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Lancet (London, England) Jun 2024Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake... (Review)
Review
Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic. The clinical presentation is usually uncomplicated, with peptic ulcer disease management based on eradicating H pylori if present, the use of acid-suppressing medications-most often proton pump inhibitors (PPIs)-or addressing complications, such as with early endoscopy and high-dose PPIs for peptic ulcer bleeding. Special considerations apply to patients on antiplatelet and antithrombotic agents. H pylori treatment has evolved, with the choice of regimen dictated by local antibiotic resistance patterns. Indications for primary and secondary prophylaxis vary across societies; most suggest PPIs for patients at highest risk of developing a peptic ulcer, its complications, or its recurrence. Additional research areas include the use of potassium-competitive acid blockers and H pylori vaccination; the optimal approach for patients at risk of stress ulcer bleeding requires more robust determinations of optimal patient selection and treatment selection, if any. Appropriate continuation of PPI use outweighs most possible side-effects if given for approved indications, while de-prescribing should be trialled when a definitive indication is no longer present.
PubMed: 38885678
DOI: 10.1016/S0140-6736(24)00155-7 -
Future Science OA Dec 2024We developed a machine learning model using EuroScore assumptions and preoperative and intraoperative risk factors to predict mortality after coronary artery bypass...
We developed a machine learning model using EuroScore assumptions and preoperative and intraoperative risk factors to predict mortality after coronary artery bypass graft (CABG). We retrospectively examined data from 108 CABG patients at King Abdullah University Hospital, classifying them into risk groups via EuroScore and predicting mortality through random forest classification. High-risk patients displayed longer surgical times and significant factors such as age and surgery choice. The median EuroScore was 0.95 (0.5-6.4). The model yielded high AUC scores (0.98, 0.95) indicating strong predictive accuracy. Our findings showed that the machine learning models combined with the EuroScore significantly improve post-CABG mortality prediction. For further validation, larger datasets are needed.
PubMed: 38884372
DOI: 10.2144/fsoa-2023-0152 -
Clinics in Colon and Rectal Surgery Jul 2024Microsatellite instability is rare in rectal cancer and associated with younger age of onset and Lynch syndrome. All rectal cancers should be tested for microsatellite... (Review)
Review
Microsatellite instability is rare in rectal cancer and associated with younger age of onset and Lynch syndrome. All rectal cancers should be tested for microsatellite instability prior to treatment decisions. Patients with microsatellite instability are relatively resistant to chemotherapy. However, recent small studies have shown dramatic response with neoadjuvant immunotherapy. Patients with Lynch syndrome have a hereditary predisposition to cancer and thus an elevated risk of metachronous cancer. Therefore, while "watch and wait" is a well-established practice for sporadic rectal cancers that obtain a complete clinical response after chemoradiation, its safety in patients with Lynch syndrome has not yet been defined. The extent of surgery for patients with Lynch syndrome and rectal cancer is controversial and there is significant debate as to the relative advantages of a segmental proctectomy with postoperative endoscopic surveillance versus a therapeutic and prophylactic total proctocolectomy. Surgical decision making for the patient with Lynch syndrome and rectal cancer is complex and demands a multidisciplinary approach, taking into account both patient- and tumor-specific factors. Neoadjuvant immunotherapy show great promise in the treatment of these patients, and further maturation of data from prospective trials will likely change the current treatment paradigm. Patients with Lynch syndrome and rectal cancer who do not undergo total proctocolectomy require yearly surveillance colonoscopies and should consider chemoprophylaxis with aspirin.
PubMed: 38882941
DOI: 10.1055/s-0043-1770717 -
The Journal of the Association of... Apr 2024Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug...
Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy Study: A Knowledge, Attitude, and Practice Study among Indian Interventional Cardiologists.
BACKGROUND
Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug management of CAD, including optimizing the duration of antiplatelet treatment regimens in the management of CAD, which is an intricate clinical issue. The available evidence indicates that East Asians have a higher bleeding risk. However, the Indian phenotype differs from that of East Asians, making this data confounding when applied to clinical decision-making among Indian patients. There is a need for a close understanding of Indian interventional cardiologists' perceptions of complex decision-making pertaining to antiplatelet agents among Indian CAD patients in real-world clinical settings.
AIM
This Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy (INDEPTH) study aims to assess the perspective of Indian interventional cardiologists regarding de-escalating from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), approach to decision-making, barriers, and related challenges in CAD management.
METHODS
A cross-sectional knowledge, attitude, and practice (KAP) study survey was carried out among Indian interventional cardiologists practicing across different regions of India. A total of 209 responses were received. Descriptive statistics was used to summarize all the parameters. IBM Statistical Package for the Social Sciences (SPSS) statistics was used for biostatistical analysis.
RESULTS
The study indicated that >90% of CAD patients received DAPT therapy immediately after percutaneous coronary intervention (PCI) (86.1%, < 0.001). About 115 (55%) of the respondents reported using calculator-based scoring for evaluating bleeding risk in patients on DAPT therapy for the management of acute coronary syndrome (ACS) with post-PCI ( = 0.167). Regarding the usual duration of DAPT therapy post-ACS, nearly half of the respondents, 94 (45%), said that 6-12 months is the usual duration for DAPT therapy in post-ACS patients, followed by > 12 months 94 (45%) of the respondents; 17 (8.1%) of the respondents reported it is 3-6 months, and lastly up to 3 months as per four (1.9%) of the respondents ( < 0.001). A total of 128 (61%) of the respondents strongly believe that balancing bleeding with ischemic risk influenced the choice of antiplatelet agent when treating established CAD. As per interventional cardiologists surveyed, the perfect de-escalation time frame for Indian CAD patients with high bleeding risk (HBR) is up to 3 months (35.9%, < 0.001), 6-12 months for medium bleeding risk (48.8%, < 0.001), and >12 months for low bleeding risk (65.6%, < 0.001). Regarding SAPT therapy, almost one-third of the respondents, 65 (31.1%), reported that they prescribed antiplatelet therapy other than aspirin in 20-40% of their SAPT-eligible patients. Furthermore, 69 (33%) of the respondents said that they preferred to prescribe clopidogrel in 50-75% of SAPT-eligible patients. While 64 (30.5%) prescribed in 25-50%, 53 (25.4%) prescribed in <25% and 23 (11%) of the respondents prescribed the drug in >75% of the SAPT-eligible patients. (p < 0.001). "Atorvastatin + clopidogrel" is the most preferred combination of SAPT primarily for the management of CAD among the majority of interventional cardiologists [33%, 95% confidence interval (CI): 1.97-2.24, < 0.001]. The study respondents also indicated a need for Indian-specific guidelines on de-escalating from DAPT to SAPT in CAD management.
CONCLUSION
The INDEPTH study indicated that the majority of CAD patients received DAPT immediately after PCI. The perfect de-escalation time frame for Indian CAD patients with "high-bleeding" risk is up to 3 and 6-12 months for "medium-bleeding" risk and >12 months for "low-bleeding" risk. One-third of respondents used clopidogrel as an antiplatelet agent in 50-75% of SAPT-eligible patients. Atorvastatin + clopidogrel is predominantly the most preferred combination of statin + SAPT for the management of CAD. Although the current international guidelines cover the Indian perspective to some extent, there is a need for Indian-specific guidelines on de-escalating from DAPT to SAPT.
Topics: Humans; India; Platelet Aggregation Inhibitors; Dual Anti-Platelet Therapy; Coronary Artery Disease; Cross-Sectional Studies; Cardiologists; Health Knowledge, Attitudes, Practice; Practice Patterns, Physicians'; Percutaneous Coronary Intervention; Female; Male; Clinical Decision-Making
PubMed: 38881086
DOI: 10.59556/japi.72.0515 -
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 the expression of FADS1, which controls the synthesis of n-6 highly...
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 the expression of FADS1, which controls the 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 proinflammatory 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.
OBJECTIVES
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2×2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 mo (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by polymerase chain reaction (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 with its placebo. Presence of ≥1 Indel I allele and an interaction term (I allele × active intervention) were covariates.
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, the presence of ≥1 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. The seAFOod polyp prevention trial and STOP-ADENOMA study were registered at International Standard Randomised Controlled Trial Number registry 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 -
Carcinogenesis Jun 2024In this study, we evaluated the effects of vitamin E δ-tocotrienol (DT3) and aspirin on Wnt signaling in human colon cancer stem cells (CCSCs) and in the prevention of...
In this study, we evaluated the effects of vitamin E δ-tocotrienol (DT3) and aspirin on Wnt signaling in human colon cancer stem cells (CCSCs) and in the prevention of adenoma formation in APCmin/+ mice. We found that knockdown of the adenomatous polyposis coli (APC) gene led to subsequent activation of Wnt signaling in colon epithelial cells (NCM460-APCsiRNA) and induction of β-catenin and its downstream target proteins c-MYC, cyclin D1, and survivin. When aspirin and DT3 were combined, cell growth and survival were inhibited and apoptosis was induced in colon epithelial cells and in CCSCs. However, DT3 and/or aspirin had little or no effect on control normal colon epithelial cells (NCM460-NCsiRNA). The induction of apoptosis was directly related to activation of caspase 8 and cleavage of BID to truncated BID. In addition, DT3 and/or aspirin-induced apoptosis was associated with cleaved PARP, elevated levels of cytosolic cytochrome c and BAX, and depletion of anti-apoptotic protein BCl-2 in CCSCs. The combination of aspirin and DT3 inhibited the self-renewal capacity, Wnt/β-catenin receptor activity, and expression of β-catenin and its downstream targets c-MYC, cyclin D1 and survivin in CCSCs. We also found that treatment with DT3 alone or combined with aspirin significantly inhibited intestinal adenoma formation and Wnt/ β-catenin signaling and induced apoptosis, compared to vehicle, in APCmin/+ mice. Our study demonstrated a rationale for further investigation of the combination of DT3 and aspirin for colorectal cancer prevention and therapy.
PubMed: 38877828
DOI: 10.1093/carcin/bgae041