title: Longitudinal changes and key determinants of meeting WHO recommended levels of physical activity during the COVID-19 pandemic in a UK-based sample: Findings from the HEBECO Study.

abstract:
BackgroundThe COVID-19 pandemic has seen government enforced restrictions on movement, with  stay-at-home orders in place for a second and third time in many nations. Such restrictions have altered physical activity (PA) habits. This study aimed to evaluate longitudinal trends in PA in a self-selected UK-based sample and the key predictors of these trends.

MethodsFrom 23 April 2020 to 30 January 2021, an online survey collected detailed measures of PA engagement in a sample of 1,947 UK-based adults. Generalised estimating equations (GEE) were fitted to explore trends in PA engagement over time, and how sociodemographic, health, lifestyle and contextual factors impacted participants attainment of Word Health Organisation (WHO) recommended levels of PA (constituting muscle strengthening activity (MSA), and moderate or vigorous PA (MVPA)).

ResultsAttainment of WHO recommended levels of total PA showed a decline. While one in five achieved the recommended levels of total PA in the first UK lockdown in April-June 2020 (19.5%, 95%, CI 17.8-21.3%) and a similar proportion in June-July 2020 (17.7%, 95%CI 16.1-19.5%), this reduced significantly during the period of eased restrictions in August-September 2020 (15.2%, 95%CI 13.7-16.9%) and the second UK lockdown in November 2020-January 2021 (14.1%, 95%CI 12.6-15.9%). The same trends were observed for MSA and MVPA individually. Better quality of life, higher socioeconomic position and higher pre-COVID-19 PA levels were associated with meeting WHO recommended PA levels, while having overweight or obesity, a limiting chronic health condition, or being in strict isolation showed the inverse associations. Time-specific associations with MSA or MVPA were observed for gender, age, ethnicity, and other health behaviours.

ConclusionAmong a self-selected sample of UK-based adults, there were reductions in PA levels throughout the first UK lockdown without reversal during the ensuing period. Based on observed associations of reduced PA with socioeconomic and health-related indices, such changes may point towards deepening health inequities during the pandemic.


title: The importance of the population age-structure: insights from Covid-19 dynamics model structured by age, time since infection and acquired immunity

abstract: The Covid-19 pandemic outbreak was followed by a huge amount of modelling studies in order to rapidly gain insights to implement the best public health policies. Most of these compartmental models involved ordinary differential equations (ODEs) systems. Such a formalism implicitly assumes that the time spent in each compartment does not depend on the time already spent in it, which is at odds with the clinical data. To overcome this "memoryless" issue, a widely used solution is to increase and chain the number of compartments of a unique reality (e.g. have infected individual move between several compartments). This allows for greater heterogeneity and thus be closer to the observed situation, but also tends to make the whole model more difficult to apprehend and parameterize. We develop a non-Markovian alternative formalism based on partial differential equations (PDEs) instead of ODEs, which, by construction, provides a memory structure for each compartment thereby allowing us to limit the number of compartments. We apply our model to the French 2021 SARS-CoV-2 epidemic and, while accounting for vaccine-induced and natural immunity, we analyse and determine the major components that contributed to the Covid-19 hospital admissions. The results indicate that the observed vaccination rate alone is not enough to control the epidemic, and a global sensitivity analysis highlights a huge uncertainty attributable to the age-structured contact matrix. Our study shows the flexibility and robustness of PDE formalism to capture national COVID-19 dynamics and opens perspectives to study medium or long-term scenarios involving immune waning or virus evolution.

category: epidemiology


title: Non-Markovian modelling highlights the importance of age structure on Covid-19 epidemiological dynamics


title: Association between psychological distress trajectories from adolescence to midlife and mental health during the pandemic: Evidence from two British birth cohorts

abstract:
BackgroundSome studies suggest worsening mental health in the early stages of the pandemic, for individuals with pre-existing mental health conditions the evidence is mixed. We examined whether different life-course trajectories of psychological distress from adolescence to midlife were associated with psychological distress, lower life satisfaction and feelings of loneliness at different stages during the pandemic.

MethodsThis study is a secondary analysis of two nationally representative British Birth cohorts, the National Child Development Study (1958) and 1970 British Cohort Study, from birth to later mid-life. We used latent variable mixture models to identify pre-pandemic longitudinal trajectories of psychological distress and a modified poisson model with robust standard errors to estimate associations with mental health outcomes during the pandemic from May 2020 to March 2021.

FindingsOur analysis identified five distinct pre-pandemic trajectories of psychological distress in both cohorts. All trajectories with prior symptoms of psychological distress were associated with a greater relative risk of mental health outcomes during the pandemic. This was the case irrespective of age of onset, severity, longevity and proximal occurrence. Those who had experienced more than one prior episode of high psychological distress, and more recent occurrences, faced the greatest risk of poor mental health during the pandemic.

InterpretationWhilst any prior episode of poor mental health put individuals at greater risk of severe mental health symptoms, those with chronic and more recent occurrence are likely to require greater mental health support.

category: psychiatry and clinical psychology


title: Development and validation of a questionnaire to measure attitudes toward COVID-19 vaccination and pandemic

abstract:
BackgroundAccurate measurement of individuals attitudes toward COVID-19 vaccination and pandemic is critical to understand the way that people respond during a major crisis such as the COVID-19 pandemic.

ObjectiveTo develop and validate a questionnaire to assess attitudes toward COVID-19 vaccination and pandemic.

MethodsWe performed a reliability and validity study in a sample of the general population in Greece. Data were collected online through social media between 15 August and 7 September 2021. Thus, a convenience sample was obtained. Reliability and validity of the questionnaire were assessed with a Delphi study, an exploratory factor analysis, and a test-retest study. Also, we calculated Cronbachs coefficient alpha for the factors that emerged from the exploratory factor analysis.

ResultsThe final study included 1959 adults from the general population in Greece. Our four-factor model explained 73% of the variance and confirmed out initial hypothesis regarding the factors of the questionnaire. In particular, we found the following four factors: (a) fear against the COVID-19 (five items), (b) information regarding the COVID-19 (two items), (c) compliance with hygiene measures (two items), and (d) trust in COVID-19 vaccination (seven items). Cronbachs coefficients alpha for the four factors that emerged from the exploratory factor analysis were greater than 0.82. Pearsons correlation coefficients for the 16 items and the four factors were greater than 0.67 (p-value<0.001 in all cases).

ConclusionsWe developed a reliable and valid questionnaire to measure attitudes toward COVID-19 vaccination and pandemic. Further studies should be conducted to expand our knowledge and infer more valid results.

category: public and global health


title: Risk-benefit analysis of the AstraZeneca COVID-19 vaccine in Australia using a Bayesian network modelling framework

abstract:
Thrombosis and Thromobocytopenia Syndrome (TTS) has been associated with the AstraZencea (AZ) COVID-19 vaccine. Australia has reported low TTS incidence of <3/100,000 after the first dose, with case fatality rate (CFR) of 5-6%. Risk-benefit analysis of vaccination has been challenging because of rapidly evolving data, changing levels of transmission, and age-specific variation in rates of TTS, COVID-19, and CFR. We aim to optimise risk-benefit analysis by developing a model that enables inputs to be updated rapidly as evidence evolves. A Bayesian network was used to integrate local and international data, government reports, published literature and expert opinion. The model estimates probabilities of outcomes under different scenarios of age, sex, low/medium/high transmission (0.05%/0.45%/5.76% of population infected over 6 months), SARS-CoV-2 variant, vaccine doses, and vaccine effectiveness. We used the model to compare estimated deaths from vaccine-associated TTS with i) COVID-19 deaths prevented under different scenarios, and ii) deaths from COVID-19 related atypical severe blood clots (cerebral venous sinus thrombosis & portal vein thrombosis). For a million people aged [≥]70 years where 70% received first dose and 35% received two doses, our model estimated <1 death from TTS, 25 deaths prevented under low transmission, and >3000 deaths prevented under high transmission. Risks versus benefits varied significantly between age groups and transmission levels. Under high transmission, deaths prevented by AZ vaccine far exceed deaths from TTS (by 8 to >4500 times depending on age). Probability of dying from COVID-related atypical severe blood clots was 58-126 times higher (depending on age and sex) than dying from TTS. To our knowledge, this is the first example of the use of Bayesian networks for risk-benefit analysis for a COVID-19 vaccine. The model can be rapidly updated to incorporate new data, adapted for other countries, extended to other outcomes (e.g., severe disease), or used for other vaccines.

HIGHLIGHTSO_LIAZ vaccination risk-benefit analysis must consider age/community transmission level
C_LIO_LIAZ vaccine benefits far outweigh risks in older age groups and during high transmission
C_LIO_LIAZ vaccine-associated TTS lower fatality than COVID-related atypical blood clots
C_LIO_LIBayesian networks utility for risk-benefit analysis of rapidly evolving situations
C_LIO_LIBNs allow integrating multiple data sources when large datasets are not available
C_LI


title: CSF and PET biomarkers for noradrenergic dysfunction in neurodegenerative diseases: a systematic review and meta-analysis

abstract: The noradrenergic system shows pathological modifications in aging and neurodegenerative diseases and is thought to be affected in the early stages of both Alzheimer and Parkinson ss diseases. We conducted a meta-analysis of noradrenergic differences in Alzheimers disease type dementia (ADD) and Parkinsons disease (PD) using CSF and PET biomarkers. CSF noradrenaline (NA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) as well as NA transporter availability (PET MeNER) levels in controls, ADD and PD patients was summarized from 26 articles (1025 patients and 839 controls in total) using a random-effects model meta-analysis. Compared with controls, PD patients showed significant reductions in CSF NA and MHPG, and PET MeNER binding in the hypothalamus. In ADD, MHPG levels were increased compared with controls. Age correlated with CSF MHPG levels in ADD, but not in PD. Noradrenergic dysfunction in neurodegenerative diseases can be detected using CSF or PET measures and may be more pronounced in PD compared to ADD.

category: neurology


title: Total correlation explanation of toxic metal concentrations and physiological biomarkers amongst NHANES participants

abstract:
IntroductionUnravelling the health effects of multiple pollutants presents scientific and computational challenges. CorEx is an unsupervised learning algorithm that can efficiently discover multiple latent factors in highly multivariate datasets. Here, we used the CorEx algorithm to perform a hypothesis free analysis of demographic, biochemical, and toxic metal biomarker data.

MethodsOur data included 77 variables from 2,750 adult participants of the National Health and Nutrition Examination Survey (NHANES 2015-2016). We used an implementation of the CorEx algorithm designed to deal with the features of bioinformatic datasets including mixed data-types. Models were fit for a range of possible latent variables and the best fit model was selected as that which resulted in the largest Total Correlation (TC) after adjustment for the number of parameters. Successive layers of CorEx were run to discovered hierarchical data structure.

ResultsThe CorEx algorithm identified 20 variable clusters at the first layer. For the majority clusters, the associations between variables were consistent with known associations - e.g. gender and the hormones, estradiol and testosterone were included in the first cluster; blood organic mercury and blood total mercury were grouped in cluster 4, and cluster 6 included the liver function enzymes ALT, AST and GGT. At the second layer, 3 branches of were identified reflecting hierarchical structure. The first branch included numerous physiological biomarkers and several exogenous biomarkers. The second branch included a number endogenous and exogenous variables previously associated with hypertension, while the third branch included mercury biomarkers and some related endogenous biomarkers.

DiscussionWe have demonstrated the CorEx algorithm as a useful tool for hypothesis free exploration of a biomedical dataset. This work extends previous implementations of CorEx by allowing mixed data-types to be modelled and the results showed that CorEx detected meaningful hierarchical structure. CorEx may facilitate exploration of novel datasets in future.

category: occupational and environmental health


title: Humoral cross-reactivity towards SARS-CoV-2 in young children with acute respiratory infection with low-pathogenicity coronaviruses

abstract: SARS-CoV-2 infection in children frequently leads to only asymptomatic and mild infections. It has been suggested that frequent infections due to low-pathogenicity coronaviruses in children, imparts immunity against SARS-CoV-2 in this age group. From a prospective birth cohort study prior to the pandemic, we identified children (n=42) with proven low-pathogenicity coronavirus infections. Convalescent sera from these samples had antibodies against the respective seasonal CoVs as demonstrated by immunofluorescence assay. We tested these samples for neutralization of SARS-CoV-2 using virus microneutralization assay. Forty serum samples showed no significant neutralization of SARS-CoV-2, while 2 samples showed inconclusive results. These findings suggest that the antibodies generated in low-pathogenicity coronavirus infections offer no protection from SARS-CoV-2 infection in young children.

category: infectious diseases


title: Appearance of IgG to SARS-CoV-2 in saliva effectively indicates seroconversion in mRNA vaccinated immunocompromised individuals

abstract:
BackgroundImmunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves the oral cavity, a primary site of infection, is presently unknown.

MethodsImmunocompromised individuals (n=404) and healthy controls (n=82) participated in a prospective clinical trial encompassing two doses of the mRNA BNT162b2 vaccine. Immunocompromised individuals included primary immunodeficiencies (PID) and secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL). Saliva and serum samples were collected at four time points from the first vaccine dose until 2 weeks after second dose. SARS-CoV-2 spike specific immunoglobulin G (IgG) responses were quantified by a multiplex bead-based assay in saliva and correlated to paired serum IgG titers determined by Elecsys(R) Anti-SARS-CoV-2 S assay.

ResultsIgG responses to the SARS-CoV-2 spike full-length trimeric glycoprotein (Spike-f) and S1 subunit in saliva in the HIV and HSCT/CAR-T groups were comparable to healthy controls. In contrast, PID, SOT, and CLL patients all displayed weaker responses which were mainly influenced by disease parameters or immunosuppressants. Salivary IgG levels strongly correlated with serum IgG titers on days 21 and 35 (rho=0.8079 and 0.7768, p=<0.0001). Receiver operating characteristic curve analysis for the predictive power of salivary IgG yielded AUC=0.95, PPV=90.7% for the entire cohort on D35.

ConclusionsSaliva conveys humoral responses induced by BNT162b2 vaccination. The predictive power makes it highly suitable for screening low responding/vulnerable groups for revaccination.

Trial RegistrationClinicalTrials.gov Identifier: NCT04780659

FundingKnut and Alice Wallenberg Foundation, Erling Perssons family foundation, Region Stockholm, Swedish Research Council, Karolinska Institutet, The Swedish Blood Cancer Foundation and the organization for PID patient group in Sweden, and Nordstjernan AB. Center for Medical Innovation (CIMED), the Swedish Medical Research Council and the Stockholm County Council (ALF).

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title: Recombinant adjuvanted zoster vaccine and reduced risk of COVID-19 diagnosis and hospitalization in older adults

abstract:
BackgroundVaccines may elicit long-term boosting of innate immune responses that can help protect against COVID-19. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and COVID-19 outcomes at Kaiser Permanente Southern California.

MethodsIn a cohort design, adults aged [≥]50 years who received [≥]1 RZV dose prior to 3/1/2020 were matched 1:2 to unvaccinated individuals and followed until 12/31/2020. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive SARS-CoV-2 test and controls had only negative tests, from 3/1/2020-12/31/2020. Adjusted odds ratios (aOR) and 95% CIs for prior receipt of RZV were estimated using logistic regression.

ResultsIn the cohort design, 149,244 RZV recipients were matched to 298,488 unvaccinated individuals. The aHRs (95% CI) for COVID-19 diagnosis and hospitalization were 0.84 (0.81-0.87) and 0.68 (0.64-0.74), respectively. In the test-negative design, 8.4% of 75,726 test-positive cases and 13.1% of 340,898 test-negative controls had received [≥]1 RZV dose. The aOR (95% CI) was 0.84 (0.81-0.86).

ConclusionRZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization, suggesting RZV elicits heterologous protection, possibly through trained immunity.


title: Investigation of Dengue Fever Outbreak in a Rural Area of Islamabad, Pakistan: A Case Control Study

abstract:
BackgroundIn the second week of October 2019, five suspected cases of dengue fever were reported from union council Sohan, Islamabad rural (population 45,747) to the health department, Islamabad Capital Territory (ICT). Outbreak investigation was conducted with the objectives to identify risk factors and recommend control measures.

MethodsOutbreak investigation was conducted from 17th October to 25th November 2019. A case was defined as, "fever and two or more of the following signs/symptoms; headache, retro-orbital pain, joint/bone pain, myalgia and petechial rash with NS1 test (Nonstructural Protein 1) positive during 8th October to 25th November 2019 among residents of Sohan". Age and sex-matched controls were recruited from the same neighborhood. All cases were positive for NS1 antigen. Blood samples from five suspected cases were collected and tested for laboratory confirmation.

ResultsA total of 547 households were surveyed and 85 cases were identified. The mean age was 34.4 years + 16.05 (range 3-71 years). The attack rate was 0.19% whereas the most affected age group was the 45-54 years (AR 0.43%). Males were predominantly affected (n=48 56.5%). Among all cases, 32% (n=27)) had stagnant water inside or around their houses (aOR 2.65, CI 1.20-5.83, P=0.005), 33% (n=28) were using mosquito repellent (aOR 0.35, CI 0.17-0.70, P<0.001), 31% (n=26) used indoor residual spray insecticide (aOR 0.48, CI 0.24-0.97, P=0.041), and 73% (n=62) used full protective clothing (aOR 0.17, CI 0.05-0.58, P<0.001). All five blood samples were tested positive for NS-1 antigen.

ConclusionThe presence of accumulated rainwater in pools and empty receptacles around houses acted as breeding grounds for Aedes aegypti mosquitos and was the most probable cause of this outbreak. Following our recommendations, the health department-initiated mosquito breeding sites control activities through residual insecticide spray and advocacy on the use of protective measures against mosquito bites.


title: Forgoing healthcare during the COVID-19 pandemic in Geneva, Switzerland - a cross-sectional population-based study

abstract:
BackgroundHealth systems around the world continue to navigate through operational challenges surfaced by the COVID-19 pandemic; these have implications for access to healthcare. In this study, we estimate the prevalence and reasons for forgoing healthcare during the pandemic in Geneva, Switzerland; a country with a universal and mandatory private health insurance coverage.

MethodsParticipants from a randomly selected population-based sample of the adult population living in the Canton of Geneva completed an online socio-demographic and lifestyle questionnaire between November 2020 and January 2021. The prevalence and reasons for forgoing healthcare since the beginning of the COVID-19 pandemic were examined descriptively, and logistic regression models were used to assess determinants for forgoing healthcare.

ResultsThe study included 5,397 participants, among which 8.0% reported having forgone healthcare since the beginning of the COVID-19 pandemic; participants with a disadvantaged financial situation (OR=2.04; 95% CI: 1.56-2.65), and those reporting an average (OR=2.55; 95% CI: 1.94-3.32) or poor health (OR=4.40; 95% CI: 2.40-7.68) were more likely to forgo healthcare. The most common reasons to forgo healthcare were appointment cancellations by healthcare providers (53.9%), fear of infection (35.3%), and personal organizational issues (11.1%).

ConclusionOur paper highlights the effects of the COVID-19 pandemic on access to healthcare and identifies population sub-groups at-risk for forgoing healthcare. These results necessitate public health efforts to ensure equitable and accessible healthcare as the COVID-19 pandemic continues.

HighlightsO_LI8% of the Geneva, Switzerland, adults renounced healthcare in the COVID-19 pandemic
C_LIO_LIMain forgoing healthcare reasons are appointment cancellation and fear of infection
C_LIO_LIUnderprivileged participants with poor health are more likely to forgo healthcare
C_LI


title: Impact of COVID-19 pandemic on diet behaviour among UK adults: a longitudinal analysis of the HEBECO study

abstract:
COVID-19 pandemic restrictions impacted dietary habits during the initial months of the pandemic, but long-term effects are unclear. In this longitudinal study, self-selected UK adults (n=1,733) completed three online surveys (May-June, August-September and November-December 2020, with a retrospective pre-pandemic component in the baseline survey), self-reporting sociodemographics, lifestyle and behaviours, including high fat, salt and sugar (HFSS) snacks, HFSS meals and fruit and vegetable (FV) intake. Data were analysed using generalised estimating equations. Monthly HFSS snacks portion intake increased from pre-pandemic levels (48.3) in May-June (57.6, p<0.001), decreased in August-September (43.7, p<0.001), before increasing back to pre-pandemic levels in November-December (49.2, p<0.001). 48.5% self-reported increased (25.9 [95% confidence interval: 24.1, 27.8]) and 47.7% self-reported decreased (24.1 [22.4,26.0]) monthly HFSS snacks portion intakes in November-December compared with pre-pandemic levels. Monthly HFSS meals portion intake decreased from pre-pandemic levels (7.1) in May-June (5.9, p<0.001), being maintained in August-September (5.9, p=0.897), and then increasing again in November-December (6.6, p<0.001), to intakes that remained lower than pre-pandemic levels (p=0.007). 35.2% self-reported increased (4.8 [4.3, 5.3]) and 44.5% self-reported decreased (5.1 [4.6,5.6]) monthly HFSS meals portion intakes in November-December compared with pre-pandemic levels. The proportion meeting FV intake recommendations was stable from pre-pandemic through to August-September (70%), but decreased in November-December 2020 (67%, p=0.034). Increased monthly HFSS snacks intake was associated with female gender, lower quality of life, and - in a time-varying manner - older age and higher HFSS meals intake. Increased monthly HFSS meals intake was associated with female gender, living with adults only and higher HFSS snacks intake. Reduced FV intake was associated with higher body mass index (BMI) and lower physical activity. These results suggest large interindividual variability in dietary change during the first year of the pandemic, with important public health implications in individuals experiencing persistent increases in unhealthy diet choices, associated with BMI, gender, quality of life, living conditions, physical activity and other dietary behaviours.

What is currently known from previous studiesO_LIThe introduction of lockdown restrictions impacted on diet behaviours during the initial months of the pandemic.
C_LIO_LIChanges in dietary behaviours have been wide ranging, with individuals making healthy and unhealthy dietary changes in high fat, salt and sugar (HFSS) snacks, HFSS meals and fruit and vegetable (FV) intake.
C_LIO_LIThese dietary changes are associated with multiple sociodemographic, lifestyle and behavioural factors.
C_LIO_LIWhether dietary changes persist across longer periods of the pandemic, and which factors are associated with any long-term dietary behaviour change is yet to be identified.
C_LI

What this paper addsO_LIAverage UK adult intakes of HFSS snacks and meals fluctuated across the pandemic, with the former returning to pre-pandemic levels and the latter remaining below pre-pandemic levels.
C_LIO_LIFV intake was stable until the end of 2020, when the proportion meeting recommended intakes declined.
C_LIO_LIAcross the first year of the pandemic, being female and having a lower quality of life were associated with an increase in HFSS snacks intake, whereas the association of age and HFSS meals intake with HFSS snacks intake varied across the pandemic. Living with adults only and having a higher intake of HFSS snacks were associated with an increase in HFSS meals intake. A higher BMI and lower physical activity level were associated with reduced FV intake.
C_LI


title: Plaque Contact Surface Area and Flow Lumen Volume Predict Stroke Risk in Extracranial Carotid Artery Stenosis

abstract: The standard indication for intervention in asymptomatic disease is currently percent stenosis in the internal carotid artery as measured by the NASCET method, which remains limited in discriminating power. CT angiography (CTA) is widely used to calculate NASCET stenosis but also offers the opportunity to analyze carotid artery plaques from a morphological perspective that has not been widely utilized. We aim to improve stroke risk stratification of patients with carotid artery stenosis using plaque 3D modeling and image analysis. Patients with CTAs appropriate for 3D reconstruction were identified from an NIH designated stroke center database, and carotid arteries were segmented and analyzed using software algorithms to calculate contact surface area between the plaque and blood flow (CSA), and volume of the flow lumen within the region of the plaque (FLV). These novel parameters factor in the 3D morphometry inherent to each carotid plaque. A total of 134 carotid arteries were analyzed, 33 of which were associated with an ipsilateral stroke. Plaques associated with stroke demonstrated statistically significant increases in average CSA and FLV when compared to those not associated with stroke. When compared to NASCET percent stenosis, CSA and FLV both demonstrated a larger area under the receiver operating characteristics curve (AUC) in predicting stroke risk in patients with carotid stenosis. The data presented here demonstrate morphological features of carotid plaques that are independent of NASCET criteria stratification and may present an improved method in assessing stroke risk in patients with carotid artery stenosis.

category: surgery


title: Association of women empowerment with anaemia and haemoglobin concentration in children in sub-Saharan Africa: a multilevel analysis

abstract:
BackgroundChildhood anaemia is an intractable public health problem, particularly in low- and middle-income countries. Womens empowerment may improve child nutrition, but information on the relationship between different dimensions of womens empowerment and childhood anaemia in sub-Saharan Africa (SSA) is limited. We assessed the associations between womens empowerment and anaemia and haemoglobin (Hb) concentration among children in SSA.

MethodsWe included 72 032 women and their singleton children aged 6-59 months from the most recent Demographic and Health Surveys conducted between 2006 and 2019 in 31 SSA countries. We constructed a four-dimensional womens empowerment index using principal components analysis and used multilevel regression to assess the associations of these dimensions with child anaemia and Hb concentration.

ResultsOf the included children, 65.8% were anaemic and the mean Hb concentration was 102.3 g/dl (SD 16.1). The odds of anaemia reduced with increasing empowerment in the dimensions of attitude towards violence [quintile (Q1) vs. Q5, OR 0.80; 95% CI 0.71-0.89, Ptrend <0.001], decision making (Q1 vs. Q5, OR 0.68; 95% CI 0.59-0.79, Ptrend <0.001), education (Q1 vs. Q5, OR 0.80; 95% CI 0.72-0.89, Ptrend <0.001), and social independence (Q1 vs. Q5, OR 0.89; 95% CI 0.79-1.00, Ptrend <0.015). Similarly, the mean Hb concentration increased with increasing womens empowerment in the dimensions of attitude towards violence (Q1 vs. Q5, mean difference (MD) 0.96 g/dl; 95% CI 0.17-1.74, Ptrend = 0.009), decision making (Q1 vs. Q5, MD 0.73 g/dl; 95% CI 0.03-1.43, Ptrend <0.001), social independence (Q1 vs. Q5, MD 1.65 g/dl; 95% CI 0.99-2.31, Ptrend <0.001) and education (Q1 vs. Q5, MD 1.01 g/dl; 95% CI 0.50-1.52, Ptrend <0.002).

ConclusionWomen empowerment was associated with reduced odds of anaemia and higher Hb concentration in children. Promotion of women empowerment may reduce the burden of childhood anaemia in SSA.

Key questionsO_ST_ABSWhat is already known?C_ST_ABSO_LIWomen empowerment may reduce maternal and child undernutrition, specifically wasting, stunting and Vitamin A deficiency.
C_LIO_LIWomen empowerment is a multidimensional concept and is often measured in an unstandardized way making it difficult to compare and interpret findings across studies.
C_LIO_LIA survey-based womens empowerment index (the SWPER index) was developed to measure women empowerment in a standardised manner across sub-Saharan African countries.
C_LI

What are the new findings?O_LIChildren of women who were empowered in the attitude towards domestic violence, decision making, education, and social independence domains had higher haemoglobin concentrations and were less likely to be anaemic than those of less empowered women.
C_LIO_LIEmpowerment in decision making seemed to have the strongest association with anaemia.
C_LI

What do the new findings imply?O_LIPromotion of women empowerment in attitude towards violence, decision making, social independence and education domains may contribute towards reducing the burden of anaemia among sub-Saharan African children.
C_LI

category: nutrition


title: The Brazilian Rare Genomes Project: validation of whole genome sequencing for rare diseases diagnosis

abstract: Rare diseases affect 3.2 to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the results of the validation of a whole genome sequencing (WGS) procedure for implementation in a clinical laboratory. In addition, we report data quality for the first 1,200 real world patients sequenced. For the validation, we sequenced a well characterized group of 76 samples, including seven gold standard genomes, using a PCR-free WGS protocol on Illumina Novaseq 6000 equipment. We compared the observed variant calls with their expected calls, observing good concordance for single nucleotide variants (SNVs; mean F-measure = 99.82%) and indels (mean F-measure = 99.57%). Copy number variants and structural variants events detection performances were as expected (F-measures 96.6% and 90.3%, respectively). Our protocol presented excellent intra- and inter-assay reproducibility, with coefficients of variation ranging between 0.03% and 0.20% and 0.02% and 0.09%, respectively. Limitations of the procedure include the inability to confidently detect variants such as uniparental disomy, balanced translocations, repeat expansion variants and low-level mosaicism. In summary, the observed performance of the test was in accordance with that seen in the best centers worldwide. The Rare Genomes Project is an important initiative to improve Brazils general population access to the innovative WGS technology which has the potential to reduce the time until diagnosis of rare diseases, bringing pivotal improvements for the quality of life of the affected individuals.

category: genetic and genomic medicine


title: COVID-19 Neutralizing Antibody Surveillance Testing for Fully Vaccinated Individuals During Delta Variant Spread

abstract: We recently performed 568 rapid neutralizing antibody (NAb) tests on 164 fully vaccinated individuals who received either Moderna or Pfizer COVID-19 vaccine regimens over 7 weeks. The NAb levels against the wild type (WA1/2020), Delta, and Kappa variants were measured and compared. Depending on each individuals medical condition and vaccination status, the NAb levels for most of the fully vaccinated people decreased within 2-6 months, while a small number of individuals either generated non-detectable amount of NAbs after full vaccination (e.g., immunocompromised), or had high NAb levels lasting beyond 6 months. Since the NAb levels vary significantly among different individuals and decrease over time, the deployment of a low-cost rapid test to monitor NAb levels against both the wild type and emerging variants among fully vaccinated individuals can play a very crucial role to control the current pandemic. Our study provides an example of using such a rapid NAb test to fill this currently unmet medical need.


title: Exhaled particles from nanometre to millimetre and their origin in the human respiratory tract

abstract: Detailed knowledge of the properties of exhaled particles from the human respiratory tract for all genders and ages is essential to determine the modes of transmission of airborne diseases. This applies not only to the current COVID-19 pandemic, but also to many others, be it measles, seasonal influenza or tuberculosis. To date, there are no data on the individual-specific concentrations and sizes of exhaled particles over the entire size range from nanometre to millimetre. Here we present a comprehensive data set, measured by particle size spectrometry and in-line holography covering the entire size range from 132 healthy volunteers aged 5 to 80 years for a defined set of breathing and vocalisation activities. We find age to have a large effect on small particle concentrations (<5 {micro}m), doubling in children during adolescence and in adults over a 30-year period. In contrast, gender, body mass index, smoking or exercise habits have no discernible influence. Particles >20 {micro}m show on average no measurable dependence on the type of vocalisation with the exception of shouting. We show evidence that particles <5 {micro}m mainly originate in the lower respiratory tract, 5-15 {micro}m in the larynx/pharynx, and >15 {micro}m in the oral cavity.


title: SARS-CoV-2 Seroprevalence among Healthcare Workers

abstract:
BackgroundMonitoring COVID-19 infection risk among health care workers (HCWs) is a public health priority. We examined the seroprevalence of SARS-CoV-2 among HCWs following the fall infection surge in Minnesota, and before and after COVID-19 vaccination. Additionally, we assessed demographic and occupational risk factors for SARS-CoV-2 infection.

MethodsWe conducted two rounds of seroprevalence testing among a cohort of HCWs: samples in round 1 were collected from 11/22/20 - 02/21/21 and in round 2 from 12/18/20 - 02/15/21. Demographic and occupational exposures assessed with logistic regression were age, sex, healthcare role and setting, and number of children in the household. The primary outcome was SARS-CoV-2 IgG seropositivity. A secondary outcome, SARS-CoV-2 infection, included both seropositivity and self-reported SARS-CoV-2 test positivity.

ResultsIn total, 459 HCWs were tested. 43/454 (9.47%) had a seropositive sample 1 and 75/423 (17.7%) had a seropositive sample 2. By time of sample 2 collection, 54% of participants had received at least one vaccine dose and seroprevalence was 13% among unvaccinated individuals. Relative to physicians, the odds of SARS-CoV-2 infection in other roles were increased (Nurse Practitioner: OR[95%CI] 1.93[0.57,6.53], Physicians Assistant: 1.69[0.38,7.52], Nurse: 2.33[0.94,5.78], Paramedic/EMTs: 3.86[0.78,19.0], other: 1.68[0.58,4.85]). The workplace setting was associated with SARS-CoV-2 infection (p=0.04). SARS-CoV-2 seroprevalence among HCWs reporting duties in the ICU vs. those working in an ambulatory clinic was elevated: OR[95%CI] 2.17[1.01,4.68].

ConclusionsSARS-CoV-2 seroprevalence in HCW increased during our study period which was consistent with community infection rates. HCW role and setting -- particularly working in the ICU -- is associated with higher risk for SARS-CoV-2 infection.


title: Initial SARS-CoV-2 viral load is associated with disease severity: a retrospective cohort study

abstract:
BackgroundWe aimed to assess the association between initial SARS-CoV-2 viral load and the subsequent hospital and intensive care unit (ICU) admission and overall survival.

MethodsAll persons with a positive SARS-CoV-2 RT-PCR result from a combined nasopharyngeal (NP) and oropharyngeal (OP) swab (first samples from unique persons only) that was collected between March 17, 2020, and March 31, 2021, in Public Health testing facilities in the region Kennemerland, province of North Holland, the Netherlands were included. Data on hospital (and ICU) admission were collected from the two large teaching hospitals in the region Kennemerland.

ResultsIn total, 20,207 SARS-CoV-2 positive persons were included in this study, of whom 310 (1.5%) were hospitalized in a regional hospital within 30 days of their positive SARS-CoV-2 RT-PCR test. When persons were categorized in three SARS-CoV-2 viral load groups, the high viral load group (Cp < 25) was associated with an increased risk of hospitalization as compared to the low viral load group (Cp > 30) (ORadjusted [95%CI]: 1.57 [1.11-2.26], p-value=0.012), adjusted for age and sex. The same association was seen for ICU admission (ORadjusted [95%CI]: 7.06 [2.15-43.57], p-value=0.007). For a subset of 243 of the 310 hospitalized patients, the association of initial SARS-CoV-2 Cp-value with in-hospital mortality was analyzed. The initial SARS-CoV-2 Cp-value of the 17 patients who deceased in the hospital was significantly lower (indicating a higher viral load) compared to the 226 survivors: median Cp-value [IQR]: 22.7 [3.4] vs. 25.0 [5.2], OR[95%CI]: 0.81 [0.68-0.94], p-value = 0.010.

ConclusionsOur data show that higher initial SARS-CoV-2 viral load is associated with an increased risk of hospital admission, ICU admission, and in-hospital mortality. We believe that our findings emphasize the added value of reporting SARS-CoV-2 viral load based on Cp-values to identify persons who are at the highest risk of adverse outcomes such as hospital or ICU admission and who therefore may benefit from more intensive monitoring.


title: Frailty trajectories in the oldest old: Is the level or the rate of change more predictive of mortality?

abstract:
BACKGROUNDIt is unclear whether frailty index (FI) change captures mortality risk better than and independently of the current FI level, i.e. whether a regular FI assessment among older adults provides additional insights for mortality risk stratification or not.

METHODSWe used data from the LASA 75-PLUS-study, which monitored health among 508 older adults (75+) between 2016-2019 every 9 months. Joint models for longitudinal and time-to-event data were used to assess the impact of both current FI and within-person FI change during the last year on mortality risk.

RESULTS20% of the participants died during 4.5 years of follow-up. Adding within-person FI change to the current FI model improved model fit and it showed that FI increases during the last year were associated with a strong increase in mortality risk. Consequently, the effect of the current FI decreased considerably and became statistically non-significant.

CONCLUSIONSThe rate of FI change was more important than the current FI level for short-term mortality prediction among the oldest old, which highlights the benefits of regular frailty assessments.


title: Frailty and rate of fractures in patients initiating antihypertensive medications: a cohort study in primary care.

abstract:
BackgroundTreatment for hypertension improves cardiovascular outcomes. Frailty is common in people treated for hypertension, and associated with increases in adverse drug effects, potentially including falls resulting in fractures. We aimed to determine the association between baseline frailty and fractures in patients initiated on antihypertensive treatment.

MethodsWe conducted a retrospective cohort study using United Kingdom primary care data, including new-users of first-line antihypertensives aged 65 years or over. We reported degree of frailty (fit, mild, moderate, severe) at antihypertensive initiation using the Electronic Frailty Index. We examined the association of frailty with fractures using multivariable Poisson regression, and assessed for interaction between antihypertensive class and frailty.

Results49634 (43%) people initiated on first-line antihypertensives were mildly or more frail. Over 4.1 years mean follow-up, 6567 (5.8%) experienced a fracture, with 3832 (58%) of these fractures occurring in frail people. Among those with severe frailty doubling of fracture risk was observed after antihypertensive initiation, compared with fit people [adjusted rate ratio 2.26 (95% CI 1.93-2.65)]. This pattern was replicated for hip and arm fractures, and strongest for spine fractures. The association between different types of antihypertensives and fractures varied by frailty (P=0.004), with a lower rate in moderately frail users of renin-angiotensin blockers compared with calcium-channel blockers (RR 0.81 95% CI 0.71-0.94)

ConclusionsFrailty is common among people initiating first-line antihypertensive treatment, and was associated with an increased fracture rate. Awareness of this is important to encourage clinicians to consider risk of falls and fractures when treating hypertension.

category: pharmacology and therapeutics


title: Current and Lifetime Somatic Symptom Burden Among Transition-aged Young Adults on the Autism Spectrum

abstract:
Background and ObjectivesSomatic symptoms are the most common cause of outpatient medical visits in the general population, yet their presence and severity in individuals on the autism spectrum has rarely been studied. We sought to assess the prevalence, impact, and clinical correlates of fourteen commonly-reported somatic symptoms in a sample of transition-aged autistic young adults.

MethodsA sample of 290 independent and cognitively able autistic young adults (aged 18-26 years; mean [SD]: 23.10 [2.38] years) was recruited from the Simons Foundation SPARK participant pool. A modified version of the Patient Health Questionnaire-15 was used to assess somatic symptom prevalence/impact, along with measures of depression, anxiety, autistic traits, and quality of life.

ResultsSomatic symptom burden was much higher in autistic young adults than previously reported in the general population. The most commonly reported current symptoms were fatigue (72.8%), sleep problems (69.0%), and menstrual problems (61.4% of females). Moderate or severe symptom levels were reported by 53.9% of females and 18.75% of males in our cohort, with the odds of females of endorsing any given symptom being 2-4 times greater than males. Both individual symptoms and total symptom burden were related to higher levels of depression, anxiety, and autistic traits, along with lower quality of life.

ConclusionDespite little research on this topic previously, somatic symptoms are highly prevalent in autistic young adults, particularly women. Future research is needed to investigate links between somatic symptoms, medical and psychiatric morbidity, and health care utilization in the autistic population.

Whats Known on This SubjectSomatic symptoms are highly prevalent in the general population and account for a large proportion of health care costs. However, few studies have investigated the prevalence, impact, or correlates of these symptoms in individuals on the autism spectrum.

What This Study AddsTo our knowledge, this is the first study to specifically assess current and lifetime somatic symptom burden, symptom onset patterns, and the clinical correlates of multisystem symptom distress in transition-aged young adults on the autism spectrum.


title: Risk factors for infection, predictors of severe disease and antibody response to COVID-19 in patients with rheumatic diseases in Portugal - a multicentre, nationwide study

abstract: In order to identify risk factors for SARS-CoV-2 infection as well as for severe/critical COVID-19 in rheumatic and musculoskeletal diseases (RMDs) patients, we conducted a multicentre observational nationwide study of adult patients prospectively-followed in the Rheumatic Diseases Portuguese Register - Reuma.pt - during the first 6 months of the pandemic. We further evaluated the development of IgG antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in patients with RMDs. We used multivariate logistic regression to compare patients with COVID-19 (COVID-19+) with those who did not develop the disease (COVID-19-) and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. COVID-19+ patients were asked to collect a blood sample for IgG testing [≥] 3 months after infection and results were compared with age-, sex- and sampling date-matched controls. Overall, 179 cases of COVID-19 were registered in Reuma.pt in the period of interest (median age 55 (IQR 20); 76.5% females) in a total of 6404 registered appointments. We found that patients treated with TNF inhibitors had reduced odds of infection (OR=0.16, 95%CI 0.10-0.26, p<0.001), severe disease (OR 0.11, 95%CI 0.01-0.84, p=0.010) and seroconversion rates (OR 0.13, 95%CI 0.02-0.91, p=0.040). Tocilizumab was also associated with a reduced risk of COVID-19 (OR 0.15, 95%CI 0.05-0.41, p<0.001). Older age, major comorbidities (diabetes, hypertension, obesity, cardiovascular disease, chronic pulmonary and kidney disease) and rituximab were associated with an increased risk of infection and worse prognosis, in line with previous reports. Importantly, most patients with inflammatory RMDs (86.2%) were able to develop a robust antibody response after SARS-CoV-2 infection, which was linked with disease severity.

category: rheumatology


title: Transfer learning for non-image data in clinical research: a scoping review

abstract:
BackgroundTransfer learning is a form of machine learning where a pre-trained model trained on a specific task is reused as a starting point and tailored to another task in a different dataset. While transfer learning has garnered considerable attention in medical image analysis, its use for clinical non-image data is not well studied. Therefore, the objective of this scoping review was to explore the use of transfer learning for non-image data in the clinical literature.

Methods and FindingsWe systematically searched medical databases (PubMed, EMBASE, CINAHL) for peer-reviewed clinical studies that used transfer learning on human non-image data. We included 83 studies in the review. More than half of the studies (63%) were published within 12 months of the search. Transfer learning was most often applied to time series data (61%), followed by tabular data (18%), audio (12%) and text (8%). Thirty-three (40%) studies applied an image-based model to non-image data after transforming data into images (e.g. spectrograms). Twenty-nine (35%) studies did not have any authors with a health-related affiliation. Many studies used publicly available datasets (66%) and models (49%), but fewer shared their code (27%).

ConclusionsIn this scoping review, we have described current trends in the use of transfer learning for non-image data in the clinical literature. We found that the use of transfer learning has grown rapidly within the last few years. We have identified studies and demonstrated the potential of transfer learning in clinical research in a wide range of medical specialties. More interdisciplinary collaborations and the wider adaption of reproducible research principles are needed to increase the impact of transfer learning in clinical research.

category: health informatics


title: Risk factors, early presentations, and clinical markers of Parkinson's disease in Primary Care in a diverse UK population

abstract:
ImportancePredictors of future Parkinsons disease (PD) have been suggested through population-based studies, but these studies over-represent white, affluent groups and may not be generalisable.

ObjectiveTo investigate the association between risk factors and pre-diagnostic presentations of PD in a uniquely diverse UK population, with universal access to health care.

Design, Setting, and ParticipantsA case-control study was conducted in East London, using primary care health records.

Main outcomes and MeasuresLogistic regression was used to determine associations between risk factors and pre-diagnostic presentations of PD with final diagnosis. Three periods (recorded <2 years, 2-5 years, and 5-10 years prior to diagnosis) were analysed.

ResultsPrimary care records were available for 1,055 patients with PD and 1,009,523 controls. The strongest associations were found for tremor (OR, 181.69; 95% CI, 151.91-217.31) and  memory complaints (OR, 9.84; 95% CI, 7.39-13.11), <2 years before PD diagnosis. However, associations for both complaints persisted up to 10 years prior to PD diagnosis. Shoulder pain was more common in those who developed PD, emerging 5 to 10 years prior to diagnosis (OR, 2.54; 95% CI, 1.77-3.65), and may be a surrogate marker for rigidity. Epilepsy showed a strongest association with subsequent PD (OR, 5.14; 95% CI, 1.26-21.0), and associations were also found for hypertension (OR, 1.71; 95% CI, 1.34-2.17) and type 2 diabetes (OR, 1.57; 95% CI, 1.31-1.87) 5 to 10 years before diagnosis. We replicated several known associations with early non motor features including hypotension, constipation, and depression. A weak but novel association was observed with prodromal hearing loss and subsequent PD, which appeared up to 10 years prior to diagnosis. No associations with future PD diagnosis were found for ethnicity or deprivation index.

Conclusions and relevanceThis study provides further evidence that a range of comorbidities and pre-diagnostic presentations are encountered in primary care prior to PD diagnosis, but for the first time in such a diverse and deprived population. Convincing temporal associations were observed for epilepsy and hearing loss with subsequent PD. The predominance of  memory symptoms hints at an excess of cognitive dysfunction in early PD in this population or difficulty in correctly ascertaining symptoms in traditionally under-represented groups.

Key pointsO_ST_ABSQuestionC_ST_ABSWhat are the pre-diagnostic manifestations of Parkinsons disease (PD) that present to primary care in a diverse and deprived population with universal access?

FindingsTremor and  memory symptoms were reported up to 10 years before diagnosis and were most strongly associated with PD. Several recognised pre-diagnostic features were replicated, but novel temporal associations between epilepsy and hearing loss with subsequent PD were observed.

MeaningThe range of symptoms that cause people to present to primary care, up to a decade before PD diagnosis, are broad. The strength of association, relative importance and interpretation of prodromal features may vary according to the population studied.


title: The paradox of the COVID-19 pandemic: the impact on patient demand in Japanese hospitals

abstract:
Analyzing data from a large, nationally distributed group of Japanese hospitals, we found a dramatic decline in both inpatient and outpatient volumes over the three waves of the COVID- 19 pandemic in Japan from February-December 2020. We identified three key reasons for this fall in patient demand. First, COVID-19-related hygiene measures and behavioral changes significantly reduced non-COVID-19 infectious diseases. Second, consultations relating to chronic diseases fell sharply. Third, certain medical investigations and interventions were postponed or cancelled. Despite the drop in hospital attendances and admissions, COVID-19 is said to have brought the Japanese health care system to the brink of collapse. In this context, we explore longstanding systematic issues, finding that Japans abundant supply of beds and current payment system may have introduced a perverse incentive to overprovide services, creating a mismatch between patient needs and the supply of health care resources. Poor coordination among health care providers and the highly decentralized governance of the health care system have also contributed to the crisis. In order to ensure the long-term sustainability of the Japanese health care system beyond COVID-19, it is essential to promote specialization and differentiation of medical functions among hospitals, to strengthen governance, and to introduce appropriate payment reform.

O_TEXTBOXHighlights{blacksquare} Patient volumes in Japanese hospitals fell sharply due to the COVID-19 pandemic.
{blacksquare}Behavioral changes and appointment cancellations contributed to the decline.
{blacksquare}Japans health system reached breaking point due to longstanding systematic issues.
{blacksquare}There is a mismatch between patient needs and the supply of health care resources.
{blacksquare}Payment reform and stronger governance are needed to future-proof the health system.

C_TEXTBOX

category: health policy


title: Impact of Salivary and Pancreatic Amylase Gene Copy Numbers on Diabetes, Obesity, and Functional Profiles of Microbiome in Northern Japanese Population

abstract: Amylase genes reside in a structurally complex locus, and their copy numbers vary greatly, especially among agricultural races. Amylase genes seem to shape the metabolic response to dietary starch, and several studies have reported their association with obesity. Besides, the effect of amylase copy numbers seems to depend on lifestyle, and the mechanism of this effect was partially explained by changes in the oral and gut microbiome compositions; however, a detailed mechanism has been unclarified. In this study, we showed their association with diabetes in addition to obesity, and further discovered a plausible mechanism of this association based on the function of commensal bacterial in a northern Japanese population. First, we confirmed that the amylase copy number in the population tends to be larger than that reported in other studies and that there is a positive association between obesity and diabetes (p =1.95E-2 and 3.28E-2). Second, we identified that relative abundance of some genus level microbiome, Capnocytophaga, Dialister, and previously reported bacteria, were significantly associated with amylase copy numbers. Finally, through functional gene-set analysis using shotgun sequencing, we observed that the abundance of genes in the Acarbose pathway in the gut microbiome was significantly decreased with an increase in the amylase copy number (p-value = 5.80E-4), which can partly explain the mechanism underlying obesity and diabetes in populations with high amylase copy numbers.


title: SARS-CoV-2 multi-variant graphene biosensor based on engineered dimeric ACE2 receptor

abstract: Fast, reliable and point-of-care systems to detect the SARS-CoV-2 infection are crucial to contain viral spreading and to adopt timely clinical treatments. Many of the rapid detection tests currently in use are based on antibodies that bind viral proteins1. However, newly appearing virus variants accumulate mutations in their RNA sequence and produce proteins, such as Spike, that may show reduced binding affinity to these diagnostic antibodies, resulting in less reliable tests and in the need for continuous update of the sensing systems2. Here we propose a graphene field-effect transistor (gFET) biosensor which exploits the key interaction between the Spike protein and the human ACE2 receptor. This interaction is one of the determinants of host infections and indeed recently evolved Spike variants were shown to increase affinity for ACE2 receptor3. Through extensive computational analyses we show that a chimeric ACE2-Fc construct mimics the ACE2 dimer, normally present on host cells membranes, better than its soluble truncated form. We demonstrate that ACE2-Fc functionalized gFET is effective for in vitro detection of Spike and outperforms the same chip functionalized with either a diagnostic antibody or the soluble ACE2. Our sensor is implemented in a portable, wireless, point-of-care device and successfully detected both alpha and gamma virus variants in patients clinical samples. As incomplete immunization, due to vaccine roll-out, may offer new selective grounds for antibody-escaping virus variants4, our biosensor opens to a class of highly sensitive, rapid and variant-robust SARS-CoV-2 detection systems.


title: ALBUMIN CREATININE RATIO AS AN INDICATOR OF NON-HEALING FOOT WOUND FORMATION IN DIABETES

abstract:
AimsTo investigate whether kidney injury, determined by albumin creatinine ratio, was associated with current non-healing foot wounds in type 2 diabetes.

Materials and MethodsEighty-nine Barbadians with diabetes were recruited. Cases had a current foot wound and controls had no current foot wound and no history of a non-healing foot wound. Cases were matched to controls using sex, age and duration of diabetes. Participants were from wound dressing and diabetes clinics at the Queen Elizabeth Hospital and Polyclinics, and from private healthcare practitioners. The relationship between albumin creatinine ratio and foot ulceration, adjusting for selected potential risk factors, was analyzed using logistic regression and presented as odds ratios.

ResultsForty-four cases and 45 controls were matched, with no statistically significant difference in matching criteria. There were statistically important differences in measures of neuropathy, blood glucose, HbA1c and Albumin:creatinine ratio between cases and controls. Cases were 3 times more likely than controls to have microalbuminuria (95% CI 0.9 - 10.2; p=0.08). Cases were 7.4 times more likely than controls to have macroalbuminuria (95% CI 1.2 - 47.5; p=0.04).

ConclusionsThe possible association of albumin:creatinine ratio with diabetic foot wounds raises the possibility of its use in earlier identification of persons on the pathway to developing diabetic foot.

category: endocrinology


title: Frequency of surveillance testing necessary to reduce transmission of the Delta variant of SARS-CoV-2

abstract: We estimate the reduction in transmission of SARS-CoV-2 achievable by surveillance testing of a susceptible population at different frequencies, comparing the cases of both the original Wuhan strain and the Delta variant. We estimate the viral dynamics using viral copy number at first detection combined with considerations arising from aerosol transmission. We take into account the recent findings that infected vaccinated adults may have live viral loads at the same level as infected unvaccinated adults. Our estimates suggest that twice weekly testing, which was adequate for the original strains of SARS-CoV-2 will be insufficient on its own to contain the spread of the Delta variant of concern. We exclude consideration of contact tracing since the rapidity of the onset of viral titre in the case of the Delta variant suggests that unless contact tracing and quarantine are performed very rapidly (i.e., much less than a day), these mitigations will be of minimal impact in reducing transmission. These crude estimates do not take into account heterogeneity of susceptibility, social activity, and compliance, nor do they include the additional reduction in transmission that could be achieved by masking and social distancing. In the setting of a large public university, these considerations suggest that risk-targeted testing of vaccinated students, staff and faculty combined with surveillance testing of all unvaccinated individuals is the most efficient way to reduce transmission of COVID-19.


title: Redefining snakebite envenoming as a zoonosis: disease incidence is driven by snake ecology, socioeconomics and anthropogenic impacts

abstract: Snakebite is the only WHO-listed, not infectious neglected tropical disease (NTD), although its eco-epidemiology is similar to that of zoonotic infections: envenoming occurs after a vertebrate host contacts a human. Accordingly, snakebite risk represents the interaction between snake and human factors, but their quantification has been limited by data availability. Models of infectious disease transmission are instrumental for the mitigation of NTDs and zoonoses. Here, we represented snake-human interactions with disease transmission models to approximate geospatial estimates of snakebite incidence in Sri Lanka, a global hotspot. Snakebites and envenomings are described by the product of snake and human abundance, mirroring directly transmitted zoonoses. We found that human-snake contact rates vary according to land cover (surrogate of occupation and socioeconomic status), the impacts of humans and climate on snake abundance, and by snake species. Our findings show that redefining snakebite as zoonosis provides a mechanistic eco-epidemiological basis to understand snakebites, and the possible implications of global environmental and demographic change for the burden of snakebite.


title: Improving vaccination coverage and offering vaccine to all school-age children will allow uninterrupted in-person schooling in King County, WA: Modeling analysis

abstract:
BackgroundThe mass rollout of COVID vaccination in early 2021 allowed local and state authorities to relax mobility and social interaction regulations in spring 2021 including lifting all restrictions for vaccinated people and restoring in-person schooling. However, the emergence and rapid spread of highly transmissible variants combined with slowing down the pace of vaccination created uncertainty around the future trajectory of the epidemic. In this study we analyze the expected benefits of offering vaccination to children age 5-11 under differing conditions for in-person schooling.

MethodsWe adapted a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington, to handle multiple variants with increased transmissibility and virulence as well as differential vaccine efficacies against each variant. Reactive social distancing is implemented driven by fluctuations in the number of hospitalizations in the county. We simulate scenarios offering vaccination to children aged 5-11 with different starting dates and different proportions of physical interactions (PPI) in schools being restored. The impact of improving overall vaccination coverage among the eligible population is also explored. Cumulative hospitalizations, percentage reduction of hospitalizations and proportion of time at maximum social distancing over the 2021-2022 school year are reported.

FindingsIn the base-case scenario with 85% vaccination coverage of 12+ year-olds, our model projects 4945 (median, IQR 4622-5341) total COVID-19 hospitalizations and 325 (median, IQR 264-400) pediatric hospitalizations if physical contacts at schools are fully restored (100% PPI) for the entire school year compared to 3675 (median, IQR 2311-4725) and 163 (median, IQR 95-226) if schools remained closed. Reducing contacts in schools to 75% PPI or 50% PPI through masking, ventilation and distancing is expected to decrease the overall cumulative hospitalizations by 2% and 4% respectively and youth hospitalizations by 8% and 23% respectively. Offering early vaccination to children aged 5-11 with 75% PPI is expected to prevent 756 (median, IQR 301-1434) hospitalizations and cut hospitalizations in the youngest age group in half compared to no vaccination. It will largely reduce the need of additional social distancing over the school year. If, in addition, 90% overall vaccination coverage is reached, 60% of remaining hospitalizations will be averted and the need of extra mitigation measures almost certainly avoided.

ConclusionsOur work highlights that in-person schooling is possible if reasonable precaution measures are taken at schools to reduced infectious contacts. Rapid vaccination of all school-aged children will provide meaningful reduction of the COVID health burden over this school year but only if implemented early. Finally, it remains critical to vaccinate as many people as possible to limit the morbidity and mortality associated with the current surge in Delta variant cases.


title: Trait, staging, and state markers of psychosis based on functional alteration of salience-related networks in the high-risk, first episode, and chronic stages

abstract:
Aberrant salience is essentially implicated in psychosis, involving the midbrain-striatum-hippocampus and anterior cingulate cortex-insula (salience network: SN) systems. However, how these two systems contribute to psychosis traits, staging, and state remains unclear. Thus, we conducted an international multi-site resting functional magnetic resonance imaging study of 209 ultra-high-risk (UHR), first-episode (FEP), and chronic (ChrP) psychosis patients and 279 healthy controls. After intensive denoising and site effect-harmonization, we found 1) reduced connectivity and increased instability of two salience-related systems in the UHR and FEP, in which the SNs significance levels/effect sizes were in the order of UHR > FEP > ChrP 2) an association between stronger connectivity of the midbrain-striatum-hippocampus system and severer delusions and hallucinations in FEP 3) attenuation of finding 2 in patients with medication and non-affective psychosis. The results suggest that the two salience-related systems are associated with psychosis traits, staging, and state in different ways.

TeaserTwo salience-related functional networks are associated with psychosis traits, staging, and state, in different ways.


title: Functional alterations of salience-related networks are associated with traits, staging, and the state of psychosis


title: Scaling Up the Discovery of Hesitancy Profiles by Identifying the Framing of Beliefs towards Vaccine Confidence in Twitter Discourse

abstract: Our study focused on the inference of the framing of confidence in the HPV vaccine throughout a collection of 422,078 tweets as well as the framing of confidence in the COVID-19 vaccines through a collection of 5,865,046 tweets. The vaccine confidence framings were inferred by using a novel Question/Answering framework enabling the derivation of a misinformation taxonomy as well as trust taxonomies for these two vaccines. These taxonomies, along with the analysis of vaccine literacy, the implied moral foundations and the tension between vaccine mandates and civil rights allowed us to discover several profiles of hesitancy for each vaccine across 138,779 Twitter users referring to confidence in HPV vaccine and 665,798 users referring to confidence in COVID-19 vaccines. These hesitancy profiles inform public health messaging approaches to effectively reach Twitter users with promise to shift or bolster vaccine attitudes.


title: Harmonization of Multi-Center Diffusion Tensor Tractography in Neonates with Congenital Heart Disease: Optimizing Post-Processing and Application of ComBat

abstract: Advanced brain imaging of neonatal macrostructure and microstructure, which has prognosticating importance, is more frequently being incorporated into multi-center trials of neonatal neuroprotection. Multicenter neuroimaging studies, designed to overcome small sample sized clinical cohorts, are essential but lead to increased technical variability. Few harmonization techniques have been developed for neonatal brain microstructural (diffusion tensor) analysis. The work presented here aims to remedy two common problems that exist with the current state of the art approaches: 1) variance in scanner and protocol in data collection can limit the researchers ability to harmonize data acquired under different conditions or using different clinical populations. 2) The general lack of objective guidelines for dealing with anatomically abnormal anatomy and pathology. Often, subjects are excluded due to subjective criteria, or due to pathology that could be informative to the final analysis, leading to the loss of reproducibility and statistical power. This proves to be a barrier in the analysis of large multi-center studies and is a particularly salient problem given the relative scarcity of neonatal imaging data. We provide an objective, data-driven, and semi-automated neonatal processing pipeline designed to harmonize compartmentalized variant data acquired under different parameters. This is done by first implementing a search space reduction step of extracting the along-tract diffusivity values along each tract of interest, rather than performing whole-brain harmonization. This is followed by a data-driven outlier detection step, with the purpose of removing unwanted noise and outliers from the final harmonization. We then use an empirical Bayes harmonization algorithm performed at the along-tract level, with the output being a lower dimensional space but still spatially informative. After applying our pipeline to this large multi-site dataset of neonates and infants with congenital heart disease (n= 398 subjects recruited across 4 centers, with a total of n=763 MRI pre-operative/post-operative time points), we show that infants with single ventricle cardiac physiology demonstrate greater white matter microstructural alterations compared to infants with bi-ventricular heart disease, supporting what has previously been shown in literature. Our method is an open-source pipeline for delineating white matter tracts in subject space but provides the necessary modular components for performing atlas space analysis. As such, we validate and introduce Diffusion Imaging of Neonates by Group Organization (DINGO), a high-level, semi-automated framework that can facilitate harmonization of subject-space tractography generated from diffusion tensor imaging acquired across varying scanners, institutions, and clinical populations. Datasets acquired using varying protocols or cohorts are compartmentalized into subsets, where a cohort-specific template is generated, allowing for the propagation of the tractography mask set with higher spatial specificity. Taken together, this pipeline can reduce multi-scanner technical variability which can confound important biological variability in relation to neonatal brain microstructure.

category: radiology and imaging


title: Ordinal regression increases statistical power to predict epilepsy surgical outcomes

abstract:
ObjectiveStudies of epilepsy surgery outcomes are often small and thus underpowered to reach statistically valid conclusions. We hypothesized that ordinal logistic regression would have greater statistical power than binary logistic regression when analyzing epilepsy surgery outcomes.

MethodsWe reviewed 10 manuscripts included in a recent meta-analysis which found that mesial temporal sclerosis (MTS) predicted better surgical outcome after a stereotactic laser amygdalohippocampectomy (SLAH). We extracted data from 239 patients from eight studies which reported four discrete Engel surgical outcomes after SLAH, stratified by the presence or absence of MTS.

ResultsThe rate of freedom from disabling seizures (Engel I) was 64.3% (110/171) for patients with MTS compared to 44.1% (30/68) without MTS. The statistical power to detect MTS as a predictor for better surgical outcome after a SLAH was 29% using ordinal regression, which was significantly more than the 13% power using binary logistic regression (paired t-test, p<0.001). Only 120 patients are needed to achieve 80% power to detect MTS as a predictor using ordinal regression, compared to 210 patients that are needed to achieve 80% power using binary logistic regression.

ConclusionOrdinal regression should be considered when analyzing ordinal outcomes (such as Engel surgical outcome), especially for datasets with small sample sizes.


title: Development of second and third-trimester population-specific machine learning pregnancy dating model (Garbhini-GA2) derived from the GARBH-Ini cohort in north India

abstract:
BackgroundThe prevalence of preterm birth (PTB) is high in lower and middle-income countries (LMIC) such as India. In LMIC, since a large proportion seeks antenatal care for the first time beyond 14-weeks of pregnancy, accurate estimation of gestational age (GA) using measures derived from ultrasonography scans in the second and third trimesters is of paramount importance. Different models have been developed globally to estimate GA, and currently, LMIC uses Hadlocks formula derived from data based on a North American cohort. This study aimed to develop a population-specific model using data from GARBH-Ini, a multidimensional and ongoing pregnancy cohort established in a district hospital in North India for studying PTB.

MethodsData obtained by longitudinal ultrasonography across all trimesters of pregnancy was used to develop and validate GA models for second and third trimesters. The first trimester GA estimated by ultrasonography was considered the Gold Standard. The second and third trimester GA model named, Garbhini-GA2 is a multivariate random forest model using five ultrasonographic parameters routinely measured during this period. Garbhini-GA2 model was compared to Hadlock and INTERGROWTH-21st models in the TEST set by estimating root-mean-squared error, bias and PTB rate.

FindingsGarbhini-GA2 reduced the GA estimation error by 23-45% compared to the published models. Furthermore, the PTB rate estimated using Garbhini-GA2 was more accurate when compared to published formulae that overestimated the rate by 1{middle dot}5-2{middle dot}0 times.

InterpretationThe Garbhini-GA2 model developed is the first of its kind developed solely using Indian population data. The higher accuracy of GA estimation by Garbhini-GA2 emphasises the need to apply population-specific GA formulae to improve antenatal care and better PTB rate estimates.

FundingCentre for Integrative Biology and Systems Medicine, IIT Madras; Department of Biotechnology, Government of India; Grand Challenges India, BIRAC.

Panel: Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSThe appropriate delivery of antenatal care and accurate delivery date estimation is heavily dependent on accurate pregnancy dating. Unlike GA estimation using crown-rump length in the first trimester, dating using foetal biometry during the second and third trimesters is prone to inaccuracies. This is a public health concern, particularly in low and middle-income countries like India, where nearly 40% of pregnant women seek their first antenatal care beyond 14 weeks of gestation. The dating formulae used in LMIC were developed using foetal biometry data from the Caucasian population, and these formulae are prone to be erroneous when used in ethnically different populations.

Added value of this studyThis study developed a dating model, the Garbhini-GA2 model for second and third trimesters of pregnancy using multiple candidate biometric predictors measured in a North Indian population. When evaluated internally, this model outperformed the currently used dating models by reducing the errors in the estimation of gestational age by 25-40%. Further, Garbhini-GA2 estimated a PTB rate similar to that estimated by the Gold Standard in our population, while the published formulae overestimated the PTB rates.

Implications of all the available evidenceOur Garbhini-GA2 model, after due validations in independent cohorts across the Southeast Asian regions, has the potential to be quickly translated for clinical use across the region. A precise dating will benefit obstetricians and neonatologists to plan antenatal and neonatal care more exactly. From an epidemiologist standpoint, using the Garbhini-GA2 dating formulae will improve the precision of the estimates of pregnancy outcomes that heavily depend on gestational age, such as preterm birth, small for gestational age and stillbirth in our population. Additionally, our dating models will improve phenotyping by reducing the risk of misclassification between outcomes for mechanistic and biomarker research.

category: obstetrics and gynecology


title: Hi-C detects genomic structural variants in peripheral blood of pediatric leukemia patients

abstract: B-cell acute lymphoblastic leukemia (B-ALL) is often driven by chromosome translocations that result in recurrent and well-studied gene fusions. Currently, fluorescent in-situ hybridization probes are employed to detect candidate translocations in bone marrow samples from B-ALL patients. Recently Hi-C, a sequencing-based technique originally designed to reconstruct the three-dimensional architecture of the nuclear genome, was shown to effectively recognize structural variants. Here, we demonstrate that Hi-C can be used as a genome-wide assay to detect translocations and other structural variants of potential clinical interest. Structural variants were identified in both bone marrow and peripheral blood samples, including an ETV6-RUNX1 translocation present in one pediatric B-ALL patient. Our report provides proof-of-principle that Hi-C could be an effective strategy to globally detect driver structural variants in B-ALL peripheral blood specimens, reducing the need for invasive bone marrow biopsies and candidate-based clinical tests.


title: COVID-19 data reporting systems in Africa reveal insights for pandemic preparedness

abstract:
BackgroundThroughout the coronavirus disease 2019 (COVID-19) pandemic, there have been a variety of practices for international reporting of COVID-19 data. African countries have used different national reporting systems to publicly share data. Analyzing the content, format, and frequency of these systems could elucidate lessons for future pandemics.

MethodsWe examined national COVID-19 reporting practices across 54 African countries through 2020. Reporting systems were compared by type of report, frequency, and data content. We also compared reporting of metrics such as a patient demographics and co-morbidities, healthcare capacity, and diagnostic testing. We further evaluated regional and country-specific reporting practices in Cameroon, Egypt, Kenya, Senegal, and South Africa as examples from different sub-regions.

ResultsNational COVID-19 reporting systems were identified in 53/54 (98.1%) countries in 2020. Reporting systems were diverse and could be categorized into social media postings, websites, press releases, situation reports, and online dashboards. Of countries with reporting systems, 36/53 (67.9%) had recurrent situation reports and/or online dashboards which provided the highest quality of data.

ConclusionsAfrican countries created diverse reporting systems to share COVID-19 data. Many countries used routinely updated situation reports or online dashboards. However, few countries reported patient demographics, co-morbidities, diagnostic testing practices, and healthcare capacity. Including these metrics as well as improving standardization and accessibility of data reporting systems could augment research and decision-making, as well as increase public awareness and transparency for national governments.


title: Tumor genomic subtypes orthogonal to mutation burden predict the efficacy of immune checkpoint therapy

abstract:
Higher-resolution tumor-agnostic biomarkers that predict response to immune checkpoint inhibitor (ICI) therapy are needed. Mutation signatures reflect underlying oncogenic processes that can affect tumor immunogenicity, and thus potentially delineate ICI treatment response among tumor types. Systematic mutational signature analysis on all solid tumors in The Cancer Genome Atlas yielded eight distinct tumor genomic subtypes, which were characterized by smoking exposure, ultraviolet light exposure, APOBEC enzyme activity, POLE mutation, mismatch repair deficiency, homologous recombination deficiency, genomic stability, and aging. The former five subtypes were construed to form an immune-responsive group acting as candidates for ICI therapy because of their high expression of immune-related genes and enrichment in cancer types with FDA approval for ICI monotherapy. Under this hypothesis, we developed a software to classify new tumors submitted to whole-exome sequencing. A pan-cancer dataset containing 973 cases treated with ICIs and clinical response was used for validation, where the classified tumor subtypes were significantly associated with ICI response, independent of cancer type and tumor mutational burden high or low status. The new tumor subtyping method can serve as a tumor-agnostic biomarker for ICI response prediction and will improve decision making in cancer treatment.

Structured abstractO_ST_ABSBackgroundC_ST_ABSIn cancer therapy, higher-resolution tumor-agnostic biomarkers that predict response to immune checkpoint inhibitor (ICI) therapy are needed. Mutation signatures reflect underlying oncogenic processes that can affect tumor immunogenicity, and thus potentially delineate ICI treatment response among tumor types.

MethodsBased on mutational signature analysis, we developed a stratification for all solid tumors in The Cancer Genome Atlas (TCGA). Subsequently, we developed a new software (GS-PRACTICE) to classify new tumors submitted to whole-exome sequencing. Using existing data from 973 pan-cancer ICI-treated cases with outcomes, we evaluated the subtype-response predictive performance.

ResultsSystematic analysis on TCGA samples identified eight tumor genomic subtypes, which were characterized by features represented by smoking exposure, ultraviolet light exposure, APOBEC enzyme activity, POLE mutation, mismatch repair deficiency, homologous recombination deficiency, genomic stability, and aging. The former five subtypes were presumed to form an immune-responsive group acting as candidates for ICI therapy because of their high expression of immune-related genes and enrichment in cancer types with FDA approval for ICI monotherapy. In the validation cohort, the samples assigned by GS-PRACTICE to the immune-reactive subtypes were significantly associated with ICI response independent of cancer type and TMB high or low status.

ConclusionsThe new tumor subtyping method can serve as a tumor-agnostic biomarker for ICI response prediction and will improve decision making in cancer treatment.

One Sentence SummaryA novel tumor genome subtyping method based on mutation signature analysis can predict response to immune checkpoint therapy orthogonally to tumor mutational burden.

category: oncology


title: Mutation burden-orthogonal tumor genomic subtypes delineate responses to immune checkpoint therapy


title: High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil

abstract:
BackgroundVisceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, although not yet recognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum in Bahia, Brazil and investigated the virological and immunological factors associated with co-infection.

Methodology and Principal FindingsWe adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n=5,346 and CSC-II, n=317) of treatment-naive HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected at the time of HIV-1 diagnosis between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house immunoassay (ELISA) with SLA (Soluble Leishmania Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46% and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10/IP-10 (p=0.0076) and a tendency of increased CXCL9/MIG (p=0.061) in individuals with DP serology for L. infantum, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH.

Conclusions/SignificanceThis study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

AUTHOR SUMMARYMore than 1 billion people live in areas endemic for leishmaniasis and are at risk of infection, which includes one third of the 38 million people living with HIV (PWH) worldwide. Leishmaniasis is a neglected tropical disease caused by infection with Leishmania parasites, transmitted by bites from infected sand flies. HIV/Leishmania co-infection is increasing worldwide, especially in Southern Europe and Brazil, due to both human and ecological factors (migration, climate change, deforestation). This study demonstrates that a worryingly high number (one out of 6) of PWH in Bahia (Northeast Brazil) show previous or ongoing infection with the parasite Leishmania infantum, determined by antibodies detection against this parasite in PWH. Using a rigorous study design with data collection over 18 years in >5500 PWH, we found similarly high numbers (16.3% and 15.5%) of PWH with antibodies against Leishmania infantum in two consecutive cohorts. Moreover, PWH with antibodies against Leishmania infantum in Bahia, Brazil displayed a worse immune profile, with lower CD4 immune cells numbers and immune activation mediated by interferon, which we confirmed in independent HIV- and Leishmania-infected cohorts from other geographic areas. Our results underscore the need to raise awareness and define public health strategies to prevent HIV/Leishmania co-infection, since therapeutic failure and mortality are strongly increased in co-infected PWH, even with antiretroviral therapy as standard of care.

category: hiv aids


title: Determination of utility of 3 minute and 6 minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary hospital in North India

abstract:
IntroductionThere have been 214 million confirmed cases of COVID-19 worldwide with a total death tally of 4.4 million. The current study aims to determine the predictive value of 3 minute and 6-minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary care hospital in North India.

MethodsThe study population consisted of adults (age more than 18 years) with a confirmed diagnosis of Covid-19 by RT-PCR on nasopharyngeal specimens. Patients with only mild illness were enrolled. After the patients were admitted to the isolation ward, the presenting history, comorbidity status, vital signs and laboratory parameters were recorded. The 3 and 6 minute walk test was performed daily from admission till discharge or progression of severity of COVID-19 and it was used to calculate BDS and NEWS2 scores.

ResultsOur study consisted of 50 patients with 34 (68%) males and the mean (SD) age of the patient population being 28.1 (6.4) years. The most common symptoms were fever, sore throat, and cough. All laboratory parameters were within normal ranges for all the patients. 96% recovered without progression, while only 4% of them progressed to moderate illness. Results of the 3 and 6 minutes walk tests, BDS and NEWS2 scores showed improvement over the course of hospital stay.

ConclusionsAlthough the walk tests and the scores improved over time, they failed to predict the disease progression.


title: Why a Globally Fair COVID-19 Vaccination? An Analysis based on Agent-Based Simulation

abstract: In this paper, an Agent-Based Model (ABM) is proposed to evaluate the impact of COVID-19 vaccination drive in different settings. The main focus is to evaluate the counter-effectiveness of disparity in vaccination drive among different regions / countries. The model proposed is simple yet novel in the sense that it captures the spatial transmission-induced activity into consideration, through which we are able to relate transmission model to the mutated variations of the virus. Some important what-if questions are asked in terms of number of deaths, and time required and percentage of population needed to be vaccinated before the pandemic is eradicate. The simulation results have revealed that it is necessary to maintain a global (rather than regional or country oriented) vaccination drive in case of a new pandemic or continual efforts against COVID-19.

category: epidemiology


title: COVID-19 Vaccine: Newspaper Coverage of the side effects of the vaccine in Nigeria

abstract:
BackgroundCOVID-19 Vaccine hesitancy is increasing globally, and this threatens the worlds ability to bring the pandemic under control. The way the media reports on the vaccine may influence or affect how the population perceive the safety and efficacy of the vaccine.

MethodsThe aim of this study was to determine how newspapers in Nigeria report stories about the vaccine and the side effects of the vaccine amidst the growing fear on the safety of the vaccine. A total of 4 national daily newspapers were randomly selected for the study. These are Leadership, Guardian, Nation and Punch newspapers. The study was anchored on agenda setting theory. Quantitative content analysis research was used for the study. The duration of the study was the day the vaccine was introduced in Nigeria: March 1st, 2021 to July 31st, 2021. An Excel sheet served as the instrument for data collection and analysis done using SPSS version 25 with the level of significance predetermined at a p-value <0.05.

ResultsKey findings from this research were: Government officials and technical experts were predominantly used by the newspapers as the source of their information. There was a mixed reporting of vaccine side effects with a significant difference between those newspaper publications that reported vaccine side effects and those that didnt. Amongst those that reported side effects, there was also a significant difference between those that communicated how and where to report the side effects as against those that didnt.

ConclusionAs part of the effort to curtail vaccine hesitancy, a continuous improvement in communicating the vaccine efficacy and safety is needed.

category: public and global health


title: Using conditional inference to quantify interaction effects of socio-demographic covariates of US COVID-19 vaccine hesitancy

abstract: COVID-19 vaccine hesitancy has become a major issue in the U.S. as vaccine supply has outstripped demand and vaccination rates slow down. At least one recent global survey has sought to study the covariates of vaccine acceptance, but an inferential model that makes simultaneous use of several socio-demographic variables has been lacking. In this article, we present such a model using US-based survey data collected by Gallup. Our study agrees with the global survey results in some respects, but is also found to exhibit significant differences. For example, women and people aged between 25-54 were found to be more vaccine hesitant. Our conditional inference tree model suggests that trust in government, age and ethnicity are the most important covariates for predicting vaccine hesitancy, and can interact in ways that make them useful for communication-based outreach, especially if conjoined with census data. In particular, we found that the most vaccine hesitant individuals were those who identified as Black Republicans with a high school (or lower) education and lower income levels, who were involuntarily unemployed and trusted in the Trump administration.


title: Hemodynamics After Fontan Procedure are Determined by Patient Characteristics and Anastomosis Placement Not Graft Selection: a Patient-Specific Multiscale Computational Study

abstract:
ObjectivesPatient-specific multiscale modeling simulates virtual surgeries of the Fontan procedure using three different graft options. Predictive modeling details post-operative outcomes that can help inform clinical decision support.

MethodsSix patients underwent preoperative cardiac magnetic resonance imaging and catheterization. Virtual surgery is carried out for each patient to test the resulting hemodynamics of three Fontan graft options: ECC, 9mm Y-graft, and 12mm Y-graft.

Results1) one-way ANOVA p>0.998 in all systemic pressures and flows between graft options, 2) p=0.706 for hepatic flow distribution between graft options, 3) local power loss differences do not affect the systemic circulation, 4) anastomosis positioning modification of the same Y-graft in the same patient changed left PA hepatic distribution from 0.66 to 0.49

ConclusionsSystemic pressures and blood flow after the Fontan procedure are not affected by graft selection but are well influenced by patient pulmonary vascular impedance. The hepatic distribution can be affected by anastomosis placement.

Ultra-mini abstractWe present the first case series of patient-specific multiscale modeling of the Fontan procedure. Despite noticeable local power loss differences, graft selection does not affect systemic pressure and flow rates or other clinically relevant quantities. Anastomosis placement can affect hepatic distribution.


title: Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2

abstract:
SARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina.

Seroconversion rates in unexposed subjects after the first and second doses were 40% and 100%, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p<0.0001).

The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p=0.005).

A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p=0.008).

Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p<0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naive subjects by two doses of the vaccine (p<0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects.

Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels.

Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.