bluuebunny/crossref_metadata_2025 huggingface dataset:
“A cross-sectional case-control study of sexual dysfunction and associated depression in postmenopausal incontinent women.”
Authors: Kaur Tanudeep , Kumari Rajesh , Sharma Jai Bhagwan , Pandey Kavita , Uppal Bharti , Sinha Deb Koushik , Anukriti Kumari
Published: July 2020

Background

Female sexual dysfunction (FSD) has higher prevalence in postmenopausal women especially with urinary incontinence (UI) and coital incontinence (CI). This study was attempted as there is dearth of literature to quantify FSD, CI and depression in UI women and their correlation with each other especially in Indian scenario.

Aim

Aim of this study was to determine the prevalence of FSD, CI and depression in postmenopausal UI women.

Material and Methods

Cross-sectional case-control study of 100 menopausal women with previously diagnosed UI with matching controls over period of 3 months were analyzed for the prevalence of FSD, CI and depression using validated questionnaires like Female Sexual Function Index (FSFI) and Primary Health Questionnaire-9 (PHQ-9). Statistical Analysis was performed using SPSS version 19.0.

Results

UI is independently associated with FSD, CI and depression (p < 0.001) with prevalence of 100%, 83%, and 100% respectively for cases versus 5%, 6%, and 4% respectively for controls. FSD and CI are also independently associated with depression (p < 0.001). Combined FSD with UI and CI with UI are also significantly associated with depression.

Conclusion

UI is independently associated with FSD, CI and depression. FSD and CI are also independently associated with depression. UI is the major determinant of depression in those with both FSD and UI or CI and UI.

Key Message Points

Female sexual dysfunction is rampant in menopausal women especially the ones who are incontinent, which jeopardizes their quality of life.

Sexually dysfunctional incontinent females feel socially outcast and are moderate to severely depressed and need addressal.

There is a dearth of literature as regards to this issue in the society which needs to be explored, hence an attempt has been made
Outcomes of Mechanically Ventilated Patients with COVID-19 Associated Respiratory Failure
Authors: King Christopher S. , Sahjwani Dhwani , Brown A. Whitney , Feroz Saad , Cameron Paula , Osborn Erik , Desai Mehul , Djurkovic Svetolik , Kasarabada Aditya , Hinerman Rachel , Lantry James , Shlobin Oksana A. , Ahmad Kareem , Khangoora Vikramjit , Aryal Shambhu , Collins A. Claire , Speir Alan , Nathan Steven
Published: July 2020

Purpose

The outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system.

Methods

Outcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review.

Results

1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 165 (16.1%) were managed with invasive mechanical ventilation. At the time of data censoring, 63/165 patients (38.1%) had died and 102/165 (61.8%) were still alive. Of the surviving 102 patients, 17 (10.3%) remained on mechanical ventilation, 51 (30.9%) were extubated but remained hospitalized, and 34 (20.6%) had been discharged. Deceased patients were older (median age of 66 vs. 55, p <0.0001). 75.7% of patients over 70 years old had died at the time of data analysis. Conversely, % of patients age 70 or younger were still alive at the time of data analysis. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status.

Conclusion

Mortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system. A substantial proportion of patients requiring invasive mechanical ventilation were not of advanced age, and this group had a reasonable chance for recovery.
A high-resolution HLA reference panel capturing global population diversity enables multi-ethnic fine-mapping in HIV host response
Authors: Luo Yang , Kanai Masahiro , Choi Wanson , Li Xinyi , Yamamoto Kenichi , Ogawa Kotaro , Gutierrez-Arcelus Maria , Gregersen Peter K. , Stuart Philip E. , Elder James T. , Fellay Jacques , Carrington Mary , Haas David W. , Guo Xiuqing , Palmer Nicholette D. , Chen Yii-Der Ida , Rotter Jerome. I. , Taylor Kent. D. , Rich Stephen. S. , Correa Adolfo , Wilson James G. , Kathiresan Sekar , Cho Michael H. , Metspalu Andres , Esko Tonu , Okada Yukinori , Han Buhm ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, McLaren Paul J. , Raychaudhuri Soumya
Published: July 2020

Defining causal variation by fine-mapping can be more effective in multi-ethnic genetic studies, particularly in regions such as the MHC with highly population-specific structure. To enable such studies, we constructed a large (N=21,546) high resolution HLA reference panel spanning five global populations based on whole-genome sequencing data. Expectedly, we observed unique long-range HLA haplotypes within each population group. Despite this, we demonstrated consistently accurate imputation at G-group resolution (94.2%, 93.7%, 97.8% and 93.7% in Admixed African (AA), East Asian (EAS), European (EUR) and Latino (LAT)). We jointly analyzed genome-wide association studies (GWAS) of HIV-1 viral load from EUR, AA and LAT populations. Our analysis pinpointed the MHC association to three amino acid positions (97, 67 and 156) marking three consecutive pockets (C, B and D) within the HLA-B peptide binding groove, explaining 12.9% of trait variance, and obviating effects of previously reported associations from population-specific HIV studies.
Development and Validation of a Web-Based Severe COVID-19 Risk Prediction Model
Authors: Woo Sang H. , Rios-Diaz Arturo J. , Kubey Alan A. , Cheney-Peters Dianna R. , Ackermann Lily L. , Chalikonda Divya M. , Venkataraman Chantel M. , Riley Joshua M. , Baram Michael
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) carries high morbidity and mortality globally. Identification of patients at risk for clinical deterioration upon presentation would aid in triaging, prognostication, and allocation of resources and experimental treatments.

Research Question

Can we develop and validate a web-based risk prediction model for identification of patients who may develop severe COVID-19, defined as intensive care unit (ICU) admission, mechanical ventilation, and/or death?

Methods

This retrospective cohort study reviewed 415 patients admitted to a large urban academic medical center and community hospitals. Covariates included demographic, clinical, and laboratory data. The independent association of predictors with severe COVID-19 was determined using multivariable logistic regression. A derivation cohort (n=311, 75%) was used to develop the prediction models. The models were tested by a validation cohort (n=104, 25%).

Results

The median age was 66 years (Interquartile range [IQR] 54-77) and the majority were male (55%) and non-White (65.8%). The 14-day severe COVID-19 rate was 39.3%; 31.7% required ICU, 24.6% mechanical ventilation, and 21.2% died. Machine learning algorithms and clinical judgment were used to improve model performance and clinical utility, resulting in the selection of eight predictors: age, sex, dyspnea, diabetes mellitus, troponin, C-reactive protein, D-dimer, and aspartate aminotransferase. The discriminative ability was excellent for both the severe COVID-19 (training area under the curve [AUC]=0.82, validation AUC=0.82) and mortality (training AUC= 0.85, validation AUC=0.81) models. These models were incorporated into a mobile-friendly website.

Interpretation

This web-based risk prediction model can be used at the bedside for prediction of severe COVID-19 using data mostly available at the time of presentation.
Barriers to online learning in the time of COVID-19: A national survey of medical students in the Philippines
Authors: Baticulon Ronnie E. , Alberto Nicole Rose I. , C. Baron Maria Beatriz , Mabulay Robert Earl C. , Rizada Lloyd Gabriel T. , Sy Jinno Jenkin , Tiu Christl Jan S. , Clarion Charlie A. , Reyes John Carlo B.
Published: July 2020

Introduction

In March 2020, the coronavirus disease 2019 (COVID-19) pandemic forced medical schools in the Philippines to stop face-to-face learning activities and abruptly shift to an online curriculum. This study aimed to identify barriers to online learning from the perspective of medical students in a developing country.

Methods

The authors sent out an electronic survey to medical students in the Philippines from 11 to 24 May 2020. Using a combination of multiple choice, Likert scale, and open-ended questions, the following data were obtained: demographics, medical school information, access to technological resources, study habits, living conditions, self-assessment of capacity for and perceived barriers to online learning, and proposed interventions. Descriptive statistics were calculated. Responses were compared between student subgroups using nonparametric tests.

Results

Among 3,670 medical students, 3,421 (93%) owned a smartphone and 3,043 (83%) had a laptop or desktop computer. To access online resources, 2,916 (79%) had a postpaid internet subscription while 696 (19%) used prepaid mobile data. Under prevailing conditions, only 1,505 students (41%) considered themselves physically and mentally capable of engaging in online learning. Barriers were classified under five categories: technological, individual, domestic, institutional, and community barriers. Most frequently encountered were difficulty adjusting learning styles, having to perform responsibilities at home, and poor communication between educators and learners.

Discussion

Medical students in the Philippines confronted several interrelated barriers as they tried to adapt to online learning. By implementing student-centered interventions, medical schools and educators play a significant role in addressing these challenges during the COVID-19 pandemic and beyond.
Validation of a new automated chemiluminescent anti-SARS-CoV-2 IgM and IgG antibody assay system detecting both N and S proteins in Japan
Authors: Yokoyama Rin , Kurano Makoto , Morita Yoshifumi , Shimura Takuya , Nakano Yuki , Qian Chungen , Xia Fuzhen , He Fan , Kishi Yoshiro , Okada Jun , Yoshikawa Naoyuki , Nagura Yutaka , Okazaki Hitoshi , Moriya Kyoji , Seto Yasuyuki , Kodama Tatsuhiko , Yatomi Yutaka
Published: July 2020

PCR methods are presently the standard for the diagnosis of Coronavirus disease 2019 (COVID-19), but additional methodologies are needed to complement PCR methods, which have some limitations. Here, we validated and investigated the usefulness of measuring serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the iFlash3000 CLIA analyzer. We measured IgM and IgG titers against SARS-CoV-2 in sera collected from 26 PCR-positive COVID-19 patients, 53 COVID-19-suspected but PCR-negative patients, and 20 and 100 randomly selected non-COVID-19 patients who visited our hospital in 2020 and 2017, respectively. The within-day and between-day precisions were regarded as good, since the coefficient variations were below 5%. Linearity was also considered good between 0.6 AU/mL and 112.7 AU/mL for SARS-CoV-2 IgM and between 3.2 AU/mL and 55.3 AU/mL for SARS-CoV-2 IgG, while the linearity curves plateaued above the upper measurement range. We also confirmed that the seroconversion and no-antibody titers were over the cutoff values in all 100 serum samples collected in 2017. These results indicate that this measurement system successfully detects SARS-CoV-2 IgM/IgG. We observed four false-positive cases in the IgM assay and no false-positive cases in the IgG assay when 111 serum samples known to contain autoantibodies were evaluated. The concordance rates of the antibody test with the PCR test were 98.1% for SARS-CoV-2 IgM and 100% for IgG among PCR-negative cases and 30.8% for SARS-CoV-2 IgM and 73.1% for SARS-CoV-2 IgG among PCR-positive cases. In conclusion, the performance of this measurement system is sufficient for use in laboratory testing.
SARS-Cov-2 cysteine-like protease (Mpro) is immunogenic and can be detected in serum and saliva of COVID-19-seropositive individuals
Authors: Martínez-Fleta Pedro , Alfranca Arantzazu , González-Álvaro Isidoro , Casasnovas Jose M , Fernández-Soto Daniel , Esteso Gloria , Cáceres-Martell Yaiza , Gardeta Sofía , Prat Salomé , Mateu-Albero Tamara , Gabrie Ligia , López-Granados Eduardo , Sánchez-Madrid Francisco , Reyburn Hugh T. , Rodríguez Frade José M. , Valés-Gómez Mar
Published: July 2020

Currently, there is a need for reliable tests that allow identification of individuals that have been infected with SARS-CoV-2 even if the infection was asymptomatic. To date, the vast majority of the serological tests for SARS-CoV-2 specific antibodies are based on serum detection of antibodies to either the viral spike glycoprotein (the major target for neutralising antibodies) or the viral nucleocapsid protein that are known to be highly immunogenic in other coronaviruses. Conceivably, exposure of antigens released from infected cells could stimulate antibody responses that might correlate with tissue damage and, hence, they may have some value as a prognostic indicator. We addressed whether other non-structural viral proteins, not incorporated into the infectious viral particle, specifically the viral cysteine-like protease, might also be potent immunogens. Using ELISA tests, coating several SARS-CoV-2 proteins produced in vitro, we describe that COVID-19 patients make high titre IgG, IgM and IgA antibody responses to the Cys-like protease from SARS-CoV-2, also known as 3CLpro or Mpro, and it can be used to identify individuals with positive serology against the coronavirus. Higher antibody titres in these assays associated with more severe disease and no cross-reactive antibodies against prior betacoronavirus were found. Remarkably, IgG antibodies specific for Mpro and other SARS-CoV-2 antigens can also be detected in saliva. In conclusion, Mpro is a potent antigen in infected patients that can be used in serological tests and its detection in saliva could be the basis for a rapid, non-invasive test for COVID-19 seropositivity.
Oral colonization by Entamoeba gingivalis and Trichomonas tenax: PCR-based study in health, gingivitis, and periodontitis
Authors: Yaseen Alaa’ , Mahafzah Azmi , Dababseh Deema , Tayem Duaa , Hamdan Ahmad A. , Al-Fraihat Esraa , Hassona Yazan , Şahin Gülşen Özkaya , Santi-Rocca Julien , Sallam Malik
Published: July 2020

The etiology of periodontitis needs further investigation, as is the place of gingivitis in its pathophysiology. A few studies linked the oral colonization by parasites (Entamoeba gingivalis and Trichomonas tenax) to the disease and its severity. The aim of this study was to estimate the prevalence of these oral parasites among healthy individuals, gingivitis and periodontitis patients in Jordan. The study was conducted by active enrolment of participants at Jordan University Hospital. The participants answered a questionnaire that included items related to possible risk factors for periodontal disease. Saliva and dental plaque samples were collected. The detection of oral parasites was done using conventional PCR and microscopic examination of wet mounts. The study population comprised a total of 237 individuals divided into three groups: healthy (n=94), gingivitis (n=53), and periodontitis (n=90). PCR results revealed that the overall prevalence of E. gingivalis was 71.7% compared to 12.2% for T. tenax. The periodontal disease group had higher prevalence of E. gingivalis and T. tenax compared to the healthy group (p<0.001). Increasing age was associated with higher prevalence of E. gingivalis (p=0.008) and T. tenax (p=0.019), in the entire study population. The number of cases of colonization detected by microscopic observation was lower for any of the oral parasites, as compared to diagnosis by PCR (40.7% vs. 71.7%, p<0.001 for E. gingivalis and 4.3% vs. 12.2%, p=0.007 for T. tenax). The higher prevalence of oral parasites among patients with periodontal disease might point to their potential contribution in the disease and its severity.

IMPORTANCE

Periodontal disease has a high prevalence globally, with adverse effects on the quality of life for affected individuals. Despite the presence of several studies that investigated the role of oral parasites in periodontal disease, reliable conclusions about this matter remained elusive mainly due to utilization of microscopy in parasite detection. The current study provides new insights into the epidemiology and prevalence of the two oral parasites (Entamoeba gingivalis and Trichomonas tenax) in patients with various stages of periodontal disease in comparison to healthy adults. In addition, we describe the potential role of oral colonization by parasites as a risk factor for development of periodontal disease and its severity using a molecular-based approach.
Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate
Authors: Olagnier David , Farahani Ensieh , Thyrsted Jacob , Cadanet Julia B. , Herengt Angela , Idorn Manja , Hait Alon , Hernaez Bruno , Knudsen Alice , Iversen Marie Beck , Schilling Mirjam , Jørgensen Sofie E. , Thomsen Michelle , Reinert Line , Lappe Michael , Hoang Huy-Dung , Gilchrist Victoria H. , Hansen Anne Louise , Ottosen Rasmus , Gunderstofte Camilla , Møller Charlotte , van der Horst Demi , Peri Suraj , Balachandran Siddarth , Huang Jinrong , Jakobsen Martin , Svenningsen Esben B. , Poulsen Thomas B. , Bartsch Lydia , Thielke Anne L. , Luo Yonglun , Alain Tommy , Rehwinkel Jan , Alcamí Antonio , Hiscott John , Mogensen Trine , Paludan Søren R. , Holm Christian K.
Published: July 2020

Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.

One Sentence Summary

NRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses.
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors
Authors: F. Oliveira A. Sofia , Ibarra Amaurys Avila , Bermudez Isabel , Casalino Lorenzo , Gaieb Zied , Shoemark Deborah K. , Gallagher Timothy , Sessions Richard B. , Amaro Rommie E. , Mulholland Adrian J.
Published: July 2020

Changeuxet al. recently suggested that the SARS-CoV-2 spike (S) protein may interact with nicotinic acetylcholine receptors (nAChRs). Such interactions may be involved in pathology and infectivity. Here, we use molecular simulations of validated atomically detailed structures of nAChRs, and of the S protein, to investigate this ‘nicotinic hypothesis’. We examine the binding of the Y674-R685 loop of the S protein to three nAChRs, namely the human α4β2 and α7 subtypes and the muscle-like αβγd receptor fromTetronarce californica. Our results indicate that Y674-R685 has affinity for nAChRs and the region responsible for binding contains the PRRA motif, a four-residue insertion not found in other SARS-like coronaviruses. In particular, R682 has a key role in the stabilisation of the complexes as it forms interactions with loops A, B and C in the receptor’s binding pocket. The conformational behaviour of the bound Y674-R685 region is highly dependent on the receptor subtype, adopting extended conformations in the α4β2 and α7 complexes and more compact ones when bound to the muscle-like receptor. In the α4β2 and αβγd complexes, the interaction of Y674-R685 with the receptors forces the loop C region to adopt an open conformation similar to other known nAChR antagonists. In contrast, in the α7 complex, Y674-R685 penetrates deeply into the binding pocket where it forms interactions with the residues lining the aromatic box, namely with TrpB, TyrC1 and TyrC2. Estimates of binding energy suggest that Y674-R685 forms stable complexes with all three nAChR subtypes. Analyses of the simulations of the full-length S protein show that the Y674-R685 region is accessible for binding, and suggest a potential binding orientation of the S protein with nAChRs.
Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine
Authors: Sahin Ugur , Muik Alexander , Derhovanessian Evelyna , Vogler Isabel , Kranz Lena M. , Vormehr Mathias , Baum Alina , Pascal Kristen , Quandt Jasmin , Maurus Daniel , Brachtendorf Sebastian , Lörks Verena , Sikorski Julian , Hilker Rolf , Becker Dirk , Eller Ann-Kathrin , Grützner Jan , Boesler Carsten , Rosenbaum Corinna , Kühnle Marie-Cristine , Luxemburger Ulrich , Kemmer-Brück Alexandra , Langer David , Bexon Martin , Bolte Stefanie , Karikó Katalin , Palanche Tania , Fischer Boris , Schultz Armin , Shi Pei-Yong , Fontes-Garfias Camila , Perez John L. , Swanson Kena A. , Loschko Jakob , Scully Ingrid L. , Cutler Mark , Kalina Warren , Kyratsous Christos A. , Cooper David , Dormitzer Philip R. , Jansen Kathrin U. , Türeci Özlem
Published: July 2020

An effective vaccine is needed to halt the spread of the SARS-CoV-2 pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 COVID-19 vaccine trial with BNT162b1, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Here we present antibody and T cell responses after BNT162b1 vaccination from a second, non-randomized open-label phase 1/2 trial in healthy adults, 18-55 years of age. Two doses of 1 to 50 µg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those in a COVID-19 convalescent human serum panel (HCS). Day 43 SARS-CoV-2 serum neutralising geometric mean titers were 0.7-fold (1 µg) to 3.5-fold (50 µg) those of HCS. Immune sera broadly neutralised pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had TH1 skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon (IFN)γ was produced by a high fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T-cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest multiple beneficial mechanisms with potential to protect against COVID-19.
Association between consumption of vegetables and COVID-19 mortality at a country level in Europe
Authors: Fonseca Susana C , Rivas Ioar , Romaguera Dora , Quijal-Zamorano Marcos , Czarlewski Wienczyslawa , Vidal Alain , Fonseca Joao A , Ballester Joan , Anto Josep M , Basagana Xavier , Cunha Luis M , Bousquet Jean
Published: July 2020

Background

Many foods have an antioxidant activity, and nutrition may mitigate COVID-19. To test the potential role of vegetables in COVID-19 mortality in Europe, we performed an ecological study.

Methods

The European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database was used to study the country consumption of Brassica vegetables (broccoli, cauliflower, head cabbage (white, red and savoy cabbage), leafy brassica) and to compare them with spinach, cucumber, courgette, lettuce and tomato. The COVID-19 mortality per number of inhabitants was obtained from the Johns Hopkins Coronavirus Resource Center. EuroStat data were used for potential confounders at the country level including Gross Domestic Product (GDP) (2019), population density (2018), percentage of people over 64 years (2019), unemployment rate (2019) and percentage of obesity (2014, to avoid missing values). Mortality counts were analyzed with quasi-Poisson regression models to model the death rate while accounting for over-dispersion.

Results

Of all the variables considered, including confounders, only head cabbage and cucumber reached statistical significance with the COVID-19 death rate per country. For each g/day increase in the average national consumption of some of the vegetables (head cabbage and cucumber), the mortality risk for COVID-19 decreased by a factor of 11, down to 13.6 %. Lettuce consumption increased COVID-19 mortality. The adjustment did not change the point estimate and the results were still significant.

Discussion

The negative ecological association between COVID-19 mortality and the consumption of cabbage and cucumber supports the a priori hypothesis previously reported. The hypothesis needs to be tested in individual studies performed in countries where the consumption of vegetables is common.
A phenome-wide association study identifying risk factors for pediatric post-concussion syndrome
Authors: Yengo-Kahn Aaron M. , Hibshman Natalie , Bonfield Christopher M. , Torstenson Eric S. , Gifford Katherine A. , Belikau Daniil , Davis Lea K. , Zuckerman Scott L. , Dennis Jessica K.
Published: July 2020

Objective

To identify risk factors and generate hypotheses for pediatric post-concussion syndrome (PCS) using a phenome-wide association study (PheWAS).

Methods

A PheWAS (case-control) was conducted following the development and validation of a novel electronic health record-based algorithm that identified PCS cases and controls from an institutional database of >2.8 million patients. Cases were patients ages 5-18 with PCS codes or keywords identified by natural language processing of clinical notes. Controls were patients with mild traumatic brain injury (mTBI) codes only. Patients with moderate or severe brain injury were excluded. All patients used our healthcare system at least three times 180 days before their injury. Exposures included all pre-injury medical diagnoses assigned at least 180 days prior.

Results

The algorithm identified 274 pediatric PCS cases (156 females) and 1,096 controls that were age and sex matched to cases. Cases and controls both had a mean of >8 years of healthcare system use pre-injury. Of 202 pre-injury medical, four were associated with PCS after controlling for multiple testing: headache disorders (OR=5.3; 95%CI 2.8-10.1;P=3.8e-7), sleep disorders (OR=3.1; 95%CI 1.8-5.2;P=2.6e-5), gastritis/duodenitis (OR=3.6, 95%CI 1.8-7.0;P=2.1e-4), and chronic pharyngitis (OR=3.3; 95%CI 1.8-6.3;P=2.2e-4).

Conclusions

These results confirm the strong association of pre-injury headache disorders with PCS and provides evidence for the association of pre-injury sleep disorders with PCS. An association of PCS with prior chronic gastritis/duodenitis and pharyngitis was seen that suggests a role for chronic inflammation in PCS pathophysiology and risk. These factors should be considered during the management of pediatric mTBI cases.
Role of intermediate care unit admission and non-invasive respiratory support during the COVID-19 pandemic: a retrospective cohort study
Authors: Grosgurin Olivier , Leidi Antonio , Farhoumand Pauline Darbellay , Carballo Sebastian , Adler Dan , Reny Jean-Luc , Pinto Bernardo Bollen , Rossel Anne , Serratrice Jacques , Agoritsas Thomas , Stirnemann Jérôme , Marti Christophe
Published: July 2020

Background

The COVID-19 pandemic has led to shortage of Intensive Care Unit (ICU) capacity. We developed a triage strategy including non-invasive respiratory support and admission to the intermediate care unit (IMCU). ICU admission was restricted to patients requiring invasive ventilation.

Objectives

The aim of this study is to describe the characteristics and outcomes of patients admitted to the intermediate care unit.

Method

Retrospective cohort including consecutive patients admitted between March 28th and April 27th 2020. The primary outcome was the proportion of patients with severe hypoxemic respiratory failure avoiding ICU admission. Secondary outcomes included the rate of emergency intubation, 28-days mortality and predictors of ICU admission.

Results

One hundred fifty seven patients with COVID-19 associated pneumonia were admitted to the IMCU. Among the 85 patients admitted for worsening respiratory failure, 52/85 (61%) avoided ICU admission. In multivariate analysis, PaO2/FiO2 (OR 0.98; 95% CI 0.96 to 0.99) and Body Mass Index (OR 0.88; 95% CI 0.78 to 0.98) were significantly associated with ICU admission. No death or emergency intubation occurred in the intermediate care unit. Among the 72 patients transferred from the ICU, 60/72 (83%) presented neurological complications.

Conclusions

Non-invasive respiratory support including High-Flow Nasal Oxygen and continuous positive airway pressure prevents ICU admission for a large proportion of patients with COVID-19 hypoxemic respiratory failure. In the context of the COVID pandemic, intermediate care units may play an important role in preserving ICU capacity by avoiding ICU admission for patients with worsening respiratory failure and allowing early discharge of ICU patients.
Going beyond clinical routine in SARS-CoV-2 antibody testing - A multiplex corona virus antibody test for the evaluation of cross-reactivity to endemic coronavirus antigens
Authors: Becker Matthias , Strengert Monika , Junker Daniel , Kerrinnes Tobias , Kaiser Philipp D. , Traenkle Bjoern , Dinter Heiko , Häring Julia , Zeck Anne , Weise Frank , Peter Andreas , Hörber Sebastian , Fink Simon , Ruoff Felix , Bakchoul Tamam , Baillot Armin , Lohse Stefan , Cornberg Markus , Illig Thomas , Gottlieb Jens , Smola Sigrun , Karch André , Berger Klaus , Rammensee Hans-Georg , Schenke-Layland Katja , Nelde Annika , Märklin Melanie , Heitmann Jonas S. , Walz Juliane S. , Templin Markus , Joos Thomas O. , Rothbauer Ulrich , Krause Gérard , Schneiderhan-Marra Nicole
Published: July 2020

Given the importance of the humoral immune response to SARS-CoV-2 as a global benchmark for immunity, a detailed analysis is needed to monitor seroconversion in the general population, understand manifestation and progression of COVID-19 disease, and ultimately predict the outcome of vaccine development. In contrast to currently available serological assays, which are only able to resolve the SARS-CoV-2 antibody response on an individual antigen level, we developed a multiplex immunoassay, for which we included spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses (NL63, OC43, 229E, HKU1) in an expanded antigen panel. Compared to three commercialin vitrodiagnostic tests, our MULTICOV-AB assay achieved the highest sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. Simultaneously, high IgG responses against endemic coronaviruses became apparent throughout all samples, but no consistent cross-reactive IgG response patterns could be defined. In summary, we have established and validated, a robust, high-content-enabled, and antigen-saving multiplex assay MULTICOV-AB, which is highly suited to monitor vaccination studies and will facilitate epidemiologic screenings for the humoral immunity toward pandemic as well as endemic coronaviruses.
Are we ready when COVID-19 vaccine is available? Study on nurses’ vaccine hesitancy in Hong Kong
Authors: Kwok Kin On , Li Kin Kit , Wei Wan In , Tang Arthur , Wong Samuel Yeung Shan , Lee Shui Shan
Published: July 2020

Introduction

Nurses are considered a trustworthy source of vaccine-related information to build public confidence in vaccination. This study estimated nurses’ influenza vaccine uptake and intention to receive COVID-19 vaccine when available, and examined the corresponding psychological antecedents.

Methods

A cross-sectional online survey among nurses was conducted during the main COVID-19 outbreak in Hong Kong between mid-March and late April 2020. Demographics, influenza vaccination, intention to have COVID-19 vaccine, the 5C vaccine hesitancy components (i.e., confidence, complacency, constraints, calculation, and collective responsibility), work stress and COVID-related work demands (i.e., insufficient supply of personal protective equipment, involvement in isolation rooms, and unfavorable attitudes towards workplace infection control policies) were reported.

Results

The influenza vaccination coverage and the proportion intending to take COVID-19 vaccine were 49% and 63%, respectively, among 1205 eligible nurses. Influenza vaccine uptake was associated with working in public hospitals and all 5C constructs, whereas stronger COVID-19 vaccination intention was associated with younger age, more confidence, less complacency and more collective responsibility towards the vaccine. COVID-19-related demands were associated with greater work stress, and hence stronger COVID-19 vaccination intention.

Conclusion

Vaccine uptake/intention was well predicted by the 5C constructs. With less work stress among nurses in the post-pandemic period, the intention to take COVID-19 vaccine will likely drop. The 5C constructs should be infused in vaccination campaigns. While a COVID-19 vaccine could be ready soon, communities are not ready to accept it. More research work is needed to boost the uptake.
Changes in the adult consequences of adolescent mental health: findings from the 1958 and 1970 British birth cohorts
Authors: Thompson Ellen Jo , Richards Marcus , Ploubidis George B. , Fonagy Peter , Patalay Praveetha
Published: July 2020

Objective

To investigate whether the associations between adolescent externalising and internalising mental health difficulties and mid-life health and social outcomes are changing across cohorts.

Methods

Data from 31,349 participants followed as part of two prospective national birth cohort studies: 1958 National Child Development Study (n=16091) and the 1970 British Cohort Study (n=15258). Adolescent mental health at age 16 years was assessed using the Rutter scales and operationalised as both a traditional 2-factor internalising and externalising and as a hierarchical bi-factor. Associations between adolescent psychopathology and health and wellbeing (mental health, general health, life satisfaction) and socio-economic (cohabitation, voting behaviour, education and employment) outcomes at ages 42 are estimated and illustrated across cohorts.

Results

The prevalence of adolescent mental health difficulties increased between those born in 1958 and 1970. Their associations with different midlife outcomes became more severe or remained similar in the 1970 compared the 1958 cohort. For instance, a stronger association with adolescent mental health difficulties was found for those born in 1970, compared with those born in 1958 for midlife psychological distress (OR 1970=1.82 [1.65;1.99], OR 1958=1.60 [1.43;1.79], cohabitation (OR 1970=0.64 [0.59;0.70], OR 1958=0.74 [1.43;1.79]), and professional occupations (OR 1970=0.75 [0.67;0.84], OR 1958=1.05 [0.88;1.24]). A hierarchical bi-factor approach to modelling adolescent mental health indicated that the associations of externalising symptoms with later outcomes were mainly explained by their shared variance with internalising symptoms.

Conclusion

A strengthening trend in the associations of adolescent mental health with adverse mid-life outcomes across two generations highlights the individual and societal burden of adolescent mental health problems might be increasing. If this trend continues to apply to more recently born cohorts, the wide-ranging implications of the increasing prevalence in adolescent mental health difficulties currently observed should be recognised and increased public health efforts to minimise adverse outcomes are needed.
Cultural values predict national COVID-19 death rates
Authors: Ruck Damian J. , Borycz Joshua , Bentley R. Alexander
Published: July 2020

National responses to a pandemic require populations to comply through personal behaviors that occur in a cultural context. Here we show that aggregated cultural values of nations, derived from World Values Survey data, have been at least as important as top-down government actions in predicting the impact of COVID-19. Whereas trust in institutions predicts lower COVID-19 deaths per capita, secular-rationalism and cosmopolitanism each predict more deaths. The effects of these cultural values register more strongly than government efficiency. This suggests that open democracies may face greater challenges in limiting a pandemic, and that all nations should consider their cultural values as actionable parameters in their future preparations.
A New Adaptive Logistic Model for Epidemics and the Resurgence of COVID-19 in the United States
Authors: Roberts David H.
Published: July 2020

The Adaptive Logistic Model (ALM) of epidemics incorporates the results of infection mitigation effects on the course of an epidemic, and well describes the histories of the COVID-19 epidemics in many countries, including the United States. In particular, it is much more successful than is a basic logistic model. However, in the U.S. these mitigation efforts have recently been relaxed in many places, resulting in the second peak in infections that started in late May of 2020. In this paper the ALM is modified to account for the relaxation of these mitigation effects, leading to the Adaptive Logistic Model 2 (ALM-2). The ALM-2 is then used to understand quantitatively the second peak of COVID-19 cases. The ALM-2 is also successfully applied to the data on deaths even though they do not yet show a second peak.
Training and reployment of non-specialists is an effective solution for the shortage of health care workers in the COVID-19 pandemic
Authors: Kuang Ming , Wu Jianfeng , Luo Yifeng , Xiao Han , Liang Ruiming , Hu Wenjie , Cheng Shouzhen , Zhou Qian , Peng Sui , Cheng KarKeung , Xiao Haipeng
Published: July 2020

Importance

In the COVID-19 pandemic many countries encounter problems arising from shortage of specialists. Short intensive training and reployment of non-specialists is an option but the effectiveness is unknown.

Objective

To investigate whether there was difference in in-hospital mortality rates between COVID-19 patients managed by a mixed team (including non-specialists who had short intensive training and operated to a strict protocol) and those managed by a specialist team of health care workers.

Design

Cohort study, from January 26, 2020 to April 7, 2020, follow up to April 7, 2020.

Setting

Multicenter - Wuhan Hankou Hospital and Wuhan Xiehe Hospital, Wuhan, China.

Participants

261 HCWs deployed to Wuhan from Guangdong emergency rescue team and the 269 COVID-19 patients they treated.

Exposure

Among 261 health care workers, 130 were in the specialist team and included 33 physicians, 32 of whom (97.0%) of whom were from relevant specialties. Each physician was in charge of 25-27 beds, with a 6-hour shift time. The mixed team included 131 health care workers, with 7 of the 28 physicians (25.0%) from relevant specialties. Each physician managed 12-13 beds, with a 4-hour shift time.

Non-specialists received short-term intensive training and then followed strict management protocols. Specialists practiced as normal.

Main Outcomes and Measures

Main outcome was in-hospital mortality of COVID-19 patients. Another outcome was rate of SARS-CoV-2 infection in health care workers.

Results

A total of 269 patients were included (144 male). In-hospital mortality rate of patients treated by the specialist teams and the mixed teams was 12.6% (20/159) and 12.7% (14/110) respectively (Difference = −0.1%, 95% CI −8.2% to 7.9%, p=.97). None of the health care workers were infected.

Conclusions and Relevance

Training and reployment of non-specialists is an effective solution for the shortage of health care workers in the COVID-19 pandemic.

Key Points

Question

Was there difference in mortality rates between COVID-19 patients managed by a mixed team (including non-specialists who had short intensive training and operated to a strict protocol) and those managed by a specialist team of health care workers (HCWs)?

Findings

In-hospital mortality rate among patients managed by specialist team (130 HCWs, 159 patients) and mixed team (131 HCWs, 110 patients) was 12.6% (20/159) and 12.7% (14/110) respectively (Difference = −0.1%, 95% CI −8.2% to 7.9%, p=.97).

Meaning

With shortage of specialist HCWs, training and reployment of non-specialists is an effective option in the management of COVID-19 patients.
Trends in demographic and clinical characteristics of patients enrolled in HIV care and subsequent Antiretroviral Therapy initiation in the Central Africa International epidemiology Database to Evaluate AIDS (CA-IeDEA) Adult Cohort 2004-2018
Authors: Adedimeji Adebola A. , Hoover Donald R. , Shi Qiuhu , Kim Hae-Young , Brazier Ellen , Ross Jonathan , Murenzi Gad , Twizere Christella , Lelo Patricia , Nsonde Dominique , Ajeh Rogers , Dzudie Anastase , Nash Denis , Yotebieng Marcel , Anastos Kathryn M. ,   for the Central Africa IeDEA Consortium
Published: July 2020

Background

The Central Africa International epidemiology Database to Evaluate AIDS (CA-IeDEA) is a prospective study investigating impact, progression and long-term outcomes of HIV/AIDS among people living with HIV (PLWH) in Burundi, Cameroon, Democratic Republic of Congo (DRC), Republic of Congo (ROC) and Rwanda. We described trends in baseline demographic, clinical and immunological characteristics of patients aged >15 years entering into HIV care in the participating CA-IeDEA site and subsequent ART initiation.

Materials and Methods

Information on socio-demographic characteristics, height, weight, body mass index (BMI), CD4 cell count, WHO staging and ART status at entry into care from 2004 to 2018 were extracted from clinic records of patients aged >15 years enrolling in HIV care at participating clinics in Burundi, Cameroon, DRC, ROC and Rwanda. We assessed trends in patient characteristics at enrollment in HIV care and ART initiation at the participating site and calculated proportions, means and medians (interquartile ranges) for the main variables of interest.

Results

Among 69,176 participants in the CA-IeDEA cohort, 39% % were from Rwanda,, 24% from ROC, 18% from Cameroon, 14% from Burundi and 5% from DRC. More women (66%) than men were enrolled in care and subsequently initiated ART. Women were also younger (32 years) than men (38 years) (p= <0.001) when they enrolled in care or subsequently initiated ART at the participating site. Trends over time show increases in median CD4 cell count of 190 cells/uL in 2004 to 334 cells/uL in 2018 at enrollment. Among those with complete data on CD4 counts (60%), women had higher median CD4 cell count at care entry in the CA-IeDEA site (299 cells/uL) versus men (249 cells/uL; p= < 0.001).Trends in proportion of patients using ART show an increase from 16% in 2004 to 75% in 2018 among those initiating ART for the first time after entry into care in the participating site. As expected, median CD4 generally increased after ART initiation (p= <0.001).

Conclusion

Trends from 2004-2018 in the characteristics of patients participating in the CA-IeDEA cohort highlight improvements over time at entry into care and subsequent ART in all participating sites.
Using Hawkes Processes to model imported and local malaria cases in near-elimination settings
Authors: Unwin H. Juliette T. , Routledge Isobel , Flaxman Seth , Rizoiu Marian-Andrei , Lai Shengjie , Cohen Justin , Weiss Daniel J. , Mishra Swapnil , Bhatt Samir
Published: July 2020

Developing new methods for modelling infectious diseases outbreaks is important for monitoring transmission and developing policy. In this paper we propose using semi-mechanistic Hawkes Processes for modelling malaria transmission in near-elimination settings. Hawkes Processes are mathematical methods that enable us to combine the benefits of both statistical and mechanistic models to recreate and forecast disease transmission beyond just malaria outbreak scenarios. These methods have been successfully used in social media and earthquake modelling, but are not yet widespread in epidemiology. By using domain-specific knowledge, we can both recreate transmission curves for malaria in China and Swaziland and disentangle the proportion of cases which are imported from those that are community based.
Abnormalities in cortical pattern of coherence in interictal migraine detected using ultra high-density EEG
Authors: Chamanzar Alireza , Haigh Sarah M , Grover Pulkit , Behrmann Marlene
Published: July 2020

Individuals with migraine generally experience photophobia and/or phonophobia during and between migraine attacks. Many different mechanisms have been postulated to explain these migraine phenomena including abnormal patterns of connectivity across the cortex. The results, however, remain contradictory and there is no clear consensus on the nature of the cortical abnormalities in migraine. Here, we uncover alterations in cortical patterns of coherence (connectivity) in interictal migraineurs during the presentation of visual and auditory stimuli, as well as at rest, to capitalize on the sensory sensitivities that are characteristic of migraine, and to reconcile the conflicting literature on migraine cortical connectivity. We used a high-density electroencephalography (HD-EEG) system, with 128 customized electrode locations, to measure inter- and intra-hemispheric coherence from 17 individuals with migraine (12 female) in the interictal period, and 18 age- and gender-matched healthy control subjects, during visual (vertical grating pattern) and auditory (modulated tone) stimulation which varied in temporal frequency (4 and 6Hz), and during rest. To ensure that participants were attending, participants performed a color detection task at fixation. Analyses of the EEG signal included characterizing the inter- and intra-hemisphere coherence between the scalp EEG channels over 2-second time intervals and over different frequency bands at different spatial distances and spatial clusters, and Pearson’s correlation coefficients (PCCs) were estimated at zero-lag. Repeated measures (between-group) analyses-of-variance with post hoc multiple comparison correction were conducted. Relative to controls, migraineurs exhibited significantly (i) faster color detection performance; (ii) lower long-distance spatial coherence of alpha-band activity during both evoked conditions, regardless of the stimulation frequency; (iii) lower coherence between the right frontal cluster and all clusters in the left hemisphere (inter-hemisphere coherence) during 4Hz auditory and visual stimulation; and (iv) lower long-distance coherence (in all frequency bands) between the right occipito-parietal cluster and all other clusters during the (4Hz and 6Hz) visual stimuli. No significant group differences were observed in the resting state data. The abnormal patterns of EEG coherence in interictal migraineurs during visual and auditory stimuli may be associated with cortical hyper-excitability in migraineurs.