title: Evolution of SARS-CoV-2 seroprevalence and clusters in school children from June 2020 to April 2021 reflect community transmission: prospective cohort study Ciao Corona

abstract:
ObjectivesTo longitudinally assess severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and clustering of seropositive children within school classes in March-April 2021 compared to June-July and October-November 2020. To examine the evolution of symptoms and the extent of under-detection of SARS-CoV-2 in children.

DesignProspective cohort study of randomly selected schools and classes.

SettingSchools remained open for physical attendance in Switzerland from May 2020 to the end of 2020/2021 school year. Lower school level (age range 7-10 years) and middle school level (8-13 years) children in primary schools, and upper school level (12-17 years) children in secondary schools were invited for SARS-CoV-2 serological testing in the Ciao Corona study in the canton of Zurich, Switzerland. Three testing rounds were completed in June-July 2020 (T1; after the first wave of SARS-CoV-2 infections), October-November 2020 (T2; during the peak of the second wave), and March-April 2021 (T3; after the second wave and with SARS-CoV-2 variants of concern becoming dominant). Parents completed questionnaires on sociodemographic information and symptoms.

Participants2487 children (median age 12 years, age range 7-17 years) recruited from 275 classes in 55 schools participated in the testing in March-April 2021; total of 2974 children participated in at least one of the 3 testing rounds.

Main outcome measuresSARS-CoV-2 serology results; clustering of seropositive children within classes; reported symptoms.

ResultsThe proportion of children who were SARS-CoV-2 seropositive increased from 1.5% (95% credible interval (CrI) 0.6% to 2.6%) in June-July 2020, to 6.6% (95% CrI 4.0% to 8.9%) in October-November, and to 16.4% (95% CrI 12.1% to 19.5%) in March-April 2021. By March-April 2021, children in upper school level (12.4%; 95% CrI 7.3% to 16.7%) were less likely to be seropositive than those in middle (19.5%; 95% CrI 14.2% to 24.4%) or lower school levels (16.0%; 95% CrI 11.0% to 20.4%). Children in the upper school level had a 5.1% (95% CI -9.4% to -0.7%) lower than expected seroprevalence by March-April 2021 than those in middle school level, based on difference-in-differences analysis. The ratio of PCR-diagnosed to all seropositive children changed from 1 to 21.7 (by June-July 2020) to 1 to 3.5 (by March-April 2021). Symptoms were reported by 37% of newly seropositive and 16% seronegative children. Potential clusters of 3 or more newly seropositive children were detected in 24 of 119 (20%) classes with a high participation rate, from which a median of 17 clusters could be expected due to random distribution of seropositive children within the classes. Clustering was lowest in middle and upper school levels. Retention rate in the cohort was high (84% of T1 participants attended T3). Among participants, supporting society and research were reported more commonly for participation than personal reasons. Fear of blood sampling was the most frequently reported reason for non-participation, reported for 64% of children.

ConclusionsBy March-April 2021, 16.4% of children and adolescents were seropositive in the canton of Zurich, Switzerland. The majority of clusters of SARS-CoV-2 seropositive children in school classes could be explained by community rather than intra-class transmission of infections. Seroprevalence and clustering was lowest in upper school levels during all timepoints.

Trial registrationClinicalTrials.gov NCT04448717.

What is already known on the topicO_LITransmission of SARS-CoV-2 in school setting largely followed community transmission in 2020.
C_LIO_LIWith implemented preventive measures, secondary attack rates were low and clustering of SARS-CoV-2 infections within classes and schools (outbreaks) were observed rarely.
C_LI

What this study addsO_LIWith high community incidence and new variants of SARS-CoV-2, seroprevalence increased in school children between October 2020 - March 2021 in the canton of Zurich in Switzerland, and was higher in lower school levels.
C_LIO_LIMost of the potential clusters of children who tested seropositive within classes could be explained by community rather than intra-class transmission of SARS-CoV-2, especially in middle and upper school levels.
C_LIO_LIMore children who tested seropositive in March-April 2021 were diagnosed and reported symptoms potentially related to SARS-CoV-2 infection more frequently than those who tested seropositive in June-July or October-November 2020.
C_LIO_LIThe most frequent reason for non-participation was fear of blood sampling (62% of children).
C_LI


title: Genome-wide Analysis Identifies Novel Gallstone-susceptibility Loci Including Genes Regulating Gastrointestinal Motility

abstract:
ObjectiveGenome-wide association studies (GWAS) have identified several risk loci for gallstone disease. As with most polygenic traits, it is likely many genetic determinants are undiscovered. The aim of this study was to identify novel genetic variants that represent new targets for gallstone research and treatment.

DesignWe performed a GWAS of 28,627 gallstone cases and 348,373 controls in the UK Biobank and a GWA meta-analysis (43,639 cases and 506,798 controls) with the FinnGen cohort. We assessed pathway enrichment using gene-based then gene-set analysis and tissue expression of implicated genes in Genotype-Tissue Expression project data. We constructed a polygenic risk score (PRS) and evaluated phenotypic traits associated with the score.

ResultsSeventy-five risk loci were identified (P<5*10-8) of which forty-six were novel. Pathway enrichment revealed associations with lipid homeostasis, glucuronidation, phospholipid metabolism and gastrointestinal motility. ANO1 and TMEM147, both in novel loci, are strongly expressed in the gallbladder and gastrointestinal tract. Both regulate gastrointestinal motility. The gallstone risk allele rs7599-A leads to suppression of hepatic TMEM147 expression suggesting the protein protects against gallstone formation. Individuals in the highest decile of the PRS demonstrated a 6-fold increased risk of gallstones compared to the lowest risk category. The PRS was strongly associated with increased body mass index, serum liver enzyme and C-reactive protein concentrations and decreased lipoprotein cholesterol concentrations.

ConclusionThis GWAS demonstrates the polygenic nature of gallstone risk and identifies 46 novel susceptibility loci. For the first time, we implicate genes influencing gastrointestinal motility in the pathogenesis of gallstones.

Summary BoxO_ST_ABSWhat is already known on this subject?C_ST_ABSO_LIGenome-wide association studies (GWAS) have identified 29 genetic variants within independent loci which increase the risk of gallstone disease.
C_LIO_LIMost of these variants lie within or near to genes that regulate lipid or bile acid metabolism. Gallstones are known to have a significant genetic component with 25-50% of gallstone disease due to genetic risk factors.
C_LIO_LIMuch of this risk is not accounted for by the known gallstone-susceptibility loci.
C_LI

What are the new findings?O_LIWe performed a GWAS in the UK Biobank (28,627 gallstone cases, 348,373 controls) and a GWA meta-analysis (43,639 cases and 506,798 controls) with the FinnGen cohort.
C_LIO_LIWe identified a total of 75 gallstone-susceptibility loci with 46 of these being new and the remaining 29 being those already identified.
C_LIO_LIWe annotated the variants based on their position within or near to genes and assessed pathway enrichment through gene-set analysis.
C_LIO_LIWe identify two novel gallstone-susceptibility loci in which the lead variants lie within genes governing gastrointestinal motility which highly expressed in gallbladder (ANO1 and TMEM147).
C_LIO_LIWe demonstrate further loci involved in primary cilia function.
C_LIO_LIWe report significant association of a polygenic risk score with gallstones using independent subsets of the study population.
C_LI

How might it impact on clinical practice in the foreseeable future?O_LIThe genes and pathways identified represent novel targets for development of medication targeting primary or secondary prevention of gallstones. This may be of particular benefit to those unable to undergo cholecystectomy.
C_LIO_LIThe individual variants or polygenic risk score identified in this GWAS could form the basis for identification of individuals with high risk of gallstones to support screening or treatment of gallstone disease. This screening may be of particular benefit in populations with elevated risk of gallstones such as haemolytic disease or bariatric surgery.
C_LI

category: gastroenterology


title: Hemodilution in High Risk Cardiac Surgery: Laboratory Values, Physiological Parameters and Outcomes

abstract:
BackgroundAcute normovolemic hemodilution (ANH) is a blood conservation strategy in cardiac surgery, predominantly used in coronary artery bypass graft (CABG) and/or valve procedures. Although higher complexity cardiac procedures may benefit from ANH, concerns for hemodynamic instability and organ injury during hemodilution hinder its wider acceptance. Laboratory and physiological parameters during hemodilution in complex cardiac surgeries have not been described.

Study Design and MethodsThis observational cohort (2019-2021) study included 169 patients who underwent thoracic aortic repair, multiple valve procedure, concomitant CABG with the aforementioned procedure, and/or redo sternotomies. Patients who received allogeneic blood were excluded. Statistical comparisons were performed between ANH (N=66) and non ANH controls (N=103). ANH consisted of removal of blood at the beginning of surgery and its return after cardiopulmonary bypass (CPB).

ResultsIntraoperatively, the ANH group received more albumin (p=0.04) and vasopressor medications (p=0.01); while urine output was no different between ANH and controls. Bilateral cerebral oximetry (rSO2) values were similar before and after hemodilution. During bypass rSO2 were discretely lower in the ANH vs. control group (right rSO2 p=0.03, left rSO2 (p=0.05). No differences in lactic acid values were detected across the procedural continuum. Postoperatively, no differences in extubation times, ICU length of stay, kidney injury, stroke or infection were demonstrated.

DiscussionThis study suggests hemodilution to be a safe and comparable blood conservation technique, even without accounting for potential benefits of reduced allogenic blood administration. The study may contribute to better understanding and wider acceptance of ANH protocols in high risk cardiac surgeries.

category: surgery


title: COVID-19 convalescent plasma donors: impact of vaccination on antibody levels, breakthrough infections and reinfection rate.

abstract: From April 2020 through May 2021 in Padova Province 3395 COVID-19 recovered patients were recruited as potential convalescent plasma donors and tested for SARS-CoV-2 antibodies. Since January 2021 COVID-19 vaccination campaign began in Italy, the impact of vaccination on antibody levels and suspect vaccine breakthrough infections in these subjects were investigated. Post-vaccination anti-Sars-Cov-2 antibody level in 54 previously infected subjects had an exponential increase compared to pre-vaccination level regardless of the number of vaccine doses. However after 100 days from vaccination SARS-CoV-2 antibody level tends to decline. Post-vaccination primary infections were detected in 15 cases, with 3 possible breakthrough infections after a full vaccination course. In these cases, antibody response after infection was present but weaker than the one of subjects vaccinated after natural infection. A trend toward stronger antibody response was observed with increasing distance between natural infection and vaccination. Additionally, 2 cases of asymptomatic reinfections are also discussed.

category: infectious diseases


title: Remdesivir for the treatment of COVID-19 disease: A retrospective comparative study of patients treated with and without Remdesivir

abstract:
BackgroundRemdesivir (RDV) in coronavirus disease 2019 (COVID-19) has been found to be beneficial in patients with severe disease; however, its role in mild-moderate disease and its optimal timing need to be identified.

ObjectiveTo assess the course of illness and final outcome in patients who received RDV at various stages of illness, and compare it to the non-RDV group.

MethodsThis is a retrospective data analysis of 1262 COVID-19 patients hospitalized from May5, 2020 to August 31, 2020. The primary outcomes were progression to mechanical ventilation (MV) or death. Kaplan Meier survival analysis and log rank test were used for evaluating primary outcomes.

Results398 patients comprised the RDV group and 260 patients comprised the non-RDV group. 2/3rd of patients were above 50 years of age in both the groups and 3/4th patients were male. Mortality rate was 5.8% in RDV group (10.4% in non-RDV group). Mortality rate was 3.6%, 4% and 16.7% when RDV was started within 5 days, 5 to 10 days and after 10 days of symptom onset respectively. Fewer patients in RDV group progressed to MV (4.0% v/s 8.2%). Earlier discharge occurred in RDV group. Use of supplemental oxygen was observed in 44.7% patients in RDV group (54.2% in non-RDV group). No significant adverse events were observed with RDV. Survival analysis showed that probability of event (death) was significant for patients with hypertension (HT) and/or diabetes mellitus (DM) in RDV group.

ConclusionEarly initiation of RDV is associated with shorter hospital stay, lower mortality as well as reduced need for supplemental oxygen and mechanical ventilation.


title: Dique Filipeia: A rehabilitation protocol for non-intubated COVID-19 in-hospital patients

abstract:
ObjectiveThe aim of this study was to evaluate the effectiveness of the "Dique Filipeia" rehabilitation protocol in patients with COVID-19 admitted to reference hospitals.

MethodsThis is an experimental study with COVID-19 patients admitted to the hospitals wards being considered eligible. The study outcomes were assessed between patients undergoing the rehabilitation protocol (Dique Filipeia group) and patients who did not receive the protocol (control group). The rehabilitation protocol consisted in classifying patients daily into four levels of severity through peripheral oxygen saturation. Severity was classified by the oxygen flow needed to maintain a saturation greater than or equal to the cut-off point of 93%. A standardized ventilatory support and functional rehabilitation exercises were performed for each severity level patient, followed by an attempt to wean oxygen.

ResultsA total of 727 patients were analyzed in the study. The Dique Filipeia group presented a lower total (132.7 {+/-} 35.3 vs 307.0 {+/-} 114.3 m3/patient; effect size 1.73) and daily (2.9 {+/-} 1.0 vs 6.8 {+/-} 3.1 m3/day/patient; effect size 1.46) oxygen expenditure than the control group. The Dique Filipeia patients presented higher hospital discharge (64.9 {+/-} 9.3 vs 35.4 {+/-} 7.5%; effect size 3.46) and lower length of stay (15.8 {+/-} 4.2 vs 29.1 {+/-} 3.4 days; effect size 3.47) than the control group. The Dique Filipeia group patients, who were demanding oxygen therapy, were using 6.2 {+/-} 4.3 L/min of oxygen at day 1. There was a statistically significant reduction from day 2 (p = 0.0001) and oxygen flow was reduced below 1L/min after day 7.

ConclusionsThe implementation of a standardized rehabilitation protocol reduced oxygen expenditure, increased hospital discharge and reduced the length of hospital stay. Dique Filipeia is a practical, feasible and safe protocol.

category: rehabilitation medicine and physical therapy


title: Association between telecommuting environment and low back pain among Japanese telecommuting workers: A cross-sectional study

abstract:
ObjectivesWe evaluated the relationship between telecommuting environment and low back pain (LBP) among desk-based workers in Japan.

MethodsThis cross-sectional study included 3,663 desk-based, telecommuting workers. LBP was assessed using a 0-10 numerical rating scale. The telecommuting environment was evaluated using subjective questions. Mixed-effects logistic regression analysis was used to evaluate this association.

ResultsThe results of mixed-effects logistic model revealed that not having a place or room to concentrate on work, desk not well-lit enough for work, lack of space on the desk to work, not having enough legroom, and uncomfortable temperature and humidity conditions in the workspace were significantly associated with higher odds of LBP.

ConclusionsOur findings suggest that telecommuting environment is associated with the prevalence of LBP.

category: occupational and environmental health


title: A new sensitive and robust next-generation sequencing platform for HIV-1 drug resistance mutations testing

abstract:
Next-generation sequencing (NGS) is a trending new platform which allows cheap, quantitative, high-throughput, parallel sequencing for minority variants with frequencies less than 20% of the HIV-1 quasi-species. In clinical setting, these advantages are crucial for choosing antiretroviral drugs with low genetic barriers and will potentially benefit treatment outcomes.

In this investigation, we implemented the Boxin HIV-1 NGS platform for genotyping the drug-resistance-associated variants in PR/RT regions. Plasmids with known mutations were used to analyze the accuracy, reproducibility, and reliability of the Boxin NGS assay. Variant frequencies reported by Boxin NGS and the theoretical value were highly concordant. The Bland-Altman plot and the coefficient of variation (7%) suggested that the method has excellent reproducibility and reliability. Sanger sequencing confirmed the existence of these known variants with frequencies equal or above 20%.

78 blood samples were obtained from AIDS patients and underwent PR/RT region genotyping by Sanger sequencing and Boxin NGS. 33 additional drug resistance mutations were identified by Boxin NGS, 23/33 mutations were minority variants with frequencies below 20%.

15 blood samples obtained from AIDS patients underwent PR/RT region genotyping by Sanger sequencing, Boxin NGS, and Vela NGS. The Bland-Altman plot suggested that the variant frequencies detected by Boxin and Vela were highly concordant. Moreover, Boxin NGS assay detected five more minority variants with frequencies ranged from 1% to 20%. In a series of samples collected from 2016 to 2017, Boxin NGS reported a M184V mutation with a frequency of 4.92%, 3 months earlier than this mutation was firstly detected by Vela NGS and Sanger sequencing.

In conclusion, Boxin NGS had good accuracy, reproducibility, and reliability. Boxin NGS was highly concordant with Sanger sequencing and Vela NGS. In terms of genotyping HIV-1 variants in PR/RT regions, Boxin NGS was more cost-efficient and appeared to have increased sensitivity without compromising sequence accuracy.

category: hiv aids


title: Paradoxical Sex-Specific Patterns of Autoantibodies Response to SARS-CoV-2 Infection

abstract:
BackgroundAmidst the millions of individuals affected directly by the pandemic, pronounced sex differences in the susceptibility and response to SARS-CoV-2 infection remain poorly understood. Emerging evidence has highlighted the potential importance of autoimmune activation in modulating not only the acute response but also recovery trajectories following SARS-CoV-2 exposure. Given that immune-inflammatory activity can be sex-biased in the setting of severe COVID-19 illness, we deliberately examined sex-specific autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease.

MethodsWe used a bead-based array containing over 90 autoantigens previously linked to a range of classic autoimmune diseases to assess autoantibody (AAB) titers in 177 participants. All participants had confirmed evidence of prior SARS-CoV-2 infection based on presence of positive anti-nucleocapsid IgG serology results (Abbott Diagnostics, Abbott Park, Illinois). We used multivariate analysis to determine whether sex-bias was associated with increased rates of AABs reactivity and symptom burden after SARS-CoV2 infection.

Results82.4% of AABs reactivity was associated with being male compared to 17.6% with female. We found a diversity of AABs responses that exhibited sex-specific patterns of frequency distribution as well as associations with symptomatology and symptom burden.

ConclusionOur results reveal a remarkable sex-specific prevalence and selectivity of AAB responses to SARS-CoV-2. Further understanding of the nature of triggered and persistent AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19.


title: Virus neutralizing antibody responses after two doses of BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine

abstract:
BackgroundLimited information is available on the effectiveness of the BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine, especially in the elderly, despite the fact that it is approved in more than 50 countries.

MethodsVirus neutralizing antibody titres, as a rapidly available but highly predictive surrogate marker, were measured after two doses of the BBIBP-CorV vaccine in 450 subjects. Results were analyzed in a multivariable model accounting for age, sex and time since the administration of the second dose of the vaccine.

FindingsSex and time since the second dose had little association with the antibody titres. Age, however, was highly relevant: measurable antibody levels were present in about 90% of individuals below the age of 50, but antibody production after BBIBP-CorV vaccination was strongly reduced with increasing age. A large number of elderly subjects, reaching 25% at 60 years, and up to 50% at ages over 80, were found not to produce any protective antibody.

InterpretationNeutralizing antibody titre, as a correlate of protection for COVID-19 disease susceptibility, should help to evaluate the effectiveness of the BBIBP-CorV vaccine. Results suggest that proper measures should be undertaken to prevent a potential outbreak of COVID-19 in BBIBP-CorV vaccinated but eventually unprotected elderly individuals.

FundingNo specific funding was used to carry out the study.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine was found to be effective, but the Phase 3 trial included few women, almost no elderly subject and no subject with preexisting medical condition. It is therefore especially important to monitor the real-world effectiveness of this vaccine, however when searching Pubmed for (Sinopharm OR BBIBP-CorV) AND vaccine AND (effectiveness OR efficacy OR antibody OR titre) in text words with no language or date restriction and with translation of the terms enabled, we found no such published study. The most rapid way to generate such evidence is the assessment of antibody response which was found to be highly predictive for disease susceptibility. This is of crucial importance as the vaccine is approved in more than 50 countries, and hundreds of millions have already been vaccinated with many planned to be vaccinated in the near future with this vaccine.

Added value of this studyVirus neutralizing antibody titres were measured after two doses of the BBIBP-CorV vaccine in 450 subjects. Results were analyzed in a multivariable model accounting for age, sex and time since the administration of the second dose of the vaccine. We found that sex and time since the second dose had little association with the antibody titres. Age, however, was highly relevant: while the vast majority of those below 50 years had measurable antibody levels, this rate quickly dropped with increasing age. In subjects aged 60 years, quarter, in those above 80 almost half had no detectable neutralizing antibody.

Implications of all the available evidenceThe real-world effectiveness of the BBIBP-CorV vaccine should be carefully monitored. Elderly subjects are especially prone to produce no protective antibody after vaccination. This should be monitored, and proper measures should be undertaken to prevent a potential outbreak of COVID-19 in BBIBP-CorV vaccinated but eventually unprotected elderly individuals.


title: High frequency, high throughput quantification of SARS-CoV-2 RNA in wastewater settled solids at eight publicly owned treatment works in Northern California shows strong association with COVID-19 incidence

abstract:
A number of recent retrospective studies have demonstrated that SARS-CoV-2 RNA concentrations in wastewater are associated with COVID-19 cases in the corresponding sewersheds. Implementing high-resolution, prospective efforts across multiple plants depends on sensitive measurements that are representative of COVID-19 cases, scalable for high throughput analysis, and comparable across laboratories. We conducted a prospective study across eight publicly owned treatment works (POTWs). A focus on SARS-CoV-2 RNA in solids enabled us to scale-up our measurements with a commercial lab partner. Samples were collected daily and results were posted to a website within 24-hours. SARS-CoV-2 RNA in daily samples correlated to incidence COVID-19 cases in the sewersheds; a 1 log10 increase in SARS-CoV-2 RNA in settled solids corresponds to a 0.58 log10 (4X) increase in sewershed incidence rate. SARS-CoV-2 RNA signals measured with the commercial laboratory partner were comparable across plants and to measurements conducted in a university laboratory when normalized by pepper mild mottle virus PMMoV RNA. Results suggest that SARS-CoV-2 RNA should be detectable in settled solids for COVID-19 incidence rates > 1/100,000 (range 0.8 - 2.3 cases per 100,000). These sensitive, representative, scalable, and comparable methods will be valuable for future efforts to scale-up wastewater-based epidemiology.

ImportanceAccess to reliable, rapid monitoring data is critical to guide response to an infectious disease outbreak. For pathogens that are shed in feces or urine, monitoring wastewater can provide a cost-effective snapshot of transmission in an entire community via a single sample. In order for a method to be useful for ongoing COVID-19 monitoring, it should be sensitive for detection of low concentrations of SARS-CoV-2, representative of incidence rates in the community, scalable to generate data quickly, and comparable across laboratories. This paper presents a method utilizing wastewater solids to meet these goals, producing measurements of SARS-CoV-2 RNA strongly associated with COVID-19 cases in the sewershed of a publicly owned treatment work. Results, provided within 24 hrs, can be used to detect incidence rates as low as approximately 1/100,000 cases and can be normalized for comparison across locations generating data using different methods.

category: public and global health


title: Adaptive hearing aid benefit in children with mild/moderate hearing loss: A registered, double-blind, randomized clinical trial

abstract:
ObjectivesWe completed a registered double-blind randomized control trial to compare acclimatization to two hearing aid algorithms by experienced pediatric hearing aid users with mild to moderate hearing loss. We hypothesized that extended use (up to 13 months) of the adaptive algorithm with integrated directionality and noise reduction, OpenSound Navigator (OSN), would result in improved performance compared to the control algorithm, omnidirectional (Omni), on auditory, cognitive and academic tasks.

DesignWe recruited 42 children, aged 6 - 13 years old, through Cincinnati Childrens Hospital Medical Centers Division of Audiology. Two children withdrew from the study due to noncompliance or discomfort. The remaining 40 children were paired by age (within one year) and hearing loss (level and configuration). The individuals from each pair were randomly assigned to a group: OSN (experimental) and Omni (control). Each child completed an audiology evaluation, hearing aid fitting, a follow up audiological appointment and two research visits up to 13 months apart. Research visit outcome measures covered speech perception (in quiet and in noise), novel grammar and word learning, cognition, academic ability and caregiver report of listening behaviours.

ResultsThe children with the experimental algorithm did not show improved performance on the outcome measures compared to the control algorithm. There was a significant relationship between age at first hearing aid use and Reading and Mathematical ability across all participants. Data from six children were not included in the analysis due to daily hearing aid usage of less than 6 hours.

ConclusionsUse of the experimental algorithm (OSN) neither enhanced nor reduced performance on auditory, cognitive and academic tasks compared to the control algorithm (Omni).

category: otolaryngology


title: A quest for the origin of the uneven spread of Covid-19 cases.

abstract: For more than one and a half years now the world is highly impacted by the Covid-19 pandemic. The covid-19 cases are, however, not evenly distributed across the countries; a few countries, particularly high-income countries have been hit harder than the countries of weak economic condition. The reasons for such an asymmetrical distribution are not clearly understood yet. In the present work, we have examined the unevenness of global distribution of Covid-19 incidences till 18th June 2021 in terms of the economic condition of countries. Subsequently, we have tried to identify the main underlying factors behind unequal Covid-19 cases. Our analysis suggests that the degree of Isolation, the diffusion of coronavirus (interconnectivity), and the percentage of elderly people in the population are the main causes of the different unequal spread of Covid-19 cases in different countries. We find that the Covid-19 infected and death cases are well describe by a power law in terms of the stated parameters.


title: Combined Metabolic Activators Improves Cognitive Functions in Alzheimer's Disease

abstract:
Alzheimers disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. Here, we analysed the brain transcriptomics data of more than 600 AD patients using genome-scale metabolic models and provided supporting evidence of mitochondrial dysfunction related to the pathophysiologic mechanisms of AD progression. Subsequently, we investigated, in a rat model of AD, the oral administration of Combined Metabolic Activators (CMAs), consisting of NAD+ and glutathione precursors, to explore the effect for improvement of biological functions in AD. CMAs includes L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate, salt form of L-carnitine. The study revealed that supplementation of the CMAs improved the AD-associated histological parameters in the animals. Finally, we designed a randomized, double-blinded, placebo-controlled human phase 2 clinical trial and showed that the administration of CMAs improves cognitive functions in AD patients. As decreased AD Assessment Scale-cognitive subscale (ADAS-Cog) score is the indicator of the improved cognitive function in AD patients, we observed a significant decrease of ADAS-Cog scores on Day 84 vs Day 0 (Log2FC= -0.37, (29% improvement), p-value=0.00001) in the CMA group. We also observed a significant decrease in the placebo group on Day 84 vs Day 0 (Log2FC= -0.19, (14% improvement), p-value=0.001) due to the recommendations of exercise and Mediterranean diet to all AD patients participated in the trial. A comprehensive analysis of the human plasma metabolome and proteome revealed that plasma levels of proteins and metabolites associated with redox metabolism are significantly improved after treatment. In conclusion, our results show that treating AD patients with CMAs leads to enhanced cognitive functions, suggesting a role for such a therapeutic regime in treating AD and other neurodegenerative diseases.

HIGHLIGHTS* Brain transcriptomics data of more than 600 AD patients is analysed.
* Performed an in vivo study using Combined Metabolic Activators (CMAs) in AD rat models.
* We performed a randomized, double-blinded, placebo-controlled human phase 2 clinical trial.
* We showed that cognitive functions in AD patients is improved 29% in the CMA group whereas 14% in the placebo group.

category: neurology


title: Integrated Genomic Analyses Identify High-Risk Factors and Actionable Targets in T-Cell Acute Lymphoblastic Leukemia

abstract: T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy often associated with poor outcomes. To identify high-risk factors and potential actionable targets for T-ALL, we perform integrated genomic and transcriptomic analyses on samples from 165 Chinese pediatric and adult T-ALL patients, of whom 85% have outcome information. The genomic mutation landscape of this Chinese cohort is very similar to the Western cohort published previously, except that the rate of NOTCH1 mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 pathways as well as transcription factors. Further analysis demonstrates that approximately 43% of the high-risk patients harbor at least one potential actionable alteration identified in this study, and T-ALLs with RAS pathway mutations are hypersensitive to MEKi in vitro and in vivo. Thus, our integrated genomic analyses not only systematically identify high-risk factors but suggest that these high-risk factors are promising targets for T-ALL therapies.

category: genetic and genomic medicine


title: Unnecessary antibiotic treatment of children hospitalized with RSV-bronchiolitis: risk factors and prescription patterns

abstract:
BackgroundRespiratory syncytial virus (RSV) is a main cause of respiratory tract infections, especially affecting young children. Antibiotics are often unnecessarily prescribed for the treatment of RSV. Such treatments can have effects on antibiotic resistance in future bacterial infections of treated patients and the general population.

ObjectivesWe sought to understand the risk factors for and patterns of unnecessary antibiotic prescription in children with RSV.

MethodsIn a single center retrospective study in Israel, we obtained data of children aged <2 years (n=1015) hospitalized for RSV-bronchiolitis during 2008-2018, and ascertained not to have bacterial coinfections. Antibiotic misuse was defined as prescription of antibiotics during hospitalization of the study population. Patient and clinical variables were assessed as predictors of unnecessary antibiotic treatment in a multivariable logistic regression model.

ResultsUnnecessary antibiotic treatment rate of children infected with RSV and ascertained not to have a bacterial coinfection was estimated at 33.4% (95% CI 30.5%-36.4%). Increased likelihood of antibiotic misuse was associated with drawing bacterial cultures, and with variables indicative of a severe patient status: lower oxygen saturation, higher body temperature, tachypnea and prior recent emergency room visit. Older age and female sex were also associated with increased likelihood of unnecessary antibiotic treatment.

ConclusionsUnnecessary antibiotic treatment in RSV patients was highly common and may be largely attributed to the physicians perception of patients severity. Improving prescription guidelines, implementing antibiotic stewardship programs and utilizing decision support systems may help achieve a better balance between prescribing and withholding antibiotic treatment.


title: Association between the COVID-19 pandemic and pertussis in France using multiple nationwide data sources

abstract:
BackgroundInterventions to mitigate coronavirus disease 19 (COVID-19) pandemic may impact other respiratory diseases such as pertussis. We aimed to study the course of pertussis in France over an 8-year period and its association with COVID-19 mitigation strategies, using multiple nationwide data sources.

MethodsWe analyzed the number of French pertussis cases between 2013 and 2020, using the PCR test results from nationwide outpatient laboratories (Source 1) and the pediatric network of 41 hospitals (Source 2), and using the reports of an office-based pediatric national network (Source 3). We conducted a quasi-experimental interrupted time-series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles, and secular trend, and included a binary variable for the first national lockdown (ordered on March 16, 2021).

ResultsWe identified 19,039 cases of pertussis from the three data sources during the study period. There was a significant decrease of pertussis cases following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.102 (95% CI 0.040-0.256) and 0.216 (95% CI 0.071-0.656) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 (median of 1 [IQR 0-2] vs. 0 [IQR 0-0] pertussis cases per month before and after lockdown, respectively, p=0.0048).

ConclusionThe drastic reduction of outpatient and hospitalized cases of pertussis strongly suggests an impact of COVID-19 mitigation measures and their consequences on pertussis epidemiology. Pertussis vaccination recommendations should be carefully followed, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.

FundingThere was no specific funding for the study.

category: epidemiology


title: Post-COVID Syndrome. A Case Series and Comprehensive Review

abstract:
The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8 to 55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143 to 258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2 to 1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.

HighlightsO_LIPCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression.
C_LIO_LIPCS is independent of severity of acute illness and humoral immune response.
C_LIO_LIAutonomic symptoms may help to classify patients with PCS.
C_LIO_LILong-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed.
C_LI


title: Educational level as a cause of type 2 diabetes mellitus: Caution from triangulation of observational and genetic evidence

abstract:
BackgroundEducation might be causal to type 2 diabetes mellitus (T2DM). We triangulated cohort and genetic evidence to consolidate the causality between education and T2DM.

MethodsWe obtained observational evidence from the English Longitudinal Study of Ageing (ELSA). Self-reporting educational attainment was categorised as high (post-secondary and higher), middle (secondary), and low (below secondary or no academic qualifications) in 6,787 community-dwelling individuals aged [≥]50 years without diabetes at ELSA wave 2, who were followed until wave 8 for the first diabetes diagnosis. Additionally, we performed two-sample Mendelian randomisation (MR) using an inverse-variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode-based estimate (WMBE) method. Steiger filtering was further applied to exclude single-nucleotide polymorphisms (SNPs) that were correlated with an outcome (T2DM) stronger than exposure (education attainment).

ResultsWe observed 598 new diabetes cases after 10.4 years of follow-up. The adjusted hazard ratios (95%CI) of T2DM were 1.20 (0.97-1.49) and 1.58 (1.28-1.96) in the middle- and low-education groups, respectively, compared to the high-education group. Low education was also associated with increased glycated haemoglobin levels. Psychosocial resources, occupation, and health behaviours fully explained these inverse associations. In the MR analysis of 210 SNPs (R2=0.0161), the odds ratio of having T2DM per standard deviation-decreasing years (4.2 years) of schooling was 1.33 (1.01-1.75; IVW), 1.23 (0.37-4.17; MR-Egger), 1.56 (1.09-2.27; WM), and 2.94 (0.98-9.09; WMBE). However, applying Steiger filtering attenuated most MR results toward the null.

ConclusionsOur inconsistent findings between cohort and genetic evidence did not support the causality between education and T2DM.

Key messagesO_ST_ABSWhat is already known on this subject?C_ST_ABS- Several pieces of evidence suggested that education attainment might play a causal role in the occurrence of T2DM.

What does this study add?- Our observational evidence suggested no direct impact of education on the risk of T2DM. The observed inverse associations were mediated through insufficient psychosocial resources, low occupation class, and unhealthy behaviours due to low education.
- In contrast, the genetic evidence suggested no causal association between education and the risk of T2DM. Notably, the significant associations from our genetic evidence resulted from the invalid genetic instrument used in the analysis.
- The observational and genetic evidence was inconsistent; therefore, our triangulated evidence did not support a causal role of education in the occurrence of T2DM.

category: endocrinology


title: Potential applications of the rapid COVID-19 antibody test kit screening in comparison to the RT-PCR in patients and personnel at the Department of Obstetrics and Gynecology.

abstract:
ObjectiveTo explore potential applications of the rapid antibody test for COVID-19 screening, in comparison to RT-PCR, for emergency obstetric and gynecological procedures, and medical personnel in the Department of Obstetrics and Gynecology.

MethodsA cross-sectional study was conducted in expected 290 participants: 230 patients and 60 medical staff, during the four-month national COVID-19 outbreak period (Aug - Sep 2020, and Dec 2020 - Jan 2021). All participants underwent both rapid antibody tests and RT-PCR (at admission for patients).

ResultsA total of 270 participants completed the study. Fever and URI symptoms were present in 6/210 patients (2.8%) while one patient (0.5%) had a history of traveling to a high-risk area. However, only two (1%) asymptomatic patients had positive IgM results. Concerning the medical personnel, 10% fell into the  patient under investigation (PUI) category. 4/60 (6.7%) IgM positive was observed in the staff cohort in which 3/4 came from non-PUI participants. Neither participant had RT-PCR positive demonstrating a 1.9% total false positive rate.

ConclusionRapid point-of-care antibody test can be used to screen either a pregnant coming for delivery, a patient who requires urgent/emergency operative procedures, or medical personnel, at least in the defined lower-prevalence COVID-19 situation.

Trial registrationThis study was approved by the Institutional Review Board of Srinakharinwirot University (IRB SWUEC119/2563F) and was registered at the Thai Clinical Trials Registry (TCTR20210613001).

category: obstetrics and gynecology


title: Correlations Between Community-Level HIV Preexposure Prophylaxis Coverage and Individual-Level Sexual Behaviors among US Men Who Have Sex with Men

abstract:
BackgroundHIV preexposure prophylaxis (PrEP) has been associated with changes in sexual behavior after PrEP initiation. However, behavioral differences may also emerge among PrEP non-users in communities with high PrEP coverage.

MethodsWe used demographic, behavioral, and sexual network data from ARTnet, a cross-sectional study of US men who have sex with men conducted during 2017-2019. Multivariable regression models with a Bayesian modeling framework in which individuals were nested within their residential geographic areas were used to estimate associations between area-level PrEP coverage and five sexual behavior outcomes (number of total, main, and casual male partners [network degree]; count of one-time partnerships; and consistent condom use in one-time partnerships), controlling for individual PrEP use.

ResultsPrEP coverage ranged from 10.3% (Philadelphia) to 38.9% (San Francisco). Total degree was highest in Miami (1.35) and lowest in Denver (0.78), while the count of one-time partners was highest in San Francisco (11.7/year) and lowest in Detroit (1.5/year). Adjusting for individual PrEP use and demographics, community PrEP coverage was associated with higher total degree (adjusted incidence rate ratio [aIRR]=1.73; 95% CrI, 0.92-3.44), casual degree (aIRR=2.05; 95% CrI, 0.90-5.07), and count of one-time partnerships (aIRR=1.90; 95% CrI, 0.46-8.54). Without adjustment for individual PrEP use, these associations were amplified. There were weaker associations with main degree (aIRR=1.21; 95% CrI, 0.48-3.20) and consistent condom use in one-time partnerships (aIRR=1.68; 95% CrI, 0.86-3.35).

ConclusionsMost of the associations between community PrEP coverage and sexual behavior were explained by individual PrEP use. However, there were residual associations after controlling for individual PrEP use, suggesting that PrEP coverage may partially drive community-level changes in sexual behavior.


title: Modelling infectious disease transmission potential as a function of human behaviour

abstract:
Mathematical modelling is an important public health tool for aiding understanding the spread of respiratory infectious diseases, such as influenza or COVID-19, and for quantifying the effects of behavioural interventions. However, such models rarely explicitly appeals to theories of human behaviour to justify model assumptions. Here we propose a novel mathematical model of disease transmission via fomites (luggage trays) at airport security screening during an outbreak. Our model incorporates the self-protective behaviour of using hand sanitiser gel in line with the extended parallel processing model (EPPM) of behaviour.

We find that changing model assumptions of human behaviour in line with the EPPM gives qualitatively different results on the optimal placement of hand sanitiser gels within an airport compared to the model with naive behavioural assumptions. Specifically, that it is preferable to place hand sanitiser gels after luggage screening in most scenarios, however in situations where individuals perceive high threat and low efficacy this strategy may need to be reviewed. This model demonstrates how existing behavioural theories can be incorporated into mathematical models of infectious disease.


title: Modeling shield immunity to reduce COVID-19 transmission in long-term care facilities

abstract: Nursing homes and other long-term care facilities in the United States have experienced severe COVID-19 outbreaks and elevated mortality rates, often following upon the inadvertent introduction of SARS-CoV-2. Following FDA emergency use approval, widespread distribution of vaccines has resulted in rapid reduction in COVID-19 cases in vulnerable, older populations. Yet, vaccination coverage remains incomplete amongst residents and healthcare workers. As such, mitigation and prevention strategies are needed to reduce the ongoing risk of transmission and mortality amongst vulnerable, nursing home populations. One such strategy is that of  shield immunity, in which recovered individuals increase their contact rates and therefore shield individuals who remain susceptible to infection. Here, we adapt recent population-scale shield immunity models to a network context. To do so, we evaluate network-based shield immunity by evaluating how restructured interactions in a bipartite network (e.g., between healthcare workers and long-term care residents) affects SARS-CoV-2 epidemic dynamics. First, we identify a series of rewiring principles that leverage viral testing, antibody testing, and vaccination information to reassign immunized healthcare workers to care for infected residents while retaining workload balance amidst an outbreak. We find a significant reduction in outbreak size when using infection and immune-based cohorting as a weekly intervention. Second, we also identify a preventative strategy using shield-immunity rewiring principles, by assigning susceptible healthcare workers to care for cohorts of immunized residents; this strategy reduces the risk that an inadvertent introduction of SARS-CoV-2 into the facility via a healthcare worker spreads to susceptible residents. Network-based epidemic modeling reveals that preventative rewiring can control the size of outbreaks at levels similar to that of isolation of infectious healthcare workers. Overall, this assessment of shield immunity provides further support for leveraging infection and immune status in network-based interventions to control and prevent the spread of COVID-19.


title: Reduced asymmetry of the hand knob area and decreased sensorimotor u-fiber connectivity in middle-aged adults with autism

abstract: Individuals with autism spectrum disorder (ASD) frequently present with impairments in motor skills (e.g., limb coordination, handwriting and balance), which are observed across the lifespan but remain largely untreated. Many adults with ASD may thus experience adverse motor outcomes in aging, when physical decline naturally occurs. The  hand knob of the sensorimotor cortex is an area that is critical for motor control of the fingers and hands. However, this region has received little attention in ASD research, especially in adults after midlife. The hand knob area of the precentral (PrChand) and postcentral (PoChand) gyri was semi-manually delineated in 49 right-handed adults (25 ASD, 24 typical comparison [TC] participants, aged 41-70 years). Using multimodal (T1-weighted, diffusion-weighted, and resting-state functional) MRI, we examined the morphology, ipsilateral connectivity and laterality of these regions. Correlations between hand knob measures with motor skills and autism symptoms, and between structural and functional connectivity measures were also investigated. The right PrChand volume was greater, and typical leftward laterality of PrChand and PoChand volume was lower in the ASD than the TC group. Furthermore, we observed increased mean diffusivity of the right PoC-PrChand u-fibers in the ASD group. In the ASD group, right PoC-PrChand u-fiber volume was negatively associated with current autism severity, and positively associated with right PoC-PrChand functional connectivity (FC). Correlations of hand knob measures were observed with manual dexterity and coordination skills but did not survive multiple comparisons correction. Our findings suggest decreased morphological laterality and u-fiber connectivity of the sensorimotor network involved in hand function in middle-aged adults with ASD. The altered morphology may relate to atypical functional asymmetries found in ASD earlier in life, but additionally, could reflect an overreliance on right hemisphere motor circuits over time. The right PoC-PrChand u-fibers may underlie compensatory self-regulation of unwanted core motor behaviors seen in ASD.

category: psychiatry and clinical psychology


title: Tobacco and Nicotine Use in the United States Army Trainee Soldiers Environment

abstract: Tobacco and nicotine use rates within the United States military population are high, and rates among young trainee soldiers are not improving over time. Trainee soldiers are heavily influenced by role models in their environment, and nicotine product use rates in this environment has not previously been evaluated. This study found that over 30% of non-trainee U.S. Army soldiers, known as cadre, within the training environment use nicotine products. For the young trainee soldier, this creates an initial Army experience that continues to foster a culture of tobacco and nicotine use. We urge changes in Army tobacco and nicotine policy to protect the vulnerable trainee soldier population.


title: Multi-Omic Analyses Characterize the Ceramide/Sphingomyelin Pathway as a Therapeutic Target in Alzheimer's Disease

abstract: Dysregulation of sphingomyelin (SM) and ceramide metabolism have been implicated in Alzheimers Disease (AD). Genome-wide and transcriptome wide association studies have identified various genes and genetic variants in lipid metabolism that are associated with AD. However, the molecular mechanisms of sphingomyelin and ceramide disruption remain to be determined. Evaluation of peripheral lipidomic profiles is useful in providing perspective on metabolic dysregulation in preclinical and clinical AD states. In this study, we focused on the sphingolipid pathway and carried out multi-omic analyses to identify central and peripheral metabolic changes in AD patients and correlate them to imaging features and cognitive performance in amyloidogenic mouse models. Our multi-omic approach was based on (a) 2114 human post-mortem brain transcriptomics to identify differentially expressed genes; (b) in silico metabolic flux analysis on 1708 context-specific metabolic networks to identify differential reaction fluxes; (c) multimodal neuroimaging analysis on 1576 participants to associate genetic variants in SM pathway with AD pathogenesis; (d) plasma metabolomic and lipidomic analysis to identify associations of lipid species with dysregulation in AD; (e) metabolite genome-wide association studies (mGWAS) to define receptors within pathway as potential drug target. Our findings from complementary approaches suggested that depletion of S1P compensated for AD cellular pathology, likely by upregulating the SM pathway, suggesting that modulation of S1P signaling may have protective effects in AD. We tested this hypothesis in APP/PS1 mice and showed that prolonged exposure to fingolimod, an S1P signaling modulator approved for treatment of multiple sclerosis, alleviated the cognitive impairment in mice. Our multi-omic approach identified potential targets in the SM pathway and suggested modulators of S1P metabolism as possible candidates for AD treatment.


title: Forecasting admissions in psychiatric hospitals before and during Covid-19

abstract:
IntroductionThe COVID-19 pandemic has strong effects on most health care systems and individual services providers. Forecasting of admissions can help for the efficient organisation of hospital care. We aimed to forecast the number of admissions to psychiatric hospitals before and during the COVID-19 pandemic and we compared the performance of machine learning models and time series models. This would eventually allow to support timely resource allocation for optimal treatment of patients.

MethodsWe used admission data from 9 psychiatric hospitals in Germany between 2017 and 2020. We compared machine learning models with time series models in weekly, monthly and yearly forecasting before and during the COVID-19 pandemic. Our models were trained and validated with data from the first two years and tested in prospectively sliding time-windows in the last two years.

ResultsA total of 90,686 admissions were analysed. The models explained up to 90% of variance in hospital admissions in 2019 and 75% in 2020 with the effects of the COVID-19 pandemic. The best models substantially outperformed a one-step seasonal naive forecast (seasonal mean absolute scaled error (sMASE) 2019: 0.59, 2020: 0.76). The best model in 2019 was a machine learning model (elastic net, mean absolute error (MAE): 7.25). The best model in 2020 was a time series model (exponential smoothing state space model with Box-Cox transformation, ARMA errors and trend and seasonal components, MAE: 10.44), which adjusted more quickly to the shock effects of the COVID-19 pandemic. Models forecasting admissions one week in advance did not perform better than monthly and yearly models in 2019 but they did in 2020. The most important features for the machine learning models were calendrical variables.

ConclusionModel performance did not vary much between different modelling approaches before the COVID-19 pandemic and established forecasts were substantially better than one-step seasonal naive forecasts. However, weekly time series models adjusted quicker to the COVID-19 related shock effects. In practice, different forecast horizons could be used simultaneously to allow both early planning and quick adjustments to external effects.

category: health informatics


title: SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before a National Lockdown, March-April 2021

abstract: In a representative serosurvey conducted March-June 2021, 64.1% (95%CrI 60.0- 68.1%) of Sitakunda subdistrict (Bangladesh) had anti-SARS-CoV-2 IgG antibodies after adjusting for age, sex, household clustering and test performance. Before the surge of Delta, most of the population had been infected despite low incidence of virologically-confirmed COVID-19.


title: SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before the Delta surge, March-June 2021


title: Evaluating discharges and readmissions using a COVID Virtual Ward model: a retrospective data study assessing patient outcomes and the likely staffing commitment

abstract:
BackgroundCOVID-19 has placed a catastrophic burden on acute hospitals. In an attempt to reduce admissions and enable safe early discharge, a COVID virtual ward (CVW) care pathway has been supported by NHS England. This includes discharging people who meet objective criteria based on acuity scores and oxygen saturations, with pulse oximeters and daily phone calls for up to 14 days. Observational studies have reported the safety of this system, but without describing the outcomes from usual care.

MethodsA retrospective study using routinely collected health data from all adults with a confirmed positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) swab result between 1st June 2020 and 31st Jan 2021 who attended the Emergency Department or Acute Medical Unit at QEHB, which does not have a CVW service. Criteria for CVW were applied using data from the first 24 hours of presentation to hospital and subsequent health outcomes were included for 28 days, including re-presentation, re-admission, ITU escalation and death. Results were compared to reported studies based in secondary care.

ResultsDuring the study period, 26,127 patients presented to QEHB hospital. 2301 had a positive SARS-CoV-2 swab. Of these, 1730 (75.2%) did not meet the criteria for the CVW and 571 (24.8%) did. Of the 571, 325 (56.9%) were discharged home within 24 hours and 246 (43.1%) were admitted for 24 hours or longer. Those admitted were older, with increased co-morbidities, 80.9% required hospital-supported acute therapies after the first 24 hours and 10.6% died. Of the 325 discharged, 44 were readmitted (13.5%), 30 (9.2%) with COVID-related symptoms, 5 (1.5%) required ITU and 1 patient (0.3%) died. These results were comparable to published studies with a CVW service.

DiscussionIn the current study, discharging patients without a CVW did not confer a greater risk of re-presentation, re-admission, ITU escalation or death. The majority of patients who remained in hospital despite meeting the CVW criteria did so for the provision of treatments or acute assessments. It remains uncertain whether a CVW delivers improvements in hard outcomes, and further research is needed.

category: respiratory medicine


title: Genetic, structural and clinical analysis of spastic paraplegia 4

abstract:
IntroductionSpastic paraplegia type 4 (SPG4), resulting from heterozygous mutations in the SPAST gene, is the most common form among the heterogeneous group of hereditary spastic paraplegias (HSPs). We aimed to study genetic and clinical characteristics of SPG4 across Canada.

MethodsThe SPAST gene was analyzed in a total of 696 HSP patients from 431 families by either HSP-gene panel sequencing or whole exome sequencing (WES). We used Multiplex ligation-dependent probe amplification to analyze copy number variations (CNVs), and performed in silico structural analysis of selected mutations. Clinical characteristics of patients were assessed, and long-term follow-up was done to study genotype-phenotype correlations.

ResultsWe identified 157 SPG4 patients from 65 families who carried 41 different SPAST mutations, six of which are novel and six are CNVs. We report novel aspects of mutations occurring in Arg499, a case with homozygous mutation, a family with probable compound heterozygous mutations, three patients with de novo mutations, three cases with pathogenic synonymous mutation, co-occurrence of SPG4 and clinically isolated syndrome, and novel or rarely reported signs and symptoms seen in SPG4 patients.

ConclusionOur study demonstrates that SPG4 is a heterogeneous type of HSP, with diverse genetic features and clinical manifestations. In rare cases, biallelic inheritance, de novo mutation, pathogenic synonymous mutations and CNVs should be considered.


title: Medication Use Patterns in COVID-19 Positive Patients in a large state-wide health system by Age Group, Comorbidity, and Month During the Pandemic in 2020

abstract:
ObjectivesMain objective was to systematically determine most frequently used medications among COVID-19 patients overall and by hospitalization status. Secondary objective was to measure use patterns of medications considered potential therapeutic options

DesignRetrospective cohort study.

SettingThe five academic medical centers of University of California Health.

ParticipantsUniversity of California COVID Research Data Set (UC CORDS) patients between March 10, 2020 and December 31, 2020.

Exposure(s)Confirmed COVID-19 positive by SARS-CoV-2 nucleic acid amplification.

Main Outcome(s) and Measure(s)Main outcomes were percentages of patients prescribed medications, overall, by age group, and by comorbidity based on hospitalization status. Use percentage by month of COVID-19 diagnosis was measured. Cumulative count of potential therapeutic options was measured over time.

ResultsDataset included 22897 unique patients with COVID-19 (mean [SD] age, 42.4 [20.4] years; 12154 [53%] female). Among the sample, 6326 28%) were non-Hispanic White, 8475 (37%) were Hispanic, 1562 (7%) Asian, and 1313 (6%) Black. A COVID-related hospitalization occurred in 3546 patients. Of the hospitalized patients, more than 30% had baseline comorbidities of hypertension (48%), hyperlipidemia (37%), and type 2 diabetes (35%). Most frequently used medications in patients overall were acetaminophen (21.2%), albuterol (14.9%), ondansetron (13.9%), and enoxaparin (10.8%). Medications used were generally similar across ages and comorbidities. Prior to May, dexamethasone was rarely used, with well under 50 COVID-19 patients that had been hospitalized to that point receiving the medication. By mid-August, more than 500 patients to that point had received dexamethasone. Hydroxychloroquine use effectively halted in COVID-19 hospitalized patients after May. Throughout the period of March to December 2020, enoxaparin was used in the most patients to that point at any instance. By mid-December, more than 2000 in the analysis cohort of hospitalized patients had received enoxaparin.

Conclusions and RelevanceIn this retrospective cohort study, across age and comorbidity groups, predominant utilization was for supportive care therapy. Dexamethasone and remdesivir experienced large increases in use. Conversely, hydroxychloroquine and azithromycin use markedly dropped. Medication utilization rapidly shifted towards more evidence-concordant treatment of patients with COVID-19 as rigorous study findings emerged.


title: Understanding transfer of learning from an online self-directed learning and clinical decision support resource (BMJ Best Practice) for health professions education: a capability approach perspective

abstract:
ObjectiveTo understand transfer of learning of an online self-directed learning and clinical decision support resource for health professionals (BMJ Best Practice) informed by Sens capability approach.

DesignA semi-structured questionnaire was used to identify the extent to which BMJ Best Practice enabled participants to achieve their valued outcomes and the factors that enabled and constrained their achievement.

SettingThis study was carried out in a single centre, which is a tertiary care medical institution containing around 1500 inpatient beds.

Participants200 physicians at Air Force Medical Center were invited to take part in this study. 184 physicians completed the online questionnaire.

Results78 percent of physicians felt that BMJ Best Practice enabled them to achieve their valued outcomes and to apply their new knowledge to inform their practice. The main factors that constrained their achievement were technological.

ConclusionSens capability approach offers an innovative and useful model to further understand health professions education since it highlights the importance of the learner perspective of valued outcomes, including the difficulties associated with the effective transfer of learning in CPD.

Strengths and limitations of this studyThis is a real-life study based on the experiences of physicians who are directly providing care to patients.

The study has strong theoretical foundations - being based as it is on Sens capability approach.

The study covers the vital subject of the application of medical knowledge in actual practice.

The research design is a cross-sectional survey; the study did not investigate whether physicians reflections on their valued outcomes and achievements might have changed over time.

This study was carried out in a single centre.

category: medical education


title: Noninvasive optical monitoring of cerebral blood flow and EEG Spectral responses after Severe Traumatic Brain Injury: A Case Report

abstract: Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.


title: Elevated levels of the cytokine LIGHT in Crohn's disease

abstract: LIGHT, encoded by the TNFSF14 gene, is a cytokine belonging to the tumor necrosis factor superfamily. Upon binding to its receptors, HVEM and LTBR, it activates inflammatory responses. We used a single-molecule immunoassay to determine the circulating levels of free LIGHT in plasma from pediatric patients with Crohns disease (N = 183) and a panel of healthy pediatric reference samples (N = 9). LIGHT levels were greatly elevated in Crohns disease (average of 305 pg/ml versus 57 pg/ml in controls, P < 0.0001). We performed correlational analyses between LIGHT levels and the clinical characteristics of the Crohns cohort, including age, Montreal classification, family history, medical/surgical therapy, and routine blood test parameters. We found statistically significant correlation between white blood cell count and free LIGHT (P < 0.046). Our results support the hypothesis that elevated levels of the cytokine contribute to the pathology of Crohns disease and that therapies to neutralize free LIGHT with antibodies may be beneficial.

category: gastroenterology


title: Community ECHO (Extension for Community Healthcare Outcomes) Project Promotes Cross-Sector Collaboration and Evidence-Based Trauma-Informed Care

abstract:
BackgroundAdverse Childhood Experiences (ACEs) are traumatic events that occur before age 18 years. ACEs, associated with negative health behaviors and chronic health disorders, disproportionately impact people from poor and marginalized communities. Toxic stress from ACEs can be prevented and treated with trauma-informed care. Inadequate training prevents the maternal and child workforce from providing evidence-based trauma-informed care. Cross-sector collaboration between pediatric care sectors is crucial to providing systems-wide trauma-informed care, but significant barriers impede cross sector communication. Training and formal cross-sector communication networks are needed to create strong systems of trauma-informed care in communities.

The Stanford ACEs Aware ECHO (Extension for Community Healthcare Outcomes) program was created with 3 workforce development goals: 1) introduce the California Office of Surgeon General-led ACEs Aware Initiative to the maternal and child health workforce in 3 California counties, 2) disseminate trauma-informed evidence-based best practices, 3) bridge community silos to increase collaboration between care sectors to promote trauma-informed care systems.

MethodsParticipants were recruited from Federally Qualified Health Centers, county public health departments, community behavioral health organizations, educational institutions, and agencies that serve low-income children and families. 100 unique participants representing 3 counties and 54 agencies joined sessions. Twelve virtual educational sessions were convened over 6 months using the Project ECHO(R) model via Zoom technology. Sessions consisted of didactic lectures and whole-group case-based discussions.

ResultsAfter completing the educational series, participants expressed commitment to increased cross-sector collaboration, and reported increased knowledge and confidence in using trauma-informed skills. After participation, a significant number of participants had also completed another recommended California ACEs Aware Initiative online training.

ConclusionAn ECHO series of virtual workforce development sessions on trauma-informed best practices promoted cross-sector communication and was associated with strong participant engagement and satisfaction. The educational series increased knowledge and confidence in use of evidence-based trauma-informed best practices.

Key MessagesO_LIAdverse Childhood Experiences (ACEs) are stressful or traumatic events that occur before the age of 18 years and are associated with high human and economic costs to society.
C_LIO_LIEvidence-based trauma-informed Care (TIC) has been shown to prevent and treat toxic stress caused by ACEs, but training programs for the maternal and child workforce have historically provided inadequate training in TIC best practices.
C_LIO_LICross-sector collaboration to provide systems-level trauma-informed care is known to improve population health and promote health equity, but funding and staffing barriers to optimized collaboration exist.
C_LIO_LIThe Project ECHO(R) (Extension for Community Healthcare Outcomes) model uses distance learning teleconferencing to create learning communities across geographic distance and care sector, educate and mentor participants, and elevate quality of care in community settings.
C_LIO_LIThe Stanford ACEs Aware ECHO effectively delivered a curriculum about TIC to a tri-county community of maternal and child workforce participants that promoted cross-sector collaboration. Participation was associated with high levels of engagement and satisfaction. Participants reported increased confidence and knowledge to provide systemic evidence-based TIC.
C_LI

category: pediatrics


title: Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism

abstract: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts is still under-represented in the genome-wide genetic studies. Here we performed whole-exome sequencing on 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combining with single-cell sequencing data from the developing human brain, we found that expression of genes with de novo mutations were specifically enriched in pre-, post-central gyrus (PRC, PC) and banks of superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and health controls, we found that the gray volume of the right BST in ASD patients significantly decreased comparing to health controls, suggesting the potential structural deficits associated with ASD. Finally, we found that there was decrease in the seed-based functional connectivity (FC) between BST/PC/PRC and sensory areas, insula, as well as frontal lobes in ASD patients. This work indicated that the combinatorial analysis with genome-wide screening, single-cell sequencing and brain imaging data would reveal brain regions contributing to etiology of ASD.


title: Real-Time SARS-CoV-2 Genotyping by High-Throughput Multiplex PCR Reveals the Epidemiology of the Variants of Concern in Qatar

abstract: Complementing whole genome sequencing strategies with high-throughput multiplex RT-qPCR genotyping allows for more comprehensive and real-time tracking of SARS-CoV-2 variants of concern. During the second and third waves of COVID-19 in Qatar, PCR genotyping, combined with Sanger sequencing of un-typeable samples, was employed to describe the epidemiology of the Alpha, Beta and Delta variants. A total of 9792 nasopharyngeal PCR-positive samples collected between April-June 2021 were successfully genotyped, revealing the importation and transmission dynamics of these three variants in Qatar.


title: K-12 School Teaching Posture Correlates with COVID-19 Disease Outcomes in Ohio

abstract: At the start of the COVID-19 pandemic, most US K-12 schools shutdown and millions of students began remote learning. By September 2020, little guidance had been provided to school districts to inform fall teaching. This indecision led to a variety of teaching postures within a given state. In this report we examine Ohio school districts in-depth, to address whether on-premises teaching impacted COVID-19 disease outcomes in that community. We observed that counties with on-premises teaching had more cumulative deaths at the end of fall semester than counties with predominantly online teaching. To provide a measure of disease progression, we developed an observational disease model and examined multiple possible confounders, such as population size, mobility, and demographics. Examination of micropolitan counties revealed that the progression of COVID-19 disease was faster during the fall semester in counties with predominantly on-premises teaching. The relationship between increased disease prevalence in counties with on-premises teaching was not related to deaths at the start of the fall semester, population size, or the mobility within that county. This research addresses the critical question whether on-premises schooling can impact the spread of epidemic and pandemic viruses and will help inform future public policy decisions on school openings.


title: An Evaluation of Liver Function Tests in SARS-CoV-2 infection in the backdrop of chronic kidney disease

abstract:
INTRODUCTIONThe SARS-CoV-2 pandemic has emerged as perhaps the most challenging global health problem of this century. The concomitant presence of co-morbidities like chronic kidney disease (CKD), diabetes, chronic heart disease etc. makes the task of patient management difficult.

AIMS AND OBJECTIVESTo assess the patterns of liver test abnormalities in patients of COVID-19 infection with and without CKD and evaluate the probable outcomes.

MATERIALs and METHODSA cross-sectional retrospective observational study done on 600 patient samples (Group 1 COVID-19 without CKD, Group 2 COVID-19 with CKD and Group 3 non COVID-19 with CKD) which were processed for Liver function test (AST, ALT and ALP) and Renal function test (Urea and Creatinine) in the Department of Biochemistry, Dr. RML Hospital New Delhi.

RESULTSAST and ALT levels were significantly higher (P < 0.05) in all COVID-19 positive patients - group 1 mean {+/-} 2 SD, (63.63 {+/-} 42.89 U/L & 50.25 {+/-} 46.53 U/L respectively) and group 2 (90.59 {+/-} 62.51 U/L & 72.09 {+/-} 67.24 U/L respectively) as compared to Group 3 (25.24 {+/-} 7.47 U/L & 24.93 {+/-} 11.44 U/L respectively) and also a statistically significant elevation is seen in these two parameters (AST & ALT) in Group 2 as compared to Group 1 (P < 0.05). There was a negative significant correlation between eGFR and AST/ALT levels in Group 1 (p < 0.05). In Group 2, a weak positive correlation was seen with ALT (p < 0.01).

No significant correlation existed between eGFR and ALP in groups 1 and 2. In Group 3, eGFRs showed strong correlations with AST and ALT levels (p < 0.01) and reduction in kidney function correlated well with increase in serum ALP levels, (p < 0.01).

CONCLUSIONSThis study most comprehensively describes that SARS-CoV-2 positive CKD patients show more elevations in serum aminotransferase levels as compared to their non-CKD counterparts, in contrast to non-COVID-19 CKD cases. Serum ALT values in SARS-CoV-2 patients show significant correlation with calculated eGFR values. Elevated ALP values in CKD patients may be used as an indicator of declining kidney function. However, more studies in this direction are needed.

category: pathology


title: Virlaza Inhibits Sars-COV-2-induced Inflammatory Response of Bronchial Epithelial Cells and Pulmonary Fibroblast

abstract: Coronavirus disease 2019 (COVID-19), which is currently a global public health emergency and beyond vaccines as a prophylactic treatment, no specific and effective therapeutical treatments are available. COVID-19 induces a massive release of proinflammatory cytokines, which drives COVID-19 progression, severity, and mortality. In addition, bronchial epithelial cells are the first pulmonary cells activated by coronavirus-2 (SARS-Cov-2) leading to massive cytokine release, which can hyperactivate lung fibroblasts, resulting in pulmonary fibrosis, a phenomenon observed even in moderate COVID-19 survivors. This in vitro study tested the hypothesis that Virlaza, a herbal medicine, could inhibit the hyperactivation of human bronchial epithelial cells (BEAS-2B) and pulmonary fibroblasts (MRC-5) induced by SARS-Cov-2. BEAS-2B (5x104/mL/well) and MRC-5 (5x104/mL/well) cells were co-cultivated with 1ml of blood of a Sars-Cov-2 infected patient for 4 hours and Virlaza (1ug/mL) was added in the first minute of the co-culture. After 4 hours, the cells were recovered and used for analysis of cytotoxicity by MTT and for mRNA expression of P2X7 receptor E iNOS. The supernatant was used to measure ATP and cytokines. Sars-Cov-2 incubation resulted in increased release of ATP, IL-1beta, IL-6, IL-8, and TNF-alpha by BEAS-2B and MRC-5 cells (p<0.001). Treatment with Virlaza resulted in reduction of ATP, IL-1beta, IL-6, IL-8, and TNF-alpha release (p<0.001). In addition, Sars-Cov-2 incubation resulted in increased expression of P2X7 receptor and iNOS (p<0.001), which has been reversed by Virlaza (p<0.001). In conclusion, Virlaza presents important anti-inflammatory effects in the context of Sars-Cov-2 infection.

category: pharmacology and therapeutics


title: Immunogenicity of mRNA-1273, BNT162b2 and Ad26.COV2.S COVID-19 vaccines

abstract:
BackgroundUnderstanding immunogenicity and effectiveness of SARS-CoV-2 vaccines is critical to guide rational use.

MethodsWe compared the immunogenicity of mRNA-1273, BNT-162b2 or Ad26.COV2.S in ambulatory adults in Massachusetts, USA. To correlate immunogenicity with effectiveness of the three vaccines, we performed an inverse-variance meta-analysis of population level effectiveness from public health reports in >40 million individuals.

ResultsA single dose of either mRNA vaccine yielded comparable antibody and neutralization titers to convalescent individuals. Ad26.COV2.S yielded lower antibody concentrations and frequently negative neutralization titers. Bulk and cytotoxic T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients, and <50% of vaccinees demonstrate CD8+ T-cell responses to spike peptides. Antibody concentrations and neutralization titers increased comparably after the first dose of either vaccine, and further in recipients of a second dose. Prior infection was associated with high antibody concentrations and neutralization even after a single dose and regardless of vaccine. Neutralization of beta, gamma and delta strains were poorer regardless of vaccine. Relative to mRNA1273, the effectiveness of BNT162b2 was lower against infection and hospitalization; and Ad26COV2.S was lower against infection, hospitalization and death.

ConclusionsVariation in the immunogenicity correlates with variable effectiveness of the three FDA EUA vaccines deployed in the USA.


title: Comparative immunogenicity and effectiveness of mRNA-1273, BNT162b2 and Ad26.COV2.S COVID-19 vaccines


title: Access to COVID-19 Vaccines in High-, Middle-, and Low-Income Countries Hosting Clinical Trials

abstract: The COVID-19 pandemic has led to the rapid development of multiple vaccines, vaccines that were tested in clinical trials located in several countries around the world. Because prior research has shown that pharmaceuticals do not receive consistent and timely authorization for use in lower-income countries where they are tested, we conducted a cross-sectional study examining the authorization or approval and delivery for COVID-19 vaccines recommended by the World Health Organization (WHO) in the countries where they were tested. While countries of varying incomes have largely authorized the COVID-19 vaccines tested within their populations for use, high-income countries have received proportionately more doses, enabling them to more fully vaccinate their populations. As many lower-income countries continue to experience inequitable shortfalls in COVID-19 vaccine supply amid the ongoing pandemic, efforts must be undertaken to ensure timely access in countries across all income groups, including those hosting clinical trials.


title: Comprehensively modeling heterogeneous symptom progression for Parkinson's disease subtyping

abstract: The Parkinsons disease (PD) is a heterogeneous neurodegenerative disease, of which the etiological and pathological mechanisms remain unclear to date. PD has been associated with diverse movement dysfunctions and non-motor symptoms (i.e., symptom heterogeneity) and progression patterns of these symptoms differ from patient to patient (i.e., progression heterogeneity). To address these, the present investigation aims at comprehensively considering full progression course of early PDs to identify subtypes, each of which can reflect unique PD progression pattern. We retrospectively analyzed the Parkinsons Progression Markers Initiative (PPMI) and the Parkinson Disease Biomarkers Program (PDBP) as the development and validation cohorts, respectively. An unsupervised deep learning model was built to model progression trajectories in diverse clinical manifestations and cerebrospinal fluid (CSF) biomarkers to produce a representation vector for each patient, encoding his/her symptom progression profile. Then by performing clustering analysis on the patients representation vectors, we identified three subtypes with distinct PD progression patterns in the PPMI cohort: Subtype I, mild baseline severity and mild symptom progression; mild baseline severity and moderate progression; and Subtype III, rapid symptom progression. Replication in the PDBP validation cohort demonstrated reproducibility of the subtypes. After that, we explored demographic factors, CSF biomarkers, neuroimaging biomarkers in brain regional atrophy, and genetic factors of the subtypes. Last, to enhance usability of the subtypes, predictive model of subtypes that relies on data at baseline and 1-year follow-up was trained. In conclusion, the identified subtypes revealed significant symptom progression patterns of PDs. Patients with similar baseline severities can even suffer from different progression pattern, leading to distinct prognosis. Demographic factors, biomarkers, and genetic components of the subtypes suggested distinct biological mechanisms and pathways potentially leading to those progression patterns. Our findings may benefit pathophysiological study, clinical practice, and clinical trials to advance PD.


title: Association of Sociodemographics with Out-of-Pocket Expenditure and Underinsurance in Skin Cancer Survivors

abstract:
BackgroundThe sociodemographic predictors of either out-of-pocket expenditure (OOP) or underinsurance among skin cancer survivors is not well reported in the literature. In this study we estimated all-cause healthcare related OOP expenditure and probability of underinsurance among insured skin cancer survivors and identified the sociodemographic predictors of these measures.

Data and MethodWe pooled Medical Expenditure Panel Survey (MEPS) data from 2011 to 2015 and identified skin cancer using Clinical Classifications Software (CCS) code. Only adult ([≥]18 years) skin cancer survivors with full year insurance coverage were included in our study (n = 1825). We used a generalized linear model (GLM) with log link and gamma distribution to estimate OOP and a logit model to estimate the probability of underinsurance. We estimated the Average Marginal Effect (AME) to quantify the variations and their statistical significance between reference level and other levels of each predictor. Our analyses accounted for the complex survey design of MEPS.

ResultsThe average all-cause OOP was $1766 per person per year for a skin cancer survivor. Among all skin cancer survivors, females, those aged 60-64 years, with some college education or a degree, with income [≥]400% of federal poverty level (FPL) and with non-managed-care private insurance incurred significantly higher OOP expenditure compared to their respective counterparts. In terms of underinsurance, females and those aged 60-64 years had higher probability, whereas, survivors with non-white race/ethnicity and income 200% of FPL or higher had lower probability of being underinsured compared to their respective counterparts.

ConclusionOur study demonstrates that OOP expenditure and underinsurance varies significantly by sociodemographic factors among skin cancer survivors.

category: health economics


title: Deep Optical Blood Analysis: COVID-19 Detection as a Case Study in Next Generation Blood Screening

abstract: A wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understood. In this paper, we present a multiple instance learning-based approach to aggregate high-resolution morphological information across many blood cells and cell types to automatically diagnose disease at a per-patient level. We integrated image and diagnostic information from across 236 patients to demonstrate not only that there is a significant link between blood and a patients COVID-19 infection status, but also that novel machine learning approaches offer a powerful and scalable means to analyze peripheral blood smears. Our results both backup and enhance hematological findings relating blood cell morphology to COVID-19, and offer a high diagnostic efficacy; with a 79% accuracy and a ROC-AUC of 0.90.

category: hematology


title: Evaluation of the antibody response and adverse reactions of the BNT162b2 vaccine of participants with prior COVID-19 infection in Japan

abstract:
IntroductionVaccination programs are important to preventing COVID-19 infection. BNT162b2 is new type of vaccine, and previous studies have shown that the antibody response was significantly elevated in patients with prior COVID-19 infection after the first vaccination. However, no study has evaluated the efficacy of the vaccination or the adverse reactions of people with prior COVID-19 infection in Japan. The aim of this study is to evaluate the antibody titer and adverse reactions of BNT162b2 vaccine among participants with prior COVID-19 infection in Japan.

MethodsThe data for this study was collected between April 15, 2021, and June 9, 2021. All of the hospital staff who received the BNT162b2 vaccine were included in this study and were sorted into either the prior infection group or the control group. We collected the data of adverse reactions through self-reporting and calculated the anti-SARS-CoV-2 spike-specific antibody titer for all participants.

ResultsThe antibody titer of the prior-infection group in first antibody test was significantly higher than that of the control group in the second antibody test. There was no significant difference in adverse reactions between the prior infection group receiving its first vaccination and the control group receiving its second vaccination.

ConclusionOur study shows that the antibody response following the first vaccination in the prior COVID-19 infection group was found to be comparable to that of the second vaccination in the control group; however, the evaluation of adverse reactions was inadequate and further, large-scale studies are needed.

category: infectious diseases


title: Leveraging of SARS-CoV-2 PCR cycle thresholds values (Ct) to forecast COVID-19 trends

abstract:
IntroductionWe assessed the usefulness of SARS-CoV-2 RT-PCR cycle thresholds (Ct) values trends produced by the LHUB-ULB (a consolidated microbiology laboratory located in Brussels, Belgium) for monitoring the epidemics dynamics at local and national levels and for improving forecasting models.

MethodsSARS-CoV-2 RT-PCR Ct values produced from April 1, 2020, to May 15, 2021, were compared with national COVID-19 confirmed cases notifications according to their geographical and time distribution. These Ct values were evaluated against both a phase diagram predicting the number of COVID-19 patients requiring intensive care and an age-structured model estimating COVID-19 prevalence in Belgium.

ResultsOver 155,811 RT-PCR performed, 12,799 were positive and 7,910 Ct values were available for analysis. The 14-day median Ct values were negatively correlated with the 14-day mean daily positive tests with a lag of 17 days. In addition, the 14-day mean daily positive tests in LHUB-ULB were strongly correlated with the 14-day mean confirmed cases in the Brussels-Capital and in Belgium with coinciding start, peak and end of the different waves of the epidemic. Ct values decreased concurrently with the forecasted phase-shifts of the diagram. Similarly, the evolution of 14-day median Ct values was negatively correlated with daily estimated prevalence for all age-classes.

ConclusionWe provide preliminary evidence that trends of Ct values can help to both follow and predict the epidemics trajectory at local and national levels, underlining that consolidated microbiology laboratories can act as epidemic sensors as they gather data that are representative of the geographical area they serve.


title: Salivary molecular testing for SARS-CoV-2: simplifying the diagnosis without losing accuracy

abstract:
BackgroundQuantitative RT-PCR on NasoPharyngeal Swab (NPS) is still considered the standard for the diagnosis of SARS-CoV-2 infection, even if saliva has been evaluated in several studies as a possible alternative. The use of point of care (POC) platforms, providing highly specific results performed on saliva could simplify the diagnosis of COVID-19 and contribute to contain the spreading of SARS-CoV-2.

MethodsWe assess the sensitivity and specificity of molecular testing performed on saliva in comparison to NPS using two different POC platforms (DiaSorin Simplexa and Cepheid Xpert(R)). NPS and saliva were collected prospectically from asymptomatic health care workers and mildly symptomatic patients. Moreover, the stability of saliva samples after storage at -80{degrees}C for up to 45 days was tested.

ResultsThe obtained results in comparison to NPS demonstrated for both DiaSorin Simplexa and Xpert(R) Xpress a specificity of 100% and a sensitivity of 90.24%. The overall agreement between the tests performed on saliva was 98%. A positive correlation in Ct values detected on saliva and on NPS was identified for all the targets shared by the tests in analysis (Orf1ab, E and N2). Both S Ct values and Orf1ab Ct values were not significantly different before and after the freezing in the tested saliva samples.

ConclusionThe obtained results demonstrated an overall performance of saliva comparable to NPS, confirming that RT-PCR performed using POCs on saliva could represent a valid public health solution for controlling SARS-CoV-2 pandemic.


title: State-dependent patterns and coupling between the vaccination schedule, population mobility and the COVID epidemic outline, in the US states

abstract:
We study the evolution of the COVID-19 epidemic in the US, since January 2020 until May 2021. Our primary goal is to understand some of the complex coupled dynamics between factors that ultimately regulate the epidemic case load. As potentially crucial factors, we focus on population mobility and vaccination patters (both related to risk of contracting the SARS-Cov2 virus). These factors may in turn depend on demographic parameters (which are unrelated to the epidemic evolution), but also on the population response to the epidemic outbreak itself. In our work, we use correlation analyses, in conjunction with open source data from US states, to investigate the type and strength (1) of the relationships between demographic measures and epidemic, mobility and vaccination timelines during our established time window; (2) of the bidirectional coupling between these timelines.

We showed that the wide between-state differences in epidemic outcome correspond to between-state differences in demographic measures (such as density, income, political affiliation). As a potential underlying mechanism, we found that demographic measures are also predictive of the degree of coupling between epidemic timelines (on one hand) and vaccination and mobility timelines (on the other hand), coupling which can be broadly interpreted as the populations behavioral response to the epidemic. In support of this idea, our analysis shows this response to be tightly correlated with epidemic outcome.

This suggests that a states demographic profile may be invaluable to generating predictions on the epidemic evolution in the respective state, and that this information may be used to understand the weaknesses of a state and how to compensate for them to improve epidemic outcome (e.g., via state centralized incentives, and customized mitigation strategies).