| 1. |
- Balgård, Matts, et al.
(författare)
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Inclusion of pharmacy students in an interprofessional training ward placement for health care students in Sweden
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- What was done?: Final year undergraduate pharmacy students, specialising clinical pharmacy,were given the opportunity to spend two weeks of their six months pharmacypractice to participate in an interprofessional training ward placement(ITWP) together with medical, nursing and physiotherapy students. During thistwo-week clinical placement, the students were collaboratively responsiblefor managing the care of geriatric inpatients while under supervision oflicensed practitioners.Why was it done?: ITWP for health care students is established at various teaching hospitals.However, to our knowledge, no such program in Scandinavia has includedpharmacy students. Clinical pharmacy is a growing profession in Sweden andother health care students will in the future work alongside with clinicalpharmacists. Therefore we set out to add pharmacy students to the ITWP team,believing that it would be a valuable experience for them to collaborate andshare knowledge with students from other health care professions. Equallyimportant, it is a way to promote the pharmacist’s competence andcontribution to the multiprofessional health care team, prior to graduation.How was it done?: A working group was formed consisting of teachers from the faculty ofpharmacy, a student representative and a working clinical pharmacist. Thegroup developed the initiative, including among other things, prerequisites,an evaluation plan, a workflow tool for clinical rounds and suggested tasksfor pharmacy students during the placement.What has been achieved?: The program has been running for three semesters and 6–8 pharmacy studentshave participated in the ITWP each semester. The initiative has beenevaluated using surveys. Participating pharmacy students expressed gainingnew knowledge and better insight into nursing care and the roles of the otherprofessions. Nursing students appreciated the support in medicationmanagement and medical students found the pharmacy students to be valuablediscussion partners that could challenge their drug-related decisions. Tutorsexpressed that the pharmacy students brought a beneficial dynamic to the ITWPteam.What next?: The opportunity for students from different professions to work together witha common objective in a real-life setting gives them valuable insight in eachother’s professional roles early in their careers. This good practiceinitiative could be used in other interprofessional training ward placementswishing to involve pharmacy students.
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| 2. |
- Johansson, Patrik, et al.
(författare)
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A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.
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| 3. |
- Mainwaring, Oliver, et al.
(författare)
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ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.
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| 4. |
- Swartling, Maria, et al.
(författare)
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Population pharmacokinetics of cefotaxime in intensive care patients
- 2022
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 78:2, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates.METHODS: This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000-3000 mg given 2-6 times daily), were collected from the first day of treatment for up to three consecutive days. In total, 263 cefotaxime samples were included in the population pharmacokinetic analysis.RESULTS: A two-compartment model with linear elimination, proportional residual error and inter-individual variability (IIV) on clearance and central volume of distribution best described the data. The typical individual was 64 years, with body weight at ICU admission of 92 kg and estimated creatinine clearance of 94 mL/min. The resulting typical value of clearance was 11.1 L/h, central volume of distribution 5.1 L, peripheral volume of distribution 18.2 L and inter-compartmental clearance 14.5 L/h. The estimated creatinine clearance proved to be a significant covariate on clearance (p < 0.001), reducing IIV from 68 to 49%.CONCLUSION: A population pharmacokinetic model was developed to describe cefotaxime pharmacokinetics and associated variability in adult ICU patients. The estimated creatinine clearance partly explained the IIV in cefotaxime clearance. However, the remaining unexplained IIV is high and suggests a need for dose individualisation using therapeutic drug monitoring where the developed model, after evaluation of predictive performance, may provide support.
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| 5. |
- Swartling, Maria, et al.
(författare)
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Therapeutic drug monitoring of vancomycin and meropenem : Illustration of the impact of inaccurate information in dose administration time
- 2023
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier. - 0924-8579 .- 1872-7913. ; 63:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To illustrate the impact of errors in documented dose administration time on therapeutic drug monitoring (TDM)-based target attainment evaluation for vancomycin and meropenem, and to explore the influence of drug and patient characteristics, and TDM sampling strategies.Methods: Bedside observations of errors in documented dose administration times were collected. Population pharmacokinetic simulations were performed for vancomycin and meropenem, evaluating different one- and two-sampling strategies for populations with estimated creatinine clearance (CLcr) of 30, 80 or 130 mL/min. The impact of errors was evaluated as the proportion of individuals incorrectly considered to have reached the target.Results: Of 143 observed dose administrations, 97% of doses were given within ±30 min of the documented time. For vancomycin, a +30 min error was predicted to result in a 0.1-3.9 percentage point increase of cases incorrectly evaluated as reaching area under the concentration-time curve during a 24-hour period (AUC24)/minimum inhibitory concentration (MIC) >400, with the largest increase for patients with augmented renal clearance and peak and trough sampling. For meropenem, a +30 min error resulted in a 1.3-6.4 and 0-20 percentage point increase of cases incorrectly evaluated as reaching 100% T>MIC, and 50% T>MIC, respectively. Overall, mid-dose and trough sampling was most favourable for both antibiotics.Conclusions: For vancomycin, simulations indicate that TDM-based target attainment evaluation is robust with respect to the observed errors in dose administration time of ±30 min; however, the errors had a potentially clinically important impact in patients with augmented renal clearance. For meropenem, extra measures to promote correct documentation are warranted when using TDM, as the impact of errors was evident even in patients with normal renal function.
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| 6. |
- Swartling, Oskar, et al.
(författare)
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CKD Progression and Mortality Among Men and Women : A Nationwide Study in Sweden
- 2021
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386. ; 78:2, s. 190-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale & Objective: Chronic kidney disease (CKD) is a global health problem with increasing prevalence. Several sex-specific differences have been reported for disease progression and mortality. Selection and survival bias might have influenced the results of previous cohort studies. The objective of this study was to investigate sex-specific differences of CKD progression and mortality among patients with CKD not receiving maintenance dialysis. Study Design: Observational cohort study. Setting & Participants: Adult patients with incident CKD glomerular filtration rate categories 3b to 5 (G3b-G5) identified between 2010 and 2018 within the nationwide Swedish Renal Registry-CKD (SRR-CKD). Exposure: Sex. Outcomes: Time to CKD progression (defined as a change of at least 1 CKD stage or initiation of kidney replacement therapy [KRT]) or death. Repeated assessments of estimated glomerular filtration rate (eGFR). Analytical Approach: CKD progression and mortality before KRT were assessed by the cumulative incidence function methods and Fine and Gray models, with death handled as a competing event. Sex differences in eGFR slope were estimated using mixed effects linear regression models. Results: 7,388 patients with incident CKD G3b, 18,282 with incident CKD G4, and 9,410 with incident CKD G5 were identified. Overall, 19.6 (95% CI, 19.2-20.0) patients per 100 patient-years progressed, and 10.1 (95% CI, 9.9-10.3) patients per 100 person-years died. Women had a lower risk of CKD progression (subhazard ratio [SHR], 0.88 [95% CI, 0.85-0.92]), and a lower all-cause (SHR, 0.90 [95% CI, 0.85-0.94]) and cardiovascular (SHR, 0.83 [95% CI, 0.76-0.90]) mortality risk. Risk factors related to a steeper decline in eGFR included age, sex, albuminuria, and type of primary kidney disease. Limitations: Incomplete data for outpatient visits and laboratory measurements and regional differences in reporting. Conclusions: Compared to women, men had a higher rate of all-cause and cardiovascular mortality, an increased risk of CKD progression, and a steeper decline in eGFR.
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