Cancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment ...of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients' functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank. In a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration. Item assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs greater than or equal to 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format). Two well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Early guidelines for minimally important differences (MIDs) for the EORTC QLQ-C30 proposed ≥10 points change as clinically meaningful for all scales. Increasing evidence that MIDs can vary by scale, ...direction of change, cancer type and estimation method has raised doubt about a single global standard. This paper identifies MID patterns for interpreting group-level change in EORTC QLQ-C30 scores across nine cancer types.
Data were obtained from 21 published EORTC Phase III trials that enroled 13,015 patients across nine cancer types (brain, colorectal, advanced breast, head/neck, lung, mesothelioma, melanoma, ovarian, and prostate). Anchor-based MIDs for within-group change and between-group differences in change over time were obtained via mean change method and linear regression, respectively. Separate MIDs were estimated for improvements and deteriorations. Distribution-based estimates were derived and compared with anchor-based MIDs.
Anchor-based MIDs mostly ranged from 5 to 10 points. Differences in MIDs for improvement vs deterioration, for both within-group and between-group, were mostly within a 2-points range. Larger differences between within-group and between-group MIDs were observed for several scales in ovarian, lung and head/neck cancer. Most anchor-based MIDs ranged between 0.3 SD and 0.5 SD distribution-based estimates.
Our results reinforce recent claims that no single MID can be applied to all EORTC QLQ-C30 scales and disease settings. MIDs varied by scale, improvement/deterioration, within/between comparisons and by cancer type. Researchers applying commonly used rules of thumb must be aware of the risk of dismissing changes that are clinically meaningful or underpowering analyses when smaller MIDs apply.
•MID patterns for interpreting group-level change are examined by QLQ-C30 scales.•Data were obtained from 21 published EORTC clinical trials across 9 cancer types.•MIDs varied by scale, improve/deteriorate, within/between groups and cancer type.•Our results reinforce claims that no single MID applies to all QLQ-C30 scales.•We present diversified MIDs to inform more accurate sample size calculations.
Increasing evidence from neuroimaging and modeling studies suggests that local lesions can give rise to global network changes in the human brain. These changes are often attributed to the ...disconnection of the lesioned areas. However, damaged brain areas may still be active, although the activity is altered. Here, we hypothesize that empirically observed global decreases in functional connectivity in patients with brain lesions can be explained by specific alterations of local neural activity that are the result of damaged tissue. We simulated local polymorphic delta activity (PDA), which typically characterizes EEG/MEG recordings of patients with cerebral lesions, in a realistic model of human brain activity. 78 neural masses were coupled according to the human structural brain network. Lesions were created by altering the parameters of individual neural masses in order to create PDA (i.e. simulating acute focal brain damage); combining this PDA with weakening of structural connections (i.e. simulating brain tumors), and fully deleting structural connections (i.e. simulating a full resection). Not only structural disconnection but also PDA in itself caused a global decrease in functional connectivity, similar to the observed alterations in MEG recordings of patients with PDA due to brain lesions. Interestingly, connectivity between regions that were not lesioned directly also changed. The impact of PDA depended on the network characteristics of the lesioned region in the structural connectome. This study shows for the first time that locally disturbed neural activity, i.e. PDA, may explain altered functional connectivity between remote areas, even when structural connections are unaffected. We suggest that focal brain lesions and the corresponding altered neural activity should be considered in the framework of the full functionally interacting brain network, implying that the impact of lesions reaches far beyond focal damage.
•We modeled how lesions affect functional connectivity (FC) in the human brain.•Locally altered activity as seen in brain lesions causes global decreases of FC.•These alterations are found even when structural connections remain intact.•Activity in focal brain lesions affects neural communication between remote areas.
The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) measures 15 health-related quality of life (HRQoL) scales relevant to the disease and ...treatment of patients with cancer. A study by Martinelli (2011) demonstrated that these scales could be grouped into three main clusters: physical, psychological and gastrointestinal. This study aims to validate Martinelli's findings in an independent dataset and evaluate whether these clusters are consistent across cancer types and patient characteristics.
Pre-defined criteria for successful validation were three main clusters should emerge with a minimum R-squared value of 0.51 using pooled baseline-data. A cluster analysis was performed on the 15 QLQ-C30 HRQoL-scales in the overall dataset, as well as by cancer type and selected patient characteristics to examine the robustness of the results.
The dataset consisted of 20,066 patients pooled across 17 cancer types. Overall, three main clusters were identified (R2 = 0.61); physical-cluster included role-functioning, physical-functioning, social-functioning, fatigue, pain, and global-health status; psychological-cluster included emotional-functioning, cognitive-functioning, and insomnia; gastro-intestinal-cluster included nausea/vomiting and appetite loss. The results were consistent across different levels of disease severity, socio-demographic and clinical characteristics with minor variations by cancer type. Global-health status was found to be strongly linked to the scales included in the physical-functioning-related cluster.
This study successfully validated prior findings by Martinelli (2011): the QLQ-C30 scales are interrelated and can be grouped into three main clusters. Knowing how these multidimensional HRQoL scales are related to each other can help clinicians and patients with cancer in managing symptom burden, guide policymakers in defining social-support plans and inform selection of HRQoL scales in future clinical trials.
•Our study validated the exploratory findings of Martinelli et al. on clustering EORTC QLQ-C30 scales.•Three main clusters were identified using data from 20,066 patients with cancer.•The three clusters included physical, psychological and gastro-intestinal related clusters.•Clusters were consistent across most socio-demographic and clinical characteristics.•The results may aid symptom burden management and inform clinical trial design.
Connectivity and network analysis in neuroscience has been applied to multiple spatial scales, but the links between these different scales have rarely been investigated. In tumor-related epilepsy, ...altered network topology is related to behavior, but the molecular basis of these observations is unknown. We elucidate the associations between microscopic features of brain tumors, local network topology, and functional patient status. We hypothesize that expression of proteins related to tumor-related epilepsy is directly correlated with network characteristics of the tumor area. Glioma patients underwent magnetoencephalography, and functional network topology of the tumor area was used to predict tissue protein expression patterns of tumor tissue collected during neurosurgery. Protein expression and network topology were interdependent; in particular between-module connectivity was selectively associated with two epilepsy-related proteins. Total number of seizures was related to both the role of the tumor area in the functional network and to protein expression. Importantly, classification of protein expression was predicted by between-module connectivity with up to 100% accuracy. Thus, network topology may serve as an intermediate level between molecular features of tumor tissue and symptomatology in brain tumor patients, and can potentially be used as a non-invasive marker for microscopic tissue characteristics.
•Tumor area network topology is related to tissue protein expression and symptoms.•Between-module connectivity predicts protein expression with up to 100% accuracy.•Brain networks may be an intermediate between molecular features and behavior.
Objective
This study was undertaken to test the hypothesis that brain tumors interfere with normal brain function by disrupting functional connectivity of brain networks.
Methods
Functional ...connectivity was assessed by computing the synchronization likelihood in a broad band (0.5–60Hz) or in the gamma band (30–60Hz) between all pairwise combinations of magnetoencephalography signals. Magnetoencephalography recordings were made at rest in 17 brain tumor patients and 15 healthy control subjects. For a given threshold of synchronization likelihood values, graphs of the suprathreshold connections between each magnetoencephalography channel and the others channels were built.
Results
In some regions, a variable number of channels without connectivity (missing connective points) at this threshold was found. The number of missing connective points was higher in patients with brain tumors than in control subjects (p < 0.0001, broad and gamma band) and was higher for left‐sided than right‐sided tumors (p = 0.008, broad band; p < 0.0001, gamma band). Individual results analysis indicates that the majority of brain tumor patients display several regions with missing connective point alterations in the affected and in the contralateral hemisphere.
Interpretation
Our findings suggest that brain tumors induce a loss of functional connectivity that affects multiple brain regions, and that left side brain tumors have the more severe consequences in this respect. Ann Neurol 2005
The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) has refined its strategy towards symptom measurement to meet the needs of researchers and clinicians ...in light of rapidly changing treatment for cancer patients. The standard use of the validated core questionnaire QLQ-C30 together with a disease-specific module can now be complemented by a user-created item list to cover novel side-effects of a tested drug/treatment. Therefore, the EORTC QLG has enhanced functionalities of the Item Library, a repository of over 850 unique items in up to 110 language versions, enabling users to develop their custom-made item list. The aim of the Item Library is to facilitate flexible, timely measurement of symptoms, complementing the use of fully validated quality of life instruments. The new strategy forms part of a larger research initiative in the EORTC QLG. The Item Library is already fully accessible to academic and pharmaceutical industry users. It is also undergoing further validation in order to answer all questions arising from the end users. Through multiple search options (symptoms, keywords, related items), users can identify items and scales that best address the side-effects to be measured. Selected items can then be added to a new questionnaire, including the corresponding conditional items, instructions, response scales and time frames. The finalised custom item list is subsequently reviewed by the Item Library's content manager, to ensure that the questionnaire is composed correctly and contains all the necessary elements and information. The approved custom questionnaires become available for all other users to browse through, export or adapt for use in their trials, creating an invaluable resource for research and broadening the portfolio of available instruments.
The preferred management of patients with suspected low-grade gliomas (S-LGG) remains controversial. The benefits of resection or radiotherapy early in the course of the disease have not been proven ...in terms of survival. Little is known about the effects of early therapy on quality of life (QOL) and cognitive status. The authors compared functional status, QOL, and cognitive status of patients suspected of having a LGG, in whom treatment was deferred, and patients with proven LGG (P-LGG), who underwent early surgery.
The authors recruited 24 patients suspected of having an LGG. These patients were matched with 24 patients with a histologically proven LGG and healthy control subjects for educational level, handedness, age, and gender. The two patient groups were also matched for tumor laterality, use of anticonvulsants, and interval between diagnosis and testing. Functional status was determined in both patient groups. QOL and cognitive status were compared between the three groups.
Matching criteria and functional status did not differ significantly between groups. Both patient groups scored worse on QOL scales than healthy control subjects. Unoperated patients with S-LGG scored better on most items than patients with P-LGG. Cognitive status was worse in both groups than in healthy control subjects, but, again, patients with S-LGG performed better than patients with P-LGG.
These data suggest that a wait-and-see policy in patients with S-LGG has no negative effect on cognitive performance and QOL.
We evaluated the implementation and effectiveness of adjunctive dexamethasone in adults with meningococcal meningitis.
We compared 2 Dutch prospective nationwide cohort studies on community-acquired ...meningococcal meningitis. A total of 258 patients with CSF culture-proven meningitis were enrolled between 1998 and 2002, before routine dexamethasone therapy was introduced, and 100 patients from March 2006 to January 2011, after guidelines recommended dexamethasone.
Dexamethasone was administered in 43 of 258 (17%) patients in the 1998-2002 cohort and in 86 of 96 (90%) patients in the 2006-2011 cohort (p < 0.001), and was started with or before the first dose of antibiotics in 12 of 258 (5%) and 85 of 96 (89%) patients (p < 0.001). Rates of unfavorable outcome were similar between cohorts (12 of 100 12% vs 30 of 258 12%; p = 0.67), also after correction for meningococcal serogroup. The rates of hearing loss (3 of 96 3% vs 19 of 237 8%; p = 0.10) and death (4 of 100 4% vs 19 of 258 7%; p = 0.24) were lower in the 2006-2011 cohort, but this did not reach significance. The rate of arthritis was lower in patients treated with dexamethasone (32 of 258 12% vs 5 of 96 5%, p = 0.046). Dexamethasone was not associated with adverse events.
Adjunctive dexamethasone is widely prescribed for patients with meningococcal meningitis and is not associated with harm. The rate of arthritis has decreased after the implementation of dexamethasone.
This study provides Class III evidence that adjuvant dexamethasone in adults with meningococcal meningitis does not increase negative outcomes such as deafness, death, or negative Glasgow Outcome Scale measures.
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