title: An optimised protocol for detection of SARS-COV-2 in stool

abstract:
AimSARS-CoV-2 has been detected in stool samples of COVID-19 patients, with potential implications for faecal-oral transmission. Compared to swab samples, the complexity of the stool matrix poses a challenge in the detection of the virus that has not yet been solved. The aim of this study was to establish a sensitive and reliable method for detecting SARS-CoV-2 in stool samples.

MethodsStool samples from individuals free of SARS-CoV-2 were homogenised in saline buffer and spiked with a known titre of inactivated virus ranging from 50 to 750 viral particles per 100 mg stool. Debris was removed via centrifugation and supernatants were concentrated by ultrafiltration. RNA was then extracted from the concentrated material using a commercial kit and SARS-CoV-2 was detected via real-time reverse-transcription polymerase chain reaction (RT-qPCR) using the CDC primers and probes.

ResultsThe RNA extraction procedure we used allowed the detection of SARS-CoV-2 via RT-qPCR in most of the stool samples tested. We could detect as few as 50 viral particles per 100 mg of stool. However, high variability was observed across samples at low viral titres. The primer set targeting the N1 region provided more reliable and precise results and for this primer set our method had a limit of detection of 1 viral particle per mg of stool.

ConclusionsHere we describe a sensitive method for detecting SARS-CoV-2 in stool samples. This method can be used to establish the persistence of SARS-CoV-2 in stool and ensure the safety of clinical practices such as faecal microbiota transplant (FMT).


title: Early immune pathology and persistent dysregulation characterise severe COVID-19

abstract: In a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust bystander CD8 T cell immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed bystander responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune defects may have clinical implications.

category: infectious diseases


title: Delayed bystander CD8 T cell activation, early immune pathology and persistent dysregulation characterise severe COVID-19


title: Modelling the effect of lockdown

abstract: 1This note models the effect of the lockdown during the first wave of COVID-19. We use SEIR type of model with a certain time lag between infection and becoming infectious. Firstly we compare the timing of the change of the coefficient of infection, growth rate of confirmed cases corresponds to the change of mobility index, and secondly we assume the change of the coefficient of infection, activity index {beta} (analogous to R0) and fit the parameter to reproduce the actual number of confirmed cases. Finally, we assume that the activity index {beta} is proportional to the square of the mobility and fit the parameters. The curves in various cuontries fits reasonably well in any cases, but estimating {beta} from various parameters (including temperature) remains as an important task.


title: Bacterial superinfection pneumonia in SARS-CoV-2 respiratory failure

abstract:
BackgroundSevere community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations.

MethodsWe obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care.

ResultsThe 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days.

ConclusionsWith use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported.

category: intensive care and critical care medicine


title: The impact of the first wave of COVID-19 on those with lifelong conditions: a case study of congenital heart disease

abstract:
ObjectivesGlobally, health care systems have been stretched to the limit by the COVID-19 pandemic. Significant changes have had to be made to the way in which non-COVID-19 related care has been delivered. Our objective was to understand, from the perspective of patients with a chronic, life-long condition (congenital heart disease, CHD) and their parents/carers, the impact of COVID-19 on the delivery of care, how changes were communicated and whether health care providers should do anything differently in a subsequent wave of COVID-19 infections.

Design and settingA series of asynchronous discussion forums set up and moderated by three patient charities via their Facebook pages.

ParticipantsPatients with CHD and parents/carers of patients with CHD.

Main outcome measuresQualitative responses to questions posted on the discussion forums.

ResultsThe forums ran over a 6-week period and involved 111 participants. Following thematic analysis of the transcripts, we identified three themes and ten subthemes related to individual condition-related factors, patient-related factors and health professional/centre factors that may have influenced how patients and parents/carers experienced changes to service delivery as a result of COVID-19.

ConclusionsOur findings, whilst collected in relation to patients with CHD, are not necessarily specific to this population and we believe reflect the experiences of many thousands of people with life-long conditions in the UK. Drawing on what participants told us in the discussion forums, we have developed recommendations related to communication, service delivery and support during the pandemic that would, we think, improve patients experience of care and, potentially, their outcomes. Although the data were collected specifically in relation to COVID-19, a number of these recommendations are relevant to the wider delivery of care to patients with chronic underlying health conditions and reflect principles of good communication and service delivery.

category: cardiovascular medicine


title: Scalable cardiovascular risk assessment using artificial intelligence-enabled event adjudication and widely available hematologic predictors.

abstract:
IntroductionResearchers routinely evaluate novel biomarkers for incorporation into clinical risk models. Although of potential benefit, such emerging markers, which are often costly or not yet commercially available, are unlikely to enable the scalable risk assessment needed for population health strategies. In contrast, the ideal inputs for population approaches would be those already widely available for most patients. We hypothesized that simple hematologic markers, available in an outpatient complete blood count without differential, would be useful to develop risk models for cardiovascular events.

MethodsUsing routine laboratory measurements as predictors and neural network-based automated event adjudication of 1,072,348 discharge summaries, we developed and validated models for prediction of heart attack, ischemic stroke, heart failure hospitalization, revascularization, and all-cause mortality.

ResultsModels with hematology indices alone showed Harrells concordance index ranging from 0.60-0.80 on an external validation set. Hematology indices added significantly in terms of discrimination and calibration performance compared to models using only demographic data and diagnostic codes for coronary artery disease, heart failure, and ischemic stroke, with the concordance index of resulting models in the range 0.75-0.85 on an external validation set. Predictive features varied by outcome, and included red blood cell, leukocyte, and platelet indices.

ConclusionWe conclude that low-cost ubiquitous inputs, if biologically informative, can provide population-level readouts of risk.


title: Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

abstract:
BackgroundCirculating lipid and lipoprotein levels have consistently been identified as risk factors for atherosclerotic cardiovascular disease (ASCVD), largely on the basis of studies focused on coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined. Here, we leveraged large scale genetic association data to identify genetic proxies for circulating lipoprotein-related traits, and employed Mendelian randomization analyses to investigate their effects on PAD risk.

MethodsGenome-wide association study summary statistics for PAD (Veterans Affairs Million Veteran Program, 31,307 cases) and CAD (CARDIoGRAMplusC4D, 60,801 cases) were used in the Mendelian Randomization Bayesian model averaging (MR-BMA) framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B lowering on PAD risk using gene regions that proxy potential lipid-lowering drug targets. Transcriptome-wide association studies were performed to identify genes relevant to circulating levels of prioritized lipoprotein subfractions.

ResultsApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability 0.86, p = 0.003) and CAD (marginal inclusion probability 0.92, p = 0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (OR 0.87 per 1 standard deviation decrease in ApoB, 95% CI 0.84 to 0.91, p = 9 x 10-10) and CAD (OR 0.66, 95% CI 0.63 to 0.69, p = 4 x 10-73), with a stronger predicted effect of ApoB-lowering on CAD (ratio of ORs 1.33, 95% CI 1.25 to 1.42, p = 9 x 10-19). Among ApoB-containing subfractions, extra-small VLDL particle concentration (XS.VLDL.P) was identified as the most likely subfraction associated with PAD risk (marginal inclusion probability 0.91, p = 2.3 x 10-4), while large LDL particle concentration (L.LDL.P) was the most likely subfraction associated with CAD risk (marginal inclusion probability 0.95, p = 0.011). Genes associated with XS.VLDL.P and L.LDL.P included canonical ApoB-pathway components, although gene-specific effects varied across the lipoprotein subfractions.

ConclusionApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, diverse effects of ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions on ASCVD, and distinct subfraction-associated genes suggest possible biologic differences in the role of lipoproteins in the pathogenesis of PAD and CAD.


title: REPEATABILITY OF A DIGITAL IMAGING TECHNOLOGY FOR DENTAL PLAQUE QUANTITATION (QRAYCAM PRO) IN CURRENT, FORMER AND NEVER SMOKERS STUDY PROTOCOL

abstract:
Although the detrimental health effects of smoking on human health are well described, the impact of smoking on dental plaque build-up lacks consistent records. This is because dental research on periodontal health has primarily relied on subjective indices with poor discriminatory power. Novel digital imaging techniques for the objective quantitation of dental plaque are now available. Quantitative Light-Induced Fluorescence (QLF) technology has been used in several studies for digital quantification and monitoring of dental plaque.

The objective of the study is to quantitate and compare short- and long-term repeatability of dental plaque among current, former, and never smokers by using a high resolution, auto-focus, hand-held QLF scanner (QRayCam Pro; Inspektor Research Systems BV, Amsterdam, NL).

Demonstration of good reproducibility of QLF technology with clear discrimination for dental plaque quantitation among current, former, and never smokers will pave the way to future application of this test for both medical and regulatory research applied not only to combustion-free tobacco products (e.g. e-cigarettes, heated tobacco products, oral tobacco/nicotine products, etc.) and smoking cessation medications, but also to consume care product for oral hygiene.

category: dentistry and oral medicine


title: The role for 11-oxygenated androgens in HPG-axis disturbances in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

abstract:
ContextHypothalamus-pituitary-gonadal (HPG)-axis disturbances are a common phenomenon in patients with classic congenital adrenal hyperplasia (CAH). 11-oxygenated androgens have been suggested to play a role in this context.

DesignCross-sectional single center study including 89 patients (N=42 men, N=55 women) with classic CAH.

Main Outcome MeasuresIndependent predictors for hypogonadism in men and secondary amenorrhea in women with CAH with a special focus on 11-ketotestosterone (11KT) and 11{beta}-hydroxyandrostenedione (11OHA4).

ResultsHypogonadotropic hypogonadism was present in 23% of men and 61% of those women currently not on contraceptives suffered from irregular menstrual cycles or amenorrhea. Testicular adrenal rest tumor (TART) was documented in 28% of men. While 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism, in stepwise logistic regression, the only significant independent predictor for hypogonadism were elevated 17-OHP levels (B = 0.006; p = 0.039). Although 11KT (5.2x) and 11OHA4 (3.7x) levels were also significantly higher in women with amenorrhea in comparison to those with a regular cycle, the only significant predictor for amenorrhea were elevated total testosterone levels (B = 1.806; p = 0.040). 11-oxygenated androgens were not different in those with TART and those without. Of note, there were no significant differences in 11OHA4 or 11KT between those with a regular cycle and those currently on hormonal contraceptives.

Conclusions11-oxygenated androgens do not seem to add additional information for explaining menstrual disturbances and hypogonadism in patients with CAH in comparison to established marker of disease control.

HighlightsO_LIThe 11-oxygenated androgens 11-ketotestosterone and 11{beta}-hydroxyandrostenedione are significantly elevated in men with CAH with hypogonadotropic hypogonadism and women with amenorrhea.
C_LIO_LIElevated 17-OHP levels in male patients and elevated testosterone levels in female patients are however the dominant predictor of HPG-axis disturbances.
C_LIO_LI11-oxygenated androgens are not predictive for testicular adrenal rest tumors in men with CAH
C_LIO_LI11-ketotestosterone and 11{beta}-hydroxyandrostenedione levels do not seem to be influenced by intake of oral contraceptives.
C_LI

category: endocrinology


title: Socioeconomic status determines COVID-19 incidence and related mortality in Santiago, Chile

abstract: The current coronavirus disease 2019 (COVID-19) pandemic has impacted dense urban populations particularly hard. Here, we provide an in-depth characterization of disease incidence and mortality patterns, and their dependence on demographic and socioeconomic strata in Santiago, a highly segregated city and the capital of Chile. We find that among all age groups, there is a strong association between socioeconomic status and both mortality -measured either by direct COVID-19 attributed deaths or excess deaths- and public health capacity. Specifically, we show that behavioral factors like human mobility, as well as health system factors such as testing volumes, testing delays, and test positivity rates are associated with disease outcomes. These robust patterns suggest multiple possibly interacting pathways that can explain the observed disease burden and mortality differentials: (i) in lower socioeconomic status municipalities, human mobility was not reduced as much as in more affluent municipalities; (ii) testing volumes in these locations were insufficient early in the pandemic and public health interventions were applied too late to be effective; (iii) test positivity and testing delays were much higher in less affluent municipalities, indicating an impaired capacity of the health-care system to contain the spread of the epidemic; and (iv) infection fatality rates appear much higher in the lower end of the socioeconomic spectrum. Together, these findings highlight the exacerbated consequences of health-care inequalities in a large city of the developing world, and provide practical methodological approaches useful for characterizing COVID-19 burden and mortality in other segregated urban centers.

category: epidemiology


title: A rising burden of adolescents obesity of age group 13-17 years among tribal population of central India: a community-based exploratory study

abstract:
BackgroundUpsurge of adolescent obesity is an upcoming national public health concern. Obese adolescents are at significant risk of becoming obese adults and its co-morbidities. This study estimates the prevalence of adolescent obesity and explore the potential determinants among young adults residing in tribal populated villages of Chhattisgarh, India.

MethodsA community-based nutritional survey was carried out among adolescent of the age group of 13-17 years.

ResultsAmong 1,296 participants, 23.4 % of young adults were either overweight or obese. Higher family earnings (Odds ratio [OR], 2.79, 95% confidence interval [CI] 1.29-6.38), Skipping breakfast (3.09, 1.11-8.30), Television viewing > 2 hours/ day (2.16, 1.3-6.2), Energy intake (2.98, 1.19-15.6), significantly increased the risk of adolescent obesity.

ConclusionPrevalence of adolescence obesity among the tribes is alarming and needs to be tackled with health system measures. Future research may require assessing the trajectory of obesity and related comorbidities in a tribal population.


title: New and Increasing Rates of Adverse Events Can be Found in Unstructured Text in Electronic Health Records using the Shakespeare Method

abstract:
BackgroundText in electronic health records (EHRs) and big data tools offer the opportunity for surveillance of adverse events (patient harm associated with medical care) (AEs) in the unstructured notes. Writers may explicitly state an apparent association between treatment and adverse outcome ("attributed") or state the simple treatment and outcome without an association ("unattributed"). We chose to study EHRs from 2006-2008 because of known heparin contamination during this timeframe. We hypothesized that the prevalence of adulterated heparin may have been widespread enough to manifest in EHRs through symptoms related to heparin adverse events, independent of clinicians documentation of attributed AEs.

ObjectiveUse the Shakespeare Method, a new unsupervised set of tools, to identify attributed and unattributed potential AEs using the unstructured text of EHRs.

MethodsWe studied 21,287 adult critical care admissions divided into three time periods. Comparisons of period 3 (7/2007 to 6/2008) to period 2 (7/2006 to 6/2007) were used to find admissions notes to review for new or increased clinical events by generating Latent Dirichlet Allocation topics among words in period 3 that were distinct from period 2. These results were further explored with frequency analyses of periods 1 (7/2001 to 6/2006) through 3.

ResultsTopics represented unattributed heparin AEs, other medical AEs, rare medical diagnoses, and other clinical events; all were verified with EHRs notes review and frequency analysis. The heparin AEs were not attributed in the notes, diagnosis codes, or procedure codes. Somewhat different from our hypothesis, heparin AEs increased in prevalence from 2001 through 2007, and decreased starting in 2008 (when heparin AEs were being published).

ConclusionsThe Shakespeare Method could be a useful supplement to AE reporting and surveillance of structured EHRs data. Future improvements should include automation of the manual review process.


title: Mitigation of COVID-19 using social distancing of the elderly in Brazil: The vertical quarantine effects in hospitalizations and deaths

abstract: Governments and epidemiologists have been proposing several mitigation strategies based on non-pharmaceutical interventions to reduce COVID-19 cases, hospitalizations, and deaths. In this work, we quantitatively compare the effects of elderly population (60 years old or more) selective isolation with a no isolation scenario using an adapted Susceptible - Exposed - Infectious - Removed (SEIR) compartmental model. For these simulated scenarios, we estimate the number of hospitalizations and deaths for different Brazilian cities, including those due to the lack of hospital beds. Our simulations show that, for Sao Paulo City, the isolation of the elderly would reduce demand for hospital beds by 9% and deaths by 16% compared to the no intervention scenario. Other Brazilian cities follow the same pattern, with median reductions of deaths ranging from 12-18%. We conclude that the social distancing of the elderly would be marginally effective and would not avoid health system collapse in several Brazilian cities.


title: Characteristics and outcomes of 118,155 COVID-19 individuals with a history of cancer in the United States and Spain

abstract:
PurposeWe aimed to describe the demographics, cancer subtypes, comorbidities and outcomes of patients with a history of cancer with COVID-19 from March to June 2020. Secondly, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza.

MethodsWe conducted a cohort study using eight routinely-collected healthcare databases from Spain and the US, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: i) diagnosed with COVID-19, ii) hospitalized with COVID-19, and iii) hospitalized with influenza in 2017-2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes.

ResultsWe included 118,155 patients with a cancer history in the COVID-19 diagnosed and 41,939 in the COVID-19 hospitalized cohorts. The most frequent cancer subtypes were prostate and breast cancer (range: 5-19% and 1-14% in the diagnosed cohort, respectively). Hematological malignancies were also frequent, with non-Hodgkins lymphoma being among the 5 most common cancer subtypes in the diagnosed cohort. Overall, patients were more frequently aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 8% to 14% and from 18% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n=242,960) had a similar distribution of cancer subtypes, sex, age and comorbidities but lower occurrence of adverse events.

ConclusionPatients with a history of cancer and COVID-19 have advanced age, multiple comorbidities, and a high occurence of COVID-19-related events. Additionaly, hematological malignancies were frequent in these patients.This observational study provides epidemiologic characteristics that can inform clinical care and future etiological studies.


title: A multivariable Mendelian randomisation study exploring the direct effects of nicotine on health compared with the other constituents of tobacco smoke: Implications for e-cigarette use

abstract:
ObjectivesGiven the popularity of e-cigarettes, and the lack of longitudinal evidence regarding their safety, novel methods are required to explore potential health effects resulting directly from nicotine use. The aim of this study was to explore the direct effects of nicotine compared with the other constituents of tobacco smoke on health outcomes associated with smoking.

DesignObservational study, using Mendelian randomisation and multivariable Mendelian randomisation analyses of summary data.

SettingSummary data from two previous genome-wide association studies, and summary data generated from UK Biobank, a prospective cohort study.

ParticipantsN = 337,010 individuals enrolled in UK Biobank, and a total of N = 341,882 individuals from two previous genome-wide association studies.

Main outcome measuresWe explored the effect of cotinine levels (as a proxy for nicotine exposure) and smoking heaviness (to capture cigarette smoke exposure) on body mass index (BMI), chronic obstructive pulmonary disease (COPD), forced vital capacity (FVC), forced expiratory volume (FEV-1), coronary heart disease (CHD), and heart rate.

ResultsIn multivariable Mendelian randomisation analyses, there was weak evidence to suggest that increased cotinine levels may cause increased heart rate among current smokers ({beta} = 0.50 bpm, 95% CI -0.06 to 1.05). There was stronger evidence to suggest that increased smoking heaviness causes decreased BMI among current smokers ({beta} = -1.81 kg/m2, 95% CI -2.64 to -0.98), as well as increased risk of COPD, decreased FEV-1 and FVC, and increased heart rate among ever and current smokers. We also found evidence to suggest that increased smoking heaviness causes increased risk of CHD among ever smokers.

ConclusionsOur combined findings are consistent with smoking-related health outcomes being caused by exposure to the non-nicotine components of tobacco smoke.


title: Prospective screening of liver fibrosis in a primary care cohort using systematic calculation of fib-4 in routine results

abstract:
Background & AimLiver fibrosis screening in primary care population is a major public health issue. The FIB-4 index is a simple non-invasive fibrosis test combining age, transaminases, platelets count, developed for the diagnosis of advanced fibrosis. The aim of our study was to evaluate the interest of liver fibrosis screening using systematic calculation of FIB-4 in routine blood analysis.

MethodsBetween December 2018 and May 2019, we conducted a prospective screening of liver fibrosis in 134 158 patients during a medical check-up including routine blood analysis. Among these patients, 29 707 had transaminases and platelets counts available and benefited from an automatic calculation of FIB-4. Results were obtained from 21 French clinical laboratories in the Bouches du Rhone region.

ResultsAmong the 29 707 patients, 2160 (7.3%) had significant fibrosis (FIB-4>2.67). Individual investigation of patients with FIB-4>2.67 allowed to screen 1267 (1267/2160: 59%) patients who were not managed for any liver disease.

ConclusionsThis work demonstrates the interest of FIB-4 for the screening of liver fibrosis in primary care population. Our study strongly supports this easy-to-implement strategy using a simple Fib-4 measure resulting from the use of available routine test results.

FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Clinical Registering NumberMR-0314071019 (INDS: French National Institute for Medical Data)

category: gastroenterology


title: A mixture of essential oils from three Cretan Aromatic Plants (thyme, Greek sage and Cretan dittany, CAPeo) inhibits SASR-CoV-2 proliferation: in vitro evidence and a Proof-of-Concept intervention study in mild ambulatory COVID-19-positive patients

abstract: The need for therapeutic regimens for the non-critically ill patients of the COVID-19 pandemic remains unmet. In this line, repurposing existing drugs, against known or predicted SARS-CoV-2 protein actions, has been advanced, while natural products have also been tested. Previous work has shown that a Cretan Aromatic Plant (Thymbra capitata (L.) Cav., Salvia fruticosa Mill. and Origanum dictamnus L.) essential oil mixture (CAPeo) has a remarkable in vitro antiviral activity against Influenza A & B and Rhinovirus 14 strains, decreasing the symptoms of upper respiratory tract infections, while proven safe in experimental animals and humans. Here, we tested CAPeo in VERO cells infected with SASR-CoV-2. We report that this mixture, at similar concentrations as those previously reported, exhibits a remarkable antiviral activity. Administration of 1 ml of a 1.5% CAPeo in olive oil, in a Proof-of-Concept intervention study in SARS-CoV-2-positive, exhibiting mild COVID-19 symptoms, humans resulted in a significant amelioration of general and local symptoms of the disease. We conclude that CAPeo may be a valuable addition for the prevention and/or treatment of mild COVID-19 ambulatory patients, pending a confirmation through a prospective randomized controlled trial in humans (NCT04705753).

category: pharmacology and therapeutics


title: Impact of COVID-19 on Migrants' Access to Primary Care:A National Qualitative Study

abstract:
BackgroundThe COVID-19 pandemic has led to considerable changes in the delivery of primary care in the UK, including rapid digitalisation, yet the extent to which these have impacted on marginalised migrant groups - already facing existing barriers to NHS care - is unknown. Understanding the perspectives and experiences of health professionals and migrants will support initiatives to deliver more effective health services, including delivery of the COVID-19 vaccine, to marginalised groups.

AimTo understand the impact of the COVID-19 pandemic on migrants and their access to primary healthcare, and implications for COVID-19 vaccine roll out.

Design and SettingPrimary care professionals, administrative staff, and migrants (foreign born; >18 years; <10 years in UK), were recruited in three phases using purposive, convenience and snowball sampling from urban, suburban and rural settings.

MethodsIn-depth semi-structured interviews were conducted by telephone. Data were analysed iteratively, informed by thematic analysis.

Results64 clinicians were recruited in Phase 1 (25 GPs, 15 nurses, 7 HCAs, 1 Pharmacists); Phase 2 comprised administrative staff (11 PMs and 5 receptionists); and in Phase 3 we recruited 17 migrants (88% asylum seekers; 65% female; mean time in UK 4 years). We found that digitalisation and virtual consultations (telephone, video, and online form-based) have amplified existing inequalities in access to healthcare for many migrants due to lack of digital literacy and access to technology, compounded by language barriers. Use of virtual consultations has resulted in concerns around building trust and the risk of missing safeguarding cues. Participants highlighted challenges around registering and accessing healthcare due to the physical closure of surgeries. Participants reported indirect discrimination, language and communication barriers, and lack of access to targeted and tailored COVID-19 information or interventions. In addition, migrants reported a range of specific beliefs around COVID-19 and on potential COVID-19 vaccines, from acceptance to mistrust, often influenced by misinformation. PCPs raised concerns that migrants may have increased risk factors for poor general health and to severe illness from COVID-19, in part due to their social and economic situation. Innovative opportunities were suggested to engage migrant groups through translated digital health advice using text templates and YouTube which merit further exploration.

ConclusionPandemic-related changes in primary care delivery may be here to stay, and some migrant groups are at risk of digital exclusion and may need targeted additional support to access services. As primary care networks operationalise the delivery of the COVID-19 vaccine, these findings provide critical information on specific strategies required to support migrant population to access primary care and overcome misinformation around COVID-19 and the COVID-19 vaccine.

How this fits inThe impact of pandemic-related shifts in primary care delivery on marginalised migrant groups, who may already face major disparities in accessing primary care, is poorly elucidated. We found that the rapid digitalisation of primary care services and physical closure of surgeries during the pandemic have amplified disparities in access to healthcare for specific migrant groups, with many lacking access to and capacity to use technology, compounded by language barriers. Migrants may be at increased risk of misinformation about COVID-19, which merits further consideration as COVID-19 vaccine roll out begins. Improved outreach to local migrant community organisations and places of worship, alongside co-designing with migrants more inclusive delivery approaches and creative integration of migrant ambassadors into information-sharing campaigns are needed. Primary care can maximise the opportunities of digitalisation for migrants through flexible engagement by multiple modalities (e.g. text, email, letter and YouTube videos) to provide targeted, translated advice and information, virtual group consultations for patients with a specific condition, and working with local leaders and NGOs to access and disseminate information through informal communication channels.

category: primary care research


title: Limited diagnostic accuracy of smartphone-based digital biomarkers for Parkinson's disease in a remotely-administered setting

abstract: Smartphone-based digital biomarker (DB) assessments provide objective measures of daily-life tasks and thus hold the promise to improve diagnosis and monitoring of Parkinsons disease (PD). To date, little is known about which tasks perform best for these purposes and how different confounds including comorbidities, age and sex affect their accuracy. Here we systematically assess the ability of common self-administered smartphone-based tasks to differentiate PD patients and healthy controls (HC) with and without accounting for the above confounds. Using a large cohort of PD patients and healthy volunteers acquired in the mPower study, we extracted about 700 features commonly reported in previous PD studies for gait, balance, voice and tapping tasks. We perform a series of experiments systematically assessing the effects of age, sex and comorbidities on the accuracy of the above tasks for differentiation of PD patients and HC using several machine learning algorithms. When accounting for age, sex and comorbidities, the highest balanced accuracy on hold-out data (73%) was achieved using random forest when combining all tasks followed by tapping using relevance vector machine (67%). Only moderate accuracies were achieved for other tasks (60% for balance, 56% for gait and 53% for voice data). Not accounting for the confounders consistently yielded higher accuracies of up to 77% when combining all tasks. Our results demonstrate the importance of controlling DB data for age and comorbidities.

category: psychiatry and clinical psychology


title: Smartphone-based digital biomarkers for Parkinson's disease in a remotely-administered setting


title: Neurocognitive measures of self-blame and risk prediction models of recurrence in major depressive disorder

abstract:
BackgroundOvergeneralised self-blaming emotions, such as self-disgust, are core symptoms of major depressive disorder (MDD) and prompt specific actions (i.e. "action tendencies"), which are more functionally relevant than the emotions themselves. We have recently shown, using a novel cognitive task, that when feeling self-blaming emotions, maladaptive action tendencies (feeling like "hiding" and like "creating a distance from oneself") and an overgeneralised perception of control are characteristic of MDD, even after remission of symptoms. Here, we probed the potential of this cognitive signature, and its combination with previously employed fMRI measures, to predict individual recurrence risk. For this purpose, we developed a user-friendly hybrid machine-/statistical-learning tool which we make freely available.

Methods52 medication-free remitted MDD patients, who had completed the Action Tendencies Task and our self-blame fMRI task at baseline, were followed up clinically over 14-months to determine recurrence. Prospective prediction models included baseline maladaptive self-blame-related action tendencies and anterior temporal fMRI connectivity patterns across a set of fronto-limbic a priori regions of interest, as well as established clinical and standard psychological predictors. Prediction models used elastic-net regularised logistic regression with nested 10-fold cross-validation.

ResultsCross-validated discrimination was highly promising (AuC[≥]0.86), and positive predictive values over 80% were achieved when including fMRI in multi-modal models, but only up to 71% (AuC[≤].74) when solely relying on cognitive and clinical measures.

ConclusionsThis shows the high potential of multi-modal signatures of self-blaming biases to predict recurrence risk at an individual level, and calls for external validation in an independent sample.


title: Physicians' Reactions to COVID-19: The Results of an International Internet Survey

abstract:
ObjectivesPhysicians across the world have been disproportionately affected by the COVID-19 pandemic. This study was designed and conducted to assess the emotional, cognitive, and behavioural reactions of physicians to the initial phase of the COVID-19 pandemic.

Materials and methodsAn online survey questionnaire using the google forms platform was constructed by the authors. The items in the questionnaire were based on clinical experience, relevant literature review and discussion with peers. A list of issues that were deemed as essential components of the experience of the pandemic relevant to physicians was arrived at. Thereafter these issues were operationalized into question form and hosted on the google forms platform. The link to this questionnaire was circulated by the authors among their peer groups in the month of April 2020.

ResultsWe received 295 responses and 3 were unusable. Most of the responses were from India, the United States of America, Australia, Canada and the United Kingdom. About 60% of the respondents identified themselves as frontline and had a decade of clinical experience. Most respondents reported being anxious due to the pandemic and also observed the same in their peers and families. A majority also observed changes in behaviour in self and others and advanced a variety of reasons and concerns. A sense of duty was the most commonly employed coping mechanism.

ConclusionPhysicians are not immune from information and misinformation, or cues in the environment. Behavioural choices are not always predicted by knowledge but by a combination of knowledge, emotional state, personality and environment. Healthcare settings need to be ready for emergencies and should focus on reducing uncertainty in physicians. These factors may also be gainfully used in the mental health promotion of physicians in COVID-19 care roles.


title: A rare missense variant in the ATP2C2 gene is associated with language impairment and related measures

abstract: At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N=360) compared to cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24,046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N=42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N=1825) (minimum p = 0.002 for nonword reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level.


title: Reference values and validation of the 1-min sit-to-stand test in healthy 5- to 16-year-old youth

abstract:
ObjectivesIt is essential to have simple, reliable and valid tests to measure childrens functional capacity in schools or medical practice. The 1-min sit-to-stand test (STS) is a quick fitness test requiring little equipment or space that is increasingly used in both healthy populations and those with chronic disease. We aimed to provide age and sex-specific reference values of STS in healthy children and adolescents and to evaluate its short-term reliability and construct validity.

Design, setting and participantsCross-sectional random sample from 6 public schools and 1 science fair in central Europe. Overall, 587 healthy participants aged 5-16 years were recruited and divided into age groups of 3 years each.

Outcomes1-minute STS. To evaluate short-term reliability, some children performed the STS twice. To evaluate construct validity, some children also performed a standing long jump (SLJ) and a maximal incremental exercise test.

ResultsData from 547 5-16 year old youth were finally included in the analyses. The median number of repetitions in 1 minute in males (females) ranged from 55 [95% CI 38 to 72] (53 [35 to 76]) in 14-16 year-olds to 59 [41 to 77] (60 [38 to 77]) in 8-10 year-olds. Children who repeated STS showed a learning effect of on average 4.8 repetitions more than the first test (95% limits of agreement -6.7 to 16.4). Moderate correlations were observed between the STS and the SLJ (r = 0.48) and the maximal exercise test (r = 0.43).

ConclusionsThe reported STS reference values can be used to interpret STS test performance in children and adolescents. The STS appears to have good test-retest reliability, but a learning effect of about 10%. The association of STS with other measures of physical fitness should be further explored in a larger study and technical standards for its conduct are needed.

Strengths and Limitations of this StudyO_LILarge sample size (N = 547)
C_LIO_LIReference values according to sex and age group (5-7, 8-10, 11-13 and 14-16)
C_LIO_LIEvaluation of test-retest reliability and construct validity
C_LIO_LIConvenience not population-based sample
C_LIO_LINot all outcomes have been measured on each participant
C_LI

category: public and global health


title: Reference values and validation of the 1-min sit-to-stand test in healthy 5- to 16-year-old youth: a cross-sectional study


title: A systematic review of the concept 'male involvement in maternal health' by natural language processing and descriptive analysis.

abstract:
IntroductionExperts agree that male involvement (MI) in maternal health (MH) is a multifaceted concept, but a universal definition is lacking, hampering comparison of findings and interpretation of the literature. This systematic review aims to examine the conceptualization of MI in MH globally and critically review commonly used indicators.

MethodsPubMed, Embase, Scopus, Web of Science and CINAHL databases were searched for quantitative literature (between the years 2000 and 2020) containing indicators or variables representing MI in MH, which was defined as the involvement, participation, engagement or support of men in all activities related to maternal health.

ResultsAfter full text review, 282 studies were included in the review. Most studies were conducted in Africa (43%), followed by North America (23%), Asia (15%) and Europe (12%). Descriptive analysis and text mining analysis showed MI in MH has been conceptualised by focusing on two main aspects: psychosocial support and instrumental support for maternal health care utilisation. Differences in measurement and topics were noted according to continent with Africa focusing on HIV prevention, North America and Europe on psychosocial health and stress, and Asia on nutrition. One third of studies used one single indicator for assessing MI in MH and no common pattern of indicators could be identified. Antenatal care attendance was the most used indicator (40%) followed by financial support (17%), presence during childbirth (17%) and HIV testing (14%). Majority of studies did not collect data from men directly.

DiscussionResearchers often focus on a single aspect of MI in MH, resulting in the usage of a narrow and simplified set of indicators. Aspects such as communication between the couple, shared decision making, participation in household tasks and the subjective feeling of being supported have received little attention. We believe a more multidimensional approach can broaden the potential of MI programs. Further research, involving experts and pilot testing, is recommended to develop consensus regarding a more robust and comprehensive set of valid and feasible indicators for assessing MI in MH.

Summary BoxO_ST_ABSWhat is already known?C_ST_ABSO_LIIncreasing male involvement (MI) in maternal health (MH) is considered to be a promising and effective intervention for improving maternal and newborn health outcomes.
C_LIO_LIMale involvement is described as a multifaceted concept in the quantitative literature, although a universal definition or evidence-based set of indicators is lacking.
C_LIO_LIIn qualitative literature male involvement is often described by men and women from different settings as the male partner "being there", meaning giving physical and emotional support.
C_LI

What are the new findings?O_LIConceptualisation of MI in MH in the literature is done by focusing on either psychosocial aspects of MI in MH or on maternal health care utilisation. The attention given to one or both aspects resulted in the use of different indicators and depended on the geographical context of the study.
C_LIO_LIOverall male involvement was most often measured by instrumental actions such as presence at health services, financial support or providing transport. Other aspects of male involvement, such as communication, emotional support and shared decision making have received little attention, especially in low- and middle-income countries.
C_LI

What do the new findings imply?O_LIMore research into other aspects of male involvement (such as the subjective feeling of perceived support and decision making) can broaden the potential of male involvement programs and also reveal and minimize potential negative side-effects of male involvement interventions.
C_LIO_LIA standardized definition and set of indicators, exploring different aspects of male involvement, could facilitate researchers to generate more robust findings, strengthening the existing evidence on male involvement programmes.
C_LI


title: A national survey of potential acceptance of COVID-19 vaccines in healthcare workers in Egypt

abstract:
BackgroundSince the start of COVID-19 outbreak investigators are competing to develop and exam vaccines against COVID-19. It would be valuable to protect the population especially health care employees from COVID-19 infection. The success of COVID-19 vaccination programs will rely heavily on public willingness to accept the vaccine.

AimsThis study aimed to describe the existing COVID-19 vaccine approval landscape among the health care providers and to identify the most probable cause of agreement or disagreement of COVID-19 vaccine.

MethodsA cross-sectional online survey was done.

ResultsThe present study included 496 health care employees, 55% were at age group from 18-45 years old. History of chronic diseases was recorded in 40.4%, and definite history of drug/food allergy in 10.1%. Only 13.5% totally agree to receive the vaccine, 32.4% somewhat agree and 40.9% disagreed to take the vaccine. Causes of disagreement were none safety, fear of genetic mutation and recent techniques and believe that the vaccine is not effective (57%, 20.2%, 17.7% and 16.6% respectively). The most trusted vaccine was the mRNA based vaccine. The age of health care employees and the presence of comorbidities or chronic diseases were the main factors related to COVID-19 acceptance (P<0.001 and 0.02 respectively).

ConclusionVaccine hesitancy is not uncommon in healthcare employees in Egypt and this may be an alarming barrier of vaccine acceptance in the rest of population. There is an urgent need to start campaigns to increase the awareness of the vaccine importance.


title: Neural Network-derived perfusion maps: a Model-free approach to computed tomography perfusion in patients with acute ischemic stroke

abstract:
PurposeIn this study we investigate whether a Convolutional Neural Network (CNN) can generate clinically relevant parametric maps from CT perfusion data in a clinical setting of patients with acute ischemic stroke.

MethodsTraining of the CNN was done on a subset of 100 perfusion data, while 15 samples were used as validation. All the data used for the training/validation of the network and to generate ground truth (GT) maps, using a state-of-the-art deconvolution-algorithm, were previously pre-processed using a standard pipeline. Validation was carried out through manual segmentation of infarct core and penumbra on both CNN-derived maps and GT maps. Concordance among segmented lesions was assessed using the Dice and the Pearson correlation coefficients across lesion volumes.

ResultsMean Dice scores from two different raters and the GT maps were > 0.70 (good-matching). Inter-rater concordance was also high and strong correlation was found between lesion volumes of CNN maps and GT maps (0.99, 0.98).

ConclusionOur CNN-based approach generated clinically relevant perfusion maps that are comparable to state-of-the-art perfusion analysis methods based on deconvolution of the data. Moreover, the proposed technique requires less information to estimate the ischemic core and thus might allow the development of novel perfusion protocols with lower radiation dose.

category: radiology and imaging


title: Validation of the German version of the Life-Space Assessment LSA-D

abstract:
ObjectivesTo develop a German version of the original University of Alabama at Birmingham (UAB) Study of Aging Life-Space Assessment (LSA-D) for measurement of community mobility in older adults within the past 4 weeks and to evaluate its psychometric properties for urban and rural populations of older adults.

DesignCross-sectional validation study.

SettingTwo study centres in urban and rural German outpatient hospital settings.

ParticipantsIn total N=83 community-dwelling older adults were recruited (n=40 from urban and n=43 from rural areas; mean age was 78.5 (SD=5.4); 49% male).

Primary and secondary outcome measuresThe final version of the translated LSA-D was related with questions about activities and instrumental activities of daily living (ADL/iADL; primary hypothesis), Timed-Up&Go-Test (TUG), self-rated health, balance confidence and history of falls, use of transportation, and sociodemographic factors to obtain construct validity. Secondary outcome measures of health included handgrip strength, screening of cognitive function and comorbidities. To assess conduct construct validity, correlations between LSA-D and all health measures were examined for total sample, urban and rural subsamples using bivariate regression and multiple adjusted regression models. Posthoc analyses included different LSA-D scoring methods for each region. All parameters were estimated using non-parametric bootstrapping procedure.

ResultsIn the multiple adjusted model for the total sample, number of ADL/iADL limitations ({beta}=-.26; 95%CI=-.42/-.08), TUG ({beta}=-.37; 95%CI=-.68/-.14), living in shared living arrangements ({beta}=.22; 95%CI=.01/.44) and history of falls in the past 6 months ({beta}=-.22; 95%CI=-.41/-.05) showed significant associations with the LSA-D composite score, while living in urban area ({beta}=-.19; 95%CI=-.42/.03) and male gender ({beta}=.15; 95%CI=-.04/.35) were not significant.

ConclusionThe LSA-D is a valid tool for measuring life-space mobility in German community-dwelling older adults within the past four weeks in ambulant urban and rural settings.

Trial registration numberDRKS00019023

Strengths and limitations of this studyO_LIGerman validation of the original UAB Life-Space Assessment (LSA-D) for community dwelling older adults in urban and rural settings
C_LIO_LIUsing bootstrapped bivariate and multiple adjusted regression models to attain construct validity of the LSA-D
C_LIO_LIRecruitment had to be stopped shortly before reaching the calculated sample size due to the decision to restrict in face-to-face research to contain the outbreak of the Covid-19 pandemic in March 2020
C_LI

category: rehabilitation medicine and physical therapy


title: Towards a platform for robot-assisted minimally-supervised therapy of hand function: design and pilot usability evaluation

abstract:
BackgroundRobot-assisted therapy can increase therapy dose after stroke, which is often considered insufficient in clinical practice and after discharge, especially with respect to hand function. Thus far, there has been a focus on rather complex systems that require therapist supervision. To better exploit the potential of robot-assisted therapy, we propose a platform designed for minimal therapist supervision, and present the preliminary evaluation of its immediate usability, one of the main and frequently neglected challenges for real-world application. Such an approach could help increase therapy dose by allowing the training of multiple patients in parallel by a single therapist, as well as independent training in the clinic or at home.

MethodsWe implemented design changes on a hand rehabilitation robot, considering aspects relevant to enabling minimally-supervised therapy, such as new physical/graphical user interfaces and two functional therapy exercises to train hand motor coordination, somatosensation and memory. Ten participants with chronic stroke assessed the usability of the platform and reported the perceived workload during a single therapy session with minimal supervision. The ability to independently use the platform was evaluated with a checklist.

ResultsParticipants were able to independently perform the therapy session after a short familiarization period, requiring assistance in only 13.46(7.69-19.23)% of the tasks. They assigned good-to-excellent scores on the SUS to the user-interface and the exercises (85.00(75.63-86.88) and 73.75(63.13-83.75) out of 100, respectively). Nine participants stated that they would use the platform frequently. Perceived workloads lay within desired workload bands. Object grasping with simultaneous control of forearm pronosupination and stiffness discrimination were identified as the most difficult tasks.

DiscussionOur findings demonstrate that a robot-assisted therapy device can be rendered safely and intuitively usable upon first exposure with minimal supervision through compliance with usability and perceived workload requirements. The preliminary usability evaluation identified usability challenges that should be solved to allow real-world minimally-supervised use. Such a platformcould complement conventional therapy, allowing to provide increased dose with the available resources, and establish a continuum of care that progressively increases therapy lead of the patient from the clinic to the home.


title: Arm-hand boost therapy during inpatient stroke rehabilitation: a pilot randomized controlled trial

abstract:
ObjectiveIt was the aim to assess feasibility, safety and potential efficacy of a new intensive, focused arm-hand BOOST program and to investigate whether there is a difference between early versus late delivery of the program in the sub-acute phase post stroke.

MethodsIn this pilot RCT, patients with stroke were randomized to the immediate group (IG): 4 weeks (4w) BOOST +4w CONTROL or the delayed group (DG): 4w CONTROL +4w BOOST, on top of their usual inpatient care program. The focused arm-hand BOOST program (1 hour/day, 5x/week, 4 weeks) consisted of group exercises with focus on scapula-setting, core-stability, manipulation and complex ADL tasks. Additionally, one hour per week the Armeo(R)Power (Hocoma AG, Switzerland) was used. The CONTROL intervention comprised a dose-matched program (24 one-hour sessions in 4w) of lower limb strengthening exercises and general reconditioning. At baseline, after 4 and 8 weeks of training, the Fugl-Meyer assessment upper extremity (FMA-UE), action research arm test (ARAT) and stroke upper limb capacity scale (SULCS) were administered.

ResultsEighteen participants (IG: n=10, DG: n=8) were included, with a median (IQR) time post stroke of 8.6 weeks (5-12). No adverse events were experienced. After 4 weeks of training, significant between-group differences were found for FMA-UE (p=0.003) and SULCS (p=0.033) and a trend for ARAT (p=0.075) with median (IQR) change scores for the IG of 9 (7-16), 2 (1-3) and 12.5 (1-18) respectively, and for the DG of 0.5 (-3-3), 1 (0-1) and 1.5 (-1-9), respectively. In the IG, 80% of patients improved beyond the minimal clinical important difference of FMA-UE after 4 weeks, compared to none of the DG patients. Between 4 and 8 weeks of training, patients in the DG tend to show larger improvements when compared to the IG, however, between-group comparisons did not reach significance.

ConclusionsResults of this pilot RCT showed that an intensive, specific arm-hand BOOST program, on top of usual care, is feasible and safe in the sub-acute phase post stroke and suggests positive, clinical meaningful effects on upper limb function, especially when delivered in the early sub-acute phase post stroke.

Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT04584177


title: Changes in the Health of Adolescent Athletes: A Comparison of Health Measures Collected Before and During the CoVID-19 Pandemic

abstract:
ContextIn the spring of 2020, schools closed to in-person teaching and sports were cancelled to control the transmission of CoVID-19. The changes that took place to the physical and mental health among young athletes during this time remain unknown, however.

ObjectiveIdentify changes in the health (mental health, physical activity and quality of life) of athletes that occurred during the CoVID-19 pandemic.

DesignCross sectional study.

SettingSample recruited via social media.

Patients or Other Participants3243 Wisconsin adolescent athletes (age=16.2{+/-}1.2 yrs., female=58% female) completed an online survey in May 2020 (DuringCoVID-19). Health measures for this cohort were compared with previously reported data for Wisconsin adolescent athletes (n=5231, age=15.7{+/-}1.2, 47% female) collected in 2016-2018 (PreCoVID-19).

Main Outcome Measure(s)Demographic information included: sex, grade and sports played. Health assessments included the Patient Health Questionnaire-9 Item (PHQ-9) to identify depression symptoms, the Pediatric Functional Activity Brief Scale (PFABS) for physical activity, and the Pediatric Quality of Life Inventory 4.0 (PedsQL) for health related quality of life (HRQoL). Univariable comparisons of these variables between groups were made via t-tests or chi-square tests. Means and 95% confidence intervals (CI) for each group were estimated by survey weighted ANOVA models.

RESULTSCompared to PreCoVID-19, a larger proportion of the During-CoVID-19 participants reported rates of moderate to severe levels of depression (9.7% vs 32.9%, p<0.001). During-CoVID-19 participants reported 50% lower (worse) PFABS scores (mean:12.2 [95%CI: 11.9, 12.5] vs 24.7 [24.5, 24.9] p<0.001) and lower (worse) PedsQL total scores compared to the PreCoVID-19 participants (78.4 [78.0, 78.8] vs. 90.9 [90.5, 91.3] p<0.001).

CONCLUSIONSDuring the CoVID-19 pandemic, adolescent athletes reported increased symptoms of depression, decreased physical activity and decreased quality of life compared to adolescent athletes in previous years.

Key pointsO_LIAdolescent athletes during CoVID-19 were three times more likely to report moderate to severe symptoms of depression compared to data collected prior to CoVID-19.
C_LIO_LIAdolescent athletes during CoVID-19 reported significantly lower physical activity and quality of life scores compared to high school athletes prior to the CoVID-19 pandemic
C_LIO_LIPost CoVID-19 policies should be implemented to improve the health of adolescent athletes in the US.
C_LI

category: sports medicine


title: Regional Variation in COVID-19 Scarce Resource Allocation Protocols

abstract:
BackgroundScarce resource allocation policies vary across the United States. Little is known about regional variation in hospital-level resource allocation protocols and variation in their application.

ObjectiveTo evaluate how scarce resource allocation policies throughout the Chicagoland area vary and whether there are differences in policy application within and amongst hospitals.

DesignTwo cross-sectional surveys.

SettingChicagoland hospitals.

ParticipantsRepresentatives from Chicagoland hospitals and triage officers at these hospitals.

MeasurementsSurvey responses and categorical variables are described by frequency of occurrence. Intra- and interhospital variation in ranking of hypothetical patients was assessed using Kappa coefficients.

ResultsEight Chicago area hospitals responded to the survey assessing scarce resource allocation protocols. For hospitals willing to describe their specific ventilator allocation protocol (n=7), the initial scoring system varied with most utilizing the sequential organ failure assessment (SOFA) score (86%) and medical comorbidities (57%). A majority gave priority to pre-defined groups in their initial scoring system (86%), all discussed withdrawal of mechanical ventilation for adult patients (100%), and a minority had exclusion criteria (43%). Forty-nine triage officers from nine hospitals responded to the second survey. Triage officer rankings of hypothetical patients had slight agreement amongst all hospitals (Kappa 0.158) and fair agreement within two hospitals with the most respondents (Kappa 0.21 and 0.25). Almost half of triage officer respondents reported using tiebreakers to rank patients (N=23/49, 47%).

ConclusionAlthough most Chicago area hospitals surveyed created guidelines for resource allocation during the COVID-19 pandemic, these guidelines and application of these protocols by triage officers varied significantly.

Funding SourceNone.

category: medical ethics


title: Evaluation of Urine SARS-COV-2 RT-PCR as a predictor of Acute Kidney Injury and disease severity in critical COVID-19 patients

abstract: The novel coronavirus disease (COVID-19) is an emerging infectious disease caused by SARS-CoV-2, which began as an outbreak in Wuhan, China and spread rapidly throughout the globe. Although the majority of infections are mild, severe and critical COVID-19 patients face deterioration of respiratory function, and may also present extrapulmonary manifestations, mostly affecting the kidney, digestive tract, heart and nervous system. Here, we prospectively evaluated the presence of SARS-CoV-2 genetic material by RT-PCR in urine samples obtained from critical care COVID-19 patients. In 51 patients included, we found higher serum creatinine levels, a longer hospital stay and a more frequent dialysis need in urine-positive patients. These findings could suggest that, in predisposed patients, a direct viral cytopathic effect may contribute to a more severe disease phenotype.

category: nephrology


title: Trans Fats Consumption and Body Mass Index in Cross Sectional Analysis

abstract:
BackgroundTrans fats remain on the market in parts of the world. Emerging evidence suggests that factors beyond calorie balance may affect fat deposition and body mass index (BMI). Trans fats are prooxidant, proinflammatory, and have shown adverse metabolic effects and increased fat deposition in animals.

ObjectiveTo assess the relation of dietary trans fatty acid consumption (dTFA) to BMI in humans.

DesignCross-sectional analysis of baseline data from a broadly-sampling study.

SettingCommunity-dwelling adults from Southern California.

Participants1018 adult men and women aged 20-85 without known diabetes, CVD, or cancer, with screening LDL 115-190mg/dL. Women of procreative potential and children were excluded.

MeasurementsHeight, weight, and waist circumference were measured, and BMI calculated (kg/m2). The Fred Hutchinson Food Frequency Questionnaire provided data on dTFA (grams/day) and calories consumed. Additional covariates included activity, chocolate consumption frequency, and mood. Regression assessed the relation of BMI (outcome) to dTFA, unadjusted and in models adjusting for age and sex, and adding calories and activity, chocolate consumption frequency, and mood.

ResultsHigher dTFA was associated with higher BMI and waist circumference. The coefficient was strengthened, not attenuated, with adjustment for calories and activity, and other assessed covariates. In the fully adjusted model, each gram/day of dTFAs was associated with 0.44 higher BMI (SE=0.12;95%CI=0.21,0.67); P<0.001 and 1cm greater waist circumference (SE=0.35;95%CI=0.37,1.7); P=0.003.

ConclusionFindings relating greater dTFA to higher BMI in humans comport with experimental data in animals, extend adverse metabolic associations of dTFA, and buttress evidence that foods composition, as well as caloric number, bears on BMI. Findings are cross-sectional but strength and consistency of association, biological gradient, and biological plausibility add "weight" to the prospect of a causal connection.

Strengths and limitations of this studyO_LIFindings are cross-sectional and rely on dietary recall.
C_LIO_LIObservational studies carry risks of bias and confounding; but randomized trials are problematic where products with potential for harm are under evaluation.
C_LIO_LIAlthough some nations have implemented plans to remove or reduce dTFAs from the food supply, dTFA remain on the market in other nations, rendering findings of continued interest.
C_LIO_LIThe association of increased dTFA with increased BMI and waist circumference fits with other documented adverse metabolic associations of dTFA and is buttressed by experimental documentation that dTFA (without excess calories) increases visceral fat in animals, supporting prospects for causality in the observed association.
C_LI

category: nutrition


title: Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer

abstract: The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. Here, we follow 3 patients with resectable disease and 4 patients with advanced unresectable disease, using exome sequencing of resected tissues and plasma samples (n=20) collected over a [~]2-year period from diagnosis through treatment to death or last follow-up. This includes 4 patients with [≥]3 serial follow-up samples, of whom 2 are exceptionally long survivors (>5 years). Plasma from 3 chronic pancreatitis cases and 3 healthy controls were used as comparison for analysis of ctDNA mutations. We show that somatic mutation profiles in ctDNA are representative of matched tumour genomes. Furthermore, we detect and track ctDNA mutations within core PDAC driver genes, including KRAS, NRAS, HRAS, TP53, SMAD4 and CDKN2A, in addition to patient-specific variants within alternative cancer drivers (TP53, MTOR, ERBB2, EGFR, PBRM1, RNF43). Multiple trackable ([≥] 2 plasma) ctDNA alterations with potential for therapeutic actionability in PDAC are also identified. These include variants predictive of treatment response to platinum chemotherapy and/or PARP inhibition and a unique chromosome 17 kataegis locus co-localising with ERBB2 driver variants and hypermutation signatures in one long-surviving patient. Finally, we demonstrate that exome profiling can facilitate the assessment of clonality within ctDNA mutations, for the determination of total ctDNA burden alongside temporal evolutionary relationships. These findings provide proof-of-concept for the use of whole exome sequencing of serial plasma samples to characterise ctDNA load and mutational profiles in patients with PDAC.

category: oncology


title: Heart rate and heart rate variability in patients with chronic inflammatory joint disease: The role of pain duration and the insular cortex

abstract: Chronic inflammatory joint diseases (CIJD) have been linked to increased cardiovascular morbidity and mortality. A decisive reason could be a dysregulation of the autonomic nervous system (ANS), which is responsible for the control of cardio-vascular function. So far, the cause of changes in ANS functions remains elusive. In this study, we investigate the role of chronic pain and the insular cortex in autonomic control of cardiac functioning in patients with CIJD. We studied the sympathetic and parasympathetic branch of the ANS through the assessment of heart rate and heart rate variability (HRV) at rest and under cognitive stimulation. Furthermore, we investigated insular cortex volume by performing surface-based brain morphometry with FreeSurfer. For this study, 22 individual age- and sex-matched pairs for the magnetic resonance imaging analyses and 14 for the HRV analyses were recruited. Pain duration was negatively correlated with the resting heart rate in patients with chronic inflammatory joint diseases (n = 19). In a multiple linear regression model including only CIJD patients with HR at rest as a dependent variable, we found a significant positive relationship between HR at rest and the volume of the left insular cortex and a significant negative relationship between HR at rest and the volume of the right insular cortex. However, we found no significant differences in HRV parameters or insular cortex volumes between both groups. In this study we provide evidence to suggest insular cortex involvement in the process of ANS changes due to chronic pain in CIJD patients.

category: pain medicine


title: Application of Optical Genome Mapping For Comprehensive Assessment of Chromosomal Structural Variants for Clinical Evaluation of Myelodysplastic Syndromes

abstract: Structural chromosomal variants [copy number variants (CNVs): losses/ gains and structural variants (SVs): inversions, balanced and unbalanced fusions/translocations] are important for diagnosis and risk-stratification of myelodysplastic syndromes (MDS). Optical genome mapping (OGM) is a novel single-platform cytogenomic technique that enables high-throughput, accurate and genome-wide detection of all types of clinically important chromosomal variants (CNVs and SVs) at a high resolution, hence superior to current standard-of-care cytogenetic techniques that include conventional karyotyping, FISH and chromosomal microarrays. In this proof-of-principle study, we evaluated the performance of OGM in a series of 12 previously well-characterized MDS cases using clinical BM samples. OGM successfully facilitated detection and detailed characterization of twenty-six of the 28 clonal chromosomal variants (concordance rate: 93% with conventional karyotyping; 100% with chromosomal microarray). These included copy number gains/losses, inversions, inter and intra-chromosomal translocations, dicentric and complex derivative chromosomes; the degree of complexity in latter aberrations was not apparent using standard technologies. The 2 missed aberrations were from a single patient within a composite karyotype, below the limit of detection. Further, OGM uncovered 6 additional clinically relevant sub-microscopic aberrations in 4 (33%) patients that were cryptic by standard-of-care technologies, all of which were subsequently confirmed by alternate platforms. OGM permitted precise gene-level mapping of clinically informative genes such as TP53, TET2 and KMT2A, voiding the need for multiple confirmatory assays. OGM is a potent single-platform assay for high-throughput and accurate identification of clinically important chromosomal variants.

category: genetic and genomic medicine


title: Automated Bias Reduction in Deep Learning Based Melanoma Diagnosis using a Semi-Supervised Algorithm

abstract: Melanoma is one of the most fatal forms of skin cancer and is often very difficult to differentiate from other benign skin lesions. However, if detected at its early stages, it can almost always be cured. Researchers and data scientists have studied this disease in-depth with the help of large datasets containing high-quality dermascopic images, such as those assembled by the International Skin Imaging Collaboration (ISIC). However, these images often lack diversity and over-represent patients with very common skin features such as light skin and having no visible body hair. In this study, we introduce a novel architecture called LatentNet which automatically detects over-represented features and reduces their weights during training. We tested our model on four distinct categories - three skin color levels corresponding to Type I, II, and III on the Fitzpatrick Scale, and images containing visible hair. We then compared the accuracy against the conventional Deep Convolutional Neural Network (DCNN) model trained using the standard approach (i.e. without detecting over-represented features) and containing the same hyper-parameters as the LatentNet. LatentNet showed significant performance improvement over the standard DCNN model with accuracy of 89.52%, 79.05%, 64.31%, and 64.35% compared to the DCNN accuracy of 90.41%, 70.82%, 45.28%, 56.52% in the corresponding categories, respectively. Differences in the average performance between the models were statistically significant (p < 0.05), suggesting that the proposed model successfully reduced bias amongst the tested categories. LatentNet is the first architecture that addresses racial bias (and other sources of bias) in deep-learning based Melanoma diagnosis.

category: health informatics


title: Using ICD-10-based Social Determinants of Health Categories to Assess Patients Risk for Acute Care Utilization

abstract:
BackgroundThere has been an increasing recognition of the influence of social, behavioral, economic, and environmental factors on overall patient health. The purpose of this project was to leverage the ICD-10 codes to identify and link social determinants of health (SDoH) to patients with a high probability of utilizing acute care services and to determine if social service intervention reduced care utilization.

MethodsWe analyzed retrospective data for active patients at a Department of Veterans Affairs Medical Center (VAMC) from 2015-2017. Eleven categories of SDoH were developed based on existing literature of the social determinants; the relevant ICD-10 codes were divided among these categories. Emergency Room (ER) visits, hospital admissions, and social work visits were determined for each patient in the cohort.

ResultsIn a cohort of 44,401 patients, the presence of ICD-10 codes within the EHR in the 11 SDoH categories was positively correlated with increased acute care utilization. Veterans with at least one SDoH risk factor were 71% (95%CI: 68% - 75%) more likely to use the ED and 71% (95%CI: 65%-77%) more likely to be admitted to the hospital. Utilization decreased with social service interventions.

ConclusionThis project demonstrates a potentially meaningful method to capture patient social risk profiles through existing EHR data in the form of ICD-10 codes, which can be used to identify the highest risk patients for intervention with the understanding that not all SDoH codes are uniformly used and some SDoHs may not be captured.


title: Real-Time Electronic Health Record Mortality Prediction During the COVID-19 Pandemic: A Prospective Cohort Study

abstract:
BackgroundThe SARS-CoV-2 virus has infected millions of people, overwhelming critical care resources in some regions. Many plans for rationing critical care resources during crises are based on the Sequential Organ Failure Assessment (SOFA) score. The COVID-19 pandemic created an emergent need to develop and validate a novel electronic health record (EHR)-computable tool to predict mortality.

Research QuestionsTo rapidly develop, validate, and implement a novel real-time mortality score for the COVID-19 pandemic that improves upon SOFA.

Study Design and MethodsWe conducted a prospective cohort study of a regional health system with 12 hospitals in Colorado between March 2020 and July 2020. All patients >14 years old hospitalized during the study period without a do not resuscitate order were included. Patients were stratified by the diagnosis of COVID-19. From this cohort, we developed and validated a model using stacked generalization to predict mortality using data widely available in the EHR by combining five previously validated scores and additional novel variables reported to be associated with COVID-19-specific mortality. We compared the area under the receiver operator curve (AUROC) for the new model to the SOFA score and the Charlson Comorbidity Index.

ResultsWe prospectively analyzed 27,296 encounters, of which 1,358 (5.0%) were positive for SARS-CoV-2, 4,494 (16.5%) included intensive care unit (ICU)-level care, 1,480 (5.4%) included invasive mechanical ventilation, and 717 (2.6%) ended in death. The Charlson Comorbidity Index and SOFA scores predicted overall mortality with an AUROC of 0.72 and 0.90, respectively. Our novel score predicted overall mortality with AUROC 0.94. In the subset of patients with COVID-19, we predicted mortality with AUROC 0.90, whereas SOFA had AUROC of 0.85.

InterpretationWe developed and validated an accurate, in-hospital mortality prediction score in a live EHR for automatic and continuous calculation using a novel model, that improved upon SOFA.

Take Home PointsO_ST_ABSStudy QuestionC_ST_ABSCan we improve upon the SOFA score for real-time mortality prediction during the COVID-19 pandemic by leveraging electronic health record (EHR) data?

ResultsWe rapidly developed and implemented a novel yet SOFA-anchored mortality model across 12 hospitals and conducted a prospective cohort study of 27,296 adult hospitalizations, 1,358 (5.0%) of which were positive for SARS-CoV-2. The Charlson Comorbidity Index and SOFA scores predicted all-cause mortality with AUROCs of 0.72 and 0.90, respectively. Our novel score predicted mortality with AUROC 0.94.

InterpretationA novel EHR-based mortality score can be rapidly implemented to better predict patient outcomes during an evolving pandemic.


title: Dynamical Pool-Size Optimization for the SARS-CoV-2 PCR Test

abstract: In this work, we put forward a novel test strategy, that allows to significantly increase the test capacity for SARS-CoV-2. The test strategy is based on an a priory risk assessment scheme, that allows to dynamically find and adapt an optimal clustering size of test pools. We, furthermore, suggest a method to overcome the efficiency loss of test clustering by avoiding concentration losses in the test samples. We validated our method with several thousand probe pools performing RT-PCR tests, and found it highly effective.


title: Impact of CancelRx on Discontinuation of Controlled Substance Prescriptions

abstract:
ObjectiveTo assess how controlled substance medication discontinuations were communicated over time

Data SourcesSecondary data from a midwestern academic health system electronic health record and pharmacy platform were collected 12-months prior to CancelRx implementation and for 12-months post implementation.

Study DesignThe study utilized an interrupted time series analysis (ITSA) to capture the proportion of controlled substance medications that were cancelled in the clinics electronic health record and also cancelled in the pharmacys dispensing software. The ITSA plotted the proportion of successful cancellation messages over time, particularly after the health systems implementation of CancelRx, a novel technology.

Data Collection/ExtractionData were extracted from the EHR and pharmacy records for patients aged 18+ who had a controlled substance discontinued by a health system provider. Information collected included patient demographics, drug information (name, dose), and dates discontinued in the clinic and pharmacy records.

Principal FindingsAfter CancelRx implementation there was a significant increase in the proportion of discontinued controlled substance medications that were communicated to the pharmacy.

ConclusionsThis study demonstrates the role that technology can play in promoting controlled substance policy and medication safety.

category: health systems and quality improvement


title: Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the hospital environment: a bacterial genome-wide association study

abstract:
BackgroundStaphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease.

MethodsTo investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage.

ResultsAll major global lineages were represented in both bacteraemia and carriage, with no evidence for different attack rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (p=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4).

Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (p=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (p=10-7.2).

ConclusionsIn an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment.

Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and hospital-associated carriage, suggesting that AMR increases the propensity not only to survive in hospital environments, but also to cause invasive disease.

category: infectious diseases


title: COVID-19 dynamics in an Ohio prison

abstract:
ImportanceIncarcerated individuals are a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Understanding SARS-CoV-2 dynamics in prisons is crucial for curbing transmission both within correctional facilities and in the surrounding community.

ObjectiveThe purpose of this study was to identify transmission scenarios that could underly rapid, widespread SARS-CoV-2 infection among inmates in Marion Correctional Institution (MCI).

DesignPublicly available data reported by the Ohio Department of Rehabilitation and Corrections (ODRC) was analyzed using mathematical and statistical models.

SettingWe consider SARS-CoV-2 transmission dynamics among MCI inmates prior to and including April 16, 2020.

ParticipantsThis study uses de-identified, publicly available SARS-CoV-2 test result data for MCI inmates.

ExposuresInmates at MCI were considered exposed to potential infection with SARS-CoV-2.

Main outcome and measuresResults from mass testing conducted on April 16, 2020 were analyzed together with time of first reported SARS-CoV-2 infection among MCI inmates.

ResultsRapid, widespread infection of MCI inmates was reported, with nearly 80% of inmates infected within three weeks of first reported inmate case. These data are consistent with i) a basic reproduction number greater than 14, together with a single initially infected inmate, ii) an initial super-spreading event resulting in several hundred initially infected inmates, together with a basic reproduction number of approximately three, and iii) earlier undetected circulation of virus among inmates prior to April.

Conclusions and relevanceMass testing data are consistent with extreme transmissibility, super-spreading events, or undetected circulation of virus among inmates. All scenarios consistent with these data attest to the vulnerabilities of prisoners to COVID-19.

Key pointsO_ST_ABSQuestionC_ST_ABSTo identify transmission characteristics consistent with timing and extent of SARS-CoV-2 infection among inmates in Marion Correctional Institution.

FindingsMathematical and statistical modeling finds three scenarios that are consistent with the observed widespread infection in Marion Correctional Institution: i) very high transmissibility corresponding to a basic reproduction number in the double digits, ii) an initial super-spreading event involving exposure of several hundred inmates, iii) undetected circulation of virus prior to the first documented case among inmates.

MeaningHigh transmissibility, super-spreading events, and challenges with disease surveillance all attest to the vulnerabilities of prison populations to SARS-CoV-2.


title: Estimating and forecasting the burden and spread of SARS-CoV2 first wave in Colombia.

abstract: AO_SCPLOWBSTRACTC_SCPLOWFollowing the rapid dissemination of COVID-19 cases in Colombia in 2020, large-scale non-pharmaceutical interventions (NPIs) were implemented as national emergencies in most of the municipalities of the country starting by a lockdown on March 20th of 2020. Using combinations of meta-population models SEAIIRD (Susceptible-Exposed-Asymptomatic-Infected-Recovered-Diseased) which describes the disease dynamics in the different localities, with movement data that accounts for the number of commuters between units and statistical inference algorithms could be an effective approach to both nowcast and forecast the number of cases and deaths in the country. Here we used an iterated filtering (IF) framework to fit the parameters of our model to the reported data across municipalities from march to late October in locations with more than 50 reported deaths and cases historically. Since the model is high dimensional (6 state variable by municipality) inference on those parameters is highly non-trivial, so we used an Ensemble-Adjustment-Kalman-Filter (EAKF) to estimate time variable system states and parameters. Our results show that the model is capable of capturing the evolution of the outbreak in the country and providing estimates of the epidemiological parameters in time. These estimates could become the base for planning future interventions as well as evaluate the impact of NPIs on the effective reproductive number ([R]eff) and the key epidemiological parameters, such as the contact rate or the reporting rate. Our approach demonstrates that real-time, publicly available ensemble forecasts can provide robust short-term predictions of reported COVID-19 deaths in Colombia. This model has the potential to be used as a forecasting and prediction tool to evaluate disease dynamics and to develop a real time surveillance system for management and control.


title: Comparison and analysis of various complementary diagnosis methods for the current situation and problems of COVID-19 diagnosis

abstract: We evaluated and compared the diagnostic performance of fluorescence immunoassay (FIA) and two types of serological diagnostic tests: enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay (ICA) for detection of SARS-CoV-2 antigen and antibody to diagnose COVID-19 infections. This study is aimed to analyze and compare the current status and problems of COVID-19 diagnosis and various alternative diagnostic methods that are viable. The enrolled subjects in our study population were tested with real-time polymerase chain reaction (RT-PCR). ELISA and immunochromatographic diagnostic kit were used to diagnose 362 positive and 3010 negative SARS-CoV-2 specimens, and antigen fluorescence immunoassay kit was used on 62 positive and 70 negative SARS-CoV-2 RT-PCR confirmed samples for diagnosis. As a result, categorizing by the patient symptom onset days, PCL COVID19 Total Ab EIA (ELISA) showed the sensitivity of 93.4% from 15 to 21 days, 94.2% from over 22 days, and the specificity of 99.97%. PCL COVID19 IgG/IgM Rapid Gold (ICA) had a sensitivity of 86.9%, 97.4%, and the specificity of 98.14% respectively. PCL COVID19 Ag Rapid FIA sensitivity was 93.8% from 0 to 7 days, 71.4% from 8 to 12 days and specificity was 98.57%. In conclusion, COVID-19 Ab ELISA and ICA, and COVID-19 Ag FIA are all complementary and applicable diagnostic methods to resolve the current problems of COVID-19 diagnosis.


title: SARS-Cov-2 prevalence, transmission, health-related outcomes and control strategies in homeless shelters: systematic review and meta-analysis

abstract:
BackgroundPeople experiencing homelessness (PEH) may be at particular risk for COVID19. We synthesised the evidence on SARS-Cov-2 infection, transmission, outcomes of disease, effects of non-pharmaceutical interventions (NPI), and the effectiveness of targeted strategies for infection prevention and control (IPC).

MethodsSystematic review of articles, reports and grey-literature indexed in electronic databases (EMBASE, WHO-Covid19, Web of Science), pre-print repositories, institutional websites, and handsearching. Empirical papers of any study design addressing Covid-19 in PEH or homeless shelters staff in English were included. (PROSPERO 2020 CRD42020187033)

FindingsOf 194 publications, 13 studies were included (two modelling, ten observational and one qualitative study). All were conducted in high-income countries. Random-effect meta-analysis of prevalence estimates yields a baseline SARS-Cov-2 prevalence of 2{middle dot}14% (95% Confidence-Interval, 95%CI=1{middle dot}02-3{middle dot}27) in PEH and 1{middle dot}72 % (95%CI=0{middle dot}31-3{middle dot}12) in staff. In outbreaks, the pooled prevalence increases to 29{middle dot}49% (95%CI=16{middle dot}44-29{middle dot}55) in PEH and 15{middle dot}18% (95%CI=8{middle dot}95-21{middle dot}42) in staff. Main IPC strategies were universal and rapid testing, expansion of non-congregate housing support, and individual measures in shelters (bed spacing, limited staff rotation).

InterpretationUp to 30% PEH and 17% staff are infected during outbreaks of SARS-Cov-2 in homeless shelters. Most studies were conducted in the USA. No studies were found on health-related outcomes or health effects of NPI. An overview and evaluation of IPC strategies for PEH, including a better understanding of disease transmission, and reliable data on PEH within Covid-19 notification systems is needed. Qualitative studies may serve to voice PEH experiences and guide future evaluations and IPC strategies.

FundingNo source of funding.

Panel 1: Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPeople experiencing homelessness (PEH) are at increased risk of infectious, chronic, and mental health adverse conditions. Due to the risk of transmission in shared accommodations, PEH may be particularly vulnerable to SARS-Cov-2 infection and worse clinical outcomes. Non-pharmaceutical interventions (NPIs) taken to mitigate the SARS-Cov-2 outbreak may have further aggravated health and social conditions. However, there is no evidence synthesis on the SARS-Cov-2 epidemiology among PEH, the correspondent clinical and other health-related outcomes as well as health effects of NPIs on these groups.

Added value of this study

We reviewed and synthesized existent evidence on the risk of infection and transmission, risk of severe course of disease, effect of NPIs on health outcomes and the effectiveness of implemented measures to avert risks and negative outcomes among PEH. Results of the identified studies suggest that both PEH and shelter staff are at high risk of SARS-Cov-2 infection, especially in case of a local outbreak. Due to the low prevalence of symptoms at the time of a positive SARS-Cov-2 test among PEH, symptom screening alone may not be efficient to control outbreaks. Instead, universal and rapid testing conjugated with expansion of non-congregate housing support, and individual measures in shelters, are discussed as sensible strategies.

Implications of all the available evidence

A comprehensive overview of NPIs and shelter strategies targeting PEH and evaluation of their effectiveness and unintended health consequences is needed. Qualitative research considering living realities of PEH can facilitate understanding of their specific needs during the pandemic.


title: COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing

abstract:
Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Here we report on standardised laboratory evaluations of LFDs, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots (UK COVID-19 testing centres, hospital, schools, armed forces). 4/64 LFDs so far have desirable performance characteristics (Orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1-6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20-0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists (156/198, 95% CI 72.4-84.3) was 78.8%. Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission.

FundingDepartment of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.


title: Understanding COVID-19 dynamics and the effects of interventions in the Philippines: A mathematical modelling study

abstract:
ObjectiveCOVID-19 appears to have caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with high-income countries, possibly because of differing demographics, socio-economics, surveillance, and policy responses. Here, we investigate the role of multiple factors on COVID-19 dynamics in the Philippines, a LMIC that has had a relatively severe COVID-19 outbreak.

MethodsWe applied an age-structured compartmental model that incorporated time-varying mobility, testing, and personal protective behaviors (through a "Minimum Health Standards" policy, MHS) to represent the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon, Central Visayas, and the National Capital Region). We estimated effects of control measures, key epidemiological parameters, and interventions.

FindingsPopulation age structure, contact rates, mobility, testing, and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases, hospitalisations, and deaths. Several of the fitted epidemiological parameters were consistent with those reported in high-income settings. The model indicated that MHS reduced the probability of transmission per contact by 15-26%. The February 2021 case detection rate was estimated at [~]9%, population recovered at [~]12%, and scenario projections indicated high sensitivity to MHS adherence.

ConclusionsCOVID-19 dynamics in the Philippines are driven by age, contact structure, mobility, and MHS adherence, and the epidemic can be understood within a similar framework as for high-income settings. Continued compliance with low-cost MHS should allow the Philippines to maintain epidemic control until vaccines are widely distributed, but disease resurgence could occur due to low population immunity and detection rates.