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- Magnusson, Marie, et al.
(author)
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A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans
- 2006
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 61:2, s. 138-147
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Journal article (peer-reviewed)abstract
- AIM: To investigate the possible effects of pentoxifylline metabolites on retinal blood flow in humans. METHODS: A randomized, placebo-controlled, four-period cross-over study that was observer blinded and partly blinded for the eight participants. On one occasion a placebo was given as an intravenous (i.v.) infusion over 100 min. On the other three occasions pentoxifylline was administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two of the pentoxifylline infusions the subjects were pretreated with either ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser doppler flowmetry (SLDF) in a selected area of the central temporal retina before, during and until 5 h after the end of infusion. Blood samples for concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken serially and areas under the curves (AUCs) were calculated. Linear mixed models were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs. 4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin. The mean AUC for M5 was significantly reduced when subjects were pretreated with rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with rifampicin significantly increased retinal blood flow assessed as mean flow, pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole), compared with placebo. The increases over placebo were more pronounced on diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6% (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and 5.1% (1.4, 7.8) over placebo, respectively. After co-administration of pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards increased flow during diastole, but a significant decrease in pulsation. When AUCs for pentoxifylline and its metabolites were used as regressor variables to retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with a positive sign indicating that they enhanced the retinal blood flow. In contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The R-M1 and M5 metabolites of pentoxifylline contributed significantly to the effects of pentoxifylline on retinal blood flow.
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| 2. |
- Midlöv, Patrik, et al.
(author)
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Medication report reduces number of medication errors when elderly patients are discharged from hospital
- 2008
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In: PHARMACY WORLD & SCIENCE. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 30:1, s. 92-98
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Journal article (peer-reviewed)abstract
- Objective To investigate whether a Medication Report can reduce the number of medication errors when elderly patients are discharged from hospital. Method We conducted a prospective intervention with retrospective controls on patients at three departments at Lund University Hospital, Sweden that where transferred to primary care. The intervention group, where patients received a Medication Report at discharge, was compared with a control group with patients of the same age, who were not given a Medication Report when discharged from the same ward one year earlier. Main outcome measures The main outcome measure was the number of medication errors when elderly patients were discharged from hospital. Results Among 248 patients in the intervention group 79 (32%) had at least one medication error as compared with 118 (66%) among the 179 patients in the control group. In the intervention group 15% of the patients had errors that were considered to have moderate or high risk of clinical consequences compared with 32% in the control group. The differences were statistically significant (P < 0.001). Conclusion Medication errors are common when elderly patients are discharged from hospital. The Medication Report is a simple tool that reduces the number of medication errors.
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| 3. |
- Ericsson, Peter, et al.
(author)
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ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations.
- 2003
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In: Pharmacology and Toxicology. - : Wiley. - 1600-0773 .- 0901-9928. ; 93:2, s. 57-65
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Journal article (peer-reviewed)abstract
- The ECL cells are endocrine/paracrine cells in the acid-producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1-2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 mul/hr the recovery of submucosal histamine was 49%, at 34 mul/hr the recovery increased to 83%. At a perfusion rate below 20 mul/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0-3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization.
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| 6. |
- Hellström, Lina, et al.
(author)
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Impact of the Lund Integrated Medicines Management (LIMM) model on medication appropriateness and drug-related hospital revisits.
- 2011
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In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 67:7, s. 741-752
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Journal article (peer-reviewed)abstract
- PurposeTo examine the impact of systematic medication reconciliations when admitted to hospital, and medication review while in hospital, on the number of inappropriate medications and unscheduled drug-related hospital revisits in elderly patients.MethodsA prospective, controlled study in 210 patients, aged 65 years or older, who were admitted to one of three internal medicine wards at a University Hospital in Sweden. Patients received either standard care or care according to the Lund Integrated Medicines Management (LIMM) model. A multi-professional team, including a clinical pharmacist, provided medication reconciliations on admission and medication reviews during the hospital stay for the LIMM group. Blinded reviewers evaluated the appropriateness of the prescribing (using the Medication Appropriateness Index) on admission and discharge, and assessed the probability that a drug-related problem was the reason for any patient readmitted to hospital or visiting the emergency department within three months of discharge (using WHO causality criteria).ResultsThere was a greater decrease in the number of inappropriate drugs in the intervention group than in the control group for both the intention-to-treat population (51% [95% CI 43-58%] versus 39% [95% CI 30-48%], p=0.0446) and the per-protocol population (60% [95% CI 51-67%] versus 44% [95% CI 34-52 %], p=0.0106). There were 6 revisits to hospital in the intervention group which were judged as ‘possibly, probably or certainly drug-related’, compared with 12 in the control group (p=0.0469).ConclusionIn this study, medication reconciliation and reviews provided by a clinical pharmacist in a multi-professional team significantly reduced the number of inappropriate drugs and unscheduled drug-related hospital revisits for elderly patients.
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| 7. |
- Midlöv, Patrik, et al.
(author)
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Clinical outcomes from the use of Medication Report when elderly patients are discharged from hospital
- 2008
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In: PHARMACY WORLD & SCIENCE. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 30:6, s. 840-845
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Journal article (peer-reviewed)abstract
- Objective The objective of this study was to investigate whether a Medication Report also can reduce the number of patients with clinical outcomes due to medication errors. Method A prospective intervention study with retrospective controls on patients at three departments at Lund University Hospital, Sweden that where transferred to primary care. The intervention group, where patients received a Medication Report at discharge, was compared with a control group with patients of the same age, who were not given a Medication Report when discharged from the same ward one year earlier. For patients with at least one medication error all contacts with hospital or primary care within 3 months after discharge were identified. For each contact it was evaluated whether this was caused by the medication error. We also compared medication errors that have been evaluated as high or moderate clinical risk with medication errors without clinical risk. Main outcome measures Need for medical care in hospital or primary care within three months after discharge from hospital. Medical care is readmission to hospital as well as visits of study population to primary and out-patient secondary health care. Results The use of Medication Report reduced the need for medical care due to medication errors. Of the patients with Medication Report 11 out of 248 (4.4%) needed medical care because of medication errors compared with 16 out of 179 (8.9%) of patients without Medication Report (p = 0.049). The use of a Medication Report significantly reduced the risk of any consequences due to medication errors, p = 0.0052. These consequences included probable and possible care due to medication error as well as administrative procedures (corrections) made by physicians in hospital or primary care. Conclusions The Medication Report seems to be an effective tool to decrease adverse clinical consequences when elderly patients are discharged from hospital care.
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| 8. |
- Reis, Margareta, et al.
(author)
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Serum disposition of sertraline, N-desmethylsertraline and paroxetine : a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression
- 2004
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In: Human Psychopharmacology. - : Wiley. - 0885-6222 .- 1099-1077. ; 19:5, s. 283-291
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Journal article (peer-reviewed)abstract
- Sertraline and paroxetine are frequently prescribed SSRIs for long-term treatment of major depression. Nevertheless, continuous follow-ups of drug concentrations prevailing in patients during the whole treatment period are not available. Hence, in a large phase IV clinical trial, a total of 353 patients with major depression were enrolled for a 6-month comparison of sertraline (50–150 mg daily) and paroxetine (20–60 mg daily). The present study reports the pharmacokinetic results of up to eight serum samples per patient.1 A profound variability was found in the interindividual steady state and trough serum levels of sertraline, desmethylsertraline and paroxetine: the coefficient of variation (CV) was 59% for sertraline, 51% for desmethylsertraline, 27% for the ratio desmethylsertraline/sertraline (50 mg/day), and 71% for paroxetine (20 mg/day). The intraindividual CV for the ratio desmethylsertraline/sertraline was only 19%, indicating intraindividual metabolizing stability over time. Both sertraline and paroxetine displayed sex differences in the dose-concentration correlation.2 It was possible to predict sertraline, but not paroxetine, steady state levels.3 The terminal elimination t½ for both drugs after 6 months of treatments was similar to data previously reported from short-term withdrawal studies.4 No correlation between serum drug concentrations and clinical effect was detected for either sertraline or paroxetine.For the future, continuous efforts are warranted to perform PK investigations in the natural clinical setting in which the drugs are usually prescribed.
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| 9. |
- Bondesson, Åsa ÅB, et al.
(author)
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A structured questionnaire to assess patient compliance and beliefs about medicines taking into account the ordered categorical structure of data
- 2009
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In: Journal of Evaluation In Clinical Practice. - : Wiley. - 1356-1294 .- 1365-2753. ; 15:4, s. 713-723
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Journal article (peer-reviewed)abstract
- RATIONALE, AIMS AND OBJECTIVE: The objectives were to describe and evaluate the structured medication questionnaire and to improve data handling of results from the Morisky four-item scale for patient compliance and Beliefs about Medicines Questionnaire-specific (BMQ-specific). METHODS: A questionnaire was developed with the purpose of being used when identifying medication errors and assessing patient compliance to and beliefs about medicines. RESULTS: A majority of the respondents (62%; CI 45-77%) had at least one medication error. Assuming that all items are equally important in the Morisky four-item scale we presented four alternative ways to create a unidimensional global scale. A two-dimensional global scale was also constructed. The results from the BMQ-specific were presented in different ways, all taking into account that the scale has ordered verbal categories: at the level addressing each specific question, at the sub-scales 'concern' and 'necessity' level and at the global level. CONCLUSIONS: The structured medication questionnaire can be used in daily practice as a tool to identify drug-related problems. The choice of how to use and present data from those scales in research depends on patient characteristics and how discriminating one would like the scales to be.
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