Assessment of Cadmium Tolerance and Oxidative Stress Response in Limulus Polyphemus

Cadmium and other heavy metals are pollutants known to have toxic effects on marine arthropods. However, tolerance to heavy metals has been observed in the American horseshoe crab Limulus polyphemus. We performed experiments to determine whether cadmium induces oxidative stress in horseshoe crabs and whether horseshoe crabs possess an increased oxidative stress response in the presence of cadmium. We performed a 24-hour cadmium exposure on late stage 19 and early stage 20-1 embryos from two different nests to establish the percentage of dead embryos at increasing concentrations. Through Probit analysis of the resulting dose response curve, the LC25 and LC37 doses of cadmium were calculated and used in subsequent experiments. Embryos were exposed to cadmium for 12 and 24 hours periods and then divided for subsequent DNA, RNA, lipid peroxidation, and superoxide dismutase analysis. Lipid peroxidation was assessed with a thiobarbituric acid reactive substances assay and oxidative defense mechanisms by a superoxide dismutase assay. Some of the differences in the levels of lipid peroxidation and superoxide dismutase in treated and untreated embryos may be significant. Further analysis on DNA and RNA will help better determine cadmium\u27s effects on horseshoe crabs and possible mechanisms of heavy metal tolerance

Assessment of Cadmium Tolerance and Oxidative Stress Response in Limulus polyphemus

Cadmium and other heavy metals are pollutants known to have toxic effects on marine arthropods. However, tolerance to heavy metals has been observed in the American horseshoe crab Limulus polyphemus. We performed experiments to determine whether cadmium induces oxidative stress in horseshoe crabs and whether horseshoe crabs possess an increased oxidative stress response in the presence of cadmium. We performed a 24-hour cadmium exposure on late stage 19 and early stage 20-1 embryos from two different nests to establish the percentage of dead embryos at increasing concentrations. Through Probit analysis of the resulting dose response curve, the LC25 and LC37 doses of cadmium were calculated and used in subsequent experiments. Embryos were exposed to cadmium for 12 and 24 hours periods and then divided for subsequent DNA, RNA, lipid peroxidation, and superoxide dismutase analysis. Lipid peroxidation was assessed with a thiobarbituric acid reactive substances assay and oxidative defense mechanisms by a superoxide dismutase assay. Some of the differences in the levels of lipid peroxidation and superoxide dismutase in treated and untreated embryos may be significant. Further analysis on DNA and RNA will help better determine cadmium’s effects on horseshoe crabs and possible mechanisms of heavy metal tolerance

Blood pressure medication and acute kidney injury after intracerebral haemorrhage: an analysis of the ATACH-II trial

Background Acute blood pressure (BP) reduction is standard of care after acute intracerebral haemorrhage (ICH). More acute BP reduction is associated with acute kidney injury (AKI). It is not known if the choice of antihypertensive medications affects the risk of AKI.Methods We analysed data from the ATACH-II clinical trial. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. We analysed antihypertensive medication from two sources. The first was a case report form that specified the use of labetalol, diltiazem, urapidil or other. We tested the hypothesis that the secondary medication was associated with AKI with χ2 test. Second, we tested the hypotheses the dosage of diltiazem was associated with AKI using Mann-Whitney U test.Results AKI occurred in 109 of 1000 patients (10.9%). A higher proportion of patients with AKI received diltiazem after nicardipine (12 (29%) vs 21 (12%), p=0.03). The 95%ile (90%–99% ile) of administered diltiazem was 18 (0–130) mg in patients with AKI vs 0 (0–30) mg in patients without AKI (p=0.002). There was no apparent confounding by indication for diltiazem use.Conclusions The use of diltiazem, and more diltiazem, was associated with AKI in patients with acute ICH

Blood Pressure Medication and Acute Kidney Injury After Intracerebral Haemorrhage: An Analysis of the ATACH-II Trial

Background Acute blood pressure (BP) reduction is standard of care after acute intracerebral haemorrhage (ICH). More acute BP reduction is associated with acute kidney injury (AKI). It is not known if the choice of antihypertensive medications affects the risk of AKI.Methods We analysed data from the ATACH-II clinical trial. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. We analysed antihypertensive medication from two sources. The first was a case report form that specified the use of labetalol, diltiazem, urapidil or other. We tested the hypothesis that the secondary medication was associated with AKI with χ2 test. Second, we tested the hypotheses the dosage of diltiazem was associated with AKI using Mann-Whitney U test.Results AKI occurred in 109 of 1000 patients (10.9%). A higher proportion of patients with AKI received diltiazem after nicardipine (12 (29%) vs 21 (12%), p=0.03). The 95%ile (90%–99% ile) of administered diltiazem was 18 (0–130) mg in patients with AKI vs 0 (0–30) mg in patients without AKI (p=0.002). There was no apparent confounding by indication for diltiazem use.Conclusions The use of diltiazem, and more diltiazem, was associated with AKI in patients with acute ICH

Hospitalizations Associated With Mental Health Conditions Among Adolescents in the US and France During the COVID-19 Pandemic

[EN] Importance The COVID-19 pandemic has been associated with an increase in mental health diagnoses among adolescents, though the extent of the increase, particularly for severe cases requiring hospitalization, has not been well characterized. Large-scale federated informatics approaches provide the ability to efficiently and securely query health care data sets to assess and monitor hospitalization patterns for mental health conditions among adolescents. Objective To estimate changes in the proportion of hospitalizations associated with mental health conditions among adolescents following onset of the COVID-19 pandemic. Design, Setting, and Participants This retrospective, multisite cohort study of adolescents 11 to 17 years of age who were hospitalized with at least 1 mental health condition diagnosis between February 1, 2019, and April 30, 2021, used patient-level data from electronic health records of 8 children¿s hospitals in the US and France. Main Outcomes and Measures Change in the monthly proportion of mental health condition¿associated hospitalizations between the prepandemic (February 1, 2019, to March 31, 2020) and pandemic (April 1, 2020, to April 30, 2021) periods using interrupted time series analysis. Results There were 9696 adolescents hospitalized with a mental health condition during the prepandemic period (5966 [61.5%] female) and 11¿101 during the pandemic period (7603 [68.5%] female). The mean (SD) age in the prepandemic cohort was 14.6 (1.9) years and in the pandemic cohort, 14.7 (1.8) years. The most prevalent diagnoses during the pandemic were anxiety (6066 [57.4%]), depression (5065 [48.0%]), and suicidality or self-injury (4673 [44.2%]). There was an increase in the proportions of monthly hospitalizations during the pandemic for anxiety (0.55%; 95% CI, 0.26%-0.84%), depression (0.50%; 95% CI, 0.19%-0.79%), and suicidality or self-injury (0.38%; 95% CI, 0.08%-0.68%). There was an estimated 0.60% increase (95% CI, 0.31%-0.89%) overall in the monthly proportion of mental health¿associated hospitalizations following onset of the pandemic compared with the prepandemic period. Conclusions and Relevance In this cohort study, onset of the COVID-19 pandemic was associated with increased hospitalizations with mental health diagnoses among adolescents. These findings support the need for greater resources within children¿s hospitals to care for adolescents with mental health conditions during the pandemic and beyond.Ms Hutch is supported by grant NLM 5T32LM012203-05 from the National Library of Medicine. Dr Aronow is supported by U24 HL148865 from the National Heart, Lung, and Blood Institute (NHLBI), NIH. Dr Cai is supported by R01 HL089778 from the NHLBI, NIH. Dr Hanauer is supported by UL1TR002240 from the National Center for Advancing Translational Sciences (NCATS), NIH. Dr Luo is supported by U01TR003528 from the NCATS, NIH, and 1R01LM013337 from the National Library of Medicine. Dr Sanchez-Pinto is supported by R01HD105939 from the National Institute of Child Health and Human Development, NIH. Dr South is supported by K23HL148394 and L40HL148910 from the NHLBI, NIH, and UL1TR001420 from the NCATS, NIH. Dr Visweswaran is supported by UL1TR001857 from the NCATS, NIH. Dr Xia is supported by R01NS098023 and R01NS124882 from the National Institute of Neurological Disorders and Stroke, NIH.Gutiérrez-Sacristán, A.; Serret-Larmande, A.; Hutch, MR.; Sáez Silvestre, C.; Aronow, BJ.; Bhatnagar, S.; Bonzel, C.... (2022). Hospitalizations Associated With Mental Health Conditions Among Adolescents in the US and France During the COVID-19 Pandemic. Jama Network Open. 5(12):1-12. https://doi.org/10.1001/jamanetworkopen.2022.4654811251

Machine learning and natural language processing methods to identify ischemic stroke, acuity and location from radiology reports.

Accurate, automated extraction of clinical stroke information from unstructured text has several important applications. ICD-9/10 codes can misclassify ischemic stroke events and do not distinguish acuity or location. Expeditious, accurate data extraction could provide considerable improvement in identifying stroke in large datasets, triaging critical clinical reports, and quality improvement efforts. In this study, we developed and report a comprehensive framework studying the performance of simple and complex stroke-specific Natural Language Processing (NLP) and Machine Learning (ML) methods to determine presence, location, and acuity of ischemic stroke from radiographic text. We collected 60,564 Computed Tomography and Magnetic Resonance Imaging Radiology reports from 17,864 patients from two large academic medical centers. We used standard techniques to featurize unstructured text and developed neurovascular specific word GloVe embeddings. We trained various binary classification algorithms to identify stroke presence, location, and acuity using 75% of 1,359 expert-labeled reports. We validated our methods internally on the remaining 25% of reports and externally on 500 radiology reports from an entirely separate academic institution. In our internal population, GloVe word embeddings paired with deep learning (Recurrent Neural Networks) had the best discrimination of all methods for our three tasks (AUCs of 0.96, 0.98, 0.93 respectively). Simpler NLP approaches (Bag of Words) performed best with interpretable algorithms (Logistic Regression) for identifying ischemic stroke (AUC of 0.95), MCA location (AUC 0.96), and acuity (AUC of 0.90). Similarly, GloVe and Recurrent Neural Networks (AUC 0.92, 0.89, 0.93) generalized better in our external test set than BOW and Logistic Regression for stroke presence, location and acuity, respectively (AUC 0.89, 0.86, 0.80). Our study demonstrates a comprehensive assessment of NLP techniques for unstructured radiographic text. Our findings are suggestive that NLP/ML methods can be used to discriminate stroke features from large data cohorts for both clinical and research-related investigations

Natural language processing of radiology reports to detect complications of ischemic stroke

Background Abstraction of critical data from unstructured radiologic reports using natural language processing (NLP) is a powerful tool to automate the detection of important clinical features and enhance research efforts. We present a set of NLP approaches to identify critical findings in patients with acute ischemic stroke from radiology reports of computed tomography (CT) and magnetic resonance imaging (MRI). Methods We trained machine learning classifiers to identify categorical outcomes of edema, midline shift (MLS), hemorrhagic transformation, and parenchymal hematoma, as well as rule-based systems (RBS) to identify intraventricular hemorrhage (IVH) and continuous MLS measurements within CT/MRI reports. Using a derivation cohort of 2289 reports from 550 individuals with acute middle cerebral artery territory ischemic strokes, we externally validated our models on reports from a separate institution as well as from patients with ischemic strokes in any vascular territory. Results In all data sets, a deep neural network with pretrained biomedical word embeddings (BioClinicalBERT) achieved the highest discrimination performance for binary prediction of edema (area under precision recall curve [AUPRC] > 0.94), MLS (AUPRC > 0.98), hemorrhagic conversion (AUPRC > 0.89), and parenchymal hematoma (AUPRC > 0.76). BioClinicalBERT outperformed lasso regression (p  Conclusions Our study demonstrates robust performance and external validity of a core NLP tool kit for identifying both categorical and continuous outcomes of ischemic stroke from unstructured radiographic text data. Medically tailored NLP methods have multiple important big data applications, including scalable electronic phenotyping, augmentation of clinical risk prediction models, and facilitation of automatic alert systems in the hospital setting

Distinguishing Admissions Specifically for COVID-19 From Incidental SARS-CoV-2 Admissions: National Retrospective Electronic Health Record Study

BackgroundAdmissions are generally classified as COVID-19 hospitalizations if the patient has a positive SARS-CoV-2 polymerase chain reaction (PCR) test. However, because 35% of SARS-CoV-2 infections are asymptomatic, patients admitted for unrelated indications with an incidentally positive test could be misclassified as a COVID-19 hospitalization. Electronic health record (EHR)–based studies have been unable to distinguish between a hospitalization specifically for COVID-19 versus an incidental SARS-CoV-2 hospitalization. Although the need to improve classification of COVID-19 versus incidental SARS-CoV-2 is well understood, the magnitude of the problems has only been characterized in small, single-center studies. Furthermore, there have been no peer-reviewed studies evaluating methods for improving classification. ObjectiveThe aims of this study are to, first, quantify the frequency of incidental hospitalizations over the first 15 months of the pandemic in multiple hospital systems in the United States and, second, to apply electronic phenotyping techniques to automatically improve COVID-19 hospitalization classification. MethodsFrom a retrospective EHR-based cohort in 4 US health care systems in Massachusetts, Pennsylvania, and Illinois, a random sample of 1123 SARS-CoV-2 PCR-positive patients hospitalized from March 2020 to August 2021 was manually chart-reviewed and classified as “admitted with COVID-19” (incidental) versus specifically admitted for COVID-19 (“for COVID-19”). EHR-based phenotyping was used to find feature sets to filter out incidental admissions. ResultsEHR-based phenotyped feature sets filtered out incidental admissions, which occurred in an average of 26% of hospitalizations (although this varied widely over time, from 0% to 75%). The top site-specific feature sets had 79%-99% specificity with 62%-75% sensitivity, while the best-performing across-site feature sets had 71%-94% specificity with 69%-81% sensitivity. ConclusionsA large proportion of SARS-CoV-2 PCR-positive admissions were incidental. Straightforward EHR-based phenotypes differentiated admissions, which is important to assure accurate public health reporting and research

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium.

PurposeIn young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.MethodsA retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.ResultsAmong the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).ConclusionTrough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor

J Am Med Inform Assoc

INTRODUCTION: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing COVID-19 with federated analyses of electronic health record (EHR) data. OBJECTIVE: We sought to develop and validate a computable phenotype for COVID-19 severity. METHODS: Twelve 4CE sites participated. First we developed an EHR-based severity phenotype consisting of six code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of ICU admission and/or death. We also piloted an alternative machine-learning approach and compared selected predictors of severity to the 4CE phenotype at one site. RESULTS: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability - up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean AUC 0.903 (95% CI: 0.886, 0.921), compared to AUC 0.956 (95% CI: 0.952, 0.959) for the machine-learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared to chart review. DISCUSSION: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine-learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly due to heterogeneous pandemic conditions. CONCLUSION: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites