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1.
J Med Virol ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666246

RESUMO

Here we analyze hospitalized and ICU COVID-19 patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1,012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1,939 = 14%), presenting a risk ratio of 2.79 (95% C.I.: [2.42, 3.16]; p-value: 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin vs. 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% C.I.: [1.42, 2.00]; p-value: 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1,294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2,644 [25%]), risk ratio 1.26 (95%CI [1.14, 1.40], p-value: 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1,047 [30%] for Black/African American vs. 263 of 1,047 [25%] for White/Caucasian, p-value: 0.02, risk ratio 1.18, 95%CI [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients. This article is protected by copyright. All rights reserved.

2.
Crit Care Med ; 49(3): 437-448, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33555777

RESUMO

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.


Assuntos
/terapia , Resultados de Cuidados Críticos , Mortalidade Hospitalar , Hospitalização , Alta do Paciente/estatística & dados numéricos , Sistema de Registros , Adulto , Idoso , Oxigenação por Membrana Extracorpórea , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal , Respiração Artificial , Vasoconstritores
3.
Inflamm Bowel Dis ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534892

RESUMO

BACKGROUND: Colectomy is the curative management for ulcerative colitis (UC). Multiple studies have reported racial disparities for colectomy before the advent of anti-TNF alpha agents. The aim of this study was to describe racial and geographic differences in colectomy rates among hospitalized patients with UC after anti-TNF therapy was introduced. METHODS: We examined all patients discharged from the hospital between 2010 and 2014 with a primary diagnosis of UC or of complications of UC. The data were evaluated for race and colectomy rates among the hospitalized patients with UC. RESULTS: The unadjusted national colectomy rate among hospitalized patients with UC between 2010 and 2014 was 3.90 per 1000 hospitalization days (95% confidence interval, 3.72-4.08). The undajusted colectomy rates in African American (2.33 vs 4.35; P < 0.001) and Hispanic patients (3.99 vs 4.35; P ≤ 0.009) were considerably lower than those for White patients. After adjustment for confounders, the incidence rate ratio for African American as compared to White patients was 0.43 (95% confidence interval, 0.32-0.58; P < 0.001). Geographic region of the United States also showed significant variation in colectomy rates, with western regions having the highest rate (4.76 vs 3.20; P < 0.001). CONCLUSIONS: Racial and geographical disparities persist for the rate of colectomy among hospitalized patients with UC. The national database analysis reveals that colectomy rates for hospitalized African American and Hispanic patients were lower than those for White patients. Further studies are important to determine the social and biologic foundations of these disparities.

4.
Infect Control Hosp Epidemiol ; : 1-3, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33172516

RESUMO

Antimicrobial resistance is a major problem in India with limited understanding of whether this issue is related to systems, prescriber characteristics, patient characteristics, or diagnostic technologies. In our survey, most of the issues lie in the easy availability of antimicrobials and the lack of electronic storage of medical and microbiological records.

5.
J Intensive Care Med ; : 885066620962445, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000661

RESUMO

BACKGROUND: Little is known about hypoxemia surrounding endotracheal intubation in the critically ill. Thus, we sought to identify risk factors associated with peri-intubation hypoxemia and its effects' on the critically ill. METHODS: Data from a multicenter, prospective, cohort study enrolling 1,033 critically ill adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 were used to identify risk factors associated with peri-intubation hypoxemia and its effects on patient outcomes. We defined hypoxemia as any pulse oximetry ≤ 88% during and up to 30 minutes following endotracheal intubation. RESULTS: In the full analysis (n = 1,033), 123 (11.9%) patients experienced the primary outcome. Five risk factors independently associated with our outcome were identified on multiple logistic regression: cardiac related reason for endotracheal intubation (OR 1.67, [95% CI 1.04, 2.69]); pre-intubation noninvasive ventilation (OR 1.66, [95% CI 1.09, 2.54]); emergency intubation (OR 1.65, [95% CI 1.06, 2.55]); moderate-severe difficult bag-mask ventilation (OR 2.68, [95% CI 1.72, 4.19]); and crystalloid administration within the preceding 24 hours (OR 1.24, [95% CI 1.07, 1.45]; per liter up to 4 liters). Higher baseline SpO2 was found to be protective (OR 0.93, [95% CI 0.91, 0.96]; per percent up to 97%). Consistent results were seen in a separate analysis on only stable patients (n = 921, 93 [10.1%]) (those without baseline hypoxemia ≤ 88%). Peri-intubation hypoxemia was associated with in-hospital mortality (OR 2.40, [95% CI 1.33, 4.31]; stable patients: OR 2.67, [95% CI 1.38, 5.17]) but not ICU length of stay (point estimate 0.9 days, [95% CI -1.0, 2.8 days]; stable patients: point estimate 1.5 days, [95% CI -0.4, 3.4 days]) after adjusting for age, body mass index, illness severity, airway related reason for intubation (i.e., acute respiratory failure), and baseline SPO2. CONCLUSIONS: Patients with pre-existing noninvasive ventilation and volume loading who were intubated emergently in the setting of hemodynamic compromise with bag-mask ventilation described as moderate-severe were at increased risk for peri-intubation hypoxemia. Higher baseline oxygenation was found to be protective against peri-intubation hypoxemia. Peri-intubation hypoxemia was associated with in-hospital mortality but not ICU length of stay. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

6.
Nucleic Acids Res ; 48(19): e114, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33035301

RESUMO

The ability to characterize repetitive regions of the human genome is limited by the read lengths of short-read sequencing technologies. Although long-read sequencing technologies such as Pacific Biosciences (PacBio) and Oxford Nanopore Technologies can potentially overcome this limitation, long segmental duplications with high sequence identity pose challenges for long-read mapping. We describe a probabilistic method, DuploMap, designed to improve the accuracy of long-read mapping in segmental duplications. It analyzes reads mapped to segmental duplications using existing long-read aligners and leverages paralogous sequence variants (PSVs)-sequence differences between paralogous sequences-to distinguish between multiple alignment locations. On simulated datasets, DuploMap increased the percentage of correctly mapped reads with high confidence for multiple long-read aligners including Minimap2 (74.3-90.6%) and BLASR (82.9-90.7%) while maintaining high precision. Across multiple whole-genome long-read datasets, DuploMap aligned an additional 8-21% of the reads in segmental duplications with high confidence relative to Minimap2. Using DuploMap-aligned PacBio circular consensus sequencing reads, an additional 8.9 Mb of DNA sequence was mappable, variant calling achieved a higher F1 score and 14 713 additional variants supported by linked-read data were identified. Finally, we demonstrate that a significant fraction of PSVs in segmental duplications overlaps with variants and adversely impacts short-read variant calling.


Assuntos
Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Duplicações Segmentares Genômicas , Análise de Sequência de DNA/métodos , Software , Algoritmos , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Humanos
7.
PLoS One ; 15(8): e0233852, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866219

RESUMO

OBJECTIVE: Hypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation. METHODS: A multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure <65 mmHg; 2) systolic blood pressure <80 mmHg and/or decrease in systolic blood pressure of 40% from baseline; 3) or the initiation or increase in any vasopressor in the 30 minutes following endotracheal intubation. RESULTS: Post-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotension: increasing illness severity; increasing age; sepsis diagnosis; endotracheal intubation in the setting of cardiac arrest, mean arterial pressure <65 mmHg, and acute respiratory failure; diuretic use 24 hours preceding endotracheal intubation; decreasing systolic blood pressure from 130 mmHg; catecholamine and phenylephrine use immediately prior to endotracheal intubation; and use of etomidate during endotracheal intubation. A model excluding unstable patients' pre-intubation (those receiving catecholamine vasopressors and/or who were intubated in the setting of cardiac arrest) was also developed and included the above variables with the exception of sepsis and etomidate. In the full cohort, the 11 variable model had a C-statistic of 0.75 (95% CI 0.72, 0.78). In the stable cohort, the 7 variable model C-statistic was 0.71 (95% CI 0.67, 0.75). In both cohorts, a clinical risk score was developed stratifying patients' risk of hypotension. CONCLUSIONS: A novel multivariable risk score predicted post-intubation hypotension with accuracy in both unstable and stable critically ill patients. STUDY REGISTRATION: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.


Assuntos
Hipotensão/etiologia , Intubação Intratraqueal/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos
8.
Nat Commun ; 11(1): 4794, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963235

RESUMO

Most human genomes are characterized by aligning individual reads to the reference genome, but accurate long reads and linked reads now enable us to construct accurate, phased de novo assemblies. We focus on a medically important, highly variable, 5 million base-pair (bp) region where diploid assembly is particularly useful - the Major Histocompatibility Complex (MHC). Here, we develop a human genome benchmark derived from a diploid assembly for the openly-consented Genome in a Bottle sample HG002. We assemble a single contig for each haplotype, align them to the reference, call phased small and structural variants, and define a small variant benchmark for the MHC, covering 94% of the MHC and 22368 variants smaller than 50 bp, 49% more variants than a mapping-based benchmark. This benchmark reliably identifies errors in mapping-based callsets, and enables performance assessment in regions with much denser, complex variation than regions covered by previous benchmarks.


Assuntos
Diploide , Complexo Principal de Histocompatibilidade/genética , Benchmarking , Linhagem Celular , Variação Genética , Genoma Humano , Haplótipos , Humanos
9.
Crit Care Med ; 48(11): e1038-e1044, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32932348

RESUMO

OBJECTIVES: Use of observational data to inform the response and care of patients during a pandemic faces unique challenges. DESIGN: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID 2019 Registry Core data and research methodology team convened over virtual meetings throughout March to June 2020 to determine best practice goals for development of a pandemic disease registry to support rapid data collection and analysis. SETTING: International, multi-center registry of hospitalized patients. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Large-scale observational data collection requires: 1) quality assurance and harmonization across many sites; 2) a transparent process for selecting from among many potential research questions; 3) the use of best practices in design of descriptive, predictive, and inferential studies; (4) innovative approaches to characterize random error in the setting of constantly updated data; (5) rapid peer-review and reporting; and (6) transitions from a focus on discovery to implementation. Herein, we describe the guiding principles to best practices and suggestions for innovations to study design and reporting within the coronavirus disease 2019 Viral Infection and Respiratory Illness Universal Study pandemic registry. CONCLUSIONS: Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry sought to develop and implement prespecified best practices combined with grassroots efforts from clinical sites worldwide in order to develop clinically useful knowledge in response to a pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Cuidados Críticos/normas , Pneumonia Viral/terapia , Sistema de Registros , Coleta de Dados , Humanos , Estudos Multicêntricos como Assunto , Pandemias , Vigilância em Saúde Pública , Projetos de Pesquisa
10.
Cell Rep ; 32(12): 108175, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32946807

RESUMO

To predict the tropism of human coronaviruses, we profile 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell transcriptomics across various healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Intestinal goblet cells, enterocytes, and kidney proximal tubule cells appear highly permissive to SARS-CoV-2, consistent with clinical data. Our analysis also predicts non-canonical entry paths for lung and brain infections. Spermatogonial cells and prostate endocrine cells also appear to be permissive to SARS-CoV-2 infection, suggesting male-specific vulnerabilities. Both pro- and anti-viral factors are highly expressed within the nasal epithelium, with potential age-dependent variation, predicting an important battleground for coronavirus infection. Our analysis also suggests that early embryonic and placental development are at moderate risk of infection. Lastly, SCARF expression appears broadly conserved across a subset of primate organs examined. Our study establishes a resource for investigations of coronavirus biology and pathology.


Assuntos
Infecções por Coronavirus/patologia , Mucosa Nasal/metabolismo , Pneumonia Viral/patologia , Receptores Virais/genética , Tropismo Viral/genética , Internalização do Vírus , Células A549 , Animais , Betacoronavirus/crescimento & desenvolvimento , Linhagem Celular , Chlorocebus aethiops , Enterócitos/metabolismo , Perfilação da Expressão Gênica , Células Caliciformes/metabolismo , Células HEK293 , Humanos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Mucosa Nasal/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Análise de Célula Única , Células Vero
11.
Artigo em Inglês | MEDLINE | ID: mdl-32943463

RESUMO

OBJECTIVE: The utility of International Classification of Diseases (ICD) codes relies on the accuracy of clinical reporting and administrative coding, which may be influenced by country-specific codes and coding rules. This study explores the accuracy and limitations of the Australian Modification of the 10th revision of ICD (ICD-10-AM) to detect the presence of cirrhosis and a subset of key complications for the purpose of future large-scale epidemiological research and healthcare studies. DESIGN/METHOD: ICD-10-AM codes in a random sample of 540 admitted patient encounters at a major Australian tertiary hospital were compared with data abstracted from patients' medical records by four blinded clinicians. Accuracy of individual codes and grouped combinations was determined by calculating sensitivity, positive predictive value (PPV), negative predictive value and Cohen's kappa coefficient (κ). RESULTS: The PPVs for 'grouped cirrhosis' codes (0.96), hepatocellular carcinoma (0.97) ascites (0.97) and 'grouped varices' (0.95) were good (κ all >0.60). However, codes under-detected the prevalence of cirrhosis, ascites and varices (sensitivity 81.4%, 61.9% and 61.3%, respectively). Overall accuracy was lower for spontaneous bacterial peritonitis ('grouped' PPV 0.75; κ 0.73) and the poorest for encephalopathy ('grouped' PPV 0.55; κ 0.21). To optimise detection of cirrhosis-related encounters, an ICD-10-AM code algorithm was constructed and validated in an independent cohort of 116 patients with known cirrhosis. CONCLUSION: Multiple ICD-10-AM codes should be considered when using administrative databases to study the burden of cirrhosis and its complications in Australia, to avoid underestimation of the prevalence, morbidity, mortality and related resource utilisation from this burgeoning chronic disease.

12.
Med Teach ; 42(11): 1301-1307, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32805157

RESUMO

OBJECTIVE: Medical students have personalities that are often shown to be perfectionistic. Perfectionism can manifest as maladaptive and lead to psychological distress. This study examined the mediating role of perfectionism on the association between personality trait profiles and levels of psychological distress. METHODS: First-year medical students completed a questionnaire containing measures of personality, perfectionism (Concern over Mistakes: CoM), stress, anxiety and depression. Latent profile analysis classified students based on their personality traits and identified a profile vulnerable to psychological distress. Structural equation models examined the mediation effects of perfectionism on the relationship between the vulnerable personality profile and distress. RESULTS: The sample totalled 376 (84% response). The vulnerable personality profile was highest in Harm Avoidance, lowest in Self-Directedness, and significantly correlated with the highest Perfectionism-CoM. High Perfectionism-CoM was associated with the highest levels of stress, anxiety and depression. Perfectionism-CoM was a significant mediator for the relationship between personality and higher levels of psychological distress. CONCLUSION: Certain personality profiles are predisposed to psychological distress such as anxiety, stress and depression. Perfectionism, as a mediator between personality and psychological distress, may be a target strategy to help increase students' self-acceptance, and self-awareness of their perfectionistic tendencies and lower their vulnerability to poor mental health.

13.
SSRN ; : 3611279, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32714119

RESUMO

To predict the tropism of human coronaviruses, we profile 28 SCARFs using scRNA-seq data from a wide range of healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Among adult organs, enterocytes and goblet cells of small intestine and colon, kidney proximal tubule cells, and gallbladder basal cells appear permissive to SARS-CoV-2, consistent with clinical data. Our analysis also suggests alternate entry paths for SARS-CoV-2 infection of the lung, CNS, and heart. We predict spermatogonial cells and prostate endocrine cells, but not ovarian cells, are highly permissive to SARS-CoV-2, suggesting male-specific vulnerabilities. Early embryonic and placental development show a moderate risk of infection. The nasal epithelium is characterized by high expression of both promoting and restricting factors and a potential age-dependent shift in SCARF expression. Lastly, SCARF expression appears broadly conserved across primate organs examined. Our study establishes an important resource for investigations of coronavirus pathology. Funding: M.S. is supported by a Presidential Postdoctoral Fellowship from Cornell University. V.B. is supported by a Career Development Fellowship at DZNE Tuebingen. Work on host-virus interactions in the Feschotte lab is funded by R35 GM122550 from the National Institutes of Health. Conflict of Interest: The authors declare that there is no conflict of interest.

14.
bioRxiv ; 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32511375

RESUMO

To predict the tropism of human coronaviruses, we profile 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell RNA-sequencing data from a wide range of healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Among adult organs, enterocytes and goblet cells of the small intestine and colon, kidney proximal tubule cells, and gallbladder basal cells appear most permissive to SARS-CoV-2, consistent with clinical data. Our analysis also suggests alternate entry paths for SARS-CoV-2 infection of the lung, central nervous system, and heart. We predict spermatogonial cells and prostate endocrine cells, but not ovarian cells, to be highly permissive to SARS-CoV-2, suggesting male-specific vulnerabilities. Early stages of embryonic and placental development show a moderate risk of infection. The nasal epithelium looks like another battleground, characterized by high expression of both promoting and restricting factors and a potential age-dependent shift in SCARF expression. Lastly, SCARF expression appears broadly conserved across human, chimpanzee and macaque organs examined. Our study establishes an important resource for investigations of coronavirus biology and pathology.

15.
Genome Res ; 30(6): 898-909, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32540955

RESUMO

Long-range sequencing information is required for haplotype phasing, de novo assembly, and structural variation detection. Current long-read sequencing technologies can provide valuable long-range information but at a high cost with low accuracy and high DNA input requirements. We have developed a single-tube Transposase Enzyme Linked Long-read Sequencing (TELL-seq) technology, which enables a low-cost, high-accuracy, and high-throughput short-read second-generation sequencer to generate over 100 kb of long-range sequencing information with as little as 0.1 ng input material. In a PCR tube, millions of clonally barcoded beads are used to uniquely barcode long DNA molecules in an open bulk reaction without dilution and compartmentation. The barcoded linked-reads are used to successfully assemble genomes ranging from microbes to human. These linked-reads also generate megabase-long phased blocks and provide a cost-effective tool for detecting structural variants in a genome, which are important to identify compound heterozygosity in recessive Mendelian diseases and discover genetic drivers and diagnostic biomarkers in cancers.

16.
World J Crit Care Med ; 9(2): 20-30, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32577413

RESUMO

BACKGROUND: Hypotension is a frequent complication in the intensive care unit (ICU) after adult cardiac surgery. AIM: To describe frequency of hypotension in the ICU following adult cardiac surgery and its relation to the hospital outcomes. METHODS: A retrospective study of post-cardiac adult surgical patients at a tertiary academic medical center in a two-year period. We abstracted baseline demographics, comorbidities, and all pertinent clinical variables. The primary predictor variable was the development of hypotension within the first 30 min upon arrival to the ICU from the operating room (OR). The primary outcome was hospital mortality, and other outcomes included duration of mechanical ventilation (MV) in hours, and ICU and hospital length of stay in days. RESULTS: Of 417 patients, more than half (54%) experienced hypotension within 30 min upon arrival to the ICU. Presence of OR hypotension immediately prior to ICU transfer was significantly associated with ICU hypotension (odds ratio = 1.9; 95% confidence interval: 1.21-2.98; P < 0.006). ICU hypotensive patients had longer MV, 5 (interquartile ranges 3, 15) vs 4 h (interquartile ranges 3, 6), P = 0.012. The patients who received vasopressor boluses (n = 212) were more likely to experience ICU drop-off hypotension (odds ratio = 1.45, 95% confidence interval: 0.98-2.13; P = 0.062), and they experienced longer MV, ICU and hospital length of stay (P < 0.001, for all). CONCLUSION: Hypotension upon anesthesia-to-ICU drop-off is more frequent than previously reported and may be associated with adverse clinical outcomes.

17.
World J Crit Care Med ; 9(2): 31-42, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32577414

RESUMO

BACKGROUND: A diverse country like India may have variable intensive care units (ICUs) practices at state and city levels. AIM: To gain insight into clinical services and processes of care in ICUs in India, this would help plan for potential educational and quality improvement interventions. METHODS: The Indian ICU needs assessment research group of diverse-skilled individuals was formed. A pan- India survey "Indian National ICU Needs" assessment (ININ 2018-I) was designed on google forms and deployed from July 23rd-August 25th, 2018. The survey was sent to select distribution lists of ICU providers from all 29 states and 7 union territories (UTs). In addition to emails and phone calls, social medial applications-WhatsApp™, Facebook™ and LinkedIn™ were used to remind and motivate providers. By completing and submitting the survey, providers gave their consent for research purposes. This study was deemed eligible for category-2 Institutional Review Board exempt status. RESULTS: There were total 134 adult/adult-pediatrics ICU responses from 24 (83% out of 29) states, and two (28% out of 7) UTs in 61 cities. They had median (IQR) 16 (10-25) beds and most, were mixed medical-surgical, 111(83%), with 108(81%) being adult-only ICUs. Representative responders were young, median (IQR), 38 (32-44) years age and majority, n = 108 (81%) were males. The consultants were, n = 101 (75%). A total of 77 (57%) reported to have 24 h in-house intensivist. A total of 68 (51%) ICUs reported to have either 2:1 or 2≥:1 patient:nurse ratio. More than 80% of the ICUs were open, and mixed type. Protocols followed regularly by the ICUs included sepsis care, ventilator- associated pneumonia (83% each); nutrition (82%), deep vein thrombosis prophylaxis (87%), stress ulcer prophylaxis (88%) and glycemic control (92%). Digital infrastructure was found to be poor, with only 46 % of the ICUs reporting high-speed internet availability. CONCLUSION: In this large, national, semi-structured, need-assessment survey, the need for improved manpower including; in-house intensivists, and decreasing patient-to-nurse ratios was evident. Sepsis was the most common diagnosis and quality and research initiatives to decrease sepsis mortality and ICU length of stay could be prioritized. Additionally, subsequent surveys can focus on digital infrastructure for standardized care and efficient resource utilization and enhancing compliance with existing protocols.

18.
Crit Care Explor ; 2(4): e0113, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32426754

RESUMO

The coronavirus disease 2019 pandemic has disproportionally strained intensive care services worldwide. Large areas of uncertainly regarding epidemiology, physiology, practice patterns, and resource demands for patients with coronavirus disease 2019 require rapid collection and dissemination of data. We describe the conception and implementation of an intensive care database rapidly developed and designed to meet data analytic needs in response to the coronavirus disease 2019 pandemic-the multicenter, international Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study. Design: Prospective cohort study and disease registry. Setting: Multinational cohort of ICUs. Patients: Critically ill patients with a diagnosis of coronavirus disease 2019. Interventions: None. Measurements and Main Results: Within 2 weeks of conception of the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study, study leadership was convened, registry case report forms were designed, electronic data entry set up, and more than 250 centers had submitted the protocol for institutional review board approval, with more than 100 cases entered. Conclusions: The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study provides an example of a rapidly deployed, international, pandemic registry that seeks to provide near real-time analytics and information regarding intensive care treatments and outcomes for patients with coronavirus disease 2019.

19.
Nat Commun ; 11(1): 1313, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152318

RESUMO

Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with a novel line of reporter mice that cognitive challenge induces local/endogenous hypoxia in hippocampal pyramidal neurons, hence enhancing expression of EPO and EPO receptor (EPOR). High-dose EPO administration, amplifying auto/paracrine EPO/EPOR signaling, prompts the emergence of new CA1 neurons and enhanced dendritic spine densities. Single-cell sequencing reveals rapid increase in newly differentiating neurons. Importantly, improved performance on complex running wheels after EPO is imitated by exposure to mild exogenous/inspiratory hypoxia. All these effects depend on neuronal expression of the Epor gene. This suggests a model of neuroplasticity in form of a fundamental regulatory circle, in which neuronal networks-challenged by cognitive tasks-drift into transient hypoxia, thereby triggering neuronal EPO/EPOR expression.


Assuntos
Encéfalo/metabolismo , Encéfalo/fisiopatologia , Eritropoetina/metabolismo , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Neurogênese , Plasticidade Neuronal , Animais , Diferenciação Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Eritropoetina/farmacologia , Feminino , Deleção de Genes , Humanos , Masculino , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Atividade Motora/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Condicionamento Físico Animal , Resistência Física/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Receptores da Eritropoetina/metabolismo , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
20.
Nat Commun ; 11(1): 166, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919373

RESUMO

A fundamental problem in biomedical research is the low number of observations available, mostly due to a lack of available biosamples, prohibitive costs, or ethical reasons. Augmenting few real observations with generated in silico samples could lead to more robust analysis results and a higher reproducibility rate. Here, we propose the use of conditional single-cell generative adversarial neural networks (cscGAN) for the realistic generation of single-cell RNA-seq data. cscGAN learns non-linear gene-gene dependencies from complex, multiple cell type samples and uses this information to generate realistic cells of defined types. Augmenting sparse cell populations with cscGAN generated cells improves downstream analyses such as the detection of marker genes, the robustness and reliability of classifiers, the assessment of novel analysis algorithms, and might reduce the number of animal experiments and costs in consequence. cscGAN outperforms existing methods for single-cell RNA-seq data generation in quality and hold great promise for the realistic generation and augmentation of other biomedical data types.


Assuntos
Pesquisa Biomédica/métodos , RNA-Seq/métodos , RNA/genética , Algoritmos , Animais , Simulação por Computador , Humanos , Camundongos , Modelos Teóricos , Redes Neurais de Computação
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