-
Trials May 2024The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence.... (Comparative Study)
Comparative Study
BACKGROUND
The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses.
METHODS
In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies.
DISCUSSION
Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses.
TRIAL REGISTRATION
ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Aortic Valve; Aspirin; Bioprosthesis; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Platelet Aggregation Inhibitors; Prospective Studies; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Thrombosis; Time Factors; Treatment Outcome
PubMed: 38755709
DOI: 10.1186/s13063-024-08175-w -
JAMA Network Open May 2024Dual antiplatelet therapy (DAPT) appears to be an effective treatment option for minor (nondisabling) acute ischemic stroke. This conclusion is based on trials that... (Meta-Analysis)
Meta-Analysis Comparative Study
IMPORTANCE
Dual antiplatelet therapy (DAPT) appears to be an effective treatment option for minor (nondisabling) acute ischemic stroke. This conclusion is based on trials that include both transient ischemic attack (TIA) and minor stroke; however, these 2 conditions may differ.
OBJECTIVE
To compare DAPT regimens specifically for minor stroke.
DATA SOURCES
PubMed was searched for randomized clinical trials published up to November 4, 2023. Search terms strategy included TIA, transient ischemic attack, minor stroke, or moderate stroke, with the filter randomized controlled trial. Unpublished data on minor stroke were sourced from authors and/or institutions.
STUDY SELECTION
Trials testing DAPT within the first 24 hours of a minor stroke (defined as a National Institutes of Health Stroke Scale score ≤5) were included by consensus. Of 1508 studies screened, 6 (0.3%) initially met inclusion criteria and were reviewed.
DATA EXTRACTION AND SYNTHESIS
The study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by multiple observers. Bayesian fixed-effect network meta-analysis was conducted. Secondary analysis performed for high-risk TIA alone.
MAIN OUTCOMES AND MEASURES
Treatments were ranked using a probability measure called surface under the cumulative rank curve (SUCRA). The primary outcome was subsequent ischemic stroke at 90 days. Secondary outcomes included major hemorrhage, mortality, and hemorrhagic stroke. The number needed to treat (NNT) and number needed to harm (NNH) were obtained.
RESULTS
Five trials were included that described 28 148 patients, of whom 22 203 (78.9%) had a minor stroke. Of these, 13 995 (63.0%) were in DAPT groups and 8208 (37.0%) in aspirin (acetylsalicylic acid) groups. Aspirin and ticagrelor had a 94% probability of being the superior treatment for minor stroke (SUCRA, 0.94) for the primary outcome. Both aspirin and ticagrelor (NNT, 40; 95% CI, 31-64) and aspirin and clopidogrel (NNT, 58; 95% CI, 39-136) were superior to aspirin alone in the prevention of recurrent ischemic stroke at 90 days. Both treatments had higher rates of major hemorrhage than aspirin alone (NNH for aspirin and ticagrelor, 284; 95% CI, 108-1715 vs NNH for aspirin and clopidogrel, 330; 95% CI, 118-3430), but neither had increased risk of hemorrhagic stroke or death. For high-risk TIA, ticagrelor and aspirin had a 60% probability (SUCRA, 0.60) and clopidogrel and aspirin had a 40% probability (SUCRA 0.40) of being a superior treatment; neither was optimum, but both were superior to aspirin alone for the primary outcome.
CONCLUSIONS AND RELEVANCE
These findings suggest that DAPT with aspirin and ticagrelor has higher probability of being the superior treatment among patients with minor stroke when presence of CYP2C19 loss-of-function alleles has not been excluded. For patients with TIA, the superiority of aspirin and ticagrelor vs aspirin and clopidogrel was not demonstrated.
Topics: Humans; Aspirin; Bayes Theorem; Dual Anti-Platelet Therapy; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 38753327
DOI: 10.1001/jamanetworkopen.2024.11735 -
Scientific Reports May 2024Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and...
Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids' addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete Freund's adjuvant-induced inflammatory von Frey model. Both induce analgesia via N-arachidonoylphenolamine (AM404) formation in the midbrain periaqueductal grey (PAG) nociception region, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways/networks, including endocannabinoid signaling, genes pertaining to mechanical nociception, and fatty acid amide hydrolase (FAAH). Both regulate the expression of key genes encoding FAAH, 2-arachidonoylglycerol (2-AG), cannabinoid receptor 1 (CNR1), CNR2, transient receptor potential vanilloid type 4 (TRPV4), and voltage-gated Ca channel. Phase 1 trial (NCT05484414) (02/08/2022) demonstrates SRP-001's safety, tolerability, and favorable pharmacokinetics, including a half-life from 4.9 to 9.8 h. Given its non-hepatotoxicity and clinically validated analgesic mechanisms, SRP-001 offers a promising alternative to ApAP, NSAIDs, and opioids for safer pain treatment.
Topics: Animals; Male; Mice; Acetaminophen; Amidohydrolases; Analgesics; Arachidonic Acids; Benzoquinones; Glycerides; Periaqueductal Gray; Transcriptome
PubMed: 38750093
DOI: 10.1038/s41598-024-61791-z -
American Journal of Public Health May 2024Providing aspirin during pregnancy is a critical intervention proven to reduce the rates of preeclampsia in patients at risk. This quality improvement project prepared...
Providing aspirin during pregnancy is a critical intervention proven to reduce the rates of preeclampsia in patients at risk. This quality improvement project prepared family medicine residents to use public health strategies to improve screening of pregnant patients at risk for preeclampsia in an underserved population. A preeclampsia awareness campaign was launched utilizing a publicly available toolkit, while a multidisciplinary team implemented systemic clinical changes to increase the rates of preeclampsia risk factor screening and aspirin prescription to prevent preeclampsia. (. 2024;114(S4):S318-S321. https://doi.org/10.2105/AJPH.2024.307667).
Topics: Humans; Aspirin; Pregnancy; Female; Pre-Eclampsia; Quality Improvement; Internship and Residency; Family Practice; Risk Factors; Mass Screening
PubMed: 38748955
DOI: 10.2105/AJPH.2024.307667 -
Scientific Reports May 2024
PubMed: 38744874
DOI: 10.1038/s41598-024-61715-x -
Experimental and Clinical... Apr 2024Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational...
Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.
OBJECTIVES
Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function.
MATERIALS AND METHODS
We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/μL.
RESULTS
Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units.
CONCLUSIONS
End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.
Topics: Humans; Thrombelastography; Liver Transplantation; Male; Female; Middle Aged; Splenectomy; Treatment Outcome; Blood Coagulation; Adult; End Stage Liver Disease; Time Factors; Blood Platelets; Predictive Value of Tests; Platelet Activation; Platelet Function Tests; Platelet Aggregation Inhibitors; Anticoagulants; Platelet Count; Blood Coagulation Tests; Aspirin; Prospective Studies
PubMed: 38742319
DOI: 10.6002/ect.2023.0329 -
ACS Applied Materials & Interfaces May 2024Drug-induced liver injury (DILI) is one of the most common reasons for acute liver failure and a major reason for the withdrawal of medications from the market. There is...
Drug-induced liver injury (DILI) is one of the most common reasons for acute liver failure and a major reason for the withdrawal of medications from the market. There is a growing need for advanced in vitro liver models that can effectively recapitulate hepatic function, offering a robust platform for preclinical drug screening applications. Here, we explore the potential of self-assembling liver spheroids in the presence of electrospun and cryomilled poly(caprolactone) (PCL) nanoscaffolds for use as a new preclinical drug screening tool. This study investigated the extent to which nanoscaffold concentration may have on spheroid size and viability and liver-specific biofunctionality. The efficacy of our model was further validated using a comprehensive dose-dependent acetaminophen toxicity protocol. Our findings show the strong potential of PCL-based nanoscaffolds to facilitate in situ self-assembly of liver spheroids with sizes under 350 μm. The presence of the PCL-based nanoscaffolds (0.005 and 0.01% w/v) improved spheroid viability and the secretion of critical liver-specific biomarkers, namely, albumin and urea. Liver spheroids with nanoscaffolds showed improved drug-metabolizing enzyme activity and greater sensitivity to acetaminophen compared to two-dimensional monolayer cultures and scaffold-free liver spheroids. These promising findings highlight the potential of our nanoscaffold-based liver spheroids as an in vitro liver model for drug-induced hepatotoxicity and drug screening.
Topics: Spheroids, Cellular; Drug Evaluation, Preclinical; Acetaminophen; Humans; Tissue Scaffolds; Liver; Chemical and Drug Induced Liver Injury; Polyesters; Cell Survival; Animals
PubMed: 38741479
DOI: 10.1021/acsami.3c17384 -
Journal of the American Board of Family... 2024Creating useful clinical quality measure (CQM) reports in a busy primary care practice is known to depend on the capability of the electronic health record (EHR). Two...
BACKGROUND
Creating useful clinical quality measure (CQM) reports in a busy primary care practice is known to depend on the capability of the electronic health record (EHR). Two other domains may also contribute: supportive leadership to prioritize the work and commit the necessary resources, and individuals with the necessary health information technology (IT) skills to do so. Here we describe the results of an assessment of the above 3 domains and their associations with successful CQM reporting during an initiative to improve smaller primary care practices' cardiovascular disease CQMs.
METHODS
The study took place within an AHRQ EvidenceNOW initiative of external support for smaller practices across Washington, Oregon and Idaho. Practice facilitators who provided this support completed an assessment of the 3 domains previously described for each of their assigned practices. Practices submitted 3 CQMs to the study team: appropriate aspirin prescribing, use of statins when indicated, blood pressure control, and tobacco screening/cessation.
RESULTS
Practices with advanced EHR reporting capability were more likely to report 2 or more CQMs. Only one-third of practices were "advanced" in this domain, and this domain had the highest proportion of practices (39.1%) assessed as "basic." The presence of advanced leadership or advanced skills did not appreciably increase the proportion of practices that reported 2 or more CQMs.
CONCLUSIONS
Our findings support previous reports of limited EHR reporting capabilities within smaller practices but extend these findings by demonstrating that practices with advanced capabilities in this domain are more likely to produce CQM reports.
Topics: Humans; Primary Health Care; Electronic Health Records; Oregon; Cardiovascular Diseases; Washington; Quality of Health Care; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Idaho; Aspirin; Quality Indicators, Health Care; Quality Improvement; Smoking Cessation; Leadership
PubMed: 38740491
DOI: 10.3122/jabfm.2023.230116R1 -
Se Pu = Chinese Journal of... Apr 2024The consumption of poultry eggs has increased in recent years owing to the abundance of production and improvements in living standards. Thus, the safety requirements of...
The consumption of poultry eggs has increased in recent years owing to the abundance of production and improvements in living standards. Thus, the safety requirements of poultry eggs have gradually increased. At present, few reports on analytical methods to determine banned veterinary drugs during egg-laying period in poultry eggs have been published. Therefore, establishing high-throughput and efficient screening methods to monitor banned veterinary drugs during egg-laying period is imperative. In this study, an analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combined with QuEChERS-based techniques was developed for the simultaneous determination of 31 banned veterinary drugs encompassing nine drug classes (macrolides, antipyretic and analgesic drugs, sulfonamides, antibacterial synergists, anticoccidials, antinematodes, quinolones, tetracyclines, amphenicols) in different types of poultry eggs. The main factors affecting the response, recovery, and sensitivity of the method, such as the extraction solvent, purification adsorbent, LC separation conditions, and MS/MS parameters, were optimized during sample pretreatment and instrumental analysis. The 31 veterinary drug residues in 2.00 g eggs were extracted with 2 mL of 0.1 mol/L ethylene diamine tetraacetic acid disodium solution and 8 mL 3% acetic acid acetonitrile solution, and salted out with 2 g of sodium chloride. After centrifugation, 5 mL of the supernatant was cleaned-up using the QuEChERS method with 100 mg of octadecylsilane-bonded silica gel (C), 50 mg of -propylethylenediamine (PSA), and 50 mg of NH-based sorbents. After nitrogen blowing and redissolution, the 31 target analytes were separated on a Waters CORTECS UPLC C analytical chromatographic column (150 mm×2.1 mm, 1.8 μm) at a flow rate, column temperature, and injection volume of 0.4 mL/min, 30 ℃, and 5 μL, respectively. Among these analytes, 26 analytes were acquired in dynamic multiple reaction monitoring (MRM) mode under positive electrospray ionization (ESI) conditions using (A) 5 mmol/L ammonium acetate (pH 4.5) and (B) acetonitrile as mobile phases. The gradient elution program was as follows: 0-2.0 min, 12%B-30%B; 2.0-7.5 min, 30%B-50%B; 7.5-10.0 min, 50%B; 10.0-10.1 min, 50%B-100%B; 10.1-12.0 min, 100%B; 12.0-12.1 min, 100%B-12%B; The five other target analytes were acquired in MRM mode under negative electrospray ionization (ESI) conditions using (A) HO and (B) acetonitrile as mobile phases. The gradient elution program was as follows: 0-2.0 min, 12%B-40%B; 2.0-6.0 min, 40%B-80%B; 6.0-6.1 min, 80%B-100%B; 6.1-8.0 min, 100%B; 8.0-8.1 min, 100%B-12%B. Matrix-matched external standard calibration was used for quantification. The results showed that all the compounds had good linear relationships within their respective ranges, with correlation coefficients of >0.99. The limits of detection (LODs) and quantitation (LOQs) were 0.3-3.0 μg/kg and 1.0-10.0 μg/kg, respectively. The average recoveries of the 31 banned veterinary drugs spiked at three levels (LOQ, maximum residue limit (MRL), and 2MRL) in poultry eggs ranged from 61.2% to 105.7%, and the relative standard deviations (RSDs) ranged from 1.8% to 17.6%. The developed method was used to detect and analyze banned veterinary drugs in 30 commercial poultry egg samples, including 20 eggs, 5 duck eggs, and 5 goose eggs. Enrofloxacin was detected in one egg with a content of 12.3 μg/kg. The proposed method is simple, economical, practical, and capable of the simultaneous determination of multiple classes of banned veterinary drugs in poultry eggs.
Topics: Tandem Mass Spectrometry; Animals; Veterinary Drugs; Eggs; Chromatography, High Pressure Liquid; Drug Residues; Poultry; Food Contamination
PubMed: 38736385
DOI: 10.3724/SP.J.1123.2023.11015 -
Chemosphere Jul 2024The effective removal of micropollutants by water treatment technologies remains a significant challenge. Herein, we develop a CoFe layered double hydroxide (CoFeLDH)...
The effective removal of micropollutants by water treatment technologies remains a significant challenge. Herein, we develop a CoFe layered double hydroxide (CoFeLDH) catalytic membrane for peroxymonosulfate (PMS) activation to achieve efficient micropollutant removal with improved mass transfer rate and reaction kinetics. This study found that the CoFeLDH membrane/PMS system achieved an impressive above 98% degradation of the probe chemical ranitidine at 0.1 mM of PMS including five more micropollutants (Sulfamethoxazole, Ciprofloxacin, Carbamazepine, Acetaminophen and Bisphenol A) at satisfactory level (above 80%). Moreover, significant improvements in water flux and antifouling properties were observed, marking the membrane as a specific advancement in the removal of membrane fouling in water purification technology. The membrane demonstrated consistent degradation efficiency for several micropollutants and across a range of pH (4-9) as well as different anionic environments, thereby showing it suitability for scale-up application. The key role of reactive species such as SO, and O - radicals in the degradation process was elucidated. This is followed by the confirmation of the occurrence of redox cycling between Co and Fe, and the presence of CoOH that promotes PMS activation. Over the ten cycles, the membrane could be operated with a flux recovery of up to 99.8% and maintained efficient performance over 24 h continuous operation. Finally, the efficiency in degrading micropollutants, coupled with reduced metal leaching, makes the CoFeLDH membrane as a promising technology for application in water treatment.
Topics: Water Purification; Water Pollutants, Chemical; Membranes, Artificial; Hydroxides; Phenols; Peroxides; Benzhydryl Compounds; Carbamazepine; Ranitidine; Acetaminophen; Sulfamethoxazole; Ciprofloxacin; Catalysis; Cobalt; Oxidation-Reduction
PubMed: 38735495
DOI: 10.1016/j.chemosphere.2024.142318