Automated Annotation of Epileptiform Burden and Its Association with Outcomes.

OBJECTIVE: This study was undertaken to determine the dose-response relation between epileptiform activity burden and outcomes in acutely ill patients. METHODS: A single center retrospective analysis was made of 1,967 neurologic, medical, and surgical patients who underwent >16 hours of continuous electroencephalography (EEG) between 2011 and 2017. We developed an artificial intelligence algorithm to annotate 11.02 terabytes of EEG and quantify epileptiform activity burden within 72 hours of recording. We evaluated burden (1) in the first 24 hours of recording, (2) in the 12-hours epoch with highest burden (peak burden), and (3) cumulatively through the first 72 hours of monitoring. Machine learning was applied to estimate the effect of epileptiform burden on outcome. Outcome measure was discharge modified Rankin Scale, dichotomized as good (0-4) versus poor (5-6). RESULTS: Peak epileptiform burden was independently associated with poor outcomes (p < 0.0001). Other independent associations included age, Acute Physiology and Chronic Health Evaluation II score, seizure on presentation, and diagnosis of hypoxic-ischemic encephalopathy. Model calibration error was calculated across 3 strata based on the time interval between last EEG measurement (up to 72 hours of monitoring) and discharge: (1) <5 days between last measurement and discharge, 0.0941 (95% confidence interval [CI] = 0.0706-0.1191); 5 to 10 days between last measurement and discharge, 0.0946 (95% CI = 0.0631-0.1290); >10 days between last measurement and discharge, 0.0998 (95% CI = 0.0698-0.1335). After adjusting for covariates, increase in peak epileptiform activity burden from 0 to 100% increased the probability of poor outcome by 35%. INTERPRETATION: Automated measurement of peak epileptiform activity burden affords a convenient, consistent, and quantifiable target for future multicenter randomized trials investigating whether suppressing epileptiform activity improves outcomes. ANN NEUROL 2021;90:300-311.

Burden of Epileptiform Activity Predicts Discharge Neurologic Outcomes in Severe Acute Ischemic Stroke.

BACKGROUND/OBJECTIVES: Clinical seizures following acute ischemic stroke (AIS) appear to contribute to worse neurologic outcomes. However, the effect of electrographic epileptiform abnormalities (EAs) more broadly is less clear. Here, we evaluate the impact of EAs, including electrographic seizures and periodic and rhythmic patterns, on outcomes in patients with AIS. METHODS: This is a retrospective study of all patients with AIS aged ≥ 18 years who underwent at least 18 h of continuous electroencephalogram (EEG) monitoring at a single center between 2012 and 2017. EAs were classified according to American Clinical Neurophysiology Society (ACNS) nomenclature and included seizures and periodic and rhythmic patterns. EA burden for each 24-h epoch was defined using the following cutoffs: EA presence, maximum daily burden < 10% versus > 10%, maximum daily burden < 50% versus > 50%, and maximum daily burden using categories from ACNS nomenclature ("rare" < 1%; "occasional" 1-9%; "frequent" 10-49%; "abundant" 50-89%; "continuous" > 90%). Maximum EA frequency for each epoch was dichotomized into ≥ 1.5 Hz versus < 1.5 Hz. Poor neurologic outcome was defined as a modified Rankin Scale score of 4-6 (vs. 0-3 as good outcome) at hospital discharge. RESULTS: One hundred and forty-three patients met study inclusion criteria. Sixty-seven patients (46.9%) had EAs. One hundred and twenty-four patients (86.7%) had poor outcome. On univariate analysis, the presence of EAs (OR 3.87 [1.27-11.71], p = 0.024) and maximum daily burden > 10% (OR 12.34 [2.34-210], p = 0.001) and > 50% (OR 8.26 [1.34-122], p = 0.035) were associated with worse outcomes. On multivariate analysis, after adjusting for clinical covariates (age, gender, NIHSS, APACHE II, stroke location, stroke treatment, hemorrhagic transformation, Charlson comorbidity index, history of epilepsy), EA presence (OR 5.78 [1.36-24.56], p = 0.017), maximum daily burden > 10% (OR 23.69 [2.43-230.7], p = 0.006), and maximum daily burden > 50% (OR 9.34 [1.01-86.72], p = 0.049) were associated with worse outcomes. After adjusting for covariates, we also found a dose-dependent association between increasing EA burden and increasing probability of poor outcomes (OR 1.89 [1.18-3.03] p = 0.009). We did not find an independent association between EA frequency and outcomes (OR: 4.43 [.98-20.03] p = 0.053). However, the combined effect of increasing EA burden and frequency ≥ 1.5 Hz (EA burden * frequency) was significantly associated with worse outcomes (OR 1.64 [1.03-2.63] p = 0.039). CONCLUSIONS: Electrographic seizures and periodic and rhythmic patterns in patients with AIS are associated with worse outcomes in a dose-dependent manner. Future studies are needed to assess whether treatment of this EEG activity can improve outcomes.

Burst Suppression: Causes and Effects on Mortality in Critical Illness.

BACKGROUND: Burst suppression in mechanically ventilated intensive care unit (ICU) patients is associated with increased mortality. However, the relative contributions of propofol use and critical illness itself to burst suppression; of burst suppression, propofol, and critical illness to mortality; and whether preventing burst suppression might reduce mortality, have not been quantified. METHODS: The dataset contains 471 adults from seven ICUs, after excluding anoxic encephalopathy due to cardiac arrest or intentional burst suppression for therapeutic reasons. We used multiple prediction and causal inference methods to estimate the effects connecting burst suppression, propofol, critical illness, and in-hospital mortality in an observational retrospective study. We also estimated the effects mediated by burst suppression. Sensitivity analysis was used to assess for unmeasured confounding. RESULTS: The expected outcomes in a "counterfactual" randomized controlled trial (cRCT) that assigned patients to mild versus severe illness are expected to show a difference in burst suppression burden of 39%, 95% CI [8-66]%, and in mortality of 35% [29-41]%. Assigning patients to maximal (100%) burst suppression burden is expected to increase mortality by 12% [7-17]% compared to 0% burden. Burst suppression mediates 10% [2-21]% of the effect of critical illness on mortality. A high cumulative propofol dose (1316 mg/kg) is expected to increase burst suppression burden by 6% [0.8-12]% compared to a low dose (284 mg/kg). Propofol exposure has no significant direct effect on mortality; its effect is entirely mediated through burst suppression. CONCLUSIONS: Our analysis clarifies how important factors contribute to mortality in ICU patients. Burst suppression appears to contribute to mortality but is primarily an effect of critical illness rather than iatrogenic use of propofol.

Social network, recovery attitudes and internal stigma among those with serious mental illness.

BACKGROUND: Social network size and strength is an important determinant of overall health. AIMS: This study describes the extent and strength of the social network among a sample of individuals with serious mental illness (SMI) and explores the relationship between an individual's social network and their experience of internal stigma and recovery attitudes. METHODS: Over a 2-year period, consecutive new patients with SMI attending two community mental health clinics were recruited and interviewed using a comprehensive battery of assessments including assessment of internalized stigma, recovery attitudes and symptom severity. RESULTS: Among the 271 patients interviewed, social network size was small across all diagnostic categories. In adjusted results, the number of friends and support from relatives and friends was significantly related to the personal confidence and hope recovery attitude ( p < .05). The number of relatives and friends and support from relatives was significantly related to internalized stigma ( p < .05). Frequency of contact with relatives or friends was not related to either recovery factors or internalized stigma. CONCLUSION: There is a significant positive relationship between the size and perceived strength of an individual's social network and internalized stigma and some recovery attitudes. Clinical programs that address any of these factors could potentially improve outcomes for this population.

Reliability of Different RBC Indices and Formulas in Discriminating between ß-Thalassemia Minor and other Microcytic Hypochromic Cases.

OBJECTIVE: Different indices and formulas of CBC parameters have been suggested as indicators of early stage screenings to detect couples with ß-thalassemia minor (BTMi). In this study, we evaluated the accuracy of five previous published formulas and compared them to our new formula (│80-MCV│×│27-MCH│) in screening of ß-thalassemia. METHODS: All couples in the premarital ß-thalassemia screening program of Roodbar, Iran, for whom molecular analysis had been done, were selected during two years. The red blood cell parameters were applied to each formula, and a ROC curve was plotted for each one to check its discriminative effectiveness in ß-thalassemia detection. RESULT: None of the studied indices and formulas demonstrated 100% precision. However, we found that the Shine-Lal formula and our formula had the highest sensitivity in identifying BTMi individuals. The highest specificity belonged to our formula and Sirdah formula. CONCLUSION: Previous studies reported different sensitivities and specificities for the formulas. This can be attributed to different kinds of HBB gene mutations in various populations. Undoubtedly, physicians in different areas should evaluate the accuracy of published formulas for their own populations in the discrimination of BTMi from other causes of microcytic hypochromic anemia.

Evaluation of Pre-Treatment Serum Levels of IL-7 and GM-CSF in Colorectal Cancer Patients.

Survival of Colorectal cancer (CRC) patients is considerably stage-dependent; therefore, early diagnosis is a pivotal factor in decreasing mortality and morbidity associated with this cancer. GM-CSF and IL-7 are reported to increase in different cancers and we aimed to investigate the pre-treatment serum levels of GM-CSF and IL-7 in Iranian patients with colorectal cancer. 127 patients (68 males and 59 females) entered this study before receiving chemotherapy or radiotherapy. A control group of 50 healthy age/sex matched individuals (27 males and 23 females) were included in the study. The serum levels of GM-CSF and IL-7 were measured using commercial enzyme linked immunosorbent assays. A significantly higher level of GM-CSF was found in the sera of patients with colorectal cancer compared to healthy age/sex matched controls (P=0.013). However, there was no significant difference between the levels of IL-7 in sera of patients and controls. We observed a significant elevation in the level of GM-CSF in poorly differentiated tumors (P=0.024). Also a significant correlation between lymphatic invasion and the level of GM-CSF in sera of CRC patients was detected (P=0.01). We found an increase of the level of IL-7 in four patients presenting moderate stages of tumor concomitant with a decrease of the level of GM-CSF. It can be concluded that the increase of the level of GM-CSF is accompanied by CRC progression in Iranian patients. Potential therapeutic effect of IL-7 in this disease, however, needs further investigations.

Serum levels of G-CSF and IL-7 in Iranian breast cancer patients.

INTRODUCTION: Breast cancer cells and tumor stroma produce different cytokines and soluble factors. Cytokines, while playing crucial roles in immune responses to tumors, also favour tumor growth and progression. IL-7 and G-CSF are two cytokines that may exert influences on the pathophysiology of breast cancer. MATERIALS AND METHODS: Sera were collected from 136 females with breast cancer before receiving chemotherapy or radiotherapy. The control group comprised of 60 healthy age-matched females without any acute or chronic diseases with no family history of breast cancer. Serum levels of IL-7 and G-CSF were measured by commercial enzyme linked immunosorbent assay. RESULTS: While there was no significant difference in the level of G-CSF between patients (92.81 ± 594.54 pg/ml) and controls (0.00 pg/ml), G-CSF level in sera of patients with advanced stages of breast cancer was elevated compared to early stages (p=0.0001). Moreover, the highest level of G-CSF was seen in patients with N3 phase tumors (p=0.0001). IL-7 was slightly but not significantly higher in the control group (0.04 ± 0.11 pg/ml) in comparison with patients (0.02 ± 0.10 pg/ml). Interestingly, a significant increase in the level of IL-7 in patients with skin involvement was observed (p=0.001). CONCLUSION: Our results showed an elevation of G-CSF in sera of patients with advanced stages of tumor, while IL-7 elevation correlated with skin involvement of breast cancer. IL-7 can be produced by keratinocytes in skin tissue and may be involved in the pathologic establishment of metastatic tumor cells in skin.