bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the impact of interventions against COVID-19: from lockdown to vaccination
Authors: Thompson James , Wattam Stephen
Published: March 2021

Coronavirus disease 2019 (COVID-19) is an infectious disease of humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first case was identified in China in December 2019 the disease has spread worldwide, leading to an ongoing pandemic. In this article, we present a detailed agent-based model of COVID-19 in Luxembourg, and use it to estimate the impact, on cases and deaths, of interventions including testing, contact tracing, lockdown, curfew and vaccination.

Our model is based on collation, with agents performing activities and moving between locations accordingly. The model is highly heterogeneous, featuring spatial clustering, over 2000 behavioural types and a 10 minute time resolution. The model is validated against COVID-19 clinical monitoring data collected in Luxembourg in 2020.

Our model predicts far fewer cases and deaths than the equivalent equation-based SEIR model. In particular, withR0= 2.45, the SEIR model infects 87% of the resident population while our agent-based model infects only around 23% of the resident population. Our simulations suggest that testing and contract tracing reduce cases substantially, but are less effective at reducing deaths. Lockdowns are very effective although costly, while the impact of an 11pm-6am curfew is relatively small. When vaccinating against a future outbreak, our results suggest that herd immunity can be achieved at relatively low levels, with substantial levels of protection achieved with only 30% of the population immune. When vaccinating in the midst of an outbreak, the challenge is more difficult. In this context, we investigate the impact of vaccine efficacy, capacity, hesitancy and strategy.

We conclude that, short of a permanent lockdown, vaccination is by far the most effective way to suppress and ultimately control the spread of COVID-19.
Socioeconomic and geographic correlates of intimate partner violence in Sri Lanka: Analysis of the 2016 Demographic and Health Survey
Authors: Bandara Piumee , Knipe Duleeka , Munasinghe Sithum , Rajapakse Thilini , Page Andrew
Published: March 2021

Intimate partner violence (IPV) is a serious public health issue and violation of human rights. The prevalence of IPV in South Asia is especially pronounced. This is the first study in Sri Lanka to examine the associations between socioeconomic position (SEP), geographical factors and IPV using nationally representative data. Data collected from Sri Lanka’s 2016 Demographic and Health Survey were analysed using multilevel logistic regression techniques. A total 16,390 eligible ever-partnered women aged 15-49 years were included in the analysis. Analyses were also stratified by ethnicity, type of violence, neighbourhood poverty and post-conflict residential status for selected variables. Consistent associations were found for low SEP and IPV. Lower educational attainment among women (OR 2.46 95% CI 1.83-3.30) and their partners (OR 2.87 95% CI 2.06-4.00), financial insecurity (OR 2.17 95% CI 1.92-2.45) and poor household wealth (OR 2.64 95% CI 2.22-3.13) were the socioeconomic factors that showed the strongest association with any IPV, after adjusting for age and religion. These associations predominately related to physical and/or sexual violence, with weak associations for psychological violence. Women living in a post-conflict environment had a higher risk (OR 2.96 95% CI 2.51-3.49) of IPV compared to other areas. Ethnic minority women (Tamil and Moor) were more likely to reside in post-conflict areas and experience poverty more acutely compared to the majority Sinhala women, which may explain the stronger associations for low SEP, post-conflict residence and IPV found among Tamil and Moor women. We found IPV is more likely to occur in the context of socioeconomic disadvantage and post-conflict regions. Further exploratory studies investigating the complex interplay of individual, household and community-level factors occurring in this context is required.
Rescaling and Small Area Estimation of Health Survey Data as applied to Smoking Rates in Allegheny County, Pennsylvania
Authors: Stacy Shaina L. , Chandra Hukum , Gurewitsch Raanan , Brink LuAnn L. , Robertson Linda B. , Wilson David O. , Yuan Jian-Min , Pyne Saumyadipta
Published: March 2021

We propose a novel, two-step method for rescaling health survey data and creating small area estimates of smoking rates using a Behavioral Risk Factor Surveillance System (BRFSS) survey administered in 2015 to participants living in Allegheny County, in the state of Pennsylvania, USA. The first step consisted of a spatial microsimulation to rescale location of survey respondents from zip codes to tracts based on census population distributions by age, sex, race, and education. The rescaling allowed us, in the second step, to utilize and select from available census tract specific ancillary data on social vulnerability for small area estimation (SAE) of local health risk using an area level version of a logistic linear mixed model. To demonstrate this new two-step algorithm, we estimated the ever-smoking rate for the census tracts of Allegheny County. The ever-smoking rate was slightly above 70% for two census tracts to the southeast of the city of Pittsburgh. Several tracts in the southern and eastern sections of Pittsburgh also had relatively high (>65%) ever-smoking rates. These small area estimates may be used in local public health efforts to target interventions and educational resources aimed at reducing cigarette smoking. Further, our new two-step methodology may be extended to small area estimation for other locations, and other health-related behaviors and outcomes.
Viability RT-PCR for SARS-CoV-2: a step forward to solve the infectivity quandary
Authors: Cuevas-Ferrando Enric , Randazzo Walter , Pérez-Cataluña Alba , Falcó Irene , Navarro David , Martin-Latin Sandra , Díaz-Reolid Azahara , Girón-Guzmán Inés , Allende Ana , Sánchez Gloria
Published: March 2021

Background

Isolation, contact tracing and restrictions on social movement are being globally implemented to prevent and control onward spread of SARS-CoV-2, even though the infection risk modelled on RNA detection by RT-qPCR remains biased as viral shedding and infectivity are not discerned. Thus, we aimed to develop a rapid viability RT-qPCR procedure to infer SARS-CoV-2 infectivity in clinical specimens and environmental samples.

Methods

We screened monoazide dyes and platinum compounds as viability molecular markers on five SARS-CoV-2 RNA targets. A platinum chloride-based viability RT-qPCR was then optimized using genomic RNA, and inactivated SARS-CoV-2 particles inoculated in buffer, stool, and urine. Our results were finally validated in nasopharyngeal swabs from persons who tested positive for COVID-19 and in wastewater samples positive for SARS-CoV-2 RNA.

Findings

We established a rapid viability RT-qPCR that selectively detects potentially infectious SARS-CoV-2 particles in complex matrices. In particular, the confirmed positivity of nasopharyngeal swabs following the viability procedure suggests their potential infectivity, while the complete prevention of amplification in wastewater indicated either non-infectious particles or free RNA.

Interpretation

The viability RT-qPCR approach provides a more accurate ascertainment of the infectious viruses detection and it may complement analyses to foster risk-based investigations for the prevention and control of new or re-occurring outbreaks with a broad application spectrum.

Fundings

This work was supported by Spanish Scientific Research Council (CSIC), Generalitat Valenciana, and MICINN co-founded by AEI/FEDER, UE.
The vaccine-elicited immunoglobulin profile in milk after COVID-19 mRNA-based vaccination is IgG-dominant and lacks secretory antibodies
Authors: Fox Alisa , Norris Caroline , Amanat Fatima , Zolla-Pazner Susan , Powell Rebecca L.
Published: March 2021

The Pfizer/BioNTech and Moderna mRNA-based COVID-19 vaccines are licensed under emergency use authorization, with millions of doses already administered globally [1]. No COVID-19 vaccines are yet under investigation for use in infants or young children. As such, the passive immunity of the antibodies (Abs) provided through milk from a vaccinated person may be one of the only ways to protect this population until pediatric COVID-19 vaccines are licensed. Our early work (as well as an expanded study being published concurrently with this report) examining the milk Ab response after SARS-CoV-2 infection demonstrated that Spike-specific IgA in milk after infection is dominant and highly correlated with a secretory Ab response [2]. Determining if secretory Abs are elicited in milk is critical, as this Ab class is highly stable and resistant to enzymatic degradation in all mucosae - not only in the infant oral/nasal cavity and gut, but in the airways and GI tract as well [3, 4]. Presently, we describe our analysis of the milk Ab response 14 days after completion of an mRNA-based COVID-19 vaccine regimen among 10 individuals. It was evident that unlike the post-infection milk Ab profile, IgG dominates after COVID-19 vaccination. One hundred percent of post-vaccine milk contained significant levels of Spike-specific IgG, with 8/10 samples exhibiting high IgG endpoint titers. Conversely, 6/10 (60%) of post-vaccine samples were positive for Spike specific IgA, with only 1 (10%) exhibiting high IgA endpoint titer. Furthermore, 5/10 (50%) post-vaccine milk samples contained Spike-specific secretory Ab, none of which were found to be high-titer. As our analyses of the immune response in milk to COVID-19 vaccination continues, it will provide a critical opportunity to address huge knowledge gaps, inform the field as to which COVID-19 vaccine, if any, is likely to provide the best milk Ab response, and highlight the need to design improved vaccines with protection of the breastfeeding infant in mind.
Hemodynamic Differences Between Women and Men with Elevated Blood Pressure in China: A Non-Invasive Assessment of 45,082 Adults Using Impedance Cardiography
Authors: Caraballo César , Mahajan Shiwani , Gu Jianlei , Lu Yuan , Spatz Erica S. , Dreyer Rachel P. , Zhang MaoZhen , Sun NingLing , Ren Yihong , Zheng Xin , Zhao Hongyu , Lu Hui , Ma Zheng J. , Krumholz Harlan M.
Published: March 2021

Background

Whether there are sex differences in hemodynamic profiles among people with elevated blood pressure is not well understood and could guide personalization of treatment.

Methods and results

We described the clinical and hemodynamic characteristics of adults with elevated blood pressure in China using impedance cardiography. We included 45,082 individuals with elevated blood pressure (defined as systolic blood pressure of ≥130 mmHg or a diastolic blood pressure of ≥80 mmHg), of which 35.2% were women. Overall, women had a higher mean systolic blood pressure than men (139.0 [±15.7] mmHg vs 136.8 [±13.8] mmHg, P<0.001), but a lower mean diastolic blood pressure (82.6 [±9.0] mmHg vs 85.6 [±8.9] mmHg, P<0.001). After adjusting for age, region, and body mass index, women <50 years old had lower systemic vascular resistance index (beta-coefficient [β] -31.7; 95% CI: -51.2, -12.2) and higher cardiac index (β 0.07; 95% CI: 0.04, 0.09) than men of their same age group, whereas among those ≥50 years old women had higher systemic vascular resistance index (β 120.4; 95% CI: 102.4, 138.5) but lower cardiac index (β -0.15; 95% CI: -0.16, -0.13). Results were consistent with a propensity score matching sensitivity analysis, although the magnitude of the SVRI difference was lower and non-significant. However, there was substantial overlap between women and men in the distribution plots of these variables, with overlapping areas ranging from 78% to 88%.

Conclusions

Our findings indicate that there are sex differences in hypertension phenotype, but that sex alone is insufficient to infer an individual’s profile.
Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 infection severity
Authors: Freitas Ana Teresa , Calhau Conceição , Antunes Gonçalo , Araújo Beatriz , Bandeira Matilde , Barreira Sofia , Bazenga Filipa , Braz Sandra , Caldeira Daniel , Santos Susana Constantino Rosa , Faria Ana , Faria Daniel , Fraga Marta , Nogueira-Garcia Beatriz , Gonçalves Lúcia , Kovalchuk Pavlo , Lacerda Luísa , Lopes Hugo , Luís Daniel , Medeiros Fábio , Melo Ana M. P. , Melo-Cristino José , Miranda Ana , Pereira Clara , Pinto Ana Teresa , Pinto João , Proença Helena , Ramos Angélica , P. R. Rato João , Rocha Filipe , César Rocha Júlio , Moreira-Rosário André , Vazão Helena , Volovetska Yuliya , Guimarães João-Tiago , Pinto Fausto
Published: March 2021

Background

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways.

Methods

This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed.

Results

The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.042). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%).

Conclusion

This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.

Trial registration

NCT04370808
Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
Authors: Tsitsiklis Alexandra , Zha Beth Shoshana , Byrne Ashley , DeVoe Catherine , Rackaityte Elze , Levan Sophia , Sunshine Sara , Mick Eran , Ghale Rajani , Love Christina , Tarashansky Alexander J. , Pisco Angela , Albright Jack , Jauregui Alejandra , Sarma Aartik , Neff Norma , Serpa Paula Hayakawa , Deiss Thomas J. , Kistler Amy , Carrillo Sidney , Ansel K. Mark , Leligdowicz Aleksandra , Christenson Stephanie , Detweiler Angela , Jones Norman G. , Wu Bing , Darmanis Spyros , Lynch Susan V. , DeRisi Joseph L. ,   COMET Consortium, Matthay Michael A. , Hendrickson Carolyn M. , Kangelaris Kirsten N. , Krummel Matthew F. , Woodruff Prescott G. , Erle David J. , Rosenberg Oren , Calfee Carolyn S. , Langelier Charles R.
Published: March 2021

Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing we assessed lower respiratory tract immune responses and microbiome dynamics in 23 COVID-19 patients, 10 of whom developed VAP, and eight critically ill uninfected controls. At a median of three days (range: 2-4 days) before VAP onset we observed a transcriptional signature of bacterial infection. At a median of 15 days prior to VAP onset (range: 8-38 days), we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset.
Optimizing SARS-CoV-2 Variant of Concern Screening: Experience from British Columbia, Canada, Early 2021
Authors: Hogan Catherine A. , Sbihi Hind , Jassem Agatha , Prystajecky Natalie , Tyson John R. , Lee Tracy D. , Tsang Frankie , Ng Corrinne , Janz Loretta , Romney Marc G. , Hoang Linda
Published: March 2021

Comprehensive and timely testing is required for SARS-CoV-2 variant of concern (VoC) screening. Whole genome sequencing (WGS) provides the broadest means to detect circulating VoCs, but requires longer turnaround time than targeted molecular testing by quantitative polymerase chain reaction (qPCR). We demonstrated the feasibility of a combined testing approach for VoC prevalence assessment in British Columbia, and showed high concordance between qPCR testing and WGS. This directly informed wider VoC screening strategy implementation, and public health efforts.
High-dimensional analysis reveals abnormal B cell subsets associated with specific changes to circulating T and myeloid cell populations in patients with idiopathic inflammatory myopathies
Authors: Wilfong Erin M. , Bartkowiak Todd , Vowell Katherine N. , Westlake Camille S. , Irish Jonathan M. , Kendall Peggy L. , Crofford Leslie J. , Bonami Rachel H.
Published: March 2021

Objectives

The idiopathic inflammatory myopathies (IIM) are a clinically heterogeneous group of conditions affecting the skin, muscle, joint, and lung in various combinations. This study aims to investigate the immunologic heterogeneity through detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) in IIM patients and healthy controls.

Methods

We collected PBMCs from 17 patients with a clinical diagnosis of inflammatory myositis in the inpatient or outpatient setting and performed immunophenotyping using mass cytometry by time of flight (CyTOF) to simultaneously characterize B, T, and myeloid cell subsets. Data were analyzed using a combination of supervised biaxial gating and unsupervised clustering algorithms including t-distributed stochastic neighbor embedding (tSNE), cluster identification, characterization, and regression (CITRUS), and marker enrichment modeling (MEM).

Results

We identified two distinct immune signatures amongst IIM patients. In one signature, increased CD19+CXCR4hiCCR7hi cells correlated with increased CD3+CXCR4hiCD38hi (r=0.62, p=0.009) and CD14+CD16-CXCR4+CD38+HLADR-(r=0.61, p=0.01) populations. In the second signature, increased CD19+CD21loCD11c+ cells correlated with an increased CD3+CD4+PD1+ (r=0.60, p=0.01) population. Other shared immunologic features amongst IIM patients compared to healthy controls included decreased surface expression of RP105/CD180 on B cells (median mass intensity 39.9 ± 16.0 v. 60.9 ± 20.1, p=0.002). In the T cell compartment, all circulating CD3+CXCR3+ subsets (2.7 ± 2.4 v. 9.6 ± 8.1% of all PBMCs, p=0.0004) were reduced.

Conclusion

Based on circulating B cell phenotype, we identified two distinct immunologic signatures in IIM patients. Future work is needed to determine the significance of these immune signatures for clinical manifestations and treatment responses.
Seroprevalence of antibodies against SARS-CoV-2 virus in the adult Norwegian population, winter 2020/2021: pre-vaccination period
Authors: Anda Erik Eik , Braaten Tonje , Borch Kristin B. , Nøst Therese H. , Chen Sairah L. F. , Lukic Marko , Lund Eiliv , Forland Frode , Leon David , Winje Brita Askeland , Kran Anne-Marte Bakken , Kalager Mette , Johansen Fridtjof Lund , Sandanger Torkjel M.
Published: March 2021

Since early 2020, over 123 million people worldwide have been diagnosed with coronavirus disease (Covid-19), but the true number of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly higher. The seroprevalence of antibodies against SARS-CoV-2 can provide crucial epidemiological information about the extent of infections independent of virologically detected case numbers. There is no large population-based SARS-CoV-2 seroprevalence survey from Norway; thus we estimated SARS-CoV-2 seroprevalence in Norway before the introduction of vaccines and described its distribution across demographic groups. In November-December 2020, a total of 110,000 people aged 16 years or older were randomly selected from the National Population Register and invited to complete a questionnaire and provide a dried blood spot (DBS) sample. The response rate was 30%; compliance rate for return of DBS samples was 88%. The national weighted and adjusted seroprevalence was 0.9% (confidence interval 0.7-1.0).

Seroprevalence was highest among those aged 16-19 years (1.9%, 0.9-2.9), those born outside the Nordic countries 1.4% (1.0-1.9), and in the counties of Oslo 1.7 % (1.2-2.2) and Vestland 1.4% (0.9-1.8). The ratio of SARS-CoV-2 seroprevalence (0.9) to the cumulative incidence of virologically detected cases by mid-December 2020 (0.8%) was slightly above one. SARS-CoV-2 seroprevalence was low before the introduction of vaccines in Norway and was comparable to virologically detected cases, indicating that most cases in the first 10 months of the pandemic were detected. Preventive measures including contact tracing have been effective, people are complying with social distancing recommendations, and local efforts to contain outbreaks have been essential.
Evaluation of The Pink Luminous Breast LED-Based Technology Device as a Screening Tool for the Early Detection of Breast Abnormalities
Authors: Ocasio-Villa Fernando , Morales-Torres Luisa , Velez-Medina Norma , Orengo Juan C. , Suarez Martinez Edu B.
Published: March 2021

Breast cancer is the leading cause of sex-specific female cancer death in the United States. Detection at earlier stages contributes to decrease the mortality rate. The mammography is considered the gold standard for breast cancer screening with an estimate sensitivity of 86.9% and a specificity 88.9%. However, these values are negatively affected by the breast, which is consider a risk factor for developing breast cancer. Herein, we validate the novel LED-based FDA Class I medical device Pink Luminous Breast (PLB) by the comparison of two breast screening imaging-based tests using a double blinded approach. The PLB works by emitting a LED red light with a harmless spectrum of 640-800 nanometers, the trans-illuminated breast tissue allows the observation of abnormalities represented by darker or shadowing areas. In this study, we evaluated the sensitivity and specificity of the PLB device as a screening tool for the early detection of breast abnormalities when compared with the mammography as the gold standard. Our results showed that PLB device has a high sensitivity (89.6%) and specificity (96.4%) for detecting breast abnormalities comparable to the adjusted mammography values: 86.3% and 68.9% respectively. Importantly, the percentage of positive dense tissue findings from a total of 340 events was 266 (78.2%) using PLB vs. 248 (72.9%) detected by the mammography. A 100% of the participants responded in a survey that they feel comfortable using the device and visualizing their breast without feeling pain or discomfort during the examination. The PLB positive validation vs the mammography brings the potential to be recommended for routinely breast screening at non-clinical settings. The PLB provides a rapid, non-invasive, portable, and easy-to-use tool for breast screening that can complement the home-based BSE technique or the CBE. In addition, the PLB can be conveniently used for screening breasts with surgical implants. PLB provides an accessible and painless breast cancer screening tool. The use of this device is not intended to replace the mammography as the gold standard for breast screening but rather to use it as an adjunct or complement tool as part of more efficient earlier detection strategies and contribute to decrease this health disparity.
Relative Pandemic Severity in Canada and Four Peer Nations During the SARS-CoV-2 Pandemic
Authors: Peng Amy , Simmons Alison E. , Amoako Afia , Tuite Ashleigh R. , Fisman David N.
Published: March 2021

Introduction

National responses to the SARS-CoV-2 pandemic have been highly variable, which may explain some of the heterogeneity in the pandemic’s health and economic impacts across the world. We sought to explore the effectiveness of the Canadian pandemic response relative to responses in four peer countries with similar political, economic and health systems, and with close historical and cultural ties to Canada (the United States, United Kingdom, France, and Australia) from March 2020 to May 2022.

Methods

We used reported age-specific mortality data to generate estimates of pandemic mortality standardized to the Canadian population. Age-specific case fatality, hospitalization, and intensive care admission probabilities for the Canadian province of Ontario were applied to estimated deaths in order to calculate hospitalizations and intensive care admissions averted by the Canadian response. The monetary value of averted hospitalizations was estimated using cost estimates from the Canadian Institute for Health Information. Age-specific quality-adjusted life-years (QALY) lost due to fatality were estimated using published estimates. QALY were monetized using a net expected benefit approach.

Results

Relative to the United States, United Kingdom, and France, the Canadian pandemic response was estimated to have averted 94,492, 64,306 and 13,641 deaths respectively, with more than 480,000 hospitalizations averted, and 1 million QALY saved, relative to the United States. A United States pandemic response applied to Canada would have resulted in more than $40 billion in economic losses due to healthcare expenditures and lost QALY; losses relative to the United Kingdom and France would have been $21 billion and $5 billion respectively. By contrast, an Australian pandemic response would have averted over 28,000 additional deaths and averted nearly $9 billion in costs in Canada.

Conclusions

Canada outperformed peer countries that aimed for mitigation, rather than elimination, of SARS-CoV-2 in the first two years of the pandemic, likely because of a more stringent public health response to disease transmission. This resulted in substantial numbers of lives saved and economic costs averted. However, comparison with Australia demonstrates that an elimination focus would have allowed Canada to save tens of thousands of lives, and would have saved substantial economic costs.
Computerized Cognitive Training in People with Depression: A Systematic Review and Meta-analysis of Randomized Clinical Trials
Authors: Gefen Eliane , Launder Nathalie H. , Davey Christopher G. , Nahum Mor , Gilboa Yafit , Finke Carsten , Malmberg Gavelin Hanna , Lautenschlager Nicola T. , Lampit Amit
Published: March 2021

Importance

Cognitive impairment is a common feature of both symptomatic and remitted states of depression that is associated with poorer psychosocial outcomes and treatment non-response. As such, finding treatments to maintain or enhance cognition in people with depression is imperative.

Objective

To investigate the efficacy and moderators of computerized cognitive training (CCT) for cognitive and functional outcomes in people with depression.

Data Sources

MEDLINE, EMBASE and PsycINFO databases were screened from inception through to 08 September 2022, with no language or publication type restrictions.

Study Selection

Two independent reviewers conducted duplicate study screening and assessed against the following inclusion criteria: (1) adults (mean age 18 years or older) with depression, (2) CCT with minimum three hours practice, (3) active or passive control group, (4) cognitive and/or functional outcomes measured at baseline and post-intervention, (5) randomized controlled trials. Of 4245 identified studies, 34 met selection criteria.

Data Extraction and Synthesis

The methods used followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction and risk of bias assessment using the revised Cochrane Risk of Bias Tool (RoB2) was conducted independently by two reviewers. Analyses were conducted using robust variance estimation.

Outcomes

The primary outcome was change from baseline to post-intervention in overall cognition. Secondary outcomes were depressive symptoms, psychiatric symptoms, psychosocial functioning, daily functioning, subjective cognition, global cognition and domain-specific cognitive function.

Results

Thirty-four studies encompassing 39 comparisons and 2041 unique participants met inclusion criteria. The pooled effect size of CCT was small for both overall cognition (g=0.28; 95% CI 0.17 to 0.38;P<.001; τ2=0.078;I2=47%; 95% prediction interval −0.31 to 0.86) and depressive symptoms (g=0.23; 95% CI 0.08 to 0.39;P=.004; τ2=0.066;I2=45%; 95% prediction interval −0.32 to 0.78). Benefits of CCT were also found for psychosocial functioning, subjective cognition, fluid reasoning, long-term memory and retrieval, low working memory, shifting, inhibition and processing speed. Greater CCT dose and multidomain programs were associated with greater cognitive response to CCT. There was no evidence for difference across clinical subtypes or between delivery modalities.

Conclusions and Relevance

This systematic review and meta-analysis indicates that CCT is an efficacious intervention for overall cognition, depressive symptoms, psychosocial functioning, subjective cognition, and many domain-specific cognitive functions for people with depression.
Reconstructing the COVID-19 epidemic in Delhi, India: infection attack rate and reporting of deaths
Authors: Pons-Salort Margarita , John Jacob , Watson Oliver J , Brazeau Nicholas F , Verity Robert , Kang Gagandeep , Grassly Nicholas C
Published: March 2021

India reported over 10 million COVID-19 cases and 149,000 deaths in 2020. To estimate exposure and the potential for further spread, we used a SARS-CoV-2 transmission model fit to seroprevalence data from three serosurveys in Delhi and the time-series of reported deaths to reconstruct the epidemic. The cumulative proportion of the population estimated infected was 48.7% (95% CrI 22.1% – 76.8%) by end-September 2020. Using an age-adjusted overall infection fatality ratio (IFR) based on age-specific estimates from mostly high-income countries (HICs), we estimate that 15.0% (95% CrI 9.3% – 34.0%) of COVID-19 deaths were reported. This indicates either under-reporting of COVID-19 deaths and/or a lower age-specific IFR in India compared with HICs. Despite the high attack rate of SARS-CoV-2, a third wave occurred in late 2020, suggesting that herd immunity was not yet reached. Future dynamics will strongly depend on the duration of immunity and protection against new variants.
Tools for measuring sexual and reproductive health and rights (SRHR) indicators in humanitarian settings
Authors: Goulart Céline M. , Giancola Amanda , Nakhuda Humaira , Ampadu Anita , Purewal Amber , Kortenaar Jean-Luc , Bassani Diego G.
Published: March 2021

Background

Effective measurement of all health indicators and especially SRHR is difficult in humanitarian settings. Displacement and insecurity due to conflict, natural disasters, and epidemics place women and girls at higher risk of SRHR-related morbidity and mortality and reduce the coverage of essential SRHR services. This scoping review describes the measurement tools, methods, and indicators used to measure SRHR coverage and outcome indicators in humanitarian settings in the past 15 years and presents an accessible dashboard that can be used by governments, researchers and implementing organizations to identify available SRHR measurement tools.

Methods

Scientific articles published between January 2004 and May 2019 were identified using Embase, Medline, PsycInfo, CINAHL, Scopus, PAIS index as well as relevant non-peer-reviewed literature available through websites of humanitarian organizations. Publications including data from low- or middle-income countries (LMICs), focused on women and/or girls living in areas impacted by a humanitarian crisis, where data was collected within five years of the crisis were included. Indicators extracted from these publications were categorized according to validated SRHR indicators recommended by the World Health Organization (WHO). Measurement tools, sampling and data collection methods, gap areas (geographical, topical and contextual), and indicators were catalogued for easy access in an interactive Tableau dashboard.

Results

Our search yielded 42,081 peer-reviewed publications and 2,569 non-peer-reviewed reports. After initial title and abstract screening, 385 publications met the inclusion criteria. SRHR indicators were categorized into nine domains: abortion, antenatal care, family planning, gender-based violence, HIV and sexually transmitted infections, maternal health, maternal mortality, menstrual and gynecological health, and obstetric care (delivery). A total of 65 tools and questionnaires measuring SRHR were identified, of which 25 were designed specifically for humanitarian settings.

Discussion

Although SRHR was measured in humanitarian settings, several gaps in measurement were identified. Abortion and gynaecological health were not consistently measured across included studies or validated WHO indicators. Toolkits and indicators identified in this review may be used to inform future SRHR data collection in humanitarian settings. However, identifying and/or developing innovative data collection methodologies should be a research priority, especially in light of the recent COVID-19 pandemic.
Occupational stress and quality of sleep among dentists in the Philippines
Authors: Dalanon Junhel , Fernandez Ivy , Estalani Cora , Chikahisa Sachiko , Shimizu Noriyuki , Locsin Rozzano , Matsuka Yoshizo
Published: March 2021

Background

Occupational stress and sleep quality share a bidirectional relationship among other comorbidities. Dentistry remains among the health professions that suffer the greatest stress.

Aim

This study aimed to evaluate the correlation between occupational stress and sleep quality among dentists in the Philippines.

Methods

The Caregiver Self-Assessment Questionnaire assessed occupational stress and the Pittsburgh Sleep Quality Index measured sleep quality in purposively sampled dentists (n=420) in the Philippines.

Results

The prevalence of occupational stress (19%) was low yet poor sleep quality (71%) was high. The global PSQI score (p=0.047) and sleep onset latency (p=0.036) were found to be associated with occupational stress.

Conclusions

This study supports the vast literature on the relationship between occupational stress and sleep quality, despite documenting an unexpected low prevalence of occupational stress in Filipino dentists. Further research on the coping mechanisms of these dentists is warranted.
A polygenic risk score for coronary heart disease performs well in individuals aged 70 years and older
Authors: Neumann Johannes T. , Riaz Moeen , Bakshi Andrew , Polekhina Galina , Thao Le T. P. , Nelson Mark R. , Woods Robyn L. , Abraham Gad , Inouye Michael , Reid Christopher M. , Tonkin Andrew M. , McNeil John , Lacaze Paul
Published: March 2021

Background

The use of a polygenic risk score (PRS) to predict coronary heart disease (CHD) events has been demonstrated in the general adult population. However, whether predictive performance extends to older individuals is unclear.

Aim

To evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of individuals aged 70 years and older.

Methods

We used data from 12,792 genotyped participants of the ASPREE trial, a randomized placebo-controlled trial investigating the effect of daily 100mg aspirin on disability-free survival in healthy older people. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrolment. We calculated a PRS comprising 1.7 million genetic variants (metaGRS). The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years.

Results

At baseline, the median population age was 73.9 years and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio 1.24 [95% confidence interval [CI] 1.08-1.42], p=0.002). The AUC of the conventional model was 70.53 (95%CI 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95%CI 68.32-75.24, p=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95%CI 0.15-0.28).

Conclusions

A PRS for CHD performs well in older people, suggesting that the clinical utility of genomic risk prediction for CHD extends to this distinct high-risk subgroup.
COVID-19 vaccine access and attitudes among people experiencing homelessness from pilot mobile phone survey in Los Angeles, CA
Authors: Kuhn Randall , Henwood Benjamin , Lawton Alexander , Kleva Mary , Murali Karthik , King Coley , Gelberg Lillian
Published: March 2021

Background

People experiencing homelessness (PEH) are at high risk for COVID-19 complications and fatality, and have been prioritized for vaccination in many areas. Yet little is known about vaccine acceptance in this population. The objective of this study was to determine the level of vaccine hesitancy among PEH in Los Angeles, CA and to understand the covariates of hesitancy in relation to COVID-19 risk, threat perception, self-protection and information sources.

Methods and findings

A novel mobile survey platform was deployed to recruit PEH from a federally qualified health center (FQHC) in Los Angeles to participate in a monthly rapid response study of COVID-19 attitudes, behaviors, and risks. Of 90 PEH surveyed, 43 (48%) expressed some level of vaccine hesitancy based either on actual vaccine offers (17/90 = 19%) or a hypothetical offer (73/90 = 81%). In bivariate analysis, those with high COVID-19 threat perception were less likely to be vaccine hesitant (OR=0.34, P=.03), while those who frequently practiced COVID-19 protective behaviors were more likely to be vaccine hesitant (OR=2.21, P=.08). In a multivariate model, those with high threat perception (OR=0.25, P=.02) were less likely to be hesitant, while those engaging in COVID-19 protective behaviors were more hesitant (OR=3.63, P=.02). Those who trusted official sources were less hesitant (OR=0.37, P=.08) while those who trusted friends and family for COVID-19 information (OR=2.70, P=.07) were more likely to be hesitant.

Conclusions

Findings suggest that targeted educational and social influence interventions are needed to address high levels of vaccine hesitancy among PEH.
Optimal allocation of PCR tests to minimise disease transmission through contact tracing and quarantine
Authors: Baker Christopher M. , Chades Iadine , McVernon Jodie , Robinson Andrew , Bondell Howard
Published: March 2021

PCR testing is a crucial capability for managing disease outbreaks, but it is also a limited resource and must be used carefully to ensure the information gain from testing is valuable. Testing has two broad uses, namely to track epidemic dynamics and to reduce transmission by identifying and managing cases. In this work we develop a modelling framework to examine the effects of test allocation in an epidemic, with a focus on using testing to minimise transmission. Using the COVID-19 pandemic as an example, we examine how the number of tests conducted per day relates to reduction in disease transmission, in the context of logistical constraints on the testing system. We show that if daily testing is above the routine capacity of a testing system, which can cause delays, then those delays can undermine efforts to reduce transmission through contact tracing and quarantine. This work highlights that the two goals of aiming to reduce transmission and aiming to identify all cases are different, and it is possible that focusing on one may undermine achieving the other. To develop an effective strategy, the goals must be clear and performance metrics must match the goals of the testing strategy. If metrics do not match the objectives of the strategy, then those metrics may incentivise actions that undermine achieving the objectives.
Quantifying and Realizing the Benefits of Targeting for Pandemic Response
Authors: Camelo Sergio , Ciocan Dragos Florin , Iancu Dan A. , Warnes Xavier S. , Zoumpoulis Spyros I.
Published: March 2021

To respond to pandemics such as COVID-19, policy makers have relied on interventions that target specific population groups or activities. Because targeting is operationally challenging and contentious, rigorously quantifying its benefits and designing practically implementable policies that achieve some of these benefits is critical for effective and equitable pandemic control. We propose a flexible framework that leverages publicly available data and a novel optimization algorithm based on model predictive control and trust region methods to compute optimized interventions that can target two dimensions of heterogeneity: age groups and the specific activities that individuals normally engage in. We showcase a complete implementation focused on the Île-de-France region of France and use this case study to quantify the benefits of dual targeting and to propose practically implementable policies. We find that dual targeting can lead to Pareto improvements, reducing the number of deaths and the economic losses. Additionally, dual targeting allows maintaining higher activity levels for most age groups and, importantly, for those groups that are most confined, thus leading to confinements that are arguably more equitable. We then fit decision trees to explain the decisions and gains of dual-targeted policies and find that they prioritize confinements intuitively, by allowing increased activity levels for group-activity pairs with high marginal economic value prorated by social contacts, which generates important complementarities. Because dual targeting can face significant implementation challenges, we introduce two practical proposals inspired by real-world interventions — based on curfews and recommendations — that achieve a significant portion of the benefits without explicitly discriminating based on age.
The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males
Authors: Croci Susanna , Venneri Mary Anna , Mantovani Stefania , Fallerini Chiara , Benetti Elisa , Picchiotti Nicola , Campolo Federica , Imperatore Francesco , Palmieri Maria , Daga Sergio , Gabbi Chiara , Montagnani Francesca , Beligni Giada , Farias Ticiana D.J. , Carriero Miriam Lucia , Sarno Laura Di , Alaverdian Diana , Aslaksen Sigrid , Cubellis Maria Vittoria , Spiga Ottavia , Baldassarri Margherita , Fava Francesca , Norman Paul J. , Frullanti Elisa , Isidori Andrea M. , Amoroso Antonio , Mari Francesca , Furini Simone , Mondelli Mario U ,   GEN-COVID multicenter study, Chiariello Mario , Renieri Alessandra , Meloni Ilaria
Published: March 2021

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired autophagy and reduced TNFα production was demonstrated in HEK293 cells transfected with TLR3-L412F plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (P=0.038). An increased frequency of autoimmune disorders as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways.
The acceptability of testing contacts of confirmed COVID-19 cases using serial, self-administered lateral flow devices as an alternative to self-isolation
Authors: Love Nicola , Ready Derren , Turner Charlie , Yardley Lucy , Rubin G. James , Hopkins Susan , Oliver Isabel
Published: March 2021

Background

Testing asymptomatic contacts of confirmed COVID-19 cases for the presence of SARS-CoV-2 could reduce onward transmission by improving case ascertainment and lessen the impact of self-isolation on un-infected individuals. This study investigated the feasibility and acceptability of implementing a ‘test to enable approach’ as part of England’s tracing strategy.

Methods

Contacts of confirmed COVID-19 cases were offered serial testing as an alternative to self-isolation using daily self-performed lateral flow device (LFD) tests for the first 7 days post exposure. Asymptomatic participants with a negative LFD result were given 24 hours of freedom from self-isolation between each test. A self-collected confirmatory PCR test was performed on testing positive or at the end of the LFD testing period.

Results

Of 1,760 contacts, 882 consented to daily testing, with 812 within 48 hours of exposure sent testing packs. Of those who declined to participate, 39.1% stated they had already accessed PCR testing. Of the 812 who were sent packs, 570 (70.2%) reported one or more LFD results; 102 (17.9%) tested positive. Concordance between reported LFD result and a supplied LFD image was 97.1%. 82.8% of PCR positive samples and 99.6% of PCR negative samples were correctly detected by LFD. The proportion of secondary cases from contacts of those who participated in the study and tested positive (6.3%; 95% CI: 3.4-11.1%) were comparable to a comparator group who self-isolated (7.6%; 95% CI: 7.3-7.8%).

Conclusion

This study shows a high acceptability, compliance and positivity rates when using self-administered LFDs among contacts of confirmed COVID-19 cases. Offering routine testing as a structured part of the contact tracing process is likely to be an effective method of case ascertainment.
SARS-CoV-2 N gene dropout and N gene Ct value shift as indicator for the presence of B.1.1.7 lineage in a widely used commercial multiplex PCR assay
Authors: Wollschlaeger P , Gerlitz N , Todt D , Pfaender S , Bollinger T , Sing A , Dangel A , Ackermann N , Korn K , Ensser A , Steinmann E , Buhl M , Steinmann J
Published: March 2021

Objectives

Increased importance in detection and surveillance of SARS-CoV-2 has been demonstrated due to the emergence of variants of concern (VOCs). In this study we evaluated if a commercially available real-time SARS-CoV-2 PCR assay can identify B.1.1.7 lineage samples by a specific N gene dropout or Ct value shift compared to the S or RdRP gene.

Methods

Patients samples with confirmed B.1.1.7 variant by whole-genome sequencing and variant-specific PCR (n=48) and non-B.1.1.7 samples (n=53) were tested by the Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay for presence of S, RdRP and N gene of SARS CoV-2. The N gene coding sequence of SARS-CoV-2 with and without D3L mutation (specific for B.1.1.7) were cloned into pCR®-TOPO vectors and Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay was performed.

Results

All studied B.1.1.7 patient samples showed significantly higher Ct values (Δ 6-10, N-gene dropout on Ct values >29) in the N gene compared to the respective values of S and RdRP gene. Receiver operating characteristic (ROC) curve analysis resulted in 100% sensitivity and specificity for ΔCt N/RdRP and ΔCt N/S. As a result of the reversed genetic experiments we found also the shift in Ct values for the 3L variant N-gene.

Conclusions

N gene dropout or Ct value shift is specific for B.1.1.7 positive samples using the Allplex™ SARS-CoV-2/FluA/FluB/RSV PCR assay. This approach can be used as a rapid tool for B.1.1.7 detection in single assay high throughput diagnostics.