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OBJECTIVE: Delayed cerebral ischemia (DCI) is a leading complication of aneurysmal subarachnoid hemorrhage (SAH) and electroencephalography (EEG) is increasingly used to evaluate DCI risk. Our goal is to develop an automated DCI prediction algorithm integrating multiple EEG features over time. METHODS: We assess 113 moderate to severe grade SAH patients to develop a machine learning model that predicts DCI risk using multiple EEG features. RESULTS: Multiple EEG features discriminate between DCI and non-DCI patients when aligned either to SAH time or to DCI onset. DCI and non-DCI patients have significant differences in alpha-delta ratio (0.08 vs 0.05, p < 0.05) and percent alpha variability (0.06 vs 0.04, p < 0.05), Shannon entropy (p < 0.05) and epileptiform discharge burden (205 vs 91 discharges per hour, p < 0.05) based on whole brain and vascular territory averaging. Our model improves predictions by emphasizing the most informative features at a given time with an area under the receiver-operator curve of 0.73, by day 5 after SAH and good calibration between 48–72 hours (calibration error 0.13). CONCLUSIONS: Our proposed model obtains good performance in DCI prediction. SIGNIFICANCE: We leverage machine learning to enable rapid, automated, multi-featured EEG assessment and has the potential to increase the utility of EEG for DCI prediction.

This retrospective case-controlled study was performed to evaluate whether Epileptiform Activity, suspected clinical seizures, and/or 2HELPS2B/S after nontraumatic Intraparenchymal Hemorrhage or Subarachnoid Hemorrhage can predict Epilepsy. Hundred and thirty-two patients were included-29 (Epilepsy), 103 (Control Group). After matching, the average effect for all three risk factors was significant as follows: (1) Epileptiform Activity (p = 0.012, odds ratio 3.14), (2) suspected seizures (p = 0.021, odds ratio 3.78), and (3) 2HELPS2B/S score (p 0.001, odds ratio 4.94). This study shows that Epileptiform Activity, suspected seizures, and particularly, the 2HELPS2B/S score in the acute phase are risk factors for the development of epilepsy after nontraumatic intraparenchymal and subarachnoid hemorrhage.

Background: Propofol is a key component for the management of sedation and shivering during targeted temperature management (TTM) following cardiac arrest. The cardiac depressant effects of propofol have not been described during TTM and may be especially relevant given the stress to the myocardium following cardiac arrest. The purpose of this study is to describe hemodynamic changes associated with propofol administration during TTM. Methods: This single center, retrospective cohort study evaluated adult patients who received a propofol infusion for at least 30 minutes during TTM. The primary outcome was the change in cardiovascular Sequential Organ Failure Assessment (cvSOFA) score 30 minutes after propofol initiation. Secondary outcomes included change in systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and vasopressor requirements (VR) expressed as norepinephrine equivalents at 30, 60, 120, 180, and 240 minutes after propofol initiation. A multivariate regression was performed to assess the influence of propofol and body temperature on MAP, while controlling for vasopressor dose and cardiac arrest hospital prognosis (CAHP) score. Results: The cohort included 40 patients with a median CAHP score of 197. The goal temperature of 33°C was achieved for all patients. The median cvSOFA score was 1 at baseline and 0.5 at 30 minutes, with a non-significant change after propofol initiation ( P = .96). SBP and MAP reductions were the greatest at 60 minutes (17 and 8 mmHg; P

BACKGROUND AND OBJECTIVES: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as “ictal-interictal-injury continuum” (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns. METHODS: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet, to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes. RESULTS: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and “other” classes, SPaRCNet exceeds the following percentages of 20 experts—ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively. DISCUSSION: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists.

Cells were first gated on size and singularity by forward scatter and side scatter. Nonviable cells were excluded by live/dead gating. CD3+ live cells were gated on CD4 and CD8. CD3+FoxP3+CD4+ cells were designated as Tregs. TIM-3 vs. PD-1 expression was assessed for each lymphocyte population.

Cells were first gated on size and singularity by forward scatter and side scatter. Nonviable cells were excluded by live/dead gating. Live cells were gated on CD11c and CD11b, then on CD45 and F4/80 to identify macrophage and dendritic cell phenotypes. Finally myeloid cells were gated for expression of TIM-3. Final populations were (A) F4/80+CD45hiCD11c-CD11bhi (B) F4/80+CD45dimCD11bhi (C) F4/80+CD45hiCD11c+CD11b+ and (D) F4/80-CD45dimCD11c+CD11b-.

Purpose: Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM-3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS.Experimental Design: C57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed.Results: Dual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P < 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples.Conclusions: This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme. Clin Cancer Res; 23(1); 124–36. ©2016 AACR.

Each mouse was individually imaged with cone beam computed tomography (CBCT) using the SARRP with a 65 kVp and 0.7 mA beam. Using the treatment planning system from the SARRP system (Muriplan) and the CBCT, the target was exactly placed 3mm below the skull's burr hole. The planning system calculated the x-ray beam's (220kVp and 13mA) time of exposure according to the prescribed dose and moved the motorized couch to its target location, after which a 3-mm beam centered on the burr hole and underlying tumor was used to administer a total of 10 Gy radiation per animal at a rate of 1.9 Gy/min (18). The isodose distribution is shown on the figure provided. The dose to adjacent organs or rest of the brain is insignificant as the beam's penumbra demonstrates complete drop off on the edge of the field (17, 50, 51)

Antibodies used for flow cytometry (clones and dilutions)

Gating strategy to assess for surface expression of TIM-3 on (A) CD4+ and (B) CD8+ T cells isolated from peripheral lymph nodes, lungs, livers, spleens, and brains.

Introduction: Positive lumpectomy margins are associated with an increased risk for ipsilateral tumor recurrence, and necessitate additional procedures to achieve acceptable margins. Re-excision rates are higher in patients with ductal carcinoma in situ (DCIS) versus those with invasive carcinoma. The purpose of this study was to investigate the clinicopathologic characteristics, surgical techniques, and other outcomes associated with re-excision over time following primary breast conserving surgery for DCIS. Methods: Our institutional Breast Cancer Database was queried for patients treated with lumpectomy as the primary procedure for pure DCIS from 2010-2021. Cases of microinvasive disease were excluded. The primary endpoint was the rate of re-excision following lumpectomy. Variables of interest included patient demographics and clinicopathologic characteristics. As a secondary analysis, adjusted odds ratios for the association of MarginProbe® with re-excisions were calculated using a multivariable logistic regression model controlling for age, tumor size, breast density and DCIS subtype. Individual comparisons of continuous variables were based on t-tests, group proportions compared with one-way ANOVA, and categorical variables compared using Chi Square tests. Results: Out of a total of 695 patients in our cohort, 221 (32%) had re-excisions. There was a statistically significant 2% decline per year in the number of re-excisions (p=0.005). Patients who underwent re-excision had larger size of DCIS (2.37 cm vs 1.37 cm, p Table 1.Clinicopathologic CharacteristicsVariableNo Re-excision (n=313)Re-Excision (n=100)P-ValueAge; mean (SD)61.48 (12.01)58.04 (13.39)0.016Age of Menopause; mean (SD)50.22 (5.18)48.13 (5.45)0.004Size of DCIS; mean (SD)1.37 (1.25)2.37 (2.00)0 and Citation Format: Joshua A Feinberg, Charles DiMaggio, Nakisa Pourkey, Jennifer Chun Kim, Jenny Goodgal, Amber Guth, Deborah Axelrod, Freya Schnabel. Meeting the challenge of successful one-stage lumpectomy for DCIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-11.

Considering the COVID-19 pandemic where concomitant occurrence of ARDS and severe acute brain injury (sABI) has increasingly coemerged, we synthesize existing data regarding the simultaneous management of both conditions. Our aim is to provide readers with fundamental principles and concepts for the management of sABI and ARDS, and highlight challenges and conflicts encountered while managing concurrent disease. Up to 40% of patients with sABI can develop ARDS. Although there are trials and guidelines to support the mainstays of treatment for ARDS and sABI independently, guidance on concomitant management is limited. Treatment strategies aimed at managing severe ARDS may at times conflict with the management of sABI. In this narrative review, we discuss the physiological basis and risks involved during simultaneous management of ARDS and sABI, summarize evidence for treatment decisions, and demonstrate these principles using hypothetical case scenarios. Use of invasive or noninvasive monitoring to assess brain and lung physiology may facilitate goal-directed treatment strategies with the potential to improve outcome. Understanding the pathophysiology and key treatment concepts for comanagement of these conditions is critical to optimizing care in this high-acuity patient population.

Rationale: 82Rb cardiac PET is largely used to study myocardial perfusion with function, and to calculate myocardial blood flow (MBF) and coronary flow reserve (CFR) or myocardial flow reserve (MFR). Although the dosing activity of 82Rb is determined by the patient weight, the infusion volume and activity concentration varies with the age of the 82Rb generator. We sought to predict the needed bolus volume of 82Rb to help evaluate the accuracy of MBF findings. Methods: Data was collected from de-identified tickets of an 82Rb generator, including the instantaneous eluted activity flow rate. The times to reach 4 activity levels of 20, 30, 40, and 45 mCi (740, 1110, 1480, and 1665 MBq respectively) were also calculated. The activity flow rate for the largest bolus was fitted to determine the functional form. The time to reach each bolus level was fitted as a function of the generator age and 95% confidence limits were created. Results: The activity flow rate was fitted with a growth-saturation model, allowing a calculation of bolus volume. The amplitude of the fit was observed to also be influenced by the time since last elution, and possibly other clinical factors. Elution times to reach the 4 activity levels were plotted vs. generator age. The linearized data was fitted and 95% confidence limits were created symmetrically around the fit. The 95% CL band allowed a prediction of elution time to achieve each bolus size for future generators, as a function only of generator age. Conclusion: A predictive model was created for elution times from this brand of 82Rb generator as a function of generator age. The value of this model is in determining if the necessary amount of activity can be extracted from a generator before reaching one of the backup infusion settings, such as volume limits per administration, given a generator age. Some sites may also wish to control the bolus duration for better MBF calculations, since predicting the time for the injection to complete may determine if MBF and CFR calculations are meaningful.

Graphical Abstract In 2006, the induced pluripotent stem cell (iPSC) was presented to the world, paving the way for the development of a magnitude of novel therapeutic alternatives, addressing a diverse range of diseases. However, despite the immense cell therapy potential, relatively few clinical trials evaluating iPSC-technology have actually translated into interventional, clinically applied treatment regimens. Herein, our aim was to determine trends in globally conducted clinical trials involving iPSCs. Data were derived both from well-known registries recording clinical trials from across the globe, and databases from individual countries. Comparisons were firstly drawn between observational and interventional studies before the latter was further analyzed in terms of therapeutic and nontherapeutic trials. Our main observations included global distribution, purpose, target size, and types of disorder relevant to evaluated trials. In terms of nontherapeutic trials, the USA conducted the majority, a large average number of participants—187—was included in the trials, and studies on circulatory system disorders comprised a slightly higher proportion of total studies. Conversely, Japan was the frontrunner in terms of conducting therapeutic trials, and the average number of participants was much lower, at roughly 29. Disorders of the circulatory, as well as nervous and visual systems, were all studied in equal measure. This review highlights the impact that iPSC-based cell therapies can have, should development thereof gain more traction. We lastly considered a few companies that are actively utilizing iPSCs in the development of therapies for various diseases, for whom the global trends in clinical trials could become increasingly important. Supplementary Information The online version contains supplementary material available at 10.1007/s12015-021-10262-3.

Background: There is abundant and even confusing information in the available literature concerning the role of internal limiting membrane (ILM) removal in macular conditions secondary to non-complicated macula-off rhegmatogenous retinal detachment (RRD) repair. This retrospective, multicenter, long-term study aimed to analyze the incidence of epiretinal membrane (ERM) proliferation and other surgical complications and to compare the postoperative microstructural and multimodal imaging findings and correlate them with the final postoperative best-corrected visual acuity (BCVA) in selected eyes.

Secondary brain injury (SBI) is defined as new or worsening injury to the brain after an initial neurologic insult, such as hemorrhage, trauma, ischemic stroke, or infection. It is a common and potentially preventable complication following many types of primary brain injury (PBI). However, mechanistic details about how PBI leads to additional brain injury and evolves into SBI are poorly characterized. In this work, we propose a mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH) of SBI. Our model, based on the Hodgkin–Huxley model, supplemented with additional dynamics for extracellular potassium, oxygen concentration, and excitotoxity, provides a high-level unified explanation for why patients with acute brain injury frequently develop SBI. We investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, and seizures can induce SBI and suggest three underlying paths for how events following PBI may lead to SBI. The proposed model also helps explain several important empirical observations, including the common association of acute brain injury with seizures, the association of seizures with tissue hypoxia and so on. In contrast to current practices which assume that ischemia plays the predominant role in SBI, our model suggests that metabolic crisis involved in SBI can also be nonischemic. Our findings offer a more comprehensive understanding of the complex interrelationship among potassium, oxygen, excitotoxicity, seizures, and SBI. NEW & NOTEWORTHY We present a novel mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH), which attempts to explain why patients with acute brain injury frequently develop seizure activity and secondary brain injury (SBI). Specifically, we investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, seizures, all common sequalae of primary brain injury (PBI), can induce SBI and suggest three underlying paths for how events following PBI may lead to SBI.

Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5–3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: [0.68–0.90]). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: [0.90–0.99]). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p = 1.69e-30 and ICC = 0.875, p = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings., Conventional magnetic resonance imaging (MRI) operates at a high magnetic field strength and requires a strict access-controlled environment, making MRI often inaccessible. Here, the authors present a portable low-field MRI device that detects intracerebral hemorrhage with high accuracy.

BACKGROUND AND PURPOSE Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head computed tomography (CT). METHODS We used the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial dataset. Patients included in this analysis (n = 895) were randomly allocated to discovery (n = 448) and independent validation (n = 447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline noncontrast head CT scans and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume. RESULTS In the discovery cohort, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.47 vs. 0.44, p = 0.008), admission NIHSS (0.69 vs. 0.57, p

Women continue to remain underrepresented in STEM, and this gender disparity is particularly pronounced in leadership positions. Through in-depth, qualitative interviews of 39 women leaders in STEM, we identify common gender microaggressions they experience, and explore how these microaggressions affect their leadership experience and outcomes in the workplace. Our findings highlight five types of gender microaggressions women most often encounter, and how and when these microaggressions occur. We explore the negative impact that microaggressions can have on women’s work identities and how they can trigger a cycle of rumination and self-doubt that may ultimately result in women choosing to leave STEM. Importantly, we surface the interventional and empowering role that allies play in triggering a redemptive sensemaking process that can support women leaders to build resilience and counter the negative effects of microaggressions.

Some of the most interesting open questions about the origins of life and molecular sciences center on chemical evolution and the spontaneous generation of new complex and functional chemical species. The spectacular polymers that underlay biology demonstrate an untapped, by modern science, creative potential. We hypothesized that prebiotic chemical evolutionary processes leading to biopolymers were not idiosyncratic one-off events. We have developed an experimental platform that accomplishes chemical evolution in the laboratory. In this paper we describe this platform and report empirical outcomes, some of which were not foreseen. We have constructed experimental platform to study evolution of chemical systems that: (i) undergo continuous recursive change with transitions to new chemical spaces while not converging, (ii) demonstrate stringent chemical selection, during which combinatorial explosion is avoided, (iii) maintain synchronicity of molecular sub-populations, and (iv) harvest environmental energy that is invested in chemical reactions. We have established general guidelines for conducting chemical evolution. Our results suggest that chemical evolution can be adapted to produce a broad array of molecules with novel structures and functions.

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.

BACKGROUND AND OBJECTIVES: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as “ictal-interictal-injury continuum” (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC. METHODS: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as “seizure (SZ),” “lateralized periodic discharges (LPDs),” “generalized periodic discharges (GPDs),” “lateralized rhythmic delta activity (LRDA),” “generalized rhythmic delta activity (GRDA),” or “other.” EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability. RESULTS: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Image: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Image: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds. DISCUSSION: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus.

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.

Background Following non-traumatic subarachnoid hemorrhage (SAH), in-hospital delayed cerebral ischemia is predicted by two chief events on continuous EEG (cEEG): new or worsening epileptiform abnormalities (EAs) and deterioration of cEEG background frequencies. We evaluated the association between longitudinal outcomes and these cEEG biomarkers. We additionally evaluated the association between longitudinal outcomes and other in-hospital complications. Methods Patients with nontraumatic SAH undergoing ≥ 3 days of cEEG monitoring were enrolled in a prospective study evaluating longitudinal outcomes. Modified Rankin Scale (mRS) was assessed at discharge, and at 3- and 6-month follow-up time points. Adjusting for baseline severity in a cumulative proportional odds model, we modeled the mRS ordinally and measured the association between mRS and two forms of in-hospital cEEG deterioration: (1) cEEG evidence of new or worsening epileptiform abnormalities and (2) cEEG evidence of new background deterioration. We compared the magnitude of these associations at each time point with the association between mRS and other in-hospital complications: (1) delayed cerebral ischemia (DCI), (2) hospital-acquired infections (HAI), and (3) hydrocephalus. In a secondary analysis, we employed a linear mixed effects model to examine the association of mRS over time (dichotomized as 0–3 vs. 4–6) with both biomarkers of cEEG deterioration and with other in-hospital complications. Results In total, 175 mRS assessments were performed in 59 patients. New or worsening EAs developed in 23 (39%) patients, and new background deterioration developed in 24 (41%). Among cEEG biomarkers, new or worsening EAs were independently associated with mRS at discharge, 3, and 6 months, respectively (adjusted cumulative proportional odds 4.99, 95% CI 1.60–15.6; 3.28, 95% CI 1.14–9.5; and 2.71, 95% CI 0.95–7.76), but cEEG background deterioration lacked an association. Among hospital complications, DCI was associated with discharge, 3-, and 6-month outcomes (adjusted cumulative proportional odds 4.75, 95% CI 1.64–13.8; 3.4; 95% CI 1.24–9.01; and 2.45, 95% CI 0.94–6.6), but HAI and hydrocephalus lacked an association. The mixed effects model demonstrated that these associations were sustained over longitudinal assessments without an interaction with time. Conclusion Although new or worsening EAs and cEEG background deterioration have both been shown to predict DCI, only new or worsening EAs are associated with a sustained impairment in functional outcome. This novel finding raises the potential for identifying therapeutic targets that may also influence outcomes. Electronic supplementary material The online version of this article (10.1007/s12028-020-01177-x) contains supplementary material, which is available to authorized users.

Background. Fertility preservation (FP) prior to gonadotoxic cancer treatment is underutilized in the United States (US) due to limited access to care. Objective. We aimed to determine the utilization of a regional FP program in an underserved region in the Southeast US. Methods. We performed an institutional review board-approved retrospective cohort study of patients enrolled in the FP program at an academic tertiary medical center from 2014 to 2018. Results. Sixty-nine reproductive age patients were enrolled in the FP program, including 29 men and 40 women between 20 and 49 years of age. Cancer diagnoses among the enrolled patients included hematologic (n = 34), breast (n = 14), testicular (n = 11), reproductive tract (n = 7), and gastrointestinal (n = 3) malignancies. Patients with reproductive tract malignancies were found to have approximately 9.7 times greater odds of proceeding with FP than patients with hematologic malignancies (P Conclusion. Utilization of a regional FP program should be considered to increase access to care to this critical resource for patients desiring future family building. Patients with hematologic malignancy may face unique barriers to FP.

The outbreak of the COVID-19 pandemic has brought a severe negative impact on the country’s economic and social life. The COVID-19 pandemic is regarded as a new form of crisis and has resulted in numerous uncertainties and developed new norms. The paper analyses the COVID-19 pandemic in Malaysia in relation to the Movement of Control Order (MCO) and the effects and changes in business and economic landscape as well as policy responses. It examines the five phases of MCO, and measures undertaken in each phase based on secondary data from various sources. It also analyses the policy responses of the Malaysian government during the COVID-19 pandemic; the new norms are discussed, too.

Background and ObjectivesDelayed cerebral ischemia (DCI) is the leading complication of subarachnoid hemorrhage (SAH). Because DCI was traditionally thought to be caused by large vessel vasospasm, transcranial Doppler ultrasounds (TCDs) have been the standard of care. Continuous EEG has emerged as a promising complementary monitoring modality and predicts increased DCI risk. Our objective was to determine whether combining EEG and TCD data improves prediction of DCI after SAH. We hypothesize that integrating these diagnostic modalities improves DCI prediction.MethodsWe retrospectively assessed patients with moderate to severe SAH (2011–2015; Fisher 3–4 or Hunt-Hess 4–5) who had both prospective TCD and EEG acquisition during hospitalization. Middle cerebral artery (MCA) peak systolic velocities (PSVs) and the presence or absence of epileptiform abnormalities (EAs), defined as seizures, epileptiform discharges, and rhythmic/periodic activity, were recorded daily. Logistic regressions were used to identify significant covariates of EAs and TCD to predict DCI. Group-based trajectory modeling (GBTM) was used to account for changes over time by identifying distinct group trajectories of MCA PSV and EAs associated with DCI risk.ResultsWe assessed 107 patients; DCI developed in 56 (51.9%). Univariate predictors of DCI are presence of high-MCA velocity (PSV ≥200 cm/s, sensitivity 27%, specificity 89%) and EAs (sensitivity 66%, specificity 62%) on or before day 3. Two univariate GBTM trajectories of EAs predicted DCI (sensitivity 64%, specificity 62.75%). Logistic regression and GBTM models using both TCD and EEG monitoring performed better. The best logistic regression and GBTM models used both TCD and EEG data, Hunt-Hess score at admission, and aneurysm treatment as predictors of DCI (logistic regression: sensitivity 90%, specificity 70%; GBTM: sensitivity 89%, specificity 67%).DiscussionEEG and TCD biomarkers combined provide the best prediction of DCI. The conjunction of clinical variables with the timing of EAs and high MCA velocities improved model performance. These results suggest that TCD and cEEG are promising complementary monitoring modalities for DCI prediction. Our model has potential to serve as a decision support tool in SAH management.Classification of EvidenceThis study provides Class II evidence that combined TCD and EEG monitoring can identify delayed cerebral ischemia after SAH.

ObjectiveTo determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy.MethodsWe performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH. We used validated diagnosis codes to identify a primary outcome of ED or inpatient revisit for epilepsy. We used multivariable Cox regression for survival analysis to identify demographic and medical risk factors for epilepsy.ResultsWe identified 29,342 survivors of SDH (mean age 71.2 [SD 16.4] years, female sex 11,954 [41.1%]). Three thousand two hundred thirty (11.0%) patients had revisits to EDs or hospitals with a diagnosis of epilepsy during the study period. Black patients (n = 1,684 [5.7%]) had significantly increased risk compared to White patients (n = 16,945 [57.7%]; hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.28–1.64, p < 0.001). Status epilepticus during the index SDH admission, although infrequent (n = 94 [0.3%]), was associated with a nearly 4-fold risk of epilepsy (HR 3.75, 95% CI 2.80–5.03, p < 0.001). Alcohol use, drug use, smoking, renal disease, and markers of injury severity (i.e., intubation, surgical intervention, length of stay, disposition other than home) were also associated with epilepsy (all p < 0.05).ConclusionsWe found an association between Black race and ED and hospital revisits for epilepsy after SDH, establishing the presence of a racial subgroup that is particularly vulnerable to post-SDH epileptogenesis.

Background and Purpose— We evaluated the association between 2 types of predictors of delayed cerebral ischemia after nontraumatic subarachnoid hemorrhage, including biomarkers of the innate immune response and neurophysiologic changes on continuous electroencephalography. Methods— We studied subarachnoid hemorrhage patients that had at least 72 hours of continuous electroencephalography and blood samples collected within the first 5 days of symptom onset. We measured inflammatory biomarkers previously associated with delayed cerebral ischemia and functional outcome, including soluble ST2 (sST2), IL-6 (interleukin-6), and CRP (C-reactive protein). Serial plasma samples and cerebrospinal fluid sST2 levels were available in a subgroup of patients. Neurophysiologic changes were categorized into new or worsening epileptiform abnormalities (EAs) or new background deterioration. The association of biomarkers with neurophysiologic changes were evaluated using the Wilcoxon rank-sum test. Plasma and cerebrospinal fluid sST2 were further examined longitudinally using repeated measures mixed-effects models. Results— Forty-six patients met inclusion criteria. Seventeen (37%) patients developed new or worsening EAs, 21 (46%) developed new background deterioration, and 8 (17%) developed neither. Early (day, 0–5) plasma sST2 levels were higher among patients with new or worsening EAs (median 115 ng/mL [interquartile range, 73.8–197]) versus those without (74.7 ng/mL [interquartile range, 44.8–102]; P =0.024). Plasma sST2 levels were similar between patients with or without new background deterioration. Repeated measures mixed-effects modeling that adjusted for admission risk factors showed that the association with new or worsening EAs remained independent for both plasma sST2 (β=0.41 [95% CI, 0.09–0.73]; P =0.01) and cerebrospinal fluid sST2 (β=0.97 [95% CI, 0.14–1.8]; P =0.021). IL-6 and CRP were not associated with new background deterioration or with new or worsening EAs. Conclusions— In patients admitted with subarachnoid hemorrhage, sST2 level was associated with new or worsening EAs but not new background deterioration. This association may identify a link between a specific innate immune response pathway and continuous electroencephalography abnormalities in the pathogenesis of secondary brain injury after subarachnoid hemorrhage.

Background: Protection from yellow dust and particulate matter is ensured by the use of respirators among the Korean citizens and workers. However, the manikins used to test the performance of the same were manufactured considering western facial specifications owing to which they do not represent Korean facial characteristics. Methods: Analysis of the data from the 6th 3D anthropometric survey of Koreans (Size Korea; 2010–2013) of 4,583 people aged 7 to 69 years was performed to obtain their facial dimensions. We subsequently clustered 44 facial measurements using Design X software, followed by the creation of the cluster centroid. Results: Three 3D head forms were developed—small, medium, and large, and their images were stored in “.stl” format for 3D printing. The facial widths and lengths of the three head forms were 127.1 mm × 90.6 mm, 143.2 mm × 104.0 mm, and 149.1 mm × 120.2 mm, respectively. Conclusion: We developed manikin head forms according to the facial dimensions of the Korean population, which was essential in evaluating respiratory protective equipment. These head forms can be used to test the performance of respirators considering the facial dimensions of the Korean population. Keywords: 3D anthropometry, Manikin head forms, Particulate matter, Respirator performance test, Yellow dust

BACKGROUND Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge. AIM To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes. METHODS Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), disease-free survival, and local recurrence-free survival (LRFS) were estimated using the Kaplan Meier method. We identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated. The effect of clinical and treatment parameters on disease outcomes was also evaluated. RESULTS We identified 2164 patients who met the eligibility criteria. The median follow-up for all patients was 3.73 [interquartile range (IQR) 2.27-6.07] years. Five-year OS was 97.7% (95%CI: 96.8%-98.6%) with 28 deaths; 5-year LRFS was 98.0% (97.2-98.8) with 31 IBTRs. We identified 37 patients with isolated IBTR, 19 (51.4%) as ductal carcinoma in situ and 18 (48.6%) as invasive disease, of whom 83.3% had an in situ component. Median time from initial diagnosis to IBTR was 1.97 (IQR: 1.03-3.5) years. Radiotherapy information was available for 30 of 37 patients. Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed. Twenty-five of thirty-two (78.1%) patients had concordant hormone receptor status, HER-2 receptor status, and estrogen receptor (ER) (P = 0.006) and progesterone receptor (PR) (P = 0.001) status from primary to IBTR were significantly associated. There were no observed changes in HER-2 status from primary to IBTR. The concordance between quadrant of primary to IBTR was 10/19 [(62.2%), P = 0.008]. Tumor size greater than 1.5 cm (HR = 0.44, 95%CI: 0.22-0.90, P = 0.02) and use of endocrine therapy upfront (HR = 0.36, 95%CI: 0.18-0.73, P = 0.004) decreased the risk of IBTR. CONCLUSION Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT, ER/PR status and quadrant were highly concordant from primary to IBTR. Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

Key Points Question Is posttraumatic epilepsy (PTE) associated with unfavorable functional outcomes after traumatic brain injury (TBI)? Findings In this cohort study that included 3296 individuals, the incidence of self-reported diagnosis of PTE at 1 year after injury among individuals who had experienced TBI was 2.8%. Patients with PTE had worse outcome scores at 1 year after injury compared with those without PTE, even after accounting for injury severity and neuroimaging findings on cranial computed tomography. Meaning These findings suggest that PTE is a significant sequela of TBI with adverse associations with recovery., This cohort study assesses the incidence, risk factors, and functional outcomes associated with self-reported posttraumatic epilepsy in patients with traumatic brain injury., Importance Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known. Objective To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort. Design, Setting, and Participants This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021. Exposure Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ). Main Outcomes and Measures Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI). Results Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P

Backgrounds As the prevalence of dementia rises, caregiver burden also increases in South Korea, especially for informal family caregivers. This study aimed to analyze factors affecting caregiver burden by the severity of dementia based on data of patients in Seoul. Methods A total of 12,292 individuals aged ≥65 years enrolled in the Seoul Dementia Management Project from 2010 to 2016 in an online database were selected. Caregiver’s burden was assessed using the Korea version of Zarit Burden Interview. Multiple regression analyses were performed to determine factors associated with primary caregiver’s burden after stratifying the severity of dementia. Results Most patients showed moderate levels of cognitive impairment (49.4%), behavior problems (82.6%), and ADL dependency (73.6%). After stratifying the severity of dementia, caregivers caring for patients with mild symptoms of dementia were experienced with higher caregiver burden if patients were under a lower score of IADL. Significant factors for caregiver burden among caregivers supporting patients with moderate symptoms of dementia include caregivers’ residence with patients, subjective health status, and co-work with secondary caregivers. Lastly, caregivers for patients with severe dementia symptoms experienced a higher caregiver burden from limited cognitive function, problematic behavior, and caregivers’ negative health status. Conclusion In terms of sample size, this study had far more patients than any other domestic or international study. It was meaningful in that it analyzed characteristics of patients with dementia and caregivers affecting the burden of caregivers in Korea. Intensive social supports with multiple coping strategies focusing on different levels of patients’ clinical symptoms and caregivers’ needs should be planned to relieve the caregiver burden.

Background: Asian Canadians and Asian Americans face COVID-19–related discrimination. The objective of this qualitative study was to explore the experiences of Asian health care workers dealing with discrimination, with a focus on racial micro-agressions, in Canada and the United States during the COVID-19 pandemic. Methods: We adopted a qualitative descriptive approach. We used convenience and snowball sampling strategies to recruit participants. We conducted individual, in-depth semistructured interviews with Asian health care workers in Canada and the US via videoconferencing between May and September 2020. Eligible participants had to self-identify as Asian and be currently employed as a health care worker with at least 1 year of full-time employment. We used an inductive thematic approach to analyze the data. Results: Thirty participants were recruited. Fifteen (50%) were Canadians and 15 (50%) were Americans; there were 18 women (60%), 11 men (37%) and 1 nonbinary person. Most of the participants were aged 25–29 years (n = 16, 53%). More than half were nurses (n = 16, 53%); the other participants were attending physicians (n = 5), physiotherapists (n = 3), resident physicians (n = 2), a midwife, a paramedic, a pharmacist and a physician assistant. Two themes emerged from the data: a surge of racial microaggressions related to COVID-19 and a lack of institutional and public acknowledgement. Participants noted that they have experienced an increase in racial microaggressions during the COVID-19 pandemic. They have also experienced threats of violence and actual violence. The largely silent organizational response to the challenges being faced by people of Asian descent and the use of disparaging terms such as “China virus” in the early stages of the pandemic were a substantial source of frustration. Interpretation: Asian health care workers have experienced challenges in dealing with racial microaggressions related to COVID-19 in the US and Canada. More research should be done on the experiences of Asian Americans and Asian Canadians, both during and after the pandemic, and supportive measures should be put in place to protect Asian health care workers.

Background Among prognostic imaging variables, the hematoma volume on admission computed tomography (CT) has long been considered the strongest predictor of outcome and mortality in intracerebral hemorrhage. Aims To examine whether different features of hematoma shape are associated with functional outcome in deep intracerebral hemorrhage. Methods We analyzed 790 patients from the ATACH-2 trial, and 14 shape features were quantified. We calculated Spearman’s Rho to assess the correlation between shape features and three-month modified Rankin scale (mRS) score, and the area under the receiver operating characteristic curve (AUC) to quantify the association between shape features and poor outcome defined as mRS>2 as well as mRS > 3. Results Among 14 shape features, the maximum intracerebral hemorrhage diameter in the coronal plane was the strongest predictor of functional outcome, with a maximum coronal diameter >∼3.5 cm indicating higher three-month mRS scores. The maximum coronal diameter versus hematoma volume yielded a Rho of 0.40 versus 0.35 ( p = 0.006), an AUC[mRS>2] of 0.71 versus 0.68 ( p = 0.004), and an AUC[mRS>3] of 0.71 versus 0.69 ( p = 0.029). In multiple regression analysis adjusted for known outcome predictors, the maximum coronal diameter was independently associated with three-month mRS (p Conclusions A coronal-plane maximum diameter measurement offers greater prognostic value in deep intracerebral hemorrhage than hematoma volume. This simple shape metric may expedite assessment of admission head CTs, offer a potential biomarker for hematoma size eligibility criteria in clinical trials, and may substitute volume in prognostic intracerebral hemorrhage scoring systems.

Background: Currently there remains controversy in the surgical management of rhegmatogenous retinal detachment (RRD) due to giant retinal tears (GRTs), a potentially blinding condition. To clarify which surgical technique is better depending on the origin and magnitude of the giant tear this study aimed to analyze the anatomical and functional outcomes. To analyze trans- and postoperative surgical complications, we used long-term final postoperative structural, optical coherence tomography (OCT) and correlated the results with the final postoperative best-corrected visual acuity (BCVA) in three different groups of eyes.Methods: Seventy-six consecutive eyes of 66 patients from three participant institutions were recruited and classified according to the degree of GRT-associated RRD extension as follows: group 1, 42 eyes with GRT-associated RRD extension < 180°; group 2, 23 eyes with GRT-associated RRD extension = 180°–270°; and group 3, 11 eyes with GRT-associated RRD extension > 270°. Structural and functional outcomes were compared across groups.Results: Of the 76 eyes analyzed, 63 were phakic, and 13 were pseudophakic. The mean age of the patients was 43.0 ±13.0 years (range, 19–76 years); 36 females, and 40 males. The mean preoperative time for GRT surgery was 1.8 weeks, the mean preoperative and postoperative BCVA was 1.87 logMAR and 0.35 logMAR, respectively (pConclusions: Multiple structural alterations in spectral-domain OCT biomarkers were observed. Eyes that developed secondary epiretinal membrane (ERM) proliferation showed significantly improved BCVA after proliferation, and the internal limiting membrane was removed. This study presents the severe consequences of macular structure and function. The structural findings correlated with the BCVA allow us to conclude severe consequences of the macular structure and that, despite a fully reattached retina without ERM proliferation, GRTs-associated RRD has a guarded functional prognosis.

Objectives The average annual healthcare expenditure among elderly patients in Korea is increasing rapidly in indirect healthcare sectors, requiring an understanding of factors related to the use of both formal and informal caregivers. This study analyzed the characteristics of caregiver use and caregiving costs among elderly patients hospitalized due to acute illness or exacerbation of chronic diseases. Methods A total of 819 study participants were selected from the 2017 Korea Health Panel Study Data. Replacement costing methods were applied to estimate the hours of informal caregiver assistance received by elderly inpatients. Elderly inpatients’ predisposing, enabling, and need factors were studied to identify the relationship between caregiver uses, based on Andersen’s behavior model. A two-part model was applied to analyze the factors related to care receipt and to estimate the incremental costs of care. Results Elderly inpatients who used tertiary hospitals (OR: 2.77, p-value p-value p-value p-value = 0.02) or financial aid (β: 0.64, p-value Conclusions This study presented significant socioenvironmental characteristics of formal and informal caregiver use and the related expenditures. Healthcare management plans that encompass multiple social levels should be implemented to ease the caregiver burden. Trial registration Retrospectively registered.

ImportanceClinical text reports from head computed tomography (CT) represent rich, incompletely utilized information regarding acute brain injuries and neurologic outcomes. CT reports are unstructured; thus, extracting information at scale requires automated natural language processing (NLP). However, designing new NLP algorithms for each individual injury category is an unwieldy proposition. An NLP tool that summarizes all injuries in head CT reports would facilitate exploration of large data sets for clinical significance of neuroradiological findings.ObjectiveTo automatically extract acute brain pathological data and their features from head CT reports.Design, Setting, and ParticipantsThis diagnostic study developed a 2-part named entity recognition (NER) NLP model to extract and summarize data on acute brain injuries from head CT reports. The model, termed BrainNERD, extracts and summarizes detailed brain injury information for research applications. Model development included building and comparing 2 NER models using a custom dictionary of terms, including lesion type, location, size, and age, then designing a rule-based decoder using NER outputs to evaluate for the presence or absence of injury subtypes. BrainNERD was evaluated against independent test data sets of manually classified reports, including 2 external validation sets. The model was trained on head CT reports from 1152 patients generated by neuroradiologists at the Yale Acute Brain Injury Biorepository. External validation was conducted using reports from 2 outside institutions. Analyses were conducted from May 2020 to December 2021.Main Outcomes and MeasuresPerformance of the BrainNERD model was evaluated using precision, recall, and F1 scores based on manually labeled independent test data sets.ResultsA total of 1152 patients (mean [SD] age, 67.6 [16.1] years; 586 [52%] men), were included in the training set. NER training using transformer architecture and bidirectional encoder representations from transformers was significantly faster than spaCy. For all metrics, the 10-fold cross-validation performance was 93% to 99%. The final test performance metrics for the NER test data set were 98.82% (95% CI, 98.37%-98.93%) for precision, 98.81% (95% CI, 98.46%-99.06%) for recall, and 98.81% (95% CI, 98.40%-98.94%) for the F score. The expert review comparison metrics were 99.06% (95% CI, 97.89%-99.13%) for precision, 98.10% (95% CI, 97.93%-98.77%) for recall, and 98.57% (95% CI, 97.78%-99.10%) for the F score. The decoder test set metrics were 96.06% (95% CI, 95.01%-97.16%) for precision, 96.42% (95% CI, 94.50%-97.87%) for recall, and 96.18% (95% CI, 95.151%-97.16%) for the F score. Performance in external institution report validation including 1053 head CR reports was greater than 96%.Conclusions and RelevanceThese findings suggest that the BrainNERD model accurately extracted acute brain injury terms and their properties from head CT text reports. This freely available new tool could advance clinical research by integrating information in easily gathered head CT reports to expand knowledge of acute brain injury radiographic phenotypes.

ObjectiveProgestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.MethodsA systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.ResultsIn total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).ConclusionFor reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.PROSPERO registration numberCRD42020179069.disease remission