A qualitative study of GP, nurse and practice manager views on using targeted case-finding to identify patients with COPD in primary care

‘Finding the missing millions’ with chronic obstructive pulmonary disease became part of the Department of Health strategy for England in 2010. Targeted case-finding within primary care is one potential pro-active strategy, but currently little is known about the views of healthcare professionals on this approach. In this study, 36 healthcare professionals (12 GPs, 14 nurses, and 10 practice managers) from 34 UK practices participated in semi-structured telephone interviews about targeted case-finding. Interviews followed an interview guide, were audio-recorded, transcribed verbatim, coded and analysed using ‘Framework Approach’. Most of those interviewed practiced opportunistic case-finding. The main perceived barriers to wider case-finding programmes were the resource implications associated with running such programmes and identifying more chronic obstructive pulmonary disease patients. Financial incentives, support from specialist clinicians, and comprehensive guidance were viewed as facilitators. While targeted case-finding is conceptually accepted by primary care staff, scepticism surrounding (1) the value of identifying those with mild disease and (2) the availability of effective targeted case-finding methods, may lead some to favour an opportunistic approach. Key concerns were a lack of unequivocal evidence for the relative benefits vs. disadvantages of diagnosing patients earlier, and resource constraints in an already over-burdened system. Barriers to practical implementation of case-finding studies may be addressed with financial, human and educational resources, such as additional staff to undertake searches and perform spirometry tests, and practical and educational support from specialist teams

Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma

Background Only a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (<= 36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas.Methods Tumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed.Results Our data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors.Conclusions Our data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas

Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma

Background Only a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (<= 36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas.Methods Tumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed.Results Our data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors.Conclusions Our data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas

The prevalence and severity of fatigue in meningioma patients and its association with patient-, tumor-and treatment-related factors

Background: Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency and severity of fatigue in meningioma patients as well as associations between the level of fatigue and patient-, tumor-, and treatment-related factors. Methods: In this multicenter cross-sectional study, meningioma patients completed questionnaires on fatigue (MFI-20), sleep (PSQI), anxiety and depression (HADS), tumor-related symptoms (MDASI-BT), and cognitive functioning (MOS-CFS). Multivariable regression models were used to evaluate the independent association between fatigue and each patient-, tumor-, and treatment-related factor separately, corrected for relevant confounders. Results: Based on predetermined in-and exclusion criteria, 275 patients, on average 5.3 (SDa=a2.0) year since diagnosis, were recruited. Most patients had undergone resection (92%). Meningioma patients reported higher scores on all fatigue subscales compared to normative data and 26% were classified as fatigued. Having experienced a complication due to resection (OR 3.6, 95% CI: 1.8-7.0), having received radiotherapy (OR 2.4, 95% CI: 1.2-4.8), a higher number of comorbidities (OR 1.6, 95% CI: 1.3-1.9) and lower educational level (low level as reference; high level OR 0.3, 95% CI: 0.2-0.7) were independently associated with more fatigue. Conclusions: Fatigue is a frequent problem in meningioma patients even many years after treatment. Both patient-and treatment-related factors were determinants of fatigue, with the treatment-related factors being the most likely target for intervention in this patient population.</p

Long-term disease burden and survivorship issues after surgery and radiotherapy of intracranial meningioma patients

BACKGROUND Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention. OBJECTIVE To assess the long-term (≥5 yr) disease burden of meningioma patients. METHODS In this multicenter cross-sectional study, patients ≥5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported. RESULTS At a median of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (–2.11, 95% CI: –3.52 to –0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls. CONCLUSION In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning

Complement activation in Glioblastoma Multiforme pathophysiology: Evidence from serum levels and presence of complement activation products in tumor tissue

Inflammation plays a key role in the pathophysiology of Glioblastoma Multiforme (GBM). Here we focus on the contribution of the so far largely ignored complement system.ELISA and immunohistochemistry were combined to assess levels and localization of critical components of the initiation- and effector pathways of the complement cascade in sera and tumor tissue from GBM patients and matched controls.Serum levels of factor-B were decreased in GBM patients whereas C1q levels were increased. C1q and factor-B deposited in the tumor tissue. Deposition of C3 and C5b-9 suggests local complement activation. MBL deficiency, based on serum levels, was significantly less frequent among GBM patients compared to controls (14% vs. 33%). Therefore low levels of MBL may protect against the initiation/progression of GBM

National survey on the current practice and attitudes toward the management of chronic subdural hematoma

BACKGROUND: Chronic subdural hematoma (CSDH) is a frequent pathological entity in daily clinical practice. However, evidence‐based CSDH‐guidelines are lacking and level I evidence from randomized clinical trials (RCTs) is limited. In order to establish and subsequently implement a guideline, insight into current clinical practice and attitudes toward CSDH‐treatment is required. The aim is to explore current practice and attitudes toward CSDH‐management in the Netherlands. METHODS: A national online survey was distributed among Dutch neurologists and neurosurgeons, examining variation in current CSDH‐management through questions on treatment options, (peri)operative management, willingness to adopt new treatments and by presenting four CSDH‐cases. RESULTS: One hundred nineteen full responses were received (8% of neurologists, N = 66 and 35% of neurosurgeons, N = 53). A majority of the respondents had a positive experience with burr‐hole craniostomy (93%) and with a conservative policy (56%). Around a third had a positive experience with the use of dexamethasone as primary (30%) and additional (33.6%) treatment. These numbers were also reflected in the treatment preferences in the presented cases. (Peri)operative management corresponded among responding neurosurgeons. Most respondents would be willing to implement dexamethasone (98%) if equally effective as surgery and tranexamic acid (93%) if effective in CSDH‐management. CONCLUSION: Variation was found regarding preferential CSDH‐treatment. However, this is considered not to be insurmountable when implementing evidence‐based treatments. This baseline inventory on current clinical practice and current attitudes toward CSDH‐treatment is a stepping‐stone in the eventual development and implementation of a national guideline

External validation of prognostic models predicting outcome after chronic subdural hematoma

Background: Several prognostic models for outcomes after chronic subdural hematoma (CSDH) treatment have been published in recent years. However, these models are not sufficiently validated for use in daily clinical practice. We aimed to assess the performance of existing prediction models for outcomes in patients diagnosed with CSDH. Methods: We systematically searched relevant literature databases up to February 2021 to identify prognostic models for outcome prediction in patients diagnosed with CSDH. For the external validation of prognostic models, we used a retrospective database, containing data of 2384 patients from three Dutch regions. Prognostic models were included if they predicted either mortality, hematoma recurrence, functional outcome, or quality of life. Models were excluded when predictors were absent in our database or available for < 150 patients in our database. We assessed calibration, and discrimination (quantified by the concordance index C) of the included prognostic models in our retrospective database. Results: We identified 1680 original publications of which 1656 were excluded based on title or abstract, mostly because they did not concern CSDH or did not define a prognostic model. Out of 18 identified models, three could be externally validated in our retrospective database: a model for 30-day mortality in 1656 patients, a model for 2 months, and another for 3-month hematoma recurrence both in 1733 patients. The models overestimated the proportion of patients with these outcomes by 11% (15% predicted vs. 4% observed), 1% (10% vs. 9%), and 2% (11% vs. 9%), respectively. Their discriminative ability was poor to modest (C of 0.70 [0.63–0.77]; 0.46 [0.35–0.56]; 0.59 [0.51–0.66], respectively). Conclusions: None of the examined models showed good predictive performance for outcomes after CSDH treatment in our dataset. This study confirms the difficulty in predicting outcomes after CSDH and emphasizes the heterogeneity of CSDH patients. The importance of developing high-quality models by using unified predictors and relevant outcome measures and appropriate modeling strategies is warranted

Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients:results from the HOVON 105/ALLG NHL 24 randomized controlled trial

BACKGROUND: To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL). METHODS: One hundred and ninety-nine patients from a phase III trial (HOVON 105/ALLG NHL 24), randomized to standard chemotherapy with or without rituximab, followed in patients ≤60 years old by 30-Gy whole-brain radiotherapy (WBRT), were asked to participate in a neuropsychological evaluation before and during treatment, and up to 2 years posttreatment. Scores were transformed into a standardized z-score; clinically relevant changes were defined as a change in z-score of ≥1 SD. The effect of WBRT was analyzed in irradiated patients. All MRIs were centrally assessed for white matter abnormalities and cerebral atrophy, and their relation with neurocognitive scores over time in each domain was calculated. RESULTS: 125/199 patients consented to neurocognitive evaluation. Statistically significant improvements in neurocognition were seen in all domains. A clinically relevant improvement was seen only in the motor speed domain, without differences between the arms. In the follow-up of irradiated patients (n = 43), no change was observed in any domain score, compared to after WBRT. Small but significant inverse correlations were found between neurocognitive scores over time and changes in white matter abnormalities (regression coefficients: −0.048 to −0.347) and cerebral atrophy (−0.212 to −1.774). CONCLUSIONS: Addition of rituximab to standard treatment in PCNSL patients did not impact neurocognitive functioning up to 2 years posttreatment, nor did treatment with 30-Gy WBRT in patients ≤60 years old. Increased white matter abnormalities and brain atrophy showed weak associations with neurocognition