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10.1101/2020.12.26.20248868 | Gender- and Age-Specific Associations of Visit-To-Visit Blood Pressure Variability with Incident Generalized Anxiety Disorder | BackgroundThere is a bidirectional relationship between blood pressure variability (BPV) and generalized anxiety disorder (GAD), but few studies have examined the gender- and age-specific effects of visit-to-visit BPV on GAD incidence. We examined the predictive value of BPV for the incidence of GAD in a family clinic cohort.
MethodsConsecutive patients with a first attendance to family medicine clinics in Hong Kong between January 1st, 2000, and December 31st, 2002, with at least three blood pressure measurements available thereafter were included. The primary endpoint was incident GAD as identified by ICD-9 coding from the local Clinical Data Analysis and Reporting System.
ResultsThis study included 48023 (50% males) patients with a median follow-up of 224 (IQR: 217-229) months. Females were more likely to develop GAD compared to males (incidence rate: 7% vs. 2%), as were patients of older age. Significant univariate predictors were female gender, older age, pre-existing cardiovascular diseases, respiratory diseases, diabetes mellitus, hypertension, and gastrointestinal diseases, various laboratory examinations and the number of blood pressure measurements. Higher baseline, maximum, minimum, SD, CV, and variability score of diastolic blood pressure significantly predicted GAD, as did all systolic blood pressure measures (baseline, latest, maximum, minimum, mean, median, variance, SD, RMS, CV, variability score).
ConclusionsThe relationships between longer term visit-to-visit BPV and incident GAD were identified. Female and older patients with higher blood pressure and higher BPV were at the highest risks of GAD. | cardiovascular medicine |
10.1101/2020.12.26.20248861 | Technological advances in elite marathon performance | There is scientific and legal controversy about recent technological advances in performance running shoes that reduce the energetic cost of running and may provide a distinct competitive advantage. To better understand the potential performance-enhancing effects of Nikes pioneering marathon racing shoes, we examined the finishing times and racing shoes of the top 50 male and 50 female runners from the World Marathon Major series in the 2010s -- before and after the introduction of new Nike shoe models (4%, NEXT%, Alphafly, and other prototypes; herein referred to as neoteric Nikes). Data for racing shoes were available for 3,886 of the 3,900 performances recorded at the four annual marathons in Boston, London, Chicago, and New York. In full cohort analyses, marathon finishing times were 2.0% or 2.8 min (138.5 {+/-} 8.1 min vs. 141.3 {+/-} 7.4 min, P<0.001) faster for male runners wearing neoteric Nikes compared to other shoes. For females, marathon finishing times were 2.6% or 4.3 min (159.1 {+/-} 10.0 min vs. 163.4 {+/-} 10.7 min, P<0.001) faster for runners wearing neoteric Nikes. In a subset of within-runner changes in marathon performances (males, n = 138; females, n = 101), marathon finishing times improved by 0.8% or 1.2 min for males wearing neoteric Nikes relative to the most recent marathon in which other shoes were worn, and this performance-enhancing effect was greater among females who demonstrated 1.6% or 3.7 min improvement (P=0.002). Our results demonstrate that marathon performances for world-class athletes are substantially faster wearing neoteric Nikes than other market-leading shoes, particularly among females. | sports medicine |
10.1101/2020.12.27.20248903 | COVID-19 severity impacts on long-term neurological manifestation after hospitalisation | BackgroundClinical investigations have argued for long-term neurological manifestations in both hospitalized and non-hospitalized COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity.
Methodsfrom a sample of 208 consecutive non-neurological patients hospitalized for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardized clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses.
ResultsAt 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%), and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses.
Conclusionspremorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations. | neurology |
10.1101/2020.12.27.20248903 | Long-term neurological manifestations of COVID-19: prevalence and predictive factors | BackgroundClinical investigations have argued for long-term neurological manifestations in both hospitalized and non-hospitalized COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity.
Methodsfrom a sample of 208 consecutive non-neurological patients hospitalized for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardized clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses.
ResultsAt 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%), and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses.
Conclusionspremorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations. | neurology |
10.1101/2020.12.26.20248491 | A genome-wide association study for nonalcoholic fatty liver disease identifies novel genetic loci and trait-relevant candidate genes in the Million Veteran Program. | Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic alanine aminotransferase elevation (cALT) without other liver diseases, we performed a trans-ancestry genome-wide association study in the Million Veteran Program including 90,408 cALT cases and 128,187 controls. In the Discovery stage, seventy-seven loci exceeded genome-wide significance - including 25 without prior NAFLD or ALT associations - with one additional locus identified in European-American-only and two in African-American-only analyses (P<5x10-8). External replication in cohorts with NAFLD defined by histology (7,397 cases, 56,785 controls) or liver fat extracted from radiologic imaging (n=44,289) validated 17 SNPs (P<6.5x10-4) of which 9 were novel (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH, and IFI30). Pleiotropy analysis showed that 61 of 77 trans-ancestry and all 17 validated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD. | genetic and genomic medicine |
10.1101/2020.12.26.20248491 | A genome-wide association study of chronic ALT-based non-alcoholic fatty liver disease in the Million Veteran Program with histological and radiological validation. | Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic alanine aminotransferase elevation (cALT) without other liver diseases, we performed a trans-ancestry genome-wide association study in the Million Veteran Program including 90,408 cALT cases and 128,187 controls. In the Discovery stage, seventy-seven loci exceeded genome-wide significance - including 25 without prior NAFLD or ALT associations - with one additional locus identified in European-American-only and two in African-American-only analyses (P<5x10-8). External replication in cohorts with NAFLD defined by histology (7,397 cases, 56,785 controls) or liver fat extracted from radiologic imaging (n=44,289) validated 17 SNPs (P<6.5x10-4) of which 9 were novel (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH, and IFI30). Pleiotropy analysis showed that 61 of 77 trans-ancestry and all 17 validated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD. | genetic and genomic medicine |
10.1101/2020.12.26.20248491 | A trans-ancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation. | Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic alanine aminotransferase elevation (cALT) without other liver diseases, we performed a trans-ancestry genome-wide association study in the Million Veteran Program including 90,408 cALT cases and 128,187 controls. In the Discovery stage, seventy-seven loci exceeded genome-wide significance - including 25 without prior NAFLD or ALT associations - with one additional locus identified in European-American-only and two in African-American-only analyses (P<5x10-8). External replication in cohorts with NAFLD defined by histology (7,397 cases, 56,785 controls) or liver fat extracted from radiologic imaging (n=44,289) validated 17 SNPs (P<6.5x10-4) of which 9 were novel (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH, and IFI30). Pleiotropy analysis showed that 61 of 77 trans-ancestry and all 17 validated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD. | genetic and genomic medicine |
10.1101/2020.12.26.20248858 | Public Search Interests related to COVID-19: Insights from Google Search Trends in Bangladesh | ObjectivePublic response monitoring is critical to reducing COVID-19 infections and developing effective public health strategies. This study explored Google search trends to understand public responses to COVID-19 concerns in Bangladesh.
MethodsWe used country-level Google search trends data to examine the association between Google search terms related to COVID-19 deaths, face masks, and COVID-19 vaccines and the actual and one-week lagged actual COVID-19 death counts from February 2, 2020, to December 19, 2020, in Bangladesh. Results: Search terms related to COVID-19 deaths, face masks, and COVID-19 vaccines increased and peaked during March and April, but then began declining gradually after June 2020. The mean relative search volume for face masks (35 points) was higher than for death information (8 points) and vaccines (16 points) throughout the study period, and searching for masks peaked (100 points) during the third week of March. Search interests for death information and face masks were negatively correlated with the actual and one-week lagged actual COVID-19 death counts.
ConclusionIn response to declining trends in COVID-19-related google search terms, policymakers should strengthen ongoing risk communication and preventive information dissemination programs to control and prevent COVID-19 cases and deaths. | health policy |
10.1101/2020.12.28.20248920 | Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan | A prospective cohort study was conducted at the Indus Hospital Karachi, Pakistan between March and June 2020 to describe the determinants of mortality among hospitalized COVID-19 patients. 186 adult patients were enrolled and all-cause mortality was found to be 36% (67/186). Those who died were older and more likely to be males (p<0.05). Temperature and respiratory rate were higher among non-survivors while Oxygen saturation was lower (p<0.05). Serum CRP, D-dimer and IL-6 were higher while SpO2 was lower on admission among non-survivors (p<0.05). Non-survivors had higher SOFA and CURB-65 scores while thrombocytopenia, lymphopenia and severe ARDS was more prevalent among them (p<0.05). Use of non-invasive ventilation in emergency room, ICU admission and invasive ventilation were associated with mortality in our cohort (p<0.05). Length of hospital stay and days of intubation were longer in non-survivors (p<0.05). Use of azithromycin, hydroxychloroquine, steroids, tocilizumab, antibiotics, IVIG or anticoagulation showed no mortality benefit (p>0.05). Multivariable logistic regression showed that age > 60 years, oxygen saturation <93% on admission, pro-calcitonin > 2 ng/ml, unit rise in temperature and SOFA score, ICU admission and sepsis during hospital stay were associated with higher odds of mortality. Larger prospective studies are needed to further strengthen these findings.
Key FindingsO_LIAge greater than 60 years is associated with in-hospital mortality among COVID-19 patients
C_LIO_LIOxygen saturation less than 93% and ICU admission are associated with higher odds of mortality
C_LIO_LIInflammatory markers including CRP, Ferritin and IL-6 were significantly higher among non-survivors
C_LIO_LISerum pro-calcitonin greater than 2 ng/ml and sepsis during hospital stay are associated with higher odds of mortality among COVID-19 patients
C_LI | infectious diseases |
10.1101/2020.12.27.20248896 | Vaccination and Non-Pharmaceutical Interventions: when can the UK relax about COVID-19? | BackgroundThe announcement of efficacious vaccine candidates against SARS-CoV-2 has been met with worldwide acclaim and relief. Many countries already have detailed plans for vaccine targeting based on minimising severe illness, death and healthcare burdens. Normally, relatively simple relationships between epidemiological parameters, vaccine efficacy and vaccine uptake predict the success of any immunisation programme. However, the dynamics of vaccination against SARS-CoV-2 is made more complex by age-dependent factors, changing levels of infection and the potential relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines.
MethodsIn this study we use an age-structured mathematical model, matched to a range of epidemiological data in the UK, that also captures the roll-out of a two-dose vaccination programme targeted at specific age groups.
FindingsWe consider the interaction between the UK vaccination programme and future relaxation (or removal) of NPIs. Our predictions highlight the population-level risks of early relaxation leading to a pronounced wave of infection, hospital admissions and deaths. Only vaccines that offer high infection-blocking efficacy with high uptake in the general population allow relaxation of NPIs without a huge surge in deaths.
InterpretationWhile the novel vaccines against SARS-CoV-2 offer a potential exit strategy for this outbreak, this is highly contingent on the infection-blocking (or transmission-blocking) action of the vaccine and the population uptake, both of which need to be carefully monitored as vaccine programmes are rolled out in the UK and other countries.
Research in contextO_ST_ABSEvidence before this studyC_ST_ABSVaccination has been seen as a key tool in the fight against SARS-CoV-2. The vaccines already developed represent a major technological achievement and have been shown to generate significant immune responses, as well as offering considerable protection against disease. However, to date there is limited information on the degree of infection-blocking these vaccines are likely to induce. Mathematical models have already successfully been used to consider age- and risk-structured targeting of vaccination, highlighting the importance of prioritising older and high-risk individuals.
Added value of this studyTranslating current knowledge and uncertainty of vaccine behaviour into meaningful public health messages requires models that fully capture the within-country epidemiology as well as the complex roll-out of a two-dose vaccination programme. We show that under reasonable assumptions for vaccine efficacy and uptake the UK is unlikely to reach herd immunity, which means that non-pharmaceutical interventions cannot be released without generating substantial waves of infection.
Implications of all the available evidenceVaccination is likely to provide substantial individual protection to those receiving two doses, but the degree of protection to the wider population is still uncertain. While substantial immunisation of the most vulnerable groups will allow for some relaxation of controls, this must be done gradually to prevent large scale public health consequences. | infectious diseases |
10.1101/2020.12.27.20248896 | Vaccination and Non-Pharmaceutical Interventions: when can the UK relax about COVID-19? | BackgroundThe announcement of efficacious vaccine candidates against SARS-CoV-2 has been met with worldwide acclaim and relief. Many countries already have detailed plans for vaccine targeting based on minimising severe illness, death and healthcare burdens. Normally, relatively simple relationships between epidemiological parameters, vaccine efficacy and vaccine uptake predict the success of any immunisation programme. However, the dynamics of vaccination against SARS-CoV-2 is made more complex by age-dependent factors, changing levels of infection and the potential relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines.
MethodsIn this study we use an age-structured mathematical model, matched to a range of epidemiological data in the UK, that also captures the roll-out of a two-dose vaccination programme targeted at specific age groups.
FindingsWe consider the interaction between the UK vaccination programme and future relaxation (or removal) of NPIs. Our predictions highlight the population-level risks of early relaxation leading to a pronounced wave of infection, hospital admissions and deaths. Only vaccines that offer high infection-blocking efficacy with high uptake in the general population allow relaxation of NPIs without a huge surge in deaths.
InterpretationWhile the novel vaccines against SARS-CoV-2 offer a potential exit strategy for this outbreak, this is highly contingent on the infection-blocking (or transmission-blocking) action of the vaccine and the population uptake, both of which need to be carefully monitored as vaccine programmes are rolled out in the UK and other countries.
Research in contextO_ST_ABSEvidence before this studyC_ST_ABSVaccination has been seen as a key tool in the fight against SARS-CoV-2. The vaccines already developed represent a major technological achievement and have been shown to generate significant immune responses, as well as offering considerable protection against disease. However, to date there is limited information on the degree of infection-blocking these vaccines are likely to induce. Mathematical models have already successfully been used to consider age- and risk-structured targeting of vaccination, highlighting the importance of prioritising older and high-risk individuals.
Added value of this studyTranslating current knowledge and uncertainty of vaccine behaviour into meaningful public health messages requires models that fully capture the within-country epidemiology as well as the complex roll-out of a two-dose vaccination programme. We show that under reasonable assumptions for vaccine efficacy and uptake the UK is unlikely to reach herd immunity, which means that non-pharmaceutical interventions cannot be released without generating substantial waves of infection.
Implications of all the available evidenceVaccination is likely to provide substantial individual protection to those receiving two doses, but the degree of protection to the wider population is still uncertain. While substantial immunisation of the most vulnerable groups will allow for some relaxation of controls, this must be done gradually to prevent large scale public health consequences. | infectious diseases |
10.1101/2020.12.27.20248917 | Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: a diagnostic accuracy study | BackgroundThere is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority.
MethodsWe performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert-MTB/RIF and sputum culture. Among consecutive, Xpert-MTB/RIF or culture-confirmed cases and Xpert-MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks.
FindingsTwo hundred controls and 100 culture- or Xpert-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0{middle dot}79 (95% CI: 0{middle dot}73-0{middle dot}84) and for Xpert-MTB-HR was 0{middle dot}84 (95% CI: 0{middle dot}79-0{middle dot}89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53{middle dot}0%, 95% CI: 45{middle dot}0-69{middle dot}0%) than CRP (28{middle dot}1%, 95% CI: 20{middle dot}2-41{middle dot}8%) (p=0{middle dot}003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert semi-quantitative load, sensitivity (at 70% specificity) of CRP (90{middle dot}3%, 95% CI: 74{middle dot}2-98{middle dot}0) and Xpert-MTB-HR (96{middle dot}8%, 95% CI: 83{middle dot}3-99{middle dot}9%) was higher.
InterpretationFor active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden.
FundingNational Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4). | infectious diseases |
10.1101/2020.12.27.20248917 | Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: a diagnostic case-control study | BackgroundThere is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority.
MethodsWe performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert-MTB/RIF and sputum culture. Among consecutive, Xpert-MTB/RIF or culture-confirmed cases and Xpert-MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks.
FindingsTwo hundred controls and 100 culture- or Xpert-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0{middle dot}79 (95% CI: 0{middle dot}73-0{middle dot}84) and for Xpert-MTB-HR was 0{middle dot}84 (95% CI: 0{middle dot}79-0{middle dot}89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53{middle dot}0%, 95% CI: 45{middle dot}0-69{middle dot}0%) than CRP (28{middle dot}1%, 95% CI: 20{middle dot}2-41{middle dot}8%) (p=0{middle dot}003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert semi-quantitative load, sensitivity (at 70% specificity) of CRP (90{middle dot}3%, 95% CI: 74{middle dot}2-98{middle dot}0) and Xpert-MTB-HR (96{middle dot}8%, 95% CI: 83{middle dot}3-99{middle dot}9%) was higher.
InterpretationFor active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden.
FundingNational Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4). | infectious diseases |
10.1101/2020.12.26.20248855 | Quantitative plasma proteomics of survivor and non-survivor COVID-19 patients admitted to hospital unravels potential prognostic biomarkers and therapeutic targets | The development of new approaches that allow early assessment of which cases of COVID-19 will likely become critical and the discovery of new therapeutic targets are urgent demands. In this cohort study, we performed proteomic and laboratorial profiling of plasma from 163 patients admitted to Bauru State Hospital (Bauru, SP, Brazil) between May 4th and July 4th, 2020, who were diagnosed with COVID-19 by RT-PCR nasopharyngeal swab samples. Plasma samples were collected upon admission for routine laboratory analyses and shotgun quantitative label-free proteomics. Based on the course of the disease, the patients were further divided into 3 groups: a) mild symptoms, discharged without admission to an intensive care unit (ICU) (n=76); b) severe symptoms, discharged after admission to an ICU (n=56); c) critical, died after admission to an ICU (n=31). White cells and neutrophils were significantly higher in severe and critical patients compared to mild ones. Lymphocytes were significantly lower in critical patients compared to mild ones and platelets were significantly lower in critical patients compared to mild and severe ones. Ferritin, TGO, urea and creatinine were significantly higher in critical patients compared to mild and severe ones. Albumin, CPK, LDH and D-dimer were significantly higher in severe and critical patients compared to mild ones. PCR was significantly higher in severe patients compared to mild ones. Proteomic analysis revealed marked changes between the groups in plasma proteins related to complement activation, blood coagulation, antimicrobial humoral response, acute inflammatory response, and endopeptidase inhibitor activity. Higher levels of IREB2, GELS, POLR3D, PON1 and ULBP6 upon admission to hospital were found in patients with mild symptoms, while higher levels of Gal-10 were found in critical and severe patients. This needs to be validated in further studies. If confirmed, pathways involving these proteins might be potential new therapeutic targets for COVID-19. | infectious diseases |
10.1101/2020.12.26.20248880 | Development of a saliva-optimized RT-LAMP assay for SARS-CoV-2 | Conventional reverse transcription quantitative polymerase chain reaction (RT-qPCR) technology has struggled to fulfill the unprecedented need for diagnostic testing created by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Complexity and cost hinder access to testing, and long turnaround-time decreases its utility. To ameliorate these issues, we focus on saliva and introduce several advances to colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) technology; RT-LAMP offers a minimal equipment alternative to RT-qPCR. First, we validated the use of the novel dye LAMPShade Violet (LSV), which improves the visual clarity and contrast of the colorimetric readout. Second, we compared different inactivation conditions on infectivity and RNA yield from saliva. Third, we developed a ten-minute RNA purification protocol from saliva. We call this magnetic bead protocol SalivaBeads. Finally, we developed a magnetic stick, StickLAMP, which provides reliable bead-based RNA purification as well as simple and low-cost access to scalable testing from saliva. | infectious diseases |
10.1101/2020.12.26.20248872 | The new Coronavirus (SARS-CoV-2) in Central America: Demographic-spatial simulations, Analyses of Molecular Variance (AMOVA) and Neutrality Tests in complete genomes from Belize, Guatemala, Cuba, Jamaica and Puerto Rico | In this work, we evaluated the levels of genetic diversity in 38 complete genomes of SARS-CoV-2 from five Central American countries (Belize, Guatemala, Cuba, Jamaica and Puerto Rico) with 04, 10, 2, 8 and 14 haplotypes, respectively, with an extension of up to 29,885 bp. All sequences were publicly available on the National Biotechnology Information Center (NCBI) platform. Using specific methodologies for paired FST, AMOVA, mismatch, demographic-spatial expansion, molecular diversity and for the time of evolutionary divergence, it was possible to notice that only 79 sites remained conserved and that the high number of polymorphisms found helped to establish a clear pattern of genetic non-structuring, based on the time of divergence between the groups. The analyses also showed that significant evolutionary divergences within and between the five countries corroborate the fact that possible rapid and silent mutations are responsible for the increase in genetic variability of the Virus, a fact that would hinder the work with molecular targets for vaccines and medications in general. | infectious diseases |
10.1101/2020.12.27.20248919 | Sodium intake and high blood pressure among adults on caloric restriction: a multi-year cross-sectional analysis of the U.S. Population, 2007-2018 | Abstract and KeywordsO_ST_ABSAimC_ST_ABSSmall studies have shown reduced sodium sensitivity of blood pressure in obese adolescents on caloric restriction. However, no study at the population level has studied such an effect. We aimed to explore the association between mean daily sodium intake and prevalent hypertension among a nationally representative sample of U.S. adults on caloric restriction who participated in the National Health Examination and Nutrition Survey over the last twelve years.
Methods and ResultsWe used a design-based regression model to explore the association between sodium intake and prevalent hypertension. We also conducted sensitivity analyses using multiple imputation chained equations and propensity score matching. We also measured the effect of a binary exposure derived from two widely recommended thresholds of sodium intake: 2.3 and 5.0 grams per day. Among 5,756 individuals, we did not detect any significant association between increased sodium and the odds of hypertension (OR: 0.97; CI 95%: 0.90; 1.05). All our sensitivity analyses are consistent with our main findings.
ConclusionOur findings suggest that people on caloric restriction--a component of healthy weight loss--would see no benefit in reducing sodium intake to lower blood pressure. These results highlight the need to explore new population-specific strategies for sodium intake reduction, including new dietary prescription approaches to improve dietary adherence and reduce the risk associated with sodium-deficient diets. | cardiovascular medicine |
10.1101/2020.12.26.20248867 | Derivation of an electronic frailty index for short-term mortality in heart failure: a machine learning approach | ObjectiveFrailty may be found in heart failure patients especially in the elderly and is associated with a poor prognosis. However, assessment of frailty status is time-consuming and the electronic frailty indices developed using health records have served as useful surrogates. We hypothesized that an electronic frailty index developed using machine learning can improve short-term mortality prediction in patients with heart failure.
MethodsThis was a retrospective observational study included patients admitted to nine public hospitals for heart failure from Hong Kong between 2013 and 2017. Age, sex, variables in the modified frailty index, Deyos Charlson comorbidity index ([≥]2), neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) were analyzed. Gradient boosting, which is a supervised sequential ensemble learning algorithm with weak prediction submodels (typically decision trees), was applied to predict mortality. Comparisons were made with decision tree and multivariate logistic regression.
ResultsA total of 8893 patients (median: age 81, Q1-Q3: 71-87 years old) were included, in whom 9% had 30-day mortality and 17% had 90-day mortality. PNI, age and NLR were the most important variables predicting 30-day mortality (importance score: 37.4, 32.1, 20.5, respectively) and 90-day mortality (importance score: 35.3, 36.3, 14.6, respectively). Gradient boosting significantly outperformed decision tree and multivariate logistic regression (area under the curve: 0.90, 0.86 and 0.86 for 30-day mortality; 0.92, 0.89 and 0.86 for 90-day mortality).
ConclusionsThe electronic frailty index based on comorbidities, inflammation and nutrition information can readily predict mortality outcomes. Their predictive performances were significantly improved by gradient boosting techniques. | cardiovascular medicine |
10.1101/2020.12.26.20248866 | Heart Rate n-Variability (HRnV) Measures for Prediction of Mortality in Sepsis Patients Presenting at the Emergency Department | BackgroundSepsis is a potentially life threatening condition that requires prompt recognition and treatment for optimal outcomes. There is little consensus on an objective way to assess for sepsis severity and risk for mortality. In recent years, heart rate variability (HRV), a measure of the cardiac autonomic regulation derived from short electrocardiogram tracings, has been found to correlate with sepsis mortality, and its use as a prognostic variable and for risk stratification has been promising. In this paper, we present using novel heart rate n-variability (HRnV) measures for sepsis mortality risk prediction and compare against current mortality prediction scores.
MethodsThis study was a retrospective cohort study on a convenience sample of patients presenting to the emergency department (ED) of Singapore General Hospital between September 2014 to April 2017. Patients were included in the study if they were above 21 years old, were suspected to have sepsis by their attending physician, triaged as emergency or urgent cases, and if they met two or more of the Systemic Inflammatory Response Syndrome (SIRS) criteria. Demographic and clinical variables were obtained from the electronic medical records, and HRV and novel HRnV parameters were calculated from five minute ECG tracings. Univariable analysis was conducted on variables obtained, with the primary outcome being 30-day in-hospital mortality (IHM). Variables selected through univariable analysis and stepwise selection were included in a multivariable logistic regression model, the results of which were presented using receiver operating curve (ROC) analysis.
ResultsOf 342 patients included for final analysis, 66 (19%) met with the primary outcome. On univariable analysis, 85 out of 142 analysed HRV and HRnV parameters showed statistical difference between groups. The final multivariable logistic regression model comprised of 21 variables including four vital signs, two HRV parameters, and 15 HRnV parameters. The area under the curve (AUC) of the model was 0.86 (95% confidence interval 0.81-0.90), outperforming several established clinical scores.
ConclusionThe use of novel HRnV measures can provide adequate power to predictive models in the risk stratification of patients presenting to the ED with sepsis. When included in a multivariable logistic regression model, the HRnV-based model outperformed traditional risk stratification scoring systems. The HRnV measures may have potential to allow for a rapid, objective, and accurate means of patient risk stratification for sepsis severity and mortality. | emergency medicine |
10.1101/2020.12.27.20248894 | Prevalence and clinical profile of SARS-CoV-2 infection among farmworkers in Monterey County, California: June-November, 2020 | As essential personnel, United States farmworkers have continued working in-person throughout the COVID-19 pandemic. We undertook prospective surveillance of SARS-CoV-2 infection and antibody prevalence among farmworkers in Californias Salinas Valley from 15 June to 30 November, 2020. Over this period, we observed 22.1% (1514/6864) positivity for current SARS-CoV-2 by nucleic acid detection among farmworkers tested at federally-qualified migrant and community health clinics, as compared to 17.2% (1255/7305) among other adults from the same communities (risk ratio, 1.29; 95% confidence interval, 1.20-1.37). In a nested study enrolling 1,115 farmworkers, prevalence of current infection was 27.7% among farmworkers reporting [≥]1 potential COVID-19 symptom, and 7.2% among farmworkers without symptoms (adjusted odds ratio 4.17; 2.86-6.09). Prevalence of anti-SARS-CoV-2 IgG antibodies increased from 10.5% (6.0-18.4%) between 16 July-31 August to 21.2% (16.6-27.4%) between 1-30 November. The high observed prevalence of infection among farmworkers underscores the need for vaccination and other preventive interventions. | epidemiology |
10.1101/2020.12.27.20232934 | A renewal equation model to assess roles andlimitations of contact tracing for diseaseoutbreak control | We propose a deterministic model capturing essential features of contact tracing as part of public health non-pharmaceutical interventions to mitigate an outbreak of an infectious disease. By incorporating a mechanistic formulation of the processes at the individual level, we obtain an integral equation (delayed in calendar time and advanced in time since infection) for the probability that an infected individual is detected and isolated at any point in time. This is then coupled with a renewal equation for the total incidence to form a closed system describing the transmission dynamics involving contact tracing. We define and calculate basic and effective reproduction numbers in terms of pathogen characteristics and contact tracing implementation constraints. When applied to the case of SARS-CoV-2, our results show that only combinations of diagnosis of symptomatic infections and contact tracing that are almost perfect in terms of speed and coverage can attain control, unless additional measures to reduce overall community transmission are in place. Under constraints on the testing or tracing capacity, a temporary interruption of contact tracing may, depending on the overall growth rate and prevalence of the infection, lead to an irreversible loss of control even when the epidemic was previously contained. | epidemiology |
10.1101/2020.12.27.20232934 | A renewal equation model to assess roles and limitations of contact tracing for disease outbreak control | We propose a deterministic model capturing essential features of contact tracing as part of public health non-pharmaceutical interventions to mitigate an outbreak of an infectious disease. By incorporating a mechanistic formulation of the processes at the individual level, we obtain an integral equation (delayed in calendar time and advanced in time since infection) for the probability that an infected individual is detected and isolated at any point in time. This is then coupled with a renewal equation for the total incidence to form a closed system describing the transmission dynamics involving contact tracing. We define and calculate basic and effective reproduction numbers in terms of pathogen characteristics and contact tracing implementation constraints. When applied to the case of SARS-CoV-2, our results show that only combinations of diagnosis of symptomatic infections and contact tracing that are almost perfect in terms of speed and coverage can attain control, unless additional measures to reduce overall community transmission are in place. Under constraints on the testing or tracing capacity, a temporary interruption of contact tracing may, depending on the overall growth rate and prevalence of the infection, lead to an irreversible loss of control even when the epidemic was previously contained. | epidemiology |
10.1101/2020.12.27.20248829 | Comparing the predictive value of suicide risk screening to the detection of suicide risk using electronic health records in an urban pediatric emergency department | ObjectiveTo compare the accuracy, sensitivity and utility of brief screening to predictive modeling for identifying suicide-related outcomes in a pediatric emergency department. Our hypothesis was that predictive modeling would be more accurate and useful compared to brief screening.
MethodsThis was a retrospective cohort study at an urban pediatric Emergency Department (PED) in the United States. Patients were aged 8 to 18 years old who presented from January 1, 2017 to June 30, 2019. Predictors included positive suicide risk screen and/or demographic, medical and mental health diagnostic Electronic Health Record (EHR) data at the time of visit. The main outcome was subsequent PED visit with suicide-related presenting problem (i.e. ideation or attempt) within a 3-month follow-up period.
ResultsOf the N=13420 individuals, n=141 had a subsequent suicide-related ED visit. Approximately 63% identified as Black Non-Hispanic. Results showed that a model based only on EHR data performed only slightly worse than the ASQ alone. Combining ASQ screening and EHR data resulted in a 17.4% improvement in sensitivity and 13.4% increase in AUC compared to the ASQ alone. The LASSO models indicated a diagnosis of major depressive disorder in addition to the ASQ improved the AUC by 9%.
Conclusions, Implications, Future DirectionsOur findings show that EHR data is helpful either in the absence or as an addition to brief suicide screening. To our knowledge, this is the first study to compare brief screening to EHR based predictive modeling and adds to our understanding of how best to identify youth at risk of suicidal behaviors in clinical care settings. | psychiatry and clinical psychology |
10.1101/2020.12.26.20248886 | Gut Microbiota Markers for Antipsychotics Induced Metabolic Disturbance in Drug Naive Patients with First Episode Schizophrenia _ A 24 Weeks Follow-up Study | BackgroundWhile cardiometabolic adverse effects associated with antipsychotic treatment is an important clinical challenge, the underlying mechanisms are unknown. Here we investigated if changes in gut microbial composition associate with the metabolic disturbance induced by the risperidone treatment of schizophrenia.
MethodsNinety-four first episode, drug naive schizophrenia patients (SZ), and 100 healthy controls (HCs) were enrolled at baseline. Six metabolic parameters (glucose, homeostasis model assessment of insulin resistance (HOMA-IR), Total cholesterol (Total-C), Low-density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol (HDL-C) and triglycerides) and body mass index (BMI) were measured for all participants. Gut microbial composition (microbials) was determined by fecal samples using 16S ribosomal RNA sequencing. Both the metabolic parameters and the gut microbiota were analyzed at baseline (all participants) and after 12 and 24 weeks of risperidone treatment (patients).
ResultsThe glucose was significantly higher in SZ than HCs at baseline (p = 0.005). After 24-weeks treatment with risperidone, the levels of BMI, glucose, HOMA-IR, Total-C, LDL-C, HDL-C and triglyceride, were significant changed compared to baseline (p < 0.01). Six microbials showed significant changes in abundance after 24 weeks of risperidone treatment in SZ (p < 0.05), and four of these (Bacteroidetes, Proteobacteria, Christensenellaceae, and Enterobacteriaceae) were associated with the changes in metabolic parameters (p < 0.05). At baseline, the abundance of the microbials Christensenellaceae and Enterobacteriaceae were significantly associated with changes in triglyceride, BMI and HOMA-IR after 24-week risperidone treatment.
ConclusionsChanges in gut microbial composition induced by risperidone treatment may be a key pathway underlying the metabolic disturbances observed in SZ patients. While these findings warrant replication in independent samples, they provide insight into the role of microbiota in SZ treatment, which can form the basis for development of better SZ treatment strategies. | psychiatry and clinical psychology |
10.1101/2020.12.26.20248891 | Perception and awareness of COVID-19 among health science students and staff of Kuwait University: An online cross-sectional study | BackgroundCoronavirus disease 2019 (COVID-19) pandemic is unprecedented. Health science students are the future frontliners to fight pandemics. Awareness and perception toward COVID-19 among health science students and staff at Kuwait University was assessed.
MethodsBetween June and July 2020, an online questionnaire was distributed to all students and staff at HCS. The questionnaire was divided into six sections: socio-demography, risk and awareness, preparedness and prevention, source of information, policies, and social stigma.
ResultsA total of 592 students and 162 staff completed the questionnaire. The prevalence of self-reported chronic condition among students and staff was 14.0% and 19.1%, respectively. Moreover, self-reported COVID-19 prevalence among students and staff was 2.7% and 1.2%, respectively. Interestingly, 54% of students and 38.3% of staff reported that they knew someone within their immediate social environment who have been/are infected with SARS-CoV-2. Among students, 92.4% wore face mask in indoor places (outside of their home) often/all the time compared to wearing it outdoors (69.3%); whereas, for staff, it was more common to wear it outdoor than in indoor places (75.9% vs. 81.5%). Both students and staff showed greatest deal of trust was in official government press release and consultation with healthcare workers.
Willingness to take COVID-19 vaccine was indicated by 50% of students strongly agreed and an additional 25.8% agreed to taking it. Interest vaccine uptake was lower among staff (28.4% and 34.6% strongly agreed or agreed, respectively). Participants strongly agreed or agreed (72.5% and 19.6% of students as well as 68.5% and 22.2% of staff) that wearing face mask in public should be obligatory. More than 18% of students and staff indicated that they would avoid contact with COVID-19 infected people.
ConclusionsResponses of students and staff were mostly similar and showed that they follow precautionary measures to control spread of COVID-19, understand the viral transmission risk, and willing to raise awareness to reduce social stigma. | public and global health |
10.1101/2020.12.27.20248899 | Predictors of COVID-19 vaccine hesitancy in the UK Household Longitudinal Study | BackgroundVaccination is crucial to address the COVID-19 pandemic but vaccine hesitancy could undermine control efforts. We aimed to investigate the prevalence of COVID-19 vaccine hesitancy in the UK population, identify which population subgroups are more likely to be vaccine hesitant, and report stated reasons for vaccine hesitancy.
MethodsNationally representative survey data from 12,035 participants were collected from 24th November to 1st December 2020 for wave 6 of the Understanding Society COVID-19 web survey. Participants were asked how likely or unlikely they would be to have a vaccine if offered and their main reason for hesitancy. Cross-sectional analysis assessed prevalence of vaccine hesitancy and logistic regression models conducted.
FindingsOverall intention to be vaccinated was high (82% likely/very likely). Vaccine hesitancy was higher in women (21.0% vs 14.7%), younger age groups (26.5% in 16-24 year olds vs 4.5% in 75+) and less educated (18.6% no qualifications vs 13.2% degree qualified). Vaccine hesitancy was particularly high in Black (71.8%), Pakistani/Bangladeshi (42.3%), Mixed (32.4%) and non-UK/Irish White (26.4%) ethnic groups. Fully adjusted models showed gender, education and ethnicity were independently associated with vaccine hesitancy. Odds ratios for vaccine hesitancy were 12.96 (95% CI:7.34, 22.89) in the Black/Black British and 2.31 (95% CI:1.55, 3.44) in Pakistani/Bangladeshi ethnic groups (compared to White British/Irish ethnicity) and 3.24 (95%CI:1.93, 5.45) for people with no qualifications compared to degree educated. The main reason for hesitancy was fears over unknown future effects.
InterpretationOlder people at greatest COVID-19 mortality risk expressed the greatest willingness to be vaccinated but Black and Pakistani/Bangladeshi ethnic groups had greater vaccine hesitancy. Vaccine programmes should prioritise measures to improve uptake in specific minority ethnic groups.
FundingMedical Research Council
Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Embase and Medline up to November 16, 2020, using key words "vaccine hesitancy" and "COVID-19" or "SARS-CoV-2". Vaccine hesitancy is complex but also context specific. Previous research about vaccine hesitancy relates to existing adult and childhood vaccines, with limited evidence currently available on willingness to be vaccinated for newly available COVID-19 vaccines. Existing vaccination programmes often have lower uptake among more socioeconomically disadvantaged groups. Uptake of vaccines has often varied across ethnic groups, but patterns have often varied across different vaccine programmes.
Added value of this studyOur study describes the sub-groups of the UK population who are more likely to be hesitant about a COVID-19 vaccine and examines possible explanations for this. We used nationally representative data from the COVID-19 survey element of the UKs largest household panel study. We asked specifically about vaccine hesitancy in relation to a COVID-19 vaccine at a time when initial results of vaccine trials were being reported in the media. We found willingness to be vaccinated is generally high across the UK population but marked differences exist across population subgroups. Willingness to be vaccinated was greater in older age groups and in men. However, some minority ethnic groups, particularly Black/Black British and Pakistani/Bangladeshi, had high levels of vaccine hesitancy but this was not seen across all minority ethnic groups. People with lower education levels were also more likely to be vaccine hesitant.
Implications of all the available evidenceThe current evidence base on vaccine hesitancy in relation to COVID-19 is rapidly emerging but remains limited. Polling data has also found relatively high levels of willingness to take up a COVID-19 vaccine and suggested greater risks of vaccine hesitancy among Black, Asian and Minority Ethnic (BAME) people. Our study suggests that the risk of vaccine hesitancy differs across minority ethnic groups considerably, with Black ethnic groups particularly likely to be vaccine hesitant within the UK. Some White minority ethnic groups are also more likely to be vaccine hesitant than White British/Irish people.
Herd immunity may be achievable through vaccination in the UK but a focus on specific ethnic minority and socioeconomic groups is needed to ensure an equitable vaccination programme. | public and global health |
10.1101/2020.12.26.20248818 | Number of tests required to flatten the curve of coronavirus disease-2019 | We developed a mathematical model to quantify the number of tests required to stop the spread of coronavirus disease 2019 (COVID-19). Our model analyses performed using the data from the U.S. suggest that the infection coefficient increases by approximately 47% upon relaxing the lockdown policy. To offset the effect of lockdown relaxation, the number of tests should increase by 2.25 times, corresponding to approximately 280,000-360,000 tests per day in April 2020. | public and global health |
10.1101/2020.12.27.20248893 | Maternity waiting home Utilization and associated factors among women who gave birth in the Digelu and Tijo district of the Arsi Zone, Oromia, Ethiopia. | BackgroundMaternity Waiting Homes (MWHs) is an intervention designed to reduce maternal and perinatal mortality. Ethiopia has introduced the intervention before three decades however; its utilization is very low. Therefore, this study is aimed to assess MWH utilization and associated factors among women who gave birth in the last 12 months in Digelu and Tijo district Arsi Zone Oromia Region, Ethiopia.
MethodsCommunity-based cross-sectional study was conducted in April 2019 on 530 randomly selected women. Data were collected by face-to-face interview using structured questionnaire. Descriptive statistics and logistics regressions were used to analyze the results. Adjusted odds ratio and 95% confidence interval were respectively calculated to measure strength of association and its statistical significance.The confidence interval was used to declare statistical significance in the final model.
ResultsOne hundred twenty-five (23.6%) of the respondents used maternity waiting home. Traveling time less than and equals to 60 minutes from a nearby health facility (AOR=0.16, 95% CI: 0.09, 0.27), womens decision power (AOR=1.81, 95% CI: 1.10, 2.96), not utilizing antenatal care (AOR=0.6, 95% CI: 0.37, 0.97) and delivering more than three children (AOR=0.56, 95% CI: 0.34, 0.90) were independently associated with utilizing the maternity waiting home.
ConclusionEven though the MWH was designed to reduce maternal and perinatal mortality, less than a quarter (23.6%) of women delivered in the last 12 months before the study in the Digelu and Tijo District had utilized the services. Increasing availability of the service, promoting antenatal care utilization, empowering women and evolving policy makers are recommended to enhance the current low utilization of the MWH. | sexual and reproductive health |
10.1101/2020.12.27.20248723 | Two year data from a preliminary study of double lesion site MRgFUS treatment of Essential Tremor targeting the thalamus and the posterior subthalamic area. | BackgroundMR-guided focused ultrasound (MRgFUS) is an effective treatment for essential tremor (ET). However, the optimal intracranial target sites remain to be determined.
ObjectiveTo assess MRgFUS induced sequential lesions in (anterior-VIM/VOP nuclei) the thalamus and then posterior subthalamic area (PSA) performed during the same procedure for alleviating ET.
Methods14 patients had unilateral MRgFUS lesions placed in anterior-VIM/VOP then PSA. Bain-Findley Spirals were collected during MRgFUS from the treated arm (BFS-TA) and throughout the study from the treated (BFS-TA) and non-treated (BFS-NTA) arms and scored by blinded assessors. Although, the primary outcome was change in the BFS-TA from baseline to 12 months we have highlighted the 24 month data.
Secondary outcomes included the Clinical Rating Scale for Tremor (CRST), Quality of Life for ET (QUEST) and PHQ-9 depression scores.
ResultsThe mean improvement in the BFS-TA from baseline to 24 months was 41.1% (p<0.001) whilst BFS-NTA worsened by 8.8% (p<0.001). Intra-operative BFS scores from the targeted arm showed a mean 27.9% (p<0.001) decrease after anterior-VIM/VOP ablation and an additional 30.1% (p<0.001) reduction from post anterior-VIM/VOP to post-PSA ablation.
Mean improvements at 24 month follow-up in the CRST-parts A, B and C were 60.7%, 30.4% and 65.6% respectively and 37.8% in QUEST-tremor score (all p<0.05). Unilateral tremor severity scores decreased in the treated arm (UETTS-TA) 72.9% (p=0.001) and non-treated arm (UETTS-NTA) 30.5% (p=0.003). At 24 months residual adverse effects were slight unsteadiness (n=1) and mild hemi-chorea (n=1).
ConclusionUnilateral anterior-VIM/VOP and PSA MRgFUS significantly diminished contralateral arm tremor with improvements in arm function, tremor related disability and quality of life, with an acceptable adverse event profile. | neurology |
10.1101/2020.12.26.20248864 | Cervical cancer screening uptake in Sub-Saharan Africa: a systematic review and meta-analysis | BackgroundCervical cancer screening and prevention programs have been given considerable attention in high-income countries, while only receiving minimal effort in many African countries. This meta-analytic review aimed to estimate the pooled uptake of cervical cancer screening uptake and identify its predictors in Sub-Saharan Africa.
MethodsPubMed, EMBASE, CINAHL, African Journals Online, Web of Science and SCOPUS electronic databases were searched. All observational studies conducted in Sub-Saharan Africa and published in English language from January 2000 to 2019 were included. The Newcastle-Ottawa Scale was applied to examine methodological quality of the studies. Inverse variance-weighted random-effects model meta-analysis was done to estimate the pooled uptake and odds ratio of predictors with 95% confidence interval. I2 test statistic was used to check between-study heterogeneity, and funnel plot and Eggers regression statistical test were used to check publication bias. To examine the source of heterogeneity, subgroup analysis based on sample size, publication year and geographic distribution of the studies was carried out.
ResultsOf 3,537 studies identified, 29 studies were included with 36,374 women. The uptake of cervical cancer screening in Sub-Saharan Africa was 12.87% (95% CI: 10.20, 15.54; I2= 98.5%). Meta-analysis of seven studies showed that knowledge about cervical cancer increased screening uptake by nearly 5-folds (OR: 4.81; 95% CI: 3.06, 7.54). Other predictors include educational status, age, HIV status, contraceptive use, perceived susceptibility, and awareness about screening locations.
ConclusionCervical screening uptake is low in Sub-Saharan Africa and influenced by several factors. Health outreach and promotion targeting identified predictors are needed to increase uptake of screening service in the region.s
Protocol registrationCRD42017079375 | obstetrics and gynecology |
10.1101/2020.12.28.20248904 | Impact of Discoordinated Care on Healthcare Utilization and Survival in Stage IV Non-Small Cell Lung Cancer Patients | BackgroundCancer patients treatment is often dispersed across multiple physician communities that may not exchange information. We measured the association between this type of discoordinated care and healthcare utilization, cost, and mortality in stage IV non-small cell lung cancer (NSCLC).
MethodsStage IV NSCLC patients [≥]65 years were identified from the Surveillance, Epidemiology, and End Results database attached to Medicare claims. A discoordinated care subgroup was selected using a novel index that approximated how many physician communities each patient encountered. Communities were defined by (1) using claims data to create a nationwide social network of healthcare providers and then (2) dividing that network into communities using cluster label propagation. Associations between discoordinated care and overall survival (OS), cancer-specific survival (CSS), hospitalizations, the burden of diagnostic imaging, and cost were assessed.
ResultsOf the 11,417 patients in our cohort, 5,855 received discoordinated care. Discoordination was associated with younger age, higher socioeconomic status, higher physician density, and lack of a home health aide. Discoordinated care was associated with improved OS and CSS (HR = 0.92, 95% CI 0.88 - 0.95 for OS). However, discoordinated patients also received 32% more MRIs (p = 0.007) and paid $494.02 more for imaging (p = 0.004). There was no association with other kinds of imaging, rates of hospitalization, or other healthcare costs, including total cost.
ConclusionsDiscoordinated care was associated with additional MRIs, but also improved survival. The reason is unclear, but discoordinated patients may be seeking the best care at the expense of continuity.
Key PointsO_ST_ABSQuestionC_ST_ABSHow does dispersing healthcare across multiple physician communities impact healthcare utilization and survival in patients with advanced stage non-small cell lung cancer?
FindingsIn this retrospective cohort study, we found that discoordinated care was associated with increased utilization of MRIs and total cost of imaging. Surprisingly, it was also associated with improved survival.
MeaningCancer patients with dispersed healthcare may be seeking care through a tertiary care center or clinical trial. This may lead to increased healthcare utilization but also improved survival. | oncology |
10.1101/2020.12.27.20248738 | Improving Polygenic Prediction in Ancestrally Diverse Populations | Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genome-wide association studies (GWAS) were predominantly conducted in individuals of European descent, the limited transferability of PRS reduces its clinical value in non-European populations and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although most of them remain under-powered. Here we present a novel PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations. PRS-CSx couples genetic effects across populations via a shared continuous shrinkage prior, enabling more accurate effect size estimation by sharing information between summary statistics and leveraging linkage disequilibrium (LD) diversity across discovery samples, while inheriting computational efficiency and robustness from PRS-CS. We show that PRS-CSx outperforms alternative methods across traits with a wide range of genetic architectures, cross-population genetic overlaps and discovery GWAS sample sizes in simulations, and improves the prediction of quantitative traits and schizophrenia risk in non-European populations. | genetic and genomic medicine |
10.1101/2020.12.27.20248738 | Improving Polygenic Prediction in Ancestrally Diverse Populations | Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genome-wide association studies (GWAS) were predominantly conducted in individuals of European descent, the limited transferability of PRS reduces its clinical value in non-European populations and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although most of them remain under-powered. Here we present a novel PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations. PRS-CSx couples genetic effects across populations via a shared continuous shrinkage prior, enabling more accurate effect size estimation by sharing information between summary statistics and leveraging linkage disequilibrium (LD) diversity across discovery samples, while inheriting computational efficiency and robustness from PRS-CS. We show that PRS-CSx outperforms alternative methods across traits with a wide range of genetic architectures, cross-population genetic overlaps and discovery GWAS sample sizes in simulations, and improves the prediction of quantitative traits and schizophrenia risk in non-European populations. | genetic and genomic medicine |
10.1101/2020.12.28.20248926 | Simulating the impacts of interregional mobility restriction on the spatial spread of COVID-19 in Japan | This study develops a spatial Susceptible-Exposed-Infectious-Recovered (SEIR) model that analyzes the effect of interregional mobility on the spatial spread of the coronavirus disease 2019 (COVID-19) outbreak in Japan. National and local governments have requested that residents refrain from traveling between 47 prefectures during the state of emergency. However, the extent to which restricting the interregional mobility prevents infection expansion has not been elucidated. Our spatial SEIR model describes the spatial spread pattern of COVID-19 when people commute to a prefecture where they work or study during the daytime and return to their residential prefecture at night. We assume that people are exposed to infection risk during their daytime activities. According to our simulation results, interregional mobility restriction can prevent geographical expansion of the infection. However, in prefectures with many infectious individuals, residents are exposed to higher infection risk when their mobility is restricted. Our simulation results also show that interregional mobility restriction plays a limited role in reducing the national total number of infected individuals. | health policy |
10.1101/2020.12.28.20248924 | A study of metabolic syndrome in patients of HIV on ART in India | Metabolic syndrome is a risk factor for cardiovascular disease. With improvement in therapy for HIV, morbidity related to metabolic syndrome becomes a focus of interest. Change in nutritional status and introduction of newer regimens of ART are changing the impact of metabolic syndrome on patients of HIV. Few studies in recent times from developing countries have addressed this question. This is a cross sectional study to study the prevalence of Metabolic Syndrome in patients of HIV on ART from clinics in a tertiary care hospital in India. Data from 1208 patients of HIV on ART was analyzed and metabolic syndrome was seen in 257(21.3%) patients.
The high prevalence of metabolic syndrome in patients of HIV in India found in this study gives an insight on the morbidity of noncommunicable diseases in patients with HIV in India in recent times. | hiv aids |
10.1101/2020.12.28.20248922 | The Ugandan Severe Acute Respiratory Syndrome -Coronavirus 2 (SARS-CoV-2) Model: A Data Driven Approach to Estimate Risk | ObjectivesThe first case of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) was identified on March 21, 2020, in Uganda. The number of cases increased to 8,287 by September 30, 2020. By May throughout June, most of the cases were predominantly imported cases of truck drivers from neighbouring countries. Uganda responded with various restrictions and interventions including lockdown, physical distancing, hand hygiene, and use of face masks in public, to control the growth rate of the outbreak. By end of September 2020, Uganda had transitioned into community transmissions and most of the reported cases were locals contacts and alerts. This study assessed risks associated with SARS-CoV-2 in Uganda, and presents estimates of the reproduction ratio in real time. An optimal control analysis was performed to determine how long the current mitigation measures such as controlling the exposure in communities, rapid detection, confirmation and contact tracing, partial lockdown of the vulnerable groups and control at the porous boarders, could be implemented and at what cost.
MethodsThe daily confirmed cases of SARS-CoV-2 in Uganda were extracted from publicly available sources. Using the data, relative risks for age, gender, and geographical location were determined. Four approaches were used to forecast SARS-CoV-2 in Uganda namely linear exponential, nonlinear exponential, logistic and a deterministic model. The discrete logistic model and the next generation matrix method were used to estimate the effective reproduction number.
ResultsResults showed that women were at a higher risk of acquiring SARS-CoV-2 than the men, and the population attributable risk of SARS-CoV-2 to women was 42.22%. Most of the women affected by SARS-CoV-2 were likely contacts of cargo truck drivers at the boarders, where high infection rates were reported. Although most deaths in Uganda were in the age group of 60-69, the highest case fatality rate per 1000 was attributable the age group of 80-89, followed by 70-79. Geographically, Amuru had the highest relative risk compared to the national risk to SARS-CoV-2. For the case of mitigation scenarios, washing hands with 70% com pliance and regular hand washing of 6 times a day, was the most effective and sustainable to reduce SARS- CoV-2 exposure. This was followed by public wearing of face masks if at least 60% of the population complied, and physical distancing by 60% of the population. If schools, bars and churches were opened without compliance, i.e., no distancing, no handwashing and no public wearing of face masks, to mitigation measures, the highest incidence was observed, leading to a big replacement number. If mitigation measures are not followed by the population, then there will be high incidences and prevalence of the virus in the population. | infectious diseases |
10.1101/2020.12.27.20248876 | The evaluation of a newly developed antigen test (QuickNavi™-COVID19 Ag) for SARS-CoV-2: A prospective observational study in Japan | IntroductionSeveral antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide, but their clinical utility has not been well established. In this study, we evaluated the analytical and clinical performance of QuickNavi-COVID19 Ag, a newly developed antigen test in Japan.
MethodsThis prospective observational study was conducted at a PCR center between October 7 and December 5, 2020. The included patients were referred from a local public health center and 89 primary care facilities. We simultaneously obtained two nasopharyngeal samples with flocked swabs; one was used for the antigen test and the other for real-time reverse transcription PCR (RT-PCR). Using the results of real-time RT-PCR as a reference, the performance of the antigen test was evaluated.
ResultsA total of 1186 patients were included in this study, and the real-time RT-PCR detected SARS-CoV-2 in 105 (8.9%). Of these 105 patients, 33 (31.4%) were asymptomatic. The antigen test provided a 98.8% (95% confident interval [CI]: 98.0%-99.4%) concordance rate with real-time RT-PCR, along with a sensitivity of 86.7% (95% CI: 78.6%-92.5%) and a specificity of 100% (95% CI: 99.7%-100%). False-negatives were observed in 14 patients, 8 of whom were asymptomatic and had a low viral load (cycle threshold (Ct) >30). In symptomatic patients, the sensitivity was 91.7% (95% CI: 82.7%-96.9%).
ConclusionQuickNavi-COVID19 Ag showed high specificity and sufficient sensitivity for the detection of SARS-CoV-2. This test is a promising potential diagnostic modality especially in symptomatic patients. | infectious diseases |
10.1101/2020.12.27.20248876 | The evaluation of a newly developed antigen test (QuickNavi™-COVID19 Ag) for SARS-CoV-2: A prospective observational study in Japan | IntroductionSeveral antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide, but their clinical utility has not been well established. In this study, we evaluated the analytical and clinical performance of QuickNavi-COVID19 Ag, a newly developed antigen test in Japan.
MethodsThis prospective observational study was conducted at a PCR center between October 7 and December 5, 2020. The included patients were referred from a local public health center and 89 primary care facilities. We simultaneously obtained two nasopharyngeal samples with flocked swabs; one was used for the antigen test and the other for real-time reverse transcription PCR (RT-PCR). Using the results of real-time RT-PCR as a reference, the performance of the antigen test was evaluated.
ResultsA total of 1186 patients were included in this study, and the real-time RT-PCR detected SARS-CoV-2 in 105 (8.9%). Of these 105 patients, 33 (31.4%) were asymptomatic. The antigen test provided a 98.8% (95% confident interval [CI]: 98.0%-99.4%) concordance rate with real-time RT-PCR, along with a sensitivity of 86.7% (95% CI: 78.6%-92.5%) and a specificity of 100% (95% CI: 99.7%-100%). False-negatives were observed in 14 patients, 8 of whom were asymptomatic and had a low viral load (cycle threshold (Ct) >30). In symptomatic patients, the sensitivity was 91.7% (95% CI: 82.7%-96.9%).
ConclusionQuickNavi-COVID19 Ag showed high specificity and sufficient sensitivity for the detection of SARS-CoV-2. This test is a promising potential diagnostic modality especially in symptomatic patients. | infectious diseases |
10.1101/2020.12.27.20248905 | Probability that an infection like Covid-19 stops without reaching herd immunity, calculated with a stochastic agent-based model. | The spread of an infection is simulated with a stochastic agent-based model. In a certain range of R0 values, the infection either rapidly comes to halt or a large proportion of the population is infected until herd immunity is achieved. Which of these two possibilities actually occurs is random. The probability of each case is determined quasi-empirically. This stochastic phenomenon may explain unexpected infection trajectories. | epidemiology |
10.1101/2020.12.26.20248883 | Covid-19, Lockdowns and Motor Vehicle Collisions: Empirical Evidence from Greece | Reduced mobility during Covid-19 lockdowns means fewer vehicles at risk of collision, but also an opportunity to speed on empty streets. Other collision risk factors that have changed during the pandemic include alcohol consumption, sleeping patterns, distraction, unemployment and economic uncertainty. Evidence on the impact of the Covid-19 pandemic on motor vehicle collisions is scarce, as such statistics are often released with a delay. The objective of this paper is to examine the impact of the first wave of the pandemic and the first lockdown on motor vehicle collisions and associated injuries and deaths in Greece. Using monthly data at the regional unit level, I provide descriptive evidence and subsequently follow a difference-in-difference econometric approach, comparing trends in 2020 to those of the previous five years while controlling for unemployment and petrol prices. I found a steep decline in collisions, injuries and deaths compared to what would have been otherwise expected. In March and April 2020, there were about 1,226 fewer collisions, 72 fewer deaths, 40 fewer serious injuries and 1,426 fewer minor injuries compared to what would have been expected in the absence of the pandemic. | public and global health |
10.1101/2020.12.26.20248883 | Covid-19, Lockdowns and Motor Vehicle Collisions: Empirical Evidence from Greece | Reduced mobility during Covid-19 lockdowns means fewer vehicles at risk of collision, but also an opportunity to speed on empty streets. Other collision risk factors that have changed during the pandemic include alcohol consumption, sleeping patterns, distraction, unemployment and economic uncertainty. Evidence on the impact of the Covid-19 pandemic on motor vehicle collisions is scarce, as such statistics are often released with a delay. The objective of this paper is to examine the impact of the first wave of the pandemic and the first lockdown on motor vehicle collisions and associated injuries and deaths in Greece. Using monthly data at the regional unit level, I provide descriptive evidence and subsequently follow a difference-in-difference econometric approach, comparing trends in 2020 to those of the previous five years while controlling for unemployment and petrol prices. I found a steep decline in collisions, injuries and deaths compared to what would have been otherwise expected. In March and April 2020, there were about 1,226 fewer collisions, 72 fewer deaths, 40 fewer serious injuries and 1,426 fewer minor injuries compared to what would have been expected in the absence of the pandemic. | public and global health |
10.1101/2020.12.26.20248865 | Non-medical COVID-19-related personal impact in medical ecological perspective: A global multileveled, mixed method study | BackgroundThe COVID-19 pandemic has led to widespread public health measures to reduce transmission, morbidity, and mortality attributed to the SARS-CoV-2 virus. While much research and focus surrounds COVID-19 vaccine development, testing, and supportive management, little is known about the determinants of non-medical, personal impact of COVID-19 prevention policies. We aimed to understand determinants of non-medical COVID-19 impact and to account for its multileveled, intersectional nature of associations.
MethodsThis cross-sectional, multi-level, convergent mixed-methods study assessed a range of beliefs, practices, and experiences relating to COVID-19. We recruited a global sample (n=7,411) using both Facebook and Amazon mTURK platforms. We constructed a novel data-driven non-medical COVID-19 Impact Score and four subcomponents ("Personal Action," "Supply-related," "Cancellations," and "Livelihood" impacts). We used generalized estimating equation models with identity link functions to determine concomitant association of individual, household, and country-level variables on the impact scores. We also classified 20,015 qualitative excerpts from 6859 respondents using an 80-code codebook.
ResultsTotal and component impact scores varied significantly by region with Asia, Africa, and Latin America and the Caribbean observing the highest impact scores. Multilevel modeling indicated that individual-level sociocultural variables accounted for much of this variation with COVID-related worry, knowledge, struggles in accessing food and supplies, and worsening mental health most strongly associated with non-medical impact. Family responsibilities, personal COVID medical experience, and health locus of control - in addition to country-level variables reflecting social and health challenge - were also significantly and independently associated with non-medical impact.
DiscussionNon-medical personal impact of COVID-19 affects most people internationally, largely in response to shutdowns, implementing prevention requirements, and through economic consequences. In the context where most of the worlds population does not have direct medical experience with COVID-19, this phenomena of non-medical impact is profound, and likely impacts sustainability of public health interventions aimed at containing COVID-19. | public and global health |
10.1101/2020.12.27.20248913 | Tumor Suppressor Immune Gene Therapy to Reverse Immunotherapy Resistance | BackgroundWhile immune checkpoint inhibitors are becoming a standard of care for multiple types of cancer, the majority of patients do not respond to this form of immunotherapy. New approaches are required overcome resistance to immunotherapies.
MethodsWe investigated the effects of adenoviral p53 (Ad-p53) gene therapy in combination with immune checkpoint inhibitors and selective IL2 or IL15 CD122/132 agonists in the aggressive B16F10 tumor model resistant to immunotherapies. To assess potential mechanisms action, pre and post Ad-p53 treatment biopsies were evaluated for changes in gene expression profiles by Nanostring IO 360 assays.
ResultsSubstantial synergy of "triplet" Ad-p53 + CD122/132 + anti-PD-1 therapy resulted in potential curative effects associated with complete tumor remissions of both primary and contralateral tumors. Interestingly, contralateral tumors which were not injected with Ad-p53 showed robust abscopal effects resulting in statistically significant decreases in tumor size and increased survival (p<0.001). None of the monotherapies or doublet treatments induced complete tumor regressions. Ad-p53 treatment increased Type I Interferon, CD8+ T cell, immuno-proteosome antigen presentation and tumor inflammation gene signatures. Ad-p53 treatment also decreased immune suppressive TGF-beta, beta-catenin, macrophage, and endothelium gene signatures, which may contribute to enhanced immune checkpoint inhibitor (CPI) efficacy. Unexpectedly, a number of previously unidentified, strongly p53 down regulated genes associated with stromal pathways and IL10 expression identified novel anti-cancer therapeutic applications.
ConclusionsThese results imply the ability of Ad-p53 to induce efficacious local and systemic anti-tumor immune responses with the potential to reverse resistance to immune checkpoint inhibitor therapy when combined with CD122/132 agonists and immune checkpoint blockade. Our findings further imply that Ad-p53 has multiple complimentary immune mechanisms of action which support future clinical evaluation of triplet Ad-p53, CD122/132 agonist and immune checkpoint inhibitor combination treatment. | oncology |
10.1101/2020.12.26.20248062 | A phase I/II trial to treat massive Africanized honeybee (Apis mellifera) stings using the new apilic antivenom | Safety, optimal minimum dose, and, preliminary effectiveness of a new generation Africanized honeybees (Apis mellifera) antivenom (AAV) were evaluated. A phase I/II, multicenter, non- randomized, single-arm clinical trial involving 20 participants showing multiple stings were studied. Participants have received either 2 to 10 vials of AAV based on the stings number together with a predefined adjuvant, symptomatic, and complementary treatment schedule. The primary safety endpoint was the presence of early adverse reactions within the first 24 hours after treatment. Preliminary efficacy through clinical evolution, including laboratory tests, was assessed at baseline and over the following four weeks. ELISA assays and mass spectrometry estimated the venom pharmacokinetics before, during, and after treatment. Twenty adult participants, 13 (65%) males, and 7 (35%) females, with a median age of 44 years and a mean body surface of 1.92 m2 (median = 1.93 m2) were recruited. The median number of stings was 52.5 ranging from 7 to more than 2,000. Envenoming severity was classified as 80% mild, 15% moderate, and 5% severe. According to the protocol, 16 (80%) participants received two AAV vials, 3 (15%) six vials, and one (5%) 10 vials. There was no discontinuation of the treatment due to acute adverse events and there were no late adverse reactions. Two patients showed mild adverse events with only transient itchy skin and erythroderma. All participants completed the infusion within two hours and there was no loss of follow-up after discharge. ELISA assays showed venom concentrations varying between 0.25 ng/mL and 1.479 ng/mL prior to treatment. Venom levels decreased in all cases during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and without symptoms, the venom levels increased again during outpatient care 10 days after discharge. Mass spectrometry showed melittin in eight participants 30 days after the treatment. Considering the promising safety results of the investigational product for the treatment of massive Africanized honeybee attacks, added to efficacy in clinical improvement and immediate decrease in blood venom level, the AAV has shown to be safe for human use.
Trial registrationUniversal Trial Number (UTN): U1111-1160-7011, Register Number: RBR-3fthf8 (http://www.ensaiosclinicos.gov.br/rg/RBR-3fthf8/). | emergency medicine |
10.1101/2020.12.26.20248878 | Direct detection of SARS-CoV-2 RNA using high-contrast pH-sensitive dyes | The worldwide COVID-19 pandemic has had devastating effects on health, healthcare infrastructure, social structure, and economics. One of the limiting factors in containing the spread of this virus has been the lack of widespread availability of fast, inexpensive, and reliable methods for testing of individuals. Frequent screening for infected and often asymptomatic people is a cornerstone of pandemic management plans. Here, we introduce two pH sensitive LAMPshade dyes as novel readouts in an isothermal RT-LAMP amplification assay for SARS-CoV-2 RNA. The resulting JaneliaLAMP (jLAMP) assay is robust, simple, inexpensive, has low technical requirements and we describe its use and performance in direct testing of contrived and clinical samples without RNA extraction. | infectious diseases |
10.1101/2020.12.26.20248878 | Direct detection of SARS-CoV-2 RNA using high-contrast pH-sensitive dyes | The worldwide COVID-19 pandemic has had devastating effects on health, healthcare infrastructure, social structure, and economics. One of the limiting factors in containing the spread of this virus has been the lack of widespread availability of fast, inexpensive, and reliable methods for testing of individuals. Frequent screening for infected and often asymptomatic people is a cornerstone of pandemic management plans. Here, we introduce two pH sensitive LAMPshade dyes as novel readouts in an isothermal RT-LAMP amplification assay for SARS-CoV-2 RNA. The resulting JaneliaLAMP (jLAMP) assay is robust, simple, inexpensive, has low technical requirements and we describe its use and performance in direct testing of contrived and clinical samples without RNA extraction. | infectious diseases |
10.1101/2020.12.28.20248943 | The Experience of Care Partners of Patients with Parkinsonism and Psychosis | BackgroundParkinsons disease psychosis (PDP) has a major impact on quality of life and care partner burden; however, little is known about the lived experiences of care partners in managing PDP.
ObjectiveTo understand how care partners of individuals with PDP experience their role and articulate their needs related to psychosis.
MethodsThis was a qualitative study of semi-structured telephone interviews. Recruitment was conducted online via the clinical study matching tool, Fox Trial Finder; study activities took place remotely via telephone interviews. Transcripts of the phone interviews were analyzed by grounded theory methods, and a codebook of key themes that emerged from the analysis was developed.
ResultsNine care partners (all female) were interviewed. Discussion topics in the codebook included (1) care partner burden and guilt; (2) communication with medical professionals; (3) coping strategies; (4) emotional reactions of the care partner to psychosis; (5) sources of knowledge about PD psychosis; (6) attitudes towards medications for PDP; (7) strategies to care for loved ones with psychosis; (8) psychosis triggers.
ConclusionsThis qualitative analysis uncovers important aspects of the care partner experience, including challenges in navigating the medical system and communicating with professionals. Providers treating patients with PDP should be aware of these constraints and provide added support for strained care partners. | neurology |
10.1101/2020.12.28.20248949 | Histopathological Profile of Cervical Biopsies in Northern Malawi: A Retrospective Study | ObjectivesThis study was carried out to determine the histopathological profile of cervical biopsies in a public tertiary hospital in Mzuzu, northern region of Malawi.
SettingA public tertiary hospital in Mzuzu, northern region of Malawi
ParticipantsThis was a retrospective study of all cervical biopsy specimen reports received in a public tertiary hospital in northern Malawi over a period of 5 years from July 2013-June 2018. Eleven reports which had missing demographic and clinical data or had inconclusive results were excluded. Demographic, clinical and histopathological data was obtained from original histology reports.
ResultsA total of 500 cervical biopsy reports were reviewed during the study period. The mean age of the patients was 41.99{+/-}12.5. Age ranged from 15 to 80 years. Cervicitis accounted for 46.0% (n=162) of the total nonmalignant lesions seen, followed by cervical intraepithelial neoplasm (CIN), at 24.4% (n=86) and endocervical polyp, at 20.5% (n=72). Squamous cell carcinoma (SCC) accounted for 15.6% (n=78) of the total cervical biopsies studied and 85.7% of all total malignant lesions. All malignant tumours had HIV.
ConclusionOur study shows that cervicitis and squamous cell carcinoma were most common among nonmalignant and malignant cervical biopsies respectively. Since the frequency of cervical cancer is high, there is need to have well detailed national policies to be put in place to increase detection of pre-invasive lesions in order to reduce the prevalence of cervical cancer.
Strengths and limitation of this study StrengthsThis paper has shown
O_LIThe need for well detailed national policies to be put in place to increase detection of pre-invasive lesions, which in turn will decrease the frequency of cervical cancer in the country.
C_LIO_LIThe importance of intensifying cervical cancer screening programmes among women and provision of long term ART to the HIV infected which may offer an opportunity for appropriate interventions to reduce morbidity, mortality and reduce complications among these women.
C_LI
LimitationsO_LIThis study used available programme health facility data and histopathological reports on cervical cancer which has its own limitations, such as incompleteness and bias in the sense that information is obtained only from people who came to the facility and underwent biopsy, leaving out those that did not seek medical care and or were not biopsied and therefore cannot be generalized to the general population.
C_LIO_LIThe study is a single-hospital-based review and as such inadequate to draw conclusions, but it does shed some light on pathological pattern of cervical cancer in Malawi.
C_LI | oncology |
10.1101/2020.12.29.20248869 | High levels of plasminogen activator inhibitor-1, tissue plasminogen activator and fibrinogen in patients with severe COVID-19 | We measured plasma levels of fibrinogen, plasminogen, tissue plasminogen activator (t-PA) and plasminogen activation inhibitor 1 (PAI-1) in blood from 37 patients with severe coronavirus disease-19 (COVID-19) and 23 controls. PAI-1, t-PA and fibrinogen levels were significantly higher in the COVID-19 group. Increased levels of PAI-1 likely result in lower plasmin activity and hence decreased fibrinolysis. These observations provide a partial explanation for the fibrin- mediated increase in blood viscosity and hypercoagulability that has previously been observed in COVID-19. Our data suggest that t-PA administration may be problematic, but that other interventions designed to enhance fibrinolysis might prove useful in the treatment of the coagulopathy that is often associated with severe COVID-19. | hematology |
10.1101/2020.12.29.20248975 | COVID-19: Can early home treatment with Azithromycin alone or with Zinc help prevent hospitalisation, death, and long-COVID-19? A review | IntroductionThe effects of the SARS-CoV-2 pandemic continues to disrupt health systems worldwide, leading to population lockdowns in many countries. Preventing hospitalisation, death and long-COVID-19 with repurposed drugs remains a priority. Hydroxychloroquine (HCQ) and azithromycin (AZM) are the most commonly used in ambulatory care, with divergent results. With the aim of decentralizing early treatment to family practitioners, we addressed the question: Can early home treatment with AZM alone or with zinc help prevent hospitalisation, death, and long-COVID-19?
MethodologyWe conducted a scoping review of articles published from 31st December 2019 to 5th November 2020 in Pubmed, Google Scholar, MedRxiv, and BioRxiv databases, and a review of undergoing clinical trials published in the Clinicaltrial.gov database.
ResultsMany studies report on outpatient treatment with a combination of AZM + HCQ versus AZM alone, and few studies propose the addition of Zinc (Zn) to AZM. In addition, we identified 5 clinical trials currently recruiting individuals for early outpatient treatment with AZM. However, we failed in identifying any study or clinical trial conducted with family practitioners responding to our question.
DiscussionThe antiviral, anti-inflammatory, immunomodulatory benefits of AZM + Zn make this drugs combination a good candidate therapy to treat flu-like-COVID-19 and atypical pneumoniae. The antibacterial action of AZM can also help disrupting the bacteria/virus cooperation that is poorly documented. Considering pros and cons of macrolide use (including antimicrobial resistance), we call for early use of this therapy by family practitioners for home treatment of individuals presenting mild or moderate symptoms under rigorous scientific guidance to prevent hospitalisation, death and long-COVID. | infectious diseases |
10.1101/2020.12.29.20248975 | COVID-19: Can early home treatment with Azithromycin alone or with Zinc help prevent hospitalisation, death, and long-COVID-19? A review | IntroductionThe effects of the SARS-CoV-2 pandemic continues to disrupt health systems worldwide, leading to population lockdowns in many countries. Preventing hospitalisation, death and long-COVID-19 with repurposed drugs remains a priority. Hydroxychloroquine (HCQ) and azithromycin (AZM) are the most commonly used in ambulatory care, with divergent results. With the aim of decentralizing early treatment to family practitioners, we addressed the question: Can early home treatment with AZM alone or with zinc help prevent hospitalisation, death, and long-COVID-19?
MethodologyWe conducted a scoping review of articles published from 31st December 2019 to 5th November 2020 in Pubmed, Google Scholar, MedRxiv, and BioRxiv databases, and a review of undergoing clinical trials published in the Clinicaltrial.gov database.
ResultsMany studies report on outpatient treatment with a combination of AZM + HCQ versus AZM alone, and few studies propose the addition of Zinc (Zn) to AZM. In addition, we identified 5 clinical trials currently recruiting individuals for early outpatient treatment with AZM. However, we failed in identifying any study or clinical trial conducted with family practitioners responding to our question.
DiscussionThe antiviral, anti-inflammatory, immunomodulatory benefits of AZM + Zn make this drugs combination a good candidate therapy to treat flu-like-COVID-19 and atypical pneumoniae. The antibacterial action of AZM can also help disrupting the bacteria/virus cooperation that is poorly documented. Considering pros and cons of macrolide use (including antimicrobial resistance), we call for early use of this therapy by family practitioners for home treatment of individuals presenting mild or moderate symptoms under rigorous scientific guidance to prevent hospitalisation, death and long-COVID. | infectious diseases |
10.1101/2020.12.28.20248967 | Postlockdown Dynamics of COVID-19 in New York, Florida, Arizona, and Wisconsin | The COVID-19 pandemic is widely studied as it continues to threaten many populations of people especially in the USA, the leading country in terms of both deaths and cases. Although vaccines are being distributed, control and mitigation strategies must still be properly enforced. More and more reports show that the spread of COVID-19 involves infected individuals first passing through a pre-symptomatic infectious stage in addition to the incubation period and that many of the infectious individuals are asymptomatic. In this study, we design and use a mathematical model to primarily address the question of who are the main drivers of COVID-19 - the symptomatic infectious or the pre-symptomatic and asymptomatic infectious in the states of Florida, Arizona, New York, Wisconsin and the entire United States. We emphasize the benefit of lockdown by showing that for all four states, earlier and later lockdown dates decrease the number of cumulative deaths. This benefit of lockdown is also evidenced by the decrease in the infectious cases for Arizona and the entire US when lockdown is implemented earlier. When comparing the influence of the symptomatic infectious versus the pre-sympomatic/asymptomatic infectious, it is shown that, in general, the larger contribution comes from the latter group. This is seen from several perspectives, as follows: (1) in terms of daily cases, (2) in terms of daily cases when the influence of one group is targeted over the other by setting the effective contact rate(s) for the non-targeted group to zero, and (3) in terms of cumulative cases and deaths for the US and Arizona when the influence of one group is targeted over the other by setting the effective contact rate(s) for the non-targeted group to zero. The consequences of the difference in the contributions of the two infectious groups is simulated in terms of testing and these simulations show that an increase in testing and isolating for the pre-symptomatic and asymptomatic infectious group has more impact than an increase in testing for the symptomatic infectious. For example, for the entire US, a 50% increase in testing for the pre-symptomatic and asymptomatic infectious group results in a 25% decrease in deaths as opposed to a lower 6% decrease in deaths when a 50% increase in testing rate for the symptomatic infectious is implemented. We also see that if the testing for infectious symptomatic is kept at the baseline value and the testing for the pre-symptomatic and asymptomatic is increased from 0.2 to 0.25, then the control reproduction number falls below 1. On the other hand, to get even close to such a result when keeping the pre-symptomatic and asymptomatic at baseline fitted values, the symptomatic infectious testing rate must be increased considerably more - from 0.4 to 1.7. Lastly, we use our model to simulate an implementation of a natural herd immunity strategy for the entire U.S. and for the state of Wisconsin (the most recent epicenter) and we find that such a strategy requires a significant number of deaths and as such is questionable in terms of success. We conclude with a brief summary of our results and some implications regarding COVID-19 control and mitigation strategies. | infectious diseases |
10.1101/2020.12.28.20248967 | Postlockdown Dynamics of COVID-19 in New York, Florida, Arizona, and Wisconsin | The COVID-19 pandemic is widely studied as it continues to threaten many populations of people especially in the USA, the leading country in terms of both deaths and cases. Although vaccines are being distributed, control and mitigation strategies must still be properly enforced. More and more reports show that the spread of COVID-19 involves infected individuals first passing through a pre-symptomatic infectious stage in addition to the incubation period and that many of the infectious individuals are asymptomatic. In this study, we design and use a mathematical model to primarily address the question of who are the main drivers of COVID-19 - the symptomatic infectious or the pre-symptomatic and asymptomatic infectious in the states of Florida, Arizona, New York, Wisconsin and the entire United States. We emphasize the benefit of lockdown by showing that for all four states, earlier and later lockdown dates decrease the number of cumulative deaths. This benefit of lockdown is also evidenced by the decrease in the infectious cases for Arizona and the entire US when lockdown is implemented earlier. When comparing the influence of the symptomatic infectious versus the pre-sympomatic/asymptomatic infectious, it is shown that, in general, the larger contribution comes from the latter group. This is seen from several perspectives, as follows: (1) in terms of daily cases, (2) in terms of daily cases when the influence of one group is targeted over the other by setting the effective contact rate(s) for the non-targeted group to zero, and (3) in terms of cumulative cases and deaths for the US and Arizona when the influence of one group is targeted over the other by setting the effective contact rate(s) for the non-targeted group to zero. The consequences of the difference in the contributions of the two infectious groups is simulated in terms of testing and these simulations show that an increase in testing and isolating for the pre-symptomatic and asymptomatic infectious group has more impact than an increase in testing for the symptomatic infectious. For example, for the entire US, a 50% increase in testing for the pre-symptomatic and asymptomatic infectious group results in a 25% decrease in deaths as opposed to a lower 6% decrease in deaths when a 50% increase in testing rate for the symptomatic infectious is implemented. We also see that if the testing for infectious symptomatic is kept at the baseline value and the testing for the pre-symptomatic and asymptomatic is increased from 0.2 to 0.25, then the control reproduction number falls below 1. On the other hand, to get even close to such a result when keeping the pre-symptomatic and asymptomatic at baseline fitted values, the symptomatic infectious testing rate must be increased considerably more - from 0.4 to 1.7. Lastly, we use our model to simulate an implementation of a natural herd immunity strategy for the entire U.S. and for the state of Wisconsin (the most recent epicenter) and we find that such a strategy requires a significant number of deaths and as such is questionable in terms of success. We conclude with a brief summary of our results and some implications regarding COVID-19 control and mitigation strategies. | infectious diseases |
10.1101/2020.12.28.20248967 | Postlockdown Dynamics of COVID-19 in New York, Florida, Arizona, and Wisconsin | The COVID-19 pandemic is widely studied as it continues to threaten many populations of people especially in the USA, the leading country in terms of both deaths and cases. Although vaccines are being distributed, control and mitigation strategies must still be properly enforced. More and more reports show that the spread of COVID-19 involves infected individuals first passing through a pre-symptomatic infectious stage in addition to the incubation period and that many of the infectious individuals are asymptomatic. In this study, we design and use a mathematical model to primarily address the question of who are the main drivers of COVID-19 - the symptomatic infectious or the pre-symptomatic and asymptomatic infectious in the states of Florida, Arizona, New York, Wisconsin and the entire United States. We emphasize the benefit of lockdown by showing that for all four states, earlier and later lockdown dates decrease the number of cumulative deaths. This benefit of lockdown is also evidenced by the decrease in the infectious cases for Arizona and the entire US when lockdown is implemented earlier. When comparing the influence of the symptomatic infectious versus the pre-sympomatic/asymptomatic infectious, it is shown that, in general, the larger contribution comes from the latter group. This is seen from several perspectives, as follows: (1) in terms of daily cases, (2) in terms of daily cases when the influence of one group is targeted over the other by setting the effective contact rate(s) for the non-targeted group to zero, and (3) in terms of cumulative cases and deaths for the US and Arizona when the influence of one group is targeted over the other by setting the effective contact rate(s) for the non-targeted group to zero. The consequences of the difference in the contributions of the two infectious groups is simulated in terms of testing and these simulations show that an increase in testing and isolating for the pre-symptomatic and asymptomatic infectious group has more impact than an increase in testing for the symptomatic infectious. For example, for the entire US, a 50% increase in testing for the pre-symptomatic and asymptomatic infectious group results in a 25% decrease in deaths as opposed to a lower 6% decrease in deaths when a 50% increase in testing rate for the symptomatic infectious is implemented. We also see that if the testing for infectious symptomatic is kept at the baseline value and the testing for the pre-symptomatic and asymptomatic is increased from 0.2 to 0.25, then the control reproduction number falls below 1. On the other hand, to get even close to such a result when keeping the pre-symptomatic and asymptomatic at baseline fitted values, the symptomatic infectious testing rate must be increased considerably more - from 0.4 to 1.7. Lastly, we use our model to simulate an implementation of a natural herd immunity strategy for the entire U.S. and for the state of Wisconsin (the most recent epicenter) and we find that such a strategy requires a significant number of deaths and as such is questionable in terms of success. We conclude with a brief summary of our results and some implications regarding COVID-19 control and mitigation strategies. | infectious diseases |
10.1101/2020.12.28.20248663 | Global surveillance of potential antiviral drug resistance in SARS-CoV-2: proof of concept focussing on the RNA-dependent RNA polymerase | Antiviral treatments for COVID-19 have involved many repurposed drugs. Currently, SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors with debated clinical impact. Among these, remdesivir has been conditionally approved for the treatment of COVID-19 patients. Although the emergence of antiviral resistance, an indirect proxy for antiviral efficacy, poses a considerable healthcare threat, an evolutionary perspective on emerging resistant mutants is still lacking.
Here we show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare, and unlikely to lead to viral fitness loss.
In more than 56,000 viral genomes from 105 countries dating from December 2019 to July 2020 we found negative selective pressure affecting nsp12 (Tajimas D = -2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Those affected known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations found globally, in silico structural models show that this rarely implies loss of stability in RdRp. No potential escape mutation were found in our local cohort of remdesivir treated patients from the first wave (n=8). Our results indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. Our study could be the starting point of a larger monitoring effort of drug resistance throughout the COVID-19 pandemic. We recommend the application of repetitive genome sequencing of SARS-CoV-2 from patients treated with antivirals to provide early insights into the evolution or antiviral resistance. | infectious diseases |
10.1101/2020.12.28.20248807 | Autoimmunity to the Lung Protective Phospholipid-Binding Protein Annexin A2 Predicts Mortality Among Hospitalized COVID-19 Patients | BackgroundAnnexin A2 is a phospholipid-binding protein involved in fibrinolysis, cell membrane stabilization and repair, and ensuring the integrity of the pulmonary microvasculature. Given the autoantibodies observed in COVID-19 and that Annexin A2 is a known target of antiphospholipid antibodies, we studied autoimmunity directed against Annexin A2 among hospitalized COVID-19 patients.
MethodsWe used ELISA to identify the levels of IgG autoantibodies recognizing Annexin A2 and A5 among 86 hospitalized cases of COVID-19. Using logistic regression, we analyzed the association between anti-Annexin A2 and A5 antibody levels with mortality after adjusting for age, sex, race and key comorbidities.
ResultsWe found higher average levels of anti-Annexin A2 antibodies among hospitalized COVID-19 patients that died when compared with non-critical hospitalized COVID-19 patients (p-value = 0.006) and critically ill COVID-19 patients (p-value = 0.04). No significant differences in anti-Annexin A5 antibody levels were identified. Regression analysis showed that anti-Annexin A2 antibody levels as measured in relative units strongly predicted mortality with an odds ratio of 9.3 (95% CI: 1.9 to 44.6, p=0.005). In contrast, anti-Annexin A5 antibody levels were not associated with higher mortality (95% CI: 0.5 to 15.2, p=0.22).
ConclusionsWe determined that anti-Annexin A2 antibodies were elevated among hospitalized COVID-19 patients and these levels predicted mortality. It is known that inhibition of Annexin A2 induces systemic thrombosis, cell death, and non-cardiogenic pulmonary edema. Autoimmunity to Annexin A2 is a potential mechanism that may explain the key clinical findings of severe COVID-19. | infectious diseases |
10.1101/2020.12.28.20248950 | COVID-19 vaccine hesitancy worldwide: a systematic review of vaccine acceptance rates | IntroductionUtility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic.
AimTo provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide.
MethodsA systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well.
ResultsSurvey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of [≥] 70%.
ConclusionsLow rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.
Graphical Abstract
O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/20248950v1_ufig1.gif" ALT="Figure 1">
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[email protected]@423aa6org.highwire.dtl.DTLVardef@186d8dorg.highwire.dtl.DTLVardef@1c0450e_HPS_FORMAT_FIGEXP M_FIG C_FIG COVID-19 vaccine acceptance rates worldwideFor countries with more than one survey study, the vaccine acceptance rate of the latest survey was used in this graph. The estimates were also based on studies from the general population, except in the following cases were no studies from the general public were found (Australia: parents/guardians; DRC: healthcare workers; Hong Kong: healthcare workers; Malta: healthcare workers). | infectious diseases |
10.1101/2020.12.28.20248552 | COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and may be modified by dexamethasone | We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with ARDS from COVID-19 or other etiologies, or without ARDS. We found no evidence of cytokine storm but instead observed complex host response dysregulation driven by genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone. Compared to other viral ARDS, COVID-19 was characterized by impaired interferon-stimulated gene expression. | intensive care and critical care medicine |
10.1101/2020.12.28.20248556 | Severe bandemia is not associated with increased risk for adverse events in general pediatric emergency department patients | BackgroundThe presence of band cells >10% of the total white blood cell (WBC) count ("bandemia") is often used as an indicator of serious bacterial illness (SBI). Results from studies of bandemia as a predictor of SBI were conflicting and little is known about the relationship between severe bandemia (SB) and clinical outcomes from SBI in children.
ObjectivesIn this retrospective patient-centered study, we hypothesized that SB (band level >20%) is not associated with adverse outcomes in an emergency department (ED) pediatric population.
MethodsMedical records from children between the ages of 2 months and 18 years with SB who presented to a tertiary referral regional hospital were studied. Outcomes were categorized as severe adverse events (SAEs) or moderate adverse events (MAEs). Multivariate logistic regressions were used to assess the association between SB and outcomes.
ResultsWe analyzed 102 patients. Mean age (standard deviation [SD]) was 5.25(0.5) years, 18 (18%) had MAE, 21 (21%) had SAE, and no patients died. Mean band levels were similar between groups: no adverse events [28 (10)] vs. SAE [31 (9)] vs. MAE [27(8)], p=0.64. Multivariate logistic regressions showed SB was not associated with any adverse events (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.9-1.1, p=0.27). Non-normal X-ray (XR) (OR 17, 95% CI 3.3-90, p<0.001) was associated with MAE, while non-normal computerized tomography (CT) scan (OR 15.4, 95% CI 2.2-100+, p=0.002) was associated with SAE.
ConclusionSevere bandemia was not associated with higher odds of adverse events among the general ED pediatric population. Clinicians should base their clinical judgment on the overall context of history, physical examinations, and other laboratory and imaging data. | intensive care and critical care medicine |
10.1101/2020.12.28.20248946 | OASIS+: leveraging machine learning to improve the prognostic accuracy of OASIS severity score for predicting in-hospital mortality | Severity scores assess the acuity of critical illness by penalizing for the deviation of physiologic measurements from normal and aggregating these penalties (also called "weights" or "subscores") into a final score (or probability) for quantifying the severity of critical illness (or the likelihood of in-hospital mortality). Although these simple additive models are human readable and interpretable, their predictive performance needs to be further improved. To address this need, we argue for replacing these simple additive models with models based on state-of-the-art non-linear supervised learning algorithms (e.g., Random Forest (RF) and eXtreme Gradient Boosting (XGB)). Specifically, we present OASIS+, a variant of the Oxford Acute Severity of Illness Score (OASIS) in which an ensemble of 200 decision trees is used to predict in-hospital mortality based on the 10 same clinical variables in OASIS. Using a test set of 9566 admissions extracted from MIMIC-III database, we show that the performance of OASIS can be substantially improved from AUC score of 0.77 to 0.83 using OASIS+. Moreover, we show that OASIS+ has superior performance compared to eight other commonly used severity scoring methods. Our results underscore the potential of improving existing severity scores by using more sophisticated machine learning algorithms (e.g., ensemble of non-linear decision tress) not just via including additional physiologic measurements. | intensive care and critical care medicine |
10.1101/2020.12.29.20248985 | The Silent Pandemic COVID -19 in the Asymptomatic Population | As the COVID-19 pandemic continues to ravage the world there is a great need to understand the dynamics of spread. Currently the seroprevalence of asymptomatic COVID-19 doubles every 3 months, this silent epidemic of new infections may be the main driving force behind the rapid increase in SARS-CoV-2 cases.
Public health official quickly recognized that clinical cases were just the tip of the iceberg. In fact a great deal of the spread was being driven by the asymptomatically infected who continued to go out, socialize and go to work. While seropositivity is an insensitive marker for acute infection it does tell us about the prevalence COVID-19 in the population.
ObjectiveDescribe the seroprevalence of SARS-CoV-2 infection in the United States over time.
MethodologyRepeated convenience samples from a commercial laboratory dedicated to the assessment of life insurance applicants were tested for the presence of antibodies to SARS-CoV-2, in several time periods between May and December of 2020. US census data were used to estimate the population prevalence of seropositivity.
ResultsThe raw seroprevalence in the May-June, September, and December timeframes were 3.0%, 6.6% and 10.4%, respectively. Higher rates were noted in younger vs. older age groups. Total estimated seroprevalence in the US is estimated at 25.7 million cases.
ConclusionsThe seroprevalence of SARS-CoV-2 demonstrates a significantly larger pool of individuals who have contract COVID-19 and recovered, implying a lower case rate of hospitalizations and deaths than have been reported so far. | epidemiology |
10.1101/2020.12.29.20247833 | Characterizing Two Outbreak Waves of COVID-19 in Spain Using Phenomenological Epidemic Modelling | Since the first case reported of SARS-CoV-2 the end of December 2019 in China, the number of cases quickly climbed following an exponential growth trend, demonstrating that a global pandemic is possible. As of December 3, 2020, the total number of cases reported are around 65,527,000 contagions worldwide, and 1,524,000 deaths affecting 218 countries and territories. In this scenario, Spain is one of the countries that has suffered in a hard way, the ongoing epidemic caused by the novel coronavirus SARS-CoV-2, namely COVID-19 disease. In this paper, we present the utilization of phenomenological epidemic models to characterize the two first outbreak waves of COVID-19 in Spain. The study is driven using a two-step phenomenological epidemic approach. First, we use a simple generalized growth model to fit the main parameters at the early epidemic phase; later, we apply our previous finding over a logistic growth model to that characterize both waves completely. The results show that even in the absence of accurate data series, it is possible to characterize the curves of case incidence, and even construct short-term forecast in the near time horizon. | epidemiology |
10.1101/2020.12.28.20248906 | SARS-CoV-2 Variant Under Investigation 202012/01 has more than twofold replicative advantage | The novel SARS-CoV-2 Variant of Concern (VOC)-202012/01 (also known as B.1.1.7), first collected in United Kingdom on September 20, 2020, is a rapidly growing lineage that in January 2021 constituted 86% of all SARS-CoV-2 genomes sequenced in England. The VOC has been detected in 40 out of 46 countries that reported at least 50 genomes in January 2021. We have estimated that the replicative advantage of the VOC is in the range 1.83-2.18 [95% CI: 1.71-2.40] with respect to the 20A.EU1 variant that dominated in England in November 2020, and in range 1.65-1.72 [95% CI: 1.46-2.04] in Wales, Scotland, Denmark, and USA. As the VOC strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. We have estimated growth rates of expanding mutations acquired by the VOC lineage to find that the L18F substitution in spike has initiated a substrain of high replicative advantage in relation to the remaining VOC substrains. The L18F substitution is of significance because it has been found to compromise binding of neutralizing antibodies. Of concern are immune escape mutations acquired by the VOC: E484K, F490S, S494P (in the receptor binding motif of spike) and Q677H, Q675H (in the proximity of the polybasic cleavage site at the S1/S2 boundary). These mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence. | epidemiology |
10.1101/2020.12.28.20248906 | SARS-CoV-2 Variant of Concern 202012/01 has about twofold replicative advantage and acquires concerning mutations | The novel SARS-CoV-2 Variant of Concern (VOC)-202012/01 (also known as B.1.1.7), first collected in United Kingdom on September 20, 2020, is a rapidly growing lineage that in January 2021 constituted 86% of all SARS-CoV-2 genomes sequenced in England. The VOC has been detected in 40 out of 46 countries that reported at least 50 genomes in January 2021. We have estimated that the replicative advantage of the VOC is in the range 1.83-2.18 [95% CI: 1.71-2.40] with respect to the 20A.EU1 variant that dominated in England in November 2020, and in range 1.65-1.72 [95% CI: 1.46-2.04] in Wales, Scotland, Denmark, and USA. As the VOC strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. We have estimated growth rates of expanding mutations acquired by the VOC lineage to find that the L18F substitution in spike has initiated a substrain of high replicative advantage in relation to the remaining VOC substrains. The L18F substitution is of significance because it has been found to compromise binding of neutralizing antibodies. Of concern are immune escape mutations acquired by the VOC: E484K, F490S, S494P (in the receptor binding motif of spike) and Q677H, Q675H (in the proximity of the polybasic cleavage site at the S1/S2 boundary). These mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence. | epidemiology |
10.1101/2020.12.30.20249037 | Primary care during the COVID-19 pandemic - observations and challenges identified through a survey and interviews with community paediatricians: the calm before the storm | BackgroundGlobally, the COVID-19 pandemic has a major impact on healthcare provision. The effects in primary care are understudied.
AimTo document changes in consultation numbers and patient management during the COVID-19 pandemic, and to identify challenges for patient care.
MethodsSurvey of 44 paediatric primary care practices on consultation numbers and patient management changes (response rate 50%), and semi-structured interviews to identify challenges for patient care.
ResultsNumbers of consultations for scheduled developmental examinations remained unchanged compared to the previous year while emergency visits were strongly reduced (mean 87.3 less/week in March-May 2020 compared to 2019, median reduction 55.0%). Children dependent on developmental therapy and with chronic health conditions were identified as patient groups receiving deteriorated care. High patient numbers, including of mildly symptomatic children presenting for health certificates, in combination with increased organisational demands and expected staff outages are priority concerns for the winter.
ConclusionPrimary care paediatricians offered stable service through the early pandemic but expect strained resources for the upcoming winter. Unambiguous guidance on which children should present to primary care and who should be tested would help to allocate resources appropriately, and this guidance needs to consider age group specific issues including high prevalence of respiratory symptoms, dependency on carers and high contact rates. | pediatrics |
10.1101/2020.12.28.20248879 | Experiences with Primary Care in the State of Utah for Gender Diverse People: Surveying the Difficulties in Accessing Healthcare | BackgroundTransgender and non-binary communities continue to be underserved in healthcare. This study seeks to better understand the barriers and difficulties faced by transgender and non-binary patients in accessing primary care and hormone therapy in Utah.
MethodsAn online survey was developed for transgender and non-binary identifying adults and was advertised via social media and the University of Utah Hospitals website.
ResultsThere were 123 respondents from Utah including 39 trans women, 49 trans men, and 35 non-binary individuals. The age ranged from 18-67 (average 30 years), and 93% were Caucasian. The majority (84%) were insured, yet 67% of respondents reported difficulty accessing primary care. Fear of discrimination and being unable to find trans-friendly providers were reported as the two largest barriers. Non-binary respondents reported fear of discrimination as a barrier to primary care at the highest percentage (92%). Nearly 3 in 4 respondents who have hormone therapy reported difficulty paying for it. One in four trans women reported accessing hormones online or from a friend.
ConclusionUtah is currently drastically underequipped to provide for the healthcare needs of transgender and non-binary communities. There needs to be an increase in trans-friendly primary care providers to curb discrimination. More resources and efforts must go into training primary care providers with necessary knowledge to properly serve transgender and non-binary patients. Finally, clear anti-discrimination laws are needed for insurance companies to reduce the financial barrier to transgender health services in Utah. | primary care research |
10.1101/2020.12.30.20249058 | Simple quantitative assessment of the outdoor versus indoor airborne transmission of viruses and covid-19 | In this paper we develop a simple model of the inhaled flow rate of aerosol particles of respiratory origin i.e. that have been exhaled by other humans. A connection is made between the exposure dose and the probability of developing an airborne disease. This allows a simple assessment of the outdoor versus indoor risk of contamination to be made in a variety of meteorological situations. It is shown quantitatively that for most cases, the outdoor risk is orders of magnitude less than the indoor risk and that it can become comparable only for extremely specific meteorological and geographical situations. It sheds a light on various observations of Covid-19 spreading in mountain valleys with temperature inversions while at the same time other areas are much less impacted.
HighlightsO_LIRisk of covid-19 airborne transmission.
C_LIO_LIQuantitative assessment of outdoor versus indoor airborne risk of transmission.
C_LIO_LIMeteorological and geographical influence on covid-19 airborne transmission.
C_LI | public and global health |
10.1101/2020.12.30.20249058 | Simple quantitative assessment of the outdoor versus indoor airborne transmission of viruses and covid-19 | In this paper we develop a simple model of the inhaled flow rate of aerosol particles of respiratory origin i.e. that have been exhaled by other humans. A connection is made between the exposure dose and the probability of developing an airborne disease. This allows a simple assessment of the outdoor versus indoor risk of contamination to be made in a variety of meteorological situations. It is shown quantitatively that for most cases, the outdoor risk is orders of magnitude less than the indoor risk and that it can become comparable only for extremely specific meteorological and geographical situations. It sheds a light on various observations of Covid-19 spreading in mountain valleys with temperature inversions while at the same time other areas are much less impacted.
HighlightsO_LIRisk of covid-19 airborne transmission.
C_LIO_LIQuantitative assessment of outdoor versus indoor airborne risk of transmission.
C_LIO_LIMeteorological and geographical influence on covid-19 airborne transmission.
C_LI | public and global health |
10.1101/2020.12.29.20249002 | Sociodemographic Characteristics of Missing Data in Digital Phenotyping | The ubiquity of smartphones, with their increasingly sophisticated array of sensors, presents an unprecedented opportunity for researchers to collect diverse, temporally-dense data about human behavior while minimizing participant burden. Researchers increasingly make use of smartphone applications for "digital phenotyping," the collection of phone sensor and log data to study the lived experiences of subjects in their natural environments. While digital phenotyping has shown promise in fields such as psychiatry and neuroscience, there are fundamental gaps in our knowledge about data collection and non-collection (i.e., missing data) in smartphone-based digital phenotyping. Here, we show that digital phenotyping presents a viable method of data collection, over long time periods, across diverse study participants with a range of sociodemographic characteristics. We examined accelerometer and GPS sensor data of 211 participants, amounting to 29,500 person-days of observation, using Bayesian hierarchical negative binomial regression. We found that iOS users had higher rates of accelerometer non-collection but lower GPS non-collection than Android users. For GPS data, rates of non-collection did not differ by race/ethnicity, education, age, or gender. For accelerometer data, Black participants had higher rates of non-collection while Asian participants had slightly lower non-collection. For both sensors, non-collection increased by 0.5% to 0.9% per week. These results demonstrate the feasibility of using smartphone-based digital phenotyping across diverse populations, for extended periods of time, and within diverse cohorts. As smartphones become increasingly embedded in everyday life, the insights of this study will help guide the design, planning, and analysis of digital phenotyping studies. | public and global health |
10.1101/2020.12.30.20249010 | Estimation of Daily Reproduction Rates in COVID-19 Outbreak. | (1) BackgroundThe estimation of daily reproduction rates throughout the infectivity period is rarely considered and only their sum Ro is calculated to quantify the level of virulence of an infectious agent;
(2) MethodsWe give the equation of the discrete dynamics of epidemic growth and we obtain an estimation of the daily reproduction rates, by using a technique of deconvolution of the series of observed new cases of Covid-19;
(3) ResultsWe give both simulation results as well as estimations for several countries for the Covid-19 outbreak;
(4) ConclusionsWe discuss the role of the noise on the precision of the estimation and we open on perspectives of forecasting methods to predict the distribution of daily reproduction rates along the infectivity period. | public and global health |
10.1101/2020.12.29.20248977 | Effects of climate conditions, mobility trends, and countermeasures on the COVID-19 outbreak in Japan | BackgroundBefore Olympic and Paralympic Games in Tokyo, whether an audience shall be allowed or not has been a subject of concern in Japan as of early June, 2021. Object: We evaluated effects of professional baseball games with audiences as an example of the large sports events, on COVID-19 infectiousness.
MethodWe regressed the effective reproduction number R(t) on a dummy variable for professional baseball games with audiences as along with temperature, humidity, mobility, and countermeasures. We examined two study periods: those including and excluding before initiation of the games in 2020.
ResultsEstimation results indicate that the period with audiences exhibited significantly lower infectiousness than when audiences were excluded before initiation of the games with audience attendance. However, audiences were found to have a negative but insignificant effect when compared to the period before initiation of the attended games.
Discussion and ConclusionThis study found no clear evidence indicating that big sports events with audiences raise the COVID-19 infectiousness. | public and global health |
10.1101/2020.12.29.20248977 | Effects of climate conditions, mobility trends, and countermeasures on the COVID-19 outbreak in Japan | BackgroundBefore Olympic and Paralympic Games in Tokyo, whether an audience shall be allowed or not has been a subject of concern in Japan as of early June, 2021. Object: We evaluated effects of professional baseball games with audiences as an example of the large sports events, on COVID-19 infectiousness.
MethodWe regressed the effective reproduction number R(t) on a dummy variable for professional baseball games with audiences as along with temperature, humidity, mobility, and countermeasures. We examined two study periods: those including and excluding before initiation of the games in 2020.
ResultsEstimation results indicate that the period with audiences exhibited significantly lower infectiousness than when audiences were excluded before initiation of the games with audience attendance. However, audiences were found to have a negative but insignificant effect when compared to the period before initiation of the attended games.
Discussion and ConclusionThis study found no clear evidence indicating that big sports events with audiences raise the COVID-19 infectiousness. | public and global health |
10.1101/2020.12.29.20248977 | Effects of the second emergency status declaration for the COVID-19 outbreak in Japan | BackgroundBefore Olympic and Paralympic Games in Tokyo, whether an audience shall be allowed or not has been a subject of concern in Japan as of early June, 2021. Object: We evaluated effects of professional baseball games with audiences as an example of the large sports events, on COVID-19 infectiousness.
MethodWe regressed the effective reproduction number R(t) on a dummy variable for professional baseball games with audiences as along with temperature, humidity, mobility, and countermeasures. We examined two study periods: those including and excluding before initiation of the games in 2020.
ResultsEstimation results indicate that the period with audiences exhibited significantly lower infectiousness than when audiences were excluded before initiation of the games with audience attendance. However, audiences were found to have a negative but insignificant effect when compared to the period before initiation of the attended games.
Discussion and ConclusionThis study found no clear evidence indicating that big sports events with audiences raise the COVID-19 infectiousness. | public and global health |
10.1101/2020.12.29.20248977 | The second COVID-19 emergency status declaration for Japan: effects as of February 7, 2021 | BackgroundBefore Olympic and Paralympic Games in Tokyo, whether an audience shall be allowed or not has been a subject of concern in Japan as of early June, 2021. Object: We evaluated effects of professional baseball games with audiences as an example of the large sports events, on COVID-19 infectiousness.
MethodWe regressed the effective reproduction number R(t) on a dummy variable for professional baseball games with audiences as along with temperature, humidity, mobility, and countermeasures. We examined two study periods: those including and excluding before initiation of the games in 2020.
ResultsEstimation results indicate that the period with audiences exhibited significantly lower infectiousness than when audiences were excluded before initiation of the games with audience attendance. However, audiences were found to have a negative but insignificant effect when compared to the period before initiation of the attended games.
Discussion and ConclusionThis study found no clear evidence indicating that big sports events with audiences raise the COVID-19 infectiousness. | public and global health |
10.1101/2020.12.29.20248977 | Interim estimation for the effect of the third COVID-19 emergency status declaration in Japan | BackgroundBefore Olympic and Paralympic Games in Tokyo, whether an audience shall be allowed or not has been a subject of concern in Japan as of early June, 2021. Object: We evaluated effects of professional baseball games with audiences as an example of the large sports events, on COVID-19 infectiousness.
MethodWe regressed the effective reproduction number R(t) on a dummy variable for professional baseball games with audiences as along with temperature, humidity, mobility, and countermeasures. We examined two study periods: those including and excluding before initiation of the games in 2020.
ResultsEstimation results indicate that the period with audiences exhibited significantly lower infectiousness than when audiences were excluded before initiation of the games with audience attendance. However, audiences were found to have a negative but insignificant effect when compared to the period before initiation of the attended games.
Discussion and ConclusionThis study found no clear evidence indicating that big sports events with audiences raise the COVID-19 infectiousness. | public and global health |
10.1101/2020.12.29.20248977 | Estimating event ban effects on COVID-19 outbreak in Japan | BackgroundBefore Olympic and Paralympic Games in Tokyo, whether an audience shall be allowed or not has been a subject of concern in Japan as of early June, 2021. Object: We evaluated effects of professional baseball games with audiences as an example of the large sports events, on COVID-19 infectiousness.
MethodWe regressed the effective reproduction number R(t) on a dummy variable for professional baseball games with audiences as along with temperature, humidity, mobility, and countermeasures. We examined two study periods: those including and excluding before initiation of the games in 2020.
ResultsEstimation results indicate that the period with audiences exhibited significantly lower infectiousness than when audiences were excluded before initiation of the games with audience attendance. However, audiences were found to have a negative but insignificant effect when compared to the period before initiation of the attended games.
Discussion and ConclusionThis study found no clear evidence indicating that big sports events with audiences raise the COVID-19 infectiousness. | public and global health |
10.1101/2020.12.29.20248969 | Reliability of Google Trends: Analysis of the Limits and Potential of Web Infoveillance During COVID-19 Pandemic and for Future Research | BackgroundAlongside the COVID-19 pandemic, government authorities around the world have had to face a growing infodemic capable of causing serious damages to public health and economy. In this context, the use of infoveillance tools has become a primary necessity.
ObjectiveThe aim of this study is to test the reliability of a widely used infoveillance tool which is Google Trends. In particular, the paper focuses on the analysis of relative search volumes (RSVs) quantifying their dependence on the day they are collected.
MethodsRSVs of the query coronavirus + covid during February 1 - December 4, 2020 (period 1), and February 20 - May 18, 2020 (period 2), were collected daily by Google Trends from December 8 to 27, 2020. The survey covered Italian regions and cities, and countries and cities worldwide. The search category was set to all categories. Each dataset was analyzed to observe any dependencies of RSVs from the day they were gathered. To do this, by calling i the country, region, or city under investigation and j the day its RSV was collected, a Gaussian distribution [Formula] was used to represent the trend of daily variations of xij = RSVsij. When a missing value was revealed (anomaly), the affected country, region or city was excluded from the analysis. When the anomalies exceeded 20% of the sample size, the whole sample was excluded from the statistical analysis. Pearson and Spearman correlations between RSVs and the number of COVID-19 cases were calculated day by day thus to highlight any variations related to the day RSVs were collected. Student t-test was used to assess the statistical significance of the differences between the average RSVs of the various countries, regions, or cities of a given dataset. Two RSVs were considered statistical confident when t < 1.5. A dataset was deemed unreliable if the confident data exceeded 20% (confidence threshold). The percentage increase{Delta} was used to quantify the difference between two values.
ResultsGoogle Trends has been subject to an acceptable quantity of anomalies only as regards the RSVs of Italian regions (0% in both period 1 and period 2) and countries worldwide (9.7% during period 1 and 10.9% during period 2). However, the correlations between RSVs and COVID-19 cases underwent significant variations even in these two datasets (Max |{Delta}| = + 625% for Italian regions, and Max |{Delta}| = +175% for countries worldwide). Furthermore, only RSVs of countries worldwide did not exceed confidence threshold. Finally, the large amount of anomalies registered in Italian and international cities RSVs made these datasets unusable for any kind of statistical inference.
ConclusionsIn the considered timespans, Google Trends has proved to be reliable only for surveys concerning RSVs of countries worldwide. Since RSVs values showed a high dependence on the day they were gathered, it is essential for future research that the authors collect queries data for several consecutive days and work with their RSVs averages instead of daily RSVs, trying to minimize the standard errors until an established confidence threshold is respected. | public and global health |
10.1101/2020.12.28.20248780 | Continuous pain report demonstrates time delay of pain ratings in Fibromyalgia | BackgroundEnhanced temporal summation (TS), measured through self-reported pain ratings, has been interpreted as indicative of central sensitisation in fibromyalgia. Greater TS in patients, however, has not been universally observed. It is also unclear whether increased pain report maintains beyond the TS period.
MethodsIn this study, we measured TS through continuously reported pain ratings. Fibromyalgia-diagnosed patients (n = 17) and matched pain-free controls (n = 13) rated painful transcutaneous electrical stimulation of various intensity levels in 18 one-minute-long blocks. Pain was rated on a 101-point visual analogue scale. The resulting continuous response was divided into TS (< 15s) and adaptation (15 - 60s) periods. Average pain values were extracted for each period alongside the timing of key events such as maximal pain ratings. The difference in temporal summation and adaptation measures between fibromyalgia and control participants was analysed using mixed-effects modelling.
ResultsThe average pain ratings for TS and adaptation periods were not significantly associated with fibromyalgia diagnosis but were with stimulation intensity. The same was true for the magnitude of the maximal rating during TS and the slope leading to that peak rating. The presence of fibromyalgia, however, did predict the time of the maximal TS rating, as well as the value and the time of the maximal adaptation rating.
ConclusionsOur study did not find homogeneously increased TS pain ratings. Instead, by utilising continuous pain data we demonstrate for the first time that the time of TS peak rating, as well as the magnitude and time of adaptation peak rating are linked to fibromyalgia diagnosis. | rheumatology |
10.1101/2020.12.30.20248944 | An in-depth analysis of phosphorylated tau in amyotrophic lateral sclerosispost-mortem motor cortex and cerebrospinal fluid | Although the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are not yet fully understood, recent studies have described alterations in tau protein in both sporadic and familial ALS. However, it is unclear whether alterations in tau contribute to ALS pathogenesis. Here, we leveraged the ALS Knowledge Portal and Project MinE data sets and identified specific genetic variants clustering within the microtubule-binding domain of MAPT, which were unique to ALS cases. Furthermore, our analysis in a large post-mortem cohort of ALS and control motor cortex demonstrates that although there was no significant difference in the presence of phosphorylated tau (pTau) neuropil threads and neurofibrillary tangles between the two groups, pTau-S396 and pTau-S404 mis-localized to the nucleus and synapses in ALS. This was specific to the C-terminus phosphorylation sites as there was a significant decrease in pTau-T181 in ALS synaptoneurosomes compared to controls. Lastly, while there was no change in total tau or pTau-T181 in ALS CSF, there was a decrease in pTau-T181:tau ratio in ALS CSF, as previously reported. Importantly, CSF tau levels were increased in ALS patients diagnosed with bulbar onset ALS, while pTau-T181:tau ratio was decreased in ALS patients diagnosed with both bulbar and limb onset. Additionally, there was an inverse correlation between tau levels in the CSF and the revised ALS functional rating scale (ALSFRS-R) as well as a correlation between pTau-T181:tau ratio and ALSFRS-R. While there were no longitudinal alterations in tau, pTau-T181 and pTau-T181:tau ratio, there was an increase in the rate of ALSFRS-R decline per month associated with increases in tau levels. This decline was also inversely correlated with increases in pTau-T181 in relation to tau levels. Taken together, our findings demonstrate that, like Alzheimers disease, hyperphosphorylated tau is mis-localized in ALS and that decreases in CSF pTau-T181 may serve as a biomarker in ALS. | neurology |
10.1101/2020.12.28.20248875 | Speech pause distribution as an early marker for Alzheimer's disease | BackgroundPause duration analysis is a common feature in the study of discourse in Alzheimers disease (AD) and may also be helpful for its early detection. However, studies involving patients with amnestic mild cognitive impairment (aMCI) have yielded varying results.
ObjectivesTo characterize the probability density distribution of speech pause durations in AD, two multi-domain amnestic MCI patients (with memory encoding deficits, a-mdMCI-E, and with retrieval impairment only, a-mdMCI-R) and healthy controls (HC) in order check whether there are significant differences between them.
Method112 picture-based oral narratives were manually transcribed and annotated for the automatic extraction and analysis of pause durations. Different probability distributions were tested for the fitting of pause durations while truncating shorter ranges. Recent findings in the field of Statistics were considered in order to avoid the inherent methodological uncertainty that this type of analysis entails.
ResultsA lognormal distribution (LND) explained the distribution of pause duration for all groups. Its fitted parameters ({micro},{sigma}) followed a gradation from the group with shorter durations and a higher tendency to produce short pauses (HC) to the group with longer pause durations and a considerably higher tendency to produce long pauses with greater variance (AD). Importantly, a-mdMCI-E produced significantly longer pauses and with greater variability than their a-mdMCI-R counterparts ( = 0.05).
ConclusionWe report significant differences at the group level in pause distribution across all groups of study that could be used in future diagnostic tools and discuss the clinical implications of these findings, particularly regarding the characterization of aMCI. | neurology |
10.1101/2020.12.28.20248957 | Comparative Study - The Impact and Profile of COVID-19 Patients Who Are Indicated for Neuroimaging: Vascular Phenomena Are Been Found in the Brain and Olfactory Bulbs | ObjectiveTo verify the impact and findings of the COVID-19 patients group that underwent brain scans in comparison to the group which only chest CT was performed.
Method876 suspected COVID-19 patients and a subsample of 232 cases with confirmed COVID-19 who underwent brain CT/MRI scan (n=35) or only chest CT (n=197) in two radiology departments, were evaluated.
Results5.59% of all suspected COVID-19 patients found had brain scans and 98.74% chest CT. There was a statistically significant difference with associations regarding the COVID-19 brain scan group for: admission to ICU, greater severity of lung injuries, the use of mechanical ventilator, seizure, sepsis, and stroke and statistical tendency for chronic renal failure and systemic arterial hypertension. 40.0% of COVID-19 patients from the brain scan group were abnormal on brain CT and/or brain MRI. 22.9% cases with any kind of bleeding or microbleeding, 8.6% with restricted diffusion lesions. One ischemic stroke case was associated with irregularity at M1 segment of the right middle cerebral artery. There was a case of left facial nerve palsy with enhancement of left geniculate ganglia. An analyse of the olfactory bulbs was possible in 12 brain MRIs and 100% had enhancement and/or microbleeding. There was no statistical difference regarding death (9.1% versus 5.2%).
In conclusionthe COVID-19 patients group on which brain CT and/or MRI needed to be performed was statically associated with the more severe COVID-19 disease, an indication to ICU, a more severe form of lung disease, use of mechanical ventilator, seizure, sepsis and stroke. Less than half of patients had abnormal brain imaging scans with all of them showing vascular brain injury lesion, being more frequently microbleeding or bleeding, followed by restricted diffusion lesions. All the olfactory bulbs evaluated showed injury by vascular phenomenon, probably methahemoglobine by microbleeding or microthrombus and/or abnormal enhancement | neurology |
10.1101/2020.12.28.20248958 | Lived experiences of pregnant and new mothers during COVID-19 pandemic: A narrative analysis of YouTube birth stories. | IntroductionThe COVID-19 pandemic has brought on unprecedented changes, not only to our daily lives but also to our healthcare system. The pandemic has particularly impacted pregnant women that must give birth with tight restrictions and significant uncertainties. Birth stories have frequently been used as a way for women to describe their experiences with the birthing process. In this uncertain time, birth stories can provide valuable insight into how pregnancy and birth stressors during a pandemic can impact the patients overall experience. This study sought to describe and understand pregnant and new mothers lived experiences during the COVID-19 pandemic.
MethodsResearchers extracted relevant YouTube birth stories using predetermined search terms and inclusion criteria. The mothers birth stories were narrated in their second or third trimester or those who had recently given birth during the study period. Birth stories were analyzed using an inductive and deductive approach to capture different aspects of the birthing experience.
ResultsOverall, eighty-three birth stories were analyzed. Within these birth stories, four broad themes and twelve subthemes emerged. Key themes included a sense of loss, hospital experiences, experiences with healthcare providers, and unique experiences during birth and postpartum. The birth stories revealed negative and positive birth experiences. Particularly, mothers were frustrated with constantly changing policies within the healthcare setting that negatively affected their birthing experience. On the other hand, support from healthcare professionals, having their partners in the delivery room, and having a positive mindset was instrumental in having a positive birth experience.
ConclusionResults from this study provided a detailed description of womens lived experience with giving birth during the COVID-19 pandemic. Healthcare providers need to provide clear communication and compassionate patient-centered care to relieve womens anxiety about uncertain and unpredictable policy as the pandemic continues to evolve. | obstetrics and gynecology |
10.1101/2020.12.28.20248962 | The ocular tissue-specificity of differentially expressed age-related macular degeneration associated genes | PurposeAge-related macular degeneration (AMD) is a leading cause of blindness in the developed world. One of the most genetically well-characterized degenerative diseases, genome-wide association studies (GWAS) have identified 52 independent common or rare AMD risk associated variants. While transcriptome-wide association analyses (TWAS) and expression quantitative trait loci (eQTL) efforts have characterized the effects of these AMD-associated genes on mRNA expression in retinal tissue, we aimed to characterize the AMD-associated transcriptional profiles of functionally distinct ocular tissues including the macular and extramacular regions of the retina and the retinal-pigment epithelium (RPE)/choroid.
MethodsUsing publicly available microarray data (NCBI GEO accession: GSE29801) comprised of retinal and RPE/choroidal tissue samples from 142 AMD patients and 151 healthy individuals (118 retina and 175 RPE/Choroid samples), tissue-specific differential gene expression analyses were conducted. Transcriptome analyses were focused on 878 genes surrounding known AMD-associated loci.
ResultsMany genes which contain clinically significant or causal variants identified via GWAS or TWAS/eQTL studies were significantly differentially expressed and display transcriptional heterogeneity across different subtypes of ocular tissue and retinal geography in AMD-associated tissues.
ConclusionThese findings demonstrate the importance of spatial heterogeneity and tissue specificity in the mRNA expression of known AMD-associated genes. Genes known to harbor rare or causal AMD- associated variants are differentially expressed in functionally distinct ocular tissues of AMD patients, suggesting they might contribute to disease regardless of mutation status. | ophthalmology |
10.1101/2020.12.30.20249018 | Cost-utility of two minimally-invasive surgical techniques for operable oropharyngeal cancer: Transoral robotic surgery versus transoral laser microsurgery | ImportanceTransoral robotic surgery (TORS) and transoral laser micro-surgery (TLM) are two different but competing minimally invasive techniques to surgically remove operable oropharyngeal squamous cell cancers (OPSCC). As of now, no comparative analysis as to the cost-utility of these techniques exists.
ObjectiveRecent population-level data suggest for TORS and TLM equivalent tumor control, but different total costs, need for adjuvant chemoradiation, and learning curves. Therefore, the objective of this study was to compare TORS and TLM from the cost-utility (C/U) point of view using a decision-analytical model from a Swiss hospital perspective.
DesignOur decision-analytical model combines decision trees and a Markov model to compare TORS and TLM strategies. Model parameters were quantified using available literature, original cost data from two Swiss university tertiary referral centers, and utilities elicited directly from a Swiss population sample using standard gamble. C/U and sensitivity analyses were used to generate results and gauge model robustness.
SettingSwiss hospital perspective
InterventionCost-utility analysis
Main outcome measureComparative cost-utility data from TLM and TORS
ResultsIn the base case analysis TLM dominates TORS. This advantage remains robust, even if the costs for TORS would reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment (pTorsAlone>0.407), whereby in an interval between 55%-62% (pTorsAlone 0.38-0.45) cost effectiveness of TORS is sensitive to the prescription of adjuvant CRT. Also, exceeding 29% of TLM patients requiring a re-operation for inadequate margins renders TORS more cost-effective.
ConclusionTLM is more cost-effective than TORS. However, this advantage is sensitive to various parameters i.e. the number of re-operations and adjuvant treatment.
Key pointsO_ST_ABSQuestionC_ST_ABSCompare cost-utility of TORS versus TLM
FindingsIn the base case analysis TLM dominates TORS, even if the costs for TORS would reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment, whereby in an interval between 55%-62% cost effectiveness of TORS is sensitive to the prescription of adjuvant CRT. Exceeding 29% of TLM patients requiring a re-operation for inadequate margins renders TORS more cost-effective.
MeaningTLM is more cost-effective than TORS. However, this advantage is sensitive to the number of re-operations and adjuvant treatment | otolaryngology |
10.1101/2020.12.28.20248193 | GestaltMatcher: Overcoming the limits of rare disease matching using facial phenotypic descriptors | A large fraction of monogenic disorders causes craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more efficiently with the support of computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this "supervised" approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we created GestaltMatcher, which uses a deep convolutional neural network based on the DeepGestalt framework. We used photographs of 17,560 patients with 1,115 rare disorders to define a "Clinical Face Phenotype Space". Distance between cases in the phenotype space defines syndromic similarity, allowing test patients to be matched to a molecular diagnosis even when the disorder was not included in the training set. Similarities among patients with previously unknown disease genes can also be detected. Therefore, in concert with mutation data, GestaltMatcher could accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism, as well as enable the delineation of novel phenotypes. | genetic and genomic medicine |
10.1101/2020.12.28.20248193 | GestaltMatcher: Overcoming the limits of rare disease matching using facial phenotypic descriptors | A large fraction of monogenic disorders causes craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more efficiently with the support of computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this "supervised" approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we created GestaltMatcher, which uses a deep convolutional neural network based on the DeepGestalt framework. We used photographs of 17,560 patients with 1,115 rare disorders to define a "Clinical Face Phenotype Space". Distance between cases in the phenotype space defines syndromic similarity, allowing test patients to be matched to a molecular diagnosis even when the disorder was not included in the training set. Similarities among patients with previously unknown disease genes can also be detected. Therefore, in concert with mutation data, GestaltMatcher could accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism, as well as enable the delineation of novel phenotypes. | genetic and genomic medicine |
10.1101/2020.12.29.20248974 | AMELIE 3: Fully Automated Mendelian Patient Reanalysis at Under 1 Alert per Patient per Year | BackgroundMany thousands of patients with a suspected Mendelian disease have their exomes/genomes sequenced every year, but only about 30% receive a definitive diagnosis. Since a novel Mendelian gene-disease association is published on average every business day, thousands of undiagnosed patient cases could receive a diagnosis each year if their genomes were regularly compared to the latest literature. With millions of genomes expected to be sequenced for rare disease analysis by 2025, and considering the current publication rate of 1.1 million new articles per annum in PubMed, manually reanalyzing the growing cases of undiagnosed patients is not sustainable.
MethodsWe describe a fully automated reanalysis framework for patients with suspected, but undiagnosed, Mendelian disorders. The presented framework was tested by automatically parsing all [~]100,000 newly published peer reviewed papers every month and matching them on genotype and phenotype with all stored undiagnosed patients. If a new article contains a possible diagnosis for an undiagnosed patient, the system provides notification. We test the accuracy of the automatic reanalysis system on 110 patients, including 61 with available trio data.
ResultsEven when trained only on older data, our system identifies 80% of reanalysis diagnoses, while sending only 0.5-1 alerts per patient per year, a 100-1,000-fold efficiency gain over manual literature surveillance of equivalent yield.
ConclusionWe show that automatic reanalysis of patients with suspected Mendelian disease is feasible and has the potential to greatly streamline diagnosis. Our system is not intended to replace clinical judgment. Rather, clinical diagnostic services could greatly benefit from a modest re-allocation of time from manual literature exploration to review of automated reanalysis alerts. Our system additionally supports a new paradigm for medical IT systems: proactive, continuously learning and consequently able to autonomously identify valuable insights as they emerge in digital health records. We have launched automated patient reanalysis, trained on the latest data, with user accounts and daily literature updates at https://AMELIE.stanford.edu. | genetic and genomic medicine |
10.1101/2020.12.29.20249005 | An Intrinsic and Extrinsic Evaluation of Learned COVID-19 Concepts using Open-Source Word Embedding Sources | IntroductionScientists are developing new computational methods and prediction models to better clinically understand COVID-19 prevalence, treatment efficacy, and patient outcomes. These efforts could be improved by leveraging documented, COVID-19-related symptoms, findings, and disorders from clinical text sources in the electronic health record. Word embeddings can identify terms related to these clinical concepts from both the biomedical and non-biomedical domains and are being shared with the open-source community at large. However, its unclear how useful openly-available word embeddings are for developing lexicons for COVID-19-related concepts.
ObjectiveGiven an initial lexicon of COVID-19-related terms, characterize the returned terms by similarity across various, open-source word embeddings and determine common semantic and syntactic patterns between the COVID-19 queried terms and returned terms specific to word embedding source.
Materials and MethodsWe compared 7 openly-available word embedding sources. Using a series of COVID-19-related terms for associated symptoms, findings, and disorders, we conducted an inter-annotator agreement study to determine how accurately the most semantically similar returned terms could be classified according to semantic types by three annotators. We conducted a qualitative study of COVID-19 queried terms and their returned terms to identify useful patterns for constructing lexicons. We demonstrated the utility of applying such terms to discharge summaries by reporting the proportion of patients identified by concept for pneumonia, acute respiratory distress syndrome, and COVID-19 cohorts.
ResultsWe observed high, pairwise inter-annotator agreement (Cohens Kappa) for symptoms (0.86 to 0.99), findings (0.93 to 0.99), and disorders (0.93 to 0.99). Word embedding sources generated based on characters tend to return more lexical variants and synonyms; in contrast, embeddings based on tokens more often return a variety of semantic types. Word embedding sources queried using an adjective phrase compared to a single term (e.g., dry cough vs. cough; muscle pain vs. pain) are more likely to return qualifiers of the same semantic type (e.g., "dry" returns consistency qualifiers like "wet", "runny"). Terms for fever, cough, shortness of breath, and hypoxia retrieved a higher proportion of patients than other clinical features. Terms for dry cough returned a higher proportion of COVID-19 patients than pneumonia and ARDS populations.
DiscussionWord embeddings are a valuable technology for learning terms, including synonyms. When leveraging openly-available word embedding sources, choices made for the construction of the word embeddings can significantly influence the phrases returned. | health informatics |
10.1101/2020.12.29.20248900 | Efficiency of Artificial Intelligence in Detecting COVID-19 Pneumonia and Other Pneumonia Causes by Quantum Fourier Transform Method | The new coronavirus (COVID-19) appeared in Wuhan in December 2019 and has been announced as a pandemic by the World Health Organization (WHO). Currently, this deadly pandemic has caused more than 1 million deaths worldwide. Therefore, it is essential to detect positive cases as early as possible to prevent the further spread of this outbreak. Currently, the most widely used COVID-19 detection technique is a real-time reverse transcription-polymerase chain reaction (RT-PCR). However, RT-PCR is time-consuming to confirm infection in the patient. Because RT-PCR is less sensitive, it provides high false-negative results. Computed tomography (CT) is recommended as a solution to this problem by healthcare professionals because of its higher sensitivity for early and rapid diagnosis. In addition, radiation used in CT poses a serious threat to patients. In this study, we propose a CNN-based method to distinguish COVID-19 pneumonia from other types of viral and bacterial pneumonia using low-dose CT images to reduce the radiation dose used in CT. In our study, we used a data set consisting of 7717 CT images of 350 patients that we collected from Canakkale Onsekiz Mart University Research Hospital. We used a CNN-based network that suppresses noise to remove interference from low-dose CT images. In the image preprocessing phase, we provided lung segmentation from CT images and applied quantum Fourier transform. By evaluating all possible variations of local knowledge at the same time with quantum Fourier transformation, the most informative spatial information was extracted. In CNN-based architecture, we used pre-trained ResNet50v2 as a feature extractor and fine-tune by training with our dataset. We visualized the efficiency of the ResNet50v2 network using the t-SNE method. We performed the classification process with a fully connected layer. We created a heat map using the GradCam technique to see where the model focuses on the images while classifying. In this experimental study, the results of 99.5%, 99.2%, 99.0%, 99.7%, and 99.1%, were obtained in the context of performance criteria such as accuracy, precision, sensitivity, specificity, and f1 score, respectively. This study revealed the artificial intelligence-based computer-aided diagnosis (CAD)system as an effective and fast method to accurately diagnose COVID-19 pneumonia. | health informatics |
10.1101/2020.12.30.20249057 | Evaluation of three rapid lateral flow antigen detection tests for the diagnosis of SARS-CoV-2 infection | IntroductionThe COVID-19 pandemic has led to high demand of diagnostic tools. Rapid antigen detection tests have been developed and many have received regulatory acceptance such as CE IVD or FDA markings. Their performance needs to be carefully assessed.
Materials and Methods158 positive and 40 negative retrospective samples collected in saline and analyzed by a laboratory-developed RT-PCR test were used to evaluate Sofia (Quidel), Standard Q (SD Biosensor), and Panbio (Abbott) rapid antigen detection tests (RADTs). A subset of the specimens was subjected to virus culture.
ResultsThe specificity of all RADTs was 100% and the sensitivity and percent agreement was 80% and 85% for Sofia, 81% and 85% for Standard Q, and 83% and 86% for Panbio, respectively. All three RADTs evaluated in this study reached a more than 90% sensitivity for samples with a high viral load as estimated from the low Ct values in the reference RT-PCR. Virus culture was successful in 80% of specimens with a Ct value <25.
ConclusionsAs expected, the RADTs were less sensitive than RT-PCR. However, they benefit from the speed and ease of testing, and lower price as compared to RT-PCR. Repeated testing in appropriate settings may improve the overall performance. | infectious diseases |
10.1101/2020.12.30.20249046 | Development of Electrospun Nanofibrous Filters for Controlling Coronavirus Aerosols | Airborne transmission of SARS-CoV-2 plays a critical role in spreading COVID-19. To protect public health, we designed and fabricated electrospun nanofibrous air filters that hold promise for applications in personal protective equipment and indoor environment. Due to ultrafine nanofibers ([~]300 nm), the electrospun air filters had a much smaller pore size compared to the surgical mask and cloth masks (a couple of microns versus tens to hundreds of microns). A coronavirus strain was used to generate aerosols for filtration efficiency tests, which can better represent SARS-CoV-2 than other agents used for aerosol generation in previous studies. The electrospun air filters showed excellent performance by capturing up to 99.9% of coronavirus aerosols, which outperformed many commercial face masks. In addition, since NaCl aerosols have been widely used in filtration tests, we compared the filtration efficiency obtained from the coronavirus aerosols and the NaCl aerosols. The NaCl aerosols were demonstrated as an eligible surrogate for the coronavirus aerosols in the filtration tests, when air filters and face masks with diverse pore sizes, morphologies, and efficiencies were used. Our work paves a new avenue for advancing air filtration by developing electrospun nanofibrous air filters for controlling SARS-CoV-2 airborne transmission. Moreover, the removal efficiency of the NaCl aerosols can be reasonably translated into understanding how air filters capture the coronavirus aerosols.
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10.1101/2020.12.30.20249034 | Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data | The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases.
Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution. | infectious diseases |
10.1101/2020.12.30.20249034 | Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data | The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases.
Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution. | infectious diseases |
10.1101/2020.12.30.20249053 | Is sickle cell disease a risk factor for severe COVID-19 : a multicenter national retrospective cohort | IntroductionCoronavirus disease (COVID-19) caused by the novel coronavirus SARS-CoV-2 is an infectious disease which has evolved into a worldwide pandemic. Growing evidence suggests that individuals with pre-existing comorbidities are at higher risk of a more serious COVID-19 illness. Sickle cell disease (SCD) is an inherited hemoglobinopathy which increases the susceptibility to infections and as a consequent has higher risks of morbidity and mortality.
The impact of COVID-19 on SCD patients could lead to further increase in disease severity and mortality. Studies that examine the effect of SCD on COVID-19 outcomes are lacking. This study aims to determine whether SCD is a risk factor for severe COVID-19 infection in regards to the requirement of non-invasive ventilation/high flow nasal cannula (NIV/HFNC), mechanical intubation (MV) or death.
MethodsRetrospective cohort study which included COVID-19 patients admitted to four Ministry of Health COVID-19 treatment facilities in Bahrain during the period of 24, February 2020, to 31, July 2020. All SCD patients with COVID-19 were included and compared to randomly selected non-SCD patients with COVID-19. Data for the selected patients were collected from the medical records. Multivariate logistic regression models were used to control for confounders and estimate the effect of SCD on the outcomes.
ResultsA total of 1,792 patients with COVID-19 were included; 38 of whom were diagnosed with SCD as well. In the SCD group, one (2.6%) patient required NIV/HFNC, one (2.6%) required MV and one (2.6%) death occurred. In comparison, 56 (3.2%) of the non-SCD patients required NIV/HFNC, 47 (2.7%) required MV and death occurred in 58 (3.3%) patients. Upon adjusting for confounders, SCD had an odds ratio of 1.847 (95% CI: 0.39 - 8.83; p=0.442).
ConclusionOur results indicate that SCD is not a risk factor for worse disease outcomes in COVID-19 patients. | infectious diseases |
10.1101/2020.12.29.20248989 | Early measurement of blood sST2 is a good predictor of death and poor outcomes in patients admitted for COVID-19 infection | ImportanceAlthough several biomarkers have shown correlation to prognosis in COVID-19 patients, their clinical value is limited because of lack of specificity, suboptimal sensibility, or poor dynamic behavior.
ObjectiveIn search of better prognostic markers in COVID-19, we hypothesized that circulating soluble ST2 (sST2) could be associated to a worse outcome, prompted by our previous knowledge of sST2 involvement in heart failure-associated lung deterioration, and by mounting evidence favoring a role of IL-33/ST2 axis in the disease.
Design, Setting and participantsOne hundred and fifty-two patients admitted for confirmed COVID-19 infection were included in a prospective non-interventional, observational study carried out in a tertiary teaching center. Blood samples were drawn at admission, 48-72 hours later and at discharge. sST2 concentrations, and routine blood laboratory were analyzed.
Main outcomesPrimary end-points were admission at intensive care unit (ICU) and, mortality. Other outcomes were a need for high oxygen flow therapy (HOF) or increasing treatment at 48/72 hours.
ResultsMedian age was 57.5 years (SD: 12.8), 60.4% males. Ten per cent of patients (n=15) were derived to ICU and/or died during admission. The rest stayed hospitalized 8(IQR:6) days on average. About 34% (n=47), 38% (n=53) and 48.5% (n=66) needed HOF, up-titrate therapy or both, respectively.
Median (IQR) sST2 serum concentration (ng/mL) rose to 53.1(30.9) at admission, peaked at 48-72h (79.5[64]) and returned to admission levels at discharge (44.9[36.7]), remaining significantly elevated above healthy donor values (18.6[15.1]).
A concentration of sST2 above 58.9 ng/mL identified patients progressing to ICU admission or death. These results remained significant after multivariable analysis. The area under the receiver operating characteristics curve (AUC) of sST2 for the occurrence of end-points was 0.776 (p=0.001). Admission sST2 was higher in patients who needed up-tritate therapy.
Conclusions and relevanceIn patients admitted for COVID-19 infection, measurement of sST2 measurement early within 24h after at admission was able to identify patients at risk of severe complications or death. | infectious diseases |
10.1101/2020.12.30.20248890 | Detection of SARS-CoV-2 in the air from hospitals and closed rooms occupied by COVID-19 patients | To understand air transmission characteristics of SARS-CoV-2 and risks for health care personnel and visitors to hospitals, we analyzed air samples collected from various enclosures in hospitals at Hyderabad and Mohali and performed closed room experiments with COVID-19 positive individuals. We collected 64 air samples from COVID and non-COVID areas of various hospitals and 17 samples from closed rooms occupied by COVID patients. 4 samples from COVID care areas were positive for SARS-CoV-2 with no obvious predilection towards ICU/non-ICU areas in the hospital samples. In the closed room experiments, where one or more COVID-19 patients spent a short duration of time, one sample - collected immediately after the departure of three symptomatic patients from the room - was positive. Our results indicate that the chance of picking up SARS-CoV-2 in the air is directly related to a number of COVID positive cases in the room, their symptomatic status, and the duration of exposure and that the demarcation of hospital areas into COVID and non-COVID areas is a successful strategy to prevent cross infections. In neutral environmental conditions, the virus does not seem to spread farther away from the patients, especially if they are asymptomatic, giving an objective evidence for the effectiveness of physical distancing in curbing the spread of the epidemic. | infectious diseases |
10.1101/2020.12.30.20249036 | Does the Pareto Principle describe parasite counts in humans? The case of hookworm in pregnant women | The Pareto Principle (PP) -- that 80% of an attribute are found in 20% of individuals -- is one way to characterize heterogeneity in infectious diseases. An alternative is the dispersion parameter (k) of the negative binomial distribution (NBD). The NBD has two parameters, while the PP is a single property which may hold for any distribution family. The objectives of the current work are: a) to obtain a relation between the PP and NBD, i.e. to specify which combinations of NBD parameters comply with the PP; b) for hookworm, a soil-transmitted intestinal parasite of humans, to identify whether the PP or the NBD is a more parsimonious description of heterogeneity of infection load. For objective a), an empirical relation is found in the form of a saw-toothed line on a plot of k against the mean, reaching an asymptote of approximately 0.24. For objective b), we estimate k and the mean from nine studies from a systematic review of hookworm in pregnant women. Seven studies had higher heterogeneity than the PP, ranging from 83:20 to 100:20: we call these super-Pareto. One study was sub-Pareto (74:20), and one was Pareto (80:20). This suggests that at least two parameters, as supplied by the NBD, are necessary to describe the heterogeneity of hookworm. The probability of reaching a target reduction in prevalence is less when there is greater aggregation, which suggests that estimating aggregation via a subsample could be worthwhile, in order to set a target coverage threshold before starting mass drug administration. | infectious diseases |
10.1101/2020.12.23.20248803 | Clinical diagnosis of COVID-19: a prompt, feasible, and sensitive diagnostic tool for COVID-19 based on a 1,757-patient cohort (The AndroCoV Clinical Scoring for COVID-19 diagnosis). | ImportanceIn the COVID-19 pandemic, a limiting barrier for more successful approaches to COVID-19 is the lack of appropriate timing for its diagnosis, during the viral replication stage, when antiviral approaches could demonstrate efficacy, precluding progression to severe stages. Three major reasons that hamper the diagnosis earlier in the disease are the unspecific and mild symptoms in the first stage, the cost- and time-limitations of the rtPCR-SARS-CoV-2, and the insufficient sensitivity of this test as desired for screening purposes during the pandemic. More sensitive and earlier methods of COVID-19 detection should be considered as key for breakthrough changes in the disease course and response to specific therapeutic strategies. Our objective was to propose a clinical scoring for the diagnosis of COVID-19 (The AndroCoV Clinical Scoring for COVID-19 Diagnosis) that has been validated in a large population sample, aiming to encourage the management of patients with high pre-clinical likelihood of presenting COVID-19, at least during the pandemics, independent of a rtPCR-SARS-COV-2 test.
Materials and methodsThis is a compounded retrospective and prospective analysis of clinical data prospectively collected from the Pre-AndroCoV and AndroCov Trials that resulted in a clinical scoring for COVID-19 diagnosis based on likelihood of presenting COVID-19 according to the number of symptoms, presence of anosmia, and known positive household contact, in a variety of combinations of scoring criteria, aiming to the detect scorings that provided the highest pre-test probability and accuracy. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and accuracy were calculated for subjects screened in two different periods and altogether, for females, males, and both, in a total of nine different scenarios, for combinations between one, two, or three or more symptoms, or presence of anosmia in subjects without known positive household contacts, and no symptoms, one, two, or three or more symptoms, or presence of anosmia or ageusia in subjects with known positive household contacts.
Results1,757 patients were screened for COVID-19. Among the multiple combinations, requiring two or more symptoms with or without anosmia or ageusia for subjects without known contact and one or more symptoms with or without anosmia or ageusia with known positive contacts presented the highest accuracy (80.4%), and higher pretest probability and accuracy than virtually all rtPCR-SARS-CoV-2 commercially available kit tests.
ConclusionThe AndroCoV Clinical Scoring for COVID-19 Diagnosis was demonstrated to be a feasible, quick, inexpensive and sensitive diagnostic tool for clinical diagnosis of COVID-19. A clinical diagnosis of COVID-19 should avoid delays and missed diagnosis, and reduce costs, and should therefore be recommended as a first-line option for COVID-19 diagnosis for public health policies, at least while SARS-CoV-2 is the prevailing circulating virus.
Key PointsO_ST_ABSQuestionC_ST_ABSIs a clinical diagnosis of COVID-19 sensitive, accurate, and feasible?
FindingsThe present analysis of a 1,757-subject cohort of the AndroCoV trials demonstrated that clinical scoring for COVID-19 diagnosis can deliver a more sensitive and prompter diagnosis than the current gold-standard diagnostic method, rtPCR-SARS-CoV-2, with an accuracy above 80%.
MeaningA clinical diagnosis of COVID-19 avoids missed diagnosis due to insufficient sensitivity or incorrect timing of the performance of rtPCR-SARS-CoV-2, reduces costs, avoid delays on specific managements, and allows the testing of potentially effective antiviral therapeutic approaches that should work if administered in the early stage of COVID-19 | infectious diseases |
10.1101/2020.12.28.20248965 | PREDICTORS OF UPTAKE OF A POTENTIAL COVID-19 VACCINE AMONG NIGERIAN ADULTS | BackgroundThe Coronavirus diseases (COVID-19) pandemic is not abating and there is no approved treatment yet. The development of vaccines is hoped to help in addressing this disease outbreak. However, in the face of anti-vaccines uprise, it is important to understand the factors that may influence the uptake of COVID-19 vaccines as this will influence how successful the fight against COVID-19 will be in the long term.
MethodsA cross-sectional study among 776 adult Nigerians (age [≥]18 years) was conducted in the 36 States of Nigeria and the Capital City with online questionnaire. The questionnaire consisted of 5 sections: socio-demographic characteristics of respondents, respondents knowledge of COVID-19, respondents risk perception of COVID-19, vaccination history of respondents, and willingness to receive COVID-19 vaccine. Descriptive analysis of variables was done and multivariate analysis using logistic regression was carried out to determine the predictors of uptake of a potential COVID-19 vaccine. The level of significance was predetermined at a p-value < 0.05. Data analysis was done with SPSS version 21.
ResultsMost of the respondents were male (58.1%). Most participants were willing to take a potential COVID-19 vaccine (58.2%), while 19.2% would not take it with 22.6% indecisive. 53.5% would prefer a single dose COVID-19 vaccine. For vaccine uptake, being male (p= 0.002) and the perception that "vaccines are good" (p< 0.001) were the positive predictor of uptake of a potential COVID-19 vaccine.
ConclusionMost Nigerians were willing to take a potential COVID-19 vaccine with the male gender and perception that "vaccines are good" being positive predictors. There is a need for public enlightenment aim at encouraging those that are indecisive or averse to receiving COVID-19 vaccines. | infectious diseases |
10.1101/2020.12.29.20248986 | Insights into the molecular mechanism of anticancer drug ruxolitinib repurposable in COVID-19 therapy | Due to non-availability of specific therapeutics against COVID-19, repurposing of approved drugs is a reasonable option. Cytokines imbalance in COVID-19 resembles cancer; exploration of anti-inflammatory agents, might reduce COVID-19 mortality. The current study investigates the effect of ruxolitinib treatment in SARS-CoV-2 infected alveolar cells compared to the uninfected one from the GSE5147507 dataset. The protein-protein interaction network, biological process and functional enrichment of differentially expressed genes were studied using STRING App of the Cytoscape software and R programming tools. The present study indicated that ruxolitinib treatment elicited similar response equivalent to that of SARS-CoV-2 uninfected situation by inducing defense response in host against virus infection by RLR and NOD like receptor pathways. Further, the effect of ruxolitinib in SARS-CoV-2 infection was mainly caused by significant suppression of IFIH1, IRF7 and MX1 genes as well as inhibition of DDX58/IFIH1-mediated induction of interferon-I and -II signalling. | infectious diseases |