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International Journal of Molecular... Jun 2024This report describes major pathomechanisms of disease in which the dysregulation of host inflammatory processes is a major factor, with cardiovascular disease (CVD) as... (Review)
Review
This report describes major pathomechanisms of disease in which the dysregulation of host inflammatory processes is a major factor, with cardiovascular disease (CVD) as a primary model, and reviews strategies for countermeasures based on synergistic interaction between various agents, including drugs and generally regarded as safe (GRAS) natural medical material (NMM), such as , spice phytochemicals, and fruit seed flavonoids. The 15 well-defined CVD classes are explored with particular emphasis on the extent to which oxidative stressors and associated ischemia-reperfusion tissue injury contribute to major symptoms. The four major categories of pharmaceutical agents used for the prevention of and therapy for CVD: statins, beta blockers (β-blockers), blood thinners (anticoagulants), and aspirin, are presented along with their adverse effects. Analyses of major cellular and molecular features of drug- and NMM-mediated cardioprotective processes are provided in the context of their development for human clinical application. Future directions of the evolving research described here will be particularly focused on the characterization and manipulation of calcium- and calcineurin-mediated cascades of signaling from cell surface receptors on cardiovascular and immune cells to the nucleus, with the emergence of both protective and pathological epigenetic features that may be modulated by synergistically-acting combinations of drugs and phytochemicals in which phytochemicals interact with cells to promote signaling that reduces the effective dosage and thus (often) toxicity of drugs.
Topics: Humans; Phytochemicals; Cardiovascular Diseases; Animals
PubMed: 38892364
DOI: 10.3390/ijms25116176 -
AAPS PharmSciTech Jun 2024Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply...
Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.
Topics: Powders; Rheology; Drug Contamination; Excipients; Acetaminophen; Cellulose; Pharmaceutical Preparations; Quality Control; Aspirin; Chemistry, Pharmaceutical; Lactose; Drug Compounding; Lubricants; Bulk Drugs
PubMed: 38890193
DOI: 10.1208/s12249-024-02856-0 -
The Journal of Arthroplasty Jun 2024Low-dose aspirin is an effective venous thromboembolism (VTE) prophylactic medication in primary total joint arthroplasty (TJA), but the efficacy and safety of the...
BACKGROUND
Low-dose aspirin is an effective venous thromboembolism (VTE) prophylactic medication in primary total joint arthroplasty (TJA), but the efficacy and safety of the different formulations of chewable and enteric-coated have not been compared. The purpose of this study was to investigate the VTE rates and gastrointestinal (GI) complication rates of chewable and enteric-coated 81 mg aspirin BID for VTE prophylaxis in primary TJA.
METHODS
A retrospective, single-institution cohort study was performed on patients who underwent primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) from 2017 to 2021. Comparisons were made between 4,844 patients who received chewable, non-coated aspirin 81 mg and 4,388 patients who received enteric-coated 81 mg aspirin. Power analysis demonstrated that 1,978 and 3,686 patients were needed per group to achieve a power of 80% for 90-day VTE rates (utilizing inferiority testing) and GI complications (utilizing superiority testing), respectively. Patients had similar baseline characteristics. Statistical analyses were done utilizing T-tests and Chi-Square tests, with statistical significance defined as a P-value < 0.05.
RESULTS
There were no significant differences in the incidences of postoperative VTE (0.31 versus 0.55%; P = 0.111) or GI complications (0.14 versus 0.14%; P = 1.000) between patients who received either chewable or enteric-coated 81 mg aspirin BID in the overall comparison that included both THA and TKA patients combined, or THA patients alone. However, the VTE incidence for TKA patients alone was significantly lower with chewable than enteric-coated aspirin (0.22 versus 0.62%; P = 0.037), with no difference in GI complications (0.13 versus 0.19%; P = 0.277).
CONCLUSIONS
Low-dose aspirin in an enteric-coated formulation is inferior to chewable aspirin for VTE prophylaxis in primary TKA, but not inferior in THA patients. Both formulations have a similar GI complication rate. Therefore, it is reasonable to consider a transition from enteric-coated to uncoated chewable low-dose aspirin.
PubMed: 38889809
DOI: 10.1016/j.arth.2024.06.023 -
Journal of Clinical Oncology : Official... Jun 2024JCO Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of...
JCO Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by mutational status was a preplanned study. gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant ( = .13). Overall survival was similarly improved for patients with gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.
PubMed: 38889377
DOI: 10.1200/JCO.23.01680 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries... (Review)
Review
Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid.
PubMed: 38888755
DOI: 10.1007/s00210-024-03240-2 -
Acta Cardiologica Jun 2024Effective treatment of non-ST-segment elevation acute coronary syndromes (NSTEACS) requires careful assessment of both ischaemic and bleeding risks. We aimed to analyse...
BACKGROUND
Effective treatment of non-ST-segment elevation acute coronary syndromes (NSTEACS) requires careful assessment of both ischaemic and bleeding risks. We aimed to analyse risk distribution and evaluate antiplatelet prescription behaviours in real-life settings.
METHODS
Data from 1100 NSTEACS patients in Buenos Aires, Argentina, from the Buenos Aires I Registry, with a 15-month follow-up, were analysed. In-hospital and 6-month GRACE scores, CRUSADE, and Precise DAPT scores were calculated.
RESULTS
The mean age was 65.4 ± 11.5 years with a majority being male (77.2%). In-hospital mortality was 2.7%, primarily due to cardiovascular causes (1.8%). Bleeding events occurred in 20.9% of patients, with 4.9% classified as ≥ BARC 3. Predominance of low bleeding (71.3%) and ischaemic (55.8%) risks on admission was observed. At 6 months, the low-risk Precise category (70.9%) and GRACE (44.1%) categories prevailed. Linear correlation analysis showed a moderately positive correlation ( = 0.61, < .05) between ischaemic-haemorrhagic risks. Regarding the prescription of antiplatelet agents, in the low ischaemic-haemorrhagic risk group, there was a predominance of aspirin + clopidogrel (41.2%) over other high-potency antiplatelet regimens (aspirin + ticagrelor or prasugrel). In the low ischaemic and high haemorrhagic risk group, aspirin and clopidogrel were also predominant (58%).
CONCLUSIONS
Our analysis underscores the significant relationship between ischaemic and haemorrhagic risks during NSTEACS hospitalisation. Despite the majority of patients falling into the low-intermediate risk category, the prescription of P2Y12 inhibitors in real-life settings does not consistently align with these risks.
PubMed: 38888102
DOI: 10.1080/00015385.2024.2365606 -
Cureus May 2024Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays...
Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays have only detected IgG and IgM isotypes of this antibody. However, newer assays also detect the IgA isotype. The problem lies in the largely unknown significance of this IgA isotype. This paper describes a middle-aged male who presented with hypertensive emergency and was later found to have IgA anti-beta-2 glycoprotein I antibodies. He was treated with multiple anti-hypertensives, aspirin, and statin therapy. In addition to the case, we discuss the implications of this IgA isotype and how it may relate to antiphospholipid syndrome, despite not currently being included in the laboratory diagnostic criteria for the disease.
PubMed: 38887346
DOI: 10.7759/cureus.60560 -
Analytical Chemistry Jul 2024This study investigated the added value of combining both near-infrared (NIR) and Raman spectroscopy into a single NIRaman Combi Fiber Probe for in-line blend potency...
This study investigated the added value of combining both near-infrared (NIR) and Raman spectroscopy into a single NIRaman Combi Fiber Probe for in-line blend potency determination in the feed frame of a rotary tablet press. A five-component platform formulation was used, containing acetylsalicylic acid as the Active Pharmaceutical Ingredient (API). Calibration models for the determination of 1 and 5% label claim tablets were developed using NIR and Raman spectra of powder blends ranging from 0.75 to 1.25% and 3.75 to 6.25% API, respectively. Step-change experiments with deliberate 10% deviation steps from the label claims were performed, from which the collected spectra were used for model validation. For model development and validation, low-level data fusion was explored through concatenation of preprocessed NIR and Raman spectra. Mid-level data fusion was also evaluated, based on extracted features of the preprocessed data. Herewith, score vectors were extracted by transforming preprocessed spectra through Principal Component Analysis, followed by critical feature selection through Elastic Net Regression. Partial Least Squares regression was applied to regress singular, low-level or mid-level fused data versus blend potency. It could be concluded that irrespective of the data fusion technique, an increase in Step-Change Sensitivity (SCS) and decrease in Root Mean Squared Error (RMSE) was observed when predicting the 5% step-change experiment. For the prediction of the 1% step-change experiment, no added benefit with regard to SCS and RMSE was observed due to the addition of the noisy NIR spectra.
Topics: Spectrum Analysis, Raman; Tablets; Spectroscopy, Near-Infrared; Aspirin; Principal Component Analysis; Calibration
PubMed: 38887018
DOI: 10.1021/acs.analchem.4c01134 -
Perioperative Medicine (London, England) Jun 2024The purpose of the current study was to assess the efficacy of tranexamic acid (TXA) on reducing bleeding in cardiac surgical patients with preoperative antiplatelet... (Review)
Review
BACKGROUND
The purpose of the current study was to assess the efficacy of tranexamic acid (TXA) on reducing bleeding in cardiac surgical patients with preoperative antiplatelet therapy (APT).
METHODS
Five electronic databases were searched systematically for randomized-controlled trials (RCTs) assessing the impact of intravenous TXA on post-operative bleeding on cardiac surgical patients with preoperative APT until May 2024. Primary outcome of interest was post-operative blood loss. Secondary outcomes of interest included the incidence of reoperation due to post-operative bleeding, post-operative transfusion requirements of red blood cells (RBC), fresh-frozen plasma (FFP), and platelet concentrates. Mean difference (MD) with 95% confidence interval (CI) or odds ratios (OR) with 95% CI was employed to analyze the data. Subgroup and meta-regression analyses were performed to assess the possible influence of TXA administration on reducing bleeding and transfusion requirements.
RESULTS
A total of 12 RCTs with 3018 adult cardiac surgical patients (TXA group, 1510 patients; Control group, 1508 patients) were included. The current study demonstrated that TXA significantly reduced post-operative blood loss (MD = - 0.38 L, 95% CI: - 0.73 to - 0.03, P = 0.03; MD = - 0.26 L, 95% CI: - 0.28 to - 0.24, P < 0.00001; MD = - 0.37 L, 95% CI: - 0.63 to - 0.10, P = 0.007) in patients receiving dual antiplatelet therapy (DAPT), aspirin, or clopidogrel, respectively. Patients in TXA group had significantly lower incidence of reoperation for bleeding as compared to those in Control group. The post-operative transfusion of RBC and FFP requirements was significantly lower in TXA group than Control group. Subgroup analyses showed that studies with DAPT discontinued on the day of surgery significantly increased the risk of post-operative blood loss [(MD: - 1.23 L; 95% CI: - 1.42 to - 1.04) vs. (MD: - 0.16 L; 95% CI: - 0.27 to - 0.05); P < 0.00001 for subgroup difference] and RBC transfusion [(MD: - 3.90 units; 95% CI: - 4.75 to - 3.05) vs. (MD: - 1.03 units; 95% CI: - 1.96 to - 0.10); P < 0.00001 for subgroup difference] than those with DAPT discontinued less than 5-7 days preoperatively.
CONCLUSIONS
This meta-analysis demonstrated that TXA significantly reduced post-operative blood loss and transfusion requirements for cardiac surgical patients with preoperative APT. These potential clinical benefits may be greater in patients with aspirin and clopidogrel continued closer to the day of surgery.
TRIAL REGISTRATION NUMBER
CRD42022309427.
PubMed: 38886771
DOI: 10.1186/s13741-024-00418-3 -
Paediatric and Perinatal Epidemiology Jun 2024Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring.
BACKGROUND
Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring.
OBJECTIVES
We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health.
METHODS
The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma.
RESULTS
Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias.
CONCLUSIONS
We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.
PubMed: 38886184
DOI: 10.1111/ppe.13097