title: A Cloth Facemask Causes No Major Respiratory or Cardiovascular Perturbations during Moderate to Heavy Exercise

abstract:
ObjectivesTo investigate whether wearing a cloth facemask could affect physiological and perceptual responses to exercise at distinct exercise intensities in non-trained men and women.

MethodsIn a crossover design, participants (17 men and 18 women) underwent a progressive square-wave test at four intensities (i. at 80% of the ventilatory anerobic threshold [80%VAT]; ii. at VAT; iii. at the respiratory compensation point [RCP]; iv. at exercise peak [Peak] to exhaustion), with or without a triple-layered cloth mask (Mask or No-Mask). Several physiological, metabolic and perceptual measures were analyzed.

ResultsMask reduced inspiratory capacity at all exercise intensities vs. No-Mask (p<0.0001), irrespective of sex. Mask reduced respiratory frequency vs. No-Mask (p=0.001) at Peak (-8.3 breaths{middle dot}min-1; CI: -5.8, -10.8), RCP (-6.9 breaths{middle dot}min-1; CI: -4.6, -9.2) and VAT (-6.5 breaths{middle dot}min-1; CI: -4.1, -8.8), but not at Baseline or at 80%VAT. Mask also reduced tidal volume (p<0.0001) at both RCP (-0.5L; CI: -0.3, -0.6) and Peak (-0.8L; CI: -0.6, -0.9), but not at Baseline, 80%VAT or VAT. Shallow breathing index was increased with Mask at Peak compared to No-Mask (11.3; CI: 7.5, 15.1), but not at any other intensities. Mask did not change heart rate, lactate, ratings of perceived exertion, blood pressure or oxygen saturation.

ConclusionsWearing a cloth facemask during exercise at moderate to heavy intensities is unlikely to incur significant respiratory or cardiovascular changes, irrespective of sex. These data can inform new exercise recommendations for health during the COVID-19 pandemic and debunk unfounded allegations of harmful effects of masks during exercise. ClinicalTrials.gov: NCT04887714

What are the new findings?{checkmark} Using a progressive square-wave test, we showed that wearing a cloth facemask during exercise increased breathing difficulty, but this was dependent upon the exercise intensity.
{checkmark}Respiratory variables (e.g., inspiratory capacity, respiratory frequency, shallow breathing index) were affected at higher rather than lower intensities.
{checkmark}Mask wearing did not change heart rate, lactate, ratings of perceived exertion, blood pressure or oxygen saturation at any exercise intensity.
{checkmark}There were no substantial sex differences on the effects of mask wearing during exercise.

How might it impact on clinical practice in the future?{checkmark} These data can debunk unfounded allegations on harmful effects of masks during exercise, and help inform new exercise recommendations for health during the COVID-19 pandemic, particularly where facemasks remain necessary.

category: sports medicine


title: REACT-1 round 15 final report: Increased breakthrough SARS-CoV-2 infections among adults who had received two doses of vaccine, but booster doses and first doses in children are providing important protection

abstract:
BackgroundIt has been nearly a year since the first vaccinations against SARS-CoV-2 were delivered in England. The third wave of COVID-19 in England began in May 2021 as the Delta variant began to outcompete and largely replace other strains. The REal-time Assessment of Community Transmission-1 (REACT-1) series of community surveys for SARS-CoV-2 infection has provided insights into transmission dynamics since May 2020. Round 15 of the REACT-1 study was carried out from 19 October to 5 November 2021.

MethodsWe estimated prevalence of SARS-CoV2 infection and used multiple logistic regression to analyse associations between SARS-CoV-2 infection in England and demographic and other risk factors, based on RT-PCR results from self-administered throat and nose swabs in over 100,000 participants. We estimated (single-dose) vaccine effectiveness among children aged 12 to 17 years, and among adults compared swab-positivity in people who had received a third (booster) dose with those who had received two vaccine doses. We used splines to analyse time trends in swab-positivity.

ResultsDuring mid-October to early-November 2021, weighted prevalence was 1.57% (1.48%, 1.66%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). Weighted prevalence increased between rounds 14 and 15 across most age groups (including older ages, 65 years and over) and regions, with average reproduction number across rounds of R=1.09 (1.08, 1.11). During round 15, there was a fall in prevalence from a maximum around 20-21 October, with an R of 0.76 (0.70, 0.83), reflecting falls in prevalence at ages 17 years and below and 18 to 54 years. School-aged children had the highest weighted prevalence of infection: 4.95% (4.39%, 5.58%) in those aged 5 to 12 years and 5.21% (4.61%, 5.87%) in those aged 13 to 17 years. In multiple logistic regression, age, sex, key worker status and presence of one or more children in the home were associated with swab positivity. There was evidence of heterogeneity between rounds in swab positivity rates among vaccinated individuals at ages 18 to 64 years, and differences in key demographic and other variables between vaccinated and unvaccinated adults at these ages. Vaccine effectiveness against infection in children was estimated to be 56.2% (41.3%, 67.4%) in rounds 13, 14 and 15 combined, adjusted for demographic factors, with a similar estimate obtained for round 15 only. Among adults we found that those who received a third dose of vaccine were less likely to test positive compared to those who received only two vaccine doses, with adjusted odds ratio (OR) =0.38 (0.26, 0.55).

DiscussionSwab-positivity was very high at the start of round 15, reaching a maximum around 20 to 21 October 2021, and then falling through late October with an uncertain trend in the last few days of data collection. The observational nature of survey data and the relatively small proportion of unvaccinated adults call into question the comparability of vaccinated and unvaccinated groups at this relatively late stage in the vaccination programme. However, third vaccine doses for eligible adults and the vaccination of children aged 12 years and over are associated with lower infection risk and, thus, remain a high priority (with possible extension to children aged 5-12 years). These should help reduce SARS-CoV-2 transmission during the winter period when healthcare demands typically rise.

category: epidemiology


title: Bionomics of Aedes aegypti during the 2016-2017 dengue outbreaks in Ouagadougou, Burkina Faso.

abstract:
BackgroundDengues emergence in West Africa was typified by the Burkina Faso outbreaks in 2016 and 2017, the nations largest to date. In both years, we undertook three-month surveys of Aedes populations in or near the capital city Ouagadougou, where the outbreak was centered.

MethodologyIn urban, peri-urban and rural localities we collected indoor and outdoor resting mosquito adults, characterized larval habitats and containers producing pupae and reared immature stages to adulthood in the laboratory for identification. All mosquito adults were identified morphologically. Host species from which bloodmeals were taken were identified by PCR Generalized mixed models were used to investigate relationships between adult or larval densities and multiple explanatory variables.

ResultsFrom samples in 1,791 houses, Ae. aegypti was the most abundant mosquito in the two urban localities where it occurred in 46% of containers sampled and comprised over 85% of collections. Results indicated a highly exophilic and anthropophilic (>90% bloodmeals of human origin) vector population, but with a relatively high proportion of bloodfed females caught inside houses. Habitats producing most pupae were waste tires (37% of total pupae), animal troughs (44%) and large water barrels (30%).

While Stegomyia indices were not reliable indicators of adult mosquito abundance, shared influences on adult and immature stage densities included rainfall and container water level, collection month and container type/ purpose. Spatial analysis showed autocorrelation of densities, with partial overlap in adult and immature stage hotspots.

ConclusionResults provide an evidence base for the selection of appropriate vector control methods to minimize the risk, frequency and magnitude of future outbreaks in Ouagadougou. An integrated strategy combining community-driven practices, waste disposal and insecticide-based interventions is indicated. The prospects of developing a regional approach to arbovirus control in west Africa or across Africa was discussed

Author SummaryAedes aegypti is the most efficient vector of human diseases including yellow fever, dengue chikungunya and Zika. West Africa is an emerging hotspot for dengue, as illustrated by Burkina Fasos outbreaks in 2016 and 2017. Coincidentally, this study investigated the bionomics and behavior of Ae. aegypti in urban, peri-urban and rural localities of Ouagadougou, from August to October in each year. The results from over 1700 homes showed that Ae. aegypti preferentially fed on humans and rested primarily outdoors. The most common pupal productive habitats were discarded vehicle tires, animal water troughs and large water barrels. Infestation rates were higher in the urban and peri-urban localities. A range of community-based control measures are suitable for consideration in a vector control program to prevent outbreaks. Further work is required but the study provides the most complete contemporary description of an Ae. aegypti population in West Africa and provides sufficient evidence to develop programs for prevention and control of outbreaks. The potential of a regional based vector control program for west Africa is discussed briefly.

category: public and global health


title: Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

abstract: A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. We utilised the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the repeat expansion in CSF of people with C9orf72-associated FTD/ALS. We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intra- and inter-plate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) DPRs in the CSF of samples collected through the Genetic FTD Initiative. We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had 8-fold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.

category: neurology


title: Rare genetic variants in dominant developmental disorder loci cause milder related phenotypes in the general population

abstract: Many rare diseases are known to be caused by deleterious variants in Mendelian genes, however the same variants can also be found in people without the associated clinical phenotypes. The penetrance of these monogenic variants is generally unknown in the wider population, as they are typically identified in small clinical cohorts of affected individuals and families with highly penetrant variants. Here, we investigated the phenotypic effect of rare, potentially deleterious variants in genes and loci that are known to cause monogenic developmental disorders (DD) in a large population cohort. We used UK Biobank to investigate phenotypes associated with rare protein-truncating and missense variants in 599 dominant DD genes using whole exome sequencing data from [~]200,000 individuals, and rare copy number variants overlapping known DD loci using SNP-array data from [~]500,000 individuals. We found that individuals with these likely deleterious variants had a mild DD-related phenotype, including lower fluid intelligence, slower reaction times, lower numeric memory scores and longer pairs matching times compared to the rest of the UK Biobank cohort. They were also shorter, with a higher BMI and had significant socioeconomic disadvantages, being less likely to be employed or be able to work, and having a lower income and higher deprivation index. Our findings suggest that many monogenic DD genes routinely tested within paediatric genetics have intermediate penetrance and may cause lifelong milder, sub-clinical phenotypes in the general adult population.

category: genetic and genomic medicine


title: Delivering HIV pre-exposure prophylaxis (PrEP) care online: A scoping review.

abstract:
ObjectivesHIV pre-exposure prophylaxis (PrEP), in which people take HIV medication to prevent HIV acquisition, is a highly effective method of HIV prevention; however, global implementation of PrEP is patchy. PrEP provision will need to be upscaled significantly to achieve UNAIDS/WHO goals of elimination of HIV transmission. Online provision of PrEP care could enhance access to, and delivery of, care at scale. We explored the extent to which PrEP care has been delivered online to inform the development of a novel online PrEP clinic.

DesignScoping review.

Data sourcesEmbase, MEDLINE, Web of Science, CINAHL, PsycINFO, ASSIA, PUBMED, Open Grey, and EThOS databases.

Eligibility criteriaEnglish language articles describing a service that delivered one or more element of PrEP-related care online, published from 2009 onwards.

Data extraction and synthesisData were extracted using matrices and synthesised using summary statistics and thematic analysis. The Mixed Methods Appraisal Tool was used to assess study quality.

ResultsFifty-nine articles were included: eight randomised controlled trials, 12 non-randomised quantitative studies, 30 descriptive quantitative studies, 14 qualitative studies, and four reviews of online content. Seven studies detailed comprehensive PrEP care pathways that used a combination of online, face-to-face and telephone based care. Of the remaining studies, the majority focused on HIV testing outside a PrEP context. Care tended to be delivered via websites (n=41), video chat, and smartphone apps (both n=10). The acceptability and feasibility of delivering elements of care online was high.

ConclusionsOnline PrEP care appears feasible and acceptable, offering convenience and a means to overcome some of the reported barriers to face-to-face care. Services tended to focus on a single element of PrEP-related care or use a combination of online, face-to-face and phone-based care. Additional formative work is needed to inform the development of complete online PrEP care pathways.

Strengths and limitations of this studyO_LIThis scoping review provides a comprehensive, critical overview of existing literature related to online provision of HIV pre-exposure prophylaxis (PrEP)-related care.
C_LIO_LIWe developed a comprehensive definition of PrEP care which took into consideration all essential elements of care required for safe and appropriate PrEP prescribing.
C_LIO_LIEstablished guidelines for conducting and reporting scoping reviews were followed throughout.
C_LIO_LIWe conducted an exhaustive search of nine databases.
C_LIO_LIThe heterogeneity in design and aim of the included studies limited our ability to synthesise findings.
C_LI

category: hiv aids


title: The effect of anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, on endogenous immune response to COVID-19 vaccination

abstract:
As the COVID-19 pandemic evolves, and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of SARS-CoV-2 infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of six months, serum samples were collected from the prevention population (nursing home residents and staff) enrolled in the BLAZE-2 clinical trial who had received either bamlanivimab (4200 mg) or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines, as part of the US vaccination program. This post-hoc analysis assessed the immune response to vaccination for the subset of participants (N=135) without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not significantly bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo participants mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk-category and vaccine type, with any observed differences unlikely to be clinically meaningful. These findings are pertinent for informing public health policy with results that suggest a complementary role for COVID-19 monoclonal antibodies (mAbs) with COVID-19 vaccines and that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 mAb infusion.

One Sentence SummaryIndividuals infused with an anti-SARS-CoV-2 antibody demonstrated a robust immune response to subsequent full COVID-19 vaccination.

category: infectious diseases


title: Assessment of twenty-two SARS-CoV-2 rapid antigen tests against SARS-CoV-2: A laboratory evaluation study

abstract:
BackgroundRapid antigen testing is widely used as a way of scaling up population-level testing. To better inform antigen test deployment in Australia, we evaluated 22 commercially available antigen tests against the currently circulating delta variant, including an assessment of culture infectivity.

MethodsAnalytical sensitivity was evaluated against SARS-CoV-2 B.1.617.2 (Delta), reported as TCID50/mL, cycle threshold (Ct) and viral load (RNA copies/mL). Specificity was assessed against non-SARS-CoV-2 viruses. Clinical sensitivity and correlation with cell culture infectivity was assessed using the Abbott PanBio COVID-19 Ag test.

ResultsNineteen kits consistently detected SARS-CoV-2 antigen equivalent to 1.3 x 106 copies/mL (5.8 x 103 TCID50 /mL). Specificity for all kits was 100%. Compared to RT-PCR the Abbott PanBio COVID-19 Ag test was 52.6% (95% CI, 41.6% to 63.3%) concordant, with a 50% detection probability for infectious cell culture at 5.9 log10 RNA copies/mL (95% CI, 5.3 to 6.5 log10 copies/mL). Antigen test concordance was 97.6% (95% CI, 86.3% to 100.0%) compared to cell culture positivity.

ConclusionsAntigen test positivity correlated with positive viral culture, suggesting antigen test results may determine SARS-CoV-2 transmission risk. Analytical sensitivity varied considerably between kits highlighting the need for ongoing systematic post-market evaluation to inform test selection and deployment.


title: Antigenic and virological properties of an H3N2 variant that will likely dominate the 2021-2022 Northern Hemisphere influenza season

abstract: Influenza viruses have circulated at very low levels during the COVID-19 pandemic, and population immunity against these viruses is low. Influenza virus cases have been increasing in the Northern Hemisphere involving an H3N2 strain (3C.2a1b.2a2) with a hemagglutinin (HA) that has several substitutions relative to the 2021-2022 H3N2 vaccine strain. Here, we show that one of these substitutions eliminates a key glycosylation site on HA and alters sialic acid binding. Using glycan array profiling, we show that the 3C.2a1b.2a2 H3 maintains binding to an extended bi-antennary sialoside and replicates to high titers in human airway cells. We found that antibodies elicited by the 2021-2022 Northern Hemisphere influenza vaccine poorly neutralize the new H3N2 strain. Together, these data indicate that 3C.2a1b.2a2 H3N2 viruses efficiently replicate in human cells and could potentially cause an antigenic mismatch if they continue to circulate at high levels during the 2021-2022 influenza season.


title: Evaluation of an ultra-rapid antibiotic susceptibility testing method on positive blood cultures with Escherichia coli

abstract:
Blood stream infection (BSI) is related to high mortality and morbidity. Early antimicrobial therapy is crucial in treating patients with BSI. The most common Gram-negative bacteria causing BSI is Escherichia coli. Targeted effective treatment of patients with BSI is only possible if it is based on antibiotic susceptibility testing (AST) data after blood culture positivity. However, there are very few methods available for rapid phenotypic AST and the fastest method takes 4 h. Here we analyzed the performance of a 30 min ultra-rapid method for AST of E. coli directly from positive blood cultures (BC). In total, 51 positive BC with E. coli were studied, and we evaluated the ultra-rapid method directly on positive BC as well as on E. coli colonies cultured on agar plates. The results obtained by the new method were compared with disk diffusion.

The method provided accurate AST result in 30 min to Ciprofloxacin and Gentamicin for 92% and 84% of the positive BC samples, respectively. For E. coli isolates retrieved from agar plates, 86% and 96% of the AST results were accurate for Ciprofloxacin and Gentamicin, respectively, after 30 min of assay time. When time to result was modulated in-silico from 30 to 60 minutes for the agar plate samples, accuracy of AST results went up to 92% for Ciprofloxacin and to 100% for Gentamicin.

The present study shows that the method is reliable and delivers ultra-rapid AST data in 30 minutes directly from positive BC and as well as from agar plates.


title: Sporadic, late-onset, and multistage diseases

abstract: Somatic mutations can cause cancer and have recently been linked with a range of non-malignant diseases. Multistage models can characterise how mutations lead to cancer, and may also be applicable to these other diseases. Here we found the incidence of over 60% of common diseases in UK Biobank were consistent with a multistage model with an ordered sequence of stages, as approximated by a Weibull distribution, with the log of incidence linearly related to the log of age and the slope often interpreted as the number of stages. A model where the stages can occur in any order was also explored, as was stratification by smoking and diabetes status. Most importantly, we find that many diseases are low risk when young but then become inevitable in old age, but many other diseases do not, being more sporadic with a modest and modifiable risk that slowly increases with age.


title: Potential severity, mitigation, and control of Omicron waves depending on pre-existing immunity and immune evasion

abstract: We assess the potential consequences of the upcoming SARS-CoV-2 waves caused by the Omicron variant. Our results suggest that even in those regions where the Delta variant is controlled at the moment by a combination of non-pharmaceutical interventions and population immunity, a significant Omicron wave can be expected. We stratify the population according to prior immunity status, and characterize the possible outbreaks depending on the population level of pre-existing immunity and the immune evasion capability of Omicron. We point out that two countries having similar effective reproduction numbers for the Delta variant can experience very different Omicron waves in terms of peak time, peak size and total number of infections among the high risk population.


title: Heterogenous Cellular and Humoral Immune Trajectories after SARS-CoV-2 Infection: Compensatory Responses in a Population-Based Cohort

abstract:
To better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses.

One Sentence SummaryPresence of heterogenous immune response trajectories after SARS-CoV-2 infection with potential compensatory role of T cells among individuals with low antibody responses.


title: Projected epidemiological consequences of the Omicron SARS-CoV-2 variant in England, December 2021 to April 2022

abstract: The Omicron B.1.1.529 SARS-CoV-2 variant was first detected in late November 2021 and has since spread to multiple countries worldwide. We model the potential consequences of the Omicron variant on SARS-CoV-2 transmission and health outcomes in England between December 2021 and April 2022, using a deterministic compartmental model fitted to epidemiological data from March 2020 onwards. Because of uncertainty around the characteristics of Omicron, we explore scenarios varying the extent of Omicrons immune escape and the effectiveness of COVID-19 booster vaccinations against Omicron, assuming the level of Omicrons transmissibility relative to Delta to match the growth in observed S gene target failure data in England. We consider strategies for the re-introduction of control measures in response to projected surges in transmission, as well as scenarios varying the uptake and speed of COVID-19 booster vaccinations and the rate of Omicrons introduction into the population. These results suggest that Omicron has the potential to cause substantial surges in cases, hospital admissions and deaths in populations with high levels of immunity, including England. The reintroduction of additional non-pharmaceutical interventions may be required to prevent hospital admissions exceeding the levels seen in England during the previous peak in winter 2020-2021.


title: The COVID-19 pandemic amplified long-standing racial disparities in the United States criminal justice system

abstract: During the first year of the COVID-19 pandemic, the number of incarcerated people in the United States decreased by at least 16%--the largest, fastest reduction in prison population in American history. Using an original dataset curated from public sources on prison demographics across all 50 states and the District of Columbia, we show that incarcerated white people benefited disproportionately from this decrease in the U.S. prison population, and the fraction of incarcerated Black and Latino people sharply increased. This pattern deviates from a decade-long trend before 2020 and the onset of COVID-19, during which the proportion of incarcerated Black people was declining. Using case studies of select states, we explore and quantify mechanisms that could explain these disparities: temporary court closures that led to fewer prison admissions, changes in the frequency of police interactions, and state-level prison release policies that sought to de-densify congregate settings. These findings illuminate how systemic inequalities pervade juridicial and penal institutions and are key features of mass incarceration in America.


title: Identification of Intimate Partner Violence from Free Text Descriptions in Social Media

abstract:
Intimate Partner Violence (IPV) is a significant public health problem that adversely affects the well-being of victims. IPV is often under-reported and non-physical forms of violence may not be recognized as IPV, even by victims. With the increasing popularity of social media and due to the anonymity provided by some of these platforms, people feel comfortable sharing descriptions of their relationship problems in social media. The content generated in these platforms can be useful in identifying IPV and characterizing the prevalence, causes, consequences, and correlates of IPV in broad populations. However, these descriptions are in the form of free text and no corpus of labeled data is available to perform large-scale computational and statistical analyses.

Here, we use data from established questionnaires that are used to collect self-report data on IPV to train machine learning models to predict IPV from free text. Using Universal Sentence Encoder (USE) along with multiple machine learning algorithms (Random Forest, SVM, Logistic Regression, Naive Bayes), we develop DO_SCPLOWETECTC_SCPLOWIPV, a tool for detecting IPV in free text. Using DO_SCPLOWETECTC_SCPLOWIPV, we comprehensively characterize the predictability of different types of violence (Physical Abuse, Emotional Abuse, Sexual Abuse) from free text. Our results show that a general model that is trained using examples of all violence types can identify IPV from free text with area under the ROC curve (AUROC) 89%. We also train type-specific models and observe that Physical Abuse can be identified with greatest accuracy (AUROC 98%), while Sexual Abuse can be identified with high precision but relatively low recall. While our results indicate that the prediction of Emotional Abuse is the most challenging, DO_SCPLOWETECTC_SCPLOWIPV can identify Emotional Abuse with AUROC above 80%. These results establish DO_SCPLOWETECTC_SCPLOWIPV as a tool that can be used to reliably detect IPV in the context of various applications, ranging from flagging social media posts to detecting IPV in large text corpuses for research purposes. DO_SCPLOWETECTC_SCPLOWIPV is available as a web service at https://ipvlab.case.edu/ipvdetect/.


title: The impact of COVID-19 restrictions on older adults' loneliness: Evidence from high-frequency panel data

abstract:
BACKGROUNDIt is unclear how strong and long lasting the effects of (recurring) COVID-19 restrictions are on older adults loneliness.

METHODS469 retired older Austrians (60+) provided 9,732 repeated observations of loneliness across 30 waves of the Austrian Corona Panel Project between March 2020 and March 2022. Ordinal mixed regression models were used to estimate the effect of the strictness of COVID-19 restrictions (stringency index, range=0-100) on older adults loneliness.

RESULTSThe proportion of older adults who reported to be often lonely correlated (r=0.45) with the stringency index over time: both peaked during lock-downs (stringency index=82, often lonely=10-13%) and were lowest during the summer of 2020 (stringency index=36, often lonely=4-6%). Results from regression models indicate, that when the stringency index increased, loneliness also increased. In turn, as COVID-19 restrictions loosened, levels of loneliness decreased again. Older adults who lived alone were more affected in terms of loneliness by COVID-19 restriction measures compared to those living with others.

CONCLUSIONSMore stringent COVID-19 restrictions were associated with an increased in (situational) loneliness among older adults in Austria, and this effect was stronger among those who lived alone. Efforts should be made to enable older adults, in particular those who live alone, to have save in-person contact during periods of strict pandemic restriction measures.


title: The impact of COVID-19 restrictions on older adults'loneliness: Evidence from high-frequency panel data inAustria


title: Contraception in breast cancer survivors from the FEERIC case-control study (performed on behalf of the Seintinelles research network)

abstract:
ObjectiveTo compare the prevalence of contraception in breast cancer (BC) patients at risk of unintentional pregnancy (i.e. not currently pregnant or trying to get pregnant) and matched controls.

DesignThe FEERIC study (Fertility, Pregnancy, Contraception after BC in France) is a prospective, multicenter case-control study. Data were collected through online questionnaires completed on the Seintinelles* research platform.

SettingNot applicable

Patient(s)BC patients aged 18-43 years, matched for age and parity to cancer-free volunteer controls in a 1:2 ratio.

Intervention(s)None

ResultsIn a population of 1278 women at risk of unintentional pregnancy, the prevalence of contraception at study inclusion did not differ significantly between cases (340/431, 78.9%) and controls (666/847, 78.6%, p=0.97). However, the contraceptive methods used were significantly different, with a higher proportion of copper IUD use in BC survivors (59.5% versus 25.0% in controls p<0.001). For patients at risk of unintentional pregnancy, receiving information about chemotherapy-induced ovary damage at BC diagnosis (OR= 2.47 95%CI [1.39 - 4.37] and anti-HER2 treatment (OR=2.46, 95% CI [1.14 - 6.16]) were significantly associated with the use of a contraception in multivariate analysis.

DiscussionIn this large French study, BC survivors had a prevalence of contraception use similar to that for matched controls, though almost one in five women at risk of unintentional pregnancy did not use contraception. Dedicated consultations at cancer care centers could further improve access to information and contraception counseling.

category: oncology


title: Patterns of convergence and divergence between bipolar disorder type I and type II: evidence from integrative genomic analyses

abstract: Genome-wide association studies (GWAS) analyses have revealed genetic evidence of bipolar disorder (BD), but little is known about genetic structure of BD subtypes. We aimed to investigate genetic overlap and distinction of bipolar type I (BDI) & type II (BDII) by conducting integrative post-GWAS analyses. This study utilized single nucleotide polymorphism (SNP)-level approaches to uncover correlated and distinct genetic loci. Transcriptome-wide association analyses (TWAS) were then approached to pinpoint functional genes expressed in specific brain tissues and blood. Next, we performed cross-phenotype analysis including exploring the potential causal associations between BDI & II and drug responses and comparing the difference of genetic structures among four different psychiatric traits. Our results find SNP-level evidence revealed three genomic loci, SLC25A17, ZNF184 and RPL10AP3 shared by BDI & II, while one locus (i.e., MAD1L1) and significant gene sets involved in calcium channel activity, neural and synapsed signals that distinguished two subtypes. TWAS data implicated different genes effecting BDI & II through expression in specific brain regions (e.g., nucleus accumbens for BDI). Cross-phenotype analyses indicated that BDI & II share continuous genetic structures with schizophrenia (SCZ) and major depression disorder (MDD), which help fill the gaps left by the dichotomy of mental disorder. These combined evidences illustrate genetic convergence and divergence between BDI & II and provide an underlying biological and trans-diagnostic insight into major psychiatric disorders.


title: S Gene Target Failure (SGTF) in Commercial Multiplex RT-PCR assay as indicator to detect SARS-CoV-2 VOC B.1.1.7 lineage in Tamil Nadu, India

abstract: Emergence of Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) Variants of Concern (VOC) possessing improved virulence, transmissibility and/or immune-escape capabilities has raised significant public health concerns. In order to identify VOCs, WHO recommends Whole-Genome Sequencing approach, which is costly and involves longer completion time. Hence, potential role of commercial multiplex RT-PCR kit to screen variants rapidly is being attempted in this study. A total of 1200 suspected COVID samples from different districts of Tamil Nadu State (India) were screened with Thermo TaqPath RT-PCR kit and Altonas Realstar RT-PCR Assay kit. Among 1200 screened, S-gene target failure (SGTF) phenomenon were identified in 112 samples while testing with TaqPath RT-PCR Kit. 100% concordant results were observed between SGTF phenomenon and whole-genome sequencing (WGS) results in detecting SARS-CoV-2 VOC B.1.1.7. TaqPath RT-PCR assay testing can be utilized by laboratories to screen rapidly the VOC B.1.1.7 variants, thus enabling early detection of B.1.1.7 variant infection and transmission in population. This in turn will pave way to implement suitable preventive measures by appropriate authorities to control the transmission of the viral variant.


title: Molecular and clinical signatures in Acute Kidney Injury define distinct subphenotypes that associate with death, kidney, and cardiovascular events

abstract:
IntroductionAKI is a heterogeneous syndrome defined via serum creatinine and urine output criteria. However, these markers are insufficient to capture the biological complexity of AKI and not necessarily inform on future risk of kidney and clinical events.

MethodsData from ASSESS-AKI was obtained and analyzed to uncover different clinical and biological signatures within AKI. We utilized a set of unsupervised machine learning algorithms incorporating a comprehensive panel of systemic and organ-specific biomarkers of inflammation, injury, and repair/health integrated into electronic data. Furthermore, the association of these novel biomarker-enriched subphenotypes with kidney and cardiovascular events and death was determined. Clinical and biomarker concentration differences among subphenotypes were evaluated via classic statistics. Kaplan-Meier and cumulative incidence curves were obtained to evaluate longitudinal outcomes.

ResultsAmong 1538 patients from ASSESS-AKI, we included 748 AKI patients in the analysis. The median follow-up time was 4.8 years. We discovered 4 subphenotypes via unsupervised learning. Patients with AKI subphenotype 1 ( injury cluster) were older (mean age {+/-} SD): 71.2 {+/-} 9.4 (p<0.001), with high ICU admission rates (93.9%, p<0.001) and highly prevalent cardiovascular disease (71.8%, p<0.001). They were characterized by the highest levels of KIM-1, troponin T, and ST2 compared to other clusters (P<0.001). AKI subphenotype 2 ( benign cluster) is comprised of relatively young individuals with the lowest prevalence of comorbidities and highest levels of systemic anti-inflammatory makers (IL-13). AKI Subphenotype 3 ( chronic inflammation and low injury) comprised patients with markedly high pro-BNP, TNFR1, and TNFR2 concentrations while presenting low concentrations of KIM-1 and NGAL. Patients with AKI subphenotype 4 ( inflammation-injury) were predominantly critically ill individuals with the highest prevalence of sepsis and stage 3 AKI. They had the highest systemic (IL-1B, CRP, IL-8) and kidney inflammatory biomarker activity (YKL-40, MCP-1) as well as high kidney injury levels (NGAL, KIM-1). AKI subphenotype 3 and 4 were independently associated with a higher risk of death compared to subphenotype 2. Moreover, subphenotype 3 was independently associated with CKD outcomes and CVD events.

ConclusionWe discovered four clinically meaningful AKI subphenotypes with statistical differences in biomarker composites that associate with longitudinal risks of adverse clinical events. Our approach is a novel look at the potential mechanisms underlying AKI and the putative role of biomarkers investigation.

category: nephrology


title: Deficiency of U4atac snRNA secondarily results in ciliary defects

abstract: In the human genome, about 750 genes contain one intron excised by the minor spliceosome. This spliceosome comprises its own set of snRNAs, among which U4atac. Its non-coding gene, RNU4ATAC, has been found mutated in Taybi-Linder (MOPD1/TALS), Roifman (RFMN) and Lowry-Wood syndromes (LWS). These rare developmental disorders, whose physiopathological mechanisms remain unsolved, associate ante- and post-natal growth retardation, microcephaly, skeletal dysplasia, intellectual disability, retinal dystrophy and immunodeficiency. Here, we report a homozygous RNU4ATAC mutation in the Stem II domain, n.16G>A, in two unrelated patients presenting with both typical traits of the Joubert syndrome (JBTS), a well-characterized ciliopathy, and of TALS/RFMN/LWS, thus widening the clinical spectrum of RNU4ATAC-associated disorders and indicating ciliary dysfunction as a mechanism downstream of minor splicing defects. This finding is supported by alterations of primary cilium function in TALS and JBTS/RFMN fibroblasts, as well as by u4atac zebrafish model, which exhibit ciliopathy-related phenotypes and ciliary defects. Altogether, our data indicate that alteration of cilium biogenesis is part of the physiopathological mechanisms of TALS/RFMN/LWS, secondarily to defects of minor intron splicing.


title: Integrated Analyses of Growth Differentiation Factor-15 Concentration and Cardiometabolic Diseases in Humans

abstract: Growth differentiation factor 15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6,610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across 3 different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant rs1058587 in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine-mapping identified 4 independent putative causal signals at the locus. Mendelian randomisation (MR) analysis did not find evidence of a causal relationship between GDF15 concentration and cardiometabolic traits. Using reverse MR, we identified a potential causal association of body mass index on GDF15 (IVW pFDR=0.0072). Taken together, our data do not support a role for elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.

category: cardiovascular medicine


title: Modelling to infer the role of animals in gambiense human African trypanosomiasis transmission and elimination in DRC

abstract:
Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly approaching, there remain fundamental questions about the presence of non-human animal transmission cycles and their potential role in slowing progress towards, or even preventing, EoT. In this study we focus on the country with the most gHAT disease burden, the Democratic Republic of Congo (DRC), and use mathematical modelling to assess whether animals may contribute to transmission in specific regions, and if so, how their presence could impact the likelihood and timing of EoT.

By fitting two model variants - one with, and one without animal transmission - to the human case data from 2000-2016 we estimate model parameters for 158 endemic health zones of DRC. We evaluate the statistical support for each model variant in each health zone and infer the contribution of animals to overall transmission and how this could impact predicted time to EoT.

We conclude that there are 24/158 health zones where there is moderate or high statistical support for some animal transmission. However, - even in these regions - we estimate that animals would be extremely unlikely to maintain transmission on their own. Animal transmission could hamper progress towards EoT in some settings, with projections under continuing interventions indicating that the number of health zones expected to achieve EoT by 2030 reduces from 68 to 61 if animals are included in the model. With supplementary vector control (at a modest 60% tsetse reduction) added to medical screening and treatment interventions, the predicted number of health zones meeting the goal increases to 147/158 for the model including animals. This is due to the impact of vector reduction on transmission to and from all hosts.

Author summaryElimination of African sleeping sickness by 2030 is an ambitious goal, not least because of the unclear role that animals might play in transmission. We use mathematical models, fitted to case data from DRC to assess and quantify the contribution of animals to the human case burden.

We found that 24/158 geographic regions included in this study had statistical evidence of animal transmission, although it appears extremely unlikely that animals could maintain transmission on their own. Animals could, however, delay elimination; using our model without animal transmission we predicted that 68 regions are expected to achieve elimination by 2030, whereas this reduces to 61 with animals. If vector control to reduce fly populations (which transmit the disease to and from hosts) are controlled in addition to medical interventions, then 147 regions are predicted to reach elimination by 2030 even with animal transmission.


title: Childhood trajectories of internalising and externalising problems associated with a polygenic risk score for neuroticism in a UK birth cohort study

abstract:
Neuroticism represents a personality disposition towards experiencing negative emotions more frequently and intensely. Longitudinal studies suggest that neuroticism increases risk of several psychological and physical problems. Improved understanding of how this trait manifests in early life could help inform preventative strategies in those liable to neuroticism.

This study explored how a polygenic risk score (PRS) for neuroticism is expressed from infancy to late childhood across various psychological outcomes and how it associates with trajectories of internalising and externalising problems from ages 4-11 in the Avon Longitudinal Study of Parents and Children (N=5,279). We employed multivariable linear and ordinal regression models to estimate associations between a child neuroticism PRS and psychological outcomes. A three-level mixed-effect model was employed to characterise child internalising and externalising trajectories and estimate how a child PRS associated with both their overall levels and rates of change.

We found evidence that the PRS for neuroticism was associated with a more sensitive temperament in early infancy in addition to higher emotional and behavioural problems and a higher risk of being diagnosed with a variety of clinical disorders, particularly anxiety disorders, in childhood. We also found strong evidence that the PRS for neuroticism was associated with overall levels of internalising and externalising trajectories, with a larger magnitude of effect on the internalising trajectory. The PRS was also associated with slower rates of reduction of internalising problems.

Our findings using a large, well-characterised birth cohort study suggest that phenotypic manifestations of a PRS for adult neuroticism can be detected as early as in infancy and that this PRS associates with several mental health problems and differences in emotional trajectories across childhood.


title: Neurodevelopmental outcomes at one year in offspring of mothers who test positive for SARS-CoV-2 during pregnancy

abstract:
ImportanceEpidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring.

ObjectiveTo determine whether in utero exposure to the novel coronavirus SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.

DesignRetrospective cohort

ParticipantsLive offspring of all mothers who delivered between March and September 2020 at one of six Massachusetts hospitals across two health systems.

ExposureSARS-CoV-2 infection confirmed by PCR during pregnancy

Main Outcome and MeasuresNeurodevelopmental disorders determined from ICD-10 diagnostic codes over 12 months; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record.

ResultsThe cohort included 7,772 live births (7,466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean maternal age of 32.9 years; offspring were 9.9% Asian, 8.4% Black, and 69.0% white; 15.1% were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers (14% versus 8.7%; p=.003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses (crude OR 2.17 [95% CI 1.24-3.79, p=0.006]) as well as models adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR 1.86 [95% CI 1.03-3.36, p=0.04]). Third-trimester infection was associated with effects of larger magnitude (adjusted OR 2.34, 95% CI 1.23-4.44, p=0.01)

Conclusion and RelevanceOur results provide preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these effects.

Trial RegistrationNA

Key PointsO_ST_ABSQuestionC_ST_ABSDoes COVID-19 exposure in utero increase the risk for neurodevelopmental disorders in the first year of life?

FindingsIn a cohort of babies delivered during COVID-19, those born to mothers with a positive SARS-CoV-2 PCR test during pregnancy were more likely to receive a neurodevelopmental diagnosis in the first 12 months after delivery, even after accounting for preterm delivery.

MeaningThese preliminary findings suggest that COVID-19 exposure may impact neurodevelopment, and highlight the need for prospective investigation of outcomes in children exposed to COVID-19 in utero.


title: One year of child neurology telemedicine: a data-driven analysis of 14,820 encounters

abstract:
IntroductionDetermining the long-term impact of telemedicine in care across the diagnostic and age spectrum of child neurology during the COVID-19 pandemic and with the re-opening of outpatient clinics.

MethodsAn observational cohort study of 34,837 in-person visits and 14,820 telemedicine outpatient pediatric neurology visits between October 1, 2019 and April 9, 2021. We assessed differences in care across visit types, time-period observed, time between follow-ups, patient portal activation rates and demographic factors.

Results26,399 patients were observed in this study (median age 11.4 years [interquartile range, 5.5-15.9]; 13,209 male). We observed a higher proportion of telemedicine for epilepsy (ICD10 G40: OR 1.4, 95% CI 1.3-1.5) and a lower proportion for movement disorders (ICD10 G25: OR 0.7, 95% CI 0.6-0.8; ICD10 R25: OR 0.7, 95% CI 0.6-0.9). Infants were more likely to be seen in-person after re-opening clinics than by telemedicine (OR 1.6, 95% CI 1.5-1.8) as were individuals with neuromuscular disorders (OR 0.6, 95% CI 0.6-0.7). Racial and ethnic minority populations and those with highest social vulnerability had lower rates of telemedicine participation throughout the pandemic (OR 0.8, 95% CI 0.8-0.8; OR 0.7, 95% CI 0.7-0.8).

DiscussionTelemedicine implementation was followed by continued use even once in-person clinics were available. Pediatric epilepsy care can often be performed using telemedicine while young children and patients with neuromuscular disorders often require in-person assessment. Prominent barriers for socially vulnerable families and racial and ethnic minorities persist.


title: Racial disparity in distant recurrence-free survival in localized breast cancer patients: A pooled analysis of NSABP trials

abstract:
BackgroundBlack race is associated with worse outcome in patients with breast cancer. We evaluated distant relapse-free survival (DRFS) between Black and White women with localized breast cancer who participated in NCI-sponsored clinical trials.

MethodsWe analyzed pooled data from eight National Surgical Adjuvant Breast and Bowel Project (NSABP) trials including 9,702 women with localized breast cancer treated with adjuvant chemotherapy (AC, n=7,485) or neoadjuvant chemotherapy (NAC, n=2,217), who self-reported as Black (n=1,070) or White (n=8,632). The association between race and DRFS was analyzed using log-rank tests and multivariate Cox regression.

ResultsAfter adjustment for covariates including age, tumor size, nodal status, body mass index and taxane use, and treatment (AC vs. NAC), Black race was associated with an inferior DRFS in ER-positive (HR 1.24 [95% CI 1.05-1.46], p=0.01), but not in ER-negative disease (HR 0.97 [95% CI 0.83-1.14], p=0.73), and significant interaction between race and ER status was observed (p=0.03). There was no racial disparity in DRFS among patients with pathologic complete response (pCR) (Log-rank p =0.8). For patients without pCR, black race was associated with worse DRFS in ER-positive (HR 1.67 [95% CI 1.14-2.45], p=0.01), but not in ER-negative disease (HR 0.91 [95% CI 0.65-1.28], p=0.59).

ConclusionBlack race was associated with significantly inferior DRFS in ER-positive localized breast cancer treated with AC or NAC, but not in ER-negative disease. In the NAC group, racial disparity was also observed in patients with residual ER-positive breast cancer at surgery, but not in those who had a pathologic complete response.

Lay SummaryBlack women with breast cancer have worse outcome compared to White women. We investigated if this held true in the context of clinical trials which provide controlled treatment setting. Black women with cancer containing estrogen receptors (ER) had worse outcome than White women. If breast cancers did not contain ER there was no racial disparity in outcome. Moreover, we observed racial disparity in women who received chemotherapy before their cancer was removed, but only if they had cancer with ER and residual disease upon completion of treatment. If cancer disappeared upon pre-surgical chemotherapy, there was no racial disparity.


title: The Michigan Genomics Initiative: a biobank linking genotypes and electronic clinical records in Michigan Medicine patients

abstract: The recent wave of biobank repositories linking individual-level genetic data with dense clinical health history has introduced a dramatic paradigm shift in phenotyping for human genetic studies. The mechanism by which biobanks recruit participants can vary dramatically according to factors such as geographic catchment and sampling strategy. These enrollment differences leave an imprint on the cohort, defining the demographics and the utility of the biobank for research purposes. Here we introduce the Michigan Genomics Initiative (MGI), a rolling enrollment, single health system biobank currently consisting of >85,000 participants recruited primarily through surgical encounters at Michigan Medicine. A strong ascertainment effect is introduced by focusing recruitment on individuals in Southeast Michigan undergoing surgery. MGI participants are, on average, less healthy than the general population, which produces a biobank enriched for case counts of many disease outcomes, making it well suited for a disease genetics cohort. A comparison to the much larger UK Biobank, which uses population representative sampling, reveals that MGI has higher prevalence for nearly all diagnosis- code-based phenotypes, and larger absolute numbers of cases for many phenotypes. GWAS of these phenotypes replicate many known findings, validating the genetic and clinical data and their proper linkage. Our results illustrate that single health-system biobanks that recruit participants through opportunistic sampling, such as surgical encounters, produce distinct patient profiles that provide an ideal resource for exploring the genetics of complex diseases.


title: Decreased retinal vascular complexity is an early biomarker of MI supported by a shared genetic control.

abstract: There is increasing evidence that the complexity of the retinal vasculature (measured as fractal dimension, Df) might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present here a genome-wide association study (GWAS) aimed to elucidate the genetic component of Df and to analyse its relationship with CAD. To this end, we obtained Df from retinal fundus images and genotyping information from [~]38,000 white-British participants in the UK Biobank. We discovered 9 loci associated with Df, previously reported in pigmentation, retinal width and tortuosity, hypertension, and CAD studies. Significant negative genetic correlation estimates endorse the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD fatal outcomes. This strong association motivated us to developing a MI predictive model combining clinical information, Df, a CAD polygenic risk score and using a random forest algorithm. Internal cross validation evidenced a considerable improvement in the area under the curve (AUC) of our predictive model (AUC=0.770) when comparing with an established risk model, SCORE, (AUC=0.719). Our findings shed new light on the genetic basis of Df, unveiling a common control with CAD, and highlights the benefits of its application in individualised MI risk prediction.

category: health informatics


title: Towards long term monitoring: Seizure detection with reduced electroencephalogram channels

abstract: Epilepsy is a prevalent condition characterised by recurrent, unpredictable seizures. The diagnosis of epilepsy is by surface electroencephalography (EEG), a time-consuming and uncomfortable process for patients. The diagnosis of seizures using EEG over a brief monitoring period has variable success, dependent on patient tolerance and seizure frequency. Further, the availability of hospital resources, and hardware and software specifications inherently limit the capacity to perform long-term data collection whilst maintaining patient comfort. The application and maintenance of the standard number of electrodes restrict recording time to a maximum of approximately ten days. This limited monitoring period also results in limited data for machine learning models for seizure detection and classification. This work examines the literature on the impact of reduced electrodes on data accuracy and reliability in seizure detection. We present two electrode ranking models that demonstrate the decline in seizure detection performance associated with reducing electrodes. We assert the need for further research in electrode reduction to advance solutions toward portable, reliable devices that can simultaneously provide patient comfort, long-term monitoring and contribute to multimodal patient care solutions.

category: health systems and quality improvement


title: HIV Phylogenetics Reveals Overlapping Transmission Networks among Cities and Key Populations in Pakistan

abstract: The first case of HIV in Pakistan was documented in 1987, with multiple subtypes and circulating recombinant forms being introduced and currently circulating in the country. Since then, there has been a shift in the country from a low prevalence/high risk to a high-risk concentrated epidemic. Pakistans epidemic is concentrated among key populations at greater risk of HIV infection including people who inject drugs (PWID), Hijra sex workers (HSW), female sex workers (FSW), male sex workers (MSW), and men who have sex with men (MSM). This study focused on the geographical aspect as well as on the interactions between key populations at higher risk of contracting HIV. We aimed at understanding the behavior of these key populations at a molecular level with high granularity as well as investigating the possibility of multiple HIV-1 introductions in Pakistan. In this cross-sectional biological and behavioral survey, we collected dried blood spots (DBS) for the purposes of seroprevalence estimates and molecular epidemiology from individuals in 17 cities in Pakistan representing four key populations: PWID, HSW, MSW, and FSW. A total of 1153 envelope sequences (reference positions in HXB2: 7860-8274) of HIV were sequenced using a Sanger-based sequencing approach. To identify clusters based on the introduction of the virus in Pakistan from foreign countries we added 3623 publicly available HIV envelope sequences to our dataset. Phylogeographic inference suggests at least 15 independent introductions of the virus into Pakistan, with a total of 12 clusters ranging from 3 to 675 sequences in size containing sequences from Pakistan and neighboring countries exclusively. Our phylogenetic analysis shows a significant degree of connectivity and directionality suggesting broad and overlapping networks of HIV-1 transmission among cities and key populations in Pakistan.


title: Efficient control of IL-6, CRP and Ferritin in Covid-19 patients with two variants of Beta-1,3-1,6 glucans in combination, within 15 days in an open-label prospective clinical trial

abstract:
ObjectiveIn this study, we evaluated the efficiency of the combination of two variants AFO-202 and N-163 strains of Aureobasidium Pullulans produced in comparison with the control arm, which underwent a conventional regimen of treatment alone, for a shorter duration of 15 days.

MethodsA total of 40 RT-PCR positive Covid-19 patients divided into two groups (Gr): Gr. 1 control (n=22) - Standard treatment; Gr. 2 (n =18) - Standard treatment + combination of AFO-202 and N-163 beta glucans for 15 days. Biomarkers of relevance to cytokine storm and coagulopathy were evaluated at baseline on Day 7 and Day 15.

ResultsThe C-reactive protein (CRP), which declined from 33.95 mg/l to 5.07 mg/l in control and from 33.95 mg/l to 5.64 mg/l in the treatment arm on Day 7, increased to 14.6 mg/l in the former while it continued to be under control in the treatment arm at 5.68 mg/l on Day 15. The same trend was observed in Ferritin, whose values were 560.58 ng/ml at baseline to 261.44 ng/ml (day-7) and 182.40 ng/ml (day-15) in the treatment group, while it was 535.24 ng/ml at baseline, 116.66 ng/ml on day 7 and 291.95 ng/ml on day 15 in the control group. IL-6 showed a higher decrease in treatment group compared to the control group. The difference between day 7 and day 15 values were statically significant.

ConclusionA statistically significant control of IL-6, CRP and Ferritin in Covid-19 patients who orally consumed AFO-202 and N-163 strains of Aureobasidium Pullulans produced Beta glucans together in 15 days make us recommend this safe food supplement be consumed by Covid-19 patients along with conventional treatments, especially to the vulnerable population, as a prophylaxis amidst the prolonged pandemic with evolution of mutated strains of SARS-COV2.


title: Impact of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority on Disease Dynamics. Implications for SARS-CoV-2

abstract:
BackgroundThe speed of vaccine development has been a singular achievement during the SARS-CoV-2 pandemic, though uptake has not been universal. Vaccine opponents often frame their opposition in terms of the rights of the unvaccinated. Our objective was to explore the impact of mixing of vaccinated and unvaccinated populations on risk among vaccinated individuals.

MethodsWe constructed a simple Susceptible-Infectious-Recovered (SIR) compartmental model of a respiratory infectious disease with two connected sub-populations: vaccinated individuals and unvaccinated individuals. We simulated a spectrum of patterns of mixing between vaccinated and unvaccinated groups that ranged from random mixing to like-with-like mixing (complete assortativity), where individuals preferentially have contact with others with the same vaccination status. We evaluated the dynamics of an epidemic within each subgroup, and in the population as a whole.

ResultsThe relative risk of infection was markedly higher among unvaccinated individuals than among vaccinated individuals. However, the contact-adjusted contribution of unvaccinated individuals to infection risk during the epidemic was disproportionate, with unvaccinated individuals contributing to infections among the vaccinated at a rate higher than would have been expected based on contact numbers alone. As assortativity increased, attack rates among the vaccinated decreased, but the contact-adjusted contribution to risk among vaccinated individuals derived from contact with unvaccinated individuals increased.

InterpretationWhile risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to the unvaccinated, the choices of unvaccinated individuals impact the health and safety of vaccinated individuals in a manner disproportionate to the fraction of unvaccinated individuals in the population.


title: Genomic and Virological Characterization of SARS-CoV-2 Variants in a Subset of Unvaccinated and Vaccinated U.S. Military Personnel

abstract:
The emergence of SARS-CoV-2 variants complicates efforts to control the COVID-19 pandemic. Increasing genomic surveillance of SARS-CoV-2 is imperative for early detection of emerging variants, to trace the movement of variants, and to monitor effectiveness of countermeasures. Additionally, determining the amount of viable virus present in clinical samples is helpful to better understand the impact these variants have on viral shedding. In this study, we analyzed nasal swab samples collected between March 2020 and early November 2021 from a cohort of United States (U.S.) military personnel and healthcare system beneficiaries stationed worldwide as a part of the Defense Health Agencys (DHA) Global Emerging Infections Surveillance (GEIS) program. SARS-CoV-2 quantitative real time reverse-transcription PCR (qRT-PCR) positive samples were characterized by next-generation sequencing and a subset was analyzed for isolation and quantification of viable virus. Not surprisingly, we found that the Delta variant is the predominant strain circulating among U.S. military personnel beginning in July 2021 and primarily represents cases of vaccine breakthrough infections (VBIs). Among VBIs, we found a 50-fold increase in viable virus in nasal swab samples from Delta variant cases when compared to cases involving other variants. Notably, we found a 40-fold increase in viable virus in nasal swab samples from VBIs involving Delta as compared to unvaccinated personnel infected with other variants prior to the availability of approved vaccines. This study provides important insight about the genomic and virological characterization of SARS-CoV-2 isolates from a unique study population with a global presence.

ImpactThe COVID-19 pandemic is currently a leading cause of death globally and new SARS-CoV-2 variants continue to emerge. Genomic surveillance of variants is necessary to characterize mutations that could affect transmissibility and spread, antigenicity or virulence. Furthermore, wet lab studies are necessary to evaluate how genetic differences may affect viral fitness and transmissibility. The Delta variant is currently the predominant strain globally and determining factors that drive its ability to spread rapidly is important. In this study, we characterized SARS-CoV-2 positive samples from U.S. military personnel and their beneficiaries by next-generation sequencing and isolation of viable virus. Consistent with other studies, we found higher levels of infectious virus from Delta samples when compared to non-Delta infections. Strikingly, we found the difference in titer between Delta and other strains to be so profound as to be unaffected by vaccination status, suggesting that increased transmissibility of the Delta variant is in part due to higher amounts of virus shedding. This helps explain the rapid spread of the Delta variant and provides the impetus to increase control measures such as vaccination, boosters, masking and distancing requirements. It will be necessary to continue genomic and virological characterization of new variants, such as Omicron.


title: Machine learning identified distinct serum lipidomic signatures in hospitalized COVID-19-positive and COVID-19-negative patients

abstract:
BackgroundLipids are involved in the interaction between viral infection and the host metabolic and immunological response. Several studies comparing the lipidome of COVID-19-positive hospitalized patients vs. healthy subjects have already been reported. It is largely unknown, however, whether these differences are specific to this disease. The present study compared the lipidomic signature of hospitalized COVID-19-positive patients with that of healthy subjects, and with COVID-19-negative patients hospitalized for other infectious/inflammatory diseases. Potential COVID-19 biomarkers were identified.

MethodsWe analyzed the lipidomic signature of 126 COVID-19-positive patients, 45 COVID-19-negative patients hospitalized with other infectious/inflammatory diseases and 50 healthy volunteers. Results were interpreted by machine learning.

ResultsWe identified acylcarnitines, lysophosphatidylethanolamines, arachidonic acid and oxylipins as the most altered species in COVID-19-positive patients compared to healthy volunteers. However, we found similar alterations in COVID-19-negative patients. By contrast, we identified lysophosphatidylcholine 22:6-sn2, phosphatidylcholine 36:1 and secondary bile acids as the parameters that had the greatest capacity to discriminate between COVID-19-positive and COVID-19-negative patients.

ConclusionThis study shows that COVID-19 infection shares many lipid alterations with other infectious/inflammatory diseases, but differentiating them from the healthy population. Also, we identified some lipid species the alterations of which distinguish COVID-19-positive from Covid-19-negative patients. Our results highlight the value of integrating lipidomics with machine learning algorithms to explore the pathophysiology of COVID-19 and, consequently, improve clinical decision making.


title: The role of sub-genomic RNA in discordant results from RT-PCR tests for COVID-19.

abstract:
Reverse transcription-PCR (RT-PCR) is the standard method of diagnosing COVID-19. An inconclusive test result occurs when one RT-PCR target is positive for SARS-CoV-2 and one RT-PCR target is negative within the same sample. An inconclusive result generally requires retesting. One reason why a sample may yield an inconclusive result is that one target is at a higher concentration than another target. It was hypothesized that concentration differences across targets may be due to the transcription of sub-genomic RNA, as this would result in an increase in the concentration of gene targets near the 3 end of the SARS-CoV-2 genome. A panel of six digital droplet (dd)PCR assays was designed to quantitate the ORF1, E-gene, and N-gene of SARS-CoV-2. This panel was used to quantify viral cultures of SARS-CoV-2 that were harvested during the eclipse phase and at peak infectivity in such a way as to maximize gene-to-gene copy ratios. Eleven clinical nasopharyngeal swabs were also tested with this panel. In culture, infected cells showed higher N-gene/ORF1 copy ratios than culture supernatants. Both the highest specific infectivity (copies/pfu) and the highest differences between gene targets were observed at 6 hours post-infection (eclipse phase) in infected cells. The same trends in the relative abundance of copies across different targets observed in infected cells was observed in clinical samples, though trends were more pronounced in infected cells. This study showed that a greater copy number of N-gene relative to E-gene and ORF1 transcripts could potentially explain inconclusive results for some RT-PCR tests on low viral load samples. The use of N-gene RT-PCR target(s) as opposed to ORF1 targets for routine testing is supported by this data.

Author SummaryThis paper provides insight into a drawback of the standard method of testing for COVID-19 (RT-PCR). The results presented here propose an explanation for why inconclusive results sometimes occur with this method. These results can aid microbiologists in the interpretation of inconclusive test results. These results can also aid in decisions about which COVID-19 test a laboratory should use, as there are a plethora of options available. This is important because this standard testing method will remain a critical tool - globally - for managing the COVID-19 pandemic and any future viral pandemics and epidemics. Thus, it is important to investigate every facet of the testing method. The findings presented here are applicable to any virus which makes sub-genomic transcripts as part of its life cycle. Trends observed in viral cultures are presented alongside the same trends observed in clinical samples. Unlike similar papers in the field, this paper did not strive to develop a new methodology or tool.


title: Analytical Solution of a New SEIR Model Based on Latent Period-Infectious Period Chronological Order

abstract: The Susceptible-Infectious-Recovered (SIR) and SIR derived epidemic models have been commonly used to analyze the spread of infectious diseases. The underlying assumption in these models, such as Susceptible-Exposed-Infectious-Recovered (SEIR) model, is that the change in variables E, I or R at time t is dependent on a fraction of E and I at time t. This means that after exposed on a day, this individual may become contagious or even recover on the same day. However, the real situation is different: an exposed individual will become infectious after a latent period (l) and then recover after an infectious period (i). In this study, we proposed a new SEIR model based on the latent period-infectious period chronological order (Liu X., Results Phys. 2021; 20:103712). An analytical solution to equations of this new SEIR model was derived. From this new SEIR model, we obtained a propagated curve of infectious cases under conditions l>i. Similar propagated epidemic curves were reported in literature. However, the conventional SEIR model failed to simulate the propagated epidemic curves under the same conditions. For l<i, the new SEIR models generated bell-shaped curves for infectious cases, and the curve is near symmetrical to the vertical line passing the curve peak. This characteristic can be found in many epidemic curves of daily COVID-19 cases reported from different countries. However, the curve generated from the conventional SEIR model is a right-skewed bell-shaped curve. An example for applying the analytical solution of the new SEIR model equations to simulate the reported daily COVID-19 cases was also given in this paper.


title: Estimating the population-level effects of Ontario's overdose prevention sites and consumption and treatment services: interrupted time series analysis with synthetic controls

abstract:
BackgroundOntario recently implemented overdose prevention sites and consumption and treatment services (OPS/CTS) to stem the harms of the opioid epidemic. We tested whether operating any site improved local opioid-related health service use and mortality rates.

MethodsWe used monthly counts of all opioid-related emergency department (ED) visits, hospitalizations, and deaths between January 2014 and December 2020 for our outcomes. For each public health unit (PHU) that implemented any OPS/CTS, we created a synthetic control as a weighted combination of unexposed PHU. We estimated the population-level effects of operating any site using controlled interrupted time series with segmented regression and adjusted for time varying confounders (i.e. OPS/CTS capacity, naloxone kits distributed, and persons receiving opioid agonist treatment per 100,000 population). We repeated the analysis using a multiple baseline approach to estimate province-wide effects.

ResultsBetween 2017 and 2020, nine out of 34 PHU implemented at least one OPS/CTS. ED visit (RR=0.96, 95%CI: 0.92 - 0.99) and hospitalization (RR=0.95, 95%CI: 0.92 - 0.98) trends declined faster among treated units. Improvements in local ED visit rate trends were observed for the majority of treated units. Hospitalization rates declined faster for London (RR=0.97, 95%CI: 0.95 - 0.99) and Niagara (RR=0.95, 95%CI: 0.92 - 0.98); while mortality rates declined faster for Hamilton (RR=0.93, 95%CI: 0.90 - 0.96), Niagara (RR=0.97, 95%CI: 0.94 - 0.99) and Guelph (RR=0.94, 95%CI: 0.88 - 1.00).

ConclusionAlthough OPS/CTS are not sufficient to stem the harms of the opioid overdose epidemic on their own, they play a critical role in local harm reduction strategies.

category: addiction medicine


title: Using controlled interrupted time series to estimate the population-level effects of Ontario's recently implemented overdose prevention sites and consumption and treatment services


title: Adherence to the EAT-Lancet diet and risk of incident type 2 diabetes: the Danish Diet, Cancer and Health cohort

abstract:
ObjectiveIn 2019 the EAT-Lancet Commission proposed a dietary pattern, defined to be globally environmentally sustainable, but untested directly in population studies with regards to health. We investigated adherence to the EAT-Lancet diet and risk of incident type 2 diabetes in a Danish setting.

Research design and methodsIn total, 54,232 participants aged 50-64 years at inclusion (1993-1997) with no previous cancer or diabetes diagnoses were included. Dietary data were collected using a validated 192-item food frequency questionnaire, and scored 0 (non-adherence) or 1 (adherence) point for each of the 14 dietary components of the EAT-Lancet diet (range 0-14 points). Incident type 2 diabetes cases were identified using the Danish National Diabetes Register. Hazard ratios and 95% confidence intervals (CI) were estimated using multivariable-adjusted Cox proportional hazards models.

ResultsDuring follow-up (median 15 years), 7130 participants developed type 2 diabetes. There was a 22% (95% CI: 14%; 29%) lower risk of type 2 diabetes among those with the greatest adherence to the EAT-Lancet diet (11-14 points) compared to those with the lowest adherence (0-7 points). After further adjusting for potential mediators, the corresponding risk was 17% (95% CI: 8%; 24%) lower.

ConclusionAdherence to the EAT-Lancet diet was associated with a lower risk of developing type 2 diabetes in a middle-aged Danish population.


title: Workplace Contact Patterns in England during the COVID-19 Pandemic: Analysis of the Virus Watch prospective cohort study

abstract:
BackgroundWorkplaces are an important potential source of SARS-CoV-2 exposure; however, investigation into workplace contact patterns is lacking. This study aimed to investigate how workplace attendance and features of contact varied between occupations and over time during the COVID-19 pandemic in England.

MethodsData were obtained from electronic contact diaries submitted between November 2020 and November 2021 by employed/self-employed prospective cohort study participants (n=4,616). We used mixed models to investigate the main effects and potential interactions between occupation and time for: workplace attendance, number of people in shared workspace, time spent sharing workspace, number of close contacts, and usage of face coverings.

FindingsWorkplace attendance and contact patterns varied across occupations and time. The predicted probability of intense space sharing during the day was highest for healthcare (78% [95% CI: 75-81%]) and education workers (64% [59%-69%]), who also had the highest probabilities for larger numbers of close contacts (36% [32%-40%] and 38% [33%-43%] respectively). Education workers also demonstrated relatively low predicted probability (51% [44%-57%]) of wearing a face covering during close contact. Across all occupational groups, levels of workspace sharing and close contact were higher and usage of face coverings at work lower in later phases of the pandemic compared to earlier phases.

InterpretationMajor variations in patterns of workplace contact and mask use are likely to contribute to differential COVID-19 risk. Across occupations, increasing workplace contact and reduced usage of face coverings presents an area of concern given ongoing high levels of community transmission and emergence of variants.


title: Development and Validation of Suspicious Liver Lesion Deep Learning Algorithm for Computed Tomography

abstract: In this work, we report the results of a deep-learning based liver lesion detection algorithm. While several liver lesion segmentation and classification algorithms have been developed, none of the previous work has focused on detecting suspicious liver lesions. Furthermore, their generalizability remains a pitfall due to their small sample size and sample homogeneity. Here, we developed and validated a highly generalizable deep-learning algorithm for detection of suspicious liver lesions. The algorithm was trained and tested on a diverse dataset containing CT exams from over 2,000 hospital sites in the United States. Our final model achieved an AUROC of 0.84 with a specificity of 0.99 while maintaining a sensitivity of 0.33.

category: radiology and imaging


title: Development of a Natural Language Processing Algorithm for the Classification of Suspicious Liver Lesions from Radiology Reports

abstract: Here, we developed and validated a highly generalizable natural language processing algorithm based on deep-learning. Our algorithm was trained and tested on a highly diverse dataset from over 2,000 hospital sites and 500 radiologists. The resulting algorithm achieved an AUROC of 0.96 for the presence or absence of liver lesions while achieving a specificity of 0.99 and a sensitivity of 0.6.


title: Change in the trend of long-term care service usage following COVID-19 pandemic in Japan: a survey using nationwide statistical summary in 2018-2021

abstract:
AimSocial restriction due to coronavirus disease 2019 (COVID-19) pandemic forced long-term care (LTC) service users to refrain from using services as before, of which degree of change we aim to evaluate in this study.

MethodsWe retrospectively analyzed publicly-distributed nationwide statistics summarizing the monthly number of public LTC insurance users in Japan in the period between April 2018 and March 2021. The degree of decline was quantified as odds ratio (OR), where the ratio of a certain month to the reference month was divided by the ratio in the previous year.

ResultsThe use of LTC services showed unimodal serial change: it started to decline in March 2020 and reached its largest decline in May 2020, which had insufficiently recovered even as of late 2020. The degree of decline was specifically large in services provided in facilities for community-dwelling elderly individuals (adjusted OR 0.719 (95%CI: 0.664 [~] 0.777) in short-stay services and adjusted OR 0.876 (95%CI: 0.820 [~] 0.935) in outpatient services) but was non-significant in other types of service, including those provided for elderly individuals living in nursing homes.

ConclusionsCurrent study showed that community-dwelling elderly individuals who had used outpatient or short-stay services were the segments which were specifically affected by the COVID-19 pandemic in 2020 Japan. It underlines the need for further investigation for the medium- or long-term influence on the mental and physical health of these LTC service users as well as their family caregivers.

category: geriatric medicine


title: Waning of mRNA-1273 vaccine effectiveness against SARS-CoV-2 infection in Qatar

abstract:
BACKGROUNDIn early 2021, Qatar launched a mass immunization campaign with Modernas mRNA-1273 COVID-19 vaccine. We assessed persistence of real-world mRNA-1273 effectiveness against SARS-CoV-2 infection and against COVID-19 hospitalization and death.

METHODSEffectiveness was estimated using test-negative, case-control study design, between January 1 and December 5, 2021. Effectiveness was estimated against documented infection (a PCR-positive swab, regardless symptoms), and against any severe (acute-care hospitalization), critical (ICU hospitalization), or fatal COVID-19.

RESULTSBy December 5, 2021, 2,962 breakthrough infections had been recorded among those who received two mRNA-1273 doses. Of these infections, 19 progressed to severe COVID-19 and 4 to critical, but none to fatal disease. mRNA-1273 effectiveness against infection was negligible for the first two weeks after the first dose, increased to 65.5% (95% CI: 62.7-68.0%) 14 or more days after the first dose, and reached its peak at about 90% in the first three months after the second dose. Effectiveness declined gradually starting from the fourth month after the second dose and was below 50% by the 7th month after the second dose. Effectiveness against severe, critical, or fatal COVID-19 reached its peak at essentially 100% right after the second dose, and there was no evidence for declining effectiveness over time. Effectiveness against symptomatic versus asymptomatic infection demonstrated the same pattern of waning, but effectiveness against symptomatic infection was consistently higher than that against asymptomatic infection and waned more slowly.

CONCLUSIONSmRNA-1273-induced protection against infection appears to wane month by month after the second dose. Meanwhile, protection against hospitalization and death appears robust with no evidence for waning for several months after the second dose.


title: Evaluation of SARS-CoV-2 Antibody Point of Care Devices in the Laboratory and Clinical Setting

abstract:
SARS-CoV-2 Antibody tests have been marketed to diagnose previous SARS-CoV-2 infection and as a test of immune status. There is a lack of evidence on the performance and clinical utility of these tests. We aimed to carry out an evaluation of 14 point of care (POC) SARS-CoV-2 antibody tests.

Serum from participants with previous RT-PCR (Real-Time Polymerase chain reaction) confirmed SARS-CoV-2 infection and pre-pandemic controls were used to determine specificity and sensitivity of each POC device. Changes in sensitivity with increasing time from infection were determined on a cohort of participants. Corresponding neutralising antibody status was measured to establish whether the detection of antibodies by the POC device correlated with immune status. Paired capillary and serum samples were collected to ascertain whether POC devices performed comparably on capillary samples.

Sensitivity and specificity varied between the POC devices and in general did not meet the manufacturers reported performance characteristics signifying the importance of independent evaluation of these tests. The sensitivity peaked at >20 days following symptoms onset however sensitivity of 3 POC devices evaluated at extended time points showed that sensitivity declined with time and this was particularly marked at >140 days post infection onset. This is relevant if the tests are to be used for sero-prevelence studies. Neutralising antibody data showed positive antibody results on POC devices did not necessarily confer high neutralising antibody titres and these POC devices cannot be used to determine immune status to the SARS-CoV-2 virus. Comparison of paired serum and capillary results showed that there was a decline in sensitivity using capillary blood. This has implications in the utility of the test as they are designed to be used on capillary blood by the general population.

category: pathology


title: Forecasting COVID-19 infection trends in the EU-27 countries, the UK and Switzerland due to SARS-CoV-2 Variant of Concern Omicron

abstract:
BackgroundOn November 26, 2021, WHO designated the variant B.1.1.529 as a new SARS-CoV-2 variant of concern (VoC), named Omicron, originally identified in South Africa. Several mutations in Omicron indicate that it may have an impact on how it spreads, resistance to vaccination, or the severity of illness it causes.

MethodsWe used our previous modelling algorithms to forecast the spread of Omicron aggregated in the EU-27 countries, the United Kingdom and Switzerland, and report trends in daily cases with a 7-day moving average. We followed EQUATORs TRIPOD guidance for multivariable prediction models. Modelling included a third-degree polynomial curve in existing epidemiological trends on the spread of Omicron in South Africa, a five-parameter logistic (5PL) asymmetrical sigmoidal curve following a parametric growth in Europe, and a new Gaussian curve to estimate a downward trend after a peak.

ResultsUp to January 15, 2022, we estimated a background rate projection in EU-27 countries, the UK and Switzerland of about 145,000 COVID-19 daily cases without Omicron, which increases up to 440,000 COVID-19 daily cases in the worst scenario of Omicron spread, and 375,000 in the "best" scenario. Therefore, Omicron might represent a relative increase from the background daily rates of COVID-19 infection in Europe of 1.03-fold or 2.03-fold, that is up to a 200% increase.

ConclusionThis warning pandemic surge due to Omicron is calling for further reinforcing of COVID-19 universal hygiene interventions (indoor ventilation, social distance, and face masks), and anticipating the need of new lockdowns in Europe.

category: respiratory medicine


title: Epidemiological analysis of hospitalized cases of COVID-19 in in-digenous people in an Amazonian region: cross-sectional study with data from the surveillance of acute and severe respiratory syn-dromes in Brazil

abstract: Indigenous people are considered more vulnerable to new infectious agents. In view of the novel coronavirus causing COVID-19, health authorities are concerned about the possible impact of the pandemic on reaching vulnerable populations, such as the indigenous people of the Brazilian Amazon. Thus, we aimed to carry out an epidemiological analysis of serious cases and deaths from COVID-19 in indigenous population in the state of Para, Brazil. The data was obtained from the public Ministry of Health platform. Data analysis was performed using the Statistical Package for the Social Sciences 20, Chi-square of adherence, the independence test and G test. For spatial distribution was used ArcGIS. We observed 123 COVID-19 cases: 46 deaths (37.40%), male gender (76-61.79%), age above 60 years (61-49.6%), the most frequent risk factor was chronic cardiovascular disease (18-14.63%). The predictors of death were: invasive ventilation has (10.73) more chances for the outcome death, those not vaccinated against influenza have (3.41) and age (1.4). COVID-19 occurrence was higher in municipalities that have villages with health care or commerce, or with migrants from the Warao ethnic group. Notifications should take into consideration the specific issues of indigenous people so that effective control measures can be defined.


title: Metagenome-wide association study of gut microbiome features for myositis

abstract:
ObjectiveThe clinical relevance and pathogenic role of gut microbiome in both myositis and its associated interstitial lung disease (ILD) are still unclear. The purpose of this study was to investigate the role of gut microbiome in myositis through comprehensive metagenomic-wide association studies (MWAS).

MethodsWe conducted MWAS of the myositis gut microbiome in a Chinese cohort by using whole-genome shotgun sequencing of high depth, including 30 myositis patients and 31 healthy controls (HC). Among the myositis patients, 11 developed rapidly progressive interstitial lung disease (RP-ILD) and 10 had chronic ILD (C-ILD). Our MWAS consisted of both overall distribution level of the bacteria analysis and pathway analysis. Receiver operating characteristic curve (ROC) analysis was performed to identify novel gut bacterial species associated with myositis or myositis-associated RP-ILD, and to evaluate their diagnostic values.

ResultsApparent discrepancy in {beta} diversities of metagenome was found in the comparison of myositis and HC, RP-ILD and C-ILD in myositis. Analysis for overall distribution level of the bacteria showed Alistipes onderdonkii, Parabacteroides distasonis and Escherichia coli were upregulated, Lachnospiraceae bacterium GAM79, Roseburia intestinalis, and Akkermansia muciniphila were downregulated in patients with myositis compared to HC. Bacteroides thetaiotaomicron, Parabacteroides distasonis and Escherichia coli were upregulated, Bacteroides A1C1 and Bacteroides xylanisolvens were downregulated in RP-ILD cases compared with C-ILD cases. A variety of biological pathways related to metabolism were enriched in the myositis and HC, RP-ILD and C-ILD comparison. And in the analyses for microbial contribution in metagenomic biological pathways, we have found that E. coli played an important role in the pathway expression in both myositis group and myositis-associated RP-ILD group. Anti-PL-12 antibody, anti-Ro-52 antibody, and anti-EJ antibody were found to have positive correlation with bacterial diversity (Shannon-wiener diversity index and Chao1, richness estimator) between myositis group and control groups. The combination of E. coli and R. intestinalis could distinguish myositis group from Healthy controls effectively. R. intestinalis can also be applied in the distinguishment of RP-ILD group vs. C-ILD group in myositis paitents.

ConclusionOur MWAS study first revealed the link between gut microbiome and pathgenesis of myositis, which may help us understand the role of gut microbiome in the etiology of myositis and myositis-associated RP-ILD.

category: rheumatology


title: Changing of therapeutic trends between the 1st and 2nd wave did not reduce COVID-19 related mortality of renal transplant recipients: a national registry study.

abstract:
SARS-CoV-2 pandemic evolved in two consecutive waves over 2020 (for France: 1st wave from March 1 to July 31; and 2nd wave from August 1 to December 31). Improvements in the management of COVID-19 led to a reduction of mortality rates in hospitalized patients during the second wave. Whether this progress also benefited to kidney transplant recipients (KTR), a population particularly vulnerable to severe COVID-19, remained unclear.

In France, 957 KTR were hospitalized for COVID-19 in 2020 and their data were prospectively collected in the French SOT COVID registry. The presentation, management, and outcomes of the 359 KTR diagnosed during the 1st wave were compared to those of the 598 of the 2nd wave. Baseline comorbidities were largely similar between KTR of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs 58.4%, p<0.001) or CNI (32.1% vs 16.6%, p<0.001) was less frequent during the 2nd wave. Hydroxychloroquine and azithromycin that were commonly used during the 1st wave (21.7% and 30.9%, respectively) were almost abandoned during the 2nd. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, p<0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, p=0.48).

We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality in KTR. Our data indirectly support the importance of vaccination and monoclonal neutralizing anti-SARS-CoV-2 antibodies to protect KTR from severe COVID-19.

category: transplantation


title: Tele-Rapid Response Team (Tele-RRT): Implementation and outcomes of Safety Network System. Before and after cohort study.

abstract:
BackgroundRapid Response Teams were developed to provide interventions for deteriorating patients. Their activation depends on timely detection of deterioration. Automated calculation of warning signs may lead to early recognition, and improvement of RRT effectiveness.

MethodThis was a "Before" and "After" study, in the "Before" period ward nurses activated RRT after manually recording vital signs and calculating warning scores. In the "After" period, vital signs and warning calculations were automatically relayed to RRT through a wireless monitoring network.

ResultsThe "After" group had significantly lower incidence and rates of cardiopulmonary resuscitation compared to the "Before" group (2.3 / 1000 inpatient days versus 3.8 / 1000 inpatient days respectively, p = 0.01), the "Before" group had a significantly higher hospital length of stay, and significantly fewer visits by the RRT. In multivariable logistic regression model, being in the "After" group decreases odds of CPR by 30% (OR = 0.7 [95% CI: 0.44 - 0.97]; p = 0.02). There was no difference between groups in unplanned ICU admission or readmission.

ConclusionAutomated activation of the RRT resulted in significant reduction of CPR events and rate, reduction of hospital length of stay, and increase in the number of visits by the RRT. There was no difference in unplanned ICU admission or readmission.