| 1. |
- Wallin, Anders, 1950, et al.
(författare)
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Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
- 2007
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Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
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| 2. |
- Håkansson, Stellan, et al.
(författare)
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Group B streptococcal carriage in Sweden : a national study on risk factors for mother and infant colonisation
- 2008
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - Stockholm : Wiley. - 0001-6349 .- 1600-0412. ; 87:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background. To study group B streptococcus (GBS) colonisation in parturients and infants in relation to obstetric outcome and to define serotypes and antibiotic resistance in GBS isolates acquired. Methods. A population-based, national cohort of parturients and their infants was investigated. During 1 calendar week in 2005 all women giving birth (n=1,754) were requested to participate in the study. Results. A total of 1,569 mother/infant pairs with obstetric and bacteriological data were obtained. Maternal carriage rate was 25.4% (95% confidence interval (CI): 23.3-27.6). In GBS-positive mothers with vaginal delivery and no intrapartum antibiotics, the infant colonisation rate was 68%. Some 30% of infants were colonised after acute caesarean section, and 0% were colonised after an elective procedure. Duration of transport of maternal recto/vaginal swabs of more than 1 day impeded culture sensitivity. Infant mMales were more frequently colonised than females (76.9 versus 59.8%, odds ratio (OR): 2.16; 95% CI: 1.27-3.70), as were infants born after rupture of membranes ≥24 h (p =0.039). Gestational age, birth weight and duration of labor did not significantly influence infant colonisation. Some 30% of parturients with at least one risk factor for neonatal disease received intrapartum antibiotics. The most common GBS serotypes were type III and V. Some 5% of the isolates were resistant to clindamycin and erythromycin, respectively. Conclusions. Maternal GBS prevalence and infant transfer rate were high in Sweden. Males were more frequently colonised than females. The sensitivity of maternal cultures decreased with the duration of sample transport. Clindamycin resistance was scarce. The use of intrapartum antibiotics was limited in parturients with obstetric risk factors for early onset group B streptococcal disease.
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| 3. |
- Ivarsson, Tord, 1946, et al.
(författare)
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Categorical and dimensional aspects of co-morbidity in obsessive-compulsive disorder (OCD)
- 2008
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 17:1, s. 20-31
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Tidskriftsartikel (refereegranskat)abstract
- Objective Obsessive-compulsive disorder (OCD) defined at the diagnostic level encompasses divergent symptoms and is often associated with other psychiatric problems. The present study examines OCD versus co-morbid symptom patterns in OCD in children and adolescents in order to investigate the presence of diagnostic heterogeneity. Subjects and methods A total of 113 outpatients with primary OCD participated. The patients’ and primary caretakers’ responses on semi-structured interviews (child version of Schedule for Affective Disorders and Schizophrenia and the Children’s Yale-Brown Obsessive Compulsive Scale) and parents’ responses on the Child Behaviour Checklist were used in the study. Psychiatric diagnoses were related to CBCL syndrome scores and CBCL scores were compared with the Swedish normative data. Results Co-morbid diagnoses were very common and only one out of five patients had only OCD. The most common group was the neuropsychiatric disorders (47%) where tic disorders were most common (27%), especially among boys (40.8%; P = .006, Fisher’s exact test). Also anxiety disorders were common (39.8%) as were affective disorders (24.8%) neither with any gender differences. Diagnoses of disruptive disorders were less common (8.8%), almost exclusively of the oppositional kind (ODD) (8.8%). From the dimensional point of view using the CBCL, patients with OCD scored higher than Swedish youngster generally do, and some gender differences were seen in that girls scored higher on anxiety and depression while both girls and boys had high scores on thought problems, attention problems and especially aggressive behaviour. Comorbidities explained from 25 to 50% scores of the CBCL sub-syndrome scales, often with both main effects and through complex patterns of interaction with gender, OCD-severity and other co-morbid problems. Conclusions While co-morbid problems is an important facet of OCD, sub-syndromal levels of symptoms that can be assessed using a dimensional approach, is a large part of the total symptom burden in these youngsters. Our data indicate contributions of different pathways for girls and for boys for several comorbid problems together with OCD-severity.
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| 4. |
- Mårtensson, Lena, 1958, et al.
(författare)
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Acupuncture versus subcutaneous injections of sterile water as treatment for labour pain
- 2008
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Ingår i: Acta Obstetricia et Gynecologica. - : Wiley. - 0001-6349 .- 1600-0412. ; 87, s. 171-177
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Tidskriftsartikel (refereegranskat)abstract
- Background. Two methods for pain relief and relaxation during labour are sterile water injections and acupuncture. In several studies, sterile water injections have been shown to provide good pain relief, particularly for low back pain during labour. The acupuncture studies for pain relief during labour are not as concordant. Therefore, the aim of this study was to explore if there were any differences between acupuncture and sterile water injections regarding pain relief and relaxation during labour. Methods. A randomised controlled trial. Some 128 pregnant women at term were randomly assigned to receive acupuncture (no 62) sterile water injections (no. 66). The primary endpoint was to compare the differences between pre-treatment pain levels and maximum pain in the 2 groups. Results. The main results of this study were that sterile water injections yielded greater pain relief (pB0.001) during childbirth compared to acupuncture. The secondary outcome showed that women in the sterile water group had a higher degree of relaxation (pB0.001) compared to the acupuncture group. The women’s own assessment of the effects also favoured sterile water injections (pB0.001). There were no significant differences regarding requirements for additional pain relief after treatment between the 2 groups. Conclusions. Women given sterile water injection experience less labour pain compared to women given acupuncture.
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| 5. |
- Mårtensson, Lena, et al.
(författare)
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Sterile water injections as treatment for low-back pain during labour : A review
- 2008
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Ingår i: Australian and New Zealand journal of obstetrics and gynaecology. - : Blackwell Publishing. - 0004-8666 .- 1479-828X. ; 48:4, s. 369-374
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Forskningsöversikt (refereegranskat)abstract
- Background: Some women have severe low-back pain during childbirth. It has been shown that sterile water injections reduce this pain. This method, which is easy to learn and very cheap can be a good pain relief alternative primarily in countries with limited available pain relief options. Aims: The aim of this article was to describe published research concerning sterile water injections for treatment of low-back pain during labour. Methods: Three databases were searched from their inception until February, 2008. The inclusion criteria were trials elucidating the pain relief effect of sterile water injections during childbirth. The search terms were labour, birth, obstetrics, parturient, pregnancy, pain relief, analgesia, injection, papules, blocks and sterile water. The computerised literature searches yielded 64 trials, 55 of which failed to meet our inclusion criteria. We used the Jadad Score Instrument to assess the quality of the remaining nine articles, of which six were of adequate quality. Results: All studies in this review had similar alms, designs and measurement instruments and they reported good pain relief particularly, for low-back pain during childbirth. In all studies the pain score reduction is approximately, 60% and the effect remains up to two hours. Conclusions: Sterile water injections seem to be a good alternative for low-back pain during childbirth.
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| 6. |
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| 7. |
- Schultz, Kristofer, et al.
(författare)
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Reduced CSF CART in dementia with Lewy bodies.
- 2009
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 453:2, s. 104-6
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Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD). The underlying neurobiological mechanism of DLB is not fully understood and no generally accepted biomarkers are yet available for the diagnosis of DLB. In a recent MRI study, DLB patients displayed hypothalamic atrophy whereas this region was not affected in AD patients. Cocaine and amphetamine regulated transcript (CART) is a neuropeptide expressed selectively in neurons in the hypothalamus. Here, we found that CSF CART levels were significantly reduced by 30% in DLB patients (n = 12) compared to controls (n = 12) as well as to AD patients (n = 14) using radioimmunoassay. Our preliminary results suggest that reduced CSF CART is a sign of hypothalamic dysfunction in DLB and that it may serve as a biomarker for this patient group.
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| 8. |
- Tranvik, Lena, et al.
(författare)
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"Gemensamma värderingar"
- 2009
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Ingår i: Miljötrender från SLU. - 1403-4743. ; , s. 2-2
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 9. |
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| 10. |
- Wallin, Johan, 1974-
(författare)
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Dose Adaptation Based on Pharmacometric Models
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many drugs exhibit major variability in both pharmacokinetic (PK) and pharmacodynamic (PD) parameters that prevents the use of the same dose for all patients. Variability can occur both between patients (IIV) as well as within patients over the course of time (IOV). In a drug with narrow therapeutic range and substantial IIV, dose selection may require individual adaptation. Adaptation can either be made before (a priori) or after (a posteriori) first drug administration. The former implies basing the dose on prior information known to be influential, such as kidney function indicators, weight or concomitant medication, whereas a posteriori dose adaptations are based on post-treatment observations. Often individualization cannot be based on the clinical outcome itself. In such cases, drug concentrations or biomarkers may be valuable for dose individualisation. In this thesis two therapeutic areas where dosing is critical have been investigated regarding the possibilities of a priori and a posteriori dose adaptation; anticancer treatment where myelosuppression is dose limiting, and tacrolimus used for immunosuppression in paediatric transplantation. In tacrolimus previously published models were found to be of little value for dose adaptation in the early critical days post-transplantation. New PK models were developed and used to suggest new dosing regimens tailored for the paediatric population, recognizing the changing pharmacokinetics in the early time post-transplantation. For several anticancer drugs covariates were identified that partly explained IIV in myelosuppression. IOV were found to be lower than IIV which implies that individual dose adaptations a posteriori can be valuable. Dose adaptation, using Bayesian principles in order to simultaneously minimise the risk of severe toxicity or subtherapeutic levels, was evaluated using simulations. Type and amount of data needed, as well as variability parameters influential on the outcome, were evaluated. Results show drug concentrations being of little value, if neutrophil counts are available. The models discussed in this thesis have been implemented in MS Excel macros for Bayesian forecasting, to allow widespread distribution to clinical settings without necessitating access to specific statistical software.
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| 11. |
- Wallin, Johan E., et al.
(författare)
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A tool for neutrophil guided dose adaptation in chemotherapy
- 2009
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Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 93:3, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy dosing in anticancer treatment is a balancing act between achieving concentrations that are effective towards the malignancy and that result in acceptable side-effects. Neutropenia is one major side-effect of many antitumor agents, and is related to an increased risk of infection. A model capable of describing the time-course of myelosuppression from administered drug could be used in individual dose selection. In this paper we describe the transfer of a previously developed semi-mechanistic model for myelosuppression from NONMEM to a dosing tool in MS Excel, with etoposide as an example. The tool proved capable to solve a differential equation system describing the pharmacokinetics and pharmacodynamics, with estimation performance comparable to NONMEM. In the dosing tool the user provides neutrophil measures from a previous treatment course and request for the dose that results in a desired nadir in the upcoming course through a Bayesian estimation procedure.
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| 12. |
- Wallin, Johan E, et al.
(författare)
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Population pharmacokinetics of tacrolimus in pediatric hematopoietic stem cell transplant recipients: new initial dosage suggestions and a model-based dosage adjustment tool.
- 2009
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Ingår i: Therapeutic drug monitoring. - 1536-3694. ; 31:4, s. 457-66
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Tidskriftsartikel (refereegranskat)abstract
- The population pharmacokinetics of tacrolimus was described in 22 pediatric hematopoietic stem cell transplant recipients, and a model-based dosage adjustment tool that may assist with therapy in new patients was developed. Patients received tacrolimus by continuous intravenous (IV) infusion (0.03 mg x kg(-1) x d(-1)) starting 2 days before transplantation, with conversion to oral therapy 2-3 weeks after transplant. Population pharmacokinetic analysis was performed using NONMEM. A Bayesian dosage adjustment tool that searches for individual parameter estimates to describe concentration measurements, counterbalanced by the final population model, was created in Excel. Typical clearance was 106 mL x h(-1) x kg(-0.75), typical distribution volume was 3.71 L/kg, and typical bioavailability was 15.7%. Tacrolimus clearance decreased with increasing serum creatinine, and bioavailability decreased with postoperative day. A Bayesian dosage adjustment tool capable of suggesting an initial infusion rate based on patient covariate values and devising a further individualized dosage regimen as drug concentration measures become available was developed. Predictions from the model showed that current IV dose recommendations of 0.03 mg x kg(-1) x d(-1) may potentially produce toxic drug concentrations in this patient population, whereas current oral conversion of 4 times the adjusted IV dose may lead to subtherapeutic concentrations. A more suitable infusion rate to obtain a steady state concentration of 12 ng/mL was predicted to be 0.035 mg x kg(-0.75) x (-1)d. An additional loading dose of 0.07 mg x kg(-1) x d(-1) (total dose: 0.07 mg x kg(-1) x d(-1) + 0.035 mg x kg(-0.75) x d(-1)) during the first 24 hours of therapy should allow rapid achievement of steady state concentrations. A conversion factor of 6 from IV to enteric therapy may be more suitable. Such dosage recommendations may be site specific. The appropriateness of targets was not investigated in this study. The Bayesian dosing adjustment tool and suggested dose recommendations need to be evaluated in a prospective study before they can be applied in the clinical setting.
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| 13. |
- Wallin, Johan, 1974-, et al.
(författare)
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Population pharmacokinetics of tacrolimus in paediatric haematopoietic stem cell transplant recipients : New initial dosage suggestions and a model based dosage adjustment tool
- 2009
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Ingår i: Therapeutic Drug Monitoring. - Philadelphia PA, US : Lippincott Williams & Wilkins. - 0163-4356 .- 1536-3694. ; 31:4, s. 457-466
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Tidskriftsartikel (refereegranskat)abstract
- The population pharmacokinetics of tacrolimus was described in 22 paediatric haematopoietic stem cell transplant recipients and a model-based dosage adjustment tool that may assist with therapy in new patients was developed. Patients received tacrolimus by continuous intravenous infusion (0.03mg/kg/day) starting two days before transplantation, with conversion to oral therapy 2-3 weeks post-transplant. Population pharmacokinetic analysis was performed using NONMEM. A dosage adjustment tool that searches for individual parameter estimates to describe concentration measurements, counter-balanced by the final population model, was created in Excel. Typical clearance was 106 mL/h/kg0.75, typical distribution volume was 3.71 L/kg and typical bioavailability was 15.7%. Tacrolimus clearance decreased with increasing serum creatinine and bioavailability decreased with post-operative day. Predictions from the model showed that current intravenous dose recommendations of 0.03 mg/kg/day may produce potentially toxic drug concentrations in the patient population, whereas current oral conversion of four times the adjusted intravenous dose may lead to subtherapeutic concentrations. We suggest a dose of 0.035mg/kg0.75/day to ensure satisfactory levels, and an oral conversion factor of six times the intravenous dose. A dosage adjustment tool was developed that is capable of suggesting an initial infusion rate based on patient weight and serum creatinine and of devising a further individualised dosage as individual drug concentration measurements become available. The tool also allows the clinicia to graphically examine the concentration-time profile of tacrolimus under different infusion rates, with or without a loading dose.
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| 14. |
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