| 1. |
- Byström, Anna, et al.
(författare)
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Lateral movement of the saddle relative to the equine spine in rising and sitting trot on a treadmill
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Saddle slip, defined as a progressive lateral displacement of the saddle during ridden exercise, has recently been given attention in the scientific press as a potential sign of lameness. The aim of this study was to objectively quantify the normal lateral movement (oscillations) of the saddle relative to the horse in non-lame horses, and associate this movement to the movements of the horse and rider. Data from seven Warmblood dressage horses competing at Grand Prix (n = 6) or FEI Intermediate (n = 1) level, ridden by their usual riders, were used. Simultaneous kinetic, kinematic and saddle pressure measurements were conducted during sitting and rising trot on a force-measuring treadmill. The maximum lateral movement of the caudal part of the saddle relative to the horse's spine (MAX) was determined for each diagonal step. A mixed model was applied, with MAX as outcome, and T6 and S3 vertical position, rigid body rotation angles (roll, pitch, yaw) of the horse's and rider's pelvis, vertical ground reaction forces, saddle force, and rider position (rising in rising trot, sitting in rising trot or sitting in sitting trot) as explanatory variables. The least square means for MAX were 14.3 (SE 4.7) mm and 23.9 (SE 4.7) mm for rising and sitting in rising trot, and 20.3 (SE 4.7) mm for sitting trot. A 10 mm increase in maximum pelvic height at push off increased MAX by 1.4 mm (p<0.0001). One degree increase in rider pelvis roll decreased MAX 1.1 mm, and one degree increase in rider pelvis yaw increased MAX 0.7 mm (both p<0.0001). The linear relationships found between MAX and movements of both horse and rider implies that both horse and rider movement asymmetries are reflected in the lateral movements or oscillations of the saddle in non-lame horses.
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| 2. |
- Dalén, Johan, et al.
(författare)
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Identifying Predictors of First-Line Subcutaneous TNF-Inhibitor Persistence in Patients with Inflammatory Arthritis : A Decision Tree Analysis by Indication
- 2023
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Ingår i: Advances in Therapy. - 0741-238X .- 1865-8652. ; 40:10, s. 4657-4674
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Treatment persistence is a proxy for efficacy, safety and patient satisfaction, and a switch in treatment or treatment discontinuation has been associated with increased indirect and direct costs in inflammatory arthritis (IA). Hence, there are both clinical and economic incentives for the identification of factors associated with treatment persistence. Until now, studies have mainly leveraged traditional regression analysis, but it has been suggested that novel approaches, such as statistical learning techniques, may improve our understanding of factors related to treatment persistence. Therefore, we set up a study using nationwide Swedish high-coverage administrative register data with the objective to identify patient groups with distinct persistence of subcutaneous tumor necrosis factor inhibitor (SC-TNFi) treatment in IA, using recursive partitioning, a statistical learning algorithm. Methods: IA was defined as a diagnosis of rheumatic arthritis (RA), ankylosing spondylitis/unspecified spondyloarthritis (AS/uSpA) or psoriatic arthritis (PsA). Adult swedish biologic-naïve patients with IA initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017. Treatment persistence of SC-TNFi was derived based on prescription data and a defined standard daily dose. Patient characteristics, including age, sex, number of health care contacts, comorbidities and treatment, were collected at treatment initiation and 12 months before treatment initiation. Based on these characteristics, we used recursive partitioning in a conditional inference framework to identify patient groups with distinct SC-TNFi treatment persistence by IA diagnosis. Results: A total of 13,913 patients were included. Approximately 50% had RA, while 27% and 23% had AS/uSpA and PsA, respectively. The recursive partitioning algorithm identified sex and treatment as factors associated with SC-TNFi treatment persistence in PsA and AS/uSpA. Time on treatment in the groups with the lowest treatment persistence was similar across all three indications (9.5–11.3 months), whereas there was more variation in time on treatment across the groups with the highest treatment persistence (18.4–48.9 months). Conclusions: Women have low SC-TNFi treatment persistence in PsA and AS/uSpA whereas male sex and golimumab are associated with high treatment persistence in these indications. The factors associated with treatment persistence in RA were less distinct but may comprise disease activity and concurrent conventional systemic disease-modifying anti-rheumatic drug (DMARD) treatment.
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| 3. |
- Hellberg, Victoria, et al.
(författare)
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Cisplatin and oxaliplatin toxicity : importance of cochlear kinetics as a determinant for ototoxicity
- 2009
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Ingår i: Journal of the National Cancer Institute. - Cary : Oxford University Press. - 0027-8874 .- 1460-2105. ; 101:1, s. 37-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained.METHODS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration-time curve (AUC). Statistical tests were two-sided.RESULTS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 microM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 microg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 microM x minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics.CONCLUSION: Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.
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| 4. |
- Hernlund, Elin, et al.
(författare)
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Adaptation strategies of the Icelandic horse with induced forelimb lameness at walk, trot and tölt
- 2024
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Ingår i: Equine Veterinary Journal. - 0425-1644 .- 2042-3306. ; 56, s. 617-630
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective Lameness assessment in the gaited Icelandic horse is complex. We aimed to describe their kinematic and temporal adaptation strategies in response to forelimb lameness at walk, trot and tolt.Study designIn vivo experiment.Methods Ten clinically non-lame Icelandic horses were measured before and after reversible forelimb lameness induction. Upper body and limb kinematics were measured using 11 inertial measurement units mounted on the poll, withers, pelvis (tubera sacrale) and all four limbs and hoofs (Equimoves (R), 500 Hz). Horses were measured on a straight line at walk and trot in-hand and at walk, trot and tolt while ridden. Linear mixed models were used to compare baseline and lame conditions (random factor = 'horse'), and results are presented as the difference in estimated marginal means or percentage of change.Results Lameness induction significantly (p < 0.05) increased head vertical movement asymmetry at walk (HDmin/HDmaxHAND: 18.8/5.7 mm, HDmin/HDmaxRIDDEN: 9.8/0.3 mm) and trot (HDmin/HDmaxHAND: 18.1/7.8 mm, HDmin/HDmaxRIDDEN: 24.0/9.3 mm). At the tolt, however, HDmin did not change significantly (1.1 mm), but HDmax increased by 11.2 mm (p < 0.05). Furthermore, pelvis vertical movement asymmetry (PDmax) increased by 4.9 mm, sound side dissociation decreased (-8.3%), and sound diagonal dissociation increased (6.5%). Other temporal stride variables were also affected, such as increased stance duration of both forelimbs at walk, tolt and in-hand trot.Main limitations Only one degree of lameness (mild) was induced with an acute lameness model.Conclusions Classical forelimb lameness metrics, such as vertical head and withers movement asymmetry, were less valuable at tolt compared to walk and trot, except for HDmax. Therefore, it is advised to primarily use the walk and trot to detect and quantify forelimb lameness in the Icelandic horse.
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| 5. |
- Hernlund, Emma
(författare)
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Mitochondria and cellular energy metabolism in platinum chemotherapy
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chemotherapy is a major strategy in the treatment of cancer. Unfortunately, treatment of advanced cancers often fails due to tumor resistance to chemotherapeutic drugs. Studies of cell death signaling induced by chemotherapeutic agents are of importance to develop strategies for improved therapy, either by development of new drugs or by potentiation of existing drugs. Discovery of markers for prediction of therapeutic outcome is also of great importance for identification of responsive patients and thereby improved treatment. This thesis presents results on apoptotic stress-signaling induced by the platinum chemotherapeutic drug cisplatin, and on combining chemotherapeutic drugs with inhibitors of cell metabolism as a potentiation strategy. MEKK1, a kinase in the MAPK-signaling pathway, was shown to be responsible for cisplatin induced activation of the mitochondrial proapoptotic protein Bak, as seen by conformational change of this protein. However, activation of Bak was not sufficient to induce apoptosis unless signaling from another protein of the MAPK pathway, JNK, was present. Gel filtration experiments revealed Bak complexes of sizes between 80 to 170 kDa in cells with cisplatin-induced onset of apoptosis. By chemical inhibition and gene knock-out, JNK was shown to be crucial for the formation of these complexes. p53 is involved in responses to platinum drugs. Here, a novel mechanism for negative regulation of p53 translocation to mitochondria is presented. Induction of iNOS after cisplatin treatment was shown to inhibit mitochondrial translocation of p53 as evaluated by chemical inhibition of iNOS. There was no upregulation of iNOS after treatment with oxaliplatin; however, addition of exogenous nitric oxide abrogated mitochondrial translocation of p53 after treatment with this drug. Seventeen clinical and experimental drugs were screened for potentiation of apoptosis together with glycolysis inhibitor 2-deoxyglucose (DG) and inhibitor of fatty acid beta-oxidation etomoxir in HCT116 colon carcinoma cells. DG was more potent than etomoxir in this respect. Cytotoxic responses to combination treatment varied and included apoptosis, necrosis and growth arrest. The combination of cisplatin and DG showed substantial increase in apoptotic response compared to cisplatin alone. Because treatment of ovarian cancer involves platinum drugs, this combination was further studied in two ovarian carcinoma cell lines and primary ovarian carcinoma cells purified from ascites. In the cell lines, higher use of glucose was coupled to increased resistance to cisplatin and carboplatin. In the primary tumor cells, low expression of mitochondrial beta-F1-ATPase correlated with reduced cisplatin IC50 in the presence of DG.
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| 6. |
- Hernlund, Elin, et al.
(författare)
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Non-banked curved tracks influence movement symmetry in two-year-old Standardbred trotters
- 2021
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Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known regarding how trotting through curves affects locomotion symmetry in Standardbred trotters.Objectives: To investigate differences in objectively measured Standardbred trotter vertical motion symmetry between straight and non-banked, curved sections of oval trotting tracks during exercise warm-up, using a wireless inertial measurement unit (IMU) system.Study design: Cross-sectional, observational study.Methods: Sixteen horses were included. Mixed models were used to assess associations between symmetry, track segment (straight vs curve) and stride duration.Results: Significant results for forelimb parameters were dependent on interactions between track segments and stride duration. At mean stride duration (0.611 second), during the curved track segment horses showed a lower maximum vertical position of the head after push-off of the outside forelimb (estimate -2.3 mm, P < 0.0001, 95% CI -1.7 to -2.9) and higher minimum vertical position of the head during stance of the outside forelimb (estimate -1.8 mm, P < 0.0001, 95% CI -1.2 to -2.5) compared to straight track, mimicking outside forelimb impact and push-off asymmetry during track curves. For hindlimb parameters, during the curve there was a decreased downward motion of the pelvis during outer hindlimb stance (estimate-0.7 mm, P < 0.0001, 95% CI -0.4 to -1.0), mimicking outside hindlimb impact asymmetry.Main limitations: Horses were evaluated going in one direction only on the track (clockwise).Conclusions: Systematic differences between straight and curved track segments were found but did not fully correspond to previously described findings for horses lunged in circles. Effect sizes were overall small. Data in our study were collected from horses trotting on 1000 m tracks with curve radii of 80-85 m. On non-banked tracks of this size, collecting IMU symmetry data at jogging speeds without distinguishing between straight and curved parts is unlikely to adversely affect clinical decision-making.
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| 7. |
- Hernlund, Emma, et al.
(författare)
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Ovarian carcinoma cells with low levels of beta-F1-ATPase are sensitive to combined platinum and 2-deoxy-D-glucose treatment.
- 2009
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Ingår i: Molecular Cancer Therapeutics. - : American Association for Cancer Research. - 1535-7163 .- 1538-8514. ; 8:7, s. 1916-1923
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Tidskriftsartikel (refereegranskat)abstract
- We have here examined chemopotentiating effects of glycolysis inhibitor 2-deoxy-d-glucose (DG) in two epithelial ovarian carcinoma (EOC) cell lines and 17 freshly isolated ascitic EOC cell samples, and we identify low expression of the beta-F1-ATPase involved in mitochondrial ATP production as a candidate marker for sensitivity to this strategy. Although in the majority of samples, DG per se did not induce apoptosis, cotreatment with DG potentiated apoptosis and total antiproliferative effects of cisplatin and, to a lesser degree, carboplatin. In the cell lines, combination treatment with DG and cisplatin or carboplatin at noninhibitory concentrations prevented posttreatment regrowth in drug-free medium over a total of 5 days. DG per se allowed complete recuperation in drug-free medium. The more platinum-resistant a cell line was, the more sensitive it was to potentiation by DG and showed higher glucose uptake, DG-sensitive lactate production, and lower beta-F1-ATPase levels. In the ascitic samples, DG reduced the median IC(50) for cisplatin by 68% and, in the most sensitive samples, up to 90%, and DG-mediated potentiation correlated with low expression of beta-F1-ATPase. By contrast, cisplatin sensitivity did not correlate with beta-F1-ATPase levels. The findings validate targeting cancer cell glucose metabolism for potentiating platinum chemotherapy in EOC and indicate that reduced beta-F1-ATPase/oxidative phosphorylation distinguishes cells that are amenable to this strategy.
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| 8. |
- Hernlund, Emma, et al.
(författare)
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The phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 is effective in inhibiting regrowth of tumour cells after cytotoxic therapy
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:3, s. 396-406
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Regrowth of tumour cells between cycles of chemotherapy is a significant clinical problem. Treatment strategies where antiproliferative agents are used to inhibit tumour regrowth between chemotherapy cycles are attractive, but such strategies are difficult to test using conventional monolayer culture systems.METHODS:We used the in vitro tumour spheroid model to study regrowth of 3-D colon carcinoma tissue after cytotoxic therapy. Colon carcinoma cells with wild-type or mutant phosphatidyl inositol 3-kinase catalytic subunit (PI3KCA) or KRAS alleles were allowed to form multicellular spheroids and the effects of different pharmacological compounds were studied after sectioning and staining for relevant markers of cell proliferation and apoptosis.RESULTS:Studies using colon cancer cells with gene disruptions suggested that the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway was essential for proliferation in 3-D culture. The dual PI3K-mTOR inhibitor NVP-BEZ235, currently in clinical trials, was found to inhibit phosphorylation of the mTOR target 4EBP1 in 3-D cultured cells. The ability of NVP-BEZ235 to inhibit tumour cell proliferation and to induce apoptosis was markedly more pronounced in 3-D cultures compared to monolayer cultures. It was subsequently found that NVP-BEZ235 was effective in inhibiting regrowth of 3-D cultured cells after treatment with two cytotoxic inhibitors of the ubiquitin-proteasome system (UPS), methyl-13-hydroxy-15-oxokaurenoate (MHOK) and bortezomib (Velcade®).CONCLUSIONS:The dual PI3K-mTOR inhibitor NVP-BEZ235 was found to reduce cell proliferation and to induce apoptosis in 3-D cultured colon carcinoma cells, NVP-BEZ235 is a promising candidate for use in sequential treatment modalities together with cytotoxic drugs to reduce the cell mass of solid tumours.
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| 9. |
- Kjellander, Christian, et al.
(författare)
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Costs of Hospital Care and Productivity Loss Due to Sickle Cell Disease in Sweden: A Retrospective Study
- 2022
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Ingår i: Value in Health. - : Elsevier BV. - 1098-3015 .- 1524-4733. ; 25:1, s. S248-S248
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Sickle cell disease (SCD) is an inherited disorder of hemoglobin, associated with significant morbidity and mortality. Although the disease is most prevalent in Africa, it has been increasingly common in Western countries due to migration. The number of SCD patients in Sweden is unknown and the comprehensive national registries in Sweden provide a unique opportunity to address the objective to assess the burden of SCD.Methods: Using Sweden’s national patient registry, the 1-year prevalence of SCD with crisis (at least one registration of ICD-10 code D57.0 during the identification period, 2001-2018) was estimated during a 13-year follow-up period (2006-2018). Costs for hospital care of SCD (any ICD-10 D57) were estimated through hospital remuneration amounts based on diagnosis-related group. Productivity losses due to sick leave or disability for SCD, from the Swedish Social Insurance Agency, were assessed for working-age patients (18-65 years) and costed with Swedish mean salary, plus social security contributions.Results: The 1-year prevalence of SCD with crisis increased during the follow-up period from 139 patients in year 2006 to 260 in 2018. A total of 2,427 inpatients stays were recorded with SCD (ICD-10 D57) as main reason for stay (observed in 2,632 SCD patient years) over the study period. In addition, 7,213 outpatient visits due to SCD were recorded. These stays and visits were estimated to cost 76.4 million (M) Swedish Krona (SEK) and 31.0 M SEK, respectively. Productivity losses due to sick leaves and disability pension amounted to 14.8 M SEK and 68.3 M SEK, respectively.Conclusions: This study demonstrates that SCD with crisis is associated with economic burden to society, health care and patients in Sweden and increasing prevalence and costs over the years of follow up. In total, for the years 2006-2018, the cost of hospital care and productivity losses for SCD amounted to 190.6 M SEK.
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| 10. |
- Kjellander, Christian, et al.
(författare)
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Economic burden of sickle cell disease in Sweden : a population-based national register study with 13 years follow up
- 2023
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Ingår i: Frontiers in Hematology. - : Frontiers Media S.A.. - 2813-3935. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Sickle cell disease (SCD) describes a group of inherited disorders of hemoglobin. Globally, SCD occurs in approximately 300,000-400,000 births annually and is most prevalent in malaria-endemic countries. However, migration has impacted the epidemiology of SCD but data on the matter are scarce. The objective of this study was to describe the epidemiology, treatment uptake, and economic burden of SCD in Sweden, a country with substantial immigration over the last decades.Methods: This nationwide retrospective observational registry cohort study identified patients with SCD from 2001 to 2018 and followed them from 2006 to 2018. Using data from high-quality population-based Swedish registers, we estimated prevalence, treatment uptake, and SCD-related health care resource use, sick leave and disability pension.Results: Between 2006 and 2018 the number of patients with SCD increased from 504 to 670; inpatient hospital stays and outpatient visits increased by 200% and 300%, respectively. Patients with pain crises had approximately twice the number of inpatient episodes and outpatient visit per year, and had higher productivity losses compared to patients without crises.Conclusion: In an era of emerging treatments for SCD, we have, to the best of our knowledge, for the first time comprehensively described epidemiological and economic aspects of SCD in a country where the disease is still rare and not well recognized by the healthcare system.
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