Early surgery prolongs professional activity in IDH mutant low-grade glioma patients: a policy change analysis

BackgroundUntil 2015, Dutch guidelines recommended follow-up and biopsy rather than surgery as initial care for suspected low-grade gliomas (LGG). Given evidence that surgery could extend patient survival, our center stopped following this guideline on January 1, 2010 and opted for early maximal safe resection of LGG. The effects of early surgery on the ability of patients to work remains little documented. MethodsA total of 104 patients operated on at our center between January 2000 and April 2013 and diagnosed with the WHO 2016 grade 2 astrocytoma, IDH mutant or oligodendroglioma, IDH mutant and deleted 1p19q were included. The clinical characteristics, survival, and work history of patients operated on before or after January 2010 were obtained from the patients' records and compared. The minimal follow-up was 8 years. ResultsAs per policy change, the interval between radiological diagnosis and first surgery decreased significantly after 2010. Likewise, before 2010, 25.8% of tumors were initially biopsied, 51.6% were resected under anesthesia, and 22.5% under awake conditions versus 14.3%, 23.8%, and 61.9% after this date (p < 0.001). The severity of permanent postoperative neurological deficits decreased after 2010. In total, 82.5% of the patients returned to work postoperatively before 2010 versus 100% after 2010. The postoperative control of epilepsy increased significantly after 2010 (74.4% vs. 47.9%). The median time from diagnosis to a definitive incapacity to work increased by more than 2 years after 2010 (88.7 vs. 62.2 months). ConclusionA policy shift towards early aggressive surgical treatment of IDH mutant LGG is safe and prolongs the patients' ability to work

International practice variation in perioperative laboratory testing in glioblastoma patients-a retrospective cohort study

Purpose Although standard-of-care has been defined for the treatment of glioblastoma patients, substantial practice variation exists in the day-to-day clinical management. This study aims to compare the use of laboratory tests in the perioperative care of glioblastoma patients between two tertiary academic centers-Brigham and Women's Hospital (BWH), Boston, USA, and University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. Methods All glioblastoma patients treated according to standard-of-care between 2005 and 2013 were included. We compared the number of blood drawings and laboratory tests performed during the 70-day perioperative period using a Poisson regression model, as well as the estimated laboratory costs per patient. Additionally, we compared the likelihood of an abnormal test result using a generalized linear mixed effects model. Results After correction for age, sex, IDH1 status, postoperative KPS score, length of stay, and survival status, the number of blood drawings and laboratory tests during the perioperative period were 3.7-fold (p < 0.001) and 4.7-fold (p < 0.001) higher, respectively, in BWH compared to UMCU patients. The estimated median laboratory costs per patient were 82 euros in UMCU and 256 euros in BWH. Furthermore, the likelihood of an abnormal test result was lower in BWH (odds ratio [OR] 0.75, p < 0.001), except when the prior test result was abnormal as well (OR 2.09, p < 0.001). Conclusions Our results suggest a substantially lower clinical threshold for ordering laboratory tests in BWH compared to UMCU. Further investigating the clinical consequences of laboratory testing could identify over and underuse, decrease healthcare costs, and reduce unnecessary discomfort that patients are exposed to.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Chronic, unexplained pain

Chronic, unexplained pain (CUP) is a common clinical problem. The core symptom in this heterogeneous group of patients is pain for which no medical explanation is found. Patients also have many other characteristics (symptoms and psychosocial features) in common. Pathophysiologically, increased sensitivity for painful stimuli and abnormal pain processing in the brain seem to be of importance, but the empirical evidence for these mechanisms is limited. Part 1 of this thesis focused on epidemiological aspects of CUP. It is a common diagnosis in the Neurology outpatient clinic (15% of all new patients). At follow-up, the diagnosis is rarely revised to an 'explained' form of pain. In a cohort study in 422 CUP-patients, we found that several psychological factors are associated with pain severity and quality of life. However, the prognostic value of these factors for the clinical course of patients was poor. The second part of this thesis focused on pathophysiology. In a quantitative sensory testing study, we found that CUP-patients display increased sensitivity to several types of pain, but their sensitivity for non-painful heat and cold was decreased. CUP-patients were less susceptible to distraction from pain: the decrease in pain scores that is usually found in healthy subjects during distraction was not found in CUP-patients. Functional MRI revealed that the cerebral processing of pain in CUP during distraction is associated with abnormally high brain activity in pain registration areas (posterior insula), but low activity in pain modulatory regions such as the dorsolateral prefrontal cortex. In conclusion, the results in this thesis support the notion that CUP is a complex biopsychosocial problem, with a central role for abnormal, augmented pain processing in the central nervous syste

Prevalence and predictors of unexplained neurological symptoms in an academic neurology outpatient clinic--an observational study.

Item does not contain fulltextOBJECTIVES: (a) To determine the prevalence of unexplained symptoms among newly referred patients in a Dutch academic outpatient clinic for general neurology; (b) To identify factors that can serve as characteristics and possibly as screening instruments for unexplained symptoms in this population. METHODS: Observational study, consisting of self-assessment questionnaires. Patients and resident neurologists completed self-designed questionnaires, which included questions about possible features of unexplained symptoms. Patients also completed the Hospital Anxiety and Depression Scale (HADS), evaluating the existence of anxiety and depressive symptoms. Diagnosis of unexplained symptoms was based on the final classification of the patient's symptoms as non-organic, after assessment by a senior neurologist. In the analysis, separate predicting factors and groups of factors were adjusted for age, sex and HADS-score, and analysed as possible characteristics of unexplained symptoms. RESULTS: 35% of the patients (208 total, 174 completed questionnaires) were considered to suffer from unexplained symptoms.Young age (p < 0.001) and female sex (p = 0.007) were significantly associated with unexplained symptoms, high HADS-scores were not (p = 0.10). Characteristics associated with unexplained symptoms were the resident's preliminary impression of symptoms being non-organic, after reading of the referral letter [OR 96.8, 95% confidence interval (95 %-CI) 29.7-315, PPV 82%, NPV 96%] and after the first encounter (OR 305, 95 %-CI 37.3-2494.6, PPV 83%, NPV 98%), but before the actual history taking and neurological examination. The only other non-demographic characteristic of unexplained symptoms was a visit in order to obtain a second opinion (OR 2.43, 95 %-CI 1.15-5.10). Clustering of these factors, however, did not have sufficient predictive power to result in an accurate screening instrument. CONCLUSIONS: Unexplained symptoms are common in the neurology outpatient clinic and are to some extent predicted by the physician's preliminary judgement of symptoms. However, history taking and neurological examination remain indispensable for the detection of less obvious organic disorders

Samenvatting van de Nederlandse richtlijn voor de diagnostiek en behandeling van verworven aplastische anemie bij volwassenen

Item does not contain fulltex

NEUROCOGNITIVE CHANGES AFTER AWAKE SURGERY FOR DIFFUSE GLIOMA; A RETROSPECTIVE COHORT STUDY

Scientific Assessment and Innovation in Neurosurgical Treatment Strategie