bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection in a pregnant patient on immunosuppressive treatment
Authors: Bergantin Maria Rhona G. , Navarra Sandra V.
Published: February 2021

Patients on immunosuppressive therapies have greater susceptibility to a broad range of infections and pose a special challenge during pregnancy and lactation. Anti-microbials must be given with due consideration to side-effects, drug-drug interactions, and importantly safety to the growing foetus and the breastfeeding baby. This chapter further elucidates on modes of transmission and prevention of some infections which can significantly impact materno-foetal outcomes. Systemic autoimmune diseases must be kept under good control during pregnancy since untreated disease carries its own risks to both the mother and the developing foetus. Whilst infections are an important complication of immunosuppressive drugs used for many autoimmune rheumatic diseases, their clinical manifestations may be masked or absent among immunosuppressed individuals.
Vaccination before or during pregnancy
Authors: Varley Cara D. , Winthrop Kevin L.
Published: February 2021

In general, live attenuated vaccines are contraindicated in pregnancy and with immunosuppression, especially biologics. Prior to pregnancy and initiation of immunosuppressive therapy, attempts should be made to administer recommended vaccines to protect the health of both the woman and child. There is limited safety and efficacy data for many inactivated, toxoid, and subunit/conjugate vaccines in the setting of pregnancy and biologic therapy. In addition, vaccines in general may have diminished immunogenicity if administered during biologic therapy. This chapter focuses on the current recommendations, immunogenicity, and contraindications for vaccination of women of child-bearing age with rheumatic diseases who may be taking or considering initiation of disease-modifying antirheumatic drugs (DMARDs).
Myositis and pregnancy
Authors: Shipa Muhammed , Isenberg David
Published: February 2021

Pregnancy outcome in patients with inflammatory myositis (IM) remains poorly understood but, current data suggest active disease can increase the risk of adverse foetal outcome. Flare of previously diagnosed myositis or new onset of myositis during the puerperal period has been described. However, a favourable outcome has been noted if myositis is in remission. Caution should be excised with the treatment options, but the use of azathioprine (<2 mg/kg/day), hydroxychloroquine, cyclosporine, and tacrolimus are compatible with pregnancy and can be continued during breastfeeding. Inflammatory myopathies (IIM) comprise a group of diseases of unknown cause resulting in muscle inflammation and subsequent muscle weakness.
Correlation of Genomic Compartments with Contrastive Modes of Functional Losses of Host Specificity Determinants During Pathotype Differentiation in Pyricularia oryzae
Authors: Asuke Soichiro , Magculia Nicole John , Inoue Yoshihiro , Vy Trinh Thi Phuong , Tosa Yukio
Published: February 2021

The specificity between pathotypes of Pyricularia oryzae and genera of gramineous plants is governed by gene-for-gene interactions. Here, we show that avirulence genes involved in this host specificity have undergone different modes of functional losses dependent on or affected by genomic compartments harboring them. The avirulence of an Eleusine pathotype on wheat is controlled by five genes, including PWT3, which played a key role in the evolution of the Triticum pathotype (the wheat blast fungus). We cloned another gene using an association of its presence or absence with pathotypes and designated it as PWT6. PWT6 was widely distributed in a lineage composed of Eleusine and Eragrostis isolates but was completely absent in a lineage composed of Lolium and Triticum isolates. On the other hand, PWT3 homologs were present in all isolates, and their loss of function in Triticum isolates was caused by insertions of transposable elements or nucleotide substitutions. Analyses of whole-genome sequences of representative isolates revealed that these two genes were located in different genomic compartments; PWT6 was located in a repeat-rich region, while PWT3 was located in a repeat-poor region. These results suggest that the course of differentiation of the pathotypes in P. oryzae appears to be illustrated as processes of functional losses of avirulence genes but that modes of the losses are affected by genomic compartments in which they reside.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Characterization of lncRNAs and mRNAs Involved in Powdery Mildew Resistance in Cucumber
Authors: Nie Jingtao , Wang Huasen , Zhang Wanlu , Teng Xue , Yu Chao , Cai Run , Wu Gang
Published: February 2021

Powdery mildew (PM) is a severe fungal disease of cucumber worldwide. Identification of genetic factors resistant to PM is of great importance for marker-assisted breeding to ensure cucumber production. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to play important roles in plant development and immunity; however, whether they have a role in PM response in cucurbit crops remains unknown. We performed strand-specific RNA sequencing and miRNA sequencing using RNA from cucumber leaves of two near-isogenic lines (NILs), S1003 and NIL (Pm5.1) infected with PM, and systematically characterized the profiles of cucumber lncRNAs and messenger RNA (mRNAs) responsive to PM. In total, we identified 12,903 lncRNAs and 25,598 mRNAs responsive to PM. Differential expression (DE) analysis showed that 119 lncRNAs and 136 mRNAs correlated with PM resistance. Functional analysis of these DE lncRNAs and DE mRNAs revealed that they are significantly associated with phenylpropanoid biosynthesis, phenylalanine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and endocytosis. Particularly, two lncRNAs, LNC_006805 and LNC_012667, might play important roles in PM resistance. In addition, we also predicted mature miRNAs and competing endogenous RNA (ceRNA) networks of lncRNA–miRNA–mRNA involved in PM resistance. A total of 49 DE lncRNAs could potentially act as target mimics for 106 miRNAs. Taken together, our results provide an abundant resource for further exploration of cucumber lncRNAs, mRNAs, miRNAs, and ceRNAs in PM resistance, and will facilitate the molecular breeding for PM-resistant varieties to control this severe disease in cucumber.
Relations between earthquake distributions, geological history, tectonics and rheology on the continents
Authors: Jackson James , McKenzie Dan , Priestley Keith
Published: February 2021

This paper is concerned with the distribution of earthquakes, particularly their depths, with the temperature of the material in which they occur, and with the significance of both for the rheology and deformation of the continental lithosphere. Earthquakes on faults are generated by the sudden release of elastic energy that accumulates during slow plate motions. The nonlinear high-temperature creep that localizes such energy accumulation is, in principle, well understood and can be described by rheological models. But the same is not true of seismogenic brittle failure, the main focus of this paper, and severely limits the insights that can be obtained by simulations derived from geodynamical modelling of lithosphere deformation. Through advances in seismic tomography, we can now make increasingly detailed maps of lithosphere thickness on the continents. The lateral variations are dramatic, with some places up to 300 km thick, and clearly relate to the geological history of the continents as well as their present-day deformation. Where the lithosphere thickness is about 120 km or less, continental earthquakes are generally confined to upper crustal material that is colder than about 350°C. Within thick lithosphere, and especially on its edges, the entire crust may be seismogenic, with earthquakes sometimes extending into the uppermost mantle if the Moho is colder than 600°C, but the continental mantle is generally aseismic. Earthquakes in the continental lower crust at 400–600°C require the crust to be anhydrous and so are a useful guide or proxy to both composition and strength. These patterns and correlations have important implications for the geological evolution of the continents. They can be seen to have influenced features as diverse as the location of post-collisional rifting; cratonic basin formation; the location, origin and timing of granulite-facies metamorphism; and the formation, longevity and strength of cratons. In addition, they have important consequences for earthquake hazard assessment in the slowly deforming edges and interiors of continental shields or platforms, where the large seismogenic thickness can host very large earthquakes.

This article is part of a discussion meeting issue ‘Understanding earthquakes using the geological record'.
The earthquake cycle in the dry lower continental crust: insights from two deeply exhumed terranes (Musgrave Ranges, Australia and Lofoten, Norway)
Authors: Menegon Luca , Campbell Lucy , Mancktelow Neil , Camacho Alfredo , Wex Sebastian , Papa Simone , Toffol Giovanni , Pennacchioni Giorgio
Published: February 2021

This paper discusses the results of field-based geological investigations of exhumed rocks exposed in the Musgrave Ranges (Central Australia) and in Nusfjord (Lofoten, Norway) that preserve evidence for lower continental crustal earthquakes with focal depths of approximately 25–40 km. These studies have established that deformation of the dry lower continental crust is characterized by a cyclic interplay between viscous creep (mylonitization) and brittle, seismic slip associated with the formation of pseudotachylytes (a solidified melt produced during seismic slip along a fault in silicate rocks). Seismic slip triggers rheological weakening and a transition to viscous creep, which may be already active during the immediate post-seismic deformation along faults initially characterized by frictional melting and wall-rock damage. The cyclical interplay between seismic slip and viscous creep implies transient oscillations in stress and strain rate, which are preserved in the shear zone microstructure. In both localities, the spatial distribution of pseudotachylytes is consistent with a local (deep) source for the transient high stresses required to generate earthquakes in the lower crust. This deep source is the result of localized stress amplification in dry and strong materials generated at the contacts with ductile shear zones, producing multiple generations of pseudotachylyte over geological time. This implies that both the short- and the long-term rheological evolution of the dry lower crust typical of continental interiors is controlled by earthquake cycle deformation.

This article is part of a discussion meeting issue ‘Understanding earthquakes using the geological record’.
Administration of tocilizumab to patients with high concentrations of IL-6 in the course of COVID-19 is associated with a better prognosis
Authors: Flisiak Robert , Jaroszewicz Jerzy , Rogalska Magdalena , Łapiński Tadeusz , Berkan-Kawińska Aleksandra , Bolewska Beata , Tudrujek-Zdunek Magdalena , Kozielewicz Dorota , Rorat Marta , Leszczyński Piotr , Kłos Krzysztof , Kowalska Justyna , Pabjan Paweł , Piekarska Anna , Mozer-Lisewska Iwona , Tomasiewicz Krzysztof , Pawłowska Małgorzata , Simon Krzysztof , Polańska Joanna , Zarębska-Michaluk Dorota
Published: February 2021

Background

Despite the direct viral activity, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore tocilizumab (TCZ), a monoclonal antibody against IL-6 receptors, became considered as a possible therapeutic option.

Methods

Patients were selected from the SARSTer national database, which included 2332 individuals with COVID-19 and the current study included 825 adult patients with moderate to severe course. The retrospective analysis was performed in 170 patients treated with TCZ and 655 without this medication or any other anti-cytokine therapy. The end-points of treatment effectiveness were a rate of death, need for mechanical ventilation, and clinical improvement.

Results

Patients treated with TCZ were balanced compared to non-TCZ regarding gender, age, BMI, and prevalence of coexisting conditions. The reduced death rate was demonstrated in patients treated with TCZ and baseline IL-6 >100 pg/ml (hazard ratio [HR]: 0.27, 95% confidence interval [CI]:0.10-0.78), or those needing oxygen supplementations who worsened within 7 days of hospitalization (HR: 0.38, 95% CI:0.16-0.88). The best effectiveness of TCZ was achieved in patients with a combination of baseline IL-6>100 pg/ml and either SpO2≤90% (HR for death, mechanical ventilation, and clinical improvement after 21 or 28 days: 0.07, 0.14, 5.53, 5.18 respectively) or requiring oxygen supplementation (HR for death and clinical improvement after 21 or 28 days, 0.18, 2.66, 2.85 respectively).

Conclusions

Tocilizumab administered for COVID-19 in patients with a baseline concentration of IL-6>100 pg/ml is associated with reduced mortality and faster clinical improvement, particularly if there is a need for oxygen supplementation due to SpO2≤90%.
Application of a 27-protein candidate cardiovascular surrogate endpoint to track risk ascendancy and resolution in COVID-19
Authors: Paterson Clare , Hagar Yolanda , Hinterberg Michael A. , Charney Alexander W. , Valle Diane M. Del , Filbin Michael R. , Gnjatic Sacha , Goldman Jason D. , Hacohen Nir , Heath James R. , Hillenbrand Rainer , Jennings Lori L. , Kim-Schulze Seunghee , Magis Andrew T. , Merad Miriam , Mouskas Konstantinos , Simons Nicole W. , Williams Stephen A.
Published: February 2021

Background

There is an urgent need for tools allowing the early prognosis and subsequent monitoring of individuals with heterogeneous COVID-19 disease trajectories. Pre-existing cardiovascular (CV) disease is a leading risk factor for COVID-19 susceptibility and poor outcomes, and cardiac involvement is prevalent in COVID-19 patients both during the acute phase as well as in convalescence. The utility of traditional CV risk biomarkers in mild COVID-19 disease or across disease course is poorly understood. We sought to determine if a previously validated 27-protein predictor of CV outcomes served a purpose in COVID-19.

Methods

The 27-protein test of residual CV (RCV) risk was applied without modification to n=860 plasma samples from hospitalized and non-hospitalized SARS-CoV-2 infected individuals at disease presentation from three independent cohorts to predict COVID-19 severity and mortality. The same test was applied to an additional n=991 longitudinal samples to assess sensitivity to change in CV risk throughout the course of infection into convalescence.

Results

In each independent cohort, RCV predictions were significantly related to maximal subsequent COVID-19 severity and to mortality. At the baseline blood draw, the mean protein-predicted likelihood of an event in subjects who died during the study period ranged from 88-99% while it ranged from 8-36% in subjects who were not admitted to hospital. Additionally, the test outperformed existing risk predictors based on commonly used laboratory chemistry values or presence of comorbidities. Application of the RCV test to sequential samples showed dramatic increases in risk during the first few days of infection followed by risk reduction in the survivors; a period of catastrophically high cardiovascular risk (above 50%) typically lasted 8-12 days and had not resolved to normal levels in most people within that timescale.

Conclusions

The finding that a 27-protein candidate CV surrogate endpoint developed in multi-morbid patients prior to the pandemic is both prognostic and acutely sensitive to the adverse effects of COVID-19 suggests that this disease activates the same biologic risk-related mechanisms. The test may be useful for monitoring recovery and drug response.
Unmet need of essential treatments for critical illness in Malawi
Authors: Kayambankadzanja Raphael Kazidule , Schell Carl Otto , Mbingwani Isaac , Mndolo Samson Kwazizira , Castegren Markus , Baker Tim
Published: February 2021

Background

Critical illness is common throughout the world and has been the focus of a dramatic increase in attention in the COVID-19 pandemic. Severely deranged vital signs can identify critical illness, are simple to check and treatments that aim to correct derangements are established, basic and low-cost. The aim of the study was to estimate the unmet need of essential treatments for severely deranged vital signs in all adults admitted to hospitals in Malawi.

Methods

We conducted a cross-sectional study with follow-up of adult hospitalized patients in Malawi. All in-patients aged ≥18 on single days Queen Elizabeth Central Hospital (QECH) and Chiradzulu District Hospital (CDH) were screened.. Patients with hypoxia (oxygen saturation <90%), hypotension (systolic blood pressure <90mmHg) and reduced conscious level (Glasgow Coma Score <9) were included in the study. The a-priori defined essential treatments were oxygen therapy for hypoxia, intravenous fluid for hypotension and an action to protect the airway for reduced consciousness (placing the patient in the lateral position, insertion of an oropharyngeal airway or endo-tracheal tube or manual airway protection).

Results

Of the 1135 hospital in-patients screened, 45 (4.0%) had hypoxia, 103 (9.1%) had hypotension, and 17 (1.5%) had a reduced conscious level. Of those with hypoxia, 40 were not receiving oxygen (88.9%). Of those with hypotension, 94 were not receiving intravenous fluids (91.3%). Of those with a reduced conscious level, nine were not receiving an action to protect the airway (53.0%).

Conclusion

There was a large unmet need of essential treatments for critical illness in two hospitals in Malawi.
Identification of Nonverbal Communication Tools for Use in Dementia
Authors: Khan Zunera , Da Silva Miguel Vasconcelos , Eno-Amooquaye Jemuwem , Nowicki Steven , Nunez Kayleigh , Francis Paul , Ballard Clive
Published: February 2021

Introduction

Non-verbal communication remains a relatively unexplored area in dementia care with a lack of validated assessment tools available to measure non-verbal communication function in dementia.

Methods

This scoping review identifies assessment scales of nonverbal communication in dementia and evaluates the psychometric properties and clinical utility of these instruments. Relevant publications in English, from 1947 to 2017, were identified through an extensive search strategy in Medline, Psychinfo and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane and generic search engines (Google) and available off-line resources. Quality judgement criteria was formulated and used to evaluate the psychometric aspects of the scales.

Results

Forty-one tools were identified measuring various communication channels including verbal, nonverbal (e.g., facial expressions, gestures, eye contact) and functional, communication means; within various settings and populations, for instance, those assessing cognition and verbal language difficulties secondary to stroke, aphasia and nonverbal cues associated with pain. A number of tools presented psychometrics qualities; only nine of the forty-one tools specifically focussed on nonverbal communication, however, comprehensive assessment of nonverbal communication function was not presented in majority of the identified tools. Two tools provided a detailed assessment of nonverbal communication, the Emory dyssemia Index (EDI) and the Threadgold Communication Tool (TCT).

Conclusion

Based on the psychometric qualities and criteria regarding sensitivity and clinical utility, we concluded that although it is difficult to recommend one particular tool, the EDI and TCT are the most appropriate scales currently available. Further research should focus on improving these scales by further testing their validity, reliability and clinical utility in dementia.
Effect of RBD mutations in spike glycoprotein of SARS-CoV-2 on neutralizing IgG affinity
Authors: Hayashi Takuma , Yaegashi Nobuo , Konishi Ikuo
Published: February 2021

Background

Certain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subspecies (B.1.1.7, B.1.351, and B.1.1.248).

Methods

We investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F and N501Y on neutralizing antibodies in serum derived from COVID-19-positive patients.

Results

Our results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients.

Conclusions

Infection with SARS-CoV-2 subspecies that cause serious symptoms in humans may spread globally.
The mobility gap: estimating mobility levels required to control Canada’s winter COVID-19 surge
Authors: Brown Kevin A. , Soucy Jean-Paul R. , Buchan Sarah A. , Sturrock Shelby L. , Berry Isha , Stall Nathan M. , Jüni Peter , Ghasemi Amir , Gibb Nicholas , MacFadden Derek R. , Daneman Nick
Published: February 2021

Background

Non-pharmaceutical interventions remain a primary means of suppressing COVID-19 until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures in seven Canadian provinces to quantify the mobility level needed to suppress COVID-19 (mobility threshold), and the difference relative to current mobility levels (mobility gap).

Methods

We conducted a longitudinal study of weekly COVID-19 incidence from March 15, 2020 to January 16, 2021, among provinces with 20 COVID-19 cases in at least 10 weeks. The outcome was weekly growth rate defined as the ratio of current cases compared to the previous week. We examined the effects of average time spent outside the home (non-residential mobility) in the prior three weeks using a lognormal regression model accounting for province, season, and mean temperature. We calculated the COVID-19 mobility threshold and gap.

Results

Across the 44-week study period, a total of 704,294 persons were infected with COVID-19. Non-residential mobility dropped rapidly in the spring and reached a median of 36% (IQR: 31,40) in April 2020. After adjustment, each 5% increase in non-residential mobility was associated with a 9% increase in the COVID-19 weekly growth rate (ratio=1.09, 95%CI: 1.07,1.12). The mobility gap increased through the fall months, which was associated with increasing case growth.

Interpretation

Mobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control COVID-19 through winter 2021. Mobility measures from anonymized smartphone data can be used to guide the provincial and regional implementation and loosening of physical distancing measures.
Stochastic social behavior coupled to COVID-19 dynamics leads to waves, plateaus and an endemic state
Authors: Tkachenko Alexei V. , Maslov Sergei , Wang Tong , Elbanna Ahmed , Wong George N. , Goldenfeld Nigel
Published: February 2021

It is well recognized that population heterogeneity plays an important role in the spread of epidemics. While individual variations in social activity are often assumed to be persistent, i.e. constant in time, here we discuss the consequences of dynamic heterogeneity. By integrating the stochastic dynamics of social activity into traditional epidemiological models we demonstrate the emergence of a new long timescale governing the epidemic, in broad agreement with empirical data. Our Stochastic Social Activity model captures multiple features of real-life epidemics such as COVID-19, including prolonged plateaus and multiple waves, which are transiently suppressed due to the dynamic nature of social activity. The existence of a long timescale due to the interplay between epidemic and social dynamics provides a unifying picture of how a fast-paced epidemic typically will transition to an endemic state.
Socioeconomic Disparities and COVID-19 Vaccination Acceptance: Experience from Israel
Authors: Caspi Gil , Dayan Avshalom , Eshal Yael , Liverant-Taub Sigal , Twig Gilad , Shalit Uri , Lewis Yair , Shina Avi , Caspi Oren
Published: February 2021

COVID-19 vaccination acceptance has a key role in mitigating the pandemic. Concern has been raised that vaccination rates will be limited in demographically defined areas of lower income. Israel’s rapid vaccination campaign may allow to assess these assumptions in real-world and to devise tools for effectively focusing the vaccination efforts. We analyzed the correlation between COVID-19 vaccination rates, socioeconomic status (SES) and active COVID-19 disease burden. We carried out a nationwide study, based on data provided by Ministry of Health of COVID-19 vaccination rates in all municipalities in Israel up to January 12th, 2021. Municipal Vaccination rates of population older than 60 significantly correlated with the socioeconomic status (r=0.83, 95% confidence interval [0.79 to 0.87]). Finally, we established a novel metric for focusing the vaccination efforts based on % vaccinations and active disease burden. In Israel, a case-model country for COVD-19 vaccinations, vaccination rates were strongly correlated with SES. The study findings demonstrate the need to directly target vaccination acceptance to socio-economically disadvantaged populations and suggest potential tools for policymakers to focus their efforts.
Prediction Models for Severe Manifestations and Mortality due to COVID-19: A Rapid Systematic Review
Authors: Miller Jamie L. , Tada Masafumi , Goto Michihiko , Mohr Nicholas , Lee Sangil
Published: February 2021

Background

Throughout 2020, the coronavirus disease 2019 (COVID-19) has become a threat to public health on national and global level. There has been an immediate need for research to understand the clinical signs and symptoms of COVID-19 that can help predict deterioration including mechanical ventilation, organ support, and death. Studies thus far have addressed the epidemiology of the disease, common presentations, and susceptibility to acquisition and transmission of the virus; however, an accurate prognostic model for severe manifestations of COVID-19 is still needed because of the limited healthcare resources available.

Objective

This systematic review aims to evaluate published reports of prediction models for severe illnesses caused COVID-19.

Methods

Searches were developed by the primary author and a medical librarian using an iterative process of gathering and evaluating terms. Comprehensive strategies, including both index and keyword methods, were devised for PubMed and EMBASE. The data of confirmed COVID-19 patients from randomized control studies, cohort studies, and case-control studies published between January 2020 and July 2020 were retrieved. Studies were independently assessed for risk of bias and applicability using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). We collected study type, setting, sample size, type of validation, and outcome including intubation, ventilation, any other type of organ support, or death. The combination of the prediction model, scoring system, performance of predictive models, and geographic locations were summarized.

Results

A primary review found 292 articles relevant based on title and abstract. After further review, 246 were excluded based on the defined inclusion and exclusion criteria. Forty-six articles were included in the qualitative analysis. Inter observer agreement on inclusion was 0.86 (95% confidence interval: 0.79 - 0.93). When the PROBAST tool was applied, 44 of the 46 articles were identified to have high or unclear risk of bias, or high or unclear concern for applicability. Two studied reported prediction models, 4C Mortality Score from hospital data and QCOVID from general public data from UK, and were rated as low risk of bias and low concerns for applicability.

Conclusion

Several prognostic models are reported in the literature, but many of them had concerning risks of biases and applicability. For most of the studies, caution is needed before use, as many of them will require external validation before dissemination. However, two articles were found to have low risk of bias and low applicability can be useful tools.
High variability in transmission of SARS-CoV-2 within households and implications for control
Authors: Toth Damon J.A. , Beams Alexander B. , Keegan Lindsay T. , Zhang Yue , Greene Tom , Orleans Brian , Seegert Nathan , Looney Adam , Alder Stephen C. , Samore Matthew H.
Published: February 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a high risk of transmission in close-contact indoor settings, which may include households. Prior studies have found a wide range of household secondary attack rates and may contain biases due to simplifying assumptions about transmission variability and test accuracy.

Methods

We compiled serological SARS-CoV-2 antibody test data and prior SARS-CoV-2 test reporting from members of 9,224 Utah households. We paired these data with a probabilistic model of household importation and transmission. We calculated a maximum likelihood estimate of the importation probability, mean and variability of household transmission probability, and sensitivity and specificity of test data. Given our household transmission estimates, we estimated the threshold of non-household transmission required for epidemic growth in the population.

Results

We estimated that individuals in our study households had a 0.41% (95% CI 0.32% – 0.51%) chance of acquiring SARS-CoV-2 infection outside their household. Our household secondary attack rate estimate was 36% (27% – 48%), substantially higher than the crude estimate of 16% unadjusted for imperfect serological test specificity and other factors. We found evidence for high variability in individual transmissibility, with higher probability of no transmissions or many transmissions compared to standard models. With household transmission at our estimates, the average number of non-household transmissions per case must be kept below 0.41 (0.33 – 0.52) to avoid continued growth of the pandemic in Utah.

Conclusions

Our findings suggest that crude estimates of household secondary attack rate based on serology data without accounting for false positive tests may underestimate the true average transmissibility, even when test specificity is high. Our finding of potential high variability (overdispersion) in transmissibility of infected individuals is consistent with characterizing SARS-CoV-2 transmission being largely driven by superspreading from a minority of infected individuals. Mitigation efforts targeting large households and other locations where many people congregate indoors might curb continued spread of the virus.
Cholesterol-lowering Decreased mTOR Complex 2 Signaling and Enhanced Antitumor Immunity
Authors: Wang Yanping , You Sungyong , Su Shengchen , Yeon Austin , Lo Eric M. , Kim Sungjin , Mohler James L. , Freeman Michael R. , Kim Hyung L.
Published: February 2021

Cholesterol-lowering interventions are employed widely and safely to reduce risk of cardiovascular disease. Cholesterol may have complex and opposing effects on immunity. We lowered serum cholesterol to clinically relevant levels in mice and evaluated the final adaptive immune response. Mice treated with oral ezetimibe exhibited enhanced antitumor immunity against syngeneic cancers in a CD8+ lymphocyte-dependent manner, produced immunity that was transferrable through lymphocytes, and enhanced central CD8+ T cell memory. In both mice and patients undergoing prostatectomy, lowering serum cholesterol inhibited mTORC2 signaling in lymphocytes and increased infiltration of CD8+ lymphocytes into prostate tumors. Lymphocyte-specific mTORC2 knockout mice demonstrated enhanced CD8+ lymphocyte function and antitumor capacity. In a prospective clinical trial, cholesterol-lowering intervention prior to prostatectomy decreased the proliferation of normal prostate and low-grade adenocarcinomas. Here, we show that lowering serum cholesterol may be an effective strategy to decrease signaling through mTORC2 and enhance antitumor CD8+ T cell memory.
The implementation and outcome of a 2-year prospective audit and feedback based antimicrobial stewardship program at a private tertiary care hospital
Authors: Thakkar Pooja , Singhal Tanu , Shah Sweta , Bhavsar Rohit , Ladi Shweta , John Roshan Elizabeth , Chavhan Rubina , Naik Reshma
Published: February 2021

Purpose

Antimicrobial resistance has emerged as a major public health problem with India being one of the worst affected nations. Hence effective antimicrobial stewardship programs (AMSP) are needed. We report the design, implementation and results of a prospective audit and feedback based AMSP at a private tertiary care hospital.

Methods

During the study period – January 2018 to December 2019 – the prescription of restricted antimicrobials required the filling of a justification form which was reviewed by the antimicrobial stewardship committee (AMSC) at 48-72 hours. Patients in whom the restricted antimicrobial was stopped earlier than 48 hours were not applicable for review. The eligible prescriptions were judged as justified/unjustified by AMSC based on the patient’s clinical and previous antimicrobial history, course and results of investigations/ cultures, and communicated to the treating team. Compliance to the recommendations of the AMSC was measured. Days of therapy for each restricted antimicrobial/1000 patient days was calculated. Colistin resistance rates in pathogens causing central line associated blood stream infections were compared with previous years.

Results

A total of 2397 restricted antimicrobials in 1366 patients were prescribed in the study period of which 1801 prescriptions were applicable for review (75%). Overall, 1.4% of admitted patients were prescribed restricted antimicrobials. The total days of therapy with restricted antimicrobials was 41.5/1000 patient days. The AMSC committee adjudged 12.5% of prescriptions as unjustified and recommendations for de-escalation were accepted in 89%. There was no significant difference in any of the study outcomes between 2018 and 2019. Colistin resistance rates in CLABSI remained stable as compared to previous years.

Conclusion

The prospective audit and feedback component of AMSP provides insights into the use of restricted antimicrobials. This component should be considered by hospitals for inclusion in their program on an ongoing basis even if limited for a few drugs and in few areas of the hospital.
“This is really like waiting for war and this is not good” – Intertwining between pandemic experiences, and the development of professional action of healthcare professionals in critical care at the beginning of the COVID-19 pandemic in Germany: a qualitative study
Authors: Hörold Madlen , Drewitz Karl Philipp , Brunnthaler Vreni , Piel Julia , Rohr Magdalena , Hrudey Ilona , Hasenpusch Claudia , Ulrich Angela , Otto Niklas , Brandstetter Susanne , Apfelbacher Christian
Published: February 2021

Healthcare professionals (HCPs) are facing remarkable challenges in their daily work since the outbreak of the COVID-19 pandemic. Being well prepared is crucial for dealing with such a pandemic. The aim of our study was to explore HCPs’ subjective perspectives on their professional action and coping strategies in critical care during the preparation and coping phase after the outbreak of the COVID-19 pandemic in Germany.

Together with HCPs working in critical care, we collaboratively designed an interview study based on an ethnomethodological approach. We performed semi-structured qualitative interviews via telephone or video call and analysed the data based on grounded theory.

Our research interest was focused on HCPs (qualified nurses, physicians, medical students) working in critical care during the first wave of the COVID-19 pandemic in Germany between April and July 2020.

Our sample consisted of 39 HCPs (19 nurses, 17 physicians, three medical students, 18/39 female) from ten German federal states. All participants were involved in the acute care of COVID-19 infected patients in hospitals and had a mean professional experience of 14.8±10.1 years, 15 participants held a management position (e.g. senior physician or head nurse). We recruited participants via personal contacts and snowballing.

Initial and focused coding resulted in seven categories: Creating structural measures, handling operational changes, dealing with personal protective equipment, building up knowledge and skills, managing information, perceiving peer support and experiencing emotions.

Professional action and subjectively perceived preparedness (professional and emotional) interacted with each other. Their interrelation was not static, but rather dynamic and ambiguous according to the situation. The findings of our study can be beneficial in developing guidelines, policy interventions or personnel and work practice strategies.
Using simulated infectious disease outbreaks to guide the design of individually randomized vaccine trials
Authors: Madewell Zachary J. , Piontti Ana Pastore Y , Zhang Qian , Burton Nathan , Yang Yang , Longini Ira M. , Halloran M. Elizabeth , Vespignani Alessandro , Dean Natalie E.
Published: February 2021

Background/Aims

Novel strategies are needed to make vaccine efficacy trials more robust given the uncertain epidemiology of outbreaks. Spatially resolved mathematical and statistical models can help investigators identify sites at highest risk of future transmission and prioritize these for inclusion in trials. Models can also characterize the uncertainty in whether transmission will occur at a site, and how nearby or connected sites may have correlated outcomes. A structure is needed for how trials can use models to address key design questions, including how to prioritize sites, the optimal number of sites, and how to allocate participants across sites.

Methods

We illustrate the added value of models using the motivating example of Zika vaccine trial planning during the 2015-2017 Zika epidemic. We used a stochastic, spatially resolved, agent-based transmission model (GLEAM) to generate 1,142 epidemics and site-level incidence at 100 high-risk sites in the Americas. We considered several strategies for prioritizing sites (average site-level incidence of infection across epidemics, median incidence, probability of exceeding 1% incidence), selecting the number of sites, and allocating sample size across sites (equal enrollment, proportional to average incidence, proportional to rank). To evaluate each design, we stochastically simulated trials in each hypothetical epidemic by drawing observed cases from site-level incidence data.

Results

When constraining the overall trial sample size, the optimal number of sites represents a balance between prioritizing highest-risk sites and having enough sites to reduce the chance of observing too few endpoints. The optimal number of sites remained roughly constant despite varying the targeted number of events, although it is necessary to increase the total sample size to achieve the desired power. Though different ranking strategies returned different site orders, they performed similarly with respect to trial power. Instead of enrolling participants equally from each site, investigators can allocate participants proportional to projected incidence, though this did not provide an advantage in our example because the top sites had a roughly similar risk profile. Sites from the same geographic region may have similar outcomes, so optimal combinations of sites may be those that are more geographically dispersed, even when these are not the highest ranked sites.

Conclusions

Mathematical and statistical models may assist in the design of successful vaccination trials by capturing uncertainty and correlation in future transmission. Although many factors affect site selection, such as logistical feasibility, models can help investigators optimize site selection and the number and size of participating sites.
The effects of time-restricted eating vs. standard dietary advice on weight, metabolic health and the consumption of processed food: A pragmatic randomised controlled trial in community-based adults
Authors: Phillips Nicholas Edward , Mareschal Julie , Schwab Nathalie , Manoogian Emily N.C. , Borloz Sylvie , Ostinelli Giada , Gauthier-Jaques Aude , Umwali Sylvie , Rodriguez Elena Gonzalez , Aeberli Daniel , Hans Didier , Panda Satchidananda , Rodondi Nicolas , Naef Felix , Collet Tinh-Hai
Published: February 2021

Weight loss is key to control the increasing prevalence of metabolic syndrome (MS) and its components, i.e. central obesity, hypertension, prediabetes, and dyslipidaemia. We characterised the relationships between eating duration, unprocessed and processed food consumption, and metabolic health. During 4 weeks of observation, 213 adults used a smartphone application to record food and drink consumption, which was annotated for food processing levels following the NOVA classification. Consumption of unprocessed food items showed the highest number of significant associations with MS components after age and sex. In a pragmatic randomised controlled trial, we compared the metabolic benefits of 12h time-restricted eating (TRE) to standard dietary advice (SDA) in 54 adults with an eating duration >14h and at least one MS component. After 6 months, those randomised to TRE lost 1.6% of initial body weight (SD 2.9, p=0.01), compared to the absence of weight loss with SDA (−1.1%, SD 3.5, p=0.19). There was no significant difference in weight loss between TRE and SDA (between-group difference −0.88%, 95% confidence interval −3.1 to 1.3, p=0.43). Our results show the potential of smartphone records to predict metabolic health and highlight that further research is needed to understand individual responses to TRE.
Paclitaxel-Coated or Uncoated Devices: Significant Differences in Patient Populations and Mortality Led to Study Incomparability
Authors: Zhang Chenyang , Yin Guosheng
Published: February 2021

The SWEDEPAD trial reported an unplanned interim analysis to show no difference in the mortality rate between the paclitaxel-coated and uncoated groups (Nordanstig et al., 2020), which contradicts the long-term risk of paclitaxel-coated devices claimed by a meta-analysis (Katsanos et al., 2018). However, there existed significant differences in mortality rates between the SWEDEPAD trial and the trials included in the meta-analysis, which were caused by significant differences in the patient populations. As a result, the SWEDEPAD trial and meta-analysis results are not directly comparable. An updated meta-analysis including the SWEDPEPAD trial and all studies in the meta-analysis (Katsanos et al., 2018) shows marginal differences in mortality rates between the paclitaxel-coated and control groups at two years with Bayesian relative risk (RR) 1.39 (95% credible interval (CrI) [1.01, 2.39]) and frequentist RR 1.16 (95% confidence interval (CI) [0.99, 1.36]) and differences in mortality rates during the entire follow-up period with Bayesian RR 1.29 (95% CrI [1.01, 1.72]) and frequentist RR 1.13 (95% CI [0.99, 1.28]) under random-effects models. Given the relatively short follow-up thus far in the SWEDEPAD trial (with a mean follow-up of 2.49 years) and the paclitaxel-coated risk being long-term (e.g., 4 or 5 years), the interim results on the risk of paclitaxel-coated devices reported by the SWEDEPAD trial warrant further investigation.
COVID-19 vaccine uptake among healthcare workers in the fourth country to authorize BNT162b2 during the first month of rollout
Authors: Barry Mazin , Temsah Mohamad-Hani , Aljamaan Fadi , Saddik Basema , Al-Eyadhy Ayman , Alenezi Shuliweeh , Alamro Nurah , Alhuzaimi Abdullah N , Alhaboob Ali , Alhasan Khalid , Alsohime Fahad , Alaraj Ali , Halwani Rabih , Jamal Amr , Temsah Omar , Alzamil Fahad , Somily Ali , Al-Tawfiq Jaffar A.
Published: February 2021

Background

The Kingdom of Saudi Arabia (KSA) was the fourth country in the world to authorize the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine, which it rolled out on December 17, 2020 and first targeted at healthcare workers (HCWs). This study assesses vaccine uptake among this group during the first month of its availability.

Methods

A national cross-sectional, pilot-validated, self-administered survey was conducted among HCWs in the KSA between December 27, 2020 and January 3, 2021. The survey included sociodemographic details, previous contact with COVID-19 patients, previous infection with COVID-19, receiving (or registering with the Ministry of Health website to receive) the COVID-19 vaccine, sources of HCWs’ information on vaccines, awareness of emerging variants of concern, and anxiety level using the 7-item Generalized Anxiety Disorder assessment. A descriptive bivariate analysis and multivariate logistic binary regression analysis were performed. The primary evaluated outcome was vaccine uptake.

Results

Of the 1,058 participants who completed the survey, 704 (66.5%) were female, and 626 (59.2%) were nurses. Of all the respondents, 352 (33.27%) were enrolled to receive or had already received the vaccine, while 706 (66.73%) had not registered. In a bivariate analysis, not enrolling for vaccination was more likely in females than males (78.5% vs. 21.5%, P < 0.001), HCWs between the ages of 20 and 40 years than those > 40 years (70.4% vs. 29.6%, P = 0.005), Saudi HCWs than expatriates (78% vs 22%, P < 0.001), and among HCWs who used social media as a source of information than those who did not (69.8% vs. 38.6%, P < 0.001). In a multivariate analysis, independent factors for not enrolling to receive the vaccine included being female (aOR = 0.287, 95%CI = 0.206–0.401, P < 0.001), being less than 40 years of age (aOR = 1.021, 95%CI = 1.002–1.040, P = 0.032), and using social media as a source of information (aOR = 0.207, 95%CI = 0.132-1.354, P = 0.001). Factors associated with uptake were being a Saudi national (aOR = 1.918, 95%CI = 1.363–2.698, P < 0.001), working in an intensive care unit (aOR = 1.495, 95%CI = 1.083–2.063, P = 0.014), and working at a university hospital (aOR = 1.867, 95%CI = 1.380–2.525, P < 0.001).

Conclusions

A low level of vaccine uptake was observed especially in female HCWs, those younger than 40 years old, and those who used social media as their source of vaccine information. This survey provides important information for public health authorities in order to scale up vaccination campaigns targeting these HCWs to increase vaccine enrollment and uptake.
Discontinuation of isolation for persons with COVID-19: Is 10 days really safe?
Authors: Felix Alvina Clara , de Paula Anderson V , Ribeiro Andreia Cristina , da Silva Francini Camila , Inemami Marta , Costa Angela A , Leal Cibele Odete D , Figueiredo Walter M , Sérgio Pannuti Claudio , Romano Camila Malta
Published: February 2021

Background

The detection of SARS-CoV-2 RNA by real-time polymerase chain reaction (PCR) in respiratory samples from COVID-19 patients is not a direct indication of the presence of viable viruses. The isolation of SARS-CoV-2 in cell culture system however, can acts as surrogate marker of infectiousness. Cell culture based studies performed mostly with hospitalized and moderate/severe COVID-19 claims that no replication competent virus is found after 9 days of the symptoms onset in respiratory samples. Therefore, it is now recommended 10 days isolation before patient discharge.

Methods

We cell-cultured 29 SARS-COV-2 RT-PCR positive respiratory samples at the 10th day after the illness in Vero E6 cells. After two passages, cytopathic effect and cycle threshold (CT) lower than the obtained in the original sample were used to determine positivity.

Findings

We found viable particles in (7/29) 24% of samples tested. The positivity in cell culture was strongly associated (p<0.0001) to the low cycle thresholds in clinical samples (Ct <21).

Conclusion

This data adds important knowledge to the current protocols for de-isolation of patients with non-hospitalized mild COVID-19.