bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging of the gastrointestinal tract shows reduced small bowel motility and altered chyme in cystic fibrosis compared to controls
Authors: Dellschaft Neele S , Ng Christabella , Hoad Caroline , Marciani Luca , Spiller Robin , Stewart Iain , Menys Alex , Barr Helen , Gowland Penny A , Major Giles , Smyth Alan R
Published: February 2021

Cystic fibrosis (CF) is a genetic disease affecting mucosal secretions. Most patients experience digestive symptoms, but the mechanisms are incompletely understood. Here we explore causes and consequences of slower gastrointestinal transit using magnetic resonance imaging (MRI).

Twelve people with CF and 12 healthy controls, matched for age and gender, underwent MRI scans both fasted and after standardised meals over a period of 6.5 hours. Images were assessed for small bowel motility, longitudinal relaxation time (T1) of ascending colon chyme, chyme texture and appearance of the colon wall.

Small bowel motility scores were significantly lower in CF than in healthy controls in the fasting state (CF median 40 arbitrary units IQR [31, 46] vs Control 86 a.u. [52, 106],P=0.034). This difference was less pronounced postprandially. Furthermore, ascending colon chyme T1was lower in CF than in controls (CF 0.59 s [0.38, 0.77] vs Control 0.79 s [0.55, 1.31],P=0.010). The difference in texture between small bowel and colon chyme, seen in health, was diminished in CF (difference in Haralick contrast 0.90 a.u. [0.38, 1.67] vs Control 2.11 a.u. [0.71, 3.30],P=0.010). Ascending colon mucosa in CF participants had an abnormal appearance compared to controls (Score 1-3, CF 2 [1, 3] vs Controls 1 [1, 1],P=0.019).

Reduced small bowel motility and water content of ascending colon chyme are consistent with slower transit and constipation. MRI provides unique insights into chyme texture in the small bowel (suggesting bacterial overgrowth) and the appearance of the colon mucosa (suggesting altered mucus) in CF.

Key point summary

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People with cystic fibrosis (CF) have intrusive digestive symptoms and severe gut complications, but mechanisms are incompletely understood.

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In this study, 12 people with CF were compared to healthy controls, undergoing repeated MRI scans before and after standardised meals.

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Fasted small bowel motility is reduced in people with CF, consistent with slower transit. In addition, a reduced colonic chyme water content and abnormal appearance of small bowel and colonic chyme as well as colonic mucosa suggest small bowel bacterial overgrowth, fat malabsorption and abnormal mucus production

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These MRI outcomes hold promise in the assessment of therapeutic interventions.
Clustering of Countries for COVID-19 Cases based on Disease Prevalence, Health Systems and Environmental Indicators
Authors: Rizvi Syeda Amna , Umair Muhammad , Cheema Muhammad Aamir
Published: February 2021

The coronavirus has a high basic reproduction number (R0) and has caused the global COVID-19 pandemic. Governments are implementing lockdowns that are leading to economic fallout in many countries. Policy makers can take better decisions if provided with the indicators connected with the disease spread. This study is aimed to cluster the countries using social, economic, health and environmental related metrics affecting the disease spread so as to implement the policies to control the widespread of disease. Thus, countries with similar factors can take proactive steps to fight against the pandemic. The data is acquired for 79 countries and 18 different feature variables (the factors that are associated with COVID-19 spread) are selected. Pearson Product Moment Correlation Analysis is performed between all the feature variables with cumulative death cases and cumulative confirmed cases individually to get an insight of relation of these factors with the spread of COVID-19. Unsupervised k-means algorithm is used and the feature set includes economic, environmental indicators and disease prevalence along with COVID-19 variables. The learning model is able to group the countries into 4 clusters on the basis of relation with all 18 feature variables. We also present an analysis of correlation between the selected feature variables, and COVID-19 confirmed cases and deaths. Prevalence of underlying diseases shows strong correlation with COVID-19 whereas environmental health indicators are weakly correlated with COVID-19.
Public Covid-19 X-ray datasets and their impact on model bias - a systematic review of a significant problem
Authors: Cruz Beatriz Garcia Santa , Bossa Matías Nicolás , Sölter Jan , Husch Andreas Dominik
Published: February 2021

Computer-aided-diagnosis for COVID-19 based on chest X-ray suffers from weak bias assessment and limited quality-control. Undetected bias induced by inappropriate use of datasets, and improper consideration of confounders prevents the translation of prediction models into clinical practice. This study provides a systematic evaluation of publicly available COVID-19 chest X-ray datasets, determining their potential use and evaluating potential sources of bias.

Only 5 out of 256 identified datasets met at least the criteria for proper assessment of risk of bias and could be analysed in detail. Remarkably almost all of the datasets utilised in 78 papers published in peer-reviewed journals, are not among these 5 datasets, thus leading to models with high risk of bias. This raises concerns about the suitability of such models for clinical use.

This systematic review highlights the limited description of datasets employed for modelling and aids researchers to select the most suitable datasets for their task.
Worries about COVID-19 infection and psychological distress at work and while commuting
Authors: Uehara Masamichi , Ishimaru Tomohiro , Ando Hajime , Tateishi Seiichiro , Eguchi Hisashi , Tsuji Mayumi , Mori Koji , Matsuda Shinya , Fujino Yoshihisa
Published: February 2021

Objective

This study examined the relationship between worry about COVID-19 infection in the workplace and while commuting to work and psychological distress in Japan.

Methods

An internet monitor study was conducted. Out of a total of 33,302 participants, 26,841 people were included. The subjects were asked single-item questions about whether they were worried about COVID-19 infection in general, at work and while commuting to work. Kessler 6 (K6) was used to assess psychological distress.

Results

The OR was significantly higher in association with worry about infection in the workplace at 1.71 (95%CI 1.53–1.92) and worry about infection while commuting at 1.49 (95%CI 1.32–1.67).

Conclusions

This study suggests the need for psychological intervention to reduce worry about infection in response to public mental health challenges associated with the COVID-19 pandemic.
SARS-CoV-2 detection by rRT-PCR on self-collected anterior nares swabs or saliva compared with clinician-collected nasopharyngeal swabs — Denver and Atlanta, August – November, 2020
Authors: Marx Grace E. , Smith-Jeffcoat Sarah E. , Biggerstaff Brad J. , Koh Mitsuki , Nawrocki Courtney C. , Travanty Emily A. , Totten Sarah E. , Scott Tracy , De Hey Jesse Chavez-Van , Carlson Jesse J. , Wendel Karen A. , Burakoff Alexis W. , Hoffman Adam , Rebolledo Paulina A. , Schechter Marcos C. , Wang Yun F. , Moore Brooks L. , Atallah Hany Y. , Sexton D. Joseph , Hartloge Claire , Paulick Ashley , Miller Halie K. , Sleweon Sadia , Rosetti Rebecca , Shragai Talya , O’Laughlin Kevin , Stewart Rebekah J. , da Silva Juliana , Biedron Caitlin ,   CDPHE COVID-19 Laboratory Response Team,   CDC COVID-19 Response GA-10 Team,   CDC COVID-19 Response Lab Task Force, Thomas Jennifer D. , Kirking Hannah L. , Tate Jacqueline E. , Rowan Sarah E.
Published: February 2021

Nasopharyngeal swabs (NPS) collected by trained healthcare professionals are the preferred specimen for SARS-CoV-2 testing. Self-collected specimens might decrease patient discomfort, conserve healthcare resources, and be preferred by patients. During August – November 2020, 1,806 adults undergoing SARS-CoV-2 testing in Denver, Colorado and Atlanta, Georgia, provided self-collected anterior nares swabs (ANS) and saliva specimens before NPS collection. Compared to NPS, sensitivity for SARS-CoV-2 detection by rRT-PCR appeared higher for saliva than for ANS (85% versus 80% in Denver; 67% versus 58% in Atlanta) and higher among participants reporting current symptoms (94% and 87% in Denver; 72% and 62% in Atlanta, for saliva and ANS, respectively) than among those reporting no symptoms (29% and 50% in Denver; 50% and 44% in Atlanta, for saliva and ANS, respectively). Compared to ANS, saliva was more challenging to collect and process. Self-collected saliva and ANS are less sensitive than NPS for SARS-CoV-2 detection; however, they offer practical advantages and might be most useful for currently symptomatic patients.
Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated individuals
Authors: Kissler Stephen M. , Fauver Joseph R. , Mack Christina , Tai Caroline G. , Breban Mallery I. , Watkins Anne E. , Samant Radhika M. , Anderson Deverick J. , Metti Jessica , Khullar Gaurav , Baits Rachel , MacKay Matthew , Salgado Daisy , Baker Tim , Dudley Joel T. , Mason Christopher E. , Ho David D. , Grubaugh Nathan D. , Grad Yonatan H.
Published: February 2021

Background

The alpha and delta SARS-CoV-2 variants have been responsible for major recent waves of COVID-19 despite increasing vaccination rates. The reasons for the increased transmissibility of these variants and for the reduced transmissibility of vaccine breakthrough infections are unclear.

Methods

We quantified the course of viral proliferation and clearance for 173 individuals with acute SARS-CoV-2 infections using longitudinal quantitative RT-PCR tests conducted using anterior nares/oropharyngeal samples (n = 199,941) as part of the National Basketball Association’s (NBA) occupational health program between November 28th, 2020, and August 11th, 2021. We measured the duration of viral proliferation and clearance and the peak viral concentration separately for individuals infected with alpha, delta, and non-variants of interest/variants of concern (non-VOI/VOC), and for vaccinated and unvaccinated individuals.

Results

The mean viral trajectories of alpha and delta infections resembled those of non-VOI/VOC infections. Vaccine breakthrough infections exhibited similar proliferation dynamics as infections in unvaccinated individuals (mean peak Ct: 20.5, 95% credible interval [19.0, 21.0] vs. 20.7 [19.8, 20.2], and mean proliferation time 3.2 days [2.5, 4.0] vs. 3.5 days [3.0, 4.0]); however, vaccinated individuals exhibited faster clearance (mean clearance time: 5.5 days [4.6, 6.6] vs. 7.5 days [6.8, 8.2]).

Conclusions

Alpha, delta, and non-VOI/VOC infections feature similar viral trajectories. Acute infections in vaccinated and unvaccinated people feature similar proliferation and peak Ct, but vaccinated individuals cleared the infection more quickly. Viral concentrations do not fully explain the differences in infectiousness between SARS-CoV-2 variants, and mitigation measures are needed to limit transmission from vaccinated individuals.
Healthcare-associated COVID-19 in England: a national data linkage study
Authors: Bhattacharya Alex , Collin Simon M , Stimson James , Thelwall Simon , Nsonwu Olisaeloka , Gerver Sarah , Robotham Julie , Wilcox Mark , Hopkins Susan , Hope Russell
Published: February 2021

Objectives

Nosocomial transmission was an important aspect of SARS-CoV-1 and MERS-CoV outbreaks. Healthcare-associated SARS-CoV-2 infection has been reported in single and multi-site hospital-based studies in England, but not nationally.

Methods

Admission records for all hospitals in England were linked to SARS-CoV-2 national test data for the period 01/03/2020 to 31/08/2020. Case definitions were: community-onset community-acquired (CO.CA), first positive test (FPT) <14 days pre-admission, up to day 2 of admission; hospital-onset indeterminate healthcare-associated (HO.iHA), FPT on day 3-7; hospital-onset probable healthcare-associated (HO.pHA), FPT on day 8-14; hospital-onset definite healthcare-associated (HO.HA), FPT from day 15 of admission until discharge; community-onset possible healthcare-associated (CO.pHA), FPT ≤14 days post-discharge.

Results

One-third (34.4%, 100,859/293,204) of all laboratory-confirmed COVID-19 cases were linked to a hospital record. HO.pHA and HO.HA cases represented 5.3% (15,564/293,204) of all laboratory-confirmed cases and 15.4% (15,564/100,859) of laboratory-confirmed cases among hospital patients. CO.CA and CO.pHA cases represented 86.5% (253,582/293,204) and 5.1% (14,913/293,204) of all laboratory-confirmed cases, respectively.

Conclusions

Up to 1 in 6 SARS-CoV-2 infections among hospitalised patients with COVID-19 in England during the first 6 months of the pandemic could be attributed to nosocomial transmission, but these represent less than 1% of the estimated 3 million COVID-19 cases in this period.
Sensorimotor deficits in distance runners with medial plantar pain
Authors: Funk Colton , Fraser John J. , Resch Jacob , Hertel Jay
Published: February 2021

Context

Medial plantar pain is a complex and multifactorial condition experienced by some distance runners, which makes etiological differentiation and diagnosis challenging.

Objective

To assess plantar sensation, pain perception and sensitivity, intrinsic foot strength, and foot morphology before and after a 9.7 km run in long-distance runners with and without medial plantar pain.

Design

Descriptive laboratory study

Setting

Laboratory.

Patients

Seven distance runners with medial plantar pain (four males, three females; aged 22.3±3.7 years; BMI 22.3±3.5 kg/m2) and seven matched healthy controls (four males, three females; aged 20.3±1.0 years; BMI 22.0±1.7 kg/m2) were recruited from a public university.

Intervention(s)

Participants ran a six-mile course in their own footwear at a self-selected pace.

Main Outcome Measures

Pain visual analogue scale (VAS), pressure pain thresholds (PPT), plantar sensation, foot morphology, weight-bearing dorsiflexion (WBDF), forefoot joint mobility, toe flexion, intrinsic foot muscle strength, and a seated neural provocation test were analyzed pre-and post-run utilizing mixed model group by time ANOVAs, post hoc effect size point estimates, and 95% confidence intervals.

Results

A significant group by time interaction was observed for PPT at the mid-arch (Control: pre: 83.0±27.4N, post: 79.5±22.6N; Symptomatic: pre: 90.5±31.9N, post: 70.1±32.7 N; p=.03) and posterior tibialis (PT) (Control: pre: 75.7±19.5 N, post: 65.7±14.2N; Symptomatic: pre: 75.8±20.4 N, post: 51.1±11.9 N; p=.05) sites. PPT in the posterior tibialis significantly decreased in the symptomatic group following the run (ES=1.5, 95% CI: 0.3, 2.7). Both groups demonstrated significantly decreased plantar sensation thresholds at the base of the 5th metatarsal (p=.04), PPT at the calcaneal tuberosity (p=.001), and increased TMT extension (p=.01) and WBDF (p=.01) following the run.

Conclusions

The etiology of medial plantar pain observed in our sample was likely attributed to central sensitization and running-induced sensory changes. Clinicians should include sensorimotor testing when managing patients with medial plantar pain.

Key Points

Medial plantar pain is a unique pathologic entity that has not been previously well described and likely caused by central sensitization. Clinicians should include sensorimotor testing and interventions when managing patients with medial plantar pain.
Co-development of a best practice checklist for mental health data science: A Delphi study
Authors: Kirkham E.J. , Crompton C.J. , Iveson M.H. , Beange I. , McIntosh A. , Fletcher-Watson S.
Published: February 2021

Background

Mental health research is commonly affected by difficulties in recruiting and retaining participants, resulting in findings which are based on a sub-sample of those actually living with mental illness. Increasing the use of Big Data for mental health research, especially routinely-collected data, could improve this situation. However, steps to facilitate this must be enacted in collaboration with those who would provide the data - people with mental health conditions.

Methods

We used the Delphi method to create a best practice checklist for mental health data science. Twenty participants with both expertise in data science and personal experience of mental illness worked together over three phases. In the Phase 1, participants rated a list of 63 statements and added any statements or topics that were missing. Statements receiving a mean score of 5 or more (out of 7) were retained. These were then combined with the results of a rapid thematic analysis of participants’ comments to produce a 14-item draft checklist, with each item split into two components: best practice now and best practice in the future. In Phase 2, participants indicated whether or not each item should remain in the checklist, and items that scored more than 50% endorsement were retained. In Phase 3 participants rated their satisfaction with the final checklist.

Results

The final checklist was made up of 14 “best practice” items, with each item covering best practice now and best practice in the future. At the end of the three phases, 85% of participants were (very) satisfied with the two best practice checklists, with no participants expressing dissatisfaction.

Conclusions

Increased stakeholder involvement is essential at every stage of mental health data science. The checklist produced through this work represents the views of people with experience of mental illness, and it is hoped that it will be used to facilitate trustworthy and innovative research which is inclusive of a wider range of individuals.
Knowledge, attitudes and perceptions towards COVID-19 vaccinations: a cross-sectional community survey in Bangladesh
Authors: Islam Md. Saiful , Siddique Abu Bakkar , Akter Rejina , Tasnim Rafia , Sujan Md. Safaet Hossain , Ward Paul R , Sikder Md. Tajuddin
Published: February 2021

Background

Several vaccines have been approved against coronavirus disease (COVID-19) and distributed globally in different regions. However, general community knowledge, attitudes and perceptions towards COVID-19 vaccinations are poorly understood. Thus, the study aimed to investigate community knowledge, attitudes and perceptions towards COVID-19 vaccinations in Bangladesh.

Methods

An exploratory and anonymous population-based e-survey was conducted among 1658 general individuals (55.6% male; mean age=23.17±6.05 years; age range=18-65 years). The survey was conducted using a semi-structured and self-reported questionnaire containing informed consent along with four sections (i.e., socio-demographics, knowledge, attitudes, and perceptions). Multiple linear regression was performed to determine the variables predicting knowledge, and attitudes towards COVID-19 vaccinations.

Results

The mean scores of knowledge and attitudes were 2.83±1.48 (out of 5) and 9.34±2.39 (out of 12) respectively. About a quarter of participants thought that the COVID-19 vaccination available in Bangladesh is safe, only 60% will have the vaccination and about two-thirds will recommend it to family and friends. In the multiple regression model, higher SES, having university/ higher levels of education, holding nuclear families and having previous history of essential vaccines uptake were associated with knowledge; whilst attitudes were significantly associated with being female and having previous history of essential vaccines uptake. Just over half of the participants thought that everyone should be vaccinated and 61% responded that health workers should be vaccinated first on priority basis. 95% vaccine should be administered free of charge in Bangladesh and almost 90% believed that the COVID-19 vaccine used in Bangladesh may have side effects.

Conclusions

The findings reflect inadequate knowledge but more positive attitudes towards COVID-19 vaccine among the general population in Bangladesh. In order to improve knowledge, immediate health education programs need to be initiated before mass vaccination schedule.
Retrospective study of the first wave of COVID-19 in Spain: analysis of counterfactual scenarios
Authors: Steinegger Benjamin , Granell Clara , Rapisardi Giacomo , Gómez Sergio , Matamalas Joan T. , Soriano-Paños David , Gómez-Gardeñes Jesús , Arenas Alex
Published: February 2021

One of the most important questions on the COVID-19 pandemic is ascertaining the correct timing to introduce non-pharmaceutical interventions (NPIs), based mainly on mobility restrictions, to control the rising of the daily incidence in a specific territory. Here, we make a retrospective analysis of the first wave of the epidemic in Spain and provide a set of useful insights to optimize actions in the near future. We have reconstructed the exposure times, from infection to detectability, to correctly estimate the reproduction number Rt. This enables us to analyze counterfactual scenarios to understand the impact of earlier or later responses, decoupling containment measures from natural immunity. Our results quantify the differences in the number of fatalities for earlier and later responses to the epidemic in Spain.

Teaser

“We propose a backward analysis of pandemic incidence in a region to determine the correct timing of authorities’ non-pharmaceutical interventions to fight COVID-19”
An exploratory study on the correlation of population SARS-CoV-2 cycle threshold values to local disease dynamics
Authors: Tso Chak Foon , Garikipati Anurag , Green-Saxena Abigail , Mao Qingqing , Das Ritankar
Published: February 2021

Introduction

Despite limitations on the use of cycle threshold (CT) values for individual patient care, population distributions of CT values may be useful indicators of local outbreaks.

Methods

Specimens from the greater El Paso area were processed in the Dascena COVID-19 Laboratory. Daily median CT value, daily transmission rate R(t), daily count of COVID-19 hospitalizations, daily change in percent positivity, and rolling averages of these features were plotted over time. Two-way scatterplots and linear regression evaluated possible associations between daily median CT and outbreak measures. Cross-correlation plots determined whether a time delay existed between changes in the daily median CT value and measure of community disease dynamics.

Results

Daily median CT was negatively correlated with the daily R(t), the daily COVID-19 hospitalization count (with a time delay), and the daily change in percent positivity among testing samples. Despite visual trends suggesting time delays in the plots for median CT and outbreak measures, a statistically significant delay was only detected between changes in median CT and COVID-19 hospitalization count.

Conclusions

This study adds to the literature by analyzing samples collected from an entire geographical area, and contextualizing the results with other research investigating population CT values.
Convalescent plasma for preventing critical illness in COVID-19: A phase 2 trial and immune profile
Authors: Sturek Jeffrey M. , Thomas Tania A. , Gorham James D. , Sheppard Chelsea A. , Raymond Allison E. , Guex Kristen Petros De , Harrington William B. , Barros Andrew J. , Madden Gregory R. , Alkabab Yosra M. , Lu David , Liu Qin , Poulter Melinda D. , Mathers Amy J. , Thakur Archana , Kubicka Ewa M. , Lum Lawrence G. , Heysell Scott K.
Published: February 2021

Rationale

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring rapid adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting.

Objectives

We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28 day mortality.

Methods

In a single-arm phase II study, patients >18 years-old with respiratory symptoms documented with COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 hours of admission. Detection of respiratory tract SARS-CoV-2 by polymerase chain reaction and circulating anti-SARS-CoV-2 antibody titers were measured before and at time points after CIP transfusion.

Measurements and Main Results

Twenty-nine patients were transfused CIP and forty-eight contemporaneous controls were identified with comparable baseline characteristics. Levels of anti-SARS-CoV-2 IgG, IgM, and IgA anti-spike, anti-receptor-binding domain, and anti-nucleocapsid significantly increased from baseline to post-transfusion for all proteins tested. In patients transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298).

Conclusions

Transfusion of high-titer CIP to patients early after admission with COVID-19 respiratory disease was associated with reduced ICU transfer and 28-day mortality but was not statistically significant. Follow up randomized trials may inform the use of CIP for COVID-19 or future coronavirus pandemics.
A comparison of performance metrics for cloth face masks as source control devices for simulated cough and exhalation aerosols
Authors: Lindsley William G. , Blachere Francoise M. , Beezhold Donald H. , Law Brandon F. , Derk Raymond C. , Hettick Justin M. , Woodfork Karen , Goldsmith William T. , Harris James R. , Duling Matthew G. , Boutin Brenda , Nurkiewicz Timothy , Noti John D.
Published: February 2021

Universal mask wearing is recommended by the Centers for Disease Control and Prevention to help control the spread of COVID-19. Masks reduce the expulsion of respiratory aerosols (called source control) and offer some protection to the wearer. However, masks vary greatly in their designs and construction materials, and it is not clear which are most effective. Our study tested 15 reusable cloth masks (which included face masks, neck gaiters, and bandanas), two medical masks, and two N95 filtering facepiece respirators as source control devices for aerosols ≤ 7 µm produced during simulated coughing and exhalation. These measurements were compared with the mask filtration efficiencies, airflow resistances, and fit factors. The source control collection efficiencies for the cloth masks ranged from 17% to 71% for coughing and 35% to 66% for exhalation. The filtration efficiencies of the cloth masks ranged from 1.4% to 98%, while the fit factors were 1.3 to 7.4 on an elastomeric manikin headform and 1.0 to 4.0 on human test subjects. The correlation coefficients between the source control efficacies and the other performance metrics ranged from 0.31 to 0.66 and were significant in all but one case. However, none of the alternative metrics were strong predictors of the source control performance of cloth masks. Our results suggest that a better understanding of the relationships between source control performance and metrics like filtration efficiency, airflow resistance, and fit factor are needed to develop simple methods to estimate the effectiveness of masks as source control devices for respiratory aerosols.
Mortality in COVID-19 amongst women on Hormone Replacement Therapy or Combined Oral Contraception: A cohort study
Authors: Dambha-Miller Hajira , Hinton William , Joy Mark , Feher Michael , Lusignan Simon de
Published: February 2021

Objective

To investigate the association between Hormone Replacement Therapy (HRT) or Combined Oral Contraception (COCP) use, and the likelihood of death in women with COVID-19.

Design

A cohort study

Setting

465 general practices in England within the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database.

Population

1,863,478 women aged over 18 years

Methods

We identified a cohort of women with COVID-19 from the computerised medical records of the RCGP RSC database. Mixed-effects logistic regression models were used to quantify the association between HRT or COCP use, and all-cause mortality among women with COVID-19 in unadjusted and adjusted models.

Results

There were 5451 COVID-19 cases within the cohort. HRT was associated with a significantly lower likelihood of all-cause mortality in COVID-19 (adjusted OR 0.22, 95%□CI 0.05 to 0.94). There were no reported events for all-cause mortality in women prescribed COCPs. This prevented further examination of the impact of COCP.

Conclusions

Women on HRT with COVID-19 had a lower likelihood of death. Further work is needed in larger cohorts to examine the association of COCP in COVID-19. Our findings support the current hypothesis that oestrogens may contribute a protective effect against COVID-19 severity.

Funding

This study was funded by a School for Primary Care National Institute for Health Research grant (SPCR2014-10043).
Fat-enlarged Axillary Lymph Nodes are Associated with Node-Positive Breast Cancer in Obese Patients
Authors: diFlorio-Alexander Roberta M. , Song Qingyuan , Dwan Dennis , Austin-Strohbehn Judith A. , Muller Kristen E. , Kinlaw William B. , MacKenzie Todd A. , Karagas Margaret R. , Hassanpour Saeed
Published: February 2021

Purpose

Obesity-associated fat infiltration of organ systems is accompanied by organ dysfunction and poor cancer outcomes. Obese women demonstrate variable degrees of fat infiltration of axillary lymph nodes (LNs), and they are at increased risk for node-positive breast cancer. However, the relationship between enlarged axillary nodes and axillary metastases has not been investigated. The purpose of this study is to evaluate the association between axillary metastases and fat-enlarged axillary nodes visualized on mammograms and breast MRI in obese women with a diagnosis of invasive breast cancer.

Methods

This retrospective case-control study included 431 patients with histologically confirmed invasive breast cancer. The primary analysis of this study included 306 patients with pre-operative MRI and body mass index (BMI) > 30 (201 node-positive cases and 105 randomly selected node-negative controls) diagnosed with invasive breast cancer diagnosed between April 1, 2011, and March 1, 2020. The largest visible LN was measured in the axilla contralateral to the known breast cancer on breast MRI. Multivariate logistic regression models were used to assess the association between node-positive status and LN size adjusting for age, BMI, tumor size, tumor grade, tumor subtype, and lymphovascular invasion.

Results

A strong likelihood of node-positive breast cancer was observed among obese women with fat-expanded lymph nodes (adjusted OR for the 4th vs. 1st quartile for contralateral LN size on MRI: 9.70; 95% CI: 4.26, 23.50; p < 0.001). The receiver operating characteristic curve for size of fat-enlarged nodes in the contralateral axilla identified on breast MRI had an area under the curve of 0.72 for predicting node-positive breast cancer and this increased to 0.80 when combined with patient and tumor characteristics.

Conclusion

Fat expansion of axillary lymph nodes was associated with a high likelihood of axillary metastases in obese women with invasive breast cancer independent of BMI and tumor characteristics.
The impact of COVID-19 on children with oesophageal atresia and/or tracheo-oesophageal fistula (OA/TOF)
Authors: Stewart A. , Smith C. , Eaton S. , De Coppi P. , Wray J.
Published: February 2021

Purpose

The COVID-19 pandemic has resulted in a global health crisis of unparalleled magnitude. The direct risk to the health of children is low. However, disease containment measures have society-wide impacts. This study explored the pandemic experiences of parents of children with oesophageal atresia/tracheo-oesophageal fistula in the UK.

Design

An online forum was conducted using a private group on Facebook, in collaboration with a patient support group. Thematic analysis was used to identify key themes.

Results

The online forum ran between 7th November-18th December 2020 with 109 participants. Themes related to healthcare and non-healthcare impacts. Parents experienced changes and limitations to healthcare access, anxiety regarding health risks, “collateral” damage to well-being because of isolation and an impact on finances and employment. Parents described a transition from worry about direct health risks to concern about the impact of isolation on socialisation and development. A process of risk-benefit analysis led some to transition to a more “normal life”, while others continued to isolate. Benefits to their child’s health from isolation, positive experiences with remote healthcare and a gradual easing of anxiety were also identified.

Implications and relevance

This study highlights the wide-ranging impact of the COVID-19 pandemic on children and their families. Although focussed on oesophageal atresia/tracheo-oesophageal fistula, the emerging themes will be relevant to many children with complex, chronic health conditions. There are implications for healthcare delivery, including telehealth, during and after the pandemic period. Accurate and consistent messaging is required. Third sector organisations are ideally positioned support this.
Adrenaline (epinephrine) compared to selective beta-2-agonist in adults or children with acute asthma: a systematic review and meta-analysis
Authors: Baggott Christina , Hardy Jo , Sparks Jenny , Sabbagh Doñah , Beasley Richard , Weatherall Mark , Fingleton James
Published: February 2021

Background

International asthma guidelines recommend against adrenaline administration in acute asthma unless associated with anaphylaxis or angioedema. However, administration of intra-muscular adrenaline in addition to nebulised selective β2-agonist is recommended for acute severe or life-threatening asthma in many pre-hospital guidelines. We conducted a systematic review to determine the efficacy of adrenaline in comparison to selective β2-agonist in acute asthma.

Methods

We included peer-reviewed publications of randomised controlled trials (RCTs) that enrolled children or adults in any healthcare setting and compared adrenaline by any route to selective β2-agonist by any route for an acute asthma exacerbation. The primary outcome was treatment failure, as indicated by hospitalisation, stay >24hrs in emergency department, need for intubation, or death.

Results

Thirty-eight of 1,140 studies were included, involving 2,275 participants. Overall quality of evidence was low. There was significant statistical heterogeneity, I2=56%. The pooled odds ratio for treatment failure with adrenaline versus selective β2-agonist was 0.99 (0.74 to 1.34), p=0.96. There was strong evidence that recruitment age-group was associated with different estimates of the risk of treatment failure; with studies recruiting adults-only having a lower risk of treatment failure with adrenaline. It was not possible to determine whether adrenaline in addition to selective β2-agonist improved outcomes.

Conclusion

The limited evidence available suggests that adrenaline and selective β2-agonists have similar efficacy in acute asthma and does not support the use of adrenaline in addition to selective β2-agonists in acute asthma. There is a need for high-quality double-blind RCTs to address this issue.

PROSPERO registration number CRD42017079472
Moment-to-moment brain signal variability reliably predicts psychiatric treatment outcome
Authors: Månsson Kristoffer N. T. , Waschke Leonhard , Manzouri Amirhossain , Furmark Tomas , Fischer Håkan , Garrett Douglas D.
Published: February 2021

Biomarkers of psychiatric treatment response remain elusive. Functional magnetic resonance imaging (fMRI) has shown promise, but low reliability has limited the utility of typical fMRI measures as harbingers of treatment success. Strikingly, temporal variability in brain signals has already proven a sensitive and reliable indicator of individual differences, but has not yet been examined in relation to psychiatric treatment outcomes. Here, 45 patients with social anxiety disorder were scanned twice (11 weeks apart) using simple task-based and resting-state fMRI to capture moment-to-moment neural variability. After fMRI test-retest, patients underwent a 9-week cognitive-behavioral therapy. Reliability-based 5-fold cross-validation showed that task-based brain signal variability was the strongest contributor in a treatment outcome prediction model (total rACTUAL,PREDICTED = .77) - outperforming self-reports, resting-state neural variability, and standard mean-based measures of neural activity. Notably, task-based brain signal variability showed excellent test-retest reliability (intraclass correlation coefficient = .80), even with a task length less than 3 minutes long. Rather than a source of undesirable “noise”, moment-to-moment fMRI variability may instead serve as a highly reliable and efficient prognostic indicator of clinical outcome.
A proteomics workflow reveals predictive autoantigens in idiopathic pulmonary fibrosis
Authors: Leuschner Gabriela , Mayr Christoph H. , Ansari Meshal , Seeliger Benjamin , Frankenberger Marion , Kneidinger Nikolaus , Hatz Rudolf A. , Hilgendorff Anne , Prasse Antje , Behr Jürgen , Mann Matthias , Schiller Herbert B.
Published: February 2021

Rationale

The diagnosis of idiopathic pulmonary fibrosis (IPF) requires exclusion of known underlying autoimmunity, as present in interstitial lung diseases associated with connective tissue diseases (CTD-ILD). However, autoantibodies of unknown significance have been repeatedly detected in IPF patients.

Objectives

We aimed to characterize autoreactivities in IPF patients beyond clinically established autoimmune panels by establishing an unbiased assay for de novo discovery of autoantigens in different forms of ILD and healthy controls.

Methods

We developed the proteomic Differential Antigen Capture (DAC) assay, capturing patient antibodies from plasma, followed by affinity purification of lung proteins coupled to mass spectrometry. Plasma antibodies from patients with IPF (n=35), CTD-ILD (n=24) and age-matched controls (n=32) were analyzed and validated in an independent cohort (IPF: n=40; CTD-ILD: n=20). Plasma antibody binding profiles were associated with clinical meta-data including diagnosis, lung function and transplant free survival.

Measurements and Main Results

We identified 586 putative autoantigens in both study cohorts with a broad heterogeneity among disease entities and cohorts. The prevalence of autoantibodies was higher in IPF compared to CTD-ILD. We identified a predictive autoimmune signature that was significantly associated with reduced transplant free survival in IPF. In particular, presence of autoantibodies to Thrombospondin 1 (THBS1) was associated with a significantly reduced survival in patients with IPF (p=0.002), independent of the study cohort, suggesting clinical relevance as predictive biomarker.

Conclusions

Unbiased proteomic profiling reveals that the overall prevalence of autoantibodies is similar in IPF and CTD-ILD patients and identifies novel IPF specific autoantigens associated with patient survival.
Lesion Symptom Mapping of Domain-Specific Cognitive Impairments using Routine Imaging in Stroke
Authors: Moore Margaret Jane , Demeyere Nele
Published: February 2021

Background and Purpose

This large-scale lesion-symptom mapping study aimed to investigate the necessary neuro-anatomical substrates of 5 cognitive domains frequently affected post stroke: Language, Attention, Praxis, Number, and Memory. This study aims to demonstrate the validity of using routine clinical brain imaging from a large, real-world patient cohort for lesion-symptom mapping.

Methods

Behavioural cognitive screening data from the Oxford Cognitive Screen and routine clinical neuroimaging from 573 acute patients was used in voxel-based lesion-symptom mapping analyses. Patients were classed as impaired or not on each of the subtests within 5 cognitive domains.

Results

Distinct patterns of lesion damage were associated with different domains. Language functions were associated with damage to left hemisphere fronto-temporal areas. Visuo-spatial functions were associated with damage to posterior occipital areas (Visual Field) and the right temporo-parietal region (Visual Neglect). Different memory impairments were linked to distinct voxel clusters within the left insular and opercular cortices. Deficits which were not associated with localised voxels (e.g. praxis, executive function) represent distributed functions.

Conclusion

The standardised, brief Oxford Cognitive Screen was able to reliably differentiate distinct neural correlates critically involved in supporting domain-specific cognitive abilities. By demonstrating and replicating known brain anatomy correlates within real-life clinical cohorts using routine CT scans, we open up VLSM techniques to a wealth of clinically relevant studies which can capitalise on using existing clinical brain imaging.
Ultrasensitive assay for saliva-based SARS-CoV-2 antigen detection
Authors: Ren A , Sohaei D , Zacharioudakis I , Sigal GB , Stengelin M , Mathew A , Campbell C , Padmanabhan N , Romero D , Joe J , Soosaipillai A , Kulasingam V , Mazzulli T , Li XA , McGeer A , Diamandis EP , Prassas I
Published: February 2021

Widespread SARS-CoV-2 testing is highly valuable for identifying asymptomatic/pre-symptomatic individuals to slow community disease transmission. However, there remains a technological gap for highly reliable, easy, and quick SARS-CoV-2 diagnostic tests that are suitable for frequent mass testing. Compared to the conventional nasopharyngeal (NP) swab-based tests, saliva-based methods are attractive due to easier and safer sampling protocols. Despite its merits in rapid turn-around-time and high throughput compared to traditional PCR-based technologies, the widespread use of saliva-based SARS-CoV-2 rapid antigen tests is hindered by limited analytical sensitivity of current methods. Here, we report the first ultrasensitive, saliva-based SARS-CoV-2 antigen assay with an analytical sensitivity of < 0.32 pg/ml, corresponding to 4 viral RNA copies/µl, which is comparable to that of PCR-based tests. Using the novel electrochemiluminescence (ECL)-based S-PLEX immunoassay, we measured the SARS-CoV-2 nucleocapsid (N) antigen concentration in 105 saliva samples obtained from non-COVID-19 and COVID-19 patients. Our assay displayed absolute specificity and high sensitivity (90.2%), where it correctly identified samples with viral loads up to 35 CT cycles by saliva-based PCR. Paired NP swab-based PCR results were also obtained for 86 cases for comparison. Our assay showed high concordance with saliva-based and NP swab-based PCR in samples with negative (< 0.32 pg/ml) and strongly positive (> 2 pg/ml) N antigen concentrations. Our study unveiled the ultrasensitivity and specificity of the saliva-based S-PLEX assay, demonstrating its clinical value as a high throughput, complementary alternative to PCR-based techniques. The novel technique is especially valuable in cases where compliance to frequent swabbing may be problematic (e.g. schools, nursing homes, etc.).
Repurposing Colchicine for the Management of COVID-19: A Systematic Review and Meta-analysis
Authors: Mohanty Rashmi Ranjan , Meher Bikash Ranjan , Padhy Biswa Mohan , Das Smita
Published: February 2021

Many anti-inflammatory drugs like, tocilizumab, N-acetylcystiene and etolizumab has been repurposed for the management of COVID-19 with variable success. Colchicine exhibits anti-inflammatory activity by tubulin disruption and inhibition of leucocyte-mediated inflammatory activities like production of superoxide and release of various cytokines which are central to the pathophysiology of COVID-19. So, this systematic review and meta-analysis assessed the currently available data on the use of colchicine for the treatment of COVIDLJ19. A total of 3 studies (2 RCTS and 1 observational study) including 402 patients were included out of which 194 patients received colchicine. The random effect model showed the overall pooled OR to be 0.32 (95%CI: 0.18 to 0.56) for the primary outcome (Clinical deterioration) which was statistically significant (p <0.0001). Also there was increase in adverse effect (diarrhoea) with use of colchicine as suggested by the pooled OR (OR=4.56, 95%CI: 2.04 to 10.15, P=0.0002). With the limited number of available studies, it has shown statistically significant reduction in clinical deterioration in COVID-19. Though there was an increase in adverse effect in the form of diarrhoea, it was mild and self-limiting.
Chyawanprash for the prevention of COVID-19 infection among healthcare workers: A Randomized Controlled Trial
Authors: Gupta Arun , Madan Amit , Yadav Babita , Mundada Pallavi , Singhal Richa , Pandey Yogesh Kumar , Agarwal Riju , Tripathi Arunabh , Rana Rakesh , Sharma B. S. , Rao BCS , Bharti  , Srikanth Narayanam , Dhiman K. S.
Published: February 2021

Background

Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are at high risk of exposure, the standard of care is personal protection from getting infected. Whether Ayurvedic rasayana drug like Chyawanprash can prevent symptomatic infection in frontline health care workers is unknown.

Objective

To evaluate the effect of the combination of Chyawanprash and Standard Preventive Regimen compared to the use of Standard Preventive Regimen alone on the proportion of RT-PCR confirmed COVID-19 infections among frontline healthcare workers (HCWs).

Methods

An open-label randomized controlled trial was conducted in the HCWs between 25 to 60 years age currently working in an environment with chance of direct exposure to COVID-19 cases. The interventions to be compared in this trial were Standard Preventive Regimen as per institutional guidelines and based on their roles (Group I) and Ayurvedic Intervention viz., Chyawanprash 12 g twice for 30 days from day of randomization plus Standard Preventive Regimen (Group II). The incidence of RT PCR confirmed COVID-19 cases in both groups, was the primary outcome measure. Evaluation of the safety of the study drug (by any statistically significant change in various biochemical and hematological parameters and occurrence of any adverse drug reactions); incidence of any other infective diseases (bacterial /viral/ fungal / etc.) like upper respiratory tract illness during the study period and any change in the immunoglobulins like IgG, IgM and IgE and inflammatory markers like TNF alpha, IL-6 and IL-10 were the secondary outcome measures.

Results

Out of 193 participants who completed the study, no participant in both groups was COVID-19 positive at the end of one month. In post intervention follow-up, 4 subjects in Group I and 2 subjects in Group II were COVID-19 positive. No adverse drug reaction or any serious adverse event was reported during the study. No clinically significant change in the safety parameters was observed before and after the study. Statistically significant rise in Serum IgG level was seen in Group II but other inflammatory and immune markers did not show statistically significant difference.

Conclusion

Chyawanprash was well tolerated by all the participants in the intervention group but to prove its adaptogenic effect and efficacy as an add-on to the standard care in preventing the occurrence of COVID-19, clinical trial for longer duration with larger sample size is needed.

Trial registration

Clinical Trials Registry of India vide CTRI/2020/05/025275 dated 20/05/2020

Date of IEC approval

19.5.2020