bluuebunny/crossref_metadata_2025 huggingface dataset:
Priority Setting of Ventilators in the COVID-19 Pandemic from the public’s perspective
Authors: Asghari Fariba , Parsapour Alireza , Gooshki Ehsan Shamsi
Published: June 2020

Background

Ventilator allocation plan for public health crisis should be developed through recognizing the values of society and engaging the general public. This study was conducted to assess the Iranian citizens’ attitude about a number of principles and criteria for allocation of ventilators in current COVID-19 epidemic.

Materials and Methods

An electronic self-administered questionnaire was publicly distributed through social networks of Telegram and WhatsApp to perform this cross-sectional study. The questionnaire consisted of 11 statements about the selection and prioritization of patients for the use of a ventilator.

Results

1262 persons, including 767 citizens and 495 health care providers participated in this study. More than 95% of participants agreed upon the necessity to avoid discrimination and avoid prioritization according to patients’ gender, economic and political status. While 40.9% of citizens and 49.6% of healthcare workers believed that a ventilator can be disconnected from a patient with a poor prognosis to help a patient who has a better prognosis (P-value=0.13), 34.3% of people and 29.6% of healthcare workers believed that the earlier admitted patients have the right to receive the device even if the likeliness of his/her survival is less than the next patient (P-value=0.009).

Conclusions

This study showed that people accept maximizing health benefits as a measure of ventilator allocation in the pandemic of COVID-19. At the same time, periodic evaluation of patients and disconnecting the device from a patient that no longer benefits from ICU services requires its scientific and ethical basis to be brought in public discourse.
Outcomes following acute poor-grade aneurysmal subarachnoid bleed - Is early definitive treatment better than delayed management?
Authors: Gittins Adam , Talbott Nick , Gilani Ahmed A , Packer Greg , Browne Richard , Mullhi Randeep , Khan Zaheed , Whitehouse T , Belli Antonio , Mehta Rajnikant L , Gao-Smith Fang , Veenith Tonny
Published: June 2020

Background/Objective

Patients with poor-grade subarachnoid bleed (pSAH, World Federation of Neurosurgeons grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 hours (IM) and delayed management after 24 hours (DM) in patients following pSAH.

Methods

This was a retrospective population-based study, including patients with pSAH who received definitive management between 1st January 2011 and 31st December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio (OR) of favourable outcome (Glasgow Outcome Scale (GOS) 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale (GOS). The secondary outcomes included adjusted OR of a favourable outcome at discharge, three months and six months following discharge and survival rate at 28 days, three months, six months and 12 months following haemorrhage.

Results

111 patients were included in this study: 53 (48%) received immediate management (IM) and 58 (41%) received delayed management (DM). The mean time delay from referral to intervention was 14.9±5.8 hours in IM patients, compared to 79.6±106.1 hours in DM patients. At 12 months following discharge, the adjusted OR for favourable outcome in IM versus DM patients was 0.96 (CI 0.17, 5.39; p=0.961). At hospital discharge, three months and six months, the adjusted OR for favourable outcome was 3.85 (CI 1.38, 10.73; p=0.010), 1.04 (CI 0.22, 5.00; p=0.956) and 0.98 (CI 0.21, 4.58; p=0.982), respectively. There were no differences in survival rate between the groups at 28 days, three months, six months and 12 months (71.7% in IM group vs 82.8% in DM group at 12 months, p=0.163).

Conclusions

IM and DM after pSAH are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.
Serology-informed estimates of SARS-COV-2 infection fatality risk in Geneva, Switzerland
Authors: Perez-Saez Javier , Lauer Stephen A , Kaiser Laurent , Regard Simon , Delaporte Elisabeth , Guessous Idris , Stringhini Silvia , Azman Andrew S ,   for the Serocov-POP Study Group
Published: June 2020

The infection fatality risk (IFR) is the average number of deaths per infection by a pathogen and is key to characterizing the severity of infection across the population and for specific demographic groups. To date, there are few empirical estimates of IFR published due to challenges in measuring infection rates.1,2 Outside of closed, closely surveilled populations where infection rates can be monitored through viral surveillance, we must rely on indirect measures of infection, like specific antibodies. Representative seroprevalence studies provide an important avenue for estimating the number of infections in a community, and when combined with death counts can lead to robust estimates of the IFR.
Association of genetic liability to smoking initiation with e-cigarette use in young adults
Authors: Khouja Jasmine N , Wootton Robyn E , Taylor Amy E , Smith George Davey , Munafò Marcus R
Published: June 2020

Background

Smoking and e-cigarette use are strongly associated, but it is currently unclear whether this association is causal, or due to shared factors that influence both behaviours such as a shared genetic liability. The aim of this study was to investigate whether polygenic risk scores (PRS) for smoking initiation are associated with ever use of e-cigarettes.

Methods and Findings

PRS of smoking initiation were calculated for young adults (aged 23 to 26 years) of European ancestry in the Avon Longitudinal Study of Parents and Children using the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5×10−8 to 0.5 were used to calculate five PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and both self-reported smoking initiation and self-reported e-cigarette use, as well as a number of negative control outcomes (socioeconomic position at birth, externalising disorders in childhood and risk-taking in young adulthood). We observed positive associations of similar magnitude between smoking initiation PRS and both smoking initiation (OR = 1.29, 95% CI 1.19 to 1.39) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34) by the age of 24 years. At lower p-value thresholds, we observed an association between smoking initiation PRS and ever e-cigarette use among never smokers. We also found evidence of associations between smoking initiation PRS and some negative control outcomes, particularly when less stringent p-value thresholds were used but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth).

Conclusions

Our results indicate that there may be a shared genetic aetiology between smoking and e-cigarette use, and also with socioeconomic position, externalising disorders in childhood, and risky behaviour more generally. Taken together, this indicates that there may be a common genetic vulnerability to both smoking and e-cigarette use, which may reflect a broad risk-taking phenotype.
The origin and early spread of SARS-CoV-2 in Europe
Authors: Nadeau Sarah A. , Vaughan Timothy G. , Sciré Jérémie , Huisman Jana S. , Stadler Tanja
Published: June 2020

The investigation of migratory patterns of the SARS-CoV-2 pandemic before border closures in Europe is a crucial first step towards an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures. Based on SARS-CoV-2 genomes, we reconstruct a partial transmission tree of the early pandemic, including inferences of the geographic location of ancestral lineages and the number of migration events into and between European regions. We find that the predominant lineage spreading in Europe has a most recent common ancestor in Italy and was probably seeded by a transmission event in either Hubei or Germany. We do not find evidence for preferential migration paths from Hubei into different European regions or from each European region to the others. Sustained local transmission is first evident in Italy and then shortly thereafter in the other European regions considered. Before the first border closures in Europe, we estimate that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. In summary, our analysis offers a view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures. This information will enable further study of the necessity and timeliness of border closures.

Significance Statement

We estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures based on viral genome sequences using a phylodynamic model with geographic structure. We confirm that the predominant European outbreak most likely started in Italy and spread from there. This outbreak was probably seeded by a transmission event in either Hubei or Germany. In particular, we find that before the first border closures in Europe, the rate of new cases occurring from within-country transmission was within the estimated bounds on the rate of new migration cases.
At-home self-collection of saliva, oropharyngeal swabs and dried blood spots for SARS-CoV-2 diagnosis and serology: post-collection acceptability of specimen collection process and patient confidence in specimens
Authors: Valentine-Graves Mariah , Hall Eric , Guest Jodie , Adam Elizabeth , Valencia Rachel , Hardee Isabel , Shinn Katlin , Sanchez Travis , Siegler Aaron J , Sullivan Patrick
Published: June 2020

Background

Options to increase the ease of testing for SARS-CoV-2 infection and immune response are needed. Self-collection of diagnostic specimens at home offers an avenue to allow people to test for SARS-CoV-2 infection or immune response without traveling to a clinic or laboratory. Before this study, survey respondents indicated willingness to self-collect specimens for COVID-related tests, but hypothetical willingness can differ from post-collection acceptability after participants collect specimens.

Methods

153 US adults were enrolled in a study of the willingness and feasibility of patients to self-collect three diagnostic specimens (saliva, oropharyngeal swab (OPS) and dried blood spot (DBS) card) while observed by a clinician through a telehealth session. After the specimens were collected, 148 participants participated in a survey about the acceptability of the collection, packing and shipping process, and their confidence in the samples collected for COVID-related laboratory testing.

Results

A large majority of participants (>84%) reported that collecting, packing and shipping of saliva, OPS, and DBS specimens were acceptable. Nearly nine in 10 (87%) reported being confident or very confident that the specimens they collected were sufficient for laboratory analysis. There were no differences in acceptability for any specimen type, packing and shipping, or confidence in samples by gender, age, race/ethnicity, or educational level.

Conclusions

Self-collection of specimens for SARS-CoV-2 testing and preparing and shipping specimens for analysis were acceptable in a diverse group of US adults. Further refinement of materials and instructions to support self-collection of saliva, OPS and DBS specimens for COVID-related testing is needed.

Trial registration

No intervention was tested in this study
Differential impacts of contact tracing and lockdowns on outbreak size in COVID-19 model applied to China
Authors: Browne Cameron J. , Gulbudak Hayriye , Macdonald Joshua C.
Published: June 2020

Rapid growth of the COVID-19 epidemic in China induced extensive efforts of contact tracing and social-distancing/lockdowns, which quickly contained the outbreak and has been replicated to varying degrees around the world. We construct a novel infectious disease model incorporating these distinct quarantine measures (contact tracing and self-quarantine) as reactionary interventions dependent on current infection levels. Derivation of the final outbreak size leads to a simple inverse proportionality relationship with self-quarantine rate, revealing a fundamental principle of exponentially increasing cumulative cases when delaying mass quarantine or lockdown measures beyond a critical time period. In contrast, contact tracing results in a proportional reduction in reproduction number, flattening the epidemic curve but only having sizable impact on final size when a large proportion of contacts are “perfectly” traced. We fit the mathematical model to data from China on reported cases and quarantined contacts, finding that lockdowns had an overwhelming influence on outbreak size and duration, whereas contact tracing played a role in reducing peak number of infected. Sensitivity analysis and simulations under different re-opening scenarios illustrate the differential effects that responsive contact tracing and lockdowns can have on current and second wave outbreaks.
Direct structural connections between auditory and visual motion selective regions in humans
Authors: Gurtubay-Antolin A. , Battal C. , Maffei C. , Rezk M. , Mattioni S , Jovicich J. , Collignon O.
Published: June 2020

In humans, the occipital middle-temporal region (hMT+/V5) specializes in the processing of visual motion, while the Planum Temporale (hPT) specializes in auditory motion processing. It has been hypothesized that these regions might communicate directly to achieve fast and optimal exchange of multisensory motion information. In this study, we investigated for the first time in humans the existence of direct white matter connections between visual and auditory motion-selective regions using a combined functional- and diffusion-MRI approach. We found reliable evidence supporting the existence of direct white matter connections between individually and functionally defined hMT+/V5 and hPT. We show that projections between hMT+/V5 and hPT do not overlap with large white matter bundles such as the Inferior Longitudinal Fasciculus (ILF) nor the Inferior Frontal Occipital Fasciculus (IFOF). Moreover, we did not find evidence for the existence of reciprocal projections between the face fusiform area and hPT, supporting the functional specificity of hMT+/V5 – hPT connections. Finally, evidence supporting the existence of hMT+/V5 – hPT connections was corroborated in a large sample of participants (n=114) from the human connectome project. Altogether, this study provides first evidence supporting the existence of direct occipito-temporal projections between hMT+/V5 and hPT which may support the exchange of motion information between functionally specialized auditory and visual regions and that we propose to name the middle (or motion) occipito-temporal track (MOTT).
Dissecting the DNA binding landscape and gene regulatory network of p63 and p53
Authors: Riege Konstantin , Kretzmer Helene , Sahm Arne , McDade Simon S. , Hoffmann Steve , Fischer Martin
Published: June 2020

The transcription factor (TF) p53 is the best-known tumor suppressor, but its ancient sibling p63 (ΔNp63) is a master regulator of epidermis development and a key oncogenic driver in squamous cell carcinomas (SCC). Despite multiple gene expression studies becoming available in recent years, the limited overlap of reported p63-dependent genes has made it difficult to decipher the p63 gene regulatory network (GRN). In particular, analyses of p63 response elements differed substantially among the studies. To address this intricate data situation, we provide an integrated resource that enables assessing the p63-dependent regulation of any human gene of interest. Here, we use a novel iterative de novo motif search approach in conjunction with extensive publicly available ChIP-seq data to achieve a precise global distinction between p53 and p63 binding sites, recognition motifs, and potential co-factors. We integrate all these data with enhancer:gene associations to predict p63 target genes and identify those that are commonly de-regulated in SCC and, thus, may represent candidates for therapeutic interventions.
Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival
Authors: Gagliardi Paolo Armando , Dobrzyński Maciej , Jacques Marc-Antoine , Dessauges Coralie , Ender Pascal , Blum Yannick , Hughes Robert M , Cohen Andrew R. , Pertz Olivier
Published: June 2020

Cell death events continuously challenge epithelial barrier function, yet are crucial to eliminate old or critically damaged cells. How such apoptotic events are spatio-temporally organized to maintain epithelial homeostasis remains unclear. We observe waves of Extracellular Signal-Regulated Kinase (ERK) and AKT serine/threonine kinase (Akt) activity pulses that originate from apoptotic cells and propagate radially to healthy surrounding cells. This requires Epidermal Growth Factor Receptor (EGFR) and matrix metalloproteinase (MMP) signaling. At the single-cell level, ERK/Akt waves act as spatial survival signals that locally protect cells in the vicinity of the epithelial injury from apoptosis for a period of 3-4h. At the cell population level, ERK/Akt waves maintain epithelial homeostasis (EH) in response to mild or intense environmental insults. Disruption of this spatial signaling system results in the inability of a model epithelial tissue to ensure barrier function in response to environmental insults.
The balancing act ofNipponites mirabilis(Nostoceratidae, Ammonoidea): managing hydrostatics during a complex ontogenetic trajectory
Authors: Peterman David J. , Mikami Tomoyuki , Inoue Shinya
Published: June 2020

Nipponitesis a heteromorph ammonoid with a complex and unique morphology that obscures its mode of life and ethology. The seemingly aberrant shell of this Late Cretaceous nostoceratid seems deleterious. However, hydrostatic simulations suggest that this morphology confers several advantages for exploiting a quasi-planktic mode of life. Virtual, 3D models ofNipponites mirabiliswere used to compute various hydrostatic properties through 14 ontogenetic stages. At each stage,Nipponiteshad the capacity for neutral buoyancy and was not restricted to the seafloor. Throughout ontogeny, horizontally facing to upwardly facing soft body orientations were preferred. These orientations were aided by the obliquity of the shell’s ribs, which were parallel to former positions of the aperture during life. Static orientations were somewhat fixed, inferred by stability values that are slightly higher than extantNautilus. The initial open-whorled, planispiral phase is well suited to horizontal backwards movement with little rocking.Nipponitesthen deviates from this coiling pattern with a series of alternating U-shaped bends in the shell. This modification allows for proficient rotation about the vertical axis, while possibly maintaining the option for horizontal backwards movement by redirecting its hyponome. These particular hydrostatic properties likely result in a tradeoff between hydrodynamic streamlining, suggesting thatNipponitesassumed a low energy lifestyle of slowly pirouetting in search for planktic prey. Each computed hydrostatic property influences the others in some way, suggesting thatNipponitesmaintained a delicate hydrostatic balancing act throughout its ontogeny in order to facilitate this mode of life.
ZBTB38 is dispensable for hematopoiesis and antibody responses
Authors: Wong Rachel , Bhattacharya Deepta
Published: June 2020

Members of the broad complex, tram track, bric-a-brac and zinc finger (BTB-ZF) family of transcription factors, such as BCL-6, ZBTB20, and ZBTB32, regulate antigen-specific B cell differentiation, plasma cell longevity, and the duration of antibody production. We found that ZBTB38, a different member of the BTB-ZF family that binds methylated DNA at CpG motifs, is highly expressed by germinal center B cells and plasma cells. To define the functional role of ZBTB38 in B cell responses, we generated mice conditionally deficient in this transcription factor. Germinal center B cells lacking ZBTB38 dysregulated very few genes relative to wild-type and heterozygous littermate controls. Accordingly, mice with hematopoietic-specific deletion ofZbtb38showed normal germinal center B cell numbers and antibody responses following immunization with hapten-protein conjugates. Memory B cells from these animals functioned normally in secondary recall responses. Despite expression of ZBTB38 in hematopoietic stem cells, progenitors and mature myeloid and lymphoid lineages were also present in normal numbers in mutant mice. These data demonstrate that ZBTB38 is dispensable for hematopoiesis and antibody responses. These conditional knockout mice may instead be useful in defining the functional importance of ZBTB38 in other cell types and contexts.
Catalytic domain plasticity of MKK7 reveals structural mechanisms of allosteric activation and new targeting opportunities
Authors: Schröder Martin , Tan Li , Wang Jinhua , Liang Yanke , Gray Nathanael S. , Knapp Stefan , Chaikuad Apirat
Published: June 2020

MKK7 (MEK7) is a key regulator of the JNK stress signaling pathway and targeting MKK7 has been proposed as a chemotherapeutic strategy. Detailed understanding of the MKK7 structure and factors that impact its activity is therefore of critical importance. Here, we present a comprehensive set of MKK7 crystal structures revealing insights into catalytic domain plasticity and the role of the N-terminal regulatory helix, conserved in all MAP2Ks, mediating kinase activation. Crystal structures harboring this regulatory helix revealed typical structural features of active kinase, providing exclusively a first model of the MAP2K active state. A small molecule screening campaign yielded multiple scaffolds, including type-II irreversible inhibitors a binding mode that has not been reported previously. We also observed an unprecedented allosteric pocket located in the N-terminal lobe for the approved drug ibrutinib. Collectively, our structural and functional data expand and provide alternative targeting strategies for this important MAP2K kinase.
A natural variant of the essential host geneMMS21restricts the parasitic 2-micron plasmid inSaccharomyces cerevisiae
Authors: Hays Michelle , Young Janet M. , Levan Paula , Malik Harmit S.
Published: June 2020

Ongoing antagonistic coevolution with selfish genetic elements (SGEs) can drive the evolution of host genomes. Here, we investigated whether natural variation allows someSaccharomyces cerevisiaestrains to suppress 2-micron (2μ) plasmids, multicopy nuclear parasites that have co-evolved with budding yeasts. To quantitatively measure plasmid stability, we developed a new method, Single-Cell Assay for Measuring Plasmid Retention (SCAMPR) that measures copy number heterogeneity and 2μ plasmid loss in live cells. Next, in a survey of 52 naturalS. cerevisiaeisolates we identified three strains that lack endogenous 2μ plasmids and reproducibly inhibit mitotic plasmid stability. Thus, their lack of endogenous 2μ plasmids is genetically determined, rather than the result of stochastic loss. Focusing on one isolate (Y9 ragi strain), we determined that plasmid restriction is heritable and dominant. Using bulk segregant analysis, we identified a high-confidence Quantitative Trait Locus (QTL) for mitotic plasmid instability on Y9 chromosome V. We show that a single amino acid change inMMS21is associated with increased 2-micron instability.MMS21is an essential gene, encoding a SUMO E3 ligase and a member of the Smc5/6 complex, which is involved in sister chromatid cohesion, chromosome segregation, and DNA repair. Our analyses leverage natural variation to uncover a novel means by which budding yeasts can overcome a highly successful genetic parasite.
Biased agonists of the chemokine receptor CXCR3 differentially drive formation of Gαi:β-arrestin complexes
Authors: Zheng Kevin , Smith Jeffrey S. , Warman Anmol , Choi Issac , Gundry Jaimee N. , Pack Thomas F. , Inoue Asuka , Caron Marc G. , Rajagopal Sudarshan
Published: June 2020

G-protein-coupled receptors (GPCRs), the largest family of cell surface receptors, signal through the proximal effectors G proteins and β-arrestins to influence nearly every biological process. Classically, the G protein and β-arrestin signaling pathways have largely been considered separable. Recently, direct interactions between Gαprotein and β-arrestin have been described and suggest a distinct GPCR signaling pathway. Within these newly described Gα:β-arrestin complexes, Gαi/o, but not other Gαprotein subtypes, have been appreciated to directly interact with β-arrestin, regardless of canonical GPCR Gαprotein subtype coupling. However it is unclear how biased agonists differentially regulate this newly described Gαi:β-arrestin interaction, if at all. Here we report that endogenous ligands (chemokines) of the GPCR CXCR3, CXCL9, CXCL10, and CXCL11, along with two small molecule biased CXCR3 agonists, differentially promote the formation of Gαi:β-arrestin complexes. The ability of CXCR3 agonists to form Gαi:β-arrestin complexes does not correlate well with either G protein signaling or β-arrestin recruitment. Conformational biosensors demonstrate that ligands that promoted Gαi:β-arrestin complex formation generated similar β-arrestin conformations. We find these Gαi:β-arrestin complexes can associate with CXCR3, but not with ERK. These findings further support that Gαi:β-arrestin complex formation is a distinct GPCR signaling pathway and enhance our understanding of biased agonism.
Chemoprophylaxis of COVID-19 with hydroxychloroquine - a study of health care workers attitude, adherence to regime and side effects
Authors: Bhattacharyya Debajyoti , Raizada Neeraj , Nagappa Bharathnag , Tomar Arvind , Maurya Prateek , Chaudhary Ashok , George Mini , Katiyal Deepty , Rajora Srishti , Singh Nikky
Published: June 2020

Background

There are apprehensions amongst healthcare worker (HCWs) about COVID-19. The HCWs have been given hydroxychloroquine (HCQ) chemoprophylaxis for seven weeks as per Government of India guidelines.

Objectives

To assess the apprehensions amongst HCWs about COVID-19 and to document accessibility, adherence and side effects related to HCQ prophylaxis in HCWs.

Methods

A longitudinal follow up study was conducted in a tertiary care hospital. HCQ was given in the dose of 400 mg twice on day one, and then 400 mg weekly for seven weeks. 391 HCWs were interviewed using semi structured questionnaire.

Results

62.2% HCWs expressed perceived danger posted by COVID-19 infection. Doctors (54%) showed least acceptance and paramedics (88%) showed highest acceptance to chemoprophylaxis. 17.5% participants developed at least one of the side effects to HCQ. Females and nursing profession were significantly associated with adverse effects. Common side effects were gastro-intestinal symptoms, headache and abnormal mood change. Most of these were mild, not requiring any intervention. Gender, professions and perceived threat of COVID-19 were significantly associated with acceptance and adherence to HCQ prophylaxis.

Conclusion

Two third of HCWs had perceived danger due to COVID-19. Three fourth of the HCWs accepted chemoprophylaxis and four out of five who accepted had complete adherence to prophylaxis schedule. One out of five had developed at least one of side effects; however, most of these were mild not requiring any intervention.
Modelling the impact of reducing control measures on the COVID-19 pandemic in a low transmission setting
Authors: Scott Nick , Palmer Anna , Delport Dominic , Abeysuriya Romesh , Stuart Robyn , Kerr Cliff C. , Mistry Dina , Klein Daniel J. , Sacks-Davis Rachel , Heath Katie , Hainsworth Samuel , Pedrana Alisa , Stoove Mark , Wilson David P. , Hellard Margaret
Published: June 2020

Aims

We assessed COVID-19 epidemic risks associated with relaxing a set of physical distancing restrictions in the state of Victoria, Australia – a setting with low community transmission – in line with a national framework that aims to balance sequential policy relaxations with longer-term public health and economic need.

Methods

An agent-based model, Covasim, was calibrated to the local COVID-19 epidemiological and policy environment. Contact networks were modelled to capture transmission risks in households, schools and workplaces, and a variety of community spaces (e.g. public transport, parks, bars, cafes/restaurants) and activities (e.g. community or professional sports, large events). Policy changes that could prevent or reduce transmission in specific locations (e.g. opening/closing businesses) were modelled in the context of interventions that included testing, contact tracing (including via a smartphone app), and quarantine.

Results

Policy changes leading to the gathering of large, unstructured groups with unknown individuals (e.g. bars opening, increased public transport use) posed the greatest risk, while policy changes leading to smaller, structured gatherings with known individuals (e.g. small social gatherings) posed least risk. In the model, epidemic impact following some policy changes took more than two months to occur. Model outcomes support continuation of working from home policies to reduce public transport use, and risk mitigation strategies in the context of social venues opening, such as >30% population-uptake of a contact-tracing app, physical distancing policies within venues reducing transmissibility by >40%, or patron identification records being kept to enable >60% contact tracing.

Conclusions

In a low transmission setting, care should be taken to avoid lifting sequential COVID-19 policy restrictions within short time periods, as it could take more than two months to detect the consequences of any changes. These findings have implications for other settings with low community transmission where governments are beginning to lift restrictions.
Coronavirus Disease 2019 (COVID-19): Knowledge, attitudes, practices (KAP) and misconceptions in the general population of Katsina State, Nigeria
Authors: Isah Murtala Bindawa , Abdulsalam Mahmud , Bello Abubakar , Ibrahim Muawiyya Idris , Usman Aminu , Nasir Abdullahi , Abdulkadir Bashir , Usman Ahmed Rufai , Ibrahim Kabir Matazu , Sani Aminu , Aliu Ma’awuya , Kabir Shema’u Abba , Shuaibu Abdullahi , Nass Shafique Sani
Published: June 2020

Introduction

Over six million cases of Coronavirus Disease 2019 (COVID-19) were reported globally by the second quarter of 2020. The various forms of interventions and measures adopted to control the disease affected people’s social and behavioural practices.

Aim

This study aims to investigate COVID-19 related knowledge, attitudes and practices (KAP) as well as misconceptions in Katsina state, one of the largest epicentres of the COVID-19 outbreak in Nigeria.

Methods

The study is a cross-sectional survey of 722 respondents using an electronic questionnaire through the WhatsApp media platform.

Results

One thousand five hundred (1500) questionnaires were sent to the general public with a response rate of 48% (i.e. 722 questionnaires completed and returned). Among the respondents, 60% were men, 45% were 25-39 years of age, 56% held bachelor’s degree/equivalent and above and 54% were employed. The study respondents’ correct rate in the knowledge questionnaire was 80% suggesting high knowledge of the disease. A significant correlation (P < 0.05) exists between the average knowledge score of the respondents and their level of education (τb = 0.16). Overall, most of the respondents agreed that the COVID-19 will be successfully controlled (84%) and the Nigerian government would win the fight against the pandemic (71%). Men were more likely than female (P < 0.05) to have recently attended a crowded place. Being more educated (bachelor’s degree or equivalent and above vs diploma or equivalent and below) is associated with good COVID-19 related practices. Among the respondents, 83% held at least one misconception related to COVID-19, with the most frequent being that the virus was created in a laboratory (36%). Respondents with a lower level of education received and trust COVID-19 related information from local radio and television stations and respondents at all levels of education selected that they would trust health unit and health care workers for relevant COVID-19 information.

Conclusion

Although there is high COVID-19 related knowledge among the sample, misconceptions are widespread among the respondents. These misconceptions have consequences on the short- and long-term control efforts against the disease and hence should be incorporated in targeted campaigns. Health care related personnel should be at the forefront of the campaign.
Agreement between arterial and capillary pH, pCO2 and lactate in patients in the emergency department
Authors: Collot V. , Malinverni S. , Schweitzer E. , Haltout J. , Mols P. , Bartiaux M.
Published: June 2020

Study objective

The primary objective of the study was a quantitative analysis to assess the mean difference and 95% confidence interval of the difference between capillary and arterial blood gas analyses for pH, pCO2 and lactate. Secondary objective was to measure the sensitivity and specificity of capillary samples to detect altered pH, hypercarbia and lactic acidosis.

Methods

Adults admitted to the ED for whom the treating physician deemed necessary an arterial blood gas analysis (BGA) were screened for inclusion. Simultaneous arterial and capillary samples were drawn for BGA. Agreement between the two methods for pH, pCO2 and lactate were studied with Bland-Altman bias plot analysis. Sensitivity, specificity, positive and negative predictive value as well as AUC were calculated for the ability of capillary samples to detect pH values outside normal ranges, hypercarbia and hyperlactatemia.

Results

197 paired analyses were included in the study. Mean difference for pH, between arterial and capillary BGA was 0.0095, 95% limits of agreement were -0.048 to 0.067. For pCO2, mean difference was -0.3 mmHg, 95% limits of agreement were -8.5 to 7.9 mmHg. Lactate mean difference was -0.93 mmol/L, 95% limits of agreement were -2.7 to 0.8 mmol/L. At a threshold of 7.34 for capillary pH had 98% sensitivity and 97% specificity to detect acidemia; at 45.9 mmHg capillary pCO2 had 89% sensitivity and 96% specificity to detect hypercarbia. Finally at a threshold of 3.5 mmol/L capillary lactate had 66% sensitivity to detect lactic acidosis.

Conclusion

Capillary measures of pH, pCO2 and lactate can’t replace arterial measurements although there is high concordance between the two methods for pH and pCO2 and moderate concordance for lactate. Capillary blood gas analysis had good accuracy when used as a screening tool to detect altered pH and hypercarbia but insufficient sensitivity and specificity when screening for lactic acidosis.
Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in Uganda
Authors: Nannyonga Betty K , Wanyenze Rhoda K , Kaleebu Pontiano , Ssenkusu John M , Lutalo Tom , Makumbi Fredrick Edward , Kwizera Arthur , Byakika Pauline , Kirungi Willford , Bosa Henry Kyobe , Ssembatya Vincent A , Mwebesa Henry , Atwine Diana , Aceng Jane Ruth , Woldermariam Yonas Tegegn ,   all members of the Uganda SARS-COV-2 Scientific Advisory Committee
Published: June 2020

Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of SARS-COV-2 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.
Diagnostic accuracy of the 4AT for delirium detection: systematic review and meta-analysis
Authors: Tieges Zoë , MacLullich Alasdair M. J. , Anand Atul , Brookes Claire , Cassarino Marica , O’Connor Margaret , Ryan Damien , Saller Thomas , Arora Rakesh C. , Chang Yue , Agarwal Kathryn , Taffet George , Quinn Terence , Shenkin Susan. D. , Galvin Rose
Published: June 2020

Objective

Detection of delirium in hospitalised older adults is recommended in national and international guidelines. The 4 ‘A’s Test (4AT) is a short (<2 min) instrument for delirium detection that is used internationally as a standard tool in clinical practice. We performed a systematic review and meta-analysis of diagnostic test accuracy of the 4AT for delirium detection.

Methods

We searched MEDLINE, EMBASE, PsycINFO, CINAHL,clinicaltrials.govand the Cochrane Central Register of Controlled Trials, from 2011 (year of 4AT release on the websitewww.the4AT.com) until 21 December 2019. Inclusion criteria were: older adults (≥ 65y); diagnostic accuracy study of the 4AT index test when compared to delirium reference standard (standard diagnostic criteria or validated tool). Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled estimates of sensitivity and specificity were generated from a bivariate random effects model.

Results

17 studies (3702 observations) were included. Settings were acute medicine, surgery, a care home, and the emergency department. Three studies assessed performance of the 4AT in stroke. The overall prevalence of delirium was 24.2% (95% CI 17.8-32.1%; range 10.5-61.9%). The pooled sensitivity was 0.88 (95% CI 0.80-0.93) and the pooled specificity was 0.88 (95% CI 0.82-0.92). Excluding the stroke studies, the pooled sensitivity was 0.86 (95% CI 0.77-0.92) and the pooled specificity was 0.89 (95% CI 0.83-0.93). The methodological quality of studies varied but was moderate to good overall.

Conclusions

The 4AT shows good diagnostic test accuracy for delirium in the 17 available studies. These findings support its use in routine clinical practice in delirium detection.

PROSPERO Registration number CRD42019133702.

Key points

The 4AT is a short delirium assessment tool that is widely used internationally in clinical practice.

This systematic review and meta-analysis of diagnostic accuracy studies of the 4AT included 3702 observations in 17 studies from nine countries.

Studies recruited from a range of settings including the Emergency Department, and medical, stroke, and surgical wards.

The 4AT had a pooled sensitivity of 0.88 and pooled specificity of 0.88.

The methodological quality of studies varied but was moderate to good overall.
Assessing the influence of parental anxiety on childhood anxiety during the COVID-19 pandemic in the United Arab Emirates
Authors: Saddik Basema , Hussein Amal , Albanna Ammar , Elbarazi Iffat , Al-Shujairi Arwa , Sharif-Askari Fatemeh Saheb , Temsah Mohamad-Hani , Stip Emmanuel , Hamid Qutayba , Halwani Rabih
Published: June 2020

The COVID-19 pandemic originated in Wuhan, China on December 31st and spread into international borders, leading to a public health crisis and complete shutdown of countries. The strict quarantine measures taken by governments kept a large number of people, around the world, in isolation and affected many aspects of people’s lives. These unprecedented changes triggered a wide variety of psychological problems ranging from panic disorders, anxiety and depression. In this study, we aim to explore anxiety levels among parents, teachers and the general community amid the COVID-19 pandemic in the UAE, as well as identify emotional and anxiety disorders in children. Using a web-based cross-sectional survey we collected data from 2,200 self-selected assessed volunteers. Demographic information, knowledge and beliefs about COVID-19, generalized anxiety disorder (GAD) using the (GAD-7) scale, emotional problems in children using the strengths and difficulties questionnaire (SDQ), worry and fear about COVID-19, coping mechanisms and general health information were collected. The overall prevalence of GAD in the general population was 71% with younger people (59.8%) and females (51.7%) reporting the highest levels of anxiety. Parents who were teachers reported the highest percentage of emotional problems in children (26.7%) compared to parents only (14.6%) or teachers only (4.7%). Multivariate logistic regression for GAD-7 score showed that females, participants who felt public fear was justifiable, persons who worried about COVID-19, persons who intended to take the COVID-19 vaccine and smokers were all associated with anxiety. Multivariate logistic regression for SDQ showed parents who had severe anxiety levels were 7 times more likely to report more emotional problems in their children (OR=7.00, 95% CI, 3.45 to 14.0) than less anxious parents. Findings suggest the urgency of policy makers to develop effective screening and coping strategies for parents and teachers and more specifically for vulnerable children.
Mediation analysis in sibling designs: an application to the effect of prenatal antidepressant exposure on toddler depression mediated by gestational age at birth
Authors: Wood Mollie E. , Eilertsen Espen , Ystrom Eivind , Nordeng Hedvig , Hernandez-Diaz Sonia
Published: June 2020

Background

Mediation analysis requires strong assumptions of no unmeasured confounding. Sibling designs offer a method for controlling confounding shared within families, but no previous research has done mediation analysis using sibling models.

Methods

We demonstrate the validity of the sibling mediation approach using simulation, and show its application using the example of prenatal antidepressant exposure and toddler anxiety and depression, with gestational age at birth as a mediator. We used data from the Norwegian Mother and Child Cohort Study, a cohort comprising 41% of births in Norway between 1999 and 2008 to identify 91,333 pregnancies, of which 25,776 were part of sibling groups.

Results

In simulations, sibling models were less biased than cohort models in cases where non-shared confounding was weaker than shared confounding, and when stronger non-shared confounding was controlled, but more biased otherwise. In the full cohort, the estimated mean difference in depression/anxiety scale z-scores for natural direct effects (NDE) were 0.31 (95% confidence interval 0.23 to 0.39) and 0.14 (95% CI 0.03 to 0.24), without and with adjustment for non-shared confounders, respectively. The natural indirect effect was 0.01 (95% CI 0.00 to 0.02) after adjustment. Adjustment for shared and non-shared confounding showed similar point estimates with wider confidence intervals (NDE 0.18, 95% CI −0.21 to 0.47; NIE −0.01, 95% CI −0.06 to 0.06).

Conclusions

Findings suggest that the modest association between prenatal antidepressant exposure and anxiety/depression is not mediated by gestational age and is likely explained by both shared confounders and non-shared confounders, and chance.
COVID-19 pandemic-related lockdown: response time is more important than its strictness
Authors: Loewenthal Gil , Abadi Shiran , Avram Oren , Halabi Keren , Ecker Noa , Nagar Natan , Mayrose Itay , Pupko Tal
Published: June 2020

The rapid spread of SARS-CoV-2 and its threat to health systems worldwide have led governments to take acute actions to enforce social distancing. Previous studies used complex epidemiological models to quantify the effect of lockdown policies on infection rates. However, these rely on prior assumptions or on official regulations. Here, we use country-specific reports of daily mobility from people cellular usage to model social distancing. Our data-driven model enabled the extraction of mobility characteristics which were crossed with observed mortality rates to show that: (1) the time at which social distancing was initiated is of utmost importance and explains 62% of the number of deaths, while the lockdown strictness or its duration are not as informative; (2) a delay of 7.49 days in initiating social distancing would double the number of deaths; and (3) the expected time from infection to fatality is 25.75 days and significantly varies among countries.
COVID-19 and children with cancer: Parents' experiences, anxieties, and support needs
Authors: Darlington Anne-Sophie , Morgan Jessica E , Wagland Richard , Sodergren Samantha , Culliford David , Gamble Ashley , Phillips Bob
Published: June 2020

Background
Children with cancer were considered to be extremely clinically vulnerable to severe COVID-19 disease if they were to contract SARS-CoV-2 due to immune suppression as a result of anti-cancer treatment. The aim was to explore experiences, information and support needs, and decision-making of parents with a child with cancer in response to the early phase of the COVID-19 pandemic in the UK.

Methods
Parents of a child with cancer completed a survey in April 2020, as the UK moved into a period of "lockdown", with restrictions of movement outside of the home. An online survey was developed to capture parents' experiences, information and support needs, and decision-making, using closed statements and open text boxes. Descriptive quantitative analyses and qualitative thematic content analysis were undertaken.

Findings
171 parents/caregivers completed the survey. 85% of parents worried about the virus and the majority of parents were vigilant about virus (92%) or cancer symptoms (93.4%). For two-thirds (69.6%) hospital was no longer considered a safe place. Parents worried about their own health (81.1%) and about the child getting the virus from them (89.1%). Eight overarching themes, related to the virus: 1) risk of infection, 2) information, guidance and advice, 3) health care provision, 4) fears and anxieties; or related to lockdown/isolation: 5) psychological and social impact, 6) keeping safe under lockdown, 7) provisions and dependence, and 8) employment and income.

Interpretation
This is the first study to report experiences of parents of a child with cancer during the SARS-CoV-2/COVID-19 pandemic. The study demonstrated that the majority of parents are worried about SARS-CoV-2, and worried about transmitting the virus to their child. Hospital was no longer a safe place, and parents were worried about suboptimal cancer care. Parents describe fear and anxiety and the psychological, social and economic impact of isolation as a family.