| 1. |
- Arbring, Kerstin, 1961-
(author)
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Two worlds, one goal : A Clinician’s Perspective on Laboratory Analyses in Anticoagulant Treatment
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Almost precisely a century ago, in the 1920s and 1930s, cattle bled to death in North America after being fed moldy hay containing sweet clover, the yellow Melilotus officinalis, and the white Melilotus albus. The toxic substance in the hay inhibiting blood coagulation was identified and named dicumarol. Further development resulted in warfarin, an oral anticoagulant that has been used for over 70 years and still is, even though newer direct-acting oral anticoagulants (DOACs) are mainly replacing it. For some patients, warfarin is still the drug of choice. A safe warfarin treatment needs repeated blood sample analysis (PT-INR), and with the new DOACs come new laboratory challenges. The aim of this thesis was to investigate ways laboratory methods can contribute to improving oral anticoagulant treatment. Paper I explores genetic variants of the enzyme targeted by warfarin, VKORC1. The result shows that the haplotype VKORC1*2 is the most important of the VKORC1 haplotypes for warfarin dosage, with a lower dose requirement. The VKORC1*2 haplotype was also related to more unstable PT-INR levels. Paper II describes a cross-section study comparing warfarin treatment control, as PT-INRs within the intended therapeutic range, in primary health care centers (PHCCs) and specialized anticoagulation clinics (ACCs). Both settings showed good therapeutic control, with at least as good therapeutic control in the PHCCs as in the ACCs. Today, almost all warfarin treatment in our region is centralized to ACCs. Paper III focuses on the modification of a point-of-care PT method. A ratio of PT from two different dilutions of each patient sample was calculated and used as an indirect measure of DOAC activity. There were close correlations between the PT ratio and drug concentrations measured at the hospital laboratory. The detection level varies between DOACs and may limit its use in some situations. Paper IV evaluated the MRX PT DOAC, an assay based on the PT ratio principle. It was found to be able to detect potentially interfering DOAC levels in plasma samples. Confirmatory testing is recommended, as is sensitivity improvement for the detection of specific interferences.
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| 2. |
- Holmqvist, Annica, et al.
(author)
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Age as a potential predictor of acute side effects during chemoradiotherapy in primary cervical cancer patients
- 2022
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In: BMC Cancer. - London, United Kingdom : BioMed Central (BMC). - 1471-2407. ; 22:1
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Journal article (peer-reviewed)abstract
- Background Toxicity during chemoradiotherapy (CRT) in cervical cancer patients might limit the chances of receiving an optimal treatment and to be cured. Few studies have shown relationships between acute side effects and patients age. Here, the association between age and acute side effects such as nausea/vomiting, diarrhea and weight loss during CRT was analysed in cervical cancer patients.MethodsThis study included 93 patients with primary cervical cancer stage IBI to IVA who received CRT from 2013 to 2019. The frequency of symptoms/toxicity grade was analysed by using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.ResultsPatients ≥ 52 years had a significantly higher frequency of nausea/vomiting and increased grade ≥ 3 toxicity during CRT compared to younger patients (p<0.001, p = 0.001). Toxicity grade ≥ 3 of nausea/vomiting was associated with increased frequency of weight loss (p = 0.001), reduced ADL (p = 0.001) and dose modifications of both radiotherapy (RT) (p = 0.020) and chemotherapy (CT) (p = 0.030) compared to toxicity grade 2. The frequency of diarrhea (p = 0.015) and weight loss (p = 0.020) was higher in older patients compared to younger.Conclusions Older patients have an increased risk of acute side effects as nausea/vomiting, diarrhea and weight loss. Age could be useful in predicting acute side effects in primary cervical cancer patients with CRT.
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| 3. |
- Holmqvist, Annica, et al.
(author)
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Urologic, lymphedema, pelvic pain and gastrointestinal symptoms increase after radiotherapy in patients with primary uterine tumors : a prospective longitudinal Swedish cohort study
- 2021
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In: Clinical and Translational Oncology. - : SPRINGER INTERNATIONAL PUBLISHING AG. - 1699-048X .- 1699-3055. ; 23:9, s. 1752-1760
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Journal article (peer-reviewed)abstract
- Purpose Radiotherapy (RT) causes an inflammatory reaction of the tissue which leads to fibrosis and reduced functioning of the pelvic organs. Few studies have shown significant relationships between side effects and RT in uterine tumors. Here, the urological, lymphedema, pelvic pain and gastrointestinal (GI) symptoms were studied before and after RT in patients with primary uterine tumors using the EORTC QLQ-EN24, specifically designed for uterine cancer patients. Methods This prospective cohort study comprised patients with primary uterine tumors who received pelvic radiotherapy (RT). A total of 43 patients were included from May 2014 to February 2019. Patients completed the questionnaires for global health status and functioning before the start of RT and at 3 and 12 months after RT. Results We found a significant worsening of the urological symptoms 3 months after RT which persisted up to 12 months after RT compared to baseline values prior to start of RT (p = 0.007). An exacerbation of the urinary symptoms was seen in patients with vaginal brachytherapy/boost compared to patients with pelvic RT at 12 months after RT (p = 0.053). The severity of lymphedema symptoms increased from RT start to 12 months after RT (p = 0.019) and the pelvic pain were higher at 3 months after RT compared to before RT (p = 0.004). Also, the level of GI symptoms was significantly higher 12 months after RT compared to the RT start (p < 0.001). Conclusions The urologic, lymphedema, pelvic pain and GI symptoms all increase after RT.
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| 4. |
- Iselius, Sofia, et al.
(author)
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Late adverse events in patients with pelvic cancer after oncologic treatment-intervention and treatment effect
- 2023
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In: Supportive Care in Cancer. - : SPRINGER. - 0941-4355 .- 1433-7339. ; 31:5
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Journal article (peer-reviewed)abstract
- PurposeFew studies have focused on the late adverse events after oncologic treatment in pelvic cancer patients. Here, the treatment effect/interventions were studied on late side effects as GI, sexual, and urinary symptoms in pelvic cancer patients who visited a highly specialized rehabilitation clinic in Linkoping.MethodsThis retrospective longitudinal cohort study included 90 patients who had at least one visit at the rehabilitation clinic for late adverse events at Linkoping University hospital between 2013 to 2019. The toxicity of the adverse events was analyzed by using the common terminology criteria for adverse events (CTCAE).ResultsBy comparing the toxicity of symptoms between visits 1 and 2, we showed that the GI symptoms decreased with 36.6% (P = 0.013), the sexual symptoms with 18.3% (P < 0.0001), and urinary symptoms with 15.5% (P = 0.004). Patients who received bile salt sequestrant had a significant improvement in grade of GI symptoms as diarrhea/fecal incontinence at visit 2 compared to visit 1 where 91.3% were shown to have a treatment effect (P = 0.0034). The sexual symptoms (vaginal dryness/pain) significantly improved due to local estrogens between visits 1 and 2 where 58.1% had a reduction of symptoms (P = 0.0026).ConclusionThe late side effects as GI, sexual, and urinary symptoms was significantly reduced between visits 1 and 2 at the specialized rehabilitation center in Linkoping. Bile salt sequestrants and local estrogens are effective treatments for side effects as diarrhea and vaginal dryness/pain.
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| 5. |
- Kumar Jeengar, Manish, et al.
(author)
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Local administration of 4-Thiouridine, a novel molecule with potent antiinflammatory properties, protects against experimental colitis and arthritis
- 2020
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In: International Immunopharmacology. - : ELSEVIER. - 1567-5769 .- 1878-1705. ; 85
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Journal article (peer-reviewed)abstract
- Previous studies in a rat model of Sephadex induced lung inflammation showed that 4-Thiouridine (4SU), a thiol substituted nucleoside, was very effective in reducing edema, leukocyte influx and TNF levels in bronchoalvelolar lavage fluid. However, little is known about the factors and mechanisms underlying these effects. In the present study, we have used two separate mouse models of chronic inflammation, a model of dextran sulphate sodium (DSS) induced colitis and a model of antigen induced arthritis, to evaluate the anti-inflammatory effect of 4-thiouridine. We have analyzed a broad spectrum of inflammatory mediators in order to delineate the mechanisms behind a potential anti-inflammatory effect of 4SU. Colitis was induced in C57BL/6 mice by administration of 3.5% DSS in drinking water for 5 days and the potential anti-colitic effect of 4SU was assessed by monitoring the disease activity index (DAI), measurement of colon length and histopathological analysis of colon tissue. We analyzed tissue myeloperoxidase (MPO) activity, serum pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF), mRNA and protein expression of pro-inflammatory cytokines, COX-2, and NF-kappa B activity in colitis tissue. Intracolonic administration of 4SU (5 mg/kg & 10 mg/kg.) significantly inhibited MPO activity and reduced the levels of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF) as well as COX-2. Further, NF-kappa B activation was also blocked by attenuating the phosphorylation of IkB kinase (IKK alpha/beta) in DSS-induced colitis tissues. Arthritis was induced by intra-articular injection of mBSA in the knee of NMRI mice pre-immunized with mBSA and 4SU was administered locally by direct injection into the knee joint. The antiarthritic potential of 4SU was calculated by histopathological scores and histochemical analysis of joint tissue. Further, immunohistochemistry was used to study inflammatory cell infiltration and expression of cytokines and adhesion molecules in the synovium. Local administration of 50-100 mg/kg 4SU at the time of arthritis onset clearly prevented development of joint inflammation and efficiently inhibited synovial expression of CD18, local cytokine production and recruitment of leukocytes to the synovium. Taken together, our data clearly demonstrates a potent anti-inflammatory effect of 4SU in two experimental models. In conclusion 4SU could be a new promising candidate for therapeutic modulation of chronic inflammatory diseases like ulcerative colitis and arthritis.
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| 7. |
- Tufvesson Stiller, Helena, et al.
(author)
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Patient reported experiences of Swedish patients being investigated for cancer during the Covid-19 pandemic
- 2023
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In: Supportive Care in Cancer. - : Springer Nature. - 0941-4355 .- 1433-7339. ; 31:7
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Journal article (peer-reviewed)abstract
- Background: Patient reported experiences in individuals being investigated for cancer have been recorded in a nationwide survey in Sweden, providing an opportunity to assess the impact of the Covid-19-pandemic.Material and Methods: Questionnaires from 45920 patients were analyzed to assess the experience of being investigated for cancer. Data from before the Covid-19-pandemic (2018–2019) was compared to data acquired during the pandemic (2020–2021), using chi-square and Wilcoxon rank sum tests. Both, patients who were cleared from suspicion of cancer and those who were diagnosed with cancer were included.Results: Fewer patients in total visited health services during the pandemic. However, patients that did seek help did so to a similar extent during as prior to the pandemic. Patient waiting time was perceived to be shorter during the pandemic and judged as neither too long nor too short by most patients. The emotional support to patients improved during the pandemic, whereas the support to next of kin declined. A majority of patients received the results from the investigation in a meeting with the physician. Although there was a preference for receiving results in a meeting with the physician, the pandemic has brought an increasing interest in receiving results by phone.Conclusion: Swedish cancer healthcare has shown resilience during the Covid-19-pandemic, maintaining high patient satisfaction while working under conditions of extraordinary pressure. Patients became more open to alternatives to physical “in person” health care visits which could lead to more digital visits in the future. However, support to significant others demands special attention.
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| 8. |
- Tufvesson Stiller, Helena, et al.
(author)
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Perception of information to Swedish melanoma patients in routine clinical practice - a cross-sectional survey
- 2022
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In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 22:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Comprehensible, relevant information empowers patients, allowing them to take an active part in their care. We aim to investigate how Swedish melanoma patients perceive information provided in routine clinical practice and explore the correlation between satisfaction with information, symptoms and functioning scales, and quality of life.METHODS: A cross-sectional study where EORTC QLQ-C30, EORTC QLQ-INFO25 and EQ-5D-3L questionnaires were sent to 1213 patients by post and 792 responded (65%).RESULTS: Only 0.5% reported that they wished to have received less information. The amount of information received and the satisfaction with that information was age-dependent, where older patients reported receiving less information than younger patients. Middle-aged patients were more satisfied with the information compared to both younger and older patients. The perception of having received sufficient information correlated negatively with anxiety. Higher satisfaction with the information also correlated positively with scores for functioning scales and negatively with degree of symptoms. No difference was perceived in information levels between disease stage apart from the scale "information about other services", where patients with more severe disease reported receiving more information. Men and women reported equal satisfaction concerning the information received.CONCLUSIONS: Patients lack sufficient information and age affects the perception of it. It is of utmost importance to tailor the information to suit the individual needs of a given patient, as satisfaction with the information received correlates with the patient's well-being.
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