title: Using FIB-4 score as a screening tool in the assessment of significant liver fibrosis (F2) in patients with transfusion dependent beta thalassaemia: a cross sectional study

abstract:
ObjectiveTo evaluated the performance of FIB-4 score as a screening tool to detect significant liver fibrosis (F2) compared to transient elastography (TE), among chronic transfusion-dependent beta-thalassemia (TDT) patients, in a resource-poor setting.

DesignA cross-sectional study

SettingAdolescent and Adult Thalassaemia Care Center (University Medical Unit), Kiribathgoda, Sri Lanka.

Participants45 TDT patients who have undergone more than 100 blood transfusions with elevated serum ferritin >2000ng/mL, were selected for the study. Patients who were serologically positive for hepatitis C antibody were excluded.

Outcome measuresTE and FIB-4 score were estimated at the time of recruitment in all participants. Pre-defined cut-off values for F2, extracted from previous studies for TE and FIB-4 score, were compared. A new cut-off value for FIB-4 score was estimated using ROC curve analysis to improve the sensitivity for F2 prediction.

ResultsOf the selected 45 TDT patients, 22(49%) were males. FIB-4 score showed a significant linear correlation with TE (r= 0.52;p< 0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand, it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4, we improved the pick-up rate of F2 to 72%.

ConclusionsRegardless of the cut-off point, FIB-4 score cannot be used as a good screening tool to pick-up F2 in patients with TDT, irrespective of their splenectomy status. On the contrary, at 1.3 cut off value though FIB-4 is a very poor detector for F2 fibrosis it will not erroneously diagnose F2 fibrosis in those who dont have it.

Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThere is limited information available on the applicability of FIB-4 score to assess significant liver fibrosis in patients with transfusion-dependent beta-thalassemia (TDT).
C_LIO_LIThe present study among a Sri Lankan TDT population had their liver fibrosis assessed by FIB-4 score biomarker compared with Transient elastography (TE).
C_LIO_LISmall sample size of the study is one of the major limitations.
C_LIO_LIEven though the liver biopsy is the gold standard method of assessing liver fibrosis, non-invasive TE was used as the reference standard in our study
C_LI


title: Distinct Vaccine Efficacy Rates Among Health Care Workers During a COVID-19 Outbreak in Jordan

abstract:
BACKGROUNDWe aimed to assess the efficacy of 3 COVID-19 vaccines in a population of health care workers at a tertiary cancer center in Amman, Jordan.

METHODSWe evaluated the records of 2855 employees who were fully vaccinated with 1 of 3 different vaccines and those of 140 employees who were not vaccinated. We measured the number of SARS-CoV-2 infections that occurred at least 14 days after the second vaccine dose.

RESULTSThe 100-day cumulative incidence of PCR-confirmed SARS-CoV-2 infections was 19.3% {+/-} 3.3% for unvaccinated employees and 1.7% {+/-} 0.27% for fully vaccinated employees. The 100-day cumulative infection rates were 0.7% {+/-} 0.22% in BNT162b2 vaccine recipients (n = 1714), 3.6% {+/-} 0.77% in BBIBP-CorV recipients (n = 680), and 2.3% {+/-} 0.73% in ChAdOx1 recipients (n = 456). We used Cox regression analyses to compare the risks of SARS-CoV-2 infection among the different vaccine recipient groups and found a significantly higher infection risk in BBIBP-CorV (hazard ratio [HR] = 2.9 {+/-} 0.31) and ChAdOx1 recipients (HR = 3.0 {+/-} 0.41) compared to BNT162b2 recipients (P = .00039 and .0074, respectively). Vaccinated employees who had no previously confirmed SARS-CoV-2 infections were at a markedly higher risk for breakthrough infections than those who experienced prior infections (HR = 5.7 {+/-} 0.73, P = .0178).

CONCLUSIONSOur study offers a real-world example of differential vaccine efficacy among a high-risk population during a national outbreak. We also show the important synergism between a previous SARS-CoV-2 infection and vaccination.

FundingNone

category: infectious diseases


title: Waning Effectiveness of SARS-CoV-2 mRNA Vaccines in Older Adults: A Rapid Review

abstract: The U.S. Centers for Disease Control and Prevention (CDC) and other health agencies have recently recommended a booster dose of COVID-19 vaccines for specific vulnerable groups including adults 65 years and older. There is limited evidence whether vaccine effectiveness in older adults decreases over time, especially against severe COVID-19. We performed a rapid review of published studies available through 04 November 2021 that provide effectiveness data on mRNA vaccines approved/licensed in the United States and identified eight eligible studies which evaluated vaccine effectiveness in older adults. There is evidence of a decline in vaccine effectiveness against both SARS-CoV-2 infection and severe COVID-19 in older adults among studies which analyzed data up to July-October 2021. Our findings suggest that vaccine effectiveness diminishes in older adults, which supports the current recommendation for a booster dose in this population.


title: Development of an effective immune response in adults with Down Syndrome after SARS-CoV-2 vaccination

abstract:
Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to COVID-19 and may impair the generation of protective immunity after vaccine administration. The cellular and humoral responses of 55 DS patients who received a complete SARS-CoV-2 vaccination regime at one to three (V1) and six (V2) months were characterised. SARS-CoV-2-reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1, and increased at V2. Likewise, a sustained increase of SARS-CoV-2-specific circulating Tfh (cTfh) cells was observed one to three months after vaccine administration. Specific IgG antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, though IgG titers decreased significantly between both timepoints.

SUMMARYThe work shows the cellular and humoral responses to SARS-CoV-2 vaccination of individuals with Down syndrome (DS) after one to three (V1) and six (V2) months. An effective immune response after six months was observed in 98% of DS individuals.


title: A prospective, single-center study to evaluate the clinical performance of Meril ABFind in individuals vaccinated against COVID-19

abstract:
BackgroundAccurate rapid antibody detection kits requiring minimum infrastructure are beneficial in detecting post-vaccination antibodies in large populations. ChAdOx1-nCOV (COVISHIELD) and BBV-152 (Covaxin) vaccines are primarily used in India.

MethodsIn this single-centre prospective study, performance of Meril ABFind was investigated by comparing with Abbott SARS-CoV-2 IgG II Quant (Abbott Quant), GenScript cPass SARS-CoV-2 neutralization antibody detection kit (GenScript cPass), and COVID Kawach MERILISA (MERILISA) in 62 vaccinated health care workers (HCW) and 40 pre-pandemic samples.

ResultsIn the vaccinated subjects, Meril ABFind kit displayed high sensitivity of 93.3% (CI, 89.83%-96.77%), 94.92% (CI, 91.88%-97.96%), and 90.3% (CI, 86.20%-94.4%) in comparison to Abbott Quant, MERILISA, and GenScript cPass respectively. The results of the Meril ABFind in the COVISHIELD-vaccinated group were excellent with 100% sensitivity in comparison to the other three kits. In the Covaxin-vaccinated group, Meril ABFind displayed sensitivity ranging from 80% to 88.9%. In control samples, there were no false positives detected by Meril ABFind, while Abbott Quant, MERILISA, and GenScript cPass reported 2.5%, 10.0%, and 12.5% false positives, respectively. In the pre-pandemic controls, specificity of Meril ABFind was 100%, Abbott Quant 97.5%, MERILISA 90%, and GenScript cPass 87.5%.

ConclusionThe Meril ABFind kit demonstrated satisfactory performance when compared with the three commercially available kits and was the only kit without false positives in the pre-pandemic samples. This makes it a viable option for rapid diagnosis of post vaccination antibodies.


title: Machine Learning for Sudden Cardiac Death Prediction in the Atherosclerosis Risk in Communities Study

abstract:
IntroductionSudden cardiac death (SCD) is a devastating consequence often without antecedent expectation. Current risk stratification methods derived from baseline independently modeled risk factors are insufficient. Novel random forest machine learning (ML) approach incorporating time-dependent variables and complex interactions may improve SCD risk prediction.

MethodsAtherosclerosis Risk in Communities (ARIC) study participants were followed for adjudicated SCD. ML models were compared to standard Poisson regression models for interval data, an approximation to Cox regression, with stepwise variable selection. Eighty-two time-varying variables (demographics, lifestyle factors, clinical characteristics, biomarkers, etc.) collected at four visits over 12 years (1987-98) were used as candidate predictors. Predictive accuracy was assessed by area under the receiver operating characteristic curve (AUC) through out-of-bag prediction for ML models and 5-fold cross validation for the Poisson regression models.

ResultsOver a median follow-up time of 23.5 years, 583 SCD events occurred among 15,661 ARIC participants (mean age 54 years and 55% women). Compared to different Poisson regression models (AUC at 6-year ranges from 0.77-0.83), the ML model improved prediction (AUC at 6-year 0.89). Top predictors identified by ML model included prior coronary heart disease, which explained 47.9% of the total phenotypic variance, diabetes mellitus, hypertension, and T wave abnormality in any of leads I, aVL, or V6. Using the top ML predictors to select variables, the Poisson regression model AUC at 6-year was 0.77 suggesting that the non-linear dependencies and interactions captured by ML, are the main reasons for its improved prediction performance.

ConclusionsApplying novel ML approach with time-varying predictors improves the prediction of SCD. Interactions of dynamic clinical characteristics are important for risk-stratifying SCD in the general population.

category: cardiovascular medicine


title: Waning COVID-19 Vaccine Effectiveness for BNT162b2 and CoronaVac in Malaysia: An Observational Study

abstract:
BackgroundEvaluation of vaccine effectiveness over time against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) is important. Evidence on effectiveness over time for the CoronaVac vaccine is lacking despite its widespread use globally. In Malaysia, a diverse set-up of COVID-19 vaccines was rolled out nationwide, and the waning of vaccine protection is a concern. We aimed to investigate and compare waning vaccine effectiveness against COVID-19 infections, COVID-19 related ICU admission and COVID-19 related deaths for BNT162b2 and CoronaVac vaccines.

MethodsIn this observational study, we consolidated nationally representative data on COVID-19 vaccination and patients outcomes. Data on all confirmed COVID-19 cases from 1 to 30 September 2021 were used to compare vaccine effectiveness between the  early group (fully vaccinated in April to June 2021) and the  late group (fully vaccinated in Jul to Aug 2021). We used a negative binomial regression model to estimate vaccine effectiveness against COVID-19 infections for both  early and  late groups, by comparing the rates of infection for individuals vaccinated in the two different periods relative to the unvaccinated. Among confirmed COVID-19 cases, we used logistic regression to estimate and compare vaccine effectiveness against ICU admission and deaths between the two different periods.

FindingsFor BNT162b2, vaccine effectiveness against COVID-19 infections declined from 90.8% (95% CI 89.4, 92.0) in the late group to 79.1% (95% CI 75.8, 81.9) in the late group. Vaccine effectiveness for BNT162b2 against ICU admission and deaths were comparable between the two different periods. For CoronaVac, vaccine effectiveness waned against COVID-19 infections from 74.4% in the late group (95% CI 209 70.4, 77.8) to 30.0% (95% CI 18.4, 39.9) in the early group. It also declined significantly against ICU admission, dropping from 56.1% (95% CI 51.4, 60.2) to 29.9% (95% CI 13.9, 43.0). For deaths, however, CoronaVacs effectiveness did not wane after three to five months of full vaccination.

InterpretationVaccine effectiveness against COVID-19 infections waned after three to five months of full vaccination for both BNT162b2 and CoronaVac in Malaysia. Additionally, for CoronaVac, protection against ICU admission declined as well. Evidence on vaccine effectiveness over time informs evolving policy decisions on vaccination.

category: epidemiology


title: Non-alcoholic steatohepatitis patients exhibit reduced CD47, and increased sphingosine, cholesterol and MCP1 levels in the erythrocyte membranes

abstract: Non-alcoholic steatohepatitis (NASH) constitutes a significant cause of deaths, liver transplantations and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NASH, present phosphatidylserine exposure which is then recognized by Kupffer cells. This event leads to erythrophagocytosis, and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NASH patients release the chemokine MCP1, leading to increased TNF- release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. In addition, increased MCP1 release could be either signal-induced, or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 by ELISA, and cholesterol and sphingosine with thin-layer chromatography. 18 patients (8 men, 10 women aged 56.7{+/-}11.5 years) and 14 healthy controls (7 men, 7 women aged 39.3{+/-}15.5 years) participated in our study. The erythrocyte CD47 levels were decreased in the erythrocyte membranes of NASH patients (844{+/-}409 pg/ml) compared to healthy controls (2969{+/-}1936 pg/ml) with P(Healthy>NAFLD)=99.1%, while the levels of MCP1 were increased in NASH patients (389{+/-}255 pg/ml), compared to healthy controls (230{+/-}117 pg/ml) with P(Healthy<NAFLD)=88.9%. Moreover, in erythrocyte membranes there was a statistically significant accumulation of sphingosine and cholesterol in NASH patients, compared to healthy controls. Our results imply that erythrocytes release chemotactic "find me" signals (MCP1), while containing reduced "do not eat me" signals (CD47). These molecules can lead to erythrophagocytosis. Next, increased "goodbye" signals (sphingosine and cholesterol) could augment inflammation by metabolic reprogramming.

category: gastroenterology


title: The statistical analysis of daily data associated with different parameters of the New Coronavirus COVID-19 pandemic in Georgia and their monthly interval prediction from September 1, 2021 to December 31, 2021

abstract:
The lockdown introduced in Georgia on November 28, 2020 contributed to positive trends in the spread of COVID-19 until February - the first half of March 2021. Then, in April-May 2021, the epidemiological situation worsened significantly, and from June to the end of December COVID - situation in Georgia was very difficult.

In this work results of the next statistical analysis of the daily data associated with New Coronavirus COVID-19 infection of confirmed (C), recovered (R), deaths (D) and infection rate (I) cases of the population of Georgia in the period from September 01, 2021 to December 31, 2021 are presented. It also presents the results of the analysis of monthly forecasting of the values of C, D and I. As earlier, the information was regularly sent to the National Center for Disease Control & Public Health of Georgia and posted on the Facebook page https://www.facebook.com/Avtandil1948/.

The analysis of data is carried out with the use of the standard statistical analysis methods of random events and methods of mathematical statistics for the non-accidental time-series of observations. In particular, the following results were obtained.

Georgias ranking in the world for Covid-19 monthly mean values of infection and deaths cases in investigation period (per 1 million population) was determined. Among 157 countries with population [≥] 1 million inhabitants in October 2021 Georgia was in the 4 place on new infection cases, and in September - in the 1 place on death. Georgia took the best place in terms of confirmed cases of diseases (thirteenth) in December, and in mortality (fifth) - in October.

A comparison between the daily mortality from Covid-19 in Georgia from September 01, 2021 to December 31, 2021with the average daily mortality rate in 2015-2019 shows, that the largest share value of D from mean death in 2015-2019 was 76.8 % (September 03, 2021), the smallest 18.7 % (November 10, 2021).

As in previous work [9,10] the statistical analysis of the daily and decade data associated with coronavirus COVID-19 pandemic of confirmed, recovered, deaths cases and infection rate of the population of Georgia are carried out. Maximum daily values of investigation parameters are following: C = 6024 (November 3, 2021), R = 6017 (November 15, 2021), D = 86 (September 3, 2021), I = 12.04 % (November 24, 2021). Maximum mean decade values of investigation parameters are following: C = 4757 (1 Decade of November 2021), R = 4427 (3 Decade of November 2021), D = 76 (2 Decade of November 2021), I = 10.55% (1 Decade of November 2021).

It was found that as in spring and summer 2021 [9,10], from September to December 2021 the regression equations for the time variability of the daily values of C, R, D and I have the form of a tenth order polynomial.

Mean values of speed of change of confirmed -V(C), recovered - V(R), deaths - V(D) and infection rate V(I) coronavirus-related cases in different decades of months for the indicated period of time were determined. Maximum mean decade values of investigation parameters are following: V(C) = +139 cases/day (1 Decade of October 2021), V(R) = +124 cases/day (3 Decade of October 2021), V(D) = +1.7 cases/day (3 Decade of October 2021), V(I) = + 0.20 %/ day (1 decades of October 2021).

Cross-correlations analysis between confirmed COVID-19 cases with recovered and deaths cases shows, that from September 1, 2021 to November 30, 2021 the maximum effect of recovery is observed on 12 and 14 days after infection (CR=0.77 and 0.78 respectively), and deaths - after 7, 9, 11, 13 and 14 days (0.70[≤]CR[≤]0.72); from October 1, 2021 to December 31, 2021 - the maximum effect of recovery is observed on 14 days after infection (RC=0.71), and deaths - after 9 days (CR=0.43). In Georgia from September 1, 2021 to November 30, 2021 the duration of the impact of the delta variant of the coronavirus on people (recovery, mortality) could be up to 28 and 35 days respectively; from October 1, 2021 to December 31, 2021 - up to 21 and 29 days respectively.

Comparison of daily real and calculated monthly predictions data of C, D and I in Georgia are carried out. It was found that in investigation period of time daily and mean monthly real values of C, D and I practically fall into the 67% - 99.99% confidence interval of these predicted values.

Traditionally, the comparison of data about C and D in Georgia (GEO) with similar data in Armenia (ARM), Azerbaijan (AZE), Russia (RUS), Turkey (TUR) and in the World (WRL) is also carried out.


title: Attitudes towards vaccines, intent to vaccinate and the relationship with COVID-19 vaccination rates in individuals with schizophrenia

abstract:
BackgroundPeople with schizophrenia are at high risk for developing severe COVID-19 outcomes but recent evidence suggests that this population have lower vaccination rates than the general population. This gap in vaccination rates could be explained by attitudinal and structural barriers.

AimsThis study explored the role of potential attitudinal barriers by comparing schizophrenia patients with participants from the general population regarding COVID-19 vaccination rates, general attitudes towards vaccines, and willingness to take a COVID-19 vaccine.

MethodWe conducted a cross-sectional study between April 2021 and October 2021. 100 schizophrenia patients and 72 controls were recruited. Attitudes towards vaccines were assessed with the Vaccination Attitudes Examination Scale. COVID-19 vaccination rates, sociodemographic, clinical and health-related variables were also assessed.

ResultsIn our study, the proportion of individuals with schizophrenia were under-vaccinated despite similar general attitudes towards vaccination and higher willingness to be vaccinated against COVID-19 compared to the participants from the general population. In patients, negative attitudes toward vaccines was related to higher level of negative psychotic symptoms and higher level of paranoid ideation. As a whole, participants with more negative attitudes towards vaccines were less likely to be vaccinated against COVID-19 and had lower levels of trust in institutions.

ConclusionsVaccine hesitancy does not appear to be a major barrier for COVID-19 vaccine uptake amongst people with schizophrenia. This study suggests that disparities in COVID-19 vaccination rates in schizophrenia do not seem related to attitudinal but rather structural barriers.

Significant outcomesO_LIIn both groups, non-vaccinated individuals had higher general negative attitudes towards vaccines.
C_LIO_LIPeople with schizophrenia were under-vaccinated (64% versus 77.8%) despite similar general attitudes towards vaccination and higher willingness to be vaccinated in non vaccinated against COVID-19 compared to the controls (41.7% versus 21.5%).
C_LIO_LIGeneral positive attitudes towards vaccines were negatively associated with persecutory ideation and negative symptoms in patients.
C_LI

LimitationsO_LIOur two sample groups sere composed exclusively of French individuals, potentially limiting the generalizability of our results.
C_LIO_LIThe cross-sectional design of our study.
C_LI

category: psychiatry and clinical psychology


title: Testing key messages about extending cervical screening intervals

abstract:
ObjectivesWe tested the impact of different messages about the rationale for extended screening intervals on acceptability of an extension.

MethodsWomen in England aged 25-49 years (n=2931) were randomised to read different messages about extending intervals from 3 to 5 years. Outcome measures were general acceptability and six components from the Theoretical Framework of Acceptability (TFA).

ResultsThe control group were less likely to find the change acceptable (43%) than the groups who saw additional messages (47-63%). Women who saw messages about interval safety, test accuracy or the speed of cell changes had more positive affective attitudes, higher ethicality beliefs, a better understanding of the reasons for the interval change and were more likely to believe that 5-year intervals would be safe. Being up-to-date with screening and previous abnormal results were associated with finding 5-yearly screening unacceptable.

ConclusionsEmphasising the slow development of cell changes following an HPV negative result and the safety of longer intervals, alongside messages about the accuracy of HPV primary screening is important.

Practical implicationsCampaigns explaining the rationale for increased screening intervals are likely to improve acceptability. Though some women who feel at increased risk, may remain worried even when the rationale is explained.

category: public and global health


title: Real-world monitoring of BNT162b2 vaccine-induced SARS-CoV-2 B and T cell immunity in naive healthcare workers: a prospective single center study

abstract:
BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. To prevent the massive COVID-19 burden, several vaccination campaigns were initiated. We performed a single center observational trial to evaluate adaptive immunity in naive healthcare workers upon BNT162b2 vaccination.

MethodsSerological analysis was performed through conventional immunoassays. Antibody functionality was analyzed via in vitro neutralization assays. Circulating receptor-binding domain (RBD) specific B cells were assessed via flowcytometry. The induction of SARS-CoV-2 specific T cells was investigated through interferon-{gamma} release assay combined with flowcytometric profiling of activated CD4 and CD8 T cells.

ResultsThree months after vaccination, all but one of the subjects (N = 31) displayed vaccine-induced neutralizing antibodies. In 10 out of 31 subjects, circulating RBD specific B cells were found of which the rate showed moderate correlation to serological parameters. Specific interferon-{gamma} release was present in all subjects and correlated with the significant upregulation of CD69 on CD4+ and CD8+ T cells and CD40L on CD4+ T cells. Interestingly, no relation was found between B and T cell parameters. In addition, one symptomatic breakthrough infection with the SARS-CoV-2 alpha variant of concern was reported.

ConclusionThree months post vaccination, both humoral and cellular immune responses are detectable in all but one participant. No correlation was found between the magnitude of both B and T cell responses.


title: Phylodynamic analysis of SARS-CoV-2 spread in Rio de Janeiro, Brazil, highlights how metropolitan areas act as dispersal hubs for new variants.

abstract:
During the first semester of 2021, all of Brazil has suffered an intense wave of COVID-19 associated with the Gamma variant. In July, the first cases of Delta variant were detected in the state of Rio de Janeiro. In this work, we have employed phylodynamic methods to analyze more than 1,600 genomic sequences of Delta variant collected until September in Rio de Janeiro to reconstruct how this variant has surpassed Gamma and dispersed throughout the state. After the introduction of Delta, it has initially spread mostly in the homonymous city of Rio de Janeiro, the most populous of the state. In a second stage, dispersal occurred to mid- and long-range cities, which acted as new close-range hubs for spread. We observed that the substitution of Gamma by Delta was possibly caused by its higher viral load, a proxy for transmissibility. This variant turnover prompted a new surge in cases, but with lower lethality than was observed during the peak caused by Gamma. We reason that high vaccination rates in the state of Rio de Janeiro were possibly what prevented a higher number of deaths.

Impact statementUnderstanding how SARS-CoV-2 spreads is vital to propose efficient containment strategies, especially when under the perspective of new variants emerging in the next year. Still, models of SARS-CoV-2 dispersal are still largely based in large cities from high-income countries, resulting in an incomplete view of the possible scenarios consequent of a new variant introduction. The work improves this discussion by reconstructing the spatio-temporal dispersal of Delta variant since its introduction in Rio de Janeiro, a densely populated region in South America. We also analyzed the epidemiological outcome of this spread, with a decrease in lethality rate uncommon to the observed in other countries.

Data summaryFour supplementary figures, one supplementary table and one supplementary file are available with the online version of this article. Raw short reads of the newly sequenced genomes are available at SRA-NCBI database (https://www.ncbi.nlm.nih.gov/sra) under the BioProject PRJNA774631 and the assembled genomes are deposited at GISAID database (https://www.gisaid.org/) under the accession numbers listed in Table S1. Other genomic sequences used in the analyses are listed in Table S2. Epidemiological data for the state of Rio de Janeiro was obtained from https://www.saude.rj.gov.br/informacao-sus/dados-sus/2020/11/covid-19.


title: Evaluation of Trans-Sodium Crocetinate (TSC) on Peripheral Oxygenation in Healthy Individuals Using Transcutaneous Oximetry

abstract:
IntroductionTrans sodium crocetinate (TSC) is a synthetic carotenoid with a unique mechanism of action that improves the diffusion of oxygen by reducing oxygen transfer resistance within plasma, and it is currently being developed to enhance oxygen delivery to hypoxic tissues in multiple conditions. The goals of this study were to evaluate safety, pharmacokinetics, and pharmacodynamic properties of escalating doses of TSC on peripheral oxygenation utilizing transcutaneous oxygen measurements, when administered to healthy subjects breathing supplemental oxygen.

MethodsThis was a dose-escalation, single-center, randomized, phase 1 study aimed at assessing the safety, pharmacokinetic and pharmacodynamic properties of TSC at doses of 0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg as an intravenous bolus. Thirty healthy adult subjects of 18 to 55 years of age were enrolled and allocated to one of the five dose groups or placebo. Venous blood samples were collected for pharmacokinetic evaluations of TSC at 1, 10, 30 minutes, and 1.5 hours after the start of injection of the study drug. Pharmacodynamic assessment of tissue oxygenation was performed while the subjects breathed supplemental oxygen at 6 L/minute for 70 minutes prior to study drug administration: the first 10 minutes was to allow for equilibration, and the subsequent 60 minutes served as a baseline period (Period 1), followed by a time-matched 60-minute intervention period (Period 2). Tissue oxygenation readings were obtained by transcutaneous oximetry (TcpO2) measurement using four TcpO2 sensors placed on the lower limbs of subjects lying in a supine or semi-recumbent position. TcpO2 values were recorded over a 2-hour time period: 60 minutes prior to study drug administration (Period 1) and 60 minutes post administration of the study drug (Period 2).

ResultsTSC was safe and well tolerated at all doses tested. The pharmacokinetic analyses demonstrated that clearance decreased at escalating doses of TSC. The results of the primary pharmacodynamic analysis revealed high levels of variability in the 60-minute baseline TcpO2 levels, however despite such variability, time-matched TcpO2 measurements demonstrated observed increases in median TcpO2 values in subjects who received TSC, relative to those who received a placebo. The high variability observed across the four sensors suggested that the data could not be pooled across all four sensors, therefore, additional supplemental analyses were performed. The results of the supplemental analyses indicated that the TcpO2 intra-subject slopes of the TSC treatment groups were consistently positive during the study intervention period, and therefore suggestive of an increase in TcpO2 levels. This was not observed in the placebo group. Based on this analysis, all TSC dose groups had a greater increase in TcpO2 levels than the placebo group, with the 2.5 mg/kg dose demonstrating the most notable increase over the 1-hour intervention period (Period 2).

ConclusionsTSC administered as a single IV bolus dose ranging from 0.5 mg/kg to 2.5 mg/kg to healthy subjects breathing supplemental oxygen, was safe and well tolerated. Pharmacokinetic assessments demonstrated that TSC plasma concentrations increased with escalating dose and that increasing TSC dose was associated with a decrease in clearance. The high levels of variability in TcpO2 levels did not allow for pooling of sensor measurements for primary analysis; however, supplemental analysis of individual sensor measurements demonstrated an observed dose effect of TSC on peripheral tissue oxygenation relative to placebo.

category: pharmacology and therapeutics


title: Clinical Utility of Combined Optical Genome Mapping and 523-gene Next Generation Sequencing Panel For Comprehensive Evaluation of Myeloid Cancers.

abstract: The standard-of-care (SOC) for genomic testing of myeloid cancers primarily relies on karyotyping and fluorescent in situ hydridization (FISH) (cytogenetic analysis) and targeted gene panels ([≤]54 genes) that harbor hotspot pathogenic variants (molecular genetic analysis). Both cytogenetic and molecular testing workup is necessary for the identification and detection of large structural variants (SVs) and small variants like single nucleotide variants (SNV) and indels, respectively. Despite this combinatorial approach, [~]50% of myeloid cancer genomes remain cytogenetically normal, and the limited sequencing variant profiles obtained from targeted panels are unable to resolve the genetic etiology of these myeloid tumors. In this study, we evaluated the performance and clinical utility of optical genome mapping (OGM) and a 523-gene next-generation sequencing (NGS) panel for comprehensive genomic profiling of 15 myeloid tumors and compared it to SOC cytogenetic methods (karyotyping and FISH) and a 54-gene NGS panel. OGM and the 523-gene NGS panel were found to have an analytical concordance of 100% with karyotyping, FISH, and the 54-gene panel, respectively. Additionally, OGM better characterized and resolved the structural variants previously reported by karyotyping in five cases, such as identifying the genomic content of marker and ring chromosomes. OGM also identified several additional translocations and eleven copy number variations (CNVs), of which the CNVs were validated/confirmed by the 523-gene panel. The 523-gene panel identified seven additional clinically relevant SNVs (two tier 1A variants and five tier 2C variants, as per the ACMG/AMP guidelines) in four cases. The simultaneous visualization of SVs and small NGS detected sequence variants (SNVs and small indels) from OGM and 523-gene NGS panel, respectively in the NxClinical software v6.1 identified two clinically relevant compound heterozygous events in two samples. This study demonstrates the higher sensitivity, resolution, accuracy, and ability to reveal cryptic and clinically relevant novel variants in myeloid cancers as compared to SOC methodologies. Our cost-effective approach of using OGM and a 523-gene NGS panel for comprehensive genomic profiling of myeloid cancers will not only increase the yield of actionable targets leading to improved clinical outcomes but also help resolve our ongoing conundrum of apparently genomically normal myeloid cancers by providing more answers.

category: genetic and genomic medicine


title: EFCAB4B (CRACR2A) genetic variants associated with COVID-19 fatality

abstract: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than 235 million cases worldwide and 4.8 million deaths (October 2021). Severe COVID-19 is characterised in part by vascular thrombosis and a cytokine storm due to increased plasma concentrations of factors secreted from endothelial and T-cells. Here, using patient data recorded in the UK Biobank, we demonstrate the importance of variations in Rab46 (CRACR2A) with clinical outcomes. Using logistic regression analysis, we determined that three single nucleotide polymorphisms (SNPs) in the gene EFCAB4B cause missense mutations in Rab46, which are associated with COVID-19 fatality independently of risk factors. All three SNPs cause changes in amino acid residues that are highly conserved across species, indicating their importance in protein structure and function. Two SNPs, rs17836273 (A98T) and rs36030417 (H212Q), cause amino acid substitutions in important functional domains: the EF-hand and coiled-coil domain respectively. By using molecular modelling, we suggest that the substitution of threonine at position 98 causes structural changes in the EF-hand calcium binding domain. Since Rab46 is a Rab GTPase that regulates both endothelial cell secretion and T-cell signalling, these missense variations may play a role in the molecular mechanisms underlying the thrombotic and inflammatory characteristics observed in patients with severe COVID-19 outcomes.


title: Development and validation of the Symptom Burden Questionnaire™ for Long COVID: a Rasch analysis

abstract:
ObjectiveTo describe the development and initial validation of a novel patient-reported outcome measure of Long COVID symptom burden, the Symptom-Burden Questionnaire for Long COVID (SBQ-LC).

Method and FindingsThis multi-phase, prospective mixed-methods study took place between April and August 2021 in the United Kingdom (UK). A conceptual framework and initial item pool were developed from published systematic reviews. Further concept elicitation and content validation was undertaken with adults with lived experience (n = 13) and clinicians (n = 10), and face validity was confirmed by the Therapies for Long COVID Study Patient and Public Involvement group (n = 25). The draft SBQ-LC was field tested by adults with self-reported Long COVID recruited via social media and international Long COVID support groups (n = 274). Thematic analysis of interview and survey transcripts established content validity and informed construction of the draft questionnaire. Rasch analysis of field test data guided item and scale refinement and provided evidence of the final SBQ-LCs measurement properties. The Rasch-derived SBQ-LC is composed of 17 independent scales with promising psychometric properties. Respondents rate symptom burden during the past 7-days using a dichotomous response or 4-point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that may be converted to a linear (0 - 100) score. Higher scores represent higher symptom burden.

ConclusionsThe SBQ-LC is a comprehensive patient-reported assessment of Long COVID symptom burden developed using modern psychometric methods. It measures symptoms of Long COVID important to individuals with lived experience and may be used to evaluate the impact of interventions and inform best practice in clinical management.

category: health informatics


title: Evaluation of an emergency safe supply drug and managed alcohol program in COVID-19 isolation hotel shelters for people experiencing homelessness

abstract:
BackgroundDuring a COVID-19 outbreak in the congregate shelter system in Halifax, Nova Scotia, Canada, a multidisciplinary health care team provided an emergency "safe supply" of pharmaceutical-grade medications and beverage-grade alcohol to facilitate isolation in COVID-19 hotel shelters for residents who are dependent on these substances. We aimed to evaluate (a) substances and dosages provided, and (b) effectiveness and safety of the program.

MethodsWe retrospectively reviewed medical records of all COVID-19 isolation hotel shelter residents during May 2021. We extracted data on medication and alcohol dosages provided each day. The primary outcome was residents prematurely leaving isolation against public health orders. Adverse events included (a) overdose; (b) intoxication; and (c) diversion, selling, or sharing of medications or alcohol.

ResultsOver 25 days, 77 isolation hotel residents were assessed (mean age 42 {+/-} 14 years; 24% women). Sixty-two (81%) residents were provided medications, alcohol, or cigarettes. Seventeen residents (22%) received opioid agonist treatment medications (methadone, buprenorphine, or slow-release oral morphine) and 27 (35%) received hydromorphone tablets. Thirty-one (40%) residents received stimulant tablets with methylphenidate (27; 35%), dextroamphetamine (8; 10%), or lisdexamfetamine (2; 3%). Six residents (8%) received benzodiazepines. Forty-two (55%) residents received alcohol, including 41 (53%) with strong beer, three (3%) with wine, and one (1%) with hard liquor. Over 14 days in isolation, mean daily dosages increased of hydromorphone (45 {+/-} 32 to 57 {+/-} 42mg), methylphenidate (51 {+/-} 28 to 77 {+/-} 37mg), dextroamphetamine (33 {+/-} 16 to 46 {+/-} 13mg), and alcohol (12.3 {+/-} 7.6 to 13.0 {+/-} 6.9 standard drinks). Six residents (8%) left isolation prematurely, but four of those residents returned. Over 1,059 person-days in isolation, there were zero overdoses. Documented concerns regarding intoxication occurred six times (0.005 events/person-day) and medication diversion or sharing three times (0.003 events/person-day).

ConclusionsAn emergency safe supply and managed alcohol program, paired with housing, was associated with low rates of adverse events and high rates of successful completion of the 14-day isolation period in COVID-19 isolation hotel shelters. This supports the effectiveness and safety of emergency safe supply prescribing and managed alcohol in this setting.

category: addiction medicine


title: The Impact of State Paid Sick Leave Policies on Longitudinal Weekday Workplace Mobility During the COVID-19 Pandemic

abstract:
ObjectivesTo evaluate whether the Families First Coronavirus Response Act (FFCRA) modified the association between pre-existing state paid sick leave (PSL) and weekday workplace mobility between February 15 and July 7, 2020.

MethodsThe 50 US states and Washington, D.C. were divided into exposure groups based on the presence or absence of pre-existing state PSL policies. Derived from Google COVID-19 Community Mobility Reports, the outcome was measured as the daily percent change in weekday workplace mobility. Mixed-effects, interrupted time series regression was performed to evaluate weekday workplace mobility after the implementation of the FFCRA on April 1st, 2020.

ResultsStates with pre-existing PSL policies exhibited a greater drop in mobility following the passage of the FFCRA ({beta}=-8.86,95%CI:-11.6,-6.10,P< 001). This remained significant after adjusting for state-level health, economic, and sociodemographic indicators ({beta}=-3.13,95%CI:-5.92,-0.34,P=.039).

ConclusionsPre-existing PSL policies contributed to a significant decline in weekday workplace mobility after the FFCRA, which may have influenced local health outcomes.

Policy implicationsThe presence of pre-existing state policies may differentially influence the impact of federal legislation enacted during emergencies.

category: health policy


title: Increased airborne transmission of COVID-19 with new variants. Implications for health policies.

abstract:
New COVID-19 variants, either of higher viral load such as delta or higher contagiousness like omicron, can lead to higher airborne transmission than historical strains. This paper highlights their implications for health policies, based on a clear analytical understanding and modeling of the airborne contamination paths, of the dose following exposure, and the importance of the counting unit for pathogens, itself linked to the dose-response law. Using the counting unit of Wells, i.e. the quantum of contagium, we develop the conservation equation of quanta which allows deriving the value of the quantum concentration at steady state for a well-mixed room. The link with the monitoring concentration of carbon dioxide is made and used for a risk analysis of a variety of situations for which we collected CO2 time-series observations. The main conclusions of these observations are that 1) the present norms of ventilation, are both insufficient and not respected, especially in a variety of public premises, leading to high risk of contamination and that 2) air can often be considered well-mixed. Finally, we insist that public health policy in the field of airborne transmission should be based on a multi parameter analysis such as the time of exposure, the quantum production rate, mask wearing and the infector proportion in the population in order to evaluate the risk, considering the whole complexity of dose evaluation. Recognizing airborne transmission requires thinking in terms of time of exposure rather than in terms of proximal distance.

HighlightsO_LIRelative airborne risk assessment following variant viral load and contagiousness
C_LIO_LIIndoor analytical risk assessment including absence of ventilation
C_LIO_LIAdequacy of the present norms of ventilation to Covid-19 pandemic
C_LIO_LIObservation of non-compliance to standards concerning CO2 Indoor Air Quality
C_LI


title: SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against SARS-CoV-2 Delta and Omicron that can be predicted by anti-S antibody concentrations in serological assays

abstract:
BackgroundRecent data on immune evasion of new SARS-CoV-2 variants raise concerns about antibody-based COVID-19 therapies. Therefore in this study the in-vitro neutralization capacity against SARS-CoV-2 variants Wuhan D614G, Delta and Omicron in sera of convalescent individuals with and without boost by vaccination was assessed.

Methods and FindingsThis in-vitro study included 66 individuals with a history of SARS-CoV-2 infection, divided into subgroups without (n=29) and with SARS-CoV-2 vaccination (n=37). We measured SARS-CoV-2 antibody concentrations by serological assays (anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S) and neutralizing titers against Wuhan D614G, Delta and Omicron in a pseudovirus neutralization assay.

Sera of the majority of unvaccinated convalescents did not effectively neutralize Delta and Omicron (4/29, 13.8% and 19/29, 65.5%, resp.). Neutralizing titers against Wuhan D614G, Delta and Omicron were significantly higher in vaccinated compared to unvaccinated convalescents (p<0.0001) with 11.1, 15.3 and 60-fold higher geometric mean of 50%-neutralizing titers (NT50) in vaccinated compared to unvaccinated convalescents. The increase in neutralizing titers was already achieved by one vaccination dose. Neutralizing titers were highest in the first 3 months after vaccination. Concentrations of anti-S antibodies in the serological assays anti-SARS-CoV-2 QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S predict neutralization capacity against Wuhan D614G, Delta and Omicron. While Wuhan D614G was neutralized in-vitro by Bamlanivimab, Casirivimab and Imdevimab, Omicron was resistant to these monoclonal antibodies.

ConclusionsThese findings confirm substantial immune evasion of Delta and Omicron which can be overcome by vaccination of convalescents. This informs strategies for choosing of plasma donors in COVID-19 convalescent plasma programs that shall select specifically vaccinated convalescents with very high titers of anti-S antibodies.


title: Pooled RNA: extraction free testing of saliva for SARS-CoV-2 detection

abstract: The key to limiting SARS-CoV-2 spread is to identify virus-infected individuals (both symptomatic and asymptomatic) and isolate them from the general population. Hence, routine weekly testing for SARS-CoV-2 in all asymptomatic (capturing both infected and non-infected) individuals is considered critical in situations where a large number of individuals congregate such as schools, prisons, aged care facilities and industrial workplaces. Such testing is hampered by operational issues such as cost, test availability, access to healthcare workers and throughput. We developed the SalivaDirect RT-qPCR assay to increase access to SARS-CoV-2 testing via a low-cost, streamlined protocol using self-collected saliva. To expand the single sample testing protocol, we explored multiple extraction-free pooled saliva testing workflows prior to testing with the SalivaDirect assay. A pool size of five, with or without heat inactivation at 65{degrees}C for 15 minutes prior to testing resulted in a positive agreement of 98% and 89%, respectively, and an increased Ct value shift of 1.37 and 1.99 as compared to individual testing of the positive clinical saliva specimens. Applying this shift in Ct value to 316 individual, sequentially collected, SARS-CoV-2 positive saliva specimen results reported from six clinical laboratories using the original SalivaDirect assay, 100% of the samples would have been detected (Ct value >45) had they been tested in the 1:5 pool strategy. The availability of multiple pooled testing workflows for laboratories can increase test turnaround time, permitting results in a more actionable time frame while minimizing testing costs and changes to laboratory operational flow.


title: Sero-Prevalence of Covid-19 among workers in Malaysia

abstract:
From the beginning of the pandemic in Feb 2020, Malaysia has been through 4 waves of outbreak, the magnitude of each wave is several orders larger than the preceding one. By the end of the fourth wave in October 2021, Malaysia has among the highest death toll in Asia, cumulative incidence of confirmed cases has reached 7.0% (>30% in Klang Valley). However it remains uncertain what is the true proportion of the population infected.

We conducted a sero-survey on 1078 workers from 17 worksites in Klang Valley and Perak between July and September 2021. We tested them for SARS-CoV-2-specific antibodies using Ecotest, a lateral flow immunoassay (LFIA). The ability of antibody testing to detect prior infection depends on the assay and sero-reversion. We therefore adjusted the prevalence estimates to correct for potential misclassification bias due to the use of LFIA and sero-reversion using test sensitivity and specificity results estimated from an independent validation study.

The mean age of the workers was 32 years, 89% were male and migrant workers comprised 81% of all subjects, 59% the subjects were from Klang valley. 33% of workers had prior RT-PCR confirmed Covid-19 infections. We estimated 82.2 percent of workers had been infected by Covid-19 by July-September 2021. Prevalence was 99.9% among migrant workers and 12.1% among local workers. Klang Valley, the most industrialized region in Malaysia where most migrant workers are found, had 100% prevalence, giving an infection-to-case ratio (ICF) of [~]3.

Our sero-prevalence results show that the incidence of Covid19 is extremely high among migrant workers in Malaysia, consistent with findings from other countries such as Kuwait and Singapore which also hosted large number of migrant workers.


title: Ulcerative Colitis Host-Microbiome Response to Hyperbaric Oxygen Therapy

abstract:
ObjectiveThis study examined the host-microbe changes underpinning treatment response to hyperbaric oxygen therapy (HBOT) in ulcerative colitis.

DesignPre- and post-intervention mucosal tissue and fecal samples from two clinical trials, along with fecal samples from healthy controls and fecal and mucosal tissue from disease severity matched UC controls. Mucosal tissue bulk-RNA sequencing, digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed, in addition to 16S rRNA, shotgun metagenomics, metabolomics, and metaproteomics of fecal samples. Fecal colonization experiments in IL10-/- germ-free mice were performed to confirm observations.

ResultsProteomics identified associations between HBOT response status and neutrophil degranulation, with specificity of effect for azurophilic granules. DSP identified a specific HBOT effect on reducing neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with an accompanying proportional increase in Firmicutes and a secondary bile acid lithocholic acid. The reduction in diversity was due to reductions in mucinophiles, with differences in Akkermansia muciniphila strains being associated with HBOT response status. Proteomics observed an accompanying effect for HBOT on MUC2. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared to stool obtained from HBOT non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses.

ConclusionHBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients, and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A. muciniphila, may contribute to HBOT non-response.


title: Factors Affecting Medication Adherence Among patient with Schizophrenia: A Literature Review

abstract: This review aimed to summarize empirical evidence concerning to the factors relating to medication adherence among patients with schizophrenia. A comprehensive search was implemented to recruit articles which met the present eligibility criteria. Twenty articles were included, all of which were quantitative studies. Greater awareness of illness (insight), previous history of medication adherence, positive attitude toward medication, types of atypical antipsychotics, less severe psychotic symptoms, and social support, self-efficacy, general health status, gender men, lower socioeconomic status, living alone, length of illness, drug abuse, education level, severity of illness for example being in the acute phase, participating in mental health services, health facilities, marital status, receiving monotherapy were identified as factors of medication adherence. Implications to clinical practice include providing psychoeducation to patients and family by increasing their knowledge about illness and medication.


title: Evolution of the spatial distribution of alcohol consumption following alcohol control policies: a 25-year cross-sectional study in a Swiss urban population

abstract:
BackgroundAlcohol consumption is a major risk factor for multiple chronic diseases and overall mortality. Consequently, multiple alcohol control policies have been implemented in Switzerland. Recent evidence shows that population-wide policies may have impacted some population subgroups and places differently. While the determinants of alcohol consumption are complex, understanding where interventions are needed is necessary for implementing targeted policies. Spatial statistics and modeling allow incorporating this spatial context into the analysis of alcohol consumption and its determinants.

MethodsWe used the 1993-2018 Bus Sante annual population-based surveys including 18,515 participants aged 35-74 years residing in the canton of Geneva, Switzerland. We assessed the existence of spatial clustering of alcohol consumption the local Morans I spatial statistics. To evaluate how the spatial distribution of alcohol consumption may have changed over time, we subdivided the study sample into three subsamples according to periods of alcohol-control policies implementation: before (Period 1 (P1): 1993.01.01-1999.06.30), during (Period 2 (P2): 1999.07.01-2009.10.31), and after (Period 3 (P3): 2009.11.01-2018.12.31). We also investigated socio-demographic and built environment determinants of alcohol consumption across periods and provided a comparison of the performance and results of global ordinary least squares (OLS), local geographically weighted regression (GWR), and multiscale GWR (MGWR) models.

ResultsWe found spatial clustering of alcohol consumption in the three analyzed periods. Alcohol consumption in local clusters markedly decreased across periods despite increasing alcohol outlet accessibility. The spatial distribution of higher alcohol consumption clusters (i.e., hot spots) and of lower alcohol consumption clusters (i.e., cold spots) changed slightly across periods. Alcohol consumption in hot spots remained above recommendations in P3 (26.0 g/day, SD {+/-} 17.2 g/day), particularly for women. Cold spots increased in size (4.6% of the participants in P1, 9.3% in P3), particularly in the period following the implementation of policies (P2 to P3) while hot spots remained stable (3.2% of the participants). Alcohol consumption was significantly higher in hot spots than cold spots in all three periods (p < 0.001).

The MGWR model outperformed the OLS and GWR models in most cases and revealed that alcohol consumption was influenced by a mix of global and local relationships. Several of these relationships evolved across periods. Interestingly, in models adjusted for individual-level determinants, we found significant positive relationships between bar density and alcohol consumption in P1 and between density of off-premises alcohol outlets and alcohol consumption in P2. However, these two associations were not significant in P3 potentially due to alcohol control policies.

ConclusionOur results reveal that certain areas and subgroups in need of public health intervention and show that a mix of global and local processes best model alcohol consumption. In addition, this study highlights the potential of geospatial approaches to provide a refined understanding of the determinants of alcohol consumption, and the spatial scales at which they vary.


title: Limited cross-variant immunity after infection with the SARS-CoV-2 Omicron variant without vaccination

abstract: SARS-CoV-2 Delta and Omicron strains are the most globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease1, Omicron infection causes less severe disease, mostly upper respiratory symptoms2,3. The question arises whether rampant spread of Omicron could lead to mass immunization, accelerating the end of the pandemic. Here we show that infection with Delta, but not Omicron, induces broad immunity in mice. While sera from Omicron-infected mice only neutralize Omicron, sera from Delta-infected mice are broadly effective against Delta and other VOCs, including Omicron. This is not observed with the WA1 ancestral strain, although both WA1 and Delta elicited a highly pro-inflammatory cytokine response and replicated to similar titers in the respiratory tracts and lungs of infected mice as well as in human airway organoids. Pulmonary viral replication, pro-inflammatory cytokine expression, and overall disease progression are markedly reduced with Omicron infection. Analysis of human sera from Omicron and Delta breakthrough cases reveals effective cross-variant neutralization induced by both viruses in vaccinated individuals. Together, our results indicate that Omicron infection enhances preexisting immunity elicited by vaccines, but on its own may not induce broad, cross-neutralizing humoral immunity in unvaccinated individuals.


title: Multisystemic inflammatory syndrome following COVID-19 mRNA vaccine in children: a national post-authorization pharmacovigilance study

abstract:
ImportanceMultisystem inflammatory syndrome in children (MIS-C) is the most severe life-threatening clinical entity associated with pediatric SARS-CoV-2 infection. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown.

ObjectiveTo assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children.

Design, Setting, and ParticipantsPost-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12- 17-year-old children between June 15th, 2021 and January 1st, 2022, were reported. Each case was assessed for WHO MIS-C criteria. Causality assessment followed 2019 WHO recommendations.

ExposureCOVID-19 mRNA vaccine.

Main Outcome and MeasuresThe main outcome was the reporting rate of post-vaccine hyper-inflammatory syndrome per 1,000,000 COVID-19 mRNA vaccine doses in 12-17-year-old children. This reporting rate was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. Secondary outcomes included the comparison of clinical features between post-vaccine hyper-inflammatory syndrome and post SARS-CoV-2 MIS-C.

ResultsFrom June 2021 to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 9 presented a multisystemic hyper-inflammatory syndrome. All cases fulfilled MIS-C WHO criteria. Main clinical features included male predominance (8/9, 89%), cardiac involvement (8/9, 89%), digestive symptoms (7/9, 78%), coagulopathy (5/9, 54%), cytolytic hepatitis (4/9, 46%), and shock (3/9, 33%). 3/9 (33%) required intensive care unit transfer, and 2/9 (22%) hemodynamic support. All cases recovered. Only three cases had evidence of previous SARS-CoV-2 infection. The reporting rate was 1.1 (95%CI [0.5; 2.1]) per 1,000,000 doses injected. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. Clinical features (inflammatory parameters, cytopenia) slightly differed from post-SARS-CoV-2 MIS-C, along with short-term outcomes (less PICU transfer than MIS-C).

Conclusion and RelevanceVery few cases of hyper-inflammatory syndromes with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of MIS-C among same age children infected by SARS-CoV-2, supports the benefit of SARS-CoV-2 vaccination in children. Further studies are required to explore specific pathways of this entity compared to post-SARS-CoV-2 MIS-C.

Key pointsO_ST_ABSQuestionC_ST_ABSIs COVID-19 mRNA vaccine in 12-17-year-old children associated with subsequent multisystemic hyper-inflammatory syndrome?

FindingsThe French national pharmacovigilance system identified 9 children with a hyper-inflammatory syndrome with multi-organ involvement following COVID-19 mRNA vaccination (reporting rate 1.1 [0.5; 2.1] per 1,000,000 doses), of which only three had evidence of previous SARS-CoV-2 infection. All cases fulfilled WHO definition for MIS-C, but clinical and immunological features, along with short-term outcomes, slightly differed from classical post SARS-CoV-2 MIS-C.

MeaningVery rare cases of hyper-inflammatory syndrome can occur following COVID-19 mRNA vaccine in 12-17-year-old children. The very low rate of this entity, compared to classical post-SARS-CoV-2 MIS-C, supports the benefit of SARS-CoV-2 vaccination in children.

category: pediatrics


title: Effectiveness of mRNA COVID-19 Vaccines against Omicron among Veterans

abstract:
BackgroundWe estimated vaccine effectiveness (VE) of mRNA vaccines among US Veterans during periods of Delta and Omicron variant dominance. Patients included in this study were largely 65 years or older (62,834, 55%), male (101,259, 88%), and non-Hispanic white (66,986, 58%).

MethodsWe used SARS-CoV-2 laboratory test results to conduct a matched test-negative case-control study to estimate VE of three and two doses of mRNA vaccines against infection (regardless of symptoms), and a matched case-control study to estimate VE against COVID-19-related hospitalization and death. We estimated VE as (1-odds ratio) x 100%. Severity of disease was measured using hospital length of stay (LOS) and admission to an intensive care unit (ICU).

ResultsAgainst infection, booster doses had 7-times higher VE - 59% (95% confidence interval [CI], 57 to 61) - than 2-dose VE (7%; 95% CI, 3 to 10) during the Omicron period. For the Delta period, estimated VE against infection was 90% (95% CI, 88 to 92) among boosted vaccinees, 64% higher than VE among 2-dose vaccinees [55% (95% CI, 51 to 58)]. Against hospitalization, booster dose VE was 87% (95% CI, 80 to 91) during Omicron and 95% (95% CI, 91 to 97) during Delta; the 2-dose VE was 44% (95% CI, 26 to 58) during Omicron and 75% (95% CI, 70 to 80) during Delta. Against death, estimated VE with a booster dose was 94% (95% CI, 85 to 98) during Omicron and 96% (95% CI, 88 to 99) during Delta, while the 2-dose VE was 75% (95% CI, 52 to 87) during Omicron and 93% (95% CI, 85 to 97) during Delta. During the Omicron period, average hospital LOS was 4 days shorter [3 days (95%CI, 3 to 4 days)] than during the Delta period.

ConclusionsA mRNA vaccine booster is more effective against infection, hospitalization, and death than 2-dose vaccination among an older male population with comorbidities.


title: Effectiveness of mRNA COVID-19 Booster Vaccines against Omicron and Delta Variants among US Veterans


title: SARS-CoV-2 induces human endogenous retrovirus type W envelope protein expression in blood lymphocytes and in tissues of COVID-19 patients.

abstract:
Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes.

Graphical abstract

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title: OMICRON-ASSOCIATED CHANGES IN SARS-COV-2 SYMPTOMS IN THE UNITED KINGDOM

abstract: In a nationally representative UK community study, SARS-CoV-2 Omicron infections were associated with fewer lower, and more upper, respiratory tract symptoms. Increases in sore throat (also common in PCR-negative participants), and a marked reduction in loss of taste/smell (previously highly specific), make Omicron harder to detect with symptom-based testing algorithms.


title: Automatic colorectal cancer screening using deep-learning on spatial light interference microscopy data

abstract: The surgical pathology workflow currently adopted in the clinic uses staining to reveal tissue architecture within thin sections. A trained pathologist then conducts a visual examination of these slices and, as the investigation is based on an empirical assessment, a certain amount of subjectivity is unavoidable. Furthermore, the reliance on such external contrast agents like hematoxylin and eosin (H&E), albeit a well-established method, makes it difficult to standardize color balance, staining strength, and imaging conditions, hindering automated computational analysis. In response to these challenges, we applied spatial light interference microscopy (SLIM), a label-free method that generates contrast based on the intrinsic tissue refractive index signatures. Thus, we reduce human bias and make the image data comparable across instruments and clinics. We applied a Mask R-CNN deep learning algorithm to the SLIM data to achieve an automated colorectal cancer screening procedure, i.e., classifying normal vs. cancer specimens. Our results obtained on a tissue microarray consisting of specimens from 132 patients, resulted in 91% accuracy for gland detection, 99.71% accuracy in gland-level classification, and 97% accuracy in core-level classification. A SLIM tissue scanner accompanied by an application-specific deep learning algorithm may become a valuable clinical tool, enabling faster and more accurate assessment by the pathologist.

category: pathology


title: (Mis) Communicating The Gut Microbiome: A Cross-Sectional Assessment of Social Media Video Content

abstract:
BackgroundSocial media platforms, such as YouTube, are an integral means of disseminating information about health and wellness to the public. However, anecdotal reports have cited that the human gut microbiome has been a particular focus of dubious, misleading and, on occasion, harmful media content. Despite these claims, there have been no published studies investigating this phenomenon within popular social media platforms.

AimThis study aims to (1) evaluate the accuracy and credibility of YouTube videos related to the human gut microbiome and (2) investigate the correlation between content engagement metrics and information quality, as defined by validated criteria.

MethodsIn this cross-sectional study, videos about the human gut microbiome were searched on the UK version of YouTube on 20th September 2021. The 600 most viewed videos were extracted and screened for relevance. Information content and characteristics were extracted and independently rated using the DISCERN quality criteria by two researchers.

ResultsOverall, 319 videos accounting for 62,354,628 views were included. 73.4% of the videos were produced in North America, and over 78.6% were uploaded between 2019-2021. 41.0% of videos were produced by non-profit organizations. 16% of the videos had an advertisement for a product or promoted a health-related intervention for financial purposes. Videos by non-medical educational creators had the highest total and preferred viewership. Daily viewership was highest for videos by internet media sources. The average DISCERN and HONcode scores were 49.5 (0.68) out of 80 and 5.05 (2.52) out of 8, respectively. DISCERN scores for videos by medical professionals (53.2 (0.17)) were significantly higher than videos by independent content creators (39.1 (5.58)), (p<0.01). Videos with promotional material scored significantly lower DISCERN scores than videos without any advertisements or product promotion (p<0.01). There was no correlation between DISCERN scores and total viewership, daily viewership or preferred viewership (number of likes).

ConclusionsThe overall credibility of information about human gut microbiome on YouTube is poor. Moreover, there was no correlation between the video information quality and the level of public engagement. The significant disconnect between reliable sources of information and the public suggests that there is an immediate need for cross-sector initiatives in order safeguard vulnerable viewers from the potentially harmful effects of misinformation and disinformation.


title: Analysis of screening results of high-risk population of stroke in Northern Henan Province

abstract:
ObjectivesThrough the screening analysis of stroke population in Northern Henan from 2014 to 2020, to understand the distribution characteristics of high-risk population of stroke and the correlation between high-risk population of stroke and risk factors, to provide basis for stroke prevention and treatment in Northern Henan province.

MethodsA random cluster sampling method was used for screening the high-risk population of stroke in Northern Henan Province, and a questionnaire survey, physical examination and laboratory examination were conducted on the respondents (those who lived in the local area for half a year or more) aged above 40 years old who voluntarily participated in and signed the informed consent, and then the data were sorted and analyzed.

ResultsA total of 16815 people were participated in screening of high-risk population of stroke in Northern Henan Province, including 6366 males and 10448 females, accounting for 37.86% and 62.14%, respectively; 8855 people were urban household registration, and 7960 people were rural household registration; the age range was 40-80 years old; statistical results demonstrated that there were 3428 people at high-risk of stroke, 3629 people were at moderate risk of stroke, and 8428 people were at low-risk of stroke, accounting for 20.39%, 21.58% and 50.01% in the total screening people, respectively; there were 365 transient Islamic attacks (TIA) patients and 965 stroke patients in the total screening participants in Northern Henan province from 2014 to 2020, accounting for 2.17% and 5.74% in the total screening people, respectively.

After further data sorting, we obtained 2588 valid data of high-risk of stroke, there were significant differences in gender, household registration type and age (P<0.01); the incidence rate of high-risk population of stroke was related to dyslipidemia, atrial fibrillation, smoking, lack of exercise, overweight, family history of stroke, hypertension and diabetes mellitus (P<0.01); the top three highest exposure rates of risk factors were diabetes mellitus (67.16%), overweight (62.60%), and lack of exercise (58.27%) in the high-risk population of stroke. A total of 606 valid data of stroke were screened out, there were significant differences in gender and age (P<0.01); the incidence rate of stroke was related to dyslipidemia, smoking, lack of exercise, overweight, stroke family history, hypertension and diabetes mellitus (P<0.01), the top three highest exposure rates of risk factors of stroke were hypertension (73.27%), overweight (42.08%) and lack of exercise (33.83%) in the stroke patients.

ConclusionThe incidence rate of stroke high-risk population and stroke patients was lower in Northern Henan Province compared with national average incidence rate in China, and there are statistical differences at gender and age for the incidence rate of stroke high-risk population and stroke patients in Northern Henan Province. There was the highly correlation between risk factors (dyslipidemia, atrial fibrillation, smoking, lack of exercise, overweight, stroke family history, hypertension and diabetes) and stroke high-risk population or stroke. Regular population screening and early prevention should be taken to reduce the incidence rate of stroke.

category: neurology


title: PRACTICE OF EARLY BREASTFEEDING INITIATION ON PRIMIGRAVIDA WITH A CULTURAL PERSPECTIVE: A SYSTEMATIC REVIEW

abstract:
One of the health aspects in the development process is the development of human resource potential (HR). What plays a role in this potential of human resources is good nutritional status from an early age. In addition to these factors, the quality of human resource formation is also influenced by the environment that shapes human character. namely the socio-cultural environment (Soekirman, 2005). One of the cultural interactions that affect nutritional status as a condition for the formation of quality human resources is the practice of breastfeeding and the practice of early breastfeeding initiation (IMD). There have been many previous studies that have written that there are still many mothers who do not practice IMD, where one of the reasons mentioned is the belief that the first milk that comes out is dirty and unhealthy, so it is not suitable to be given to babies (Roesli, 2008). The purpose of this literature study is to determine the influence of culture in the practice of early breastfeeding initiation.

The articles used in the literature review were obtained through databases of international journal providers such as Proquest, Google Scholar and Science Direct. The journal was taken from 2019 to 2021. Researchers used keywords, namely transcultural nursing, breastfeeding (according to MESH/Medical Subject Heading) and 20 articles were analyzed using PRISMA diagrams. The analysis found that most mothers did not practice early breastfeeding because of certain beliefs about early breastfeeding, such as early breastfeeding was not as good as exclusive breastfeeding, dirty early breast milk, unhealthy early breastfeeding given to babies and the habit of mothers who immediately gave additional food immediately. after the baby is born.

category: nursing


title: PLWHA's Perspective on Community Stigma for Getting Social Support and Improving Life Quality in the Digital Era

abstract: Community stigma against HIV/AIDS is still a problem that must be faced by people living with HIV/AIDS (PLWHA). The existence of stigmatization and discrimination received by PLWHA causes the lack of social support they get. Social support is very important for PLWHA to improve their quality of life. In this digital era where the development of technology and social media is an alternative for PLWHA to get social support online through their community, by sharing information and experiences. This systematic review was conducted through Scopus, Science Direct, ProQuest, and SAGE. The selection of articles followed inclusion criteria, including articles published in the last five years and published in English and discussing perspectives on stigma. Articles published not in English and articles with unclear literature reviews were excluded from this study. The PRISMA flow chart and JBI assessment checklist were used to assess the risk of bias and article quality. 20 relevant articles will be reviewed. The results of the study found that in this digital era PLWHA can take advantage of technological developments and social media to improve their quality of life by getting social support through the online communities they follow.


title: CBioExplorer: a web and standalone application for screening, validation, and annotation of cancer survival related biomarkers from molecular level to clinical settings

abstract: Cancer is one of the main killers threatening human life and health. The exploration of biomarkers that can predict the long-term survival of cancer patients is of great significance for the risk stratification, treatment and prognosis of cancer patients. However, the screening and validation process involving biomarkers is a complicated process. Currently, there are no unified tools for physicians and researchers to explore tumor biomarkers. Herein, we present CBioExplorer (Cancer Biomarker Explorer), a user-friendly web server and standalone application that includes 5 major modules (dimensionality reduction, benchmark experiment, prediction model, clinical annotation; and, biological annotation) and integrated a novel R package CuratedCancerPrognosisData that reviewed, curated and integrated the gene expression data and corresponding clinical data of 47,210 clinical samples from 268 gene expression studies of 43 common blood and solid tumors, for screening, validation, and annotation of cancer survival related biomarkers based on 6 machine learning survival learners from molecular level to clinical settings. The web server is available at http://cbioexplorer.znhospital.cn:8383/CBioExplorer/, and the standalone app and source code of CBioExplorer and CuratedCancerPrognosisData can be found at https://github.com/liuxiaoping2020/CBioExplorer or https://gitee.com/liuxiaoping2020/CBioExplorer.

category: oncology


title: Artificial Intelligence in laryngeal endoscopy: Systematic Review and Meta-Analysis

abstract:
BackgroundEarly and proper diagnosis of laryngeal lesions is necessary to begin treatment of the patient as soon as possible with the possibility of preserve organ functions. Imaging examinations are oft aided by artificial intelligence (AI) to improve quality and facilitate appropriate diagnosis. The aim of the study is to investigate of the diagnostic utility of AI in laryngeal endoscopy.

MethodsFive electronic databases (PubMed, Embase, Cochrane, Scopus, Web of Science) were searched for studies published before October 15, 2021 implementing artificial intelligence (AI) enhanced models assessing images of laryngeal lesions taken during laryngeal endoscopy. Outcomes were analyzed in terms of accuracy, sensitivity and specificity.

ResultsAll 13 included studies presented overall low risk of bias. The overall accuracy of AI models was very high (from 0.806 to 0.997) and the number of images used to build and evaluate the models ranged from 120 to 24,667. The accuracy was significantly higher in studies using larger database. The pooled sensitivity and specificity for identification of healthy laryngeal tissue (8 studies) was 0.91 (95% CI: 0.83-0.98) and 0.97 (95% CI: 0.96-0.99), respectively. The same values for differentiation between benign and malignant lesions (7 studies) were 0.91 (95% CI: 0.86-0.96) and 0.95 (95% CI: 0.90-0.99), respectively. The analysis was extended to a comparison of sensitivity and specificity of AI models assessing Narrow Band Imaging (3 studies) and white light endoscopy images (4 studies). The results were similar for both methods, no subgroup effect was revealed (p = 0.406 for sensitivity and p = 0.817 for specificity).

ConclusionsIn assessing images of laryngeal lesions, AI demonstrates extraordinarily high accuracy, sensitivity, and specificity. AI enhanced diagnostic tools should be introduced into everyday clinical work. The performance of AI diagnoses increases efficacy with the size of the image database when using similar standards for evaluating images. The multicentre cooperation should concentrate on creation of huge database of laryngeal lesions images and implement their sharing, which allows building AI modes with the best performance, based on vast amount of images for learning and testing.

category: otolaryngology


title: Use of unstructured text in prognostic clinical prediction models: a systematic review

abstract:
ObjectiveThis systematic review aims to assess how information from unstructured clinical text is used to develop and validate prognostic risk prediction models. We summarize the prediction problems and methodological landscape and assess whether using unstructured clinical text data in addition to more commonly used structured data improves the prediction performance.

Materials and MethodsWe searched Embase, MEDLINE, Web of Science, and Google Scholar to identify studies that developed prognostic risk prediction models using unstructured clinical text data published in the period from January 2005 to March 2021. Data items were extracted, analyzed, and a meta-analysis of the model performance was carried out to assess the added value of text to structured-data models.

ResultsWe identified 126 studies that described 145 clinical prediction problems. Combining text and structured data improved model performance, compared to using only text or only structured data. In these studies, a wide variety of dense and sparse numeric text representations were combined with both deep learning and more traditional machine learning methods. External validation, public availability, and explainability of the developed models was limited.

ConclusionOverall, the use of unstructured clinical text data in the development of prognostic prediction models has been found beneficial in addition to structured data in most studies. The EHR text data is a source of valuable information for prediction model development and should not be neglected. We suggest a future focus on explainability and external validation of the developed models, promoting robust and trustworthy prediction models in clinical practice.


title: Pharmaceutical Payments to Japanese Certificated Hematologists: A Retrospective Analysis of Personal Payments from Pharmaceutical Companies between 2016 and 2019

abstract:
BackgroundA growing and significant financial relationship exist between physicians and pharmaceutical companies. However, little is known about the characteristics and trends of personal payments from pharmaceutical companies to hematologists. This study was aimed to evaluate the financial relationship between hematology specialists and pharmaceutical companies in Japan between 2016 and 2019.

MethodsDescriptive analyses were performed to evaluate personal payments from 92 major pharmaceutical companies to all board-certificated hematologists in Japan. Furthermore, trend of payments over four years were evaluated by generalized estimating equations.

ResultsAmong the 4,183 hematology specialists, 2,706 (64.7%) received a total of US$36,291,434 ({yen}3,955,766,292). The personal payments were worth $13,411 (standard deviation: $34,856) on average, with a median of $2,471 (Interquartile range: $851 $9,677) over the four-year period, respectively. Only the top 10% of specialists accounted for 76.8% of the total payments. The average payment values constantly increased from $4,259 to $5,574 between 2016 and 2019, with a significant mean annual increase rate of 11.2% (95%CI: 9.1% 13.4%). The proportion of hematology specialists with payments also slightly increased by 1.8% (95%CI: 0.6% 3.0%) per year.

ConclusionsMost Japanese board-certified hematology specialists received substantial personal payments. These payments are becoming increasingly more prevalent and greater among hematology specialists.


title: Nature and Trends of Pharmaceutical Payments to Board Certificated Respiratory Specialists in Japan between 2016 and 2019

abstract:
BackgroundThere are financial relationships between healthcare professionals and pharmaceutical companies, and these relationships have historically caused conflicts of interest and unduly influenced patient care. However, little was known about such relationship and its effect in clinical practice among specialists in respiratory medicine.

MethodsBased on the retrospective analysis of payment data made available by all 92 pharmaceutical companies in Japan, this study evaluated the magnitude and trend of financial relationships between all board-certified Japanese respiratory specialists and pharmaceutical companies between 2016 and 2019. Magnitude and prevalence of payments for specialists were analyzed descriptively. The payment trends were assessed using the generalized estimating equations for the payment per specialist and the prevalence of specialists with payments.

ResultsAmong all 7,114 respiratory specialists certified as of August, 2021, 4,413 (62.0%) received a total of USD($) 53,547,391 and 74,195 cases from 72 (78.3%) pharmaceutical companies between 2016 and 2019. The mean{+/-}SD and median (interquartile range) four-year combined payment values per specialist were $12,134{+/-}$34,045 and $2,210 ($715{square}$8,178) respectively. At maximum, one specialist received $495,332 personal payments over the four years. Both payments per specialist and prevalence of specialists with payments significantly increased during the four-year period, with 7.8% (95% CI: 5.5{square}9.8; p<0.001) in payments and 1.5% (95% CI: 0.61% {square}2.4%; p = 0.001) in prevalence of specialists with payments, respectively.

ConclusionMajority of respiratory specialists had increasingly received substantial personal payments from pharmaceutical companies for the reimbursement of lecturing, consulting, and writing between 2016 and 2019. These increasing financial relationships with pharmaceutical companies might cause conflicts of interest among respiratory physicians.


title: Detection of SARS-CoV-2 variant Mu, Beta, Gamma, Lambda, Delta, Alpha, and Omicron in wastewater settled solids using mutation-specific assays is associated with regional detection of variants in clinical samples

abstract:
Changes in the circulation of SARS-CoV-2 variants of concern (VOCs) may require changes in public health response to the COVID-19 pandemic, as they have the potential to evade vaccines and pharmaceutical interventions and may be more transmissive relative to other SARS-CoV-2 variants. As such, it is essential to track and prevent their spread in susceptible communities.We developed digital RT-PCR assays for mutations characteristic of VOCs and used them to quantify those mutations in wastewater settled solids samples collected from a publicly owned treatment works (POTW) during different phases of the COVID-19 pandemic. Wastewater concentrations of single mutations characteristic to each VOC, normalized by the concentration of a conserved SARS-CoV-2 N gene, correlate to regional estimates of the proportion of clinical infections caused by each VOC. These results suggest targeted RT-PCR assays can be used to detect variants circulating in communities and inform public health response to the pandemic.

ImportanceWastewater represents a pooled biological sample of the contributing community and thus a resource of assessing community health. Here we show that emergence, spread, and disappearance of SARS-CoV-2 infections caused by variants of concern are reflected in the presence of variant genomic RNA in wastewater settled solids. This work highlights an important public health use case for wastewater.

category: infectious diseases


title: Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique

abstract:
BackgroundSoil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure.

MethodologyWe evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference.

Principal findingsIgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure.

ConclusionsWe provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers could be used as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens.

AUTHOR SUMMARYParasitic worms and Plasmodium falciparum, the causal agent of malaria, are among the most relevant parasitic diseases of our time and efforts are under way for their control and, ultimately, elimination. An accurate diagnosis is relevant for case management, but also allows calculating the prevalence and evaluating the effectiveness of treatment and control measures. Unfortunately, current diagnostic methods for parasitic worms are not optimal and many infections remain undetected. As for P. falciparum, current diagnostic techniques are satisfactory but do not allow for ascertaining exposure, which is relevant for evaluating control measures. Here we investigated the utility of measuring antibodies to these parasites as a diagnostic method. Our results indicate that it is possible to detect current infection with parasitic worms and P. falciparum using antibody detection with a moderate to high accuracy. We also show that antibodies could distinguish a population from Southern Mozambique, where these infections are prevalent, from a Spanish population never exposed to those parasites. Importantly, we used a platform that allows for the simultaneous detection of immunoglobulins to different parasites, which would be extremely useful as a tool to integrate control and elimination programs for several pathogens.


title: COVID-19 breakthrough infection after inactivated vaccine induced robust antibody responses and cross-neutralization of SARS-CoV-2 variants, but less immunity against omicron

abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants in patients with COVID-19 who had been fully vaccinated with CoronaVac (n = 78), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 (n = 170), and individuals who had received AZD1222 as a third vaccination (n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68-100) days. Blood samples were collected at median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2) were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which activities are exceeding 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibody against omicron. Further investigation is needed to assess the long-term persistence of antibody against omicron variant.

category: allergy and immunology


title: Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-lead Electrocardiograms

abstract: Artificial intelligence (AI) models applied to 12-lead electrocardiogram (ECG) waveforms can predict atrial fibrillation (AF), a heritable and morbid arrhythmia. We hypothesized that there may be a genetic basis for ECG-AI based risk estimates. We applied an ECG-AI model for predicting incident AF to ECGs from 39,986 UK Biobank participants without AF. We then performed a genome-wide association study (GWAS) of the predicted AF risk. We identified three signals (P<5x10-8) at established AF susceptibility loci marked by the sarcomeric gene TTN, and sodium channel genes SCN5A and SCN10A. We also identified two novel loci near the genes VGLL2 and EXT1. In contrast, a GWAS of risk estimates from a clinical variable model indicated a different genetic profile. Predicted AF risk from an ECG-AI model is influenced by genetic variation implicating sarcomeric, ion channel, and height pathways. ECG-AI models may identify individuals at risk for disease via specific biological pathways.

category: cardiovascular medicine


title: Data-driven research on eczema: systematic characterization of the field and recommendations for the future

abstract:
BackgroundThe past decade has seen a substantial rise in the employment of modern data-driven methods to study atopic dermatitis (AD) / eczema.

ObjectiveTo summarise the past and future of data-driven AD research, and identify areas in the field that would benefit from the application of these methods.

MethodsWe retrieved the publications that applied multivariate statistics (MS), artificial intelligence (AI, including machine learning-ML), and Bayesian statistics (BS) to AD and eczema research from the SCOPUS database over the last 50 years. We conducted a bibliometric analysis to highlight the publication trends and conceptual knowledge structure of the field, and applied topic modelling to retrieve the key topics in the literature.

ResultsFive key themes of data-driven research on AD and eczema were identified: (1) allergic co-morbidities, (2) image analysis and classification, (3) disaggregation, (4) quality of life, and (5) risk factors and prevalence. ML&AI methods mapped to studies investigating quality of life, prevalence, risk factors, allergic co-morbidities and disaggregation of AD/eczema, but seldom in studies of therapies. MS was employed evenly between the topics, particularly in studies on risk factors and prevalence. BS was focused on three key topics: treatment, risk factors and allergy. The use of AD or eczema terms was not uniform, with studies applying ML&AI methods using the term eczema more often. Within MS, papers using cluster and factor analysis were often only identified with the term AD. In contrast, those using logistic regression and latent class/transition models were "eczema" papers.

ConclusionsResearch areas that could benefit from the application of data-driven methods include the study of the pathogenesis of the condition and related risk factors, its disaggregation into validated subtypes, and personalized severity management and prognosis. We highlight Bayesian statistics as a new and promising approach in AD and eczema research.

category: dermatology