title: Forecasting Preventive Dental Quality Measures

abstract: Dental quality measures objectively measure the efficiency and performance of dental providers and organizations. While these measures in conjunction with established benchmarks are used routinely for self-assessment, forecasting them ahead of time in a data-driven and evidence-based manner has the potential to assist in assessing future dental treatment needs, oral disease burden, care utilization patterns, and strategic decision making for sustained performance improvement complementing traditional descriptive visualization dashboards. The present study modeled the temporal trends of four key preventive dental quality measures related to caries prevention (Adult New Caries, Sealants (6-9yrs.), Sealants (12-15yrs.), Fluoride Varnish) sampled monthly from (Dec. 2010 to July 2017) averaged across ten Family Health Center Dental Centers (FQHC), Wisconsin, using auto-regressive integrated moving average time series models. Five-month ahead forecasts along with their 95% confidence levels and mean absolute percentage error were determined across the four measures (Adult New Caries: 1.8%, Sealants (6-9yrs.): 0.90%, Sealants (12-15yrs.): 0.30%, Fluoride Varnish: 0.15%). Model diagnostics revealed auto-regressive integrated moving average models to sufficiently capture the temporal patterns of these measures and the forecast estimates of Adult New Caries and Sealants (12-15yrs.) revealed the need for increased efforts for improved preventive care utilization. Forecasting preventive dental quality measures can provide insights into expected treatment needs ahead of time and can assist in optimal resource and staff allocation with potential to prescribe suitable interventions to shift the trajectory from predicted outcomes to desired outcomes in a targeted manner. While the present study investigated organization level preventive dental quality measures, the time series approach presented is as such generic and expected to translate across similar settings.

category: dentistry and oral medicine


title: Vaccines alone are no silver bullets: a modeling study on the impact of efficient contact tracing on COVID-19 infection and transmission

abstract:
BackgroundThe computer simulation presented in this study aimed to investigate the effect of contact tracing on COVID-19 transmission and infection in the context of rising vaccination rates.

MethodsThis study proposed a deterministic SEIRV model with contact tracing and vaccination components. We initialized some parameters using the Malaysian COVID-19 data to inform the model. We defined contact tracing effectiveness as the proportion of contacts of a positive case that was successfully traced and vaccination rate as the proportion of daily doses administered per population in Malaysia. Sensitivity analyses on the untraced and infectious populations were conducted. The study presented in silico findings on multiple scenarios by varying the contact tracing effectiveness and daily vaccination rates.

ResultsAt a vaccination rate of 1.4%, a contact tracing with the effectiveness of 70% could delay the peak of untraced asymptomatic cases by 17 days and reduce the highest number of daily cases by 70% compared with a 30% contact tracing effectiveness. A similar trend was observed for symptomatic cases when a similar experiment setting was used. We also performed sensitivity analyses by using different combinations of contact tracing effectiveness and vaccination rates. In all scenarios, the effect of contact tracing on COVID-19 incidence persisted for both asymptomatic and symptomatic cases.

ConclusionDespite testing only on two public health and social measures (PHSMs), we observed the scenario with low contact tracing and increasing vaccination rates successfully mimicked the current transmission trend in Malaysia. Hence, while vaccines are progressively rolled out, efficient contact tracing must be rapidly implemented concurrently to reach, find, test, isolate, and support the affected populations to bring the pandemic under control.

category: epidemiology


title: Prelacteal Feeding and Associated Factors among Mothers of Infants Aged 6 to 12 Months in Chitwan District, Nepal: A Community Based Cross-sectional Study

abstract:
BackgroundA Prelacteal feed is any food except mothers milk provided to a newborn before breastfeeding is established. Prelacteal feeding is a major barrier to exclusive breastfeeding and is associated with newborn infection. It is a prevalent practice in Nepal. This study aimed to investigate prelacteal feeding practice and associated factors among mothers of infants aged 6 to 12 months in Chitwan district, Nepal.

MethodsA community-based cross-sectional study was conducted. 297 mothers of infants aged 6 to 12 months were selected using a systematic random sampling technique. Descriptive statistics, univariate and binomial logistic regression analysis were done to identify the factors associated with prelacteal feeding practice. Variable with a p-value <0.05 were identified as statistically significant factors.

ResultThe prevalence of prelacteal feeding was 40.1% (95% CI: 34.5%-45.7%). Formula milk (n=109), animal milk (n=13), Plain water (n=6) were some of the types of prelacteal feed reported. Respondents in the 25-29 years age group were about 58.2% less likely to practice prelacteal feeding (adjusted odds ratio (AOR)=0.415, 95% confidence interval (CI):0.209-0.837) as compared to the respondents belonging to 35 years or more age group. Economic status was another factor associated with prelacteal feeding practice. Those mothers with poorer economic status were about 57.9 % (AOR= 0.421, CI: 0.179-0.992) less likely to practice prelacteal feeding than the mothers belonging to the richest. Similarly, mothers having poor knowledge on prelacteal feeding were found about three (AOR= 2.661, CI: 1.514-4.674) times more likely to have prelacteal feeding than those mothers who had good knowledge about prelacteal feeding. Home delivery and caesarean section in case of institutional delivery were two major reasons stated for providing prelacteal feeding.

ConclusionPrelacteal feeding was commonly practiced in the Chitwan district, Nepal. Mothers age, economic status, mothers knowledge of prelacteal feeding practices, and mode of delivery were factors associated with prelacteal feeding practices. Therefore, awareness and knowledge on the risk associated with prelacteal feeding, promotion of institutional delivery, timely initiation of breastfeeding, and avoidance of prelacteal feeding are important measures for preventing prelacteal feeding practices in Chitwan district, Nepal.

category: nutrition


title: Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancer

abstract:
Immunotherapy has changed the standard of treatment for many cancers. However, the same treatments showed disappointing outcomes in cervical cancer so far. Thus, understanding the mechanisms that support the immune tolerance of cervical cancer will provide a way to design new strategies to enhance immunotherapies. Here, we characterized cellular compositions of the immune infiltrates in cervical cancer and investigated if the tumor immune landscape is a predictor for patient prognosis. The fraction of ten immune infiltrates of cervical and other cancers were analyzed by using QuanTIseq software base on the bulk mRNA sequencing data from The Cancer Genome Atlas Program (TCGA). Cervical cancer is one of the cancers that had the lowest percentage of total immune infiltrates, but it had the highest ratio for CD8 T cells to all immune infiltrates among all solid cancers. Both the principal components (PCA) analysis and heatmap with dendrogram analysis showed that cervical cancer had a similar immune infiltrated microenvironment with other squamous cell carcinomas, such as head and neck cancer and lung squamous cell cancer. The PCA and heatmap with dendrogram analysis showed that cervical cancer and HPV positive head and neck cancers were clustered more closer and partially separated with HPV negative head and neck cancer. Further analysis showed that HPV-positive cervical and head and neck cancers had a significantly higher level of CD8 T cells and M1-liked macrophages, but a lower level of M2 macrophages. The survival analysis showed that a higher level of CD8 T cells was associated with a better patient prognosis. However, immuno-suppressive immune infiltrates including M2 macrophages and Treg cells that are known to suppress anti-tumor immunity also demonstrated positive patient overall survival. Our study provided a conceptual framework to understand the tumor immune microenvironment of cervical cancer. Our results also demonstrated that the immune infiltrates can be a prognosis marker for cervical cancer.

Simple SummaryCervical cancer is the most common gynecologic cancer and the fourth leading cause of cancer-related death in women worldwide. There are relatively limited treatment options for late-stage cervical cancer. Immunotherapy is a new therapeutic treatment developed with great success in treating many cancers, but the same treatment has not been producing satisfactory results in many cases of cervical cancer. In the present study, we provided a comprehensive immune characterization specifically for cervical cancer. We determined the prognostic value of a specific subtype of tumor-infiltrating immune cells for clinical outcomes and demonstrated that HPV infection affected the immune cell infiltration and induce pro-inflammatory phenotypes. Our study provides a systematic insight into the tumor immune microenvironment of cervical cancers and offers a conceptual framework for the future design of rational combination treatment strategies to improve immunotherapy outcomes.

category: obstetrics and gynecology


title: Multi-omics Data Analyses Construct Tumor Microenvironment and Identify the Immune-Related Prognosis Signatures in Colorectal Cancer

abstract:
BackgroundThe tumor immune microenvironment (TIME) plays a key role in occurrence, progression and prognosis of colorectal cancer (CRC). However, the genetic and epigenetic alterations and potential mechanisms in the TIME of CRC are still unclear.

MethodsWe investigated the immune-related differences in three types of genetic or epigenetic alterations (gene expression, somatic mutation, and DNA methylation) and considered the potential roles that these alterations have in the immune response and the immune-related biological processes by analyzing the multi-omics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step method based on LASSO regression and Cox regression was used to construct the prognostic prediction model. Cross validation was performed to validate the model.

ResultsA total of 1,745 differentially expressed genes, 178 differentially mutated genes and 1,961 differentially methylation probes were identified between the high-immunity group and the low-immunity group. We retained 15 genetic and epigenetic variables after using LASSO regression and Cox regression. For the prognostic predictions on the TCGA profiles, the performance of the model with 1-year, 3-year, and 5-year areas under the curve (AUCs) equal to 0.861, 0.797, and 0.875. Finally, the overall risk score model was constructed based on genetic, epigenetic, demographic and clinical characteristics, which comprised 18 variables and achieved a high degree of accuracy on the 1-year (AUC = 0.865), 3-year (AUC = 0.839), and 5-year (AUC = 0.914) survival predictions. Kaplan-Meier survival analysis demonstrated that the overall survival of the high-risk group was significantly poorer compared with the low-risk group. Prognostic nomogram, calibration plot and cross validation showed excellent predictive performance.

ConclusionsOur study provides a new clue to explore the TIME of CRC patients in genetic and epigenetic aspects. Meanwhile, the prognostic model also has clinical prognostic value and may provide new indicators for the treatment of CRC patients.

category: oncology


title: Analysis of alternative Covid-19 mitigation measures in school classrooms: an agent-based model of SARS-CoV-2 transmission

abstract: 1.The SARS-CoV-2 epidemic continues to have major impacts on childrens education, with schools required to implement infection control measures that have led to long periods of absence and classroom closures. We have developed an agent-based epidemiological model of SARS-CoV-2 transmission that allows us to quantify projected infection patterns within primary school classrooms, and related uncertainties; the basis of our approach is a contact model constructed using random networks, informed by structured expert judgement. The effectiveness of mitigation strategies are considered in terms of effectiveness at supressing infection outbreaks and limiting pupil absence. Covid-19 infections in schools in the UK in Autumn 2020 are re-examined and the model used for forecasting infection levels in autumn 2021, as the more infectious Delta-variant was emerging and school transmission thought likely to play a major role in an incipient new wave of the epidemic. Our results were in good agreement with available data. These findings indicate that testing-based surveillance of infections in the classroom population with isolation of positive cases is a more effective mitigation measure than bubble quarantine, both for reducing transmission in primary schools and for avoiding pupil absence, even accounting for insensitivity of self-administered tests. Bubble quarantine entails large numbers of pupils being absent from school, with only modest impact on classroom infection levels. However, maintaining reduced contact rates within the classroom can have a major beneficial impact for managing Covid-19 in school settings.

category: health policy


title: Alternative Covid-19 mitigation measures in school classrooms: analysis using an agent-based model of SARS-CoV-2 transmission


title: Waning immunity of the BNT162b2 vaccine: A nationwide study from Israel

abstract:
BackgroundStarting December 2020, Israel began a mass vaccination campaign against coronavirus administering the Pfizer BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no SARS-CoV-2 infections, a resurgent COVID-19 outbreak initiated mid June 2021. Possible reasons for the breakthrough were reduced vaccine effectiveness against the Delta variant, and waning immunity. The aim of this study was to quantify the extent of waning immunity using Israels national-database.

MethodsData on all PCR positive test results between July 11-31, 2021 of Israeli residents who became fully vaccinated before June 2021 were used in this analysis. Infection rates and severe COVID-19 outcomes were compared between individuals who were vaccinated in different time periods using a Poisson regression, stratifying by age group and adjusting for possible confounding factors.

ResultsThe rates of both documented SARS-CoV-2 infections and severe COVID-19 exhibit a statistically significant increase as time from second vaccine dose elapsed. Elderly individuals (60+) who received their second dose in March 2021 were 1.6 (CI: [1.3, 2]) times more protected against infection and 1.7 (CI: [1.0, 2.7]) times more protected against severe COVID-19 compared to those who received their second dose in January 2021. Similar results were found for different age groups.

ConclusionsThese results indicate a strong effect of waning immunity in all age groups after six months. Quantifying the effect of waning immunity on vaccine effectiveness is critical for policy makers worldwide facing the dilemma of administering booster vaccinations.

category: infectious diseases


title: The COVID-19 Pandemic and Mental Health Concerns on Twitter in the United States

abstract:
BackgroundMental health illness is a growing problem in recent years. During the COVID-19 pandemic, mental health concerns (such as fear and loneliness) have been actively discussed on social media.

ObjectiveIn this study, we aim to examine mental health discussions on Twitter during the COVID-19 pandemic in the United States and infer the demographic composition of Twitter users who had mental health concerns.

MethodsCOVID-19 related tweets from March 5th, 2020 to January 31st, 2021 were collected through Twitter streaming API using COVID-19 related keywords (e.g., "corona", "covid19", "covid"). By further filtering using mental health keywords (e.g., "depress", "failure", "hopeless"), we extracted mental health-related tweets from the US. Topic modeling using the Latent Dirichlet Allocation model was conducted to monitor users discussions surrounding mental health concerns. Demographic inference using deep learning algorithms (including Face++ and Ethnicolr) was performed to infer the demographic composition of Twitter users who had mental health concerns during the COVID-19 pandemic.

ResultsWe observed a positive correlation between mental health concerns on Twitter and the COVID-19 pandemic in the US. Topic modeling showed that "stay-at-home", "death poll" and "politics and policy" were the most popular topics in COVID-19 mental health tweets. Among Twitter users who had mental health concerns during the pandemic, Males, White, and 30-49 age group people were more likely to express mental health concerns. In addition, Twitter users from the east and west coast had more mental health concerns.

ConclusionsThe COVID-19 pandemic has a significant impact on mental health concerns on Twitter in the US. Certain groups of people (such as Males, White) were more likely to have mental health concerns during the COVID-19 pandemic.


title: Localized and Whole-Room Effects of Portable Air Filtration Units on Aerosol Particle Deposition and Concentration in a Classroom Environment

abstract:
In indoor environments with limited ventilation, recirculating portable air filtration (PAF) units may reduce COVID-19 infection risk via not only the direct aerosol route (i.e., inhalation) but also via an indirect aerosol route (i.e., contact with the surface where particles deposited). We systematically investigated the impact of PAF units in a mock classroom, as a supplement to background ventilation, on localized and whole-room surface deposition and particle concentration. Fluorescently tagged particles with a volumetric mean diameter near two micrometers were continuously introduced into the classroom environment via a breathing simulator with a prescibed inhalation-exhalation waveform. Deposition velocities were inferred on >50 horizontal and vertical surfaces throughout the classroom, while aerosol concentrations were spatially monitored via optical particle spectrometry. Results revealed a particle decay rate consistent with expectations based upon the reported clean air delivery rates of the PAF units. Additionally, the PAF units reduced peak concentrations by a factor of around 2.5 compared to the highest concentrations observed and led to a statistically significant reduction in deposition velocities for horizontal surfaces >2.5 m from the aerosol source. Our results not only confirm PAF units can reduce particle concentrations but also demonstrate that they may lead to reduced particle deposition throughout an indoor environment when properly positioned.

Practical ImplicationsO_LIPortable air filtration units should be prioritized in classrooms as part of a multi-layed strategy to mitigate potentially infectious particle transmission by direct aerosol transmission via inhalation and indirect aerosol transmission via particle deposition to surfaces and later contact with said surfaces.
C_LIO_LIWhen placing portable air filtration unit(s) within a classrom space, one should consider the airflow field within the classroom, the characteristic operational mode (heating vs. cooling) of the heating, ventilation, and air conditioning system, the predominantly occupied areas of the classroom, and interference with the regular teaching and learning activities.
C_LI


title: Evaluation of height as a disease risk factor through a phenome-wide association study of genetically-predicted height

abstract:
BackgroundHeight has been associated with many clinical traits but whether such associations are causal versus secondary to confounding remains unclear in many cases. To systematically examine this question, we performed a Mendelian Randomization-Phenome-wide association study (MR-PheWAS) using clinical and genetic data from a national healthcare system biobank.

Methods and FindingsAnalyses were performed using data from the US Veterans Affairs (VA) Million Veteran Program in non-Hispanic White (EA, n=222,300) and non-Hispanic Black (AA, n=58,151) adults in the US. We estimated height genetic risk based on 3290 height-associated variants from a recent European-ancestry genome-wide meta-analysis. We compared associations of measured and genetically-predicted height with phenome-wide traits derived from the VA electronic health record, adjusting for age, sex, and genetic principal components. We found 345 clinical traits associated with measured height in EA and an additional 17 in AA. Of these, 127 were associated with genetically-predicted height at phenome-wide significance in EA and 2 in AA. These associations were largely independent from body mass index. We confirmed several previously described MR associations between height and cardiovascular disease traits such as hypertension, hyperlipidemia, coronary heart disease (CHD), and atrial fibrillation, and further uncovered MR associations with venous circulatory disorders and peripheral neuropathy. As a number of traits associated with genetically-predicted height frequently co-occur with diabetes mellitus and/or CHD, we evaluated effect modification by diabetes and CHD status of genetically-predicted height associations with risk factors for and complications of diabetes and CHD. We found modification of effects of MR associations by diabetes for skin and bone infections and by CHD status for atrial fibrillation/flutter.

ConclusionsWe conclude that height may be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study.


title: Barrier gesture relaxation during vaccination campaign in France: modelling impact of waning immunity

abstract: Non-pharmaceutical interventions have been implemented intermittently for more than a year in most countries of the world to mitigate COVID-19 epidemic. In France, while the vaccination campaign is progressing, the French government has decided to remove many public health restrictions such as business closure, lockdowns and curfews. Nonetheless, social distancing, mask wearing, and hand washing (also called barrier gestures) are still recommended. We utilize an age-structured compartmental SEIR model that takes into account SARS-CoV-2 waning immunity, vaccination, and increased transmissibility from variants of concern, to estimate if barrier gestures can be relaxed without causing a resurgence of severe infections. This model assumes that susceptibility to infection is a function of immunity status, which depends on initial infection severity and vaccination status. It is calibrated on confirmed COVID-19 cases from the French surveillance database, and accounts for changes in contact behaviors due to implementation of nation-wide public health policies. We study partial and full relaxation of barrier gestures occurring from August to December 2021 under various immunity duration assumptions. Maintaining application of barrier gestures appears essential to avoid a resurgence of severe infections that would exceed health care capacities, while surmounting vaccine hesitancy represents the key to consider their relaxation. Immunity duration assumptions significantly influence the short-term dynamic of the epidemic which should be considered for further modelling.


title: National Excess Mortality from Sub-National data: Method and Application for Argentina

abstract: Currently, many countries have not yet reported 2020 or 2021 mortality data to allow an estimate of excess mortality during the COVID-19 pandemic. However, some countries have sub-national mortality data, at the state, province or city level. I present a simple method to allow estimation of national level mortality and excess mortality from sub-national data, using the case of Argentina and projecting excess mortality up to August 2021.


title: Assessing sustainability factors for rural sanitation coverage in Kenya, Zambia, Nepal, and Bhutan: A qualitative case study analysis

abstract:
BACKGROUNDFew countries are likely to achieve universal sanitation within the next decade as sustaining sanitation coverage remains a critical challenge. The purpose of this study is to investigate factors that may have supported or hindered sustainability of sanitation coverage 1-2 years after the completion of an integrated, area-wide sanitation program in four countries.

METHODSBetween 2014 and 2018, the SSH4A approach was implemented in 15 countries in Africa and Asia, four of which are included in this qualitative study. We conducted focus group discussions and interviews with beneficiaries, implementors, and decision-makers to identify sustainability factors and used household survey data to characterize sub-national sanitation coverage throughout implementation, and 1-2 years after.

RESULTSOur data revealed behavioral, contextual, and service delivery factors that were related to the sustainability of sanitation improvements. Service delivery factors included follow-up hygiene promotion, access to materials (e.g., plastic, cement), local government commitment post-implementation, functioning monitoring systems, uptake of the supply chain by private sector, capacity for innovation. Contextual and behavioral factors included poverty, soil type, road networks, social cohesion, desire for improved latrines, maintenance and cleaning, and knowledge of sanitation benefits.

DISCUSSIONThe presence or absence of sustainability factors identified through this research may have implications on where certain programmatic approaches will work, and where adaptations may be required. Through comparing sustainability factors with sub-national slippage rates, we were able to illustrate how local service delivery systems may respond to barriers (e.g., poverty, lack of affordable sanitation options, changes in population density) and enablers (e.g., sufficient resource allocation, passionate leadership, social cohesion). Understanding the programmatic and contextual factors that either drive or hinder long-term sanitation coverage may allow for greater program impact through adapting implementation based on existing challenges in service delivery and context.

category: public and global health


title: Longitudinal tau PET using flortaucipir: Comparison of (semi)quantitative parameters

abstract:
PurposeSemi-quantitative PET measures can be affected by changes in blood flow, whereas quantitative measures are not. The aim of the study was to compare semi-quantitative(SUVr) and quantitative(R1, BPND) parameters of longitudinal tau PET scans with [18F]flortaucipir, with respect to changes in blood flow.

MethodsSubjects with subjective cognitive decline(SCD; n=38) and Alzheimers disease(AD) patients(n=24) underwent baseline(BL) and 2-year follow-up(FU) dynamic [18F]flortaucipir PET scans. BPND and R1 were estimated using RPM and SUVr(80-100min) was calculated (cerebellar gray as reference). For each region-of-interest ((trans)entorhinal, limbic and neocortical) and parameter, %change was calculated. Regional SUVrs were compared to corresponding DVR (= BPND+1) using paired T-tests. Additionally, simulations were performed to model effects of flow changes on BPND and SUVr in different binding categories. Thereafter, %bias for SUVr with respect to underlying binding and flow were evaluated.

ResultsIn SCD, there was a difference between %change in the (trans)entorhinal ROI (DVR 2.56% vs SUVr 1.85%) only. In AD, a difference was found in the limbic ROI (DVR 6.61% vs SUVr 7.52%) only. R1 changes were small(+0.7% in SCD and -1.6% in AD). Simulations illustrated with increasing flow a decreased %bias for SUVr in low binding conditions, whereas a slightly increased bias was observed in high binding conditions.

ConclusionSUVr provided an accurate estimate of specific binding for [18F]flortaucipir over a two-year follow-up. However, simulations showed that flow changes can affect [18F]flortaucipir SUVr, hence DVR/BPND should be preferred in more advanced disease stages and/or conditions that could induce significant flow changes like pharmacotherapeutic interventions.

category: radiology and imaging


title: Short-Term Immune Response After Inactivated SARS-CoV-2 (CoronaVac, Sinovac) And ChAdOx1 nCoV-19 (Vaxzevria, Oxford-AstraZeneca) Vaccinations in Thai Health Care Workers

abstract:
BackgroundInactivated SARS-CoV-2 (CoronaVac(R),Sinovac, or SV) and ChAdOx1 nCoV-19 (Vaxzevria(R),Oxford-Astra Zeneca, or AZ) vaccines have been administered to the health care workers (HCWs) in Thailand.

ObjectiveTo determine the short-term immune response after the SV and AZ vaccinations in HCWs.

MethodsIn this prospective cohort study, HCWs who completed a 2-dose regimen of the SV or AZ were included. Immune response was evaluated by surrogate viral neutralization test (sVNT) and anti-SARS-CoV-2 total antibody. Blood samples were analyzed at 4 and 12 weeks after the complete SV vaccination and at 4 weeks after each dose of the AZ vaccination. The primary outcome was the seroconversion rate at 4-weeks after complete immunization.

ResultsOverall, 185 HCWs with a median (IQR) age of 40.5(30.3-55.8) years (94 HCWs in the SV group and 91 in the AZ group) were included. At 4 weeks after completing the SV vaccination, 60.6% (95%CI:50.0-70.6%) had seroconversion evaluated by sVNT([≥]68%inhibition), comparable to the patients recovered from mild COVID-19 infection(69.0%), with a rapid reduction to 12.2%(95%CI:6.3-20.8) at 12 weeks. In contrast, 85.7%(95%CI:76.8-92.2%) HCWs who completed the second dose of the AZ for 4 weeks had seroconversion, comparable to the COVID-19 pneumonia patients(92.5%). When using the anti-SAR-CoV-2 total antibody level([≥]132 U/ml) criteria, only 71.3% HCWs in the SV group had seroconversion, compared to 100% in the AZ group.

ConclusionA rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SAR-CoV-2 variants of concern.


title: Environmental Exposure to Volatile Organic Compounds is Associated with Endothelial Injury

abstract:
ObjectiveVolatile organic compounds (VOCs) are airborne toxicants abundant in outdoor and indoor air. High levels of VOCs are also present at various Superfund and other hazardous waste sites; however, little is known about the cardiovascular effects of VOCs. We hypothesized that ambient exposure to VOCs exacerbate cardiovascular disease (CVD) risk by depleting circulating angiogenic cells (CACs).

Approach and ResultsIn this cross-sectional study, we recruited 603 participants with low-to-high CVD risk and measured 15 subpopulations of CACs by flow cytometry and 16 urinary metabolites of 12 VOCs by LC/MS/MS. Associations between CAC and VOC metabolite levels were examined using generalized linear models in the total sample, and separately in non-smokers. In single pollutant models, metabolites of ethylbenzene/styrene and xylene, were negatively associated with CAC levels in both the total sample, and in non-smokers. The metabolite of acrylonitrile was negatively associated with CD45dim/CD146+/CD34+/AC133+ cells and CD45+/CD146+/AC133+, and the toluene metabolite with AC133+ cells. In analysis of non-smokers (n=375), multipollutant models showed a negative association with metabolites of ethylbenzene/styrene, benzene, and xylene with CD45dim/CD146+/CD34+ cells, independent of other VOC metabolite levels. Cumulative VOC risk score showed a strong negative association with CD45dim/CD146+/CD34+ cells, suggesting that total VOC exposure has a cumulative effect on pro-angiogenic cells. We found a non-linear relationship for benzene, which showed an increase in CAC levels at low, but depletion at higher levels of exposure. Sex and race, hypertension, and diabetes significantly modified VOC associated CAC depletion.

ConclusionLow-level ambient exposure to VOCs is associated with CAC depletion, which could compromise endothelial repair and angiogenesis, and exacerbate CVD risk.

category: cardiovascular medicine


title: Inferring Transmission Fitness Advantage of SARS-CoV-2 Variants of Concern in Wastewater Using Digital PCR

abstract: Throughout the global COVID-19 pandemic, SARS-CoV-2 genetic variants of concern (VOCs) have repeatedly and independently arisen. VOCs are characterized by increased transmissibility, increased virulence, or reduced neutralization by antibodies obtained from prior infection or vaccination. Tracking the introduction and transmission of VOCs relies on sequencing, typically whole-genome sequencing of clinical samples. Wastewater surveillance is increasingly used to track the introduction and spread of SARS-CoV-2 variants through sequencing approaches. Here, we adapt and apply a rapid, high-throughput method for detection and quantification of the frequency of two deletions characteristic of the B.1.1.7, B.1.351, and P.1 VOCs in wastewater. We further develop a statistical approach to analyze temporal dynamics in drop-off RT-dPCR assay data to quantify transmission fitness advantage, providing data similar to that obtained from clinical samples. Digital PCR assays targeting signature mutations in wastewater offer near real-time monitoring of SARS-CoV-2 VOCs and potentially earlier detection and inference on transmission fitness advantage than clinical sequencing.


title: Microbial Community of Small Intestine in Acute Severe Pancreatitis Patients: a Pilot Study

abstract:
Purpose of the study: to describe the composition of the microbiota of the initial sections of the small intestine in patients with severe necrotizing acute pancreatitis.

Objectives of the studyO_LIDetermine the composition of the microbiota of the initial sections of the small intestine upon admission to the ICU;
C_LIO_LIDetermine the differences in the composition of the microbiota of the initial sections of the small intestine, depending on the timing of the onset of the disease.
C_LI

IntroductionDisturbance of intestinal homeostasis is a leading factor in the pathogenesis and progression of systemic inflammation in patients with severe acute pancreatitis. The development of systemic complications occurs due to both mesenteric hypoperfusion and dysregulation of intestinal motility, and the destruction of the intestinal barrier, with the translocation of bacterial bodies and their substrates. Which increases the risk of developing POI and increasing mortality. With the advent of methods for high-throughput sequencing of microbiome samples - for example, in the 16S rRNA format - the possibilities for studying the structure of microbial communities have significantly expanded. In this regard, there is more and more evidence of the relationship between the state of human health and microflora inhabiting various parts of the body.

Materials and methodsThe study included 7 patients with a diagnosis of severe necrotizing acute pancreatitis (6 men, 1 woman), the mean age was 54.1 {+/-} 14.4 years. The patients were divided into two groups. Group 1 (n = 4) included patients admitted 2-4 days after the onset of a pain attack. Group 2 (n = 3) - patients admitted no later than 24 hours from the onset of the disease. The bacterial composition of jejunal wash samples was studied using 16S RNA sequencing. The severity of the condition was assessed using the integral scales APACHE II, SOFA, SAPS II. In patients of the main group, APACHE II was 22 {+/-} 2.83 points (18; 24), SOFA - 6.8 {+/-} 0.5 points (6; 7), SAPSII - 32.9 {+/-} 6.4 points (24.7; 40), in patients of the comparison group, APACHE II is 18.0 {+/-} 3.7 points (12; 22), SOFA - 4.0 {+/-} 2.6 points (2; 7), SAPSII - 24.4 {+/-} 5.0 points (20.9; 30.1).

Material was collected at the time of installation of a sterile multifunctional intestinal catheter for Treitzs ligament, no later than 12 hours from the moment of admission to the ICU. At the time of sampling, patients were not receiving antibiotic therapy.

ResultsA more severe course was associated with a reduced representation in the microbiome of the species Nesseria mucosa and Parvimonas micra inhabiting the mucosal layer, as well as Megasphaera micronuciformis. The share of Streptococcus genera (S. rubneri / parasanguinis / australis species) and Actinomyces and a number of genera from the Enterobacteriaceae family in such patients, on the contrary, was higher.

Interest disclosureSample preparation, sequencing and analysis of these microbiome samples was carried out by Knomics LLC during a commercial project for VneshPromFarm LLC, the manufacturer of saline electrolyte solution (SES).

category: gastroenterology


title: Endophenotype Effect Sizes Provide Evidence Supporting Variant Pathogenicity in Monogenic Disease Susceptibility Genes

abstract: Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) are proxies for variant pathogenicity. Effect sizes were associated with pathogenic ClinVar assertions (P<0.001 for each trait) and discriminated pathogenic from non-pathogenic variants (area under the curve 0.82-0.83 across endophenotypes). Large effect size thresholds provided evidence supporting pathogenicity for up to 35% of rare variants of uncertain significance or not in ClinVar in disease susceptibility genes, using an effect size threshold of [≥] 0.5 times the endophenotype standard deviation. We propose that variant associations with quantitative endophenotypes for monogenic diseases can provide evidence supporting pathogenicity.

category: genetic and genomic medicine


title: Comparison of Object Detection Approaches Applied to Field Images of Papanicolaou Stained Cytology Slides

abstract: Papanicolaou is an inexpensive and non-invasive method, generally applied to detect cervical cancer, that can also be useful to detect cancer on oral cavities. Although oral cancer is considered a global health issue with 350.000 people diagnosed over a year it can successfully be treated if diagnosed at early stages. The manual process of analyzing cells to detect abnormalities is time-consuming and subject to variations in perceptions from different professionals. To evaluate a possible solution to the automation of this process, in this paper we employ the object detection deep learning approach in the analysis of this type of image using 3 models: RetinaNet, Faster R-CNN, and Mask R-CNN. We trained and tested the models using images from 6 cytology slides (4 cancer cases and 2 healthy samples) and our results show that Mask R-CNN was the best model for localization and classification of nuclei with an IoU of 0.51 and recall of abnormal nuclei of 0.67.

category: pathology


title: How Strong Is a Mother's Love? Exploring the Mediating Role of Mother-Child Relationship Quality on the Link between Child Abuse Experiences and Adult Intimate Partner Violence Perpetration

abstract:
PurposeIntimate partner violence (IPV) has detrimental effects on individuals physical and mental health. Intergenerational violence transmission theory posits that child abuse (CA) is an important determinant of later IPV perpetration due to socially learned aggression and expectations of violence in romantic relationships. However, less research exists on family protective factors like the mother-child relationship, the strength of which may mediate this link. The present study explored the association between mother-child relationships, child abuse, and adult IPV perpetration--specifically, whether mother-child relationship quality mediated the effects on the link between child abuse and later IPV.

MethodsThis study analyzed data from individuals who completed Waves I and Wave IV of the National Longitudinal Study of Adolescent Health (N=3718 respondents). Structural equation modeling (SEM) was used to investigate mediation dynamics between CA, mother-child relationship, and adult IPV perpetration.

ResultsStructural equation model fit the data well (CFI = .918, RMSEA = .051 [.045, .057]). The mediation model revealed that the direct effect of childhood abuse on IPV was .067 (p<.001), while the indirect effect of childhood abuse on IPV (i.e., the effect operating through the mother-child relationship) was .005 (p<.001).

ConclusionsWhile CA remains a significant risk factor for adult IPV perpetration, findings suggest that high-quality mother-child relationships may have a buffering effect and aid in preventing intergenerational violence transmission. Continued efforts to research, fund, and implement interventions that build healthy family dynamics are needed to support traumatized children into adulthood and end intergenerational violence.


title: Melodic Intonation Therapy for aphasia: A multi-level meta-analysis

abstract:
AO_SCPLOWBSTRACTC_SCPLOWMelodic Intonation Therapy (MIT) is a prominent rehabilitation programme for individuals with post-stroke aphasia. The present meta-analysis investigated the efficacy of MIT while considering outcome measure quality, experimental design, influence of spontaneous recovery, MIT protocol, and level of generalisation.

An extensive literature search identified 606 studies in major databases and trials registers; of those, 22 studies, overall 129 participants, met all eligibility criteria. Multi-level mixed- and random-effects models served to separately meta-analyse RCT and non-RCT data.

RCT evidence on validated measures revealed a small-to-moderate standardised effect in non-communicative language expression for MIT, with substantial uncertainty. Unvalidated measures attenuated MITs effect size compared to validated tests. MITs effect size was 5.7 times larger for non-RCT data compared to RCT data. Effect size in non-RCT data decreased with number of months post-stroke, suggesting confound through spontaneous recovery. Variation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression such as everyday communication ability.

The current results confirm the promising role of MIT in improving trained/untrained performance with unvalidated measures, alongside validated repetition tasks; whilst highlighting possible limitations in promoting everyday communication ability.

category: neurology


title: Melodic Intonation Therapy for aphasia: A multi-level meta-analysis of randomised-controlled-trial and individual-participant data


title: Melodic Intonation Therapy for aphasia: A multi-level meta-analysis of randomised controlled trials and individual participant data


title: Neural Correlates and Functional Cognitive Maps in Breast Cancer Survivors Receiving Different Chemotherapy Regimens; a QEEG/HEG-based Investigation

abstract:
BackgroundPost-chemotherapy cognitive impairment commonly known as "chemobrain" or "chemofog" is a well-established clinical disorder affecting various cognitive domains including attention, visuospatial working memory, executive function, etc. Although several studies have confirmed the chemobrain in recent years, scant experiments have evaluated the potential neurotoxicity of different chemotherapy regimens and agents. In this study, we aimed to evaluate the extent of attention deficits, one of the commonly affected cognitive domains, among breast cancer patients treated with different chemotherapy regimens through neuroimaging techniques.

MethodsBreast cancer patients treated with two commonly prescribed chemotherapy regimens, AC-T and TAC, and healthy volunteers were recruited. Near-infrared hemoencephalography (nirHEG) and quantitative electroencephalography (qEEG) assessments were recorded for each participant at rest and during task performance to compare the functional cortical changes associated with each chemotherapy regimen.

ResultsThe qEEG analysis revealed increased power of high alpha/low beta or sensorimotor rhythm (SMR) frequency in left fronto-centro-parietal regions involved in dorsal and ventral attention networks (DAN and VAN) in the AC-T-treated group comparing to the TAC and control group. The AC-T group also had the highest current source density (CSD) values in DAN and VAN-related centers in 10 and 15 Hz associated with the lowest Z-scored FFT coherence in the mentioned regions.

ConclusionsThe mentioned findings revealed increased cognitive workload and lack of cognitive ease in breast cancer patients treated with the AC-T regimen proposing the presumable neurotoxic sequelae of this chemotherapy regimen in comparison with the TAC regimen.


title: The resurgence risk of COVID-19 in the presence of immunity waning and ADE effect: a mathematical modelling study

abstract: Since the end of 2020, the mass vaccination has been actively promoted and seemed to be effective to bring the COVID-19 pandemic under control. However, the fact of immunity waning and the possible existence of antibody-dependent enhancement (ADE) make the situation uncertain. We developed a dynamic model of COVID-19 incorporating vaccination and immunity waning, which was calibrated by using the data of accumulative vaccine doses administered and the COVID-19 epidemic in 2020 in mainland China. We explored how long the current vaccination program can prevent China in a low risk of resurgence, and how ADE affects the long-term trajectory of COVID-19 epidemics. The prediction suggests that the vaccination coverage with at least one dose reach 95.87%, and with two-doses reach 77.92% on August 31, 2021. However, even with the mass vaccination, randomly introducing infected cases in the post-vaccination period can result in large outbreaks quickly in the presence of immunity waning, particularly for SARS-CoV-2 variants with higher transmission ability. The results showed that with the current vaccination program and a proportion of 50% population wearing masks, mainland China can be protected in a low risk of resurgence till 2023/01/18. However, ADE effect and higher transmission ability for variants would significantly shorten the protective period for more than 1 year. Furthermore, intermittent outbreaks can occur while the peak values of the subsequential outbreaks are decreasing, meaning that subsequential outbreaks boosted the immunity in the population level, which further indicating that catching-up vaccination program can help to mitigate the possible outbreaks, even avoid the outbreaks. The findings reveal that integrated effects of multiple factors, including immunity waning, ADE, relaxed interventions, and higher transmission ability of variants, make the control of COVID-19 much more difficult. We should get ready for a long struggle with COVID-19, and should not totally rely on COVID-19 vaccine.


title: Symptomatology associated with the diffusion of the SARS-CoV-2 Lambda variant in Peru: An infodemiologic analysis

abstract: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) Lambda variant rapidly diffused across Peru following its identification in December 2020, and had now spread worldwide. In this study, we investigated infodemiologic trends in symptomatology associated with the Coronavirus Disease 2019 (COVID-19) following the spread of SARS-CoV-2 Lambda variant in Peru, enabling infodemiologic surveillance of SARS-CoV-2 in regions with high circulation of this new variant. Weekly Google Trends scores were obtained for key symptom keywords between March 1st, 2020 and July 4th, 2021, whilst case count data were obtained from Peruvian Ministry of Health. Multiple time series linear regression was used to assess trends in each score series, using the week of December 27th as cutoff for emergence of the Lambda variant. The significance of such trends was tested for each time period, before and after the cutoff date. A total 2,075,484 confirmed SARS-CoV-2 infections in Peru in relation to Google Trends data were analyzed. After Lambda variant emergence, searches for "diarrhea" demonstrated a change from a negative to positive correlation with weekly case counts and anticipated dynamic changes in case counts by 1-5 weeks. Searches for "shortness of breath" and "headache" remained consistently positively correlated to weekly case counts before and after Lambda emergence. No changes in searches for other common cold symptoms were observed, while no specific trends were observed for "taste loss" or "smell loss". Diarrhea, headache, and shortness of breath appear to be the most important symptoms for infodemiologic tracking the current outbreak in Peru and other regions with high circulation of SARS-CoV-2 Lambda variant.


title: Explant analysis of Utah electrode arrays implanted in human cortex for brain-computer-interfaces

abstract:
Brain-computer interfaces are being developed to restore movement for people living with paralysis due to injury or disease. Although the therapeutic potential is great, long-term stability of the interface is critical for widespread clinical implementation. While many factors can affect recording and stimulation performance including electrode material stability and host tissue reaction, these factors have not been investigated in human implants. In this clinical study, we sought to characterize the material integrity and biological tissue encapsulation via explant analysis in an effort to identify factors that influence electrophysiological performance.

We examined a total of six Utah arrays explanted from two human participants involved in intracortical BCI studies. Two Pt arrays were implanted for 980 days in one participant (P1) and two Pt and two iridium oxide (IrOx) arrays were implanted for 182 days in the second participant (P2). We observed that the recording quality followed a similar trend in all 6 arrays with an initial increase in peak-to-peak voltage during the first 30-40 days and gradual decline thereafter in P1.

Using optical and two-photon microscopy (TPM) we observed a higher degree of tissue encapsulation on both arrays implanted for longer durations in participant P1. We then used scanning electron microscopy and energy dispersive X-ray spectroscopy to assess material degradation. All measures of material degradation for the Pt arrays were found to be more prominent in the participant with a longer implantation time. Two IrOx arrays were subjected to brief survey stimulations, and one of these arrays showed loss of iridium from majority of the stimulated sites. Recording performance appeared to be unaffected by this loss of iridium, suggesting that the adhesion of IrOx coating may have been compromised by the stimulation, but the metal layer did not detach until or after array removal.

In summary, both tissue encapsulation and material degradation were more pronounced in the arrays that were implanted for a longer duration. Additionally, these arrays also had lower signal amplitude and impedance. New biomaterial strategies that minimize fibrotic encapsulation and enhance material stability should be developed to achieve high quality recording and stimulation for longer implantation periods.

category: pharmacology and therapeutics


title: Towards the global equilibrium of COVID-19: statistical analysis of country-level data

abstract:
ObjectivesThe time-varying effect of COVID-19 on a population of a given country or territory can be measured by the Reproduction Number (R) and the Case Fatality Rate (CFR). In our study, we explore the dynamics of these two measures to test whether the virus has reached its equilibrium point and to identify the main factors explaining the current R and CFR variability across countries.

DesignA retrospective study of publicly available country-level data.

SettingFifty countries having the highest number of confirmed COVID-19 cases at the end of September 2021.

ParticipantsAggregated data including 213 976 306 COVID-19 cases confirmed in the selected fifty countries from the start of the epidemic to September 30, 2021.

Primary and secondary outcome measuresThe daily values of COVID-19 R and CFR measures were estimated using country-level data from the Our World in Data website.

ResultsThe mean values of country-level moving averages of R and CFR went down from 1.118 and 6.3%, respectively, on June 30, 2020 to 1.083 and 3.6% on September 30, 2020 and to 1.015 and 1.8% by September 30, 2021. In parallel, the 10% to 90% inter-percentile range of R and CFR moving averages decreased from 0.288 and 13.3%, respectively, on June 30, 2020, to 0.151 and 7.7% on September 30, 2020, and to 0.107 and 3.3% by September 30, 2021. According to a comparison of the country-level 180-day moving averages of R and CFR calculated on September 30, 2021, an increase of 1% in the Delta variant share is associated with an increase of 0.0009 (95% CI 0.000 to 0.002) in the average Reproduction Number R, while an increase of 1% in the total percentage of confirmed COVID-19 cases per countrys population is associated with a decrease of 0.005 (95% CI 0.000 to 0.010) in the average R. Also, an increase of 1% in the total percentage of fully vaccinated people per countrys population is associated with a decrease of 0.04% (95% CI 0.01% to 0.06%) in the average CFR. Other virological, demographic, economic, immunization, or stringency factors were not statistically significantly associated with either R or CFR across the explored countries.

ConclusionsThe slow decrease in the country-level moving averages of R, approaching the level of 1.0 and accompanied by repeated outbreaks ("waves") in various countries, may indicate that COVID-19 has reached its point of a stable endemic equilibrium. A regression analysis implies that only a prohibitively high level of herd immunity (about 63%) may stop the endemic by reaching a stable disease-free equilibrium. It also appears that fully vaccinating about 70% of a countrys population should be sufficient for bringing the CFR close to the level of a seasonal flu (about 0.1%). Thus, while the currently available vaccines prove to be effective in reducing the mortality from the existing COVID-19 variants, they are unlikely to stop the spread of the virus in the foreseeable future. It is noteworthy that no statistically significant effects of government measures restricting the peoples behavior (such as lockdowns) were found in the analyzed data.

Strengths and limitations of this studyO_LIIn this study, we have explored the long-term trends in country-level Reproduction Number and the Case Fatality Rate of COVID-19.
C_LIO_LIOur study also investigated the long-term statistical dependence of the COVID-19 Reproduction Number and the Case Fatality Rate on epidemiological, demographic, economic, immunization, and government policy factors in each country.
C_LIO_LIThe findings of this study may have important implications for the health policy-makers worldwide.
C_LIO_LIThe officially reported numbers of daily COVID-19 confirmed cases depend on the local testing policy and usually underestimate the true number of carriers in the population.
C_LIO_LIThe officially reported numbers of daily COVID-19 deaths in some countries may include all deceased individuals who tested positive for COVID-19, disregarding their actual cause of death, and exclude victims who were not tested for COVID-19.
C_LI


title: Prediction of vaccine efficacy of the Delta variant

abstract: The emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.


title: COVID-19 vaccine hesitancy among Algerian medical students: a cross-sectional study in five universities.

abstract:
Vaccine hesitancy is a limiting factor in global efforts to contain the current pandemic, wreaking havoc on public health. As todays students are tomorrows doctors, it is critical to understand their attitudes toward the COVID-19 vaccine. To our knowledge, this study was the first national one to look into the attitudes of Algerian medical students toward the SARS-CoV-2 vaccine using an electronic convenience survey.

383 medical students from five Algerian universities were included, with a mean age of 21.02. 85.37% (n=327) of respondents had not taken the COVID-19 vaccine yet and were divided into three groups; the vaccine acceptance group (n=175, 53.51%), the vaccine-hesitant group (n=75, 22.93%), and the vaccine refusal group (n=77, 23.54%).

Gender, age, education level, university, and previous experience with COVID-19 were not significant predictors for vaccine acceptance. The confirmed barriers to the COVID-19 vaccine concern available information, effectiveness, safety, and adverse effects.

This work highlights the need for an educational strategy about the safety and effectiveness of the COVID-19 vaccine. Medical students should be educated about the benefits of vaccination for themselves and their families and friends.

The Vaccine acceptant students influence should not be neglected with a possible ambassador role to hesitant and resistant students.

Graphical abstract

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title: Spatial equity of COVID-19 vaccination services in Aotearoa

abstract:
AimThis research examines the spatial equity, and associated health equity implications, of the geographic distribution of Covid-19 vaccination services in Aotearoa New Zealand.

MethodWe mapped the distribution of Aotearoas population and used the enhanced-two-step-floating-catchment-method (E2SFCA) to estimate spatial access to vaccination services, taking into account service supply, population demand, and distance between populations and services. We used the Gini coefficient and both global and local measures of spatial autocorrelation to assess the spatial equity of vaccination services across Aotearoa. Additional statistics included an analysis of spatial accessibility for priority populations, including M[a]ori (Indigenous people of Aotearoa), Pacific, over 65-year-olds, and people living in areas of high socioeconomic deprivation. We also examined vaccination service access according to rurality, and by District Health Board region.

ResultsSpatially accessibility to vaccination services varies across Aotearoa, and appears to be better in major cities than rural regions. A Gini coefficient of 0.426 confirms that spatial accessibility scores are not shared equally across the vaccine-eligible population. Furthermore, priority populations including M[a]ori, older people, and residents of areas with socioeconomic constraint have, on average, statistically significantly lower spatial access to vaccination services. This is also true for people living in rural areas. Spatial access to vaccination services, also varies significantly by District Health Board (DHB) region as does equality of access, and the proportion of DHB priority population groups living in areas with poor access to vaccination services. A strong and significant positive correlation was identified between average spatial accessibility and the M[a]ori vaccination rate ratio of DHBs.

ConclusionCovid-19 vaccination services in Aotearoa are not equitably distributed. Priority populations, with the most pressing need to receive Covid-19 vaccinations, have the worst access to vaccination services.


title: Two years later - changes in abdominal organs: First observations from the UK Biobank longitudinal imaging study

abstract: Longitudinal studies provide unique insights into the impact of environmental factors and lifespan issues on health and disease. Here we investigate changes in body composition in 3,088 free-living participants, part of the UK Biobank in-depth imaging study. All participants underwent neck-to-knee MRI scans at the first imaging visit and after approximately two years (second imaging visit). Image-derived phenotypes for each participant were extracted using a fully-automated image processing pipeline, including volumes of several tissues and organs: liver, pancreas, spleen, kidneys, total skeletal muscle, iliopsoas muscle, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), as well as fat and iron content in liver, pancreas and spleen. Overall, no significant changes were observed in BMI, body weight, or waist circumference over the scanning interval, despite some large individual changes. A significant decrease in grip strength was observed, coupled to small, but statistically significant, decrease in all skeletal muscle measurements. Significant increases in VAT and intermuscular fat in the thighs were also detected in the absence of changes in BMI, waist circumference and ectopic-fat deposition. Adjusting for disease status at the first imaging visit did not have an additional impact on the changes observed. In summary, we show that even after a relatively short period of time significant changes in body composition can take place, probably reflecting the obesogenic environment currently inhabited by most of the general population in the United Kingdom.


title: Precision MRI Phenotyping Enables Detection of Small Changes in Body Composition for Longitudinal Cohorts


title: Hybrid immunity versus vaccine-induced immunity against SARS CoV2 in Patients with Autoimmune Rheumatic Diseases

abstract:
IntroductionSingle-dose COVID-19 vaccines in healthy individuals with past COVID-19 infections seem to provide better immunity than double doses in COVID-19 unexposed individuals. However, it is not known whether the same is true for patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressants.

MethodsWe identified 30 patients with AIRD who took a single dose of the ChAdOx1 vaccine post-COVID-19 infection. Age, sex and disease similar patients were enrolled in to three groups of 30 each who had (1) past infection with COVID-19 but no vaccine, (2) a single dose of ChAdOx1 and (3) double doses of ChAdOx1. Sera were collected from each patient approximately 30 days after last vaccine dose or since the onset of COVID19 symptoms (in the unvaccinated group). Antibodies to spike protein were estimated and virus neutralization potential of sera was tested.

ResultsBaseline characteristics including drug usage was similar betweenthe groups. Seroconversion occurred in 25(83%), 23(77%), 27(90%), and 30(100%) in natural infection, single-dose vaccine, double dose vaccine, and infection +single dose vaccine groups respectively. Mean antibody titres (10076.8{+/-}8998) in the last group were at least 6-100x higher than in the other 3 groups. Also, the infection +vaccine group had the highest neutralization potential of 83.37 % as compared to 45.4% in the fully vaccinated group.

ConclusionThe hybrid immunity with a single dose of the vector-based vaccine post-infection seems to be superior to double dosage of the vaccine in patients with AIRD. A universal vaccination strategy involving a single dose of vaccine for all individuals with previous COVID-19 infection seems to be effective in these patients also.

What is already known about this subject?A single dose of an RNA based COVID-19 vaccine after COVID-19 natural infection provides superior immune protection as compared to double doses of vaccines in infection naive persons

A second dose of vaccine in healthy people who had infection previously does not increase the immune protection but may paradoxically induce tolerance

Vaccine responses in patients with autoimmune rheumatic diseases(AIRD) may be suboptimal due to underlying disease or the use of immunosuppressants.

What does this study add?Hybrid-induced immunity (single vaccine post COVID-19 infection) produces adequate vaccine responses in patients with AIRD, non-inferior to double dose of vaccine

Besides mRNA vaccines, the adenoviral vector vaccine AZD1222 also demonstrates this hybrid phenomenon.

How might this impact on clinical practice?Vaccination policies can consider providing only a single vaccine in those who had previous COVID-19 infection. This strategy has been shown not to be harmful for patients with AIRD. This will help reduce vaccine shortages.

category: rheumatology


title: Individualized diversity in the extracellular metabolome of live human gliomas

abstract: Cancer metabolism is of increasing interest for drug development but few methods exist to evaluate live human malignancies. We utilized high molecular weight (HMW) microdialysis with elevated flow rate pumps under an investigational device exemption to sample the microenvironments of live human gliomas and adjacent brain during neurosurgical resections. Untargeted metabolic profiles spanning over 300 named metabolites were captured from 20{micro}L of microdialysate representing 10 minutes of intra-operative collection time. Five patients were each analyzed via 3 catheters with analysis of >300 named metabolites and 5 drugs. Rank-based analyses and machine learning highlighted metabolic heterogeneity across and between patients, as well as marked metabolic convergence within the most aggressive regions of molecularly diverse tumors. A novel glioma-associated metabolite, guanidinoacetatic acid (GAA), topped the list of extracellular glioma metabolites reflecting altered amino acid and energy metabolism. Intraoperative HMW microdialysis offers improved opportunities to accelerate individualized translational progress for glioma.


title: WHAT FUELS SUBOPTIMAL CARE OF PERIPHERAL INTRAVENOUS CATHETER-RELATED INFECTIONS IN HOSPITALS? A QUALITATIVE STUDY OF DECISION-MAKING AMONG SPANISH NURSES

abstract:
BackgroundPeripheral intravenous catheters (PIVC) are commonly used in hospital worldwide. However, PIVC are not exempt from complications. Catheter-related bloodstream infections (CRBSI) increase morbidity and mortality rates, and costs for the healthcare organization. PIVC care is shaped by the complex mix of professional and organizational culture, such as knowledge gaps, low perception of impact of PIVCs on patient safety, or lack of hospital guidelines.

AimTo explore determinants of decision-making about the prevention of PIVC-BSI among nurses in Spanish hospitals.

MethodsWe conducted a descriptive qualitative study with semi-structured interviews in three public hospitals, the Balearic Islands Health Care Service in Spain. We considered hospital ward nurses working routinely with inpatients at any of the three hospitals for enrolment in the study. We approached relevant informants to identify suitable participants who recruited other participants through a  snowball technique. Fourteen inpatient nurses from the hospital took part in this study between September and November 2018. We employed several triangulation strategies to underpin the methodological rigour of our analysis and conducted the member checking, showing the information and codes applied in the recording of the interviews to identify the coherence and any discrepancies of the discourse by participants. We used the COREQ checklist for this study.

FindingsWe identified four major themes in the analysis related to determinants of care: The fog of decision-making in PIVC; The taskification of PIVC care; PIVC care is accepted to be suboptimal, yet irrelevant; and PIVC care gaps may reflect behavioural shortcomings, yet solutions proposed to involve education and training.

ConclusionThe clinical management of PIVCs appear ambiguous, unclear, and fragmented, with no clear professional responsibility and no nurse leadership, causing a gap in preventing infections. Furthermore, the perception of low risk on PIVC care impact can cause a relevant lack of adherence to the best evidence and patient safety. Implementing facilitation strategies could improve the fidelity of the best available evidence regarding PIVC care and raise awareness among nurses of impact that excellence of care.

category: nursing


title: Immunity status in patients with periprosthetic knee joint infection

abstract:
Implant-associated infection is one of the most severe complications after total replacement of larger joints. The diagnosis of periprosthetic infection are often impeded as 5-34% of bacteriological tests are false-negative. Now the investigations of the immune status of patients suspected of periprosthetic infection are considered perspective as these are aimed at finding the most significant indicators for underlying the diagnosis of this pathology. In this research, we assessed immunology indicators in peripheral blood of patients with periprosthetic infection in their knee joints. We determined immunology characteristics associated with the clinical aspects of the progressing pathology. Our findings can be used as the basis for further search of pathophysiological mechanisms of periprosthetic infection progress in the knee joint as well as defining new diagnostic approaches.

Reviewers:

Ivanov A.N., MD, DSc;

Prof. Puchinyan D.M., MD, DSc

category: orthopedics


title: Dose-effect relationship of ginger interposed moxibustion for allergic rhinitis: study protocol for a randomised, placebo-controlled and parallel clinical trial

abstract:
IntroductionAllergic rhinitis has a severe impact on patients life quality, and the incidence rate keeps increasing. Moxibustion is widely used for treating allergic rhinitis, and quantity is the basis of moxibustion efficacy. The purpose of this study is to evaluate the relationship between the different quantities of moxibustion and the efficacy of moxibustion in the treatment of allergic rhinitis. This study may be conductive to the standardization of moxibustion and furnish the mechanism of dose-effect relationship of moxibustion with data and new ideas.

Methods and analysisThis randomized, placebo-controlled clinical trial will include 33 patients with allergic rhinitis who will be randomly assigned into three groups in a 1:1:1 ratio: high-dose moxibustion group, low-dose moxibustion group and sham moxibustion control group. All groups will be treated once every other day, 20 days for one treatment course. And the patients will receive treatment for 2 courses with an interval of 2 days between courses. We will conduct a follow-up 30 days later after completion of treatments. The primary outcome measure is Total Nasal Symptom Score, carried out at baseline, 3, 6 and 10 weeks. Secondary outcome measure is Rhino Conjunctivitis Quality of Life Questionnaire, carried out at baseline, 6 and 10 weeks.

Ethics and disseminationThis trail has been approved by the IRB of Shanghai TCM-Integrated Hospital, Shanghai University of TCM. The results of the trial will be disseminated in peer-reviewed journals.

Trial registration numberChiCTR2100050373; Pre-results.

Strengths and limitations of this studyO_LIA randomised, placebo-controlled and parallel clinical trial will be conducted to test if ginger interposed moxibustion would have curative effect on allergic rhinitis and reveal the preliminary dose-effect relationship of moxibustion.
C_LIO_LIThis study will set high-dose moxibustion group and low-dose moxibustion group to test if more quantities of ginger interposed moxibustion would achieve better therapeutic effects on allergic rhinitis.
C_LIO_LIFurther study should be carried out to test if the curative effect of ginger interposed moxibustion would be positively correlated with the quantities.
C_LI

category: otolaryngology


title: Centers for Mendelian Genomics: A decade of facilitating gene discovery

abstract: Mendelian disease genomic research has undergone a massive transformation over the last decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration. Over the last 10 years, the NIH-supported Centers for Mendelian Genomics (CMGs) have played a major role in this research and clinical evolution. We highlight the cumulative gene discoveries facilitated by the program, biomedical research leveraged by the approach, and the larger impact on the research community. Mendelian genomic research extends beyond generating lists of gene-phenotype relationships, it includes developing tools, training the larger community to use these tools and approaches, and facilitating collaboration through data sharing. Thus, the CMGs have also focused on creating resources, tools, and training for the larger community to foster the understanding of genes and genome variation. The CMGs have participated in a wide range of data sharing activities, including deposition of all eligible CMG data into AnVIL (NHGRIs Genomic Data Science Analysis, Visualization, and Informatics Lab-Space), sharing candidate genes through Matchmaker Exchange (MME) and the CMG website, and sharing variants in Geno2MP and VariantMatcher. The research genomics output remains exploratory with evidence that thousands of disease genes, in which variant alleles contribute to disease, remain undiscovered, and many patients with rare disease remain molecularly undiagnosed. Strengthening communication between research and clinical labs, continued development and sharing of knowledge and tools required for solving previously unsolved cases, and improving access to data sets, including high-quality metadata, are all required to continue to advance Mendelian genomics research and continue to leverage the Human Genome Project for basic biomedical science research and clinical utility.


title: Real-world evaluation of AI driven COVID-19 triage for emergency admissions: External validation & operational assessment of lab-free and high-throughput screening solutions

abstract:
BackgroundUncertainty in patients COVID-19 status contributes to treatment delays, nosocomial transmission, and operational pressures in hospitals. However, typical turnaround times for batch-processed laboratory PCR tests remain 12-24h. Although rapid antigen lateral flow testing (LFD) has been widely adopted in UK emergency care settings, sensitivity is limited. We recently demonstrated that AI-driven triage (CURIAL-1.0) allows high-throughput COVID-19 screening using clinical data routinely available within 1h of arrival to hospital. Here we aimed to determine operational and safety improvements over standard-care, performing external/prospective evaluation across four NHS trusts with updated algorithms optimised for generalisability and speed, and deploying a novel lab-free screening pathway in a UK emergency department.

MethodsWe rationalised predictors in CURIAL-1.0 to optimise separately for generalisability and speed, developing CURIAL-Lab with vital signs and routine laboratory blood predictors (FBC, U&E, LFT, CRP) and CURIAL-Rapide with vital signs and FBC alone. Models were calibrated during training to 90% sensitivity and validated externally for unscheduled admissions to Portsmouth University Hospitals, University Hospitals Birmingham and Bedfordshire Hospitals NHS trusts, and prospectively during the second-wave of the UK COVID-19 epidemic at Oxford University Hospitals (OUH). Predictions were generated using first-performed blood tests and vital signs and compared against confirmatory viral nucleic acid testing. Next, we retrospectively evaluated a novel clinical pathway triaging patients to COVID-19-suspected clinical areas where either model prediction or LFD results were positive, comparing sensitivity and NPV with LFD results alone. Lastly, we deployed CURIAL-Rapide alongside an approved point-of-care FBC analyser (OLO; SightDiagnostics, Israel) to provide lab-free COVID-19 screening in the John Radcliffe Hospitals Emergency Department (Oxford, UK), as trust-approved service improvement. Our primary improvement outcome was time-to-result availability; secondary outcomes were sensitivity, specificity, PPV, and NPV assessed against a PCR reference standard. We compared CURIAL-Rapides performance with clinician triage and LFD results within standard-care.

Results72,223 patients met eligibility criteria across external and prospective validation sites. Model performance was consistent across trusts (CURIAL-Lab: AUROCs range 0.858-0.881; CURIAL-Rapide 0.836-0.854), with highest sensitivity achieved at Portsmouth University Hospitals (CURIAL-Lab:84.1% [95% Wilsons score CIs 82.5-85.7]; CURIAL-Rapide:83.5% [81.8 - 85.1]) at specificities of 71.3% (95% Wilsons score CIs: 70.9 - 71.8) and 63.6% (63.1 - 64.1). For 3,207 patients receiving LFD-triage within routine care for OUH admissions between December 23, 2021 and March 6, 2021, a combined clinical pathway increased sensitivity from 56.9% for LFDs alone (95% CI 51.7-62.0) to 88.2% with CURIAL-Rapide (84.4-91.1; AUROC 0.919) and 85.6% with CURIAL-Lab (81.6-88.9; AUROC 0.925). 520 patients were prospectively enrolled for point-of-care FBC analysis between February 18, 2021 and May 10, 2021, of whom 436 received confirmatory PCR testing within routine care and 10 (2.3%) tested positive. Median time from patient arrival to availability of CURIAL-Rapide result was 45:00 min (32-64), 16 minutes (26.3%) sooner than LFD results (61:00 min, 37-99; log-rank p<0.0001), and 6:52 h (90.2%) sooner than PCR results (7:37 h, 6:05-15:39; p<0.0001). Sensitivity and specificity of CURIAL-Rapide were 87.5% (52.9-97.8) and 85.4% (81.3-88.7), therefore achieving high NPV (99.7%, 98.2-99.9). CURIAL-Rapide correctly excluded COVID-19 for 58.5% of negative patients who were triaged by a clinician to  COVID-19-suspected (amber) areas.

ImpactCURIAL-Lab & CURIAL-Rapide are generalisable, high-throughput screening tests for COVID-19, rapidly excluding the illness with higher NPV than LFDs. CURIAL-Rapide can be used in combination with near-patient FBC analysis for rapid, lab-free screening, and may reduce the number of COVID-19-negative patients triaged to enhanced precautions ( amber) clinical areas.

category: health informatics


title: Identifying Online Advice-Seekers for Recovering from Opioid Use Disorder

abstract:
BackgroundOnline communities can provide social support for those recovering from opioid use disorder. However, advice-seekers on these platforms risk exposure to uncurated medical advice, potentially harming their health or recovery efforts. The objective of this analysis is to combine text annotation, social network analysis, and statistical modeling to identify advice-seekers on online social media for buprenorphine-naloxone use and study their characteristics.

MethodsWe collected 5,258 posts and their comments from Reddit between 2014 and 2019. Among 202 posts which met our inclusion criteria, we annotated each post to determine which were advice-seeking (n=137) and not advice-seeking (n=65). We also annotated each posting users medication use stage and quantified their connectedness using social network analysis. In order to analyze the relationship between advice-seeking with a users social connectivity and medication use stage, we constructed four models which varied in explanatory variables.

ResultsThe stepwise model (containing "total degree" (P=0.002), "using: inducting/tapering" (P<0.001), and "using: other" (P=0.01) as significant explanatory variables) outperformed all other models. We found that users with fewer connections and who are currently using buprenorphine-naloxone are more likely to seek advice than users who are well-connected and no longer using the medication, respectively. Importantly, advice-seeking behavior is most accurately predicted using a combination of network characteristics and medication use status, rather than either factor alone.

ConclusionsOur findings provide insights for the clinical care of people recovering from opioid use disorder and the nature of online medical advice-seeking overall. Clinicians should be especially attentive (e.g., through frequent follow-up) to patients who are inducting or tapering buprenorphine-naloxone or signal limited social support.

category: addiction medicine


title: Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination

abstract:
What is already known about this topic?The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July--December 2021.

What is added by this report?Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July--December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage.

What are the implications for public health practice?Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen.

category: epidemiology


title: You aren't what you eat, you become what you eat

abstract: Obesity (and the consequent obesity epidemic) is a complex, adaptive process, taking place over a time span of many years. Energy intake is recognized as a potentially important driver of obesity, especially in the context of an identifiable energy imbalance which, it is surmised, must lead to weight gain. Similarly, energy expenditure must play an important role. However, both show an enormous degree of individual variation. Therefore, measuring them is an exceedingly difficult task, especially in the context of large populations and long time periods. It has been argued that population-level observed weight gain can be traced back to very small daily energy imbalances while, at the same time, positing that a much larger maintenance energy gap is responsible for maintaining the energy requirements of the increased weight population. In this paper we examine the relation between BMI and energy intake as functions of age. The convexity of the BMI curves as a function of age and gender demonstrate the enhanced obesity risk apparent in young adults and women, and imply that no settling points exist at the population level. Consistent with other studies, overall weight increases are consistent with a very small daily energy imbalance, about 7 cal. Consumption as a function of age shows a small, steady, linear decrease of about 8 cal per year, and can be associated with a maximal energy excess/deficit of about 250cal for the youngest and oldest age groups. By examining weight differences between age groups as a function of age, we argue that this excess/deficit is an important motor for the observed weight differences, and argue that the apparent energy imbalance of 250 cal, due to excess consumption, leads to an effective imbalance of only 7 cal due to the existence of various physiological and behavioral mechanisms that enhance weight homeostasis and effectively reduce the energy excess from 250 cal to 7 cal. We discuss several possibilities for such mechanisms.


title: SIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study

abstract:
BackgroundSIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) from non-metastatic intracranial ependymoma in children aged 3 to 21 years, treated with a staged management strategy. Chemotherapy efficacy in ependymoma is debated and therefore the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide and cyclophosphamide (VEC) was an additional primary outcome. We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers.

Methods74 participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation and 1q status were evaluated, alongside hTERT, ReLA, Tenascin-C, H3K27me3 and pAKT expression.

ResultsFive- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.003, HR=2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (p=0.005, HR=2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (p=0.003, HR=2.70, 95%CI 1.49-6.10 and p=0.014, HR=5.8, 95%CI 1.2-28 respectively) and H3K27me3 loss with worse OS (p=0.003, HR=4.6, 95%CI 1.5-13.2). DNA methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding a prespecified 45% RR.

ConclusionsRR of STR to VEC exceeded the pre-specified criterion for efficacy. However, cases of inaccurate treatment stratification highlighted the need for rapid central review. Prognostic associations for 1q gain, H3K27me3 and hTERT were confirmed.

category: pediatrics


title: LED transillumination of the chest and abdomen in the diagnosis of neonatal conditions

abstract:
Air leak syndromes, such as pneumothorax and pneumoperitoneum, are commonly diagnosed in Neonatal Intensive Care Units. However, this finding is usually detected with radiographic studies when the neonate is in poor condition. LED transillumination is an alternative method that allows a fast, inexpensive, and non-invasive diagnosis. We aimed to evaluate the clinical utility of LED transillumination in neonates by comparing the results to chest and abdomen radiograph as reference test.

Methodologydiagnostic and prospective study that included 56 neonates. We used a simple and inexpensive handcrafted LED transilluminator to evaluate the chest and abdomen of patients, blind to the final diagnosis. The findings were compared to the radiographs.

Resultsthe study presented 3 true positive pneumothorax cases (sensibility 100%, 95%CI 29.24-100; specificity 100%, 95%CI 93.28-100), 1 true positive pneumoperitoneum case (sensibility 100%, 95%CI 2.50-100; specificity 100%, 95%CI 93.51-100), 10 true positive and 5 false negatives cases of gastric dilation (sensibility 66.67%, 95%CI 38.38-88.18; specificity 100%, 95%CI 91.19-100; negative likelihood ratio 0.33, 95%CI 0.16-0.68) and 4 true positive cases of dilation of bowel loops (sensibility 100%, 95%CI 39.76-100; specificity 100%, 95%CI 93.02-100).

DiscussionLED transillumination is a safe, inexpensive, and easy-to-use clinical tool that may be employed to promote early intervention during severe cases of air leak syndrome that require immediate action, especially in low-income and rural areas. Further research with larger sample sizes is required to properly define the efficacy and usefulness of LED transillumination in routine use.


title: Prevalence, Patterns, Clinico-social and Behavioural factors associated with the Consumption of Sugar Sweetened Beverages among Undergraduate Medical Students of Central India

abstract:
BackgroundExcessive consumption of Sugar Sweetened Beverages (SSBs) in adolescents has become a global issue. As its link to obesity and non-communicable diseases is clear, it is imperative to understand SSB consumption behaviours in the future healthcare professionals.

ObjectiveTo document the prevalence, patterns and clinic-social and behavioural factors predicting high intake of SSBs among medical students.

MethodsThis cross-sectional study was conducted using a self-reported, web-based, questionnaire. All the students and interns who were part of a publicly funded premiere teaching hospital during October and November 2019 were included. The semi-structured questionnaire enquired regarding socio-demographic, clinical details, amount, behavioural patterns and money spent in connection with SSB consumption. Data were analysed using IBM SPSS version 24.

ResultsThe mean (SD) age of participants was 19.3 (1.6) years, 71.7% being males. The current prevalence of SSB consumption was 90.5 %. Also, 49.9% and 29.1% participants preferred soft drinks and sweetened fruit juice respectively. Multivariable analysis showed that male gender (aOR 1.83, 95% CI 1.03-3.25), current alcohol consumption (aOR 4.09, 95% CI 1.25-13.42), and recent (last week) consumption of a SSB predicted high intake of SSBs (aOR 7.36, 95% CI 3.41-15.87) whereas, preference of energy/sports category of drinks predicted low intake of SSBs (aOR 0.10, 95% CI 0.02-0.47).

ConclusionThe consumption of SSBs among medical students was high. Targeted health education and behaviour change interventions should be provided to males, alcohol users and frequent consumers.

category: nutrition


title: COVID-19 OUTCOMES IN PREGNANCY: A REVIEW OF 275 SCREENED STUDIES

abstract: In December 2019, a novel strain of severe acute respiratory syndrome (SARS-CoV-2), was declared as a cause of respiratory illness, called coronavirus 2019 (COVID-19), characterized by fever and cough. In diagnostic imaging, the afflicted population showed pathognomonic findings of pneumonia. What started out as an epidemic in China, rapidly spread across geographical locations with a significant daily increase in the number of affected cases. According to the World Health Organization (WHO) reports, the range of worldwide mortality is 3 to 4%. Maternal adaptations and immunological changes predispose pregnant women to a prolonged and severe form of pneumonia, which results in higher rates of maternal, fetal, and neonatal morbidity and mortality. There is limited data about the consequences of COVID-19 in pregnancy, thereby limiting the prevention, counseling, and management of these patients. The objective of this literature review is to explore pregnancy and perinatal outcomes of COVID-19, complications, morbidity, and mortality in this sub-population. We conducted a literature review pertaining to COVID-19 and pregnancy in databases such as: PubMed, Google Scholar, and Science Direct. The studies we chose to focus on were systematic reviews, meta-analysis, case series, and case reports. Twenty four articles were reviewed regarding COVID-19 and pregnancy, complications and their outcomes. Due to immunological changes during pregnancy as evidenced by the flaring of auto-immune diseases; pregnant women may be at an increased risk for infection. Women (19.7%) who had underlying comorbidities such as gestational DM, HTN, hypothyroidism, and autoimmune disease, COPD, or HBV infection were considered high risk. The most common maternal outcomes were premature rupture of membranes (PROM) and pre-eclampsia. Asthma was the most common comorbidity associated with maternal mortality. The most common neonatal complications were fetal distress leading to NICU admissions and preterm birth <37 weeks. The most common laboratory changes were elevated CRP and lymphocytopenia. Most patients underwent C-section due to their underlying comorbidities. Pregnant and lactating women did not shed viral particles through their vaginal mucus and milk, as evidenced by negative nucleic-acid tests of these secretions. Neonatal infections as demonstrated by positive RT-PCR were rare, but direct evidence supporting intrauterine transmission was not confirmed. Direct evidence indicating vertical transmission of COVID-19 is not available, but risk for transmission cannot be ruled out. Pregnant women should be closely monitored due to increased risk of adverse outcomes.

category: obstetrics and gynecology


title: Short Term Reduction in the Odds of Testing Positive for SARS-CoV-2; a Comparison Between Two Doses and Three doses of the BNT162b2 Vaccine

abstract: With the evidence of waning immunity of the BNT162b2 vaccine, a national third dose vaccination campaign was initiated in Israel during August 2021; other countries have announced their intention to administer a booster shot as well. Leveraging data from Maccabi Healthcare Services, we conducted a preliminary retrospective study aimed at evaluating initial short-term effectiveness of a three dose versus a two dose regimen against infection due to the Delta variant of SARS-CoV-2, using two complementary approaches; a test-negative design and a matched case-control design. We found that 7-13 days after the booster shot there is a 48-68% reduction in the odds of testing positive for SARS-CoV-2 infection and that 14-20 days after the booster the marginal effectiveness increases to 70-84%. Further studies are needed to determine the duration of protection conferred by the third dose and its effect on severe disease.

category: infectious diseases


title: The emergence of SARS-CoV-2 variants of concern is driven by acceleration of the evolutionary rate

abstract: The ongoing SARS-CoV-2 pandemic has seen an unprecedented amount of rapidly generated genome data. These data have revealed the emergence of lineages with mutations associated to transmissibility and antigenicity, known as variants of concern (VOCs). A striking aspect of VOCs is that many of them involve an unusually large number of defining mutations. Current phylogenetic estimates of the evolutionary rate of SARS-CoV-2 suggest that its genome accrues around 2 mutations per month. However, VOCs can have around 15 defining mutations and it is hypothesised that they emerged over the course of a few months, implying that they must have evolved faster for a period of time. We analysed genome sequence data from the GISAID database to assess whether the emergence of VOCs can be attributed to changes in the evolutionary rate of the virus and whether this pattern can be detected at a phylogenetic level using genome data. We fit a range of molecular clock models and assessed their statistical fit. Our analyses indicate that the emergence of VOCs is driven by an episodic increase in the evolutionary rate of around 4-fold the background phylogenetic rate estimate that may have lasted several weeks or months. These results underscore the importance of monitoring the molecular evolution of the virus as a means of understanding the circumstances under which VOCs may emerge.