| 1. |
- Vildhede, Anna
(författare)
-
In vitro and in silico Predictions of Hepatic Transporter-Mediated Drug Clearance and Drug-Drug Interactions in vivo
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The liver is the major detoxifying organ, clearing the blood from drugs and other xenobiotics. The extent of hepatic clearance (CL) determines drug exposure and hence, the efficacy and toxicity associated with exposure. Drug-drug interactions (DDIs) that alter the hepatic CL may cause more or less severe outcomes, such as adverse drug reactions. Accurate predictions of drug CL and DDI risk from in vitro data are therefore crucial in drug development.Liver CL depends on several factors including the activities of transporters involved in the hepatic uptake and efflux. The work in this thesis aimed at developing new in vitro and in silico methods to predict hepatic transporter-mediated CL and DDIs in vivo. Particular emphasis was placed on interactions involving the hepatic uptake transporters OATP1B1, OATP1B3, and OATP2B1. These transporters regulate the plasma concentration-time profiles of many drugs including statins.Inhibition of OATP-mediated transport by 225 structurally diverse drugs was investigated in vitro. Several novel inhibitors were identified. The data was used to develop in silico models that could predict OATP inhibitors from molecular structure. Models were developed for static and dynamic predictions of in vivo transporter-mediated drug CL and DDIs. These models rely on a combination of in vitro studies of transport function and mass spectrometry-based quantification of protein expression in the in vitro models and liver tissue. By providing estimations of transporter contributions to the overall hepatic uptake/efflux, the method is expected to improve predictions of transporter-mediated DDIs. Furthermore, proteins of importance for hepatic CL were quantified in liver tissue and isolated hepatocytes. The isolation of hepatocytes from liver tissue was found to be associated with oxidative stress and degradation of transporters and other proteins expressed in the plasma membrane. This has implications for the use of primary hepatocytes as an in vitro model of the liver. Nevertheless, by taking the altered transporter abundance into account using the method developed herein, transport function in hepatocyte experiments can be scaled to the in vivo situation. The concept of protein expression-dependent in vitro-in vivo extrapolations was illustrated using atorvastatin and pitavastatin as model drugs.
|
|
| 2. |
- Alvariza, Anette, et al.
(författare)
-
A person-centred approach in nursing: Validity and reliability of the Carer Support Needs Assessment Tool
- 2018
-
Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889 .- 1532-2122. ; 35, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Carer Support Needs Assessment Tool (CSNAT) was developed for use among family caregivers in palliative care for assessment of their support needs. The purpose of this study was to translate and evaluate the validity and reliability of the CSNAT in a sample of Swedish family caregivers and nurses in a palliative care context. Methods: Data for this validation study was collected during 2016 in the context of palliative home care in two larger Swedish cities. The study was conducted in three stages to reach conceptual, semantic, operational and measurement equivalence between the original UK version and the Swedish version. Stage I consisted of translation to Swedish. In Stage II, cognitive interviews were performed with 8 family caregivers and 10 nurses. Data were analyzed based on relevance, clarity and sensitivity. In Stage III, the CSNAT and related self-rating measures (caregiver burden, preparedness for caregiving and quality of life) were completed by 118 family caregivers. Data quality, construct validity and test-retest reliability were evaluated. Results: The CSNAT items were considered relevant and useful to identify areas of support needs. The Swedish CSNAT showed sound psychometric properties with satisfactory data quality and few problems with missing data across items (1.8%-6.1%). All items except one correlated as expected (rho>0.3) with caregiver burden, supporting construct validity. All items had satisfactory test-retest reliability (κw=0.45-0.75). Conclusions: This study further adds to the validity of the CSNAT and shows in addition that it is reliable and stable for use among family caregivers in palliative care. © 2018 Elsevier Ltd
|
|
| 3. |
- Alvariza, Anette, et al.
(författare)
-
Carer Support Needs and Quality of Life in Palliative Care: A Methodological and Empiri-cal Study
- 2019
-
Ingår i: 16th Word Congress of the European Association for Palliative Care (EAPC). Berlin, May 23-25, Abstract P01-148..
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Carer Support Needs Assessment Tool (CSNAT) was developed to identify support needs of family carers in the context of palliative care which aims to improve quality of life, not just of patients but also their families. Aims: This study aims to 1) evaluate validity and reliability of the CSNAT in a sample of Swedish family carers and nurses in a specialised palliative care context, 2) investigate associations between carer support needs and quality of life. Methods: The study was conducted in four stages I: translation of CSNAT to Swedish; II: cognitive interviews with 8 family carers and 10 nurses; III: completion of the CSNAT, Preparedness for Caregiving Scale, Caregiver Burden Scale, Quality of Life in Life Threatening Illness- Family Carer Version by 118 family carers (spouses/partners: mean age 68 years; 69 women and 45 men). Evaluation of data quality, construct validity and test-retest reliability; IV: Investigation of associations between carer support needs and qual- ity of life using linear regression analyses. Results: CSNAT items were considered relevant and useful to identify support needs and demonstrated sound psychometric properties with satisfactory data quality and few problems with missing data. All items had satisfactory test-retest reliability. Construct validity was supported, as CSNAT items correlated with caregiver burden and preparedness. Associations were found between CSNAT items and seven different domains that represent carer quality of life; carer state, patient wellbe- ing, quality of care, outlook, environment and finances. Having more support needs was associated with poorer quality of life. Conclusion: This study adds to the validity of the CSNAT and shows in addition that it is reliable and stable for use among family carers in pal- liative care. Associations between carer support needs and quality of life suggests that carers’ quality of life may be improved by acknowledging and addressing their needs for support.
|
|
| 4. |
- Heurlin-Norinder, Mia, 1949-
(författare)
-
Platser för lek, upplevelser och möten : Om barns rörelsefrihet i fyra bostadsområden
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is the result of two studies concerning children’s independent mobility, which means the freedom for children to walk or bike on their own or together with friends but without being escorted by parents. The studies are accomplished in four different areas and are also searching for different environmental qualities. The areas differ concerning traffic planning and architecture but also concerning commercial and cultural choice. The aim is to understand and describe how places are constructed and designed when they are used and experienced in a positive – or a negative – way by children. I emphasize, that we – through the responses in meeting with other people – learn hidden and visible rules and also how to change perspective and roles. I therefore focus on the meeting between children and other people but also on meeting between children and places. The issue is: What do places look like – what qualities or qualifications – can be notified as important to children to perceive coherence that consequently make them learn to control their environment and develop to harmonious grown-ups. The main questions are: In what degree can children’s independent mobility be related to the planning and design in the four areas? Why do some neighbourhoods/places appear as more important to children than others, making children use them in a varied way? Is it possible to describe qualities in neighbourhoods in a way that can be interpreted as meaningful for children’s development?In the first study 732 children in grade two and five in compulsory school, filled in a questionnaire and the questions focused on how they got to school, to friends, to activities etc. The results showed that in the area with more traffic than the other three areas, children were more often taken by car to school and to leisure activities. Even international research in the nineties did show that children had lost the accessibility to their neighbourhood. In the second study, 32 children in the same areas guided me around in their environment showing me the way to school and places they used to visit. At the same time they told me what they liked or disliked in their neighbourhood. Afterwards they were interviewed and they also had the opportunity to fill in so called “mobility maps”. The content in this text mainly focuses the second study. From the children’s statements, a summary of the most important differences looks as follows:I The accessibility in neighbourhoods and places: i.e. children’s independent mobility – or if they had to be escorted by grown-ups – and if they could fiddle about.II Children’s play and activities: i.e. if they had something to do, if they played in pairs or in groups and if play could take place without planning.III Children’s experiences of places and people: i.e. if they had something to show me and to tell me, if there were any meetings with other persons, if the children talked about their own yard and appreciated green areas, if they had fun or not, if they were afraid being out and if they told me any memories from some places.The theoretical framework is based on Johan Asplund’s theory on social responsivity and G. H. Mead’s theory on social relations and his view of the importance of objects. The study also is based on three different place theories as expressed by David Canter, Christian Norberg-Schulz and Clarence Crafoord and Asplund’s view of place and placelessness. This study has made it clear that everything children do in their neighbourhood can be related to concrete places and things but it differed concerning what and how they played, what they experienced and what the meetings looked like – if any.Environmental qualities arise, as I have interpreted my results, when neighbourhoods and places are safe, when there are landmarks, places for meetings, possibility of orientation and sense of locality and when the places are varied and challenging. Conclusions are drawn regarding differences in social responsivity, if there is a sense of having a place of one’s own – that in the same time is shared by other people – and if places are responding. From these statements place identity can be seen as a merging of the qualities in places and the perceived sense of place as described above. To have opportunity to investigate the neighbourhood is also an important part of children’s informal learning. They learn how to read the surroundings and how to find the way in a town or in an environment. They get to know the neighbourhood and the world outside and so they also learn how to behave and how to control themselves and even the life. Results showed though that the children in the four areas made those experiences but, certainly, in different ways.
|
|
| 5. |
- Karlgren, Maria, et al.
(författare)
-
Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs) : Influence of Protein Expression on Drug - Drug Interactions
- 2012
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:10, s. 4740-4763
-
Tidskriftsartikel (refereegranskat)abstract
- The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1, The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
|
|
| 6. |
- Norinder, Maria
(författare)
-
A person-centred approach to support family caregivers in specialised home care : The Carer Support Needs Assessment Tool Intervention
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Family caregivers are crucial providers of support and care for patients with lifethreatening illness and many report unmet support needs. With the use of quantitative and qualitative methods this thesis aimed to evaluate the Carer Support Needs Assessment Tool (CSNAT) and explore experiences and potential effects of utilising the Carer Support Needs Assessment Tool Intervention (CSNAT-I) among family caregivers and registered nurses in the context of specialised home care. The results showed that the CSNAT tool was valid and reliable for use among family caregivers in specialised home care (I). Family caregivers reported most the need for additional support concerning “Knowing what to expect in the future” (I, II). They reported and described how higher levels of need for more support were associated with poorer quality of life (II). The intervention was effective in significantly increasing family caregivers’ preparedness for caregiving (p = 0.002) (IV). Participating nurses expressed that their everyday clinical practice changed while learning to use the CSNAT-I and they experienced professional and personal growth (III). Their assessments and supportive inputs shifted from reactive towards proactive and more in collaboration with family caregivers. When utilizing the CSNAT-I, family caregivers experienced their conversations with nurses as co-created, providing new perspectives and insights which increased their involvement and helped in finding solutions (V).In conclusion, this thesis gives further weight to the importance of addressing family caregivers' support needs as a part of nursing.
|
|
| 7. |
- Norinder, Maria, et al.
(författare)
-
Enabling professional and personal growth among home care nurses through using the Carer Support Needs Assessment Tool Intervention-An interpretive descriptive study
- 2023
-
Ingår i: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702. ; 32:13-14, s. 4092-4102
-
Tidskriftsartikel (refereegranskat)abstract
- Aim To explore nurses' experiences of supporting family caregivers in specialised home care while learning to use the Carer Support Needs Assessment Tool Intervention. Background The Carer Support Needs Assessment Tool Intervention can provide guidance for discussions with family caregivers in specialised home care concerning their specific support needs. Little attention has been paid to how nurses experience the use of the intervention in their everyday practice. Design This longitudinal study adopted an inductive qualitative approach using interpretive description. Methods Interviews were conducted at two time points. A total of 22 interviews took place with 12 nurses recruited from six specialised home care services. Data were analysed using interpretive description. Results Nurses' everyday clinical practice changed while learning to use the Carer Support Needs Assessment Tool Intervention, and they experienced professional and personal growth. Their supportive inputs shifted from being reactive towards being more proactive. Their approach changed from taking on great professional responsibility, towards a shared responsibility with family caregivers. The support altered from ad hoc contacts in the hallway, towards scheduled trustful conversations. Nurses were concerned about the amount of time and energy this kind of support might require. They pointed to the importance of holding good nursing skills to conduct this new way of having conversations. Conclusion Nurses' everyday clinical practice can be further developed through the use of the Carer Support Needs Assessment Tool Intervention. Nurses may develop both professionally and personally, increasing their ability to provide person-centred support. Relevance to Clinical Practice With the use of the Carer Support Needs Assessment Tool Intervention, nurses can create trusting conversations with family caregivers of patients with life-threatening illnesses cared for in specialised home care. Reporting Method Reporting of the study follows the Consolidated Criteria For Reporting Qualitative Research (COREQ) checklist (File S1). Patient or Public Contribution Participating nurses were involved in discussing the study design.
|
|
| 8. |
- Norinder, Maria, et al.
(författare)
-
Ett personcentrerat förhållningssätt för att stödja närstående i den specialiserade palliativa hemsjukvården : CSNAT interventionen (CSNAT-I)
- 2022
-
Konferensbidrag (refereegranskat)abstract
- Bakgrund: Närstående är betydelsefulla för patienter som vårdas i hemmet vid livets slut och tar ofta ett stort ansvar. De ger ofta den sjuke både socialt och existentiellt stöd samtidigt som de ibland utför omfattande vård. I sin nya vårdande roll riskerar närstående sin egen hälsa och välbefinnande. Kontinuerligt och anpassat stöd för den närstående kan göra det möjligt för närstående att på bästa sätt stödja patienten men även att upprätthålla sin egen hälsa och välbefinnande.Syfte: Att undersöka sjuksköterskors förväntningar och farhågor inför att prova en personcentrerad intervention för närstående i specialiserad palliativ hemsjukvård.Metod: CSNAT-I testas vid sex specialiserade hemsjukvårdsenheter i Sverige. CSNAT interventionen består av 1) ett formulär med 15 frågor om behov av stöd strukturerat kring 15 områden inom praktiska, emotionella, existentiella och sociala aspekter och 2) en personcentrerad process som utifrån fem steg guidar bedömning och beslut om stödinsatser utifrån närståendes egna reflektioner och prioriteringar. Intervjuer har genomförts med 11 sjuksköterskor. För analys används tolkande beskrivning.Resultat: Resultat från de hittills 11 genomförda intervjuerna visar att sjuksköterskorna saknar ett strukturerat arbetssätt som gör det möjligt identifiera närståendes individuella stödbehov under hela patientens vårdtid. Förhoppningar framkom om att CSNAT-I ska ge plats för närståendesamtal i det dagliga arbetet, ge guidning i samtalet så att så att alla närstående har samma möjlighet till stöd utifrån sina egna behov vilket de hoppades skulle göra stödet mer effektivt. Farhågor uttrycktes om att de föreställde sig att samtalen skulle kunna ta mycket tid i deras dagliga arbete.Betydelse: Ger en ökad kunskap om sjuksköterskors förväntningar och farhågor inför en ny intervention för att stödja närstående. Kunskapen kan hjälpa till i utveckling och implementering av framtida interventioner.
|
|
| 9. |
- Norinder, Maria, et al.
(författare)
-
Family caregivers’ experiences of discussing their needs with a nurse during specialised home care utilizing the carer support needs assessment tool intervention : A qualitative study
- 2023
-
Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 66
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The Carer Support Needs Assessment Tool Intervention (CSNAT-I) was designed to help family caregivers identify, reflect upon, and express their support needs in a conversation with a health care professional and gain tailored support. The CSNAT-I has shown positive effects for both nurses and family caregivers but for more comprehensive understanding this study aims to examine family caregivers' experiences of discussing their needs with a nurse during specialised home care, utilizing the CSNAT-I.Methods The study used an inductive qualitative descriptive design based on framework analysis. Data was collected using individual semi-structured telephone interviews with 10 family caregivers, with a median age of 66, from four specialised home care services.Results Family caregivers appreciated having scheduled meetings with nurses utilizing the CSNAT-I which gave them an opportunity to focus on what was important to them. Family caregivers experienced that the conversations were co-created with a flexible dialogue. The conversations provided new perspectives and insights which helped in finding possible solutions. Family caregivers felt empowered by the co-created conversation and took on a more active role in involving the rest of their family to find support to themselves and the patients.Conclusion The CSNAT-I can facilitate communication between family caregivers and nurses leading to adequate supportive inputs. The intervention gives family caregivers an increased opportunity to be involved in their own support, which may enhance their sense of security. According to family caregivers’ experiences, CSNAT-I may be an adequate way to support family caregivers to reflect and discuss their needs.
|
|
| 10. |
- Norinder, Maria, et al.
(författare)
-
Higher levels of unmet support needs in spouses are associated with poorer quality of life - a descriptive cross-sectional study in the context of palliative home care
- 2021
-
Ingår i: BMC Palliative Care. - : BioMed Central (BMC). - 1472-684X. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundFamily caregivers often report having unmet support needs when caring for someone with life-threatening illness. They are at risk for psychological distress, adverse physical symptoms and negatively affected quality of life. This study aims to explore associations between family caregivers' support needs and quality of life when caring for a spouse receiving specialized palliative home care.MethodsA descriptive cross-sectional design was used: 114 family caregivers completed the Carer Support Needs Assessment Tool (CSNAT) and the Quality of Life in Life-Threatening Illness - Family caregiver version (QOLLTI-F) and 43 of them also answered one open-ended question on thoughts about their situation. Descriptive statistics, multiple linear regression analyses, and qualitative content analysis, were used for analyses.ResultsHigher levels of unmet support needs were significantly associated with poorer quality of life. All CSNAT support domains were significantly associated with one or more quality of life domains in QOLLTI-F, with the exception of the QoL domain related to distress about the patient condition. However, family caregivers described in the open-ended question that their life was disrupted by the patient's life-threatening illness and its consequences. Family caregivers reported most the need of more support concerning knowing what to expect in the future, which they also described as worries and concerns about what the illness would mean for them and the patient further on. Lowest QoL was reported in relation to the patient's condition, and the family caregiver's own physical and emotional health.ConclusionWith a deeper understanding of the complexities of supporting family caregivers in palliative care, healthcare professionals might help to increase family caregivers' QoL by revealing their problems and concerns. Thus, tailored support is needed.
|
|
