Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG)

The International Pharmaco-EEG Society (IPEG) presents updated guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-EEG data in man. Since the publication of the first pharmaco-EEG guidelines in 1982, technical and data processing methods have advanced steadily, thus enhancing data quality and expanding the palette of tools available to investigate the action of drugs on the central nervous system (CNS), determine the pharmacokinetic and pharmacodynamic properties of novel therapeutics and evaluate the CNS penetration or toxicity of compounds. However, a review of the literature reveals inconsistent operating procedures from one study to another. While this fact does not invalidate results per se, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. Moreover, this shortcoming hampers reliable comparisons between outcomes of studies from different laboratories and hence also prevents pooling of data which is a requirement for sufficiently powering the validation of novel analytical algorithms and EEG-based biomarkers. The present updated guidelines reflect the consensus of a global panel of EEG experts and are intended to assist investigators using pharmaco-EEG in clinical research, by providing clear and concise recommendations and thereby enabling standardisation of methodology and facilitating comparability of data across laboratories

Loss of Consciousness at Onset of Aneurysmal Subarachnoid Hemorrhage is Associated with Functional Outcomes in Good-Grade Patients

BACKGROUND Transient loss of consciousness (LOC) is one of the most common presentations of aneurysmal subarachnoid hemorrhage (SAH) and may be an indicator of early brain injury. The aim of the current study was to examine the association of LOC to functional outcomes in patients with good-grade SAH. METHODS We searched the Subarachnoid Hemorrhage International Trialists Repository for patients that presented with LOC at ictus of SAH. A propensity score analysis was performed on good-grade patients (defined as World Federation of Neurosurgical Societies grades 1-3) to balance selected covariates between those with and without LOC. Primary outcome was Glasgow Outcome Score (GOS) at 3 months (with poor outcome defined as GOS of 1-3). Secondary outcomes were delayed cerebral ischemia (DCI), rebleed, length of hospital stay, and time to death. RESULTS A propensity score-matching algorithm identified 337 patients (168 with LOC at ictus, and 168 without). The proportion of patients with poor functional outcome at 3-months was significantly higher in those who had LOC at ictus compared to the matched cohort without LOC (30% vs. 19%; P = 0.02). There was a non-significant trend toward higher mortality in patients with LOC (19% vs. 13%; P = 0.14). There were no differences in the secondary outcomes. CONCLUSIONS LOC of at ictus of SAH is associated with higher rate of unfavorable functional outcomes but not mortality, DCI or rebleed in good-grade SAH patients. Future studies should further investigate the putative mechanisms by which LOC mediates early brain injury in SAH

Grading of carotid artery stenosis with multidetector-row CT angiography: visual estimation or caliper measurements?

To assess the optimal method for grading carotid artery stenosis with computed tomographic angiography (CTA), we compared visual estimation to caliper measurements, and determined inter-observer variability and agreement relative to digital subtraction angiography (DSA). We included 46 patients with symptomatic carotid stenosis for whom CTA and DSA of 55 carotids was available. Stenosis quantification by CTA using visual estimation (CTAVE) (method 1) was compared with caliper measurements using subjectively optimized wide window settings (method 2) or predefined contrast-dependent narrow window settings (method 3). Measurements were independently performed by two radiologists and two residents. To determine accuracy and inter-observer variability, we calculated linear weighted kappa, performed a Bland-Altman analysis and calculated mean difference (bias) and standard deviation of differences (SDD). For inter-observer variability, kappa analysis was “very good” (0.85) for expert observers using CTAVE compared with “good” (0.61) for experts using DSA. Compared with DSA, method 1 led to overestimation (bias 5.8–8.0%, SDD 10.6–14.4), method 3 led to underestimation (bias −6.3 to −3.0%, SDD 13.0–18.1). Measurement variability between DSA and visual estimation on CTA (SDD 11.5) is close to the inter-observer variability of repeated measurements on DSA that we found in this study (SDD 11.6). For CTA of carotids, stenosis grading based on visual estimation provides better agreement to grading by DSA compared with stenosis grading based on caliper measurements

The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies

Adjustment for prognostic covariates can lead to increased power in the analysis of randomized trials. However, adjusted analyses are not often performed in practice

The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults

Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier

Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. Weevaluated whether PSVs inBRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.Peer reviewe

Body mass index and outcome after revascularization for symptomatic carotid artery stenosis.

To determine whether the obesity paradox exists in patients who undergo carotid artery stenting (CAS) or carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. We combined individual patient data from 2 randomized trials (Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis and Stent-Protected Angioplasty vs Carotid Endarterectomy) and 3 centers in a third trial (International Carotid Stenting Study). Baseline body mass index (BMI) was available for 1,969 patients and classified into 4 groups: <20, 20-<25, 25-<30, and ≥30 kg/m(2). Primary outcome was stroke or death, investigated separately for the periprocedural and postprocedural period (≤120 days/>120 days after randomization). This outcome was compared between different BMI strata in CAS and CEA patients separately, and in the total group. We performed intention-to-treat multivariable Cox regression analyses. Median follow-up was 2.0 years. Stroke or death occurred in 159 patients in the periprocedural (cumulative risk 8.1%) and in 270 patients in the postprocedural period (rate 4.8/100 person-years). BMI did not affect periprocedural risk of stroke or death for patients assigned to CAS (ptrend = 0.39) or CEA (ptrend = 0.77) or for the total group (ptrend = 0.48). Within the total group, patients with BMI 25-<30 had lower postprocedural risk of stroke or death than patients with BMI 20-<25 (BMI 25-<30 vs BMI 20-<25; hazard ratio 0.72; 95% confidence interval 0.55-0.94). BMI is not associated with periprocedural risk of stroke or death; however, BMI 25-<30 is associated with lower postprocedural risk than BMI 20-<25. These observations were similar for CAS and CEA