independently reviewed and selected trials for inclusion, extracted data, assessed risk of bias, and performed analysis using Review Manager and Trial Sequential Analysis. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcomes were the proportion of participants with an unfavorable functional outcome, the proportion of participants with one or more serious adverse events, and quality of life. We identified five randomized trials comparing ketamine versus sufentanil, fentanyl, other sedatives, or saline (total N = 149 participants). All outcomes were at overall high risk of bias. The proportions of participants with one or more serious adverse events did not differ between ketamine and sufentanil or fentanyl (relative risk 1.45, 95% confidence interval 0.81-2.58; very low certainty). Trial sequential analysis showed that further trials are needed. The level of evidence regarding the effects of ketamine on functional outcome and serious adverse events in patients with severe acute brain injury is very low. Ketamine may markedly, modestly, or not at all affect these outcomes. Large randomized clinical trials at low risk of bias are needed.

The effect of sodium-glucose cotransporter type 2 inhibitors on left ventricular diastolic function: current status and prospects

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) or gliflozins, are a new class of cardiovascular drugs with a proven clinical efficacy and a beneficial effect on prognosis in patients with heart failure with preserved ejection fraction (HFpEF). Impaired left ventricular (LV) diastolic function (DF) is an important element in the pathogenesis of HFpEF. Experimental studies have found intracellular mechanisms for the so-called diastolic effects in gliflozins. Studies using laboratory models of experimental HFpEF have demonstrated a positive effect of dapagliflozin and empagliflozin on the elastic properties of cardiomyocyte myofilaments, the dynamics of myocardial fibrosis, and intracellular sodium and calcium homeostasis. The significance of anti-inflammatory, antioxidant properties of gliflozins in improving the cardiomyocyte DF has been experimentally established. The effect of SGLT2 inhibitors on LV DF in patients at high risk for cardiovascular diseases and their complications, that has been demonstrated in relatively small clinical studies, is due to primary cardiac and secondary effects. Results of individual studies confirmed the protective (in relation to myocardial relaxation) properties of gliflozins in the conditions of a diastolic stress test. The regression of LV diastolic dysfunction associated with the SGLT2 inhibitor treatment found in small observational studies is important in the context of the significant beneficial effect of empagliflozin and dapagliflozin on the prognosis of cardiovascular diseases that has been demonstrated in large randomized clinical trials in patients with HFpEF.

Common Practice Patterns in the Diagnosis and Management of Acute Retinal Necrosis: A Survey Study of Uveitis Specialists

ABSTRACT Purpose Due to lack of large randomized clinical trials to determine best practices in treating acute retinal necrosis (ARN), there is not a clear consensus amongst ophthalmologists on how to best manage this potentially blinding condition. The aim of this study is to survey common practice patterns and analyze the factors that affect ophthalmologists’ management of ARN. Methods An anonymous survey was distributed to uveitis and retina specialists who are members of the American Uveitis Society (AUS) via email to query practice patterns regarding ARN. The survey included 22 questions with an additional 10 questions based on response. Survey question topics included demographic information, diagnostic testing, antiviral therapy, corticosteroids, and surgical procedures. Results 67 surveys were included for analysis. Most respondents (87%) always or frequently obtain intraocular aqueous fluid for diagnostic PCR testing. The majority of respondents would administer intravitreal antiviral injections to a unilateral immunocompetent ARN patient (67%), but would be even more likely to do so for a bilateral immunosuppressed ARN patient (87%). Respondents tend to treat ARN with systemic rather than local corticosteroids, with the majority (63%) of respondents initiating corticosteroid treatment 48 hours after treatment. Most respondents (79%) never perform a vitrectomy to manage ARN unless the patient has a retinal detachment or tear. The majority (63%) rarely or never perform prophylactic laser barricade, but may consider laser treatment if there is extensive retinal involvement. Conclusion Current practice patterns for diagnosis and management of ARN among AUS members generally align with the suggested practices outlined by the American Academy of Ophthalmology.

Effect of amino acid supplementation on short-term complications after gastrointestinal tumor surgery: the AMIGITS randomized clinical trial.

There is a scarcity of large randomized clinical trials on the efficacy and safety of high-dose amino acid supplementation (AAS) in patients with gastrointestinal tumors undergoing surgical treatment. This pragmatic, randomized, controlled, single-center, open-label, parallel-group AMIGITS trial was performed in a tertiary care teaching hospital. Patients with gastrointestinal tumors were randomly assigned to receive either AAS or standard care (SC). Amino acid targets were 2.0g/kg per day in the AAS group and 1.2g/kg per day in the SC group. The AAS group received additional amino acids intravenously, while the SC group received an iso-energetic 5% glucose intravenously. Overall, 407 patients (AAS group, 204; SC group, 203) were included in this study. During the intervention, the actual mean daily energy intake did not differ significantly between the AAS and SC groups (25.53 vs. 25.16kcal/kg per day, P=0.493). However, the actual mean daily amino acid intake was significantly higher in the AAS group than that in the SC group (1.81 vs. 0.94g/kg per day, P<0.001). The infection incidence during hospitalization and that within 30 days of surgery was significantly lower in the AAS group than that in the SC group (P=0.031 and P=0.024, respectively). The 30-day postoperative incidence of amino acid treatment-related adverse events and other complications did not significantly differ between the two groups. The postoperative hospital stay was significantly different between the two groups (P<0.001). AAS was associated with a reduced infection incidence within 30 days of major surgery in patients with gastrointestinal tumors and can be a promising strategy.

Antimalarial Drugs at the Intersection of SARS-CoV-2 and Rheumatic Diseases: What Are the Potential Opportunities?

Background and Objectives: The coronavirus disease of 2019 (COVID-19) pandemic has posed a serious threat to humanity and is considered a global health emergency. Antimalarial drugs (ADs) have been used in the treatment of immuno-inflammatory arthritis (IIA) and coronavirus infection (COVID-19). The aim of this review is to analyze the current knowledge about the immunomodulatory and antiviral mechanisms of action, characteristics of use, and side effects of antimalarial drugs. Material and Methods: A literature search was carried out using PubMed, MEDLINE, SCOPUS, and Google Scholar databases. The inclusion criteria were the results of randomized and cohort studies, meta-analyses, systematic reviews, and original full-text manuscripts in the English language containing statistically confirmed conclusions. The exclusion criteria were summary reports, newspaper articles, and personal messages. Qualitative methods were used for theoretical knowledge on antimalarial drug usage in AIRDs and SARS-CoV-2 such as a summarization of the literature and a comparison of the treatment methods. Results: The ADs were considered a "candidate" for the therapy of a new coronavirus infection due to mechanisms of antiviral activity, such as interactions with endocytic pathways, the prevention of glycosylation of the ACE2 receptors, blocking sialic acid receptors, and reducing the manifestations of cytokine storms. The majority of clinical trials suggest no role of antimalarial drugs in COVID-19 treatment or prevention. These circumstances do not allow for their use in the treatment and prevention of COVID-19. Conclusions: The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for COVID-19. Furthermore, the need for high doses in the treatment of viral infections increases the likelihood of gastrointestinal side effects, the prolongation of QT, and retinopathy. Large randomized clinical trials (RCTs) have refuted the fact that there is a positive effect on the course and results of COVID-19.

Intracoronary imaging guidance of percutaneous coronary interventions: how and when to apply validated metrics to improve the outcome.

Percutaneous coronary intervention (PCI) is still burdened by a substantial number of complications despite constant technological advances, including the advent of intracoronary imaging (ICI) techniques. ICI modalities have been instrumental for the understanding the mechanism of PCI failure. Thanks to the ability to detail the pre-intervention coronary anatomy and identify the features indicative of sub-optimal stent deployment, ICI techniques can be utilised to improve coronary interventions in different clinical scenarios. More recently large randomized clinical trials on ICI guidance confirmed the clinical effectiveness of this approach especially in complex high-risk interventions.

O-023 Does flushing with oil-based contrast during hysterosalpingography (HSG) increase the live birth rate as compared to water-based contrast: a prospective cohort study

Abstract Study question What is the effectiveness of oil-based contrast during HSG compared to water-based contrast? Summary answer HSG with oil-based contrast increased the live birth rate as compared to water-based contrast. What is known already Tubal flushing has long been thought to increase live birth rate in infertile couples. A large randomised clinical trial (RCT) in The Netherlands confirmed the long-term hypothesis that HSG with oil-based contrast (Lipiodolâ) increased the live birth rate as compared to HSG with water-based contrast. We assessed whether this treatment effect was also achieved with oil-based contrast in Chinese women. Study design, size, duration We performed a prospective cohort study between May 4, 2020 and March 30, 2022. A total of 1187 women were included in the analysis.These women were categorized into two groups based on the contrast they used: the Oil-Soluble Contrast Media (OSCM) group, which employed poppy seed oil, consisting of 569 cases, and the Water-Soluble Contrast Media (WSCM) group, which used iodixanol, comprising 618 cases. Participants/materials, setting, methods This study was conducted at Shanghai Jiao Tong University International Peace Maternity and Child Health Hospital .The primary outcome was ongoing pregnancy rate within 6 months after the examination.Secondary outcomes included clinical pregnancies, miscarriage, ectopic pregnancy and thyroid Stimulating Hormone. Main results and the role of chance The ongoing pregnancy rate of the oil group is significantly higher than that of the water group (24.1% versus 17.2%, rate ratio [RR], 1.53; 95% confidence interval [CI], 1.14 to 2.06; P = 0.004). Women in the oil group also achieved higher clinical pregnancy rate (32.2% versus 22.2%, RR, 1.67; 95% CI, 1.27 to 2.18, P &amp;lt; 0.001), higher live birth rate (23.9% versus 16.8%, RR, 1.56; 95% CI, 1.16 to 2.09, P = 0.003), and bore higher risk of miscarriage (8.0% versus 5.0%, RR, 1.67; 95% CI, 1.02 to 2.72, P = 0.04) than water group. Limitations, reasons for caution The sample size along with the data was obtained from a cohort study in a single center. Wider implications of the findings Tubal flushing with oil-based contrast medium is an effective treatment to improve the pregnancy outcomes of infertile women that should be part of every infertility work-up. Trial registration number not applicable

Effect of a behavioral nudge on adoption of an electronic health record-agnostic pulmonary embolism risk prediction tool: a pilot cluster nonrandomized controlled trial.

Our objective was to determine the feasibility and preliminary efficacy of a behavioral nudge on adoption of a clinical decision support (CDS) tool. We conducted a pilot cluster nonrandomized controlled trial in 2 Emergency Departments (EDs) at a large academic healthcare system in the New York metropolitan area. We tested 2 versions of a CDS tool for pulmonary embolism (PE) risk assessment developed on a web-based electronic health record-agnostic platform. One version included behavioral nudges incorporated into the user interface. A total of 1527 patient encounters were included in the trial. The CDS tool adoption rate was 31.67%. Adoption was significantly higher for the tool that included behavioral nudges (39.11% vs 20.66%; P < .001). We demonstrated feasibility and preliminary efficacy of a PE risk prediction CDS tool developed using insights from behavioral science. The tool is well-positioned to be tested in a large randomized clinical trial. Clinicaltrials.gov (NCT05203185).

Association of Herbal Tea and Follicle-Stimulating Hormone, Anthropometric Parameters, and Fasting Blood Glucose Levels Among Polycystic Ovarian Syndrome Women: A Systematic Review and Meta-Analysis of Clinical Trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to test our hypothesis that herbal tea may improve anthropometric parameters, metabolic factors, and hormone levels in women with polycystic ovarian syndrome (PCOS). A literature search was conducted on Information Sciences Institute, Medline (PubMed), Scopus, Embase, and Google Scholar, up to March 2023 without applying language or date restrictions. RCTs that assigned herbal tea vs. placebo on PCOS women and evaluated changes in anthropometric measurements, metabolic indices, or hormonal profiles were included. Six RCTs with 235 PCOS women (119 in the intervention and 116 in the control group) were included. Meta-analysis showed that herbal tea consumption led to significant decreases in weight (weighted mean difference [WMD], -2.02 kg; 95% confidence interval [CI], -3.25, -0.80), body mass index (BMI) (WMD, -0.88 kg/m2; 95% CI, -1.47, -0.28) and fasting blood glucose (FBG) (WMD, -6.47 mg/dL; 95% CI, -8.49, -4.45), compared to the control group. Herbal tea supplementation has also significantly increased follicle-stimulating hormone (FSH) concentration (WMD, 0.56 IU/L; 95% CI, 0.17, 0.95). Meanwhile, the effect of herbal tea on the waist/hip ratio, hip circumference, waist circumference, body fat, fasting insulin, FBG/insulin ratio, luteinizing hormone, total testosterone, and dehydroepiandrosterone sulfate was not significant. Herbal tea might be a potential supplemental therapy to manage weight, BMI, FBG, and FSH in PCOS women. Further large randomized clinical trials are recommended to affirm these findings.

Mechanical Valves: Past, Present, and Future-A Review.

The mechanical valve was first invented in the 1950s, and since then, a wide variety of prostheses have been developed. Although mechanical valves have outstanding durability, their use necessitates life-long treatment with anticoagulants, which increases the risk of bleeding and thromboembolic events. The current guidelines recommend a mechanical prosthetic valve in patients under 50-60 years; however, for patients aged 50-70 years, the data are conflicting and there is not a clear-cut recommendation. In recent decades, progress has been made in several areas. First, the On-X mechanical valve was introduced; this valve has a lower anticoagulant requirement in the aortic position. Second, a potential alternative to vitamin K-antagonist treatment, rivaroxaban, has shown encouraging results in small-scale trials and is currently being tested in a large randomized clinical trial. Lastly, an innovative mechanical valve that eliminates the need for anticoagulant therapy is under development. We attempted to review the current literature on the subject with special emphasis on the role of mechanical valves in the current era and discuss alternatives and future innovations.