title: Smoking and Vaping Among a National Sample of U.S. Adults During the COVID-19 Pandemic

abstract:
IntroductionWith 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.

MethodsIn August 2020, we conducted a cross-sectional survey of a nationally-representative sample of adults age >18 in NORCs 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.

Results1024 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).

ConclusionsCigarette 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.


title: Conceptualizing centers of excellence: A global evidence

abstract:
ObjectiveGlobally, interest in excellence has grown exponentially, with public and private institutions shifting their attention from meet targets to achieving excellence. Centers of Excellence (CoEs) are standing at the forefront of healthcare, research, and innovations responding to the worlds most complex problems. However, their potential is hindered by conceptual ambiguity. We conducted a global synthesis of the evidence to conceptualize CoEs.

DesignScoping review, following Arksey and OMalleys framework and methodological enhancement by Levac et al to analyze the evidence and the PRISMA-ScR to guide the retrieval and inclusion of the evidence.

Data sourcesPubMed, Scopus, CINAHL, Google Scholar, and the Google engine from their inception to 01 January 2021.

EligibilityPapers that describe CoE as the main theme, which could be defining, theorizing, implementing, or evaluating a CoE.

ResultsThe search resulted in 52,161 potential publications, with 78 articles met the eligibility criteria. The 78 articles were from 33 countries, of which 35 were from the United States of America, 3 each from Nigeria, South Africa, Spain, and India, and 2 each from Ethiopia, Canada, Russia, Colombia, Sweden, Greece, and Peru. The rest 17 were from various countries. The articles involved six thematic areas - healthcare, education, research, industry, information technology, and general concepts on CoE. The analysis documented success stories of using the brand "Center of Excellence" - an influential brand to stimulate technical skills, innovation, and technology. We identified 12 essential foundations of CoE - specialized expertise; infrastructure; innovation; high-impact research; quality service; accreditation or standards; leadership; organizational structure; strategy; collaboration and partnership; sustainable funding or financial mechanisms; and entrepreneurship.

ConclusionsCoEs have significant scientific, political, economic, and social impacts. A comprehensive framework is needed to guide and inspire an institution as a CoE and to help government and funding institutions shape and oversee CoEs.

Strengths and limitations of this study- To the best of our knowledge, this is the first scoping review to conceptualize centers of excellence based on global evidence.
- The study followed Arksey and OMalleys framework and methodological enhancement by Levac et al to and the PRISMA-ScR methodological frameworks.
- Five databases were systematically searched to identify scientific and gray literature
- The study was limited by language restrictions.

category: medical education


title: A systematic review of resting state functional MRI connectivity changes and cognitive impairment in multiple sclerosis

abstract:
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 pointsO_LICognitive impairment in multiple sclerosis (MS) is increasingly being researched with advanced magnetic resonance imaging (MRI) measures, including resting state functional MRI (rs-fMRI)
C_LIO_LIThe rs-fMRI functional connectivity (FC) metric is associated with cognitive impairment, and has the potential to be a biomarker of cognitive decline.
C_LIO_LIA 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.
C_LIO_LIFC changes dont appear to be linked to clinical and methodological factors such as disease phenotype, disease duration and brain region or network studied.
C_LIO_LIOverall, 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.
C_LI

category: neurology


title: Altered transcriptome-proteome coupling indicates aberrant proteostasis in Parkinson's disease

abstract:
The correlation between mRNA and protein levels has been shown to decline in the ageing brain, possibly reflecting age-dependent changes in the proteostasis. It is thought that impaired proteostasis may be implicated in the pathogenesis of Parkinsons disease (PD), but evidence derived from the patient brain is currently limited. Here, we hypothesized that if impaired proteostasis occurs in PD, this should be reflected in the form of altered correlation between transcriptome and proteome compared to healthy ageing.

To test this hypothesis, we integrated transcriptomic data with proteomics from prefrontal cortex tissue of 17 PD patients and 11 demographically matched healthy controls and assessed gene-specific correlations between RNA and protein level. To control for the effects of ageing, brain samples from 4 infants were included in the analyses.

In the healthy aged brain, we observed a genome-wide decreased correlation between mRNA and protein levels. Moreover, a group of genes encoding synaptic vesicle proteins exhibited inverse correlations. This phenomenon likely reflects the spatial separation of mRNA and protein into the neuronal soma and synapsis, respectively, commonly characterizing these genes. Most genes showed a significantly lower correlation between mRNA and protein levels in PD compared to neurologically healthy ageing, consistent with a proteome-wide decline in proteostasis. Genes showing an inverse correlation in PD were enriched for proteasome subunits, suggesting that these proteins show accentuated spatial separation of transcript and protein between the soma and axon/synapses in PD neurons. Moreover, the PD brain was characterized by increased positive mRNA-protein correlation for some genes encoding components of the mitochondrial respiratory chain, suggesting these may require tighter regulation in the face of mitochondrial pathology characterizing the PD brain.

Our results are highly consistent with a proteome-wide impairment of proteostasis in the PD brain and strongly support the hypothesis that aberrant proteasomal function is implicated in the pathogenesis of PD. Moreover, our findings have important implications for the correct interpretation of differential gene expression studies in PD. In the presence of disease-specific altered coupling of transcriptome and proteome, measured differences in mRNA levels cannot be used to infer changes at the protein-level and should be supplemented with direct determination of proteins nominated by the analyses.


title: Detecting impaired language processing in MCI patients using around-the-ear cEEgrid electrodes

abstract: Mild cognitive impairment (MCI) is the term used to identify those individuals with subjective and objective cognitive decline but with preserved activities of daily living and an absence of dementia. While MCI can impact functioning in different cognitive domains, most notably episodic memory, relatively little is known about the comprehension of language in MCI. In this study we used around-the-ear electrodes (cEEGrids) to identify impairments during language comprehension in MCI patients. In a group of 23 MCI patients and 23 age-matched controls, language comprehension was tested in a two-word phrase paradigm. We examined the oscillatory changes following word onset as a function of lexico-semantic single-word retrieval (e.g. swrfeq versus swift) and multi-word binding processes (e.g. horse preceded by swift versus preceded by swrfeq). Electrophysiological signatures (as measured by the cEEGrids) were significantly different between MCI patients and controls. In controls, lexical retrieval was associated with a rebound in the alpha/beta range and binding was associated with a post-word alpha/beta suppression. In contrast, both the single-word retrieval and multi-word binding signatures were absent in the MCI group. The signatures observed using cEEGrids in controls were comparable to those signatures obtained with a full-cap EEG set-up. Importantly, our findings suggest that MCI patients have impaired electrophysiological signatures for comprehending single-words and multi-word phrases. Moreover, cEEGrids set-ups provide a non-invasive and sensitive clinical tool for detecting early impairments in language comprehension in MCI.


title: Barriers to early initiation of breastfeeding in healthy neonates in an urban hospital setting.

abstract:
BackgroundBreastfeeding is a key intervention to improve global targets on nutrition, health and survival. The World Health Organization (WHO) recommends early initiation of breastfeeding to prevent infections in the newborn and achieve targets of exclusive breastfeeding for the first six months of life. Early initiation of breastfeeding improves neonatal-maternal bonding, reduces jaundice and prevents gastrointestinal and respiratory tract infections. Global prevalence of early initiation of breastfeeding is 45% and 51% for Tanzania. The recommended prevalence is at least 80% by WHO guidelines.

ObjectiveTo explore barriers to early initiation of breastfeeding in a hospital setting.

MethodsA descriptive exploratory qualitative study with semi-structured individual interviews was employed to explore the barriers to early initiation of breastfeeding in a hospital setting. Three midwives and six mothers were interviewed. The interview topic guide covered experiences and challenges of early initiation of breastfeeding. Data was analyzed using Systematic Text Condensation as described by Malterud.

ResultsParticipants perceived that inadequate breastfeeding information especially on ideal time to start breastfeeding contributed to delayed initiation. The practices and environment post-delivery such as perineal tear repair and dirty labor room prevented women from initiating breastfeeding immediately.

ConclusionsThe barriers identified were related to gaps in knowledge, immediate postpartum practices and individual perceptions of a non-conducive environment.

category: nutrition


title: Interpregnancy interval and pregnancy loss in a rural South Africa: A population-based cohort study

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

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

What is known alreadyIPIs >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, durationPopulation-based cohort involving 8940 women aged 16-35 years who reported two consecutive singleton pregnancies between 2000 and 2017.

Participants/materials, setting, methodsStudy 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 chanceIPIs >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 cautionPossible 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 findingsFamily 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 numberN/A.

category: obstetrics and gynecology


title: Temperature at conception and pregnancy loss in rural KwaZulu-Natal Province, South Africa: Implications for climate change policy in sub-Saharan African settings

abstract:
BackgroundGlobal warming is projected to cause a substantial rise in temperatures with serious health implications across sub-Saharan Africa. Although South African policy makers have drafted a climate change adaptation plan, potential health threats posed by increasing temperatures on womens reproductive health are overlooked due to the lack of local population-based evidence. We sought to address the gap in the evidence around global warming and womens reproductive health in sub-Saharan Africa by using one of the continents largest prospective cohorts from rural KwaZulu-Natal Province, South Africa to investigate the relationship between temperature at conception and pregnancy loss.

MethodsOur study sample consisted of 36341 pregnancies from 16765 women from the uMkhanyakude District of KwaZulu-Natal, South Africa between 2000-2017. Average monthly temperatures for the study locale during the study period were obtained from the South African Weather Services. An adjusted logistic regression model was used to investigate the relationship between temperature at conception and pregnancy loss (miscarriage or stillbirth).

ResultsThe rate of pregnancy loss in the study sample was 1.9 (95% Confidence interval [CI]: 1.7-2.0) per 100 pregnancies. We observed a 4% higher odds of pregnancy loss for each 1{degrees}C increase in temperature (Adjusted Odds Ratio: 1.04, 95% CI: 1.01-1.08).

ConclusionThere is a clear relationship between temperature and pregnancy loss in our sub-Saharan African setting. The effects of global warming will likely exacerbate the existing challenges for womens reproductive health in this region. Pregnancy outcomes should be given adequate attention when sub-Saharan African governments draft policies in response to global warming.


title: COVID-19 Implications of the Physical Interaction of Artificial Fog on Respiratory Aerosols

abstract:
IntroductionArtificial fog is used in the film, television, and live entertainment industries to enhance lighting, as a visual effect, and to create a specific sense of mood or atmosphere. This study investigated whether the suspension time of respiratory aerosols spiked with tagged DNA tracers would change in the presence of glycerin- or glycol-containing artificial fogs.

Methods & MaterialsRespiratory aerosols with tagged DNA tracers were sprayed into a closed environment without and with glycerin- or glycol-containing artificial fog, with air samples taken at regular intervals to determine the decay of tagged DNA tracer over time. The study treatments included Control (no fog), Glycerin Low (3 mg/m3), Glycerin High ([~]15 mg/m3), Glycol Low ([~]5 mg/m3), and Glycol High ([~]40 mg/m3).

ResultsAll artificial fog treatments had lower mean log reduction curves compared to the Control treatment. Compared to the Control and Glycerin Low treatments, the differences in mean log reduction for nearly all other artificial fog treatments were statistically significant (p<0.001); the difference between Control and Glycerin Low treatments was not statistically significant (p=0.087). The differences in mean log reduction between treatments using the same artificial fog type were not statistically significant.

ConclusionArtificial fog use does not increase suspension time of respiratory aerosols, and therefore does not appear to increase the risk of airborne transmission of diseases from respiratory aerosols, such as COVID-19. Of the two types of artificial fogs investigated, that containing glycol decreased suspension time more than that containing glycerin. In practice, the additional reduction in suspension time provided by the physical interaction of respiratory aerosols with artificial fog does not suggest any practical benefit for using artificial fog as a control measure.

category: occupational and environmental health


title: The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

abstract:
PurposeIn 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.

MethodsThe 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.

ResultsThe 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.

ConclusionEstablishment 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.

category: genetic and genomic medicine


title: Hospitalization of mild cases of community-acquired pneumonia decreased more than severe ones during the COVID-19 epidemic

abstract:
ObjectiveThe 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.

MethodsUsing 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.

ResultsA 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).

ConclusionsOur 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.

category: infectious diseases


title: Predicting clinical outcomes in the Machine Learning era: The Piacenza score a purely data driven approach for mortality prediction in COVID-19 Pneumonia

abstract:
BackgroundSeveral models have been developed to predict mortality in patients with COVID-19 pneumonia, but only few have demonstrated enough discriminatory capacity. Machine-learning(ML) algorithms represent a novel approach for data-driven prediction of clinical outcomes with advantages over statistical modelling. We developed the Piacenza score, a ML-based score, to predict 30-day mortality in patients with COVID-19 pneumonia.

Methods852 patients (mean age 70years, 70%males) were enrolled from February to November 2020. The dataset was randomly splitted into derivation and test. The Piacenza score was obtained through the Naive Bayes classifier and externally validated on 86 patients. Using a forward-search algorithm the following six features were identified: age; mean corpuscular haemoglobin concentration; PaO2 /FiO2 ratio; temperature; previous stroke; gender. In case one or more of the features are not available for a patient, the model can be re-trained using only the provided features.

We also compared the Piacenza score with the 4C score and with a Naive Bayes algorithm with 14 variables chosen a-priori.

ResultsThe Piacenza score showed an AUC of 0.78(95% CI 0.74-0.84, Brier-score 0.19) in the internal validation cohort and 0.79(95% CI 0.68-0.89, Brier-score 0.16) in the external validation cohort showing a comparable accuracy respect to the 4C score and to the Naive Bayes model with a-priori chosen features, which achieved an AUC of 0.78(95% CI 0.73-0.83, Brier-score 0.26) and 0.80(95% CI 0.75-0.86, Brier-score 0.17) respectively.

ConclusionA personalized ML-based score with a purely data driven features selection is feasible and effective to predict mortality in patients with COVID-19 pneumonia.


title: The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein

abstract: Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the SARS-CoV-2 Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil is generating new viral lineages that might be more resistant to neutralization than parental variants of concern.


title: Diagnostic accuracy of rapid antigen tests in pre-/asymptomatic close contacts of individuals with a confirmed SARS-CoV-2 infection

abstract:
BackgroundPre-/asymptomatic close contacts of SARS-CoV-2 infected individuals were tested at day 5 after contact by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Diagnostic accuracy of antigen-detecting rapid diagnostic tests (Ag-RDT) in pre-/asymptomatic close contacts was up till now unknown.

MethodsWe performed a prospective cross-sectional diagnostic test accuracy study. Close contacts (e.g. selected via the test-and-trace program or contact tracing app) aged [≥]16 years and asymptomatic when requesting a test, were included consecutively and tested at day 5 at four Dutch public health service test sites. We evaluated two Ag-RDTs (BD Veritor System Ag-RDT (BD), and Roche/SD Biosensor Ag-RDT (SD-B)) with RT-PCR as the reference standard. Virus culture was performed in RT-PCR positive individuals to determine the viral load cut-off above which 95% was culture positive, as a proxy of infectiousness.

ResultsOf 2,678 BD-tested individuals, 233 (8.7%) were RT-PCR positive and BD detected 149 (sensitivity 63.9%; 95% confidence interval 57.4%-70.1%). Out of 1,596 SD-B-tested individuals, 132 (8.3%) were RT-PCR positive and SD-B detected 83 (sensitivity 62.9%; 54.0%-71.1%). When applying an infectiousness viral load cut-off [≥] 5.2 log10 gene copies/mL, the sensitivity was 90.1% (84.2%-94.4%) for BD, 86.8% (78.1% to 93.0%) for SD-B overall, and 88.1% (80.5%-93.5%) for BD, 85.1% (74.3%-92.6%) for SD-B for those still asymptomatic at the actual time of sampling. Specificity was >99% for both Ag-RDTs in all analyses.

ConclusionsThe sensitivity for detecting SARS-CoV-2 of both Ag-RDTs in pre-/asymptomatic close contacts is over 60%, increasing to over 85% after applying an infectiousness viral load cut-off.

Trial registration numberNot applicable. A study protocol is available upon request.


title: Generation of Inhibitory Autoantibodies to ADAMTS13 in Coronavirus Disease 2019

abstract:
ObjectivesIt 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.

DesignObservational prospective controlled multicenter study.

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

Patients90 patients with confirmed COVID-19 of mild to critical severity and 30 healthy controls participated in this study.

Measuerements and Main ResultsAntibodies 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.

ConclusionThe 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.


title: Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients

abstract: Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses and ex vivo assays. Patterns of clinical features, parasite burden and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, in particular in the hematopoietic niche of bone marrow and spleen.


title: COVID-19 collateral damage: psychological distress and behavioral changes among older adults during the first outbreak in Stockholm, Sweden

abstract:
IntroductionDuring the first wave of the COVID-19 pandemic, Swedish public health authorities provided recommendations for 70+ year old people. They were strongly encouraged to self-isolate but remain physically active in a safe manner. This study aimed to explore the indirect, negative effects of COVID-19 restrictions (collateral damage) by exploring to what extent adherence to such recommendations might have impacted the lives and health of older adults living in central Stockholm.

MethodsAn ad-hoc phone questionnaire was administered by trained staff between May and June 2020 to a random sample of older adults 68+ years old (n=1231), who had attended the regular follow-up assessment of the longitudinal Swedish National study on Aging and Care in Kungsholmen (SNAC-K) during 2016-2019. We explored three dimensions of collateral damage, namely psychological distress (feelings of worry, stress and loneliness), reductions in social and physical activities, and reductions in medical and social care use. Logistic regression models were used to test the association between age, sex, education and living arrangement, and the risk of collateral damage.

ResultsVast majority of participants adhered to the recommendations, with over three quarters practicing self-isolation (n=928). Half of the sample reported psychological distress, 55.3% reported reductions in social or physical activity, and 11.3% reported decreased medical or social care use. Over three quarters of participants were affected by at least one of the three collateral damage dimensions. Female sex was the strongest sociodemographic predictor of individual as well as co-occurring dimensions of collateral damage.

ConclusionCOVID-19 and its restrictions during the first half of 2020 have had a negative effect on the health and lives of a majority of elderly living in central Stockholm. Women were at a particularly higher risk of these negative consequences. We emphasize the need for predefined, evidence-based interventions to address these negative consequences.

STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis study uses a large sample of older adults from a well-characterized population-based study (SNAC-K)
C_LIO_LISeveral dimensions of the indirect, negative effects (collateral damage) of the COVID-19 pandemic are explored in this study
C_LIO_LIAs Swedens response to COVID-19 differed from most countries, this study provides a unique opportunity of comparison with other settings
C_LIO_LIThe cross-sectional design of this study does not allow to establish temporality between the onset of the pandemic and studied outcomes
C_LIO_LIThe results of this study may not be generalisable to the entire elderly population in Sweden as participants are from an urban, affluent area in Stockholm
C_LI

category: epidemiology


title: Serological response to COVID-19 vaccination in IBD patients receiving biologics

abstract:
ObjectiveThe impact of medications on COVID-19 vaccine efficacy in IBD patients is unknown, as patients with immunosuppressed states and/or treated with immunosuppressants were excluded from vaccine trials. To address this, we evaluated serological responses to COVID-19 vaccination with the SARS-CoV-2 spike (S) mRNA BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (NIH-Moderna) vaccines in IBD patients enrolled in an ongoing SARS-CoV-2 sero-survey at the Icahn School of Medicine at Mount Sinai in New York City.

DesignWe obtained sera from 48 patients who had undergone vaccination with one or two vaccine doses. Sera were tested for SARS-CoV-2 anti-RBD total immunoglobulins and IgG (Siemens COV2T and sCOVG assays), anti-Spike IgG (in-house ELISA), and anti-nucleocapsid antibodies (Roche).

ResultsAll IBD patients (15/15) who completed two-dose vaccine schedules achieved seroconversion to high levels. Two IBD patients with history of COVID-19 infections and who were seropositive at baseline seroconverted to high levels after the first dose. Concurrent biologic use was 85% (41/48), including 33% of patients (16) on TNF antagonist monotherapy, 42% (17) on vedolizumab monotherapy, 6% (3) on vedolizumab combination therapy with thiopurine, and 8% (4) ustekinumab; 1 patient was receiving guselkumab for psoriasis. Three patients (6%) were on oral steroids at the time of vaccination.

ConclusionIBD patients receiving biologics can seroconvert with robust serological responses after complete Pfizer-BioNTech and NIH-Moderna COVID-19 vaccination. In IBD-patients with previous SARS-CoV-2 seroconversion, a single dose of either vaccine can induce high index values, mirroring findings from the general population.

category: gastroenterology


title: COVID-19 Neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital

abstract: Many patients with SARS-CoV-2 infection develop neurological signs and symptoms, though, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological, and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical center. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit (ICU). Hospital-associated complications were common, including 8 (20%) with deep vein thrombosis/pulmonary embolism (DVT/PE), 7 (17%) patients with acute kidney injury requiring dialysis, and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 hours of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischemic changes in all brains, both global and focal; large and small infarcts, many of which appeared hemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, though none had evidence of vasculitis. Eighteen (44%) contained pathologies of neurodegenerative diseases, not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR (qRT-PCR), RNAscope, and immunocytochemistry with primers, probes, and antibodies directed against the spike and nucleocapsid regions. qRT-PCR revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in nasal epithelia. RNAscope and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in COVID-19 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but rather likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischemia. Further studies are needed to define whether these pathologies, if present in patients who survive COVID-19, might contribute to chronic neurological problems.

category: pathology


title: Oral health inequality in people with severe mental illness: a cross-sectional study using National Health and Nutrition Examination Survey 1999-2016

abstract:
OBJECTIVETo explore whether people with severe mental illness (SMI) experience worse oral health compared to the general population, and the risk factors for poor oral health in people with SMI.

METHODThis study used cross-sectional data from the National Health and Nutrition Examination Survey (1999-2016) including on self-rated oral health, ache in mouth, tooth loss, periodontitis stage, and number of decayed, missing, and filled teeth. Candidate risk factors for poor oral health included demographic characteristics, lifestyle factors, physical health comorbidities, and dental hygiene behaviours. The authors used ordinal logistic regression and zero-inflated negative binomial models to explore predictors of oral health outcomes.

RESULTS53,348 cases were included in the analysis, including 718 people with SMI. In the fully adjusted model, people with SMI were more likely to suffer from tooth loss (OR 1.40, 95% CI: 1.12-1.75). In people with SMI, the risk factors identified for poor oral health outcomes were older age, white ethnicity, lower income, smoking history, and diabetes. Engaging in physical activity and daily use of dental floss were associated with better oral health outcomes.

CONCLUSIONSPeople with SMI experience higher rates of tooth loss than the general population, and certain subgroups are particularly at risk. Having a healthy lifestyle such as performing regular physical exercise and flossing may lower the risk of poor oral health. These findings suggest opportunities for targeted prevention and early intervention strategies to mitigate adverse oral health outcomes.

Significant outcomes (x3)O_LIPeople with severe mental illness were at 40% higher risk of tooth loss when compared to the general population.
C_LIO_LIOlder adults, smokers and people with diabetes were at particularly high risk of poor oral health.
C_LIO_LIPhysical exercise and daily use of dental floss were associated with better oral health outcomes.
C_LI

Limitations (x3)O_LIThe number of cases with data on periodontal disease was limited.
C_LIO_LIThe study was cross-sectional so causation could not be inferred.
C_LIO_LIThe analysis used prescriptions of antipsychotic and mood stabilising medication as a proxy measure of severe mental illness, as clinical diagnoses were not available in the dataset.
C_LI

Data availability statementThe NHANES 1999-2016 data is available at CDC website: https://www.cdc.gov/nchs/nhanes/index.htm, and is accessible and free to download for everyone.

category: psychiatry and clinical psychology


title: Adverse clinical outcomes in people at clinical high-risk for psychosis related to activity and glutamate function in the hippocampus.

abstract: Preclinical models suggest that psychosis involves alterations in activity and glutamate function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal-connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (ppeakFWE =.003, t=4.4, z=4.19) and a poor functional outcome (ppeakFWE <.001, t=5.52, z=4.81 and ppeakFWE <.001, t=5.25, z=4.62) were associated with a negative correlation between hippocampal activation and hippocampal Glx concentration at baseline. In addition, there was a negative association between hippocampal Glx concentration and hippocampo-striatal connectivity (ppeakFWE =.016, t=3.73, z=3.39, ppeakFWE =.014, t=3.78, z=3.42, ppeakFWE =.011, t=4.45, z=3.91, ppeakFWE =.003, t=4.92, z=4.23) in the total CHR sample, not seen in healthy volunteers. As predicted by preclinical models, adverse clinical outcomes in people at risk for psychosis are associated with altered interactions between hippocampal activity and glutamatergic function.


title: Pulmonary Fibrosis after COVID-19 is Associated with Severity of Illness and Blood Leukocyte Telomere Length

abstract: The risk factors for development of fibrotic interstitial lung abnormalities (ILA) after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalization remain unclear. At 4 months after hospitalization, fibrotic ILA was more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission, and leukocyte telomere length are independent risk factors for fibrotic ILA. These fibrotic changes correlate with lung function, cough and measures of frailty, but not with dyspnea.

category: respiratory medicine


title: Anterior Spinal Artery Syndrome due to Intervertebral Disc Herniation: A systematic review

abstract:
ObjectiveAnterior spinal artery syndrome (ASAS) has been rarely reported as a complication of intervertebral disc herniation (IVDH). Precipitation factors, presentation, evaluation, treatment strategy, and degrees of recovery have not yet been well documented.

MethodsSystematic review was conducted according to PRISMA guidelines to review and summarize for the qualitative synthesis of the data from reported cases of anterior spinal artery syndrome due to intervertebral disc herniation from 1980 to February 2021.

ResultsA total of 12 cases were reviewed, the median age was 48.5 years. Motor weakness with or without pain was the most frequent presenting symptom accompanying bowel or bladder incontinence (25%) or diminished pain and temperature sensation with spared dorsal column sensation. 40% of conservatively treated patients had complete recovery without any residual deficit. Whereas all patients who managed surgically regained fully functional status with shorter recovery intervals.

ConclusionAbrupt onset of motor weakness is a potential warning symptom of spinal cord infarction, rarely attributed to ASA compression by a herniated disc. Moreover, an accompanying diminished pain and temperature sensation with spared dorsal column sensation is further intimation. Reestablishment of blood flow may bear a favorable outcome.


title: Validation of a NGS panel, with automated analysis, designed for detection of medically actionable tumor biomarkers for Latin America.

abstract: The genomic characterization of solid tumors and a rapidly growing repertoire of target drugs are revolutionizing cancer treatment. Next-generation sequencing (NGS) panels are progressively used in clinical practice for target therapy in high-income countries. In contrast, limited access to tumor sequencing, among other barriers, precludes precision cancer treatment in low- and middle-income countries. To build towards the implementation of precision oncology in Chile and Latin America, we designed a 25-gene panel that contains predictive biomarkers for currently or near-future available therapies in Latin America. Library preparation was optimized to account for DNA integrity variability in Formalin-Fixed Paraffin-Embedded (FFPE) tissue. The bioinformatic pipeline removes FFPE-induced artifacts and known germline variants; while identifying possible discrepancies in somatic mutations due to Latin Americans underrepresentation in the reference genome databases. Analytic sensitivity and accuracy were assessed using commercial standard controls for FFPE DNA and for germline BRCA1 and BRCA2 mutations, which are biomarkers for PARP inhibitors. Our panel detects small insertions and deletions and single nucleotide variants (SNVs) with 100% sensitivity and specificity down to allelic frequencies of 0.05, and with 100% between-run and within-run reproducibility for non-synonymous variants. The workflow was validated in 265 clinical samples, including breast, colorectal, gastric, ovarian, and gallbladder tumors and blood, leading to identifying 131 actionable variants. Therefore, this NGS panel constitutes an accurate and sensitive method for routine tumor biopsies that could replace multiple non-NGS assays and costly large NGS panels in the Latin American clinical context. The proposed streamlined assay and automated analysis are expected to facilitate the implementation of precision medicine in Latin America.

category: oncology


title: Alternative splicing of OAS1 alters the risk for severe COVID-19

abstract: A locus containing OAS1/2/3 has been identified as a risk locus for severe COVID-19 among Europeans ancestry individuals, with a protective haplotype of [~]75 kilobases derived from Neanderthals. Here, we show that among several potentially causal variants at this locus, a splice variant of OAS1 occurs in people of African ancestry independently of the Neanderthal haplotype and confers protection against COVID-19 of a magnitude similar to that seen in individuals without African ancestry.


title: Implementation of a multi-modal training program for the management of comorbid mental disorders in drug and alcohol settings: Pathways to Comorbidity Care (PCC)

abstract:
BackgroundClinical 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).

MethodsA 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.

ResultsSignificant 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.

ConclusionsThe 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.

category: health systems and quality improvement


title: Exploring causal relationships between COVID-19 and cardiometabolic disorders: A bi-directional Mendelian randomization study

abstract:
BackgroundMore than 100 million cases of COVID-19 have been reported worldwide. A number of risk factors for infection or severe infection have been identified, however observational studies were subject to confounding bias. In addition, there is still limited knowledge about the complications or medical consequences of the disease.

MethodsHere we performed bi-directional Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of around 30 cardiometabolic disorders (CMD) or traits. Genetic correlation (rg) was assessed by LD score regression(LDSC). The latest GWAS summary statistics from the COVID-19 Host Genetics Initiative was used, which comprised comparisons of general population controls with critically ill, hospitalized and any infected cases.

ResultsOverall we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of type 2 diabetes mellitus(T2DM), chronic kidney disease(CKD), ischemic stroke (especially large artery stroke[LAS]) and heart failure(HF) when compared to the general population. On the other hand, our findings suggested that liability to atrial fibrillation (AF), stroke (especially LAS), obesity, diabetes (T1DM and T2DM), low insulin sensitivity and impaired renal function (low eGFR and diabetic kidney disease) may be causal risk factors for COVID-19 or severe disease. In genetic correlation analysis, T2DM, CAD, obesity, fasting insulin, CKD, gout, stroke and urate showed positive rg with critical or hospitalized infection. All above findings passed multiple testing correction at a false discovery rate (FDR)<0.05.

ConclusionsIn summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 and severe disease and a number of CM disorders. Further replications and prospective studies are required to verify the findings.


title: Low levels of protective humoral immunity following mild or asymptomatic infection with SARS-CoV-2 in a community-based serological study

abstract: The degree of protective humoral immunity after mild or asymptomatic SARS-CoV-2 infection is not known. We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding--a surrogate measure of protection against SARS-CoV-2 infection--in a large and diverse community-based seroprevalence study. Comparisons were made across three groups of seropositive participants that differed in the severity of infection and engagement with clinical care (N=790). The clinical group was seropositive for prior infection, symptomatic, and diagnosed with COVID-19 by a healthcare provider. The symptomatic group was seropositive and reported one or more symptoms of infection but received no clinical care. The asymptomatic group was seropositive but reported no symptoms. 86.2% of all infections were mild or asymptomatic; 13.8% received clinical care. Of the clinical cases, 96.3% were outpatient; only 3.7% required hospitalization. Moderate or high levels of neutralizing activity were detected following 27.5% of clinical infections, in comparison with 5.4% of symptomatic and 1.5% of asymptomatic infections. The majority of infections in the general population are mild or asymptomatic and likely result in low levels of antibody-mediated protective immunity.


title: Heterogeneous immunological recovery trajectories revealed in post-acute COVID-19

abstract: The immunological picture of how different patients recover from COVID-19, and how those recovery trajectories are influenced by infection severity, remain unclear. We investigated 140 COVID-19 patients from diagnosis to convalescence using clinical data, viral load assessments, and multi-omic analyses of blood plasma and circulating immune cells. Immune-phenotype dynamics resolved four recovery trajectories. One trajectory signals a return to pre-infection healthy baseline, while the other three are characterized by differing fractions of persistent cytotoxic and proliferative T cells, distinct B cell maturation processes, and memory-like innate immunity. We resolve a small panel of plasma proteins that, when measured at diagnosis, can predict patient survival and recovery-trajectory commitment. Our study offers novel insights into post-acute immunological outcomes of COVID-19 that likely influence long-term adverse sequelae.


title: Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine reported to EudraVigilance database

abstract: The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford-AstraZeneca vaccine amid reports of blood clot events and death of a vaccinated person, despite the European Medicines Agency and the World Health Organization assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with Oxford-AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to Pulmonary Embolism; 1 fatality to Thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events. The EMAs Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients characteristics and comorbidities, may enable assessment of the causality with higher specificity.


title: COVID-19 IN IRAQ, THE RURAL INITIATION (AL-MUTHANNA PROVINCE AS AN EXAMPLE)

abstract:
A sustained pneumonia outbreak associated with a novel coronavirus named acute respiratory coronavirus 2 syndrome (SARS-CoV-2) was identified in Wuhan, Hubei Province, China in December 2019 which was later called COVID-19. The first confirmed case of COVID-19 was reported in Najaf/ Iraq on 24th February. This paper provided some information on COVID-19 infection in the Province of Al-Muthanna / South Iraq, which was then statistically analyzed and concluded. Confirmed cases of COVID-19 infections were reported by the Iraqi Ministry of Health in the Province of Al-Muthanna. The first foci started and the first dead infected individual was from Hilal which refers mainly to the role or rural places in starting and transmission of COVID-19 in Iraq. Many of the infections resulted in non-traveling persons because they were contaminated by contact (96%). Therefore, contact is perceived to be the best-recognized form of transmission. It was also reported that infections in Soweir District of Samawah City were the highest (45%) compared to other areas of the region. They should also be observed, however, that the steps to enforce and monitor the curfew are directly related to the direction of the City Centre, because the more they drive away from the city centers, the less stringent the procedures. Infections were focused between the ages of 20 and 50 years old, as that is the expected result, because these ranges are at the core of active age groups including social and sports events.

Graphical abstract

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title: 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

abstract: 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.


title: SARS-CoV-2 show no infectivity at later stages in a prolonged COVID-19 patient despite positivity in RNA testing

abstract: Inpatient COVID-19 cases present enormous costs to patients and health systems. Many hospitalized patients may still test COVID-19 positive, even after resolution of symptoms. Thus, a pressing concern for clinicians is the safety of discharging these asymptomatic patients if they have any remaining infectivity. This case report explores the viral viability in a patient with persistent COVID-19 over the course of a two-month hospitalization. Positive nasopharyngeal swab samples, analyzed by quantitative reverse transcription polymerase chain reactions (qRT-PCR), were collected and isolated in the laboratory, and infectious doses were analyzed throughout the hospitalization period. The patient experienced waning symptoms by hospital day 40 and had no viable virus growth in the laboratory by hospital day 41, suggesting no risk of infectivity, despite positive RT-PCR results, which prolonged his hospital stay. Notably, this case showed infectivity for at least 24 days from disease onset, which is longer than the discontinuation of transmission-based precautions recommendation by CDC. Thus, our findings suggest that the timeline for discontinuing transmission-based precautions may need to be extended for patients with prolonged illness. Additional large-scale studies are needed to draw definitive conclusions on the appropriate clinical management for these patients.


title: Targeted Hybridization Capture of SARS-CoV-2 and Metagenomics Enables Genetic Variant Discovery and Nasal Microbiome Insights

abstract:
The emergence of novel SARS-CoV-2 genetic variants that may alter viral fitness highlights the urgency of widespread next-generation sequencing (NGS) surveillance. To profile genetic variants, we developed and clinically validated a hybridization capture SARS-CoV-2 NGS assay, integrating novel methods for panel design using dsDNA biotin-labeled probes, and built accompanying software. The positive and negative percent agreement were defined in comparison to an orthogonal RT-PCR assay (PPA and NPA: both 96.7%). The limit of detection was established to be 800 copies/ml with an average fold-enrichment of 46,791x. We identified novel 107 mutations, including 24 in the functionally-important spike protein. Further, we profiled the full nasopharyngeal microbiome using metagenomics and found overrepresentation of 7 taxa and macrolide resistance in SARS-CoV-2-positive patients. This hybrid capture NGS assay, coupled with optimized software, is a powerful approach to detect and comprehensively map SARS-CoV-2 genetic variants for tracking viral evolution and guiding vaccine updates.

TEASERThis is the first target hybridization capture-based NGS assay to detect SARS-CoV-2 genetic variants for tracking viral evolution.


title: Agreement of parent- and child-reported wheeze: are they associated with FeNO and lung function?

abstract:
In epidemiological studies, childhood asthma is usually assessed with questionnaires directed at parents or children, and these may give different answers. We studied how well parents and children agreed when asked to report symptoms of wheeze and investigated whose answers were closer to measurable traits of asthma.

LuftiBus in the school is a cross-sectional survey of respiratory health among Swiss schoolchildren aged 6-17 years. We applied questionnaires to parents and children asking about wheeze and exertional wheeze in the past year. We assessed agreement between parent-child answers with Cohens kappa (k), and associations of answers from children and parents with physiological measurements (i.e. FeNO and FEV1/FVC), using quantile regression.

We received questionnaires from 3079 children and their parents. Agreement was poor for reported wheeze (k=0.37) and exertional wheeze (k=0.36). Median FeNO varied when wheeze was reported by children (19 ppb, IQR: 9-44), parents (22 ppb, IQR: 12-46), both (31 ppb, IQR: 16-55) or neither (11 ppb, IQR: 7-19). Median absolute FEV1/FVC was the same when wheeze was reported by children (84%, IQR: 78-89) and by parents (84%, IQR: 78-89), lower when reported by both (82%, IQR: 78-87) and higher when reported by neither (87%, IQR: 82-91). For exertional wheeze findings were similar. Results did not differ by age or sex.

Our findings suggest that surveying both parents and children and combining their responses can help us to better identify children with measurable asthma traits.

Take home messageThere is poor agreement between schoolchildren and their parents when reporting current wheeze. However, wheeze correlates best with lung function and FeNO when reported by both children and parents.


title: Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

abstract: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.


title: Data-driven estimate of SARS-CoV-2 herd immunity threshold in populations with individual contact pattern variations

abstract: The development of efficacious vaccines has made it possible to envision mass vaccination programs aimed at suppressing SARS-CoV-2 transmission around the world. Here we use a data-driven age-structured multilayer representation of the population of 34 countries to estimate the disease induced immunity threshold, accounting for the contact variability across individuals. We show that the herd immunization threshold of random (un-prioritized) mass vaccination programs is generally larger than the disease induced immunity threshold. We use the model to test two additional vaccine prioritization strategies, transmission-focused and age-based, in which individuals are inoculated either according to their behavior (number of contacts) or infection fatality risk, respectively. Our results show that in the case of a sterilizing vaccine the behavioral strategy achieves herd-immunity at a coverage comparable to the disease-induced immunity threshold, but it appears to have inferior performance in averting deaths than the risk vaccination strategy. The presented results have potential use in defining the effects that the heterogeneity of social mixing and contact patterns has on herd immunity levels and the deployment of vaccine prioritization strategies.


title: A convergence based assessment of relative differences in age-stratified susceptibility and infectiousness for SARS-CoV-2 variants of B.1.1.7 lineage

abstract:
We propose (a) a method for aggregating and processing age-stratified subregional time series data for positive tests of infection given partial sampling for variant-of-concern biomarkers, and (b) a simple model-based theoretical framework for interpreting these processed data, to assess whether observed heterogeneity in age-specific relative differences can be explained by environmental effects alone.

We then apply this strategy to public-domain subregional time series data with S-gene target failure (SGTF) sampling as a proxy for B.1.1.7 lineage, from weeks 45 to 50 of 2020 from England. For the time period in question, we observe convergence toward a 1.27 (95% CI 1.17-1.38) times higher ratio of SGTF to non-SGTF infection for 0-9-year-olds than for the total population, and a 1.16 (95% CI 1.09-1.23) times higher ratio for 10-19-year-olds. These are roughly comparable to previous findings, but this time we find high-significance evidence for adequate compatibility with our proposed modelling framework criteria to conclude that these relative elevations for 0-19-year-olds are very unlikely to be explained by environmental effects alone. We also find possible indications that 0-19-year-olds might experience a higher relative increase in infectiousness than susceptibility for B.1.1.7.


title: Depressive rumination is correlated with brain responses during self-related processing

abstract:
BackgroundRumination, a tendency to focus on negative self-related thoughts, is a central symptom of depression. Studying the self-related aspect of such symptoms is challenging due to the need to distinguish self effects per se from the emotional content of task stimuli. This study employs an emotionally neutral self-related paradigm to investigate possible altered self processing in depression and its link to rumination.

MethodsPeople with unipolar depression (MDD; n = 25) and controls (n = 25) underwent task-based EEG recording. Late event-related potentials were studied along with low frequency oscillatory power. EEG metrics were compared between groups and correlated with depressive symptoms and reported rumination.

ResultsThe MDD group displayed a difference in late potentials across fronto-central electrodes between self-related and non-self-related conditions. No such difference was seen in controls. The magnitude of this difference was positively related with depressive symptoms and reported rumination. MDD also had elevated theta oscillation power at central electrodes in self-related conditions, which was not seen in controls.

ConclusionsRumination appears linked to altered self-related processing in depression, independently of stimuli-related emotional confounds. This connection between self-related processing and depression may point to self-disorder being a core component of the condition.


title: Functional neural network for decision processing, a racing network of programmable neurons with fuzzy logic where the target operating model relies on the network itself

abstract: In this paper, we are introducing a novel model of artificial intelligence, the functional neural network for modeling of human decision-making processes. This neural network is composed of multiple artificial neurons racing in the network. Each of these neurons has a similar structure programmed independently by the users and composed of an intention wheel, a motor core and a sensory core representing the user itself and racing at a specific velocity. The mathematics of the neurons formulation and the racing mechanism of multiple nodes in the network will be discussed, and the group decision process with fuzzy logic and the transformation of these conceptual methods into practical methods of simulation and in operations will be developed. Eventually, we will describe some possible future research directions in the fields of finance, education and medicine including the opportunity to design an intelligent learning agent with application in business operations supervision. We believe that this functional neural network has a promising potential to transform the way we can compute decision-making and lead to a new generation of neuromorphic chips for seamless human-machine interactions.


title: Prevalence and determinants of serum antibodies to SARS-CoV-2 in the general population of the Gardena Valley

abstract:
BackgroundCommunity-based studies are essential to quantify the spread of SARS-CoV-2 infection and for unbiased characterization of its determinants and outcomes. We conducted a cross-sectional study in the Gardena valley, a major Alpine touristic destination which was struck in the expansion phase of the COVID-19 pandemic over the winter 2020.

MethodsWe surveyed 2244 representative study participants who underwent swab and serum antibody tests. We made multiple comparisons among the Abbott and Diasorin bioassays and serum neutralization titers. Seroprevalence accounted for the stratified design, non-response and test accuracy. Determinants and symptoms predictive of infection were analyzed by weighted multiple logistic regression.

ResultsSARS-CoV-2 seroprevalence was 26.9% (95% confidence interval: 25.2%, 28.6%) by June 2020. The serum antibody bioassays had modest agreement with each other. Receiver operating characteristic curve analysis on the serum neutralizing capacity showed better performance of the Abbott test at lower than the canonical threshold. Socio-demographic characteristics showed no clear evidence of association with seropositivity, which was instead associated with place of residence and economic activity. Loss of taste or smell, fever, difficulty in breathing, pain in the limbs, and weakness were the most predictive symptoms of positive antibody test results. Fever and weakness associations were age-dependent.

ConclusionThe Gardena valley had one of the highest SARS-CoV-2 infection prevalence in Europe. The age-dependent risk associated with COVID-19 related symptoms implies targeted strategies for screening and prophylaxis planning.

category: public and global health


title: A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment

abstract:
INTRODUCTIONWhite matter (WM) energy supply is crucial for axonal function and myelin maintenance. Providing ketones, the brains alternative fuel to glucose, is a therapeutic strategy to bypass the brains glucose-specific energy deficit in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or ketone uptake in specific WM fascicles in MCI has not previously been described.

METHODSThis 6-month interventional study included MCI participants randomized to a placebo (n = 16) or ketogenic medium chain triglyceride (kMCT; n = 17) drink. A neurocognitive battery and brain imaging were performed pre- and post-intervention. WM fascicle uptake of ketone and glucose and structural properties were assessed using positron emission tomography and diffusion imaging, respectively.

RESULTSKetone uptake was increased by 2.5 to 3.2-fold in nine fascicles of interest (P < 0.001) only in the kMCT group, an effect seen both in deep WM and in fascicle cortical endpoints. Improvement in processing speed was associated with WM ketone uptake globally and in individual fascicles, most importantly the fornix (r = +0.61; P = 0.014).

DISCUSSIONA 6-month ketogenic supplementation in MCI improved WM energy supply globally. The significant positive association with processing speed suggests that ketones may have a role in myelin integrity in MCI.

category: radiology and imaging


title: 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.

abstract:
BackgroundCovid-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.

MethodWe 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.

ResultsWe 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.

ConclusionLockdowns 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 PointsO_LINeuropsychiatric symptoms of people with dementia (e.g., anxiety, depressive symptoms, apathy, agitation) were found to worsen during lockdown in the majority of studies.
C_LIO_LICognitive decline affecting memory, orientation concentration and communication was observed by caregivers within few weeks after lockdown.
C_LIO_LIThe 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.
C_LIO_LIThere is little research conducted in care home residents with dementia (only 2 papers found).
C_LIO_LIIncrease consumption of antipsychotics and benzodiazepines has occurred in people with dementia during lockdown.
C_LIO_LIEvidence indicates that isolation measures quickly damaged peoples with dementia cognitive and mental health and probably accelerated overall decline.
C_LI


title: Post-stroke reorganization of transient brain activity characterizes deficits and recovery of cognitive functions

abstract:
Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to assess spatial and temporal changes of brain networks after stroke. While large-scale spatial patterns of these networks were preserved after stroke, their durations were altered, with stroke subjects exhibiting a varied pattern of longer and shorter network activations compared to healthy individuals. These temporal alterations were associated with white matter damage and were behavior-specific. Specifically, restoration of healthy brain dynamics paralleled recovery of cognitive functions, but was not significantly correlated to motor recovery. These findings underscore the critical importance of network temporal properties in dissecting the pathophysiology of brain changes after stroke, thus shedding new light on the clinical potential of time-resolved methods for fMRI analysis.

Significance StatementUnderstanding the pathophysiology of a disorder is pivotal to design effective treatment. In this regard, recent advances in stroke research settled a new clinical concept: connectional diaschisis, which suggested that post-stroke impairments arise from both focal structural changes (tied to the injury) and widespread alterations in functional connectivity. fMRI time-resolved methods consider structural and temporal properties of brain networks as interdependent features. They are, thus, better suited to capture the intertwine between structural and functional changes. Here we leveraged a dynamic functional connectivity framework based on the clustering of hemodynamic-informed transients in a large and heterogeneous stroke population assessed longitudinally. We showed that lesions led to an unbalance in the brain dynamics that was associated with white matter fibers disruption and was restored as deficits recovered. Our work showed the potential of a time-resolved method to reveal clinically relevant dynamics of large-scale brain networks.


title: Improving postpartum hemorrhage risk prediction using longitudinal electronic medical records

abstract:
ObjectivePostpartum hemorrhage (PPH) remains a leading cause of preventable maternal mortality in the US. Our goal was to develop a novel risk assessment tool and compare its accuracy to those used in current practice.

Materials and MethodsWe used a PPH digital phenotype we developed and validated previously to identify 6,639 cases from our delivery cohort (N=70,948). Using a vast array of known and potential risk factors extracted from electronic medical records available prior to delivery, we trained a gradient boosting model in a subset of our cohort. In a held-out test sample, we compared performance of our model to three clinical risk tools and one previously published model.

ResultsOur 24-feature model achieved an area under the curve (AUC) of 0.71 (95% confidence interval [CI], 0.69-0.72), higher than all other tools (research-based AUC: 0.67 [95%CI, 0.66-0.69], clinical AUCs: 0.55 [95%CI, 0.54-0.56] to 0.61 [95%CI, 0.59-0.62]). Five features were novel including red blood cell indices and infection markers measured standardly upon admission. Additionally, we identified inflection points for several vital signs and labs where risk rose substantially. Most notably, patients with median intrapartum systolic blood pressure above 132mmHg had an 11% [interquartile range, 4%] median increase in relative risk for PPH.

ConclusionsWe developed a novel approach for predicting PPH and identified clinical feature thresholds that can guide intrapartum monitoring for PPH risk. Our results suggest our model is an excellent candidate for prospective evaluation and could ultimately reduce PPH morbidity and mortality through early detection and prevention.


title: CNVxplorer: a web tool to assist clinical interpretation of CNVs in rare disease patients

abstract: Copy Number Variants (CNVs) are an important cause of rare diseases. Array-based Comparative Genomic Hybridization tests yield a [~]12% diagnostic rate, with [~]8% of patients presenting CNVs of unknown significance. CNVs interpretation is particularly challenging on genomic regions outside of those overlapping with previously reported structural variants or disease-associated genes. Recent studies showed that a more comprehensive evaluation of CNV features, leveraging both coding and non-coding impacts can significantly improve diagnostic rates. However, currently available CNV interpretation tools are mostly gene-centric or provide only non-interactive annotations difficult to assess in the clinical practice. Here we present CNVxplorer, a web server suited for the functional assessment of CNVs in a clinical diagnostic setting. CNVxplorer mines a comprehensive set of clinical, genomic, and epigenomic features associated with CNVs. It provides sequence constraint metrics, impact on regulatory elements and topologically associating domains, as well as expression patterns. Analyses offered cover (a) agreement with patient phenotypes; (b) visualizations of associations among genes, regulatory elements and transcription factors; (c) enrichment on functional and pathway annotations; and (d) co-occurrence of terms across PubMed publications related to the query CNVs. A flexible evaluation workflow allows dynamic re-interrogation in clinical sessions. CNVxplorer is publicly available at http://cnvxplorer.com


title: Accuracy of Computable Phenotyping Approaches for SARS-CoV-2 Infection and COVID-19 Hospitalizations from the Electronic Health Record

abstract:
ObjectiveReal-world data have been critical for rapid-knowledge generation throughout the COVID-19 pandemic. To ensure high-quality results are delivered to guide clinical decision making and the public health response, as well as characterize the response to interventions, it is essential to establish the accuracy of COVID-19 case definitions derived from administrative data to identify infections and hospitalizations.

MethodsElectronic Health Record (EHR) data were obtained from the clinical data warehouse of the Yale New Haven Health System (Yale, primary site) and 3 hospital systems of the Mayo Clinic (validation site). Detailed characteristics on demographics, diagnoses, and laboratory results were obtained for all patients with either a positive SARS-CoV-2 PCR or antigen test or ICD-10 diagnosis of COVID-19 (U07.1) between April 1, 2020 and March 1, 2021. Various computable phenotype definitions were evaluated for their accuracy to identify SARS-CoV-2 infection and COVID-19 hospitalizations.

ResultsOf the 69,423 individuals with either a diagnosis code or a laboratory diagnosis of a SARS-CoV-2 infection at Yale, 61,023 had a principal or a secondary diagnosis code for COVID-19 and 50,355 had a positive SARS-CoV-2 test. Among those with a positive laboratory test, 38,506 (76.5%) and 3449 (6.8%) had a principal and secondary diagnosis code of COVID-19, respectively, while 8400 (16.7%) had no COVID-19 diagnosis. Moreover, of the 61,023 patients with a COVID-19 diagnosis code, 19,068 (31.2%) did not have a positive laboratory test for SARS-CoV-2 in the EHR. Of the 20 cases randomly sampled from this latter group for manual review, all had a COVID-19 diagnosis code related to asymptomatic testing with negative subsequent test results. The positive predictive value (precision) and sensitivity (recall) of a COVID-19 diagnosis in the medical record for a documented positive SARS-CoV-2 test were 68.8% and 83.3%, respectively. Among 5,109 patients who were hospitalized with a principal diagnosis of COVID-19, 4843 (94.8%) had a positive SARS-CoV-2 test within the 2 weeks preceding hospital admission or during hospitalization. In addition, 789 hospitalizations had a secondary diagnosis of COVID-19, of which 446 (56.5%) had a principal diagnosis consistent with severe clinical manifestation of COVID-19 (e.g., sepsis or respiratory failure). Compared with the cohort that had a principal diagnosis of COVID-19, those with a secondary diagnosis had a more than 2-fold higher in-hospital mortality rate (13.2% vs 28.0%, P<0.001). In the validation sample at Mayo Clinic, diagnosis codes more consistently identified SARS-CoV-2 infection (precision of 95%) but had lower recall (63.5%) with substantial variation across the 3 Mayo Clinic sites. Similar to Yale, diagnosis codes consistently identified COVID-19 hospitalizations at Mayo, with hospitalizations defined by secondary diagnosis code with 2-fold higher in-hospital mortality compared to those with a primary diagnosis of COVID-19.

ConclusionsCOVID-19 diagnosis codes misclassified the SARS-CoV-2 infection status of many people, with implications for clinical research and epidemiological surveillance. Moreover, the codes had different performance across two academic health systems and identified groups with different risks of mortality. Real-world data from the EHR can be used to in conjunction with diagnosis codes to improve the identification of people infected with SARS-CoV-2.

category: health informatics


title: Compliance to 4Ds of antimicrobial stewardship practices in a tertiary care centre

abstract:
BackgroundIndiscriminate 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.

MethodsWe 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.

ResultsOf 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.

ConclusionInternist 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.


title: Adapting French COVID-19 vaccination campaign duration to variant dissemination

abstract:
BackgroundThe outbreak of SARS-CoV-2 virus has caused a major international health crisis with serious consequences in terms of public health and economy. In France, two lockdown periods were decided in 2020 to avoid the saturation of intensive care units (ICU) and an increase in mortality. The rapid dissemination of variant SARS-CoV-2 VOC 202012/01 has strongly influenced the course of the epidemic. Vaccines have been rapidly developed. Their efficacy against the severe forms of the disease has been established, and their efficacy against disease transmission is under evaluation. The aim of this paper is to compare the efficacy of several vaccination strategies in the presence of variants in controlling the COVID-19 epidemic through population immunity.

MethodsAn agent-based model was designed to simulate with different scenarios the evolution of COVID-19 pandemic in France over 2021 and 2022. The simulations were carried out ignoring the occurrence of variants then taking into account their diffusion over time. The expected effects of three Non-Pharmaceutical Interventions (Relaxed-NPI, Intensive-NPI, and Extended-NPI) to limit the epidemic extension were compared. The expected efficacy of vaccines were the values recently estimated in preventing severe forms of the disease (75% and 94%) for the current used vaccines in France (Pfizer-BioNTech and Moderna since January 11, 2021, and AstraZeneca since February 2, 2021). All vaccination campaigns reproduced an advanced age-based priority advised by the Haute Autorite de Sante. Putative reductions of virus transmission were fixed at 0, 50, 75 and 90%. The effects of four vaccination campaign durations (6-month, 12-month, 18-month and 24-month) were compared.

ResultsIn the absence of vaccination, the presence of variants led to reject the Relaxed-NPI because of a high expected number of deaths (170 to 210 thousands) and the significant overload of ICUs from which 35 thousand patients would be deprived. In comparison with the situation without vaccination, the number of deaths was divided by 7 without ICU saturation with a 6-month vaccination campaign. A 12-month campaign would divide the number of death by 3 with Intensive-NPI and by 6 with Extended-NPI (the latter being necessary to avoid ICU saturation). With 18-month and 24-month vaccination campaigns without Extended-NPI, the number of deaths and ICU admissions would explode.

ConclusionAmong the four compared strategies the 6-month vaccination campaign seems to be the best response to changes in the dynamics of the epidemic due to the variants. The race against the COVID-19 epidemic is a race of vaccination strategy. Any further vaccination delay would increase the need of strengthened measures such as Extended-NPI to limit the number of deaths and avoid ICU saturation.


title: Treatment and Cost -outcomes of a simplified antiretroviral treatment strategy for hepatitis C among HCV and HIV co-infected patients in Ukraine

abstract:
BackgroundWe conducted a demonstration project of an integrated HIV and viral hepatitis testing and treatment strategy using generic ledipasvir/sofosbuvir (LDV/SOF).

MethodsEligible HCV viraemic adults from two clinics in Kyiv were treated with LDV/SOF +/-weight-based ribavirin for 12 weeks. Clinical assessments were performed at screening and week 24 and as needed; treatment was dispensed every 4 weeks. The primary outcome was sustained virologic response (SVR)12 weeks after treatment. Program costs in 2018 USD were estimated per patient treated using observed resource utilization, local unit, and antiretroviral therapy (ART) costs over the 24-week period.

Results868 participants initiated on treatment, 87% (755) were PWID and 55.5% (482) were HIV co-infected. The common genotypes were 1 (74.1%) and 3 (22%) and SVR was achieved in 831/868 (95.7%) by intention-to-treat analysis. The average cost per patient treated was $680, assuming generic LDV/SOF and ribavirin pricing and standard quantitative HCV viral load testing. Medications comprised 38% of the average cost/patient, laboratory tests 26%, events (clinic visits, counselling) 10%, and indirect costs 26%. ART accounted for 60% of all drug costs, with HCV medications just 40%.

ConclusionGeneric LDV/SOF +/- ribavirin provided produced exceptionally good outcomes including amongst patients with genotype 3 HCV and PWID at an average cost of <$700/patient year, including ART for those with HIV. Under the assumptions of generic drug pricing but higher laboratory costs, an average cost of $750/patient is likely a reasonable estimate for this intervention in Ukraine, excluding costs for scaling or maintaining the treatment program.


title: Modelling the population-level protection conferred by COVID-19 vaccination

abstract:
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines work predominantly by eliciting neutralizing antibodies (NAbs), how the protection they confer depends on the NAb response to vaccination is unclear. Here, we collated and analysed in vitro dose-response curves of >70 NAbs and constructed a landscape defining the spectrum of neutralization efficiencies of NAbs elicited. We mimicked responses of individuals by sampling NAb subsets of known sizes from the landscape and found that they recapitulated responses of convalescent patients. Combining individual responses with a mathematical model of within-host SARS-CoV-2 infection post-vaccination, we predicted how the population-level protection conferred would increase with the NAb response to vaccination. Our predictions captured the outcomes of vaccination trials. Our formalism may help optimize vaccination protocols, given limited vaccine availability.

One sentence summaryViremic control by the spectrum of neutralizing antibodies elicited by vaccination determines COVID-19 vaccine efficacies.