A systematic review of pregnancy-related clinical intervention of drug regimens due to pharmacokinetic reasons

Background and objectivePublished works have discussed the pharmacokinetic interactions of drugs with pregnancy, but none comprehensively identify all the approved United States Food and Drug Administration (FDA) and European Medicines Administration (EMA) drugs that have a pregnancy-related intervention. The objective of this systematic review is to comprehensively identify medications that have clinically meaningful interventions due to pharmacokinetic reasons.MethodsAn in-depth search of clinical data using the PDR3D: Reed Tech Navigator™ for Drug Labels was conducted from 1 June to 12 August 2022. The PDR3D was analyzed using the search terms “pregnant” and “pregnancy” within the proper label section. Regarding the US labels, the terms were searched under the “dosage and administration” section, whereas with the EU labels, the terms were searched within the “posology and method of administration” section. If a finding was discovered within the search, the rest of the label was analyzed for further information. Clinical relevance was based on whether an intervention was needed.ResultsUsing the search strategy, 139 US and 20 EU medications were found to have clinically meaningful interventions in pregnancy. The most common explanations for clinical relevance included hepatic metabolism, protein binding, renal elimination, and P-gp influence. Of the US labels: 40 were found to undergo hepatic metabolism, 11 were found to be influenced by renal elimination, 12 were found to be influenced by protein binding, 7 were found to be influenced by P-gp, and the remaining drugs required further research. Of the EU labels: 11 were found to undergo hepatic metabolism, 3 were found to be influenced by renal elimination, 3 were found to be influenced by protein binding, 1 was found to be influenced by P-gp, and the remaining drugs required further research.ConclusionThis comprehensive review of clinically relevant interventions in pregnancy will potentially aid in the treatment of pregnant females when they are undergoing therapy, provide intervention and dosing guidance for physicians, and save time for prescribers and pharmacists. Advances in non-clinical predictions for pregnancy dosing may guide the need for a future clinical evaluation

E-learning : a form for competence development?

Titel: E-learning - en form för kompetensutveckling? Författare: Emely Andersson Helena Någård Handledare: Anders Nilsson Institution:Institutionen för Ekonomi och Management Blekinge Tekniska Högskolan Kurs: Magisterarbete i företagsekonomi, EFE 610 Syfte: Syftet med uppsatsen är att kartlägga de faktorer som ligger till grund vid valet av e-learning som kompetensutvecklingsform samt vilka olika verktyg av e-learning som finns. Metod: Insamlingen av data har skett genom både personliga intervjuer och e-mail intervjuer med företag som använder någon form av e-learning i sin verksamhet. Vi har också varit i kontakt med sakkunniga som har erfarenhet av e-learning för att få ett bredare perspektiv på området. Slutsats: Slutsatsen vi har dragit är att det beror på flera olika faktorer om e-learning passar in i företaget och varje företag måste utvärdera dessa faktorer. Genom att titta på olika företag har vi hittat vissa gemensamma faktorer hos dessa företag. Huvudfaktorerna som har störst betydelse för om e-learning passar in i företaget är personalen, kostnaderna och vilka kunskaper det är som skall förmedlas. Personalen är viktig att ta hänsyn till eftersom det är personalen som ska ta del av kompetensutvecklingen. Kostnader är alltid viktiga för företagen att ta hänsyn till, en bedömning av vad alternativen kostar i jämförelse med e-learning. Vi anser att det inte är all kunskap som går att förmedla via e-learning därför måste denna faktor också beaktas innan beslut fattas. Det finns också ett antal bifaktorer som har en viss betydelse dock inte lika stor som huvudfaktorerna. Bifaktorerna är organisationsstruktur, ledning, teknik, flexibilitet och arbetsmiljö. Abstract Title: E-learning - a form for competence development? Authors: Emely Andersson Helena Någård Tutor: Anders Nilsson Department: Department of Business and Management Blekinge Institute of Technology Course: Master thesis in Business Administration, EFE 610 Purpose: Our purpose with this thesis is to study what factors that are important when the company should decide if they should use e-learning as a form for competence development. Also to see what diffrent kinds of e-learning that can be used. Approach: We gathered the data we needed through interviews with companies that use some form of e-learning today. To get a vider perspective on the subject we also got in touch with experts who have a lot of experience of education and competence development. Results: There are several different factors that affects the choice if e-learning should be used for competence development in the company. The main factors are the employees, the costs and the knowledge that is to be spread. The employees are important because it?s them who shall take part of the competence development. Costs are always important for companies and they need to look at the alternatives to e-learning and what diffrent costs there are. We think that not all knowledge can?t be spread trough e-learning, therefor the decisionmakers must consider what kind of knowledge the competence development is about. There are also other facotors that are important but not as important as the main factors. This factors are structure of the organisation, management, technic, flexibility and work environment

E-learning : a form for competence development?

Titel: E-learning - en form för kompetensutveckling? Författare: Emely Andersson Helena Någård Handledare: Anders Nilsson Institution:Institutionen för Ekonomi och Management Blekinge Tekniska Högskolan Kurs: Magisterarbete i företagsekonomi, EFE 610 Syfte: Syftet med uppsatsen är att kartlägga de faktorer som ligger till grund vid valet av e-learning som kompetensutvecklingsform samt vilka olika verktyg av e-learning som finns. Metod: Insamlingen av data har skett genom både personliga intervjuer och e-mail intervjuer med företag som använder någon form av e-learning i sin verksamhet. Vi har också varit i kontakt med sakkunniga som har erfarenhet av e-learning för att få ett bredare perspektiv på området. Slutsats: Slutsatsen vi har dragit är att det beror på flera olika faktorer om e-learning passar in i företaget och varje företag måste utvärdera dessa faktorer. Genom att titta på olika företag har vi hittat vissa gemensamma faktorer hos dessa företag. Huvudfaktorerna som har störst betydelse för om e-learning passar in i företaget är personalen, kostnaderna och vilka kunskaper det är som skall förmedlas. Personalen är viktig att ta hänsyn till eftersom det är personalen som ska ta del av kompetensutvecklingen. Kostnader är alltid viktiga för företagen att ta hänsyn till, en bedömning av vad alternativen kostar i jämförelse med e-learning. Vi anser att det inte är all kunskap som går att förmedla via e-learning därför måste denna faktor också beaktas innan beslut fattas. Det finns också ett antal bifaktorer som har en viss betydelse dock inte lika stor som huvudfaktorerna. Bifaktorerna är organisationsstruktur, ledning, teknik, flexibilitet och arbetsmiljö. Abstract Title: E-learning - a form for competence development? Authors: Emely Andersson Helena Någård Tutor: Anders Nilsson Department: Department of Business and Management Blekinge Institute of Technology Course: Master thesis in Business Administration, EFE 610 Purpose: Our purpose with this thesis is to study what factors that are important when the company should decide if they should use e-learning as a form for competence development. Also to see what diffrent kinds of e-learning that can be used. Approach: We gathered the data we needed through interviews with companies that use some form of e-learning today. To get a vider perspective on the subject we also got in touch with experts who have a lot of experience of education and competence development. Results: There are several different factors that affects the choice if e-learning should be used for competence development in the company. The main factors are the employees, the costs and the knowledge that is to be spread. The employees are important because it?s them who shall take part of the competence development. Costs are always important for companies and they need to look at the alternatives to e-learning and what diffrent costs there are. We think that not all knowledge can?t be spread trough e-learning, therefor the decisionmakers must consider what kind of knowledge the competence development is about. There are also other facotors that are important but not as important as the main factors. This factors are structure of the organisation, management, technic, flexibility and work environment

Understanding Statin-Roxadustat Drug–Drug-Disease Interaction Using Physiologically-Based Pharmacokinetic Modeling

A different drug–drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared with healthy volunteers (HVs), depending on the interplay between drug–drug and disease (drug-drug-disease interaction (DDDI)). Physiologically-based pharmacokinetic (PBPK) modeling, in lieu of a clinical trial, is a promising tool for evaluating these complex DDDIs in patients. However, the prediction confidence of PBPK modeling in the severe CKD population is still low when nonrenal pathways are involved. More mechanistic virtual disease population and robust validation cases are needed. To this end, we aimed to: (i) understand the implications of severe CKD on statins (atorvastatin, simvastatin, and rosuvastatin) pharmacokinetics (PK) and DDI; and (ii) predict untested clinical scenarios of statin-roxadustat DDI risks in patients to guide suitable dose regimens. A novel virtual severe CKD population was developed incorporating the disease effect on both renal and nonrenal pathways. Drug and disease PBPK models underwent a four-way validation. The verified PBPK models successfully predicted the altered PKs in patients for substrates and inhibitors and recovered the observed statin-rifampicin DDIs in patients and the statin-roxadustat DDIs in HVs within 1.25- and 2-fold error. Further sensitivity analysis revealed that the severe CKD effect on statins PK is mainly mediated by hepatic BCRP for rosuvastatin and OATP1B1/3 for atorvastatin. The magnitude of statin-roxadustat DDI in patients with severe CKD was predicted to be similar to that in HVs. PBPK-guided suitable dose regimens were identified to minimize the risk of side effects or therapeutic failure of statins when co-administered with roxadustat