bluuebunny/crossref_metadata_2025 huggingface dataset:
Details of COVID-19 Disease Mitigation Strategies in 17 K-12 Schools in Wood County, Wisconsin
Authors: Falk Amy , Benda Alison , Falk Peter , Steffen Sarah , DeCoster Mikaela , Gandhi Monica , Høeg Tracy Beth
Published: March 2021

Importance

With the current COVID-19 return-to-school guidelines, over half of America’s K-12 students are being denied access to full time in-person education, leading to harmful academic, emotional and health consequences.

Objective

To describe the specific details of mitigation strategies employed at 17 K-12 schools in Wisconsin during a time of exceptionally high COVID-19 community disease prevalence where in-school transmission was minimal. The aim of this report is to assist school districts and governing bodies in developing full-time return to school plans.

Design

Retrospective cohort

Setting

Wood County, Wisconsin, August 31–November 29, 2020

Participants

5,530 students and staff from 17 schools in 4 school districts

Main outcomes and measures

Distancing between primary and secondary students in school

School ventilation details

Masking among teachers

Lunch, recess and bussing practices

Results

89.3% of elementary students included in our study did not maintain 6 feet of physical distancing in the classroom and 94.8% were within 6 feet in lunchrooms. The majority of secondary students (86.2%) were able to maintain 6 feet of distancing in the classroom but no students were greater than 6 feet in the hallways. 58.8% of schools did not install new ventilation systems prior to the school year. Students ate lunch indoors. Bussing of students continued and all elementary children were allowed to go without masks at recess.

Conclusion and relevance

In the setting of high community COVID-19 disease transmission, 6 feet of distance between elementary students and major ventilation system renovations in primary or secondary schools do not appear to be necessary to minimize disease spread. Requiring masks at recess and prohibiting bussing also appears unnecessary. These findings may inform guidance on the safe reopening of schools and allow for more children to return to in-person schooling.
Network-based Modeling of COVID-19 Dynamics: Early Pandemic Spread in India
Authors: Bhattachayya Rupam , Banerjee Sayantan , Mohammed Shariq , Baladandayuthapani Veera
Published: March 2021

Modeling the dynamics of COVID-19 pandemic spread is a challenging and relevant problem. Established models for the epidemic spread such as compartmental epidemiological models e.g. Susceptible-Infected-Recovered (SIR) models and its variants, have been discussed extensively in the literature and utilized to forecast the growth of the pandemic across different hot-spots in the world. The standard formulations of SIR models rely upon summary-level data, which may not be able to fully capture the complete dynamics of the pandemic growth. Since the disease spreads from carriers to susceptible individuals via some form of contact, it inherently relies upon a network of individuals for its growth, with edges established via direct interaction, such as shared physical proximity. Using individual-level COVID-19 data from the early days (January 30 to April 15, 2020) of the pandemic in India, and under a network-based SIR model framework, we performed state-specific forecasting under multiple scenarios characterized by the basic reproduction number of COVID-19 across 34 Indian states and union territories. We validated our short-term projections using observed case counts and the long-term projections using national sero-survey findings. Based on healthcare availability data, we also performed projections to assess the burdens on the infrastructure along the spectrum of the pandemic growth. We have developed an interactive dashboard summarizing our results. Our predictions successfully identified the initial hot-spots of India such as Maharashtra and Delhi, and those that emerged later, such as Madhya Pradesh and Kerala. These models have the potential to inform appropriate policies for isolation and mitigation strategies to contain the pandemic, through a phased approach by appropriate resource prioritization and allocation.
Evaluation of serum antibodies against SARS-CoV□2 in healthcare workers who participated in the operation of charter flights for the evacuation of Japanese residents from Hubei Province
Authors: Suzuki Tetsuya , Hayakawa Kayoko , Ainai Akira , Iwata-Yoshikawa Naoko , Sano Kaori , Nagata Noriyo , Suzuki Tadaki , Wakimoto Yuji , Akiyama Yutaro , Miyazato Yusuke , Nakamura Keiji , Ide Satoshi , Nomoto Hidetoshi , Nakamoto Takato , Ota Masayuki , Moriyama Yuki , Sugiki Yuko , Saito Sho , Morioka Shinichiro , Ishikane Masahiro , Kinoshita Noriko , Kutsuna Satoshi , Ohmagari Norio
Published: March 2021

There are several recommendations for the use of personal protective equipment (PPE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the selection of appropriate PPE for the current situation remains controversial. We measured serum antibody titers for SARS-CoV-2 in 10 participants who were engaged in the operation of charter flights for the evacuation of Japanese residents from Hubei Province. All participants wore PPE in accordance with Centers for Disease Control and Prevention guidelines. A total of 17 samples were tested, and all were seronegative. Hence, we conclude that the current PPE recommendation is effective to protect healthcare workers from SARS-CoV-2 infection.
The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification
Authors: Chora Joana R. , Iacocca Michael A. , Tichy Lukas , Wand Hannah , Kurtz C. Lisa , Zimmermann Heather , Leon Annette , Williams Maggie , Humphries Steve E. , Hooper Amanda J. , Trinder Mark , Brunham Liam R. , Pereira Alexandre Costa , Jannes Cinthia E. , Chen Margaret , Chonis Jessica , Wang Jian , Kim Serra , Johnston Tami , Soucek Premysl , Kramarek Michal , Leigh Sarah E. , Carrie Alain , Sijbrands Eric J. , Hegele Robert A. , Freiberger Tomas , Knowles Joshua W. , Bourbon Mafalda
Published: March 2021

Purpose

In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia (FH) Variant Curation Expert Panel (VCEP) was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. Here, we provide consensus recommendations for the most common FH-causing gene, LDLR, where >2,300 unique FH-associated variants have been identified.

Methods

The multidisciplinary FH VCEP met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate and commentary, consensus among experts was reached.

Results

The consensus LDLR variant modifications to existing ACMG/AMP guidelines include: 1) alteration of population frequency thresholds; 2) delineation of loss-of-function variant types; 3) functional study criteria specifications; 4) co-segregation criteria specifications; and 5) specific use and thresholds for in silico prediction tools, among others.

Conclusion

Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of FH patients.
SGLT2 inhibitors and the risk of diabetic ketoacidosis among adults with Type 2 Diabetes: A systematic review and meta-analysis
Authors: Colacci Michael , Fralick John , Odutayo Ayodele , Fralick Michael
Published: March 2021

Importance

The risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear.

Objective

To examine the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials.

Data Sources

Searches of PubMed, EMBASE and CENTRAL (inception to 15 April 2019) without language restrictions; conference proceedings; and reference lists.

Study Selection

Randomized controlled trials and observational studies that quantified the rate of diabetic ketoacidosis with an SGLT2 inhibitor in comparison to another diabetes medication or placebo.

Data Extraction and Synthesis

Two independent investigators abstracted study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method.

Main Outcome and Measures

Absolute event rates and hazard ratios for diabetic ketoacidosis were extracted from each study.

Results

Seven randomized trials encompassing 42,375 participants and five cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1000 person years. Four randomized trials were included in the meta-analysis, and compared to placebo or comparator medication, SGLT2 inhibitors had a 2.4-fold higher risk of DKA (Relative Risk⍰[RR] =⍰2.46 [95% CI, 1.16-5.21]; I2⍰=⍰0%; P⍰= 0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1000 person years and a 1.7-fold higher rate of DKA compared to another diabetes medication (RR⍰=⍰1.74 [95% CI, 1.01-2.93]; I2⍰=⍰45%; P⍰= 0.12).

Conclusions and Relevance

In adults with type 2 diabetes, SGLT2 inhibitors increase the risk of DKA in both observational studies and large randomized clinical trials.

Registration

CRD42019146855

Funding Source

None

KEY MESSAGES

‐

Case reports and observational studies have suggested that SGLT2 inhibitors may be associated with an increased risk of DKA, but this finding has not been reproduced in older meta-analyses of randomized controlled trials.

‐

In this systematic review and meta-analysis of randomized trials and observational studies including over 350,000 patients, SGLT2 inhibitors were found to be associated with twice the risk of diabetic ketoacidosis versus placebo or a comparator medication.

‐

Patients receiving an SGLT2 inhibitors should be counselled on this risk and provided with appropriate sick-day medication management.
The effect of Covid-19 isolation measures on the cognition and mental health of people living with dementia: a rapid systematic review of one year of evidence
Authors: Suárez-González Aida , Rajagopalan Jayeeta , Livingston Gill , Alladi Suvarna
Published: March 2021

Background

Covid-19 control policies have entailed lockdowns and confinement. Although these isolation measures are thought to be particularly hard and possibly harmful to people with dementia, their specific impact during the pandemic has not yet been synthesised. We aimed to examine and summarise the global research evidence describing the effect of Covid-19 isolation measures on the health of people living with dementia.

Method

We searched Pubmed, PsycINFO and CINAHL up to February 2021 for peer-reviewed quantitative studies of the effects of isolation measures during Covid-19 on cognitive, psychological and functional symptoms of people with any kind of dementia or mild cognitive impairment. We summarised the findings of included papers following current guidelines for rapid reviews.

Results

We identified 15 eligible papers, examining a total of 6,442 people with dementia. 13/15 were conducted in people living in the community and 2 in care homes. 60% (9/15) studies reported changes in cognition with 77% (7/9) of them describing declined cognition by >50% of respondents. 93% (14/15) of studies reported worsening or new onset of behavioural and psychological symptoms. 46% (7/15) studies reported changes in daily function, 6 of them reporting a functional decline in a variable proportion of the population studied.

Conclusion

Lockdowns and confinement measures brought about by the pandemic have damaged the cognitive and psychological health and functional abilities of people with dementia across the world. It is urgent that infection control measures applied to people with dementia are balanced against the principles of non-maleficence. This systematic review makes 4 specific calls for action.

Key Points

Neuropsychiatric symptoms of people with dementia (e.g., anxiety, depressive symptoms, apathy, agitation) were found to worsen during lockdown in the majority of studies.

Cognitive decline affecting memory, orientation concentration and communication was observed by caregivers within few weeks after lockdown.

The deterioration reported occurred in a short window of time (between 1 and 4 months) and it is unlikely to be attributable to the natural variation of the course of dementia.

There is little research conducted in care home residents with dementia (only 2 papers found).

Increase consumption of antipsychotics and benzodiazepines has occurred in people with dementia during lockdown.

Evidence indicates that isolation measures quickly damaged people’s with dementia cognitive and mental health and probably accelerated overall decline.
Compliance to 4Ds of antimicrobial stewardship practices in a tertiary care centre
Authors: Dixit Diksha , Ranka Rajat , Panda Prasan Kumar
Published: March 2021

Background

Indiscriminate use of antimicrobials has been a cause of concern worldwide in recent years because of the potential to give rise to antimicrobial resistance and difficult to treat infections. Antimicrobial Stewardship describes the practice of promoting the selection of the right drug, dosage, delivery route, and duration of antimicrobial therapy (4Ds) to curtail these concerns. Nevertheless, it is important to quantify the magnitude of the problem in terms of the percentage of adherence with respect to each of the 4Ds described above. This will aid in the identification of areas for potential interventions to improve use.

Methods

We undertook a prospective review of the medical records of patients admitted in the medicine wards of a tertiary care centre in Northern India. All those patients who were prescribed on antimicrobials were included and their records reviewed for the indication, drug, dose, delivery, and duration (or by asking the treating physician if not documented). Adherence to the guidelines was determined by referring to the updated literature (local, national, or international standard treatment guidelines or textbooks) for each specific disease condition.

Results

Of the total 304 patients, the choice of drugs was appropriate and matched the guidelines in 218 (72%) patients. Adherence to the right dose in 210 (69%), route of delivery in 216 (71%), and to duration in 197 (65%) were observed. Full adherence to all the above mentioned parameters was observed in 196 (64.5%). Maximum adherence was observed in the treatment of skin and soft tissue infections (100 %) while minimum adherence was observed while administering medical prophylaxis (40 %). Among the non-adherents, over-prescription was observed in 10 (3.3 %), under-prescription in 12 (3.9 %), choice was inappropriate in 46 (15.1 %) and in 30 (10 %) patients, antimicrobials were not indicated but prescribed.

Conclusion

Internist practices antimicrobial stewardship with respect to the prevalent guidelines for right prescription in 2/3rd admitted patients, a sub-optimal one. Right drug, dose, delivery route, duration of therapy are practiced in 72%, 69%, 71%, and 65% patients respectively. To increase adherence to 100%, bedside stewardship practices in form of prospective audit and feedback must be improved.
ExPheWas: a browser for gene-based pheWAS associations
Authors: Legault Marc-André , Perreault Louis-Philippe Lemieux , Dubé Marie-Pierre
Published: March 2021

Structured Abstract

Motivation

The relationship between protein coding genes and phenotypes has the potential to inform on the underlying molecular function in disease etiology. We conducted a phenome-wide association study (pheWAS) of protein coding genes using a principal components analysis-based approach in the UK Biobank.

Results

We tested the association between 19,114 protein coding gene regions and 1,210 phenotypes including anthropometric measurements, laboratory biomarkers, cancer registry data, hospitalization and death record codes and algorithmically-defined cardiovascular outcomes. We report the pheWAS results in a user-friendly web-based browser. Taking atrial fibrillation, a common cardiac arrhythmia, as an example, ExPheWas identified genes that are known drug targets for the treatment of arrhythmias and genes involved in biological processes implicated in cardiac muscle function. We also identifiedMYOTas a possible atrial fibrillation gene.

Availability and implementation

The ExPheWas browser and API are available athttp://exphewas.statgen.org/

Contact

Marie-Pierre.Dube@mhi-rc.org
Modelling the impact of rapid tests, tracing and distancing in lower-income countries suggest that optimal policies vary with rural-urban settings
Authors: Jiang Xilin , Gong Wenfeng , Dobreva Zlatina , Gao Ya , Quaife Matthew , Fraser Christophe , Holmes Chris
Published: March 2021

Low- and middle-income countries (LMICs) remain of high potential for hotspots for COVID-19 deaths and emerging variants given the inequality of vaccine distribution and their vulnerable healthcare systems. We aim to evaluate containment strategies that are sustainable and effective for LMICs. We constructed synthetic populations with varying contact and household structures to capture LMIC demographic characteristics that vary across communities. Using an agent- based model, we explored the optimal containment strategies for rural and urban communities by designing and simulating setting-specific strategies that deploy rapid diagnostic tests, symptom screening, contact tracing and physical distancing. In low-density rural communities, we found implementing either high quality (sensitivity > 50%) antigen rapid diagnostic tests or moderate physical distancing could contain the transmission. In urban communities, we demonstrated that both physical distancing and case finding are essential for containing COVID-19 (average infection rate < 10%). In high density communities that resemble slums and squatter settlements, physical distancing is less effective compared to rural and urban communities. Lastly, we demonstrated contact tracing is essential for effective containment. Our findings suggested that rapid diagnostic tests could be prioritised for control and monitor COVID-19 transmission and highlighted that contact survey data could guide strategy design to save resources for LMICs. An accompanying open source R package is available for simulating COVID-19 transmission based on contact network models.
Hospitalization of mild cases of community-acquired pneumonia decreased more than severe ones during the COVID-19 epidemic
Authors: Nagano Hiroyuki , Takada Daisuke , Shin Jung-ho , Morishita Tetsuji , Kunisawa Susumu , Imanaka Yuichi
Published: March 2021

Objective

The epidemic of the coronavirus disease 2019 (COVID-19) has affected the entire health care systems. Our aim was to assess the impact of the COVID-19 epidemic on the number and severity of cases for community-acquired pneumonia (CAP) in Japan.

Methods

Using claims data from the Quality Indicator/Improvement Project (QIP) database, we included urgent cases of inpatients for CAP from August 1, 2018, to July 30, 2020. We compared the monthly ratio of inpatient cases from August 2018 to July 2019 and August 2019 to July 2020 as a year-over-year comparison. We also compared this ratio according to the severity score “A-DROP” and performed an interrupted time series analysis (ITS) to evaluate the impact of the COVID-19 epidemic on the monthly number of inpatient cases.

Results

A total of 67,900 inpatient cases for CAP in 262 hospitals were included. During the COVID-19 epidemic (defined as the period between March and July 2020), the number of inpatient cases for CAP drastically decreased during the epidemic compared with the same period in the past year (−48.1%), despite only a temporary reduction in the number of other urgent admissions. The number of inpatient cases decreased according to the severity of pneumonia. Milder cases showed a greater decrease in the year-over-year ratio than severe ones (mild −55.2%, moderate −45.8%, severe −39.4%, and extremely severe − 33.2%). The ITS analysis showed that the COVID-19 epidemic reduced the monthly number of inpatient cases for CAP significantly (estimated decrease: −1233 cases; 95% CI, −521 to −1955).

Conclusions

Our study showed a significant reduction in the number of inpatient cases for CAP during the COVID-19 epidemic in Japan. The milder cases showed a greater decrease in the year-over-year ratio of the number of inpatient cases.
Generation of Inhibitory Autoantibodies to ADAMTS13 in Coronavirus Disease 2019
Authors: Doevelaar Adrian A. N. , Bachmann Martin , Hölzer Bodo , Seibert Felix S. , Rohn Benjamin J. , Witzke Oliver , Dittmer Ulf , Brenner Thorsten , Paniskaki Krystallenia , Yilmaz Serap , Dittmer Rita , Schneppenheim Sonja , Babel Nina , Budde Ulrich , Westhoff Timm H.
Published: March 2021

Objectives

It has recently been shown that von Willebrand factor (vWf) multimers may be a key driver of immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding.

Design

Observational prospective controlled multicenter study.

Setting

Blood samples and clinical data of patients with COVID-19 were collected regularly during hospitalization in the period from April to November 2020.

Patients

90 patients with confirmed COVID-19 of mild to critical severity and 30 healthy controls participated in this study.

Measuerements and Main Results

Antibodies to ADAMTS13 occurred in 31 (34.4%) patients with COVID-19. Generation of ADAMTS13 antibodies was associated with a significantly lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p=0.0041), increased disease severity (severe or critical disease in 90% vs. 62.3%, p=0.0189), and a trend to a higher mortality (35.5% vs. 18.6%, p=0.0773). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen.

Conclusion

The present study demonstrates for the first time, that generation of antibodies to ADAMTS13 is a frequent finding in COVID-19. Generation of these antibodies is associated with a lower ADAMTS13 activity and an increased risk of an adverse course of the disease suggesting an inhibitory effect on the protease. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.
Interpregnancy interval and pregnancy loss in a rural South Africa: A population-based cohort study
Authors: Moodley Y. , Herbst Kobus , Tanser F.
Published: March 2021

Study question

What is the relationship between interpregnancy interval (IPI) and pregnancy loss in a a rural sub-Saharan African (SSA) setting?

Summary answer

IPIs >60 months, but not <6 months, were associated with a higher odds of pregnancy loss in our SSA setting.

What is known already

IPIs >60 months are detrimental to both fetal and maternal health, while contradictory findings exist for IPIs <6 months. No studies have investigated the relationship between IPI and pregnancy loss in SSA settings, despite high pregnancy loss rates and exponential population growth in the SSA region.

Study design, size, duration

Population-based cohort involving 8940 women aged 16-35 years who reported two consecutive singleton pregnancies between 2000 and 2017.

Participants/materials, setting, methods

Study participants were from the uMkhanyakude District in KwaZulu-Natal, South Africa. We obtained data on pregnancy-related characteristics and other variables relevant to pregnancy loss from regular surveys conducted by the Africa Health Research Institute (AHRI) as part of its demographic and health surveillance platform. IPI was determined as the time in months between the end of the first pregnancy and the start of the second pregnancy. Pregnancy loss was defined as either miscarriage or stillbirth. We used an adjusted logistic regression model to investigate the relationship between IPI and pregnancy loss.

Main results and the role of chance

IPIs >60 months were associated with an almost three-fold higher odds of pregnancy loss (Adjusted Odds Ratio: 2.64, 95% Confidence Interval:1.71-4.09) when compared with IPIs of 6-60 months. IPIs <6 months conferred a similar odds of pregnancy loss when compared with IPIs of 6-60 months (Adjusted Odds Ratio: 0.82, 95% Confidence Interval: 0.35-1.91).

Limitations, reasons for caution

Possible recall bias around some of the pregnancy-related data. Inability to adjust our multivariate statistical analysis for certain sexually transmitted diseases which are known risk factors for pregnancy loss.

Wider implications of the findings

Family planning services in SSA should consider discouraging IPIs >60 months. Although IPIs <6 months had no impact on pregnancy loss, these should also be discouraged in SSA, given the potential socioeconomic consequences for the already vulnerable women of this region.

Study funding/competing interest(s)

The corresponding author was supported with a postdoctoral fellowship under a National Institute of Health grant (R01 HD084233). The AHRI demographic and health surveillance platform is supported by the Wellcome Trust (201433/Z/16/Z), and the South African Population Research Infrastructure Network. No competing interests are declared.

Trial registration number

N/A.
A systematic review of resting state functional MRI connectivity changes and cognitive impairment in multiple sclerosis
Authors: Jandric Danka , Doshi Anisha , Scott Richelle , Paling David , Rog David , Chataway Jeremy , Schoonheim Menno , Parker Geoff , Muhlert Nils
Published: March 2021

Cognitive impairment is common in multiple sclerosis (MS) and resting state functional MRI (rs-fMRI) functional connectivity (FC) is increasingly used to study its pathophysiology. However, results remain difficult to interpret, showing both high and low FC associated with cognitive impairment. We conducted a systematic review of rs-fMRI studies in MS to understand whether the direction of FC change relates to cognitive dysfunction, and how this may be influenced by the choice of methodology. Embase, Medline and PsycINFO were searched for studies assessing cognitive function and rs-fMRI FC in adults with MS. Fifty-seven studies were included in a narrative synthesis. Of these, 50 found an association between cognitive impairment and FC abnormalities. Worse cognition was linked to high FC in 18 studies, and to low FC in 17 studies. Nine studies found patterns of both high and low FC related to poor cognitive performance, in different regions or for different MR metrics. There was no clear link to increased FC during early stages of MS and reduced FC in later stages, as predicted by common models of MS pathology. Throughout, we found substantial heterogeneity in study methodology, and carefully consider how this may impact on the observed findings. These results indicate an urgent need for greater standardisation in the field – in the choice of MRI analysis and the definition of cognitive impairment. Through this we will be closer to using rs-fMRI FC as a biomarker in clinical studies, and as a tool to understand mechanisms underpinning cognitive symptoms in MS.

Key points

Cognitive impairment in multiple sclerosis (MS) is increasingly being researched with advanced magnetic resonance imaging (MRI) measures, including resting state functional MRI (rs-fMRI)

The rs-fMRI functional connectivity (FC) metric is associated with cognitive impairment, and has the potential to be a biomarker of cognitive decline.

A main challenge to developing a FC biomarker is the lack of consistency in the direction of FC changes associated with cognitive impairment, with cognitive deficits associated with both lower and higher FC.

FC changes don’t appear to be linked to clinical and methodological factors such as disease phenotype, disease duration and brain region or network studied.

Overall, there is substantial heterogeneity in study methodology, suggesting an acute need to standardise the study of cognitive impairment in MS and its investigation by rs-fMRI methods.
A Prospective Study of Long-Term Outcomes Among Hospitalized COVID-19 Patients with and without Neurological Complications
Authors: Frontera Jennifer A. , Yang Dixon , Lewis Ariane , Patel Palak , Medicherla Chaitanya , Arena Vito , Fang Taolin , Andino Andres , Snyder Thomas , Madhavan Maya , Gratch Daniel , Fuchs Benjamin , Dessy Alexa , Canizares Melanie , Jauregui Ruben , Thomas Betsy , Bauman Kristie , Olivera Anlys , Bhagat Dhristie , Sonson Michael , Park George , Stainman Rebecca , Sunwoo Brian , Talmasov Daniel , Tamimi Michael , Zhu Yingrong , Rosenthal Jonathan , Dygert Levi , Ristic Milan , Ishii Haruki , Valdes Eduard , Omari Mirza , Gurin Lindsey , Huang Joshua , Czeisler Barry M. , Kahn D. Ethan , Zhou Ting , Lin Jessica , Lord Aaron S. , Melmed Kara , Meropol Sharon , Troxel Andrea B. , Petkova Eva , Wisniewski Thomas , Balcer Laura , Morrison Chris , Yaghi Shadi , Galetta Steven
Published: March 2021

Background

Little is known regarding long-term outcomes of patients hospitalized with COVID-19.

Methods

We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep.

Results

Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N=196 neurological patients and N=186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 2.03, 95%CI 1.22-3.40, P=0.01), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P=0.01) and were less likely to return to work than controls (41% versus 64%, P=0.04). Cognitive and Neuro-QOL metrics were similar between groups.

Conclusions

Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.
Underlying cardiovascular risk and major adverse cardiovascular events after acute respiratory infection: a population-based cohort study of over 4.2 million individuals in England, 2008-2018
Authors: Davidson Jennifer A , Banerjee Amitava , Smeeth Liam , McDonald Helen I , Grint Daniel , Herrett Emily , Forbes Harriet , Pebody Richard , Warren-Gash Charlotte
Published: March 2021

Background

While acute respiratory infections (ARIs) can lead to cardiovascular complications, the effect of underlying cardiovascular risk profile on ARI incidence and cardiovascular complications in those without established cardiovascular disease (CVD) is unknown. Whether to consider individuals at raised cardiovascular risk a priority group for vaccination against respiratory infections therefore remains unclear.

Methods

We conducted a cohort study in individuals aged 40-64 years without established CVD or a chronic health condition eligible for influenza vaccination, using Clinical Practice Research Datalink GOLD and Aurum data from 01/09/2008-31/08/2018 linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England. We classified cardiovascular risk based on diagnosed hypertension and overall predicted cardiovascular risk estimated using QRISK2 score (≥10% compared with <10%). Using multivariable Poisson regression models, we obtained incidence rate ratios (IRR) for ARI. Among individuals who had an ARI, we then used multivariable Cox regression to obtain hazard ratios (HR) for the risk of major adverse cardiovascular events (MACE) within one year of infection.

Findings

4,212,930 individuals were included; 12·5% had hypertension and 14·4% had a QRISK2 score ≥10%. After adjusting for confounders, patients with hypertension (IRR 1·04, 95% CI 1·03-1·05) or QRISK2 score ≥10% (IRR 1·39, 1·37-1·40) had a higher incidence of ARI. Of the 442,408 individuals with an ARI, 4,196 had a MACE within one year of infection. After adjustment, hypertension (HR 1·98, 1·83-2·15) and QRISK2 score ≥10% (HR 3·65, 3·42-3·89) were associated with substantial increased risk of a MACE after infection.

Interpretation

People without diagnosed CVD but who have raised cardiovascular risk, measured by diagnosed hypertension or, in particular, overall predicted cardiovascular risk, have increased incidence of both ARI and cardiovascular complications following an ARI.
Smoking and Vaping Among a National Sample of U.S. Adults During the COVID-19 Pandemic
Authors: Kalkhoran Sara , Levy Douglas E. , Rigotti Nancy A.
Published: March 2021

Introduction

With concerns about cigarette smoking being a risk factor for severe disease from COVID-19, understanding nicotine and tobacco use patterns is important for preventive efforts. We aimed to understand changes in product use behaviors among U.S. adult combustible cigarette smokers and electronic cigarette (e-cigarette) users.

Methods

In August 2020, we conducted a cross-sectional survey of a nationally-representative sample of adults age >18 in NORC’s AmeriSpeak Panel who reported past 6-month use of combustible cigarettes or e-cigarettes. Multivariable logistic regression assessed factors associated with increased product use and quit attempts since hearing about COVID-19.

Results

1024 past 6-month cigarette smokers and/or e-cigarette users were surveyed. Among cigarette smokers, 45% reported no change in cigarette smoking and 33% increased cigarette smoking since hearing about COVID-19. Higher stress was associated with increased cigarette smoking. Among e-cigarette users, 41% reported no change in and 23% reported increasing e-cigarette use. 26% of cigarette smokers and 41% of e-cigarette users tried to quit because of COVID-19. Higher perceived risk of COVID-19 was associated with attempts to quit combustible cigarettes (AOR 2.37, 95% CI 1.59-3.55) and e-cigarettes (AOR 3.14, 1.73-5.70).

Conclusions

Cigarette and e-cigarette use patterns varied in response to the COVID-19 pandemic. Most cigarette smokers and e-cigarette users perceived product use as increasing COVID-19-related health risks, and this was associated with attempts to quit. Others, especially those reporting higher stress, increased product use. Proactive provision of cessation support to smokers and e-cigarette users may help mitigate stress-related increases in product use during the COVID-19 pandemic.
Transdiagnostic Neural Signatures in common Pediatric Psychiatric Disorders: a data-driven meta-analysis of functional neuroimaging studies
Authors: Dugré Jules R. , Eickhoff Simon B. , Potvin Stéphane
Published: March 2021

BACKGROUND

In the last decades, neuroimaging studies have attempted to unveil the neurobiological markers underlying pediatric psychiatric disorders. However, children diagnosed with such disorders are likely to receive an additional diagnosis in the following years. Yet, the vast majority of neuroimaging studies focus on a single nosological category, which limit our understanding of the shared/specific neural correlates between these disorders. Therefore, we aimed to investigate the transdiagnostic neural signatures through a novel meta-analytical method.

METHOD

A data-driven meta-analysis was carried out which grouped similar experiments topographic map together, irrespectively of nosological categories and task-characteristics. Then, activation likelihood estimation meta-analysis was performed on each group of experiments to extract spatially convergent brain regions.

RESULTS

One hundred forty-seven experiments were retrieved (3199 subjects): 79 attention-deficit/hyperactivity disorder, 32 conduct/oppositional defiant disorder, 14 anxiety disorders, 22 major depressive disorders. Four significant groups of experiments were observed. Functional characterization suggested that these groups of aberrant brain regions may be implicated internally/externally directed processes, attentional control of affect, somato-motor and visual processes. Furthermore, despite that some differences in rates of studies involving major depressive disorders were noticed, nosological categories were evenly distributed between these four sets of regions. Additionally, main effects of task characteristics were observed.

CONCLUSIONS

By using a data-driven meta-analytic method, we observed four significant groups of aberrant brain regions that may reflect transdiagnostic neural signature of pediatric psychiatric disorders. Overall, results of this study underscore the importance of studying pediatric psychiatric disorders simultaneously rather than independently.
Implementation of a multi-modal training program for the management of comorbid mental disorders in drug and alcohol settings: Pathways to Comorbidity Care (PCC)
Authors: Louie Eva , Morley Kirsten C. , Giannopoulos Vicki , Uribe Gabriela , Wood Katie , Marel Christina , Mills Katherine L , Teesson Maree , Edwards Michael , Childs Steven , Rogers David , Dunlop Adrian , Baillie Andrew , Haber Paul S.
Published: March 2021

Background

Clinical guidelines recommend evidence-based treatments for comorbid mental and substance use disorders but these are not reliably translated into practice. We aimed to evaluate the impact of the Pathways to Comorbidity Care (PCC) training program for alcohol and other drug (AOD) clinicians to improve the management of comorbidity and to identify barriers and facilitators of implementation according to the Consolidated Framework for Implementation Research (CFIR).

Methods

A controlled before-and-after study using PCC training was conducted across 6 matched sites in Australia including 35 clinicians. Controls received standard workplace training. PCC training included seminar presentations, workshops conducted by local ‘clinical champions’, individual clinical supervision, and access to an online information portal. A mixed methods approach examined i) identification (screening, assessment) and treatment (treatment, referral) of comorbidity in practice (N = 10 clinical files per clinician), ii) self-efficacy, knowledge and attitudes of clinicians, iii) barriers and facilitators of implementation.

Results

Significant improvements were observed in the PCC group but not the control sites with regards to the rate of clinical files showing identification of comorbidity (+50% v −12% change from baseline respectively; X2 (1, N = 340) = 35.29, p = .01) with only a trend for improvements in the rate of files demonstrating treatment of comorbidity (X2 (1, N = 340) = 10.45, p = .06). There were significant improvements in the PCC relative to the control group for clinician self-efficacy (F (1,33) = 6.40, p = .02) and knowledge and attitudes of comorbidity monitoring (F (1,33) = 8.745, p = .01). Barriers included inner setting (e.g. allocated time for learning) and characteristics of individuals (e.g. resistance). Facilitators included intervention characteristics (e.g. credible sources), inner setting (e.g. leadership) and outer setting domains (e.g. patient needs). Clinical champions were identified as an important component of the implementation process.

Conclusions

The PCC training package effectively improved identification of comorbidity, self-efficacy and attitudes towards screening and monitoring of comorbidity. Specific barriers included provision of allocated time for learning. Specific facilitators included provision of a credible clinical supervisor, strong leadership engagement and an active clinical champion.
The responsiveness of gait and balance outcomes to disease progression in Friedreich ataxia
Authors: Milne Sarah C , Kim Seok Hun , Murphy Anna , Larkindale Jane , Farmer Jennifer , Malapira Ritchie , Danoudis Mary , Shaw Jessica , Ramakrishnan Tyagi , Rasouli Fatemeh , Yiu Eppie M , Georgiou-Karistianis Nellie , Tai Geneieve , Zesiewicz Theresa , Delatycki Martin B , Corben Louise A
Published: March 2021

Objective

To identify gait and balance measures that are responsive to change during the timeline of a clinical trial in Friedreich ataxia (FRDA) we administered a battery of potential measures three times over a 12-month period.

Methods

Sixty-one ambulant individuals with FRDA underwent assessment of gait and balance at baseline, six months and 12 months. Outcomes included: GAITRite® spatiotemporal gait parameters; Biodex Balance System Postural Stability Test (PST) and Limits of Stability; Berg Balance Scale (BBS); Timed 25 Foot Walk Test; Dynamic Gait Index (DGI); SenseWear MF Armband step and energy activity; and the Friedreich Ataxia Rating Scale Upright Stability Subscale (FARS USS). The standardised response mean (SRM) or correlation coefficients were reported as effect size indices for comparison of internal responsiveness. Internal responsiveness was also analysed in subgroups.

Results

SenseWear Armband daily step count had the largest effect size of all the variables over six months (SRM=-0.615), while the PST medial-lateral index had the largest effect size (SRM=0.829) over 12 months. The FARS USS (SRM=0.824) and BBS (SRM=-0.720) were the only outcomes able to detect change over 12 months in all subgroups. The DGI was the most responsive outcome in children, detecting a mean change of −2.59 (95% CI −3.52 to −1.66,p<0.001, SRM=-1.429).

Conclusions

The FARS USS and BBS are highly responsive and can detect change in a wide range of ambulant individuals with FRDA. However, therapeutic effects in children may be best measured by the DGI.
Direct induction of hemogenic endothelial progenitors from hPSCs by defined factors revealed by single-cell transcriptome analysis
Authors: Randolph Lauren N. , Jiang Yuqian , Chang Yun , Bao Xiaoping , Lian Xiaojun Lance
Published: March 2021

Transcription factors (TFs) play critical roles in stem cell maintenance and differentiation. Using single cell RNA sequencing, we investigated TFs expressed in hemogenic endothelial (HE) progenitors differentiated from human pluripotent stem cells (hPSCs) and identified upregulated expression of SOXF factorsSOX7, SOX17, andSOX18in the HE population. To test whether overexpression of these factors increases HE differentiation efficiency, we established inducible hPSC lines and found onlySOX17improved differentiation. Temporal expression analysis further revealedSOX17was turned on immediately before VE-Cadherin, indicating SOX17 may be a causative factor for HE differentiation. UponSOX17knockdown via CRISPR-Cas13d, HE differentiation was significantly abrogated. Strikingly, we discoveredSOX17overexpression alone is sufficient to generate more than 50% CD34+VE-cadherin+CD73-cells that could be directed to hematopoietic progenitors, which emerged via an endothelial-to-hematopoietic transition and significantly upregulated definitive hematopoietic transcriptional programs. Functional assays showed that these progenitors can differentiate into blood cells from multiple lineages. Our analyses reveal an uncharacterized function ofSOX17in directing hPSCs differentiation towards HE cells.

Significance Statement

Hemogenic endothelial (HE) cells have been generated from human pluripotent stem cells (hPSCs) to study blood development. However, their full transcriptomic characterization and key genes involving in directing HE differentiation is unclear. Utilizing single cell RNA-seq analysis, we find that SOX17 is solely expressed in HE cells and is also required for HE differentiation. Strikingly, we find that overexpression of SOX17 alone is sufficient to program hPSCs into CD34+VE-cadherin+CD73-HE cells, which could further differentiate into blood progenitors. Our research reveals that SOX17 is sufficient to direct hPSCs differentiation to HE cells.

Classification

Physical Sciences/Engineering; Biological Sciences/Cell Biology.
Correlation analysis of target selectivity and side effects of FDA-approved kinase inhibitors
Authors: Bayazeid Omer , Rahman Taufiq
Published: March 2021

Kinase inhibitors (KIs) represent a popular class of therapeutic agents and chemical probes but most of them tend to be polypharmacological. Receptor and non-receptor Tyrosine KIs can target more than 100 kinases simultaneously compare to other KIs. We here analyze the molecular targets of 41 U.S. Food and Drug Administration (FDA)-approved KIs. We chose 18 drugs (Tyrosine KIs) and sought out to evaluate their selectivity profile and engagement with a number of targets in vivo at clinically relevant doses. We also wanted to see whether there prevails any correlation between the target engagement profile and the reported side effects for specific KIs chosen as test cases. To explore all clinical targets of the 18 KIs, we considered the free (unbound) maximum serum concentration (Cmax) of each KI and only chose targets for which the cognate affinities lie within the reported free Cmaxvalues, thereby allowing plausible interaction in clinical doses. We retrieved the side effects of those KIs that is reported in the FDA adverse event reporting system. We illustrate how correlation analysis of target−side effect can give a new insight into the off target of KIs and their effect on increasing the toxicity of KIs. These analyses could aid our understanding of the structural-activity relationship of KIs.