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Supportive Care in Cancer : Official... Jun 2024We assumed that in Palliative Care, even in common clinical situations, the choice of drugs differs substantially between physicians. Therefore, we assessed the practice... (Comparative Study)
Comparative Study
PURPOSE
We assumed that in Palliative Care, even in common clinical situations, the choice of drugs differs substantially between physicians. Therefore, we assessed the practice of pharmaceutical treatment choices of physicians for cancer pain and opioid-induced nausea and vomiting (OINV) and the rationale for their choices.
METHODS
An online survey was conducted with physicians covering the following domains: i) Cancer pain therapy: non-opioids in addition to opioids: choice of drug ii) prevention of OINV: choice of drug and mode of application. Current guidelines concerning cancer pain therapy and prevention of OINV were compared.
RESULTS
Two-hundred-forty European physicians responded to our survey. i) Use of non-opioids in addition to opioids for the treatment of cancer pain: Only 1.3% (n = 3) of respondents never used an additional non-opioid. Others mostly used: dipyrone/metamizole (49.2%, n = 118), paracetamol/acetaminophen (34.2%, n = 82), ibuprofen / other NSAIDs (11.3%, n = 27), specific Cox2-inhibitors (2.1%, n = 5), Aspirin (0.4%, n = 1), no answer (2.9%, n = 7). ii) Antiemetics to prevent OINV: The drugs of choice were metoclopramide (58.3%, n = 140), haloperidol (26.3%, n = 63), 5-HT3 antagonists (9.6%, n = 23), antihistamines (1.3%, n = 3) and other (2.9%, n = 7); no answer (1.7%, n = 4). Most respondents prescribed the substances on-demand (59.6%, n = 143) while others (36.3%, n = 87) provided them as around the clock medication. Over both domains, most physicians answered that their choices were not based on solid evidence from randomized controlled trials (RCTs). Guidelines were inconsistent regarding if and what non-opioid to use for cancer pain and recommend anti-dopaminergic drugs for prevention or treatment of OINV.
CONCLUSIONS
Physician's practice in palliative care for the treatment of cancer pain and OINV differed substantially. Respondents expressed the lack of high-quality evidence- based information from RCTs. We call for evidence from methodologically high-quality RCTs to be available to inform physicians about the benefits and harms of pharmacological treatments for common symptoms in palliative care.
Topics: Humans; Analgesics, Opioid; Cancer Pain; Nausea; Vomiting; Practice Guidelines as Topic; Practice Patterns, Physicians'; Antiemetics; Palliative Care; Male; Europe; Health Care Surveys; Surveys and Questionnaires; Female; Middle Aged; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38879720
DOI: 10.1007/s00520-024-08628-7 -
Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
The American Journal of Clinical... Jun 2024A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated...
Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: A secondary analysis of the seAFOod polyp prevention trial.
BACKGROUND
A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for pro-inflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs.
OBJECTIVE
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2 x 2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 months (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by PCR blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention versus placebo. Presence of at least one Indel I allele and an interaction term (I allele x active intervention) were co-variates.
RESULTS
In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR] 0.92, 95% confidence interval 0.74, 1.16), mirroring original seAFOod trial analysis. However, presence of at least one I allele identified EPA users with a significant reduction in colorectal polyp number (IRR 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR.
CONCLUSIONS
The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted.
TRIAL REGISTRATION
The seAFOod polyp prevention trial and STOP-ADENOMA study are registered with https://www.isrctn.com as ISRCTN05926847.
PubMed: 38879016
DOI: 10.1016/j.ajcnut.2024.06.004 -
European Journal of Pharmaceutical... Jun 2024Dual antiplatelet therapy with aspirin and clopidogrel has reduced ischemic vascular events significantly. Genetic influence, especially those in clopidogrel...
Dual antiplatelet therapy with aspirin and clopidogrel has reduced ischemic vascular events significantly. Genetic influence, especially those in clopidogrel pharmacokinetic-relevant genes partially accounts for interindividual pharmacodynamic variability of clopidogrel. However, most studies have concentrated on the genetic variations in introns, exons, or promoters of the candidate genes, and the association between genetic variations in 3'-UTR in clopidogrel pharmacokinetic-relevant genes and clopidogrel response is unknown. In our study, ten different algorithms were applied to pick potential miRNAs targeting the clopidogrel pharmacokinetic-relevant genes. Furthermore, the correlation between miRNA expression profiles and mRNA expression of corresponding clopidogrel pharmacokinetic-relevant genes was analyzed. Through comprehensive analysis, including bioinformatics prediction and correlation analysis of miRNA and mRNA expression profiles, miR-218-5p and miR-506-5p were supposed to regulate the expression of PON1 via binding with its 3'-UTR. Moreover, PON1 rs854551 and rs854552 were located in miRNA recognizing sequences and may serve as potential miRSNPs possibly affecting PON1 expression. The rs854552 polymorphism was genotyped and platelet reactivity index (PRI) indicative of clopidogrel response was measured in 341 Chinese coronary artery disease (CAD) patients 24 h after administration of 300 mg clopidogrel. Our results showed that PON1 rs854552 had a significant influence on PRI in CAD patients, especially in patients with CYP2C19 extensive metabolic phenotype. In conclusion, PON1 rs854552 polymorphisms may affect clopidogrel response. Bioinformatics prediction followed by functional validation could aid in decoding the contribution of unexplained variations in the 3'-UTR in drug-metabolizing enzymes on clopidogrel response.
PubMed: 38878906
DOI: 10.1016/j.ejps.2024.106830 -
Clinical Drug Investigation Jun 2024Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited.
BACKGROUND
Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited.
OBJECTIVE
We estimate potentially clinically important DDI prevalence and examine the association between DDIs and (1) adverse drug events (ADEs), (2) emergency hospital attendance and (3) health-related quality of life (HRQoL) in an older community-dwelling population in Ireland.
METHODS
This is a prospective cohort study of community-dwelling older adults (N = 904) aged ≥ 70 years from 15 general practices in Ireland recruited in 2010 (wave-1) and followed-up over 2 years (wave-2; 2012-2013), with linked national pharmacy claims data. Individuals dispensed two or more drugs (wave-1: N = 842; wave-2: N = 763) were included. DDI prevalence at baseline, follow-up and 6 months prior to each health outcome was estimated. Multi-level regression was used to model the association between DDI-exposure and health outcomes at follow-up. DDI prevalence, adjusted incidence-rate ratios (aIRR), adjusted odds ratios (aOR), β coefficients and robust standard error (RSE) from multi-level regression analyses, and 95% confidence intervals (CIs) are reported.
RESULTS
At wave-1, n = 196 (23.3% [95% CI 20.5-26.3]), individuals were potentially exposed to ≥ 1 DDI, increasing to n = 345 (45.2% [41.7-48.9]) at wave-2. At 2-year follow-up, the median number of ADEs was 3 (interquartile range [IQR 2-5]); 229 (30.1%) had ≥ 1 emergency hospital attendance, and the mean EQ-5D was 0.74 (± 0.23). Evidence for the association between DDI-exposure and emergency hospital attendance at follow-up was lacking (aOR = 1.38 [0.42-4.53]). DDI-exposure was associated with an increasing number of ADEs (aIRR = 1.26 [1.03-1.55]), and decreasing EQ-5D utility (β = - 0.07, [-0.11 to -0.04], RSE = 0.02). Aspirin-warfarin, clarithromycin-prednisolone, amiodarone-furosemide, clarithromycin-salbutamol, rosuvastatin-warfarin, amiodarone-bisoprolol, and aspirin-nicorandil were common DDIs 6 months preceding these health outcomes.
CONCLUSIONS
We found a two-fold increase in DDI prevalence between wave 1 and 2. DDI exposure was associated with increasing ADEs and declining HRQoL at 2-year follow-up. Common DDIs involved anticoagulants, cardiovascular and antimicrobial drugs, which should be targeted for medicine optimisation.
Topics: Humans; Prospective Studies; Aged; Drug Interactions; Female; Male; Aged, 80 and over; Quality of Life; Drug-Related Side Effects and Adverse Reactions; Independent Living; Ireland; Cohort Studies; Prevalence; Emergency Service, Hospital
PubMed: 38878216
DOI: 10.1007/s40261-024-01369-9 -
Age and Ageing Jun 2024Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent... (Review)
Review
Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.
Topics: Humans; Peripheral Arterial Disease; Aged; Endovascular Procedures; Risk Factors; Chronic Limb-Threatening Ischemia; Vascular Surgical Procedures; Age Factors; Practice Guidelines as Topic
PubMed: 38877714
DOI: 10.1093/ageing/afae114 -
Clinical and Translational Science Jun 2024This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral...
This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.
Topics: Humans; Cytochrome P-450 CYP2C19; Atrial Fibrillation; Male; Female; Aged; Coronary Artery Bypass; Middle Aged; Clopidogrel; Postoperative Complications; Genotype; Platelet Aggregation Inhibitors; Platelet Aggregation; Incidence; Aspirin
PubMed: 38877696
DOI: 10.1111/cts.13862 -
Frontiers in Veterinary Science 2024The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)-induced immune...
AIMS
The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)-induced immune stress.
METHODS
Two hundred and forty one-day-old male Arbor Acres chicks were randomly divided into four groups (saline, LPS, saline + AEE and LPS + AEE) with six replicates of ten broilers each. The saline group and LPS group were fed the normal diet, while the other two groups received normal diet plus 0.1 g/kg AEE. Broilers in the LPS and LPS + AEE groups were injected intraperitoneally with 0.5 mg/kg B.W LPS in saline for seven consecutive days beginning at 14 days of age, while broilers in the saline and saline + AEE groups were injected with saline only.
RESULTS
The results showed that AEE improved the ileal morphology and increased the ratio of villus height to crypt depth of immune-stressed broilers. LPS-induced immune stress significantly reduced the expression of the genes for the tight junction proteins , zonula occludens-1 (), and , in the ileum, while AEE significantly up-regulated the expression of these genes. Compared with the saline group, the LPS-treated chickens showed significantly increased mRNA expression of the inflammatory factors tumor necrosis factor-α (), interleukin-1β (), interleukin-6 (), interleukin-10 (), cyclooxygenase-2 (), and microsomal Prostaglandin E Synthesase-1 () in the ileum, while they were significantly decreased by AEE supplementation. In addition, analysis of the ileal bacterial composition showed that compared with saline and LPS + AEE groups, the proportion of Firmicutes and in the LPS group was lower, while the proportion of Proteobacteria and was higher. Similarly, Line Discriminant Analysis Effect Size (LEfSe) analysis showed that compared with the LPS group, was dominant in the saline group, while the LPS + AEE group was rich in , , Ruminococcaceae, , , Oscillospiraceae, and .
CONCLUSION
These results indicate that dietary supplementation with 0.1 g/kg AEE could protect the intestinal health by improving the intestinal villus morphology, enhancing the expression of tight junction genes and alleviating inflammation to resist the immune stress caused by LPS stimulation in broilers, and the mechanism may involve -related signal transduction and improved intestinal microbiota composition.
PubMed: 38872795
DOI: 10.3389/fvets.2024.1401909 -
Clinical and Applied... 2024Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk...
BACKGROUND
Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk of aspirin-induced bleeding and carefully balancing its benefits against potential risks. The objective of this study was to create a practical nomogram for predicting bleeding risk in patients with a history of myocardial infarction treating with aspirin.
METHODS
A total of 2099 myocardial infarction patients with aspirin were enrolled. The patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation. Boruta analysis was utilized to identify clinically significant features associated with bleeding. Logistic regression model based on independent bleeding risk factors was constructed and presented as a nomogram. Model performance was assessed from three aspects: identification, calibration, and clinical utility.
RESULTS
Boruta analysis identified eight clinical features from 25, and further multivariate logistic regression analysis selected four independent risk factors: hemoglobin, platelet count, previous bleeding, and sex. A visual nomogram was created based on these variables. The model achieved an area under the curve of 0.888 (95% CI: 0.845-0.931) in the training dataset and 0.888 (95% CI: 0.808-0.968) in the test dataset. Calibration curve analysis showed close approximation to the ideal curve. Decision curve analysis demonstrated favorable clinical net benefit for the model.
CONCLUSIONS
Our study focused on creating and validating a model to evaluate bleeding risk in patients with a history of myocardial infarction treated with aspirin, which demonstrated outstanding performance in discrimination, calibration, and net clinical benefit.
Topics: Humans; Nomograms; Myocardial Infarction; Aspirin; Hemorrhage; Female; Male; Middle Aged; Aged; Risk Factors; Platelet Aggregation Inhibitors; Risk Assessment
PubMed: 38870349
DOI: 10.1177/10760296241262789