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- Ekblom, Anna Gerber, et al.
(författare)
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Hand Function in Adults with Radial Longitudinal Deficiency.
- 2014
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Ingår i: Journal of Bone and Joint Surgery. American Volume. - 1535-1386 .- 0021-9355. ; 96:14, s. 1178-1184
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Tidskriftsartikel (refereegranskat)abstract
- Functional impairment in individuals with radial longitudinal deficiency can be influenced by several factors, including a short and bowed forearm, radial deviation of the wrist, a non-functional or absent thumb, limited finger motion, and impaired grip strength, but their relationship with activity and participation in adults with radial deficiency is not known.METHODS: Twenty individuals, eighteen to sixty years of age, who had Bayne type-II to V radial longitudinal deficiency, were examined in the context of the International Classification of Functioning, Disability and Health. Body function and structure were evaluated by measures of range of motion, grip strength, key pinch, sensibility, and radiographic parameters. Activity was evaluated by the Box and Block Test and the Sollerman test, and participation was evaluated by QuickDASH (the short form of the Disabilities of Arm, Shoulder and Hand outcome measure) and by the Medical Outcomes Study 12-Item Short Form Health Survey. Statistical correlations among assessments of body function and structure, activity, and participation were examined.RESULTS: The mean total active motion of the wrist (43°) and mean total active motion of the digits (377°) were less than the norms. The mean radial deviation of the wrist was 31°. The mean grip strength (4.0 kg), key pinch (1.4 kg), and scores for the Box and Block Test (55 blocks per minute) and the Sollerman test on hand function (56 points) were considerably lower than the norms. The mean scores were 18 points for QuickDASH, 51 points for Short Form-12 physical component summary, and 53 points for Short Form-12 mental component summary. Significant relationships were found between the Box and Block Test and grip strength (p = 0.012), key pinch (p < 0.001), and total active motion of digits (p < 0.001); between the Sollerman test and the total active motion of elbow (p < 0.001) and the total active motion of digits (p < 0.001); between the QuickDASH and forearm length (p < 0.001), the total active motion of elbow (p = 0.001), and the total active motion of digits (p < 0.001); between the Short Form-12 physical component summary and grip strength (p = 0.016), forearm length (p < 0.001), total active elbow motion (p < 0.001), and total active digit motion (p < 0.001); and between the Short-Form-12 mental component summary and radial deviation of the wrist (p = 0.019). No significant correlations were found between the radiographic measurement of the radial deviation of the wrist (total forearm angle) and the Box and Block Test (p = 0.244), the Sollerman test (p = 0.775), QuickDASH (p = 0.156), Short Form-12 physical component summary (p = 0.107), or Short Form-12 mental component summary (p = 0.129).CONCLUSIONS: In individuals with radial longitudinal deficiency, grip strength, key pinch, forearm length, and elbow and digital motion seem to be more important for the individual's activity and participation than the radial angulation of the wrist.LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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- Ekblom, Anna Gerber, et al.
(författare)
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Hand function in children with radial longitudinal deficiency
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: In children with hypoplasia or aplasia of the radius (radial longitudinal deficiency) manual activity limitations may be caused by several factors; a short and bowed forearm, radial deviation of the wrist, a non-functional or absent thumb, limited range of motion in the fingers and impaired grip strength. The present study investigates the relation between these variables and activity and participation in children with radial dysplasia. Methods: Twenty children, age 4-17 years, with radial longitudinal dysplasia Bayne type II-IV were examined with focus on the International Classification of Functioning and Health, version for Children and Youth (ICF-CY) context. Body function/structure was evaluated by measures of range of motion, grip strength, sensibility and radiographic parameters. Activity was examined by Box and Block Test and Assisting Hand Assessment (AHA). Participation was assessed by Children's Hand-use Experience Questionnaire (CHEQ). Statistical correlations between assessments of body function/structure and activity as well as participation were examined. Results: The mean total active motion of wrist (49.6 degrees) and digits (447 degrees) were less than norms. The mean hand forearm angle was 34 degrees radially. Ulnar length ranged from 40 to 80% of age-related norms. Grip strength (mean 2.7 kg) and Box and Block Test (mean 33.8 blocks/minute) were considerably lower than for age-related norms. The mean score for the AHA was 55.9 and for CHEQ Grasp efficiency 69.3. The AHA had significant relationship with the total range of motion of digits (p = 0.042). Self-experienced time of performance (CHEQ Time) had significant relationship with total active motion of wrist (p = 0.043). Hand forearm angle did not show any significant relationship with Box and Block Test, AHA or CHEQ. Conclusion: In radial longitudinal deficiency total range of motion of digits and wrist may be of more cardinal importance to the child's activity and participation than the angulation of the wrist.
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- Malm-Erjefalt, Monika, et al.
(författare)
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Effect on the Gastrointestinal Absorption of Drugs from Different Classes in the Biopharmaceutics Classification System, When Treating with Liraglutide
- 2015
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 12:11, s. 4166-4173
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Tidskriftsartikel (refereegranskat)abstract
- Like other GLP-1 receptor agonists used for treatment of type 2 diabetes, liraglutide delays gastric emptying. In this clinical absorption study, the primary objective was to investigate the effect of liraglutide (at steady state) on the rate and/or extent of gastrointestinal (GI) absorption of concomitantly orally taken drugs from three classes of the Biopharmaceutics Classification System (BCS). To provide a general prediction on liraglutide drugdrug absorption interaction, single-dose pharmacokinetics of drugs representing BCS classes II (low solubility-high permeability; atorvastatin 40 mg and griseofulvin 500 mg), III (high solubilitylow permeability; lisinopril 20 mg), and IV (low solubility-low permeability; digoxin 1 mg) were studied in healthy subjects at steady state of liraglutide 1.8 mg, or placebo, in a two-period crossover design. With liraglutide, the oral drugs atorvastatin, lisinopril, and digoxin showed delayed t(max) (by <= 2 h) and did not meet the criterion for bioequivalence for C-max (reduced C-max by 27-38%); griseofulvin had similar tmax and 37% increased C-max. Although the prespecified bioequivalence criterion was not met by all drugs, the overall plasma exposure (AUC) of griseofulvin, atorvastatin, lisinopril, and digoxin only exhibited minor changes and was not considered to be of clinical relevance.
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- Savic, Radojka M., et al.
(författare)
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Population pharmacokinetics of cladribine in patients with multiple sclerosis
- 2017
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 56:10, s. 1245-1253
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to characterize the concentration-time course of cladribine (CdA) and its main metabolite 2-chloroadenine (CAde), estimate interindividual variability in pharmacokinetics (PK), and identify covariates explaining variability in the PK of CdA. This population PK analysis was based on the combined dataset from four clinical studies in patients with multiple sclerosis (MS): three phase I studies, including one food and one drug-drug interaction study, and one phase III clinical study. Plasma and urine concentration data of CdA and CAde were modeled simultaneously. The analysis comprised a total of 2619 CdA and CAde plasma and urine concentration observations from 173 patients with MS who received an intravenous infusion or oral tablet doses of CdA as a single agent or in combination with interferon (IFN) beta-1a. CdA PK data were best described by a three-compartment model, while a one-compartment model best described the PK of CAde. CdA renal clearance (CLR) was correlated with creatinine clearance (CLCR), predicting a decrease in the total clearance of 19%, 30% and 40% for patients with mild (CLCR = 65 ml/min), moderate (CLCR = 40 ml/min) and severe (CLCR = 20 ml/min) renal impairment, respectively. Food decreased the extent of CdA absorption by 11.2% and caused an absorption delay. Coadministration with IFN beta-1a was found to increase non-CLR (CLNR) by 21%, resulting in an increase of 11% in total clearance. Both CdA and CAde displayed linear PK after intravenous and oral administration of CdA, with CdA renal function depending on CLCR.
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- Zingmark, Per-Henrik, et al.
(författare)
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Population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients
- 2003
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 56:2, s. 173-183
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: This analysis was performed to investigate the population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients using a nonlinear mixed effects modelling approach. METHODS: One thousand five hundred and forty-six acute stroke patients (774 on active treatment) from 166 centres were included in three randomized, double-blind, placebo-controlled phase III efficacy and safety studies. A total dose of 68 mg kg(-1) clomethiazole edisilate was given as a three-phase i.v.-infusion over 24 h. Three blood samples were drawn from all patients to characterize the pharmacokinetics. Sedation was monitored throughout the entire treatment period and the degree of sedation was measured on a discrete ordinal scale with six levels. Models were fitted to the data using the software NONMEM. RESULTS: Clomethiazole was characterized by a two-compartment pharmacokinetic model with interindividual variability in all structural parameters. For a patient weighing 75 kg, the average CL, V1, Q, and V2 was estimated to be 52.7 l h(-1), 82.5 l, 167 l h(-1) and 335 l, respectively. The interindividual variability in CL, V1, Q and V2 was estimated to be 48%, 53%, 42% and 54%, respectively. Increasing body weight and concomitant administration of liver enzyme inducing drugs were found to increase clearance (by 0.5 l h(-1) kg(-1) and 40%, respectively). Increasing weight also increased the volume of distribution (1.1 l kg(-1) for V1 and 4.7 l kg(-1) for V2). A six-category proportional odds model with a component including the natural course of sedation following placebo administration, a drug component (present or absent) and an interindividual variability component described the degree of sedation. Stroke severity as measured on the NIH-stroke scale on admission and drug treatment were the most important predictors of sedation, but a nonlinear increase in sedation with increasing age was also found. Increasing body weight increased the sedative drug effect. CONCLUSIONS: The pharmacokinetics of clomethiazole were characterized in acute stroke patients and the analysis excluded several possible covariates of interest in drug development. The time course of sedation could be quantitatively described during the first 24 h following an acute stroke in the presence or absence of clomethiazole treatment.
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