title: Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States

abstract:
ImportanceUnderstanding the severity of post-vaccination COVID-19 breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations.

ObjectiveEstimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection.

Design, setting, and participantsThe Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration consists of four US longitudinal cohorts from integrated health systems and academic centers. Adults ([≥]18 years old), in-care, fully vaccinated by June 30, 2021 with HIV, and matched PWoH (on date fully vaccinated, age group, race/ethnicity, and sex) were the source population. Those who experienced a post-vaccination SARS-CoV-2 breakthrough infection were eligible. Severe COVID-19 breakthrough illness was defined as hospitalization due to COVID-19. Discrete time proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals ([,]) of severe breakthrough illness by HIV status adjusting for demographics, COVID-19 vaccine type, and clinical factors. The proportion of patients requiring mechanical ventilation or died was compared by HIV status.

ExposureHIV infection

OutcomeSevere COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis.

ResultsAmong 1,241 PWH and 2,408 PWoH with breakthrough infections, the cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs. 6.7%, respectively, risk difference=-0.67% [-2.58%, 1.23%]). The risk of severe breakthrough illness was 59% higher in PWH with CD4 counts <350 cells/mm3 compared with PWoH (aHR=1.59 [0.99, 2.46]). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 count increased the risk of severe breakthrough illness, while previous COVID-19 reduced the risk. Among all patients, 10% were mechanically ventilated and 8% died, with no difference by HIV status.

Conclusions and RelevanceThe risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. However, PWH with moderate and severe immune suppression had a higher risk of severe breakthrough infection. Recommendations for additional vaccine doses and risk-reduction strategies for PWH with moderate immune suppression may be warranted.

Key PointsO_ST_ABSQuestionC_ST_ABSIn 2021, among fully vaccinated people with COVID-19 breakthrough illness, was the risk of severe illness higher in people with HIV (PWH) compared to people without HIV (PWoH)?

FindingsPWH with <350 cells/mm3 have a 59% increased risk of severe breakthrough illness compared to PWoH.

MeaningVaccinations effectively reduce the risk of severe COVID-19 infection in both PWH and PWoH; however, PWH having a CD4 count <350 cells/mm3 are at higher risk of severe breakthrough infection compared to PWoH. PWH with moderate immune suppression should be considered for additional vaccine dosages and other risk-reduction measures.


title: Universal two-dimensional labeled probe-mediated melting curve analysis based on multiplex PCR for rapid typing of plasmodium in a single closed tube

abstract: Nowadays, malaria is still one of the major public health problems which commonly caused by four plasmodium species, especially in the epidemic of COVID-19 harboring similar symptoms of fever or fatigue, which easily result in misdiagnosis. The disadvantages of previous traditional detection methods, such as time-consuming, costly, complicated operation, strong professionalism, indistinguishable typing and so on, lead to the dilemma of difficulty to meet the clinical requirements of rapid, easy and accurate typing of common plasmodiums. Herein, we developed and maximally optimized a universal two-dimensional labelled probe-mediated melting curve analysis (UP-MCA) assay based on multiplex PCR for rapid and accurate typing of five plasmodiums, including novel human plasmodium, Plasmodium knowlesi (Pk), in a single closed tube following genome extraction. The assay showed the limit of detection (LOD) of 10 copies per reaction and can accurately distinguish plasmodium species from intra-plasmodium and other pathogens. In addition, we also proposed and verified different methods of fluorescence-quenching and two dimensional labelled tag for probes that are suitable for UP-MCA assay. Furthermore, its clinical performance was evaluated by 184 samples and showed sensitivity of 100% (164/164) and specificity of 100% (20/20) at 99% confidence interval, respectively, with the microscopy method as gold standard. Taken together, the UP-MCA system showed excellent sensitivity, specificity and accuracy for genotyping of plasmodium, and it meets the requirements of rapidity and convenience for plasmodium detection in clinical routine and has great potential for clinical translation.

category: infectious diseases


title: Linking Genotype to Phenotype: Further Exploration of Mutations in SARS-CoV-2 Associated with Mild or Severe Outcomes

abstract:
We previously interrogated the relationship between SARS-CoV-2 genetic mutations and associated patient outcomes using publicly available data downloaded from GISAID in October 2020 [1]. Using high-level patient data included in some GISAID submissions, we were able to aggregate patient status values and differentiate between severe and mild COVID-19 outcomes. In our previous publication, we utilized a logistic regression model with an L1 penalty (Lasso regularization) and found several statistically significant associations between genetic mutations and COVID-19 severity. In this work, we explore the applicability of our October 2020 findings to a more current phase of the COVID-19 pandemic.

Here we first test our previous models on newer GISAID data downloaded in October 2021 to evaluate the classification ability of each model on expanded datasets. The October 2021 dataset (n=53,787 samples) is approximately 15 times larger than our October 2020 dataset (n=3,637 samples). We show limitations in using a supervised learning approach and a need for expansion of the feature sets based on progression of the COVID-19 pandemic, such as vaccination status. We then re-train on the newer GISAID data and compare the performance of our two logistic regression models. Based on accuracy and Area Under the Curve (AUC) metrics, we find that the AUC of the re-trained October 2021 model is modestly decreased as compared to the October 2020 model. These results are consistent with the increased emergence of multiple mutations, each with a potentially smaller impact on COVID-19 patient outcomes. Bioinformatics scripts used in this study are available at https://github.com/JPEO-CBRND/opendata-variant-analysis. As described in Voss et al. 2021, machine learning scripts are available at https://github.com/Digital-Biobank/covid_variant_severity.


title: Can We Really Trust the Findings of the COVID-19 Research? Quality Assessment of Randomized Controlled Trials Published on COVID-19

abstract:
ObjectiveTo evaluate the quality of randomized controlled trials (RCTs) published on Coronavirus Disease-19 (COVID-19) and to investigate the reasons behind compromising the quality, if found.

MethodsA systematic literature search was performed in PubMed, Google Scholar, and Cochrane CENTRAL to identify the Randomized Controlled Trails published on Coronavirus Disease-19 between 1st Dec 2019 to 31st Aug 2021. Research articles met with study criteria were included in the study. Assessment of quality of randomized controlled trials was done using modified Jadad scale.

Results21,259 records of randomized controlled trials were identified through database searching, out of which 90 randomized controlled trials were included in the study and, 34 (37.8%) were of high-quality, 46 (51.1%) were of moderate quality, and 10 (11.1 %) were of low-quality studies. There were 40 (44.4%), 38 (42.2%), and 12 (13.3%) randomized controlled trials published in the early, middle, and late terms with Jadad score 5.12{+/-}1.67, 5.34{+/-}1.32, and 5.68{+/-}1.50 respectively (P=0.52). When comparing the blinding status, appropriate blinding, and methods to evaluate adverse events in randomized controlled trials with modified Jadad score, a significant difference was observed (P<0.001). A significant moderate positive correlation was found between the impact factor of the journal and the modified Jadad scale score (R2= 0.48, P<0.001).

ConclusionFindings from our study indicate that accelerated publication of Coronavirus Disease-19 researches along with the fast-track review process has resulted in lowering study quality scores. With the emergence of stronger evidence, Coronavirus Disease-19 clinical studies with lower methodological quality should be revisited.

Impacts on practiceO_LIThere have been numerous sacrifices and tragedies in the clinical response to covid-19. Revising the quality of randomized controlled trials published on COVID-19 as we enter the third wave of the pandemic and beyond, will improve the evidence-based practice of medications for clinical pharmacy services.
C_LIO_LICOVID-19 Patients will benefit from evidence-based pharmaceutical care through reduced drug-related problems.
C_LI


title: Efficacy and Safety of Fixed Combination of Hydroxychloroquine with Azithromycin Versus Hydroxychloroquine and Placebo in Patients with Mild COVID-19: Randomized, double blind, Placebo controlled trial

abstract:
To determine the efficacy and safety of fixed combination of hydroxychloroquine/azithromycin (HCQ+AZT) compared to hydroxychloroquine (HCQ) alone or placebo in mild COVID-19 outpatients to avoid hospitalization.

Materials and methodsThis randomized, parallel, double-blind clinical trial included male and female patients aged 18 and 76 years non COVID vaccinated, who were diagnosed with mild COVID-19 infection. All patients underwent liver and kidney profile test, as well as a health questionnaire and clinical revision to document that they did not have uncontrolled comorbidities. They were randomly assigned to one of the three treatment arms: 1) hydroxychloroquine with azithromycin 200 mg/250 mg every 12 hours for five days followed by hydroxychloroquine 200 mg every 12 hours for 5 days; 2) hydroxychloroquine 200 mg every 12 hours for ten days; or 3) placebo every 12 hours for ten days. The primary outcome of the study was hospitalization, while the secondary outcomes were disease progression, pneumonia, use of supplemental oxygen, and adverse events. This study was registered in clinicaltrials.gov with the NCT number of 04964583.

ResultsA total of 92 participants were randomized. Of whom, 30 received HCQ+AZT, 31 received HCQ, and 31 received placebo. The median age was 37 years, 27.2% of the participants had comorbidities, and the global incidence of hospitalization was 2.2%. The incidence of hospitalization was 6.7% (2/30) in the HCQ+AZT group compared to the HCQ or placebo groups, in which there were no hospitalizations. Progression of disease was higher in the HCQ group [RR=3.25 (95% CI, 1.19-8.87)] compared with placebo group. There was no statistical difference between the HCQ+AZT group and the placebo group in progression of disease. The incidence of pneumonia was 30% in the HCQ+AZT group, 32.2% in the HCQ group, and 9.6% in the placebo group (HCQ + AZT vs Placebo; p=0.06). There was a significant risk of pneumonia versus placebo only in the HCQ group [RR=3.33 (95% CI, 1.01-10.9)]. Supplemental oxygen was required by 20% (6/30) of the patients in the HCQ+AZT group, 6.4 (2/31) of the patients in the HCQ group, and 3.2% (1/31) of the patients in the placebo group,[(HCQ + AZT vs Placebo; p=0.100), (HCQ vs Placebo, p=0.610)]. There was no statistical difference between groups for negative test (PCR) on day 11. The most frequent adverse events were gastrointestinal symptoms. No lengthening of the QT interval was observed in patients receiving HCQ+AZT or HCQ.

ConclusionThe use of HCQ+AZT does not decrease the risk of hospitalization in patients with mild COVID-19. The use of HCQ increases the risk of progression and pneumonia.


title: Seroprevalence, correlates and kinetics of SARS-CoV-2 Nucleocapsid IgG antibody in healthcare workers at a tertiary hospital: a prevaccine census study

abstract:
BackgroundHealthcare workers are perceived to be a high-risk group for acquiring SAR-CoV-2 infection, and more so in countries where COVID-19 vaccination uptake is low. Serosurveillance may best determine the true extent of SARS-CoV-2 infection since most infected HCWs may be asymptomatic or present with only mild symptoms. Over time, determining the true extent of SARS-CoV-2 infection could inform hospital management and staff whether the preventive measures instituted are effective and valuable in developing targeted solutions.

MethodsThis was a census survey study conducted at the Aga Khan University Hospital, Nairobi, between November 2020 and February 2021 before the implementation of the COVID-19 vaccination. The SARS-CoV-2 nucleocapsid IgG test was performed using a chemiluminescent assay.

ResultsOne thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted value (for assay sensitivity of 86%) was 21.4% (95% CI; 19.2-23.7). The HCW groups with higher prevalence included pharmacy (25.6%), outreach (24%), hospital-based nursing (22.2%) and catering staff (22.6%). Independent predictors of a positive IgG result included prior COVID-19 like symptoms, odds ratio (OR) 1.9 [95% confidence interval (CI) 1.3-2.9, p=0.002], and a prior positive SARS-CoV-2 PCR result OR 11.0 (CI: 7.2-18.0, p<0.001). Age, sex, comorbidities or working in a COVID-19 designated area were not associated with seropositivity. The odds of testing positive for IgG after a positive PCR test were lowest if the antibody test was performed more than 2 months later; OR 0.7 (CI: 0.48-0.95, p= 0.025).

ConclusionsThe prevalence of anti-SARS-CoV-2 nucleocapsid IgG among HCWs was lower than in the general population. Staff working in clinical areas were not at increased risk when compared to staff working in non-clinical areas.


title: Dynamics of anti-Spike IgG antibody titer after the third BNT162b2 COVID-19 vaccination in the Japanese health care workers

abstract:
IntroductionMany countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity is insufficient. This study aimed to evaluate anti-spike immunoglobulin G (IgG) titers in the health care workers after the third BNT162b2 vaccination.

MethodsDynamics of anti-spike IgG titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations between anti-spike IgG titer, baseline characteristics, and adverse reactions were also evaluated.

ResultsThe geometric mean titer of anti-spike IgG one month after the third vaccination was 17400 AU/ml, which increased to approximately 30 times immediately before the third vaccination and approximately twice that one month after the second vaccination. In addition, participants with anti-spike IgG titers less than 10000 AU/ml after the second vaccination tended to have higher increases in ant-spike IgG titers before and after the third vaccination.

The decline rate of anti-spike IgG was significantly slower after the third vaccination as 35.7% than that after the second vaccination as 59.1%. The anti-spike IgG titer was significantly negatively associated with age (r = -0.31). Participants who had a headache at the vaccination showed significantly higher anti-spike IgG titer than those without a headache.

ConclusionsThe anti-spike IgG induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the anti-spike IgG with a slower decline rate.


title: Rapid displacement of SARS-CoV-2 variants within Japan correlates with cycle threshold values on routine RT-PCR testing

abstract:
BackgroundThe rapid spread of SARS-CoV-2 worldwide has led to the emergence of new variants due to the presence of mutations that alter viral characteristics, but there have been few studies on trends in viral lineages in Japan, an island country. We hypothesized that changes in cycle threshold (Ct) values on reverse transcription polymerase chain reaction (RT-PCR) reflect the prevalent variants during a given period.

MethodsWe performed next-generation sequencing of positive samples to identify the viral lineages in Japan in 2021 and compared variant prevalence with the average Ct values on routine RT-PCR using 4 primer sets.

ResultsBased on 3 sequencing runs, the highly transmissible Alpha variant, which prevailed over other lineages, such as R.1, from April 2021, was dominated by the even stronger Delta variant between July and August 2021 in Japan. The decrease in our routine RT-PCR Ct values with 4 primer sets correlated with these fluctuations in lineage prevalence over time.

ConclusionsWe confirmed that our RT-PCR protocol reflects the trends in SARS-CoV-2 variant prevalence over time regardless of sequence mutation. This may aid in the tracking of new variants in the population.


title: A needle in a haystack: metagenomic DNA sequencing to quantify Mycobacterium tuberculosis DNA and diagnose tuberculosis

abstract:
BackgroundTuberculosis (TB) remains a significant cause of mortality worldwide. Metagenomic next-generation sequencing has the potential to reveal biomarkers of active disease, identify coinfection, and improve detection for sputum-scarce or culture-negative cases.

MethodsWe conducted a large-scale comparative study of 427 plasma, urine, and oral swab samples from 334 individuals from TB endemic and non-endemic regions to evaluate the utility of a shotgun metagenomic DNA sequencing assay for tuberculosis diagnosis.

FindingsWe found that the choice of a negative, non-TB control cohort had a strong impact on the measured performance of the diagnostic test: the use of a control patient cohort from a nonendemic region led to a test with nearly 100% specificity and sensitivity, whereas controls from TB endemic regions exhibited a high background of nontuberculous mycobacterial DNA, limiting the diagnostic performance of the test. Using mathematical modeling and quantitative comparisons to matched qPCR data, we found that the burden of Mycobacterium tuberculosis DNA constitutes a very small fraction (0.04 or less) of the total abundance of DNA originating from mycobacteria in samples from TB endemic regions.

InterpretationOur findings suggest that the utility of a metagenomic sequencing assay for tuberculosis diagnostics is limited by the low burden of M. tuberculosis in extrapulmonary sites and an overwhelming biological background of nontuberculous mycobacterial DNA.

FundingThis work was supported by the National Institutes of Health, the Rainin Foundation, the National Science Foundation, and the Bill and Melinda Gates Foundation.


title: Pathogen detection and characterization from throat swabs using unbiased metatranscriptomic analyses

abstract:
ObjectiveInfectious diseases are common but are not easily or readily diagnosed with current methodologies. This problem is further exacerbated with the constant presence of mutated, emerging, and novel pathogens. One of the most common sites of infection by many pathogens is the human throat. Yet, there is no universal diagnostic test that can distinguish these pathogens. Metatranscriptomic (MT) analysis of the throat represents an important and novel development in infectious disease detection and characterization, as it is able to identify all pathogens in a fully unbiased approach.

DesignTo test the utility of an MT approach to pathogen detection, throat samples were collected from participants before, during, and after an acute sickness.

ResultsClear sickness-associated shifts in pathogenic microorganisms are detected in the participants along with important insights into microbial functions and antimicrobial resistance genes.

ConclusionsMT analysis of the throat represents an effective method for the unbiased identification and characterization of pathogens. Since MT data include all microorganisms in the sample, this approach should allow for not only the identification of pathogens, but also an understanding of the effects of the resident throat microbiome in the context of human health and disease.


title: Early detection of patients with narcotic use disorder using a modified MEDD score based on the analysis of real-world prescription patterns

abstract:
BackgroundAddiction to prescription narcotics is a global issue, and detection of individuals with a narcotic use disorder (NUD) at an early stage can help prevent narcotics misuse and abuse. We developed a novel index to detect early NUD based on a real-world prescription pattern analysis in a large hospital.

MethodsWe analyzed narcotic prescriptions of 221 887 patients prescribed by 8737 doctors from July 2000 to June 2018. For the early detection of patients who could potentially progress to developing NUD after a long history of narcotic prescription, a weighted morphine equivalent daily dose (wt-MEDD) score was developed based on the number of prescription dates on which the actual MEDD was higher than the intended MEDD. Performance of the wt-MEDD scoring system in detecting patients diagnosed with NUD by doctors was compared with that of other NUD high risk indexes such as the MEDD scoring system, number of days on prescribed narcotics, the frequency/duration of prescription, narcotics prescription across multiple doctors, and the number of early refills of narcotics.

ResultsA wt-MEDD score cut-off value of 10.5 could detect all outliers, as well as patients diagnosed with NUD with 100% sensitivity and 99.6% specificity. The wt-MEDD score showed the highest sensitivity and specificity in identifying NUD among all indexes. Further, combining the wt-MEDD score with other NUD high risk indexes improved the prediction performance.

ConclusionWe developed a novel index to distinguish patients with vulnerable use patterns of narcotics. The wt-MEDD score showed excellent performance in detecting early NUD.

category: addiction medicine


title: Comparative and Integrated Analysis of Plasma Extracellular Vesicles Isolations Methods in Healthy Volunteers and Patients Following Myocardial Infarction

abstract: Plasma extracellular vesicle (EV) number and composition are altered following myocardial infarction (MI), but to properly understand the significance of these changes it is essential to appreciate how the different isolation methods affect EV characteristics, proteome and sphingolipidome. Here, we compared plasma EV isolated from platelet-poor plasma from four healthy donors and six MI patients at presentation and 1-month post-MI using ultracentrifugation, polyethylene glycol precipitation, acoustic trapping, size-exclusion chromatography (SEC) or immunoaffinity capture. The isolated EV were evaluated by Nanoparticle Tracking Analysis, Western blot, transmission electron microscopy, an EV-protein array, untargeted proteomics (LC-MS/MS) and targeted sphingolipidomics (LC-MS/MS). The application of the five different plasma EV isolation methods in patients presenting with MI showed that the choice of plasma EV isolation method influenced the ability to distinguish elevations in plasma EV concentration following MI, enrichment of EV-cargo (EV-proteins and sphingolipidomics) and associations with the size of the infarct determined by cardiac magnetic resonance imaging 6 months-post-MI. Despite the selection bias imposed by each method, a core of EV associated proteins and lipids was detectable using all approaches. However, this study highlights how each isolation method comes with its own idiosyncrasies and makes the comparison of data acquired by different techniques in clinical studies problematic.

category: cardiovascular medicine


title: Assessment of magnitude and spectrum of cardiovascular disease admissions and outcomes in Saint Paul Hospital Millennium Medical College, Addis Ababa: A retrospective study

abstract:
BackgroundCardiovascular diseases remain the leading cause of death in the world and approximately 80% of all cardiovascular-related deaths occur in low and middle income countries including Ethiopia.

MethodsThe aim of the study was to assess the magnitude and spectrum of cardiovascular admissions and its outcomes among medical patients admitted to both Medical Ward and ICU of St. Paul Teaching Hospital from 1st of Jan 2020 to 1st of Jan 2021.

ResultsOut of 1,165 annual medical admissions, the prevalence of cardiovascular diseases(CVD) was 30.3%. About 60%(212) of patients had advanced congestive heart failure of diverse causes. Hypertensive heart disease (HHD) was the next predominant diagnosis (41%), and also the leading cause of cardiac diseases followed by rheumatic valvular heart disease(RVHD) (18%) and Ischemic heart disease (IHD) (12.2%), respectively. Yong age, rural residence and female sex were associated with RVHD(p=0.001). Stroke also accounted for 20% of CVD admission (hemorrhagic stroke-17% Vs Ischemic stroke-83%). Hypertension was the predominate risk factor for CVD and present in 46.7%(168) of patients. The mean hospital stay was 12days and in hospital mortality rate was 24.3%, septic shock being the commonest immediate cause of death followed by fatal arrhythmia, brain herniation, and massive PTE.

ConclusionCardiovascular diseases were highly prevalent in the study area causing significant morbidity and mortality. Therefore, Comprehensive approach is needed to timely screen for risk reduction, delay or prevent diseases development and subsequent complications.


title: Predictors of Developmental Defects of Enamel in the Primary Maxillary Central Incisors using Bayesian Model Selection

abstract: Localized non-inheritable developmental defects of tooth enamel (DDE) are classified as enamel hypoplasia (EH), opacity (OP) and post-eruptive breakdown (PEB) using the Enamel Defects Index. To better understand the etiology of DDE, and in particular possibly modifiable variables, we assessed the linkages amongst exposome variables during the specific time duration of the development of the DDE. In general, the human primary central maxillary incisor teeth develop between 13-14 weeks in utero and 3-4 weeks postpartum of a full-term delivery, followed by tooth eruption at about 1 year of age. We utilized existing datasets of mother and child dyad data that encompassed 12 weeks gestation through birth and early infancy, and child DDE outcomes from digital images of the erupted primary maxillary central incisor teeth. We applied a Bayesian modeling paradigm to assess the important predictors of EH, OP, and PEB. The results of Gibbs variable selection showed a key set of predictors: mothers pre-pregnancy body mass index (BMI); maternal serum levels of calcium and phosphorus at gestational week 28; childs gestational age; and both mothers and childs functional vitamin D deficiency (FVDD). In this sample of healthy mothers and children, significant predictors for OP included the child having a gestational period > 36 weeks and FVDD at birth, and for PEB included a mothers pre-pregnancy BMI < 21.5 and higher serum phosphorus level at week 28.

category: dentistry and oral medicine


title: Systematic comparison of Mendelian randomization studies and randomized controlled trials using electronic databases

abstract: Mendelian Randomization (MR) uses genetic instrumental variables to make causal inferences. Whilst sometimes referred to as "natures randomized trial", it has distinct assumptions that make comparisons between the results of MR studies with those of actual randomized controlled trials (RCTs) invaluable. To scope the potential for (semi-)-automated triangulation of MR and RCT evidence, we mined ClinicalTrials.Gov, PubMed and EpigraphDB databases and carried out a series of 26 manual literature comparisons among 54 MR and 77 RCT publications. We found that only 11% of completed RCTs identified in ClinicalTrials.Gov submitted their results to the database. Similarly low coverage was revealed for Semantic Medline (SemMedDB) semantic triples derived from MR and RCT publications -25% and 12%, respectively. Among intervention types that can be mimicked by MR, only trials of pharmaceutical interventions could be automatically matched to MR results due to insufficient annotation with MeSH ontology. A manual survey of the literature highlighted the potential for triangulation across a number of exposure/outcome pairs if these challenges can be addressed. We conclude that careful triangulation of MR with RCT evidence should involve consideration of similarity of phenotypes across study designs, intervention intensity and duration, study population demography and health status, comparator group, intervention goal and quality of evidence.

category: epidemiology


title: COVID-19 vaccine coverage among immigrants and refugees in Alberta: a population-based cross-sectional study

abstract:
IntroductionStudies have shown that immigrants have lower vaccination rates than the Canadian-born population. We sought to assess COVID-19 vaccine coverage and factors associated with uptake among foreign-born immigrants relative to the non-immigrant population in Alberta, Canada.

MethodsIn this cross-sectional study, we analyzed population-based linked administrative health data from Alberta to examine vaccine coverage for 3,931,698 Albertans, of which 731,217 were immigrants. We calculated COVID-19 vaccination coverage as the proportion of eligible Albertans with a record of receiving at least one dose of a COVID-19 vaccine as of November 29, 2021. We used multivariable logistic regression to examine the association of vaccine coverage with migration status (immigrants: four categories based on time since migration and non-immigrants) adjusting for socio-demographic variables.

ResultsOverall, COVID-19 vaccination coverage was higher among immigrants (78.2%; 95% CI: 78.1%-78.3%) compared to non-immigrants (76.0%; 95% CI: 75.9%-76.0%). Coverage among immigrants differed by continent of origin, with North America, Oceania, and Europe having the lowest coverage. Although vaccine coverage was relatively uniform across neighborhood income quintiles for immigrants, immigrants living in rural areas had lower vaccine coverage compared to non-immigrants living in rural areas. Multivariable logistic regression analysis showed a significant interaction between age category and migration status. While immigrants below 50 years of age generally had significantly higher vaccine coverage compared to non-immigrants, there was some variation based on time since migration. Immigrants above 50 years of age showed significantly lower coverage compared to non-immigrants of the same age.

ConclusionPublic health interventions should focus on older immigrants, immigrants living in rural areas, and immigrants from specific continental backgrounds in order to improve COVID-19 vaccination coverage.


title: Disentangling the rhythms of human activity in the built environment for airborne transmission risk

abstract:
Since the outset of the COVID-19 pandemic, substantial public attention has focused on the role of seasonality in suppressing transmission. Misconceptions have relied on seasonal mediation of respiratory diseases driven solely by environmental variables. However, seasonality is expected to be driven by host social behavior, particularly in highly susceptible populations. A key gap in understanding the role of social behavior in respiratory disease seasonality is our incomplete understanding of the seasonality of indoor human activity.

We leverage a novel data stream on human mobility to characterize activity in indoor versus outdoor environments in the United States. We use a mobile app-based location dataset encompassing over 5 million locations nationally. We classify locations as primarily indoor (e.g. stores, offices) or outdoor (e.g. playgrounds, farmers markets), disentangling location-specific visitor counts into indoor and outdoor, to arrive at a fine-scale measure of indoor to outdoor human activity across time and space.

We find the proportion of indoor to outdoor activity during a baseline year is seasonal, peaking in winter months. The measure displays a latitudinal gradient with stronger seasonality at northern latitudes and an additional summer peak in southern latitudes. We statistically fit this baseline indoor-outdoor activity measure to inform incorporation of this complex empirical pattern into infectious disease dynamic models. However, we find that the disruption of the COVID-19 pandemic caused these patterns to shift significantly from baseline, and the empirical patterns are necessary to predict spatio-temporal heterogeneity in disease dynamics.

Our work empirically characterizes, for the first time, the seasonality of human social behavior at a large-scale with high spatio-temporal resolution, and provides a parsimonious parameterization of seasonal behavior that can be included in infectious disease dynamics models. We provide critical evidence and methods necessary to inform the public health of seasonal and pandemic respiratory pathogens and improve our understanding of the relationship between the physical environment and infection risk in the context of global ecological change.


title: Introduction and Establishment of SARS-CoV-2 Gamma Variant in New York City in Early 2021

abstract:
BackgroundMonitoring the emergence and spread of SARS-CoV-2 variants is an important public health objective. Travel restrictions, aimed to prevent viral spread, have major economic consequences and unclear effectiveness despite considerable research. We investigated the introduction and establishment of the Gamma variant in New York City (NYC) in 2021.

MethodsWe performed phylogeographic analysis on 15,967 Gamma sequences available on GISAID and sampled between March 10th through May 1st, 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC.

FindingsWe identified 16 phylogenetically-distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes). Most of the NYC clusters were introduced from Florida and Illinois; only one was introduced from outside the United States (US). By the time the first Gamma case was reported by genomic surveillance in NYC on March 10th, the majority (57%) of circulating Gamma lineages had already been established in the city for at least two weeks.

InterpretationDespite the expansion of SARS-CoV-2 genomic surveillance in NYC, there was a substantial gap between Gamma variant introduction and establishment in January/February 2021, and its identification by genomic surveillance in March 2021. Although travel from Brazil to the US was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.


title: Using a real-world network to model the tradeoff between stay-at-home restriction, vaccination, social distancing and working hours on COVID-19 dynamics.

abstract:
BackgroundHuman behavior, economic activity, vaccination, and social distancing are inseparably entangled in epidemic management. This study aims to investigate the effects of various parameters such as stay-at-home restrictions, work hours, vaccination and social distance on the containment of pandemics such as COVID-19.

MethodsTo achieve this, we developed an agent-based model based on a time-dynamic graph with stochastic transmission events. The graph is constructed from a real-world social network. The graphs edges have been categorized into three categories: home, workplaces, and social environment. The conditions needed to mitigate the spread of wild-type (WT) COVID-19 and the delta variant have been analyzed. Our purposeful agent-based model has carefully executed tens of thousands of individual-based simulations. We propose simple relationships for the trade-offs between effective reproduction number (Re), transmission rate, work hours, vaccination, and stay at home restrictions.

ResultsFor the WT, it has been found that a 13% increase in vaccination impacts the reproduction number, like the magnitude of decreasing nine hours of work to four and a single day of stay-at-home order. For the delta, 16% vaccination has the same effect. Also, since we can keep track of household and non-household infections, we observed that the change in household transmission rate does not significantly alter the Re. Household infections are not limited by transmission rate due to the high frequency of connections. For COVID-19s specifications, the Re depends on the non-household transmissions rate.

ConclusionsVaccination and transmission reduction are almost interchangeable. Without vaccination or teaching people how to lower their transmission probability significantly, changing work hours or weekend restrictions will only make people more frustrated


title: Association of assisted reproductive technology with long-term offspring cardiometabolic health: a multi-cohort study

abstract:
ObjectivesTo examine association of conception by assisted reproductive technology (ART) with offspring cardio-metabolic health outcomes, and whether these differ by offspring age.

DesignMulti-cohort study.

SettingFourteen population-based cohort studies with offspring from the UK, Ireland, France, the Netherlands, Portugal, Greece, Italy, Norway, Singapore, and Australia for meta-analysis of various ages. Four cohorts (three European and one Singaporean) with repeated measures for pooled age-change (from 3 to 26 years) trajectory analysis.

ParticipantsYoung people sampled from the general population with complete data on mode of conception, confounders, and [≥]1 cardio-metabolic outcome measured after birth.

ExposuresConception by ART versus natural conception (NC).

Main outcome measuresSystolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), glucose, insulin, and glycated haemoglobin (HbA1c).

ResultsBetween 35,780 (605 ART) and 4,502 (67 ART) offspring were included in meta-analysis of various ages for each outcome. Mean age at outcome assessment ranged from 13 months to 27.4 years, with most cohorts ((11/14) having mean age <10 years. Compared with NC, ART-conceived offspring had similar SBP (mean difference (ART minus NC): -0.89mmHg; 95%CI: -1.91 to 0.14), DBP (-0.50mmHg; -1.65 to 0.66), and HR (0.02beats/min; -1.00 to 1.03). Cholesterol measures were higher in ART-conceived than NC offspring, for TC (mean % difference: 2.54%; 0.46 to 4.61), HDLc (4.17%; 1.79 to 6.56), and LDLc (4.95%; 0.99 to 8.92), whereas triglycerides were similar (-1.53%; -6.19 to 3.13). No clear differences were seen for glucose (0.25%; -1.38 to 1.88), insulin (-5.04%; -13.20 to 3.12), or HbA1c (-0.07%; -0.14 to 0.00). Trajectory models in up to 17,244 (244 ART) offspring showed that early life trajectory differences were consistent with the above pooled results and showed higher SBP emerging from mid-adolescence to adulthood with ART (e.g., predicted mean difference in SBP at age 26 years for ART versus NC was 5.06mmHg; 1.76 to 8.35).

ConclusionsChildren conceived through ART had higher cholesterol and similar blood pressure and hyperglycaemic/insulin resistance measures compared with NC children. Whilst overall this is reassuring, our trajectory analysis in a sub-group of cohorts suggested that those conceived by ART may go on to develop higher blood pressure in early adulthood. Our study shows the importance of follow-up into adulthood and requires validation by independent studies with different study designs including within-sibship and mechanistic studies.


title: Morphometric and molecular analysis of Schistosomes eggs recovered from human urines in communities along the shore-line of Oyan-dam in Ogun State, Nigeria

abstract:
BackgroundThere are growing concerns that communities characterized with surface water, where both humans and livestock interact for agricultural, domestic, cultural, and recreational purposes, are likely to support hybridization between schistosome species infecting humans and livestock. This study therefore investigated the possible human infections with hybrid schistosomes in four schistosomiasis endemic communities along the banks of Oyan dam in Ogun State, Nigeria.

MethodsHuman urine samples were collected in Imala-Odo, Abule-Titun, Apojula and Ibaro-Oyan communities. Recovered eggs were counted, photographed, and measured with IC Measure for Total Length, Maximum Width, and a ratio of egg shape. Eighty-seven unusual Schistosoma eggs shaped were molecularly characterised by PCR amplification of Schistosoma specific Dra1 gene. The amplicons were further subjected to PCR amplification of schistosome ITS-2 rDNA and right representative samples with varying gel band sizes were sequenced.

ResultsA total of 1,984 Schistosoma eggs were analysed. The egg morphometrics were within the range of 70.90 - 262.30 m and 30.10 - 102.60 m for total length and width respectively. The length to width ratio was 1.60 - 4.06m. Majority of the eggs have the typical round-to-oval shaped eggs (1345, 67.8 %), followed by eggs with atypical spindle-shaped (639, 32.2 %) and eggs without spines (22, 1.1 %). Egg morphotypes were significantly different (p = 0.017). PCR amplification of Dra1 gene and ITS2 confirmed 54 (62.1%) of the eggs and 33 (61.1%) of Schistosoma origin. Sequencing of two of the DNA samples produced sequences similar to vertebrate S. magrebowiei (accession number UZAI01000474.1) and Asian S. japonicum (accession number SKCS01001458.1).

ConclusionThese findings suggest possibly that hybrids schistosome may be circulating in the human population in the study areas.

Author summaryHuman schistosomiasis is one of the most common neglected tropical diseases in Africa. The disease is caused by a water-borne trematode parasite, and transmission among human requires contact with infested water bodies. There are growing concerns that communities characterized with infested surface water, where both humans and livestock interact are likely to support hybridization between schistosome species infecting humans and livestock. We therefore screened human urine samples using morphological and molecular methods, for the presence of hybrid schistosomes in four communities along the banks of Oyan dam in Ogun State, Nigeria. Our findings show the possible occurrence of hybrid schistosomes in the study area, which call for urgent public health interventions.


title: Parent-reported assessment scores reflect ASD severity in 2- to 7- year-old children

abstract: We investigated the relationship between parent-reported assessments and autism spectrum disorder (ASD) severity. Parents evaluated 9573 children with ASD on five subscales: combinatorial receptive language, expressive language, sociability, sensory awareness, and health using Autism Treatment Evaluation Checklist (ATEC) and Mental Synthesis Evaluation Checklist (MSEC). Scores in every subscale improved with age and there were clear differences between the three diagnostic categories. The differences between mild and moderate ASD as well as between moderate and severe ASD reached statistical significance in each subscale and in every age group in children 3 years of age and older. These findings demonstrate a consistent relationship between childrens diagnoses and their assessments.

category: pediatrics


title: Longitudinal association between depressive symptoms and self-directed passive aggression: A random intercept cross-lagged panel analysis

abstract:
BackgroundSelf-directed passive aggression (SD-PAB) is defined as any behaviour harming one-self by inactivity and omission of own needs. Depressive disorders are a severe mental disorder that results from the interaction between stress exposure, coping strategies, and vulnerability. Previous cross-sectional studies found SD-PAB to be associated with depressive symptoms and to represent a mediator of the relationship between cognitive risk factors and depressive symptoms. Therefore, SD-PAB may be a potential target of prevention or treatment in the context of depressive disorders. However, prospective studies on the relationship between depressive symptoms and SD-PAB are lacking. The current study aimed at closing this gap by examining the associations of subjective stress, SD-PAB, and depressive symptoms cross-sectionally and over time.

MethodIn two assessment cohorts students participated three times [M1: start of the semester (n = 352); M2: start of the exam period (n = 293); M3 = end of the exam period (n = 276)] in an online survey (depressive symptoms; self-perceived stress; SD-PAB). Cross-sectional data was analysed using regression models. Longitudinal data was analysed using Random Intercept Cross-lagged Panel Models.

ResultsAcross all time points, SD-PAB demonstrated a unique cross-sectional association with depressive symptoms when controlled for self-perceived stress ({beta} = .27 - .33; all ps < .001). Furthermore, at M2 [{beta} = .14, t(289) = 3.71, p < .001] and M3 [{beta} = .15, t(272) = 3.51, p < .001] the relationship between depressive symptoms and self-perceived stress was stronger for individuals reporting higher levels of SD-PAB. Depressive symptoms at M1 are a marginal significant predictor of SD-PAB at M2 ({beta} = .31; p = .067) and depressive symptoms at M2 are a marginal significant predictor for SD-PAB at M3 ({beta} = .17; p = .074). However, there was no evidence for SD-PAB predicting the course of depressive symptoms.

ConclusionSD-PAB may represent a symptom of depressive disorders and a moderator of unsuccessful stress coping but does not predict the course of depressive symptoms over time.

category: psychiatry and clinical psychology


title: High prevalence of burnout syndrome among medical and nonmedical residents during the COVID-19 pandemic

abstract:
BackgroundSince the beginning of the COVID-19 pandemic, health professionals have been working under extreme conditions, increasing the risk of physical and mental illness. We evaluated the prevalence of burnout and its associated factors among postgraduate student residents in health professions during the global health crisis.

MethodsHealthcare residents were recruited from all across Brazil between July and September 2020 through digital forms containing instruments for assessing burnout (Oldenburg Burnout Inventory (OLBI)), resilience (brief resilient coping scale (BRCS)) and anxiety, stress and depression (depression, anxiety and stress scale (DASS-21) and Patient Health Questionnaire (PHQ-9)). Additionally, the relationships between burnout and chronic diseases, autonomy and educational adequacy in the residency programme, personal protective equipment (PPE), workload and care for patients with COVID-19 were evaluated. The chi-square test, Students t test, Pearsons correlation test and logistic regression were performed.

ResultsA total of 1,313 participants were included: mean (standard deviation) age, 27.8 (4.4) years; female gender, 78.1%; white race, 59.3%; and physicians, 51.3%. The overall prevalence of burnout was 33.4%. The odds (odds ratio [95% confidence interval]) of burnout were higher in the presence of pre-existing diseases (1.76 [1.26- 2.47]) and weekly work > 60 h (1.36 [1.03-1.79]) and were lower in the presence of high resilience (0.84 [0.81-0.88]), autonomy (0.87 [0.81-0.93]), and educational structure (0.77 [0.73-0.82]), adequate availability of PPE (0.72 [0.63-0.83]) and non-white race (0.63 [0.47-0.83]). Burnout was correlated with anxiety (r = 0.47; p < 0.05), stress (r: 0.58; p < 0.05) and depression (r: 0.65; p < 0.05).

ConclusionsWe observed a high prevalence of burnout among residents during the COVID-19 pandemic. Individual characteristics and conditions related to the work environment were associated with a higher or lower occurrence of the syndrome.


title: Patterns of impaired neurocognitive performance on Global Neuropsychological Assessment (GNA), and their brain structural correlates in recent-onset and chronic schizophrenia: A pilot study

abstract: Cognitive deficits are established as a fundamental feature of schizophrenia; however, their pattern and how they are affected by chronicity are still unclear. Although a generalized stable impairment affecting multiple cognitive domains is commonly seen from the onset, some longitudinal studies have shown evidence of neuroprogression, and selective deterioration in certain cognitive domains. We assessed cognitive performance in patients with recent-onset (n = 17, duration of illness [≤] 2 years) and chronic schizophrenia (n = 14, duration [≥] 15 years), and healthy adults (n = 16) using the Global Neuropsychological Assessment and examined correlations between cognitive scores and gray matter volumes computed from T1-weighted MRI images. We also measured and analyzed differences between patient groups for negative and positive symptoms, psychotic exacerbations, and medication exposure, and studied their correlations with cognitive performances. We observed cognitive deficits affecting multiple domains in both recent-onset and chronic schizophrenia samples. Selectively greater impairment of perceptual comparison/processing speed was found in adults with chronic schizophrenia (p = 0.009, {eta}2partial = 0.25). In the full sample (n = 47), perceptual comparison speed correlated significantly with gray matter volumes in the anterior and medial temporal lobes, predominantly on the left side (TFCE, FWE p < 0.01). These results indicate that along with generalized deficit across multiple cognitive domains, selectively greater impairment of perceptual comparison/processing speed appears to characterize chronic schizophrenia. This pattern might indicate an accelerated or premature cognitive aging. Gray matter volumetric deficits in the anterior-medial temporal lobes especially of left side might underlie the impaired perceptual comparison/processing speed seen in schizophrenia.


title: A Systematic Review of Long-term Antidepressant Outcomes in Comorbid Depression and Type 2 Diabetes

abstract:
BackgroundDepression is a common and chronic comorbidity affecting approximately one in four people with type 2 diabetes (T2DM), and often lasting several years. Past systematic reviews have been unable to identify evidence for long-term (12+ months) antidepressant treatment outcomes in comorbid depression and type 2 diabetes. These reviews are >10years old, included only randomised controlled trials or had limited search strategies. We aimed to systematically review observational studies for long-term outcomes of antidepressant treatment in adults with comorbid depression and T2DM, including broader, up-to-date searches.

Methods and findingsThis review was pre-registered on PROSPERO (CRD42020182788). We searched seven databases using terms related to depression, T2DM and antidepressant medication. From 14,389 reports retrieved, 63 were screened at full text stage and 0 met inclusion criteria. The reasons for exclusion at full text stage were: Studies did not meet inclusion criteria for antidepressant treatment (n = 50); studies did not meet inclusion criteria for T2DM (n = 36); studies did not meet inclusion criteria for depression (n = 29); studies did not include follow-up time (n = 25); studies did not meet inclusion criteria for observational study (n = 14); studies did not include any measurable outcomes (n = 5); studies did not include a suitable comparison (n = 3).

ConclusionsWe found no evidence concerning long-term outcomes of antidepressant treatment in individuals with comorbid depression and T2DM. Insufficient ascertainment of antidepressant prescription, case identification, and short follow-up times are the primary reasons for this. Research is urgently required to determine long-term outcomes associated with antidepressant treatment in this patient group.


title: The UTHealth Psychological Autopsy Interview Schedule (UTH PAIS): Description and Reliability of Diagnoses and Transdiagnostic Personality Measures

abstract: Few studies have used psychological autopsies to evaluate large and diverse populations on transdiagnostically relevant variables such as personality, temperament, and trauma exposure, rather they tend to focus on specific psychiatric disorders or manner of death. We therefore developed the UT Health Psychological Autopsy Interview Schedule (UTH-PAIS). The measure is described, and our results show that that the PAIS diagnoses and dimensions can be reliably assessed. Furthermore, we were able to show that our sample of donated brains overall matches the demographic characteristics of larger pool of individuals receiving a medical autopsy. In the Discussion we review the strengths and potential limitations of the study and outline in which context the PAIS will prove to be useful.


title: Hair concentrations of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in cannabis consumers psychiatric patients

abstract: Among young consumers of cannabis, a brief psychotic disorder (BPD) can be either the clinical manifestation of acute cannabis psychosis (ACP) or an announcement of schizophrenias onset. Clinicians are faced with the difficulty of making a differential diagnosis between disorders of the schizophrenic field and disorders induced by cannabis. To date, no clinical or even less paraclinical criteria have made it possible to differentiate syndromes whose prognoses and management are different. Since 2010, we measured delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in head hair among New Caledonian patients, all cannabis consumers (n = 256). We wanted to determine if these patients, cannabis users, suffering from different mental pathologies, present particular phenotypes of capillary cannabinoid concentrations (THC and CBD). At the time of initial psychiatric consultation, a sample of 3 cm proximal length of head hair was prepared for analysis, and THC and CBD were then assayed by Gas Chromatography coupled with Mass Spectrometry (Limit Of Quantitation: 0.05 ng/mg). At the end of the 6 months medico-psychologic follow-up from the initial evaluation, four groups of cannabis users were identified according to the final psychiatric diagnosis: control, acute cannabis psychosis (ACP), chronic psychosis (CP), and other personality disorders (OPD) groups. In this study, a high hair level of THC detected (> 0.7 ng/mg) associated with a low hair CBD/THC ratio (< 0.26) are two parameters that taken together could be good markers of CP development. For OPD and ACP, hair CBD/THC ratios were higher in the ACP group (> 0.43) than in the OPD group (< 0.32). This study highlights, once again, the protective role of CBD against the deleterious effects of THC. In association with clinical evaluation, this toxicological approach could be helpful for psychiatric diagnosis and would allow early management of BPD in cannabis consumers. For a consumer who does not present with a psychiatric disorder, it could give an information about the possibility of belonging to a group of patients at high risk of psychiatric decompensation. This provides an additional argument for efforts to control cannabis consumption by patients.


title: A Text Message Intervention to Support Latino Dementia Family Caregivers (CuidaTEXT): Feasibility study

abstract:
ObjectivesTo test the feasibility, acceptability, and preliminary efficacy of CuidaTEXT: a tailored text message intervention to support Latino dementia family caregivers.

MethodsCuidaTEXT is a six-month, bilingual, and bidirectional intervention tailored to caregiver needs (e.g., education, problem-solving, resources). We enrolled 24 Latino caregivers in a one-arm trial, and assessed feasibility, acceptability, and preliminary efficacy within six months.

ResultsRecruitment took 61 days and enrollment took 20. None of the participants unsubscribed from CuidaTEXT, and 83.3% completed the follow up survey. Most participants (85.7%) reported reading most text messages thoroughly. Participants reported high levels of satisfaction with the intervention (3.6 on a scale from 1 to 4). CuidaTEXT helpfulness was high (3.5-3.8 on a 1 to 4 scale). Compared to baseline, at six months caregiver behavioral symptom distress (0-60) decreased from 19.8 to 12.0, and depression (0-30) from 8.8 to 5.4 (p<0.05).

ConclusionsCuidaTEXT demonstrated high levels of feasibility, acceptability, and preliminary efficacy among Latino caregivers.

Clinical implicationsCuidaTEXTs feasibility and potential for widespread implementation holds promise in supporting Latino caregivers of people with dementia.


title: The effect of antidepressants on severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis

abstract:
IntroductionClinical depression and the subsequent low immunity is a comorbidity that can act as a risk factor for severity of COVID-19 cases. Antidepressants such as SSRI and SNRI are associated with immune-modulatory effects, which dismiss inflammatory response and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on prognosis and severity of COVID-19 in hospitalized patients.

MethodsA systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to January 16, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", "SNRI", "TCA", "MAOI", and "Antidepressant". The pooled risk ratio (RR) with 95% CI was assessed using a fixed or random-effect model. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ).

ResultsTwelve studies were included in our systematic review. Three of them were experimental with 1751, and nine of them were observational with 290,950 participants. Seven out of twelve articles revealed the effect of antidepressants on reducing severity of COVID-19. SSRI medications, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine and also among the SNRI drugs Venlafaxine are also reasonably associated with reduced risk of intubation or death. There were four studies showing no significant effect and one study showing the negative effect of antidepressants on prognosis of covid-19. The meta-analysis on clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.745; 95% CI: 0.580-0.956)

ConclusionsMost of the evidence supports that the use of antidepressant medications, mainly Fluvoxamine may decrease the severity and improve the outcome in hospitalizes patients with sars-cov-2. Some studies showed contradictory findings regarding the effects of antidepressants on severity of COVID-19. Further experimental studies should be conducted to clarify the effects of antidepressants on severity of COVID-19.


title: COVID-19 and Curcumin: Using VOSviewer software to explore scientific landscape, A bibliometric analysis

abstract:
BackgroundCurcumin is derived from Turmeric which is a spice with an old history in the oriental world. For this reason, it was a subject for continuous research over years and some studies reported preliminary positive results in arthritis and metabolic syndrome. When COVID-19 declared as a global pandemic, debates exploded again regarding its effects in mitigating deleterious effects of the viral infection. However, being a traditional remedy flooded readers with thousands of publications, some of these was scientifically rigid and others were fraudulent. We aim to use VOSviewer software to visualize scientific landscape in this topic, to highlight the trends and identify main supporting bodies.

MethodsWe searched Web of Science (WOS) core collection database for publications between December 2019 and April 2022. Data collected include: year of publication, keywords, type of the document, author names, affiliations, abstracts and number of citations. VOSviewer 1.6.18 was used to analyze co-citation, co-occurrence, and publication trends. Analysis considered one weight attribute which is "total link strength attributes".

ResultsA total of 205 publications (N=205) were included in the analysis. Most studies were original research articles (50.7%). Mean citation count of the top 10 cited articles was 37.9 (range 22 and 111). Country of corresponding author of these 10 studies was India in 5 (50%), Iran in 3 (30%). Organizational analysis revealed 5 Iranian universities as being the main research bodies with total link strengths (TLS) of 100. Co-occurrence of keywords identified "viral inhibition, oxidative stress, molecular docking, NF-kB pathway" as the most frequent mentioned keywords. Trend analysis showed negative trend with less publications covering this topic, chronologically.

ConclusionCurcumin resided within the oriental tradition for years, it is no surprise that main supporting bodies were oriental. VOSviewer provides an easy, user-friendly options to handle bibliographic data.

category: public and global health


title: COVID-19 vaccine effectiveness against SARS-CoV-2 infection in the United States prior to the Delta and Omicron-associated surges: a retrospective cohort study of repeat blood donors

abstract: To inform public health policy, it is critical to monitor COVID-19 vaccine effectiveness (VE), including against acquiring infection. We estimated VE using a retrospective cohort study among repeat blood donors who donated during the first half of 2021, demonstrating a viable approach for monitoring of VE via serological surveillance. Using Poisson regression, we estimated overall VE was 88.8% (95% CI: 86.2-91.1), adjusted for demographic covariates and variable baseline risk. Time since first reporting vaccination, age, race-ethnicity, region, and calendar time were statistically significant predictors of incident infection. Studies of VE during periods of Delta and Omicron spread are underway.


title: COVID-19 in the Mexican Social Security Institute (IMSS) population. Prevalent symptoms

abstract:
BackgroundThe disease caused by the new coronavirus SARS-CoV-2, COVID-19, which appeared in early 2020 in Mexico, was the second leading cause of mortality in the country that year and has generated an increasing demand for medical care. By January 2022, 4.13 million cases and 300 thousand direct deaths have been documented.

ObjectiveTo describe the main symptoms of people with a positive test for SARS-CoV-2 treated at the Mexican Institute of Social Security (IMSS) by sex, age group, and IMSS delegation.

Methods4.5 million epidemiological reports were registered in the IMSS epidemiological surveillance system between February 2020 and November 2021. They were analyzed, reporting for those with either a positive PCR or rapid test, the prevalence of symptoms by sex, groups of age, and IMSS delegation.

ResultsAmong the population treated at the IMSS, six symptoms are observed as the most prevalent in general, as well as by sex, age groups, and state of residence: cefalea, fever, cough, myalgia, odynophagia, and arthralgias.

ConclusionsA better understanding of the clinical picture with which confirmed cases of COVID-19 present contributes to reporting timely diagnoses, considering the particularities by sex, age, and place of residence.


title: MOSAIC (MOthers' AdvocateS In the Community) for Pregnant Women and Mothers of Children Under 5 with Experience of Intimate Partner Violence: A pilot randomized trial study protocol

abstract:
BackgroundPregnancy and motherhood increase the risk for long-term exposure to physical, psychological and sexual intimate partner violence (IPV; sexual or physical violence by current or former partners). Pregnant women and mothers with children under 5 who have experienced IPV exhibit poor physical and mental health and obstetric outcomes. Depression and posttraumatic stress disorder (PTSD) are the two most common mental health consequences of IPV. There is good evidence that women with good social support have better mental health and IPV outcomes.

MethodsThis study will develop MOthers AdvocateS In the Community (MOSAIC) Plus intervention for pregnant women and mothers with children under the age of 5. MOSAIC uses trained mentor mothers and has been found to reduce subsequent IPV. This study will blend the original MOSAIC intervention with principles of interpersonal psychotherapy (IPT) to address symptoms of depression, PTSD, and prevent subsequent risk of IPV. We will conduct a pilot randomized trial of the MOSAIC Plus intervention compared to the traditional MOSAIC intervention to determine its feasibility and acceptability. Study samples include focus groups (n=36), open trial (n=15), and a randomized pilot trial including 40 pregnant women and mothers with children under 5 who report current/recent of IPV and elevated symptoms of maternal depression and/or PTSD. The studys primary outcome will be changes in maternal depressive and PTSD symptoms. Secondary outcomes will include reduction in subsequent IPV, improvement in functioning, changes in social support and effectiveness in obtaining resources.

DiscussionThis is a formative study evaluating the feasibility and acceptability of a mentor mother intervention for pregnant women and mothers with children under 5. Promising results of this study will be used for a larger, fully-powered randomized trial evaluating the effectiveness of a mentor mother intervention in preventing subsequent IPV and reducing depressive and PTSD symptoms in this population.

Strengths and limitations of this studyO_LIThe study is informed by a robust qualitative approach to intervention development that involves a series of focus group discussions.
C_LIO_LIThis study aims to develop an intervention that reduces future intimate partner violence, while also addressing related maternal mental health outcomes.
C_LIO_LIA rigorous and reproducible design includes randomization, clear inclusion criteria, manualized treatment protocols and fidelity assessments.
C_LIO_LIThe study will use reliable and validated measures.
C_LIO_LIGiven the small sample size, results from the pilot randomized trial are underpowered to draw firm conclusions about effectiveness.
C_LI


title: Impairment and characteristics of postural control sub-components in people with COPD: a scoping review.

abstract:
PurposeImpairment of postural control is a common extra-respiratory manifestation in people with COPD. However, the precise characteristics of this alteration are not clearly known. The "Systems Framework for Postural Control" which define postural control sub-components, is a relevant tool to explore this field. The main aim of this review was to identify which postural control sub-components are impaired in patients with COPD and to summarize characteristics for each sub-component. A secondary aim was to precise the relation between postural control and activities of daily living.

Materials and methodsA scoping review was conducted, according to the JBI methodology. Pubmed, Cochrane Library, Scielo, Google Scholar, Open Grey and HAL were searched from inception to March 2021. The search was performed in English and French.

ResultsSeventy-seven articles were included. There was evidence of a potential impairment for most of the postural control sub-components. Characteristics of every sub-component alteration were heterogeneous. Even if the relation was poorly studied, reduced postural control seemed to be associate with difficulties in activities of daily living.

ConclusionPatients with COPD could experiment impairment among a wide range of postural control sub-components. Future research must clarify if a common pattern of modification exits for this alteration.

Implications for rehabilitationO_LIImpairment of postural control is a common extra-respiratory manifestation in patients with COPD and so clinicians must include it in their clinical reasoning
C_LIO_LINumerous postural control sub-components could be altered in patients with COPD, suggesting that postural control assessment must be holistic.
C_LIO_LIThis scoping review shows that characteristics of postural control impairment are varied and that there may be no common pattern at the COPD population level.
C_LI

category: rehabilitation medicine and physical therapy


title: RATING: Medical-knowledge-guided rheumatoid arthritis assessment from multimodal ultrasound images via deep learning

abstract: Ultrasound (US) examination has been commonly utilized in clinical practice for assessing the rheumatoid arthritis (RA) activity, which is hampered by low intra-observer and inter-observer agreement as well as considerable time and expense to train experienced radiologists. Here, we present the Rheumatoid ArthriTIs kNowledge Guided (RAT ING) model that scores RA activity and generates interpretable features to assist radiologists decision-making. The RATING model achieved an accuracy of 86.1% (95% confidence interval (CI)=82.5%-90.1%) in the clinical trial setting, and achieved an accuracy of 85.0% (95% CI=80.5%-89.1%) on the US images collected from an external medical center. An AI-assisted reader study demonstrated that the RATING model improved the average accuracy of ten radiologists from 41.4% to 64.0%. Automated AI models for the assessment of RA may facilitate US RA examination and provide support for clinical decision-making.

category: rheumatology


title: Attitude towards gender inequitable norms and associated factors among male youths in Arba Minch town, Southern Ethiopia

abstract:
BackgroundGender inequitable norms are common cultural traditions across the world, which characterized women as someone who deserves less basic life support and fundamental human rights than men. The unfairness of such practices has demolished womens quality of life. Studies are limited to measuring some factors in Ethiopia. The information obtained from this study will help to take an evidence-based approach to reduce gender inequitable norms.

ObjectiveTo assess attitude towards gender inequitable norms and associated factors among male youths from August 16th- 30th, 2020 at Arba Minch town, Southern Ethiopia.

MethodsA community-based cross-sectional study was conducted among 423 male youths. Gender-Equitable Men Scale was used to measure the attitudes towards gender inequitable norms. The study participants were selected using a simple random sampling technique by allocating a proportion to each kebeles. Both bivariable and multivariable logistic regression analyses were performed to identify associated factors. The level of statistical significance was set at a p-value of less than 0.05 in multivariable logistic regression.

ResultsThe overall prevalence of favorable attitude towards gender inequitable norms among male youths was 47.3% with 95% CI (42%, 52%). No formal education, lower household income, not participating in youth clubs, poor knowledge, and having a prior history of physical violence during childhood were factors significantly associated with a favorable attitude towards gender inequitable norms.

Conclusion and recommendationAlmost half of the participants had a favorable attitude towards gender inequitable norms. Proactive measures need to be taken to curb the problem by taking integrated interventions for youths like enrolling in school, enhancing participation in a youth club, prevent childhood physical violence, increasing household income, and creating awareness on gender inequitable norms to change traditional beliefs that undermine women.

category: sexual and reproductive health


title: Discovery of Neurocognitive Phenotypes of Autism By Analyzing Functional Connectivity in the Default Mode Network and Dorsolateral Prefrontal Cortex

abstract:
Autism spectrum disorder (ASD) is a neurodevelopmental disorder usually presenting as reduced social interaction, lessened verbal communication, and repetitive behavior. Diagnosing ASD is extremely difficult because of its wide variety of symptoms, so it can only be diagnosed through behavioral tests and analysis of developmental history. Resting-state fMRI can help researchers discover a neural substrate for ASD to diagnose it earlier. One prominent fMRI database for ASD research is the Autism Brain Imaging Data Exchange, a large-scale collection of anonymized functional MRI scans subdivided by age, gender, handedness, and scores on behavioral assessments.

This analysis focused on two brain networks: the default mode network (DMN), which is active when minds wander, and the executive network, which is active during the performance of tasks. The medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and angular gyrus are nodes of the DMN, and the dorsolateral prefrontal cortex (DLPFC) is the main node in the executive network. Both networks are affected by ASD.

This research used preprocessed resting-state fMRI data to establish neurocognitive phenotypes for ASD. Bivariate correlation was used to compare connectivity in the DMN and DLPFC between ASD and control fMRI scans, and these differences were analyzed for correlations with each patients assessment scores. After the Benjamini-Hochberg procedure was applied to reduce the false discovery rate, analysis of these metrics revealed that in ASD patients there was underconnectivity between the right PCC and the right mPFC, while in control patients there was overconnectivity between the right angular gyrus and left DLPFC. ASD is extremely heritable, so phenotypic research is absolutely necessary for discovering more about the genetic causes of ASD, which will speed up ASD diagnosis and help researchers develop more targeted treatments for ASD.

category: neurology


title: Chromatin remodeler developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders

abstract: Alcohol affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. To explore the etiology of FASD, we collected an exceptional cohort of 80 severely alcohol-exposed and 100 control newborns and performed genome-wide DNA methylation and gene expression analyses of placentas. DPPA4, FOXP2, and TACR3 with significantly decreased DNA methylation were discovered - particularly the regulatory region of DPPA4 in the early alcohol-exposed placentas. When human embryonic stem cells (hESCs) were exposed to alcohol in vitro, significantly altered regulation of DPPA2, a closely linked heterodimer of DPPA4, was observed. While the regulatory region of DPPA4 was unmethylated in both control and alcohol-exposed hESCs, alcohol-induced decreased DNA methylation similar to placenta was seen in in vitro differentiated mesodermal and ectodermal cells. Furthermore, common genes with alcohol-associated DNA methylation changes in placenta and hESCs were linked exclusively to the neurodevelopmental pathways, which emphasizes the value of placental tissue when analyzing the effects of prenatal environment on human development. Our study shows the effects of early alcohol exposure on human embryonic and extraembryonic cells, introduces candidate genes for alcohol-induced developmental disorders, and reveals potential biomarkers for prenatal alcohol exposure.

category: genetic and genomic medicine


title: An umbrella review of the evidence linking oral health and systemic health: from the prevalence to clinical and circulating markers

abstract: Oral conditions are highly prevalent worldwide. Recent studies have been supporting a potential bidirectional association of oral disorders with systemic noncommunicable diseases (NCDs). Robust evidence supports the greater prevalence of oral conditions in people suffering from NCDs limiting the ability of oral self-care. As for the relationship with other NCDs, the lines of evidence have increased exponentially but not always with the proper coherence. This umbrella review of meta-analyses appraises the strength and validity of the evidence for the association between oral health and systemic health. An extensive search included systematic reviews that have provided meta-analytic estimates on the association of an oral condition with a NCD. The overall strength of evidence was found to be unfavorable and with methodological inconsistencies. Twenty-two NCDs, four types of cancer and circulating levels of CRP were strongly associated with oral diseases. Among the significant NCDs are diabetes mellitus, cardiovascular diseases, depression, neurodegenerative conditions, rheumatic diseases, inflammatory bowel disease, gastric helicobacter pylori, stroke, obesity, diabetes mellitus or asthma. Most evidence is unlikely to change which indicates a relatively robust consistency of the available body of evidence.


title: Investigation of the association between high arachidonic acid synthesis and colorectal polyp incidence: a Mendelian randomisation approach

abstract:
Background & AimsArachidonic acid (ARA) is causally associated with colorectal cancer (CRC), a major public health concern. However, it is uncertain if ARA contributes to the development of colorectal polyps which are pre-malignant precursors of CRC. Therefore, this study aimed to investigate the association between lifelong exposure to elevated ARA and colorectal polyp incidence using Mendelian randomisation.

MethodsSummary level GWAS data from European, Singaporean, and Chinese cohorts (n=10,171) identified 4 single nucleotide polymorphisms (SNPs) associated with blood ARA levels (p< 5 x 10-8). After pruning, 1 SNP was retained (rs174547; p=3.0x10-971) for 2-stage Mendelian randomisation to infer the causal effect of ARA on self-reported colorectal polyp outcomes within the UK Biobank (1,391 cases; 462,933 total).

ResultsNo association between ARA and colorectal polyp incidence was observed [OR= 1.00 (95% CI: 0.99, 1.00); P-value = 0.50).

ConclusionsBlood levels of ARA do not associate with colorectal polyp incidence. This work supports the contention that downstream lipid mediators, such as PGE2, are key for polyp formation during early-stage colorectal carcinogenesis


title: The dynamic reproduction index: accurate determination from incidence and application for an early warning system

abstract:
Two methods of calculating the reproduction index from daily new infection data are considered, one by using the generation time tG as a shift (RG), and an incidence-based method directly derived from the differential equation system of an SIR epidemic dynamics model (RI). While the former is shown to have few in common with the true reproduction index, we find that the latter provides a sensitive detection device for intervention effects and other events affecting the epidemic, making it well-suited for diagnostic purposes in policy making. Furthermore, we introduce a similar quantity, [Formula], which can be calculated directly from RG. It shows largely the same behaviour as RI, with less fine structure. However, it is accurate in particular in the vicinity of R = 1, where accuracy is important for the corrrect prediction of epidemic dynamics. We introduce an entirely new, self-consistent method to derive, from both quantities, an improved [Formula] which is both accurate and contains the details of the epidemic spreading dynamics. Hence we obtain R accurately from data on daily new infections (incidence) alone. Moreover, by using RI instead of RG in plots of R versus incidence, orbital trajectories of epidemic waves become visible in a particularly insightful way, demonstrating that the widespread use of only incidence as a diagniostic tool is clearly inappropriate.

PACS numbers:


title: Aging in India: Comparison of Conventional and Prospective Measures, 2011

abstract: Conventional measurements of aging do not take into account the dynamic nature of aging-related characteristics over time. Therefore, in order to refine the estimates of aging, demographers have proposed prospective measures based on remaining life expectancy, Sanderson and Scherbov (2007). We compared these new measures with conventional aging measures using the data from the Census of India 2011 and Sample Registration System life tables 2009-2013. In conventional aging measures, we used life expectancy at age 60 and the old age dependency ratio (OADR), whereas for new measures of aging, we applied the threshold of old age based on the remaining life expectancy and prospective old age dependency ratio (POADR). Both measures of aging provided different estimates of the aging population at the national and subnational levels. At national level, application of prospective measures increased the number of older dependents from 66.4 million to 71.8 million (OADR: 8.6% vs. POADR: 10.6%). We observed profound variation at sub-national level in India. We also observed that the prospective ageing measures not only provided higher estimates of ageing burden in India, but also altered the gender and rural urban differential in ageing. Considering the heterogeneity of life expectancies across Indian states, prospective measures provide more accurate refined estimates of aging burden in India as they are based on length of life expectancy. Application of these measures has great policy relevance in India.


title: Overestimation of School-Based Deworming Coverage Resulting from School-Based Reporting

abstract:
BackgroundSoil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. DeWorm3 is a cluster-randomized trial, conducted in three study sites in Benin, India, and Malawi, designed to assess the feasibility of interrupting STH transmission with community-wide MDA as a potential strategy to replace SBD. This analysis examines data from the DeWorm3 trial to quantify discrepancies between school-level reporting of SBD and gold standard individual-level survey reporting of SBD.

Methodology/Principal FindingsPopulation-weighted averages of school-level SBD calculated at the cluster level were compared to aggregated individual-level SBD estimates to produce a Mean Squared Error (MSE) estimate for each study site. In order to estimate individual-level SBD coverage, these MSE values were applied to SBD estimates from the control arm of the DeWorm3 trial, where only school-level reporting of SBD coverage had been collected.

In each study site, SBD coverage in the school-level datasets was substantially higher than that obtained from individual-level datasets, indicating possible overestimation of school-level SBD coverage. When applying observed MSE to project expected coverages in the control arm, SBD coverage dropped from 89.1% to 70.5% (p-value < 0.001) in Benin, from 97.7% to 84.5% (p-value < 0.001) in India, and from 41.5% to 37.5% (p-value < 0.001) in Malawi.

Conclusions/SignificanceThese estimates indicate that school-level SBD reporting is likely to significantly overestimate program coverage. These findings suggest that current SBD coverage estimates derived from school-based program data may substantially overestimate true pediatric deworming coverage within targeted communities.


title: Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: The Framingham Heart Study

abstract:
BackgroundExpression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression and may reveal molecular mechanisms of disease. The present study describes an eQTM resource of CpG-transcript pairs.

MethodsDNA methylation was measured in blood samples from 1,045 Framingham Heart Study (FHS) participants using the Illumina 450K BeadChip and in 1,070 FHS participants using the Illumina EPIC array. Blood gene expression data were collected from all 2,115 participants using RNA sequencing (RNA-seq). The association between DNA methylation and gene expression was quantified for all cis (i.e., within 1Mb) and trans (>1Mb) CpG-transcript pairs. Significant results (p<1E-7 for cis and <1E-14 for trans) were subsequently tested for enrichment of biological pathways and of clinical traits.

ResultsWe identified 70,047 significant cis CpG-transcript pairs where the top most significant eGenes (i.e., gene transcripts associated with a CpG) were enriched in biological pathways related to cell signaling, and for 1,208 clinical traits (enrichment false discovery rate [FDR] [≤] 0.05). We also identified 246,667 significant trans CpG-transcript pairs where the top most significant eGenes were enriched in biological pathways related to activation of the immune response, and for 1,191 clinical traits (enrichment FDR [≤] 0.05). Using significant cis CpG-transcript pairs, we identified significant mediation of the association between CpG sites and cardiometabolic traits through gene expression and identified shared genetic regulation between CpGs and transcripts associated with these cardiometabolic traits.

ConclusionsWe developed a robust and powerful resource of eQTM CpG-transcript pairs that can help inform future functional studies that seek to understand the molecular basis of disease.


title: Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease

abstract: DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify DNA methylation quantitative trait loci (mQTLs) in 4,126 Framingham Heart Study participants. Our mQTL mapping identified 94,362,817 cis-mQTLvariant-CpG pairs (for 210,156 unique autosomal CpGs) at P<1e-7 and 33,572,145 trans-mQTL variant-CpG pairs (for 213,606 unique autosomal CpGs) at P<1e-14. Using cis-mQTL variants for 1,258 CpGs associated with seven cardiovascular disease risk factors, we found 104 unique CpGs that colocalized with at least one cardiovascular disease trait. For example, cg11554650 (PPP1R18) colocalized with type 2 diabetes, driven by a single nucleotide polymorphism (rs2516396). We performed Mendelian randomization (MR) analysis and demonstrated 58 putatively causal relations of CVD risk factor-associated CpGs to one or more risk factors (e.g., cg05337441 [APOB] with LDL; MR P=1.2e-99, and 17 causal associations with coronary artery disease (e.g. cg08129017 [SREBF1] with coronary artery disease; MR P=5e-13). We also showed that three CpGs, e.g., cg14893161 (PM20D1), are putatively causally associated with COVID-19 severity. To assist in future analyses of the role of DNA methylation in disease pathogenesis, we have created a browsable and downloadable resource of mQTLs through the NCBI Molecular QTL Browser.


title: Heterogeneity of resting-state EEG features in juvenile myoclonic epilepsy and controls.

abstract: Abnormal EEG features are a hallmark of epilepsy, and abnormal frequency and network features are apparent in EEGs from people with idiopathic generalised epilepsy in both ictal and interictal states. Here, we characterise differences in the resting-state EEG of individuals with juvenile myoclonic epilepsy (JME) and assess factors influencing the heterogeneity of these EEG features. We collected EEG data from 147 participants with JME through the Biology of Juvenile Myoclonic Epilepsy (BIOJUME) study. 95 control EEGs were acquired from two independent studies (Chowdhury et al. (2014) and EU-AIMS Longitudinal European Autism Project). We extracted frequency and functional network-based features from 10-20s epochs of resting-state EEG, including relative power spectral density (PSD), peak alpha frequency, network topology measures and Brain Network Ictogenicity (BNI): a computational measure of the propensity of networks to generate seizure dynamics. The influence of covariates such as age, sex, antiseizure medication, EEG time and epoch length were investigated for each EEG feature prior to testing for differences between JME and control EEGs using univariate, multivariable and receiver operating curve (ROC) analysis. Additionally, associations of clinical phenotypes (seizure type, seizure control) with EEG features were investigated in the JME cohort. P-values were corrected for multiple comparisons. Univariate analysis showed significant differences in PSD in delta (2-5Hz) (p=0.0007, hedges g=0.55) and low-alpha (6-9Hz) (p=2.9x10-8, g=0.80) frequency bands, peak alpha frequency (p=0.000007, g=0.66), functional network mean degree (p=0.0006, g=0.48) and BNI (p=0.00006, g=0.56) between JME and controls. Since age (p=0.009) and epoch length (p=1.7x10-8) differed between the two groups and were potential confounders, we controlled for these covariates in multivariable analysis where disparities in EEG features between JME and controls remained. ROC analysis showed low-alpha PSD was optimal at distinguishing JME from controls, with an area under the curve of 0.72. Lower average normalized clustering coefficient and shorter average normalized path length were associated with poorer seizure control in JME patients. To conclude, individuals with JME have increased power of neural oscillatory activity at low-alpha frequencies, along with increased BNI compared to controls, supporting evidence from studies in other epilepsies with considerable external validity. In addition, the impact of confounders on different frequency-based and network-based EEG features observed in this study highlights the need for careful consideration and control of these factors in future EEG research in IGE particularly for their use as biomarkers.


title: Theoretical derivation and clinical validation of the resolution limit of human eye to spherical lens change：A Self-controlled Study

abstract:
Background/AimsTo deduce theoretically and verify the resolution limit of human eye to spherical lens change for more reasonable design of the trial lenses.

MethodsFirst, the resolution limit of discernible change in spherical power was derived based on the optical model. Then, the volunteers were observed to see if they could perceive the changes in spherical power as per the resolution limit and compare the difference in the best corrected visual acuity obtained with the resolution limit and interval of 0.25D.

ResultsAssuming that the cone cell diameter is 3 m and the pupil diameter of 4 mm, the theoretically resolution limit was 0.05D. When the diopter of spherical power was increased, the ratios of ability to perceive 0.05D spherical lens change were 98.3% and 96.7% in right and left eyes. When the diopter of spherical power was decreased, the ratios of ability to perceive 0.05D spherical lens change were 78.9% and 83.2% in right and left eyes. The best corrected visual acuity obtained with the 0.05 D interval trial lens was significantly better than in the 0.25 D interval on both eyes (Right eye -0.04{+/-}0.07 vs -0.02{+/-}0.06, t=6.729, P<0.001; Left eye -0.07{+/-}0.06 vs -0.04{+/-}0.06, t=8.825, P<0.001).

ConclusionThe resolution limit of human eye to spherical lens change was about 0.05D and the better corrected visual acuity can be obtained by adjusting the spherical power at an interval of 0.05D.

What is already known on this topicAt present, the spherical power is generally adjusted at 0.25D for optometry. In clinical practice, we find that a more than 80% of myopia patients with clear red prototypes will directly see clear green in case of a decrease by 0.25D, unable to achieve the red-green balance.

What this study addsMore than 80% of myopia patients can perceive the changes in spherical power as per 0.05D.

How this study might affect research, practice or policyAdjusting the spherical power per 0.05 D can help us to achieve a higher full correction rate (>80%) and realize better visual acuity.

[Synopsis/Precis]The resolution limit of human eye to spherical lens change is about 0.05D and better corrected visual acuity can be obtained by adjusting the spherical power at an interval of 0.05D than 0.25D.

category: ophthalmology


title: Feedback of Individual Genetic and Genomics Research Results: A Qualitative Study Involving Grassroots Communities in Uganda

abstract:
BackgroundGenetics and genomics research (GGR) is associated with several challenges including, but not limited to, implications of sharing research findings with participants and their family members, issues of confidentiality, determining appropriate methods for providing genetic or genomic information to individuals tested, and ownership of DNA obtained from the samples. Additionally, GGR holds significant potential risk for social and psychological harms.

A considerable amount of research has been conducted with resultant literature and global debate on return of genetic and genomics testing results, but such investigations are limited in the African setting, including Uganda.

The objective of the study was to assess perceptions of grassroots communities on if and how feedback of individual genetics and genomics testing results should be carried out in a Ugandan setting.

MethodsThis was a cross-sectional study that employed a qualitative exploratory approach. A total of 42 individuals from grassroots communities representing three major ethnic groupings participated in five deliberative focus group discussions. Data were analysed through content analysis along the main themes of the study. NVivo software (QSR international 2020) was used to support data analysis and illustrative quotes were extracted.

ResultsOf the 42 respondents 23 (55%) were male with an age range of 18-77 years. Most (70%) were small scale farmers, and the majority were Christians, who were married and had children. They all lived in a rural community in one of the three regions of the country and had no prior participation in GGR. All the respondents were willing to undergo genetics testing and receive feedback of results with the main motivation being diagnostic and therapeutic benefits as well as facilitating future health planning. Content analysis identified three themes and several sub-themes including 1) the need to know one s health status; 2) ethical considerations for feedback of findings and 3) extending feedback of genetics findings to family and community

ConclusionParticipation in hypothetical genetics and genomics research as well as feedback of testing results is acceptable to individuals in grassroots communities. The strong therapeutic misconception linked to GGR is concerning and has implications for consent processes and genetic counselling. Privacy and confidentiality, benefits, risks as well as implications for sharing need to be considered for such feedback of results to be conducted appropriately.

category: medical ethics


title: Low knowledge about hepatitis B prevention among pregnant women in the Democratic Republic of the Congo

abstract: Infants infected perinatally with hepatitis B (HBV) are at the highest risk of developing chronic hepatitis and associated sequelae. Prevention of mother-to-child transmission (PMTCT) of HBV requires improved screening and awareness of the disease. This study evaluated existing HBV knowledge among pregnant mothers (n = 280) enrolled in two HBV screening studies in two urban maternity centers in Kinshasa, Democratic Republic of the Congo. All mothers responded to three knowledge questions upon study enrollment. Baseline levels of knowledge related to HBV transmission, treatment, and symptoms were low across all participants; 60% of participants responded "I dont know" to all questions. HBV-positive women who participated in both studies (n= 46) were asked the same questions during both studies and showed improved knowledge after screening and treatment, despite no formal educational component in either study. These findings highlight the need for intensified education initiatives in highly endemic areas to improve PMTCT efforts.


title: Reproducibility of Survey Measurements of Sexual Orientation in the USA.

abstract:
Survey measurements of sexual orientation have become increasingly common in national population surveys although validation of these measurements is rare and inherently problematic. We instead assess the reproducibility of parallel measurements from two independent samples of the USA population made in the 2008-2018 General Social Surveys and the adult probability subsets of the 2013-2018 National Health Interview Survey (Ns = 12,098 and 190,113).

Restricting analysis to the categories gay/lesbian, bisexual, and straight, we obtain similar estimates of the proportion of the U.S. population who consider themselves gay/lesbian (NHIS: 1.59% vs. GSS: 1.93%, p = 0.059) but not bisexual (NHIS: 1.03% vs. GSS: 2.90%, p < 0.001). Fitting multinomial logistic regression models controlling for year, gender, birth cohort, education, and race, we find that compared to the NHIS, the GSS had 1.248 (p=0.022) times higher relative odds of eliciting a response of Gay-Lesbian (vs. Straight) and 2.980 (p<0.001) times higher relative odds of eliciting a response of Bisexual (vs. Straight). Expanding the model by adding 3-way interaction terms for orientation-by-predictor-by-survey, we find that we cannot reject the null hypothesis that trends over time and across subpopulations in reporting of sexual orientation were statistically equivalent for the two survey programs.