title: Prevalence and Time of Diagnosis of Endometriosis across Racial and Ethnic Groups in the US

abstract:
BackgroundEndometriosis is associated with substantial adverse health and psychosocial consequences. However, the prevalence of endometriosis across different racial and ethnic groups in the US has not been established and to what extent the difference in prevalence might be associated with systemic barriers to receiving the diagnosis is unknown. We aimed to estimate the prevalence of endometriosis across different racial and ethnic groups and examine the association between race/ethnicity and the time of diagnosis

MethodsUsing cross-sectional data from the National Health and Nutrition Examination Survey 1999-2006, we estimated race/ethnicity-specific prevalence of self-reported diagnosis of endometriosis among 5,557 women aged 20-54 years. Multivariable generalized linear regression model examined the association between race/ethnicity and the age of endometriosis diagnosis, accounting for socioeconomic indicators, health insurance, lifestyle and reproductive characteristics.

ResultsEndometriosis was prevalent in 9.0% overall, 11.1% among non-Hispanic white, 5.8% among non-Hispanic black, 2.7% among Hispanic, and 6.4% among the other racial and ethnic groups combined. The mean age of endometriosis diagnosis was 29.0 years (range 13-52). Compared with non-Hispanic white, non-Hispanic black women were diagnosed on average at 2.6 years older (95% confidence interval [CI], 0.5-4.6), Hispanic women 3.8 years older (95% CI 1.5-6.2), and women in the other group 1.0 years younger (95% CI, -4.6 to 2.5).

ConclusionsPrevalence of endometriosis varied across different racial and ethnic groups Among women with a diagnosis of endometriosis, black and Hispanic women were diagnosed at older ages than non-Hispanic white women. Future research is needed to determine whether such age disparity in endometriosis diagnosis persists.


title: Optimising activity and diet compositions for dementia prevention: Protocol for the ACTIVate prospective longitudinal cohort study

abstract:
IntroductionApproximately 40% of late-life dementia may be prevented by addressing modifiable risk factors, including physical activity and diet. Yet, it is currently unknown how multiple lifestyle factors interact to influence cognition. The ACTIVate Study aims to 1) Explore associations between 24-hour time-use and diet compositions with changes in cognition and brain function; and 2) Identify durations of time-use behaviours and the dietary compositions to optimise cognition and brain function.

Methods and analysisThis three-year prospective longitudinal cohort study will recruit 448 adults aged 60-70 years across Adelaide and Newcastle, Australia. Time-use data will be collected through wrist-worn activity monitors and the Multimedia Activity Recall for Children and Adults (MARCA). Dietary intake will be assessed using the Australian Eating Survey food frequency questionnaire. The primary outcome will be cognitive function, assessed using the Addenbrookes Cognitive Examination-III (ACE-III). Secondary outcomes include structural and functional brain measures using Magnetic Resonance Imaging (MRI), cerebral arterial pulse measured with Diffuse Optical Tomography (Pulse-DOT), neuroplasticity using simultaneous Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG), and electrophysiological markers of cognitive control using event-related potential (ERP) and time-frequency analyses. Compositional data analysis, testing for interactions between time-point and compositions, will assess longitudinal associations between dependent (cognition, brain function) and independent (time-use and diet compositions) variables.

ConclusionsThe ACTIVate Study will be the first to examine associations between time-use and diet compositions, cognition and brain function. Our findings will inform new avenues for multidomain interventions that may more effectively account for the co-dependence between activity and diet behaviours for dementia prevention.

Ethics and disseminationEthics approval has been obtained from University of South Australias Human Research Ethics committee (202639). Findings will be disseminated through peer reviewed manuscripts, conference presentations, targeted media releases and community engagement events.

Registration DetailsAustralia New Zealand Clinical Trials Registry (ACTRN12619001659190).

Strengths and limitationsO_LIThe ACTIVate Study will collect comprehensive measures of lifestyle behaviours and dementia risk over time in 448 older adults aged 60-70 years.
C_LIO_LIUsing newly developed Compositional Data Analysis (CoDA) techniques we will examine the associations between time-use and diet compositions, cognition and brain function.
C_LIO_LIData will inform the development of a digital tool to help older adults obtain personalised information about how to reduce their risk of cognitive decline based on changes to time use and diet.
C_LIO_LIRecruitment will be focussed on older adults to maximise the potential of making an impact on dementia prevention in the next 10 years.
C_LIO_LIFindings may not be generalisable to younger adults.
C_LI

category: geriatric medicine


title: Features importance in seizure classification using scalp EEG reduced to single timeseries

abstract: Seizure detection and seizure-type classification are best performed using intra-cranial or full-scalp electroencephalogram (EEG). In embedded wearable systems however, recordings from only a few electrodes are available, reducing the spatial resolution of the signals to a handful of timeseries at most. Taking this constraint into account, we tested the performance of multiple classifiers using a subset of the EEG recordings by selecting a single trace from the montage or performing a dimensionality reduction over each hemispherical space. Our results support that Random Forest (RF) classifiers lead most ef-ficient and stable classification performances over Support Vector Machines (SVM). Interestingly, tracking the feature importances using permutation tests reveals that classical EEG spectrum power bands display different rankings across the classifiers: low frequencies (delta, theta) are most important for SVMs while higher frequencies (alpha, gamma) are more relevant for RF and Decision Trees. We reach up to 94.3% {mp} 5.3% accuracy in classifying absence from tonic-clonic seizures using state-of-art sampling methods for unbalanced datasets and leave-patients-out fold cross-validation policy.

category: health informatics


title: Machine Learning Methods to Predict Survival in Patients Following Traumatic Aortic Injury

abstract: The National Trauma Data Bank (NTDB) is a resource of diagnostic, treatment, and outcomes information in trauma patients. We leverage the NTDB and machine learning techniques to predict survival following traumatic aortic injury. We create two predictive models using the NTDB - 1) using all data and, 2) using only data available in the first hour after arrival (prospective data). Seven discriminative model types were tested before and after feature engineering to reduce dimensionality. The top performing model was XGBoost, achieving an overall accuracy of 0.893 using all data and 0.855 using prospective data. Feature engineering improved performance of all models. Glasgow Coma Scale score was the most important factor for survival, and thoracic endovascular aortic repair was more common in patients that survived. Smoking, pneumonia, and urinary tract infection predicted poor survival. We also note concerning disparities in outcomes for black and uninsured patients that may reflect differences in care.


title: Variations in Non-Pharmaceutical Interventions by State Correlate with COVID-19 Disease Outcomes

abstract: The COVID-19 pandemic highlighted the lack of understanding around effective public health interventions to curtail the spread of an emerging respiratory virus. Here, we examined the public health approaches implemented by each state to limit the spread and burden of COVID-19. Our analysis revealed that stronger statewide interventions positively correlated with fewer COVID-19 deaths, but some neighboring states with distinct intervention strategies had similar SARS-CoV-2 case trajectories. Additionally, more than two weeks is needed to observe an impact on SARS-CoV-2 cases after an intervention is implemented. These data provide a critical framework to inform future interventions during emerging pandemics.

category: infectious diseases


title: Effects of SARS-CoV-2 P.1 introduction and the impact of COVID-19 vaccination on the epidemiological landscape of Sao Jose Do Rio Preto, Brazil

abstract: The emergence of the new Brazilian variant of concern, P.1 lineage (Gamma), raised concern about its impact on the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Using 272 whole-genome sequences combined with epidemiological data, we showed that P.1 introduction in Sao Jose do Rio Preto, Sao Paulo, Brazil, was followed by the displacement of eight circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection. Our findings support that the P.1 variant is associated with an increase in mortality risk and severity of COVID-19 cases in younger aged groups, which corresponds to the unvaccinated population at the time. Moreover, our data highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.


title: Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study

abstract:
ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.

MethodsWe conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.

ResultsOf 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain.

ConclusionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.


title: Emerging and Continuing Trends in Opioid Overdose Decedent Characteristics during COVID-19

abstract:
BackgroundSince COVID-19 erupted in the United States, little is known about how state-level opioid overdose trends and decedent characteristics have varied throughout the country.

ObjectiveInvestigate changes in annual overdose death rates, substances involved, and decedent demographics in opioid overdose deaths across nine states; assess whether 2019-2020 trends were emerging (i.e., change from 2019-2020 was non-existent from 2018-2019) or continuing (i.e., change from 2019-2020 existed from 2018-2019).

DesignCross-sectional study using vital statistics data to conduct a retrospective analysis comparing 2020 to 2019 and 2019 to 2018 across nine states.

SettingAlaska, Colorado, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Utah, and Wyoming.

ParticipantsOpioid-related overdose deaths in 2018, 2019, and 2020.

MeasurementsAnnual overdose death rate, proportion of overdose deaths involving specific substances, and decedent demographics (age, sex, race, and ethnicity).

ResultsWe find emerging increases in annual opioid-related overdose death rates in Alaska (55.3% [P=0.020]), Colorado (80.2% [P<0.001]), Indiana (40.1% [P=0.038]), North Carolina (30.5% [P<0.001]), and Rhode Island (29.6% [P=0.011]). Decreased heroin-involved overdose deaths were emerging in Alaska (-49.5% [P=0.001]) and Indiana (-58.8% [P<0.001]), and continuing in Colorado (-33.3% [P<0.001]), Connecticut (-48.2% [P<0.001]), Massachusetts (39.9% [P<0.001]), and North Carolina (-34.8% [P<0.001]). Increases in synthetic opioid presence were emerging in Alaska (136.5% [P=0.019]) and Indiana (27.6% [P<0.001]), and continuing in Colorado (44.4% [P<0.001]), Connecticut (3.6% [P<0.05]), and North Carolina (14.6% [P<0.001]). We find emerging increases in the proportion of male decedents in Colorado (15.2% [P=0.008]) and Indiana (12.0% [P=0.013]).

LimitationsDelays from state-specific death certification processes resulted in varying analysis periods across states.

ConclusionThese findings highlight emerging changes in opioid overdose dynamics across different states, which can inform state-specific public health interventions.

category: addiction medicine


title: Promoting resilience in healthcare workers during the COVID-19 pandemic with a brief online intervention

abstract:
IntroductionThe psychological wellbeing of healthcare workers has been impacted by the high levels of stress many have experienced during the COVID-19 pandemic. This study aimed to examine the feasibility and acceptability of a brief online course focused on introducing skills that could increase resilience and decreases emotional distress in healthcare workers during the pandemic.

Materials and MethodsEmployees of a large healthcare system completed a survey at baseline, one month, and two months later. The online course, called Resilience Training for Healthcare Workers, consists of three 12-20 minute videos focused on evidence-based skills that support aspects of emotional resilience: mindfulness, mentalization, and self-compassion.

ResultsA total of 554 participants completed the baseline survey, endorsing moderate to high levels of emotional distress. Of those who completed all three assessments and participated in the course (n = 38), significant improvements in resilience and reductions in emotional distress were found across two months, in comparison to those who did not participate in the course.

DiscussionThese findings suggest that a brief, online intervention can improve the mental health of healthcare workers during a crisis such as the COVID-19 pandemic.

category: psychiatry and clinical psychology


title: DNA methylation patterns associated with cyanogenic cassava exposure and konzo in Sub-Saharan Africa

abstract: Main TextKonzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks and is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo, remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic- sensitive regions of the genome, providing the first study of epigenomic alterations associated with sub-lethal cyanide exposure and a clinical phenotype.

category: genetic and genomic medicine


title: Assessing optimal time between doses in two-dose vaccination regimen in an ongoing epidemic of SARS-CoV-2

abstract:
The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals.

Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. Simulations for each time window and for different types of vaccines and production rates were run to find the optimal time window between doses, that is, the one that minimizes the number of deaths.

We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to apply the second dose as soon as possible, while for high first-dose efficacy, the optimal window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the optimal window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.

category: epidemiology


title: Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes.

abstract:
IntroductionKidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-) gene (TNF) polymorphisms on kidney graft survival.

MethodsWe performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function (PNF) and death-censored kidney allograft survival in 1,271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands.

ResultsThe G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of PNF (odds ratio: 2.05; 95%-CI: 1.06-3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05-2.19, P = 0.028).

ConclusionKidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF- blockade in improving kidney transplantation outcomes.

category: transplantation


title: Right Ventricular Dysfunction in Ventilated Patients with COVID-19 (COVID-RV)

abstract:
PurposeCOVID-19 is associated with cardiovascular complications, with right ventricular dysfunction (RVD) commonly reported. The combination of acute respiratory distress syndrome (ARDS), injurious invasive ventilation, micro/macro thrombi and the potential for direct myocardial injury create conditions where RVD is likely to occur. No study has prospectively explored the prevalence of RVD, and its association with mortality, in a cohort requiring mechanical ventilation.

MethodsProspective, multi-centre, trans-thoracic echocardiographic, cohort study of ventilated patients with COVID-19 in Scottish intensive care units. RVD was defined as the presence of severe RV dilatation and interventricular septal flattening. To explore role of myocardial injury, high sensitivity troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured in all patients.

ResultsOne hundred and twenty-one patients were recruited to COVID-RV, 118 underwent imaging and it was possible to determine the primary outcome in 112. RVD was present in seven (6.2% [95%CI; 2.5%, 12.5%]) patients. Thirty-day mortality was 85.7% in those with RVD, compared to 44.8% in those without (p=0.051). Patients with RVD were more likely to have; pulmonary thromboembolism (p<0.001), higher plateau pressure (p=0.048), lower dynamic compliance (p=0.031), higher NT-proBNP (p<0.006) and more frequent abnormal troponin (p=0.048). Abnormal NT-proBNP (OR 4.77 [1.22, 21.32], p=0.03) and abnormal Troponin (16.54 [4.98, 67.12], p<0.001) independently predicted 30-day mortality.

ConclusionCOVID-RV demonstrates a prevalence of RVD in ventilated patients with COVID-19 of 6.2% and is associated with a mortality of 85.7%. Association is observed between RVD and each of the aetiological domains of; ARDS, ventilation, micro/macro thrombi and myocardial injury.

category: intensive care and critical care medicine


title: Emergence and spread of a B.1.1.28-derived lineage with Q675H and Q677H Spike mutations in Uruguay

abstract: Uruguay was able to control the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein we analyzed the country-wide genetic diversity of SARS-CoV-2 between November, 2020 and April, 2021. Our findings identified that the most prevalent viral variant during late 2020 was a B.1.1.28 sublineage carrying mutations Q675H+Q677H in the viral Spike, now designated as lineage P.6. This new lineage P.6 probably arose around November 2020, in Montevideo, Uruguays capital department and rapidly spread to other Uruguayan departments, with evidence of further local transmission clusters, also spread sporadically to the USA and Spain. The Q675H and Q677H mutations are in the proximity of the polybasic cleavage site at the S1/S2 boundary and also arose independently in many SARS-CoV-2 lineages circulating worldwide. Although the lineage P.6 was replaced by the Variant of Concern (VOC) P.1 as the predominant viral strain in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H+Q677H in VOCs should be of worldwide interest.


title: Amplitude-integrated EEG amplitudes differ between wakefulness and sleep states in children

abstract:
IntroductionInterpretation of pediatric amplitude-integrated EEG (aEEG) is hindered by the lack of knowledge on physiological background patterns in children. The aim of this study was to assess the amplitudes and bandwidths of background patterns during wakefulness and sleep in children from long-term EEGs.

MethodsForty long-term EEGs from patients < 18 years of age without or only solitary interictal epileptiform discharges were converted into aEEGs. Upper and lower amplitudes ({micro}V) of the C3 - C4, P3 - P4, C3 - P3, C4 - P4, and Fp1 - Fp2 channels were measured during wakefulness and sleep. Bandwidths (BW, {micro}V) were calculated, and sleep states assessed during the episodes of interest. A sensitivity analysis excluded patients who received antiepileptic drugs.

ResultsMedian age was 9.9 years (interquartile range 6.1 - 14.7). All patients displayed continuous background patterns. Amplitudes and BW differed between wakefulness (C3-C4 channel: upper 35 (27 - 49), lower 13 (10 - 19), BW 29 (21 - 34)) and sleep. During sleep, episodes with high amplitudes (upper 99 (71 - 125), lower 35 (25 - 44), BW 63 (44 - 81)) corresponded to sleep states N2 - N4. These episodes were interrupted by low amplitudes that were the dominating background pattern towards the morning (upper 39 (30 - 51), lower 16 (11 - 20), BW 23 (19 - 31), sleep states REM, N1, and N2). With increasing age, amplitudes and bandwidths declined. The sensitivity analysis yielded no differences in amplitude values or bandwidths.

ConclusionaEEG amplitudes and bandwidths were low during wakefulness and light sleep and high during deep sleep in stable children undergoing 24 hour EEG recordings. aEEG values were not altered by antiepileptic drugs in this study.

category: pediatrics


title: Development and validation of a neuroimaging biomarker for electroconvulsive therapy outcome in depression: a multicenter machine learning analysis

abstract:
BackgroundElectroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, mono-center studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers.

ObjectiveTo develop and validate neuroimaging biomarkers for ECT outcome in a multi-center setting.

MethodsMultimodal data (i.e., clinical, sMRI and resting-state fMRI) was collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluated which data modalities or combinations thereof could provide the best predictions for treatment response ([≥]50% symptom reduction) or remission (HAM-D score [≤]7) using a support vector machine classifier.

ResultsRemission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82-0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers, and remained acceptable when validated using leave-one-site-out cross-validation (0.70-0.73 AUC).

ConclusionsThese results show that multimodal neuroimaging data is able to provide good prediction of remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. This suggests that these biomarkers are robust, indicating that future development of a clinical decision support tool applying these biomarkers may be feasible.

category: radiology and imaging


title: Development and validation of a multimodal neuroimaging biomarker for electroconvulsive therapy outcome in depression: a multicenter machine learning analysis


title: Advances in Classifying the Stages of Diabetic Retinopathy Using Convolutional Neural Networks in Low Memory Edge Devices

abstract: Diabetic Retinopathy (DR) is a severe complication that may lead to retinal vascular damage and is one of the leading causes of vision impairment and blindness. DR broadly is classified into two stages - non-proliferative (NPDR), where there are almost no symptoms, except a few microaneurysms, and proliferative (PDR) involving a huge number of microaneurysms and hemorrhages, soft and hard exudates, neo-vascularization, macular ischemia or a combination of these, making it easier to detect. More specifically, DR is usually classified into five levels, labeled 0-4, from 0 indicating no DR to 4 which is most severe. This paper firstly presents a discussion on the risk factors of the disease, then surveys the recent literature on the topic followed by examining certain techniques which were found to be highly effective in improving the prognosis accuracy. Finally, a convolutional neural network model is proposed to detect all the stages of DR on a low-memory edge microcontroller. The model has a size of just 5.9 MB, accuracy and F1 score both of 94% and an inference speed of about 20 frames per second.

category: ophthalmology


title: Perceptions of gender equity and markers of achievement in a National Institute for Health Research (NIHR) Biomedical Research Centre (BRC): A qualitative study.

abstract:
BackgroundThe need to improve gender equity (GE) in academic medicine is well documented. Biomedical Research Centres (BRCs), partnerships between leading National Health Service (NHS) organisations and universities in England, conduct world-class translational research funded by the National Institute for Health Research (NIHR). In 2011, eligibility for BRC funding was restricted to universities demonstrating sustained GE success recognised by the Athena SWAN Charter for Women in Science Silver awards. Despite this structural change, GE research in BRC settings is underdeveloped, yet critical to the acceleration of womens advancement and leadership.

ObjectivesTo explore both womens and mens perceptions of GE and current markers of achievement in a BRC setting.

MethodsThematic analysis of data from two discrete research projects: 53 GE survey respondents free text comments (34 women, 16 men), and 16 semi structured interviews with women affiliated to the NIHR Oxford BRC.

ResultsFour major themes emerged from the analysis: perceptions of the Athena Swan Charter for Women in Science (GE policy); views on monitoring GE in BRCs; views on current markers of achievement in academia and GE; and recommendations for actions to improve GE in BRC settings. Monitoring of GE in BRCs was deemed to be important, but complex. Participants felt current markers of achievement were not equitable to women as they did not take contextual factors into account such as maternity leave and caring responsibilities. BRC specific organisational policies and metrics are required to monitor and catalyse GE.

ConclusionsMarkers of achievement for monitoring GE in BRCs should take into account contextual factors specific to BRCs and womens career progression and professional advancement. GE markers of achievement should be complimented with broader aspects of equality, diversity and inclusion.

category: health policy


title: Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-vaccine; Preliminary Study

abstract: The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection. We found that the risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigagions into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.


title: Performance of Immunoglobulin G Serology on Finger Prick Capillary Dried Blood Spot Samples to Measure SARS-CoV-2 Humoral Immunogenicity

abstract:
ImportanceMeasuring humoral immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 vaccines and finding population-level correlates of protection against coronavirus disease presents an immediate challenge to public health practitioners.

ObjectiveTo study the diagnostic accuracy and predictive value of finger prick capillary dried blood spot samples tested using an anti-immunoglobulin G (IgG) serology assay to measure SARS-CoV-2 seropositivity and the humoral immunogenicity of COVID-19 vaccination.

Design, Setting and ParticipantsThis cross-sectional study enrolled participants (n= 644) who had paired DBS and serum samples collected by finger prick and venipuncture, respectively, in British Columbia, Canada between January 12th, 2020 and May 21st, 2021. Samples were tested by a multiplex electrochemiluminescence assay for SARS-CoV-2 anti-Spike (S), -Nucleocapsid (N) and -receptor binding domain (RBD) IgG reactivity using a Meso Scale Discovery (MSD) platform. Additionally, unpaired DBS samples (n= 6,706) that were collected in the province during the same time period were included for analysis of SARS-CoV-2 anti-N IgG reactivity.

ExposureCollection of a capillary dried blood spot by finger prick alone or paired with serum by venipuncture.

OutcomeHumoral immune response to SARS-CoV-2 measured by detection of anti-S, -N or - RBD IgG.

ResultsIn comparison to a paired-serum reference, dried blood spot samples possess a sensitivity of 80% (95% CI: 61%-91%) and specificity of 97% (95% CI: 95%-98%). Receiver operator characteristic curve analysis (ROC) found that participant DBS samples tested for anti-SARS-CoV-2 IgG by MSD V-PLEX COVID-19 Coronavirus Panel 2 assay accurately classify SARS-CoV-2 seroconversion at an 88% percent rate, AUC= 88% (95% CI: 81%-96%). Modelling found that a dried blood spot-based testing approach has a high positive predictive value (98% [95% CI: 98%-99%]) in a theoretical population with seventy-five percent COVID-19 vaccine coverage. At lower vaccine coverages of fifteen and forty-five percent, the tests positive predictive value decreased, and the negative predictive value increased.

ConclusionWe demonstrate that dried blood spot collected samples, when tested using an electrochemiluminescence assay, provide a valid alternative to traditional venipuncture and should be considered to reliably detect SARS-CoV-2 seropositivity.

Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the diagnostic accuracy and predictive value of immunoglobulin G serology on finger prick capillary dried blood spot samples to measure SARS-CoV-2 humoral immunogenicity?

FindingsIn comparison to a paired-serum reference, dried blood spot samples tested for anti-SARS-CoV-2 IgG possess a sensitivity of 80% (95% CI: 61%-91%) and specificity of 97% (95% CI: 95%-98%). Dried blood spot testing has a positive predictive value of 98% (95% CI: 98%-99%) when modelled in a theoretical population with COVID-19 vaccine coverage of seventy-five percent.

MeaningDried blood spot samples have equal diagnostic accuracy to serum collected by venipuncture when tested by electrochemiluminescence assay and should be considered to reliably detect SARS-CoV-2 seropositivity.


title: Prospective examination of mental health in university students during the COVID-19 pandemic

abstract:
BackgroundThe impact of changing social restrictions on the mental health of students during the COVID-19 pandemic warrants exploration.

AimsTo prospectively examine changes to university students mental health during the pandemic.

MethodsStudents completed repeated online surveys at three time points (October 2020 (baseline), February 2021, March 2021) to explore relationships between demographic and psychological factors (loneliness and positive mood) and mental health outcomes (depression, anxiety, and stress).

ResultsA total of 893 students participated. Depression and anxiety levels were higher at all timepoints than pre-pandemic normative data (p<.001). Scores on all mental health measures were highest in February, with depression and anxiety remaining significantly higher in March than baseline. Female students and those with previous mental health disorders were at greatest risk of poor mental health outcomes. Lower positive mood and greater loneliness at baseline were associated with greater depression and anxiety at follow-ups. Baseline positive mood predicted improvement of depression and anxiety at follow-ups.

ConclusionDepression and anxiety were significantly higher than pre-pandemic norms, with female students and those with previous mental health difficulties being at greatest risk. Given these elevated rates, universities should ensure adequate support is available to meet potentially increased demand for services.


title: Seroprevalence of SARS-CoV-2 antibodies and retrospective mortality in a refugee camp, Dagahaley, Kenya

abstract:
BackgroundCamps of forcibly displaced populations are considered to be at risk of large COVID-19 outbreaks. Low screening rates and limited surveillance led us to conduct a study in Dagahaley camp, located in the Dadaab refugee complex in Kenya to estimate SARS-COV-2 seroprevalence and, mortality and to identify changes in access to care during the pandemic.

MethodsTo estimate seroprevalence, we conducted a cross-sectional survey among a sample of individuals (n=587) seeking care at the two main health centres and among all household members (n=619) of community health workers and traditional birth attendants working in the camp. We used a rapid immunologic assay (BIOSYNEX(R) COVID-19 BSS [IgG/IgM]) and adjusted for test performance and mismatch between the sampled population and that of the general camp population. To estimate mortality, we exhaustively interviewed all households (n=12860) in the camp about deaths occurring from January 2019 through March 2021.

ResultsWe included 1206 participants in the seroprevalence study. In total, 8% (95% CI: 6.6%-9.7%) had a positive serologic test. After adjusting for test performance and standardizing on age, we estimated a seroprevalence of 5.8% (95% CI: 1.6%-8.4%). The mortality rate for 10,000 persons per day was 0.05 (95% CI 0.05-0.06) prior to the pandemic and 0.07 (95% CI 0.06-0.08) during the pandemic, representing a significant 42% increase (p<0.001). MSF health centre consultations and hospital admissions decreased by 38% and 37% respectively.

ConclusionWe estimated that the number of infected people was 67 times higher than the number of reported cases. Participants aged 50 years or more where among the most affected. The mortality survey shows an increase in the mortality rate during the pandemic compared to before the pandemic. A decline in attendance at health facilities was observed and sustained despite the easing of restrictions.

Summary BoxO_ST_ABSWhat is already known?C_ST_ABSO_LIAt the early stage of the COVID-19 pandemic, models predicted the risk of a large-scale COVID-19 outbreaks in camps of forcibly displaced populations that would have created excess mortality caused directly by the disease and indirectly by reduced access to care and/or congestion in health facilities.
C_LIO_LITo date, this prediction has not materialized in most camps, the lower than expected number of cases and deaths could be attributed to a population characteristics and early implementation of confinement; alternatively, it could be an underestimate caused by limited screening and testing capacity and lack of morbidity and mortality surveillance.
C_LIO_LIThe actual impact of COVID-19 on these populations therefore remains an open question.
C_LI

What are the new findings?O_LIIn Dagahaley camps in Kenya, we estimated that the number of infected people was 67 times higher than the number of reported cases.
C_LIO_LIParticipants aged 50 years and over, who are most at risk of severe illness, were among the most affected.
C_LIO_LIWe observed an increase in mortality rates during the pandemic, and a decrease in the use of health facilities, which continued despite the easing of restrictions, but access for severe cases was less impacted.
C_LI

What do the new findings imply?O_LITo our knowledge, this is the first combined survey of COVID-19 seroprevalence and retrospective mortality in a forcibly displaced population living in a camp.
C_LIO_LIDespite mitigation measures, the virus has circulated, which should prompt rapid vaccination as most of the population remains susceptible; the collateral effects of the pandemic on access to care must be addressed and public confidence restored in order to limit the risk of excess mortality.
C_LIO_LIThe varying situations of forcibly displaced populations living in camps around the world support the need for further research at other sites.
C_LI

category: public and global health


title: Accuracy verification of low-cost CO2 concentration measuring devices for general use as a countermeasure against COVID-19

abstract: Within the context of the COVID-19 pandemic, CO2 sensors that measure ventilation conditions and thereby reduce the risk of airborne infection, are gaining increasing attention. We investigated and verified the accuracy of 12 relatively low-cost sensor models that retail for less than $45 and are advertised as infection control measures on a major e-commerce site. Our results indicate that 25% of the tested sensors can be used to identify trends in CO2 concentration, if correctly calibrated. However, 67% of sensors did not respond to the presence of CO2, which suggests that a type of pseudo-technique is used to display the CO2 concentration. We recommend that these sensors are not suitable for infection prevention purposes. We also found that all 67% of the sensors that did not respond to CO2 responded strongly to alcohol. Owing to the widespread use of alcohol in preventing the spread of infectious diseases, sensors that react to alcohol can display inaccurate values, resulting in inappropriate ventilation behavior. Therefore, we strongly recommended that these sensors not be used. Based on our results, we offer practical recommendations to the average consumer, who does not have special measuring equipment, on how to identify inaccurate CO2 sensors.


title: Gender differences in housework and childcare among Japanese workers during the COVID-19 pandemic.

abstract:
ObjectivesAlthough gender stereotypes regarding paid work and unpaid work are changing, most wives are responsible for taking care of the family and home in Japan. It is unclear how time spent on housework and childcare has changed between working men and women during the COVID-19 pandemic in Japan. The purpose of this study is to investigate how working men and womens responsibilities for housework and childcare changed during the COVID-19 pandemic in Japan depending on occupation, job type, and the number of employees in the workplace.

MethodsA cross-sectional analysis (N=14,454) was conducted using data from an internet monitoring study (CORoNa Work Project), which was conducted in December 2020. A multilevel logistic model with nested prefectures of residence was conducted to estimate the odds ratio (OR) for change in time devoted to housework and childcare among men and women adjusting for age, household income, frequency of telecommuting, presence of spouse who work, occupation, job type, the number of employees in the workplace, and the incidence rate of COVID-19 by prefecture.

ResultsRegardless of occupation related factors, more women than men reported increased time spent on housework and childcare. Furthermore, women were significantly more likely to experience an increase in time spent on those activities than men (housework: OR 1.97, 95% CI [1.75, 2.21], p < 0.001; childcare: OR 1.66, 95% CI [1.37, 2.02], p < 0.001).

ConclusionsThe time spent by women on housework and childcare increased significantly compared to men during the COVID-19 pandemic in Japan.

category: occupational and environmental health


title: Development of a Post-Acute Sequelae of COVID-19 (PASC) Symptom Lexicon Using Electronic Health Record Clinical Notes

abstract:
ObjectiveTo develop a comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon from clinical notes to support PASC symptom identification and research.

MethodsWe identified 26,117 COVID-19 positive patients from the Mass General Brighams electronic health records (EHR) and extracted 328,879 clinical notes from their post-acute infection period (day 51-110 from first positive COVID-19 test). The PASC symptom lexicon incorporated Unified Medical Language System(R) (UMLS) Metathesaurus concepts and synonyms based on selected semantic types. The MTERMS natural language processing (NLP) tool was used to automatically extract symptoms from a development dataset. The lexicon was iteratively revised with manual chart review, keyword search, concept consolidation, and evaluation of NLP output. We assessed the comprehensiveness of the lexicon and the NLP performance using a validation dataset and reported the symptom prevalence across the entire corpus.

ResultsThe PASC symptom lexicon included 355 symptoms consolidated from 1,520 UMLS concepts. NLP achieved an averaged precision of 0.94 and an estimated recall of 0.84. Symptoms with the highest frequency included pain (43.1%), anxiety (25.8%), depression (24.0%), fatigue (23.4%), joint pain (21.0%), shortness of breath (20.8%), headache (20.0%), nausea and/or vomiting (19.9%), myalgia (19.0%), and gastroesophageal reflux (18.6%).

Discussion and ConclusionPASC symptoms are diverse. A comprehensive PASC symptom lexicon can be derived using a data-driven, ontology-driven and NLP-assisted approach. By using unstructured data, this approach may improve identification and analysis of patient symptoms in the EHR, and inform prospective study design, preventative care strategies, and therapeutic interventions for patient care.


title: Increased Autotaxin levels in severe COVID-19, correlating with IL-6 levels, endothelial dysfunction biomarkers, and impaired functions of dendritic cells

abstract: Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalysing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signalling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signalling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNAseq datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, that exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, worth of suggesting that its pharmacological targeting might represent an additional therapeutic option.

category: allergy and immunology


title: NSTEMI Decide: Development of a Decision Aid for Older Adults with Non ST Elevation Myocardial Infarction

abstract:
BackgroundMany patients hospitalized with non-ST elevation myocardial infarction (NSTEMI) are older adults (age [≥]75), in whom invasive coronary angiography confers potential benefits but also higher risks than the general population. Our goal was to therefore develop a patient decision aid (PtDA) to assist with shared decision making (SDM) between cardiologists and older adults with this condition.

MethodsWe followed International Patient Decision Aid Standards to develop the NSTEMI Decide PtDA. The initial prototype was based on structured interviews from 20 patients and 20 clinicians. Risks and benefits of invasive coronary angiography were derived from the available literature in older adults, with an emphasis on findings from randomized trials. The PtDA was then revised through an iterative, user-centered design approach with rapid prototyping using input from both clinician and patients to meet the needs of both stakeholders.

ResultsThe PtDA went through 8 iterations. The final decision aid was 11 pages and included background information (6 pages), explanation of benefits and risks (4 pages), and a summary (1 page). Large font ([≥]26 point) was used to accommodate visual difficulties. Language was tailored to an 8th grade reading level. Based on the best available literature, we included benefits of invasive coronary angiography (recurrent myocardial infarction, repeat revascularization) and risks (stroke, bleeding, acute kidney injury). The final PtDA was converted to a mobile health application to increase usability on portable digital devices in the clinical setting.

ConclusionsWe developed the first PtDA tailored to older adults hospitalized with NSTEMI. This PtDA will be prospectively tested to evaluate dimensions including feasibility of use, satisfaction with care, medical knowledge, and decisional conflict.

category: cardiovascular medicine


title: Age-specific rate of severe and critical SARS-CoV-2 infections estimated with multi-country seroprevalence studies

abstract: Knowing the age-specific rates at which individuals infected with SARS-CoV-2 develop severe and critical disease is essential for designing public policy, for epidemic modeling, and for individual risk evaluation. In this study, we present the first estimates of these rates using multi-country serology studies, and data on hospital admissions and mortality from early to mid-2020. We integrated data from those sources using a Bayesian model that accounts for the high heterogeneity between data sources and for the uncertainty associated to the estimates reported from each data source. Our results show that the risk of severe and critical disease increases exponentially with age, but much less steeply than the risk of fatal illness. Importantly, the estimated rate of severe disease outcome in adolescents is between one and two orders of magnitude larger than the reported rate of vaccine side-effects, showing how these estimates are relevant for health policy. Finally, we validate our results by showing that they are in close agreement with the estimates obtained from an indirect method that uses reported infection fatality rates estimates and hospital mortality data.


title: What is the suitability of clinical vignettes in benchmarking the performance of online symptom checkers? An audit study

abstract:
ObjectiveTo assess the suitability of primary care vignettes in benchmarking the performance of online symptom checkers

DesignObservational study using publicly available, free online symptom checkers

ParticipantsThree symptom checkers (Healthily, Ada and Babylon) that provided consultations in English. 139 standardized patient vignettes were compiled by RCGP. Three independent GPs interpreted the vignettes to arrive at a "Gold Standard" consisting of 3 dispositions and divided into one of three categories of triage urgency: (1) emergency care required, (2) primary care required and (3) self-care.

Main outcome measuresSix professional non-medical and lay inputters simulated 2774 standardized patient evaluations using 3 online symptom checkers (OSC). We recorded when OSC provided a triage recommendation and whether it correctly recommended the appropriate triage recommendation across three categories of triage urgency (emergency care, primary care or self-care). We collected data on whether the solution appeared within the first 3 dispositions in each of the standards across 2774 standardized patient evaluations.

ResultsWhen benchmarked against the Gold Standard, Healthily provided an appropriate triage recommendation 61.9% of the time compared to 45.3% and 42.4% of the time for Babylon and Ada respectively. There was poor agreement between OSC consultation outcome and Gold Standard dispositions. When compared to the Gold Standard, Healthily gave an unsafe "under-triage" recommendation 28.6% of the time overall across the three categories compared to 43.3% for Ada and 47.5% for Babylon (P<0.001).

ConclusionsOSCs recommended  very unsafe triages only <4% of the time suggesting that the online consultation tools are generally working at a safe level of risk. Primary care vignettes are a helpful tool to support development of OSC, but not ideally suited to benchmark the performance of different OSC. Real-world evidence studies involving general practice are recommended to benchmark the performance of OSC in the community setting.

Strengths and limitations of this studyO_LI139 independently created primary care vignettes covering 18 subcategories of primary care were used to benchmark the performance of three online symptom checkers using 2774 unique patient simulations
C_LIO_LIA gold standard for each primary care vignette was derived using GP roundtables and single blinded testing
C_LIO_LIWe investigated the extent that different inputters using the same vignette and online symptom checker received differing consultation outcomes and triage recommendations
C_LIO_LIWe developed an accuracy matrix to objectively monitor online symptom checker consultation outcome and the safety of the triage recommendation
C_LIO_LILimitations included a different number of inputters to simulate patients across the three online symptom checkers tested
C_LI


title: Public attitudes towards COVID-19 vaccines in children: A qualitative study

abstract:
BackgroundCOVID-19 vaccinations in children remains controversial. In the UK, as of August 2021, they have not been approved, except in a few limited circumstances. To date, little qualitative research exists to explain the reasons and nuances behind public attitudes on this issue.

MethodsQualitative group and one-to-one online interviews were conducted with a diverse sample of 24 adults to explore their views on the issue of COVID-19 vaccination in children.

ResultsCOVID-19 vaccination in children was framed as a complex problem (a "minefield"). Six themes emerged to explain participants views: (1) Uncertainty over whether children can catch, transmit or be severely harmed by COVID-19; (2) Lower risk tolerance for unknown longer-term effects of the vaccine in children; (3) Association of the vaccine program with governments handling of the pandemic; (4) Local social norms as a driver of hesitancy; (5) Vaccinating children as a way to protect vulnerable adults; (6) Childrens vaccination as parental choice.

ConclusionsPublic attitudes to COVID-19 vaccination in children are likely to be met with more hesitancy compared to adult vaccinations. Public health communications will need to combat this hesitancy if vaccine uptake for children is to be pursued as a public health policy.


title: Association between physical exercise interventions and functional capacity in individuals with type 2 diabetes: a systematic review and meta-analysis of controlled trials

abstract:
BackgroundThe prevalence of type 2 diabetes mellitus increases with age and people with type 2 diabetes are more affected by reductions in functional performance. Although exercise interventions are recommended for people with diabetes, it is relevant to assess the effects of different training modes on the available functional outcomes.

ObjectiveTo summarize the effects of distinct modes of exercise training in comparison to non-exercise on the functional capacity of adults with type 2 diabetes.

MethodsA systematic review and meta-analysis of randomized (RCT) and non-randomized (NRS) controlled trials was conducted. Seven databases were searched from inception to January 2021. Eligible studies should last 8 weeks or longer, comparing structured exercise training and non-exercise control for one out of six pre-specified functional capacity outcomes (Timed Up and Go test, chair stands, walking performance, upper limb muscle strength, lower limb muscle strength, physical fitness parameter), in patients with type 2 diabetes, aged [≥]45 years or older. The risk of biases was assessed with the Checklist Downs & Black. Pooled mean differences were calculated using a random-effects model, followed by sensitivity and meta-regression analyses.

ResultsOf 17165 references retrieved, 29 trials (1557 patients) were included. Among these, 13 studies used aerobic training, 6 studies used combined training, 4 studies used resistance training, 3 studies had multiple intervention arms and 3 studies used other types of training. Exercise training was associated with an increase in functional capacity outcomes, as reflected by changes in 6-minute-walk test (51.6 meters; 95% CI 7.6% to 95.6%; I2 92%), one-repetition maximum leg-press (18.0 kg; 95% CI 4.0% to 31.9%; I2 0%), and peak oxygen consumption (2.41 mL/kg{middle dot}min; 95% CI 1.89% to 2.92%; I2 100%) compared with control groups. In sensitivity and subgroup analyses using VO2max as outcome and stratified by for the type of study (RCT or NRS), duration of diabetes diagnosis, and sex, we observed overlapping confidence intervals. Meta-regression showed no association between HbA1C levels and VO2max (p = 0.34; I2 99.6%; R{superscript 2} = 2.6%).

ConclusionStructured exercise training based on aerobic training, resistance training, combination of both, or composed by other types of training (i.e. Pilates, Tai Chi and Whole-body vibration) is associated with an improvement in functional capacity in patients with type 2 diabetes, except for the upper limb muscle strength. However, we could not identify potential effect predictors associated with directional summary estimates.

RegistrationThis systematic review was registered in the PROSPERO international prospective register of systematic reviews (CRD42020162467); date of registration: 12/15/2019. The review protocol is hosted at the Open Science Framework (OSF) (Preprint DOI: 10.31219/osf.io/kpg2m).

FundingThis study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) - Finance Code 001; National Institute of Science and Technology for Health Technology Assessment (IATS) - FAPERGS/Brasil; National Council on Technology and Scientific Development (CNPq).

category: sports medicine


title: Premature Atrial Stimulation Accentuates Conduction Abnormalities in Cardiac Surgery Patients that Develop Postoperative Atrial Fibrillation

abstract:
BACKGROUNDpostoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is associated with increased complications and negative outcomes, but the association between presurgical atrial conduction abnormalities and POAF has not been investigated clinically during premature atrial S1S2 stimulation. This clinical study sought to examine whether intraoperative premature atrial stimulation reveals increased areas of slowed and/or blocked conduction in patients that develop POAF.

METHODSHigh-density intraoperative epicardial left atrial mapping was conducted in 20 cardiac surgery patients with no prior history of atrial fibrillation (AF). In 20 patients, 6 (30%) developed POAF. A flexible-array of 240-electrodes was placed on the posterior left atrial wall in between the pulmonary veins. Activation maps were generated for sinus and premature atrial S1S2 stimulated beats. The area of conduction block (CB), conduction delay (CD) and the combination of both (CDCB) for conduction velocity <0.1, 0.1[≤]x<0.2 and <0.2 m/s, respectively were quantified.

RESULTSFor a premature atrial S2 beat with shortest cycle length captured, conduction velocity maps revealed a significantly higher area for CD (13.19{+/-}6.59 versus 6.06{+/-}4.22 mm2, p=0.028) and CDCB (17.36{+/-}8.75 versus 7.41{+/-}6.39 mm2, p=0.034), and a trend toward a larger area for CB (4.17{+/-}3.66 versus 1.34{+/-}2.86 mm2, p=0.063) in patients who developed POAF in comparison to those that remained in the sinus. Sinus and S1 paced beats did not show substantial differences in abnormal conduction areas between patients with and without POAF.

CONCLUSIONIn comparison to sinus and S1 beats, premature atrial S2 beats accentuate conduction abnormalities in cardiac surgery patients that developed POAF.

category: surgery


title: Safety and feasibility of research lumbar puncture in Huntington's disease: the HDClarity cohort and bioresource

abstract:
STRUCTURED ABSTRACTO_ST_ABSBackgroundC_ST_ABSBiomarkers are needed to monitor disease progression, target engagement and efficacy in Huntingtons disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain.

ObjectivesTo investigate the safety and feasibility of research lumbar punctures (LP) in HD.

MethodsHDClarity (NCT02855476) is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019.

ResultsOf 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e. CSF was collected), amounting to 10,610mL of CSF and 8,200mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events.

ConclusionsHDClarity is the largest CSF collection initiative to support scientific research into HD and is now established as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile.

category: neurology


title: Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients

abstract:
ObjectiveThe antisense oligonucleotide nusinersen (spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression and has improved ventilator free survival and motor function outcomes in infantile onset forms of SMA, treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients.

Methods34 SMA patients were included. We applied next-generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE), was conducted at baseline and 6 months post initiation of nusinersen therapy to assess motor function. Patients changing by [≥] 3 or [≤]0 points in the HFMSE total score were considered as responders or non-responders, respectively.

ResultsLower baseline levels of two muscle microRNAs (miR-206 and miR-133), alone or in combination, predicted the pre-determined clinical response to nusinersen after 6 months therapy. Moreover, miR-206 levels were inversely correlated with the HFMSE score.

ConclusionsLower miR-206 and miR-133 in the CSF predict more robust clinical response to nusinersen treatment in later onset SMA patients. These novel findings have high clinical relevance for identifying early treatment response to nusinsersen in later onset SMA patients and call to test the ability of miRNAs to predict more sustained long-term benefit.


title: KNOWLEDGE AND RISK PERCEPTION OF NIGERIANS TOWARDS THE CORONAVIRUS DISEASE (COVID-19)

abstract:
ABSTARCTO_ST_ABSBackgroundC_ST_ABSThe Coronavirus Disease 2019 (COVID-19) is far from over, although appreciable progress has been made to limit the devastating effects of the pandemic across the globe. Adequate knowledge and risk perception is a critical assessment that is required to ensure proper preventive measures. This study assessed these among Nigerians.

MethodsThe study was a cross-sectional assessment of 776 consenting Nigerian adults that were distributed across the 6 geo-political zones and the Federal Capital Territory. Online pre-tested, semi-structured questionnaire were used to obtain the socio-demographic data and assessed the knowledge and risk perception of the participants to COVID-19. The knowledge of COVID-19 was assessed based on the number of accurate responses given in comparison to average scores. Chi-square analysis was computed to analysis the association between socio-demographic characteristics and knowledge of COVID-19 and risk perception. Data analysis was done using SPSS version 21, the level of significance was set at value p<0.05 at 95% confidence interval.

ResultsMajority of the participants were male 451 (58.1%), there was a good knowledge of COVID-19 among 90.3% of respondents with 57% having positive risk perception. There was a statistically significant relationship between good knowledge and positive risk perception of COVID-19 (p < 0.001). Annual income (p =0.012) and the perception that "vaccines are good" significantly predict positive risk perception of COVID-19 among the respondents.

ConclusionA good knowledge of COVID-19 and vaccination against the virus were the two most important factors that determined risk perception among the population. This may be because of the widespread advocacy, and it portends a good omen at combating COVID-19 menace.

category: infectious diseases


title: COVID-19 Vaccine Uptake among U.S. Child Care Providers

abstract:
STRUCUTRED ABSTRACTO_ST_ABSObjectivesC_ST_ABSEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown.

MethodsTo characterize the vaccine uptake among U.S. child care providers, we conducted a cross-sectional survey of the child care workforce. Providers were identified through various national databases and state registries. A link to the survey was sent via email between May 26 and June 23, 2021. Out of 44,771 potential respondents, 21,663 responded (48.4%).

ResultsOverall COVID-19 vaccine uptake among U.S. child care providers (78.1%, 95% CI [77.3% to 78.9%]) was higher than that of the U.S. adult population (65%). Vaccination rates varied from 53.5% to 89.4% between states. Vaccine uptake differed significantly (p < .01) based on respondent age (70.0% for ages 25-34, 91.5% for ages 75-84), race (70.0% for Black or African Americans, 92.5% for Asian-Americans), annual household income (70.7% for <$35,000, 85.0% for>$75,000), and childcare setting (72.9% for home-based, 79.7% for center-based).

ConclusionsCOVID-19 vaccine uptake among U.S. child care providers was higher than that of the general U.S. adult population. Those who were younger, lower income, Black or African American, resided in states either in the Mountain West or the South, and/or worked in home-based childcare programs reported the lowest rates of vaccination; state public health leaders and lawmakers should prioritize these subgroups for placement on the policy agenda to realize the largest gains in vaccine uptake among providers.

Tables of Contents SummaryThis article describes the results of a national survey of childcare providers to determine the overall COVID-19 vaccine uptake and the gaps in vaccine coverage.

Whats Known on This SubjectEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown.

What This Study AddsWhile the vaccine uptake among U.S. child care providers was higher than that of U.S. adults, certain subgroups continue to warrant focused attention for outreach and/or placement on the policy agenda.


title: COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters

abstract: Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.


title: Unrestricted Online Sharing of High-frequency, High-resolution Data on SARS-CoV-2 in Wastewater to Inform the COVID-19 Public Health Response in Greater Tempe, Arizona

abstract: The COVID-19 pandemic prompted a global integration of wastewater-based epidemiology (WBE) into public health surveillance. Among early pre-COVID practitioners was Greater Tempe (population ~200,000), Arizona, where high-frequency, high-resolution monitoring of opioids began in 2018, leading to unrestricted online data release. Leveraging an existing, neighborhood-level monitoring network, wastewater from eleven contiguous catchment areas was analyzed by RT-qPCR for the SARS-CoV-2 E gene from April 2020 to March 2021 (n=1,556). Wastewater data identified an infection hotspot in a predominantly Hispanic and Native American community, triggering targeted interventions. During the first SARS-CoV-2 wave (June 2020), spikes in virus levels preceded an increase in clinical cases by 8.5{+/-}2.1 days, providing an early-warning capability that later transitioned into a lagging indicator (-2.0{+/-}1.4 days) during the December/January 2020-21 wave of clinical cases. Globally representing the first demonstration of immediate, unrestricted WBE data sharing and featuring long-term, innovative, high-frequency, high-resolution sub-catchment monitoring, this successful case study encourages further applications of WBE to inform public health interventions.


title: COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina

abstract:
In December 2019, a novel illness called coronavirus disease 2019 (COVID-19) was described in China and became pandemic in a few months. The first case was detected in Argentina on March 3, 2020.

A multicentre prospective observational cohort study on hospitalized patients with COVID- 19 was conducted in 4 hospitals in San Isidro district from March 1, 2020 to October 31. Data was obtained by the attendant physician. 668 patients were included, the median age was 54 years, and 42.7% were female. Male sex and older age were associated with COVID-19 disease and more strongly with severity. Most frequent symptoms were fever and cough followed by dyspnoea, myalgia, odynophagia, headache, anosmia, and diarrhoea. Non-severe patients had more upper respiratory symptoms while severe patients had mainly lower respiratory symptoms on admission. Most common comorbidities were arterial hypertension, diabetes, and cardiovascular disease. A great proportion of patients had normal thorax X-ray and ground-glass opacity in tomography. In severe patients, radiography and tomography had a predominant ground - glass pattern, but normal radiography and tomography on presentation were present in 22% and 5.9%, respectively. The absence of fever and normal radiology on admission neither excluded the disease nor further severity. PCR elevation was related with COVID-19 disease and with severity, while lymphopenia was more related with the disease and leukocytosis and thrombocytopenia with severity. 8, 4% of patients were health care workers. The mortality rate was 12.4%, 32.7% in severe patients and 61.2% in ventilated patients. Mortality was higher in the public hospital, probably associated with patients with older age and more comorbidities. All these observations can contribute to the knowledge of this disease in terms of diagnosis and prognosis.


title: Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells

abstract:
Food allergy affects an estimated 8% of children in the US, with increasing severity and global prevalence1. Oral immunotherapy (OIT) is a recently approved treatment with outcomes ranging from sustained tolerance to food allergen to no apparent benefit2,3. The immunological underpinnings that influence clinical outcomes of OIT still remain largely unresolved. Using single-cell RNA sequencing and paired TCR/{beta} sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper cells from 12 peanut-allergic patients longitudinally throughout OIT. We observed expanded populations of cells expressing Th1, Th2, and Th17 signatures that further separated into six clonally distinct subsets, including a Tfh1-like, a Tfh2-like, a Th2A-like, and a Th2reg-like subset. Four of these subsets demonstrated convergence of TCR sequences, suggesting antigen-driven T cell fate. Although we observed suppression during OIT of Th2 and Th1 gene signatures within effector clonotypes, Tfh clonotypes were unaffected. We also did not observe significant clonal deletion or induction among the antigen-reactive T cells characterized. Positive outcomes were associated with larger decrease of Th2 signatures in Th2A-like cells, while treatment failure was associated with high baseline inflammatory gene signatures that were unmodulated by OIT. These signatures, including expression of OX40, OX40L, STAT1, and GPR15, were most clearly present in Th1 and Th17 clonotypes, but were also more broadly detected across the CD154+ CD4 population. These results demonstrate that differential clinical response is associated both with pre-existing trait characteristics of the CD4 immune compartment and with susceptibility to modulation by OIT.

Conflict of Interest StatementA.A.T., T.M.G., J.C.L., and the Massachusetts Institute of Technology have filed patents related to the single-cell sequencing methods used in this work. J.C.L. has interests in Sunflower Therapeutics PBC, Pfizer, Honeycomb Biotechnologies, OneCyte Biotechnologies, SQZ Biotechnologies, Alloy Therapeutics, QuantumCyte, Amgen, and Repligen. J.C.L.s interests are reviewed and managed under Massachusetts Institute of Technologys policies for potential conflicts of interest. J.C.L. receives sponsored research support at MIT from Amgen, the Bill & Melinda Gates Foundation, Biogen, Pfizer, Roche, Takeda, and Sanofi. The spouse of J.C.L. is an employee of Sunflower Therapeutics PBC. T.M.G. is currently an employee of Honeycomb Biotechnologies, Inc. A.A.T. is currently an employee of Immunitas Therapeutics, Inc. W.G.S. is a consultant of Aimmune Therapeutics.


title: Cardiovascular Disease Risk Prediction Models in Haiti: Implications for Primary Prevention in Low-Middle Income Countries

abstract:
BackgroundCardiovascular diseases (CVD) are rapidly increasing in low-middle income countries (LMICs). Accurate risk assessment is essential to reduce premature CVD by targeting primary prevention and risk factor treatment among high-risk groups. Available CVD risk prediction models are built on predominantly Caucasian, high-income country populations, and have not been evaluated in LMIC populations.

ObjectiveTo compare the predicted 10-year risk of CVD and identify high-risk groups for targeted prevention and treatment in Haiti.

MethodsWe used cross-sectional data within the Haiti CVD Cohort Study, including 653 adults [≥] 40 years without known history of CVD and with complete data. Six CVD risk prediction models were compared: pooled cohort equations (PCE), adjusted PCE with updated cohorts, Framingham CVD Lipids, Framingham CVD Body Mass Index (BMI), WHO Lipids, and WHO BMI. Risk factors were measured during clinical exams. Primary outcome was continuous and categorical predicted 10-year CVD risk. Secondary outcome was statin eligibility.

ResultsSeventy percent were female, 65.5% lived on a daily income of [≤]1 USD, 57.0% had hypertension, 14.5% had hypercholesterolemia, 9.3% had diabetes mellitus, 5.5% were current smokers, and 2.0% had HIV. Predicted 10-year CVD risk ranged from 3.9% in adjusted PCE (IQR 1.7-8.4) to 9.8% in Framingham-BMI (IQR 5.0-17.8), and Spearman rank correlation coefficients ranged from 0.87 to 0.98. The percent of the cohort categorized as high risk using the uniform threshold of 10-year CVD risk [≥] 7.5% ranged from 28.8% in the adjusted PCE model to 62.0% in the Framingham-BMI model ({chi}2 = 331, p value < 0.001). Statin eligibility also varied widely.

ConclusionsIn the Haiti CVD Cohort, there was substantial variation in the proportion identified as high-risk and statin eligible using existing models, leading to very different treatment recommendations and public health implications depending on which prediction model is chosen. There is a need to design and validate CVD risk prediction tools for low-middle income countries that include locally relevant risk factors.

Trial registrationclinicaltrials.gov NCT03892265


title: Measuring vaccine efficacy against infection and disease in clinical trials: sources and magnitude of bias in COVID-19 vaccine efficacy estimates

abstract:
BackgroundPhase III trials have estimated COVID-19 vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections.

MethodsWe developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus and imperfect sensitivity and specificity of tests for infection and antibodies. We estimated expected biases in VE against symptomatic, asymptomatic and any SARS-CoV-2 infections and against disease following infection for a range of vaccine characteristics and measurement approaches, and the likely overall biases for published trial results that included asymptomatic infections.

ResultsVE against asymptomatic infection measured by PCR or serology is expected to be low or negative for vaccines that prevent disease but not infection. VE against any infection is overestimated when asymptomatic infections are less likely to be detected than symptomatic infections and the vaccine protects against symptom development. A competing bias towards underestimation arises for estimates based on tests with imperfect specificity, especially when testing is performed frequently. Our model indicates considerable uncertainty in Oxford-AstraZeneca ChAdOx1 and Janssen Ad26.COV2.S VE against any infection, with slightly higher than published, bias-adjusted values of 59.0% (95% uncertainty interval [UI] 38.4 to 77.1) and 70.9% (95% UI 49.8 to 80.7) respectively.

ConclusionMultiple biases are likely to influence COVID-19 VE estimates, potentially explaining the observed difference between ChAdOx1 and Ad26.COV2.S vaccines. These biases should be considered when interpreting both efficacy and effectiveness study results.


title: Fractality of Tics as a Quantitative Assessment Tool for Diagnosis of Tourette Syndrome

abstract: Tics manifest as brief, purposeless, and unintentional movements or noises that, for many individuals, can be suppressed temporarily with effort. Peterson and Leckman (1998) hypothesized that the chaotic temporal nature of tics could possess an inherent fractality, that is, have neighbor-to-neighbor correlation at all levels of time scale. However, demonstrating this phenomenon has eluded researchers for more than two decades, primarily because of the challenges associated with estimating the scale-invariant, power law exponent - called the fractal dimension Df - from fractional Brownian noise. Here, we confirm this hypothesis and establish the fractality of tics by examining two tic time series datasets collected 6-12 months apart in children with tics, using one-dimensional random walk models. We find that Df increases from [~]1.4 to 1.75 in order of decreasing tic severity, and is correlated with tic severity as measured by the YGTTS total tic score. We demonstrate Df to be a sensitive parameter in examining the effect of several tic suppression conditions on the tic time series. We confirm the fractal nature of tics in Tourette syndrome (TS) and extend the finding to Provisional Tic Disorder. Our findings pave the way for utilizing the fractal nature of tics as a robust quantitative tool for estimating tic severity and treatment effectiveness, as well as a marker for differentiating typical from functional tics.

category: psychiatry and clinical psychology


title: Fractality of tics as a quantitative assessment tool for Tourette syndrome.


title: COVID-19 Infection risk posed by drinking alcohol at restaurants or bars in Japan

abstract:
BackgroundOn April 25, 2021, the third state of emergency was declared in Japan. Drinking alcohol at restaurants and bars was banned.

ObjectWe used published data to evaluate drinking ban effects.

MethodWe bootstrapped the data and evaluated the risk ratio for drinking compared with non-drinking during group dining with similar frequency and numbers of participants.

ResultsThe 99% lower bound of the bootstrapped distribution of the risk ratio was less than one. Therefore the null hypothesis, that incidence in the two styles of group dining were the same, cannot be rejected.

Discussion and ConclusionResults constitute no clear evidence indicating a risk of drinking alcohol in groups. However, further analyses using collected data are necessary. Moreover, risks posed by the number of group diners or their dining frequency must be evaluated.


title: Comparison of reported main COVID-19 information sources in national and culturally and linguistically diverse communities in Australia

abstract:
BackgroundTo manage the COVID-19 pandemic effectively, governments need clear and effective communication. This is a challenge for culturally diverse communities as groups may have different informational needs and information-seeking behaviours. In this paper we present the frequency of information sources for COVID-19 in a culturally diverse area of Sydney, Australia.

MethodsThis study reports findings from two surveys. The first recruited participants across 10 languages between March 21 and July 9, 2021. The second provides a point of reference, and was an Australian, nationally-representative sample of English-speaking participants between November 4 - 18, 2020.

ResultsFor the survey in culturally and linguistically diverse communities, of 708 participants, mean age was 45.4 years (SE 0.78), and 51% of respondents were female. Across all language groups, 54.7% of participants used Australian official or public broadcasters to find out about COVID-19 (n=421). Australian commercial information sources (54.1%, n=417), social media (51.6%, n=397), and family and friends in Australia (32.7%, n=252) were common sources. Patterns varied substantially across language groups. In the nationally representative survey (n=2313), 67% of participants (n=1540) used Australian official or public broadcasters, with lower proportions for social media (31.9%, n=738) and friends, family or other personal sources (23.1%; n=533).

ConclusionAlmost 50% of participants from culturally and linguistically diverse communities did not report using Australian official or public broadcaster as main sources of information. Instead Australian commercial information sources, friends and family, overseas sources and social media were common. Though a crude comparison of the two datasets, this data can guide policy decisions for communication to different community groups. Further analysis is needed to interpret this data. Better understanding of how diverse communities seek and receive COVID-19 health information is imperative as we manage the current COVID-19 outbreak in the Sydney region.


title: Knowledge, Attitude, and Practice among the Healthcare Professionals regarding the myths on COVID-19 vaccination - Demystified.

abstract:
BackgroundCOVID-19 vaccine is the mighty weapon opted by all the countries across the globe in an attempt to eradicate the fatal COVID-19 pandemic. The myths on the COVID-19 vaccine are spreading widely, causing a hindrance to this noble preventive measure. The prevalence of such myths among the healthcare professionals may be toxic and deadly.

Aim & ObjectivesTo assess the knowledge, attitude, and practice of the healthcare professionals regarding the myths on COVID-19 vaccination and to demystify them.

Materials and MethodsAn 18-item questionnaire evaluating knowledge, attitude, and practice based on the existing myths on COVID-19 vaccination was circulated through Google Forms(R) among the 412 healthcare professionals of six disciplines belonging to a private University. The responses obtained were subjected to statistical analysis using SPSS(R) 20 software package.

ResultsA total of 385 health professionals participated in this study. The majority of them had medium knowledge (165) and positive attitude (273) with the mean knowledge and attitude scores of 3.82 {+/-} 1.55 out of 6 and 4.3 {+/-} 1.58 out of 7 respectively. Even though 312 participants got vaccinated, 72 of them failed to receive it. The knowledge scores showed a high statistically significant difference among the participants of different designations (p=0.001), but not with gender, field, and staff with different years of experience (p>0.05). The attitude scores were statistically different among participants of fields and designation (p<0.05) but not among genders (p=0.31) and staff with different years of experience (p=0.87). Knowledge and attitude scores showed a positive linear correlation and a high statistically significant difference (p<0.001).

ConclusionThis study recommends more enhanced education programs on COVID-19 vaccination for the health professionals and demands an improved knowledge, attitude, and practice among them to achieve the goal of 100% vaccination so as to completely eradicate the COVID-19 pandemic.


title: Three-dimensional printing of patient-specific lung phantoms for CT imaging: emulating lung tissue with accurate attenuation profiles and textures

abstract:
PurposePhantoms are a basic tool for assessing and verifying performance in CT research and clinical practice. Patient-based realistic lung phantoms accurately representing textures and densities are essential in developing and evaluating novel CT hardware and software. This study introduces PixelPrint, a 3D printing solution to create patient-based lung phantoms with accurate attenuation profiles and textures.

MethodsPixelPrint, a software tool, was developed to convert Patient DICOM images directly into printer instructions (G-code). The density was modeled as the ratio of filament to voxel volume to emulate attenuation profiles for each voxel. A calibration phantom was designed to determine the mapping between filament line width and Hounsfield Units (HU) within the range of human lungs. For evaluation of PixelPrint, a phantom based on a human lung slice was manufactured and scanned with the same CT scanner and protocol used for the patient scan. Density and geometrical accuracy between phantom and patient CT data was evaluated for various anatomical features in the lung.

ResultsFor the calibration phantom, measured mean Hounsfield units show a very high level of linear correlation with respect to the utilized filament line widths, (r > 0.999). Qualitatively, the CT image of the patient-based phantom closely resembles the original CT image both in texture and contrast levels, with clearly visible vascular and parenchymal structures. Regions-of-interest (ROIs) comparing attenuation illustrated differences below 15 HU. Manual size measurements performed by an experienced thoracic radiologist reveal a high degree of geometrical correlation of details between identical patient and phantom features, with differences smaller than the intrinsic spatial resolution of the scans.

ConclusionThe present study demonstrates the feasibility of 3D printed patient-based lung phantoms with accurate organ geometry, image texture, and attenuation profiles. PixelPrint will enable applications in the research and development of CT technology, including further development in radiomics.


title: Airway-specific autoantibodies identify a subset of patients with fibrotic interstitial lung disease

abstract:
BackgroundFibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airway remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD and assessed association with disease severity and outcome.

MethodsBronchoalveolar lavage (BAL) was collected from a cohort of fILD patients and total airway antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 124 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.

ResultsA subset of patients with fILD but not healthy controls had a local autoimmune signature in their airways that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased airway total IgA and IgG1 while subjects with CHP had increased airway IgA, IgG1 and IgG4. In patients with CHP, increased airway total IgA was associated with reduced survival probability.

ConclusionThe presence of airway autoantibodies identifies a unique subset of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.

category: respiratory medicine


title: Association of E484K and L452R spike protein mutations with SARS-CoV-2 infection in vaccinated persons---Maryland, January - May 2021

abstract:
BackgroundThe E484K and L452R amino acid substitutions on the spike protein of SARS-CoV-2 are associated with reduced neutralization by antibodies from acquired immunity. This study examines the respective association of these mutations with infection in persons who had previously received a COVID-19 vaccine.

MethodsGenetic sequences from SARS-CoV-2 specimens collected from Maryland residents and reported to Maryland Department of Health were linked to vaccination history. The prevalence of infections in fully vaccinated persons -- defined as being at least two weeks past receiving the final scheduled dose of a COVID-19 vaccine series -- was compared between infections caused by viruses carrying E484K to those not carrying E484K, and between infections caused by viruses carrying L452R to those not carrying L452R, using logistic regression to adjust for confounding.

ResultsOf 9,048 sequenced SARS-CoV-2 specimens examined, 265 (2.9%) were collected from fully vaccinated persons. In adjusted analysis, the E484K substitution was associated with an increase in the odds of the sequenced specimen being collected from a fully vaccinated person (OR 1.96, 95% CI, 1.36 to 2.83). The L452R mutation was not significantly associated with infections in vaccinated persons (OR 1.07, 95% CI, 0.69 to 1.68).

ConclusionThough more than 97% of SARS-CoV-2 infections were in persons who were not fully vaccinated, the E484K mutation was associated with increased odds of SARS-CoV-2 infection in vaccinated persons. Linking vaccination and sequencing data can help identify and estimate the impact SARS-CoV-2 mutations may have on vaccine effectiveness.

SummaryIn viruses sequenced for Marylands routine SARS-CoV-2 genomic surveillance, the spike protein amino acid substitution E484K was more prevalent in viruses that infected vaccinated people than in viruses that infected people who were not vaccinated.


title: Rapid comparative evaluation of SARS-CoV-2 rapid point-of-care antigen tests

abstract:
BackgroundCurrently, more than 500 different AgPOCTs for SARS-CoV-2 diagnostics are on sale (July 2021), for many of which no data about sensitivity other than self-acclaimed values by the manufacturers are available. In many cases these do not reflect real-life diagnostic sensitivities. Therefore, manufacturer-independent quality checks of available AgPOCTs are needed, given the potential implications of false-negative results.

ObjectiveThe objective of this study was to develop a scalable approach for direct comparison of the analytical sensitivities of commercially available SARS-CoV-2 antigen point-of-care tests (AgPOCTs) in order to rapidly identify poor performing products.

MethodsWe present a methodology for quick assessment of the sensitivity of SARS-CoV-2 lateral flow test stripes suitable for quality evaluation of many different products. We established reference samples with high, medium and low SARS-CoV-2 viral loads along with a SARS-CoV-2 negative control sample. Test samples were used to semi-quantitatively assess the analytical sensitivities of 32 different commercial AgPOCTs in a head-to-head comparison.

ResultsAmong 32 SARS-CoV-2 AgPOCTs tested, we observe sensitivity differences across a broad range of viral loads ([~]7.0*108 to [~]1.7*105 SARS-CoV-2 genome copies per ml). 23 AgPOCTs detected the Ct25 test sample ([~]1.4*106 copies/ ml), while only five tests detected the Ct28 test sample ([~]1.7*105 copies/ ml). In the low range of analytical sensitivity we found three saliva spit tests only delivering positive results for the Ct21 sample ([~]2.2*107 copies/ ml). Comparison with published data support our AgPOCT ranking. Importantly, we identified an AgPOCT offered in many local drugstores and supermarkets, which did not reliably recognize the sample with highest viral load (Ct16 test sample with [~]7.0*108 copies/ ml) leading to serious doubts in its usefulness in SARS-CoV-2 diagnostics.

ConclusionThe rapid sensitivity assessment procedure presented here provides useful estimations on the analytical sensitivities of 32 AgPOCTs and identified a widely-spread AgPOCT with concerningly low sensitivity.


title: TREATMENTS, RESOURCE UTILIZATION, AND OUTCOMES OF COVID-19 PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS ACROSS PANDEMIC WAVES: AN OBSERVATIONAL STUDY BY THE CANADIAN COVID-19 EMERGENCY DEPARTMENT RAPID RESPONSE NETWORK (CCEDRRN)

abstract:
BackgroundTreatment strategies for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care resource utilization, and outcomes of COVID-19 patients presenting to Emergency Departments across two pandemic waves.

MethodsThis observational study enrolled consecutive eligible COVID-19 patients presenting to 46 Emergency Departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. We used logistic regression modeling to assess the impact of pandemic wave on outcomes.

ResultsWe enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the Emergency Department. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 8.0; 95% confidence interval [CI] 6.4 - 10.0), while the use of invasive mechanical ventilation decreased (OR 0.5; 95%CI 0.4 - 0.6) in the second wave. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95%CI 0.6 - 0.8) and critical care admission (OR 0.6; 95%CI 0.4 - 0.7) decreased, while mortality remained unchanged (OR 1.0; 95%CI 0.7-1.4).

InterpretationIn patients presenting to Canadian acute care facilities, rapid uptake of steroid therapy was evident. Mortality was stable despite lower critical care utilization in the second wave.

Trial RegistrationClinicaltrials.gov, NCT04702945

category: emergency medicine