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- Millischer, V., et al.
(författare)
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Improving lithium dose prediction using population pharmacokinetics and pharmacogenomics: a cohort genome-wide association study in Sweden
- 2022
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Ingår i: Lancet Psychiatry. - 2215-0374. ; 9:6, s. 447-457
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Tidskriftsartikel (refereegranskat)abstract
- Background Lithium is the most effective treatment for bipolar disorder, resulting in strong suicide prevention effects. The therapeutic range of lithium, however, is narrow and treatment initiation requires individual titration to address inter-individual variability. We aimed to improve lithium dose prediction using clinical and genomic data. Methods We performed a population pharmacokinetic study followed by a genome-wide association study (GWAS), including two clinical Swedish cohorts. Participants in cohort 1 were from specialised outpatient clinics at Huddinge Hospital, in Stockholm, Sweden, and participants in cohort 2 were identified using the Swedish National Quality Registry for Bipolar disorder (BipolaR). Patients who received a lithium dose corresponding to at least one tablet of lithium sulphate (6 mmol) per day and had clinically relevant plasma concentrations of lithium were included in the study. Data on age, sex, bodyweight, height, creatinine concentration, estimated glomerular filtration rate (eGFR), lithium preparation, number of tablets of lithium per day, serum lithium concentration, and medications affecting kidney function (C09 antihypertensives, C03 [except C03D] sodium-retaining diuretics, and non-steroidal anti-inflammatory drugs) were obtained retrospectively for several timepoints when possible from electronic health records, BipolaR, and the Swedish prescription registry. The median time between timepoints was 1.07 years for cohort 1 and 1.09 years for cohort 2. The primary outcome of interest was the natural logarithm of total body clearance for lithium (CLLi) associated with the clinical variables. The residual effects after accounting for age and sex, representing the individual-level effects (CLLi,age/sex), were used as the dependent variable in a GWAS. Findings 2357 patients who were administered lithium (1423 women [60.4%] and 934 men [39.6%]; mean age 53.6 years [range 17-89], mainly of European descent) were included and 5627 data points were obtained. Age (variance explained [R-2]: R-cohort1(2)=0.41 and R-cohort2(2)=0.31; both p<0.0001), sex (R-cohort1(2)=0.0063 [p=0.045] and R-cohort2(2)=0.026 [p<0.0001]), eGFR (R-cohort1(2)=0.38 and R-cohort2(2)=0.0; both p<0.0001), comedication with diuretics (R-cohort1(2)=0.0058 [p=0.014] and R-cohort2(2)=0.0026 [p<0.0001]), and agents acting on the renin-aldosterone-angiotensin system (R-cohort1(2)=0.028 and R-cohort2(2)=0.015; both p<0.0001) were clinical predictors of CLLi. Notably, an association between CLLi and serum lithium was observed, with a lower CLLi being associated with higher serum lithium (R-cohort1(2)=0.13 and R-cohort2(2)=0.15; both p<0.0001). In a GWAS of CLLi,age/sex, one locus was associated with a change in CLLi (rs583503; beta=-0.053 [95% CI -0.071 to -0.034]; p<0.00000005). We also found enrichment of the associations with genes expressed in the medulla (p=0.0014, corrected FDR=0.04) and cortex of the kidney (p=0.0015, corrected FDR=0.04), as well as associations with polygenic risk scores for eGFR (p value threshold: 0.05, p=0.01), body-mass index (p value threshold: 0.05, p=0.00025), and blood urea nitrogen (p value threshold: 0.001, p=0.00043). The model based on six clinical predictors explained 61.4% of the variance in CLLi in cohort 1 and 49.8% in cohort 2. Adding genetic markers did not lead to major improvement of the models: within the subsample of genotyped individuals, the variance explained only increased from 59.32% to 59.36% in cohort 1 and from 49.21% to 50.03% in cohort 2 when including rs583503 and the four first principal components. Interpretation Our model predictors could be used clinically to better guide lithium dosage, shortening the time to reach therapeutic concentrations, thus improving care. Identification of the first genomic locus and PRS to be associated with CLLi introduces the opportunity of individualised medicine in lithium treatment. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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- Barenius, B, et al.
(författare)
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Quality of life and clinical outcome after anterior cruciate ligament reconstruction using patellar tendon graft or quadrupled semitendinosus graft: an 8-year follow-up of a randomized controlled trial
- 2010
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Ingår i: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 38:8, s. 1533-1541
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Tidskriftsartikel (refereegranskat)abstract
- Background: Randomized controlled trials after anterior cruciate ligament reconstructions with long-term follow-up including assessment of health-related quality of life are rare.Purpose: To compare clinical outcome and health-related quality of life 8 years after anterior cruciate ligament reconstruction using 2 types of graft.Study Design: Randomized controlled trial; Level of evidence, 1.Methods: Long-term follow-up of 164 patients with anterior cruciate ligament injury randomized to arthroscopic reconstruction with a quadrupled semitendinosus graft or a bone–patellar tendon–bone graft was undertaken. After a mean 8 years, 153 patients were available for follow-up, including instrumented laxity, 1-legged hop test, a knee-walking test, and assessment with International Knee Documentation Committee, Lysholm, Tegner, and patellofemoral pain score. Health-related quality of life was assessed with Knee Osteoarthritis Outcome Score and Short Form–36.Results: Patients in both graft groups retained the same stability, knee function, and health-related quality of life. The patellofemoral pain score was similar for both groups; the bone–patellar tendon–bone group had more donor site morbidity from kneeling and knee walking. In the bone–patellar tendon–bone group, 19 patients had no kneeling problems, 23 slight problems, 31 moderate problems, and 5 unable to kneel. Corresponding figures for the semitendinosus group were 25, 32, 16, and 2 ( P < .001). Patients with early reconstructions (<5 months) had a lower risk for meniscal injuries (37%) than did later reconstructed (62%, P = .008). Health-related quality of life regarding physical functioning in Short Form–36 was better for the early-reconstructed patients than for the later reconstructed (92 vs 85; P = .014). Patients without medial meniscal surgery had higher Knee Osteoarthritis Outcome Scores for all subscales than did patients with medial meniscal surgery, with most significant difference for sport and recreation (63 vs 75, P = .008).Conclusion: In the long term, the semitendinosus graft provided similar stability, knee function, and health-related quality of life but with less kneeling morbidity than did the bone–patellar tendon–bone graft.
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- Barenius, B, et al.
(författare)
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Quality of life and clinical outcome after anterior cruciate ligament reconstruction using patellar tendon graft or quadrupled semitendinosus graft: an 8-year follow-up of a randomized controlled trial (vol 38, pg 1533, 2010)
- 2011
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Ingår i: AMERICAN JOURNAL OF SPORTS MEDICINE. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 39:4, s. NP6-NP6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Barenius B, Nordlander M, Ponzer S, Tidermark J, Eriksson K. Quality of life and clinical outcome after anterior cruciate ligament reconstruction using patellar tendon graft or quadrupled semitendinosus graft: an 8-year follow-up of a randomized controlled trial. Am J Sports Med. 2010;38(8):1533-1541. (Original DOI: 10.1177/0363546510369549) In the above article, There is an error in Table 1 (page 1535). In the 3rd row of data, which shows gender distribution in the graft groups, the percentage for male distribution in the whole study population was depicted instead of the percentage of male distribution in the specified graft groups. The data for number of male patients in the groups are correct, and the error does not influence any of the other results.
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- Keshmiri, F., et al.
(författare)
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Contextualization and validation of the interprofessional collaborator assessment rubric (ICAR) through simulation : Pilot investigation.
- 2016
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Ingår i: Medical journal of the Islamic Republic of Iran. - : Iran University of Medical Sciences. - 1016-1430 .- 2251-6840. ; 30, s. 742-749
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Simulation can be used for educating, evaluating and assessing psychometric properties of an instrument. The aim of this study was to contextualize and assess the validity and reliability of the Interprofessional Collaborative Assessment tool (ICAR) in an Iranian context using simulation.METHODS:In this descriptive study, contextualization of the ICAR was assessed through several steps. Firstly, validity assessment was approved through expert panels and Delphi rounds. Secondly, reliability assessment was done by arranging a simulation video and assessing reproducibility, test-retest (ICC), internal consistency (Cronbach's Alpha) and inter-rater reliability (Kappa).The participants included 26 experts, 27 students and 6 staff of the Standardized Simulation Office of Teheran University of Medical Sciences.RESULTS:Contextualization and validity of the ICAR were approved in an Iranian context. The reliability of the tool was computed to be 0.71 according to Cronbach´s Alpha. The test-retest was calculated to be 0.76.CONCLUSION:The Iranian ICAR can be a useful tool for evaluating interprofessional collaborative competencies. The development of the instrument through a simulation scenario has been a positive prospect for researchers.
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- Klevebro, Susanna, et al.
(författare)
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Risk of SARS-CoV-2 exposure among hospital healthcare workers in relation to patient contact and type of care
- 2021
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 49:7, s. 707-712
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to assess prevalence of IgG antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and factors associated with seropositivity in a large cohort of healthcare workers (HCWs). Methods: From 11 May until 11 June 2020, 3981 HCWs at a large Swedish emergency care hospital provided serum samples and questionnaire data. Presence of IgG antibodies to SARS-CoV-2 was measured as an indicator of SARS-CoV-2 exposure. Results: The total seroprevalence was 18% and increased during the study period. Among the seropositive HCWs, 11% had been entirely asymptomatic. Participants who worked with COVID-19 patients had higher odds for seropositivity: adjusted odds ratio 1.96 (95% confidence intervals 1.59–2.42). HCWs from three of the departments managing COVID-19 patients had significantly higher seroprevalences, whereas the prevalence among HCWs from the intensive care unit (also managing COVID-19 patients) was significantly lower. Conclusions: HCWs in contact with SARS-CoV-2 infected patients had a variable, but on average higher, likelihood for SARS-CoV-2 infections.
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