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- Barregård, Lars, 1948, et al.
(författare)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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- Antonini, Angelo, et al.
(författare)
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Psychometric Properties of Clinical Indicators for Identification and Management of Advanced Parkinson’s Disease : Real-World Evidence From G7 Countries
- 2022
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Ingår i: Neurology and Therapy. - : Springer Science and Business Media LLC. - 2193-8253 .- 2193-6536. ; 11:1, s. 303-318
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Standardized and validated criteria to define advanced Parkinson’s disease (PD) or identify patient eligibility for device-aided therapy are needed. This study assessed the psychometric properties of clinical indicators of advanced PD and eligibility for device-aided therapy in a large population. Methods: This retrospective analysis of the Adelphi Parkinson’s Disease Specific Programme collected data from device-aided therapy-naïve people with PD in G7 countries. We assessed the presence of 15 clinical indicators of advancing PD and seven indicators of eligibility for device-aided therapy in patients classified with advanced PD or as eligible for device-aided therapy by the treating physician. Accuracy was assessed using area under the curve (AUC) and multivariable logistic regression models. Construct validity was examined via known-group comparisons of disease severity and burden among patients with and without each clinical indicator. Results: Of 4714 PD patients, 14.9% were classified with advanced PD and 17.5% as eligible for device-aided therapy by physician judgment. The presence of each clinical indicator was 1.9- to 7.3-fold more likely in patients classified with advanced PD. Similarly, the presence of device-aided therapy eligibility indicators was 1.8- to 5.5-fold more likely in patients considered eligible for device-aided therapy. All indicators demonstrated high clinical screening accuracy for identifying advanced PD (AUC range 0.84–0.89) and patients eligible for device-aided therapy (AUC range 0.73–0.80). The Unified Parkinson’s Disease Rating Scale (UPDRS) score, cognitive function, quality of life, and caregiver burden were significantly worse in indicator-positive patients. Conclusion: Specific clinical indicators of advanced PD and eligibility for device-aided therapy demonstrated excellent psychometric properties in a large sample, and thus may provide an objective and reliable approach for patient identification and treatment optimization.
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- Bärebring, Linnea, et al.
(författare)
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Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer– a validation study
- 2020
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 40, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). Methods: A total of 136 women and men (50–80 years) with stage I-III CRC and a wide range of baseline FFM (35.7–73.5 kg) were included in the study. Body composition was measured at study baseline within 2–9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). Results: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60–76%) or a gain in FFM of ≥5% (33–62%) was poor. Conclusion: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis. © 2020 The Author(s)
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- Chalise, P., et al.
(författare)
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Addressing Domestic Violence in Antenatal Care Environments in Nepal (ADVANCE) - study protocol for a randomized controlled trial evaluating a video intervention on domestic violence among pregnant women
- 2023
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDomestic violence (DV) prior to, and during pregnancy is associated with increased risks for morbidity and mortality. As pregnant women routinely attend antenatal care this environment can be used to offer support to women experiencing DV. We have developed a video intervention that focuses on the use of behavioral coping strategies, particularly regarding disclosure of DV experiences. The effectiveness of this intervention will be evaluated through a randomized controlled trial (RCT) and a concurrent process evaluation.MethodsAll pregnant women between 12-22 weeks of gestation attending routine antenatal care at two tertiary level hospitals in Nepal are invited to participate. DV is measured using the Nepalese version of the Abuse Assessment Screen (N-AAS). Additionally, we measure participants' mental health, use of coping strategies, physical activity, and food security through a Color-coded Audio Computer Assisted Self Interview (C-ACASI). Irrespective of DV status, women are randomized into the intervention or control arm using a computer-generated randomization program. The intervention arm views a short video providing information on DV, safety improving actions women can take with an emphasis on disclosing the violence to a trusted person along with utilizing helplines available in Nepal. The control group watches a video on maintaining a healthy pregnancy and when to seek healthcare. The primary outcome is the proportion of women disclosing their DV status to someone. Secondary outcomes are symptoms of anxiety and depression, coping strategies, the use of safety measures and attitudes towards acceptance of abuse. Follow-up is conducted after 32 weeks of gestation, where both the intervention and control group participants view the intervention video after completing the follow-up questionnaire. Additionally, a mixed methods process evaluation of the intervention will be carried out to explore factors influencing the acceptability of the intervention and the disclosure of DV, including a review of project documents, individual interviews, and focus group discussions with members of the research team, healthcare providers, and participants.DiscussionThis study will provide evidence on whether pregnant women attending regular antenatal visits can enhance their safety by disclosing their experiences of violence to a trusted person after receiving a video intervention.Trial registrationThe study is registered in ClinicalTrial.gov with identifier NCT05199935.
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- Dafsari, Haidar S., et al.
(författare)
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EuroInf 2 : Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease
- 2019
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Real-life observational report of clinical efficacy of bilateral subthalamic stimulation (STN-DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD). Methods: In this prospective, multicenter, international, real-life cohort observation study of 173 PD patients undergoing STN-DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed-up using PDQuestionnaire-8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)-III, UPDRS-IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed-rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics. Results: In all groups, PDQuestionnaire-8, UPDRS-IV, and NMSS total scores improved significantly at follow-up. Levodopa equivalent daily dose was significantly reduced after STN-DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN-DBS improved urinary/sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. Overall, STN-DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire-8 outcome. Conclusions: This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN-DBS, IJLI, and APO in a real-life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices.
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- Gottschalk Højfeldt, S, et al.
(författare)
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IgG Antibodies Cannot Explain Silent Inactivation in PEG-Asparaginase Treatment
- 2018
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Ingår i: Pediatric Blood & Cancer. 65 (S2), Abstracts from the 50th Congress of the International Society of Paediatric Oncology (SIOP) Kyoto, Japan November 16–19, 2018, e27455. PO-054. - : Wiley. - 1545-5009.
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Konferensbidrag (refereegranskat)abstract
- Background/Objectives: PEG-asparaginase represents a key element in the treatment of acute lymphoblastic leukemia (ALL), however allergic reactions and lack of asparaginase enzyme activity shortly after administration (silent inactivation) constitutes a significant challenge. Anti-PEG antibodies formed prior to PEG-asparaginase exposure are suggested to cause the latter accelerated clearance phenomenon. We investigated anti-PEG antibody responses before and during PEG-asparaginase therapy, in children treated according to NOPHO ALL2008 protocol, with and without silent inactivation and hypersensitivity. Design/Methods: PEG-asparaginase enzyme activity was determined in patients aged 1-17.9 years as part of the NOPHO ALL2008 protocol. These measurements were used to categorize patients with or without enzyme activity. In this case control study, recovery of spiked PEG-asparaginase activity after IgG complex depletion with protein G affinity chromatography was used to evaluate IgG antibodies to PEGasparaginase. 359 samples were analyzed from 40 patients with: i) no adverse phenotype (n=10), ii) silent inactivation (n=10), iii) allergy and asparaginase enzyme inactivation (n=10), iv) allergy and asparaginase enzyme activity (n=10) Results: No patients with PEG-asparaginase enzyme activity had or developed anti-PEG antibodies during treatment. Thus children with and without clinical allergy and enzyme activity could not be distinguished serologically. In contrast, IgG antibodies were detected in 19 of 20 of children without enzyme activity, regardless of allergy status. The lack of in vivo asparaginase enzyme activity was always displaying from the first PEG-asparaginase administration, but anti-PEG antibodies were only detected in pre-exposure samples in 2 of 38 patients (5%). 2 patients had missing pre-exposure samples. Conclusions: IgG responses to repeated PEG-asparaginase administrations are not the primary driver of PEGasparaginase inactivation. However these antibodies may accelerate the drug clearance. Further validation and investigation of IgM antibodies is warranted in order to gain more knowledge about the inactivation of PEG-asparaginase.
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