bluuebunny/crossref_metadata_2025 huggingface dataset:
Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations With 24-Month Growth and Neurodevelopment
Authors: Moraka Natasha O , Moyo Sikhulile , Smith Christiana , Ibrahim Maryanne , Mayondi Gloria , Leidner Jean , Powis Kathleen M , Cassidy Adam R , Kammerer Betsy , Ajibola Gbolahan , Williams Paige L , Weinberg Adriana , Musonda Rosemary , Shapiro Roger , Gaseitsiwe Simani , Lockman Shahin
Published: August 2020

Background

We sought to identify predictors of child cytomegalovirus (CMV) infection overall and by maternal HIV status and to assess associations of child CMV status with growth and neurodevelopmental outcomes at 24 months of age in Botswana.

Methods

Data and samples were used from the Botswana-based observational Tshipidi study (2010–2014), enrolling pregnant women living with and without HIV and following their infants through 2 years of age. Child plasma samples were tested at 18 months of age for anti-CMV immunoglobulin G (IgG). Associations were assessed between detectable anti-CMV IgG and growth (using the World Health Organization Child Growth Standards) and neurodevelopment (using the Bayley Scales of Infant and Toddler Development III and the Developmental Milestones Checklist) at 24 months of age.

Results

Of 317 children, 215 (68%) had detectable anti-CMV IgG at 18 months of age. Comparatively, 83% (n = 178) of HIV-unexposed uninfected (HUU) children had positive CMV serology vs 47% (n = 139) of HIV-exposed uninfected (HEU) children (P < .01); 100% of HUU vs 10.5% of HEU children breastfed. Child CMV infection was not associated with weight-for-age, weight-for-length, or length-for-age z-scores at 24 months. In HUU children, CMV infection was associated with smaller head circumference (P < .01). No difference was observed by child CMV status in any neurodevelopmental domain at 24 months.

Conclusions

We observed high CMV seropositivity in 18-month-old children in Botswana, with higher seropositivity among breastfed (HUU) children. Positive CMV serostatus was not associated with 24-month child growth or neurodevelopmental outcomes, with the exception of smaller head circumference among HUU CMV-positive children.
Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia
Authors: Son Hyo-Ju , Cho Eun Been , Bae Moonsuk , Lee Seung Cheol , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Kim Min Jae , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Kim Yang Soo , Chong Yong Pil
Published: August 2020

Background

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with significant mortality, causing worldwide concern, yet there are limited data on contributing microbiological factors. This study aimed to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia.

Methods

Adult patients with monomicrobial CRAB bacteremia in a 2700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled. Risk factors for 30-day mortality were evaluated. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and to genotyping by multilocus sequence typing.

Results

A total of 164 patients were enrolled, and 90 (55%) died within 30 days. The most common genotype among the isolates was ST191 (49%), and 12 isolates (7%) were resistant to colistin. Genotype, colistin minimum inhibitory concentration, and colistin resistance were not significantly associated with mortality, in contrast to several clinical factors. In multivariable analysis, ineradicable or not-eradicated focus (adjusted odds ratio [aOR], 4.92; 95% CI, 1.95–12.42; P = .001), septic shock (aOR, 4.72; 95% CI, 2.12–10.49; P < .001), and inappropriate antimicrobial therapy (aOR, 2.54; 95% CI, 1.05–6.16; P = .04) were independent risk factors for mortality. Among antibiotic strategies, colistin combined with tigecycline or other antibiotics were significantly associated with lower mortality after adjustment for confounding factors.

Conclusions

Clinical factors such as the nature of the infection source and source control, severity of bacteremia, and appropriateness of antibiotics, rather than microbiological factors, contribute to mortality in CRAB bacteremia. A specific antibiotic combination may help improve outcomes.
Benjamin Stillingfleet’s Notes on Paradise Lost, Lost and Found
Authors: Sugimura N K
Published: August 2020

This essay reveals that the annotated copy of Richard Bentley’s edition of Paradise Lost (1732) with MS notes attributed to Benjamin Stillingfleet (1702–1771), now housed in the British Library, is not, as has been assumed for over 170 years, in Stillingfleet’s autograph hand. Drawing on book history, biography, and manuscripts in various archives, this essay tells a three-way story about Stillingfleet’s holograph annotations on Paradise Lost, their partial transcription in the Bentley edition, and a set of‘original’ manuscript notes on the epic that Stillingfleet made while in Geneva in the early 1740s. It recounts how a predominantly male socio-literary culture—in which private manuscripts circulated among friends and were lent to antiquarians and editors alike—preserved one set of Stillingfleet’s handwritten notes in his interleaved two-volume Tonson edition of Paradise Lost (1727), while a partial copy of those notes was made by Stillingfleet’s close friend, Thomas Dampier (d. 1777), dean of Ely, in his interleaved copy of Bentley’s edition. Although Stillingfleet’s original and earlier‘sketch’ of manuscript notes appears to have been lost, the remarkably rich set of autograph notes on Milton’s epic made by Stillingfleet in the Tonson volume tantalizingly suggests what Stillingfleet’s prospective edition might have looked like, and how it positioned itself against Bentley’s edition of 1732. Stillingfleet’s autograph notes therefore significantly help in better understanding not only Milton’s reception history in the eighteenth century, but also the role his epic played in the eighteenth-century debate between the Ancients and the Moderns in English Enlightenment culture.
Nonrapid eye movement sleep electroencephalographic oscillations in idiopathic rapid eye movement sleep behavior disorder: a study of sleep spindles and slow oscillations
Authors: Sunwoo Jun-Sang , Cha Kwang Su , Byun Jung-Ick , Jun Jin-Sun , Kim Tae-Joon , Shin Jung-Won , Lee Soon-Tae , Jung Keun-Hwa , Park Kyung-Il , Chu Kon , Kim Manho , Lee Sang Kun , Kim Han-Joon , Schenck Carlos H , Jung Ki-Young
Published: August 2020

Study Objectives

We investigated electroencephalographic (EEG) slow oscillations (SOs), sleep spindles (SSs), and their temporal coordination during nonrapid eye movement (NREM) sleep in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).

Methods

We analyzed 16 patients with video-polysomnography-confirmed iRBD (age, 65.4 ± 6.6 years; male, 87.5%) and 10 controls (age, 62.3 ± 7.5 years; male, 70%). SSs and SOs were automatically detected during stage N2 and N3. We analyzed their characteristics, including density, frequency, duration, and amplitude. We additionally identified SO-locked spindles and examined their phase distribution and phase locking with the corresponding SO. For inter-group comparisons, we used the independent samples t-test or Wilcoxon rank-sum test, as appropriate.

Results

The SOs of iRBD patients had significantly lower amplitude, longer duration (p = 0.005 for both), and shallower slope (p < 0.001) than those of controls. The SS power of iRBD patients was significantly lower than that of controls (p = 0.002), although spindle density did not differ significantly. Furthermore, SO-locked spindles of iRBD patients prematurely occurred during the down-to-up-state transition of SOs, whereas those of controls occurred at the up-state peak of SOs (p = 0.009). The phase of SO-locked spindles showed a positive correlation with delayed recall subscores (p = 0.005) but not with tonic or phasic electromyography activity during REM sleep.

Conclusions

In this study, we found abnormal EEG oscillations during NREM sleep in patients with iRBD. The impaired temporal coupling between SOs and SSs may reflect early neurodegenerative changes in iRBD.
Metabolomic analysis coupled with extreme phenotype sampling identified that lysophosphatidylcholines are associated with multisite musculoskeletal pain
Authors: Liu Ming , Xie Zikun , Costello Christie A. , Zhang Weidong , Chen Liujun , Qi Dake , Furey Andrew , Randell Edward W. , Rahman Proton , Zhai Guangju
Published: August 2020

Musculoskeletal pain often occurs simultaneously at multiple anatomical sites. The aim of the study was to identify metabolic biomarkers for multisite musculoskeletal pain (MSMP) by metabolomics with an extreme phenotype sampling strategy. The study participants (n = 610) were derived from the Newfoundland Osteoarthritis Study. Musculoskeletal pain was assessed using a self-reported pain questionnaire where painful sites were circled on a manikin by participants and the total number of painful sites were calculated. Targeted metabolomic profiling on fasting plasma samples was performed using the Biocrates AbsoluteIDQ p180 kit. Plasma cytokine concentrations including tumor necrosis factor-α, interleukin-6, interleukin-1β, and macrophage migration inhibitory factor were assessed by enzyme-linked immunosorbent assay. Data on blood cholesterol profiles were retrieved from participants' medical records. Demographic, anthropological, and clinical information was self-reported. The number of reported painful sites ranged between 0 and 21. Two hundred and five participants were included in the analysis comprising 83 who had ≥7 painful sites and 122 who had ≤1 painful site. Women and younger people were more likely to have MSMP (P ≤ 0.02). Multisite musculoskeletal pain was associated with a higher risk of having incontinence, worse functional status and longer period of pain, and higher levels of low-density lipoprotein and non–high-density lipoprotein cholesterol (all P ≤ 0.03). Among the 186 metabolites measured, 2 lysophosphatidylcholines, 1 with 26 carbons with no double bond and 1 with 28 carbons with 1 double bond, were significantly and positively associated with MSMP after adjusting for multiple testing with the Bonferroni method (P ≤ 0.0001) and could be considered as novel metabolic markers for MSMP.
Risk Factors of Redo Surgery After Unilateral Focused Parathyroidectomy
Authors: Donatini Gianluca , Marciniak Camille , Lenne Xavier , Clément Guillaume , Bruandet Amélie , Sebag Frédéric , Mirallié Eric , Mathonnet Muriel , Brunaud Laurent , Lifante Jean-Christophe , Tresallet Christophe , Ménégaux Fabrice , Theis Didier , Pattou François , Caiazzo Robert
Published: August 2020

Background:

Surgical removal of hyperfunctional parathyroid gland is the definitive treatment for primary hyperparathyroidism (pHPT). Postoperative follow-up shows variability in persistent/recurrent disease rate throughout different centers.

Objective:

To evaluate the incidence of redo surgery after targeted parathyroidectomy for pHPT.

Methods:

We performed a nationwide retrospective cohort study on the “Programme de Medicalisation des Systemes d’Information,” the French administrative database that collects information on all healthcare facilities’ discharges. We extracted data from 2009 to 2018 for all patients who underwent parathyroidectomy for pHPT between January 2011 to December 2016. The primary outcome was the reoperation rate within 2 years since first surgery. Patients who had a first attempt of surgery within the previous 24 months, familial hyperparathyroidism, multiglandular disease, and renal failure were excluded. Results were adjusted according to sex and the Elixhauser Comorbidity Index. Operative volume thresholds to define high-volume centers were achieved by the Chi-Squared Automatic Interaction Detector method.

Results:

In the study period, 13,247 patients (median age 63, F/M=3.6) had a focused parathyroidectomy by open (88.7%) or endoscopic approach. Need of remedial surgery was 2.8% at 2 years. In multivariate analysis, factors predicting redo surgery were: cardiac history (P=0.008), obesity (P=0.048), endoscopic approach (P=0.005), and low-volume center (P<0.001). We evaluated that an annual caseload of 31 parathyroidectomies was the best threshold to discriminate high-volume centers and carries the lowest morbidity/failure rate.

Conclusion:

Although focused parathyroidectomy represents a standardized operation, cure rate is strongly associated with annual hospital caseload, type of procedure (endoscopic), and patients’ features (obesity, cardiac history). Patients with risk factors for redo surgery should be considered for an open surgery in a high-volume center.
Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial
Authors: Nilsson Klara , Klevebro Fredrik , Rouvelas Ioannis , Lindblad Mats , Szabo Eva , Halldestam Ingvar , Smedh Ulrika , Wallner Bengt , Johansson Jan , Johnsen Gjermund , Aahlin Eirik Kjus , Johannessen Hans-Olaf , Hjortland Geir Olav , Bartella Isabel , Schröder Wolfgang , Bruns Christiane , Nilsson Magnus
Published: August 2020

Objective:

To investigate if prolonged TTS after completed nCRT improves postoperative outcomes for esophageal and esophagogastric junction cancer.

Summary of Background Data:

TTS has traditionally been 4–6 weeks after completed nCRT. However, the optimal timing is not known.

Methods:

A multicenter clinical trial was performed with randomized allocation of TTS of 4–6 or 10–12 weeks. The primary endpoint of this sub-study was overall postoperative complications defined as Clavien-Dindo grade II-V. Secondary endpoints included complication severity according to Clavien-Dindo grade IIIb-V, postoperative 90-day mortality, and length of hospital stay. The study was registered in Clinicaltrials.gov (NCT02415101).

Results:

In total 249 patients were randomized. There were no significant differences between standard TTS and prolonged TTS with regard to overall incidence of complications Clavien-Dindo grade II–V (63.2% vs 72.6%, P = 0.134) or regarding Clavien-Dindo grade IIIb–V complications (31.6% vs 34.9%, P = 0.603). There were no statistically significant differences between standard and prolonged TTS regarding anastomotic leak (P = 0.596), conduit necrosis (P = 0.524), chyle leak (P = 0.427), pneumonia (P = 0.548), and respiratory failure (P = 0.723). In the standard TTS arm 5 patients (4.3%) died within 90 days of surgery, compared to 4 patients (3.8%) in the prolonged TTS arm (P = 1.0). Median length of hospital stay was 15 days in the standard TTS arm and 17 days in the prolonged TTS arm (P = 0.234).

Conclusion:

The timing of surgery after completed nCRT for carcinoma of the esophagus or esophagogastric junction, is not of major importance with regard to short-term postoperative outcomes.
SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study
Authors: Hurst Jillian H. , Heston Sarah M. , Chambers Hailey N. , Cunningham Hannah M. , Price Meghan J. , Suarez Liliana , Crew Carter G. , Bose Shree , Aquino Jhoanna N. , Carr Stuart T. , Griffin S. Michelle , Smith Stephanie H. , Jenkins Kirsten , Pfeiffer Trevor S. , Rodriguez Javier , DeMarco C. Todd , De Naeyer Nicole A. , Gurley Thaddeus C. , Louzao Raul , Cunningham Coleen K. , Steinbach William J. , Denny Thomas N. , Lugo Debra J. , Moody M. Anthony , Permar Sallie R. , Rotta Alexandre T. , Turner Nicholas A. , Walter Emmanuel B. , Woods Christopher W. , Kelly Matthew S.
Published: August 2020

BACKGROUND

Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children.

METHODS

We conducted a prospective cohort study of children and adolescents (<21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay.

RESULTS

Of 382 children, 289 (76%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have a history of asthma (p=0.009), and more likely to have an infected sibling contact (p=0.0007) than uninfected children. Children ages 6-13 years were frequently asymptomatic (38%) and had respiratory symptoms less often than younger children (30% vs. 49%; p=0.008) or adolescents (30% vs. 59%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p=0.002), gastrointestinal (26% vs. 9%; p=0.003), and sensory symptoms (43% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.004]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children.

CONCLUSIONS

Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while a history of asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.
Laboratory biomarkers associated with COVID-19 severity and management
Authors: Keddie S , Ziff O , Chou MKL , Taylor RL , Heslegrave A , Garr E , Lakdawala N , Church A , Ludwig D , Manson J , Scully M , Nastouli E , Chapman MD , Hart M , Lunn MP
Published: August 2020

The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure and need of higher-level care.

From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS and level of respiratory support (p≤0.001). IL-6 levels of ≥3.27pg/ml provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37mg/L of 0.91 and 0.66.

Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients.
Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study
Authors: Liu Anthony P.Y. , Li Bryan K. , Pfaff Elke , Gudenas Brian , Vasiljevic Alexandre , Orr Brent A. , Dufour Christelle , Snuderl Matija , Karajannis Matthias A. , Rosenblum Marc K. , Hwang Eugene I. , Ng Ho-Keung , Hansford Jordan R. , Szathmari Alexandru , Faure-Conter Cécile , Merchant Thomas E. , von Hoff Katja , Mynarek Martin , Rutkowski Stefan , Sahm Felix , Hawkins Cynthia , Robinson Giles W. , Gajjar Amar , Pfister Stefan M. , Bouffet Eric , Northcott Paul A. , Jones David T.W. , Huang Annie
Published: August 2020

Background

Recent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked power to integrate molecular and clinical findings. The different proposed subgroup structures also highlighted a need to reach consensus on a robust and relevant classification system.

Methods

We performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical and genomic features of patients and samples from these pineal tumor subgroups were annotated.

Findings

Four clinically and biologically relevant consensus PB subgroups were defined: PB-miRNA1 (n=96), PB-miRNA2 (n=23), PB-MYC/FOXR2 (n=34) and PB-RB1 (n=25); with PPTID (n=43) remaining as a molecularly distinct entity. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual subgroups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2,MYCamplification andFOXR2overexpression in PB-MYC/FOXR2,RB1alteration in PB-RB1, andKBTBD4insertion in PPTID. Age at diagnosis, sex predilection and metastatic status varied significantly among tumor subgroups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 and PB-RB1.

Interpretation

We systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease subgroups, laying the groundwork for future studies as well as routine use in tumor classification.
The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals
Authors: González María Mateos , Gonzalo Elena Sierra , Lopez Irene Casado , Fernández Francisco Arnalich , Pérez José Luis Beato , Monge Daniel Monge , Núñez Juan Antonio Vargas , Fenoll Rosa García , Fernández Carmen Suárez , Castro Santiago Jesús Freire , Bailon Manuel Mendez , Fraile Isabel Perales , Madrazo Manuel , Fontan Paula Maria Pesqueira , Gamboa Jeffrey Oskar Magallanes , García Andrés González , Vieitez Anxela Crestelo , Aizpuru Eva María Fonseca , Arostegui Asier Aranguren , Erdozain Ainara Coduras , Cilleros Carmen Martinez , Amigo Jose Loureiro , Epelde Francisco , Bermejo Carlos Lumbreras , Santos Juan Miguel Antón ,   for the SEMI-COVID-19 Network
Published: August 2020

Objectives

A decrease in blood cell counts, especially lymphocytes and eosinophils, has been described in patients with severe SARS-CoV-2 (COVID-19), but there is no knowledge of the potential role of their recovery in these patients’ prognosis. This article aims to analyse the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19.

Design

This work is a multicentre, retrospective, cohort study of 9,644 hospitalised patients with confirmed COVID-19 from the Spanish Society of Internal Medicine’s SEMI-COVID-19 Registry.

Setting

This study examined patients hospitalised in 147 hospitals throughout Spain.

Participants

This work analysed 9,644 patients (57.12% male) out of a cohort of 12,826 patients ≥18 years of age hospitalised with COVID-19 in Spain included in the SEMI-COVID-19 Registry as of 29 May 2020.

Main outcome measures

The main outcome measure of this work is the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Univariate analysis was performed to determine possible predictors of death and then multivariate analysis was carried out to control for potential confounders.

Results

An increase in the eosinophil count on the seventh day of hospitalisation was associated with a better prognosis, including lower mortality rates (5.2% vs 22.6% in non-recoverers, OR 0.234 [95% CI, 0.154 to 0.354]) and lower complication rates, especially regarding to development of acute respiratory distress syndrome (8% vs 20.1%, p=0.000) and ICU admission (5.4% vs 10.8%, p=0.000). Lymphocyte recovery was found to have no effect on prognosis. Treatment with inhaled or systemic glucocorticoids was not found to be a confounding factor.

Conclusion

Eosinophil recovery in patients with COVID-19 is a reliable marker of a good prognosis that is independent of prior treatment. This finding could be used to guide discharge decisions.
Machine learning and AI aided tool to differentiate COVID 19 and non-COVID 19 lung CXR
Authors: Adwibowo Andrio
Published: August 2020

One of the main challenges in dealing with the current COVID 19 pandemic is how to detect and distinguish between the COVID 19 and non COVID 19 cases. This problem arises since COVID 19 symptoms resemble with other cases. One of the golden standards is by examining the lung using the chest X ray radiograph (CXR). Currently there is growing COVID 19 cases followed by the CXR images waiting to be analyzed and this may outnumber the health capacity. Learning from that current situation and to fulfill the demand for CXRs analysis, a novel solution is required. The tool is expected can detect and distinguish the COVID 19 case lung rely on CXR. Respectively, this study aims to propose the use of AI and machine learning aided tool to distinguish the COVID 19 and non COVID 19 cases based on the CXR lung image. The compared non COVID 19 CXR cases in this study include normal (healthy), influenza A, tuberculosis, and active smoker. The results confirm that the machine learning tool is able to distinguish the COVID 19 CXR lungs based on lung consolidation. Moreover, the tool is also able to recognize an abnormality of COVID 19 lung in the form of patchy ground glass opacity.

To conclude, AI and machine learning may be considered as a detection tool to identify and distinguish between COVID 19 and non COVID 19 cases in particular epidemic areas.
Covid-19 transmission dynamics during the unlock phase and significance of testing
Authors: Paul Abhijit , Chatterjee Samrat , Bairagi Nandadulal
Published: August 2020

The pandemic disease Covid-19 caused by SARS-COV-2, which emerged from Wuhan, China, has established itself as the most devastating disease in the history of infectious disease, affecting 216 countries/territories across the world. Different countries have developed and adopted various policies to contain this epidemic and the most common were the social distancing and lockdown. Though some countries have come out of this pandemic, the infection is still increasing and remains very serious in the rest of the world. Even when the disease is not under control, many countries have withdrawn the lockdown and going through the phase-wise unlocking process, causing a further increment in the infection rate. In such a scenario, the role of the undetected class of infected individuals has become very crucial. The present study is an attempt to understand and estimate the possible epidemic burden during the unlock phase in the presence of an undetected class. We proposed a modified SEIR model and dissected the epidemiological status of different countries with the available data. With the initial establishment of the model with the epidemic data of four countries, which have already attained the epidemic peak, the study focused more on countries like India and the USA, where the epidemic curve is still growing, but the unlock process has started. As a straightforward result, we noticed a significant increase in the undetected and detected infected cases under the ongoing unlock phase. Under such conditions, our recalibration exercise showed that an increase in the testing could revert the existing growth rate of the infected cases to the lower growth rate of the lockdown period. Our present study emphasizes on the implementation of 3T principles, trace, test, and treat, to contain the epidemic. The significance of large scale testing in controlling the epidemic is true for both India and the USA though they have different socio-economic conditions. The use of repurposing drugs may further decrease the infected cases and help the disease controlling process. We believe our proposed strategy obtained through a mathematical model will help to make a better policy for the unlock phase.
COSTS ASSOCIATED WITH TRANSRADIAL ACCESS AND SAME-DAY DISCHARGE AFTER PERCUTANEOUS CORONARY INTERVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kulkarni Hemant , Thangam Manoj , Lindner Samuel , McNeely Christian , Amin Amit P.
Published: August 2020

Introduction

Transradial access for PCI (TRI) along with same day discharge (SDD) is associated with varying estimates of cost savings depending on the population studied, the clinical scenario and application to low-risk vs high-risk patients. A summary estimate of the true cost savings of TRI and SDD are unknown.

Methods

We searched the PubMed, EMBASE®, CINAHL® and Google Scholar® databases for published studies on hospitalization costs of TRI and SDD. Primary outcome of interest in all included studies was the cost saving with TRI (or SDD), inflation-corrected US$ 2018 values using the medical consumer price index. For meta-analytic synthesis, we used Hedges’ summary estimate (g) in a random-effects framework of the DerSimonian and Laird model, with inverse variance weights. Heterogeneity was quantified using the 12 statistic.

Results

The cost savings of TRI from four US studies reported a consistent and significant cost saving associated with TRI after accounting for currency inflation, of US$ 992 (95% CI US$ 8501,134). The cost savings of SDD from six US studies, after inflation-correcting to the year 2018, were US$ 3,567.58 (95% CI US$ 2,303 –4,832).

Conclusions

In conclusion, this meta-analysis demonstrates that TRI and SDD are associated with mean cost reductions of by approximately US$1,000/patient and US$ 3,600/patient, respectively, albeit with wide heterogeneity in the cost estimates. When combined with the safety of TRI and SDD, this meta-analysis underscores the value of combining TRI and SDD pathways and calls for a wide-ranging practice change in the direction of TRI and SDD.
Individualizing deep dynamic models for psychological resilience data
Authors: Köber Göran , Pooseh Shakoor , Engen Haakon , Chmitorz Andrea , Kampa Miriam , Schick Anita , Sebastian Alexandra , Tüscher Oliver , Wessa Michèle , Yuen Kenneth S.L. , Walter Henrik , Kalisch Raffael , Timmer Jens , Binder Harald
Published: August 2020

Deep learning approaches can uncover complex patterns in data. In particular, variational autoencoders (VAEs) achieve this by a non-linear mapping of data into a low-dimensional latent space. Motivated by an application to psychological resilience in the Mainz Resilience Project (MARP), which features intermittent longitudinal measurements of stressors and mental health, we propose an approach for individualized, dynamic modeling in this latent space. Specifically, we utilize ordinary differential equations (ODEs) and develop a novel technique for obtaining person-specific ODE parameters even in settings with a rather small number of individuals and observations, incomplete data, and a differing number of observations per individual. This technique allows us to subsequently investigate individual reactions to stimuli, such as the mental health impact of stressors. A potentially large number of baseline characteristics can then be linked to this individual response by regularized regression, e.g., for identifying resilience factors. Thus, our new method provides a way of connecting different kinds of complex longitudinal and baseline measures via individualized, dynamic models. The promising results obtained in the exemplary resilience application indicate that our proposal for dynamic deep learning might also be more generally useful for other application domains.
Persistence of SARS-CoV-2 in the first trimester placenta leading to vertical transmission and fetal demise from an asymptomatic mother
Authors: Shende Prajakta , Gaikwad Pradip , Gandhewar Manisha , Ukey Pawankumar , Bhide Anshul , Patel Vainav , Bhagat Sharad , Bhor Vikrant , Mahale Smita , Gajbhiye Rahul , Modi Deepak
Published: August 2020

Coronaviruses infect the respiratory tract and are known to survive in these tissues during the clinical course of infection. However, how long can SARS-CoV-2 survive in the tissues is hitherto unknown. Herein, we report a case where the virus is detected in the first trimester placental cytotrophoblast and syncytiotrophoblasts five weeks after the asymptomatic mother cleared the virus from the respiratory tract. This first trimester placental infection was vertically transmitted as the virus was detected in the amniotic fluid and fetal membranes. This congenitally acquired SARS-CoV-2 infection was associated with hydrops and fetal demise. This is the first study providing concrete evidences towards persistent tissue infection of SARS-CoV-2, its congenital transmission in early pregnancy leading to intrauterine fetal death.
OxCOVID19 Database, a multimodal data repository for better understanding the global impact of COVID-19
Authors: Mahdi Adam , Błaszczyk Piotr , Dłotko Paweł , Salvi Dario , Chan Tak-Shing , Harvey John , Gurnari Davide , Wu Yue , Farhat Ahmad , Hellmer Niklas , Zarebski Alexander , Hogan Bernie , Tarassenko Lionel
Published: August 2020

Oxford COVID-19 Database (OxCOVID19 Database) is a comprehensive source of information related to the COVID-19 pandemic. This relational database contains time-series data on epidemiology, government responses, mobility, weather and more across time and space for all countries at the national level, and for more than 50 countries at the regional level. It is curated from a variety of (wherever available) official sources. Its purpose is to facilitate the analysis of the spread of SARS-CoV-2 virus and to assess the effects of non-pharmaceutical interventions to reduce the impact of the pandemic. Our database is a freely available, daily updated tool that provides unified and granular information across geographical regions.
SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing
Authors: Rathe Jennifer A. , Hemann Emily A. , Eggenberger Julie , Li Zhaoqi , Knoll Megan L. , Stokes Caleb , Hsiang Tien-Ying , Netland Jason , Takehara Kennidy , Pepper Marion , Gale Michael
Published: August 2020

Background

To determine how serologic antibody testing outcome links with virus neutralization of SARS-CoV-2 to ascertain immune protection status, we evaluated a unique set of individuals for SARS-CoV-2 antibody detection and viral neutralization.

Methods

Herein, we compare several analytic platforms with 15 positive and 30 negative SARS-CoV-2 infected controls followed by viral neutralization assessment. We then applied these platforms in a clinically relevant population: 114 individuals with unknown histories of SARS-CoV-2 infection.

Results

In control populations, the best performing antibody detection assays were SARS-CoV-2 receptor binding domain (RBD) IgG (specificity 87%, sensitivity 100%, PPV 100%, NPV 93%), spike IgG3 (specificity 93%, sensitivity 97%, PPV 93%, NPV 97%), and nucleocapsid (NP) protein IgG (specificity 93%, sensitivity 97%, PPV 93%, NPV 97%). Neutralization of positive and negative control sera showed 100% agreement. 20 unknown individuals had detectable SARS-CoV-2 antibodies with 16 demonstrating virus neutralization. The antibody assays that best predicted virus neutralization were RBD IgG (misidentified 2), spike IgG3 (misidentified 1), and NP IgG (misidentified 2).

Conclusion

These data suggest that meaningful evaluation of antibody assay performance requires testing in an unknown population. Further, these results indicate coupling of virus neutralization analysis to a positive antibody test is required to categorize patients based on SARS-CoV-2 immune protection status following virus exposure or vaccine administration. One of the antibody detection platforms identified in this study followed by the pseudoneutralization or focus reduction assay would provide a practical testing strategy to assess for SARS-CoV-2 antibodies with optimal prediction of correlates to neutralizing immunity.

Funding

Supported by NIH grants AI148684, AI151698, AI145296, and UW funds to the Center for Innate Immunity and Immune Disease.
Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer
Authors: Brock Kristian , Homer Victoria , Soul Gurjinder , Potter Claire , Chiuzan Cody , Lee Shing
Published: August 2020

The overwhelming majority of dose-escalation clinical trials use methods that seek a maximum tolerable dose, including rule-based methods like the 3+3, and model-based methods like CRM and EWOC. These methods assume that the incidences of efficacy and toxicity always increase as dose is increased. This assumption is widely accepted with cytotoxic therapies. In recent decades, however, the search for novel cancer treatments has broadened, increasingly focusing on inhibitors and antibodies. The rationale that higher doses are always associated with superior efficacy is less clear for these types of therapies. We extracted dose-level efficacy and toxicity outcomes from 115 manuscripts reporting dose-finding clinical trials in cancer between 2008 and 2014. We analysed the outcomes from each manuscript using flexible non-linear regression models to investigate the evidence supporting the monotonic efficacy and toxicity assumptions. We found that the monotonic toxicity assumption was well-supported across most treatment classes and disease areas. In contrast, we found very little evidence supporting the monotonic efficacy assumption. Our conclusion is that dose-escalation trials routinely use methods whose assumptions are violated by the outcomes observed. As a consequence, dose-finding trials risk recommending unjustifiably high doses that are harmful to patients. We recommend that trialists consider experimental designs that allow toxicity and efficacy outcomes to jointly determine the doses given to patients and recommended for further study.
Comparisons of COVID-19 dynamics in the different countries of the World using Time-Series clustering
Authors: Alvarez Emiliano , Gabriel Brida Juan , Limas Erick
Published: August 2020

In recent months, the world has suffered from the appearance of a new strain of coronavirus, causing the COVID-19 pandemic. There are great scientific efforts to find new treatments and vaccines, at the same time that governments, companies, and individuals have taken a series of actions in response to this pandemic. These efforts seek to decrease the speed of propagation, although with significant social and economic costs. Countries have taken different actions, also with different results. In this article we use non-parametric techniques (HT and MST) with the aim of identifying groups of countries with a similar spread of the coronavirus. The variable of interest is the number of daily infections per country. Results show that there are groups of countries with differentiated contagion dynamics, both in the number of contagions plus at the time of the greatest transmission of the disease. It is concluded that the actions taken by the countries, the speed at which they were taken and the number of tests carried out may explain part of the differences in the dynamics of contagion.
Role of IgM and IgA Antibodies to the Neutralization of SARS-CoV-2
Authors: Klingler Jéromine , Weiss Svenja , Itri Vincenza , Liu Xiaomei , Oguntuyo Kasopefoluwa Y. , Stevens Christian , Ikegame Satoshi , Hung Chuan-Tien , Enyindah-Asonye Gospel , Amanat Fatima , Baine Ian , Arinsburg Suzanne , Bandres Juan C. , Milunka Kojic Erna , Stoever Jonathan , Jurczyszak Denise , Bermudez-Gonzalez Maria , Simon Viviana , Liu Sean , Lee Benhur , Krammer Florian , Zolla-Pazner Susan , Hioe Catarina E.
Published: August 2020

SARS-CoV-2 has infected millions of people and is on a trajectory to kill more than one million globally. Virus entry depends on the receptor-binding domain (RBD) of the spike protein. Although previous studies demonstrated anti-spike and –RBD antibodies as essential for protection and convalescent plasma as a promising therapeutic option, little is known about the immunoglobulin (Ig) isotypes capable of blocking virus entry. Here, we studied spike- and RBD-specific Ig isotypes in plasma/sera from two acutely infected and 29 convalescent individuals. Spike- and RBD-specific IgM, IgG1, and IgA1 antibodies were produced by all or nearly all subjects at varying levels and detected at 7–8 days post-disease onset. IgG2, IgG3, IgG4, and IgA2 were also present but at much lower levels. All samples also displayed neutralizing activity. IgM, IgG, and IgA were capable of mediating neutralization, but neutralization titers correlated better with binding levels of IgM and IgA1 than IgG.
A co-infection model for Two-Strain Malaria and Cholera with Optimal Control
Authors: Egeonu K. U. , Inyama S. C. , Omame A.
Published: August 2020

A mathematical model for two strains of Malaria and Cholera with optimal control is studied and analyzed to assess the impact of treatment controls in reducing the burden of the diseases in a population, in the presence of malaria drug resistance. The model is shown to exhibit the dynamical property of backward bifurcation when the associated reproduction number is less than unity. The global asymptotic stability of the disease-free equilibrium of the model is proven not to exist. The necessary conditions for the existence of optimal control and the optimality system for the model is established using the Pontryagin’s Maximum Principle. Numerical simulations of the optimal control model reveal that malaria drug resistance can greatly influence the co-infection cases averted, even in the presence of treatment controls for co-infected individuals.
Convalescent plasma for patients with severe COVID-19: a matched cohort study
Authors: Rogers Ralph , Shehadeh Fadi , Mylona Evangelia , Rich Josiah , Neill Marguerite , Touzard-Romo Francine , Geffert Sara , Larkin Jerome , Bailey Jeffrey A. , Lu Shaolei , Sweeney Joseph , Mylonakis Eleftherios
Published: August 2020

Background

The efficacy of convalescent plasma (CP) for the treatment of COVID-19 remains unclear.

Methods

A matched cohort analysis of hospitalized patients with severe COVID-19. The impact of CP treatment on all cause in-hospital mortality was evaluated using univariate and multivariate Cox proportional-hazards models, and the impact of CP treatment on the time to hospital discharge was assessed using a stratified log-rank analysis.

Results

64 patients who received CP a median of 7 days after symptom onset were compared to a matched control group of 177 patients. Overall in-hospital mortality was 14.9%. There was no significant difference in the risk of in-hospital mortality between the two groups (adjusted hazard ratio [aHR] 0.93, 95% confidence interval [CI] 0.39 – 2.20). There was also no significant difference in the overall rate of hospital discharge (rate ratio [RR] 1.28, 95% CI 0.91 – 1.81), but a subgroup analysis of patients 65-years-old or greater who received CP demonstrated a significantly increased hospital discharge rate among these patients (RR 1.86, 95% CI 1.03 – 3.36). There was a greater than expected frequency of transfusion reactions in the CP group (2.8% reaction rate observed per unit transfused).

Conclusions

The use of CP in this study was a safe treatment for COVID-19. There was no overall significant reduction of in-hospital mortality or increased rate of hospital discharge associated with the use of CP in this study, although there was a signal for improved outcomes among the elderly. Further adequately powered randomized studies should target this subgroup when assessing the efficacy CP treatment.
Inadequate preparedness for response to COVID-19 is associated with stress and burnout among healthcare workers in Ghana
Authors: Afulani Patience A. , Gyamerah Akua O. , Nutor Jerry John , Laar Amos , Aborigo Raymond , Malechi Hawa , Sterling Mona , Awoonor-Williams John Koku
Published: August 2020

Introduction

The COVID-19 pandemic has compounded the global crisis of stress and burnout among healthcare workers (HCWs). But few studies have empirically examined the factors driving these outcomes. We examined the association between perceived preparedness to respond to the pandemic and HCW stress and burnout and identified potential mediating factors among HCWs in Ghana.

Methods

Data are from HCWs in Ghana who completed a cross-sectional self-administered online survey; 414 and 409 HCWs completed stress and burnout questions, respectively. Perceived preparedness, stress, and burnout were measured using validated psychosocial measures. We assessed associations using linear regressions with robust standard errors.

Results

The average score for preparedness was 24 (SD = 8.8), 16.3 (SD = 5.9) for stress, and 37.4 (SD = 15.5) for burnout. In multivariate analysis, HCWs who felt somewhat prepared and prepared had lower stress (β = −1.89, 95%CI:-3.49 to −0.30 and β = –2.66, 95%CI:-4.48 to −0.84) and burnout (β = –7.74, 95%CI:−11.8 to −3.64 and β = –9.25, 95%CI:-14.1 to –4.41) scores than those who did not feel prepared. Appreciation from management and family support were associated with lower stress and burnout, while fear of infection was associated with higher stress burnout. Fear of infection partially mediated the relationship between perceived preparedness and stress/burnout, accounting for about 16 to17% of the effect.

Conclusion

Low perceived preparedness to respond to COVID-19 increases stress and burnout, and this is partly through fear of infection. Interventions to increase HCWs’ morale and capacity to respond to the pandemic are needed.

Strengths and limitations of this study

Our study is among the first to report data on COVID-19 related stress and burnout among HCWs in Africa and to identify contributing factors, including HCWs’ perceived preparedness to respond to the pandemic.

We used validated psychosocial measures of stress and burnout, as well as a perceived preparedness for COVID-19 scale developed by our team, which has high validity and reliability; this scale can facilitate similar research in other settings.

Our study shows that among healthcare workers in Ghana, low perceived preparedness to respond to the COVID-19 pandemic is associated with higher levels of stress and burnout and this association is partially mediated by fear of infection.

Perceived appreciation from management and family support on the other hand are associated with lower stress and burnout.

Findings are based on self-reported data from a cross-sectional online survey, thus, there may be social desirability bias; associations described are not causal; and the online survey may limit generalizability.
Environmental risk factors of airborne viral transmission: Humidity, Influenza and SARS-CoV-2 in the Netherlands
Authors: Ravelli Edsard , Martinez Rolando Gonzales
Published: August 2020

Objective

The relationship between specific humidity and influenza/SARS-CoV-2 in the Netherlands is evaluated over time and at regional level.

Design

Parametric and non-parametric correlation coefficients are calculated to quantify the relationship between humidity and influenza, using five years of weekly data. Bayesian spatio-temporal models—with a Poisson and a Gaussian likelihood—are estimated to find the relationship between regional humidity and the daily cases of SARS-CoV-2 in the municipalities and provinces of the Netherlands.

Results

An inverse (negative) relationship is observed between specific humidity and the incidence of influenza between 2015 and 2019. The space-time analysis indicates that an increase of specific humidity of one gram of water vapor per kilogram of air (1 g/kg) is related to a reduction of approximately 5% in the risk of COVID-19 infections.

Conclusions

The increase in humidity during the outbreak of the SARS-CoV-2 in the Netherlands helped to reduce the risk of regional COVID-19 infections. Public policies that promote higher levels of specific humidification—above 6 g/Kg—can lead to significant reductions in the spread of respiratory viruses, such as influenza and SARS-CoV-2.