Multiple Drug Use Research Articles

A Qualitative Study on the Experiences of Patients with Pulmonary Hypertension Undergoing Polypharmacy

Aims/Background Pulmonary hypertension (PH) is a severe progressive disease characterized by elevated blood pressure in the lungs. Medications are a critical form of treatment for patients with PH. This study aims to explore the experiences of patients with PH undergoing polypharmacy, thereby providing a more concrete foundation for formulating targeted intervention measures. Methods A purposive sampling method was used to select 13 PH patients treated in a grade III hospital in Zhejiang Province from December 2023 to February 2024 as the research subjects. This study is a descriptive qualitative research design, where the patients were interviewed face-to-face in a semi-structured manner. The data were analyzed, summarized and extracted using the traditional content analysis method. Results There were five themes and ten sub-themes surrounding the polypharmacy experiences of the PH patients: (1) Negative emotional experience of multidrug use, including lack of disease-related medication knowledge and insufficient ability to obtain medication information; (2) Complex physical testing of multiple drugs, including adverse reactions and complex dose titration; (3) Economic burden; (4) Coping difficulties, including insufficient drug safety, excessive reliance on medical personnel, and lack of opportunities for deep participation; (5) Desire for supports, including professional and social support, as well as those from family, colleagues and classmates. Conclusion Disease, treatment, psychological factors, and social customs affect PH patients’ drug use post-diagnosis, with varying experiences and degrees. Healthcare providers must offer tailored care and practical strategies for managing multiple drug use, considering patients’ unique experiences and needs.

Rational Exploration of 2,4-Diaminopyrimidines as DHFR Inhibitors Active against Mycobacterium abscessus and Mycobacterium avium, Two Emerging Human Pathogens.

Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections. However, existing DHFR inhibitors designed for Gram-negative bacteria often fail against mycobacterial DHFRs. Here, we detail the rational design of NTM DHFR inhibitors based on P218, a malarial DHFR inhibitor. We identified compound 8, a 2,4-diaminopyrimidine exhibiting improved pharmacological properties and activity against purified DHFR, and whole cell cultures of two predominant NTM species: Mycobacterium avium and Mycobacterium abscessus. This study underscores the potential of compound 8 as a promising candidate for the in vivo validation of DHFR as an effective treatment against NTM infections.

The association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study.

Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being. To determine the association between drugs/vaccines commonly prescribed to older people and BP risk. We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis. Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03). Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.

Twenty-year trends in peripheral artery disease, lower extremity revascularization, and lower extremity amputation in newly diagnosed type 2 diabetes

Abstract Background Trends in risk of lower extremity complications in patients with newly diagnosed type 2 diabetes (T2DM) are largely unexplored. Purpose To examine the 5-year risk trends of peripheral artery disease (PAD), lower extremity revascularization (LER), and lower extremity amputation (LEA) in patients with newly diagnosed T2DM over a 25-year study period. Methods We conducted a cohort study that included all patients in Denmark diagnosed with T2DM from 1996 to 2015, who had no prior hospital diagnosis of atherosclerotic cardiovascular disease. These patients were age- and sex-matched with up to three comparisons from the general population. Individuals were assigned to 5-year calendar periods based on their year of inclusion and were followed for 5 years. The primary outcomes were the 5-year risks of PAD, LER, and LEA. Age- and sex-adjusted hazard ratios (aHR) were computed using Cox regression analysis. Results The study cohort consisted of 288,825 newly diagnosed T2DM patients (52% males; median age 61 years) and 782,232 comparisons from the general population. From 1996-2000 to 2015-2020, the 5-year risk of PAD decreased from 2.2% to 1.2% (aHR 0.56 [95% CI 0.52-0.61]), LER from 0.7% to 0.5% (aHR 0.73 [95% CI 0.63-0.84]), and LEA from 1.0% to 0.4% (aHR 0.44 [95% CI 0.38-0.50]) in T2DM patients (Figure). Compared with the general population, the 5-year risk differences decreased from 1.4% to 0.5% for PAD, from 0.4% to 0.2% for LER, and from 0.8% to 0.3% for LEA. The distribution of LEA types (hip/thigh, knee/lower leg, or ankle/foot/toe amputation) remained largely stable over time in T2DM patients. Use of prophylactic cardiovascular medications in T2DM patients increased notably during the study period, especially use of statins (5% to 50%) and multiple antihypertensive drugs (18% to 33%). Conclusions Over recent decades, the risks of PAD, LER, and LEA have decreased in patients with newly diagnosed T2DM, approaching the risk levels observed in the general population. This coincided with a great increase in use of prophylactic cardiovascular medications among T2DM patients.Trends in lower extremity complications.

Multiple behavioural risk factors and mental health complaints among adults in Estonia

Abstract Background Behavioural risk factors are inter-related and often coincide, resulting in potentially worse mental health outcomes. This study explores the association between multiple behavioural risk factors and mental health among adults in Estonia. Methods We used nationally representative survey data from 2020 (n = 6404) to study the co-occurrence of lifestyle risk factors (smoking, alcohol consumption, physical inactivity, unhealthy diet, drug use, and high screen time) in relation to mental health indicators. Latent class analysis (LCA) was used to identify lifestyle risk profiles, while regression analysis was used to examine associations. Results Mental health outcomes were more frequent among females and younger respondents, but 54.4% of respondents reported having at least one mental health problem. Using LCA, three lifestyle classes were identified: multiple risk factors (17.9% of respondents), healthy lifestyle (76.1%), and drug use lifestyle (5.9%). Compared to individuals in healthy lifestyle class, respondents in multiple risk factors had higher odds for experiencing depressiveness (OR 1.46; CI 1.24-1.72), stress (OR 1.26; CI 1.06-1.49), and suicidal thoughts (OR 1.50; CI 1.26-1.80), as well as self-reported diagnoses of depression and insomnia, and using medications, such as antidepressants, hypnotics and sedatives. Respondents in drug use lifestyle had 1.5-2.5 times higher odds for all mental health items compared to healthy lifestyle class with largest difference found for suicidal thoughts (OR 2.46; CI 1.92-3.16) and medication use (OR 2.58; CI 1.91-3.47). Conclusions The current data highlights the importance of preventive measures targeting multiple behavioural risk factors, given that these factors often coincide. Moreover, the study showed a high proportion of individuals with at least one mental health problem, highlighting the necessity to continue efforts in preventive and interventive methods. Key messages • The study highlights the significant association between multiple behavioural risk factors and mental health outcomes. • The study also emphasizes the importance of focused interventions targeting multiple behavioural risk factors to address the increased risk of mental health problems.

Pattern of Non-prescription Drug Use in Febrile children Prior to Outpatient Visit in a Semi Urban Tertiary Hospital

Background: Use of drugs without any prior medical consultation is a common practice in lower and middle income countries which causes health hazards and misuse or overuse of drugs. Fever is a common symptom for which parents seek medical care according to their knowledge and ability. Objective: To observe the patterns of drug use, source of drugs, and identify the factors associated with the use of non-prescription drugs in febrile children. Methods: This is a hospital based observational cross sectional study conducted over a period of four months in the Ashulia Women and Children Hospital (AWCH). Study population was the febrile children attending paediatric out patient department. Data was collected from parents/caregiver through a pretested questionnaire. Result: Among 614 study children 77.2% had fever for less than 5 days and out of them 544(90.7%) children were treated with different types of drugs. Out of them 90.1% children had drugs without any prescription mostly from drug retailers (54.8%). Commonly used drug was antipyretic (99.3%) followed by antibiotic (49.1%) and antihistamine (31.9%) and 73.16% children were treated with multiple drugs. Cefixime (40.8%) was found to be a widely used antibiotic. Perception of mild illness (53.3%) was reported predominantly as a cause of using drugs without medical advice. Conclusion: This study reveals use of multiple drugs including antibiotics for treating febrile illness of children prior to medical consultation and treatment was most commonly taken from drug retailers. BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 39-42

A Molecular Fragment Representation Learning Framework for Drug-Drug Interaction Prediction.

The concurrent use of multiple drugs may result in drug-drug interactions, increasing the risk of adverse reactions. Hence, it is particularly crucial to propose computational methods for precisely identifying unknown drug-drug interactions, which is of great significance for drug development and health. However, most recent studies have limited the drug-drug interaction prediction task to identifying interactions between substructures, overlooking molecular hierarchical information. Moreover, the extracted substructures in these methods are always restricted to have the same number of atoms as contained in the molecular graph, which does not align with real-world facts. In this study, a molecular fragment representation learning framework for drug-drug interaction prediction is introduced. Initially, a fragment extraction module is designed to acquire a series of molecular fragments. Subsequently, to capture more comprehensive features, molecular hierarchical information is effectively integrated, enabling drug-drug interaction prediction by identifying pairwise interactions between molecular fragments of each drug. Comprehensive evaluations demonstrate that the proposed method achieved state-of-the-art performance in both DrugBank and Twosides datasets, particularly achieving an improved accuracy of over 20% for unseen drugs in both two datasets. Furthermore, case studies and visual analysis confirm that the proposed method can accurately identify crucial substructures influencing the interactions, which are basically consistent with functional group structures in reality. In conclusion, this method not only enhances the performance of drug-drug interaction prediction but also offers high interpretability. Source code is freely available at https://github.com/kennysyp/MFR-DDI .

Magnitude of multiple drug use and determinants of vulnerability among chronic kidney disease inpatients in Ethiopia: a multi-center study

BackgroundPatients with chronic kidney disease frequently face various nutritional and metabolic problems that necessitate the use of multiple medications. This multiple drug use can lead to several drug-related problems including adverse drug events, hospital admissions, poor medication adherence, harmful drug interactions, inadequate therapeutic outcomes, and death. Despite these challenges, there is a notable lack of studies on the extent of multiple drug use and its determinants among patients with chronic kidney disease in Ethiopia. This study aims to assess the magnitude of multiple drug use and identify the determinants of vulnerability among patients with chronic kidney disease in Ethiopia.MethodA hospital-based cross-sectional study was conducted among patients with chronic kidney disease. Eligible participants were selected using a simple random sampling technique. Frequency and percentage calculations were performed for categorical variables, while means and standard deviations were used for continuous variables. The chi-square test and t-test were used to compare the proportions and means, respectively. Binary logistic regression was used to identify the determinants of multiple drug use, with statistical significance determined by a p-value of less than 0.05 and a 95% confidence interval. Guidelines and previous literature were utilized to assess the magnitude of multiple drug use.ResultsA total of 230 patients were enrolled, with more than half being male. The overall magnitude of multiple drug use was 83.0%. Diuretics being the most frequently prescribed medication class followed by angiotensin converting enzyme inhibitors. Patients aged 65 years and above (AOR = 4.91 (95% CI 1.60-15.03)), CKD stage five (AOR) = 5.48 (95% CI 1.99–15.09)), and the presence of comorbid conditions (AOR) = 3.53 (95% CI 1.55–8.06)) were significantly associated with multiple drug use.ConclusionChronic kidney disease patients exhibited a high rate of multiple drug use. The presence of comorbid conditions, disease progression and older age are significant determinates of this vulnerability. Health care providers should pay particular attention to these factors to manage and mitigate the risks associated with multiple drug use.

EFFECTS OF CARICA PAPAPYA SEED EXTRACT ON HISTOPATHOLOGICAL CHANGES IN AMINOGLYCOSIDE-TRIGGERED ACUTE NEPHROTOXICITY IN EXPERIMENTAL RATS

Background: Nephrotoxicity is an emerging complication arising with the use of multiple drugs and dietary modifications. The objective of this study was to determine the nephroprotective effect of aqueous extract of Carica papaya seeds in aminoglycoside induced acute nephrotoxicity in rats. Methods: This Quasi Experimental study was conducted on 30 Sprague Dawley rats. After nephrotoxicity was confirmed by measuring serum urea and creatinine levels histomorphological examination of kidney tissue was done. Results: Group A, Group C and Group B had a mean serum urea level of 24.70±1.633, 82.70±2.587 and 81.00±1.247 mg/dL respectively (p<0.05), showing nephrotoxicity on day 6. On day 11, mean blood urea level for Group C was 50.60±1.857 mg/dL (p<0.05) compared to Group B with mean blood urea level 78.60±1.240. The reduced mean blood urea levels of Group C in comparison to Group B indicated nephroprotection from aqueous extract of Carica papaya seeds. In Group A, Group B and Group C the mean serum creatinine level was 0.750±0.619, 1.980±0.467 and 2.030±0.667 mg/dL (p<0.05) respectively, on day 6 indicating nephrotoxicity with Gentamycin. Group B had mean serum creatinine levels of 1.920±0.0389 at day 11 while Group C had a mean serum creatinine of 1.380±0.611 after 5 days of therapy with Carica papaya seed aqueous extract on day 11 indicating nephroprotection. Conclusion: Aqueous extract of Carica papaya seeds has significant nephroprotective effects on aminoglycoside induced acute nephrotoxicity. Pak J Physiol 2024;20(3):3?7 DOI: https://doi.org/10.69656/pjp.v20i3.1637

Abstract 31: Deacetylation Mimetic Mutation of Mitochondrial Superoxide Dismutase Attenuates Angiotensin II-Induced Hypertension by Protecting Against Oxidative Stress

Almost one-half of adults have hypertension, and blood pressure is poorly controlled in a third of patients despite the use of multiple drugs, likely due to mechanisms that are not affected by current treatments. Hypertension is linked to oxidative stress; however, common antioxidants are ineffective. Hypertension is associated with inactivation of key intrinsic mitochondrial antioxidant, superoxide dismutase 2 (SOD2), due to hyperacetylation but the role of specific SOD2 lysine residues has not been defined. Hypertension is associated with SOD2 acetylation at Lysine 68 (Circ Res. 2020;126(4):439-452) and we suggested that deacetylation mimetic mutation of K68 to Arginine in SOD2 inhibits vascular oxidative stress and attenuates hypertension. To test this hypothesis, we have developed a new deacetylation mimic SOD2-K68R mice. We performed in vivo studies in SOD2-K68R mice using angiotensin II (AngII) model of vascular dysfunction and hypertension. AngII infusion in wild-type mice induced vascular inflammation and oxidative stress, and increased blood pressure to 160 mm Hg. SOD2-K68R mutation completely prevented increase in mitochondrial superoxide, abrogated vascular oxidative stress, preserved endothelial nitric oxide production, protected vasorelaxation, and attenuated AngII-induced hypertension. AngII and cytokines contribute to vascular oxidative stress and hypertension. Treatment of wild-type aortas with AngII and cytokines in organoid culture increased mitochondrial superoxide by 2-fold which was completely prevented in aortas isolated from SOD2-K68R mice. Interestingly, ex vivo treatment of aortas isolated from hypertensive mice with Sirtuin activator resveratrol reduces SOD2 acetylation, inhibits mitochondrial superoxide, and rescues endothelial nitric oxide. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and pathogenesis of hypertension. We conclude that strategies to reduce SOD2 acetylation may have therapeutic potential in the treatment of vascular dysfunction and hypertension.

High-performance liquid chromatography coupled to Orbitrap mass spectrometry for screening of common new psychoactive substances and other drugs in biological samples.

The complexity of the drug market and the constant updating of drugs have been challenging issues for drug regulatory authorities. With the emergence of new psychoactive substances (NPS) and the nonmedical use of prescription drugs, forensic and toxicology laboratories have had to adopt new drug screening methods and advanced instrumentation. Using high-performance liquid chromatography coupled with Orbitrap mass spectrometry, we developed a screening method for common NPS and other drugs. Two milliliters of mixed solvent of n-hexane and ethyl acetate (1:1, v:v) were added to 500 μL of blood or urine sample for liquid-liquid extraction, and methanol extraction was used for hair samples. The developed method was applied to 3897 samples (including 332 blood samples, 885 urine samples, and 2680 hair samples) taken from drug addicts in a province of China during 2019-2021. For urine and blood samples, the limits of detection (LODs) ranged from 1.68 pg/mL to 10.7 ng/mL. For hair samples, the LODs ranged from 3.30 × 10-5 to 4.21 × 10-3 ng/mg. The matrix effects of urine, blood, and hair samples were in the range of 47.6%-121%, 39.8%-139%, and 6.35%-118%, respectively. And the intra-day precision was 3.5%-6.0% and the inter-day precision was 4.18%-9.90%. Analysis of the actual samples showed an overall positive detection rate of 58.9%, with 5.32% of the samples indicating the use of multiple drugs.

Deacetylation mimetic mutation of mitochondrial SOD2 attenuates ANG II-induced hypertension by protecting against oxidative stress and inflammation.

Almost one-half of adults have hypertension, and blood pressure is poorly controlled in a third of patients despite the use of multiple drugs, likely because of mechanisms that are not affected by current treatments. Hypertension is linked to oxidative stress; however, common antioxidants are ineffective. Hypertension is associated with inactivation of key intrinsic mitochondrial antioxidant, superoxide dismutase 2 (SOD2), due to hyperacetylation, but the role of specific SOD2 lysine residues has not been defined. Hypertension is associated with SOD2 acetylation at lysine 68, and we suggested that deacetylation mimetic mutation of K68 to arginine in SOD2 inhibits vascular oxidative stress and attenuates hypertension. To test this hypothesis, we have developed a new deacetylation mimetic SOD2-K68R mice. We performed in vivo studies in SOD2-K68R mice using angiotensin II (ANG II) model of vascular dysfunction and hypertension. ANG II infusion in wild-type mice induced vascular inflammation and oxidative stress and increased blood pressure to 160 mmHg. SOD2-K68R mutation completely prevented increase in mitochondrial superoxide, abrogated vascular oxidative stress, preserved endothelial nitric oxide production, protected vasorelaxation, and attenuated ANG II-induced hypertension. ANG II and cytokines contribute to vascular oxidative stress and hypertension. Treatment of wild-type aortas with ANG II and cytokines in organoid culture increased mitochondrial superoxide twofold, which was completely prevented in aortas isolated from SOD2-K68R mice. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and pathogenesis of hypertension. We conclude that strategies to reduce SOD2 acetylation may have therapeutic potential in the treatment of vascular dysfunction and hypertension.NEW & NOTEWORTHY Essential hypertension is associated with hyperacetylation of key mitochondrial antioxidant SOD2; however, the pathophysiological role of SOD2 acetylation has not been defined. Our animal study of angiotensin II hypertension model shows that deacetylation mimetic SOD2-K68R mutation prevents pathogenic increase in vascular mitochondrial superoxide, abrogates vascular oxidative stress, preserves endothelial nitric oxide, protects endothelial-dependent vasorelaxation, and attenuates hypertension. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and the pathogenesis of hypertension.

A review on drug interaction

Drug interaction occur when the response of one drug is altered by the simultaneous or closely time administration of another drug. Polypharmacy involving the simultaneous use of multiple drugs, raise concern due to unpredictable and potential severe internation. While some drug interactions are intentionally utilized in therapeutics strategies, their severity can vary making prediction challenging. Prescribing multiple medications increases the risk of drug interactions, which can occur with other drugs, foods, beverages, and herbs, both inside and outside the body. Understanding in vitro interactions is crucial to prevent drug activity loss before administration. While not all theoretical drug interactions may occur in practice, they remain a significant cause of adverse events associated with drug administration. Drug-drug interactions (DDIs) represent a significant source of medication errors in developed nations, especially among the elderly who often take multiple medications simultaneously, leading to a prevalence of 20-40%. The complexity of managing therapy increases with poly-therapy, elevating the risk of clinically significant DDIs that can either trigger adverse drug reactions or diminish clinical efficacy. DDIs are typically categorized into two groups: pharmacokinetic and pharmacodynamic. In vivo interactions at pharmacokinetic level affect absorption, distribution, biotransformation or excretion of drugs. Induction or inhibition of cytochrome P450 (CYP450) enzymes forms a major basis of drug interactions. Induction of metabolism of a substrate drug leads to treatment failure.

Opioid metabolism and drug-drug interaction in cancer.

Concomitant use of multiple drugs in most patients with cancer may result in drug-drug interactions (DDIs), potentially causing serious adverse effects. These patients often experience unrelieved cancer-related pain (CRP) during and after cancer treatment, which can lead to a reduced quality of life. Opioids can be used as part of a multimodal pain management strategy when non-opioid analgesics are not providing adequate pain relief, not tolerated, or are contraindicated. However, due to their narrow therapeutic window, opioids are more susceptible to adverse events when a DDI occurs. Clinically relevant DDIs with opioids are usually pharmacokinetic, mainly occurring via metabolism by cytochrome P450 (CYP). This article aims to provide an overview of potential DDIs with opioids often used in the treatment of moderate-to-severe CRP and commonly used anticancer drugs such as chemotherapeutics, tyrosine kinase inhibitors (TKIs), or biologics. A DDI-checker tool was used to contextualize the tool-informed DDI assessment outcomes with clinical implications and practice. The findings were compared to observations from a literature search conducted in Embase and PubMed to identify clinical evidence for these potential DDIs. The limited results mainly included case studies and retrospective reviews. Some potential DDIs on the DDI-checker were aligned with literature findings, while others were contradictory. In conclusion, while DDI-checkers are useful tools in identifying potential DDIs, it is necessary to incorporate literature verification and comprehensive clinical assessment of the patient before implementing tool-informed decisions in clinical practice.

Dual Drug Delivery in Cancer Therapy Using Graphene Oxide‐Based Nanoplatforms

Many types of cancer are currently treated using a combination of chemotherapeutics, but unfortunately, this strategy is considerably limited by severe side effects. The current development of nanocarriers enables the use of multiple drugs anchored on one unique platform thus enhancing the initiated therapeutic effect and minimizing the possibility of drug resistance. In this context, a graphene‐oxide‐based 2D nanoplatform is developed, which is functionalized using highly branched polyethylene‐glycol and a multimodal set of two drugs with various mechanisms of action, namely Pt‐based complex (a Pt(IV) prodrugs based on cisplatin) and doxorubicin (DOX). We performed in vitro 2D screening on two cancer cell lines, namely glioblastoma and osteosarcoma, that were selected as models of two aggressive tumors that remain a massive challenge in oncology. The therapeutic effect of the developed nano‐platform is higher at lower concentrations (15 μm of Pt‐drug, 0.6 μm DOX) compared to the impact of the free drugs. This indicates a possible positive effect of the accumulation and transport of the drugs using this nanoplatform. Results obtained on 3D cell models using MG63 osteosarcoma cells uncovered an understandable lowered diffusion profile of the developed nanoplatforms, compared to the application of free drugs.

Marine Compounds and Age-Related Diseases: The Path from Pre-Clinical Research to Approved Drugs for the Treatment of Cardiovascular Diseases and Diabetes.

Ageing represents a main risk factor for several pathologies. Among them, cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) are predominant in the elderly population and often require prolonged use of multiple drugs due to their chronic nature and the high proportion of co-morbidities. Hence, research is constantly looking for novel, effective molecules to treat CVD and T2DM with minimal side effects. Marine active compounds, holding a great diversity of chemical structures and biological properties, represent interesting therapeutic candidates to treat these age-related diseases. This review summarizes the current state of research on marine compounds for the treatment of CVD and T2DM, from pre-clinical studies to clinical investigations and approved drugs, highlighting the potential of marine compounds in the development of new therapies, together with the limitations in translating pre-clinical results into human application.

Amoxicillin, gemifloxacin and rabeprazole, as first-line Helicobacter pylori therapy in clinical practice: A pilot study.

Success in eradication of H. pylori is decreasing due to increasing resistant strains. In particular, side-effects due to 4-agent treatment multiple drug use are observed and treatment compliance decreases. The aim of this study was to evaluate the efficacy, reliability, and side-effect profile of the combination of amoxicillin and rabeprazole with gemifloxacin, which is a new generation quinolone, in the treatment of H. pylori infection. This study was conducted on 71 naive patients who received H. pylori eradication. All the patients were administered treatment of Amoxicillin (1000 mg twice a day) + Gemifloxacin (320 mg once a day) + rabeprazole (20 mg twice a day) for 7 days. Drug compliance and treatment tolerance were evaluated after finishing the treatment. At 1 month after the end of the treatment, H. pylori eradication was evaluated in all the patients by examining H. pylori antigen in the feces. In the evaluation after treatment, H. pylori eradication was obtained in 63 (88.7%) patients and eradication was not obtained in 8 (11.3%) patients. The treatment was not completed by 2 patients because of side-effects and noncompliance, so after exclusion of these 2 patients, successful H. pylori eradication was obtained in 63 (91.3%) of 69 patients who completed the treatment. Side-effects were seen in a total of 9 (12.7%) patients. Diarrhea, bloating, abdominal pain, and nausea-vomiting were seen in some patients, but no reflux, constipation, skin rash, listlessness-fatigue, headache, dizziness, palpitations, dry mouth, or weight loss was seen in any patient. In regions with high resistance to clarithromycin and metronidazole in particular, the combination of gemifloxacin with amoxicillin and rabeprazole can be considered for use in first-stage treatment as both the efficacy and tolerability are high.

Risk Prediction Model for Radiation-induced Dermatitis in Patients with Cervical Carcinoma Undergoing Chemoradiotherapy

PurposeRadiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). MethodsUsing EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. ResultsThe incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. ConclusionsThe risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

A Multi-Drug Concentration Gradient Mixing Chip: A Novel Platform for High-Throughput Drug Combination Screening.

Combinatorial drug therapy has emerged as a critically important strategy in medical research and patient treatment and involves the use of multiple drugs in concert to achieve a synergistic effect. This approach can enhance therapeutic efficacy while simultaneously mitigating adverse side effects. However, the process of identifying optimal drug combinations, including their compositions and dosages, is often a complex, costly, and time-intensive endeavor. To surmount these hurdles, we propose a novel microfluidic device capable of simultaneously generating multiple drug concentration gradients across an interlinked array of culture chambers. This innovative setup allows for the real-time monitoring of live cell responses. With minimal effort, researchers can now explore the concentration-dependent effects of single-agent and combination drug therapies. Taking neural stem cells (NSCs) as a case study, we examined the impacts of various growth factors-epithelial growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF)-on the differentiation of NSCs. Our findings indicate that an overdose of any single growth factor leads to an upsurge in the proportion of differentiated NSCs. Interestingly, the regulatory effects of these growth factors can be modulated by the introduction of additional growth factors, whether singly or in combination. Notably, a reduced concentration of these additional factors resulted in a decreased number of differentiated NSCs. Our results affirm that the successful application of this microfluidic device for the generation of multi-drug concentration gradients has substantial potential to revolutionize drug combination screening. This advancement promises to streamline the process and accelerate the discovery of effective therapeutic drug combinations.

Medication use among the oldest old in the Faroe Islands-A national cross-sectional study.

Aging is often associated with an increasing number of comorbidities that warrant use of multiple drugs which increases the use of potentially inappropriate medications (PIMs), drug-drug interactions (DDIs) and drug-related problems (DRPs). The aim is to assess the prevalence of polypharmacy, PIMs, DDIs and DRPs among Faroese residents aged ≥90 years. In this population-based cross-sectional study, 494 individuals ≥90 years were invited and 298 (60%) participated. A pharmacist-led medication review was performed based on self-information, electronic patient journal and the Faroese Prescription Registry. The prevalence of polypharmacy was 74% with no sex-difference. Approximately 60% of participants used PIMs, primarily benzodiazepines and proton pump inhibitors, the latter being a frequently implicated medication in DRPs. Opioid use was low compared with other Nordic studies. DRPs were observed for 79% with discrepancies in the medication lists as the most common cause, and DDIs were identified for 47% of participants, mostly moderately clinically relevant DDIs. In conclusion, the medication use among the oldest old Faroese resembled that in other Nordic countries with a high prevalence of polypharmacy and use of PIMs, especially PPIs and benzodiazepines. However, no sex-difference was noted in medication use and the use of opioids was low.