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- Békássy, Albert, et al.
(författare)
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Pharmacokinetics of cytosine arabinoside in cerebrospinal fluid and of its metabolite in leukemic cells
- 1990
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Ingår i: Medical and Pediatric Oncology. - : Wiley. - 1096-911X .- 0098-1532. ; 18:2, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Concentrations of ara-CTP in leukemic cells isolated from CSF and of ara-C in lumbar CSF were measured following intraventricular ara-C administration in two girls with refractory meningeal leukemia. CSF samples were collected with a permanent intrathecal-lumbar catheter. In contrast to the comparatively short retention of ara-C in the CSF (t1/2 1.8 to 2.9 hours), there was a high accumulation and an extremely long retention of ara-CTP in the leukemic cells (t1/2 8.1 to 36 hours). The patients included in this study had an ara-C-resistant disease. No obvious relationship was seen between concentrations of ara-C in the CSF and of ara-CTP in the leukemic cells. Similar studies were performed after simultaneous intraventricular administration of hydrocortison and ara-C. Hydrocortison did not increase ara-CTP retention in the leukemic cells, nor did it effect CSF pleocytosis.
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| 3. |
- Engström, Ingemar, 1952-, et al.
(författare)
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Relational continuity may give better clinical outcomes in patients with serious mental illness - a systematic review
- 2023
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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Forskningsöversikt (refereegranskat)abstract
- BackgroundContinuity of care is considered important for results of treatment of serious mental illness (SMI). Yet, evidence of associations between relational continuity and different medical and social outcomes is sparse. Research approaches differ considerably regarding how to best assess continuity as well as which outcome to study. It has hitherto been difficult to evaluate the importance of relational continuity of care. The aim of this systematic review was to investigate treatment outcomes, including effects on resource use and costs associated with receiving higher relational continuity of care for patients with SMI.MethodsEleven databases were searched between January 2000 and February 2021 for studies investigating associations between some measure of relational continuity and health outcomes and costs. All eligible studies were assessed for study relevance and risk of bias by at least two independent reviewers. Only studies with acceptable risk of bias were included. Due to study heterogeneity the synthesis was made narratively, without meta-analysis. The certainty of the summarized result was assessed using GRADE. Study registration number in PROSPERO: CRD42020196518.ResultsWe identified 8 916 unique references and included 17 studies comprising around 300 000 patients in the review. The results were described with regard to seven outcomes. The results indicated that higher relational continuity of care for patients with serious mental illness may prevent premature deaths and suicide, may lower the number of emergency department (ED) visits and may contribute to a better quality of life compared to patients receiving lower levels of relational continuity of care. The certainty of the evidence was assessed as low or very low for all outcomes. The certainty of results for the outcomes hospitalization, costs, symptoms and functioning, and adherence to drug treatment was very low with the result that no reliable conclusions could be drawn in these areas.ConclusionsThe results of this systematic review indicate that having higher relational continuity of care may have beneficial effects for patients with severe mental illness, and no results have indicated the opposite relationship. There is a need for better studies using clear and distinctive measures of exposure for relational continuity of care.
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- Heintz, Emelie, et al.
(författare)
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The impact of health economic evaluations in Sweden.
- 2014
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Ingår i: Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen. - : Elsevier. - 2212-0289 .- 1865-9217. ; 108:7, s. 375-82
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Tidskriftsartikel (refereegranskat)abstract
- The responsibility for healthcare in Sweden is shared by the central government, county councils and municipalities. The counties and municipalities are free to make their own prioritizations within the framework of the state healthcare laws. To guide prioritization of healthcare resources in Sweden, there is consensus that cost-effectiveness constitutes one of the three principles. The objective of this paper is to describe how cost-effectiveness, and hence health economic evaluations (HEE), have a role in pricing decisions, reimbursement of pharmaceuticals as well as the overall prioritization and allocation of resources in the Swedish healthcare system. There are various organizations involved in the processes of implementing health technologies in the Swedish healthcare system, several of which consider or produce HEEs when assessing different technologies: the Dental and Pharmaceutical Benefits Agency (TLV), the county councils' group on new drug therapies (NLT), the National Board of Health and Welfare, the Swedish Council on Health Technology Assessment (SBU), regional HTA agencies and the Public Health Agency of Sweden. The only governmental agency that has official and mandatory guidelines for how to perform HEE is TLV (LFNAR 2003:2). Even though HEEs may seem to have a clear and explicit role in the decision-making processes in the Swedish healthcare system, there are various obstacles and challenges in the use and dissemination of the results.
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| 5. |
- Janols, Lars-Olof, 1943-, et al.
(författare)
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Central stimulants in the Treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents : A naturalistic study of the prescription in Sweden 1977-2007
- 2009
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 63:6, s. 508-516
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Tidskriftsartikel (refereegranskat)abstract
- Central stimulants in the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents. A naturalistic study of the prescription in Sweden, 1977-2007. Nord J Psychiatry 2009; 63: 508-516. Background: An increased prescription of central stimulants (CS) for treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents has been reported in Sweden. Aims: To follow-up the treatment with CS as concerns total as well as regional differences in prescription rate. Efficacy and side-effects reported and gender differences in prescription over time also have been summarized. Methods: Data from the Swedish Medical Products Agency (MPA) of individual licences, annual reports about patients on individual or clinic licences from the MPA and sales statistics from the National Pharmacy (Apoteket AB) have been used. Results: The number of new licences and prescriptions increased dramatically from 1992 to 2007 and a change of preparations was seen. Great differences (fivefold) between the 21 counties of Sweden were noticed. In the follow-up reports to the MPA, a good/moderate treatment effect was reported in 92% and adverse effects were reported in 4% leading to discontinuation of medication in 46% of them. Abuse/misuse of the preparation was suspected in 0.2% of the reports. A tendency of a reduction of the proportion of boys to girls treated through individual licences has been seen. Conclusions: The study, although observational, supports good efficacy, limited adverse effects and a low degree of misuse in clinical use of CS for children and adolescents with ADHD.
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| 7. |
- Karlsson, Karin, et al.
(författare)
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Oral cladribine for B-cell chronic lymphocytic leukaemia : Report of a phase II trial with a 3-d, 3-weekly schedule in untreated and pretreated patients, and a long-term follow-up of 126 previously untreated patients
- 2002
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 116:3, s. 538-548
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Tidskriftsartikel (refereegranskat)abstract
- A phase II study was undertaken to evaluate the efficacy and toxicity of a new schedule of cladribine administration (10 mg/m2 orally daily for 3 d every 3 weeks) in 107 patients with B-cell chronic lymphocytic leukaemia (CLL). To minimize toxicity, treatment withdrawal criteria were defined. The results of the 63 previously untreated patients were retrospectively compared with 63 from an earlier study using a 5-d monthly schedule. The compiled data were analysed for prognostic factors for survival. No significant difference regarding response were seen in the two cohorts of the 126 previously untreated patients. The complete response (CR), nodular partial response (nPR) and partial response (PR) rates were 15%, 21% and 41%. Quality of response had no impact on survival. The 3- and 5-year overall survival for previously untreated patients was 73% and 58%, respectively, with a median follow-up of 54 months. Pretreatment haemoglobin < 11.0 g/dl and elevated beta-2-microglobulin had a negative influence on survival. Major infections occurred in 21% of patients in the 3-d study compared with 35% in the 5-d study. The overall response (OR) and CR rates in the 40 previously treated patients were 34% and 5% respectively. Median overall survival was 24 months and median progression-free survival for responding patients was 14 months. Cladribine used as a single agent is an effective treatment with an acceptable safety profile for pretreated and untreated B-CLL. The achievement of complete remission was not a prerequisite for long-term survival.
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| 9. |
- Lindemalm, Synnove, et al.
(författare)
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Comparison of cytotoxicity of 2-chloro- 2'-arabino-fluoro-2'-deoxyadenosine (clofarabine) with cladribine in mononuclear cells from patients with acute myeloid and chronic lymphocytic leukemia
- 2003
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Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 88:3, s. 324-332
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Clofarabine (CAFdA), one of the newer nucleoside drugs is undergoing a phase II clinical trial for the treatment of pediatric refractory/relapsed acute myeloid and lymphocytic leukemia. Although CAFdA is structurally similar to the clinically established analogs fludarabine and cladribine (CdA), its metabolism and mechanism of actions are significantly different. The present study investigates the in vitro cytotoxicity of CAFdA and CdA in mononuclear cells isolated from 52 patients with chronic lymphocytic (CLL) and acute myeloid leukemia (AML). DESIGN AND METHODS: We incubated the leukemic cells with drugs for 48 hours and cytotoxicity was then evaluated by the MTT dye assay. We also determined the levels of deoxycytidine and deoxyguanosine kinase with radio-chemical substrate-based assays and used a high performance liquid chromatographic method to measure cellular nucleotides in leukemia cells after 2 hours' incubation. RESULTS: Using equimolar concentrations of CAFdA and CdA, the in vitro cytotoxicity for the population was significantly higher with CAFdA than with CdA (median EC50 for CAFdA 0.12 microM and for CdA 0.15 microM, p<0.001). From the individual estimates the difference in cytotoxicity between CAFdA and CdA was more pronounced in cells from CLL patients (median EC50 for CAFdA 0.08 microM and for CdA 0.16 microM p<0.001) than in those from AML patients. We also found that CAFdA was phosphorylated more efficiently than CdA. No correlations were detected in this study between the levels of CdA and CAFdA nucleotides, enzymes levels and the in vitro responses. INTERPRETATION AND CONCLUSIONS: The greater in vitro cytotoxicity and cell metabolism of CAFdA compared to CdA confirm the high activity of CAFdA and encourage clinical trials with CAFdA in leukemic patients.
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