title: Study on horizon-scanning with a focus on the development of AI-based medical products: citation network analysis

abstract:
ObjectivesHorizon-scanning for innovative technologies that might be applied to medical products and require new assessment approaches/regulations will help to prepare regulators, allowing earlier access to the product for patients and an improved benefit/risk ratio. In this study, we focused on the field of AI-based medical image analysis as a retrospective example of medical devices, where many products have recently been developed and applied. We proposed and validated horizon-scanning using citation network analysis and text mining for bibliographic information analysis.

Methods and analysisResearch papers for citation network analysis which contain "convolutional*" OR "machine-learning" OR "deep-learning" were obtained from Science Citation Index Expanded (SCI-expanded) in the Web of Science (WoS). The citation network among those papers was converted into an unweighted network with papers as nodes and citation relationships as links. The network was then divided into clusters using the topological clustering method and the characteristics of each cluster were confirmed by extracting a summary of frequently cited academic papers, and the characteristic keywords, in the cluster.

ResultsWe classified 119,553 publications obtained from SCI and grouped them into 36 clusters. Hence, it was possible to understand the academic landscape of AI applications. The key articles on AI-based medical image analysis were included in one or two clusters, suggesting that clusters specific to the technology were appropriately formed. Based on the average publication year of the constituent papers of each cluster, we tracked recent research trends. It was also suggested that significant research progress would be detected as a quick increase in constituent papers and the number of citations of hub papers in the cluster.

ConclusionWe validated that citation network analysis applies to the horizon-scanning of innovative medical devices and demonstrated that AI-based electrocardiograms and electroencephalograms can lead to the development of innovative products.

Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LICitation network analysis can provide an academic landscape in the investigated research field, based on the citation relationship of research papers and objective information, such as characteristic keywords and publication year.
C_LIO_LIIt might be possible to detect possible significant research progress and the emergence of new research areas through analysis every several months.
C_LIO_LIIt is important to confirm the opinions of experts in this area when evaluating the results of the analysis.
C_LIO_LIInformation on patents and clinical trials for this analysis is currently unavailable.
C_LI


title: Prioritizing the first doses of SARS-CoV-2 vaccine to save the elderly: the case study of Italy

abstract: Many countries are currently facing high mortality caused by the circulation of SARS-CoV-2 among the elderly not yet vaccinated. Vaccine shortage poses relevant challenges to health authorities, called to act in a timely manner, and with scarcity of vaccine, and data. We have developed a model for estimating of the impact of vaccination on the mortality of the elderly following a schedule of mRNA SARS-CoV-2 vaccine that prioritize first dose administration, as alternative to the standard schedule of two doses administered 3 to 4 weeks apart. We studied the Italian scenario, considering it representative of other Countries facing similar conditions in terms of virus circulation, mortality, and vaccine shortage, in the period from February 10 to April 14 2021. Under different conditions of quantity of vaccine administration, the schedule prioritizing first doses showed always significant increase of protected individuals, and a decrease of deaths, up to 19.8% less than the standard schedule. These findings support the vaccination option of prioritizing first dose in the elderly until vaccine supplies are adequate.

category: infectious diseases


title: Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets

abstract: SARS-CoV2 is transmitted primarily through oral mouth secretions and respiratory droplets. Commercial mouthwashes, povidone iodine (PI), hydrogen peroxide (HP) and chlorhexidine (CHX) have been tested in cell culture and RT-PCR studies for their efficacy to reduce SARS-CoV2 burden. Here, we evaluated SARS-CoV2 burden in whole mouth fluid (WMF) and respiratory droplets (RD) samples before and after the use of PI, HP or CHX mouthwashes in hospitalized COVID-19 patients using RT-PCR and rapid antigen test (RAT). Thirty-six SARS-CoV2 RT-PCR-positive in-patients were randomly assigned to one of the four groups: 20 and 60 minutes after 1% w/v PI or 1.5% HP; 90 and 180 minutes after 1.5% HP or 0.2% w/v CHX. WMF and RD samples were collected concurrently at baseline and after the two different time points. RD (92%) showed a higher reduction in SARS-CoV2 burden than WMF samples (50%; p=0.008). SARS-CoV2 burden was statistically lower at both 20 minutes (p=0.02) and 60 minutes (p=0.03) with PI; at 20 minutes with HP (p=0.0001); and 90 minutes with CHX (p=0.04). The overall and individual mean logarithmic reductions in the WMF and RD samples were greater than 1.0 at 20, 60 and 90 minutes after PI, HP or CHX. RAT-positive patients at 90 minutes post-treatment (n=3) demonstrated a one log increase in virus copies. Among the three RAT-negative post-treatment patients, SARS-CoV2 burden declined by one log in two while the third patient had a slight increase in RNA copies. In conclusion, we have shown for the first time that the mouthwashes, PI, HP and CHX can reduce the SARS-CoV2 burden in the concurrently collected RD and WMF samples. RAT is more appropriate than RT-PCR to evaluate the efficacy of the mouthwashes.


title: REACT-2 Round 5: increasing prevalence of SARS-CoV-2 antibodies demonstrate impact of the second wave and of vaccine roll-out in England

abstract:
BackgroundEngland has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering the first dose to the largest number of older individuals, healthcare and care home workers.

MethodsA cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flow immunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later.

ResultsThe survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people. The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer. Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and allergies. In 971 individuals who received two doses of the Pfizer-BioNTech vaccine, the proportion testing positive was high across all age groups. Following a single dose of Pfizer-BioNTech vaccine after 21 days or more, 84.1% (82.2, 85.9) of people under 60 years tested positive (unadjusted) with a decreasing trend with increasing age, but high responses to a single dose in those with confirmed or suspected prior COVID at 90.1% (87.2, 92.4) across all age groups.

ConclusionsThere is uneven distribution of SARS-CoV-2 antibodies in the population with a higher burden in key workers and some minority ethnic groups, similar to the pattern in the first wave. Confidence in the vaccine programme is high overall although it was lower in some of the higher prevalence groups which suggests the need for improved communication about specific perceived risks. Two doses of Pfizer-BioNTech vaccine, or a single dose following previous infection, confers high levels of antibody positivity across all ages. Further work is needed to understand the relationship between antibody positivity, clinical outcomes such as hospitalisation, and transmission.


title: Long-Term SARS-CoV-2-Specific Immune and Inflammatory Responses Across a Clinically Diverse Cohort of Individuals Recovering from COVID-19

abstract: A detailed understanding of long-term SARS-CoV-2-specific T cell responses and their relationship to humoral immunity and markers of inflammation in diverse groups of individuals representing the spectrum of COVID-19 illness and recovery is urgently needed. Data are also lacking as to whether and how adaptive immune and inflammatory responses differ in individuals that experience persistent symptomatic sequelae months following acute infection compared to those with complete, rapid recovery. We measured SARS-CoV-2-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally up to 9 months following infection in a diverse group of 70 individuals with PCR-confirmed SARS-CoV-2 infection. The participants had varying degrees of initial disease severity and were enrolled in the northern California Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort. Adaptive T cell responses remained remarkably stable in all participants across disease severity during the entire study interval. Whereas the magnitude of the early CD4+ T cell immune response is determined by the severity of initial infection (participants requiring hospitalization or intensive care), pre-existing lung disease was significantly associated with higher long-term SARS-CoV2-specific CD8+ T cell responses, independent of initial disease severity or age. Neutralizing antibody levels were strongly correlated with SARS-CoV-2-specific CD4+ T but not CD8+ T cell responses. Importantly, we did not identify substantial differences in long-term virus-specific T cell or antibody responses between participants with and without COVID-19-related symptoms that persist months after initial infection.


title: The accuracy of novel antigen rapid diagnostics for SARS-CoV-2: a living systematic review and meta-analysis.

abstract:
BackgroundSARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs.

Methods and ResultsWe registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until April 30th, 2021. Descriptive analyses of all studies were performed and when more than four studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS 2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy data sets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 71.2% (95% confidence interval [CI] 68.2 to 74.0) and increased to 76.3% (CI 73.1 to 79.2) if analysis was restricted to studies that followed the Ag-RDT manufacturers instructions. The LumiraDx showed the highest sensitivity with 88.2% (CI 59.0 to 97.5). Of instrument-free Ag-RDTs, Standard Q nasal performed best with 80.2% sensitivity (CI 70.3 to 87.4). Across all Ag-RDTs sensitivity was markedly better on samples with lower Ct-values, i.e., <20 (96.5%, CI 92.6 to 98.4) and <25 (95.8%, CI 92.3 to 97.8), in comparison to those with Ct [≥]25 (50.7%, CI 35.6 to 65.8) and [≥]30 (20.9%, CI 12.5 to 32.8). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, CI 76.3 to 89.2) compared to testing after one week (61.5%, CI 52.2 to 70.0). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, CI 70.4 to 79.9) in comparison to other sample types (e.g., nasopharyngeal 71.6%, CI 68.1 to 74.9) although CIs were overlapping. Concerns of bias were raised across all data sets, and financial support from the manufacturer was reported in 24.1% of data sets. Our analysis was limited by the included studies heterogeneity in design and reporting, making it difficult to draw conclusions from.

ConclusionIn this study we found that Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.

AUTHOR SUMMARYWhy was this study done? - Antigen rapid diagnostic tests (Ag-RDTs) are considered an important diagnostic tool to fight the spread of SARS-CoV-2
- An increasing number of Ag-RDTs is offered on the market, and a constantly growing body of literature evaluating their performance is available
- To inform decision makers about the best test to choose, an up to date summary of their performance is needed

What did the researchers do and find? - On a weekly basis, we search multiple data bases for evaluations of Ag-RDTs detecting SARS-CoV-2 and post the results on www.diagnosticsglobalhealth.org
- Based on the search results up until April 30th, 2021, we conducted a systematic review and meta-analysis, including a total of 133 clinical and analytical accuracy studies
- Across all meta-analyzed studies, when Ag-RDTs were performed according to manufacturers recommendations, they showed a sensitivity of 76.3% (CI 73.1 to 79.2), with the LumiraDx (sensitivity 88.2%, CI 59.0 to 97.5) and of the instrument-free Ag-RDT Standard Q (74.9% sensitivity, CI 69.3 to 79.7) performing best.
- Across all Ag-RDTs, sensitivity increased to 95.8% (CI 92.3 to 97.8) when restricting the analysis to samples with high viral loads (i.e., a Ct-value <25) and to 83.8% (CI 76.3 to 89.2) when tests were performed on patients within the first week after symptom onset

What do these findings mean? - Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease
- Out of all assessed tests, the Lumira Dx showed the highest accuracy. The Standard Q wasthe best performing test when only considering those that dont require an instrument
- A standardization of reporting methods for clinical accuracy studies would enhance future test-comparisons


title: Machine Learning for Mechanical Ventilation Control

abstract:
AO_SCPLOWBSTRACTC_SCPLOWWe consider the problem of controlling an invasive mechanical ventilator for pressure-controlled ventilation: a controller must let air in and out of a sedated patients lungs according to a trajectory of airway pressures specified by a clinician.

Hand-tuned PID controllers and similar variants have comprised the industry standard for decades, yet can behave poorly by over- or under-shooting their target or oscillating rapidly.

We consider a data-driven machine learning approach: First, we train a simulator based on data we collect from an artificial lung. Then, we train deep neural network controllers on these simulators. We show that our controllers are able to track target pressure waveforms significantly better than PID controllers.

We further show that a learned controller generalizes across lungs with varying characteristics much more readily than PID controllers do.

category: intensive care and critical care medicine


title: FRONTLINE COMMUNITIES AND SARS-COV-2-MULTI-POPULATION MODELING WITH AN ASSESSMENT OF DISPARITY BY RACE/ETHNICITY USING ENSEMBLE DATA ASSIMILATION

abstract: AO_SCPLOWBSTRACTC_SCPLOWThe COVID-19 pandemic has imposed many strenuous effects on the global economy, community, and medical infrastructure. Since the out- break, researchers and policymakers have scrambled to develop ways to identify how COVID-19 will affect specific sub-populations so that good public health decisions can be made. To this end, we adapt the work of Evensen et al [1] which introduces a SEIR model that incorporates an age-stratified contact matrix, a time dependent effective reproduction number R, and uses ensemble data assimilation to estimate model parameters. The adaptation is an extension of Evensens modeling framework, in which we model sub-populations with varying risks of contracting SARS-CoV-2 (the virus that causes COVID-19) in a particular state, each with a characteristic age-stratified contact matrix. In this work, we will focus on 9 U.S. states as well as the District of Columbia. We estimate the effective reproductive number as a function of time for our different sub-populations and then divide them into two groups: frontline communities (FLCs) and the complement (NFLCs). Our model will account for mixing both within populations (intra-population mixing) and between populations (inter-population mixing). Our data is conditioned on the daily numbers of accumulated deaths for each sub-population. We aim to test and demonstrate methodologies that can be used to assess critical metrics of the pandemics evolution which are difficult to directly measure. The output may ultimately be of use to measure the success or failures of the pandemic response and provide experts and policymakers a tool to create better plans for a future outbreak or pandemic. We consider the results of this work to be a reanalysis of pandemic evolution across differently affected sub-populations which may also be used to improve modeling and forecasts.

category: epidemiology


title: Estimating the burden of post-COVID-19 syndrome in a population-based cohort study of SARS-CoV-2 infected individuals: Implications for healthcare service planning

abstract:
BackgroundLonger-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization.

MethodsThis population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes.

ResultsSymptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care.

ConclusionsIn this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care.

RegistrationISRCTN14990068


title: Burden of Post-COVID-19 Syndrome and Implications for Healthcare Service Planning: A Population-based Cohort Study


title: Modeling infection dynamics and mitigation strategies to support K-6 in-person instruction during the COVID-19 pandemic

abstract:
ObjectiveTo support safer in-person K-6 instruction during the coronavirus disease 2019 (COVID- 19) pandemic by providing public health authorities and school districts with a practical model of transmission dynamics and mitigation strategies.

MethodsWe developed an agent-based model of infection dynamics and preventive mitigation strategies such as distancing, health behaviors, surveillance and symptomatic testing, daily symptom and exposure screening, quarantine policies, and vaccination. The model parameters can be updated as the science evolves and are adjustable via an online user interface, enabling users to explore the effects of interventions on outcomes of interest to states and localities, under a variety of plausible epidemiological and policy assumptions.

ResultsUnder default assumptions, secondary infection rates and school attendance are substantially affected by surveillance testing protocols, vaccination rates, class sizes, and effectiveness of safety education.

ConclusionsOur model helps policymakers consider how mitigation options and the dynamics of school infection risks affect outcomes of interest. The models parameters can be immediately updated in response to changes in epidemiological conditions, science of COVID-19 transmission dynamics, testing and vaccination resources, and reliability of mitigation strategies.


title: Evaluating the trade-off between transmissibility and virulence of SARS-CoV-2 by mathematical modeling

abstract:
BackgroundAt the beginning of 2020, SARS-CoV-2 spread to all continents, and since then, mutations have appeared in different regions of the world. The appearance of more virulent mutations leads to asseverate that they are also more transmissible. We analyzed the lower and higher virulent SARS-CoV-2 epidemics to establish a relationship between transmissibility and virulence based on a mathematical model.

MethodsA compartmental mathematical model based on the CoViD-19 natural history encompassing the age-dependent fatality was applied to evaluate the SARS-CoV-2 transmissibility and virulence. The transmissibility was measured by the basic reproduction number R0 and the virulence by the proportion of asymptomatic individuals. The model parameters were fitted considering the observed data from Sao Paulo State.

ResultsThe numbers of severe CoViD-19 and deaths are three times higher, but R0 is 25% lower in more virulent SARS-CoV-2 transmission than in a less virulent one. However, the number of more virulent SARS-CoV-2 transmitting individuals is 25% lower, mainly due to symptomatic individuals isolation, explaining the increased transmission in lower virulence.

ConclusionsThe quarantine study in Sao Paulo State showed that the more virulent SARS-CoV-2 resulted in a higher number of fatalities but less transmissible than the less virulent one. One possible explanation for the number of deaths surpassing that predicted by the low virulent SARS-CoV-2 infection could be the transmission of more virulent variant(s).


title: Lower help-seeking intentions and subsequent depressive symptoms among adolescents with high autistic traits: A population-based cohort study

abstract:
BackgroundAdolescents with high autistic traits in the general population are at increased risk of depression. Despite the importance of help-seeking for early intervention, evidence on help-seeking intentions among this population is scarce.

AimsTo examine the help-seeking intentions and preferences for depression by the level of autistic traits in adolescents, and test how help-seeking intentions mediate the association between autistic traits and depressive symptoms.

MethodParticipants were from the Tokyo Teen Cohort, a population-based cohort in Japan. They were classified into two groups according to parent-rated autistic traits measured by the short-version of the Autism-Spectrum Quotient ([≥]6 as AQhigh). Help-seeking intentions and preferences were assessed at age 12 using a depression vignette. Depressive symptoms were self-rated at age 14 using the Short Mood and Feelings Questionnaire. Data were analysed using multivariable regression analysis and structural equation modelling.

ResultsOf the 2,505 adolescents in the study, 200 (8%) were classified as AQhigh. In the AQhigh-group, 40% of the adolescents reported not having help-seeking intentions, although 93% recognised the need and 97% had someone to rely on. Parents of the AQhigh-group also reported fewer help-seeking intentions. The AQhigh-group was associated with an increased risk of not having help-seeking intentions (OR 1.83, 95%CI 1.35-2.49), which explained 19% of the above association.

ConclusionsLower help-seeking intentions among adolescents with high autistic traits partially explained their increased risk for subsequent depressive symptoms. Interventions to promote help-seeking intentions among this population should involve both adolescents and their parents and ideally be provided before adolescence.

category: psychiatry and clinical psychology


title: Nationwide rollout reveals efficacy of epidemic control through digital contact tracing

abstract: Fueled by epidemiological studies of SARS-CoV-2, contact tracing by mobile phones has been put to use in many countries. A year into the pandemic, we lack conclusive evidence on its effectiveness. Here, we used a unique real world contact data set, collected during the rollout of the first Norwegian contact tracing app in the Spring of 2020, to address this gap. Our dataset involves millions of contacts between 12.5% of the adult population, and enabled us to measure the real-world app performance. The technological tracing efficacy was measured at 80%, and we estimated that at least 11.0% of the discovered close contacts could not be identified by manual contact tracing. The overall effectiveness of digital tracing depends strongly on app uptake, but significant impact can be achieved for moderate uptake numbers. Used as a supplement to manual tracing and other measures, digital tracing can be instrumental in controlling the pandemic. Our findings can thus help informing public health policies in the coming months.

category: public and global health


title: Evaluating the potential of respiratory-sinus-arrhythmia biofeedback for reducing physiological stress in adolescents with autism: a protocol for a randomized controlled study

abstract:
BackgroundPrior evidence points towards lower cardiac vagal modulation in individuals with Autism Spectrum Disorder (ASD) as compared to control groups. A cross-sectional phase in this study will gather more evidence concerning this topic. A longitudinal phase will explore the efficacy of a biofeedback intervention based on Respiratory Sinus Arrhythmia (RSA) in adolescents with ASD. Finally, a feasibility study will focus on a non-supervised RSA biofeedback intervention in this population.

MethodsThe cross-sectional phase includes the comparison of adolescents with ASD (n=38) and age and gender matched typically developing peers. A standardized assessment will be used which contains physiological, cortisol and behavioral measurements. The longitudinal phase contains a randomized, single-blinded and sham-controlled design to determine the efficacy of supervised RSA biofeedback in adolescents with ASD (n=128). A follow-up phase of 5 weeks is included to evaluate the presence of retention effects. During the latter, a feasibility study will focus on a non-supervised intervention (n=62). Assessments as described previously are scheduled after the intervention and the follow-up phase.

DiscussionFirst, more conclusive evidence will be provided for the presence of lower cardiac vagal modulation in adolescents with ASD as well as the association between these lower values and physiological and behavioral indices. Second, the supervised intervention in adolescents with ASD is hypothesized to upregulate this cardiac vagal modulation and positively change behavioral and physiological parameters. Third, evidence regarding the feasibility and acceptability of a non-supervised intervention may open novel avenues for home-based interventions in this population.

Study registrationClinicalTrials.gov, NCT04628715. Registered on 13 November 2020.

DeclarationsO_ST_ABSFundingC_ST_ABSFunding is provided by the Marguerite-Marie Delacroix foundation with grant number GV/B-363. The funder will not have any role in any part of this study.

Competing interestsThe authors declare that they have no conflict of interest.

Availability of data and materialAll data from the participants will be de-identified and provided with a unique code. The coded data will be stored for 20 years in secured databases of the Research Group for Adapted Physical Activity and Psychomotor Rehabilitation, protected by the KU Leuven and will only be accessible by researchers of collaborating labs. The key to the coded data will be stored securely and confidentially in a separate electronic file. The saliva samples will be stored under appropriate conditions during the study at the biobank of the KU Leuven and will be destroyed afterwards. Participants waive any intellectual property rights on findings that might result from the analysis of their saliva samples.

Code availabilityNot applicable.

Authors contributionsAll authors contributed to the writing of this manuscript and the grant proposal. Anoushka Thoen leads the study and data management under supervision of Tine Van Damme, who provided facilities and equipment. All authors read and approved the final manuscript.

Ethics approvalEthical approval for this study was granted by both the Ethics Committee UPC KU Leuven on July 2nd 2020 (ref. EC2020-541, version 2.0) and the Ethics Committee Research UZ/KU Leuven on October 20th 2020 (ref: S64219, version 1.0).

Consent to participateParents of the participants should provide informed consent in addition to the informed assent provided by the participants themselves. Participants may withdraw consent and participation at any time. The participants request to withdraw from the study will always be respected and reasons to withdraw are not obliged to be mentioned. The sponsor of this study is KU Leuven (Oude Markt 13, 3000 Leuven, Belgium) and will have no role in any part of this study.

Consent for publicationAuthorship to publications will be determined in accordance with the requirements published by the International Committee of Medical Journal Editors and in accordance with the requirements of the respective peer-reviewed medical journal.

AmendmentsEvery substantial adjustment to the protocol will be communicated to the Ethics Committee UPC KU Leuven and the Ethics Committee Research UZ/KU Leuven as an amendment to the protocol. Only after approval of this amendment, the adjustments can be implemented and communicated to the researchers and participants.

AuditingThe researchers will permit study-related monitoring, audits, Ethical Committee review and regulatory inspection, providing direct access to all related source data/documents.

Dissemination of study resultsThe results of this study will be used for publication in peer-reviewed journals. There will also be a general dissemination of the study results for the participants and personal results will be provided upon request.

category: rehabilitation medicine and physical therapy


title: A rigorous evaluation of optimal peptide targets for MS-based clinical diagnostics of Coronavirus Disease 2019 (COVID-19).

abstract: The Coronavirus Disease 2019 (COVID-19) global pandemic has had a profound, lasting impact on the worlds population. A key aspect to providing care for those with COVID-19 and checking its further spread is early and accurate diagnosis of infection, which has been generally done via methods for amplifying and detecting viral RNA molecules. Detection and quantitation of peptides using targeted mass spectrometry-based strategies has been proposed as an alternative diagnostic tool due to direct detection of molecular indicators from non-invasively collected samples as well as the potential for high-throughput analysis in a clinical setting; many studies have revealed the presence of viral peptides within easily accessed patient samples. However, evidence suggests that some viral peptides could serve as better indicators of COVID-19 infection status than others, due to potential misidentification of peptides derived from human host proteins, poor spectral quality, high limits of detection etc. In this study we have compiled a list of 639 peptides identified from Sudden Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples, including from in vitro and clinical sources. These datasets were rigorously analyzed using automated, Galaxy-based workflows containing tools such as PepQuery, BLAST-P, and the Multi-omic Visualization Platform as well as the open-source tools MetaTryp and Proteomics Data Viewer (PDV). Using PepQuery for confirming peptide spectrum matches, we were able to narrow down the 639 peptide possibilities to 87 peptides which were most robustly detected and specific to the SARS-CoV-2 virus. The specificity of these sequences to coronavirus taxa was confirmed using Unipept and BLAST-P. Applying stringent statistical scoring thresholds, combined with manual verification of peptide spectrum match quality, 4 peptides derived from the nucleocapsid phosphoprotein and membrane protein were found to be most robustly detected across all cell culture and clinical samples, including those collected non-invasively. We propose that these peptides would be of the most value for clinical proteomics applications seeking to detect COVID-19 from a variety of sample types. We also contend that samples taken from the upper respiratory tract and oral cavity have the highest potential for diagnosis of SARS-CoV-2 infection from easily collected patient samples using mass spectrometry-based proteomics assays.


title: A Systematic Review and Meta-Analysis on Catastrophic Cost incurred by Tuberculosis Patients and their Households

abstract:
BackgroundAs one of the World Health Organization (WHO) End Tuberculosis (TB) Strategy is to reduce the proportion of TB affected families that face catastrophic costs to 0% by 2020. This systematic review and meta-analysis aimed to estimate the pooled proportion of TB affected households who face catastrophic cost.

MethodA search of the online database through September 2020 was performed. A total of 5114 articles were found, of which 29 articles got included in quantitative synthesis. Catastrophic cost is defined if total cost related to TB exceeded 20% of annual pre-TB household income. R software was used to estimate the pooled proportion at 95% confidence intervals (CIs) using the fixed/random-effect models.

ResultThe proportion of patients faced catastrophic cost was 43% (95% CI 34-52, I2 = 99%); 32% (95% CI 29 - 35, I2 = 70%) among drug sensitive, and 80% (95% CI 74-85, I2 = 54%) among drug resistant, and 81% (95%CI 78-84%, I2 = 0%) among HIV patients. Regarding active versus passive case finding the pooled proportion of catastrophic cost was 12% (95% CI 9-16, I2 = 95%) versus 42% (95% CI 35-50, I2 = 94%). The pooled proportion of direct cost to the total cost was 45% (95% CI 39-51, I2 = 91%). The pooled proportion of patients facing catastrophic health expenditure (CHE) at cut of point of 10% of their yearly income was 45% (95% CI 35-56, I2 = 93%) while at 40% of their capacity to pay was 63% (95% CI 40-80, I2 = 96%).

ConclusionDespite the ongoing efforts, there is a significant proportion of patients facing catastrophic cost, which represent a main obstacle against TB control.

PROSPERO registrationCRD42020221283

category: health economics


title: Physical Activity Patterns Among Patients with Intracardiac Remote Monitoring Devices Before, During, and After COVID-19-related Public Health Restrictions

abstract: Nationwide public health restrictions due to the coronavirus disease 2019 (COVID-19) pandemic have disrupted peoples routine physical activities, yet little objective information is available on the extent to which physical activity has changed among patients with pre-existing cardiac diseases. Using remote monitoring data of 9,924 patients with pacemakers and implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed physical activity patterns among these patients in 2019 and 2020 from January through October. We found marked declines in physical activity among patients with implantable cardiac devices during COVID-19-related restrictions and the reduction was consistent across age and sex subgroups. Moreover, physical activity among these vulnerable patients did not return to pre-restrictions levels several months after COVID-19 restrictions were eased. Our findings highlight the need to consider the unintended consequences of mitigation strategies and develop approaches to encourage safe physical activity during the pandemic.


title: Trends in Thoracic Impedance and Arrhythmia Burden Among Patients with Implanted Cardiac Defibrillators During the COVID-19 Pandemic

abstract: Hospitalizations for acute cardiac conditions have markedly declined during the coronavirus disease 2019 (COVID-19) pandemic, yet the cause of this decline is not clear. Using remote monitoring data of 4,029 patients with implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed changes in markers of cardiac status among these patients and compared thoracic impedance and arrhythmia burden in 2019 and 2020 from January through August. We found no change in several key disease decompensation markers among patients with implanted ICD devices during the first phase of COVID-19 pandemic, suggesting that the decrease in cardiovascular hospitalizations in this period is not reflective of a true population-level improvement in cardiovascular health.


title: Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection - Surveillance for Emerging Threats to Mothers and Babies Network, 20 state, local, and territorial health departments, March 29, 2020 -January 8, 2021

abstract:
BackgroundPregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection.

MethodsPregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020-January 8, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics.

ResultsAmong 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30-39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions.

ConclusionsPregnant women with moderate-to-severe or critical COVID-19 illness were more likely to be older and have underlying medical conditions compared to pregnant women with asymptomatic infection or mild COVID-19 illness. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.

SummaryAmong pregnant women with COVID-19, older age and underlying medical conditions were risk factors for increased illness severity. These findings can be used to inform pregnant women about their risk for severe COVID-19 illness and public health messaging.

category: obstetrics and gynecology


title: Trajectories of Clinical and Laboratory Characteristics Associated with COVID-19 in Hemodialysis Patients by Survival

abstract:
IntroductionThe clinical impact of COVID-19 has not been established in the dialysis population. We evaluated the trajectories of clinical and laboratory parameters in hemodialysis (HD) patients.

MethodsWe used data from adult HD patients treated at an integrated kidney disease company who received a RT-PCR test to investigate suspicion of a SARS-CoV-2 infection between 01 May and 01 Sep 2020. Nonparametric smoothing splines were used to fit data for individual trajectories and estimate the mean change over time in patients testing positive or negative for SARS-CoV-2 and those who survived or died within 30 days of first suspicion or positive test date. For each clinical parameter of interest, the difference in average daily changes between COVID-19 positive versus negative group and COVID-19 survivor versus non-survivor group was estimated by fitting a linear mixed effects model based on measurements in the 14 days before (i.e., day-14 to day 0) day 0.

ResultsThere were 12,836 HD patients with a suspicion of COVID-19 who received RT-PCR testing (8,895 SARS-CoV-2 positive). We observed significantly different trends (p<0.05) in pre-HD systolic blood pressure (SBP), pre-HD pulse rate, body temperature, ferritin, lymphocytes, albumin, and interdialytic weight gain (IDWG) between COVID-19 positive and negative patient. For COVID-19 positive group, we observed significantly different clinical trends (p<0.05) in pre-HD pulse rate, lymphocytes, albumin and neutrophil-lymphocyte ratio (NLR) between survivors and non-survivors. We also observed that, in the group of survivors, most clinical parameters returned to pre-COVID-19 levels within 60-90 days.

ConclusionWe observed unique temporal trends in various clinical and laboratory parameters among HD patients who tested positive versus negative for SARS-CoV-2 infection and those who survived the infection versus those who died. These trends can help to define the physiological disturbances that characterize the onset and course of COVID-19 in HD patients

category: nephrology


title: Renewable Energy Use in Australian Public Hospitals

abstract:
ObjectiveAre Australian hospitals moving towards renewable energy sources for their electricity, and aligning energy choices with core business, i.e. protecting and promoting health?

DesignCross-sectional analysis of Australian state/territory amalgamated energy data

SettingHealthcares carbon footprint is approximately 7% of Australias total carbon footprint. It is unknown if Australian public hospitals are decoupling energy needs from carbon emissions over and above state/territory based renewable energy targets.

Participants693 Australian public hospitals direct energy usage (renewable & non-renewable electricity [produced/purchased], natural gas, liquefied petroleum gas, for the three consecutive years from 2016/17 to 2018/19.

Main outcome measuresAll direct energy produced/purchased and consumed (converted to kilowatt-hours).

ResultsAustralian public hospitals consumed 4,122 gigawatt-hours of energy in 2018/19. Electricity use was 2,504 (61%) GWh, natural gas 1,436 (35%) GWh and renewable energy 94 GWh (2.3%). Victoria and New South Wales combined consumed 2,494/ 4,122 GWh (60%) of total Australian public healthcare energy but each produced/purchased less than 1% renewable electricity. For Queensland, a Health GreenPower purchase comprised the majority (71/94 GWh; 76%) of renewable energy production/purchase by all Australian public hospitals. By comparison, individual tertiary education institutions produced/purchased more renewable energy than all Australian public hospitals combined (University of NSW 124 GWh/yr, Swinburne University 90 GWh/yr, 2018/19).

ConclusionsAustralian public hospitals obtain approximately 2.3% of total energy from renewable electricity. One third of hospital energy use stems from fossil gas use. The Australian public hospital system has no documented plans to transition to renewable energy, contrasting with the University sector.

O_TEXTBOXThe knownAustralian healthcare contributes approximately 7% of Australias total carbon footprint with public hospital energy use a major source of healthcare associated carbon emissions.

The newAustralian public hospitals consumed 4122 gigawatt-hours in 2018/2019. Approximately 2.3% (94/4,122 gigawatt-hours) of hospital energy was sourced from renewables, beyond state-wide renewable electricity penetration.

The implicationsAustralian public hospitals are large emitters of greenhouse gases. Hospital fossil fuel energy use and subsequent pollution continues unabated. Such increasing pollution is at odds with the ethos  first do no harm.

C_TEXTBOX


title: Autoantibodies against nephrin elucidate a novel autoimmune phenomenon in proteinuric kidney disease

abstract: Dysfunction of podocytes, cells critical for glomerular filtration, underlies proteinuria and kidney failure. Genetic forms of proteinuric kidney disease can be caused by mutations in several podocyte genes, including nephrin, a critical component of the kidney filter. In contrast, the etiology of acquired acute-onset nephrotic syndrome has remained elusive. Here we identify autoantibodies against nephrin in serum and glomeruli of a subset of adults and children with non-congenital acute nephrotic syndrome. Our findings align with published experimental animal studies and elucidate a novel autoimmune phenomenon in proteinuric kidney disease interfering with glomerular filter integrity.


title: The kidney produces a non-polymerizing form of Uromodulin that associates with reduced risk of acute kidney injury

abstract: Uromodulin (Tamm-Horsfall protein, THP) is a glycoprotein uniquely produced in the kidney. It is released by cells of the thick ascending limbs (TAL) apically in the urine, and basolaterally in the renal interstitium and systemic circulation. Processing of mature urinary THP, which polymerizes into supra-molecular filaments, requires cleavage of an external hydrophobic patch (EHP) at the C terminus. However, THP in the circulation is not polymerized, and it remains unclear if non-aggregated forms of THP exist natively in the urine. We propose that an alternative processing path, which retains the EHP domain, can lead to a non-polymerizing form of THP. We generated an antibody that specifically recognizes THP with retained EHP (THP+EHP) and established its presence in the urine in a non-polymerized native state. Proteomic characterization of urinary THP+EHP revealed its C-terminus to end at F617. In the human kidney, THP+EHP was not only detected in TAL cells, but also diffusely in the renal parenchyma. Using immunoprecipitation followed by proteomic sequencing and immunoblotting, we then demonstrated that serum THP has also retained EHP. In a small cohort of patients at risk for acute kidney injury (AKI), admission urinary THP+EHP was significantly lower in patients who subsequently developed AKI during hospitalization. Our findings uncover novel insights into uromodulin biology by establishing the presence of an alternative path for cellular processing, which could explain the release of non-polymerizing THP in the circulation. Larger studies are needed to establish the utility of urinary THP+EHP as a sensitive biomarker of kidney health and susceptibility to injury.


title: The kidney releases a non-polymerizing form of Uromodulin in the urine and circulation that retains the external hydrophobic patch domain


title: The Genetic Architecture of Alzheimers Disease Risk: A Genomic Structural Equation Modelling Study

abstract:
BackgroundTargeting modifiable risk factors may have a role in the prevention of Alzheimers disease. However, the mechanisms by which these risk factors influence Alzheimers risk remain incompletely understood. Genomic structural equation modelling can reveal patterns of shared genetic architecture that provide insight into the pathophysiology of complex traits.

MethodsWe identified genome-wide association studies for Alzheimers disease and its major modifiable risk factors: less education, hearing loss, hypertension, high alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, type 2 diabetes, sleep disturbance and socioeconomic deprivation. We performed linkage disequilibrium score regression among these traits, followed by exploratory factor analysis, confirmatory factor analysis and structural equation modelling.

ResultsWe identified complex networks of linkage disequilibrium among Alzheimers disease risk factors. The data were best explained by a bi-factor model, incorporating a Common Factor for Alzheimers risk, and three orthogonal sub-clusters of risk factors, which were validated across the two halves of the autosome. The first sub-cluster was characterised by risk factors related to sedentary lifestyle behaviours, the second by traits associated with reduced life expectancy and the third by traits that are possible prodromes of Alzheimers disease. Alzheimers disease was more genetically distinct and displayed minimal shared genetic architecture with its risk factors, which was robust to the exclusion of APOE.

ConclusionShared genetic architecture may contribute to epidemiological associations between Alzheimers disease and its risk factors. Understanding the biology reflected by this communality may provide novel mechanistic insights that could help to prioritise targets for dementia prevention.

category: neurology


title: On Cross-ancestry Cancer Polygenic Risk Scores

abstract: Polygenic risk scores (PRS) can provide useful information for personalized risk stratification and disease risk assessment, especially when combined with non-genetic risk factors. However, their construction depends on the availability of summary statistics from genome-wide association studies (GWAS) independent from the target sample. For best compatibility, it was reported that GWAS and the target sample should match in terms of ancestries. Yet, GWAS, especially in the field of cancer, often lack diversity and are predominated by European ancestry. This bias is a limiting factor in PRS research. By using electronic health records and genetic data from the UK Biobank, we contrast the utility of breast and prostate cancer PRS derived from external European-ancestry-based GWAS across African, East Asian, European, and South Asian ancestry groups. We highlight differences in the PRS distributions of these groups that are amplified when PRS methods condense hundreds of thousands of variants into a single score. While European-GWAS-derived PRS were not directly transferrable across ancestries on an absolute scale, we establish their predictive potential when considering them separately within each group. For example, the top 10% of the breast cancer PRS distributions within each ancestry group each revealed significant enrichments of breast cancer cases compared to the bottom 90% (odds ratio of 2.81 [95%CI: 2.69,2.93] in European, 2.88 [1.85, 4.48] in African, 2.60 [1.25, 5.40] in East Asian, and 2.33 [1.55, 3.51] in South Asian individuals). Our findings highlight a compromise solution for PRS research to compensate for the lack of diversity in well-powered European GWAS efforts while recruitment of diverse participants in the field catches up.

category: genetic and genomic medicine


title: Novel polygenic risk score links depression-related cortical transcriptomic changes to brain morphology and depressive symptoms in men

abstract: Our group developed a transcriptome-based polygenic risk score (T-PRS) that uses common genetic variants to capture  depression-like shifts in cortical gene expression. Here, we mapped T-PRS onto diagnosis and symptom severity in major depressive disorder (MDD) cases and controls from the Psychiatric Genomics Consortium (PGC). To evaluate potential mechanisms, we further mapped T-PRS onto discrete measures of brain morphology and broad depression risk in healthy young adults. Genetic, self-report, and/or neuroimaging data were available in 29,340 PGC participants (59% women; 12,923 MDD cases, 16,417 controls) and 482 participants in the Duke Neurogenetics Study (DNS: 53% women; aged 19.8{+/-}1.2 years). T-PRS was computed from SNP data using PrediXcan to impute cortical expression levels of MDD-related genes from a previous post-mortem transcriptome meta-analysis. Sex-specific regressions were used to test effects of T-PRS on depression diagnosis, symptom severity, and Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index in the PGC and DNS samples, respectively. T-PRS did not predict depression diagnosis (OR=1.007, 95%CI=[0.997-1.018]); however, it correlated with symptom severity in men (rho=0.175, p=7.957x10-4) in one large PGC cohort (N=762, 48% men). In DNS, T-PRS was associated with smaller amygdala volume in women ({beta}=-0.186, t=-3.478, p=.001) and less prefrontal gyrification (max[≤]-2.970, p[≤].006) in both sexes. In men, prefrontal gyrification mediated an indirect effect of T-PRS on broad depression risk (b=.005, p=.029), indexed using self-reported family history of depression. Depression-like shifts in cortical gene expression predict symptom severity in men and may contribute to disease vulnerability through their effect on cortical gyrification.


title: Novel polygenic risk score links depression-related cortical transcriptomic changes to brain morphology and symptom severity


title: Registration, Publication, and Outcome Reporting among Pivotal Clinical Trials that Supported FDA Approval of High-Risk Medical Devices Before and After FDAAA

abstract:
BackgroundSelective registration, publication, and outcome reporting of clinical trials distorts the primary clinical evidence that is available to patients and clinicians regarding the safety and efficacy of FDA-approved medical devices. The purpose of this study is to compare registration, publication, and outcome reporting among pivotal clinical trials that supported FDA approval of high-risk (Class III) medical devices before and after the U.S. Food and Drug Administration (FDA) Amendment Act (FDAAA) was enacted in 2007.

MethodsUsing publicly available data from ClinicalTrials.gov, FDA summaries, and PubMed, we determined registration, publication, and reporting of findings for all pivotal clinical studies supporting FDA approval of new high-risk cardiovascular devices between 2005 and 2020, before and after FDAAA. For published studies, we compared both the primary efficacy outcome with the PMA primary efficacy outcome and the published interpretation of findings with the FDA reviewers interpretation (positive, equivocal, or negative).

ResultsBetween 2005 and 2020, the FDA approved 156 high-risk cardiovascular devices on the basis of 165 pivotal trials, 48 (29%) of which were categorized as pre-FDAAA and 117 (71%) as post-FDAAA. Post-FDAAA, pivotal clinical trials were more likely to be registered (115 of 117 (98%) vs 24 of 48 (50%); p < 0.001), to report results (98 of 115 (85%) vs 7 of 24 (29%); p < 0.001) on ClinicalTrials.gov, and to be published (100 or 117 (85%) vs 28 of 48 (58%); p < 0.001) in peer-reviewed literature when compared to pre-FDAAA. Among published trials, rates of concordant primary efficacy outcome reporting were not significantly different between pre-FDAAA trials and post-FDAAA trials (24 of 28 (86%) vs 96 of 100 (96%); p = 0.07), nor were rates of concordant trial interpretation (27 of 28 (96%) vs 93 of 100 (93%); p = 0.44).

ConclusionsFDAAA was associated with increased registration, results reporting, and publication for trials supporting FDA approval of high-risk medical devices. Among published trials, rates of accurate primary efficacy outcome reporting and trial interpretation were high and no different post-FDAAA.

category: health policy


title: Modeling COVID-19 Nonpharmaceutical Interventions: Exploring periodic NPI strategies

abstract: In April 2020, we developed a COVID-19 transmission model used as part of RANDs web-based COVID-19 decision support tool that compares the effects of different nonphar-maceutical public health interventions (NPIs) on health and economic outcomes. An interdis-ciplinary approach informed the selection and use of multiple NPIs, combining quantitative modeling of the health/economic impacts of interventions with qualitative assessments of other important considerations (e.g., cost, ease of implementation, equity). We previously published a description of our approach as a RAND report describing how the epidemiological model, the economic model, and a systematic assessment of NPIs informed the web-tool. This paper provides further details of our model, describes extensions that we made to our model since April, presents sensitivity analyses, and analyzes periodic NPIs. Our findings suggest that there are opportunities to shape the tradeoffs between economic and health outcomes by carefully evaluating a more comprehensive range of reopening policies. We consider strategies that periodically switch between a base NPI level and a higher NPI level as our working example.


title: Impact of COVID-19 on healthcare workers at a cancer care centre

abstract:
BackgroundThe services of front-line health care workers (HCWs) have been paramount in the management of novel coronavirus disease 2019 (COVID-19). Health care professionals have been at high occupational risk of getting disease and even dying of the disease, however; they have been the subject of very limited studies in terms of COVID-19. The objectives of this study are to examine the incidence and the impact of COVID-19 infection among HCWs in terms of recovery, productivity, quality of life (QOL) and post-COVID complications.

Materials and MethodsThis was a retrospective, questionnaire based study including demographic details, workplace characteristics, symptoms, source/ spread of infection, details of recovery and the consequences of COVID-19 comprising impaired productivity/ QOL, post-COVID-19 complications and others. The data were analyzed by using IBM SPSS software (Version 23, SPSS Inc., Chicago, IL, USA).

Results and ConclusionsOut of a total of 1482 employees, 18.3% (271) were laboratory confirmed to have contracted novel contagion during the study period of 5 months. The median age at diagnosis was 29 (range, 21-62) years. Front-line workers and female workers were the most infected personnel with COVID-19. Flu-like symptoms were the most frequently experienced symptoms. The median time for recovery was 20 (range, 2-150) days. The relationship between pre-existing comorbidities and age was highly significant. The QOL and productivity were associated with pre-existing comorbidities, severity of the disease, time for recovery and post-COVID syndrome. More than a half (51.8%) of all HCWs had suffered from post-COVID complications. There was no fatality reported due to COVID-19. The post-COVID complications were related to pre-existing comorbidities, severity of disease, time for recovery and status of recovery. Further research to explore the consequences of COVID-19 is warranted. The general public needs to be aware of symptoms and management of the post-COVID syndrome.


title: Comparative performance of SARS-CoV-2 lateral flow antigen tests demonstrates their utility for high sensitivity detection of infectious virus in clinical specimens

abstract:
BackgroundRapid antigen lateral flow devices (LFDs) are set to become a cornerstone of SARS-CoV-2 mass community testing. However, their reduced sensitivity compared to PCR has raised questions of how well they identify infectious cases. Understanding their capabilities and limitations is therefore essential for successful implementation. To address this, we evaluated six commercial LFDs on the same collection of clinical samples and assessed their correlation with infectious virus culture and cycle threshold (Ct) values.

MethodsA head-to-head comparison of specificities and sensitivities was performed on six commercial rapid antigen tests using combined nasal/oropharyngeal swabs, and their limits of detection determined using viral plaque forming units (PFU). Three of the LFDs were selected for a further study, correlating antigen test result with RT-PCR Ct values and positive viral culture in Vero-E6 cells. This included sequential swabs and matched serum samples obtained from four infected individuals with varying disease severities. Detection of antibodies was performed using an IgG/IgM Rapid Test Cassette, and neutralising antibodies by infectious virus assay. Finally, the sensitivities of selected rapid antigen LFTs were assessed in swabs with confirmed B.1.1.7 variant, currently the dominant genotype in the UK.

FindingsMost of the rapid antigen LFDs showed a high specificity (>98%), and accurately detected 50 PFU/test (equivalent N1 Ct of 23.7 or RNA copy number of 3x106/ml). Sensitivities of the LFDs performed on clinical samples ranged from 65 to 89%. These sensitivities increased in most tests to over 90% for samples with Cts lower than 25. Positive virus culture was achieved for 57 out of 141 samples, with 80% of the positive cultures from swabs with Cts lower than 23. Importantly, sensitivity of the LFDs increased to over 95% when compared with the detection of infectious virus alone, irrespective of Ct. Longitudinal studies of PCR-positive samples showed that most of the tests identified all infectious samples as positive, but differences in test sensitivities can lead to missed cases in the absence of repeated testing. Finally, test performance was not impacted when re-assessed against swabs positive for the dominant UK variant B.1.1.7.

InterpretationIn this comprehensive comparison of antigen LFD and virus infectivity, we demonstrate a clear relationship between Ct values, quantitative culture of infectious virus and antigen LFD positivity in clinical samples. Our data support regular testing of target groups using LFDs to supplement the current PCR testing capacity, to rapidly identify infected individuals in situations where they would otherwise go undetected.

FundingKings Together Rapid COVID-19, Medical Research Council, Wellcome Trust, Huo Family Foundation.


title: SARS-CoV-2 antibodies detected in human breast milk post-vaccination

abstract:
ImportanceThe SARS-CoV-2 pandemic has infected over a hundred million people worldwide, with almost 2.5 million deaths at the date of this publication. In the United States, Pfizer-BioNTech and Moderna vaccines were first administered to the public starting in December 2020, and no lactating women were included in the initial trials of safety/efficacy. Research on SARS-CoV-2 vaccination in lactating women and the potential transmission of passive immunity to the infant through breast milk is needed to guide patients, clinicians and policy makers during the worldwide effort to curb the spread of this virus.

ObjectiveTo determine whether SARS-CoV-2 specific immunoglobins are found in breast milk post-vaccination, and to characterize the time course and types of immunoglobulins present.

DesignProspective cohort study

SettingProvidence Portland Medical Center, Oregon, USA

ParticipantsSix lactating women who planned to receive both doses of the Pfizer-BioNTech or Moderna vaccine between December 2020 and January 2021. Breast milk samples were collected pre-vaccination and at 11 additional timepoints, with last sample at 14 days post 2nd dose of vaccine.

ExposureTwo doses of Pfizer-BioNTech or Moderna SARS-CoV-2 vaccine.

Main Outcome(s) and Measure(s)Levels of SARS-CoV-2 specific IgA and IgG immunoglobulins in breast milk.

ResultsIn this cohort of 6 lactating women who received 2 doses of SARS-CoV-2 vaccine, we observed significantly elevated levels of SARS-CoV-2 specific IgG and IgA antibodies in breast milk beginning at Day 7 after the initial vaccine dose, with an IgG-dominant response.

Conclusions and RelevanceWe are the first to show that maternal vaccination results in SARS-CoV-2 specific immunoglobulins in breast milk that may be protective for infants.


title: Introductions and evolutions of SARS-CoV-2 strains in Japan

abstract: COVID-19 caused by SARS-CoV-2 was first identified in Japan on January 15th, 2020, soon after the pandemic originated in Wuhan, China. Subsequently, Japan experienced three distinct waves of the outbreak in the span of a year and has been attributed to new exogenous strains and evolving existing strains. Japan engaged very early on in tracking different COVID-19 sub-strains and have sequenced approximately 5% of all confirmed cases. While Japan has enforced stringent airport surveillance on cross-border travelers and returnees, some carriers appear to have advanced through the quarantine stations undetected. In this study, 17112 genomes sampled in Japan were analyzed to understand the strains, heterogeneity and temporal evolution of different SARS-CoV-2 strains. We identified 11 discrete strains with a substantial number of cases with most strains possessing the spike (S) D614G and nucleocapsid (N) 203_204delinsKR mutations. Besides these variants, ORF1ab P3371S, A4815V, S1361P, and N P151L were also detected in nearly half the samples constituting the most common strain in Japan. 115 distinct strains have been introduced into Japan and 12 of them were introduced after strict quarantine policy was implemented. In particular, the B.1.1.7 strain, that emerged in the United Kingdom (UK) in September 2020, has been circulating in Japan since late 2020 after eluding cross-border quarantine stations. Similarly, the B.1.351 strain dubbed the South African variant, P.1 Brazilian strain and R.1 strain with the spike E484K mutation have been detected in Japan. At least four exogenous B.1.1.7 sub-strains have been independently introduced in Japan as of late January 2021, and these strains carry mutations that give selective advantage including N501Y, H69_V70del, and E484K that confer increased transmissibility, reduced efficacy to vaccines and possible increased virulence. It is imperative that the quarantine policy be revised, cross-border surveillance reinforced, and new public health measures implemented to mitigate further transmission of this deadly disease and to identify strains that may engender resistance to vaccines.


title: Clinical course and outcomes of critically ill COVID-19 patients in two successive pandemic waves

abstract:
RationaleThe progress of COVID-19 from moderate to severe may be precipitous, while the heterogenous characteristics of the disease pose challenges to the management of these patients.

ObjectivesTo characterize the clinical course and outcomes of critically ill patients with COVID-19 during two successive waves.

MethodsWe leveraged the multi-center SuPAR in Adult Patients With COVID-19 (SPARCOL) study and collected data from consecutive patients requiring admission to the intensive care unit from April 1st to December 31st, 2020.

Measurements and Main ResultsOf 252 patients, 81 (32%) required intubation and mechanical ventilation. Of them, 17 (20.9%) were intubated during the first wave, while 64 (79%) during the second wave. The most prominent difference between the two waves was the overall survival (first wave 58.9% vs. second wave 15.6%, adjusted p-value=0.006). This difference is reflected in the prolonged hospitalization during the first wave. The mean ICU length of stay (19.1 vs. 11.7 days, p=0.022), hospital length of stay (28.5 vs. 17.1 days, p=0.012), and days on ventilator (16.7 vs. 11.5, p=0.13) were higher during the first wave. A significant difference between the two waves was the development of bradycardia. In the first wave, 2 (11.7%) patients developed sinus bradycardia only after admission to the intensive care unit, while in the second wave, 63 (98.4%) patients developed sinus bradycardia during hospitalization.

ConclusionsSurvival of critically ill patients with COVID-19 was significantly lower during the second wave. The majority of these patients developed sinus bradycardia during hospitalization.


title: Utility of a Clinical Scoring System for Point of Care Triaging in COVID-19 Pneumonia

abstract:
BackgroundSurges in COVID-19 disease cases can rapidly overwhelm healthcare resources; triaging to appropriate levels of care can assist in resource planning. At the beginning of the pandemic, we developed a simple triage tool, the Temple COVID-19 Pneumonia Triage Tool (TemCOV) based on a combination of clinical and radiographic features that are readily available on presentation to categorize and predict illness severity.

MethodsWe prospectively examined 579 sequential cases admitted to Temple University Hospital who were assigned severity categories on admission. Our primary outcome was to compare the performance of TemCOV in predicting patients who have the highest likely of admission to the ICU at 24 and at 72 hours to other standard triage tools: the National Early Warning System (NEWS), the Modified Early Warning System (MEWS) and the CURB65 score. Additional endpoints included need for invasive mechanical ventilation (IMV) within 72 hours, total hospital admission charges, and mortality.

Results26% of patients fell within our highest risk Category 4 and were more likely to require ICU admission at 24 hours (OR 11.51) and 72 hours (OR 8.6). Additionally they had the highest likelihood of needing IMV (OR 29.47) and in-hospital mortality (OR 2.37)., TemCOV performed similar to MEWS in predicting ICU admission at 24 hours (receive operator characteristic (ROC) curve area under the curve (AUC) 0.77 vs. 0.74, p=0.21) but better than NEWS2 and CURB65 (ROC AUC 0.77 vs. 0.69 and 0.77 vs. 0.64, respectively, p<0.01). While all severity scores had a weak correlation to hospital charges, the TemCOV performed the best among all severity scores measured (r=0.18); median hospital charges for Category 4 patients was $170,468 ($96,972-$487,556).

ConclusionTemCOV is a simple triage score that can be used upon hospitalization in patients with COVID-19 that predicts the need for hospital resources such as ICU bed capacity, invasive mechanical ventilation and personnel staffing.


title: Association of Streptococcus mutans harboring bona-fide collagen binding proteins and Candida albicans with early childhood caries recurrence

abstract: Early childhood caries (ECC) recurrence occurs in approximately 40% of treated cases within one year. The association of Streptococcus mutans and Candida albicans with the onset of ECC is well known. Also, S. mutans strains harboring collagen-binding proteins (Cbps) avidly bind to collagen-rich dentin and are linked to increased caries incidence. Here, we investigated the presence of Cbp+ S. mutans and C. albicans in saliva and dental plaque of children with varying caries statuses, as well as the salivary microbiome of these children. In this cross-sectional study, 143 children who were caries-free, treated for ECC with no signs of recurrence after 6 months, or treated for ECC and experiencing recurrence within 6 months following treatment were enrolled. Co-infection with C. albicans and S. mutans, especially Cbp+ S. mutans, was strongly associated with caries recurrence. Subjects of the recurrence group infected with Cbp+ S. mutans showed a greater burden of C. albicans and of Mutans streptococci in dentin than those infected with Cbp- S. mutans. Microbiome analysis revealed that Streptococcus parasanguinis was overrepresented in the caries recurrence group. Our findings indicate that Cbp+ S. mutans and C. albicans are intimately associated with caries recurrence, contributing to the establishment of recalcitrant biofilms.

category: dentistry and oral medicine


title: Revisiting Bias in Odds Ratios

abstract: Ratio measures of effect, such as the odds ratio (OR), are consistent, but the presumption of their unbiasedness is founded on a false premise: The equality of the expected value of a ratio and the ratio of expected values. We show that the invalidity of this assumptions is an important source of empirical bias in ratio measures of effect, which is due to properties of the expectation of ratios of count random variables. We investigate ORs (unconfounded, no effect modification), proposing a correction that leads to "almost unbiased" estimates. We also explore ORs with covariates. We find substantial bias in OR estimates for smaller sample sizes, which can be corrected by the proposed method. Bias correction is more elusive for adjusted analyses. The notion of unbiasedness of OR for the effect of interest for smaller sample sizes is challenged.


title: Seasonal patterns COVID-19 and Flu Like Illnesses comparable

abstract:
BackgroundDuring the first wave of COVID-19 it was hypothesized that COVID-19 is subject to multi-wave seasonality, similar to Influenza-Like Illnesses since time immemorial. One year into the pandemic, we aimed to test the seasonality hypothesis for COVID-19.

MethodsWe calculated the average annual time-series for Influenza-Like Illnesses based on incidence data from 2016 till 2019 in the Netherlands, and compared these with two COVID-19 time-series during 2020/2021 for the Netherlands. We plotted the time-series on a standardized logarithmic infection scale. Finally, we calculated correlation coefficients and used univariate regression analysis to estimate the strength of the association between the time-series of COVID-19 and Influenza-Like Illnesses.

ResultsThe time-series for COVID-19 and Influenza-Like Illnesses were strongly and highly significantly correlated. The COVID-19 peaks were all during flu season, and lows were all in the opposing period. Finally, COVID-19 meets the multi-wave characteristics of earlier flu-like pandemics, namely a short first wave at the tail-end of a flu season, and a longer and more intense second wave during the subsequent flu season.

ConclusionsWe conclude that seasonal patterns of COVID-19 incidence and Influenza-Like Illnesses incidence are highly similar, in a country in the temperate climate zone, such as the Netherlands. Further, the COVID-19 pandemic satisfies the criteria of earlier respiratory pandemics, namely a first wave that is short-lived at the tail-end of flu season, and a second wave that is longer and more severe.

This seems to imply that the same factors that are driving the seasonality of Influenza-Like Illnesses are causing COVID-19 seasonality as well, such as solar radiation (UV), temperature, relative humidity, and subsequently seasonal allergens and allergies.

HIGHLIGHTSO_LITime-series analysis shows that COVID-19 and historic of Influenza-Like illnesses have highly similar seasonal patterns in the Netherlands.
C_LIO_LICOVID-19 satisfies the criteria of earlier flu-like pandemics, namely a short cycle at the end of flu season, and a longer, more intense cycle during the subsequent flu season.
C_LIO_LIThe implication is that the seasonal factors driving flu season, are also responsible for COVID-19 seasonality.
C_LIO_LIWe developed and applied a new method to determine seasonality, encompassing comparative time-series analysis, a standardized logarithmic infection scale, and qualitative seasonality criteria.
C_LI


title: Seasonal pattern COVID-19 and Flu-Like Illnesses comparable


title: Epidemiological health assessment in primary health care in the State of Qatar- 2019

abstract:
ObjectivesThe Primary Health Care Corporation (PHCC) in Qatar conducted epidemiological health assessment to understand the burden of diseases impacting the PHCC registered population

DesignThis is a cross-sectional study design among all PHCC registered population between the 1st of September 2018 and the 31st of August 2019

SettingPrimary Health Care Corporation health centers

ParticipantsThe target population is all persons residing in Qatar aged (0-80) years and registered at the PHCC. Excluding patients with expired Qatar residence permit by the 31st of August

ResultsObesity rates ranged between 37% and 35% among the total population registered with the lowest rate in the central region at 34.7%. Burden of type 2 diabetes, hypertension, and dyslipidemia was the highest among population of the Central region at 13.9%, 15.7% and 11.1%, respectively. Tobacco consumption among males ranged from 25.4 % to 27.8%, with the highest rate in the Northern region. 39.9% of females in the Northern region had BMI above 30 kg/m2. Exclusive breastfeeding at 6 months was significantly lower than that at 4 months across all regions. Children in the Northern region had the highest rate of overweight/obesity based on Z-scores. Western region population had the highest number of communicable diseases notifications especially Chicken pox at 94.6 per 10,000 children

ConclusionUnderstanding the patterns of disease in the local population will enable PHCC to provide a clear set of objectives to work towards meeting population health needs


title: Unmasking the Current Scenario of Indian Biomedical Devices Industry: Ventilators being the Heart of the Discussion

abstract:
BackgroundThe Indian Biomedical Device Industry has been growing at an unprecedented rate, but several hindrances need to be acknowledged in offering access to quality, budget-friendly medical devices in India. This article explores the current loopholes of the Indian biomedical device industry along with the proposal of various innovative solutions, with emphasis on ventilators.

MethodsAn online survey with the help of Google forms was conducted from 1st November to 25th December 2020, addressing the problems of the Indian medical device industry (MDI) along with probable solutions. The survey also provides a glimpse into the complications aroused from the frequent use of ventilators during COVID-19 outburst, along with possible measures.

ResultsAccording to the survey, 51.6%, 46.5%, 55.7%, and 47.5% of respondents have agreed to  Stringent laws and implementation,  Safety testing and strict regulations,  Unfavorable duty structure, and  Reducing tax rate on domestic manufacturers, as a possible solution to advance the implementation of ISO 13485 and ISO 10651, implementation of ISO 14971, the probable cause of limitations of Indian MDI, possible measure to overcome limitations of Indian MDI, respectively. 46.7%, 47.5%, 46.2%, and 44.6% of respondents have agreed to  Surgical decompression,  Nebulized and broad-spectrum antibiotics,  PEEP, and  Adopting lung protective ventilation strategies as possible solutions to treat various ventilator complications, respectively.

ConclusionThe study briefs about the peoples perception of the Indian MDI as well as on the ventilator complications. The results complied with our hypothesis as the majority of the respondents have agreed with almost all the probable solutions in both the sections given by us as options.


title: Sequence Analysis of 20,453 SARS-CoV-2 Genomes from the Houston Metropolitan Area Identifies the Emergence and Widespread Distribution of Multiple Isolates of All Major Variants of Concern

abstract: [Abstract]Since the beginning of the SARS-CoV-2 pandemic, there has been international concern about the emergence of virus variants with mutations that increase transmissibility, enhance escape from the human immune response, or otherwise alter biologically important phenotypes. In late 2020, several "variants of concern" emerged globally, including the UK variant (B.1.1.7), South Africa variant (B.1.351), Brazil variants (P.1 and P.2), and two related California "variants of interest" (B.1.429 and B.1.427). These variants are believed to have enhanced transmissibility capacity. For the South Africa and Brazil variants, there is evidence that mutations in spike protein permit it to escape from some vaccines and therapeutic monoclonal antibodies. Based on our extensive genome sequencing program involving 20,453 virus specimens from COVID-19 patients dating from March 2020, we report identification of all important SARS-CoV-2 variants among Houston Methodist Hospital patients residing in the greater metropolitan area. Although these variants are currently at relatively low frequency in the population, they are geographically widespread. Houston is the first city in the United States to have all variants documented by genome sequencing. As vaccine deployment accelerates worldwide, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence and frequency of consequential variants and their patterns and trajectory of dissemination. This information is critical for medical and public health efforts to effectively address and mitigate this global crisis.

category: pathology


title: Reduced Frontal Cortical Tracking of Conflict between Selfish versus Prosocial Motives in Narcissistic Personality Disorder

abstract: Narcissistic Personality Disorder (NPD) entails severe impairments in interpersonal functioning that are likely driven by selfish and exploitative behavior. Here, we investigate the underlying motivational and neural mechanisms of prosocial decision-making by experimentally manipulating motivational conflict between selfish and prosocial incentives. One group of patients diagnosed with NPD and a group of healthy controls (CTL) were scanned using functional magnetic resonance imaging while performing a prosocial decision-making task. In this task, we systematically varied the level of conflict between selfish and prosocial options on each trial. We analyzed choice behavior, response times, and neural activity in regions associated with conflict monitoring to test how motivational conflict drives prosocial choice behavior. Participants in the NPD group behaved less prosocially than the CTL group overall. Varying degrees of motivational conflict between selfish and prosocial options induced response variability in both groups, but more so in the CTL group. The NPD group responded faster than the CTL group, unless choosing prosocially, which slowed response times to a level comparable to the CTL group. Additionally, neural activity tracking motivational conflict in dorsomedial prefrontal cortex was reduced in the NPD group. Collectively, low generosity in NPD appears to arise from reduced consideration of prosocial motives, which obviates motivational conflict with selfish motives and entails reduced activity in neural conflict monitoring systems. Yet, our data also indicate that NPD is not marked by an absolute indifference to others needs. This points to potentials for improving interpersonal relationships, effectively supporting the well-being of patients and their peers.


title: The prevalence, incidence and risk factors of mental health problems and mental health services use before and 9 months after the COVID-19 outbreak among the general Dutch population. A 3-wave prospective study.

abstract:
ObjectivesGain insight in the effects of the COVID-19 pandemic on the prevalence, the incidence and risk factors of mental health problems among the Dutch general population and different age groups in November-December 2020, compared to the prevalence, incidence, and risk factors in the same period in 2018 and 2019. More specifically, the prevalence, incidence and risk factors of anxiety and depression symptoms, sleep problems, fatigue, disabilities due to health problems, use of medicines for sleep problems, medicines for anxiety and depression, and mental health services use.

MethodsWe extracted data from the LISS (Longitudinal Internet studies for the Social Sciences) panel that is based a probability sample of the Dutch population of 16 years and older by Statistics Netherlands. We used three waves of the longitudinal Health module held in November-December 2018 (T1), November-December 2019 (T2) and November-December 2020 (T3), and selected respondents who were 18 years and older at T1. Data were weighted using 16 demographics profiles of the Dutch adult population (Nstudy sample=4,064). The course of mental health problems was examined with repeated measures multivariate logistic regression analyses, and the differences in incidence with multivariate logistic regression analyses. In both types of analyses, we controlled for sex, age, marital status, employment status, education level and physical disease.

ResultsThe repeated measures multivariate logistic regression analyses among the total study sample did not reveal a significant increase in the prevalence of anxiety and depression symptoms, sleep problems, fatigue, disabilities due to health problems, use of medicines for sleep problems, medicines for anxiety and depression, and mental health services use in November- December 2020, compared to November-December 2018 and 2019 (that is, T3 did not differ from T1 and T2). Among the four different age categories (18-34, 35-49, 50-64, and 65 years old and older respondents), 50-64 years respondents had a significantly lower prevalence of anxiety and depression symptoms at T3 than at T1 and T2, while T1 and T2 did not differ. A similar pattern among 65+ respondents was found for mental health services use. We found no indications that the incidence of examined health problems at T2 (no problem at T1, problem at T2) and T3 (no problem at T2, problem at T3) differed. Risk factors for mental health problems at T2 were mostly similar to risk factors at T3; sex and age were less associated with sleep problems at T3, compared to T2 .

ConclusionsThe prevalence, incidence and risk factors of examined mental health problems examined nine months after the COVID-19 outbreak appear to be very stable across the end of 2018, 2019 and 2020 among the Dutch adult population and different age categories, suggesting that the Dutch adult population (20 years and older) in general is rather resilient given all disruptions due to this pandemic.


title: Modelled Optimization of SARS-Cov-2 Vaccine Distribution: an Evaluation of Second Dose Deferral Spacing of 6, 12, and 24 weeks

abstract:
BackgroundMultiple recent studies have shown strong first dose vaccine efficacy for both Moderna mRNA-1273 and Pfizer/BioNTech BNT 162b2, which has stimulated discussion of maximizing initial population immunity during a time of vaccine shortage by using a deferred second dose strategy for these vaccines.

MethodsOur model examines the size of the effect of spacing of the second dose with 6, 12, and 24 week deferred spacing regimens relative to 3 week spacing.

ResultsDeferring the second dose from 3 weeks to 6 weeks, 12 weeks, and 24 weeks shows progressive benefit to population immunity for any given time period, even with significant one dose efficacy decay. The benefits are influenced by vaccine supply per capita.

ConclusionThe longer the second dose is deferred the larger the benefit in initial population immunity, provided one dose efficacy does not significantly wane. Monitoring one dose efficacy duration from the UK or Quebec minimizes this risk, as the gathered data will help ensure the second dose is given at an optimal time. How this information is implemented should vary depending on the population and whether the goal is to optimally protect high risk groups or to increase total population immunity as quickly as possible. Benefits to deferring the second dose are influenced by the length of deferral, one dose efficacy, and vaccine supply per capita. The time to herd immunity could be shortened by 4 weeks with the implementation of a 12 week spacing regimen or 10 weeks with a 24 week spacing regimen.


title: A new accessible adaptable COVID-19 model

abstract:
ObjectivesSophisticated epidemic models have been created to help governments and large healthcare organisations plan the necessary resources to manage the COVID-19 pandemic. Whilst helpful, current modelling systems are not widely accessible or easily adapted to different populations and circumstances. Our objective was to develop a widely applicable, easily accessible, adaptable model for projecting new COVID-19 infections and deaths that requires minimal expertise or resources to use. The model should be adaptable to different populations and able to accommodate social and pharmaceutical interventions as well as changes in the disease.

DesignA Susceptible, Infected and Removed (SIR) infectious disease model was created using widely available Microsoft Excel(C) software. The model is deterministic, generating projections based on the available data and assumptions made. It uses a process of Monitored Forecasting through Visual Matching of predicated vs observed curves to improve accuracy and facilitate adaptability. A review of the COVID-19 literature was performed in order to produce an initial set of adjustable parameters on which to base the output of the model.

SettingThis model can be adapted to different regions or countries for which the requisite input data (population size and number of deaths due to the disease) are available. This model has been successfully used with data from England, Sudan and Saudi Arabia. Data from NHS England were used for producing the illustrative results presented here. The model is a generic infectious disease forecast model which may be adapted to other epidemics.

InterventionGovernments, public health organisations, pharmaceutical companies and other public institutions may introduce interventions that affect disease transmission or severity. Other unknown factors such as new variants of the infective agent may do the same. The effects of changes in disease transmission are identified by the model when predicted and observed curves deviate. By aligning the curves an evaluation of the effect of the changes can be made.

Outcome MeasuresThe model graphically demonstrates projections for daily deaths, cumulative deaths, case mix (asymptomatic, symptomatic and severe infections requiring admission), hospital admissions and bed occupancy (ICU, general medical and total).

ResultsThe model successfully produced projections for the outcome measures using NHS England data. Users can adapt and continuously update the model correcting its projections as further local data becomes available. The Microsoft Excel platform allows the model to be used without expensive health information systems or computing infrastructure.

ConclusionWe present an SIR epidemic model that projects COVID-19 disease progression, is widely accessible, adaptable to different populations and environments as the disease progresses and is likely to be of benefit for identifying changing population healthcare needs.


title: Determinants of adolescent lung function in Indians: race, nutrition and systemic inflammation

abstract:
RationaleWhile determining normal variation of spirometric volumes, the geo-political construct of  Indian inadequately captures the diverse racial structure and varied lifestyles that exist for 1 in 5 people globally. It is necessary to determine the degree of racial heterogeneity and other underlying factors to know whether lower spirometric volumes of  Indians is normal or abnormal.

ObjectivesTo investigate the differences in spirometric volumes and their associations with overall health parameters, for adolescent children and young adults, across geo-ethnic regions within India.

MethodsData was analyzed for 2338 healthy subjects aged 9-19 years with acceptable spirometry from SOLID cohort. Associations between lung function and potential determinants (Race, anthropometry, nutrition, family/life history, airway oscillometric parameters and systemic inflammation) were examined by using multiple regression. Latent profile analysis (LPA) was performed for 903 subjects to uncover hidden sub-phenotypes.

ResultsFEV1 and FVC varied significantly between Indian genetic ancestries, being highest in Tibeto-Burmans and lowest in Dravidians. After statistical adjustments, FEV1 and FVC were positively correlated with waist-height-ratio, shoulder-height-ratio, normalized BMI, and blood hemoglobin. Lower FVC was associated with lower expiratory flows (PEF and FEF25-75), higher lung reactance (X5), higher airway resistance (R10 and R15), gastro-intestinal symptoms, and higher inflammation (IL-8 and IL-17). A sub-phenotype of thinness, higher inflammation (IFN-gamma, IL-17, TNF-alpha, IL-8) and lower FVC was identified on LPA for 35% of the sample.

ConclusionsSpirometric volumes in Indians are different between major racial subgroups but may also be abnormally low due to prevalent nutritional or environmental adversity. Care must be taken while establishing normative standards.

category: respiratory medicine


title: Factors Associated with Antenatal Care Service Utilization among Mothers with Children under five years in Sunyani Municipality, Ghana

abstract:
BackgroundMaternal and neonatal mortality remains a public health burden around the globe most especially in developing countries. A well utilized antenatal care (ANC) is however among the identified interventions to reduce this burden of maternal and neonatal mortality rates. A lot of factors therefore predispose, enable and cause mothers to identify the need to utilize this service (ANC).

Aims/objectivesThe aim of this study was to determine factors associated with the utilization of ANC service among postpartum mothers in the Sunyani municipality.

MethodsThis study employed descriptive cross-sectional survey design. A semi-structured questionnaire consisting of demographic profile of the respondents, their knowledge about ANC services and the level of ANC utilization. Logistic regression analysis techniques and chi-square were used for the categorical variables to examine the associations between the dependent and independent variables. Data analysis was done using the Statistical Package for Social Science software (SPSS) version 22.

ResultsMajority (87%) of postpartum mothers in the Sunyani municipality attended ANC at least once during their last pregnancy of which 95.6% had four or more visits and 77.1% initiated their ANC attendance within their first trimester. It was further observed that 97.3% of the mothers had good knowledge about ANC. Marital status and ANC knowledge were found to be significantly associated with ANC attendance. Husbands were found to be poorly involved in ANC services in the Sunyani municipality.

ConclusionMarital status and ANC knowledge predisposes most mothers to utilize ANC services. Hence, health education activities about ANC services and its importance should be channeled more to areas where ANC utilization is low.

category: sexual and reproductive health


title: Evaluating a first fully automated interview grounded in MMI methodology: results from a feasibility study

abstract:
ObjectivesGlobal, Covid-driven restrictions around face-to-face interviews for healthcare student selection have forced admissions staff to rapidly adopt adapted online systems before supporting evidence is available. We have developed, what we believe is, the first fully automated interview grounded in Multiple Mini-Interview (MMI) methodology. This study aimed to explore test re-test reliability, acceptability and usability of the system.

Design, setting and participantsmixed-methods feasibility study in Physician Associate (PA) programmes from two UK and one US university during 2019 - 2020.

Primary, secondary outcomesFeasibility measures (test retest reliability acceptability and usability) were assessed using intra-class correlation (ICC), descriptive statistics, thematic and content analysis.

MethodsVolunteers took (T1), then repeated (T2), the automated MMI, with a seven-day interval (+/- 2) then completed an evaluation questionnaire. Admissions staff participated in focus group discussions.

ResultsSixty-two students and seven admission staff participated; 34 students and four staff from UK and 28 students and three staff from US universities.

Good-excellent test-retest reliability was observed with T1 and T2 ICC between 0.62-0.81 (p<0.001) when assessed by individual total scores (range 80.6-119), station total scores 0.6-0.91, p<0.005, individual site (all ICC[≥] 0.76 p<0.001) and mean test retest across sites 0.82 p<0.001 (95% CI 0.7-0.9).

Admissions staff reported potential to reduce resource costs and bias through a more objective screening tool for pre-selection or to replace some MMI stations in a  hybrid model. Maintaining human interaction through  touch points was considered essential.

Users positively evaluated the system, stating it was intuitive with an accessible interface. Concepts chosen for dynamic probing needed to be appropriately tailored.

ConclusionThese preliminary findings suggest that the system is reliable, generating consistent scores for candidates and is acceptable to end-users provided human touchpoints are maintained. Thus, there is evidence for the potential of such an automated system to augment healthcare student selection processes.

category: medical education


title: Evaluating a first fully automated interview grounded in Multiple Mini Interview (MMI) methodology: results from a feasibility study