Drug-Drug Interactions in Patients with Breast Cancer

The research paper investigates the intricate landscape of drug-drug interactions (DDIs) within the context of breast cancer treatment, with a particular focus on the elderly population and the use of complementary and alternative medicine (CAM). The study underscores the heightened susceptibility of elderly patients to DDIs due to the prevalence of polypharmacy and the widespread utilization of CAM among breast cancer patients. The potential ramifications of DDIs, encompassing adverse drug events and diminished treatment efficacy, are elucidated. The paper accentuates the imperative for healthcare providers to comprehensively understand both conventional and CAM therapies, enabling them to provide patients with informed guidance regarding safe and efficacious treatment options, culminating in enhanced patient outcomes.

Spotted Hyena Optimizer Driven Deep Learning-Based Drug-Drug Interaction Prediction in Big Data Environment

Nowadays,smart healthcare and biomedical research have marked a substantial growth rate in terms of their presence in the literature,computational approaches,and discoveries,owing to which a massive quantity of experimental datasets was published and generated(Big Data)for describing and validating such novelties.Drug-drug interaction(DDI)significantly contributed to drug administration and development.It continues as the main obstacle in offering inexpensive and safe healthcare.It normally happens for patients with extensive medication,leading them to take many drugs simultaneously.DDI may cause side effects,either mild or severe health problems.This reduced victims’quality of life and increased hospital healthcare expenses by increasing their recovery time.Several efforts were made to formulate new methods for DDI prediction to overcome this issue.In this aspect,this study designs a new Spotted Hyena Optimizer Driven Deep Learning based Drug-Drug Interaction Prediction(SHODL-DDIP)model in a big data environment.In the presented SHODL-DDIP technique,the relativity and characteristics of the drugs can be identified from different sources for prediction.The input data is preprocessed at the primary level to improve its quality.Next,the salp swarm optimization algorithm(SSO)is used to select features.In this study,the deep belief network(DBN)model is exploited to predict the DDI accurately.The SHO algorithm is involved in improvising the DBN model’s predictive outcomes,showing the novelty of the work.The experimental result analysis of the SHODL-DDIP technique is tested using drug databases,and the results signified the improvements of the SHODLDDIP technique over other recent models in terms of different performance measures.

Study on Interaction Relationship for Submarine Pipeline with Axial Corrosion Defects

Corrosion is one of the main reasons to cause the operation accident of submarine oil and gas transmission pipelines. As the major corrosion pattern in submarine pipelines, the effects of corrosion clusters consisting of the adjacent corrosion defects on failure pressure are investigated through non-linear large-deformation finite element method. Typically, the failure behavior and limit strength of submarine pipeline with axial groove- groove corrosion defect pair exposed to interhal pressure are analyzed. The effects of corrosion depth and axial spacing between a pair of corrosion defects on failure pressure are concluded. An interaction relationship for corrosion defects in pipelines, as well as prediction formulations for assessing the remaining strength of corroded pipelines are proposed. The expressions based on the proposed interaction relationship give more accurate results than the methods used in the existing design guidelines.

Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions

To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process.METHODSAs standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTSSix hundred and sixty four patients (83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients.CONCLUSIONDDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.

Facial and bilateral lower extremity edema due to drug-drug interactions in a patient with hepatitis C virus infection and benign prostate hypertrophy: A case report

BACKGROUND New direct-acting antivirals(DAAs)-based anti-hepatitis C virus(HCV)therapies are highly effective in patients with HCV infection.However,safety data are lacking regarding HCV treatment with DAAs and drugs for comorbidities.CASE SUMMARY Herein,we reported a case of HCV-infection in a 46-year-old man with benign prostatic hypertrophy.The patient received sofosbuvir/velpatasvir as well as methadone maintenance therapy for drug abuse.The viral load became negative at week 1 post treatment.He developed facial and bilateral lower extremity edema 48 h after starting receiving tamsulosin.Edema disappeared 10 d after treatment with oral furosemide and spironolactone.CONCLUSION In conclusion,this is the first case of an acute edema in the course of treatment with new DAAs,methadone and tamsulosin.These agents are useful in clinical management of patients with HCV infection,particularly in men with benign prostatic hypertrophy.Clinicians should be aware of potential drug-drug interactions in this subset of patients.

Possibility of Drug-Drug Interaction in Prescription Dispensed by Community and Hospital Pharmacy

Objective: To analyze the use of all subsidized prescription drugs including their use of drug combination generally accepted as carrying a risk of severe interactions. Methodology: In a cross sectional study, we analyzed all prescriptions (n = 1014) involving two or more drugs dispensed to the population (age range 4-85 years) from all pharmacies, clinics and hospitals. Data were stratified by age and sex, and frequency of common interacting drugs. Potential drug interactions were classified according to clinical relevance as significance of severity (types A: major, B: moderate, and C: minor) and documented evidence (types 1, 2, 3, and 4). Result and Discussion: The growing use of pharmacological agents means that drug interactions are of increasing interest for public health. Monitoring of potential drug interactions may improve the quality of drug prescribing and dispensing, and it might form a basis for education focused on appropriate prescribing. To make the manifestation of adverse interaction subside, management strategies must be exercised if two interacting drugs have to be taken with each other, involving: adjusting the dose of the object drug;spacing dosing times to avoid the interaction. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action they should take. Conclusion: It is unrealistic to expect clinicians to memorize the thousands of drug-drug interactions and their clinical significance, especially considering the rate of introduction of novel drugs and the escalating appreciation of the importance of pharmacogenomics. Reliable regularly updated decision support systems and information technology are necessary to help avert dangerous drug combinations.

<i>In Vitro</i>and <i>in Vivo</i>(Mouse) Evaluation of Drug-Drug Interactions of Repaglinide with Anti-HIV Drugs

Repaglinide is type 2 short acting anti-diabetic drug which is primarily metabolized by CYP2C8 and CYP3A4 and is also a substrate of influx transporter OATP1B1. HIV drugs are potent inhibitors of CYP3A4 and OATP transporters. Several drug-drug interactions (DDIs) were noticed when protease inhibitors (PIs) coadministered with drugs metabolized by CYP3A4. The PIs are also potent mechanism based inhibitors, out which ritonavir is most potent. In the current study we evaluated in vitro (mouse and human liver microsomes) and in vivo DDIs of repaglinide with anti-HIV drugs. Out of the following tested drugs (Amprenavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir, Delavirdine, Maraviroc, Efavirenz, Nevirapine and Ketoconazole) Amprenavir (APV), Ritonavir (RTV) and Ketoconazole (KTZ) showed inhibition of OH-repaglinide formation in human and mouse liver microsomes. The positive reversible inhibitions were further tested for irreversible inhibitions where we didn’t observe any irreversible inhibitions. In vitro inhibitions were further evaluated in the in vivo pharmacokinetics (mouse) where repaglinide pharmacokinetics was altered by RTV and KTZ. The DDIs in both studies were very strong;the dose of repaglinide is reduced to 20 fold. In conclusion, there could be possible DDIs when RTV dosed with repaglinide;we have also demonstrated that mouse could be useful preclinical tool when used in conjunction with in vitro screening models for DDIs.

Study on ＂Integration of Informatization and Industrialization＂ Characteristics and Its Interaction Relationship with Industrial Design

The ＂integration of informatization and industrialization＂ is a constant development process. In China, the integration of industrial economy and information economy is an inevitable trend of economy development. The social formation of the current industrial society in China will inevitably transform into the social formation of the integration of industrial society and information society. The ＂integration of informatization and industrialization＂ provides necessary technology for economic development,which makes the society have an overall change. This paper tries to make a comparison of the basic features of different formations from the historical development process of the era, in order to summarize the basic characteristics of ＂integration of informatization and industralization＂ and its interaction relationship with industrial design.

Short-Term Drug-Drug Interaction between Sildenafil and Bosentan under Long-Term Use in Patients with Pulmonary Arterial Hypertension

Sildenafil and bosentan are often co-administered for pulmonary arterial hypertension (PAH) treatment. The plasma concentration of sildenafil can be decreased by half if co-administered with bosentan. Many patients take these agents simultaneously in the morning and the evening. The aim of this study was to examine the pharmacokinetics of sildenafil which was interfered with bosentan administration to ascertain whether these agents should be given concomitantly or separately. A two-way crossover study was conducted in 6 PAH patients with combination therapy of sildenafil and bosentan. Participants underwent the sequence of treatment phases: phase S (sildenafil administered 3 h before bosen-tan);phase B (bosentan administered 3 h before sildenafil);and phase C (administered concomitantly). Blood samples were collected on the last day of each phase. There was no significant difference in maximum plasma concentration or area under the plasma concentration-time curve (AUC0-8) between phase C and phase S (95.5 ± 24.8 vs. 72.9 ± 40.9 (p = 0.07), 209.7 ± 81.8 vs. 180.2 ± 126.4 (p = 0.24), respectively) or between phases C and B (87.8 ± 42.0 vs. 99.6 ± 33.9 (p = 0.59), 197.2 ± 88.2 vs. 240.7 ± 121.8 (p = 0.19), respectively) (ng/mL, mean ± standard deviation). Large intra-and inter-individual variability in sildenafil concentration was noted. The timing of administration of sildenafil and bosentan does not significantly influence the plasma concentration of sildenafil. Physicians do not need to be overly concerned about the timing of administration of these drugs to maximize the sildenafil concentration.

Drug-Drug Interaction Studies of Levocetirizine with Atenolol

The objective of the study was to evaluate the drug-drug interaction studies of levoceterizine with atenolol. Calibration curve studies of working standard solutions of levocetirizine and atenolol （0.01-0.1 mmol） were scanned. Maxima appeared at 231 nm for levocetirizine and 224 nm for atenolol. The calibration curve obeyed Beer Lambert＇s Law. Lone availabilities of both the drugs were studied in pH 1, pH 4, pH 7.4 and pH 9 at 37℃ on B.P. （British Pharmacopoeia） dissolution apparatus. To study the drug-drug interaction of levocetirizine （5 mg tablet） and atenolol （100 mg tablet）, both the drugs were introduced to the dissolution apparatus in simulated gastric juice （pH 1）, pH 4, pH 7.4 and pH 9 at 37℃ at zero time and measured the absorbance maxima of both the drugs at the corresponding wavelength. Graphs were plotted for availability percentage （%） of drug versus time at each set of experiment. The availability percentage （%） of levocetirizine in the buffers of pH simulated to gastric pH 4, pH 7.4 and pH 9 in the presence of atenolol was 436.78%, 376.90%, 436.78% and 436.78%, respectively, but the availability of atenolol was increased up to 214.80%, 212.96%, 214.93% and 231.51% in simulated to gastric pH and in the buffers ofpH 4, pH 7.4 and pH 9, respectively. On the basis of these studies, it is concluded that levocetirizine forms a charge-complex with atenolol; therefore, co-administration of these drugs should be avoided.

Prevalence of Potential Drug-Drug Interactions in Hospitalized Surgical Patients

The objective of this study is to estimate the prevalence and describe the characteristics of pDDIs （potential drug-drug interactions） in medical prescriptions of hospitalized surgical patients. In this cross-sectional study, we analyzed 370 medical prescriptions from the surgery unit of a Mexican public teaching hospital. The identification and classification of potential drug-drug interactions were performed with the Micromedex 2.0 electronic drug information database. Results were analyzed with descriptive statistics and we estimated OR （odds ratio） to determine associated risk factors. From the study, it was found that the prevalence of potential drug-drug interactions was 45.9%. A total of 385 interactions were identified. Of these, 54.3% were classified as major and 60.5% as pharmacodynamic. Prescriptions for more than seven drugs （OR =7.33, CI （confidence interval） = 4.59-11.71） and advanced age 〉 60 years, （OR = 1.79, CI = 1.06-2.74） were positively associated with the presence of potential drug-drug interactions. We found a high prevalence of clinically relevant pDDIs in the surgery unit. In view of this outcome, the safety of drug combinations in hospitalized surgical patients should be evaluated during the prescription process in order to prevent adverse events.

Interaction Relationship Between Corporate Social Responsibility and Corporate Performance:Evidence from 201 Chinese Listed Companies and Preliminary Study of Its Underlying Mechanism

Corporations actively fulfilling corporate social responsibility(CSR)is of more significance to society's sustainable development nowadays.This research discusses the interaction between CSR and corporate performance and then adopts other mediation variables to explain the underlying mechanism.The empirical analyses are performed on a sample of 201 listed Chinese firms.The result shows that CSR has a weak negative impact on corporate perfbnnance while being positively influenced by corporate performance significantly.Further study finds the reason may be CSR requires financial support,but has little to do with increasing shareholder wealth.

Relationship Marketing： Interactions and Management

Starting with the interactive factors of relationship, this paper analyzes the interactive feature of relationship marketing within the marketing framework. Based on the interactive model of relationship marketing, this paper puts forward suggestions concerning effective interactive management of relationship marketing from the organization.

Multidisciplinary Approach to Drug-Drug Interactions between Tacrolimus and Sofosbuvir/Velpatasvir and Glecaprevir/Pibrentasvir in Kidney Transplant Patients during Hepatitis C Treatment:A Case Series Report

The direct acting antivirals(DAAs)are now the standard of care for hepatitis C virus(HCV)treatment with high and effective sustained virologic responserate(SVR)and great safety profile,including solid organ transplant patients.There are increasing reports showing DAAs are effective with high SVR rates and safety profile in kidney transplant recipients.There are reports on drug-drug interaction(DDI)between tacrolimus with DAAs.However,data remain lacking on potential DDIs between tacrolimus and DAA regimens and the management process.This case series reports three kidney transplant patients on tacrolimus who were successfully treated for HCV with multidisciplinary approach,although there was DDI between tacrolimus with sofosbuvir/velpatasvir and glecaprevir/pibrentasvir,which required tacrolimus dose adjustment to maintain therapeutic level during and after DAA treatment.Such DDIs should be aware of and closely monitored by pharmacist and physicians with tacrolimus dose adjustment as needed during and right after DAA treatment in post-kidney transplant patients.

The Relationship Equation & Relationship Circle. The Importance of Reciprocal Interaction in Functional Relationships, Role of Context & the “Happinewness” Key.

Truly opposite is defined by identity of units with complementary anatomy or structure to form a pair,e.g.male and female.Complementary or corresponding structure or form permits reciprocal function of these units or“opposites”.Focus on“Identity”or“function”determines one’s view as to whether these units are“opposites”or“complementary”.“Identity”is unique&exclusive,whereas,function requires inclusivity,specificity&reciprocal interaction,contributed to by both units to form a dynamic partnership or pair.Contextual interaction matters as it permits an inclusive view.Inclusion&awareness of surroundings that impact on relationships and/or personal interaction is represented here by a surrounding circle or sense of purpose and represents the extension of immediate context involving both units in a paired relationship of structural complementary units within their encompassing surroundings or contextual field.Contextual reference is the ethical key to understanding situations&circumstance so serves as the key to ethics,morality&relationships.The Relationship Equation,E=1=m.c-1,provides a simple model of understanding usually viewed as complex relationships.It offers an approach to solving identity issues by viewing these as complementary and functional rather than as opposites.In place of identity as the focus it introduces context and reciprocal interaction of complementary units of a pair.Identity as part of a whole transfers the focus from self to other or both and to an awareness of higher purpose in the Oneness of function of Creation as(m.c-1)=E=1.Environmental influence is taken into account by viewing the Eco-social environment or Eco-society as important.Impact of environment on one or other unit in a pair or on both&vice versa affects relationships.Resilience&adaptation to environmental change leads to evolution when the pair thrives better in this new Eco-social environment.Being part of a functional whole,as a functional unit or as a functioning pair,adds purpose and reason for the Creation,all of Creation,including self,as one is included in all!Application of the Relationship Equation is relevant to health&wellbeing,parenting,biology,law&health law,political science,society&evolution.It is also valuable when utilized as a resolution tool as it offers functional outcomes and sense of purpose on the basis of objectivity,trust and truth to overcome conflict arising from a highly sensitized identity-oriented focus.Contextual&reciprocal units in functional pairs replace self as the basic functional principle of the whole of existence.Application of this understanding has preventive as well as therapeutic relevance.It may be used as a guide in upbringing,parenting and child care as well as conflict resolution in personal,social&political scenarios locally,nationally,internationally,globally&universally.It is the“happinewness”key.

Deep learning for drug-drug interaction prediction:A comprehensive review

The prediction of drug-drug interactions(DDIs)is a crucial task for drug safety research,and identifying potential DDIs helps us to explore the mechanism behind combinatorial therapy.Traditional wet chemical experiments for DDI are cumbersome and time-consuming,and are too small in scale,limiting the efficiency of DDI predictions.Therefore,it is particularly crucial to develop improved computational methods for detecting drug interactions.With the development of deep learning,several computational models based on deep learning have been proposed for DDI prediction.In this review,we summarized the high-quality DDI prediction methods based on deep learning in recent years,and divided them into four categories:neural network-based methods,graph neural network-based methods,knowledge graph-based methods,and multimodal-based methods.Furthermore,we discuss the challenges of existing methods and future potential perspectives.This review reveals that deep learning can significantly improve DDI prediction performance compared to traditional machine learning.Deep learning models can scale to large-scale datasets and accept multiple data types as input,thus making DDI predictions more efficient and accurate.

A Train-Bridge Dynamic Interaction Analysis Method and Its Experimental Validation

The train-bridge dynamic interaction problem began with the development of railway technology, and requires an evaluation method for bridge design in order to ensure the safety and stability of the bridge and the running train. This problem is studied using theoretical analysis, numerical simulation, and experimental study. In the train-bridge dynamic interaction system proposed in this paper, the train vehicle model is established by the rigid-body dynamics method, the bridge model is established by the finite element method, and the wheel/rail vertical and lateral interaction are simulated by the corresponding assumption and the Kalker linear creep theory, respectively. Track irregularity, structure deformation, wind load, collision load, structural damage, foundation scouring, and earthquake action are regarded as the excitation for the system. The train-bridge dynamic interaction system is solved by inter-history iteration. A case study of the dynamic response of a CRH380BL high-speed train running through a standard-design bridge in China is discussed. The dynamic responses of the vehicle and of the bridge subsystems are obtained for speeds ranging from 200 km-b-1 to 400 km.h-1, and the vibration mechanism are analyzed.

Organic anion transporters also mediate the drug–drug interaction between imipenem and cilastatin

This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.

Study on the Priority and Interaction of Food Security,Food Safety and Environmental Protection

Food security, food safety and environmental protection are major livelihood issues in front of the Chinese people. The priorities of the three are different, and there is mutually dependent and contradictory relationship among them. Facing the triple pressures of food security, food safety, and environmental protection, this paper analyzes the priority of the three from the historical development, then further analyzes the interaction between food security,food safety and environmental protection and finally puts forward the healthy development of food security, food safety and environmental protection, and the proper settlement of the three problems.

Voices of Mother's Interaction with Midwives in Natural Childbirth: A Qualitative Study

Interaction between mothers and midwives during natural childbirth is one of the important factors in relationship between mothers and midwives in natural childbirth. In this qualitative study we explored experiences of mothers and midwives in interaction with each other in natural childbirth. This study was a part of a larger study which was carried out in Iran in 2013-2014. A total of 23 participants participated in this study. 12 primiparous and multiparous women planned to have natural deliveries and 11 midwives were purposefully included for semi-structured in-depth interviews in this study. For analysis and interpretation of mothers’ and midwives’ experience, conventional content analysis was used. Data were coded in MAXqda software (version 2). Interaction between mothers and midwives could be organized and categorized in one theme “relationship”. This theme consists of two subthemes: “respect for the mother” and “interaction” and five categories: “Feeling confidence, Feeling satisfaction, Associated with sensory relationship, Understanding mother’s situation, Understanding the meaning of interaction”. Good relationship between mothers and midwives in natural childbirth could improve the experience of natural childbirth for mothers. This experience could increase woman’s tendency toward natural birth instead of cesarean section in future pregnancies. Findings of this study can be seen as a challenge for health care professionals and policy makers to upgrade care of natural childbirth based on women’s preferences and needs.