title: Experiences with Primary Care in the State of Utah for Gender Diverse People: Surveying the Difficulties in Accessing Healthcare

abstract:
BackgroundTransgender and non-binary communities continue to be underserved in healthcare. This study seeks to better understand the barriers and difficulties faced by transgender and non-binary patients in accessing primary care and hormone therapy in Utah.

MethodsAn online survey was developed for transgender and non-binary identifying adults and was advertised via social media and the University of Utah Hospitals website.

ResultsThere were 123 respondents from Utah including 39 trans women, 49 trans men, and 35 non-binary individuals. The age ranged from 18-67 (average 30 years), and 93% were Caucasian. The majority (84%) were insured, yet 67% of respondents reported difficulty accessing primary care. Fear of discrimination and being unable to find trans-friendly providers were reported as the two largest barriers. Non-binary respondents reported fear of discrimination as a barrier to primary care at the highest percentage (92%). Nearly 3 in 4 respondents who have hormone therapy reported difficulty paying for it. One in four trans women reported accessing hormones online or from a friend.

ConclusionUtah is currently drastically underequipped to provide for the healthcare needs of transgender and non-binary communities. There needs to be an increase in trans-friendly primary care providers to curb discrimination. More resources and efforts must go into training primary care providers with necessary knowledge to properly serve transgender and non-binary patients. Finally, clear anti-discrimination laws are needed for insurance companies to reduce the financial barrier to transgender health services in Utah.

category: primary care research


title: Simple quantitative assessment of the outdoor versus indoor airborne transmission of viruses and covid-19

abstract:
In this paper we develop a simple model of the inhaled flow rate of aerosol particles of respiratory origin i.e. that have been exhaled by other humans. A connection is made between the exposure dose and the probability of developing an airborne disease. This allows a simple assessment of the outdoor versus indoor risk of contamination to be made in a variety of meteorological situations. It is shown quantitatively that for most cases, the outdoor risk is orders of magnitude less than the indoor risk and that it can become comparable only for extremely specific meteorological and geographical situations. It sheds a light on various observations of Covid-19 spreading in mountain valleys with temperature inversions while at the same time other areas are much less impacted.

HighlightsO_LIRisk of covid-19 airborne transmission.
C_LIO_LIQuantitative assessment of outdoor versus indoor airborne risk of transmission.
C_LIO_LIMeteorological and geographical influence on covid-19 airborne transmission.
C_LI

category: public and global health


title: Sociodemographic Characteristics of Missing Data in Digital Phenotyping

abstract: The ubiquity of smartphones, with their increasingly sophisticated array of sensors, presents an unprecedented opportunity for researchers to collect diverse, temporally-dense data about human behavior while minimizing participant burden. Researchers increasingly make use of smartphone applications for "digital phenotyping," the collection of phone sensor and log data to study the lived experiences of subjects in their natural environments. While digital phenotyping has shown promise in fields such as psychiatry and neuroscience, there are fundamental gaps in our knowledge about data collection and non-collection (i.e., missing data) in smartphone-based digital phenotyping. Here, we show that digital phenotyping presents a viable method of data collection, over long time periods, across diverse study participants with a range of sociodemographic characteristics. We examined accelerometer and GPS sensor data of 211 participants, amounting to 29,500 person-days of observation, using Bayesian hierarchical negative binomial regression. We found that iOS users had higher rates of accelerometer non-collection but lower GPS non-collection than Android users. For GPS data, rates of non-collection did not differ by race/ethnicity, education, age, or gender. For accelerometer data, Black participants had higher rates of non-collection while Asian participants had slightly lower non-collection. For both sensors, non-collection increased by 0.5% to 0.9% per week. These results demonstrate the feasibility of using smartphone-based digital phenotyping across diverse populations, for extended periods of time, and within diverse cohorts. As smartphones become increasingly embedded in everyday life, the insights of this study will help guide the design, planning, and analysis of digital phenotyping studies.


title: Estimation of Daily Reproduction Rates in COVID-19 Outbreak.

abstract:
(1) BackgroundThe estimation of daily reproduction rates throughout the infectivity period is rarely considered and only their sum Ro is calculated to quantify the level of virulence of an infectious agent;

(2) MethodsWe give the equation of the discrete dynamics of epidemic growth and we obtain an estimation of the daily reproduction rates, by using a technique of deconvolution of the series of observed new cases of Covid-19;

(3) ResultsWe give both simulation results as well as estimations for several countries for the Covid-19 outbreak;

(4) ConclusionsWe discuss the role of the noise on the precision of the estimation and we open on perspectives of forecasting methods to predict the distribution of daily reproduction rates along the infectivity period.


title: Effects of climate conditions, mobility trends, and countermeasures on the COVID-19 outbreak in Japan

abstract:
BackgroundBefore Olympic and Paralympic Games in Tokyo, whether an audience shall be allowed or not has been a subject of concern in Japan as of early June, 2021. Object: We evaluated effects of professional baseball games with audiences as an example of the large sports events, on COVID-19 infectiousness.

MethodWe regressed the effective reproduction number R(t) on a dummy variable for professional baseball games with audiences as along with temperature, humidity, mobility, and countermeasures. We examined two study periods: those including and excluding before initiation of the games in 2020.

ResultsEstimation results indicate that the period with audiences exhibited significantly lower infectiousness than when audiences were excluded before initiation of the games with audience attendance. However, audiences were found to have a negative but insignificant effect when compared to the period before initiation of the attended games.

Discussion and ConclusionThis study found no clear evidence indicating that big sports events with audiences raise the COVID-19 infectiousness.


title: Effects of the second emergency status declaration for the COVID-19 outbreak in Japan


title: The second COVID-19 emergency status declaration for Japan: effects as of February 7, 2021


title: Interim estimation for the effect of the third COVID-19 emergency status declaration in Japan


title: Estimating event ban effects on COVID-19 outbreak in Japan


title: Reliability of Google Trends: Analysis of the Limits and Potential of Web Infoveillance During COVID-19 Pandemic and for Future Research

abstract:
BackgroundAlongside the COVID-19 pandemic, government authorities around the world have had to face a growing infodemic capable of causing serious damages to public health and economy. In this context, the use of infoveillance tools has become a primary necessity.

ObjectiveThe aim of this study is to test the reliability of a widely used infoveillance tool which is Google Trends. In particular, the paper focuses on the analysis of relative search volumes (RSVs) quantifying their dependence on the day they are collected.

MethodsRSVs of the query coronavirus + covid during February 1 - December 4, 2020 (period 1), and February 20 - May 18, 2020 (period 2), were collected daily by Google Trends from December 8 to 27, 2020. The survey covered Italian regions and cities, and countries and cities worldwide. The search category was set to all categories. Each dataset was analyzed to observe any dependencies of RSVs from the day they were gathered. To do this, by calling i the country, region, or city under investigation and j the day its RSV was collected, a Gaussian distribution [Formula] was used to represent the trend of daily variations of xij = RSVsij. When a missing value was revealed (anomaly), the affected country, region or city was excluded from the analysis. When the anomalies exceeded 20% of the sample size, the whole sample was excluded from the statistical analysis. Pearson and Spearman correlations between RSVs and the number of COVID-19 cases were calculated day by day thus to highlight any variations related to the day RSVs were collected. Student t-test was used to assess the statistical significance of the differences between the average RSVs of the various countries, regions, or cities of a given dataset. Two RSVs were considered statistical confident when t < 1.5. A dataset was deemed unreliable if the confident data exceeded 20% (confidence threshold). The percentage increase{Delta} was used to quantify the difference between two values.

ResultsGoogle Trends has been subject to an acceptable quantity of anomalies only as regards the RSVs of Italian regions (0% in both period 1 and period 2) and countries worldwide (9.7% during period 1 and 10.9% during period 2). However, the correlations between RSVs and COVID-19 cases underwent significant variations even in these two datasets (Max |{Delta}| = + 625% for Italian regions, and Max |{Delta}| = +175% for countries worldwide). Furthermore, only RSVs of countries worldwide did not exceed confidence threshold. Finally, the large amount of anomalies registered in Italian and international cities RSVs made these datasets unusable for any kind of statistical inference.

ConclusionsIn the considered timespans, Google Trends has proved to be reliable only for surveys concerning RSVs of countries worldwide. Since RSVs values showed a high dependence on the day they were gathered, it is essential for future research that the authors collect queries data for several consecutive days and work with their RSVs averages instead of daily RSVs, trying to minimize the standard errors until an established confidence threshold is respected.


title: Continuous pain report demonstrates time delay of pain ratings in Fibromyalgia

abstract:
BackgroundEnhanced temporal summation (TS), measured through self-reported pain ratings, has been interpreted as indicative of central sensitisation in fibromyalgia. Greater TS in patients, however, has not been universally observed. It is also unclear whether increased pain report maintains beyond the TS period.

MethodsIn this study, we measured TS through continuously reported pain ratings. Fibromyalgia-diagnosed patients (n = 17) and matched pain-free controls (n = 13) rated painful transcutaneous electrical stimulation of various intensity levels in 18 one-minute-long blocks. Pain was rated on a 101-point visual analogue scale. The resulting continuous response was divided into TS (< 15s) and adaptation (15 - 60s) periods. Average pain values were extracted for each period alongside the timing of key events such as maximal pain ratings. The difference in temporal summation and adaptation measures between fibromyalgia and control participants was analysed using mixed-effects modelling.

ResultsThe average pain ratings for TS and adaptation periods were not significantly associated with fibromyalgia diagnosis but were with stimulation intensity. The same was true for the magnitude of the maximal rating during TS and the slope leading to that peak rating. The presence of fibromyalgia, however, did predict the time of the maximal TS rating, as well as the value and the time of the maximal adaptation rating.

ConclusionsOur study did not find homogeneously increased TS pain ratings. Instead, by utilising continuous pain data we demonstrate for the first time that the time of TS peak rating, as well as the magnitude and time of adaptation peak rating are linked to fibromyalgia diagnosis.

category: rheumatology


title: An in-depth analysis of phosphorylated tau in amyotrophic lateral sclerosispost-mortem motor cortex and cerebrospinal fluid

abstract: Although the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are not yet fully understood, recent studies have described alterations in tau protein in both sporadic and familial ALS. However, it is unclear whether alterations in tau contribute to ALS pathogenesis. Here, we leveraged the ALS Knowledge Portal and Project MinE data sets and identified specific genetic variants clustering within the microtubule-binding domain of MAPT, which were unique to ALS cases. Furthermore, our analysis in a large post-mortem cohort of ALS and control motor cortex demonstrates that although there was no significant difference in the presence of phosphorylated tau (pTau) neuropil threads and neurofibrillary tangles between the two groups, pTau-S396 and pTau-S404 mis-localized to the nucleus and synapses in ALS. This was specific to the C-terminus phosphorylation sites as there was a significant decrease in pTau-T181 in ALS synaptoneurosomes compared to controls. Lastly, while there was no change in total tau or pTau-T181 in ALS CSF, there was a decrease in pTau-T181:tau ratio in ALS CSF, as previously reported. Importantly, CSF tau levels were increased in ALS patients diagnosed with bulbar onset ALS, while pTau-T181:tau ratio was decreased in ALS patients diagnosed with both bulbar and limb onset. Additionally, there was an inverse correlation between tau levels in the CSF and the revised ALS functional rating scale (ALSFRS-R) as well as a correlation between pTau-T181:tau ratio and ALSFRS-R. While there were no longitudinal alterations in tau, pTau-T181 and pTau-T181:tau ratio, there was an increase in the rate of ALSFRS-R decline per month associated with increases in tau levels. This decline was also inversely correlated with increases in pTau-T181 in relation to tau levels. Taken together, our findings demonstrate that, like Alzheimers disease, hyperphosphorylated tau is mis-localized in ALS and that decreases in CSF pTau-T181 may serve as a biomarker in ALS.

category: neurology


title: Speech pause distribution as an early marker for Alzheimer's disease

abstract:
BackgroundPause duration analysis is a common feature in the study of discourse in Alzheimers disease (AD) and may also be helpful for its early detection. However, studies involving patients with amnestic mild cognitive impairment (aMCI) have yielded varying results.

ObjectivesTo characterize the probability density distribution of speech pause durations in AD, two multi-domain amnestic MCI patients (with memory encoding deficits, a-mdMCI-E, and with retrieval impairment only, a-mdMCI-R) and healthy controls (HC) in order check whether there are significant differences between them.

Method112 picture-based oral narratives were manually transcribed and annotated for the automatic extraction and analysis of pause durations. Different probability distributions were tested for the fitting of pause durations while truncating shorter ranges. Recent findings in the field of Statistics were considered in order to avoid the inherent methodological uncertainty that this type of analysis entails.

ResultsA lognormal distribution (LND) explained the distribution of pause duration for all groups. Its fitted parameters ({micro},{sigma}) followed a gradation from the group with shorter durations and a higher tendency to produce short pauses (HC) to the group with longer pause durations and a considerably higher tendency to produce long pauses with greater variance (AD). Importantly, a-mdMCI-E produced significantly longer pauses and with greater variability than their a-mdMCI-R counterparts ( = 0.05).

ConclusionWe report significant differences at the group level in pause distribution across all groups of study that could be used in future diagnostic tools and discuss the clinical implications of these findings, particularly regarding the characterization of aMCI.


title: Comparative Study - The Impact and Profile of COVID-19 Patients Who Are Indicated for Neuroimaging: Vascular Phenomena Are Been Found in the Brain and Olfactory Bulbs

abstract:
ObjectiveTo verify the impact and findings of the COVID-19 patients group that underwent brain scans in comparison to the group which only chest CT was performed.

Method876 suspected COVID-19 patients and a subsample of 232 cases with confirmed COVID-19 who underwent brain CT/MRI scan (n=35) or only chest CT (n=197) in two radiology departments, were evaluated.

Results5.59% of all suspected COVID-19 patients found had brain scans and 98.74% chest CT. There was a statistically significant difference with associations regarding the COVID-19 brain scan group for: admission to ICU, greater severity of lung injuries, the use of mechanical ventilator, seizure, sepsis, and stroke and statistical tendency for chronic renal failure and systemic arterial hypertension. 40.0% of COVID-19 patients from the brain scan group were abnormal on brain CT and/or brain MRI. 22.9% cases with any kind of bleeding or microbleeding, 8.6% with restricted diffusion lesions. One ischemic stroke case was associated with irregularity at M1 segment of the right middle cerebral artery. There was a case of left facial nerve palsy with enhancement of left geniculate ganglia. An analyse of the olfactory bulbs was possible in 12 brain MRIs and 100% had enhancement and/or microbleeding. There was no statistical difference regarding death (9.1% versus 5.2%).

In conclusionthe COVID-19 patients group on which brain CT and/or MRI needed to be performed was statically associated with the more severe COVID-19 disease, an indication to ICU, a more severe form of lung disease, use of mechanical ventilator, seizure, sepsis and stroke. Less than half of patients had abnormal brain imaging scans with all of them showing vascular brain injury lesion, being more frequently microbleeding or bleeding, followed by restricted diffusion lesions. All the olfactory bulbs evaluated showed injury by vascular phenomenon, probably methahemoglobine by microbleeding or microthrombus and/or abnormal enhancement


title: Lived experiences of pregnant and new mothers during COVID-19 pandemic: A narrative analysis of YouTube birth stories.

abstract:
IntroductionThe COVID-19 pandemic has brought on unprecedented changes, not only to our daily lives but also to our healthcare system. The pandemic has particularly impacted pregnant women that must give birth with tight restrictions and significant uncertainties. Birth stories have frequently been used as a way for women to describe their experiences with the birthing process. In this uncertain time, birth stories can provide valuable insight into how pregnancy and birth stressors during a pandemic can impact the patients overall experience. This study sought to describe and understand pregnant and new mothers lived experiences during the COVID-19 pandemic.

MethodsResearchers extracted relevant YouTube birth stories using predetermined search terms and inclusion criteria. The mothers birth stories were narrated in their second or third trimester or those who had recently given birth during the study period. Birth stories were analyzed using an inductive and deductive approach to capture different aspects of the birthing experience.

ResultsOverall, eighty-three birth stories were analyzed. Within these birth stories, four broad themes and twelve subthemes emerged. Key themes included a sense of loss, hospital experiences, experiences with healthcare providers, and unique experiences during birth and postpartum. The birth stories revealed negative and positive birth experiences. Particularly, mothers were frustrated with constantly changing policies within the healthcare setting that negatively affected their birthing experience. On the other hand, support from healthcare professionals, having their partners in the delivery room, and having a positive mindset was instrumental in having a positive birth experience.

ConclusionResults from this study provided a detailed description of womens lived experience with giving birth during the COVID-19 pandemic. Healthcare providers need to provide clear communication and compassionate patient-centered care to relieve womens anxiety about uncertain and unpredictable policy as the pandemic continues to evolve.

category: obstetrics and gynecology


title: The ocular tissue-specificity of differentially expressed age-related macular degeneration associated genes

abstract:
PurposeAge-related macular degeneration (AMD) is a leading cause of blindness in the developed world. One of the most genetically well-characterized degenerative diseases, genome-wide association studies (GWAS) have identified 52 independent common or rare AMD risk associated variants. While transcriptome-wide association analyses (TWAS) and expression quantitative trait loci (eQTL) efforts have characterized the effects of these AMD-associated genes on mRNA expression in retinal tissue, we aimed to characterize the AMD-associated transcriptional profiles of functionally distinct ocular tissues including the macular and extramacular regions of the retina and the retinal-pigment epithelium (RPE)/choroid.

MethodsUsing publicly available microarray data (NCBI GEO accession: GSE29801) comprised of retinal and RPE/choroidal tissue samples from 142 AMD patients and 151 healthy individuals (118 retina and 175 RPE/Choroid samples), tissue-specific differential gene expression analyses were conducted. Transcriptome analyses were focused on 878 genes surrounding known AMD-associated loci.

ResultsMany genes which contain clinically significant or causal variants identified via GWAS or TWAS/eQTL studies were significantly differentially expressed and display transcriptional heterogeneity across different subtypes of ocular tissue and retinal geography in AMD-associated tissues.

ConclusionThese findings demonstrate the importance of spatial heterogeneity and tissue specificity in the mRNA expression of known AMD-associated genes. Genes known to harbor rare or causal AMD- associated variants are differentially expressed in functionally distinct ocular tissues of AMD patients, suggesting they might contribute to disease regardless of mutation status.

category: ophthalmology


title: Cost-utility of two minimally-invasive surgical techniques for operable oropharyngeal cancer: Transoral robotic surgery versus transoral laser microsurgery

abstract:
ImportanceTransoral robotic surgery (TORS) and transoral laser micro-surgery (TLM) are two different but competing minimally invasive techniques to surgically remove operable oropharyngeal squamous cell cancers (OPSCC). As of now, no comparative analysis as to the cost-utility of these techniques exists.

ObjectiveRecent population-level data suggest for TORS and TLM equivalent tumor control, but different total costs, need for adjuvant chemoradiation, and learning curves. Therefore, the objective of this study was to compare TORS and TLM from the cost-utility (C/U) point of view using a decision-analytical model from a Swiss hospital perspective.

DesignOur decision-analytical model combines decision trees and a Markov model to compare TORS and TLM strategies. Model parameters were quantified using available literature, original cost data from two Swiss university tertiary referral centers, and utilities elicited directly from a Swiss population sample using standard gamble. C/U and sensitivity analyses were used to generate results and gauge model robustness.

SettingSwiss hospital perspective

InterventionCost-utility analysis

Main outcome measureComparative cost-utility data from TLM and TORS

ResultsIn the base case analysis TLM dominates TORS. This advantage remains robust, even if the costs for TORS would reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment (pTorsAlone>0.407), whereby in an interval between 55%-62% (pTorsAlone 0.38-0.45) cost effectiveness of TORS is sensitive to the prescription of adjuvant CRT. Also, exceeding 29% of TLM patients requiring a re-operation for inadequate margins renders TORS more cost-effective.

ConclusionTLM is more cost-effective than TORS. However, this advantage is sensitive to various parameters i.e. the number of re-operations and adjuvant treatment.

Key pointsO_ST_ABSQuestionC_ST_ABSCompare cost-utility of TORS versus TLM

FindingsIn the base case analysis TLM dominates TORS, even if the costs for TORS would reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment, whereby in an interval between 55%-62% cost effectiveness of TORS is sensitive to the prescription of adjuvant CRT. Exceeding 29% of TLM patients requiring a re-operation for inadequate margins renders TORS more cost-effective.

MeaningTLM is more cost-effective than TORS. However, this advantage is sensitive to the number of re-operations and adjuvant treatment

category: otolaryngology


title: GestaltMatcher: Overcoming the limits of rare disease matching using facial phenotypic descriptors

abstract: A large fraction of monogenic disorders causes craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more efficiently with the support of computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this "supervised" approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we created GestaltMatcher, which uses a deep convolutional neural network based on the DeepGestalt framework. We used photographs of 17,560 patients with 1,115 rare disorders to define a "Clinical Face Phenotype Space". Distance between cases in the phenotype space defines syndromic similarity, allowing test patients to be matched to a molecular diagnosis even when the disorder was not included in the training set. Similarities among patients with previously unknown disease genes can also be detected. Therefore, in concert with mutation data, GestaltMatcher could accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism, as well as enable the delineation of novel phenotypes.

category: genetic and genomic medicine


title: AMELIE 3: Fully Automated Mendelian Patient Reanalysis at Under 1 Alert per Patient per Year

abstract:
BackgroundMany thousands of patients with a suspected Mendelian disease have their exomes/genomes sequenced every year, but only about 30% receive a definitive diagnosis. Since a novel Mendelian gene-disease association is published on average every business day, thousands of undiagnosed patient cases could receive a diagnosis each year if their genomes were regularly compared to the latest literature. With millions of genomes expected to be sequenced for rare disease analysis by 2025, and considering the current publication rate of 1.1 million new articles per annum in PubMed, manually reanalyzing the growing cases of undiagnosed patients is not sustainable.

MethodsWe describe a fully automated reanalysis framework for patients with suspected, but undiagnosed, Mendelian disorders. The presented framework was tested by automatically parsing all [~]100,000 newly published peer reviewed papers every month and matching them on genotype and phenotype with all stored undiagnosed patients. If a new article contains a possible diagnosis for an undiagnosed patient, the system provides notification. We test the accuracy of the automatic reanalysis system on 110 patients, including 61 with available trio data.

ResultsEven when trained only on older data, our system identifies 80% of reanalysis diagnoses, while sending only 0.5-1 alerts per patient per year, a 100-1,000-fold efficiency gain over manual literature surveillance of equivalent yield.

ConclusionWe show that automatic reanalysis of patients with suspected Mendelian disease is feasible and has the potential to greatly streamline diagnosis. Our system is not intended to replace clinical judgment. Rather, clinical diagnostic services could greatly benefit from a modest re-allocation of time from manual literature exploration to review of automated reanalysis alerts. Our system additionally supports a new paradigm for medical IT systems: proactive, continuously learning and consequently able to autonomously identify valuable insights as they emerge in digital health records. We have launched automated patient reanalysis, trained on the latest data, with user accounts and daily literature updates at https://AMELIE.stanford.edu.


title: An Intrinsic and Extrinsic Evaluation of Learned COVID-19 Concepts using Open-Source Word Embedding Sources

abstract:
IntroductionScientists are developing new computational methods and prediction models to better clinically understand COVID-19 prevalence, treatment efficacy, and patient outcomes. These efforts could be improved by leveraging documented, COVID-19-related symptoms, findings, and disorders from clinical text sources in the electronic health record. Word embeddings can identify terms related to these clinical concepts from both the biomedical and non-biomedical domains and are being shared with the open-source community at large. However, its unclear how useful openly-available word embeddings are for developing lexicons for COVID-19-related concepts.

ObjectiveGiven an initial lexicon of COVID-19-related terms, characterize the returned terms by similarity across various, open-source word embeddings and determine common semantic and syntactic patterns between the COVID-19 queried terms and returned terms specific to word embedding source.

Materials and MethodsWe compared 7 openly-available word embedding sources. Using a series of COVID-19-related terms for associated symptoms, findings, and disorders, we conducted an inter-annotator agreement study to determine how accurately the most semantically similar returned terms could be classified according to semantic types by three annotators. We conducted a qualitative study of COVID-19 queried terms and their returned terms to identify useful patterns for constructing lexicons. We demonstrated the utility of applying such terms to discharge summaries by reporting the proportion of patients identified by concept for pneumonia, acute respiratory distress syndrome, and COVID-19 cohorts.

ResultsWe observed high, pairwise inter-annotator agreement (Cohens Kappa) for symptoms (0.86 to 0.99), findings (0.93 to 0.99), and disorders (0.93 to 0.99). Word embedding sources generated based on characters tend to return more lexical variants and synonyms; in contrast, embeddings based on tokens more often return a variety of semantic types. Word embedding sources queried using an adjective phrase compared to a single term (e.g., dry cough vs. cough; muscle pain vs. pain) are more likely to return qualifiers of the same semantic type (e.g., "dry" returns consistency qualifiers like "wet", "runny"). Terms for fever, cough, shortness of breath, and hypoxia retrieved a higher proportion of patients than other clinical features. Terms for dry cough returned a higher proportion of COVID-19 patients than pneumonia and ARDS populations.

DiscussionWord embeddings are a valuable technology for learning terms, including synonyms. When leveraging openly-available word embedding sources, choices made for the construction of the word embeddings can significantly influence the phrases returned.

category: health informatics


title: Efficiency of Artificial Intelligence in Detecting COVID-19 Pneumonia and Other Pneumonia Causes by Quantum Fourier Transform Method

abstract: The new coronavirus (COVID-19) appeared in Wuhan in December 2019 and has been announced as a pandemic by the World Health Organization (WHO). Currently, this deadly pandemic has caused more than 1 million deaths worldwide. Therefore, it is essential to detect positive cases as early as possible to prevent the further spread of this outbreak. Currently, the most widely used COVID-19 detection technique is a real-time reverse transcription-polymerase chain reaction (RT-PCR). However, RT-PCR is time-consuming to confirm infection in the patient. Because RT-PCR is less sensitive, it provides high false-negative results. Computed tomography (CT) is recommended as a solution to this problem by healthcare professionals because of its higher sensitivity for early and rapid diagnosis. In addition, radiation used in CT poses a serious threat to patients. In this study, we propose a CNN-based method to distinguish COVID-19 pneumonia from other types of viral and bacterial pneumonia using low-dose CT images to reduce the radiation dose used in CT. In our study, we used a data set consisting of 7717 CT images of 350 patients that we collected from Canakkale Onsekiz Mart University Research Hospital. We used a CNN-based network that suppresses noise to remove interference from low-dose CT images. In the image preprocessing phase, we provided lung segmentation from CT images and applied quantum Fourier transform. By evaluating all possible variations of local knowledge at the same time with quantum Fourier transformation, the most informative spatial information was extracted. In CNN-based architecture, we used pre-trained ResNet50v2 as a feature extractor and fine-tune by training with our dataset. We visualized the efficiency of the ResNet50v2 network using the t-SNE method. We performed the classification process with a fully connected layer. We created a heat map using the GradCam technique to see where the model focuses on the images while classifying. In this experimental study, the results of 99.5%, 99.2%, 99.0%, 99.7%, and 99.1%, were obtained in the context of performance criteria such as accuracy, precision, sensitivity, specificity, and f1 score, respectively. This study revealed the artificial intelligence-based computer-aided diagnosis (CAD)system as an effective and fast method to accurately diagnose COVID-19 pneumonia.


title: Evaluation of three rapid lateral flow antigen detection tests for the diagnosis of SARS-CoV-2 infection

abstract:
IntroductionThe COVID-19 pandemic has led to high demand of diagnostic tools. Rapid antigen detection tests have been developed and many have received regulatory acceptance such as CE IVD or FDA markings. Their performance needs to be carefully assessed.

Materials and Methods158 positive and 40 negative retrospective samples collected in saline and analyzed by a laboratory-developed RT-PCR test were used to evaluate Sofia (Quidel), Standard Q (SD Biosensor), and Panbio (Abbott) rapid antigen detection tests (RADTs). A subset of the specimens was subjected to virus culture.

ResultsThe specificity of all RADTs was 100% and the sensitivity and percent agreement was 80% and 85% for Sofia, 81% and 85% for Standard Q, and 83% and 86% for Panbio, respectively. All three RADTs evaluated in this study reached a more than 90% sensitivity for samples with a high viral load as estimated from the low Ct values in the reference RT-PCR. Virus culture was successful in 80% of specimens with a Ct value <25.

ConclusionsAs expected, the RADTs were less sensitive than RT-PCR. However, they benefit from the speed and ease of testing, and lower price as compared to RT-PCR. Repeated testing in appropriate settings may improve the overall performance.

category: infectious diseases


title: Development of Electrospun Nanofibrous Filters for Controlling Coronavirus Aerosols

abstract:
Airborne transmission of SARS-CoV-2 plays a critical role in spreading COVID-19. To protect public health, we designed and fabricated electrospun nanofibrous air filters that hold promise for applications in personal protective equipment and indoor environment. Due to ultrafine nanofibers ([~]300 nm), the electrospun air filters had a much smaller pore size compared to the surgical mask and cloth masks (a couple of microns versus tens to hundreds of microns). A coronavirus strain was used to generate aerosols for filtration efficiency tests, which can better represent SARS-CoV-2 than other agents used for aerosol generation in previous studies. The electrospun air filters showed excellent performance by capturing up to 99.9% of coronavirus aerosols, which outperformed many commercial face masks. In addition, since NaCl aerosols have been widely used in filtration tests, we compared the filtration efficiency obtained from the coronavirus aerosols and the NaCl aerosols. The NaCl aerosols were demonstrated as an eligible surrogate for the coronavirus aerosols in the filtration tests, when air filters and face masks with diverse pore sizes, morphologies, and efficiencies were used. Our work paves a new avenue for advancing air filtration by developing electrospun nanofibrous air filters for controlling SARS-CoV-2 airborne transmission. Moreover, the removal efficiency of the NaCl aerosols can be reasonably translated into understanding how air filters capture the coronavirus aerosols.

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/20249046v1_ufig1.gif" ALT="Figure 1">
View larger version (59K):
org.highwire.dtl.DTLVardef@1a40a5eorg.highwire.dtl.DTLVardef@a4af7forg.highwire.dtl.DTLVardef@1fdd2c5org.highwire.dtl.DTLVardef@118a34e_HPS_FORMAT_FIGEXP  M_FIG Table of Contents

C_FIG


title: Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data

abstract:
The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases.

Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.


title: Is sickle cell disease a risk factor for severe COVID-19 : a multicenter national retrospective cohort

abstract:
IntroductionCoronavirus disease (COVID-19) caused by the novel coronavirus SARS-CoV-2 is an infectious disease which has evolved into a worldwide pandemic. Growing evidence suggests that individuals with pre-existing comorbidities are at higher risk of a more serious COVID-19 illness. Sickle cell disease (SCD) is an inherited hemoglobinopathy which increases the susceptibility to infections and as a consequent has higher risks of morbidity and mortality.

The impact of COVID-19 on SCD patients could lead to further increase in disease severity and mortality. Studies that examine the effect of SCD on COVID-19 outcomes are lacking. This study aims to determine whether SCD is a risk factor for severe COVID-19 infection in regards to the requirement of non-invasive ventilation/high flow nasal cannula (NIV/HFNC), mechanical intubation (MV) or death.

MethodsRetrospective cohort study which included COVID-19 patients admitted to four Ministry of Health COVID-19 treatment facilities in Bahrain during the period of 24, February 2020, to 31, July 2020. All SCD patients with COVID-19 were included and compared to randomly selected non-SCD patients with COVID-19. Data for the selected patients were collected from the medical records. Multivariate logistic regression models were used to control for confounders and estimate the effect of SCD on the outcomes.

ResultsA total of 1,792 patients with COVID-19 were included; 38 of whom were diagnosed with SCD as well. In the SCD group, one (2.6%) patient required NIV/HFNC, one (2.6%) required MV and one (2.6%) death occurred. In comparison, 56 (3.2%) of the non-SCD patients required NIV/HFNC, 47 (2.7%) required MV and death occurred in 58 (3.3%) patients. Upon adjusting for confounders, SCD had an odds ratio of 1.847 (95% CI: 0.39 - 8.83; p=0.442).

ConclusionOur results indicate that SCD is not a risk factor for worse disease outcomes in COVID-19 patients.


title: Early measurement of blood sST2 is a good predictor of death and poor outcomes in patients admitted for COVID-19 infection

abstract:
ImportanceAlthough several biomarkers have shown correlation to prognosis in COVID-19 patients, their clinical value is limited because of lack of specificity, suboptimal sensibility, or poor dynamic behavior.

ObjectiveIn search of better prognostic markers in COVID-19, we hypothesized that circulating soluble ST2 (sST2) could be associated to a worse outcome, prompted by our previous knowledge of sST2 involvement in heart failure-associated lung deterioration, and by mounting evidence favoring a role of IL-33/ST2 axis in the disease.

Design, Setting and participantsOne hundred and fifty-two patients admitted for confirmed COVID-19 infection were included in a prospective non-interventional, observational study carried out in a tertiary teaching center. Blood samples were drawn at admission, 48-72 hours later and at discharge. sST2 concentrations, and routine blood laboratory were analyzed.

Main outcomesPrimary end-points were admission at intensive care unit (ICU) and, mortality. Other outcomes were a need for high oxygen flow therapy (HOF) or increasing treatment at 48/72 hours.

ResultsMedian age was 57.5 years (SD: 12.8), 60.4% males. Ten per cent of patients (n=15) were derived to ICU and/or died during admission. The rest stayed hospitalized 8(IQR:6) days on average. About 34% (n=47), 38% (n=53) and 48.5% (n=66) needed HOF, up-titrate therapy or both, respectively.

Median (IQR) sST2 serum concentration (ng/mL) rose to 53.1(30.9) at admission, peaked at 48-72h (79.5[64]) and returned to admission levels at discharge (44.9[36.7]), remaining significantly elevated above healthy donor values (18.6[15.1]).

A concentration of sST2 above 58.9 ng/mL identified patients progressing to ICU admission or death. These results remained significant after multivariable analysis. The area under the receiver operating characteristics curve (AUC) of sST2 for the occurrence of end-points was 0.776 (p=0.001). Admission sST2 was higher in patients who needed up-tritate therapy.

Conclusions and relevanceIn patients admitted for COVID-19 infection, measurement of sST2 measurement early within 24h after at admission was able to identify patients at risk of severe complications or death.


title: Detection of SARS-CoV-2 in the air from hospitals and closed rooms occupied by COVID-19 patients

abstract: To understand air transmission characteristics of SARS-CoV-2 and risks for health care personnel and visitors to hospitals, we analyzed air samples collected from various enclosures in hospitals at Hyderabad and Mohali and performed closed room experiments with COVID-19 positive individuals. We collected 64 air samples from COVID and non-COVID areas of various hospitals and 17 samples from closed rooms occupied by COVID patients. 4 samples from COVID care areas were positive for SARS-CoV-2 with no obvious predilection towards ICU/non-ICU areas in the hospital samples. In the closed room experiments, where one or more COVID-19 patients spent a short duration of time, one sample - collected immediately after the departure of three symptomatic patients from the room - was positive. Our results indicate that the chance of picking up SARS-CoV-2 in the air is directly related to a number of COVID positive cases in the room, their symptomatic status, and the duration of exposure and that the demarcation of hospital areas into COVID and non-COVID areas is a successful strategy to prevent cross infections. In neutral environmental conditions, the virus does not seem to spread farther away from the patients, especially if they are asymptomatic, giving an objective evidence for the effectiveness of physical distancing in curbing the spread of the epidemic.


title: Does the Pareto Principle describe parasite counts in humans? The case of hookworm in pregnant women

abstract: The Pareto Principle (PP) -- that 80% of an attribute are found in 20% of individuals -- is one way to characterize heterogeneity in infectious diseases. An alternative is the dispersion parameter (k) of the negative binomial distribution (NBD). The NBD has two parameters, while the PP is a single property which may hold for any distribution family. The objectives of the current work are: a) to obtain a relation between the PP and NBD, i.e. to specify which combinations of NBD parameters comply with the PP; b) for hookworm, a soil-transmitted intestinal parasite of humans, to identify whether the PP or the NBD is a more parsimonious description of heterogeneity of infection load. For objective a), an empirical relation is found in the form of a saw-toothed line on a plot of k against the mean, reaching an asymptote of approximately 0.24. For objective b), we estimate k and the mean from nine studies from a systematic review of hookworm in pregnant women. Seven studies had higher heterogeneity than the PP, ranging from 83:20 to 100:20: we call these super-Pareto. One study was sub-Pareto (74:20), and one was Pareto (80:20). This suggests that at least two parameters, as supplied by the NBD, are necessary to describe the heterogeneity of hookworm. The probability of reaching a target reduction in prevalence is less when there is greater aggregation, which suggests that estimating aggregation via a subsample could be worthwhile, in order to set a target coverage threshold before starting mass drug administration.


title: Clinical diagnosis of COVID-19: a prompt, feasible, and sensitive diagnostic tool for COVID-19 based on a 1,757-patient cohort (The AndroCoV Clinical Scoring for COVID-19 diagnosis).

abstract:
ImportanceIn the COVID-19 pandemic, a limiting barrier for more successful approaches to COVID-19 is the lack of appropriate timing for its diagnosis, during the viral replication stage, when antiviral approaches could demonstrate efficacy, precluding progression to severe stages. Three major reasons that hamper the diagnosis earlier in the disease are the unspecific and mild symptoms in the first stage, the cost- and time-limitations of the rtPCR-SARS-CoV-2, and the insufficient sensitivity of this test as desired for screening purposes during the pandemic. More sensitive and earlier methods of COVID-19 detection should be considered as key for breakthrough changes in the disease course and response to specific therapeutic strategies. Our objective was to propose a clinical scoring for the diagnosis of COVID-19 (The AndroCoV Clinical Scoring for COVID-19 Diagnosis) that has been validated in a large population sample, aiming to encourage the management of patients with high pre-clinical likelihood of presenting COVID-19, at least during the pandemics, independent of a rtPCR-SARS-COV-2 test.

Materials and methodsThis is a compounded retrospective and prospective analysis of clinical data prospectively collected from the Pre-AndroCoV and AndroCov Trials that resulted in a clinical scoring for COVID-19 diagnosis based on likelihood of presenting COVID-19 according to the number of symptoms, presence of anosmia, and known positive household contact, in a variety of combinations of scoring criteria, aiming to the detect scorings that provided the highest pre-test probability and accuracy. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and accuracy were calculated for subjects screened in two different periods and altogether, for females, males, and both, in a total of nine different scenarios, for combinations between one, two, or three or more symptoms, or presence of anosmia in subjects without known positive household contacts, and no symptoms, one, two, or three or more symptoms, or presence of anosmia or ageusia in subjects with known positive household contacts.

Results1,757 patients were screened for COVID-19. Among the multiple combinations, requiring two or more symptoms with or without anosmia or ageusia for subjects without known contact and one or more symptoms with or without anosmia or ageusia with known positive contacts presented the highest accuracy (80.4%), and higher pretest probability and accuracy than virtually all rtPCR-SARS-CoV-2 commercially available kit tests.

ConclusionThe AndroCoV Clinical Scoring for COVID-19 Diagnosis was demonstrated to be a feasible, quick, inexpensive and sensitive diagnostic tool for clinical diagnosis of COVID-19. A clinical diagnosis of COVID-19 should avoid delays and missed diagnosis, and reduce costs, and should therefore be recommended as a first-line option for COVID-19 diagnosis for public health policies, at least while SARS-CoV-2 is the prevailing circulating virus.

Key PointsO_ST_ABSQuestionC_ST_ABSIs a clinical diagnosis of COVID-19 sensitive, accurate, and feasible?

FindingsThe present analysis of a 1,757-subject cohort of the AndroCoV trials demonstrated that clinical scoring for COVID-19 diagnosis can deliver a more sensitive and prompter diagnosis than the current gold-standard diagnostic method, rtPCR-SARS-CoV-2, with an accuracy above 80%.

MeaningA clinical diagnosis of COVID-19 avoids missed diagnosis due to insufficient sensitivity or incorrect timing of the performance of rtPCR-SARS-CoV-2, reduces costs, avoid delays on specific managements, and allows the testing of potentially effective antiviral therapeutic approaches that should work if administered in the early stage of COVID-19


title: PREDICTORS OF UPTAKE OF A POTENTIAL COVID-19 VACCINE AMONG NIGERIAN ADULTS

abstract:
BackgroundThe Coronavirus diseases (COVID-19) pandemic is not abating and there is no approved treatment yet. The development of vaccines is hoped to help in addressing this disease outbreak. However, in the face of anti-vaccines uprise, it is important to understand the factors that may influence the uptake of COVID-19 vaccines as this will influence how successful the fight against COVID-19 will be in the long term.

MethodsA cross-sectional study among 776 adult Nigerians (age [≥]18 years) was conducted in the 36 States of Nigeria and the Capital City with online questionnaire. The questionnaire consisted of 5 sections: socio-demographic characteristics of respondents, respondents knowledge of COVID-19, respondents risk perception of COVID-19, vaccination history of respondents, and willingness to receive COVID-19 vaccine. Descriptive analysis of variables was done and multivariate analysis using logistic regression was carried out to determine the predictors of uptake of a potential COVID-19 vaccine. The level of significance was predetermined at a p-value < 0.05. Data analysis was done with SPSS version 21.

ResultsMost of the respondents were male (58.1%). Most participants were willing to take a potential COVID-19 vaccine (58.2%), while 19.2% would not take it with 22.6% indecisive. 53.5% would prefer a single dose COVID-19 vaccine. For vaccine uptake, being male (p= 0.002) and the perception that "vaccines are good" (p< 0.001) were the positive predictor of uptake of a potential COVID-19 vaccine.

ConclusionMost Nigerians were willing to take a potential COVID-19 vaccine with the male gender and perception that "vaccines are good" being positive predictors. There is a need for public enlightenment aim at encouraging those that are indecisive or averse to receiving COVID-19 vaccines.


title: Insights into the molecular mechanism of anticancer drug ruxolitinib repurposable in COVID-19 therapy

abstract: Due to non-availability of specific therapeutics against COVID-19, repurposing of approved drugs is a reasonable option. Cytokines imbalance in COVID-19 resembles cancer; exploration of anti-inflammatory agents, might reduce COVID-19 mortality. The current study investigates the effect of ruxolitinib treatment in SARS-CoV-2 infected alveolar cells compared to the uninfected one from the GSE5147507 dataset. The protein-protein interaction network, biological process and functional enrichment of differentially expressed genes were studied using STRING App of the Cytoscape software and R programming tools. The present study indicated that ruxolitinib treatment elicited similar response equivalent to that of SARS-CoV-2 uninfected situation by inducing defense response in host against virus infection by RLR and NOD like receptor pathways. Further, the effect of ruxolitinib in SARS-CoV-2 infection was mainly caused by significant suppression of IFIH1, IRF7 and MX1 genes as well as inhibition of DDX58/IFIH1-mediated induction of interferon-I and -II signalling.


title: Imprecise assessment of mask use may obscure associations with SARS-CoV-2 positivity

abstract: Masks are effective measures to prevent the transmission of SARS-CoV-2, however, lack of a national mandate coupled with poor adherence has led to suboptimal levels of transmission reduction. Although data has suggested that mask adherence is high, few studies have captured details on how mask wearing changes with activities and how these behaviors are associated with SARS-CoV-2 positivity. We recruited an online sample of 3,058 respondents from three US states (MD, FL, IL; n[~]1000/state) between September 16 - October 15, 2020. The median age of the sample was 47; 53% were female, 56% were white and 22% were working outside the home. Seventy three percent of the sample reported always wearing a mask indoors and outdoors based on local guidelines, however, 78% of participants who reported always wearing a mask reported taking their mask off when outside the home. While overall masking according to guidelines was not significantly associated with SARS-CoV-2 positivity, sometimes, often or always removing a mask during activities were significantly associated with SARS-CoV-2 positivity (adjusted odds ratio for always vs never removing mask: 9.92; 95% CI: 1.16 - 85.1). These findings suggest that masks were most effective when worn without removal reflecting the need for consistent use.


title: Mitochondrial DNA copy number and trimethylamine levels in the blood: new insights on cardiovascular disease biomarkers

abstract:
Among cardiovascular disease (CVD) biomarkers, the mitochondrial DNA copy number (mtDNAcn) is a promising candidate. A growing attention has been also dedicated to trimethylamine-N-oxide (TMAO), an oxidative derivative of the gut metabolite trimethylamine (TMA). With the aim to identify biomarkers predictive of CVD, we investigated TMA, TMAO and mtDNAcn in a population of 389 coronary artery disease (CAD) patients and 151 healthy controls, in association with established risk factors for CVD (gender, age, hypertension, smoking, diabetes, glomerular filtration rate (GFR)). MtDNAcn was significantly lower in CAD patients and in hypertensive subjects; it correlates with GFR and TMA, but not with TMAO. A biomarker including mtDNAcn, gender, and hypertension (but neither TMA nor TMAO) emerged as a good predictor of CAD. Our findings support the usage of mtDNAcn as a plastic biomarker to monitor the exposure to risk factors and the efficacy of preventive interventions for a personalized CAD risk reduction.

Highlights- mtDNAcn measured in whole blood is associated to the cardiovascular health status in humans;
- mtDNAcn is reduced in CAD and hypertension, and inversely correlates with GFR;
- mtDNA, gender and hypertension together represent a good predictive biomarker for CAD;
- TMA metabolism is different in healthy and CAD subjects;
- TMA and TMAO are not good predictors of CAD.

category: cardiovascular medicine


abstract:
Background and aimCOVID-19 is putting extraordinary pressure on emergency departments (EDs). To support decision making in the ED, we aimed to develop a simple and valid model for predicting mortality and need for intensive care unit (ICU) admission in suspected COVID-19 patients.

MethodsFor model development, we retrospectively collected data of patients who were admitted to 4 large Dutch hospitals with suspected COVID-19 between March and August 2020 (first wave of the pandemic). Based on prior literature we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. Logistic regression analyses with post-hoc uniform shrinkage was used to obtain predicted probabilities of in-hospital death and of the need for ICU admission, both within 28 days after hospital admission. We assessed model performance (Area Under the ROC curve (AUC); calibration plots) with temporal validation in patients who presented between September and December 2020 (second wave). We used multiple imputation to account for missing values.

ResultsThe development data included 5,831 patients, of whom 629 (10.8%) died and 5,070 (86.9%) were discharged within 28 days after admission. ICU admission was fully recorded for 2,633 first wave patients in 2 hospitals, with 214 (8%) ICU admissions within 28 days. A simple model - COVID Outcome Prediction in the Emergency Department (COPE) - with age, respiratory rate, C-reactive protein, lactic dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well-calibrated and showed good discrimination in 3,252 second wave patients (AUC in 4 hospitals: 0.82 [0.78; 0.86]; 0.82 [0.74; 0.90]; 0.79 [0.70; 0.88]; 0.83 [0.79; 0.86]). COPE was also able to identify patients at high risk of needing IC in 706 second wave patients with complete information on ICU admission (AUC: 0.84 [0.78; 0.90]; 0.81 [0.66; 0.95]). The models are implemented in web-based and mobile applications.

ConclusionCOPE is a simple tool that is well able to predict mortality and need for ICU admission for patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making.

CONTRIBUTION TO THE LITERATUREO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIPrediction models have the potential to support decision making about hospital admission of patients presenting to the emergency department with suspected COVID-19
C_LIO_LIMost currently available models that were independently assessed contain a high risk of bias
C_LIO_LIPromising models were developed in different patient selections and included predictors that are not quickly and objective obtainable in emergency departments
C_LI

What this study addsO_LIA simple and objective tool ("COPE") is well able to predict mortality and need for ICU admission for patients who present to the ED with suspected COVID-19
C_LIO_LICOPE may support ED physicians to identify high-risk patients - i.e. those at high risk of deterioration and/or death - requiring treatment in the ICU, intermediate-risk patients requiring admission to the clinical ward, and low-risk patients who can potentially be sent home
C_LI

category: emergency medicine


title: COVID Outcome Prediction in the Emergency Department (COPE): Development and validation of a model for predicting death and need for intensive care in COVID-19 patients


title: Cyproterone Acetate and risk of Meningioma

abstract:
Cyproterone acetate (CPA) is a synthetic steroid hormone. We assessed the association between the use of CPA and the risk of developing meningioma.

In a historical prospective cohort study, using Danish national healthcare registers we included a cohort of 5,730,654 individuals, among whom 1,982 were exposed to CPA. During follow-up, we identified 8,957 cases of meningioma, of which 16 were exposed to CPA. From 2013 to 2019 the number of new users increased from 18.1 to 62.3 new users per million, while the proportion of new users who were transgender increased from 18.4 to 68.3%. Analyses showed a significantly increased risk of meningioma according to cumulative dose of CPA; 0.1-10 grams of CPA, incidence rate 78.8 (95% CI 15.7-141.9) per 100.000 person years and adjusted hazard ratio 7.0 (3.1-15.6); >10 grams of CPA, incidence 187.5 (71.3-303.7) and adjusted hazard ratio 19.2 (10.3-35.8), as compared to the background population.

In conclusion, the cumulative dose of CPA was associated with an increased incidence and hazard ratio of meningioma, showing a dose-response relationship. The number of new CPA users increased more than 3-fold from 2013 to 2019, primarily driven by new transgender users.

category: epidemiology


title: Percentage of reported Covid-19 cases in Colombia: Estimating the true scale of the pandemic

abstract: At the outbreak of a virus, data on cases is sparse and commonly severe cases, with a higher probability of a fatal resolution, are detected at a larger rate than mild cases. In addition, in an under-sampling situation, the number of total cases is under-estimated leading to a biased case fatality rate estimation, most likely inflating the virus mortality. In this communication, we present a method to estimate the sub-report in a country that accounts for both the delay time between symptoms onset to death and the countrys demographics. The method is based on the comparison of the corrected case fatality rate (CFR) of the target country with the one of a benchmark country. Using reported data from Instituto Nacional de Salud up to December 28, we utilize our method to provide a comprehensive estimate of the Covid-19 sub-report in Colombia, its regions and some of its cities during 2020.


title: Co-circulation of SARS-CoV-2 and Influenza under vaccination scenarios

abstract: The interaction and possibly interference between viruses infecting a host population is addressed in this work. We model two viral diseases with a similar transmission mechanism and for which a vaccine exists. The vaccine is characterized by its coverage, induced temporary immunity, and efficacy. The population dynamics of both diseases consider infected individuals of each illness and hosts susceptible to one but recovered from the other. We do not incorporate co-infection. Two main transmission factors affecting the effective contact rates are postulated: i) the virus with a higher reproduction number can superinfect the one with a lower reproduction number, and ii) there exists some induced (indirect) protection induced by vaccination against the weaker virus that reduces the probability of infection by the stronger virus. Our results indicate that coexistence of the viruses is possible in the long term, even considering the absence of superinfection. Influenza and SARS-CoV-2 are employed to exemplify this last point, observing that the time-dependent effective contact rate may induce either alternating outbreaks of each disease or synchronous outbreaks. Finally, for a particular parameter range, a backward bifurcation has been observed for dynamics without vaccination.


title: Co-circulation of two viral populations under vaccination


title: Cardiometabolic risks of SARS-CoV-2 hospitalization using Mendelian Randomization

abstract:
IntroMany cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences.

Methods & materialsWe applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n=2,956) and multi-ethnic populations (COVID-19 GWAS n=10,808) to better understand extant causal associations between Type II Diabetes (GWAS n=659,316), BMI (n=681,275), diastolic and systolic blood pressure, and pulse pressure (n=757,601 for each) and COVID-19 hospitalization risk across populations.

ResultsAlthough no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI: 1.67, 0.96-2.92) and pulse pressure (OR, 95% CI: 1.27, 0.97-1.66) in the multi-ethnic sample.

ConclusionsType II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.


title: Race and ethnicity do not impact eligibility for remdesivir- a single-center experience

abstract: As the Coronavirus-2019 (COVID-19) pandemic continues, multiple therapies are rapidly being tested for efficacy in clinical trials. Clinical trials should be racially and ethnically representative of the population that will eventually benefit from these medications. There are multiple potential barriers to racial and ethnic minority enrollment in clinical trials, one of which could be that inclusion and exclusion criteria select for certain racial or ethnic groups disproportionately. In this observational cohort study at a single health care system, we examined if there were differences in eligibility for treatment with remdesivir based on clinical trial criteria for racial and ethnic minorities compared to non-Hispanic Whites. 201 electronic medical record charts were reviewed manually. Self-identified Whites were older than other racial or ethnic groups. At the time of presentation, Black, Latinx, and White participants met inclusion criteria for remdesivir at similar rates (72%, 80%, and 73% respectively), exclusion criteria at similar rates (43%, 38% and 49% for Black, Latinx and White participants respectively). In this study, there was no difference in eligibility for remdesivir based on race or ethnicity alone.


title: Lockdown Effects on Sars-CoV-2 Transmission - The evidence from Northern Jutland

abstract: The exact impact of lockdowns and other NPIs on Sars-CoV-2 transmission remain a matter of debate as early models assumed 100% susceptible homogenously transmitting populations, an assumption known to overestimate counterfactual transmission, and since most real epidemiological data are subject to massive confounding variables. Here, we analyse the unique case-controlled epidemiological dataset arising from the selective lockdown of parts of Northern Denmark, but not others, as a consequence of the spread of mink-related mutations in November 2020. Our analysis shows that while infection levels decreased, they did so before lockdown was effective, and infection numbers also decreased in neighbour municipalities without mandates. Direct spill-over to neighbour municipalities or the simultaneous mass testing do not explain this. Instead, control of infection pockets possibly together with voluntary social behaviour was apparently effective before the mandate, explaining why the infection decline occurred before and in both the mandated and non-mandated areas. The data suggest that efficient infection surveillance and voluntary compliance make full lockdowns unnecessary at least in some circumstances.


title: Unsupervised Discovery of Risk Profiles on Negative and Positive COVID-19 Hospitalized Patients

abstract: COVID-19 is a viral disease that affects people in different ways: Most people will develop mild symptoms; others will require hospitalization, and a few others will die. Hence identifying risk factors is vital to assist physicians in the treatment decision. The objective of this paper is to determine whether unsupervised analysis of risk factors of positive and negative COVID-19 subjects may be useful for the discovery of a small set of reliable and clinically relevant risk-profiles. We selected 13367 positive and 19958 negative hospitalized patients from the Mexican Open Registry. Registry patients were described by 13 risk factors, three different outcomes, and COVID-19 test results. Hence, the dataset could be described by 6144 different risk-profiles per age group. To discover the most common risk-profiles, we propose the use of unsupervised learning. The data was split into discovery (70%) and validation (30%) sets. The discovery set was analyzed using the partition around medoids (PAM) method and robust consensus clustering was used to estimate the stable set of risk-profiles. We validated the reliability of the PAM models by predicting the risk-profile of the validation set subjects. The clinical relevance of the risk-profiles was evaluated on the validation set by characterizing the prevalence of the three patient outcomes: pneumonia diagnosis, ICU, or death. The analysis discovered six positives and five negative COVID-19 risk-profiles with strong statistical differences among them. Henceforth PAM clustering with consensus mapping is a viable method for unsupervised risk-profile discovery among subjects with critical respiratory health issues.


title: Identical trends of SARS-Cov-2 transmission and retail and transit mobility during non-lockdown periods

abstract: Recent literature strongly supports the idea that mobility reduction and social distancing play a crucial role in transmission of SARS-Cov-2 infections. It was shown during the first wave that mobility restrictions reduce significantly infection transmission. Here we document the reverse relationship by showing, between the first two Covid-19 waves, a high positive correlation between the trends of SARS-Cov-2 transmission and mobility. These two trends oscillate simultaneously and increased mobility following lockdown relaxation has a significant positive relationship with increased transmission. From a public health perspective, these results highlight the importance of following the evolution of mobility when relaxing mitigation measures to anticipate the future evolution of the spread of the SARS-Cov-2.


title: Antemortem vs. postmortem histopathological and ultrastructural findings in paired transbronchial biopsies and lung autopsy samples from three patients with confirmed SARS-CoV-2 infection

abstract:
BackgroundAcute respiratory distress syndrome (ARDS) is the major cause of death in coronavirus disease 2019 (COVID-19). Multiple autopsy-based reports of COVID-19 lung pathology describe diffuse alveolar damage (DAD), organizing pneumonia (OP) and fibrotic change, but data on early pathological changes as well as during progression of the disease are rare.

Research questionComparison of histopathological and ultrastructural findings in paired transbronchial biopsies (TBBs) and autopsy material from three patients with confirmed SARS-CoV-2-infection.

MethodsWe prospectively enrolled 3 patients with confirmed SARS-CoV-2 infection. Full clinical evaluation was performed including high-resolution computed tomography (HR-CT). We took TBBs at different time points during the disease and autopsy tissue samples after the patients death.

ResultsSARS-CoV-2 was detected by RT-PCR and/or FISH in all TBBs. Lung histology revealed pneumocyte hyperplasia and capillary congestion in one patient who died short after hospital admission with detectable virus in 1/2 autopsy samples from the lung. SARS-CoV-2 was detected in 2/2 autopsy samples from a patient with a fulminant course of the disease and very short latency between biopsy and autopsy, both showing widespread DAD. In a third patient with a prolonged course, i.e. five weeks of ICU treatment with ECMO, autopsy samples showed extensive interstitial fibrosis without detectable virus by RT-PCR and/or FISH.

InterpretationWe report the course of COVID-19 in paired TBB and autopsy samples from three patients at an early stage, in rapidly progressive and in a prolonged disease course. Our findings illustrate vascular, organizing and fibrotic patterns of COVID-19-induced lung injury and suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.

category: pathology


title: Respiratory and non-respiratory manifestations in children admitted with COVID 19 in Rio de Janeiro city, Brazil

abstract:
IntroductionCOVID 19 is still a challenge in pediatrics due to variety of symptoms and different presentations

AimTo describe clinical, laboratorial and treatment of confirmed COVID-19 pediatric admitted in hospitals.

MethodsA retrospective study was conducted in children (0-18 years), admitted between March and November 15, 2020, with confirmed COVID-19 by reverse transcription polymerase chain reaction or serological tests. Clinical data about symptoms, laboratorial exams and treatments were analysed. Patients were evaluated according predominant (PRS) or non-predominant respiratory symptoms (non-PRS)

ResultsSixty-four patients were evaluated, being the median age 5.6 years. Forty-seven (73.4%) children were admitted with PRS and 17 (26.4%) with non-PRS. The main symptoms in the PRS group were fever in 74.5% of children and cough in 66%; and fever in 76.5% and edema/cavitary effusion in 29.4% in the non-PRS group. The median of C-reactive protein (in mg/dl) was 2.5 in the PRS group and 6.1 in the non-PRS group. Antibiotics were used in 85.1% of the PRS group and 94.1% of non-group. Comorbidity was present in 30/47 (63.8%) of PRS group and 8/17 (47.1%) of non-PRS group (p=0.22). Length of stay until 7 days in patients with comorbidity was present in 27/64 (42.1%) and more than 7 days in 11/64 (17.1%) (p= 0.2)

ConclusionNon-PRS represented more than one quarter of admitted patients. Fever was the main symptom detected, elevated CRP was frequent and antibiotics were commonly prescribed. Comorbidity was found in both groups and his presence was not associated with a longer length of stay.

category: pediatrics


title: A cross-sectional study on the drug usage of insomnia in the Chinese medicine hospital in Long gang, Shenzhen

abstract:
IntroductionInsomnia was widely distributed among the population, and it was a risk factor for many diseases. To evaluate the condition of usage of drugs in Chinese hospital of Longgang, Shenzhen, we carried this cross-sectional research. We extracted the information of drug usage, symptoms of patients by R software (version 4.0.2) from Hospital Information System (HIS). The research was registered in Chinese Clinical Trial Registry, ChiCTR2000040703.

MethodsA retrospective, cross-sectional study was conducted in Shenzhen Hospital of Beijing University of Chinese Medicine (Long Gang). Insomnia patients from Jan 1, 2016 to Nov 10, 2020 were included to cross-sectional study. We analyzed the basic information, the condition of drug usage and the relation of symptoms and drug usage by R software (version 4.0.2).

ResultsTotally 9439 patients were included in the study. The average age of these patients was 45.81years (SD 13.97 years). Anxiety, dreaminess, dizzy, palpitation, headache, thirsty, weakness, chest distress, annoyance, abdominal distension, bad moods, difficulty falling asleep and bitter taste were core symptoms of insomnia. Totally 14256 times (67.65%) patients received drug prescription and more than one insomnia drug was administered in 8355 patients. The 10 most used drugs ranged from more to less were Estazolam(29.99%), Zaoren Anshen Capsule(15.50%), Oryzanol(14.82%), Diazepam(14.51%), Flupentixol and Melitracen(14.30%), Alprazolam(8.12%), Zolpidem Tartrate(5.29%), vitamin B6(4.76%), Sertraline(4.03%), Clonazepam(2.97%).

ConclusionThe drug usage for insomnia in the Chinese medicine hospital in Long gang, Shenzhen were mainly included benzodiazepine, nonbenzodiazepine, Chinese patent medicines, anti-anxiety and anti-depression drugs, oryzanol and vitamin B6. The usage of Oryzanol and vitamin B6 should be abused in Chinese medicine hospital, and the usage of Chinese medicine should be more rigorous evaluated. The nonbenzodiazepine should be promoted and broader understood in Chinese medicine hospital in Longgang, Shenzhen.

category: psychiatry and clinical psychology


title: An analysis of patients' perspectives on qualitative olfactory dysfunction using social media

abstract:
BackgroundThe impact of qualitative olfactory disorders is underestimated. Parosmia is the triggered perception of distorted odours whereas phantosmia is the perception of odours in the absence of a trigger. Both can arise from post-infectious anosmia and have increased substantially since the outbreak of COVID-19.

Methodology/PrincipalThematic analysis of a social media support group for parosmia and phantosmia was used to articulate the perspectives and concerns of those affected by these debilitating olfactory disorders.

ResultsA novel symptom (olfactory perseveration) was identified where a triggered, identifiable, and usually unpleasant olfactory percept persisted in the absence of an ongoing stimulus. Fluctuations in intensity and duration of perseveration, parosmia and phantosmia were observed. Coffee, meat, onion, and toothpaste were identified as common triggers of these disorders, but people struggled to describe the distortions, using words associated with disgust and revulsion. Common strategies to avoid triggers may result in a diet lacking in both nutrition and reward. The emotional aspect of living with qualitative olfactory dysfunction was evident and highlighted the detrimental impact on mental health.

ConclusionsThe data acquired can inform rehabilitation strategies and drive our ongoing research into understanding the molecular triggers associated with parosmia, and research into patient benefit.


title: Patient-Reported Outcomes of Ugandans Living with Autoimmune Rheumatic Diseases

abstract:
PurposeThis study aimed to assess the patient-reported outcomes (PROs) in rheumatic patients attending two tertiary rheumatology clinics in Uganda.

MethodsA cross-sectional, clinical audit of patients aged 16 years or older with a confirmed diagnosis of rheumatic disease and receiving disease modifying anti-rheumatic drugs (DMARDs) was conducted between September and December 2020. Health index and overall self-rated health status were assessed using the ED-5D-5L tool. Comparisons for variables was performed using Students t-test or Mann-Whitney U for continuous numerical data while categorical data was compared using either X2 tests or Fishers exact tests as appropriate.

ResultsWe enrolled 74 eligible patients: 48 (64.9%) had rheumatoid arthritis (RA), 14 (18.9%) had systemic lupus erythematosus (SLE), and 12 (16.2%) had other autoimmune rheumatic disorders. Majority (n=69, 93.2%) were female with a mean {+/-}SD age of 45 {+/-} 17 years. Fourteen (18.9%) patients were on concomitant herbal medication while using DMARDs and 26 (35.1%) self-reported at least 1 adverse drug reactions to the DMARDS. Any level of problem was reported by 54 (72.5%) participants for mobility, 47 (63.5%) for self-care, 56 (75.6%) for usual activity, 66 (89.1%) for pain and discomfort, and 56 (75.6%) for anxiety/depression. Patients with SLE had higher median health index compared to those other autoimmune rheumatic disorders (p<0.0001). Overall self-rated health status was comparable across clinical diagnoses (p=0.2), but better for patients who received care from private (Nsambya Hospital) compared to public hospital (Mulago Hospital) (65 vs. 50, p=0.009).

ConclusionThere is a substantial negative impact of autoimmune rheumatic diseases on quality of life of patients, especially those receiving care from a public facility in Uganda.

Clinical SignificanceO_LIAdverse drug reactions to DMARDs was reported by more than one-third of the patients
C_LIO_LISLE patients have better quality of life compared to patients with other autoimmune rheumatic disease.
C_LIO_LIConcomitant use of herbal medication is common and associated with lower health index and lower overall self-rated health status.
C_LIO_LIAutoimmune rheumatic diseases impose a heavy financial burden on affected patients, over 70% of the study patients required financial support for management of their disease and a high proportion of these patients were not on their DMARD therapy the week prior to their scheduled clinic appoints.
C_LI


title: Gut Microbiome Predicts Clinically Important Improvement in Patients with Rheumatoid Arthritis

abstract:
BackgroundRapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity.

MethodsWhole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups. Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up.

ResultsWe determined that MCII status can explain a significant proportion of the overall compositional variance in the gut microbiome (R2 = 3.8%, P = 0.005, PERMANOVA). Additionally, by looking at patients baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Ruminococcus sp. Functional profiling identified thirteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine and L-methionine, to be differentially abundant between the MCII patient groups. In addition to these observations at baseline, we found microbiome features that vary differently in fold-change (from baseline to follow-up) between the two patient groups. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patient will achieve MCII (balanced accuracy = 90.0%), demonstrating potential clinical utility of gut microbiome profiles.

ConclusionsOur findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, the gut microbiome may aid in the development of non-invasive tools for predicting future prognosis in RA.

Trial registrationN/A


title: Efficacy of B12 fortified nutrient bar and yogurt in improving plasma B12 concentrations Results from two double blind randomised placebo controlled trials

abstract:
BackgroundDietary vitamin B12 (B12) deficiency is common in Indians. It may affect hematologic and neurocognitive systems and maternal deficiency predisposes offspring to neural tube defects and non-communicable disease. Long-term tablet supplementation is not sustainable.

ObjectiveTo study efficacy of B12 fortified nutrient bar and yogurt in improving plasma B12 concentrations in children and adults.

MethodsTwo double-blind, placebo-controlled randomised directly observed therapy (DOT) trials were conducted: 1. Healthy children (10-13Y) were fed nutrient bar fortified with B12 (2 mcg), multiple micronutrients (B12 1.8 mcg) or placebo for 120 days. 2. Healthy adults (18-50Y) were fed yogurt fortified with B12 (2 mcg) or Propionibacterium (1x108cfu/g) or placebo for 120 days. B12, folate, homocysteine and hemoglobin concentrations and anthropometry were measured before and post intervention.

ResultsWe randomised 164 children and 118 adults; adherence was 96% and 82% respectively. In children, B12 fortified bars increased B12 concentrations significantly above baseline (B12 alone: median +91 pmol/l, B12+ multiple micronutrients: +82 pmol/l) compared to placebo. In adults, B12 fortified yogurt increased B12 significantly (median +38 pmol/l) compared to placebo, but Propionibacterium did not. In both trials, homocysteine fell significantly with B12 supplementation. There was no significant difference in different groups in anthropometry and hemoglobin.

ConclusionsB12 fortified foods are effective in improving B12 status in Indian children and adults. They could be used to improve vitamin B12 status in the national programs for children, adolescents and women of reproductive age. They could also be used as over the counter products.

Brief HighlightsVitamin B12 deficiency is common in India. Culturally acceptable fortified foods will help reduce it. We performed two RCTs (children and adults) with B12 fortified nutrient bar and yogurt at near RDA doses and found significant improvement in B12 status. This has important implications for nutritional policy.

category: nutrition


title: Strategies to minimize SARS-CoV-2 transmission in classroom settings: Combined impacts of ventilation and mask effective filtration efficiency

abstract: The impact of the COVID-19 pandemic continues to be significant and global. As the global community learns more about the novel coronavirus SARS-CoV-2, there is strong evidence that a significant modality of transmission is via the long-range airborne route, referred to here as aerosol transmission. In this paper, we evaluate the efficacy of ventilation, mask effective filtration efficiency, and the combined effect of the two on the reduction of aerosol infection probability for COVID-19 in a classroom setting. The Wells-Riley equation is used to predict the conditional probability of infection for three distinct airborne exposure scenarios: (1) an infectious instructor exposing susceptible students; (2) an infectious student exposing other susceptible students; and (3) an infectious student exposing a susceptible instructor. Field measurements were performed in a classroom using a polydisperse neutralized salt (NaCl) aerosol, generated in a size range consistent with human-generated SARS-CoV-2 containing bioaerosols, as a safe surrogate. Measurements included time-resolved and size-resolved NaCl aerosol concentration distributions and size-resolved effective filtration efficiency of different masks with and without mask fitters. The measurements were used to validate assumptions and inputs for the Wells-Riley model. Aerosol dynamics and distribution measurements confirmed that the majority of the classroom space is uniform in aerosol concentration within a factor of 2 or better for distances > 2 m from the aerosol source. Mask effective filtration efficiency measurements show that most masks fit poorly with estimated leakage rates typically > 50%, resulting in significantly reduced effective filtration efficiency. However, effective filtration efficiencies approaching the mask material filtration efficiency were achievable using simple mask fitters. Wells-Riley model results for the different scenarios suggest that ventilation of the classroom alone is not able to achieve infection probabilities less than 0.01 (1%) for air exchanges rates up to 10 h-1 and an event duration of one hour. The use of moderate to high effective filtration efficiency masks by all individuals present, on the other hand, was able to significantly reduce infection probability and could achieve reductions in infection probability by 5x, 10x, or even >100x dependent on the mask used and use of a mask fitter. This enables conditional infection probabilities < 0.001 (0.1%) or even < 0.0001 (0.01%) to be reached with the use of masks and mask fitters alone. Finally, the results demonstrate that the reductions provided by ventilation and masks are synergistic and multiplicative. The results reinforce the use of properly donned masks to achieve reduced aerosol transmission of SARS-CoV-2 and other infectious diseases transmitted via respiratory aerosol indoors and provide new motivation to further improve the effective filtration efficiency of common face coverings through improved design, and/or the use of mask fitters.

category: occupational and environmental health


title: The drug development pipeline for glioblastoma - a cross sectional assessment of the FDA Orphan Drug Product designation database

abstract:
BackgroundGlioblastoma multiforme (GBM) is the most common malignant brain tumor among adult patients and represents an almost universally fatal disease. Novel therapies for GBM are being developed under the orphan drug legislation and the knowledge on the molecular makeup of this disease has been increasing rapidly. However, the clinical outcomes in GBM patients with currently available therapies are still dismal. An insight into the current drug development pipeline for GBM is therefore of particular interest.

ObjectivesTo provide a quantitative clinical-regulatory insight into the status of FDA orphan drug designations for compounds intended to treat GBM.

MethodsQuantitative cross-sectional analysis of the U.S. Food and Drug Administration Orphan Drug Product database between 1983 and 2020. STROBE criteria were respected.

ResultsFour orphan drugs out of 161 (2,4%) orphan drug designations were approved for the treatment for GBM by the FDA between 1983 and 2020. Fourteen orphan drug designations were subsequently withdrawn for unknown reasons. The number of orphan drug designations per year shows a growing trend. In the last decade, the therapeutic mechanism of action of designated compounds intended to treat glioblastoma shifted from cytotoxic drugs (median year of designation 2008) to immunotherapeutic approaches and small molecules (median year of designation 2014 and 2015 respectively) suggesting an increased focus on precision in the therapeutic mechanism of action for compounds the development pipeline.

ConclusionDespite the fact that current pharmacological treatment options in GBM are sparse, the drug development pipeline is steadily growing. In particular, the surge of designated immunotherapies detected in the last years raises the hope that elaborate combination possibilities between classical therapeutic backbones (radiotherapy) and novel, currently experimental therapeutics may help to provide better therapies for this deadly disease in the future.

Article summaryO_ST_ABSStrengths and limitationsC_ST_ABSO_LIThis study provides a quantitative overview on the drug development pipeline for pediatric and adult oncology in general and specifically for the indication glioblastoma
C_LIO_LIAnalyzing the therapeutic mechanisms of designated compounds in glioblastoma reveals an increased focus on personalized and targeted therapies
C_LIO_LIThe precise reasons for failure of approved drugs and for withdrawal of approved drugs in glioblastoms are unknown
C_LIO_LIFor the analysis, only the databases "FDALabel" (https://nctr-crs.fda.gov/fdalabel/ui/search) and the FDA Orphan drug product designation database (https://www.accessdata.fda.gov/scripts/opdlisting/oopd/) were considered
C_LI

category: oncology


title: Integrative Bioinformatics Analysis Reveals Noninvasive miRNA Biomarkers for Lung Cancer

abstract: Non-small cell lung cancer (NSCLC), a subtype of lung cancer, affects millions of people. While chemotherapy and other treatments have improved, the 5 year survival rate of NSCLC patients is still only 21%. Early diagnosis is essential for increasing survival as treatments have higher effectiveness at earlier stages of NSCLC. Noninvasive blood-based liquid biopsy tests for NSCLC may be useful for diagnosis and prognosis. MicroRNA (miRNA) and messenger RNA present in blood can serve as biomarkers for such tests. The present study identified 13 miRNAs that are underexpressed in the tissue and blood of NSCLC patients using Gene Expression Omnibus data. Following Kaplan Meier analysis, miR-140-3p, miR-29c, and miR-199a were selected as candidate biomarkers and demonstrated statistically significant prognostic power. An ROC analysis of miR-140-3p expression between NSCLC patients and controls had an area under curve value of 0.85. Functional enrichment analysis of the miRNA target genes revealed several overrepresented pathways relevant to cancer. Eight target genes were hub genes of the protein protein interaction network and possessed significant prognostic power. A combination of IL6, SNAI1, and CDK6 achieved a hazard ratio of 1.4 with p < 0.001. These biomarkers are especially valuable because they can be identified in blood and reflect the tumor state. Since all miRNAs were underexpressed in both tissue and blood, detecting expression of a biomarker miRNA in blood provides information on its expression in tissue as well. These miRNAs may be useful biomarkers for NSCLC prognostic and diagnostic tests and should be further studied.


title: Tele-Rehabilitation for People with Visual Disabilities During COVID-19 Pandemic: Lesson Learned

abstract:
BackgroundThe COVID-19 outbreak poses a global crisis in health care delivery system, including habilitation and rehabilitation services. In the present study, we shared our experiences on telerehabilitation services established primarily for students with visual disabilities (SwVD) amidst COVID-19 pandemic and its outputs.

MethodsFollowing the lockdown declared on March 23, 2020, the rehabilitative team of a tertiary eye center in north India received information that many VCS were stranded in schools for the blind in Delhi, and feeling with anxiety and panic in absence of teachers. Shortly, the room for vision rehabilitation clinic was set-up for tele-facilities. The intended services was explained while disseminating the mobile numbers. A semi-structured questionnaire consisting of closed and open-ended was developed to record COVID-19 knowledge and concerns. Inductive content analysis was used to report the qualitative information.

ResultsAs of June 30, 2020, a total of 492 clients contacted the team, with maximum from Delhi (41.5%), and predominantly males (78.8%). Around 80.3% of callers were VCS with age range of 11 to 30 years. The two most frequently encountered health needs were itching in eyes (36.1%) and headache (29%). Television news was the most used medium among callers to get COVID-19 information. Cough is a less frequently known mode of transmission (28%), similarly handwashing as a less known for prevention (17.2%). Eight concerns were recorded based on qualitative data analysis.

ConclusionTele-rehabilitation provides valuable insights and has the potential to address various concerns, uncertainty, anxiety, and fear among SVD during the pandemic.


title: Argon Laser Photocoagulation for Treatment of Presumed Trematode-induced Granulomatous Anterior Uveitis in Children

abstract:
Background/AimsTo assess the safety and efficacy of argon laser photocoagulation as a new modality for the treatment of presumed trematode-induced granulomatous anterior uveitis (PTGAU) in children.

MethodsForty-eight eyes of 48 children with PTGAU with pearl-like nodule(s) in the anterior chamber were included in this prospective non- randomised controlled clinical trial. Patients were divided into two groups: group A (23 eyes) was treated with one session of argon laser applied to the anterior chamber nodules, and group B (25 eyes) received medical treatment in the form of topical steroid and cycloplegic eye drops with trans-septal triamcinolone injection.All cases were followed up for 3 monthswith measurement of VA, assessment of anterior chamber reaction, and size of the pearl-like nodules.

ResultsIn group A, 22 eyes (95.65%) showed regression of the pearl- like nodules with resolution of the anterior chamber reaction (flare and cells) and improvement in visual acuity from 0.52{+/-}0.12 to 0.06 {+/-} 0.08logMAR (p value <0.001). Such improvement was maintained within the 3-month follow-up period. In group B, 23 eyes (92%) showed initial regression of the granulomas,whichwas maintained in only 14 eyes (56%),with 9 eyes experiencing recurrence after 3 months of follow-up.

ConclusionArgon laser photocoagulation is a safe and effective novel treatment for PTGAU with pearl-like nodules in the anterior chamber in children. Larger studies with longer follow-up periods are needed to confirm these results.

PRECISArgon laser photocoagulation is a novel non-invasive line of treatment that can be added to the armamentarium for presumed trematode-induced granulomatous anterior uveitis in children.