Pharmacological Classes Research Articles

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therapeutic area where drug repurposing has shown the most prominent impact. This review presents a compilation of medications that have been repurposed for the treatment of various types of cancers. It describes the initial therapeutic and pharmacological classes of the repurposed drugs and their new applications and mechanisms of action in cancer treatment. The review reports on drugs from various pharmacological classes that have been successfully repurposed for cancer treatment, including approved ones and those in clinical trials and preclinical development. It stratifies drugs based on their anticancer repurpose as multi-type, type-specific, and mechanism-directed, and according to their pharmacological classes. The review also reflects on the future potential that drug repurposing has in the clinical development of novel anticancer therapies.

Safety assessment of (S)-Equol: Subchronic toxicity study in Sprague Dawley Rats

(S)-Equol is a chemically synthesized nutraceutical compound and its consumption provides several health benefits for humans. The new nutraceutical, enantiopure (S)-Equol was studied for acute and sub-chronic toxicity in Sprague Dawley Rats. The oral acute toxicity study showed that (S)-Equol is safe > 2000–5000 mg/kg body weight and it classified into GHS category 5/Unclassified. The repeated dose administration of (S)-Equol at dose levels of 20, 60, and 160 mg/kg body weight for 14 days and 250, 500, and 1000 mg/kg body weight for 90-consecitve days. The 14 days repeated-dose toxicity study showed no adverse effects in Sprague Dawley rats. The 90-day repeated dose toxicity study showed a reduction in body weight gain than that of control group. No treatment-related contrary effects were perceived on haematology, clinical chemistry, coagulation, urine parameters analysed, organ weights (absolute and relative), neurological and ophthalmological examination. No treatment-related abnormal gross pathological findings were obtained from gross necropsy. However, as a treatment-related effect, a significant decrease in cholesterol levels for 14 and 90 days of repeated dose administration was observed, which is considered as a pharmacological class effect of the (S)-Equol. In comparison to the corresponding vehicle control group, the high dose treatment group for both sexes showed no treatment-related histopathological abnormalities. For female rats, the no-observed-adverse-effect-level (NOAEL) was 250 mg/kg/day and for male rats, the lowest-observed-adverse-effect level (LOAEL) was 250 mg/kg/day.

Effect of age on hypnotics’ efficacy and safety in insomnia: A systematic review and meta-analysis

ObjectiveThis systematic review and meta-analysis evaluates the efficacy in improving sleep quality and safety of hypnotics in individuals aged 65 years or older compared to those under 65 years. MethodsMEDLINE, EMBASE, Web of Science, and EBM Reviews were searched for randomized clinical trials comparing hypnotics to the placebo in adults with chronic insomnia between Jan 2000 and Dec 2022. The efficacy outcome included all participant self-assessments sleep quality questionnaires. The safety outcome included acceptability and tolerance. Standardized mean differences (SMD) was estimated using a random effect model. ResultsWe included 17 and 53 clinical trials with 3688 and 14,720 participants in the ≥65 years and <65 years group respectively. The SMD for the sleep quality outcome was −0.36 [Confidence interval (CI) 95 %: 0.45;-0.26] in the ≥65 years group compared to −0.51 [95%CI: 0.61; −0.41] in the <65 years group (p = 0.02). Differences in efficacy were observed between pharmacological classes. The overall SMD for the tolerance outcome was - 0.25 [95%CI: 0.34; −0.16] favoring the placebo group (p < 0.001). In the ≥65 years group the SMD was −0.07 [95%CI: 0.21; 0.08] compared to −0.31 [95%CI: 0.41; −0.21] in the <65 years group (p = 0.01). There were no differences for acceptability. ConclusionWe found that some hypnotics classes could be less effective in older individuals. We encourage authors to include details on multimorbidity and polypharmacy in their publications.

Pharmacovigilance study of tyrosine kinase inhibitors: Analysis of adverse reactions

The aim of the study is to analyze reports of adverse drug reactions published in the scientific literature occurring during and after the use of kinase inhibitors for the treatment of rheumatologic diseases to determine their type, frequency, and severity. The search was conducted in the MEDLINE and PubMed databases from January 2005 to May 2022. We found a total of 291 publications, from which we selected suitable ones for data extraction. We conducted descriptive and variation analyses as the main statistical analyses. We determined mean values, standard deviation, minimum, maximum, and 95% confidence intervals. The PICOS tool was used to evaluate the results. The analyzed population includes patients with rheumatologic and oncologic diseases. There is a significant interest in the drug safety of kinase inhibitors, as they represent a rapidly evolving and reliable pharmacological class. Clarifying the safety profile of their representatives remains important. In-depth review of full-text publications shows that the high frequency of reported serious ADRs is rather due to increased interest in reporting and publishing these cases than to their high frequency of occurrence.

Bridging gap in treatment of polycystic ovarian syndrome through drug repurposing: what we achieved and where we are?

Polycystic ovarian syndrome (PCOS) is one of the chief causes of infertility in women of reproductive age. Several drugs belonging to the oral contraceptive class have been approved for the treatment of PCOS. Nonetheless, the capability to target only a few symptoms of PCOS and fatal side effects are key hurdles to their use. Therefore, repurposing existing drugs can be promising in managing PCOS efficiently. Drugs from different pharmacological classes like antidiabetics (metformin, rosiglitazone, pioglitazone, and semaglutide), statins (simvastatin and atorvastatin), antiandrogen drugs (finasteride and flutamide), etc. demonstrated significant potential in managing PCOS. The present review offers a comprehensive overview of all the medications examined as potential repurposed options for the efficient treatment of PCOS. The pathogenesis of PCOS, existing therapies for PCOS and their challenges, drug repurposing and its significance is also explained. The small-molecular drugs from various pharmacological classes and different phytoceuticals repurposed against PCOS are discussed along with their anti-PCOS activity mechanisms. Moreover, novel drug targets responsible for PCOS and opportunities for drug repurposing are briefed. The repurposed drugs in clinical trials for PCOS and drug repurposing challenges are discussed. Thus, drug repurposing can serve as a potential way to effectively treat PCOS, reducing the extent of infertility and improving the quality of life of women.

Pharmaceutical Residues in Fishes and Macro Invertebrates around the Wastewater Treatment Plant Site at the University Teaching Hospital of Yaoundé, Cameroon

Introduction: Hospital effluents are one of the main sources of dissemination of pharmaceutical residues in hydro system. Worldwide, analyses of these effluents have revealed the presence of various pharmaceuticals. Very few studies assessing the contamination of solid matrices by pharmaceutical residues have been carried out in Africa, specifically in Cameroon. Objectives: The study aimed to detect pharmaceutical residues in solid environmental matrices at sites around the discharge of the effluent from the Yaoundé University Teaching Hospital. Methods: Four hundred and fifty-nine (459) macro invertebrates and twenty (20) Nile tilapia were collected in three sampling sites before and beyond the wastewater treatment plant of the Yaoundé University Teaching Hospital. The specimens were conserved in a cooler prior to freeze drying and grinding. The powders were sent for analysis at the Sefako Makgatho Health Sciences University in South Africa. The analysis was carried out using an ultra-high-performance liquid chromatography coupled with a triple quadrupole tandem mass spectrometer. Results: A total of ninety-nine pharmaceutical residues related to seventeen pharmacological classes were detected in all samples of macro invertebrates (72) and Nile tilapia (55 for fish viscera and 58 for fish flesh) collected. Antibiotics were the most represented (23.2 %), followed by anti-inflammatory (18.2 %), and anti-parasitics (9.1 %). More than half (53.6 %) of the drug residues detected in the fish samples were of the anti-inflammatory (21,71 %), antihypertensive (17,67 %) and antibiotic (13,13 %) classes. The number of drug residues detected in the macroinvertebrates before the treatment plant (41) was smaller than those detected after the treatment plant (67). Conclusion: Five therapeutic classes (antibiotics, anti-inflammatories, antihypertensive, antiparasitics and hormones) were mostly represented.These results are in line with the importance of considering diet of fishes and/or humans as an exposure pathway based on the great similarity in pharmaceutical composition between macroinvertebrates and Nile tilapia.

Trends and patterns of antimicrobial consumption at Benjamin Mkapa Zonal Referral Hospital, Dodoma, Tanzania: a cross-sectional retrospective analysis

ObjectiveThis study assessed the trends and patterns of antimicrobial consumption (AMC) from 2020 to 2021, 2021–2022 and 2022–2023 at the Benjamin Mkapa Zonal Referral Hospital (BMH) in Dodoma, Tanzania.DesignA retrospective...

Chronotropic Incompetence across Heart Failure Categories.

The HF syndrome is characterized by an autonomic unbalance with sympathetic hyperactivity which contributes to increased myocardial oxygen demand, oxidative stress, peripheral vasoconstriction, afterload mismatch with a progressive desensitization and down-regulation of cardiac β1-receptors. These changes, together with a few other structural and peripheral changes, lead to chronotropic incompetence (CI), such as the inability to increase heart rate (HR) consistently with activity or demand. CI, regardless of the method and cut-off adopted to define it, is associated with reduced exercise capacity and a worse prognosis. Furthermore, different pharmacological classes might interfere with the physiologic exercise-induced HR response, thus generating some confusion. In particular, the β-blockers, albeit lowering peak HR, are known to improve prognosis and left ventricular inotropic reserve so that their withdrawal should be avoided at least in HF with reduced and mildly reduced ejection fraction. Similarly, a still debated strategy to counterbalance a blunted exercise-induced HR response, is represented by rate-adapting pacing. The present review, besides supplying an overview on possible CI definitions, discusses the clinical impact of CI and potential pharmacological and non-pharmacological therapeutic strategies.

Drug-eluting devices versus angioplasty in infrapopliteal artery disease:an updated systematic review and meta-analysis

Abstract Background Clinically driven target lesion revascularization (CD-TLR) and restenosis are common complications in individuals with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease undergoing percutaneous transluminal angioplasty (PTA). Drug-eluting balloons, stents, and resorbable scaffolds have emerged as an alternative therapy that may decrease the recurrence of these complications compared to PTA. However, their efficacy and safety are still controversial. Purpose This study aims to update and provide new insights about coated balloons, stents, and resorbable scaffolds as drug-eluting devices compared to PTA in patients with CLTI and infrapopliteal artery disease. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing drug-eluting devices, such as stents, coated balloons, and resorbable scaffolds, to PTA in patients with CLTI and infrapopliteal artery disease. The primary endpoint of interest was (1) CD-TLR. We only included trials defining this outcome as angiographically confirmed restenosis associated with wound changes or change in Rutherford classification at 12 months follow-up. This study also reported the following secondary outcomes: (2) binary restenosis and (3) amputation. We performed a subgroup analysis of the drug-eluting devices and between the drug-eluting pharmacological class, comparing the limus drug family subgroup and Pactlitaxel subgroup. Results We included 6 RCTs, encompassing 1263 patients, of whom 761 (60.2%) received a drug-eluting device. The mean age was 70.94 years. In the pooled analysis, the primary endpoint of CD-TLR was not statistically significant(OR 0.79; 95% CI 0.56-1.12; p=0.64; figure 1A). Although binary restenosis (OR: 0.62; 95% CI 0.36-1.05; p= 0.04; Fig.1B) was not statistically significant, our subgroup analysis of different drug-eluting pharmacological classes was significantly different(p&amp;lt;0.01; Fig.1B). Furthermore, the -limus family subgroup presented with a significant lower (OR 0.39; 95% CI 0.25 - 0.61; p&amp;lt;0.01; Fig. 1B) binary restenosis. There was no significant difference in the amputation endpoint (OR: 1.12; 95% CI 0.52 - 2.49; p= 0.74) and among the drug-eluting devices subgroup (p=0.63; Fig. 1A) for the CD-TLR endpoint. Conclusion In this updated meta-analysis of patients with CLTI and infrapopliteal artery, drug-eluting devices were not associated with CD-TLR compared to PTA. However, the -limus drug family is associated with a more significant reduction in the binary restenosis endpoint.

Empirically establishing drug exposure records directly from untargeted metabolomics data.

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data independent of clinical records. Our library facilitates stratification of individuals in clinical studies based on the empirically detected medications, exemplified by drug-dependent microbiota-derived N-acyl lipid changes in a cohort with human immunodeficiency virus. The GNPS Drug Library holds potential for broader applications in drug discovery and precision medicine.

A novel immunopharmacological biocompound

The publication is devoted to topical issues of experimental study of new biocompounds, based on the creation of a consortium of biological composite compounds – biological active substances (metabiotics) produced by strains 59T and 60T of saprophytic compounds of the genus Bacillus subtilis. These strains are very promising for the creation of hepatopicts, new medicinal substances, in the creation and development of a new pharmacological class of hepatoprotectors. Previous studies have shown the safety and hepatoprotective effect of biologically active drugs. It is worth noting that the very effective compounds are the produced biologically active substances – metabolites of bacterial origin, on the basis of which it seems appropriate to create a new class of drugs – metabiotics. The absence of vegetative probiotic cells in such compounds will reduce the additional immune load on the body. The combined use of these compounds provides a potentiated pharmacological effect. In this regard, it seemed appropriate, under the conditions of modeling toxic liver damage by carbon tetrachloride, to conduct an experimental assessment of the immunotropic effect of biologically active substances (BAS) on laboratory animals in order to confirm the effect on cellular factors of immunity. The purpose of the study was to study the effect of the combined use of dietary supplements produced by Bacillus subtilis microorganisms on indicators of cellular immunity in laboratory animals with toxic liver damage. Acute toxic hepatitis was reproduced in white laboratory rats with repeated intragastric administration of carbon tetrachloride. The comparison drug was a registered hepatoprotective drug – ursosan. The immunotropic effect was assessed using factors such as: phagocytic activity of macrophages and neutrophils (FA), NBT test, quantitative assessment of antibody-forming cells, T and B lymphocytes. As a result of the studies performed, reliable data were obtained on an increase in the number of T and B lymphocytes, antibody-forming cells, as well as an increase in FA, which confirms the activation of all parts of cellular immunity in conditions of acute toxic liver damage. The data obtained allow us to recommend the studied biocompound for the creation of new drug candidates of microbiological origin, hepatoprotective agents with immunotropic effects.

Metagenomic insights into plasmid-mediated antimicrobial resistance in poultry slaughterhouse wastewater: antibiotics occurrence and genetic markers.

Slaughterhouse wastewater represents important convergence and concentration points for antimicrobial residues, bacteria, and antibiotic resistance genes (ARG), which can promote antimicrobial resistance propagation in different environmental compartments. This study reports the assessment of the metaplasmidome-associated resistome in poultry slaughterhouse wastewater treated by biological processes, employing metagenomic sequencing. Antimicrobial residues from a wastewater treatment plant (WWTP) that treats poultry slaughterhouse influents and effluents were investigated through high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Residues from the macrolide, sulfonamide, and fluoroquinolone classes were detected, the latter two persisting after the wastewater treatment. The genetic markers 16S rRNA rrs (bacterial community) and uidA (Escherichia coli) were investigated by RT-qPCR and the sul1 and int1 genes by qPCR. After treatment, the 16S rRNA rrs, uidA, sul1, and int1 markers exhibited reductions of 0.67, 1.07, 1.28, and 0.79 genes copies, respectively, with no statistical significance (p > 0.05). The plasmidome-focused metagenomics sequences (MiSeq platform (Illumina®)) revealed more than 100 ARG in the WWTP influent, which can potentially confer resistance to 14 pharmacological classes relevant in the human and veterinary clinical contexts, in which the qnr gene (resistance to fluoroquinolones) was the most prevalent. Only 7.8% of ARG were reduced after wastewater treatment, and the remaining 92.2% were associated with an increase in the prevalence of ARG linked to multidrug efflux pumps, substrate-specific for certain classes of antibiotics, or broad resistance to multiple medications. These data demonstrate that wastewater from poultry slaughterhouses plays a crucial role as an ARG reservoir and in the spread of AMR into the environment.

Medicación pediátrica de alto riesgo: propuesta de listado a través de la técnica de consenso interdisciplinar

IntroductionPediatric patients are more likely to experience medication-related errors and serious associated harms. The identification of high-risk medications (HRM) and their study in special populations, such as children with excess body weight, is a part of safety improvement strategies. ObjectiveTo generate, through a consensus technique structured by an interdisciplinary group of pediatricians and hospital pharmacists, an operational and updated list of HRM for hospital use in children over 2 years of age. The document was part of a collaboration project between the Spanish Society of Hospital Pharmacists and the Spanish Society of Pediatric Hospital Medicine. MethodsThe study was carried out in two sequential phases: a) preparation of a preliminary list of HRM through bibliographic review and b) subsequent application of the double-round Delphi method to agree on a definitive list of HRM. The results obtained were validated by calculating the probability of chance agreement and the modified Kappa statistic for each drug. ResultsThe original list obtained by bibliographic review included 26 pharmacological classes and 96 drugs. Of the total of 37 experts, 32 (86.4%) completed both rounds of the Delphi. The final consensus list of HRM incorporated 24 pharmacological classes and 100 drugs. The modified Kappa statistic reflected a high percent agreement (94.9%) in the consensus reached by the participants. ConclusionThis list can establish a tool for future studies and interventions to improve the safety of medications in general pediatric population, as well as in high-risk subgroups, such as pediatric patients with excess body weight.

An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury.

The recent rise in acute kidney injury (AKI) incidence, with approximately 30% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI. By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported. Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors. By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts.

Polypills in the Management of Cardiovascular Risk-A Perspective.

Cardiovascular disease and cardiovascular risk factors are global healthcare problems, given their high prevalence and the recognized low rates of adequate control despite the abundant body of evidence on different therapeutic options. The World Heart Federation has scrutinized the reasons for poor control of cardiovascular risk factors. Among these reasons, patients' poor adherence to treatment regimens as well as limited rates of evidence-based therapy prescription from healthcare providers play a substantial role in the challenge of cardiovascular risk management. Polypills are fixed-dose combinations including two or more active drugs, from different pharmacological classes, combined in a single dosage form. Polypills were designed to simplify the clinical management of pharmacotherapy and increase adherence to treatment. From this perspective, we discuss the current literature on the use of polypills in the primary and secondary prevention of cardiovascular disease as well as future challenges and the potentials of this treatment strategy.

Empagliflozin: Primus Inter Pares Among Sodium-Glucose Cotransporter-2 Inhibitors?

Sodium/glucose cotransporter-2 (SGLT2) inhibitors are a novel class of antidiabetic medications which have proved capable of providing breakthrough cardiovascular (CV) benefits in a variety of clinical scenarios, including patients with heart failure or obesity, irrespective of diabetic status. Several SGLT2 inhibitors are available, but the most prominent ones are canagliflozin, dapagliflozin, and empagliflozin. Several studies have focused on empagliflozin and its effects on the risk of heart failure incidence and recurrences. Most recently, empagliflozin has been recently tested in patients with recent myocardial infarction in the EMPAgliflozin on Hospitalization for Heart Failure and Mortality in Patients With aCuTe Myocardial Infarction randomized trial, with apparently ambiguous findings. The present viewpoint succinctly illustrates the main features of SGLT2 inhibitors as a pharmacologic class, their ever expanding role as a CV medication, and the comparative effectiveness of different individual SGLT2 inhibitors, explicitly commenting on the recent data on empagliflozin in patients with acute myocardial infarction. The reader will find in this article a poignant perspective on this novel avenue for CV prevention and treatment, which greatly expands the management armamentarium of CV practitioners. Indeed, we make the case that SGLT2 inhibitors have a clearly favorable class effect, with differences between individual agents mainly suitable for personalization of care and minimization of side effects.

Adverse Drug Reactions Reporting Profile in Tertiary Referral Hospital: A Retrospective Pharmacovigilance Study in Indonesia

Background: Pharmacovigilance is administered to several pharmacological classes of drugs worldwide. However, there are still insufficient data regarding the prevalence and general characteristics of drug reactions, especially in developing countries. Objective: This study aimed to determine the prevalence and characteristics of ADRs, including the pharmacological class involved, and report and classify the clinical manifestations associated with ADRs. Methods: This retrospective study was based on patient ADR reports during observation. Prevalence, patient demographics, and other data were evaluated using descriptive statistics. Results: Of 773 reports that met the inclusion criteria, most were doctors (80.6%), followed by pharmacists (18.7%). Of the total cases, 430 (55.6%) occurred in the women. Most suspected ADRs occurred in the 19-60 years age group (583; 75.4%). The highest incidence of ADR was observed in patients using antineoplastic agents (19.5%), systemic antibacterials (16.4%), or antihypertensives (12.5%). The majority of clinical manifestations were gastrointestinal disorders (41.7%), and approximately 309 (40%) ADR cases continued with antagonists/antidotes. Approximately 62% of the patients who experienced ADRs recovered. Conclusion: Antineoplastic, systemic antibacterial, and antihypertensive drugs appeared to be the most common drugs used for suspected ADR cases in this hospital. ADR reporting has been running well, but not all healthcare workers have participated actively. Hopefully, the results of this research will contribute to the upcoming strategies for pharmacovigilance activities in this hospital and other healthcare facilities to improve the quality and quantity of ADR reporting and increase the safety of medication usage.

Pharmacological Prescription at the End of Life: Quality Assessment in the Transition of Care to a Community Palliative Care Support Team.

Appropriate pharmacological management is a cornerstone of quality in palliative care (PC), focusing on comfort and quality of life. Therapeutic review is crucial in PC, aiming to optimize symptom relief, reduce adverse effects, and manage drug interactions. This study aims to delve into the real-world pharmacological prescription practices within a Community Palliative Care Support Team (CPCST) in the northern region of Portugal, comparing practices at admission and at the last consultation before death. It is an observational, cross-sectional, retrospective study without intervention involving patients admitted to a CPCST in 2021. Data were obtained from clinical records, and the statistical analysis included descriptive and inferential measures. Sixty-four patients were included, with an average age of 77.34 years, referred mainly by a specialized Hospital Palliative Care Support Team (65.63%). Polypharmacy was present, with a significant increase in opioids, antipsychotics, prokinetics, antiemetics, antispasmodics, and local corticosteroids, and a reduction in drugs for peptic ulcer and gastroesophageal reflux treatment, antithrombotics, hypolipidemics, antihypertensives, and antidiabetics, among others. The oral route was preferred, decreasing between the two analyzed moments (85.5% versus 49.1%). Pro re nata (PRN) medications increased significantly (p ≤ 0.001). The prescription profile reflects a focus on symptom relief. The deprescription of drugs for chronic comorbidities suggests adaptation to care goals. At the end of life, PRN medications increase significantly (1.34 versus 3.26, p ≤ 0.001), administered as needed to soothe fluctuating symptoms. The pharmacological classes that have significantly increased are relevant in alleviating common symptoms in PC. The use of alternative routes for medication administration increases as instability of the oral route occurs, leading to a reduction in orally administered medications. Among these alternatives, the subcutaneous route shows the largest increase. The findings underscore the importance of flexible and responsive medication strategies in end-of-life care.

Thiazide diuretics versus loop diuretics in stage 3-5 CKD: impact on cardiorenal outcomes

ABSTRACT Objectives The association between diuretic use and cardiorenal outcomes remains limited in patients with stage 3–5 chronic kidney disease (CKD) and hypertension. To address this gap, we aim to investigate the long-term clinical impact of diuretic use with its pharmacological classification in Taiwanese patients with stage 3–5 CKD and hypertension who were concurrently received angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). Methods Using data from the National Health Insurance Research Database (January 2008 to December 2019), we focused on individuals with stage 3–5 CKD receiving ACEIs/ARBs between 2010 and 2018. We categorized the cohort into non-diuretic, loop diuretic (furosemide), thiazide diuretic, and combination diuretic groups. We used a Cox proportional hazards regression model with propensity score matching to analyze the influence of diuretics on all-cause mortality, cardiovascular (CV) death, and cardiorenal adverse outcomes. Results The study included 59,719 patients, with 17,585 in the non-diuretic group and 42,134 in the diuretic group. Diuretics including furosemide use was significantly associated the risks of hospitalization for decompensated congestive heart failure (CHF), acute renal failure (ARF), end-stage renal disease (ESRD) requiring dialysis, CV mortality, and all-cause mortality (p-value <0.001). Thiazide diuretics showed no such adverse outcomes associations. The group receiving both thiazide and furosemide was more associated with all-cause mortality than the nondiuretic, thiazide, and furosemide monotherapy groups (all p-value <0.001). Conclusion Among stage 3–5 CKD patients on ACEIs/ARBs, loop diuretics exposure was associated with increased mortality and hospitalization for cardiorenal events, while thiazide diuretics exposure in isolation had no such associations. In the present data, we cannot evaluate the relationship between furosemide-associated adverse outcomes and worse renal function. These findings highlight the need for randomized controlled trials to assess the safety of loop diuretics in this population, urging caution in their prescription without a clear clinical indication.

Adherence to guidelines in curative treatment of venous thromboembolism in cancer patients: Insights from a retrospective Tunisian study.

To describe the management and treatment practices of venous thromboembolism (VTE) in cancer patients, assess compliance with the 2023 European Society for Medical Oncology recommendations, and identify factors that may limit or influence their application. We conducted, in a Tunisian center, a retrospective study that included patients treated for cancer or hematologic malignancies and diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism between January 1, 2022, and August 1, 2023. The study involved 90 patients. DVTs were significantly predominant (81.1%). VTE mostly occurred within 3 months of the cancer diagnosis (41.1%). All patients received anticoagulant treatment. The most frequently prescribed class of anticoagulants was direct oral anticoagulants (42.2%), followed by low molecular weight heparin (36.7%), and finally vitamin K antagonists (21.1%). Financial constraints and/or refusal of social security to provide the treatment were the main cause for changes in the anticoagulant therapy (16.7%). Deaths (25.5%) and repermeabilization of the initially thrombosed venous network on imaging (11.1%) were the two primary reasons for treatment discontinuation. Bleeding complication was the cause of treatment modification or discontinuation in 7.7% and 5.5% of patients, respectively. Overall, guidelines were fully followed in 49 patients (54.4%) concerning the choice of pharmacological class, dose and duration of treatment. Financial constraints experienced by patients were significantly and independently associated with lower adherence to recommendations (p=0.032). Adherence to guidelines is insufficient. Measures must be implemented to enhance the management of VTE and to develop strategies for improving access to anticoagulants.