High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial).

INTRODUCTION: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). METHODS: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. DISCUSSION: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Incidence of clinically relevant psychiatric symptoms during glioblastoma treatment: an exploratory study.

PURPOSE: In addition to neurological symptoms glioblastoma (GBM) patients can experience psychiatric complaints, which are often hard to recognize and difficult to treat. Research on psychiatric symptoms during glioblastoma treatment is limited, but can have significant impact on quality of life, treatment processes and even survival. The aim of this study is to explore the incidence of clinically relevant psychiatric symptoms, during glioblastoma treatment and active surveillance. METHODS: Medical records of 302 GBM patients were reviewed from diagnostic surgery until discontinuation of treatment or active surveillance. Clinical relevance was defined as psychiatric symptoms that interfered with the oncological treatment and required referral to a psychiatrist. "Referred" versus "non-referred" GBM patients were compared using the Pearson Chi-Square test, Fisher's Exact Test or Mann Whitney-U test. RESULTS: Psychiatric symptoms occurred in 11.5% of patients during glioblastoma treatment or active surveillance, most often mood or behavioral symptoms, followed by psychotic symptoms. Referral occurred mainly during concomitant chemoradiation or adjuvant chemotherapy (64.3%). In 28.6% of patients psychiatric symptoms were thought to be attributive to medication. Treatment was discontinued in 17.9% of patients and temporarily interrupted in 3.6%. Possible risk factors included male gender, history of psychiatric disorder, postoperative delirium, non-frontal tumor location, anti-epileptic drug use at baseline and corticosteroid initiation during treatment. CONCLUSION: The found incidence of 11.5% and the high number of patients discontinuing treatment due to psychiatric symptoms justify more research in this, to date, understudied topic in scientific literature. Further prospective studies are needed to identify risk factors and unravel possible effects on survival.

[Cognitive impairment in patients with COPD: a review]. / Cognitieve beperkingen bij patiënten met COPD: een overzicht.

COPD (Chronic Obstructive Pulmonary Disease) is a respiratory disease characterized by progressive and largely irreversible airway limitation and extrapulmonary problems. The prevalence of COPD increases with age. Mental health problems, including cognitive capacity limitations, occur frequently. Patients with COPD may have problems with cognitive functioning, either globally or in single cognitive domains, such as information processing, attention and concentration, memory, executive functioning and self-regulation. Possible causes are hypoxemia, hypercapnia, exacerbations and decreased physical activity. Cognitive problems in these patients may be related to structural brain abnormalities, such as gray matter pathologic changes and the loss of white matter integrity. Because of the negative impact on health and daily life, it is important to assess cognitive functioning in patients with COPD in order to optimize patient-oriented treatment and to reduce personal discomfort, hospital admissions and mortality.

Recurrent pain is associated with decreased selective attention in a population-based sample.

Studies which have examined the impact of pain on cognitive functioning in the general population are scarce. In the present study we assessed the predictive value of recurrent pain on cognitive functioning in a population-based study (N=1400). Furthermore, we investigated the effect of pain on cognitive functioning in individuals with specific pain complaints (i.e. back pain, gastric pain, muscle pain and headache). Cognitive functioning was assessed using the Stroop Color-Word Interference test (Stroop interference), the Letter-Digit-Substitution test (LDST) and the Visual Verbal learning Task (VVLT). Pain was measured with the COOP/WONCA pain scale (Dartmouth Primary Care Cooperative Information Project/World Organization of National Colleges, Academies, and Academic Associations of General Practice /Family Physicians). We controlled for the effects of age, sex, level of education and depressive symptoms. It was demonstrated that pain had a negative impact on the performance on the Stroop interference but not on the VVLT and the LDST. This indicates that subjects who reported extreme pain had more problems with selective attention and were more easily distracted. Effects were in general larger in the specific pain groups when compared to the associations found in the total group. Implications of these findings are discussed. The experience of recurrent pain has a negative influence on selective attention in a healthy population.

Predictive value of mild cognitive impairment for dementia. The influence of case definition and age.

BACKGROUND/AIMS: In population studies, different mild cognitive impairment (MCI) definitions have been used to predict dementia at a later stage. This study compared predictive values of different MCI definitions for dementia, and the effect of age on the predictive values was investigated. METHODS: This study was conducted as part of an ongoing longitudinal study into the determinants of cognitive aging, the Maastricht Aging Study. RESULTS: MCI best predicted dementia when multiple cognitive domains were considered and subjective complaints were not (sensitivity: 0.66, specificity: 0.78). Age had a strong influence on the sensitivity of MCI for dementia (age 60-70 years: sensitivity = 0.56; age 70-85 years: sensitivity = 0.70). CONCLUSION: The inclusion of multiple cognitive domains and participants aged 70 years and older leads to the best prediction of dementia, regardless of subjective complaints.

Cognition after major surgery in the elderly: test performance and complaints.

There is evidence that older people in particular have a higher risk of cognitive dysfunction after surgery under general anaesthesia. We have investigated the severity and character of postoperative cognitive dysfunction after major non-cardiac surgery in patients older than 65 yr. Also, cognitive complaints were studied. Cognitive function was assessed using cognitive tests measuring memory and attention, such as ability to shift between two sequences, ability to ward off distractions, simple cognitive speed and speed of general information processing. These tests were performed before, 1 week (short-term) and 3 months (long-term) after surgery. Cognitive performance of the patients was compared with that of healthy subjects not undergoing surgery who were also subjected to repeated cognitive measurements. After 1 week, patients had a poorer performance on tests measuring simple cognitive speed and speed of general information processing. Three months after surgery, patients and controls showed improved cognitive performance compared with the first measurement. These results suggest that major non-cardiac surgery in older patients causes short-term but not long-term cognitive dysfunction. However, after 6 months, 14 of 48 patients (29%) reported having experienced a decline in cognitive abilities after discharge from hospital. Eight of these 14 patients (17%) were still experiencing these cognitive complaints and reported 'not being the same since the operation'. These findings emphasize that cognitive complaints after major surgery may not reflect actual changes in cognitive performance but may be caused by other factors such as depression or awareness of age-related changes.

An operation under general anesthesia as a risk factor for age-related cognitive decline: results from a large cross-sectional population study.

OBJECTIVE: To evaluate the factor 'operation under general anesthesia' as a possible risk factor for age-related cognitive decline. DESIGN: A retrospective, population-based, cross-sectional study. SETTING: Maastricht Aging Study (MAAS), Maastricht, The Netherlands. PARTICIPANTS: 1257 normal healthy subjects aged 24 to 86 years. Of the 1257 healthy subjects, 946 subjects appeared to have undergone at least one operation under general anesthesia. MEASUREMENTS: The history of an operation under general anesthesia, number of operations, duration of anesthesia, cognitive performance, subjective health, and subjective memory were measured. RESULTS: A history of an operation under general anesthesia, the number of operations, and the total duration of anesthesia significantly contributed to the number of subjective health-related complaints but did not predict cognitive performance or memory complaints. Subjects with a history of an operation under general anesthesia felt less healthy than subjects who had never undergone an operation under general anesthesia. No interactions with age were found. CONCLUSION: The present study found no support for the notion that a history of an operation under general anesthesia is a determinant or risk factor for accelerated age-related cognitive decline.

Differentiation between transmural perioperative myocardial infarction and subendocardial injury after coronary artery bypass grafting using biochemical tests, elaborated by cluster and discriminant analysis.

The aim of this study is to differentiate between transmural perioperative myocardial infarction (T-PMI) and subendocardial perioperative myocardial injury (S-PMI) as a complication of coronary artery bypass grafting (CABG). Seventy-three patients undergoing CABG were followed post operatively by measuring troponin T, CK-MB isoenzyme mass concentration (CK-MB mass), creatine kinase MB isoenzyme activity (CK-MB activity), creatine kinase (CK), alpha hydroxybutyrate dehydrogenase (HBD), and aspartate aminotransferase (AST) at five sampling times. Lacking a proper definition of the gold standard for the diagnosis of perioperative myocardial infarction, a statistical procedure was used. Supported by the cluster analysis method of Ward, patients were assigned to a patient group with a perioperative myocardial infarction (PMI) or a patient group without a PMI (non-PMI) as a confirmation of interpretation of the biochemical results. Using the results of electrocardiogram (ECG) and echocardiography, the PMI patient group was split into a T-PMI patient group and a S-PMI patient group. With discriminant analysis, two canonic discriminant functions were drawn up to differentiate between patients suffering from a T-PMI or S-PMI and non-PMI patients.

Are the classical markers sufficient to describe uremic solute accumulation in dialyzed patients? Hippurates reconsidered.

Interdependencies of accumulated solutes, analyzed by liquid chromatography in dialyzed and non-dialyzed patients, were studied by multivariate statistical analysis. In principal component analysis, three principal components (PC1-PC3) were retained from the data on 22 accumulated compounds in dialyzed patients, whereas only one principal component was retained from analogous data of a non-dialyzed patient group. PC1 in the dialyzed patient group comprises concentrations of hippuric acid, p-hydroxyhippuric acid, tryptophan, and five unidentified fluorescent solutes in serum. Concentrations of the classical markers urea, uric acid, creatinine, and phosphate were closely related to PC2 in these patients. Indoleacetic acid and two unidentified fluorescent compounds constitute PC3. The compounds associated with the groups found by principal component analysis may be characterized by chemical structure and by the mechanism of their excretion via the remaining nephrons of dialyzed patients. In the non-dialyzed group, most of the solutes could be described by a single PC. This PC and PC1 from the dialyzed group correlated significantly with residual renal function, and with total ultraviolet absorbance and total fluorescence emission. The data suggest that it is of value to introduce a marker of uremic solute retention in addition to urea, to account for renal-function-related "organic-acid-like" compounds that are excreted by renal tubular secretion in dialyzed patients. The hippurates may serve this purpose.