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RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.
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In patients with post-myocardial infarction ventricular septal defects, temporary left ventricular support using Impella 5.5 can decrease shunting, facilitate peri-infarct tissue remodeling, and allow for assessment of myocardial recovery prior to repair. When there is inadequate cardiac recovery, implantation of a durable left ventricular assist device such as HeartMate 3 at time of repair can be safely performed. A right ventriculotomy provides multiple advantages when performing VSD repair and concomitant HeartMate 3 placement.
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BACKGROUND: Dental Patient Reported Outcomes (PROs) relate to a dental patient's subjective experience of their oral health. How practitioners and patients value PROs influences their successful use in practice. METHODS: Semi-structured interviews were conducted with 22 practitioners and 32 patients who provided feedback on using a mobile health (mHealth) platform to collect the pain experience after dental procedures. A themes analysis was conducted to identify implementation barriers and facilitators. RESULTS: Five themes were uncovered: (1) Sense of Better Care. (2) Tailored Follow-up based on the dental procedure and patient's pain experience. (3) Effective Messaging and Alerts. (4) Usable Digital Platform. (5) Routine mHealth Integration. CONCLUSION: Frequent automated and preferably tailored follow-up messages using an mHealth platform provided a positive care experience for patients, while providers felt it saved them time and effort. Patients thought that the mHealth questionnaires were well-developed and of appropriate length. The mHealth platform itself was perceived as user-friendly by users, and most would like to continue using it. PRACTICAL IMPLICATIONS: Patients are prepared to use mobile phones to report their pain experience after dental procedures. Practitioners will be able to close the post-operative communication gap with their patients, with little interruption of their workflow.
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Teléfono Celular , Humanos , Dolor , Odontólogos , Medición de Resultados Informados por el Paciente , OdontologíaRESUMEN
The family Hadakaviridae, including the genus Hadakavirus, accommodates capsidless viruses with a 10- or 11-segmented positive-sense (+) RNA genome. Currently known hosts are ascomycetous filamentous fungi. Although phylogenetically related to polymycovirids with a segmented double-stranded RNA genome and certain encapsidated picorna-like viruses, hadakavirids are distinct in their lack of a capsid ('hadaka' means naked in Japanese) and their consequent inability to be pelleted by conventional ultracentrifugation; they show ribonuclease susceptibility in host tissue homogenates. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hadakaviridae, which is available at ictv.global/report/hadakaviridae.
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Ascomicetos , Virus ARN , Virus , Virus ARN/genética , Genoma Viral , Virus/genética , Proteínas de la Cápside/genética , Replicación Viral , Virión/genéticaRESUMEN
Background Approximately half of adults with chronic obstructive pulmonary disease (COPD) remain undiagnosed. Chest CT scans are frequently acquired in clinical practice and present an opportunity to detect COPD. Purpose To assess the performance of radiomics features in COPD diagnosis using standard-dose and low-dose CT models. Materials and Methods This secondary analysis included participants enrolled in the Genetic Epidemiology of COPD, or COPDGene, study at baseline (visit 1) and 10 years after baseline (visit 3). COPD was defined by a forced expiratory volume in the 1st second of expiration to forced vital capacity ratio less than 0.70 at spirometry. The performance of demographics, CT emphysema percentage, radiomics features, and a combined feature set derived from inspiratory CT alone was evaluated. CatBoost (Yandex), a gradient boosting algorithm, was used to perform two classification experiments to detect COPD; the two models were trained and tested on standard-dose CT data from visit 1 (model I) and low-dose CT data from visit 3 (model II). Classification performance of the models was evaluated using area under the receiver operating characteristic curve (AUC) and precision-recall curve analysis. Results A total of 8878 participants (mean age, 57 years ± 9 [SD]; 4180 female, 4698 male) were evaluated. Radiomics features in model I achieved an AUC of 0.90 (95% CI: 0.88, 0.91) in the standard-dose CT test cohort versus demographics (AUC, 0.73; 95% CI: 0.71, 0.76; P < .001), emphysema percentage (AUC, 0.82; 95% CI 0.80, 0.84; P < .001), and combined features (AUC, 0.90; 95% CI: 0.89, 0.92; P = .16). Model II, trained on low-dose CT scans, achieved an AUC of 0.87 (95% CI: 0.83, 0.91) on the 20% held-out test set for radiomics features compared with demographics (AUC, 0.70; 95% CI: 0.64, 0.75; P = .001), emphysema percentage (AUC, 0.74; 95% CI: 0.69, 0.79; P = .002), and combined features (AUC, 0.88; 95% CI: 0.85, 0.92; P = .32). Density and texture features were the majority of the top 10 features in the standard-dose model, whereas shape features of lungs and airways were significant contributors in the low-dose CT model. Conclusion A combination of features representing parenchymal texture and lung and airway shape on inspiratory CT scans can be used to accurately detect COPD. ClinicalTrials.gov registration no. NCT00608764 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Vliegenthart in this issue.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Adulto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Pulmón/diagnóstico por imagenRESUMEN
INTRODUCTION: In 2018, the United Network for Organ Sharing (UNOS) implemented a new heart allocation system which prioritized patients on temporary support devices and left-ventricular assist device (LVAD) patients with complications. These changes have the potential to impact outcomes for patients bridged to transplant with an LVAD. METHODS: We performed a retrospective study of 168 adult heart transplant recipients at our center between 2016 and 2020 evaluating post-transplant outcomes before and after UNOS allocation changes. Donor and recipient data were retrieved from chart review and national databases. The primary outcome of this study was severe primary graft dysfunction (PGD) with secondary outcomes of 30-day readmission, 30-day mortality, and 1-year mortality. RESULTS: Incidence of severe PGD was similar in the overall cohort before and after the changes (10% vs. 15%, respectively, p = .3) and increased in the LVAD-bridged cohort (12% vs. 40%, respectively, p < .01). Secondary outcomes of readmission and survival were similar between all groups. Blood transfusion was predictive of severe PGD in multivariable modeling (OR 1.3 [1.11-1.59], p < .01).
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Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Disfunción Primaria del Injerto , Adulto , Humanos , Trasplante de Corazón/efectos adversos , Estudios Retrospectivos , Corazón Auxiliar/efectos adversos , Disfunción Primaria del Injerto/epidemiología , Disfunción Primaria del Injerto/etiología , Resultado del TratamientoRESUMEN
Throughout the opto-electronic devices industry, organic materials with considerable nonlinear optical (NLO) capabilities are being used. By employing 4,6-di(thiophen-2-yl)pyrimidine as a standard molecule, a series for new dyes (DMBMB1-DMBMB6) are created in the present paper by altering their functionalization with various electron acceptor (A) functional groups. The density functional fheory (DFT) and time dependent DFT (TD-DFT) based calculations have been performed to explore NLO responses by adjustment of different A units. The energy gap (Egap) of their highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) was ranged between 0.22-2.43 eV which was also used to calculate their global chemical parameters (GRPs). All the new dyes were subjected to UV-Vis studies revealing their frequencies being red shifted from starting dye (DMBMB). The theoretical investigations like frontier molecular orbital (FMO) and natural bond orbital (NBO) analysis was used to investigate their intramolecular charge transfer (ICT). The dye DMBMB6 had the greatest linear polarizability, first hyperpolarizability (αtotal), and second order hyperpolarizability (ßtotal) for all the developed dyes. In conclusion, due of their low ICT, all the dyes showed potential NLO features. Scientific researchers would be able to harness these NLO features to discover NLO materials for current and future uses.
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OBJECTIVES: Most pediatric patients on ventricular assist device (VAD) survive to transplantation. Approximately 15% will die on VAD support, and the circumstances at the end-of-life are not well understood. We, therefore, sought to characterize patient location and invasive interventions used at the time of death. DESIGN: Retrospective database study of a cohort meeting inclusion criteria. SETTING: Thirty-six centers participating in the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Registry. PATIENTS: Children who died on VAD therapy in the period March 2012 to September 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 117 of 721 patients (16%) who died on VAD, the median (interquartile range) age was 5 years (1-16 yr) at 43 days (17-91 d) postimplant. Initial goals of therapy were bridge to consideration for candidacy for transplantation in 60 of 117 (51%), bridge to transplantation in 44 of 117 (38%), bridge to recovery 11 of 117 (9%), or destination therapy (i.e., VAD as the endpoint) in two of 117 (2%). The most common cause of death was multiple organ failure in 35 of 117 (30%), followed by infection in 12 of 117 (10%). Eighty-five of 92 (92%) died with a functioning device in place. Most patients were receiving invasive interventions (mechanical ventilation, vasoactive infusions, etc.) at the end of life. Twelve patients (10%) died at home. CONCLUSIONS: One-in-six pediatric VAD patients die while receiving device support, with death occurring soon after implant and usually from noncardiac causes. Aggressive interventions are common at the end-of-life. The ACTION Registry data should inform future practices to promote informed patient/family and clinician decision-making to hopefully reduce suffering at the end-of-life.
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Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Humanos , Niño , Preescolar , Estudios de Cohortes , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/etiología , Estudios Retrospectivos , Corazón Auxiliar/efectos adversos , Muerte , Resultado del TratamientoRESUMEN
Despite technological advances, challenges exist in US dental care, including variations in quality of care, access and untreated dental needs. The implementation of learning health systems (LHSs) in dentistry can help to address these challenges. LHSs use robust informatics infrastructure including data and technology to continuously measure and improve the quality and safety of care and can help to reduce costs and improve patient outcomes. The use of EHRs and standardized diagnostic terminologies are highlighted, as they allow for the storage and sharing of patient data, providing a comprehensive view of a patient's medical and dental history, and can be used to identify patterns and trends to improve the delivery of care. The BigMouth Dental Data Repository is an example of an informatic platform that aggregates patient data from multiple institutions and is being used to for scientific inquiry to improve oral health.
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Informática , Salud Bucal , Humanos , Atención OdontológicaRESUMEN
The Human papillomaviruses type 16 E7 oncoprotein is a 98-amino-acid, 11-kilodalton acidic oncoprotein with three conserved portions. Due to its interaction with the pRb-E2F complex, CKII, CKI (mostly p21), and even HDAC1, it possesses strong transformative and carcinogenic qualities that inhibit normal differentiation and cell cycle regulation. Here, we target the E7 oncoprotein using two prior research active compounds: asarinin and thiazolo[3,2-a]benzimidazole-3(2H)-one,2-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo), and valproic acid as a control. We are performing molecular docking followed by molecular dynamic analysis. By acting as competitive inhibitors in the binding site, it was hypothesized that both drugs would inhibit E7-mediated pRb degradation and E7-mediated p21 degradation, resulting in decreased cell cycle progression, immortalization, and proliferation. In addition, we expect that the direct inhibitory action of valproic acid in E7 will target the CKII-mediated phosphorylation pathway necessary for destabilizing p130 and pRb. According to the results of the dynamic simulation, stable interactions exist between every compound. Despite the instability of E7 protein, stability results indicate that both natural chemicals are preferable, with thiazolo outperforming valproic acid.
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Proteínas Oncogénicas Virales , Neoplasias del Cuello Uterino , Femenino , Humanos , Proteínas Oncogénicas Virales/química , Proteínas Oncogénicas Virales/metabolismo , Simulación del Acoplamiento Molecular , Virus del Papiloma Humano , Proteína de Retinoblastoma , Neoplasias del Cuello Uterino/tratamiento farmacológico , Ligandos , Ácido Valproico/farmacologíaRESUMEN
BACKGROUND: Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care. METHODS: This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as "too late" (death or declined for transplant due to being too sick) and/or "care escalation" (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. "Late referral" was defined as those referred too late and/or had care escalation. RESULTS: Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8-21.5, p=0.004). CONCLUSIONS: Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.
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BACKGROUND: Serological evaluation is essential for investigating the extent of COVID-19 in the studied population and evaluating the potential effectiveness of serum antibodies as a protective factor against future disease. OBJECTIVE: The study aimed to provide data on the seroprevalence and pattern of immune response to SARS-CoV-2 infection and the associated factors among outpatients and their caregivers. METHODS: A cross-sectional study involving 208 patients and caregivers who presented at the Family Medicine Clinic. A structured self-administered questionnaire was used to collect data on sociodemographic and COVID-19-related factors. The SARS-CoV-2 antibodies were assayed with the Realy Tech Rapid Test Device. Inferential statistical analyses were used to determine the associations between SARS-CoV-2 antibody outcomes and other variables. RESULTS: The ages of the participants ranged from 18 to 80 years, with a mean age of 38.87± 11.82 years and with female preponderance. The crude prevalence of anti-SARS-CoV-2 seropositivity was 20.7% (95% CI=1.14-1.28); of which 17.1% was for IgG, 2.9% for IgM, and 0.7% for both IgG and IgM. The overall corrected prevalence was 20.3%. The only identified predictor of anti-SARS-CoV-2 seropositivity in this study was the previous family history of COVID-19 infection (OR=36.548, CI=1.371-74.364, p=0.032). CONCLUSION: The identified predictor and other important outcomes will be useful in forming strategies for the prevention and management of COVID-19 infection.
CONTEXTE: L'évaluation sérologique est essentielle pour déterminer l'étendue du COVID-19 dans la population étudiée et évaluer l'efficacité potentielle des anticorps sériques en tant que facteur de protection contre une maladie future. OBJECTIF: L'étude visait à fournir des données sur la séroprévalence et le profil de la réponse immunitaire à l'infection par le SRAS-CoV-2 et les facteurs associés chez les patients ambulatoires et leurs soignants. MÉTHODES: Il s'agit d'une étude transversale portant sur 208 patients et soignants qui se sont présentés à la clinique de médecine familiale. Un questionnaire structuré auto-administré a été utilisé pour recueillir des données sur les facteurs sociodémographiques et liés au COVID-19. Les anticorps antiSRAS-CoV-2 ont été dosés à l'aide du dispositif de test rapide Realy Tech. Des analyses statistiques inférentielles ont été utilisées pour déterminer les associations entre les résultats des anticorps anti-SRAS-CoV-2 et d'autres variables. RÉSULTATS: Les participants étaient âgés de 18 à 80 ans, avec un âge moyen de 38,87± 11,82 ans et une prépondérance féminine. La prévalence brute de la séropositivité anti-SARSCoV-2 était de 20,7 % (IC à 95 % = 1,14-1,28), dont 17,1 % pour les IgG, 2,9 % pour les IgM et 0,7 % pour les IgG et les IgM. La prévalence globale corrigée était de 20,3 %. Le seul facteur prédictif identifié de la séropositivité anti-SARS-CoV-2 dans cette étude était les antécédents familiaux d'infection par COVID-19 (OR=36,548, CI=1,371-74,364, p=0,032). CONCLUSION: Le facteur prédictif identifié et d'autres résultats importants seront utiles pour élaborer des stratégies de prévention et de prise en charge de l'infection par COVID-19. Mots-clés: Profil sérologique, SRAS-CoV-2, patients externes, soignants et nord du Nigeria.
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Consequences of warming and postwarming events on photosynthetic thermotolerance (PT ) and photoprotective responses in tropical evergreen species remain elusive. We chose Citrus to answer some of the emerging questions related to tropical evergreen species' PT behaviour including (i) how wide is the genotypic variation in PT ? (ii) how does PT respond to short-term warming and (iii) how do photosynthesis and photoprotective functions respond over short-term warming and postwarming events? A study on 21 genotypes revealed significant genotypic differences in PT , though these were not large. We selected five genotypes with divergent PT and simulated warming events: Tmax 26/20°C (day-time highest maximum/night-time lowest maximum) (Week 1) < Tmax 33/30°C (Week 2) < Tmax 36/32°C (Week 3) followed by Tmax 26/16°C (Week 4, recovery). The PT of all genotypes remained unaltered despite strong leaf megathermy (leaf temperature > air temperature) during warming events. Though moderate warming showed genotype-specific stimulation in photosynthesis, higher warming unequivocally led to severe loss in net photosynthesis and induced higher nonphotochemical quenching. Even after a week of postwarming, photoprotective mechanisms strongly persisted. Our study points towards a conservative PT in evergreen citrus genotypes and their need for sustaining higher photoprotection during warming as well as postwarming recovery conditions.
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Citrus/fisiología , Termotolerancia/fisiología , Citrus/genética , Genotipo , Calor , Fotosíntesis/fisiología , Hojas de la Planta/fisiología , Clima TropicalRESUMEN
AIM: The goal was to use a deep convolutional neural network to measure the radiographic alveolar bone level to aid periodontal diagnosis. MATERIALS AND METHODS: A deep learning (DL) model was developed by integrating three segmentation networks (bone area, tooth, cemento-enamel junction) and image analysis to measure the radiographic bone level and assign radiographic bone loss (RBL) stages. The percentage of RBL was calculated to determine the stage of RBL for each tooth. A provisional periodontal diagnosis was assigned using the 2018 periodontitis classification. RBL percentage, staging, and presumptive diagnosis were compared with the measurements and diagnoses made by the independent examiners. RESULTS: The average Dice Similarity Coefficient (DSC) for segmentation was over 0.91. There was no significant difference in the RBL percentage measurements determined by DL and examiners ( p=.65 ). The area under the receiver operating characteristics curve of RBL stage assignment for stages I, II, and III was 0.89, 0.90, and 0.90, respectively. The accuracy of the case diagnosis was 0.85. CONCLUSIONS: The proposed DL model provides reliable RBL measurements and image-based periodontal diagnosis using periapical radiographic images. However, this model has to be further optimized and validated by a larger number of images to facilitate its application.
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Aprendizaje Profundo , Periodontitis , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Periodontitis/diagnósticoRESUMEN
Automatic differentiation represents a paradigm shift in scientific programming, where evaluating both functions and their derivatives is required for most applications. By removing the need to explicitly derive expressions for gradients, development times can be shortened and calculations can be simplified. For these reasons, automatic differentiation has fueled the rapid growth of a variety of sophisticated machine learning techniques over the past decade, but is now also increasingly showing its value to support ab initio simulations of quantum systems and enhance computational quantum chemistry. Here, we present an open-source differentiable quantum chemistry simulation code and explore applications facilitated by automatic differentiation: (1) calculating molecular perturbation properties, (2) reoptimizing a basis set for hydrocarbons, (3) checking the stability of self-consistent field wave functions, and (4) predicting molecular properties via alchemical perturbations.
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The HIV-1 Gag protein playing a key role in HIV-1 viral assembly has recently been shown to interact through its nucleocapsid domain with the ribosomal protein L7 (RPL7) that acts as a cellular co-factor promoting Gag's nucleic acid (NA) chaperone activity. To further understand how the two proteins act together, we examined their mechanism individually and in concert to promote the annealing between dTAR, the DNA version of the viral transactivation element and its complementary cTAR sequence, taken as model HIV-1 sequences. Gag alone or complexed with RPL7 was found to act as a NA chaperone that destabilizes cTAR stem-loop and promotes its annealing with dTAR through the stem ends via a two-step pathway. In contrast, RPL7 alone acts as a NA annealer that through its NA aggregating properties promotes cTAR/dTAR annealing via two parallel pathways. Remarkably, in contrast to the isolated proteins, their complex promoted efficiently the annealing of cTAR with highly stable dTAR mutants. This was confirmed by the RPL7-promoted boost of the physiologically relevant Gag-chaperoned annealing of (+)PBS RNA to the highly stable tRNALys3 primer, favoring the notion that Gag recruits RPL7 to overcome major roadblocks in viral assembly.
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Infecciones por VIH/genética , VIH-1/genética , Proteínas Ribosómicas/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Secuencia de Aminoácidos/genética , Infecciones por VIH/virología , VIH-1/patogenicidad , Interacciones Huésped-Patógeno/genética , Humanos , Chaperonas Moleculares/genética , Conformación de Ácido Nucleico , Ácidos Nucleicos/genética , ARN Viral/genética , Ensamble de Virus/genéticaRESUMEN
BACKGROUND: To identify whether the risk of intracerebral hemorrhage is higher in patients with coronavirus disease 2019 (COVID-19), we compared the risk factors, comorbidities, and outcomes in patients intracerebral hemorrhage and COVID-19 and those without COVID-19. METHODS: We analyzed the data from the Cerner deidentified COVID-19 data set derived from 62 health care facilities. The data set included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated with suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: There were a total of 154 (0.2%) and 667 (0.3%) patients with intracerebral hemorrhage among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of intracerebral hemorrhage in patients with COVID-19 (odds ratio 0.5; 95% confidence interval 0.5-0.6; p < .0001) after adjustment for sex, age strata, race/ethnicity, hypertension, diabetes mellitus, nicotine dependence/tobacco use, hyperlipidemia, atrial fibrillation, congestive heart failure, long-term anticoagulant use, and alcohol abuse. The proportions of patients who developed pneumonia (58.4% versus 22.5%; p < .0001), acute kidney injury (48.7% versus 31.0%; p < .0001), acute myocardial infarction (11% versus 6.4%; p = .048), sepsis (41.6% versus 22.5%; p < .0001), and respiratory failure (61.7% versus 42.3%; p < .0001) were significantly higher among patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19. The in-hospital mortality among patients with intracerebral hemorrhage and COVID-19 was significantly higher compared with that among those without COVID-19 (40.3% versus 19.0%; p < .0001). CONCLUSIONS: Our analysis does not suggest that rates of intracerebral hemorrhage are higher in patients with COVID-19. The higher mortality in patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19 is likely mediated by higher frequency of comorbidities and adverse in-hospital events.
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COVID-19 , Hemorragia Cerebral/epidemiología , Comorbilidad , Mortalidad Hospitalaria , Hospitalización , Humanos , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage (aSAH) is the incongruence in therapeutic benefit observed between phase II and subsequent phase III clinical trials. Therefore, identifying areas for improvement in the methodology and interpretation of results is necessary to increase the value of phase II trials. We performed a systematic review of phase II trials that continued into phase III trials, evaluating a therapeutic agent for the treatment of cerebral ischemia associated with aSAH. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for systematic reviews, and review was based on a peer-reviewed protocol (International Prospective Register of Systematic Reviews no. 222965). A total of nine phase III trials involving 7,088 patients were performed based on eight phase II trials involving 1558 patients. The following therapeutic agents were evaluated in the selected phase II and phase III trials: intravenous tirilazad, intravenous nicardipine, intravenous clazosentan, intravenous magnesium, oral statins, and intraventricular nimodipine. Shortcomings in several design elements of the phase II aSAH trials were identified that may explain the incongruence between phase II and phase III trial results. We suggest the consideration of the following strategies to improve phase II design: increased focus on the selection of surrogate markers of efficacy, selection of the optimal dose and timing of intervention, adjustment for exaggerated estimate of treatment effect in sample size calculations, use of prespecified go/no-go criteria using futility design, use of multicenter design, enrichment of the study population, use of concurrent control or placebo group, and use of innovative trial designs such as seamless phase II to III design. Modifying the design of phase II trials on the basis of lessons learned from previous phase II and phase III trial combinations is necessary to plan more effective phase III trials.
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Isquemia Encefálica , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Infarto Cerebral/complicaciones , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Humanos , Estudios Multicéntricos como Asunto , Nicardipino/uso terapéutico , Nimodipina/uso terapéutico , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Resultado del Tratamiento , Vasoespasmo Intracraneal/complicaciones , Vasoespasmo Intracraneal/etiologíaRESUMEN
We sought to characterize strokes in children with ventricular assist devices. Of 407 patients in the ACTION registry (4/1/18-5/3/2021), 45 (11%) experienced 52 strokes (45 ischemic and 7 hemorrhagic). Median time to stroke was 23.5 days and 19/52 (37%) occurred ≤ 10 days. Stroke rate was 0.09 and 0.63 strokes per patient-year for implantable continuous and paracorporeal devices, respectively. Patients with stroke were younger, more likely to have congenital heart disease and have been on extracorporeal membrane oxygenation at time of VAD. Based on these data, ACTION is now focused on decreasing strokes in these higher-risk patients with particular attention to the peri-implant period.
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Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca , Corazón Auxiliar , Accidente Cerebrovascular , Niño , Insuficiencia Cardíaca/etiología , Corazón Auxiliar/efectos adversos , Humanos , Sistema de Registros , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoRESUMEN
OBJECTIVES: Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus maybe candidates for acute revascularization treatments (intravenous thrombolysis and/or mechanical thrombectomy). MATERIALS AND METHODS: We analyzed the data from 62 healthcare facilities to determine the odds of receiving acute revascularization treatments in severe acute respiratory syndrome coronavirus infected patients and determined the odds of composite of death and non-routine discharge with severe acute respiratory syndrome coronavirus infected and non-infected patients undergoing acute revascularization treatments after adjusting for potential confounders. RESULTS: Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments (odds ratio 0.6, 95% confidence interval 0.5-0.8, p = 0.0001). Among ischemic stroke patients who received acute revascularization treatments, severe acute respiratory syndrome coronavirus infection was associated with increased odds of death or non-routine discharge (odds ratio 3.0, 95% confidence interval 1.8-5.1). The higher odds death or non-routine discharge (odds ratio 2.1, 95% confidence interval 1.9-2.3) with severe acute respiratory syndrome coronavirus infection were observed in all ischemic stroke patients without any modifying effect of acute revascularization treatments (interaction term for death (p = 0.9) or death or non-routine discharge (p = 0.2). CONCLUSIONS: Patients with acute ischemic stroke with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments. Severe acute respiratory syndrome coronavirus infection was associated with a significantly higher rate of death or non-routine discharge among acute ischemic stroke patients receiving revascularization treatments.