| 1. |
- Schepke, Elizabeth, et al.
(author)
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DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study
- 2022
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In: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 48:6
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Journal article (peer-reviewed)abstract
- Aims: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients. Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
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| 2. |
- Bodén, Stina, et al.
(author)
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C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer
- 2020
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:7, s. 1482-1491
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Journal article (peer-reviewed)abstract
- Background: Inflammation has been implicated in colorectal cancer etiology, but the relationship between C-reactive protein (CRP) and colorectal cancer risk is unclear. We aimed to investigate the association between prediagnostic plasma CRP concentrations and the risk of clinical and molecular colorectal cancer subtypes.Methods: We used prospectively collected samples from 1,010 matched colorectal cancer case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of colorectal cancer, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag time, and (using unconditional logistic regression) body mass index.Results: CRP was not associated with colorectal cancer risk, regardless of clinical or molecular colorectal cancer subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk [OR per 1 unit increase in natural logarithm (In) transformed CRP, 1.32; 95% confidence interval (CI), 1.01-1.73]. CRP levels increased over time, but average time trajectories were similar for cases and controls (P-interaction = 0.19).Conclusions: Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in colorectal cancer etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Impact: Future efforts to establish the putative role of chronic, low-grade inflammation in colorectal cancer development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.
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| 3. |
- Bodén, Stina, et al.
(author)
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Plasma concentrations of gut hormones acyl ghrelin and peptide YY and subsequent risk of colorectal cancer and molecular tumor subtypes
- 2023
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In: Cancer Prevention Research. - : American Association for Cancer Research. - 1940-6207 .- 1940-6215. ; 16:2, s. 75-87
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Journal article (peer-reviewed)abstract
- Obesity and metabolic dysfunction are implicated in colorectal cancer development. Appetite-regulating gut hormones might have a role in colorectal cancer risk. We investigated whether circulating levels of the gut hormones ghrelin (analyzed as acyl ghrelin) and Peptide YY (PYY) were associated with subsequent colorectal cancer risk, including clinical and molecular tumor subtypes. We also provide descriptive data on these hormones in relation to background participant characteristics and metabolic biomarkers. This population-based study included 1,010 matched case-control pairs with a median of 12.3 years of follow-up. Acyl ghrelin and PYY were measured by multiplex immunoassay. Data on KRAS and BRAF mutations and microsatellite instability (MSI) status were available for 704 and 708 cases, respectively. Conditional logistic regression models estimated association to colorectal cancer risk. Partial correlation and linear regression were used to investigate relationships between background and metabolic variables and variation in plasma gut hormone concentrations. Acyl ghrelin was not clearly associated with colorectal cancer risk (multivariable OR per 1 SD increase: 1.11; 95% CI, 1.00-1.23). Positive associations were observed for specific subtypes, in particular BRAF-mutated colorectal cancer and right-sided colon cancer, although with nonsignificant heterogeneity. PYY was not related to colorectal cancer risk (multivariable OR per 1 SD: 1.04; 95% CI, 0.95-1.14) or any tumor subtype. In the control participants, ghrelin was inversely correlated with BMI, and PYY was positively correlated with C-peptide and insulin levels. These findings provide limited support for a possible role for ghrelin in colorectal cancer development, primarily in specific anatomical and molecular tumor subtypes.PREVENTION RELEVANCE: The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.
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| 4. |
- Costa, Raquel, et al.
(author)
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Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal : Results from the IMAgiNE EURO study
- 2022
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In: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 137-153
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Journal article (peer-reviewed)abstract
- Objective: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. Methods: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. Results: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). Conclusion: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal.
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| 5. |
- de Dios, Eddie, 1987, et al.
(author)
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Comparison of the patient-derived modified Japanese Orthopaedic Association scale and the European myelopathy score
- 2024
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In: European Spine Journal. - : SPRINGER. - 0940-6719 .- 1432-0932. ; 33:3, s. 1205-1212
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Journal article (peer-reviewed)abstract
- Purpose: To compare the patient-derived modified Japanese Orthopaedic Association (P-mJOA) scale with the European myelopathy score (EMS) for the assessment of patients with degenerative cervical myelopathy (DCM). Methods: In this register-based cohort study with prospectively collected data, included patients were surgically treated for DCM and had reported both P-mJOA and EMS scores at baseline, 1-year follow-up, and/or 2-year follow-up to the Swedish Spine Register. P-mJOA and EMS scores were defined as severe (P-mJOA 0–11 and EMS 5–8), moderate (P-mJOA 12–14 and EMS 9–12), or mild (P-mJOA 15–18 and EMS 13–18). P-mJOA and EMS mean scores were compared, and agreement was evaluated with Spearman’s rank correlation coefficient (ρ), the intraclass correlation coefficient (ICC), and kappa (κ) statistics. Results: Included patients (n = 714, mean age 63.2years, 42.2% female) completed 937 pairs of the P-mJOA and the EMS. The mean P-mJOA and EMS scores were 13.9 ± 3.0 and 14.5 ± 2.7, respectively (mean difference –0.61 [95% CI –0.72 to –0.51; p < 0.001]). Spearman’s ρ was 0.84 (p < 0.001), and intra-rater agreement measured with ICC was 0.83 (p < 0.001). Agreement of severity level measured with unweighted and weighted κ was fair (κ = 0.22 [p < 0.001]; κ = 0.34 [p < 0.001], respectively). Severity levels were significantly higher using the P-mJOA (p < 0.001). Conclusion: The P-mJOA and the EMS had similar mean scores, and intra-rater agreement was high, whereas severity levels only demonstrated fair agreement. The EMS has a lower sensitivity for detecting severe myelopathy but shows an increasing agreement with the P-mJOA for milder disease severity. A larger interval to define severe myelopathy with the EMS is recommended.
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| 6. |
- Drandić, Daniela, et al.
(author)
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Women's perspectives on the quality of hospital maternal and newborn care around the time of childbirth during the COVID-19 pandemic : Results from the IMAgiNE EURO study in Slovenia, Croatia, Serbia, and Bosnia-Herzegovina
- 2022
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In: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 54-69
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Journal article (peer-reviewed)abstract
- Objective: To assess the quality of maternal and newborn care (QMNC) in countries of the former Yugoslavia. Method: Women giving birth in a facility in Slovenia, Croatia, Serbia, and Bosnia-Herzegovina between March 1, 2020 and July 1, 2021 answered an online questionnaire including 40 WHO standards-based quality measures. Results: A total of 4817 women were included in the analysis. Significant differences were observed across countries. Among those experiencing labor, 47.4%–62.3% of women perceived a reduction in QMNC due to the COVID-19 pandemic, 40.1%–69.7% experienced difficulties in accessing routine antenatal care, 60.3%–98.1% were not allowed a companion of choice, 17.4%–39.2% reported that health workers were not always using personal protective equipment, and 21.2%–53.8% rated the number of health workers as insufficient. Episiotomy was performed in 30.9%–62.8% of spontaneous vaginal births. Additionally, 22.6%–55.9% of women received inadequate breastfeeding support, 21.5%–62.8% reported not being treated with dignity, 11.0%–30.5% suffered abuse, and 0.7%–26.5% made informal payments. Multivariate analyses confirmed significant differences among countries, with Slovenia showing the highest QMNC index, followed by Croatia, Bosnia-Herzegovina, and Serbia. Conclusion: Differences in QMNC among the countries of the former Yugoslavia during the COVID-19 pandemic were significant. Activities to promote high-quality, evidence-based, respectful care for all mothers and newborns are urgently needed. ClinicalTrials.gov Identifier: NCT04847336.
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| 7. |
- Edin, Sofia, et al.
(author)
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Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer : possible implications for immunotherapy
- 2024
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In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130
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Journal article (peer-reviewed)abstract
- Background: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC.Methods: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8+), Th1 cells (T-bet+), T regulatory cells (FoxP3+), B cells (CD20+), and macrophages (CD68+) in a cohort of 257 CRC patients.Results: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts.Conclusion: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC.
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| 8. |
- Ekbäck, Erik, et al.
(author)
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Training for Awareness, Resilience and Action (TARA) for medical students : a single-arm mixed methods feasibility study to evaluate TARA as an indicated intervention to prevent mental disorders and stress-related symptoms
- 2022
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In: BMC Medical Education. - : BioMed Central (BMC). - 1472-6920. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Medical students have a higher risk for depression, anxiety, stress-related symptoms, burnout, and suicide, and more rarely seek professional help or treatment than the general population. Appeals are being made to address the mental health and resilience of physicians-to-be. The novel program Training for Awareness, Resilience, and Action (TARA) was originally developed to treat depressed adolescents, targeting specific neuroscientific findings in this population. TARA has shown feasibility and preliminary efficacy in clinically depressed adolescents and corresponding brain-changes in mixed community adolescent samples. The present study investigated the feasibility and acceptability of TARA as a potential indicated prevention program for symptoms of depression, anxiety, stress and burnout in Swedish medical students.Methods: We conducted a single-arm trial with 23 self-selected students in their early semesters of medical school (mean age 25.38 years, 5 males and 18 females), with or without mental disorders. All participants received TARA. Self-reported symptoms of depression, anxiety, perceived stress and psychological inflexibility were collected before (T0) and after the intervention (T1). Qualitative data on the participants’ experiences of TARA were collected in focus-group interviews conducted halfway through the program and upon completion of the program. Individual interviews were also conducted 2 years later. Qualitative content analysis was performed.Results: The mean attendance rate was 61.22% and the dropout rate was 17.40%. The Child Session Rating Scale administered after every session reflected an overall acceptable content, mean total score 34.99 out of 40.00. Trends towards improvement were seen across all outcome measures, including the Hospital Anxiety and Depression Scale Anxiety (t = 1.13, p = 0.29) and Depression (t = 1.71, p = 0.11) subscales, Perceived Stress Scale (t = 0.67, p = 0.51) and Avoidance and Fusion Questionnaire for youth (t = 1.64, p = 0.10). None of the participants deteriorated markedly during the intervention. Qualitative content analysis resulted in a main theme labeled: “An uncommon meeting-ground for personal empowerment”, with 4 themes; “Acknowledging unmet needs”, “Entering a free zone”, “Feeling connected to oneself and others” and “Expanding self-efficacy”.Conclusion: TARA is feasible and acceptable in a mixed sample of Swedish medical students. The students’ reports of entering an uncommon meeting-ground for personal empowerment supports effectiveness studies of TARA in this context.
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| 9. |
- Hermansen, Anna, et al.
(author)
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Dizziness and balance outcomes after two different postoperative rehabilitation approaches following neck surgery : analyses of a multicenter randomized controlled trial
- 2023
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In: Physiotherapy Theory and Practice. - Philadelphia, PA, United States : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 39:4, s. 750-760
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Journal article (peer-reviewed)abstract
- Background Dizziness and balance problems are common symptoms in patients with cervical radiculopathy. Objective To evaluate the effect of neck surgery postoperatively combined with either structured rehabilitation or standard approach in patients with cervical radiculopathy and dizziness and/or balance problems, and investigate factors influencing dizziness and balance at 6-month follow-up.Methods Individuals (n = 149) with cervical radiculopathy and dizziness and/or balance problems were randomized preoperatively to structured postoperative rehabilitation or standard postoperative approach. Outcomes were intensity of dizziness and subjective balance, and clinical measures of balance.Results Self-reported measures improved at three months (p < 0.001 to p = .007) and the standing balance at six months (p = .008). No between-group differences. Baseline values, neck pain, and physical activity level explained 23-39% of the variance in 6-month outcomes for self-reported measures. Baseline values and physical activity level explained 71% of the variance in walking balance, and lower baseline scores were significantly associated with standing balance impairments (OR 0.876).Conclusion Patients improved significantly in dizziness and subjective balance intensity shortly after surgery, and in standing balance at 6 months, independent of postoperative rehabilitation. Neck pain, physical activity, and neck muscle function influenced dizziness and balance, although preoperative values and neck pain were of most importance for 6-month outcomes.
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| 10. |
- Holmqvist, Anna, et al.
(author)
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Fatigue and cognitive fatigability in patients with chronic pain
- 2024
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In: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 24:1
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Journal article (peer-reviewed)abstract
- Objectives: Fatigue is common in patients with chronic pain. Still, there is a lack of studies examining objectively measurable cognitive aspects of fatigue: cognitive fatigability (CF). We aimed to investigate the presence of CF in patients with chronic pain and its relation to self-rated fatigue, attention, pain characteristics, sleep disturbance, depression, and anxiety.Methods: Two hundred patients with chronic pain and a reference group of 36 healthy subjects underwent a comprehensive neuropsychological test battery, including measurement of CF with the Wechsler Adult Intelligence Scale-III Coding subtest, and self-assessment of trait and state fatigue.Results: The patients with chronic pain did not show more CF as compared to the reference group. There was an association between CF and processing speed on a test of sustained and selective attention in the chronic pain group, while self-rated fatigue measures and pain characteristics were not associated with CF. Self-rated fatigue measures were highly correlated with self-rated pain intensity, spreading of pain, depression, anxiety, and sleep disturbance.Conclusions: The findings highlight the distinction between objective and subjective aspects of fatigue in chronic pain, and that the underlying causes of these different aspects of fatigue need to be studied further.
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