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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Coomans, Marijke B., et al.
(författare)
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Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?
- 2019
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Ingår i: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 21:11, s. 1447-1457
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Tidskriftsartikel (refereegranskat)abstract
- Background. Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients functioning. Methods. Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. Results. Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5-10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (amp;gt;= 10 points difference) physical, role, and social functioning (betas ranged from -11.3 to -15.9, all P amp;lt; 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of -12.3, P amp;lt; 0.001), independent of other factors. Conclusions. Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients functioning as measured with a self-report questionnaire.
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| 3. |
- van der Laan, Sander W., et al.
(författare)
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Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study
- 2016
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:9, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
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| 4. |
- Coomans, Marijke, et al.
(författare)
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The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials
- 2019
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Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 116, s. 190-198
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.
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| 5. |
- Holmes, Michael V., et al.
(författare)
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Mendelian randomization of blood lipids for coronary heart disease
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 36:9, s. 539-539
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a priormeta-analysis (threshold P < 2 x 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P <= 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestrictedallele score (48SNPs) was associated with CHD(OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
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| 6. |
- Reijneveld, Jaap C, et al.
(författare)
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Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033) : a randomised, open-label, phase 3 intergroup study.
- 2016
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 17:11, s. 1533-1542
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low-grade glioma has been shown to have no significant effect on progression-free survival. If these treatments have a different effect on health-related quality of life (HRQOL), it might affect the choice of therapy. We postulated that temozolomide compromises HRQOL and global cognitive functioning to a lesser extent than does radiotherapy.METHODS: We did a prospective, phase 3, randomised controlled trial at 78 medical centres and large hospitals in 19 countries. We enrolled adult patients (aged ≥18 years) with histologically confirmed diffuse (WHO grade II) astrocytoma, oligodendroglioma, or mixed oligoastrocytoma, with a WHO performance status of 2 or lower, without previous chemotherapy or radiotherapy, who needed active treatment other than surgery. We randomly assigned eligible patients (1:1) using a minimisation technique, stratified by WHO performance status (0-1 vs 2), age (<40 years vs ≥40 years), presence of contrast enhancement on MRI, chromosome 1p status (deleted vs non-deleted vs indeterminate), and the treating medical centre, to receive either radiotherapy (50·4 Gy in 28 fractions of 1·8 Gy for 5 days per week up to 6·5 weeks) or temozolomide chemotherapy (75 mg/m(2) daily, for 21 of 28 days [one cycle] for 12 cycles). The primary endpoint was progression-free survival (results published separately); here, we report the results for two key secondary endpoints: HRQOL (assessed using the European Organisation for Research and Treatment of Cancer's [EORTC] QLQ-C30 [version 3] and the EORTC Brain Cancer Module [QLQ-BN20]) and global cognitive functioning (assessed using the Mini-Mental State Examination [MMSE]). We did analyses on the intention-to-treat population. This study is closed and is registered at EudraCT, number 2004-002714-11, and at ClinicalTrials.gov, number NCT00182819.FINDINGS: Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 eligible patients to either radiotherapy (n=240) or temozolomide chemotherapy (n=237). The difference in HRQOL between the two treatment groups was not significant during the 36 months' follow-up (mean between group difference [averaged over all timepoints] 0·06, 95% CI -4·64 to 4·75, p=0·98). At baseline, 32 (13%) of 239 patients who received radiotherapy and 32 (14%) of 236 patients who received temozolomide chemotherapy had impaired cognitive function, according to the MMSE scores. After randomisation, five (8%) of 63 patients who received radiotherapy and three (6%) of 54 patients who received temozolomide chemotherapy and who could be followed up for 36 months had impaired cognitive function, according to the MMSE scores. No significant difference was recorded between the groups for the change in MMSE scores during the 36 months of follow-up.INTERPRETATION: The effect of temozolomide chemotherapy or radiotherapy on HRQOL or global cognitive functioning did not differ in patients with low-grade glioma. These results do not support the choice of temozolomide alone over radiotherapy alone in patients with high-risk low-grade glioma.FUNDING: Merck Sharp & Dohme-Merck & Co, National Cancer Institute, Swiss Cancer League, National Institute for Health Research, Cancer Research UK, Canadian Cancer Society Research Institute, National Health and Medical Research Council, European Organisation for Research and Treatment of Cancer Cancer Research Fund.
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