| 1. |
- Englund, Gunilla, et al.
(författare)
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Cytochrome P450 Inhibitory Properties of Common Efflux Transporter Inhibitors
- 2014
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Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 42:3, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- Drug transporter inhibitors are important tools to elucidate the contribution of transporters to drug disposition both in vitro and in vivo. These inhibitors are often unselective and affect several transporters as well as drug metabolizing enzymes, which can make experimental results difficult to interpret with confidence. We therefore tested 14 commonly used P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug-resistance associated protein (MRP) inhibitors as inhibitors of cytochrome P450 (P450) enzyme activities using recombinant enzymes. A subset of P-gp and/or CYP3A inhibitors were selected (cyclosporin A, elacridar, ketoconazole, quinidine, reserpine, and tacrolimus) for a comparison of P450 inhibition in human microsomes and hepatocytes. Most P-gp inhibitors showed CYP3A4 inhibition, with potencies often in a similar range as their P-gp inhibition, as well as less potent CYP2C19 inhibition. Other P450 enzymes were not strongly inhibited except a few cases of CYP2D6 inhibition. MRP and BCRP inhibitors showed limited P450 inhibition. Some inhibitors showed less P450 inhibition in human hepatocytes than human liver microsomes, for example, elacridar, probably due to differences in binding, permeability limitations, or active, P-gp mediated efflux of the inhibitor from the hepatocytes. Quinidine was a potent P450 inhibitor in hepatocytes but only showed weak inhibition in microsomes. Quinidine shows an extensive cellular uptake, which may potentiate intracellular P450 inhibition. Elacridar, described as a potent and selective P-gp inhibitor, displayed modest P450 inhibition in this study and is thus a useful model inhibitor to define the role of P-gp in drug disposition without interference with other processes.
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| 2. |
- Lindqvist, Olav, et al.
(författare)
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Complexity in Non-Pharmacological Caregiving Activities at the End of Life : An International Qualitative Study
- 2012
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Ingår i: PLoS Medicine. - San Francisco : Public Library of Science. - 1549-1277 .- 1549-1676. ; 9:2, s. e1001173-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In late-stage palliative cancer care, relief of distress and optimized well-being become primary treatment goals. Great strides have been made in improving and researching pharmacological treatments for symptom relief; however, little systematic knowledge exists about the range of non-pharmacological caregiving activities (NPCAs) staff use in the last days of a patient's life. Methods and Findings: Within a European Commission Seventh Framework Programme project to optimize research and clinical care in the last days of life for patients with cancer, OPCARE9, we used a free-listing technique to identify the variety of NPCAs performed in the last days of life. Palliative care staff at 16 units in nine countries listed in detail NPCAs they performed over several weeks. In total, 914 statements were analyzed in relation to (a) the character of the statement and (b) the recipient of the NPCA. A substantial portion of NPCAs addressed bodily care and contact with patients and family members, with refraining from bodily care also described as a purposeful caregiving activity. Several forms for communication were described; information and advice was at one end of a continuum, and communicating through nonverbal presence and bodily contact at the other. Rituals surrounding death and dying included not only spiritual/religious issues, but also more subtle existential, legal, and professional rituals. An unexpected and hitherto under-researched area of focus was on creating an aesthetic, safe, and pleasing environment, both at home and in institutional care settings. Conclusions: Based on these data, we argue that palliative care in the last days of life is multifaceted, with physical, psychological, social, spiritual, and existential care interwoven in caregiving activities. Providing for fundamental human needs close to death appears complex and sophisticated; it is necessary to better distinguish nuances in such caregiving to acknowledge, respect, and further develop end-of-life care.
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| 3. |
- Lindqvist, Olav, et al.
(författare)
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Four essential drugs needed for quality care of the dying : a Delphi-study based international expert consensus opinion
- 2013
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Ingår i: Journal of Palliative Medicine. - : Mary Ann Liebert Inc. - 1096-6218 .- 1557-7740. ; 16:1, s. 38-43
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: The majority of dying patients do not have access to necessary drugs to alleviate their most common symptoms, despite evidence of drug efficacy. Our aim was to explore the degree of consensus about appropriate pharmacological treatment for common symptoms in the last days of life for patients with cancer, among physicians working in specialist palliative care. Material and methods: Within OPCARE9, a European Union seventh framework project aiming to optimize end-of-life cancer care, we conducted a Delphi survey among 135 palliative care clinicians in nine countries. Physicians were initially asked about first and second choice of drugs to alleviate anxiety, dyspnea, nausea and vomiting, pain, respiratory tract secretions (RTS), as well as terminal restlessness. Results: Based on a list of 35 drugs mentioned at least twice in the first round (n=93), a second Delphi round was performed to determine ≤5 essential drugs for symptom alleviation in the last 48 hours of life that should be available even outside specialist palliative care. There was ≥80% consensus among the participants (n=90) regarding morphine, midazolam, and haloperidol as essential drugs. For RTS, there was consensus about use of an antimuscarinic drug, with 9%-27% of the physicians each choosing one of four different drugs. Conclusion: Based on this consensus opinion and other literature, we suggest four drugs that should be made available in all settings caring for dying patients with cancer, to decrease the gap between knowledge and practice: morphine (i.e., an opioid), midazolam (a benzodiazepine), haloperidol (a neuroleptic), and an antimuscarinic.
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| 4. |
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| 5. |
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| 6. |
- Lundquist, Gunilla, et al.
(författare)
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Information of imminent death or not : does it make a difference?
- 2011
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Ingår i: Journal of Clinical Oncology. - Orlando, FL : Grune & Stratton. - 0732-183X .- 1527-7755. ; 29:29, s. 3927-3931
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study examines whether end-of-life care for patients with cancer who were informed about imminent death differs from care for those patients with cancer who were not informed. Patients and Methods: This study included all cancer deaths between 2006 and 2008 for which the patient did not lose his or her decision-making capacities until hours or days before death (N=13,818). These patients were taken from a national quality register for end-of-life care. The majority of the patients—91% (n=12,609) —had been given information about imminent death; 9% (n=1,209) had not been informed. Because of the difference in sample size, a matching procedure was performed to minimize bias. This resulted in a comparison of 1,191 informed and 1,191 uniformed patients. Nonparametric methods were used for statistical analyses. Results: Informed patients significantly more often had parenteral drugs prescribed as needed (ie, PRN), had his or her family informed, died in his or her preferred place, and had family who were offered bereavement support. There was no difference in symptom control (ie, pain, anxiety, confusion, nausea, and respiratory tract secretions) between the groups. Conclusion: Providing information of imminent death to a patient with cancer at the end of life does not seem to increase pain or anxiety, but it does seem to be associated with improved care and to increase the likelihood of fulfilling the principles of a good death.
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| 7. |
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| 8. |
- Lundquist, Patrik, et al.
(författare)
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Functional ATP-Binding Cassette Drug Efflux Transporters in Isolated Human and Rat Hepatocytes Significantly Affect Assessment of Drug Disposition
- 2014
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Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 42:3, s. 448-458
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Tidskriftsartikel (refereegranskat)abstract
- Freshly isolated hepatocytes are considered the gold standard for in vitro studies of hepatic drug disposition. To ensure a reliable supply of cells, cryopreserved human hepatocytes are often used. ABC-superfamily drug efflux transporters are key elements in hepatic drug disposition. These transporters are often considered lost after isolation of hepatocytes. In the present study, the expression and activity of ABC transporters BCRP, BSEP, P-gp, MRP2, MRP3, and MRP4 in human and rat cryopreserved hepatocytes were investigated. In commercially available human cryopreserved hepatocytes, all drug efflux transporters except human BCRP (hBCRP) exhibited similar expression levels as in fresh liver biopsies. Expression levels of hBCRP were 60% lower in cryopreserved human hepatocytes than in liver tissue, which could lead to, at most, a 2.5-fold reduction in hBCRP-mediated efflux. Fresh rat hepatocytes showed significantly lower levels of rat BCRP compared with liver expression levels; expression levels of other ABC transporters were unchanged. ABC transporters in human cryopreserved cells were localized to the plasma membrane. Functional studies could demonstrate P-gp and BCRP activity in both human cryopreserved and fresh rat hepatocytes. Inhibiting P-gp-mediated efflux by elacridar in in vitro experiments significantly decreased fexofenadine efflux from hepatocytes, resulting in an increase in apparent fexofenadine uptake. The results from the present study clearly indicate that ABC transporter-mediated efflux in freshly isolated as well as cryopreserved rat and human hepatocytes should be taken into account in in vitro experiments used for modeling of drug metabolism and disposition.
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| 9. |
- Raijmakers, Natasja J. H., et al.
(författare)
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Issues and needs in end-of-life decision making : An international modified Delphi study
- 2012
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Ingår i: Palliative Medicine. - : SAGE Publications. - 0269-2163 .- 1477-030X. ; 26:7, s. 947-953
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Tidskriftsartikel (refereegranskat)abstract
- Background: end-of-life decision making is an important aspect of end-of-life care that can have a significant impact on the process of dying and patients' comfort in the last days of life. Aim: the aim of our study was to identify issues and considerations in end-of-life decision making, and needs for more evidence among palliative care experts, across countries and professions. Participants: 90 palliative care experts from nine countries participated in a modified Delphi study. Participants were asked to identify important issues and considerations in end-of-life decision making and to rate the need for more evidence. Results: experts mentioned 219 issues in end-of-life decision making related to the medical domain, 122 issues related to the patient wishes and 92 related to relatives' wishes, regardless of profession or country (p > 0.05). In accordance, more than 90% of the experts rated the comfort and wishes of the patient and the potential futility of treatment as important considerations in end-of-life decision making, although some variation was present. When asked about issues that are in need of more evidence, 87% mentioned appropriate indications for using sedatives and effects of artificial hydration at the end of life. A total of 83% mentioned adequate communication approaches. Conclusions: palliative care experts from different professions in different countries encounter similar issues in end-of-life decision making. Adequate communication about these issues is universally experienced as a challenge, which might benefit from increased knowledge. This shared experience enables and emphasizes the need for more international research.
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| 10. |
- Sjögren, Anita, 0, et al.
(författare)
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Human blastocysts for the development of embryonic stem cells
- 2004
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Ingår i: Reproductive BioMedicine Online. - 1472-6483 .- 1472-6491. ; 9:3, s. 326-9
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Tidskriftsartikel (refereegranskat)abstract
- Establishment of human embryonic stem cells (hES) from surplus human IVF embryos has been successful when both fresh and frozen-thawed cleavage stage embryos have been cultured to the blastocyst stage. This study reports the characteristics of the starting material, the blastocysts, for hES cell lines that were first derived at the University of Gothenburg, Sahlgrenska University Hospital in 1999. Twenty-two hES cell lines were derived by Cellartis AB from 114 blastocysts, giving an overall success rate of 19.3%. The blastocysts from which the hES cell lines were established were of varying morphological quality, both fresh and frozen-thawed. Two techniques of hES establishment were applied, i.e. direct application of the blastocysts on feeder cells or the standard immunosurgery method. It was further found that the efficiency by which frozen-thawed embryos gave rise to new hES cell lines was 3.7 times better than with fresh surplus embryos. These findings suggest that frozen-thawed embryos are superior to fresh surplus human embryos in hES cell establishment, which also avoids specific ethical problems associated with embryo donation in a fresh IVF cycle.
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| 11. |
- Stenberg, Gunilla, et al.
(författare)
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Patterns of reported problems in women and men with back and neck pain : similarities and differences
- 2014
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 46:7, s. 668-675
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine similarities and differences in problem areas reported by women and men who seek physiotherapy for back or neck pain. Methods: Principal component analysis (PCA) was used to analyse questionnaire data including demographics, pain, domestic work, stress, health status, physical disability, psychosocial and physical workload, kinesiophobia and self-efficacy. Most of the questions were recruited from a number of scales, e.g. EuroQol (EQ-5D), Neck Disability Index (NDI), Oswestry Disability Questionnaire (ODQ), Tampa Scale for Kinesiophobia, and Functional-Efficacy-Scale. Results: A total of 118 patients (84 women, 34 men) completed the questionnaire. Men and women scored similarly on physical disability, functional self-efficacy and kinesiophobia, but women scored higher on stress reactions and pain intensity. PCA showed that questions about physical disability and functional self-efficacy comprised the first component and explained most of the variance in this patient group. Questions about stress and social support at work constituted the second component. Questions about domestic workload and pain comprised the third component. Gender differences were found in the second and third components. Conclusion: In general, women and men answered questions similarly, but there were differences: more women reported stress, pain and low support at work and more men reported a lower domestic workload.
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| 12. |
- Stenberg, Gunilla, 1968-, et al.
(författare)
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Similarities and differences : patterns of reported problems and ICF classification in women and men with back or neck pain seeking physiotherapy treatment
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The primary aim of this study was to examine similarities and differences in problem areas reported by women and men who seek physiotherapy treatment for back or neck pain. A second aim was to evaluate the appropriateness of ICF classification in relation to gender.Methods: Principal component analysis (PCA) and partial least squares of latent structures (PLS) were used to analyse questionnaire data including background data, questions about pain, domestic work, stress, EQ-5D, Neck Disability Index (NDI), Oswestry Disability Questionnaire (ODQ), psychosocial and physical workload, Tampa Scale and Functional Self-Efficacy Scale.Results: One hundred and eighteen patients (84 women and 34 men) completed the questionnaire. Men and women scored similarly on the NDI, ODQ, Functional Self Efficacy, and Tampa Scale, but women rated higher on stress reactions. PCA showed that questions from the NDI, ODQ and Functional Self-Efficacy Scale explained most of the variance in this patient group. Questions about stress and social support at work constituted the second component. Questions about domestic workload and pain comprised the third component. Gender differences were found in the two last components.Conclusion: Further investigation of the impact of gender on neck and back pain in different cultures is important.
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| 13. |
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