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10.1101/2021.01.12.20249097 | A rising burden of adolescents obesity of age group 13-17 years among tribal population of central India: a community-based exploratory study | BackgroundUpsurge of adolescent obesity is an upcoming national public health concern. Obese adolescents are at significant risk of becoming obese adults and its co-morbidities. This study estimates the prevalence of adolescent obesity and explore the potential determinants among young adults residing in tribal populated villages of Chhattisgarh, India.
MethodsA community-based nutritional survey was carried out among adolescent of the age group of 13-17 years.
ResultsAmong 1,296 participants, 23.4 % of young adults were either overweight or obese. Higher family earnings (Odds ratio [OR], 2.79, 95% confidence interval [CI] 1.29-6.38), Skipping breakfast (3.09, 1.11-8.30), Television viewing > 2 hours/ day (2.16, 1.3-6.2), Energy intake (2.98, 1.19-15.6), significantly increased the risk of adolescent obesity.
ConclusionPrevalence of adolescence obesity among the tribes is alarming and needs to be tackled with health system measures. Future research may require assessing the trajectory of obesity and related comorbidities in a tribal population. | epidemiology |
10.1101/2021.01.12.21249674 | New and Increasing Rates of Adverse Events Can be Found in Unstructured Text in Electronic Health Records using the Shakespeare Method | BackgroundText in electronic health records (EHRs) and big data tools offer the opportunity for surveillance of adverse events (patient harm associated with medical care) (AEs) in the unstructured notes. Writers may explicitly state an apparent association between treatment and adverse outcome ("attributed") or state the simple treatment and outcome without an association ("unattributed"). We chose to study EHRs from 2006-2008 because of known heparin contamination during this timeframe. We hypothesized that the prevalence of adulterated heparin may have been widespread enough to manifest in EHRs through symptoms related to heparin adverse events, independent of clinicians documentation of attributed AEs.
ObjectiveUse the Shakespeare Method, a new unsupervised set of tools, to identify attributed and unattributed potential AEs using the unstructured text of EHRs.
MethodsWe studied 21,287 adult critical care admissions divided into three time periods. Comparisons of period 3 (7/2007 to 6/2008) to period 2 (7/2006 to 6/2007) were used to find admissions notes to review for new or increased clinical events by generating Latent Dirichlet Allocation topics among words in period 3 that were distinct from period 2. These results were further explored with frequency analyses of periods 1 (7/2001 to 6/2006) through 3.
ResultsTopics represented unattributed heparin AEs, other medical AEs, rare medical diagnoses, and other clinical events; all were verified with EHRs notes review and frequency analysis. The heparin AEs were not attributed in the notes, diagnosis codes, or procedure codes. Somewhat different from our hypothesis, heparin AEs increased in prevalence from 2001 through 2007, and decreased starting in 2008 (when heparin AEs were being published).
ConclusionsThe Shakespeare Method could be a useful supplement to AE reporting and surveillance of structured EHRs data. Future improvements should include automation of the manual review process. | epidemiology |
10.1101/2021.01.12.21249674 | New and Increasing Rates of Adverse Events Can be Found in Unstructured Text in Electronic Health Records using the Shakespeare Method | BackgroundText in electronic health records (EHRs) and big data tools offer the opportunity for surveillance of adverse events (patient harm associated with medical care) (AEs) in the unstructured notes. Writers may explicitly state an apparent association between treatment and adverse outcome ("attributed") or state the simple treatment and outcome without an association ("unattributed"). We chose to study EHRs from 2006-2008 because of known heparin contamination during this timeframe. We hypothesized that the prevalence of adulterated heparin may have been widespread enough to manifest in EHRs through symptoms related to heparin adverse events, independent of clinicians documentation of attributed AEs.
ObjectiveUse the Shakespeare Method, a new unsupervised set of tools, to identify attributed and unattributed potential AEs using the unstructured text of EHRs.
MethodsWe studied 21,287 adult critical care admissions divided into three time periods. Comparisons of period 3 (7/2007 to 6/2008) to period 2 (7/2006 to 6/2007) were used to find admissions notes to review for new or increased clinical events by generating Latent Dirichlet Allocation topics among words in period 3 that were distinct from period 2. These results were further explored with frequency analyses of periods 1 (7/2001 to 6/2006) through 3.
ResultsTopics represented unattributed heparin AEs, other medical AEs, rare medical diagnoses, and other clinical events; all were verified with EHRs notes review and frequency analysis. The heparin AEs were not attributed in the notes, diagnosis codes, or procedure codes. Somewhat different from our hypothesis, heparin AEs increased in prevalence from 2001 through 2007, and decreased starting in 2008 (when heparin AEs were being published).
ConclusionsThe Shakespeare Method could be a useful supplement to AE reporting and surveillance of structured EHRs data. Future improvements should include automation of the manual review process. | epidemiology |
10.1101/2021.01.12.21249495 | Mitigation of COVID-19 using social distancing of the elderly in Brazil: The vertical quarantine effects in hospitalizations and deaths | Governments and epidemiologists have been proposing several mitigation strategies based on non-pharmaceutical interventions to reduce COVID-19 cases, hospitalizations, and deaths. In this work, we quantitatively compare the effects of elderly population (60 years old or more) selective isolation with a no isolation scenario using an adapted Susceptible - Exposed - Infectious - Removed (SEIR) compartmental model. For these simulated scenarios, we estimate the number of hospitalizations and deaths for different Brazilian cities, including those due to the lack of hospital beds. Our simulations show that, for Sao Paulo City, the isolation of the elderly would reduce demand for hospital beds by 9% and deaths by 16% compared to the no intervention scenario. Other Brazilian cities follow the same pattern, with median reductions of deaths ranging from 12-18%. We conclude that the social distancing of the elderly would be marginally effective and would not avoid health system collapse in several Brazilian cities. | epidemiology |
10.1101/2021.01.12.21249672 | Characteristics and outcomes of 118,155 COVID-19 individuals with a history of cancer in the United States and Spain | PurposeWe aimed to describe the demographics, cancer subtypes, comorbidities and outcomes of patients with a history of cancer with COVID-19 from March to June 2020. Secondly, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza.
MethodsWe conducted a cohort study using eight routinely-collected healthcare databases from Spain and the US, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: i) diagnosed with COVID-19, ii) hospitalized with COVID-19, and iii) hospitalized with influenza in 2017-2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes.
ResultsWe included 118,155 patients with a cancer history in the COVID-19 diagnosed and 41,939 in the COVID-19 hospitalized cohorts. The most frequent cancer subtypes were prostate and breast cancer (range: 5-19% and 1-14% in the diagnosed cohort, respectively). Hematological malignancies were also frequent, with non-Hodgkins lymphoma being among the 5 most common cancer subtypes in the diagnosed cohort. Overall, patients were more frequently aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 8% to 14% and from 18% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n=242,960) had a similar distribution of cancer subtypes, sex, age and comorbidities but lower occurrence of adverse events.
ConclusionPatients with a history of cancer and COVID-19 have advanced age, multiple comorbidities, and a high occurence of COVID-19-related events. Additionaly, hematological malignancies were frequent in these patients.This observational study provides epidemiologic characteristics that can inform clinical care and future etiological studies. | epidemiology |
10.1101/2021.01.12.21249493 | A multivariable Mendelian randomisation study exploring the direct effects of nicotine on health compared with the other constituents of tobacco smoke: Implications for e-cigarette use | ObjectivesGiven the popularity of e-cigarettes, and the lack of longitudinal evidence regarding their safety, novel methods are required to explore potential health effects resulting directly from nicotine use. The aim of this study was to explore the direct effects of nicotine compared with the other constituents of tobacco smoke on health outcomes associated with smoking.
DesignObservational study, using Mendelian randomisation and multivariable Mendelian randomisation analyses of summary data.
SettingSummary data from two previous genome-wide association studies, and summary data generated from UK Biobank, a prospective cohort study.
ParticipantsN = 337,010 individuals enrolled in UK Biobank, and a total of N = 341,882 individuals from two previous genome-wide association studies.
Main outcome measuresWe explored the effect of cotinine levels (as a proxy for nicotine exposure) and smoking heaviness (to capture cigarette smoke exposure) on body mass index (BMI), chronic obstructive pulmonary disease (COPD), forced vital capacity (FVC), forced expiratory volume (FEV-1), coronary heart disease (CHD), and heart rate.
ResultsIn multivariable Mendelian randomisation analyses, there was weak evidence to suggest that increased cotinine levels may cause increased heart rate among current smokers ({beta} = 0.50 bpm, 95% CI -0.06 to 1.05). There was stronger evidence to suggest that increased smoking heaviness causes decreased BMI among current smokers ({beta} = -1.81 kg/m2, 95% CI -2.64 to -0.98), as well as increased risk of COPD, decreased FEV-1 and FVC, and increased heart rate among ever and current smokers. We also found evidence to suggest that increased smoking heaviness causes increased risk of CHD among ever smokers.
ConclusionsOur combined findings are consistent with smoking-related health outcomes being caused by exposure to the non-nicotine components of tobacco smoke. | epidemiology |
10.1101/2021.01.13.21249262 | Prospective screening of liver fibrosis in a primary care cohort using systematic calculation of fib-4 in routine results | Background & AimLiver fibrosis screening in primary care population is a major public health issue. The FIB-4 index is a simple non-invasive fibrosis test combining age, transaminases, platelets count, developed for the diagnosis of advanced fibrosis. The aim of our study was to evaluate the interest of liver fibrosis screening using systematic calculation of FIB-4 in routine blood analysis.
MethodsBetween December 2018 and May 2019, we conducted a prospective screening of liver fibrosis in 134 158 patients during a medical check-up including routine blood analysis. Among these patients, 29 707 had transaminases and platelets counts available and benefited from an automatic calculation of FIB-4. Results were obtained from 21 French clinical laboratories in the Bouches du Rhone region.
ResultsAmong the 29 707 patients, 2160 (7.3%) had significant fibrosis (FIB-4>2.67). Individual investigation of patients with FIB-4>2.67 allowed to screen 1267 (1267/2160: 59%) patients who were not managed for any liver disease.
ConclusionsThis work demonstrates the interest of FIB-4 for the screening of liver fibrosis in primary care population. Our study strongly supports this easy-to-implement strategy using a simple Fib-4 measure resulting from the use of available routine test results.
FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Clinical Registering NumberMR-0314071019 (INDS: French National Institute for Medical Data) | gastroenterology |
10.1101/2021.01.11.20248947 | A mixture of essential oils from three Cretan Aromatic Plants (thyme, Greek sage and Cretan dittany, CAPeo) inhibits SASR-CoV-2 proliferation: in vitro evidence and a Proof-of-Concept intervention study in mild ambulatory COVID-19-positive patients | The need for therapeutic regimens for the non-critically ill patients of the COVID-19 pandemic remains unmet. In this line, repurposing existing drugs, against known or predicted SARS-CoV-2 protein actions, has been advanced, while natural products have also been tested. Previous work has shown that a Cretan Aromatic Plant (Thymbra capitata (L.) Cav., Salvia fruticosa Mill. and Origanum dictamnus L.) essential oil mixture (CAPeo) has a remarkable in vitro antiviral activity against Influenza A & B and Rhinovirus 14 strains, decreasing the symptoms of upper respiratory tract infections, while proven safe in experimental animals and humans. Here, we tested CAPeo in VERO cells infected with SASR-CoV-2. We report that this mixture, at similar concentrations as those previously reported, exhibits a remarkable antiviral activity. Administration of 1 ml of a 1.5% CAPeo in olive oil, in a Proof-of-Concept intervention study in SARS-CoV-2-positive, exhibiting mild COVID-19 symptoms, humans resulted in a significant amelioration of general and local symptoms of the disease. We conclude that CAPeo may be a valuable addition for the prevention and/or treatment of mild COVID-19 ambulatory patients, pending a confirmation through a prospective randomized controlled trial in humans (NCT04705753). | pharmacology and therapeutics |
10.1101/2021.01.12.21249692 | Impact of COVID-19 on Migrants' Access to Primary Care:A National Qualitative Study | BackgroundThe COVID-19 pandemic has led to considerable changes in the delivery of primary care in the UK, including rapid digitalisation, yet the extent to which these have impacted on marginalised migrant groups - already facing existing barriers to NHS care - is unknown. Understanding the perspectives and experiences of health professionals and migrants will support initiatives to deliver more effective health services, including delivery of the COVID-19 vaccine, to marginalised groups.
AimTo understand the impact of the COVID-19 pandemic on migrants and their access to primary healthcare, and implications for COVID-19 vaccine roll out.
Design and SettingPrimary care professionals, administrative staff, and migrants (foreign born; >18 years; <10 years in UK), were recruited in three phases using purposive, convenience and snowball sampling from urban, suburban and rural settings.
MethodsIn-depth semi-structured interviews were conducted by telephone. Data were analysed iteratively, informed by thematic analysis.
Results64 clinicians were recruited in Phase 1 (25 GPs, 15 nurses, 7 HCAs, 1 Pharmacists); Phase 2 comprised administrative staff (11 PMs and 5 receptionists); and in Phase 3 we recruited 17 migrants (88% asylum seekers; 65% female; mean time in UK 4 years). We found that digitalisation and virtual consultations (telephone, video, and online form-based) have amplified existing inequalities in access to healthcare for many migrants due to lack of digital literacy and access to technology, compounded by language barriers. Use of virtual consultations has resulted in concerns around building trust and the risk of missing safeguarding cues. Participants highlighted challenges around registering and accessing healthcare due to the physical closure of surgeries. Participants reported indirect discrimination, language and communication barriers, and lack of access to targeted and tailored COVID-19 information or interventions. In addition, migrants reported a range of specific beliefs around COVID-19 and on potential COVID-19 vaccines, from acceptance to mistrust, often influenced by misinformation. PCPs raised concerns that migrants may have increased risk factors for poor general health and to severe illness from COVID-19, in part due to their social and economic situation. Innovative opportunities were suggested to engage migrant groups through translated digital health advice using text templates and YouTube which merit further exploration.
ConclusionPandemic-related changes in primary care delivery may be here to stay, and some migrant groups are at risk of digital exclusion and may need targeted additional support to access services. As primary care networks operationalise the delivery of the COVID-19 vaccine, these findings provide critical information on specific strategies required to support migrant population to access primary care and overcome misinformation around COVID-19 and the COVID-19 vaccine.
How this fits inThe impact of pandemic-related shifts in primary care delivery on marginalised migrant groups, who may already face major disparities in accessing primary care, is poorly elucidated. We found that the rapid digitalisation of primary care services and physical closure of surgeries during the pandemic have amplified disparities in access to healthcare for specific migrant groups, with many lacking access to and capacity to use technology, compounded by language barriers. Migrants may be at increased risk of misinformation about COVID-19, which merits further consideration as COVID-19 vaccine roll out begins. Improved outreach to local migrant community organisations and places of worship, alongside co-designing with migrants more inclusive delivery approaches and creative integration of migrant ambassadors into information-sharing campaigns are needed. Primary care can maximise the opportunities of digitalisation for migrants through flexible engagement by multiple modalities (e.g. text, email, letter and YouTube videos) to provide targeted, translated advice and information, virtual group consultations for patients with a specific condition, and working with local leaders and NGOs to access and disseminate information through informal communication channels. | primary care research |
10.1101/2021.01.13.21249660 | Limited diagnostic accuracy of smartphone-based digital biomarkers for Parkinson's disease in a remotely-administered setting | Smartphone-based digital biomarker (DB) assessments provide objective measures of daily-life tasks and thus hold the promise to improve diagnosis and monitoring of Parkinsons disease (PD). To date, little is known about which tasks perform best for these purposes and how different confounds including comorbidities, age and sex affect their accuracy. Here we systematically assess the ability of common self-administered smartphone-based tasks to differentiate PD patients and healthy controls (HC) with and without accounting for the above confounds. Using a large cohort of PD patients and healthy volunteers acquired in the mPower study, we extracted about 700 features commonly reported in previous PD studies for gait, balance, voice and tapping tasks. We perform a series of experiments systematically assessing the effects of age, sex and comorbidities on the accuracy of the above tasks for differentiation of PD patients and HC using several machine learning algorithms. When accounting for age, sex and comorbidities, the highest balanced accuracy on hold-out data (73%) was achieved using random forest when combining all tasks followed by tapping using relevance vector machine (67%). Only moderate accuracies were achieved for other tasks (60% for balance, 56% for gait and 53% for voice data). Not accounting for the confounders consistently yielded higher accuracies of up to 77% when combining all tasks. Our results demonstrate the importance of controlling DB data for age and comorbidities. | psychiatry and clinical psychology |
10.1101/2021.01.13.21249660 | Smartphone-based digital biomarkers for Parkinson's disease in a remotely-administered setting | Smartphone-based digital biomarker (DB) assessments provide objective measures of daily-life tasks and thus hold the promise to improve diagnosis and monitoring of Parkinsons disease (PD). To date, little is known about which tasks perform best for these purposes and how different confounds including comorbidities, age and sex affect their accuracy. Here we systematically assess the ability of common self-administered smartphone-based tasks to differentiate PD patients and healthy controls (HC) with and without accounting for the above confounds. Using a large cohort of PD patients and healthy volunteers acquired in the mPower study, we extracted about 700 features commonly reported in previous PD studies for gait, balance, voice and tapping tasks. We perform a series of experiments systematically assessing the effects of age, sex and comorbidities on the accuracy of the above tasks for differentiation of PD patients and HC using several machine learning algorithms. When accounting for age, sex and comorbidities, the highest balanced accuracy on hold-out data (73%) was achieved using random forest when combining all tasks followed by tapping using relevance vector machine (67%). Only moderate accuracies were achieved for other tasks (60% for balance, 56% for gait and 53% for voice data). Not accounting for the confounders consistently yielded higher accuracies of up to 77% when combining all tasks. Our results demonstrate the importance of controlling DB data for age and comorbidities. | psychiatry and clinical psychology |
10.1101/2021.01.13.21249739 | Neurocognitive measures of self-blame and risk prediction models of recurrence in major depressive disorder | BackgroundOvergeneralised self-blaming emotions, such as self-disgust, are core symptoms of major depressive disorder (MDD) and prompt specific actions (i.e. "action tendencies"), which are more functionally relevant than the emotions themselves. We have recently shown, using a novel cognitive task, that when feeling self-blaming emotions, maladaptive action tendencies (feeling like "hiding" and like "creating a distance from oneself") and an overgeneralised perception of control are characteristic of MDD, even after remission of symptoms. Here, we probed the potential of this cognitive signature, and its combination with previously employed fMRI measures, to predict individual recurrence risk. For this purpose, we developed a user-friendly hybrid machine-/statistical-learning tool which we make freely available.
Methods52 medication-free remitted MDD patients, who had completed the Action Tendencies Task and our self-blame fMRI task at baseline, were followed up clinically over 14-months to determine recurrence. Prospective prediction models included baseline maladaptive self-blame-related action tendencies and anterior temporal fMRI connectivity patterns across a set of fronto-limbic a priori regions of interest, as well as established clinical and standard psychological predictors. Prediction models used elastic-net regularised logistic regression with nested 10-fold cross-validation.
ResultsCross-validated discrimination was highly promising (AuC[≥]0.86), and positive predictive values over 80% were achieved when including fMRI in multi-modal models, but only up to 71% (AuC[≤].74) when solely relying on cognitive and clinical measures.
ConclusionsThis shows the high potential of multi-modal signatures of self-blaming biases to predict recurrence risk at an individual level, and calls for external validation in an independent sample. | psychiatry and clinical psychology |
10.1101/2021.01.13.21249460 | Physicians' Reactions to COVID-19: The Results of an International Internet Survey | ObjectivesPhysicians across the world have been disproportionately affected by the COVID-19 pandemic. This study was designed and conducted to assess the emotional, cognitive, and behavioural reactions of physicians to the initial phase of the COVID-19 pandemic.
Materials and methodsAn online survey questionnaire using the google forms platform was constructed by the authors. The items in the questionnaire were based on clinical experience, relevant literature review and discussion with peers. A list of issues that were deemed as essential components of the experience of the pandemic relevant to physicians was arrived at. Thereafter these issues were operationalized into question form and hosted on the google forms platform. The link to this questionnaire was circulated by the authors among their peer groups in the month of April 2020.
ResultsWe received 295 responses and 3 were unusable. Most of the responses were from India, the United States of America, Australia, Canada and the United Kingdom. About 60% of the respondents identified themselves as frontline and had a decade of clinical experience. Most respondents reported being anxious due to the pandemic and also observed the same in their peers and families. A majority also observed changes in behaviour in self and others and advanced a variety of reasons and concerns. A sense of duty was the most commonly employed coping mechanism.
ConclusionPhysicians are not immune from information and misinformation, or cues in the environment. Behavioural choices are not always predicted by knowledge but by a combination of knowledge, emotional state, personality and environment. Healthcare settings need to be ready for emergencies and should focus on reducing uncertainty in physicians. These factors may also be gainfully used in the mental health promotion of physicians in COVID-19 care roles. | psychiatry and clinical psychology |
10.1101/2021.01.13.21249460 | Physicians' Reactions to COVID-19: The Results of an International Internet Survey | ObjectivesPhysicians across the world have been disproportionately affected by the COVID-19 pandemic. This study was designed and conducted to assess the emotional, cognitive, and behavioural reactions of physicians to the initial phase of the COVID-19 pandemic.
Materials and methodsAn online survey questionnaire using the google forms platform was constructed by the authors. The items in the questionnaire were based on clinical experience, relevant literature review and discussion with peers. A list of issues that were deemed as essential components of the experience of the pandemic relevant to physicians was arrived at. Thereafter these issues were operationalized into question form and hosted on the google forms platform. The link to this questionnaire was circulated by the authors among their peer groups in the month of April 2020.
ResultsWe received 295 responses and 3 were unusable. Most of the responses were from India, the United States of America, Australia, Canada and the United Kingdom. About 60% of the respondents identified themselves as frontline and had a decade of clinical experience. Most respondents reported being anxious due to the pandemic and also observed the same in their peers and families. A majority also observed changes in behaviour in self and others and advanced a variety of reasons and concerns. A sense of duty was the most commonly employed coping mechanism.
ConclusionPhysicians are not immune from information and misinformation, or cues in the environment. Behavioural choices are not always predicted by knowledge but by a combination of knowledge, emotional state, personality and environment. Healthcare settings need to be ready for emergencies and should focus on reducing uncertainty in physicians. These factors may also be gainfully used in the mental health promotion of physicians in COVID-19 care roles. | psychiatry and clinical psychology |
10.1101/2021.01.13.21249460 | Physicians' Reactions to COVID-19: The Results of an International Internet Survey | ObjectivesPhysicians across the world have been disproportionately affected by the COVID-19 pandemic. This study was designed and conducted to assess the emotional, cognitive, and behavioural reactions of physicians to the initial phase of the COVID-19 pandemic.
Materials and methodsAn online survey questionnaire using the google forms platform was constructed by the authors. The items in the questionnaire were based on clinical experience, relevant literature review and discussion with peers. A list of issues that were deemed as essential components of the experience of the pandemic relevant to physicians was arrived at. Thereafter these issues were operationalized into question form and hosted on the google forms platform. The link to this questionnaire was circulated by the authors among their peer groups in the month of April 2020.
ResultsWe received 295 responses and 3 were unusable. Most of the responses were from India, the United States of America, Australia, Canada and the United Kingdom. About 60% of the respondents identified themselves as frontline and had a decade of clinical experience. Most respondents reported being anxious due to the pandemic and also observed the same in their peers and families. A majority also observed changes in behaviour in self and others and advanced a variety of reasons and concerns. A sense of duty was the most commonly employed coping mechanism.
ConclusionPhysicians are not immune from information and misinformation, or cues in the environment. Behavioural choices are not always predicted by knowledge but by a combination of knowledge, emotional state, personality and environment. Healthcare settings need to be ready for emergencies and should focus on reducing uncertainty in physicians. These factors may also be gainfully used in the mental health promotion of physicians in COVID-19 care roles. | psychiatry and clinical psychology |
10.1101/2021.01.12.21249315 | A rare missense variant in the ATP2C2 gene is associated with language impairment and related measures | At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N=360) compared to cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24,046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N=42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N=1825) (minimum p = 0.002 for nonword reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level. | psychiatry and clinical psychology |
10.1101/2021.01.14.21249789 | Reference values and validation of the 1-min sit-to-stand test in healthy 5- to 16-year-old youth | ObjectivesIt is essential to have simple, reliable and valid tests to measure childrens functional capacity in schools or medical practice. The 1-min sit-to-stand test (STS) is a quick fitness test requiring little equipment or space that is increasingly used in both healthy populations and those with chronic disease. We aimed to provide age and sex-specific reference values of STS in healthy children and adolescents and to evaluate its short-term reliability and construct validity.
Design, setting and participantsCross-sectional random sample from 6 public schools and 1 science fair in central Europe. Overall, 587 healthy participants aged 5-16 years were recruited and divided into age groups of 3 years each.
Outcomes1-minute STS. To evaluate short-term reliability, some children performed the STS twice. To evaluate construct validity, some children also performed a standing long jump (SLJ) and a maximal incremental exercise test.
ResultsData from 547 5-16 year old youth were finally included in the analyses. The median number of repetitions in 1 minute in males (females) ranged from 55 [95% CI 38 to 72] (53 [35 to 76]) in 14-16 year-olds to 59 [41 to 77] (60 [38 to 77]) in 8-10 year-olds. Children who repeated STS showed a learning effect of on average 4.8 repetitions more than the first test (95% limits of agreement -6.7 to 16.4). Moderate correlations were observed between the STS and the SLJ (r = 0.48) and the maximal exercise test (r = 0.43).
ConclusionsThe reported STS reference values can be used to interpret STS test performance in children and adolescents. The STS appears to have good test-retest reliability, but a learning effect of about 10%. The association of STS with other measures of physical fitness should be further explored in a larger study and technical standards for its conduct are needed.
Strengths and Limitations of this StudyO_LILarge sample size (N = 547)
C_LIO_LIReference values according to sex and age group (5-7, 8-10, 11-13 and 14-16)
C_LIO_LIEvaluation of test-retest reliability and construct validity
C_LIO_LIConvenience not population-based sample
C_LIO_LINot all outcomes have been measured on each participant
C_LI | public and global health |
10.1101/2021.01.14.21249789 | Reference values and validation of the 1-min sit-to-stand test in healthy 5- to 16-year-old youth: a cross-sectional study | ObjectivesIt is essential to have simple, reliable and valid tests to measure childrens functional capacity in schools or medical practice. The 1-min sit-to-stand test (STS) is a quick fitness test requiring little equipment or space that is increasingly used in both healthy populations and those with chronic disease. We aimed to provide age and sex-specific reference values of STS in healthy children and adolescents and to evaluate its short-term reliability and construct validity.
Design, setting and participantsCross-sectional random sample from 6 public schools and 1 science fair in central Europe. Overall, 587 healthy participants aged 5-16 years were recruited and divided into age groups of 3 years each.
Outcomes1-minute STS. To evaluate short-term reliability, some children performed the STS twice. To evaluate construct validity, some children also performed a standing long jump (SLJ) and a maximal incremental exercise test.
ResultsData from 547 5-16 year old youth were finally included in the analyses. The median number of repetitions in 1 minute in males (females) ranged from 55 [95% CI 38 to 72] (53 [35 to 76]) in 14-16 year-olds to 59 [41 to 77] (60 [38 to 77]) in 8-10 year-olds. Children who repeated STS showed a learning effect of on average 4.8 repetitions more than the first test (95% limits of agreement -6.7 to 16.4). Moderate correlations were observed between the STS and the SLJ (r = 0.48) and the maximal exercise test (r = 0.43).
ConclusionsThe reported STS reference values can be used to interpret STS test performance in children and adolescents. The STS appears to have good test-retest reliability, but a learning effect of about 10%. The association of STS with other measures of physical fitness should be further explored in a larger study and technical standards for its conduct are needed.
Strengths and Limitations of this StudyO_LILarge sample size (N = 547)
C_LIO_LIReference values according to sex and age group (5-7, 8-10, 11-13 and 14-16)
C_LIO_LIEvaluation of test-retest reliability and construct validity
C_LIO_LIConvenience not population-based sample
C_LIO_LINot all outcomes have been measured on each participant
C_LI | public and global health |
10.1101/2021.01.13.21249728 | A systematic review of the concept 'male involvement in maternal health' by natural language processing and descriptive analysis. | IntroductionExperts agree that male involvement (MI) in maternal health (MH) is a multifaceted concept, but a universal definition is lacking, hampering comparison of findings and interpretation of the literature. This systematic review aims to examine the conceptualization of MI in MH globally and critically review commonly used indicators.
MethodsPubMed, Embase, Scopus, Web of Science and CINAHL databases were searched for quantitative literature (between the years 2000 and 2020) containing indicators or variables representing MI in MH, which was defined as the involvement, participation, engagement or support of men in all activities related to maternal health.
ResultsAfter full text review, 282 studies were included in the review. Most studies were conducted in Africa (43%), followed by North America (23%), Asia (15%) and Europe (12%). Descriptive analysis and text mining analysis showed MI in MH has been conceptualised by focusing on two main aspects: psychosocial support and instrumental support for maternal health care utilisation. Differences in measurement and topics were noted according to continent with Africa focusing on HIV prevention, North America and Europe on psychosocial health and stress, and Asia on nutrition. One third of studies used one single indicator for assessing MI in MH and no common pattern of indicators could be identified. Antenatal care attendance was the most used indicator (40%) followed by financial support (17%), presence during childbirth (17%) and HIV testing (14%). Majority of studies did not collect data from men directly.
DiscussionResearchers often focus on a single aspect of MI in MH, resulting in the usage of a narrow and simplified set of indicators. Aspects such as communication between the couple, shared decision making, participation in household tasks and the subjective feeling of being supported have received little attention. We believe a more multidimensional approach can broaden the potential of MI programs. Further research, involving experts and pilot testing, is recommended to develop consensus regarding a more robust and comprehensive set of valid and feasible indicators for assessing MI in MH.
Summary BoxO_ST_ABSWhat is already known?C_ST_ABSO_LIIncreasing male involvement (MI) in maternal health (MH) is considered to be a promising and effective intervention for improving maternal and newborn health outcomes.
C_LIO_LIMale involvement is described as a multifaceted concept in the quantitative literature, although a universal definition or evidence-based set of indicators is lacking.
C_LIO_LIIn qualitative literature male involvement is often described by men and women from different settings as the male partner "being there", meaning giving physical and emotional support.
C_LI
What are the new findings?O_LIConceptualisation of MI in MH in the literature is done by focusing on either psychosocial aspects of MI in MH or on maternal health care utilisation. The attention given to one or both aspects resulted in the use of different indicators and depended on the geographical context of the study.
C_LIO_LIOverall male involvement was most often measured by instrumental actions such as presence at health services, financial support or providing transport. Other aspects of male involvement, such as communication, emotional support and shared decision making have received little attention, especially in low- and middle-income countries.
C_LI
What do the new findings imply?O_LIMore research into other aspects of male involvement (such as the subjective feeling of perceived support and decision making) can broaden the potential of male involvement programs and also reveal and minimize potential negative side-effects of male involvement interventions.
C_LIO_LIA standardized definition and set of indicators, exploring different aspects of male involvement, could facilitate researchers to generate more robust findings, strengthening the existing evidence on male involvement programmes.
C_LI | public and global health |
10.1101/2021.01.11.21249324 | A national survey of potential acceptance of COVID-19 vaccines in healthcare workers in Egypt | BackgroundSince the start of COVID-19 outbreak investigators are competing to develop and exam vaccines against COVID-19. It would be valuable to protect the population especially health care employees from COVID-19 infection. The success of COVID-19 vaccination programs will rely heavily on public willingness to accept the vaccine.
AimsThis study aimed to describe the existing COVID-19 vaccine approval landscape among the health care providers and to identify the most probable cause of agreement or disagreement of COVID-19 vaccine.
MethodsA cross-sectional online survey was done.
ResultsThe present study included 496 health care employees, 55% were at age group from 18-45 years old. History of chronic diseases was recorded in 40.4%, and definite history of drug/food allergy in 10.1%. Only 13.5% totally agree to receive the vaccine, 32.4% somewhat agree and 40.9% disagreed to take the vaccine. Causes of disagreement were none safety, fear of genetic mutation and recent techniques and believe that the vaccine is not effective (57%, 20.2%, 17.7% and 16.6% respectively). The most trusted vaccine was the mRNA based vaccine. The age of health care employees and the presence of comorbidities or chronic diseases were the main factors related to COVID-19 acceptance (P<0.001 and 0.02 respectively).
ConclusionVaccine hesitancy is not uncommon in healthcare employees in Egypt and this may be an alarming barrier of vaccine acceptance in the rest of population. There is an urgent need to start campaigns to increase the awareness of the vaccine importance. | public and global health |
10.1101/2021.01.13.21249757 | Neural Network-derived perfusion maps: a Model-free approach to computed tomography perfusion in patients with acute ischemic stroke | PurposeIn this study we investigate whether a Convolutional Neural Network (CNN) can generate clinically relevant parametric maps from CT perfusion data in a clinical setting of patients with acute ischemic stroke.
MethodsTraining of the CNN was done on a subset of 100 perfusion data, while 15 samples were used as validation. All the data used for the training/validation of the network and to generate ground truth (GT) maps, using a state-of-the-art deconvolution-algorithm, were previously pre-processed using a standard pipeline. Validation was carried out through manual segmentation of infarct core and penumbra on both CNN-derived maps and GT maps. Concordance among segmented lesions was assessed using the Dice and the Pearson correlation coefficients across lesion volumes.
ResultsMean Dice scores from two different raters and the GT maps were > 0.70 (good-matching). Inter-rater concordance was also high and strong correlation was found between lesion volumes of CNN maps and GT maps (0.99, 0.98).
ConclusionOur CNN-based approach generated clinically relevant perfusion maps that are comparable to state-of-the-art perfusion analysis methods based on deconvolution of the data. Moreover, the proposed technique requires less information to estimate the ischemic core and thus might allow the development of novel perfusion protocols with lower radiation dose. | radiology and imaging |
10.1101/2021.01.13.21249715 | Validation of the German version of the Life-Space Assessment LSA-D | ObjectivesTo develop a German version of the original University of Alabama at Birmingham (UAB) Study of Aging Life-Space Assessment (LSA-D) for measurement of community mobility in older adults within the past 4 weeks and to evaluate its psychometric properties for urban and rural populations of older adults.
DesignCross-sectional validation study.
SettingTwo study centres in urban and rural German outpatient hospital settings.
ParticipantsIn total N=83 community-dwelling older adults were recruited (n=40 from urban and n=43 from rural areas; mean age was 78.5 (SD=5.4); 49% male).
Primary and secondary outcome measuresThe final version of the translated LSA-D was related with questions about activities and instrumental activities of daily living (ADL/iADL; primary hypothesis), Timed-Up&Go-Test (TUG), self-rated health, balance confidence and history of falls, use of transportation, and sociodemographic factors to obtain construct validity. Secondary outcome measures of health included handgrip strength, screening of cognitive function and comorbidities. To assess conduct construct validity, correlations between LSA-D and all health measures were examined for total sample, urban and rural subsamples using bivariate regression and multiple adjusted regression models. Posthoc analyses included different LSA-D scoring methods for each region. All parameters were estimated using non-parametric bootstrapping procedure.
ResultsIn the multiple adjusted model for the total sample, number of ADL/iADL limitations ({beta}=-.26; 95%CI=-.42/-.08), TUG ({beta}=-.37; 95%CI=-.68/-.14), living in shared living arrangements ({beta}=.22; 95%CI=.01/.44) and history of falls in the past 6 months ({beta}=-.22; 95%CI=-.41/-.05) showed significant associations with the LSA-D composite score, while living in urban area ({beta}=-.19; 95%CI=-.42/.03) and male gender ({beta}=.15; 95%CI=-.04/.35) were not significant.
ConclusionThe LSA-D is a valid tool for measuring life-space mobility in German community-dwelling older adults within the past four weeks in ambulant urban and rural settings.
Trial registration numberDRKS00019023
Strengths and limitations of this studyO_LIGerman validation of the original UAB Life-Space Assessment (LSA-D) for community dwelling older adults in urban and rural settings
C_LIO_LIUsing bootstrapped bivariate and multiple adjusted regression models to attain construct validity of the LSA-D
C_LIO_LIRecruitment had to be stopped shortly before reaching the calculated sample size due to the decision to restrict in face-to-face research to contain the outbreak of the Covid-19 pandemic in March 2020
C_LI | rehabilitation medicine and physical therapy |
10.1101/2021.01.12.21249685 | Towards a platform for robot-assisted minimally-supervised therapy of hand function: design and pilot usability evaluation | BackgroundRobot-assisted therapy can increase therapy dose after stroke, which is often considered insufficient in clinical practice and after discharge, especially with respect to hand function. Thus far, there has been a focus on rather complex systems that require therapist supervision. To better exploit the potential of robot-assisted therapy, we propose a platform designed for minimal therapist supervision, and present the preliminary evaluation of its immediate usability, one of the main and frequently neglected challenges for real-world application. Such an approach could help increase therapy dose by allowing the training of multiple patients in parallel by a single therapist, as well as independent training in the clinic or at home.
MethodsWe implemented design changes on a hand rehabilitation robot, considering aspects relevant to enabling minimally-supervised therapy, such as new physical/graphical user interfaces and two functional therapy exercises to train hand motor coordination, somatosensation and memory. Ten participants with chronic stroke assessed the usability of the platform and reported the perceived workload during a single therapy session with minimal supervision. The ability to independently use the platform was evaluated with a checklist.
ResultsParticipants were able to independently perform the therapy session after a short familiarization period, requiring assistance in only 13.46(7.69-19.23)% of the tasks. They assigned good-to-excellent scores on the SUS to the user-interface and the exercises (85.00(75.63-86.88) and 73.75(63.13-83.75) out of 100, respectively). Nine participants stated that they would use the platform frequently. Perceived workloads lay within desired workload bands. Object grasping with simultaneous control of forearm pronosupination and stiffness discrimination were identified as the most difficult tasks.
DiscussionOur findings demonstrate that a robot-assisted therapy device can be rendered safely and intuitively usable upon first exposure with minimal supervision through compliance with usability and perceived workload requirements. The preliminary usability evaluation identified usability challenges that should be solved to allow real-world minimally-supervised use. Such a platformcould complement conventional therapy, allowing to provide increased dose with the available resources, and establish a continuum of care that progressively increases therapy lead of the patient from the clinic to the home. | rehabilitation medicine and physical therapy |
10.1101/2021.01.12.21249586 | Arm-hand boost therapy during inpatient stroke rehabilitation: a pilot randomized controlled trial | ObjectiveIt was the aim to assess feasibility, safety and potential efficacy of a new intensive, focused arm-hand BOOST program and to investigate whether there is a difference between early versus late delivery of the program in the sub-acute phase post stroke.
MethodsIn this pilot RCT, patients with stroke were randomized to the immediate group (IG): 4 weeks (4w) BOOST +4w CONTROL or the delayed group (DG): 4w CONTROL +4w BOOST, on top of their usual inpatient care program. The focused arm-hand BOOST program (1 hour/day, 5x/week, 4 weeks) consisted of group exercises with focus on scapula-setting, core-stability, manipulation and complex ADL tasks. Additionally, one hour per week the Armeo(R)Power (Hocoma AG, Switzerland) was used. The CONTROL intervention comprised a dose-matched program (24 one-hour sessions in 4w) of lower limb strengthening exercises and general reconditioning. At baseline, after 4 and 8 weeks of training, the Fugl-Meyer assessment upper extremity (FMA-UE), action research arm test (ARAT) and stroke upper limb capacity scale (SULCS) were administered.
ResultsEighteen participants (IG: n=10, DG: n=8) were included, with a median (IQR) time post stroke of 8.6 weeks (5-12). No adverse events were experienced. After 4 weeks of training, significant between-group differences were found for FMA-UE (p=0.003) and SULCS (p=0.033) and a trend for ARAT (p=0.075) with median (IQR) change scores for the IG of 9 (7-16), 2 (1-3) and 12.5 (1-18) respectively, and for the DG of 0.5 (-3-3), 1 (0-1) and 1.5 (-1-9), respectively. In the IG, 80% of patients improved beyond the minimal clinical important difference of FMA-UE after 4 weeks, compared to none of the DG patients. Between 4 and 8 weeks of training, patients in the DG tend to show larger improvements when compared to the IG, however, between-group comparisons did not reach significance.
ConclusionsResults of this pilot RCT showed that an intensive, specific arm-hand BOOST program, on top of usual care, is feasible and safe in the sub-acute phase post stroke and suggests positive, clinical meaningful effects on upper limb function, especially when delivered in the early sub-acute phase post stroke.
Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT04584177 | rehabilitation medicine and physical therapy |
10.1101/2021.01.12.20248726 | Changes in the Health of Adolescent Athletes: A Comparison of Health Measures Collected Before and During the CoVID-19 Pandemic | ContextIn the spring of 2020, schools closed to in-person teaching and sports were cancelled to control the transmission of CoVID-19. The changes that took place to the physical and mental health among young athletes during this time remain unknown, however.
ObjectiveIdentify changes in the health (mental health, physical activity and quality of life) of athletes that occurred during the CoVID-19 pandemic.
DesignCross sectional study.
SettingSample recruited via social media.
Patients or Other Participants3243 Wisconsin adolescent athletes (age=16.2{+/-}1.2 yrs., female=58% female) completed an online survey in May 2020 (DuringCoVID-19). Health measures for this cohort were compared with previously reported data for Wisconsin adolescent athletes (n=5231, age=15.7{+/-}1.2, 47% female) collected in 2016-2018 (PreCoVID-19).
Main Outcome Measure(s)Demographic information included: sex, grade and sports played. Health assessments included the Patient Health Questionnaire-9 Item (PHQ-9) to identify depression symptoms, the Pediatric Functional Activity Brief Scale (PFABS) for physical activity, and the Pediatric Quality of Life Inventory 4.0 (PedsQL) for health related quality of life (HRQoL). Univariable comparisons of these variables between groups were made via t-tests or chi-square tests. Means and 95% confidence intervals (CI) for each group were estimated by survey weighted ANOVA models.
RESULTSCompared to PreCoVID-19, a larger proportion of the During-CoVID-19 participants reported rates of moderate to severe levels of depression (9.7% vs 32.9%, p<0.001). During-CoVID-19 participants reported 50% lower (worse) PFABS scores (mean:12.2 [95%CI: 11.9, 12.5] vs 24.7 [24.5, 24.9] p<0.001) and lower (worse) PedsQL total scores compared to the PreCoVID-19 participants (78.4 [78.0, 78.8] vs. 90.9 [90.5, 91.3] p<0.001).
CONCLUSIONSDuring the CoVID-19 pandemic, adolescent athletes reported increased symptoms of depression, decreased physical activity and decreased quality of life compared to adolescent athletes in previous years.
Key pointsO_LIAdolescent athletes during CoVID-19 were three times more likely to report moderate to severe symptoms of depression compared to data collected prior to CoVID-19.
C_LIO_LIAdolescent athletes during CoVID-19 reported significantly lower physical activity and quality of life scores compared to high school athletes prior to the CoVID-19 pandemic
C_LIO_LIPost CoVID-19 policies should be implemented to improve the health of adolescent athletes in the US.
C_LI | sports medicine |
10.1101/2021.01.14.21249845 | Regional Variation in COVID-19 Scarce Resource Allocation Protocols | BackgroundScarce resource allocation policies vary across the United States. Little is known about regional variation in hospital-level resource allocation protocols and variation in their application.
ObjectiveTo evaluate how scarce resource allocation policies throughout the Chicagoland area vary and whether there are differences in policy application within and amongst hospitals.
DesignTwo cross-sectional surveys.
SettingChicagoland hospitals.
ParticipantsRepresentatives from Chicagoland hospitals and triage officers at these hospitals.
MeasurementsSurvey responses and categorical variables are described by frequency of occurrence. Intra- and interhospital variation in ranking of hypothetical patients was assessed using Kappa coefficients.
ResultsEight Chicago area hospitals responded to the survey assessing scarce resource allocation protocols. For hospitals willing to describe their specific ventilator allocation protocol (n=7), the initial scoring system varied with most utilizing the sequential organ failure assessment (SOFA) score (86%) and medical comorbidities (57%). A majority gave priority to pre-defined groups in their initial scoring system (86%), all discussed withdrawal of mechanical ventilation for adult patients (100%), and a minority had exclusion criteria (43%). Forty-nine triage officers from nine hospitals responded to the second survey. Triage officer rankings of hypothetical patients had slight agreement amongst all hospitals (Kappa 0.158) and fair agreement within two hospitals with the most respondents (Kappa 0.21 and 0.25). Almost half of triage officer respondents reported using tiebreakers to rank patients (N=23/49, 47%).
ConclusionAlthough most Chicago area hospitals surveyed created guidelines for resource allocation during the COVID-19 pandemic, these guidelines and application of these protocols by triage officers varied significantly.
Funding SourceNone. | medical ethics |
10.1101/2021.01.13.21249576 | Evaluation of Urine SARS-COV-2 RT-PCR as a predictor of Acute Kidney Injury and disease severity in critical COVID-19 patients | The novel coronavirus disease (COVID-19) is an emerging infectious disease caused by SARS-CoV-2, which began as an outbreak in Wuhan, China and spread rapidly throughout the globe. Although the majority of infections are mild, severe and critical COVID-19 patients face deterioration of respiratory function, and may also present extrapulmonary manifestations, mostly affecting the kidney, digestive tract, heart and nervous system. Here, we prospectively evaluated the presence of SARS-CoV-2 genetic material by RT-PCR in urine samples obtained from critical care COVID-19 patients. In 51 patients included, we found higher serum creatinine levels, a longer hospital stay and a more frequent dialysis need in urine-positive patients. These findings could suggest that, in predisposed patients, a direct viral cytopathic effect may contribute to a more severe disease phenotype. | nephrology |
10.1101/2021.01.13.21249701 | Trans Fats Consumption and Body Mass Index in Cross Sectional Analysis | BackgroundTrans fats remain on the market in parts of the world. Emerging evidence suggests that factors beyond calorie balance may affect fat deposition and body mass index (BMI). Trans fats are prooxidant, proinflammatory, and have shown adverse metabolic effects and increased fat deposition in animals.
ObjectiveTo assess the relation of dietary trans fatty acid consumption (dTFA) to BMI in humans.
DesignCross-sectional analysis of baseline data from a broadly-sampling study.
SettingCommunity-dwelling adults from Southern California.
Participants1018 adult men and women aged 20-85 without known diabetes, CVD, or cancer, with screening LDL 115-190mg/dL. Women of procreative potential and children were excluded.
MeasurementsHeight, weight, and waist circumference were measured, and BMI calculated (kg/m2). The Fred Hutchinson Food Frequency Questionnaire provided data on dTFA (grams/day) and calories consumed. Additional covariates included activity, chocolate consumption frequency, and mood. Regression assessed the relation of BMI (outcome) to dTFA, unadjusted and in models adjusting for age and sex, and adding calories and activity, chocolate consumption frequency, and mood.
ResultsHigher dTFA was associated with higher BMI and waist circumference. The coefficient was strengthened, not attenuated, with adjustment for calories and activity, and other assessed covariates. In the fully adjusted model, each gram/day of dTFAs was associated with 0.44 higher BMI (SE=0.12;95%CI=0.21,0.67); P<0.001 and 1cm greater waist circumference (SE=0.35;95%CI=0.37,1.7); P=0.003.
ConclusionFindings relating greater dTFA to higher BMI in humans comport with experimental data in animals, extend adverse metabolic associations of dTFA, and buttress evidence that foods composition, as well as caloric number, bears on BMI. Findings are cross-sectional but strength and consistency of association, biological gradient, and biological plausibility add "weight" to the prospect of a causal connection.
Strengths and limitations of this studyO_LIFindings are cross-sectional and rely on dietary recall.
C_LIO_LIObservational studies carry risks of bias and confounding; but randomized trials are problematic where products with potential for harm are under evaluation.
C_LIO_LIAlthough some nations have implemented plans to remove or reduce dTFAs from the food supply, dTFA remain on the market in other nations, rendering findings of continued interest.
C_LIO_LIThe association of increased dTFA with increased BMI and waist circumference fits with other documented adverse metabolic associations of dTFA and is buttressed by experimental documentation that dTFA (without excess calories) increases visceral fat in animals, supporting prospects for causality in the observed association.
C_LI | nutrition |
10.1101/2021.01.13.20248620 | Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer | The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. Here, we follow 3 patients with resectable disease and 4 patients with advanced unresectable disease, using exome sequencing of resected tissues and plasma samples (n=20) collected over a [~]2-year period from diagnosis through treatment to death or last follow-up. This includes 4 patients with [≥]3 serial follow-up samples, of whom 2 are exceptionally long survivors (>5 years). Plasma from 3 chronic pancreatitis cases and 3 healthy controls were used as comparison for analysis of ctDNA mutations. We show that somatic mutation profiles in ctDNA are representative of matched tumour genomes. Furthermore, we detect and track ctDNA mutations within core PDAC driver genes, including KRAS, NRAS, HRAS, TP53, SMAD4 and CDKN2A, in addition to patient-specific variants within alternative cancer drivers (TP53, MTOR, ERBB2, EGFR, PBRM1, RNF43). Multiple trackable ([≥] 2 plasma) ctDNA alterations with potential for therapeutic actionability in PDAC are also identified. These include variants predictive of treatment response to platinum chemotherapy and/or PARP inhibition and a unique chromosome 17 kataegis locus co-localising with ERBB2 driver variants and hypermutation signatures in one long-surviving patient. Finally, we demonstrate that exome profiling can facilitate the assessment of clonality within ctDNA mutations, for the determination of total ctDNA burden alongside temporal evolutionary relationships. These findings provide proof-of-concept for the use of whole exome sequencing of serial plasma samples to characterise ctDNA load and mutational profiles in patients with PDAC. | oncology |
10.1101/2021.01.14.21249826 | Heart rate and heart rate variability in patients with chronic inflammatory joint disease: The role of pain duration and the insular cortex | Chronic inflammatory joint diseases (CIJD) have been linked to increased cardiovascular morbidity and mortality. A decisive reason could be a dysregulation of the autonomic nervous system (ANS), which is responsible for the control of cardio-vascular function. So far, the cause of changes in ANS functions remains elusive. In this study, we investigate the role of chronic pain and the insular cortex in autonomic control of cardiac functioning in patients with CIJD. We studied the sympathetic and parasympathetic branch of the ANS through the assessment of heart rate and heart rate variability (HRV) at rest and under cognitive stimulation. Furthermore, we investigated insular cortex volume by performing surface-based brain morphometry with FreeSurfer. For this study, 22 individual age- and sex-matched pairs for the magnetic resonance imaging analyses and 14 for the HRV analyses were recruited. Pain duration was negatively correlated with the resting heart rate in patients with chronic inflammatory joint diseases (n = 19). In a multiple linear regression model including only CIJD patients with HR at rest as a dependent variable, we found a significant positive relationship between HR at rest and the volume of the left insular cortex and a significant negative relationship between HR at rest and the volume of the right insular cortex. However, we found no significant differences in HRV parameters or insular cortex volumes between both groups. In this study we provide evidence to suggest insular cortex involvement in the process of ANS changes due to chronic pain in CIJD patients. | pain medicine |
10.1101/2021.01.14.21249826 | Heart rate and heart rate variability in patients with chronic inflammatory joint disease: The role of pain duration and the insular cortex | Chronic inflammatory joint diseases (CIJD) have been linked to increased cardiovascular morbidity and mortality. A decisive reason could be a dysregulation of the autonomic nervous system (ANS), which is responsible for the control of cardio-vascular function. So far, the cause of changes in ANS functions remains elusive. In this study, we investigate the role of chronic pain and the insular cortex in autonomic control of cardiac functioning in patients with CIJD. We studied the sympathetic and parasympathetic branch of the ANS through the assessment of heart rate and heart rate variability (HRV) at rest and under cognitive stimulation. Furthermore, we investigated insular cortex volume by performing surface-based brain morphometry with FreeSurfer. For this study, 22 individual age- and sex-matched pairs for the magnetic resonance imaging analyses and 14 for the HRV analyses were recruited. Pain duration was negatively correlated with the resting heart rate in patients with chronic inflammatory joint diseases (n = 19). In a multiple linear regression model including only CIJD patients with HR at rest as a dependent variable, we found a significant positive relationship between HR at rest and the volume of the left insular cortex and a significant negative relationship between HR at rest and the volume of the right insular cortex. However, we found no significant differences in HRV parameters or insular cortex volumes between both groups. In this study we provide evidence to suggest insular cortex involvement in the process of ANS changes due to chronic pain in CIJD patients. | pain medicine |
10.1101/2021.01.13.21249611 | Application of Optical Genome Mapping For Comprehensive Assessment of Chromosomal Structural Variants for Clinical Evaluation of Myelodysplastic Syndromes | Structural chromosomal variants [copy number variants (CNVs): losses/ gains and structural variants (SVs): inversions, balanced and unbalanced fusions/translocations] are important for diagnosis and risk-stratification of myelodysplastic syndromes (MDS). Optical genome mapping (OGM) is a novel single-platform cytogenomic technique that enables high-throughput, accurate and genome-wide detection of all types of clinically important chromosomal variants (CNVs and SVs) at a high resolution, hence superior to current standard-of-care cytogenetic techniques that include conventional karyotyping, FISH and chromosomal microarrays. In this proof-of-principle study, we evaluated the performance of OGM in a series of 12 previously well-characterized MDS cases using clinical BM samples. OGM successfully facilitated detection and detailed characterization of twenty-six of the 28 clonal chromosomal variants (concordance rate: 93% with conventional karyotyping; 100% with chromosomal microarray). These included copy number gains/losses, inversions, inter and intra-chromosomal translocations, dicentric and complex derivative chromosomes; the degree of complexity in latter aberrations was not apparent using standard technologies. The 2 missed aberrations were from a single patient within a composite karyotype, below the limit of detection. Further, OGM uncovered 6 additional clinically relevant sub-microscopic aberrations in 4 (33%) patients that were cryptic by standard-of-care technologies, all of which were subsequently confirmed by alternate platforms. OGM permitted precise gene-level mapping of clinically informative genes such as TP53, TET2 and KMT2A, voiding the need for multiple confirmatory assays. OGM is a potent single-platform assay for high-throughput and accurate identification of clinically important chromosomal variants. | genetic and genomic medicine |
10.1101/2021.01.13.21249774 | Automated Bias Reduction in Deep Learning Based Melanoma Diagnosis using a Semi-Supervised Algorithm | Melanoma is one of the most fatal forms of skin cancer and is often very difficult to differentiate from other benign skin lesions. However, if detected at its early stages, it can almost always be cured. Researchers and data scientists have studied this disease in-depth with the help of large datasets containing high-quality dermascopic images, such as those assembled by the International Skin Imaging Collaboration (ISIC). However, these images often lack diversity and over-represent patients with very common skin features such as light skin and having no visible body hair. In this study, we introduce a novel architecture called LatentNet which automatically detects over-represented features and reduces their weights during training. We tested our model on four distinct categories - three skin color levels corresponding to Type I, II, and III on the Fitzpatrick Scale, and images containing visible hair. We then compared the accuracy against the conventional Deep Convolutional Neural Network (DCNN) model trained using the standard approach (i.e. without detecting over-represented features) and containing the same hyper-parameters as the LatentNet. LatentNet showed significant performance improvement over the standard DCNN model with accuracy of 89.52%, 79.05%, 64.31%, and 64.35% compared to the DCNN accuracy of 90.41%, 70.82%, 45.28%, 56.52% in the corresponding categories, respectively. Differences in the average performance between the models were statistically significant (p < 0.05), suggesting that the proposed model successfully reduced bias amongst the tested categories. LatentNet is the first architecture that addresses racial bias (and other sources of bias) in deep-learning based Melanoma diagnosis. | health informatics |
10.1101/2021.01.13.21249774 | Automated Bias Reduction in Deep Learning Based Melanoma Diagnosis using a Semi-Supervised Algorithm | Melanoma is one of the most fatal forms of skin cancer and is often very difficult to differentiate from other benign skin lesions. However, if detected at its early stages, it can almost always be cured. Researchers and data scientists have studied this disease in-depth with the help of large datasets containing high-quality dermascopic images, such as those assembled by the International Skin Imaging Collaboration (ISIC). However, these images often lack diversity and over-represent patients with very common skin features such as light skin and having no visible body hair. In this study, we introduce a novel architecture called LatentNet which automatically detects over-represented features and reduces their weights during training. We tested our model on four distinct categories - three skin color levels corresponding to Type I, II, and III on the Fitzpatrick Scale, and images containing visible hair. We then compared the accuracy against the conventional Deep Convolutional Neural Network (DCNN) model trained using the standard approach (i.e. without detecting over-represented features) and containing the same hyper-parameters as the LatentNet. LatentNet showed significant performance improvement over the standard DCNN model with accuracy of 89.52%, 79.05%, 64.31%, and 64.35% compared to the DCNN accuracy of 90.41%, 70.82%, 45.28%, 56.52% in the corresponding categories, respectively. Differences in the average performance between the models were statistically significant (p < 0.05), suggesting that the proposed model successfully reduced bias amongst the tested categories. LatentNet is the first architecture that addresses racial bias (and other sources of bias) in deep-learning based Melanoma diagnosis. | health informatics |
10.1101/2021.01.14.21249618 | Using ICD-10-based Social Determinants of Health Categories to Assess Patients Risk for Acute Care Utilization | BackgroundThere has been an increasing recognition of the influence of social, behavioral, economic, and environmental factors on overall patient health. The purpose of this project was to leverage the ICD-10 codes to identify and link social determinants of health (SDoH) to patients with a high probability of utilizing acute care services and to determine if social service intervention reduced care utilization.
MethodsWe analyzed retrospective data for active patients at a Department of Veterans Affairs Medical Center (VAMC) from 2015-2017. Eleven categories of SDoH were developed based on existing literature of the social determinants; the relevant ICD-10 codes were divided among these categories. Emergency Room (ER) visits, hospital admissions, and social work visits were determined for each patient in the cohort.
ResultsIn a cohort of 44,401 patients, the presence of ICD-10 codes within the EHR in the 11 SDoH categories was positively correlated with increased acute care utilization. Veterans with at least one SDoH risk factor were 71% (95%CI: 68% - 75%) more likely to use the ED and 71% (95%CI: 65%-77%) more likely to be admitted to the hospital. Utilization decreased with social service interventions.
ConclusionThis project demonstrates a potentially meaningful method to capture patient social risk profiles through existing EHR data in the form of ICD-10 codes, which can be used to identify the highest risk patients for intervention with the understanding that not all SDoH codes are uniformly used and some SDoHs may not be captured. | health informatics |
10.1101/2021.01.14.21249618 | Using ICD-10-based Social Determinants of Health Categories to Assess Patients Risk for Acute Care Utilization | BackgroundThere has been an increasing recognition of the influence of social, behavioral, economic, and environmental factors on overall patient health. The purpose of this project was to leverage the ICD-10 codes to identify and link social determinants of health (SDoH) to patients with a high probability of utilizing acute care services and to determine if social service intervention reduced care utilization.
MethodsWe analyzed retrospective data for active patients at a Department of Veterans Affairs Medical Center (VAMC) from 2015-2017. Eleven categories of SDoH were developed based on existing literature of the social determinants; the relevant ICD-10 codes were divided among these categories. Emergency Room (ER) visits, hospital admissions, and social work visits were determined for each patient in the cohort.
ResultsIn a cohort of 44,401 patients, the presence of ICD-10 codes within the EHR in the 11 SDoH categories was positively correlated with increased acute care utilization. Veterans with at least one SDoH risk factor were 71% (95%CI: 68% - 75%) more likely to use the ED and 71% (95%CI: 65%-77%) more likely to be admitted to the hospital. Utilization decreased with social service interventions.
ConclusionThis project demonstrates a potentially meaningful method to capture patient social risk profiles through existing EHR data in the form of ICD-10 codes, which can be used to identify the highest risk patients for intervention with the understanding that not all SDoH codes are uniformly used and some SDoHs may not be captured. | health informatics |
10.1101/2021.01.14.21249793 | Real-Time Electronic Health Record Mortality Prediction During the COVID-19 Pandemic: A Prospective Cohort Study | BackgroundThe SARS-CoV-2 virus has infected millions of people, overwhelming critical care resources in some regions. Many plans for rationing critical care resources during crises are based on the Sequential Organ Failure Assessment (SOFA) score. The COVID-19 pandemic created an emergent need to develop and validate a novel electronic health record (EHR)-computable tool to predict mortality.
Research QuestionsTo rapidly develop, validate, and implement a novel real-time mortality score for the COVID-19 pandemic that improves upon SOFA.
Study Design and MethodsWe conducted a prospective cohort study of a regional health system with 12 hospitals in Colorado between March 2020 and July 2020. All patients >14 years old hospitalized during the study period without a do not resuscitate order were included. Patients were stratified by the diagnosis of COVID-19. From this cohort, we developed and validated a model using stacked generalization to predict mortality using data widely available in the EHR by combining five previously validated scores and additional novel variables reported to be associated with COVID-19-specific mortality. We compared the area under the receiver operator curve (AUROC) for the new model to the SOFA score and the Charlson Comorbidity Index.
ResultsWe prospectively analyzed 27,296 encounters, of which 1,358 (5.0%) were positive for SARS-CoV-2, 4,494 (16.5%) included intensive care unit (ICU)-level care, 1,480 (5.4%) included invasive mechanical ventilation, and 717 (2.6%) ended in death. The Charlson Comorbidity Index and SOFA scores predicted overall mortality with an AUROC of 0.72 and 0.90, respectively. Our novel score predicted overall mortality with AUROC 0.94. In the subset of patients with COVID-19, we predicted mortality with AUROC 0.90, whereas SOFA had AUROC of 0.85.
InterpretationWe developed and validated an accurate, in-hospital mortality prediction score in a live EHR for automatic and continuous calculation using a novel model, that improved upon SOFA.
Take Home PointsO_ST_ABSStudy QuestionC_ST_ABSCan we improve upon the SOFA score for real-time mortality prediction during the COVID-19 pandemic by leveraging electronic health record (EHR) data?
ResultsWe rapidly developed and implemented a novel yet SOFA-anchored mortality model across 12 hospitals and conducted a prospective cohort study of 27,296 adult hospitalizations, 1,358 (5.0%) of which were positive for SARS-CoV-2. The Charlson Comorbidity Index and SOFA scores predicted all-cause mortality with AUROCs of 0.72 and 0.90, respectively. Our novel score predicted mortality with AUROC 0.94.
InterpretationA novel EHR-based mortality score can be rapidly implemented to better predict patient outcomes during an evolving pandemic. | health informatics |
10.1101/2021.01.12.21249581 | Dynamical Pool-Size Optimization for the SARS-CoV-2 PCR Test | In this work, we put forward a novel test strategy, that allows to significantly increase the test capacity for SARS-CoV-2. The test strategy is based on an a priory risk assessment scheme, that allows to dynamically find and adapt an optimal clustering size of test pools. We, furthermore, suggest a method to overcome the efficiency loss of test clustering by avoiding concentration losses in the test samples. We validated our method with several thousand probe pools performing RT-PCR tests, and found it highly effective. | health informatics |
10.1101/2021.01.12.21249700 | Impact of CancelRx on Discontinuation of Controlled Substance Prescriptions | ObjectiveTo assess how controlled substance medication discontinuations were communicated over time
Data SourcesSecondary data from a midwestern academic health system electronic health record and pharmacy platform were collected 12-months prior to CancelRx implementation and for 12-months post implementation.
Study DesignThe study utilized an interrupted time series analysis (ITSA) to capture the proportion of controlled substance medications that were cancelled in the clinics electronic health record and also cancelled in the pharmacys dispensing software. The ITSA plotted the proportion of successful cancellation messages over time, particularly after the health systems implementation of CancelRx, a novel technology.
Data Collection/ExtractionData were extracted from the EHR and pharmacy records for patients aged 18+ who had a controlled substance discontinued by a health system provider. Information collected included patient demographics, drug information (name, dose), and dates discontinued in the clinic and pharmacy records.
Principal FindingsAfter CancelRx implementation there was a significant increase in the proportion of discontinued controlled substance medications that were communicated to the pharmacy.
ConclusionsThis study demonstrates the role that technology can play in promoting controlled substance policy and medication safety. | health systems and quality improvement |
10.1101/2021.01.13.21249734 | Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the hospital environment: a bacterial genome-wide association study | BackgroundStaphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease.
MethodsTo investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage.
ResultsAll major global lineages were represented in both bacteraemia and carriage, with no evidence for different attack rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (p=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4).
Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (p=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (p=10-7.2).
ConclusionsIn an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment.
Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and hospital-associated carriage, suggesting that AMR increases the propensity not only to survive in hospital environments, but also to cause invasive disease. | infectious diseases |
10.1101/2021.01.14.21249782 | COVID-19 dynamics in an Ohio prison | ImportanceIncarcerated individuals are a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Understanding SARS-CoV-2 dynamics in prisons is crucial for curbing transmission both within correctional facilities and in the surrounding community.
ObjectiveThe purpose of this study was to identify transmission scenarios that could underly rapid, widespread SARS-CoV-2 infection among inmates in Marion Correctional Institution (MCI).
DesignPublicly available data reported by the Ohio Department of Rehabilitation and Corrections (ODRC) was analyzed using mathematical and statistical models.
SettingWe consider SARS-CoV-2 transmission dynamics among MCI inmates prior to and including April 16, 2020.
ParticipantsThis study uses de-identified, publicly available SARS-CoV-2 test result data for MCI inmates.
ExposuresInmates at MCI were considered exposed to potential infection with SARS-CoV-2.
Main outcome and measuresResults from mass testing conducted on April 16, 2020 were analyzed together with time of first reported SARS-CoV-2 infection among MCI inmates.
ResultsRapid, widespread infection of MCI inmates was reported, with nearly 80% of inmates infected within three weeks of first reported inmate case. These data are consistent with i) a basic reproduction number greater than 14, together with a single initially infected inmate, ii) an initial super-spreading event resulting in several hundred initially infected inmates, together with a basic reproduction number of approximately three, and iii) earlier undetected circulation of virus among inmates prior to April.
Conclusions and relevanceMass testing data are consistent with extreme transmissibility, super-spreading events, or undetected circulation of virus among inmates. All scenarios consistent with these data attest to the vulnerabilities of prisoners to COVID-19.
Key pointsO_ST_ABSQuestionC_ST_ABSTo identify transmission characteristics consistent with timing and extent of SARS-CoV-2 infection among inmates in Marion Correctional Institution.
FindingsMathematical and statistical modeling finds three scenarios that are consistent with the observed widespread infection in Marion Correctional Institution: i) very high transmissibility corresponding to a basic reproduction number in the double digits, ii) an initial super-spreading event involving exposure of several hundred inmates, iii) undetected circulation of virus prior to the first documented case among inmates.
MeaningHigh transmissibility, super-spreading events, and challenges with disease surveillance all attest to the vulnerabilities of prison populations to SARS-CoV-2. | infectious diseases |
10.1101/2021.01.15.21249818 | Estimating and forecasting the burden and spread of SARS-CoV2 first wave in Colombia. | AO_SCPLOWBSTRACTC_SCPLOWFollowing the rapid dissemination of COVID-19 cases in Colombia in 2020, large-scale non-pharmaceutical interventions (NPIs) were implemented as national emergencies in most of the municipalities of the country starting by a lockdown on March 20th of 2020. Using combinations of meta-population models SEAIIRD (Susceptible-Exposed-Asymptomatic-Infected-Recovered-Diseased) which describes the disease dynamics in the different localities, with movement data that accounts for the number of commuters between units and statistical inference algorithms could be an effective approach to both nowcast and forecast the number of cases and deaths in the country. Here we used an iterated filtering (IF) framework to fit the parameters of our model to the reported data across municipalities from march to late October in locations with more than 50 reported deaths and cases historically. Since the model is high dimensional (6 state variable by municipality) inference on those parameters is highly non-trivial, so we used an Ensemble-Adjustment-Kalman-Filter (EAKF) to estimate time variable system states and parameters. Our results show that the model is capable of capturing the evolution of the outbreak in the country and providing estimates of the epidemiological parameters in time. These estimates could become the base for planning future interventions as well as evaluate the impact of NPIs on the effective reproductive number ([R]eff) and the key epidemiological parameters, such as the contact rate or the reporting rate. Our approach demonstrates that real-time, publicly available ensemble forecasts can provide robust short-term predictions of reported COVID-19 deaths in Colombia. This model has the potential to be used as a forecasting and prediction tool to evaluate disease dynamics and to develop a real time surveillance system for management and control. | infectious diseases |
10.1101/2021.01.14.21249620 | Comparison and analysis of various complementary diagnosis methods for the current situation and problems of COVID-19 diagnosis | We evaluated and compared the diagnostic performance of fluorescence immunoassay (FIA) and two types of serological diagnostic tests: enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay (ICA) for detection of SARS-CoV-2 antigen and antibody to diagnose COVID-19 infections. This study is aimed to analyze and compare the current status and problems of COVID-19 diagnosis and various alternative diagnostic methods that are viable. The enrolled subjects in our study population were tested with real-time polymerase chain reaction (RT-PCR). ELISA and immunochromatographic diagnostic kit were used to diagnose 362 positive and 3010 negative SARS-CoV-2 specimens, and antigen fluorescence immunoassay kit was used on 62 positive and 70 negative SARS-CoV-2 RT-PCR confirmed samples for diagnosis. As a result, categorizing by the patient symptom onset days, PCL COVID19 Total Ab EIA (ELISA) showed the sensitivity of 93.4% from 15 to 21 days, 94.2% from over 22 days, and the specificity of 99.97%. PCL COVID19 IgG/IgM Rapid Gold (ICA) had a sensitivity of 86.9%, 97.4%, and the specificity of 98.14% respectively. PCL COVID19 Ag Rapid FIA sensitivity was 93.8% from 0 to 7 days, 71.4% from 8 to 12 days and specificity was 98.57%. In conclusion, COVID-19 Ab ELISA and ICA, and COVID-19 Ag FIA are all complementary and applicable diagnostic methods to resolve the current problems of COVID-19 diagnosis. | infectious diseases |
10.1101/2021.01.14.21249851 | SARS-Cov-2 prevalence, transmission, health-related outcomes and control strategies in homeless shelters: systematic review and meta-analysis | BackgroundPeople experiencing homelessness (PEH) may be at particular risk for COVID19. We synthesised the evidence on SARS-Cov-2 infection, transmission, outcomes of disease, effects of non-pharmaceutical interventions (NPI), and the effectiveness of targeted strategies for infection prevention and control (IPC).
MethodsSystematic review of articles, reports and grey-literature indexed in electronic databases (EMBASE, WHO-Covid19, Web of Science), pre-print repositories, institutional websites, and handsearching. Empirical papers of any study design addressing Covid-19 in PEH or homeless shelters staff in English were included. (PROSPERO 2020 CRD42020187033)
FindingsOf 194 publications, 13 studies were included (two modelling, ten observational and one qualitative study). All were conducted in high-income countries. Random-effect meta-analysis of prevalence estimates yields a baseline SARS-Cov-2 prevalence of 2{middle dot}14% (95% Confidence-Interval, 95%CI=1{middle dot}02-3{middle dot}27) in PEH and 1{middle dot}72 % (95%CI=0{middle dot}31-3{middle dot}12) in staff. In outbreaks, the pooled prevalence increases to 29{middle dot}49% (95%CI=16{middle dot}44-29{middle dot}55) in PEH and 15{middle dot}18% (95%CI=8{middle dot}95-21{middle dot}42) in staff. Main IPC strategies were universal and rapid testing, expansion of non-congregate housing support, and individual measures in shelters (bed spacing, limited staff rotation).
InterpretationUp to 30% PEH and 17% staff are infected during outbreaks of SARS-Cov-2 in homeless shelters. Most studies were conducted in the USA. No studies were found on health-related outcomes or health effects of NPI. An overview and evaluation of IPC strategies for PEH, including a better understanding of disease transmission, and reliable data on PEH within Covid-19 notification systems is needed. Qualitative studies may serve to voice PEH experiences and guide future evaluations and IPC strategies.
FundingNo source of funding.
Panel 1: Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPeople experiencing homelessness (PEH) are at increased risk of infectious, chronic, and mental health adverse conditions. Due to the risk of transmission in shared accommodations, PEH may be particularly vulnerable to SARS-Cov-2 infection and worse clinical outcomes. Non-pharmaceutical interventions (NPIs) taken to mitigate the SARS-Cov-2 outbreak may have further aggravated health and social conditions. However, there is no evidence synthesis on the SARS-Cov-2 epidemiology among PEH, the correspondent clinical and other health-related outcomes as well as health effects of NPIs on these groups.
Added value of this study
We reviewed and synthesized existent evidence on the risk of infection and transmission, risk of severe course of disease, effect of NPIs on health outcomes and the effectiveness of implemented measures to avert risks and negative outcomes among PEH. Results of the identified studies suggest that both PEH and shelter staff are at high risk of SARS-Cov-2 infection, especially in case of a local outbreak. Due to the low prevalence of symptoms at the time of a positive SARS-Cov-2 test among PEH, symptom screening alone may not be efficient to control outbreaks. Instead, universal and rapid testing conjugated with expansion of non-congregate housing support, and individual measures in shelters, are discussed as sensible strategies.
Implications of all the available evidence
A comprehensive overview of NPIs and shelter strategies targeting PEH and evaluation of their effectiveness and unintended health consequences is needed. Qualitative research considering living realities of PEH can facilitate understanding of their specific needs during the pandemic. | infectious diseases |
10.1101/2021.01.13.21249563 | COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing | Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Here we report on standardised laboratory evaluations of LFDs, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots (UK COVID-19 testing centres, hospital, schools, armed forces). 4/64 LFDs so far have desirable performance characteristics (Orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1-6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20-0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists (156/198, 95% CI 72.4-84.3) was 78.8%. Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission.
FundingDepartment of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research. | infectious diseases |
10.1101/2021.01.13.21249563 | COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing | Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Here we report on standardised laboratory evaluations of LFDs, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots (UK COVID-19 testing centres, hospital, schools, armed forces). 4/64 LFDs so far have desirable performance characteristics (Orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1-6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20-0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists (156/198, 95% CI 72.4-84.3) was 78.8%. Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission.
FundingDepartment of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research. | infectious diseases |
10.1101/2021.01.14.21249848 | Understanding COVID-19 dynamics and the effects of interventions in the Philippines: A mathematical modelling study | ObjectiveCOVID-19 appears to have caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with high-income countries, possibly because of differing demographics, socio-economics, surveillance, and policy responses. Here, we investigate the role of multiple factors on COVID-19 dynamics in the Philippines, a LMIC that has had a relatively severe COVID-19 outbreak.
MethodsWe applied an age-structured compartmental model that incorporated time-varying mobility, testing, and personal protective behaviors (through a "Minimum Health Standards" policy, MHS) to represent the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon, Central Visayas, and the National Capital Region). We estimated effects of control measures, key epidemiological parameters, and interventions.
FindingsPopulation age structure, contact rates, mobility, testing, and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases, hospitalisations, and deaths. Several of the fitted epidemiological parameters were consistent with those reported in high-income settings. The model indicated that MHS reduced the probability of transmission per contact by 15-26%. The February 2021 case detection rate was estimated at [~]9%, population recovered at [~]12%, and scenario projections indicated high sensitivity to MHS adherence.
ConclusionsCOVID-19 dynamics in the Philippines are driven by age, contact structure, mobility, and MHS adherence, and the epidemic can be understood within a similar framework as for high-income settings. Continued compliance with low-cost MHS should allow the Philippines to maintain epidemic control until vaccines are widely distributed, but disease resurgence could occur due to low population immunity and detection rates. | infectious diseases |
10.1101/2021.01.14.21249848 | Understanding COVID-19 dynamics and the effects of interventions in the Philippines: A mathematical modelling study | ObjectiveCOVID-19 appears to have caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with high-income countries, possibly because of differing demographics, socio-economics, surveillance, and policy responses. Here, we investigate the role of multiple factors on COVID-19 dynamics in the Philippines, a LMIC that has had a relatively severe COVID-19 outbreak.
MethodsWe applied an age-structured compartmental model that incorporated time-varying mobility, testing, and personal protective behaviors (through a "Minimum Health Standards" policy, MHS) to represent the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon, Central Visayas, and the National Capital Region). We estimated effects of control measures, key epidemiological parameters, and interventions.
FindingsPopulation age structure, contact rates, mobility, testing, and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases, hospitalisations, and deaths. Several of the fitted epidemiological parameters were consistent with those reported in high-income settings. The model indicated that MHS reduced the probability of transmission per contact by 15-26%. The February 2021 case detection rate was estimated at [~]9%, population recovered at [~]12%, and scenario projections indicated high sensitivity to MHS adherence.
ConclusionsCOVID-19 dynamics in the Philippines are driven by age, contact structure, mobility, and MHS adherence, and the epidemic can be understood within a similar framework as for high-income settings. Continued compliance with low-cost MHS should allow the Philippines to maintain epidemic control until vaccines are widely distributed, but disease resurgence could occur due to low population immunity and detection rates. | infectious diseases |
10.1101/2021.01.13.21249725 | The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres | The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+ effector:effector memory T cells, and proliferating CD4+ and CD8+ T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19. | infectious diseases |
10.1101/2021.01.14.21249690 | Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarray | The emergence and rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of varying lengths and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multi-coronavirus arrays to identify specific antibody reactivity. High level IgG, IgM and IgA reactivity to structural proteins S, M and N, as well as accessory proteins, of SARS-CoV-2 were observed that was specific to COVID-19 patients. Overlapping 100, 50 and 30 amino acid fragments of SARS-CoV-2 proteins identified antigenic regions. Numerous proteins of SARS-CoV, MERS-CoV and the endemic human coronaviruses, HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients. | infectious diseases |
10.1101/2021.01.13.21249412 | Real-time optical analysis of a colorimetric LAMP assay for SARS-CoV-2 in saliva with a handheld instrument improves accuracy compared to endpoint assessment | Controlling the course of the COVID-19 pandemic will require widespread deployment of consistent and accurate diagnostic testing of the novel coronavirus SARS-CoV-2. Ideally, tests should detect a minimum viral load, be minimally invasive, and provide a rapid and simple readout. Current FDA-approved RT-qPCR-based standard diagnostic approaches require invasive nasopharyngeal swabs and involve laboratory-based analyses that can delay results. Recently, a loop mediated isothermal nucleic acid amplification (LAMP) test that utilizes colorimetric readout received FDA approval. This approach utilizes a pH indicator dye to detect drop in pH from nucleotide hydrolysis during nucleic acid amplification. This method has only been approved for use with RNA extracted from clinical specimens collected via nasopharyngeal swabs. In this study, we developed a quantitative LAMP-based strategy to detect SARS-CoV-2 RNA in saliva. Our detection system distinguished positive from negative sample types using a handheld instrument that monitors optical changes throughout the LAMP reaction. We used this system in a streamlined LAMP testing protocol that could be completed in less than two hours to directly detect inactivated SARS-CoV-2 in minimally processed saliva that bypassed RNA extraction, with a limit of detection (LOD) of 50 genomes/reaction. The quantitative method correctly detected virus in 100% of contrived clinical samples spiked with inactivated SARS- CoV-2 at either 1X (50 genomes/reaction) or 2X (100 genomes/reaction) of the LOD. Importantly the quantitative method was based on dynamic optical changes during the reaction so was able to correctly classify samples that were misclassified by endpoint observation of color. | infectious diseases |
10.1101/2021.01.13.21249629 | A Novel Multiplex PCR Based Detection Assay Using Saliva or Nasopharyngeal Samples for SARS-Cov-2, Influenza A and B: Clinical Validation and Utility for Mass Surveillance. | BackgroundThe COVID-19 pandemic has resulted in a significant diversion of human and material resources to COVID-19 diagnostics, to the extent that testing of viral pathogens normally contributing to seasonal respiratory tract infections have been markedly neglected. The global health burden due to influenza viruses and co-infection in COVID-19 patients remains undocumented but clearly pose serious public health consequences. To address these clinical and technical challenges, we have optimized and validated a highly sensitive RT-PCR based multiplex assay for the detection of SARS-CoV-2, Influenza A and B viruses in a single test.
MethodsThis study evaluated clinical specimens (n=1411) that included 1019 saliva and 392 nasopharyngeal swab (NPS) samples collected in either healthcare or community setting. Samples were tested using two assays: FDA-EUA approved SARS-CoV-2 assay that targets N and ORF1ab gene, and the PKamp RT-PCR based assay that targets SARS-CoV-2, Influenza viruses A and B. The limit of detection (LoD) studies was conducted as per the FDA guidelines using SARS-CoV-2 and Influenza A and B reference control materials.
ResultsOf the 1019 saliva samples, 17.0% (174/1019) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with our multiplex assay compared to SARS-specific assay [91.9% (160/174) vs. 87.9% (153/174)], respectively. Of the 392 NPS samples, 10.4% (41/392) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with our multiplex assay compared to SARS-specific assay [97.5% (40/41) vs. 92.1% (39/41)], respectively. The Ct values for SARS-CoV-2 were comparable between the two assays, whereas the Ct values of the housekeeping gene was significantly lower with multiplex assay compared to SARS-specific assay. The LoD was established as 60 copies/ml for SARS-CoV-2 and 180 copies/ml for Influenza A and B viruses for both saliva and NPS samples.
ConclusionThis study presents clinical validation of a multiplex PCR assay for testing SARS-CoV-2, Influenza A and B viruses, using NPS and saliva samples, and demonstrates the feasibility of implementing the assay without disrupting the existing laboratory workflow. This novel assay uses the same instruments, sample types, supplies, and laboratory personnel as needed for the testing of SARS-CoV-2 virus. | infectious diseases |
10.1101/2021.01.13.21249749 | Mass Testing with Contact Tracing Compared to Test and Trace for Effective Suppression of COVID-19 in the UK: A rapid review | BackgroundMaking testing available to everyone and tracing contacts might be the gold standard towards the control of COVID-19, particularly when significant transmissions are without symptoms. This study evaluated the effectiveness of mass testing and contact tracing in the suppression of COVID-19 compared to conventional Test and Trace in the UK.
DesignA rapid review of available evidence
Primary research questionIs there evidence that mass testing and tracing could suppress community spread of SARS-CoV-2 infections better than Test and Trace?
Secondary research questionWhat is the proportion of asymptomatic cases of SARS-CoV-2 reported during mass testing interventions?
MethodsLiterature was searched in September through December 2020 in Google Scholar, ScienceDirect, Mendeley and PubMed.
ResultsLiterature search yielded 286 articles from Google Scholar, 20 from Science Direct, 14 from Mendeley, 27 from Pubmed and 15 through manual search. Altogether 35 articles were included, making a sample size of close to a million participants.
ConclusionThere was a very low level but promising evidence of 76.9% (95% CI: 46.2 - 95.0, P=0.09) majority vote in favour of the intervention under the primary objective. The overall proportion of asymptomatic cases among those tested positive and tested sample populations under the secondary objective was 40.7% (95% CI: 38.8- 42.5) and 0.01% (95% CI: 0.01 - 0.012) respectively. Conventional test and trace should be superseded by a decentralised and regular mass rapid testing and contact tracing, championed by GP surgeries and low cost community services. | infectious diseases |
10.1101/2021.01.13.20249038 | Nasopharyngeal and serological anti SARS-CoV-2 IgG/IgA responses in COVID-19 patients. | BackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.
MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.
ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.
ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response. | infectious diseases |
10.1101/2021.01.12.21249665 | Understanding non-adherence to tuberculosis medications in India using urine drug metabolite testing: a cohort study | BackgroundSuboptimal adherence to tuberculosis (TB) treatment is associated with increased disease recurrence and death. Little research has been conducted in India to understand TB medication non-adherence.
MethodsWe enrolled adult drug-susceptible TB patients, about half of whom were people living with HIV (PLHIV), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for non-adherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for non-adherence and identified factors associated with non-adherence (negative urine test) using multivariable logistic regression. We also assessed the association between non-adherence and unfavorable treatment outcomes.
ResultsOf 650 patients in the cohort, 77 (11.8%) had a negative urine test result. Non-adherence was independently associated with daily wage labor (aOR 3.1, CI: 1.3--7.7), smear-positive pulmonary disease (aOR 2.1, CI: 1.1--4.1), alcohol use (aOR 2.3, CI: 1.1--4.8), and spending 60 minutes or more picking up medication refills (aOR 9.1, CI: 1.8--45.4). PLHIV reported greater barriers to picking up medications than non-PLHIV. Among 167 patients who reported missing doses, common reasons reported included traveling away from home, forgetting, feeling depressed, and running out of pills. The odds of non-adherence was 3.8 (CI: 2.1--6.9) times higher among patients with unfavorable treatment outcomes compared to those with favorable outcomes.
ConclusionAddressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify non-adherent patients to facilitate early intervention during treatment.
Key pointsWe evaluated adherence to tuberculosis medications in 650 Indian patients by conducting urine isoniazid tests collected during unannounced home visits. Structural barriers to collecting medication refills and psychosocial barriers emerged as the most important factors contributing to medication non-adherence. | infectious diseases |
10.1101/2021.01.13.21249753 | School and community reopening during the COVID-19 pandemic: a mathematical modeling study | BackgroundThe closure of communities, including schools, has been adopted to control the coronavirus disease 2019 (COVID-19) epidemic in most countries. Operating schools safely during the pandemic requires a balance between health risks and the need for in-person learning. We use compartmental models to explore school reopening scenarios.
MethodsUsing demographic and epidemiological data between July 31 and November 23, 2020 from the city of Toronto, we developed a Susceptible-Exposed-Asymptomatic-Infectious-Recovered-Hospitalized-Isolated model. Our model with age, household, and community transmission allow us to study the impact of schools open in September 2020. The model mimics the transmission in households, the community, and schools, accounting for differences in infectiousness between adults and children and youth and adults working status. We assessed the extent to which school opening may have contributed to COVID-19 resurgence in the fall and simulated scenarios for the safe reopening of schools up to May 31, 2021. We further considered the impact of the introduction of the new variant of concern.
FindingsThough a slight increase in infections among adults (2.8%) and children (5.4%) is anticipated by the end of the year, safe school opening is possible with stringent nonpharmaceutical interventions (NPIs) decreasing the risk of transmission in the community and the household. We found that while school reopening was not the key driver in virus resurgence, but rather it was community spread that determined the outbreak trajectory, brief school closures did reduce infections when transmission risk within the home was low. When considered possible cross-infection amongst households, communities, and schools, we found that home transmission was crucial for mitigating the epidemic and safely operating schools. Simulating the introduction of a new strain with higher infectiousness, we observed substantial increases in infections, even when both schools and communities are closed.
InterpretationSchools can open safely under strict maintenance of strict public health measures in the community. The gradual opening of schools and communities can only be achieved by maintaining NPIs and mitigating household transmission risk to avoid the broader escape of infections acquired in schools into the community via households. If the new COVID-19 strain is more infectious for children, public spaces, including schools, should be closed, and additional NPIs, including the use of masks, should be extended to toddlers.
FundingThis research was supported by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada, and York University Research Chair program.
Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe design of a gradual school reopening strategy remains at the heart of decision-making on reopening after shut-downs to control the epidemic. Although available studies have assessed the risk of school reopening by modelling the transmission across schools and communities, it remains unclear whether the risk is due to increased transmission in adults or children and youth.We used GoogleScholar and PubMed searches to identify previous published works. We used te following terms: "school closure", "covid 19 school closure", "reopening schools", "reopening screening school", "school household second wave model". The search of the studies ended in January 2021. Papers in other languages than English and letters were excluded from the search. Two modelling studies examined the effects of screening and delayed school reopening, two other agent-based modelling studies explored the epidemic spread across different age groups.
Added-value of this studyWe find that the resurgence of COVID-19 in Toronto in fall 2020 mainly resulted from the increase of contact rate among adults in the community, and that the degree of in-person attendance had the most significant impact on transmission in schools. To our knowledge, our work is the first to investigate the resurgence in infections following school reopening and the impact of risk mitigation measures in schools operation during the pandemic. Our novel and comprehensive model considers the age and household structure, but also considers three different settings, school, household and community. We further examined the effects of self-screening procedures, class size, and schooling days on transmission, which enabled us to compare scenarios of school reopening separately for both adults and children and youth, and model the cross-infection between them to avoid potential underestimation. We found that after schools opened, reducing household transmission was crucial for mitigating the epidemic since it can reduce cross-infection amongst households, communities and schools. Lastly, given the recent report of SARS-CoV-2 variant (VOC202012/01), we investigated the impact of the new variant that may be more infectious in children and youth.
Implications of all the available evidenceOur analysis can inform policymakers of planning the safe reopening of schools during COVID-19. We suggest that integrating strict NPIs and school control measures are crucial for safe reopening. When schools are open, reducing transmission risk at home and community is paramount in curbing the spread of COVID-19. Lastly, if children are more susceptible to the new COVID-19 VOC, both schools and community must be closed, the time children spend in essential services locations minimized, and NPIs for those aged less than three years enforced. | infectious diseases |
10.1101/2021.01.13.21249254 | An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients | BackgroundDiagnosing SARS CoV-2 infection with certainty is essential for appropriate case management. We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.
MethodsFrom August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.
ResultsThe overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT- qPCR were 72% (95%CI 62%-81%), 99% (95% CI95%-100%), 99% (95%CI 93%-100%), and 78% (95%CI 70%-85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct [≤] 25 regardless of TSO: TSO [≤] 4 days 92% (95%CI 75%-99%), TSO > 4 days 100% (95%CI 54%-100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.
ConclusionThis study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. Thus, negative results from RAD needs to be confirmed by RT-qPCR prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak. | infectious diseases |
10.1101/2021.01.12.20249080 | Early Analysis of a potential link between viral load and the N501Y mutation in the SARS-COV-2 spike protein | A new variant of SARS-CoV-2 has emerged which is increasing in frequency, primarily in the South East of England (lineage B.1.1.7 (1); VUI-202012/01). One potential hypothesis is that infection with the new variant results in higher viral loads, which in turn may make the virus more transmissible. We found higher (sequence derived) viral loads in samples from individuals infected with the new variant with median inferred viral loads were three-fold higher in individuals with the new variant. Most of the new variants were sampled in Kent and Greater London. We observed higher viral loads in Kent compared to Greater London for both the new variant and other circulating lineages. Outside Greater London, the variant has higher viral loads, whereas within Greater London, the new variant does not have significantly higher viral loads compared to other circulating lineages. Higher variant viral loads outside Greater London could be due to demographic effects, such as a faster variant growth rate compared to other lineages or concentration in particular age-groups. However, our analysis does not exclude a causal link between infection with the new variant and higher viral loads. This is a preliminary analysis and further work is needed to investigate any potential causal link between infection with this new variant and higher viral loads, and whether this results in higher transmissibility, severity of infection, or affects relative rates of symptomatic and asymptomatic infection
Document Description and PurposeThis is an updated report submitted to NERVTAG in December 2020 as part of urgent investigations into the new variant of SARS-COV-2 (VUI-202012/01). It makes full use of (and is restricted to) all sequence data and associated metadata available to us at the time this original report was submitted and remains provisional. Under normal circumstances more genomes and metadata would be obtained and included before making this report public. We will update this preprint when more genomes and metadata are available and before submitting for peer review. | infectious diseases |
10.1101/2021.01.14.21249831 | Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients | BackgroundIncreased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in multiple neutrophil functions and circulating cytokine levels over time during COVID-19 may help define disease severity and guide care and decision making.
MethodsBlood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil oxidative burst, neutrophil extracellular trap formation (NETosis), phagocytosis and cytokine levels were assessed ex vivo. Lung tissue was obtained immediately post-mortem for immunostaining.
ResultsElevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified in COVID-19 plasma both at the first measurement and at multiple timepoints across hospitalization (p < 0.0001). Neutrophils had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis correlated with both leukocytosis and neutrophilia. Neutrophils and NETs were identified within airways and alveoli in the lung parenchyma of 40% of SARS-CoV-2 infected lungs. While elevations in IL-8 and ANC correlated to COVID-19 disease severity, plasma IL-8 levels alone correlated with death.
ConclusionsCirculating neutrophils in COVID-19 exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 and circulating neutrophil function may be potential COVID-19 disease biomarkers. | allergy and immunology |
10.1101/2021.01.13.21249429 | Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients | Several studies suggest that hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections. We hypothesized that the high levels of the inflammatory cytokine Angiopoietin-2 (ANGPT2) reported in hospitalized COVID-19 patients might promote hypercoagulation through ANGPT2 binding to thrombomodulin with resulting inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Plasma was collected from critically ill COVID-19 patients treated in the intensive care unit (ICU) at Uppsala University Hospital and ANGPT2 was measured at admission (61 patients) and after ten days (40 patients). ANGPT2 levels were compared with biochemical parameters, clinical outcome, and survival. We found that ANGPT2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. To test causality, we administered ANGPT2 to wildtype mice and found that it shortened bleeding time in a tail injury model. In further support of a role for ANGPT2 in physiological coagulation, bleeding time was increased in endothelial-specific Angpt2 knockout mice. Using in vitro assays, we found that ANGPT2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data reveal a novel mechanism for ANGPT2 in hypercoagulation and suggest that Angiopoietin-2 inhibition may be tested in the treatment of hypercoagulation in severe COVID-19 infection. | cardiovascular medicine |
10.1101/2021.01.13.21249429 | Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients | Several studies suggest that hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections. We hypothesized that the high levels of the inflammatory cytokine Angiopoietin-2 (ANGPT2) reported in hospitalized COVID-19 patients might promote hypercoagulation through ANGPT2 binding to thrombomodulin with resulting inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Plasma was collected from critically ill COVID-19 patients treated in the intensive care unit (ICU) at Uppsala University Hospital and ANGPT2 was measured at admission (61 patients) and after ten days (40 patients). ANGPT2 levels were compared with biochemical parameters, clinical outcome, and survival. We found that ANGPT2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. To test causality, we administered ANGPT2 to wildtype mice and found that it shortened bleeding time in a tail injury model. In further support of a role for ANGPT2 in physiological coagulation, bleeding time was increased in endothelial-specific Angpt2 knockout mice. Using in vitro assays, we found that ANGPT2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data reveal a novel mechanism for ANGPT2 in hypercoagulation and suggest that Angiopoietin-2 inhibition may be tested in the treatment of hypercoagulation in severe COVID-19 infection. | cardiovascular medicine |
10.1101/2021.01.12.21249697 | Mortality of Diabetes-related Acute Metabolic Emergencies in COVID-19 patients: a systematic review and meta-analysis | PurposeLittle is known on the mortality rate in COVID-19 related acute metabolic emergencies, namely diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS), combined DKA/HHS, and euglycaemic diabetic ketoacidosis (EDKA).
MethodsA systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January 1, 2020 to January 9, 2021 to identify all case report series, cross-sectional studies, and meta-analyses of case reports describing mortality rate in DKA, HHS, and EDKA, in COVID-19 patients. The Joanna Briggs Institute critical appraisal checklist for case reports was used for quality assessment.
ResultsFrom 313 identified publications, 4 fulfilled the inclusion criteria and analyzed qualitatively and quantitatively. A systematic review and meta-analysis with subgroup analyses examined mortality rate in a total of 152 COVID-19 patients who had developed DKA, HHS, combined DKA/HHS, or EDKA. Combined mortality rate and confidence intervals (CI) were estimated using random effects model. The study was registered to PROSPERO database (ID: 230737).
ResultsCombined mortality rate was found to be 27.1% [95% CI: 11.2-46.9%]. Heterogeneity was considerable (I2=83%; 95% CI: 56-93%), corrected to 67% according to Von Hippel adjustment for small meta-analyses. Funnel plot presented no apparent asymmetry; Eggers and Beggs test yielded in P=0.44 and P=0.50, respectively. Sensitivity analysis failed to explain heterogeneity.
ConclusionCOVID-19 related acute metabolic emergencies (DKA, HHS, and EDKA) are characterized by considerable mortality; thus, clinicians should be aware of timely detection and immediate treatment commencing. | endocrinology |
10.1101/2021.01.13.21249507 | Epidemiology of the early COVID-19 epidemic in Orange County, California: comparison of predictors of test positivity, mortality, and seropositivity | COVID-19 is one of the largest public health emergencies in modern history. Here we present a detailed analysis from a large population center in Southern California (Orange County, population of 3.2 million) to understand heterogeneity in risks of infection, test positivity, and death. We used a combination of datasets, including a population-representative seroprevalence survey, to assess the true burden of disease as well as COVID-19 testing intensity, test positivity, and mortality. In the first month of the local epidemic, case incidence clustered in high income areas. This pattern quickly shifted, with cases next clustering in much higher rates in the north-central area which has a lower socio-economic status. Since April, a concentration of reported cases, test positivity, testing intensity, and seropositivity in a north-central area persisted. At the individual level, several factors (e.g., age, race/ethnicity, zip codes with low educational attainment) strongly affected risk of seropositivity and death. | epidemiology |
10.1101/2021.01.13.21249507 | Epidemiology of the early COVID-19 epidemic in Orange County, California: comparison of predictors of test positivity, mortality, and seropositivity | COVID-19 is one of the largest public health emergencies in modern history. Here we present a detailed analysis from a large population center in Southern California (Orange County, population of 3.2 million) to understand heterogeneity in risks of infection, test positivity, and death. We used a combination of datasets, including a population-representative seroprevalence survey, to assess the true burden of disease as well as COVID-19 testing intensity, test positivity, and mortality. In the first month of the local epidemic, case incidence clustered in high income areas. This pattern quickly shifted, with cases next clustering in much higher rates in the north-central area which has a lower socio-economic status. Since April, a concentration of reported cases, test positivity, testing intensity, and seropositivity in a north-central area persisted. At the individual level, several factors (e.g., age, race/ethnicity, zip codes with low educational attainment) strongly affected risk of seropositivity and death. | epidemiology |
10.1101/2021.01.14.21249809 | Evaluating the effects of re-opening plans on dynamics of COVID-19 in SP | Coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in early March 2020. In Brazil, Sao Paulo is the most affected state, comprising about 20% of the countrys cases. With no vaccine available to date, distancing measures have been taken to reduce virus transmission. To reduce the pandemics effect on the economy, the government of Sao Paulo has proposed a plan consisting of five phases of the gradual re-opening of activities. In this context, we have developed a mathematical model to simulate the gradual re-opening plan on the transmission dynamics of COVID-19, in the city of Sao Paulo. The model shows that a precipitous reopening can cause a higher peak of the disease, which may compromise the local health system. Waiting for the reduction in the incidence of infected individuals for at least 15 days to phase transition is the most efficient strategy compared to the fixed-period scenario at each phase of the re-opening plan. | epidemiology |
10.1101/2021.01.15.21249871 | Impact of COVID-19 on Care-Home Mortality and Life Expectancy in Scotland | IntroductionCOVID-19 deaths are commoner among care-home residents, but the mortality burden has not been quantified.
MethodsCare-home residency was identified via a national primary care registration database linked to national mortality data. Life expectancy was estimated using Makeham-Gompertz models, to (i) describe yearly life expectancy from Nov 2015 to Oct 2020 (ii) compare life expectancy (during 2016-2018) between care-home residents and the wider Scottish population and (iii) apply care-home life expectancy estimates to COVID-19 death counts to estimate years of life lost (YLL).
ResultsAmong care-home residents, life expectancy in 2015/16 to 2019/20 ranged from 2.7 to 2.3 years for women and 2.3 to 1.8 years for men. Life expectancy was lowest in 2019/20. Age-sex specific life expectancy in 2016-2018 in care-home residents was lower than in the Scottish population (10 and 2.5 years in those aged 70 and 90 respectively). Rather than using national life tables, applying care-home specific life expectancies to COVID-19 deaths yields, mean YLLs for care-home residents were 2.6 and 2.2 for women and men respectively, with total care-home resident YLLs of 3,560 years in women and 2,046 years in men. In people aged over-70, approximately half of deaths and a quarter of YLL attributed to COVID-19 were accounted for by the 5% of over-70s who were care-home residents.
ConclusionPrioritising care-home residents for vaccination is justified not only in terms of total deaths, but also in terms of years of life lost.
Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed to 1st December 2020, with the terms ("nursing home" OR "care-home" OR "long-term care" OR "residential care") AND ("mortality" OR "life expectancy" OR "length of stay"). We also searched for studies specific to the impact of the COVID-19 pandemic on those living in care-homes. We restricted our search to publications in English. Usual care-home life expectancy, in a UK context, has not previously been defined. One systematic review of length of stay was identified, which found significant heterogeneity in factors and associations. The impact of COVID-19 on excess mortality among care-home residents was noted, but the impact on life expectancy was not reported. Studies evaluating life expectancy among older people in the COVID-19 pandemic have not taken account of residency in their estimates.
Added value of this studyUsing Scottish national representative linked data we describe the usual life expectancy of older adults (aged [≥]70 years) living in care-homes, compared to older people living elsewhere. Deaths among care-home residents account for a considerable proportion of all mortality in older adults, around 19% for men and 30% for women. Life expectancy in care-home residents during the pandemic fell by almost 6 months, from 2.7 to 2.3 years in men and 2.1 to 1.8 years in women. In total, over 5,600 Years of Life were Lost (YLL) by care-home residents in Scotland who died with COVID-19. Around half of COVID-19 deaths and a quarter of YLL in those aged 70 years and over occurred among care-home residents. During the COVID-19 pandemic a smaller proportion of deaths among care-home residents occurred in hospitals.
Implications of all the available evidencePrioritising the 5% of older adults who are care-home residents for vaccination against COVID-19 is justified both in terms of total deaths and total years of life lost. Individual and societal planning for care needs in older age relies on understanding usual care-home life expectancy and patterns of mortality. Understanding life expectancy may help clinicians, residents and their families make decisions about their health care, facilitating more informed discussions around their priorities and wishes. Population-wide estimates of YLL and burden of disease should take account of residency status, given the significant differences between life expectancy of those living in care-homes from their peers in other settings. | epidemiology |
10.1101/2021.01.15.21249870 | Variability of Individual Infectiousness Derived from Aggregate Statistics of COVID-19 | The quantification of spreading heterogeneity in the COVID-19 epidemic is crucial as it affects the choice of efficient mitigating strategies irrespective of whether its origin is biological or social. We present a method to deduce temporal and individual variations in the basic reproduction number R directly from epidemic trajectories at a community level. Using epidemic data from the 98 districts in Denmark we estimate an overdispersion factor k for COVID-19 to be about 0.11 (95% confidence interval 0.08 - 0.18), implying that 10 % of the infected cause between 70 % to 87 % of all infections. | epidemiology |
10.1101/2021.01.15.21249731 | SARS-CoV-2 reinfection in a cohort of 43,000 antibody-positive individuals followed for up to 35 weeks | BackgroundReinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. Risk and incidence rate of SARS-CoV-2 reinfection were assessed in a large cohort of antibody-positive persons in Qatar.
MethodsAll SARS-CoV-2 antibody-positive persons with a PCR-positive swab [≥]14 days after the first-positive antibody test were individually investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those antibody-negative.
ResultsAmong 43,044 anti-SARS-CoV-2 positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab [≥]14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the risk of reinfection was estimated at 0.10% (95% CI: 0.08-0.11%). The incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), risk of infection was estimated at 2.15% (95% CI: 2.08-2.22%) and incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing.
ConclusionsReinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy [~]95% for at least seven months. | epidemiology |
10.1101/2021.01.15.21249731 | SARS-CoV-2 reinfection in a cohort of 43,000 antibody-positive individuals followed for up to 35 weeks | BackgroundReinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. Risk and incidence rate of SARS-CoV-2 reinfection were assessed in a large cohort of antibody-positive persons in Qatar.
MethodsAll SARS-CoV-2 antibody-positive persons with a PCR-positive swab [≥]14 days after the first-positive antibody test were individually investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those antibody-negative.
ResultsAmong 43,044 anti-SARS-CoV-2 positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab [≥]14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the risk of reinfection was estimated at 0.10% (95% CI: 0.08-0.11%). The incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), risk of infection was estimated at 2.15% (95% CI: 2.08-2.22%) and incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing.
ConclusionsReinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy [~]95% for at least seven months. | epidemiology |
10.1101/2021.01.15.21249388 | Ethnic differences in the incidence of clinically diagnosed influenza: an England population-based cohort study 2008-2018 | We used primary and linked secondary healthcare data to investigate the incidence of clinically diagnosed influenza/influenza-like-illness (ILI) by ethnicity in England from 2008-2018. We identified higher incidence rate ratios for influenza/ILI among South Asian (1.70, 95% CI 1.66-1.75), Black (1.48, 1.44-1.53) and Mixed (1.22, 1.15-1.30) groups compared to White ethnicity.
People from ethnic minority backgrounds are represented disproportionately among patients with severe COVID-19. Recent research has found people of Black and South Asian ethnicity have increased risk of SARS-CoV-2 infection, COVID-19-related hospitalization and death, independent of deprivation, occupation, household size, and underlying health conditions(1,2).
The COVID-19 pandemic has reinforced the importance of seasonal influenza vaccination. By preventing influenza-related hospitalization, vaccination can minimize the risk of hospital-acquired COVID-19 (co-) infection for these individuals and reduce health service pressures, particularly the need for isolation of patients with respiratory symptoms awaiting COVID-19 test results.
In the UK, influenza vaccine is routinely recommended for adults aged [≥]65 years, or people <65 years with underlying health conditions. These recommendations formed the basis of the original guidance to identify patients at moderate- and high-risk of COVID-19. Influenza vaccine recommendations were expanded for the 2020/21 season to include all adults [≥]50 years(3). However, vaccine uptake among clinical risk groups is low, particularly for Black and Mixed Black ethnic groups(4). In addition, people of non-White ethnicity have higher risk of severe outcomes following influenza infection(5,6). It is unclear whether this is driven by the risk of infection or complications, with most research focused on distal outcomes rather than initial infection risk.
Here we investigate the incidence of influenza and influenza-like-illness (ILI) by ethnicity from 2008-2018 among people not eligible for routine influenza vaccination, to consider disparities in infection risk. | epidemiology |
10.1101/2021.01.15.21249881 | Modeling the impact of racial and ethnic disparities on COVID-19 epidemic dynamics | The impact of variable infection risk by race and ethnicity on the dynamics of SARS-CoV-2 spread is largely unknown. Here, we fit structured compartmental models to seroprevalence data from New York State and analyze how herd immunity thresholds (HITs), final sizes, and epidemic risk changes across groups. A simple model where interactions occur proportionally to contact rates reduced the HIT, but more realistic models of preferential mixing within groups increased the threshold toward the value observed in homogeneous populations. Across all models, the burden of infection fell disproportionately on minority populations: in a model fit to Long Island serosurvey and census data, 81% of Hispanics or Latinos were infected when the HIT was reached compared to 34% of non-Hispanic whites. Our findings, which are meant to be illustrative and not best estimates, demonstrate how racial and ethnic disparities can impact epidemic trajectories and result in unequal distributions of SARS-CoV-2 infection. | epidemiology |
10.1101/2021.01.15.21249881 | Modeling the impact of racial and ethnic disparities on COVID-19 epidemic dynamics | The impact of variable infection risk by race and ethnicity on the dynamics of SARS-CoV-2 spread is largely unknown. Here, we fit structured compartmental models to seroprevalence data from New York State and analyze how herd immunity thresholds (HITs), final sizes, and epidemic risk changes across groups. A simple model where interactions occur proportionally to contact rates reduced the HIT, but more realistic models of preferential mixing within groups increased the threshold toward the value observed in homogeneous populations. Across all models, the burden of infection fell disproportionately on minority populations: in a model fit to Long Island serosurvey and census data, 81% of Hispanics or Latinos were infected when the HIT was reached compared to 34% of non-Hispanic whites. Our findings, which are meant to be illustrative and not best estimates, demonstrate how racial and ethnic disparities can impact epidemic trajectories and result in unequal distributions of SARS-CoV-2 infection. | epidemiology |
10.1101/2021.01.14.21249824 | Development of at-home sample collection logistics for large scale SARS-CoV-2 seroprevalence studies | In the midst of a pandemic, serologic studies are a valuable tool to understand the course of the outbreak and guide public health and general pandemic management. However, given significant safety constraints including social distancing and stay-at-home orders, sample collection becomes more difficult given traditional phlebotomy protocols. For such studies, a representative sample of the underlying population is paramount to elicit meaningful insights that capture the spread of the infection, particularly when different sub-populations face varying disease burden. We aimed to address these challenges by conducting a fully remote study to investigate the seroprevalence of SARS-CoV-2 in the state of Massachusetts. Leveraging electronic study engagement and at-home self-collection of finger-prick samples, we enrolled 2,066 participants representative of the ethnic and racial composition of Massachusetts. SARS-CoV-2 total IgG seropositivity was 3.15%, and follow-up measurements at days 7, 15, 45, and 90 indicate a generally durable antibody response. A higher risk of infection was observed for healthcare workers and their cohabitants and those with comorbidities, as well as lower-income, less educated, Hispanic, and those in the age groups of 18-29 and 50-59-years-old. High engagement and positive feedback from the participants and quality of self-collected specimens point to the usefulness of this design for future population-level serological studies that more effectively and safely reach a broad representative cohort, thus yielding more comprehensive insights into the burden of infection and disease in populations.
Key pointsO_ST_ABSQuestionC_ST_ABSWe aimed to implement a fully remote seroprevalence study for SARS-CoV-2, leveraging electronic methods and at-home self-collection of specimens to engage a representative study population.
FindingsThe population enrolled reflected the ethnic and racial composition of Massachusetts, revealing a SARS-CoV-2 seroprevalence of 3.15% and higher risk of previous infection associated with healthcare workers/their cohabitants, those with comorbidities, lower-income, less educated, Hispanic, and those in age groups 18-29 and 50-59 years old.
MeaningHigh engagement and positive feedback from participants as well as quality of self-collected specimens point to the usefulness of this design for future population-level serological studies. | epidemiology |
10.1101/2021.01.14.21249791 | Importance of patient bed pathways and length of stay differences in predicting COVID-19 bed occupancy in England | ObjectivesPredicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patients "bed pathway" - the sequence of transfers between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy.
DesignWe obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020.
ResultsIn both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: "Ward, CC, Ward", "Ward, CC", "CC" and "CC, Ward". Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days.
For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities.
ConclusionsWe identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occupancy for COVID-19. | epidemiology |
10.1101/2021.01.13.21249642 | Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020 | BackgroundThere is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection.
MethodsA large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis.
FindingsBetween 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.3 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days.
InterpretationA prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included.
FundingDepartment of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments. | epidemiology |
10.1101/2021.01.14.21249829 | Direct Simulation of the CoVid-19 epidemic | AO_SCPLOWBSTRACTC_SCPLOWWe introduce an agent-based model to simulate the epidemiological dynamics of COVID-19. Most computational models proposed to study this epidemic do no take into account human mobility. We present a direct simulation model where mobility plays a key role and propose as well four quarantine strategies. The results show that the no-quarantine strategy does lead to a high peak of contagions with no rebound. Quarantined strategies, for their part, show a re-emergence of the epidemic with smaller and softer peaks. | epidemiology |
10.1101/2021.01.14.21249386 | Epidemiological Investigation of New SARS-CoV-2 Variant of Concern 202012/01 in England | Lighthouse Labs network tests for the presence of RNA of SARS-CoV-2, the causative agent of COVID-19. The Thermofisher TaqPath assay targets three regions of SARS-CoV-2; ORF1ab, N and S-genes. The assay identified a drop in S-gene target detection among positive samples due to the circulation of a new SARS-CoV-2 Variant of Concern (VOC) designated as 202012/01. By end of December 2020, 60% of daily positive test results at Alderley Park Lighthouse Labs, were linked to the new Variant of Concern. This timeline view identifies the rapid spread of the variant across the country. | epidemiology |
10.1101/2021.01.14.21249797 | Modelling the Spreading of the SARS-CoV-2 in Presence of the Lockdown and Quarantine Measures by a "Kinetic-Type Reactions" Approach | We propose a realistic model for the evolution of the COVID-19 pandemic subject to the lockdown and quarantine measures, which takes into account the time-delay for recovery or death processes. The dynamic equations for the entire process are derived by adopting a kinetic-type reactions approach. More specifically, the lockdown and the quarantine measures are modelled by some kind of inhibitor reactions where susceptible and infected individuals can be trapped into inactive states. The dynamics for the recovered people is obtained by accounting people who are only traced back to hospitalised infected people. To get the evolution equation we take inspiration from the Michaelis-Mentens enzyme-substrate reaction model (the so-called MM reaction) where the enzyme is associated to the available hospital beds, the substrate to the infected people, and the product to the recovered people, respectively. In other words, everything happens as if the hospitals beds act as a catalyzer in the hospital recovery process. Of course, in our case the reverse MM reactions has no sense in our case and, consequently, the kinetic constant is equal to zero. Finally, the O.D.E.s for people tested positive to COVID-19 is simply modelled by the following kinetic scheme S + I {Rightarrow} 2I with I {Rightarrow} R or I {Rightarrow} D, with S, I, R, and D denoting the compartments Susceptible, Infected, Recovered, and Deceased people, respectively. The resulting kinetic-type equations provide the O.D.E.s, for elementary reaction steps, describing the number of the infected people, the total number of the recovered people previously hospitalised, subject to the lockdown and the quarantine measure, and the total number of deaths. The model foresees also the second wave of Infection by Coronavirus. The tests carried out on real data for Belgium, France and Germany confirmed the correctness of our model. | epidemiology |
10.1101/2021.01.13.21249773 | Optimal piecewise constant vaccination and lockdown policies for COVID-19 | We formulate a controlled system of ordinary differential equations, with vaccination and lockdown interventions as controls, to simulate the mitigation of COVID-19. The performance of the controls is measured through a cost functional involving vaccination and lockdown costs as well as the burden of COVID19 quantified in DALYs. We calibrate parameters with data from Mexico City and Valle de Mexico. By using differential evolution, we minimize the cost functional subject to the controlled system and find optimal policies that are constant in time intervals of a given size. The main advantage of these policies relies on its practical implementation since the health authority has to make only a finite number of different decisions. Our methodology to find optimal policies is relatively general, allowing changes in the dynamics, the cost functional, or the frequency the policymaker changes actions. | epidemiology |
10.1101/2021.01.13.21249759 | Bayesian Variable Selection Utilizing Posterior Probability Credible Intervals | In recent years, there has been growing interest in the problem of model selection in the Bayesian framework. Current approaches include methods based on computing model probabilities such as Stochastic Search Variable Selection (SSVS) and Bayesian LASSO and methods based on model choice criteria, such as the Deviance Information Criterion (DIC). Methods in the first group compute the posterior probabilities of models or model parameters often using a Markov Chain Monte Carlo (MCMC) technique, and select a subset of the variables based on a prespecified threshold on the posterior probability. However, these methods rely heavily on the prior choices of parameters and the results can be highly sensitive when priors are changed. DIC is a Bayesian generalization of the Akaikes Information Criterion (AIC) that penalizes for large number of parameters, it has the advantage that can be used for selection of mixed effect models but tends to prefer overparameterized models. We propose a novel variable selection algorithm that utilizes the parameters credible intervals to select the variables to be kept in the model. We show in a simulation study and a real-world example that this algorithm on average performs better than DIC and produces more parsimonious models. | epidemiology |
10.1101/2021.01.12.21249694 | Optimal SARS-CoV-2 vaccine allocation using real-time seroprevalence estimates in Rhode Island and Massachusetts | As three SARS-CoV-2 vaccines come to market in Europe and North America in the winter of 2020-2021, distribution networks will be in a race against a major epidemiological wave of SARS-CoV-2 that began in autumn 2020. Rapid and optimized vaccine allocation is critical during this time. With 95% efficacy reported for two of the vaccines, near-term public health needs require that distribution is prioritized to the elderly, health-care workers, teachers, essential workers, and individuals with co-morbidities putting them at risk of severe clinical progression. Here, we evaluate various age-based vaccine distributions using a validated mathematical model based on current epidemic trends in Rhode Island and Massachusetts. We allow for varying waning efficacy of vaccine-induced immunity, as this has not yet been measured. We account for the fact that known COVID-positive cases may not be included in the first round of vaccination. And, we account for current age-specific immune patterns in both states. We find that allocating a substantial proportion (> 75%) of vaccine supply to individuals over the age of 70 is optimal in terms of reducing total cumulative deaths through mid-2021. As we do not explicitly model other high mortality groups, this result on vaccine allocation applies to all groups at high risk of mortality if infected. Our analysis confirms that for an easily transmissible respiratory virus, allocating a large majority of vaccinations to groups with the highest mortality risk is optimal. Our analysis assumes that health systems during winter 2020-2021 have equal staffing and capacity to previous phases of the SARS-CoV-2 epidemic; we do not consider the effects of understaffed hospitals or unvaccinated medical staff. Vaccinating only seronegative individuals avoids redundancy in vaccine use on individuals that may already be immune, and will result in 1% to 2% reductions in cumulative hospitalizations and deaths by mid-2021. Assuming high vaccination coverage (> 28%) and no major relaxations in distancing, masking, gathering size, or hygiene guidelines between now and spring 2021, our model predicts that a combination of vaccination and population immunity will lead to low or near-zero transmission levels by the second quarter of 2021. | epidemiology |
10.1101/2021.01.14.21249792 | The Relationship between Chronological Age, Dental Age, and Salivary Alkaline Phosphatase in Indonesian Children Aged 8-14 Years: A Cross-Sectional Study | BackgroundInability to predict dental age accurately has long been the Achilles heel of pediatric dentistry. Whilst dental age has an important aspect in clinical practice, saliva can be one of the most practically important diagnostic tools to estimate biological age.
AimsThis study was aimed to analyze a correlation between chronological age, dental age, and salivary alkaline phosphatase in Indonesian children aged 8-14 years.
MethodsThis study was an observational study with cross-sectional design. Twenty healthy children (10 boys; age 10.504 {+/-} 1.895 years) were selected by a consecutive sampling. Chronological age was assessed by recording date of birth. Dental age was assessed by orthopantamogram following Demirjians method. Salivary samples were collected by passive drool method and estimation of alkaline phosphatase was done by autoanalyzer.
ResultsNormality test was assessed using Kolmogorov-Smirnov and Shapiro-Wilk test. Statistical analyses were assessed using Spearmans rank-order correlation coefficients. Results are presented as mean {+/-} standard deviation (SD). Mean chronological age was10.504 {+/-} 1.895 years, mean Demirjians score was 91.74 {+/-} 5.972, and mean salivary alkaline phosphatase was 291.563 {+/-} 115.135 pg/ml. There is a very strong positive correlation between chronological age and dental age (r=+0.804; p<0.001). On the contrary, levels of salivary alkaline phosphatase was negatively correlated to dental age (r=-0.780; p<0.001) and chronological age (r=-0.508; p=0.022).
ConclusionsThis study showed a strong correlation between dental age, chronological age, and salivary alkaline phosphatase; hence, estimation of dental age and salivary alkaline phosphatase in Indonesian children during early and late childhood has significant meaning to chronological age. | forensic medicine |
10.1101/2021.01.13.21249763 | Machine learning approach for biopsy-based identification of eosinophilic esophagitis reveals importance of global features | GoalEosinophilic esophagitis (EoE) is an allergic inflammatory condition characterized by eosinophil accumulation in the esophageal mucosa. EoE diagnosis includes a manual assessment of eosinophil levels in mucosal biopsies--a time-consuming, laborious task that is difficult to standardize. One of the main challenges in automating this process, like many other biopsy-based diagnostics, is detecting features that are small relative to the size of the biopsy.
ResultsIn this work, we utilized hematoxylin- and eosin-stained slides from esophageal biopsies from patients with active EoE and control subjects to develop a platform based on a deep convolutional neural network (DCNN) that can classify esophageal biopsies with an accuracy of 85%, sensitivity of 82.5%, and specificity of 87%. Moreover, by combining several downscaling and cropping strategies, we show that some of the features contributing to the correct classification are global rather than specific, local features.
ConclusionsWe report the ability of artificial intelligence to identify EoE using computer vision analysis of esophageal biopsy slides. Further, the DCNN features associated with EoE are based on not only local eosinophils but also global histologic changes. Our approach can be used for other conditions that rely on biopsy-based histologic diagnostics.
Impact StatementDeep convolutional neural network (DCNN), together with a systematic downscaling approach, can classify esophageal biopsies with high accuracy and reveals a global nature of the histologic features of eosinophilic esophagitis. Our approach of systematic analysis of the image size versus downscaling tradeoff can be used to improve disease classification performance and insight gathering in digital pathology. | gastroenterology |
10.1101/2021.01.14.21249458 | Multi-strain fermented milk promotes gut microbiota recovery after Helicobacter pylori therapy: a randomised, controlled trial | BACKGROUNDHelicobacter pylori (Hp) eradication therapy can alter gut microbiota, provoking gastro-intestinal (GI) symptoms that can be improved by probiotics. The effect on Hp patients of a Test fermented milk containing yogurt and three Lacticaseibacillus (L. paracasei CNCM I-1518, CNCM I-3689, L. rhamnosus CNCM I-3690) strains was assessed on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota composition and metabolites. In this aim, a randomized, double-blind, controlled trial was performed in 136 adults under Hp-treatment (14-day amoxicillin, clarithromycin, pantoprazole), who consumed the Test or a Control product for 28 days. Feces were analysed for gut microbiota composition, short chain fatty acids (SCFA), calprotectin, and viability of ingested strains.
RESULTSNo effect of Test product was observed on AAD occurrence or duration, rating scores or number of days of GI symptoms. Hp-treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and of calprotectin, and a decrease of SCFA concentration. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj=0.02), Escherichia-Shigella (padj=0.0082) and Klebsiella (padj= 0.013) were significantly less abundant, and concentrations of major SCFA (p=0.035) and valerate (p = 0.045) were higher. Viable Lp and Lr strains from the Test product were mainly detected during product consumption in feces.
CONCLUSIONSThe study showed that 14-day Hp triple therapy alters gut bacterial and fungal community, their metabolites and gut inflammatory markers. Consumption of a multi-strain fermented milk can induce faster recovery of the microbiota composition and SCFA production and limit the bloom of pathobionts. (ClinicalTrials.gov, NCT02900196; First Posted : September 14, 2016; https://www.clinicaltrials.gov/ct2/show/NCT02900196). | gastroenterology |
10.1101/2021.01.13.21249766 | Epidemiology and antibiotic resistance profile of Helicobacter pylori infection in Cameroon: a systematic review with meta-analysis | ObjectivesAlthough global epidemiology of Helicobacter pylori (HP) infection is well characterized, country-specific figure is more accurate for context-specific tailored interventions. The aim was to determine the prevalence, factors associated with infection, antibiotic resistance profile, and genotypes of HP in Cameroon.
DesignA systematic review with meta-analysis.
ParticipantsPeople living in Cameroon regardless of their clinical profile.
Data sources and synthesisObservational studies published in PubMed, EMBASE, African Index Medicus, African Journals Online, and Health Sciences and Diseases up to October 12th, 2020. Study selection, data extraction, and methodological quality assessment were done by two independent authors. Random-effect meta-analysis served to pool prevalence data.
ResultsFifteen studies were included. None investigated the genotypes of HP. Among symptomatic patients, the most common used test, urea breath test on gastric biopsy, yielded a prevalence 57.8% (95% confidence interval (CI): 34.3-79.5) of HP infection. This prevalence significantly varied between 47.0% (95%CI: 43.0-51.0) for antigen test in stool samples and 71.2% (95%CI: 59.1-81.9) for Giemsa on gastric biopsy; p = 0.0006. One study in asymptomatic children reported the prevalence of 52.3% (95%CI: 44.9-59.6) using antigen test for stool samples. Among the six studies investigating factors associated with HP infection, one performed a multivariable model and identified being student as protective factor compared to being employed (Odds ratio: 0.09; 95%CI: 0.02-0.49). For antibiotics used for first line treatment, HP was resistant to amoxicillin (85.6-97.1%), metronidazole (93.2-97.9%), and clarithromycin (13.6-44.7%) as reported in two studies.
LimitationData were from six of the ten regions of Cameroon, hindering the generalizability of the findings to the country.
ConclusionThis study depicted a high prevalence of HP infection and a worrying resistance profile to first-line antibiotics. When waiting for well-conducted studies, updated guidelines are needed for clinical practice for first-line antibiotic treatment.
RegistrationPROSPERO, CRD42020220084.
Strengths and limitations of this studyO_LINot all the 10 regions of the country were represented in this study, hindering the generalizability of the findings.
C_LIO_LIWe were not able to substantially investigate sources of heterogeneity in the prevalence of Helicobacter pylori infection due to scarcity of data.
C_LIO_LIEvidence investigating factors associated with Helicobacter pylori infection are weak and there was scarcity on data exploring antibiotic resistance profile of Helicobacter pylori.
C_LIO_LIThis study is the first to provide an estimate of the epidemiology and resistance profile of Helicobacter pylori in Cameroon.
C_LI | gastroenterology |
10.1101/2021.01.15.21249724 | Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments | BackgroundThe COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment.
This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within 24-48 hours of their test result.
MethodsA multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (within 24-48 hours of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology.
ResultsPrior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1,013 recruits to PRINCIPLE at the start of October 2020 to 2,802 recruits by 20th December 2020.
While procedural caveats were identified by the public consultation, out of 2,639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached.
ConclusionsThis paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness.
This approach increased recruitment, and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions.
Trial registrationPRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research.
EudraCT number: 2020-001209-22
ISRCTN registry: ISRCTN86534580
REC number: 20/SC/058
IRAS number: 281958 | primary care research |
10.1101/2021.01.15.21249864 | Sleep disorders predict the one-year onset, persistence, but not remission of psychotic experiences in 10-11 year old children: a longitudinal analysis of the ABCD cohort data | The relationship between sleep disorder and psychotic experiences in preadolescence has not been extensively studied despite the potential for intervention. The current study addresses this relationship using the Adolescent Brain Cognitive Development (ABCD) cohort, which provides baseline data from 11,830 10 to 11-year-olds; for 4910 of these 1-year follow-up data is also available. A set of pre-registered multi-level regression models were applied to test whether a) sleep disorder is associated with psychotic experiences at baseline; b) baseline sleep disorder predicts psychotic experiences at follow-up; c) the persistence of sleep disorder predicts persistence of psychotic experiences at follow-up; d) the remission of sleep disorder predicts the remission of psychotic experiences at follow-up. After controlling for potential confounders, sleep disorder was associated with psychotic experiences cross-sectionally (OR=1.40, 95% CI 1.20-1.63), at one-year follow-up (OR=1.32, 95% CI 1.11-1.57), and the persistence of sleep disorder predicted the persistence of psychotic experiences (OR=1.72, 95% CI 1.44-2.04). However, remission of sleep problems did not predict remission of psychotic experiences (OR=1.041, 95% CI 0.80-1.35). The results indicate that sleep disorders in preadolescence are common and associated with psychotic experiences, although the lack of co-remission raises questions about the mechanism of association. However, given these findings, and existing evidence in later adolescence and adults, further investigation of sleep as a preventative mental health intervention in this age group is warranted. | psychiatry and clinical psychology |
10.1101/2021.01.15.21249864 | Sleep disorders predict the one-year onset, persistence, but not remission of psychotic experiences in 10-11 year old children: a longitudinal analysis of the ABCD cohort data | The relationship between sleep disorder and psychotic experiences in preadolescence has not been extensively studied despite the potential for intervention. The current study addresses this relationship using the Adolescent Brain Cognitive Development (ABCD) cohort, which provides baseline data from 11,830 10 to 11-year-olds; for 4910 of these 1-year follow-up data is also available. A set of pre-registered multi-level regression models were applied to test whether a) sleep disorder is associated with psychotic experiences at baseline; b) baseline sleep disorder predicts psychotic experiences at follow-up; c) the persistence of sleep disorder predicts persistence of psychotic experiences at follow-up; d) the remission of sleep disorder predicts the remission of psychotic experiences at follow-up. After controlling for potential confounders, sleep disorder was associated with psychotic experiences cross-sectionally (OR=1.40, 95% CI 1.20-1.63), at one-year follow-up (OR=1.32, 95% CI 1.11-1.57), and the persistence of sleep disorder predicted the persistence of psychotic experiences (OR=1.72, 95% CI 1.44-2.04). However, remission of sleep problems did not predict remission of psychotic experiences (OR=1.041, 95% CI 0.80-1.35). The results indicate that sleep disorders in preadolescence are common and associated with psychotic experiences, although the lack of co-remission raises questions about the mechanism of association. However, given these findings, and existing evidence in later adolescence and adults, further investigation of sleep as a preventative mental health intervention in this age group is warranted. | psychiatry and clinical psychology |
10.1101/2021.01.15.21249864 | Sleep disorders predict the one-year onset, persistence, but not remission of psychotic experiences in 10-11 year old children: a longitudinal analysis of the ABCD cohort data | The relationship between sleep disorder and psychotic experiences in preadolescence has not been extensively studied despite the potential for intervention. The current study addresses this relationship using the Adolescent Brain Cognitive Development (ABCD) cohort, which provides baseline data from 11,830 10 to 11-year-olds; for 4910 of these 1-year follow-up data is also available. A set of pre-registered multi-level regression models were applied to test whether a) sleep disorder is associated with psychotic experiences at baseline; b) baseline sleep disorder predicts psychotic experiences at follow-up; c) the persistence of sleep disorder predicts persistence of psychotic experiences at follow-up; d) the remission of sleep disorder predicts the remission of psychotic experiences at follow-up. After controlling for potential confounders, sleep disorder was associated with psychotic experiences cross-sectionally (OR=1.40, 95% CI 1.20-1.63), at one-year follow-up (OR=1.32, 95% CI 1.11-1.57), and the persistence of sleep disorder predicted the persistence of psychotic experiences (OR=1.72, 95% CI 1.44-2.04). However, remission of sleep problems did not predict remission of psychotic experiences (OR=1.041, 95% CI 0.80-1.35). The results indicate that sleep disorders in preadolescence are common and associated with psychotic experiences, although the lack of co-remission raises questions about the mechanism of association. However, given these findings, and existing evidence in later adolescence and adults, further investigation of sleep as a preventative mental health intervention in this age group is warranted. | psychiatry and clinical psychology |
10.1101/2021.01.13.20246603 | Individual level prediction of emerging suicide events in the pharmacologic treatment of bipolar disorder | BackgroundPatients with bipolar disorder have a high lifetime risk of suicide. Predicting, preventing and managing suicidal behavior are major goals in clinical practice. Changes in suicidal thoughts and behavior are common in the course of treatment of bipolar disorder.
MethodsUsing a dataset from a randomized clinical trial of bipolar disorder treatment (N=98), we tested predictors of future suicidal behavior identified through a review of literature and applied marginal variable selection and machine learning methods. The performance of the models was assessed using the optimism-adjusted C statistic.
ResultsNumber of prior hospitalizations, number of prior suicide attempts, current employment status and Hamilton Depression Scale were identified as predictors and a simple logistic regression model was constructed. This model was compared with a model incorporating interactions with treatment group assignment, and more complex variable selection methods (LASSO and Survival Trees). The best performing models had average optimism-adjusted C-statistics of 0.67 (main effects only) and 0.69 (Survival Trees). Incorporating medication group did not improve prediction performance of the models.
ConclusionsThese results suggest that models with a few predictors may yield a clinically meaningful way to stratify risk of emerging suicide events in patients who are undergoing pharmacologic treatment for bipolar disorder.
Significance StatementThis study aims to find out whether suicide events that occur during the pharmacological treatment of bipolar disorder, a severe psychiatric disorder that is highly associated with suicide behavior, can be predicted. Using existing methods, we developed and compared several predictive models. We showed that these models performed similarly to predictive models of other outcomes, such as treatment efficacy, in unipolar and bipolar depression. This suggests that suicide events during bipolar disorder may be a feasible target for individualized interventions in the future. | psychiatry and clinical psychology |
10.1101/2021.01.14.21249855 | Predicting Emerging Themes in Rapidly Expanding COVID-19 Literature with Dynamic Word Embedding Networks and Machine Learning | Evidence from peer-reviewed literature is the cornerstone for designing responses to global threats such as COVID-19. The collection of knowledge and interpretation in publications needs to be distilled into evidence by leveraging natural language in ways beyond standard meta-analysis. Several studies have focused on mining evidence from text using natural language processing, and have focused on a handful of diseases. Here we show that new knowledge can be captured, tracked and predicted using the evolution of unsupervised word embeddings and machine learning. Our approach to decipher the flow of latent knowledge in time-varying networks of word-vectors captured thromboembolic complications as an emerging theme in more than 77,000 peer-reviewed publications and more than 11,000 WHO vetted preprints on COVID-19. Furthermore, machine learning based prediction of emerging links in the networks reveals autoimmune diseases, multisystem inflammatory syndrome and neurological complications as a dominant research theme in COVID-19 publications starting March 2021. | public and global health |
10.1101/2021.01.14.21249855 | Predicting Emerging Themes in Rapidly Expanding COVID-19 Literature with Dynamic Word Embedding Networks and Machine Learning | Evidence from peer-reviewed literature is the cornerstone for designing responses to global threats such as COVID-19. The collection of knowledge and interpretation in publications needs to be distilled into evidence by leveraging natural language in ways beyond standard meta-analysis. Several studies have focused on mining evidence from text using natural language processing, and have focused on a handful of diseases. Here we show that new knowledge can be captured, tracked and predicted using the evolution of unsupervised word embeddings and machine learning. Our approach to decipher the flow of latent knowledge in time-varying networks of word-vectors captured thromboembolic complications as an emerging theme in more than 77,000 peer-reviewed publications and more than 11,000 WHO vetted preprints on COVID-19. Furthermore, machine learning based prediction of emerging links in the networks reveals autoimmune diseases, multisystem inflammatory syndrome and neurological complications as a dominant research theme in COVID-19 publications starting March 2021. | public and global health |
10.1101/2021.01.14.21249855 | Predicting Emerging Themes in Rapidly Expanding COVID-19 Literature with Dynamic Word Embedding Networks and Machine Learning | Evidence from peer-reviewed literature is the cornerstone for designing responses to global threats such as COVID-19. The collection of knowledge and interpretation in publications needs to be distilled into evidence by leveraging natural language in ways beyond standard meta-analysis. Several studies have focused on mining evidence from text using natural language processing, and have focused on a handful of diseases. Here we show that new knowledge can be captured, tracked and predicted using the evolution of unsupervised word embeddings and machine learning. Our approach to decipher the flow of latent knowledge in time-varying networks of word-vectors captured thromboembolic complications as an emerging theme in more than 77,000 peer-reviewed publications and more than 11,000 WHO vetted preprints on COVID-19. Furthermore, machine learning based prediction of emerging links in the networks reveals autoimmune diseases, multisystem inflammatory syndrome and neurological complications as a dominant research theme in COVID-19 publications starting March 2021. | public and global health |
10.1101/2021.01.13.21249689 | Impact of training modules on physicians perspective of COVID-19: An online survey | BackgroundThe outbreak of COVID-19 has remained a massive challenge for healthcare workers specially physicians. Effective professional training has a crucial role in preparing doctors for responding to pandemics.
ObjectiveTo assess the effectiveness of existing training modules on enhancing knowledge, ensuring safe practice, and improving behavior on COVID-19 among physicians.
MethodsThis is a descriptive, cross-sectional, online survey; where a virtual questionnaire was used to collect data through online professional platforms. A pre-tested survey tool was employed to assess the impact of professional training on infection prevention and control.
ResultsTotal 161 physicians participated in this survey from 15 different countries. Most of the respondents (72%) received training from various sources like the workplace (60%) and international agencies (21%), through the in-person or online format. Knowledge assessment revealed advanced (43%) and competent (40%) understanding by the participants. Improving knowledge progression was displayed by the cohort who received professional training (p<0.00). Physicians positive behavior and good practices were observed with the training modules.
ConclusionIt became evident from this study, that professional training is effective in enhancing knowledge, improving behavior, and ensuring safe practices. Hence, designing such training modules for the physicians is warranted to tackle ongoing and future pandemics. | public and global health |
10.1101/2021.01.13.21249598 | Implementing Essential Coaching for Every Mother during COVID-19: A Pilot Pre-Post Intervention Study | ObjectivesThe primary objective was to evaluate the preliminary impact of Essential Coaching for Every Mother on self-efficacy, social support, postpartum anxiety and postpartum depression. The second objective was to explore the acceptability of the Essential Coaching for Every Mother program provided during the COVID-19 pandemic.
MethodsA prospective pre-post study was conducted with first time mothers in Nova Scotia, Canada between July 15th and September 19th, 2020. Participants completed a self-report survey at enrolment (after birth) and six-weeks postpartum. Various standardized measures were used and qualitative feedback on the program was also collected. Paired t-tests were carried out to determine changes from baseline to follow-up on psychosocial outcomes and qualitative feedback was analysed through thematic analysis.
ResultsA total of 88 women enrolled. Self-efficacy increased between baseline (B) and follow-up (F) (B:33.33; F:37.11, p=0.000) while anxiety (STAI) declined (B:38.49; F:34.79; p=0.004). In terms of acceptability, 89% of participants felt that the number of messages were just right, 84.5% felt the messages contained all the information they needed relative to caring for a newborn and 98.8% indicated they would recommend this program to other new mothers.
ConclusionEssential Coaching for Every Mother may play a role in increasing maternal self-efficacy and decreasing anxiety, although future work with a control group is needed to delineate the true effects of the program. Overall, mothers were satisfied with the Essential Coaching for Every Mother program and would recommend it for other mothers, during COVID-19 and beyond. | public and global health |
10.1101/2021.01.13.21249598 | Implementing Essential Coaching for Every Mother during COVID-19: A Pilot Pre-Post Intervention Study | ObjectivesThe primary objective was to evaluate the preliminary impact of Essential Coaching for Every Mother on self-efficacy, social support, postpartum anxiety and postpartum depression. The second objective was to explore the acceptability of the Essential Coaching for Every Mother program provided during the COVID-19 pandemic.
MethodsA prospective pre-post study was conducted with first time mothers in Nova Scotia, Canada between July 15th and September 19th, 2020. Participants completed a self-report survey at enrolment (after birth) and six-weeks postpartum. Various standardized measures were used and qualitative feedback on the program was also collected. Paired t-tests were carried out to determine changes from baseline to follow-up on psychosocial outcomes and qualitative feedback was analysed through thematic analysis.
ResultsA total of 88 women enrolled. Self-efficacy increased between baseline (B) and follow-up (F) (B:33.33; F:37.11, p=0.000) while anxiety (STAI) declined (B:38.49; F:34.79; p=0.004). In terms of acceptability, 89% of participants felt that the number of messages were just right, 84.5% felt the messages contained all the information they needed relative to caring for a newborn and 98.8% indicated they would recommend this program to other new mothers.
ConclusionEssential Coaching for Every Mother may play a role in increasing maternal self-efficacy and decreasing anxiety, although future work with a control group is needed to delineate the true effects of the program. Overall, mothers were satisfied with the Essential Coaching for Every Mother program and would recommend it for other mothers, during COVID-19 and beyond. | public and global health |
10.1101/2021.01.15.21249843 | Sterilization of disposable face masks with respect to COVID-19 shortages; a nationwide field study including 19 sterilisation departments | ObjectiveFace masks also referred to as half masks are essential to protect healthcare professionals, working in close contact with patients having Covid-19 related symptoms. During the threating deficit, healthcare institutions sought an approach to re-use face masks or to acquire imported masks. The objective of this study is to assess the quality of sterilised and imported FFP2/KN95 face mask materials.
Designprospective, bench-to-bedside
SettingGeneral healthcare including 19 hospitals in the Netherlands
InterventionsFace masks were reprocessed using a medical autoclave at 121{degrees}C.
MethodsA 48 minutes steam sterilization process of single-use face masks with 15 min holding time at a 121 {degrees}C was developed, validated and implemented in 19 different hospitals. Steam and H2O2 plasma sterilized as well as new, imported masks are tested in a custom-made, non-standard EN-149, test set-up that measures Particle Filtration Efficiency (PFE) and pressure drops.
ResultsPFE validation data of 84 masks indicated differences of 2.3{+/-}2 % (mean{+/-}SD) between the custom build test set-up and a continues flow according to the EN-149. Test data showed the mean PFE values of 444 sterilised FFP2 face masks from 19 CSSD were 90{+/-}11% (mean{+/-}SD) and of 474 imported KN95/FFP2 face masks 83{+/-}16% (mean{+/-}SD). Differences in PFE between sterilisation departments were found.
ConclusionFace masks can be reprocessed with 121 0 C steam or H2O2 plasma sterilization with minimum reduction of PFE. PFE comparison between sterilised mask and new, imported mask filter material indicates that most reprocessed masks of high quality brands outperform new imported face masks of unknown brands. Although the PFE of tested face mask material from different sterilisation departments remained efficient, different types of sterilisation equipment can result in different PFE outcomes.
Strengths and limitations of this study- Reprocessing face masks at 121 {degrees}C steam Sterilization, a simple method to be used by hospitals in times of shortages
- Laboratory findings to evaluate the safety and quality of face mask material
- The study is limited and restricted to selected FFP-2 face masks
- This study is a first of its kind in quality and safety check of the vast growing face masks, entering our markets
- The study focusses on testing environmental dry particles in a rapid test setup | public and global health |
10.1101/2021.01.14.21249637 | SARS-CoV-2 infection control implementation based on sources of infection showing directions for three age groups in Japan | BackgroundSome aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in children and adults remain unclear. This report describes different SARS-CoV-2 transmission patterns by age group in Japan.
Methods and findingsThis retrospective observational case series study analyzed transmission patterns of real-time polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections found by local health authorities and commercial laboratories during January 14 through July 31, 2020 in Japan. After ascertaining the infection source for every symptomatic case as clusters at households, daycare facilities, schools, hospitals and workplaces etc., their associated transmission patterns were analyzed. Identified cases were divided into three groups: underage, < 20; adults, 20-59; and elderly people 60 years old and older. The reproductive number (R)s of respective transmission directions found for the respective age groups were compared.
Of 26,986 total cases, 23,746 unknown cases were found, leaving 3,240 ascertained sources of infection (12.0%) comprising 125 (3.9%) underage, 2350 (72.5%) adult, and 765 (23.6%) elderly people. The respective Rs of underage infection sources directed to underage, adult, and elderly people were estimated respectively as 0.0415 (95% CI, 0.0138-0.0691), 1.11 (95% CI, 0.9171-1.3226), and 0.2811 (95% CI, 0.2074-0.3687). The respective Rs of adult infection source directed to underage, adult, and elderly people were estimated respectively as 0.0140 (95% CI, 0.0120-0.0162), 0.5392 (95% CI, 0.5236-0.5550), and 0.1135 (95% CI, 0.1074-0.1197). The respective Rs of elderly infection source directed to underage, adult, and elderly people were estimated as 0.065 (95% CI, 0.0039-0.0091), 0.3264 (95% CI, 0.3059-0.3474), and 0.3991 (95% CI, 0.3757-0.4229).
ConclusionsThe main sources of SARS-CoV-2 infection were adults and elderly people. The R of underage people directed to adults was greater than 1 because of close familial contact but they were unlikely to become carriers transmitting SARS-CoV-2 because they accounted for a minority for transmissions. Apparently, SARS-CoV-2 was transmitted among adults and elderly people, suggesting that infection control of SARS-CoV-2 should be managed specifically by generation. | public and global health |
10.1101/2021.01.15.21249886 | Early Stopping in Experimentation with Real-time Functional Magnetic Resonance Imaging Using the Sequential Probability Ratio | IntroductionFunctional magnetic resonance imaging (fMRI) often involves long scanning durations to ensure the associated brain activity can be detected. However, excessive experimentation can lead to many undesirable effects, such as from learning and/or fatigue effects, discomfort for the subject, excessive motion artifacts and loss of sustained attention on task. Overly long experimentation can thus have a detrimental effect on signal quality and accurate voxel activation detection. Here, we propose dynamic experimentation with real-time fMRI using a novel statistically-driven approach that invokes early stopping when sufficient statistical evidence for assessing the task-related activation is observed.
MethodsVoxel-level sequential probability ratio test (SPRT) statistics based on general linear models (GLMs) were implemented on fMRI scans of a mathematical 1-back task from 12 healthy teenage subjects and 11 teenage subjects born extremely preterm (EPT). This approach is based on likelihood ratios and allows for systematic early stopping based on statistical error thresholds. We adopt a two-stage estimation approach that allows for accurate estimates of GLM parameters before stopping is considered. Early stopping performance is reported for different first stage lengths, and activation results are compared with full durations. Finally, group comparisons are conducted with both early stopped and full duration scan data. Numerical parallelization was employed to facilitate completion of computations involving a new scan within every repetition time (TR).
ResultsUse of SPRT demonstrates the feasibility and efficiency gains of automated early stopping, with comparable activation detection as with full protocols. Dynamic stopping of stimulus administration was achieved in around half of subjects, with typical time savings of up to 33% (4 minutes on a 12 minute scan). A group analysis produced similar patterns of activity for control subjects between early stopping and full duration scans. The EPT group, individually, demonstrated more variability in location and extent of the activations compared to the normal term control group. This was apparent in the EPT group results, reflected by fewer and smaller clusters.
ConclusionA systematic statistical approach for early stopping with real-time fMRI experimentation has been implemented. This dynamic approach has promise for reducing subject burden and fatigue effects. | radiology and imaging |
10.1101/2021.01.15.21249886 | Early Stopping in Experimentation with Real-time Functional Magnetic Resonance Imaging Using a Modified Sequential Probability Ratio Test | IntroductionFunctional magnetic resonance imaging (fMRI) often involves long scanning durations to ensure the associated brain activity can be detected. However, excessive experimentation can lead to many undesirable effects, such as from learning and/or fatigue effects, discomfort for the subject, excessive motion artifacts and loss of sustained attention on task. Overly long experimentation can thus have a detrimental effect on signal quality and accurate voxel activation detection. Here, we propose dynamic experimentation with real-time fMRI using a novel statistically-driven approach that invokes early stopping when sufficient statistical evidence for assessing the task-related activation is observed.
MethodsVoxel-level sequential probability ratio test (SPRT) statistics based on general linear models (GLMs) were implemented on fMRI scans of a mathematical 1-back task from 12 healthy teenage subjects and 11 teenage subjects born extremely preterm (EPT). This approach is based on likelihood ratios and allows for systematic early stopping based on statistical error thresholds. We adopt a two-stage estimation approach that allows for accurate estimates of GLM parameters before stopping is considered. Early stopping performance is reported for different first stage lengths, and activation results are compared with full durations. Finally, group comparisons are conducted with both early stopped and full duration scan data. Numerical parallelization was employed to facilitate completion of computations involving a new scan within every repetition time (TR).
ResultsUse of SPRT demonstrates the feasibility and efficiency gains of automated early stopping, with comparable activation detection as with full protocols. Dynamic stopping of stimulus administration was achieved in around half of subjects, with typical time savings of up to 33% (4 minutes on a 12 minute scan). A group analysis produced similar patterns of activity for control subjects between early stopping and full duration scans. The EPT group, individually, demonstrated more variability in location and extent of the activations compared to the normal term control group. This was apparent in the EPT group results, reflected by fewer and smaller clusters.
ConclusionA systematic statistical approach for early stopping with real-time fMRI experimentation has been implemented. This dynamic approach has promise for reducing subject burden and fatigue effects. | radiology and imaging |